Effect of biomaterials hydrophobicity and roughness on biofilm development.
Most hospitalized patients are carriers of biomedical devices. Infections associated with these devices cause great morbidity and mortality, especially in patients in intensive care units. Numerous strategies have been designed to prevent biofilm development on biodevices. However, biofilm formation is a complex process not fully clarified. In the current study, roughness and hydrophobicity of different biomaterials was analyzed to assess their influences on the biofilm formation of four leading etiological causes of healthcare-associated infections, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis and Candida albicans, using a CDC biofilm reactor. Hydrophobic materials allowed the formation of more abundant and profuse biofilms. Roughness had effect on biofilm formation, but its influence was not significant when material hydrophobicity was considered.


Latent forms of transforming growth factor-beta 2 (TGF-beta 2) in breast cyst fluid.
Transforming growth factor-beta (TGF-beta) is secreted by cells in high molecular weight, latent forms and the in vivo mechanisms for the activation remain largely an enigma. Women who have palpable breast cyst with intracystic Na/K < 3 may have a higher risk of developing breast cancer than those with intracystic Na/K > 3. Finding of significantly higher concentrations of TGF-beta 2 in the Na/K > 3 group than Na/K < 3 group may explain the lower risk of breast cancer in the Na/K > 3 group. The aim of the present study was to characterise the latent forms of TGF-beta 2 in breast cyst fluid using HPLC, affinity chromatography, SDS-PAGE and immunostaining techniques. We found that TGF-beta 2 is present in high molecular weight, latent forms in breast cyst fluid: as a complex, probably with alpha 2-macroglobulin and a 56 kD protein which is likely to be a precursor form of TGF-beta 2.


Effects of single or repeated amphetamine treatment and withdrawal on lung allergic inflammation in rats.
The effects of single or repeated amphetamine (AMPH) treatment and those of AMPH withdrawals on immune-mediated lung inflammatory response were studied in rats. Two experiments were done. In the first, rats egg-albumin (OVA) sensitized were singularly or repeatedly (21 days, once daily) treated with AMPH (1.0 mg/kg) or with a similar number and volume of 0.9% NaCl. The OVA aerosol challenge was performed 12 h after the single or last repeated AMPH treatment and also 72 and 120 h after AMPH withdrawal. In the second experiment, the effects of reserpine (1.0 mg/kg/day for 5 consecutive days) on single AMPH actions on lung allergic response of rats were analyzed. Single and repeated AMPH treatment induced opposite actions on Bronchoalveolar lavage fluid (BAL) cellularity of allergic rats: single treatment decreased and repeated treatment increased the total number of cells as well as those of macrophages, neutrophils and eosinophils. Our data also showed that single but not repeated AMPH treatment decreased the number of neutrophils, monocytes and lymphocytes in the peripheral blood, and increased the total number of bone marrow cells in rats sensitized and challenged with OVA. Furthermore, it was shown that reserpine treatment precluded the effects of single AMPH treatment on cellular migration to the lung of OVA-sensitized and challenged rats. It was concluded that AMPH effects on lung inflammatory response and cell recruitment to the lung in allergic rats rely at least partially on corticosterone serum levels. The possible involvement of vesicular monoamine transporter type 2 (VMAT2) with these observed effects was discussed.


Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.
The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'.


Genome-wide RNAi Screening Identifies RFC4 as a Factor That Mediates Radioresistance in Colorectal Cancer by Facilitating Nonhomologous End Joining Repair.
Neoadjuvant chemoradiotherapy (neoCRT) is a standard treatment for locally advanced rectal cancer (LARC); however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to identify factors involved in the radioresistance of colorectal cancer and to clarify the underlying mechanisms. A genome-wide RNAi screen was used to search for candidate radioresistance genes. After RFC4 knockdown or overexpression, colorectal cancer cells exposed to X-rays both in vitro and in a mouse model were assayed for DNA damage, cytotoxicity, and apoptosis. Moreover, the regulatory effects and mechanisms of RFC4 in DNA repair were investigated in vitro. Finally, the relationships between RFC4 expression and clinical parameters and outcomes were investigated in 145 patients with LARC receiving neoCRT. RFC4, NCAPH, SYNE3, LDLRAD2, NHP2, and FICD were identified as potential candidate radioresistance genes. RFC4 protected colorectal cancer cells from X-ray-induced DNA damage and apoptosis in vitro and in vivo. Mechanistically, RFC4 promoted nonhomologous end joining (NHEJ)-mediated DNA repair by interacting with Ku70/Ku80 but did not affect homologous recombination-mediated repair. Higher RFC4 expression in cancer tissue was associated with weaker tumor regression and poorer prognosis in patients with LARC treated with neoCRT, which likely resulted from the effect of RFC4 on radioresistance, not chemoresistance. RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in colorectal cancer cells. In addition, the expression level of RFC4 predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in patients with LARC.


Social phobia symptoms, subtypes, and severity: findings from a community survey.
Our goals were (1) to ascertain the range of functional impairment attributable to social phobia in a community sample, and (2) to verify the existence of social phobia subtypes in the community, and report on their relative prevalence, severity, and levels of impairment. Community surveys were conducted contemporaneously in Winnipeg, Manitoba, and in Alberta, with a total of 1956 respondents. Instruments included the Comprehensive International Diagnostic Interview-Version 2.1 module for DSM-IV social phobia, enhanced with 6 additional (for a total of 12) social phobic situational probes to provide a more comprehensive assessment of possible subtypes, and additional questions about specific functional impairment due to social phobia. Of those persons in the community surveyed, most had no (60.4%) or few (ie, 1-3) (27.8%) social fears; few persons (3.4%) had many (ie, >/=7). Among those with DSM-IV social phobia (7.2%), classification based on number (normally distributed with median of 3, mode of 5) or content (eg, speaking-only vs other fears; performance-only vs interactional fears) of social fears failed to yield a defensible subtyping solution. Impairment increased linearly as the number of social fears was increased, with no clear threshold evident. Social phobia is associated with substantial impairment in multiple functional domains. Support for subtyping based on the extent or pattern of social fears was not provided. Rather, social phobia in the community seems to exist on a continuum of severity, with a greater number of feared situations associated with greater disability.


The study of sodium channels involved in pain responses using specific modulators.
Voltage-gated sodium channels (VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells. Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronic pain associated with tissue or nerve injury. Many long-chain peptide toxins (60-76 amino acid residues) purified from the venom of Asian scorpion Buthus martensii Karsch (BmK) are investigated to be sodium channel-specific modulators. The alpha-like neurotoxins that can bind to receptor site 3 of sodium channels, named as BmK I and BmK abT, could induce nociceptive effects in rats. On the contrast, the beta-like neurotoxins that can bind to receptor site 4 of sodium channels, named as BmK AS, BmK AS-1 and BmK IT2, could produce potent anti-nociceptive effects in animal pain models. BmK I could strongly prolong the fast inactivation of tetrodotoxin (TTX)-sensitive Na(+) currents on the rat dorsal root ganglia (DRG) neurons together with the augmentation of peak current amplitude. However, BmK IT2 and BmK ASs, potently suppressed both the peak TTX-resistant and TTX-sensitive Na(+) currents on rat small DRG neurons. Moreover, BmK ASs could decrease the excitability of small DRG neurons. Thus, the nociception/anti-nociception induced by scorpion neurotoxins may attribute to their distinct modulation on sodium channels in primary afferent sensory neurons. Therefore, the sodium channel-specific modulators from BmK venom could be used as not only pharmacological tools for better understanding the roles of VGSCs in pain signal conduction, but also lead molecules in the development of ideal analgesics targeting VGSCs.


The importance of atlantoaxial fixation after odontoidectomy.
OBJECT Although anterior odontoidectomy has been widely accepted as a procedure for decompression of the craniovertebral junction (CVJ), postoperative biomechanical instability has not been well addressed. There is a paucity of data on the necessity for and choice of fixation. METHODS The authors conducted a retrospective review of consecutively treated patients with basilar invagination who underwent anterior odontoidectomy and various types of posterior fixation. Posterior fixation included 1 of 3 kinds of constructs: occipitocervical (OC) fusion with atlantoaxial (AA) fixation, OC fusion without AA fixation, or AA-only (without OC) fixation. On the basis of the use or nonuse of AA fixation, these patients were assigned to either the AA group, in which the posterior fixation surgery involved both the atlas and axis simultaneously, regardless of whether the patient underwent OC fusion, or the non-AA group, in which the OC fusion construct spared the atlas, axis, or both. Clinical outcomes and neurological function were compared. Radiological results at each time point (i.e., before and after odontoidectomy and after fixation) were assessed by calculating the triangular area causing ventral indentation of the brainstem in the CVJ. RESULTS Data obtained in 14 consecutively treated patients with basilar invagination were analyzed in this series; the mean follow-up time was 5.75 years. The mean age was 53.58 years; there were 7 males and 7 females. The AA and non-AA groups consisted of 7 patients each. The demographic data of both groups were similar. Overall, there was significant improvement in neurological function after the operation (p = 0.03), and there were no differences in the postoperative Nurick grades between the 2 groups (p = 1.00). According to radiological measurements, significant decompression of the ventral brainstem was achieved stepwise in both groups by anterior odontoidectomy and posterior fixation; the mean ventral triangular area improved from 3.00 ± 0.86 cm2 to 2.08 ± 0.51 cm2 to 1.68 ± 0.59 cm2 (before and after odontoidectomy and after fixation, respectively; p < 0.05). The decompression gained by odontoidectomy (i.e., reduction of the ventral triangular area) was similar in the AA and non-AA groups (0.66 ± 0.42 cm2 vs 1.17 ± 1.42 cm2, respectively; p = 0.38). However, the decompression achieved by posterior fixation was significantly greater in the AA group than in the non-AA group (0.64 ± 0.39 cm2 vs 0.17 ± 0.16 cm2, respectively; p = 0.01). CONCLUSIONS Anterior odontoidectomy alone provides significant decompression at the CVJ. Adjuvant posterior fixation further enhances the extent of decompression after the odontoidectomy. Moreover, posterior fixation that involves AA fixation yields significantly more decompression of the ventral brainstem than OC fusion that spares AA fixation.


[Brain biopotential mapping in emotional and cognitive pathology].
The EEG rhythms spectral power and intracortical connections were studied in depressive and schizophrenic patients in four schematically outlined main cortical quadrants. In depressive patients two cortical quadrants--right anterior and left posterior ones appeared to be predominantly involved in negative emotions regulation. Alpha-rhythm spectral power and cortical connections in these areas were decreased, pointing to their relative hyperactivation and functional disturbances. Schizophrenics patients were divided into two groups--with the predominance of "positive" and "negative" symptoms. In the first group there was revealed the decrease of the most EEG rhythms spectral power only in parietal areas, on the second one--in all cortical areas. There was also the significant alpha-rhythm spectral power asymmetry, different in the two groups of schizophrenic patients. In "positive" schizophrenics the decrease of alpha-rhythm spectral power was revealed in parietal and occipital areas of the right hemisphere, and in "negative" ones--vice versa, these results pointing of the relatively higher activation of the right posterior quadrant in the former group and of the left posterior quadrant in the latter one. In the anterior cortical quadrants the intracortical connections were however higher in the left hemisphere in "positive" and in the right one--in "negative" schizophrenics. Thus, there are some contradictory results obtained by different methods in anterior and posterior cortical quadrants in each hemisphere, these results being of opposite directions in patients with "positive" and "negative" manifestations. "Region of interest" (ROI) in schizophrenics appeared to be predominantly the frontal and temporal ones, while the "Rhythm of interest"--beta2.


Stretch-induced upregulation of VEGF gene expression in murine pulmonary culture: a role for angiogenesis in lung development.
The authors' have shown pulmonary alveolarization (capillary and alveolar growth) both after fetal tracheal occlusion and postnatal pulmonary distension. The trophic and developmental mechanisms responsible for this growth remain largely unknown; however, experimental systems have defined an enhanced expression of angiogenic proteins in response to tissue stretch. The authors hypothesize that the stimulation of pulmonary alveolarization after stretch is secondary to upregulation of the potent endothelial cell mitogen vascular endothelial growth factor (VEGF) and that the endothelial cell represents the central stimulus of parenchymal growth. A mixed primary pulmonary cell culture obtained by enzymatic digestion of fetal, neonatal, and adult mouse lung was plated on Bioflex elastomer bottom plates, grown to confluence, rendered quiescent, and subjected to continuous cycles of stretch-relaxation with nonstretched cells as controls. Cells were harvested at time-points 0, 30 minutes, 2 hours, 4 hours, 8 hours, and 24 hours. RNA was extracted and VEGF gene expression analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Similar cell groups were harvested, processed, and analyzed utilizing Western Blot techniques. VEGF PCR of mRNA isolated from fetal sheep subjected to surgical creation of diaphragmatic hernia both with (DH-TL) and without (DH) tracheal ligation also was analyzed. VEGF mRNA isoforms 120, 164, and 188 showed increased expression in all stretched groups, which was noted by 30 minutes with maximal expression seen at 2 to 4 hours and a return to baseline expression by 24 hours. VEGF protein was similarly elevated in all stretched cell groups. In preliminary studies, DH/TL sheep showed upregulation of VEGF compared with DH sheep alone. These data show in an in vitro system that "pulmonary stretch" upregulates VEGF mRNA and protein expression supporting the role of angiogenesis in the stretch-induced pulmonary alveolarization. The authors speculate that such angiogenic activity is a rate-limiting factor in stimulating alveolar epithelial development, and as a treatment modality, therapeutic angiogenesis may provide a noninvasive method with which to treat pulmonary hypoplasia.


[Pancreatic adenocarcinoma: 10 years of progress].
Despite the pejorative prognosis of pancreatic adenocarcinoma, significant progress has been made during the past decade at all steps of tumour development. Sporadic preneoplastic lesions are better recognized and a case-by-case prophylactic resection can be proposed. Both the identification and the screening of relatives at risk are in development. Availability of FOLFIRINOX and gemcitabine plus nab-paclitaxel combinations has stopped the long period of failures with gemcitabine doublets. Improvement in chemotherapy may benefit to borderline and locally-advanced forms of this cancer. They are now better evaluated by imaging and often, induction chemotherapy is proposed that allows to achieve a tumor control and then better select patients eligible for surgery in order to avoid unuseful/incomplete resection. The role of radiation therapy and other emerging local treatments merits further assessment. More robust data are needed for prognostic and predictive biomarkers to help in the choice of treatments. Finally, intensification of supportive care and shortened delay to access the treatment should be a major goal to improve the management of this disease.


Prediction of ovarian tumor malignancy.
Ovarian cancer is the leading cause of mortality among gynecological cancers. The aim of the study was to form the decision rules for distinguishing benign from malignant ovary lesions. The research was conducted on 201 women with ovary tumor. Commonly used specific markers for ovarian cancer (biochemical marker Ca 125, ultrasound and vascular markers) were used. The significant difference in the presence of an ultrasound and vascular markers between benign and malignant ovary changes along with the significantly different level of Ca 125 is confirmed. To a specific marker certain score number was appointed and the scoring system was formed. The incidence of benign/malignant ovary changes was observed in the researched group regarding anthropometric parameters (age, marital and menopausal status and number of deliveries). There is also significant difference in the incidence of benign/malignant ovary tumor regarding these parameters. Based on combination of the scoring system and anthropometric parameters the decision rules for distinguishing benign from malignant ovary tumors were formed. The logistic regression method was used. We proved that this method has higher accuracy in prediction of malignancy in women with ovary tumors than using morphological, Doppler or anthropometric parameters separately.


Combining support vector machine learning with the discrete cosine transform in image compression.
We present an algorithm for the application of support vector machine (SVM) learning to image compression. The algorithm combines SVMs with the discrete cosine transform (DCT). Unlike a classic radial basis function networks or multilayer perceptrons that require the topology of the network to be defined before training, an SVM selects the minimum number of training points, called support vectors, that ensure modeling of the data within the given level of accuracy (a.k.a. insensitivity zone /spl epsi/). It is this property that is exploited as the basis for an image compression algorithm. Here, the SVMs learning algorithm performs the compression in a spectral domain of DCT coefficients, i.e., the SVM approximates the DCT coefficients. The parameters of the SVM are stored in order to recover the image. Results demonstrate that even though there is an extra lossy step compared with the baseline JPEG algorithm, the new algorithm dramatically increases compression for a given image quality; conversely it increases image quality for a given compression ratio. The approach presented can be readily applied for other modeling schemes that are in a form of a sum of weighted basis functions.


Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography.
Respiratory impedance comprises the resistance and reactance of the respiratory system and can provide detailed information on respiratory function. However, details of the relationship between impedance and morphological airway changes in asthma are unknown. We aimed to evaluate the correlation between imaging-based airway changes and respiratory impedance in patients with asthma. Respiratory impedance and spirometric data were evaluated in 72 patients with asthma and 29 reference subjects. We measured the intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi using three-dimensional computed tomographic analyses, and values were adjusted by body surface area (BSA, Ai/BSA, and WT/the square root (√) of BSA). Asthma patients had significantly increased respiratory impedance, decreased Ai/BSA, and increased WT/√BSA, as was the case in those without airflow limitation as assessed by spirometry. Ai/BSA was inversely correlated with respiratory resistance at 5 Hz (R5) and 20 Hz (R20). R20 had a stronger correlation with Ai/BSA than did R5. Ai/BSA was positively correlated with forced expiratory volume in 1 second/forced vital capacity ratio, percentage predicted forced expiratory volume in 1 second, and percentage predicted mid-expiratory flow. WT/√BSA had no significant correlation with spirometry or respiratory impedance. Respiratory resistance is associated with airway narrowing.


[Late spreading of tuberculosis in tubercular spondylitis].
A 65-year-old man, known to have had a gastric ulcer and chronic rheumatoid arthritis as well as alcohol and nicotine abuse, was admitted because of suspected endocarditis. Physical examination revealed marked pain on pressure over the throacic spine. Vesicular breath sounds were reduced over the entire thorax and there was a systolic murmur over Erb's point (above the right clavicle). There was a purulent bursitis over the olecranon. Abnormal laboratory tests were: elevated C-reactive protein, elevated leucocyte count (up to 33 thousand during the hospital stay). Smears from the bursitis and blood cultures revealed Staph. aureus. Computed tomography demonstrated a fracture of the 7th thoracic vertebra with a paravertebral abscess. Echocardiography showed anatherosclerotic aortic valve with floating particles. Treatment of the suspected staphylococcal bacteraemia with purulent bursitis, spondylitis and aortic valvar endocarditis was begun with broad-spectrum antibiotics, but the patient soon developed a severe acute respiratory distress syndrome and he died of multi-organ failure. Autopsy revealed as cause of death left heart failure with aortic valvar endocarditis and gelatinour pneumonia caused by late tubercular dissemination from the tubercular spondylitis. Tuberculosis can be a life-threatening infection. Uncharacteristic history and extrapulmonary manifestations can make it very difficult to arrive at the correct diagnosis.


Surgically treated pulmonary tuberculosis: report on cases from Tikur Anbessa Hospital, Addis Ababa, Ethiopia.
The treatment of pulmonary tuberculosis has evolved through multiples of treatment modalities including pulmonary surgery. In Ethiopia, though the disease is very common, there is no information regarding the patterns of surgically treated pulmonary tuberculosis and its outcome. A retrospective clinical study was conducted to investigate the patterns and outcomes of surgically treated cases of pulmonary tuberculosis. Data was collected from the clinical records of all patients operated at the chest surgery unit with a confirmed diagnosis of pulmonary tuberculosis at the Tikur Anbessa teaching specialized referral hospital (26). Twenty-six patients were admitted for surgery, 80.8% of these patients were males. The mean duration of illness before presenting to the hospital was 27.6 months. Cough and hemoptysis were the two most common presenting symptoms, occurring in 26 (100%) and 24 (92.3%). The most common feature seen in chest x-rays was a completely destroyed lung tissue in 10 (38.5%). The parts of the lung commonly involved were the left side in 16 (61.5%) and the upper lobes in 14 (53.8%). The Sputum examination for acid-fast tubercle bacilli tested positive for 24 (92.3%) of the patients. The most frequent indications for surgery were severe hemoptysis for 12 (46.2%), radiographic evidence of destroyed lung for 5 (19.2%) and strong evidence for Aspergilloma for 3 (11.5%). The most frequently performed procedure were left upper lobectomy in 10 (38%), left pneumonectomy in 7 (26.7%) and right pneumonectomy in 7 (26.7%). Nine significant (34.6%) complications occurred in the postoperative period, the commonest being postoperative pneumonia in 4 (15.4%). Two (7.7%) of the patients died. During the follow-up period six patients developed significant late postoperative complications. In the Ethiopian setting, though anti-tuberculous chemotherapy is the standard treatment for pulmonary tuberculosis in a majority of patients, there are still definite indications in which surgical management plays a vital role.


Effect of baculovirus infection on the mRNA and protein levels of the Spodoptera frugiperda eukaryotic initiation factor 4E.
The cDNA sequence of eukaryotic translation initiation factor eIF4E was derived from a Spodoptera frugiperda cDNA library. Eight tryptophan residues, typical for eIF4E, are strictly conserved in the encoded 210 amino acid protein. A polyclonal antiserum detected a 26 kDa protein in lepidopteran cell lines, but not in dipteran cells. Sf21 cells have a single eIF4E gene copy, which is transcribed into a 1500 nt transcript. Infection with AcMNPV resulted in a decrease in eIF4E mRNA starting between 12 and 24 h postinfection (p.i.), while reduced eIF4E protein levels were observed at 48 h p.i. Two forms of eIF4E were recognized that differed in their iso-electric point, of which the relative abundance did not change during infection. Mutagenesis experiments using recombinant baculoviruses revealed that the variation in mobility between these two forms did not result from a difference in the phosphorylation state of Ser-202, the serine residue that corresponds with the eIF4E phosphorylation site in mammalian eIF4E.


Flashback as screen memory.
The authors report a series of flashbacks of a combat patient's experience 18 years earlier. The flashback episodes occurred immediately after the patient's humiliating job loss. The man had no symptoms of delayed stress and no history of drug or alcohol abuse. The wartime memory served an obvious screening function by diminishing the impact of the patient's narcissistic injury just preceding the onset of the flashback sequence. The flashbacks also screened childhood and adolescent conflicts activated by the job loss.


The emergence of gender differences in depression during adolescence.
There are no gender differences in depression rates in prepubescent children, but, after the age of 15, girls and women are about twice as likely to be depressed as boys and men. In this article, three models for how gender differences in depression might develop in early adolescence are described and evaluated. According to Model 1, the causes of depression are the same for girls and boys, but these causes become more prevalent in girls than in boys in early adolescence. According to Model 2, there are different causes of depression in girls and boys, and the causes of girls' depression become more prevalent than the causes of boys' depression in early adolescence. According to Model 3, girls are more likely than boys to carry risk factors for depression even before early adolescence, but these risk factors lead to depression only in the face of challenges that increase in prevalence in early adolescence. Most studies of gender differences in depression have focused on the effects of individual variables on depression in girls and boys rather than on testing models of how these differences develop. Evidence for the variables most commonly thought to contribute to gender differences in depression in children and adolescents is reviewed, and this evidence is related to the three models for how these differences develop. It is concluded that Model 3 is best supported by the available data, although much more research is needed. Before adolescence, girls appear to develop more risk factors for depression than boys; girls also apparently face more new challenges in early adolescence than boys. It is argued that these factors combine, as specified in Model 3, to generate gender differences in depression beginning in early adolescence.


Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and signals through integrin alphaVbeta3.
Elevated plasma concentrations of Lp(a) [lipoprotein(a)] are an emerging risk factor for atherothrombotic disease. Apo(a) [apolipoprotein(a)], the unique glycoprotein component of Lp(a), contains tandem repeats of a plasminogen kringle (K) IV-like domain. In the light of recent studies suggesting that apo(a)/Lp(a) affects endothelial function, we evaluated the effects of apo(a)/Lp(a) on growth and migration of cultured HUVECs (human umbilical-vein endothelial cells). Two full-length r-apo(a) [recombinant apo(a)] variants (12K and 17K), as well as Lp(a), were able to stimulate HUVEC growth and migration to a comparable extent; 17K r-apo(a) also decreased the levels of total and active transforming growth factor-beta secreted by these cells. Using additional r-apo(a) variants corresponding to deletions and/or site-directed mutants of various kringle domains in the molecule, we were able to determine that the observed effects of full-length r-apo(a) on HUVECs were dependent on the presence of a functional lysine-binding site(s) in the apo(a) molecule. With respect to signalling events elicited by apo(a) in HUVECs, we found that 17K treatment of the cells increased the phosphorylation level of FAK (focal adhesion kinase) and MAPKs (mitogen-activated protein kinases), including ERK (extracellular-signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase). In addition, we showed that LM609, the function-blocking antibody to integrin alphaVbeta3, abrogated the effects of 17K r-apo(a) and Lp(a) on HUVECs. Taken together, the results of the present study suggest that the apo(a) component of Lp(a) signals through integrin alphaVbeta3 to activate endothelial cells.


Successful catheter cryoablation of Hisian ectopy using 2 new diagnostic criteria based on unipolar and bipolar recordings of the His electrogram.
We describe the case of a 61-year-old woman who underwent successful catheter cryoablation of a symptomatic Hisian ectopy. Diagnosis was based on features of the HV interval assessed from a bipolar recording during mapping. The location of the arrhythmic focus was identified using simultaneous unipolar and bipolar recordings of the His electrogram. This case report highlights the use of 2 new criteria for the diagnosis and mapping of Hisian ectopy, and the successful use of cryothermia for the ablation of extrasystoles arising from the His bundle.


[Consumption of polyunsaturated fatty acids by young hypertensive adults].
A properly balanced diet is a key factor in preventing the development of diet-related diseases and may assist the pharmacological treatment of many conditions. Some studies indicate on relationship between consumption of polyunsaturated fatty acids (PUFA) and positive health outcomes. To evaluate sources in diet and frequency of consumption of PUFA by young adults suffering from arterial hypertension and to identify differences in PUFA and saturated fatty acids intake de-pending on gender, age, education, BMI, history of hypertension, BP values and the number of an-tihypertensive drugs used. The study group consisted of 100 hypertensive patients, 60 males and 40 females, aged 20 – 45 years (mean age 33.4±6.6 years), without concomitant diseases. Study tool constituted the self-reported questionnaire of food products intake, its frequency and intensity assessed during last one month period. The questionnaire involved 7 groups of typical food products, which were also divided into 2 baskets: “basket of 10 healthy” and “basket of 10 unhealthy” products. Patients more often consumed products containing saturated fatty acids than PUFA. In the study group dairy products and meat dominated the diet, especially in hypertensive men. Olive oil was the most popular healthy product consumed by patients (42% of responders). People living in the city ate more often fish and plant products than those from rural areas, but overall fish consump-tion was low – only 6 to 12% of patients consumed omega-3 rich fish at least once a week. Regard-less of gender, place of living, education and other clinical factors our hypertensive patients choose more products from the “unhealthy” than “healthy” basket in the last month. Young people suffering from hypertension are characterized by unfavorable eating habits, especially low frequency of PUFA containing products consumption. Intensive educational programs to increase knowledge of young hypertensives about diet beneficial for health are still required.


Measuring changes in health over time using the EQ-5D 3L and 5L: a head-to-head comparison of measurement properties and sensitivity to change in a German inpatient rehabilitation sample.
To compare measurement properties and sensitivity to change of the standard version of the EQ-5D (3L) with a newly developed 5-level version (5L) in a multicenter sample of German rehabilitation inpatients (n = 230). Rehabilitation patients (n = 114 orthopedic, n = 54 psychosomatic, n = 62 rheumatic) were asked to complete both versions of the EQ-5D and several other questionnaires at the beginning of, the end of and 3 month after inpatient rehabilitation. 3L and 5L were compared regarding missing values, ceiling effects, redistribution properties, informativity and sensitivity to change. There were nearly no missing values in both questionnaires. Ceiling effects were 1.6 % points to 16.4 % points lower on average for the 5L. For psychosomatic patients, ceiling effects for 5L were as high as in the general German population. Absolute informativity (mean 5L: 1.76, 3L: 1.06) and relative informativity (5L: 0.76, 3L: 0.67) were both higher for 5L. 5L could better detect both positive and negative health changes in most dimensions and patient samples. Overall, patients made better use of the response levels of the 5L. Average proportion of inconsistent responses between 3L and 5L was 6.1 %. Cross-sectionally and longitudinally, 5L was associated with an improved ability to detect health changes over time, reduced ceiling effects, and improved discriminatory power. Overall, these findings were in line with previous study outcomes, although differing in magnitude. Since the sample size is moderate and generalizability of the reported results is unclear, further comparisons in other patient populations will be informative and should be encouraged.


Ipsilateral Sinus Hypoplasia and Poor Leptomeningeal Collaterals as Midline Shift Predictors.
We explore the role of dural sinus morphology, leptomeningeal collaterals, and clot localization in the development of malignant brain edema in acute ischemic stroke in anterior circulation. This is a single-center retrospective study of consecutive stroke patients with acute occlusion (middle cerebral artery M1 ± intracranial internal carotid artery) treated with intravenous thrombolysis (from November 2009 to November 2014). Admission computed tomography angiography data were evaluated for hypoplasia of dural sinuses, leptomeningeal collaterals, and clot location. Primary outcome was midline shift (<5 mm versus ≥5 mm) on follow-up computed tomography. Secondary outcomes were infarct volume and modified Rankin Scale score of 2 or lower at 90 days. Multivariate logistic regression was used. Of 86 patients (49 females), 36 (42%) had poor collaterals, 26 (30%) had ipsilesional sinus hypoplasia, and 38 (44%) had proximal clots. A midline shift of 5 mm or higher was diagnosed in 14 patients (16%). Infarct volume was larger in the group with midline shift (median: 318 mL [interquartile range {IQR} = 260-350]) than in the group without midline shift (median: 44 mL [IQR = 28-60]) (P = .007). In multivariate analysis, poor leptomeningeal collaterals (odds ratio [OR] = .11, 95% confidence interval [CI] = .03-.44, P = .002 for good collaterals) and ipsilesional sinus hypoplasia (OR = 6.43, 95% CI = 1.5-46.1, P = .008) were independently associated with a midline shift of 5 mm or higher. Patients with poor leptomeningeal collaterals and ipsilesional hypoplasia of dural sinuses are more likely to develop midline shift.


Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma.
Postoperative intrahepatic recurrence of human hepatocellular carcinoma is high. Recently, the relationship between proliferating cell activity in the cirrhotic liver and occurrence or recurrence of hepatocellular carcinoma has been reported. One hundred two resected cases of small hepatocellular carcinoma of < 3 cm in diameter without venous invasion or intrahepatic metastasis were examined to ascertain the factors affecting postoperative intrahepatic recurrence. Cumulative intrahepatic recurrence rates at 1, 3, and 5 years after surgery were 12.0%, 57.2%, and 67.6%, respectively. The log-rank test indicated that serum albumin levels of < 3.7 g/dL, alanine aminotransferase levels of more than 54 IU/L, active inflammation in the nontumorous portion, and high proliferating cell nuclear antigen labeling index in the nontumorous portion (> 23.2%) were significant risk factors for recurrence. Tumor factors, including tumor size, histological grade, or alpha-fetoprotein level, were not significant risk factors. Cox's proportional hazard model identified that serum albumin level and alanine aminotransferase level were independently associated with intrahepatic recurrence after hepatectomy. This study suggests that the principal cause linked to either a recurrence or a second new growth of hepatocellular carcinoma in the remnant liver after hepatectomy was the state of the underlying liver parenchyma as well as other tumor factors per se.


Signals elicited at the intestinal epithelium upon chitosan feeding contribute to immunomodulatory activity and biocompatibility of the polysaccharide.
Chitosan is a copolymer of N-acetylglucosamine and glucosamine derived from chitin with several applications in pharmaceutical and medical fields. This polysaccharide exhibits adjuvant properties in mucosal immune responses of humans, rats and mice. Characterization of signals elicited by chitosan at the intestinal epithelium could explain its immunomodulatory activity and biocompatibility. We fed normal rats with single doses of chitosan and 16h later, we purified intestinal epithelial cells (IECs) to assess immune and biochemical parameters. Following chitosan administration, mRNA expression and release of several cytokines and chemokines increased, injury markers maintained constitutive levels and MHC type II molecule expression was augmented. IEC supernatants showed higher levels of IL-10, IL-6 and TGF-beta. Arginase activity of IECs increased upon chitosan interaction in vivo and in vitro. Together, after chitosan feeding, mild activation of IECs occurs in vivo, with production of regulatory factors that could be relevant for its biocompatibility and immunomodulatory effects.


SHARQnet - Sophisticated harmonic artifact reduction in quantitative susceptibility mapping using a deep convolutional neural network.
Quantitative susceptibility mapping (QSM) reveals pathological changes in widespread diseases such as Parkinson's disease, Multiple Sclerosis, or hepatic iron overload. QSM requires multiple processing steps after the acquisition of magnetic resonance imaging (MRI) phase measurements such as unwrapping, background field removal and the solution of an ill-posed field-to-source-inversion. Current techniques utilize iterative optimization procedures to solve the inversion and background field correction, which are computationally expensive and lead to suboptimal or over-regularized solutions requiring a careful choice of parameters that make a clinical application of QSM challenging. We have previously demonstrated that a deep convolutional neural network can invert the magnetic dipole kernel with a very efficient feed forward multiplication not requiring iterative optimization or the choice of regularization parameters. In this work, we extended this approach to remove background fields in QSM. The prototype method, called SHARQnet, was trained on simulated background fields and tested on 3T and 7T brain datasets. We show that SHARQnet outperforms current background field removal procedures and generalizes to a wide range of input data without requiring any parameter adjustments. In summary, we demonstrate that the solution of ill-posed problems in QSM can be achieved by learning the underlying physics causing the artifacts and removing them in an efficient and reliable manner and thereby will help to bring QSM towards clinical applications.


Identification of a chromone-based retinoid containing a polyolefinic side chain via facile synthetic routes.
Attempts to prepare substituted chromones as novel retinoids revealed that some chromones were unstable under Wadsworth-Horner-Emmons reaction conditions. Hence, Wittig reactions were used to prepare chromone-based compounds as potential retinoids. Firstly, Wittig reagents prepared from 3-bromomethyl-chromen-4-one were reacted with olefinic-aldehydes to provide the target compounds with all-trans side chains in good yield. The approach supplies a useful general route to structurally diverse chromone-based compounds possessing a variety of side chains. Sequential Wittig reactions were used also to prepare a chromone-based retinoid. These novel compounds were evaluated in binding assays and a high affinity RAR ligand was identified. Crystal structures obtained for two key precursors aided the interpretation of binding data.


F-18 FDG uptake in cutaneous metastases from breast cancer.
Cutaneous metastases from internal malignancies are rare with a reported incidence between 0.7% and 10%. Among all malignancies the highest incidence of cutaneous metastasis is seen in breast cancer. We report the detection of distant dermal metastases from breast cancer on F-18 FDG PET imaging. A 73-year-old woman with metastatic left breast cancer was referred for F-18 FDG PET/CT scan, which showed multiple FDG avid lesions along cutaneous and subcutaneous nodules in the posterior neck, bilateral proximal arms, anterior chest wall, and trunk. A punch biopsy of a right lower chest wall lesion revealed invasive ductal carcinoma involving the deep dermis.


Surgery, pain, and immune function.
Research findings have demonstrated that surgery negatively affects immune function. Pain also has deleterious effects on immune function. Most research in this area has been conducted on animals. Psychoneuroimmunology provides the framework for this article. Psychoneurological phenomena, such as stress, depression, and pain, can influence immune system functioning through neuroendocrine pathways. Biological and behavioral processes appear to be closely related and need to be jointly considered when planning and providing anesthesia care. The anesthesia planning process increasingly involves aggressive assessment and treatment of postoperative pain, which may benefit immune function.


EEG source imaging of anterior temporal lobe spikes: validity and reliability.
To assess the reliability and validity of EEG source localization of anterior temporal lobe spikes through direct comparison with simultaneously recorded intracranial spike fields. We recently showed that classical anterior temporal spikes recorded in mesial temporal lobe epilepsy (MTLE) are non-propagated potentials generated in the anterolateral temporal neocortex (Wennberg et al., 2011). In this study EEG source imaging (ESI) was performed on 64 identical right anterior temporal spikes (and 48 homologous left anterior temporal spikes) in a patient with MTLE investigated with simultaneous depth and subdural intracranial EEG and 27 channel scalp EEG. The effects of different realistic forward models, low frequency filters (LFFs) and spike averaging were assessed in terms of the reliability and physiologic validity of the source solutions. Dipole mapping and distributed source modeling solutions for the grand average of all spikes were accurately localized to the superficial anterolateral temporal neocortex within 1cm of the intracranially defined spike generator, irrespective of forward model or LFF. ESI of single spikes, however, showed poor reliability (i.e., dissimilar localization results for intracranially identical spikes). Even with an optimal combination of individualized volume conductor and 3Hz LFF more than one third of single spike source solutions were physiologically invalid. Spike averaging, especially of 8 or more spikes, significantly increased the proportion of valid source solutions. ESI of individual anterior temporal spikes was limited by low reliability and a high likelihood of physiologically invalid source solutions. Spike averaging of 8 or more identical spikes prior to ESI, however, reliably produced accurate source solutions localized to the anterolateral temporal neocortex. ESI performed on averages of identical spikes can provide highly accurate noninvasive source localization of the anterolateral temporal neocortical region responsible for generating classical anterior temporal lobe spikes. The reliability and validity of ESI performed on individual spikes, however, is relatively limited.


Two-stage revision for infected endoprostheses used in tumor surgery.
Thirty-four patients with infected massive endoprostheses had two-stage revision procedures to cure the infection and retain a useful functioning limb. An antibiotic impregnated cement spacer constructed with two cement gun liners and a Kuntscher nail provided temporary stability and also allowed a high dose of local antibiotic concentration. In three patients the infection never was controlled, and one of these patients had a successful second revision surgery. Six other patients had reinfection varying from 14 to 92 months after surgery. Risk factors for reinfection were previous radiotherapy and any additional operative intervention. The overall success rate for controlling infection was 91% at 1 year and 74% at 5 years. Six patients required amputation. The mean functional outcome for the retained limbs using the Musculoskeletal Tumor Society scoring system was 77%. Two-stage revisions seem almost as effective at controlling infection in massive endoprostheses as in conventional joint replacements, particularly if additional surgical interventions can be avoided.


A kinetic study of the synthesis of ascorbate fatty acid esters catalysed by immobilized lipase in organic media.
The kinetics of the synthesis of L-ascorbyl laurate and L-ascorbyl palmitate catalysed by immobilized lipase from L-ascorbic acid and an acyl donor (lauric acid, palmic acid and their methyl and ethyl esters) in 2-methylbutan-2-ol have been investigated. The factors affecting the reaction rate (shaking speed, temperature, water activity, enzyme concentration as well as substrate concentration) are discussed. The reaction conditions have been optimized as follows: shaking speed 200 rev./min, temperature 55 degrees C, enzyme 17-20% (w/w of substrate) for these substrates. The most suitable substrate concentration for all of these substrates was 300 mmol/l. The reactions were modelled. For lauric acid, methyl laurate and ethyl laurate: K(m)=74.3, 48.97 and 55.8 mmol/l, respectively; and V(max)=0.010764, 0.0114, 0.01116 mmol.min(-1).g(-1), respectively. The most suitable substrate was methyl laurate. For palmic acid, methyl palmitate and ethyl palmitate: K(m)=102, 94.9 and 104 mmol/l, respectively; and V(max)=0.0417, 0.0424 and 0.0435 mmol.min(-1).g(-1), respectively. The most suitable substrate was methyl palmitate.


The course of non-malignant chronic pain: a 12-year follow-up of a cohort from the general population.
The high prevalence of chronic pain (duration >3 months) reported from different populations indicates a public health problem. Knowledge of the long-term course of chronic non-malignant pain is incomplete and scarce. This paper describes a follow-up of a cohort recruited from a survey in the general population. The cohort (n=214) consisted initially of individuals with widespread or located (neck-shoulder) pain or without chronic pain. The individuals were initially examined and replied to questionnaires on pain, social factors, lifestyle, medication and health care after two and 12 years. The deaths during the period were obtained from the population register. Complete data exist for 77% of the eligible individuals. After 12 years one-third of the individuals initially without pain reported chronic pain, and among those with initial chronic pain 85% still reported chronic pain. The number of painful areas was the strongest predictor of chronic pain 12 years later (OR 15.8; >3 locations vs. 0) whereas a social factor (having a close friend) decreased the risk (OR 0.44). The onset of chronic pain during the same period was related to the physical workload (work with bent positions; OR 5.31; yes vs. no). Mortality was significantly higher in the group initially reporting widespread pain compared with the other groups. The chronicity of widespread chronic pain supports early and intense intervention among individuals with located pain. The association between chronic widespread pain and increased mortality needs further investigation but may deepen the view of chronic pain as a public health problem.


[Human herpesvirus 8 (HHV8). II. Pathogenic role and sensitivity to antiviral drugs].
Human herpesvirus 8 (HHV8) has been found to be associated with three different diseases observed in Aids patients: Kaposi's sarcoma, primary effusion lymphoma, which is a rare type of non-Hodgkin lymphomas affecting the body cavities, and multicentric Castleman's disease. The role of this new herpesvirus and other lymphoid proliferations, like angioimmunoblastic lymphadenopathy or multiple myeloma, is much debatable. To date, there are several evidences for a direct role of this virus in the occurrence of the Kaposi's sarcoma, although the hypothesis of a passenger virus hypothesis cannot be totally excluded. In vitro, HHV8 is sensitive to some anti-herpesvirus drugs like foscarnet, cidofovir and adefovir, but the indications of these therapies in the prevention or the treatment of the Kaposi's sarcoma have not been documented so far.


Large-gap quantum spin Hall insulator in single layer bismuth monobromide Bi4Br4.
Quantum spin Hall (QSH) insulators have gapless topological edge states inside the bulk band gap, which can serve as dissipationless spin current channels. The major challenge currently is to find suitable materials for this topological state. Here, we predict a new large-gap QSH insulator with bulk direct band gap of ∼ 0.18 eV, in single-layer Bi4Br4, which could be exfoliated from its three-dimensional bulk material due to the weakly bonded layered structure. The band gap of single-layer Bi4Br4 is tunable via strain engineering, and the QSH phase is robust against external strain. Moreover, because this material consists of special one-dimensional molecular chain as its basic building block, the single layer Bi4Br4 could be torn to ribbons with clean and atomically sharp edges. These nanoribbons, which have single-Dirac-cone edge states crossing the bulk band gap, are ideal wires for dissipationless transport. Our work thus provides a new promising material for experimental studies and practical applications of the QSH effect.


Distributed versus localist representations: evidence from a study of item consistency in a case of classical anomia.
Models of word production and comprehension can be split into two broad classes: localist and distributed. In localist architectures each word within the lexicon is represented by a single unit. The distributed approach, on the other hand, encodes each lexical item as a pattern of activation across a set of shared units. If we assume that the localist representations are more than a convenient shorthand for distributed representations at the neuroanatomical level, it should be possible to find patients who, after brain injury, have lost specific words from their premorbid vocabulary. Following a closed head injury, JS had severe word-finding difficulties with no measurable semantic impairment nor did he make phonological errors in naming. Cueing with an initial phoneme proved relatively ineffective. JS showed a high degree of item consistency across three administrations of two tests of naming to confrontation. This consistency could not be predicted from a linear combination of psycholinguistic variables but the distribution fitted a stochastic model in which it is assumed that a proportion of items have become consistently unavailable. Further evidence is presented which suggests that these items are not, in fact, lost but rather have a very low probability of retrieval. Given phonemic cueing of sufficient length, or delayed repetition priming from a written word, the consistently unnamed items were produced by JS. Additional data is reported which seems to support a distributed model of speech production. JS's naming accuracy for one set of pictures was found to predict his performance on a second set of items only when the names of the pictures were both semantically and phonologically related (e.g., cat-rat). There was no association for pairs of pictures if they were only semantically (e.g., cat-dog) or phonologically related (e.g., cat-cap). It is argued that JS's data are best described in terms of a graded, non-linear, distributed model of speech production.


Disease prevention and health promotion in urban areas: CDC's perspective.
The mission of the Centers for Disease Control and Prevention (CDC) is to prevent disease, injury, and premature death and to promote quality of life. This mission applies to all Americans, especially to the poor and underserved. As so many people who are impoverished live in America's urban areas, the CDC has a unique and specific interest in the health problems of our urban population. The CDC has established five priorities: (1) strengthen essential public health services, (2) enrich capacity to respond to urgent threats to health, (3) develop a nationwide prevention network and program, (4) promote women's health, and (5) invest in our nation's youth. Each of these priorities will contribute to improving the health of people living in urban areas. The CDC has recently undertaken numerous initiatives to address health promotion and disease prevention issues in the urban setting. Future directions for the CDC lie in better understanding the role of socioeconomic and cultural factors in promoting health and how resources within urban areas can be used to promote health. The CDC needs to explore potential relationships with various types of partners. Solving urban health problems requires actions from many federal agencies as well as from state and local organizations.


Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats.
Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague-Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery-olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohistochemically by using antibodies against endothelial nitric oxide synthase, alpha-smooth muscle actin, macrophages, and matrix metalloproteinase-9. Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.


Isoniazid and ethambutol as a cause of optic neuropathy.
A well-recognized complication of ethambutol use is optic neuropathy, but the potential ocular toxicity of isoniazid is often overlooked. A patient developed optic neuropathy while being treated with isoniazid and ethambutol. The optic neuropathy subsided only when both drugs were discontinued, suggesting an additive toxic effect.


Prevalence of anterior polar cataracts in children and risk factors for amblyopia.
Anterior polar cataract is an opacity in the anterior capsule of the lens. Anterior polar cataract has historically been considered as a relatively benign condition. The purpose of this study was to estimate the prevalence of anterior polar cataract, to identify the risk factors for amblyopia and to estimate the risk of developing amblyopia in children with anterior polar cataract. The medical records for patients with congenital cataracts at the Eye Clinic Rigshospitalet, Rigshospitalet-Glostrup and Kennedy Center covering a ten year period from 2007 to 2016 (both metres years included) were reviewed. A total of 54 patients with anterior polar cataract were identified. The majority had unilateral anterior polar cataract (72%). Family history of childhood cataracts was frequent (27%) of patients with bilateral anterior polar cataract. There was an overrepresentation of female patients (70%). Amblyopia was found in 55% of the patients. The causes were primarily hypermetropic anisometropia (70%) and astigmatism (52%). Axial length was on average 0.88 mm (SD 0.44) shorter in the eye with anterior polar cataract compared to fellow eyes. Anterior polar cataract is a highly amblyogenic condition not because of a visually obstructing lens opacity but because of refractive errors, primarily hypermetropic anisometropia and astigmatism. Anterior polar cataract seems to represent an anomaly in global eye development resulting in reduced axial length. Patients with anterior polar cataract should be monitored to detect and treat amblyopia in time.


Fusarium keratitis--multiple states, 2006.
On March 8, 2006, CDC received a report from an ophthalmologist in New Jersey regarding three patients with contact lens--associated Fusarium keratitis during the preceding 3 months. Initial contact with several corneal disease specialty centers in the United States revealed that other centers also have seen recent increases in Fusarium keratitis. This report summarizes the public health response to date in the United States and provides important prevention messages for contact lens users.


The -1082G/A polymorphism in IL-10 gene is associated with risk of Alzheimer's disease: a meta-analysis.
The -1082G/A polymorphism in IL-10 gene has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of IL-10 -1082G/A polymorphism and AD risk by using meta-analysis. All eligible case-control studies were searched in Pubmed and Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to assess the association. A total of 2158 cases and 2088 controls in 12 case-control studies were included. The results indicated that the A allele carriers (AA+AG) had a 27% increased risk of AD, when compared with the homozygote GG (OR=1.27, 95%CI=1.02-1.58 for AA+AG vs. GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with A allele carriers in Europeans (OR=1.27 and 95%CI=1.01-1.59 for AA+AG vs. GG), but not in Asians (OR=1.37 and 95%CI=0.32-5.88 for AA+AG vs. GG). This meta-analysis suggested that the -1082G/A polymorphism of IL-10 gene would be a risk factor for AD. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of IL-10 gene and AD risk, more studies with large groups of patients are required.


WHO's embrace of traditional oriental medicines puts health and wildlife at risk.


The chemistry and biology of theta defensins.
Cyclic peptides are found in a diverse range of organisms and are characterized by their stability and role in defense. Why is only one class of cyclic peptides found in mammals? Possibly we have not looked hard enough for them, or the technologies needed to identify them are not fully developed. We also do not yet understand their intriguing biosynthesis from two separate gene products. Addressing these challenges will require the application of chemical tools and insights from other classes of cyclic peptides. Herein, we highlight recent developments in the characterization of theta defensins and describe the important role that chemistry has played in delineating their modes of action. Furthermore, we emphasize the potential of theta defensins as antimicrobial agents and scaffolds for peptide drug design.


Phase II study of spirogermanium in patients with advanced colorectal carcinoma.
Twenty one evaluable patients with advanced colorectal carcinoma were treated with continuous infusion of spirogermanium at a median daily dose of 150 mg/m2 (range 120-210) for five consecutive days every 14 days. Treatments were accomplished by using outpatient infusion devices. Fifteen patients had not received any prior radiation therapy, immunotherapy, or chemotherapy. Nineteen patients were previously untreated with chemotherapy. Five patients had received prior immunotherapy with copovithane and only two patients had received radiation therapy prior to spirogermanium therapy. None of the patients achieved a complete or partial remission. Minor tumor regressions were observed in two patients, both were less than 12 weeks in duration. The major toxicities included nausea and vomiting and neurologic side effects; however, the toxicity was completely reversible. Spirogermanium is not effective in the treatment of patients with advanced colorectal carcinoma.


[Effects of Magnetic Fe3O4 Nanoparticles on the Characteristics of Anaerobic Granular Sludge and Its Interior Microbial Community].
In this study, the effects of magnetic Fe3O4 nanoparticles (Fe3O4 NPs) on soluble microbial products (SMP), loosely bound extracellular polymeric substances (LB-EPS), and tightly bound extracellular polymeric substances (TB-EPS) in anaerobic granular sludge were examined. In addition, the anaerobic granular sludge interior microbial community dynamics were investigated using high-throughput sequencing. The results demonstrated that the removal rate of COD was 83.6% after long-term exposure in the experimental reactor, namely, the anaerobic reactor containing Fe3O4 NPs. It was reduced by 5.7% in comparison with the removal rate in the control reactor. The total amount of TB-EPS in anaerobic granular sludge in the experimental and control reactors was 178.20 mg·g-1 and 138.24 mg·g-1, respectively, while the total amount of SMP in anaerobic granular sludge was 34.88 mg·L-1 and 27.44 mg·L-1, respectively. With regard to the LB-EPS in anaerobic granular sludge in the experimental reactor, the peak of humic acid disappeared and the peak intensity of coenzyme F420 decreased slightly using excitation-emission matrix (EEM) fluorescence spectra. In terms of the microbial community dynamics in the experimental reactor, the abundance of Methanobacterium was greatly augmented from 76.15% to 86.76%; whereas, the abundance of Methanothrix decreased from 17.1% to 7.51%. This indicated that Methanothrix was more sensitive to Fe3O4 NPs. Moreover, the changes in bacterial communities were evident:①the abundance of Proteobacteria dropped from 66.44% to 47.16%; ② the abundance of Actinobacteria grew from 8.97% to 17.33%; and ③ the abundance of Bacteroidetes increased from 8.07% to 17.74%. The increasing abundance of Actinobacteria and Bacteroidetes plays a positive role in the anaerobic hydrolysis of organic matter.


Cell-cycle control and plant development.
The cell cycle is driven by the activity of cyclin-dependent kinase (CDK)-cyclin complexes. Therefore, internal and external signals converge on the regulation of CDK-cyclin activity to modulate cell proliferation in specific developmental processes and under various environmental conditions. CDK-cyclin activity is fine-tuned by multiple mechanisms, for example, transcriptional control, protein degradation, phosphorylation, and binding to CDK inhibitor. These molecular mechanisms underlie the regulation of the entry into or the exit from the cell cycle, the rate of cell cycle, or the transition from the mitotic cell cycle to the endocycle. The multiple mechanisms regulating CDK-cyclin activity coordinately enable the elaborate control of cell cycle by various upstream signals. Here, we review the molecular mechanisms that regulate the cell cycle and the endocycle in plants. We also introduce the recent progress in elucidating the regulatory mechanisms underlying plant development and the stress response in terms of cell-cycle control.


A Controlled Cortical Impact Preclinical Model of Traumatic Brain Injury.
Over the past three decades, attempts at understanding the multifaceted mechanisms underlying the pathophysiology of traumatic brain injury (TBI) have seen the development of numerous animal models to investigate changes in molecular and cellular pathways and neurobehavioral outcomes. Until now, controlled cortical impact (CCI) represents the most frequently used mechanical model to induce TBI, given its accuracy, easy of control, and, most importantly, its ability to produce brain injuries similar to those seen in humans. The CCI model is based on the use of an impact system that delivers a physical impact to the exposed dura of an animal. This chapter will describe in detail the electromagnetic CCI model of TBI in mice.


Substitution for Asn460 cripples β-galactosidase (Escherichia coli) by increasing substrate affinity and decreasing transition state stability.
Substrate initially binds to β-galactosidase (Escherichia coli) at a 'shallow' site. It then moves ∼3Å to a 'deep' site and the transition state forms. Asn460 interacts in both sites, forming a water bridge interaction with the O3 hydroxyl of the galactosyl moiety in the shallow site and a direct H-bond with the O2 hydroxyl of the transition state in the deep site. Structural and kinetic studies were done with β-galactosidases with substitutions for Asn460. The substituted enzymes have enhanced substrate affinity in the shallow site indicating lower E·substrate complex energy levels. They have poor transition state stabilization in the deep site that is manifested by increased energy levels of the E·transition state complexes. These changes in stability result in increased activation energies and lower k(cat) values. Substrate affinity to N460D-β-galactosidase was enhanced through greater binding enthalpy (stronger H-bonds through the bridging water) while better affinity to N460T-β-galactosidase occurred because of greater binding entropy. The transition states are less stable with N460S- and N460T-β-galactosidase because of the weakening or loss of the important bond to the O2 hydroxyl of the transition state. For N460D-β-galactosidase, the transition state is less stable due to an increased entropy penalty.


Validation of SPAMM tagged MRI based measurement of 3D soft tissue deformation.
This study presents and validates a novel (non-ECG-triggered) MRI sequence based on spatial modulation of the magnetization (SPAMM) to noninvasively measure 3D (quasistatic) soft tissue deformations using only six acquisitions (three static and three indentations). In the current SPAMM tagged MRI approaches, data are typically constructed from many repeated motion cycles. This has so far restricted its application to the measurement of highly repeatable and periodic movements (e.g., cardiac deformation). In biomechanical applications where soft tissue deformation is artificially induced, often by indentation, significant repeatability constraints exist, and for clinical applications, discomfort and health issues generally preclude a large number of repetitions. A novel (non-ECG-triggered) SPAMM tagged MRI sequence is presented, whereby a single 1-1 (first order) SPAMM set is acquired following a 3D transient field echo acquisition. Full 3D deformation measurement is achieved through the combination of only six acquisitions (three static and three motion cycles). The 3D deformation measurements were validated using quasistatic indentation tests and marker tracking in a silicone gel soft tissue phantom. In addition, the technique's ability to measure 3D soft tissue deformation in vivo was evaluated using indentation of the biceps region of the upper arm in a volunteer. Following comparison to marker tracking in the silicone gel phantom, the SPAMM tagged MRI based displacement measurement demonstrated subvoxel accuracy with a mean displacement difference of 72 microm and a standard deviation of 289 microm. In addition, precision of displacement magnitude was evaluated for both the phantom and the volunteer data. The standard deviations of the displacement magnitude with respect to the average displacement magnitude were 75 and 169 microm for the phantom and volunteer data, respectively. The subvoxel accuracy and precision demonstrated in the phantom in combination with the precision comparison between the phantom and the volunteer data provide confidence in the methods presented for measurement of soft tissue deformation in vivo. To the author's knowledge, since only six acquisitions are required, the presented methodology is the fastest SPAMM tagged MRI method currently available for the noninvasive measurement of quasistatic 3D soft tissue deformation.


Effect of aluminum sulfate on litter composition and ammonia emission in a single flock of broilers up to 42 days of age.
New alternatives are necessary if the environmental impact linked to intensive poultry production is to be reduced, and different litter handling methods should be explored. Among these, acidifying amendments added to poultry litters has been suggested as a management practice to help reduce the potential environmental effect involved in multiple flock cycles. There have been several studies on the use of aluminum sulfate (alum) and its benefits, but almost no data are available under farm conditions in Europe. An experiment with Ross 308 broilers from 1 to 42 days of age was conducted to evaluate the effect of alum on litter composition, the solubility of some mineral elements and NH3 emission during a single flock-rearing period in commercial houses located in southeast Spain. Broilers were placed on clean wood shavings in four commercial houses, containing 20 000 broilers each. Before filling, alum was applied at a rate of 0.25 kg/m2 to the wood shavings of two poultry houses, whereas the remaining two were used as control. Litter from each poultry house was sampled every 3 to 5 days. Ammonia emissions from the poultry houses were monitored from 37 to 42 days of age. In comparison with the control group, alum treatment significantly reduced the pH level of the litter (P < 0.001) with an average difference of 1.32 ± 0.24 units. Alum-treated litter showed, on average, a higher electrical conductivity than the control litter (5.52 v. 3.63 dS/m). The dry matter (DM) and total N and P contents did not show differences between the treatments (P > 0.05). Regarding the NH4 +-N content, alum-treated litter showed a higher value than the untreated litter, with an average difference of 0.16 ± 0.07% (on a DM basis). On average, alum-treated litter had lower water-soluble P, Zn and Cu contents than the untreated litter. Alum noticeably reduced the in-house ammonia concentration (P < 0.001), with an average of 4.8 ppm at 42 days of age (62.9% lower than the control), and ammonia emissions from 37 to 42 days of age were significantly reduced by the alum treatment (P < 0.001), representing a reduction of 73.3%. The lower pH values might have reduced ammonia volatilization from the litter, with a corresponding positive effect on the building environment and poultry health. For these reasons, litter amendment with alum could be recommended as a way of reducing the pollution potential of European broiler facilities during a single flock cycle.


The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis.
The interaction between thrombopoietin (THPO) and its receptor c-Mpl regulates downstream cytokine signaling and platelet homeostasis. Hereditary mutations of c-Mpl can either result in loss-of-function and thrombocytopenia or in gain-of-function and thrombocythemia (HT), and are important models to analyze the mechanism of c-Mpl activity. We have analyzed the effect of the c-Mpl P106L gain-of-function and the nearby loss-of-function R102P and F104S mutations, which cause HT or thrombocytopenia, respectively, on posttranslational processing, intracellular trafficking, cell surface expression, and cell proliferation. In contrast to R102P and F104S, the P106L mutant confers cytokine-independent growth and stimulates downstream signaling after THPO treatment in Ba/F3 cells. Despite their opposite function, R102P and P106L, both lead to abnormal subcellular receptor distribution, lack of membrane localization, impaired glycosylation, and elevated THPO serum levels in effected patients. These findings indicate that the activation of downstream signaling by c-Mpl P106L does not require correct processing, trafficking, and cell surface expression of c-Mpl, whereas the negative feedback loop controlling THPO serum levels requires cell surface expression of the receptor. Thus, we propose that the P106L mutation functionally separates the activity of c-Mpl in downstream signaling from that in maintaining platelet homeostasis.


Comparison of vancomycin and teicoplanin for prophylaxis of sepsis with coagulase negative staphylococci (CONS) in very low birth weight (VLBW) infants.
A prospective randomized study was performed to evaluate the efficacy of a low dose (5 mg/kg/day bid) vancomycin compared with a low dose (5 mg/kg/day once daily) teicoplanin therapy to prevent CONS sepsis in VLBW-infants. All infants received this therapy after their 4th day of life or after an eventual therapy of early onset sepsis as long as an i.v. line was in place or 1500 g body weight. Twenty-seven infants were treated with vancomycin (birth weight 1103 +/- 286 g, gest. age 28.8 +/- 1.9 weeks), 28 with teicoplanin (birth weight 1133 +/- 226 g, gest. age 29.04 +/- 2.2 weeks). The infants were observed for clinical and laboratory signs of sepsis. On day 4 of therapy and every 3rd day during therapy serum creatinine levels, tracheal aspirates, stool cultures and vancomycin/teicoplanin peak and trough levels were obtained. We could not detect any case of blood culture positive sepsis and 1 case of suspected sepsis (neg. blood cultures) in both groups, as compared with a former CONS sepsis rate of 24% in our institution's VLBW infants without antibiotic prophylaxis. Nine patients in the vancomycin and five in the teicoplanin group had tracheal colonization with CONS. In both groups peak and trough levels of antibiotics were in the bactericidal range. Serum creatinine was not normal in both groups. We conclude that teicoplanin is preventing CONS sepsis as well is vancomycin. The minimal inhibitory concentrations of both antibiotics against grampositive isolates in units using this strategy have to be observed carefully to detect emerging resistance.


Parasite-specific aptamers as biosynthetic reagents and potential pharmaceuticals.
Aptamers are short, synthetic nucleic acid molecules. They are generated by a Darwinian-type in vitro evolution method known as 'systematic evolution of ligands by exponential enrichment' (SELEX). SELEX represents an experimental platform to identify rare ligands with predetermined functionality from combinatorial nucleic acid libraries. Since its discovery about 20 years ago the method has been instrumental in identifying a large number of aptamers that recognize targets of very different chemistry and molecular complexity. Although aptamers have been converted into sophisticated biomolecular tools for a diverse set of technologies, only a limited number of aptamers have been selected as binding reagents for parasites or parasite-derived molecules. Here the published examples of aptamers that target Leishmania-, Trypanosoma- and Plasmodia-specific molecules are reviewed.


Mining a chemical database for fragment co-occurrence: discovery of "chemical clichés".
Nowadays millions of different compounds are known, their structures stored in electronic databases. Analysis of these data could yield valuable insights into the laws of chemistry and the habits of chemists. We have therefore explored the public database of the National Cancer Institute (>250,000 compounds) by pattern searching. We split the molecules of this database into fragments to find out which fragments exist, how frequent they are, and whether the occurrence of one fragment in a molecule is related to the occurrence of another, nonoverlapping fragment. It turns out that some fragments and combinations of fragments are so frequent that they can be called "chemical clichés". We believe that the fragment data can give insight into the chemical space explored so far by synthesis. The lists of fragments and their (co-)occurrences can help create novel chemical compounds by (i) systematically listing the most popular and therefore most easily used substituents and ring systems for synthesizing new compounds, (ii) being an easily accessible repository for rarer fragments suitable for lead compound optimization, and (iii) pointing out some of the yet unexplored parts of chemical space.


Fundus foveal localization based on vessel model.
The problem of automatically locating the fovea, a spot located in the center of the macula and responsible for sharp central vision, on the retinal surface image is considered. The uniqueness of the strategy presented here is the relatively small amount of computational expense of a quick and robust method conducive to real-time applications. The algorithm first identifies the main blood vessels using the modified active shape model (ASM) and then expeditiously attempts to fit the parabolic shape to the overall result to locate the fovea. A reliable tracking strategy is also proposed here to estimate the required vertex when the prior information of the optic disk is not available. When a patient's retinal vessel data have been modeled a priori and used as template, the technique brought up here should find its advantage in real-time image-guided applications like a computer-assisted photocoagulation treatment.


Regulation of Multidrug Resistance P-Glycoprotein in the Developing Blood-Brain Barrier: Interplay between Glucocorticoids and Cytokines.
P-glycoprotein (P-gp) encoded by Abcb1 provides protection to the developing brain from xenobiotics. P-gp in brain endothelial cells (BECs) derived from the developing brain microvasculature is up-regulated by glucocorticoids and inhibited by pro-inflammatory cytokines in vitro. However, little is known about how prenatal maternal glucocorticoid treatment can affect Abcb1/P-gp function and subsequent cytokine regulation in foetal BECs. We hypothesised that glucocorticoid exposure increases Abcb1/P-gp in the foetal brain microvasculature and enhances the sensitivity of Abcb1/P-gp in BECs to the inhibitory effects of cytokines. BECs isolated from dexamethasone- or vehicle-exposed foetal guinea pigs were cultured and treated with interleukin-1β, interleukin-6 or tumour necrosis factor-α, and Abcb1/P-gp expression and function were assessed. Prenatal dexamethasone exposure significantly increased Abcb1/P-gp expression/activity and cytokine receptor levels in BECs of the foetal brain microvasculature. Foetal dexamethasone exposure in vivo also increased the subsequent responsiveness of BECs to pro-inflammatory cytokines in vitro. In conclusion, maternal treatment with synthetic glucocorticoids appears to prematurely mature P-gp mediated drug resistance at the foetal BBB in vivo and profoundly impact the subsequent responsiveness of P-gp to pro-inflammatory cytokines in the foetal BEC. The significance of these findings to foetal brain protection against xenobiotics and other P-gp substrates in vivo requires further elaboration. However, the results of the present study may have implications for human pregnancy and foetal brain protection, particularly in cases of preterm birth combined with infection.


Fat laden macrophages in tracheal aspirates as a marker of reflux aspiration: a negative report.
Refluxed gastric material aspirated into the lungs is an important cause of acute and chronic pulmonary disease. Currently, the presence of fat-laden macrophages (FLM) in tracheobronchial secretions of children is a conventional marker for reflux aspiration. However, this assay is limited by its apparent lack of specificity. The aim of this study was to reevaluate the role of this assay in diagnosing reflux aspiration. The tracheal aspirates of sixty-four consecutive children with clinically significant gastroesophageal reflux undergoing upper gastrointestinal endoscopy under general anesthesia, and 34 other children from the routine operative schedule were evaluated. Both groups were further subdivided on the basis of presence or absence of associated respiratory symptoms. After intubation, tracheal aspirates were collected, fixed, and stained for FLM. By grading the amount of intracellular fat present, a semiquantitative lipid index was computed. Tracheal aspirates with a lipid index of 100 or greater were considered positive. Twenty-four of the 64 children with reflux symptoms and 14 of 34 children without reflux symptoms were positive for FLM. Sixteen of 37 children with both gastroesophageal reflux and respiratory symptoms and 10 of 26 children negative for both tested positive for FLM. The mean lipid index of the subgroup of children with both reflux and respiratory symptoms was not significantly different from that of the subgroup that was negative for both conditions. Despite computing a semiquantitative lipid index, an index of 100 or greater only had a sensitivity of 38% and specificity of 59%. Assay of FLM in the tracheal aspirates of children considered at risk of reflux aspiration is not a sensitive or specific as a marker for reflux aspiration.


Achieving nitrogen-doped carbon/MnO2 nanocomposites for catalyzing the oxygen reduction reaction.
The design and synthesis of cheaper and more stable catalysts with comparable electrocatalytic performance to commercial Pt/C towards the oxygen reduction reaction is of importance for their application in fuel cells and metal-air batteries. Herein, we report the generation of nitrogen-doped carbon/MnO2 nanocomposites via pyrolyzing the polypyrrole/MnO2 precursor that is obtained based on the direct redox reaction between polypyrrole and KMnO4. The achieved sample presents an onset and half-wave potential of -0.048 and -0.124 V vs. Hg/HgO, respectively, and a current retention of 93% after 20 000 s chronoamperometry measurement. Meanwhile, it shows stronger methanol tolerance, endowing it with great potential for the corresponding applications. The excellent oxygen reduction reaction catalytic activity originates from the synergistic effect between nitrogen-doped carbon and MnO2, where the former one is helpful for MnO2 to achieve a higher Mn3+/Mn4+ ratio and a higher number of oxygen vacancies, and the existence of the latter one is beneficial for generating a higher ID/IG ratio in the carbon layer. These both contribute to the achievement of large numbers of active sites for the electrocatalytic process.


Hairy cell leukemia: bone marrow changes following splenectomy and alpha-interferon therapy.
Thirty hairy cell leukemia patients were evaluated repeatedly for their bone marrow (BM) histology. At the time of diagnosis, 18 (60%) had diffuse, 9 (30%) had interstitial, and 2 (10%) had a mixed (diffuse and interstitial) pattern of BM disease. The follow-up BM specimens were obtained at intervals of 3-24 months, and the follow-up observation period was 12-94 months. In patients who were nontreated or only splenectomized, no significant changes were observed except of a persistent megaloblastoid picture of the red cell series and an increase of BM fibrosis. In the alpha-interferon treated patients a complete disappearance of hairy cells was observed in one and a dramatic reduction in five. The hairy cell index was reduced from a mean of 0.8 before to 0.1 after alpha-interferon therapy; most patients displayed megaloblastoid erythropoiesis. In the complete responder features of myelodysplasia were present.


Vitreochorioretinal degeneration associated with trichomegaly.
A 15-year-old white boy had bilateral vitreochorioretinal degeneration associated with trichomegaly. Findings on electroretinography and fluorescein angiography provided additional information on the retinal changes not noted in 3 previously reported cases having these associated features. Although similar on ophthalmoscopy, fluourescein angiography, and by electroretinography, the retinal disease in our patient differed from cases of gyrate atrophy of the choroid and retina in having normal plasma ornithine levels.


Correlation Between Hump Dimensions and Curve Severity in Idiopathic Scoliosis Before and After Conservative Treatment.
Prospective study in 150 consecutive outpatients affected by adolescent idiopathic scoliosis (AIS). The purposes were to (1) identify a correlation between hump dimensions and the severity of scoliotic curve, and (2) evaluate how the treatment influenced the main parameters of scoliosis. The existence of a relationship between clinical deformities and curve severity in AIS is still debated. Furthemore, only a few studies have investigated the effectiveness of conservative treatment for idiopathic scoliosis taking into account both clinical and radiologic factors. 150 consecutive outpatients (mean age 12.8 ± 1.9 years) affected by AIS were subjected to conservative brace-based treatment. 134 participants completed the treatment protocol. Two parameters were considered to evaluate the treatment progress: the hump and the Cobb angle. Measurements were determined at the beginning and the end of treatment. Statistical analyses were performed in the whole sample and after dividing the study participants into 4 subgroups: patients with lumbar (n = 66) or thoracic curves (n = 68), patients ranging in age between 6 and 13 years (n = 89) and patients ≥ 14 years of age (n = 45). A positive correlation was detected between the hump dimension and curve severity at the beginning and the end of treatment, except for lumbar curves at baseline. The deformity was effectively corrected by the orthotic treatment (Cobb angle: 29.4 ± 8.5° at baseline and 19.3 ± 9.8° at the end of treatment; hump severity: 11.6 ± 5.6 mm at baseline and 6.2 ± 4.6 mm at the end). In addition, our data indicate that the hump correction is more evident than that of the curve registered in Cobb degrees. A significant correlation exists between the hump dimension and curve severity both at the beginning and the end of treatment, except for lumbar curves at baseline. The brace treatment confirmed its effectiveness in arresting the deformity progression and inducing a remodeling both of the scoliotic curve and the hump.


Neurochemical and Neuroendocrine Effects of Ibogaine in Rats: Comparison to MK-801.
Ibogaine (IBO) is a naturally-occurring indole compound that is being evaluated as a potential medication for substance use disorders. Although the precise mechanism of IBO action is unclear, recent in vitro data show this drug displays properties similar to the noncompetitive N-methyl-d-aspartate (NMDA) antagonist MK-801. The purpose of the present work was to compare In Vivo neurobiological effects of IBO and MK-801 in rats. Groups of male rats (n = 6-8/group) were decapitated 30 and 60 min after receiving intraperitoneal (i.p.) IBO (10 & 100 mg/kg), MK-801 (0.1 & 1.0 mg/kg) or vehicle. Trunk blood was collected for the analysis of plasma prolactin and corticosterone; brains were harvested and dissected for determination of dopamine (DA), serotonin (5-HT) and their metabolites. Both IBO and MK-801 increased corticosterone secretion, but only IBO elevated plasma prolactin. IBO produced dramatic reductions in tissue DA levels with concurrent increases in the metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of IBO-induced changes in DA transmission was observed in the striatum, olfactory tubercle, and hypothalamus. The effects of MK-801 on DA metabolism did not mimic IBO, as MK-801 tended to increase DA and its metabolites. Neither drug appreciably affected 5-HT systems. Our results suggest that the effects of IBO on neuroendocrine function and DA transmission are not due to MK-801-like properties of IBO. Thus, the In Vivo mechanism of IBO action cannot be explained simply on the basis of antagonism at NMDA receptors.


The dopamine D4 receptor gene, birth weight, maternal depression, maternal attention, and the prediction of disorganized attachment at 36 months of age: A prospective gene×environment analysis.
Efforts to understand the developmental pathways for disorganized attachment reflect the importance of disorganized attachment on the prediction of future psychopathology. The inconsistent findings on the prediction of disorganized attachment from the dopamine D4 receptor (DRD4) gene, birth weight, and maternal depression as well as the evidence supporting the contribution of early maternal care, suggest the importance of exploring a gene by environment model. Our sample is from the Maternal Adversity, Vulnerability, and Neurodevelopment project; consisting of 655 mother-child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 genotype was obtained with buccal swabs and categorized according to the presence of the 7-repeat allele. Maternal depression was assessed with the Center for Epidemiologic Studies Depression Scale at the prenatal, 6-, 12-, and 24-month assessments. Maternal attention was measured at 6-months using a videotaped session of a 20-min non-feeding interaction. Attachment was assessed at 36-months using the Strange Situation Procedure. The presence of the DRD4 7-repeat allele was associated with less disorganized attachment, β=-1.11, OR=0.33, p=0.0008. Maternal looking away frequency showed significant interactions with maternal depression at the prenatal assessment, β=0.003, OR=1.003, p=0.023, and at 24 months, β=0.004, OR=1.004, p=0.021, as at both time points, women suffering from depression and with frequent looking away behavior had an increased probability of disorganized attachment in their child, while those with less looking away behavior had a decreased probability of disorganized attachment in their child at 36 months. Our models support the contribution of biological and multiple environmental factors in the complex prediction of disorganized attachment at 36 months.


[Orthopaedic relevance of baby carrying].
Recently, various ways of carrying a baby have become popular again. Different methods and options of infant carrying are largely influenced by current fashion trends. The term of baby carrying refers to carrying the infant close to the caregiver's body with special devices, which aid attachment parenting. The authors often face the question in the pediatric orthopedic clinic: what kind of carrying method to recommend to the parents. In this article the authors briefly present the different means of carrying devices and they review the literature regarding orthopedic consequences of baby carrying. For the healthy development of a child, position and correct support of the hips and the spine are essential, whereas the carrier's spinal protection is also an important aspect. After reviewing the literature, the authors conclude that baby carrying with an adequate device has advantages from orthopaedic point of view.


Chromosomal location by in situ hybridization of the human Sau3A family of DNA repeats.
The Sau3A family is a human, clustered, highly repetitive, GC-rich DNA family. In situ hybridization studies with a plasmid carrying a Sau3A monomer as a probe have shown that Sau3A sequences are preferentially concentrated in the heterochromatic regions of human acrocentric chromosomes (D and G groups, both in pericentromeric regions and in cytological satellites) and in pericentromeric heterochromatin of chromosome 1. The same chromosomal locations were observed by using as probes two recombinant phages which carry Sau3A-positive genomic sectors. The two sectors differ for the relative proportions of monomer and multiples of Sau3A repeats, which show different extents of homology to the cloned monomer, and for the presence, in one of the two, of a small amount of an unrelated repeat (alphoid DNA). The similarity of the results obtained with the three probes suggests that heterogeneous Sau3A repeats share the same chromosomal localizations and that the two analyzed genomic sectors may not contain significant amounts of repetitive DNAs other than the Sau3A family. A comparison between the chromosomal locations of Sau3A and EcoRI families of repeats has confirmed that each family is characterized by specific chromosomal locations and that single heterochromatic regions may contain both.


The effect of graded hypoxia on the embryonic chick heart.
Embryonic ventricular function in the chick was measured in response to graded levels of hypoxia. Myocardial contractility, as measured by cinephotoanalysis and expressed as shortening fraction, was significantly depressed after 1 hour of moderate hypoxia (6% O2) and after 5 hours of milder (16% O2 and 11% O2) levels of hypoxia (P less than .05). Microscopy confirmed associated myocyte damage with cell death noted after 5 hours of moderate hypoxic stress. Heart rate change was not related to the severity of hypoxia. The greatest level of tachycardia was noted with conditions of mildest hypoxia (16% O2). The data confirm that cardiac contractility, as measured by shortening fraction, is depressed on exposure to hypoxia, with impairment of function related to the severity of the hypoxic conditions.


Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI).
Assessment of disease severity in systemic vasculitis encompasses mortality, which is now uncommon, and morbidity, which is increasing in significance. Morbidity includes permanent scars or damage, an evolving concept offering a novel perspective which may be particularly valuable in chronic disease. We have developed a method for assessing damage in systemic vasculitis, but the relationship between damage and disease severity was unknown. Therefore, we examined whether the number of items of damage or the pattern of damage varied with the severity of systemic vasculitis. We established the characteristics of severe disease by examining fatal vasculitis as an example of the most severe disease possible. We then showed that more damage occurred in fatal vasculitis, more systems were damaged, and critical damage akin to organ failure was more common in fatal than non-fatal vasculitis. These observations were reproduced in specific diagnostic groups, namely classical Wegener's granulomatosis and systemic rheumatoid vasculitis. Thus, severe disease was characterized by many items of damage, multisystem damage and critical damage. This pattern of damage was also seen in a subgroup of patients with non-fatal vasculitis, who also have severe disease.