[On the centenary of József Török's death (1813-1894) a physician and scientist].
The author investigates the career of József Török (1813-1894), who was a physician, surgeon, and a lecturer in chemistry and sciences at the College of the Reformed Church at Debrecen. Török's reputation was established, nevertheless, by his famous work, the First class medical waters and spas of the two Hungarian homelands. On their natural, chemical and therapeutical power, which he finished in 1847. Török, born in a family of a reformed clergyman, was educated in Debrecen, studied medicine at the university of Pest and spent two years at the universities of Paris, Berlin and Vienna. At Paris he attended the courses of Eluard Chassaignac, at Berlin those of Schönlein and Dieffenbach and at Vienna Rokitansky, Skoda and Hebre were his professors. Though returning to Hungary he practiced as a private doctor and later lectured in dietetics, he was unable--probably owing to his Calvinist faith--to receive a full time post at the university and in 1847 accepted the invitation of the College of Debrecen to lecture in chemistry, botany and mineralogy. He took part as a head physician in legal forensic medicine, and public health. The author emphasizes that Török not only introduced chemistry into secondary school education of human anthropology but created a new curriculum of science for secondary schools as well. His enterprise was a very important innovation in Hungarian public school education. His other main contribution was his famous book on the mineral waters of Hungary, which was awarded by the Hungarian Academy of Sciences in 1847. This balneological work detailed the spas of 19th century Hungary, and--in its second edition in 1859--gave an elaborated bibliography for such books published between 1631-1856. The work was a real breakthrough in Hungarian balneology. The author also investigates the interests of Török in the flora and fauna of the surrounding area of Debrecen, and his geological publications as well.


[The liver splenosis in a patient following a procedure for the malignant seminoma].
Splenosis is characterized by a presence of islets of the splenic tissue in the abdominal and, rarely, also in the thoracic cavity, most frequently as a consequence of the splenic injury. The authors describe a case of splenosis in a patient followed-up after surgery and radiotherapy for the testicular seminoma and who, 42 years ago, had splenectomy for polytrauma. With respect to the location of the splenosis in the hepatic region, the differential diagnosis was difficult, bearing in mind a possibility of the malignancy relaps. Although splenosis was highly suspected, based on the results of the examinations conducted, with respect to the preexisting malignancy, the tumor was excised. The histopathologist confirmed the diagnosis of splenosis. This case is rare in the literature, considering the time gap between the diagnosis of splenosis and the trauma.


Obstructive sleep apnea: the effect of bariatric surgery after 12 months. A prospective multicenter trial.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, particularly in bariatric patients. It is known to be tightly linked with metabolic abnormalities and cardiovascular morbidity. Obesity is the most noteworthy individual risk factor for OSA. The aim of this study was to investigate the effect of a laparoscopic Roux-en-Y gastric bypass (LRYGB) on OSA one year after surgery. In this prospective multicenter study standard overnight cardiorespiratory recording was conducted 12 months after bariatric surgery in 132 patients who had OSA in the baseline recording prior to the operation. The main outcome measures were changes in the prevalence of OSA and apnea-hypopnea index (AHI). In addition, the changes in anthropometric and demographic measurements including weight, body mass index (BMI), and waist and neck circumference were evaluated. A sleep symptom questionnaire was administered at baseline and at 12 months. The prevalence of OSA decreased from 71% at baseline to 44% at 12 months after surgery (p < 0.001). OSA was cured in 45% and cured or improved in 78% of the patients, but moderate or severe OSA still persisted in 20% of the patients after the operation. De novo OSA occurred in eight percent of the patients, and total AHI decreased from 27.8 events/h to 9.9 events/h (p < 0.001). LRYGB is effective in treating OSA. However, the findings demonstrate that a postoperative cardiorespiratory recording is needed in order to identify the patients with persistent moderate to severe OSA after the operation. ClinalTrials.gov; No.: NCT01080404; URL: www.clinicaltrials.gov.


The role of Ca2+ in cadmium-induced renal tubular cell injury.
Changes in rat renal proximal tubule cell gene expression were studied in vitro using a cadmium metallothionein (CdMT) exposure model. Increased expression of MT together with alterations in the expression of several other stress protein products were demonstrated by 35S-two-dimensional gel electrophoresis. Stress proteins with estimated molecular masses of 32, 70 and 90 kDa were observed to be increased after 4 h of exposure. These changes preceded the onset of cell injury. Internal stores of Ca2+ were not found to be measurably altered, as measured by the changes in fluorescence of the dye FURA-2. These data suggest that the observed alterations in gene expression are directly mediated by Cd2+ and not secondary to increased availability of Ca2+ within the target cell population, perhaps mediated by the transacting factor which regulates MT synthesis. The calcuria resulting from in vivo exposure to Cd2+ in workers or CdMT exposure in animal models may be secondary to alterations in renal proximal tubule cell gene expression.


Effect of prolactin on galactose cataractogenesis.
Prolactin has been known to affect the water and electrolyte balance. Because increased lens hydration has been shown to be a common phenomenon in most, if not all types of cataracts, we have been interested in investigating a possible role of prolactin in sugar cataract induction and progression. For this study, we have used morphological and biochemical approaches. The prolactin delivery method involved intraperitoneal implantation of one or more pellets in Sprague-Dawley female rats. Following implantation of the desired number of prolactin or control (nonprolactin) pellets, animals were either fed galactose and lab chow, or lab chow diet. Gross morphological observations of whole lenses, slit-lamp examination of lenses and light microscopic analysis of lens sections showed that in the galactose-fed prolactin group, galactose associated alteration progressed faster and total opacification (mature cataract development) was achieved earlier than in the nonprolactin group. The levels of galactose and dulcitol were higher in the lenses of galactose-fed prolactin treated rats as compared to lenses from nonprolactin (control) rats. No significant difference in lens Na+-K+ ATPase activity between the prolactin and nonprolactin group was observed. Our results indicate that prolactin accelerates galactose-induced cataractogenesis in rats.


Gold-Catalyzed Domino Synthesis of Functionalized Benzofurans and Tetracyclic Isochromans via Formal Carboalkoxylation.
A domino synthesis of benzofurans with the modification of side chains from α-alkoxyalkyl o-alkynylaryl ethers (n = 0) and electron-rich arenes has been developed. In the present domino reaction, which would proceed via the α-alkoxyalkylation of arenes with an intermediate in the migratory cycloisomerization of o-alkynylaryl ethers followed by the nucleophilic addition of benzofurans to benzyl ethers, a cationic Au(III) catalyst activates the C-C π bond and the C-O σ bond. The present method could be extended to Au(I)-catalyzed domino synthesis of tetracyclic isochromans from α-alkoxyalkyl (o-alkynylaryl)methyl ethers (n = 1) and aryl methoxymethyl ethers.


Thymosin fails to reconstitute normal estradiol levels into neonatally thymectomized rats.
Neonatal thymectomy into female rats reduced estradiol plasmatic levels during the first 60 days. This disturbance was not corrected by thymosin opotherapy. Comparison with male rats and testosterone disturbance was discussed.


[Near infrared spectroscopy synergy interval wavelength selection method using the LSSVM model].
The present paper proposes a wavelength selection algorithm based on nonlinear factors named Synergy interval least squares support vector machines (siLSSVM). siLSSVM combines the interval strategy of wavelength selection method with the idea of synergy interval and overcomes the disadvantages of the traditional wavelength selection methods, i. e. ignoring the nonlinear factors. Taking the near infrared spectrum data of apple sugar as performance verification object of this new algorithm, comparing new algorithm with siPLS, the model performance has been greatly improved. The root-mean-square error (RMSEP) in new algorithm has increased respectively by 37.43% and 47.88% under the model of PLS and LSSVM, with increases of 6.04% and 7.31% in the correlative coefficient (RP). The examples illustrate that siLSSVM can efficiently select the optimum wavelength interval for spectrum data with strong nonlinear factors. This algorithm greatly improves the prediction accuracy and robustness of the model, which provides a new prospect for near infrared spectral with nonlinear factors to select wavelength.


Microsatellites for mahoganies: twelve new loci for Swietenia macrophylla and its high transferability to Khaya senegalensis.
A new set of 12 microsatellite markers was developed and characterized for big-leaf mahogany (Swietenia macrophylla King, Meliaceae) and its transferability assayed in the African mahogany, Khaya senegalensis (Desr.) A. Juss. (Meliaceae), to study population and conservation genetics of these threatened tropical timber species. Using an enriched library approach twelve novel microsatellite loci were identified for S. macrophylla. The number of alleles per locus ranged from 5 to 14 and mean observed and expected heterozygosities were 0.819 and 0.822, respectively. Twenty microsatellite loci developed for S. macrophylla (12 from this study and eight previously published) were tested for K. senegalensis and 10 polymorphic were characterized. The results show the highly informative content of the new SSR loci for Swietenia macrophylla and the high effectiveness of these microsatellites for population genetics, gene flow, and mating system studies in Khaya senegalensis.


Comparing the performance of UASB and GRABBR treating low strength wastewaters.
Anaerobic technologies have proved successful in the treatment of various high strength wastewaters with perceptible advantages over aerobic systems. The applicability of anaerobic processes to treat low strength wastewaters has been increasing with the evolution of high-rate reactors capable of achieving high sludge retention time (SRT) when operating at low HRT. However, the performance of these systems can be affected by high variations in flow and wastewater composition. This paper reports on the comparative study carried out with two such high rate reactors systems to evaluate their performances when used for the treatment of low strength wastewaters at high hydraulic rates. One of the two systems is the most commonly used upflow anaerobic sludge blanket (UASB) reactor in which all reactions occur within a single vessel. The other is the granular bed baffled reactor (GRABBR) that encourages different stages of anaerobic digestion in separate vessels longitudinally across the reactor. The reactors, with equal capacity of 10 litres, were subjected to increasing organic loading rates (OLRs) and hydraulic retention times (HRTs) of up to 60 kg COD m(-3) d(-1) and 1 h respectively. Results show that the GRABBR has greater processes stability at relatively low HRTs, whilst the UASB seems to be better equipped to cope with organic overloads or shockloads. The study also shows that the GRABBR enables the harvesting of biogas with greater energetic value and hence greater re-use potential than the UASB. Biogas of up to 86% methane content is obtainable with GRABBR treating low strength wastewaters.


[Spinal muscular atrophy: disappearance of RNA fluorescence of degenerating motor neurons. An acridine orange study].
The histochemical distribution of nucleic acids has been studied in degenerating motor neurons of 9 children who died with spinal muscular atrophy, using the fluorochrome acridine orange. Ribonucleic acid (RNA) fluorescence disappeared abruptly from involved motor neurons without chromatolysis, attenuation of intensity, or other intermediate transitions that follow axotomy or hypoxic insults. We found a nearly identical pattern in 3 adults with amyotrophic lateral sclerosis. The findings in older subjects are complicated, however, by the presence of cytoplasmic lipofuscin. The autofluorescence of this pigment is inhibited by acridine orange. Our results support the hypothesis that spinal muscular atrophy is a disturbance of the genetically coded mechanism that arrests the programmed physiological death of surplus motor neuroblasts after a certain time in embryonic life, so that the normal lethal developmental process becomes pathological by persisting postnatally. A failure of RNA transcription seems to be primary and results in a failure of synthesis of neurotransmitters, of enzymes, and of cytoplasmic proteins. Consequent inanition leads to cell death.


Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time.
Infants with congenital diaphragmatic hernia (CDH) are at high risk of sensorineural hearing loss (SNHL). Extracorporeal membrane oxygenation is known to increase this risk, but little is known about other potential causes. We evaluated the impact of several risk factors on SNHL development in CDH survivors not treated with extracorporeal membrane oxygenation. All high-risk CDH survivors consecutively treated between 1999 and 2005 were included. SNHL was diagnosed based on formal assessment with standard audiologic tests. Patients with and without SNHL were compared for patient-related and treatment-related risk factors. Subsequently, a logistic regression analysis was performed to identify independent risk factors associated with SNHL development. Out of 87 CDH survivors, 82 had a formal audiologic evaluation and 40 (49%) had SNHL. Patients with SNHL had significantly lower gestational age (P = .045); higher prevalence of sepsis (P < .001); older age at audiologic examination (P < .001); more episodes of hypocapnia (P = .045); higher prevalence of inhaled nitric oxide use (P = .005); longer mechanical ventilation (P = .009); and longer aminoglycosides (P = .006), furosemide (P = .004), and pancuronium bromide (P = .001) treatments. On logistic regression analysis, the only variable independently associated with the development of SNHL was patient's age at audiologic follow-up (P = .012). Several risk factors were associated with SNHL development at univariate analysis. After logistic regression, only age at evaluation remained independently associated with SNHL. Routine audiologic follow-up is advocated in all CDH patients. Further studies are needed to define if other (genetic) factors may be involved in the pathogenesis of SNHL in patients with CDH.


Plasma fatty acid status in Moroccan children: increased lipid peroxidation and impaired polyunsaturated fatty acid metabolism in protein-calorie malnutrition.
In previous studies on plasma fatty acid and antioxidant status in 29 malnourished Moroccan children (12 with mild protein-calorie malnutrition, 17 with severe protein-calorie malnutrition) compared to 15 healthy control children from the same area, we pointed out that these populations were heterogeneous in terms of their essential fatty acid and antioxidant status. The aim of the present study was to classify the children using the Waterlow classification and their essential fatty acid status. The discrepancies in lipid parameters, nutritional and inflammatory markers, blood oxidative indexes, antioxidant micronutrients or trace elements (selenium, zinc, vitamin E) related to polyunsaturated fatty acids were checked in these populations. Eight of the control subjects and nine of the severe protein-calorie malnutrition children were essential fatty acid-deficient, compared to only one of the mild protein-calorie malnutrition group. Examination of the essential fatty acid-sufficient subjects with mild protein-calorie malnutrition, compared to the essential fatty acid-sufficient control subjects, showed only a decrease in Z scores and a non-significant decrease in selenium and vitamin E. In severely malnourished children, albumin, cholesterol and low density lipoprotein (LDL) cholesterol, plasma selenium, vitamin E and zinc were low, whereas inflammatory proteins and triglycerides were high. These features worsened with essential fatty acid deficiency. In all protein-calorie malnutrition subjects, there was oxidative stress (increase in thiobarbituric-acid reactants, imbalance between plasma polyunsaturated fatty acid, vitamin E and selenium levels), even in the absence of essential fatty acid deficiency. Monounsaturated fatty acids, oleic acid/stearic acid (C18:1 n-9/C18:0) delta9 desaturase and n-3 and n-6 elongase activity indexes increased. The C18:1/C18:0 delta9 desaturase activity index was negatively correlated to Z scores (r = -0.44, P< 0.01 for Z score weight, r = -0.39, P < 0.01 for Z score height), albumin (r = -0.82, P < 0.01) and zinc (r = -0.51, P< 0.01) levels. In essential fatty acid-deficient, severe protein-calorie malnutrition subjects, delta6 desaturase activity was impaired, and there was a non-significant decrease in arachidonic acid. Essential fatty acid deficiency is a type of malnutrition, and is associated with an aggravation of all parameters in severe protein-calorie malnutrition. The increase in the C18:1/C18:0 delta9 desaturase activity and enhanced lipid peroxidation without any essential fatty acid deficiency could be early markers of protein-calorie malnutrition.


The origin, migration and fine morphology of human primordial germ cells.
Human primordial germ cells (PGCs) were observed ultrastructurally in stages from their endodermal to gonadal locations. Primitive PGCs in the hind-gut epithelium of the 4-week embryo, were recognized as well demarcated cells from the neighboring cells. At the time fo separation, the basal lamina of the epithelium was broken, then, through the gap so opened, the PGCs started to escape into the outer mesenchyme. In embryos at five weeks, PGCs were in the migration stage, and were found in the dorsal mesentery, at the coelomic angle and in the forming germinal ridge. In embryos at six weeks or later, almost all PGCS were accumulated in the gonad. The PGC was characterized by its large size and the large and round nucleus with conspicuous nucleolus, and by the presence of abundant glycogen particles and a considerable number of lipid droplets in the cytoplasm. Alkaline phosphatase activity was demonstrated selectively on the plasma membrane of the PGC. The shape of PGC was irregular, often had pseudopodia in PGCs in the separation and migration stages, suggesting their amoeboid movement in vivo, but was generally round or elliptic in PGCs in the settlement stage. The PGC was usually surrounded by and in close association with adjacent somatic cells.


Treatment regimens for pregnant women with falciparum malaria.
With increasing parasite drug resistance, the WHO has updated treatment recommendations for falciparum malaria including in pregnancy. This review assesses the evidence for choice of treatment for pregnant women. Relevant studies, primarily those published since 2010, were identified from reference databases and were used to identify secondary data sources. Expert commentary: WHO recommends use of intravenous artesunate for severe malaria, quinine-clindamycin for uncomplicated malaria in first trimester, and artemisinin combination therapy for uncomplicated malaria in second/third trimesters. Because fear of adverse outcomes has often excluded pregnant women from conventional drug development, available data for novel therapies are usually based on preclinical studies and cases of inadvertent exposure. Changes in antimalarial drug disposition in pregnancy have been observed but are yet to be translated into specific treatment recommendations. Such targeted regimens may become important as parasite resistance demands that drug exposure is optimized.


[Clinical and morphological characteristics and some mechanisms of portal gastroduodenopathy in liver cirrhosis].
We have found out the clinical presentations and peculiarities of endoscopic and morphologic view of pathologies of mucous membrane of gastroduodenal zone caused by liver cirrhosis. We have examined 74 patients with liver cirrhosis of viral and nonviral etiology using the clinical, endoscopic, morphologic and immunohistochemical methods.We have found that during liver cirrhosis morphometric rates of epithelial cells of mucous coat of stomach that produce somatostatin and endothelin-1 decrease and morphometric rates of epithelial cells that produce nitrogen oxide synthase increase. We have also found out that during liver cirrhosis proliferate activity decrease and apoptosis of epithelial cell of mucous coat of stomach increase.


Hyperthermia and radiation therapy for inoperable or recurrent parotid carcinoma. A phase I/II study.
The treatment of advanced, inoperable, or recurrent parotid tumors represents a clinical challenge. The results obtained with conventional radiotherapy are disappointing. To improve the early response and local control of parotid tumors, local microwave hyperthermia was used in combination with ionizing radiation in a biinstitutional Phase I/II study. From 1984 to 1991, 13 patients (20 lesions) with advanced (10 lesions) or recurrent (10 lesions) parotid tumors (15 primaries and the remaining 5 nodal metastases), were treated with 300-915 MHz of external hyperthermia after external irradiation. Heat was applied twice weekly at a minimum desired temperature of 42.0 degrees C for 30 minutes at steady state. Ionizing radiation was delivered using photon, electron, or mixed electron-photon beams; the prescribed total dose was 70 Gy and 30 Gy for untreated and previously treated lesions, respectively; the median computed total dose was 66 Gy for previously untreated patients (range, 56-70 Gy) and 30 Gy for previously irradiated patients (range, 28-32 Gy). Acute side effects were limited. Major acute toxicities included three patients (15%) with superficial necrosis, two of three who healed spontaneously in 4 and 6 months. Clinical response evaluated during the third month after the completion of therapy found that 16/20 patients (80%) had a complete response (CR), and 4 (20%) had a partial response. Four out of 16 patients who had CRs (20%) had a local recurrence, resulting in an actuarial local control at 5 years of 62.3 +/- 13.2%. The combined treatment of local microwave hyperthermia and ionizing radiation proved to be feasible and moderately toxic for patients with advanced, inoperable, or recurrent parotid tumors. Even if clinical result evaluation was not the study endpoint, early response, and 5-year local control rates were encouraging.


The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition.
The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at theta=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte.


[Recommendations for the evaluation and follow-up of the continuous quality improvement].
Continual improvement of the quality in a medical laboratory is based on the implementation of tools for systematically evaluate the quality management system and its ability to meet the objectives defined. Monitoring through audit and management review, addressing complaints and nonconformities and performing client satisfaction survey are the key for the continual improvement.


FGF1 protects against APAP-induced hepatotoxicity via suppression of oxidative and endoplasmic reticulum stress.
Acetaminophen (APAP) overdose/abuse is the leading cause of acute liver failure in many countries. Fibroblast growth factor 1 (FGF 1) is a metabolic regulator with several physiological functions. Previous studies suggested that FGF1 promotes differentiation and maturation of liver-derived stem cells. In this study, we investigated the protective effects of FGF1 against APAP-induced hepatotoxicity in mice. APAP markedly increased circulating levels of ALT and AST, while FGF1 significantly inhibited increases in the serum levels of ALT and AST, as compared to littermates. In addition, histopathological evaluation of the livers revealed that FGF1 prevented APAP-induced centrilobular necrosis. Livers exhibited severe inflammation, apoptosis, oxidative stress and endoplasmic reticulum stress in response to APAP toxicity, whereas these changes were reversed by a single injection of FGF1. In conclusion, our findings suggest that FGF1 protects mice from APAP-induced hepatotoxicity through suppression of inflammation, apoptosis, and oxidative and endoplasmic reticulum stress. Therefore, FGF1 may represent a promising therapeutic agent for APAP-induced acute liver injury.


Statistical mechanics of spike events underlying phase space partitioning and sequence codes in large-scale models of neural circuits.
Cortical circuits operate in an inhibition-dominated regime of spiking activity. Recently, it was found that spiking circuit models in this regime can, despite disordered connectivity and asynchronous irregular activity, exhibit a locally stable dynamics that may be used for neural computation. The lack of existing mathematical tools has precluded analytical insight into this phase. Here we present analytical methods tailored to the granularity of spike-based interactions for analyzing attractor geometry in high-dimensional spiking dynamics. We apply them to reveal the properties of the complex geometry of trajectories of population spiking activity in a canonical model of locally stable spiking dynamics. We find that attractor basin boundaries are the preimages of spike-time collision events involving connected neurons. These spike-based instabilities control the divergence rate of neighboring basins and have no equivalent in rate-based models. They are located according to the disordered connectivity at a random subset of edges in a hypercube representation of the phase space. Iterating backward these edges using the stable dynamics induces a partition refinement on this space that converges to the attractor basins. We formulate a statistical theory of the locations of such events relative to attracting trajectories via a tractable representation of local trajectory ensembles. Averaging over the disorder, we derive the basin diameter distribution, whose characteristic scale emerges from the relative strengths of the stabilizing inhibitory coupling and destabilizing spike interactions. Our study provides an approach to analytically dissect how connectivity, coupling strength, and single-neuron dynamics shape the phase space geometry in the locally stable regime of spiking neural circuit dynamics.


[Acupoint embedding for female functional constipation:a randomized controlled trial].
To compare the effects between acupoint embedding and oral medication for female functional constipation. Fifty-six female patients were randomized into an embedding group and a medication group (1:1).There were 22 cases in the embedding group and 26 cases in the medication group with total 8 patients dropped out. The main embedding acupoints were Zhongwan (CV 12), bilateral Tianshu (ST 25) and Guanyuan (CV 4), combined with Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Zhigou (TE 6) and Shangjuxu (ST 37). It was given once a week. Oral lactulose was applied in the medication group, 3 times a day. The treatment cycle was 8 weeks. The primary outcome was the percentage of patients whose weekly average number of complete spontaneous bowel movement (CSBM) was increased ≥ 2 compared with baseline during the last 6 weeks in the treatment period. The secondary efficacy indices were compared before and after treatment as well as at follow-up at the 12th week, including the weekly average number and increased number of CSBM, the quality of life of patients with constipation (PAC-QOL), the Bristol stool character score, and the assessment of difficulty in defecation. The percentage of patients whose weekly average number of CSBMs were increased ≥ 2 in the embedding group significantly increased compared with that in the medication group (P<0.05). The weekly average number of CSBM in the two groups increased after treatment compared with those before treatment (both P<0.01); the score of Bristol stool character improved (both P<0.01); the scores of PAC-QOL and difficulty in defecation decreased (all P<0.01). The increasing time of weekly average CSBM in the embedding group was higher than that in the medication group (P<0.01); the score of PAC-QOL in the embedding group after treatment was better than that in the medication group (P<0.01); the Bristol stool character and difficulty degree in the embedding group after treatment were superior to those in the medication group (both P<0.05). The acupoint embedding significantly improve the CSMB, Bristol stool character, the difficulty of defecation, and the quality of life for female patients with functional constipation.


Anti-inflammatory activity of the aqueous extract from Rhizoma smilacis glabrae.
Our previous paper has reported that the aqueous extract from Rhizoma smilacis glabrae (RSG) (RSG ext) selectively inhibited the effector phase of delayed-type hypersensitivity (DTH) without suppressing humoral immune response. In the present study, a remarkable inhibitory activity was exhibited by the extract against both primary and secondary hind paw swelling of adjuvant arthritis in rats. RSG ext also significantly reduced the inflammatory edema induced by carrageenan in either naive or bilaterally adrenalectomized rats, suggesting the independence of the anti-inflammatory action on the function of pituitary-adrenal axis. The PGE2 content in the carrageenan-induced inflammatory tissue was also decreased remarkably by the extract. Furthermore, RSG ext showed a distinct inhibition on the formation of cotton-induced granuloma formation. However, as compared with a steroidal agent, prednisolone, the extract did not affect the vitamin C content in adrenal gland as well as the weights of some organs. These results suggest that RSG ext may act as a therapeutic agent of immunoinflammatory diseases through a selective suppression on the cellular immune response involved in inflammations as well as through a direct anti-inflammatory mechanism including inhibiting PGE2.


Oxidation as a crucial reaction for cholesterol to induce tissue degeneration: CD36 overexpression in human promonocytic cells treated with a biologically relevant oxysterol mixture.
Oxidative stress, inflammation and altered cholesterol metabolism and levels are among the pathogenetic mechanisms of cognitive impairment that may accompany aging. Within the research area of hypercholesterolemia and age-related disease processes, the molecular mechanisms of cholesterol interaction with the inflammatory cells of the macrophage lineage are yet to be elucidated. We thus investigated the effect of both non-oxidized and oxidized cholesterol on monocytic cell differentiation and foam cell formation, as it occurs within vascular lesions during progression of atherosclerosis. In vitro experiments performed on human U937 promonocytic cells showed that a biologically representative mixture of oxysterols markedly stimulated CD36 expression and synthesis. In contrast, non-oxidized cholesterol did not exert any effect on CD36 mRNA and protein levels. Furthermore, the oxysterol-induced up-regulation of CD36 appeared to be based on the subsequent activation of protein kinase Cdelta (PKCdelta), extracellular signal-regulated kinase 1/2 (ERK1/2) and peroxisome proliferator-activated receptor gamma (PPARgamma). Cells overexpressing CD36 were indeed able to actively take up oxidized low-density lipoproteins, and become foam cells. The essential role of ERK pathway and CD36 receptor in oxysterol-induced foam cell formation was proved by the prevention of the latter event when monocytic cells were incubated in the presence of MEK1/2 selective inhibitor or anti-CD36 specific antibody. These experimental findings point to cholesterol oxidation as an essential reaction for this sterol to exert cellular stress and tissue damage in age-related diseases in which inflammation represents a main driving force.


30-Day Potentially Avoidable Readmissions Due to Adverse Drug Events.
To analyze the patterns of potentially avoidable readmissions due to adverse drug events (ADEs) to identify the most appropriate risk reduction interventions. In this observational study, we analyzed a random sample of 534 potentially avoidable 30-day readmissions from 10,275 consecutive discharges from the medical department of an academic hospital. Readmissions due to ADEs were reviewed to identify the causative drugs and the severity and interventions to prevent them. Seventy cases (13.1%) of readmission were partially or predominantly due to ADEs, of which, 58 (82.9%) were serious ADEs. Overall, 65 (92.9%) of the ADEs have been confirmed to be preventable. Inappropriate prescribing was identified as the cause of ADE in 34 cases (48.6%) mainly involving diuretics, analgesics, or antithrombotics: misprescribing n = 19 (27.1%), underprescribing n = 8 (11.4%), and overprescribing n = 7 (10.0%). The remaining half of preventable ADEs (n = 36; 51.4%) were related to suboptimal patient monitoring/education, such as adherence issues (n = 6; 8.6%) or lack of monitoring (n = 31; 44.3%). In 64 cases (91.4%), the readmission could have been potentially prevented by better monitoring for drug efficacy/disease control, or for predictable side effect. Thirty-three (97.1%) of the 34 ADEs due to inappropriate prescribing could have also been prevented by better monitoring. Adverse drug events accounted for approximately 13% of 30-day preventable readmissions. A half were due to prescription errors involving mainly diuretics, analgesics, or antithrombotics, and the other half were due to suboptimal patient monitoring/education, most frequently with antineoplastics. Both these avoidable causes may represent opportunities to reduce the total drug-related adverse events.


Spectrum and risk factors of complications after gastric bypass.
To study the spectrum of and risk factors for complications after gastric bypass (GBP). Prospective cohort study. Academic tertiary referral center. All morbidly obese patients who underwent open or laparoscopic GBP between January 2003 and December 2006. Complications were stratified by grade: grade I, only bedside procedure; grade II, therapeutic intervention but without lasting disability; grade III, irreversible deficits; and grade IV, death. Data were analyzed using logistic regression to identify independent risk factors of complications after GBP. Predictors investigated were age, race, sex, marital and insurance status, body mass index, obesity-associated comorbidities, American Society of Anesthesiologists Physical Status Class, operating room time, open or laparoscopic approach, and surgeon experience. Of the 404 morbidly obese patients who underwent consecutive open (n = 72) or laparoscopic (n = 332) GBP, 74 (18.3%) experienced 107 complications. Grade I and II complications were more frequent after open GBP (grade I, 19.4% after open vs 3.9% after laparoscopic operations, P < .001; grade II, 20.8% after open vs 8.4% after laparoscopic operations, P < .001), and 55% were wound related. Grades III and IV complications occurred in only 4 patients (1%), and frequency was similar for open and laparoscopic cases. Three factors were independently predictive of complications: diabetes mellitus (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3; P = .02), early surgeon experience (OR, 2.5; 95% CI, 1.4-4.2; P = .001), and open approach (OR, 3.9; 95% CI, 2.1-7.3; P < .001). Complications occurred in 18.3% of patients, but 95% were treated without leading to lasting disability. Presence of diabetes, early surgeon experience, and an open approach are risk factors of complications.


[Prevalence of Moraxella catarrhalis colonization in asymptomatic carriers under 6 years of age].
To determine the prevalence of upper respiratory tract colonization by Moraxella catarrhalis in children under six years of age. A survey was conducted between January and December 1998 in Mexico City, among children aged 2 months to 5 years, selected through cluster sampling. Pharyngeal samples were taken for M. catarrhalis identification. The minimal inhibitory concentration to different antibiotics was obtained and beta-lactamases were determined by the iodometric test. Statistical analysis consisted of frequency distributions, odds ratios, 95% confidence intervals, and Mantel-Haenszel chi 2. Statistical significance was set at p < 0.05. After excluding 37 children, the study population was 604 children from Mexico City; M. catarrhalis was present in 130 pharyngeal specimens (22.9%). Most of the strains were positive for beta-lactamase production (75.4%). Eighty percent of the strains was resistant to penicillin and 70% to ampicillin and amoxicillin. None were resistant to cefotaxime, imipenem, meropenem and erythromycin. Prevalence of M. catarrhalis upper respiratory tract colonization is similar to that of other respiratory pathogens. These findings warrant future research on the role of M. catarrhalis as an etiologic agent in acute and chronic respiratory infections in Mexico.


Properties of polyethylene glycol 660 12-hydroxy stearate at a triglyceride/water interface.
This study proposed a method to understand the surfactant role in the first step of the formulation of a novel generation of lipidic nanocapsules. A dynamic rheological protocol was applied using a pendant drop tensiometer in order to determine the interfacial properties of the initial mixture implied in the first formulation step. The response, in terms of interfacial elasticities, described how this mixture led to monodisperse nanometer size range structures after a physico-chemical constraint.


Decrease in arterial pressure following heparin injection prior to cardiopulmonary bypass.
Evidence exists in the literature that heparin has vasodilating properties. We recorded arterial blood pressure changes that occur after administration of 300 units/kg of beef-lung heparin prior to cardiopulmonary bypass. In 37 out of 43 patients there was a significant decrease in arterial pressure following administration of beef-lung sodium heparin. Systolic blood pressure fell approximately 10 mmHg (1.3 kPa) and diastolic blood pressure fell about 5 mmHg (0.65 kPa). Heart rates remained unchanged. In 7 of the 43 patients in whom pulmonary artery catheters were placed, cardiac output was determined and systemic vascular resistance was calculated. On the basis of these calculations, it seems that a decrease in systemic vascular resistance is responsible for the decrease in arterial blood pressure noted following sodium heparin.


Thyroid hormones in extreme longevity.
The aim of the present review was to summarize knowledge about thyroid hormones (THs) and longevity. Longevity is a complex multifactorial phenomenon on which specific biological pathways, including hormonal networks involved in the regulation of homeostasis and survival, exert a strong impact. THs are the key responsible for growth, metabolism rate and energy expenditure, and help in maintaining cognition, bone and cardiovascular health. THs production and metabolism are fine tuned, and may help the organism to cope with a variety of environmental challenges. Experimental evidence suggests that hypothyroid state may favor longevity by reducing metabolism rate, oxidative stress and cell senescence. Data from human studies involving healthy subjects and centenarians seem to confirm this view, but THs changes observed in older patients affected by chronic diseases cannot be always interpreted as a protective adaptive mechanism aimed at reducing catabolism and prolonging survival. Medications, selected chronic diseases and multi-morbidity can interfere with thyroid function, and their impact is still to be elucidated.


Promotion of angiogenesis by sustained release of rhGM-CSF from heparinized collagen/chitosan scaffolds.
A novel dermal substitute of combining recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) with a porous heparinized collagen/chitosan scaffolds was developed, considering the inadequate angiogenesis during repair of full-thickness skin defects. The physicochemical properties of heparinized collagen/chitosan scaffolds were examined and in vitro release pattern of rhGM-CSF from scaffolds was measured by ELISA. Four groups of composite scaffolds (heparinized or unheparinized scaffolds loaded with or without rhGM-CSF) were fabricated for subcutaneous implantation in young adult male Sprague-Dawley (SD) rats. Tissue specimens were harvested at different time points after implantation for histopathological, immunohistochemical observation, and Western blotting analysis. The heparinized scaffolds (H(1)E) showed slower biodegradation and sustained release of rhGM-CSF in vitro, although no significantly different release pattern was observed between the H(1)E and unheparinized scaffolds (H(0)E). In vivo investigation revealed that the heparinized scaffolds loaded with rhGM-CSF (H(1)E/rhGM-CSF) had the best cellular adhesion and migration, new vessel formation, and highest expression of VEGF and TGF-β1, indicating promoted angiogenesis. This study demonstrated that composite dermal substitute of combining rhGM-CSF with a porous heparinized collagen/chitosan scaffolds could be a potential therapeutic agent for full-thickness skin defects because of its sustained delivery of rhGM-CSF.


The longitudinal relation between patterns of goal management and psychological health in people with arthritis: The need for adaptive flexibility.
Due to their disease, patients with polyarthritis face the task of reconciling their threatened personal goals with their capabilities. Previous cross-sectional research on patients with chronic disease related higher levels of goal management strategies to lower levels of distress and higher levels of well-being. This study was the first to focus longitudinally on goal management patterns that combined strategies originating from different goal management theories. Our first study objective was to identify patterns that consisted of various strategies of goal management among patients with polyarthritis. Subsequently, the cross-sectional and longitudinal relationships between these patterns and the psychological health of the patients were studied. A longitudinal questionnaire study with three measurements of goal management and psychological health was conducted among 331 patients with polyarthritis. Stability of goal management over time was analysed with ANOVAs. Patterns were identified using cluster analysis at baseline, based on the following strategies: Goal maintenance, goal adjustment, goal disengagement, and goal reengagement. Longitudinal relationships between the patterns and psychological health (specifically: Depression, anxiety, purpose in life, positive affect, and social participation) were analysed using a generalized estimating equations analysis. Three goal management patterns were found: 'Moderate engagement', 'Broad goal management repertoire', and 'Holding on'. Patients with the 'Broad goal management repertoire' pattern had the highest level of psychological health. The 'Holding on' pattern was identified as the most unfavourable in terms of psychological health. Over time, stable differences in levels of psychological health between the patterns were found. This study was the first to reveal patterns of several goal management strategies and their longitudinal relationship to psychological health. Psychosocial support for arthritis patients with lower psychological health should focus on helping patients to become familiar with a broad range of goal management strategies when dealing with threatened goals. What is already known on this subject? Polyarthritis is a collective term for a variety of disorders associated with autoimmune pathologies that may affect all aspects of a person's physical, psychological, and social functioning. Patients often experience difficulties in maintaining and achieving goals in several domains of life due to disease symptoms. The process of emotional adaptation to polyarthritis is characterized by searching equilibrium between desires and constraints and reacting constructive to stressors. Goal management strategies are ways to minimize the perceived disparity between the actual and the preferred situation with regard to personal goals and are applied both consciously and unconsciously. Cross-sectional, higher levels of goal management strategies have been related to lower levels of distress and higher levels of well-being both in patients with polyarthritis and in other patient groups. What does this study add? Contributes to our understanding of how combinations of goal management strategies relate to psychological health. Identifies patterns of goal management that are longitudinally related to psychological health. Provides clear guidance for improving psychological health of people with polyarthritis.


Thrombolytic therapy in acute ischaemic stroke: the jury needs more evidence.
Randomised controlled trials have shown that thrombolytic therapy for acute ischaemic stroke may reduce the rate of death and disability at three- or six-month follow-up, but may also increase the risk of haemorrhage and early death. Probable predictors of increased risk are severe neurological deficit and early signs of infarction on computed tomography, but these remain to be confirmed. More research is needed to determine which stroke patients will benefit from thrombolysis and the best regimen to use.


Using yellow rocket as a trap crop for diamondback moth (Lepidoptera: Plutellidae).
Yellow rocket, Barbarea vulgaris (R. Br.) variety arcuata, was evaluated as a trap crop for diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), in cabbage, Brassica oleracea L. variety capitata, in 2003 and 2004. In 2003, the numbers of P. xylostella larvae found in field plots of cabbage alone were 5.2-11.3 times higher than those on cabbage plants in plots that included cabbage and several rows of yellow rocket. In an outdoor experiment in screenhouses, P. xylostella oviposition on cabbage was compared among six treatments that varied in the percentage of yellow rocket in relation to cabbage (0, 4, 8, 16, 24, and 32% of the plants were yellow rocket). Results indicated that the percentage of eggs laid on cabbage decreased as the percentage of yellow rocket in the treatment increased, but this decrease was not significant beyond 20% of the plants being yellow rocket. In 2004, the numbers of P. xylostella larvae in field plots of cabbage alone were 1.6-2.4 and 1.7-2.8 times higher than numbers in treatments with 10 and 20% trap crop, respectively. Sticky trap and sweep net captures of P. xylostella adults indicated that within-field dispersal was reduced by the presence of yellow rocket and aggregation occurred around yellow rocket plants. Our study suggests that using yellow rocket as a trap crop may reduce P. xylostella infestations in cabbage fields, and this possibility is discussed in the context of general crop and insect pest management practices in crucifers.


[Contribution of teaching organizations to the process of partnership between faculty and clinical nurses].
The rapid changes that are occurring in the societies have affected daily life of organizations that also need to equip and adapt themselves to correspond to this need. The first initiatives were related to the search for transformations in the organization structure and in the applied management model in order to form work teams, exchange and share information. The main purpose of this study is to point out five disciplines on the learning organization proposed by SENGE (1990) as a reference that can contribute to the process of faculty and clinical nursing partnership. Authors believe that continuous development and learning of those disciplines by nurses can enable the consolidation of this partnership between academic and clinical nursing institutions.


Long-term changes of water quality in aquaculture-dominated lakes as revealed by sediment geochemical records in Lake Taibai (Eastern China).
The rapid development and exploitation of the Yangtze River basin in order to ensure human food security and increase living space in recent decades has resulted in significant potential for degradation of water quality in the river and in hundreds of lakes. Understanding how lake environments have evolved to their present state under a variety of external influences is crucial for evaluating their current status and anticipating future scenarios of environmental changes. However, the lakes along the middle reaches of the Yangtze River (MRY) are as yet little studied. Here, we described the long-term anthropogenic environmental transformations of a small lake (Lake Taibai) in the MRY area, based on a detailed quantitative geochemical analysis of the aliphatic hydrocarbons, nutrients (N and P), biogenic silica (BSi), and major and trace elements present in a dated sediment core retrieved from the lake. Our data revealed that levels of short-chain n-alkanes, αβ-hopanes and the trace elements arsenic (As) and cadmium (Cd) were all low for the entire record in sediments prior to ca. 1970, reflecting unpolluted natural state of the lake. Pronounced anthropogenic effects began to appear in sediments deposited in the subsequent years ca. 1970-1990, during which the levels of all these components were elevated, most likely driven by input of nitrogen (N) and phosphorus (P) containing chemical fertilizers, pesticides and diesel oil respectively. Since ca. 1990, changes of short-chain n-alkane levels in the sediment suggested the lake had undergone dramatic eutrophication in which existing anthropogenic stressors were exacerbated by technological advances that extended the use of chemical fertilizer into aquaculture. This pattern contrasted with an otherwise comparable lake in the lower Yangtze River basin, Lake Changdang, in which trace element and petroleum pollution were much more prominent due to dramatic urbanization and industrialization of the catchment.


Self-assembly of polyisoprenoyl gemcitabine conjugates: influence of supramolecular organization on their biological activity.
An amphiphilic prodrug of gemcitabine, a cytidine analogue used clinically against various tumors, had been previously synthesized by covalent coupling to squalene, a natural isoprenoid chain. The resulting bioconjugate self-assembled spontaneously in water as nanoparticles, displaying an impressive activity both in vitro and in vivo. The aim of the present study was to determine the influence of the length of the isoprene moiety on the structure of the nanoparticles, in an attempt to establish a relationship between the chemical structure of the prodrug, its supramolecular organization, and its pharmacological activity. Remarkably, gemcitabine-squalene and gemcitabine-5-isoprenes, which differ only in the position of two methyl groups on the hydrophobic chain, displayed different supramolecular organizations and different anticancer activities on some cell lines. This difference in activity was related to the ability of nanoparticles to be internalized by cells.


Paradox lost: genetic diversity and the success of aquatic invasions.
There is mounting evidence that reduced genetic diversity in invasive populations is not as commonplace as expected. Recent studies indicate that high propagule vectors, such as ballast water and shellfish transplantations, and multiple introductions contribute to the elimination of founder effects in the majority of successful aquatic invasions. Multiple introductions, in particular, can promote range expansion of introduced populations through both genetic and demographic mechanisms. Closely related to vectors and corridors of introduction, propagule pressure can play an important role in determining the genetic outcome of introduction events. Even low-diversity introductions have numerous means of avoiding the negative impact of diversity loss. The interaction of high propagule vectors and multiple introductions reveal important patterns associated with invasion success and deserve closer scrutiny.


Mechanism of Aloe Vera extract protection against UVA: shelter of lysosomal membrane avoids photodamage.
The premature aging (photoaging) of skin characterized by wrinkles, a leathery texture and mottled pigmentation is a well-documented consequence of exposure to sunlight. UVA is an important risk factor for human cancer also associated with induction of inflammation, immunosuppression, photoaging and melanogenesis. Although herbal compounds are commonly used as photoprotectants against the harmful effects of UVA, the mechanisms involved in the photodamage are not precisely known. In this study, we investigated the effects of Aloe Vera (Aloe barbadensis mil) on the protection against UVA-modulated cell killing of HaCaT keratinocytes. Aloe Vera exhibited the remarkable ability of reducing both in vitro and in vivo photodamage, even though it does not have anti-radical properties. Interestingly, the protection conferred by Aloe Vera was associated with the maintenance of membrane integrity in both mimetic membranes and intracellular organelles. The increased lysosomal stability led to a decrease in lipofuscinogenesis and cell death. This study explains why Aloe Vera extracts offer protection against photodamage at a cellular level in both the UV and visible spectra, leading to its beneficial use as a supplement in protective dermatological formulations.


Target-enrichment strategies for next-generation sequencing.
We have not yet reached a point at which routine sequencing of large numbers of whole eukaryotic genomes is feasible, and so it is often necessary to select genomic regions of interest and to enrich these regions before sequencing. There are several enrichment approaches, each with unique advantages and disadvantages. Here we describe our experiences with the leading target-enrichment technologies, the optimizations that we have performed and typical results that can be obtained using each. We also provide detailed protocols for each technology so that end users can find the best compromise between sensitivity, specificity and uniformity for their particular project.


Clergy health day: ministering to the ministers.
Mercy Hospital, Port Huron, MI, held a Clergy Health Day for ministers from the community. The program, which included components on physical, mental/emotional, and spiritual health of the clergy, was judged helpful by both participants and those persons in the hospital responsible for the program.


Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.
Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.


Complete reversal of tumoral calcinosis after subtotal parathyroidectomy in a hemodialysis patient.
Tumoral calcinosis is a rare complication of chronic hemodialysis whose mechanism is incompletely understood. The treatment is challenging and should target the main precipitating factors, most notably secondary hyperparathyroidism and calcium-phosphate (Ca x P) product elevation. In this 41-year-old patient, tumoral calcinosis developed in the right hip and subacromial bursa of the right shoulder after 3 years of chronic hemodialysis. Laboratory tests showed hyperparathyroidism with Ca x P elevation. Subtotal parathyroidectomy was performed. Eight months later, there was no evidence of tumoral calcinosis at either of the previously affected sites. The effectiveness of parathyroidectomy in our patient underlies the key role played by secondary hyperparathyroidism in the pathogenesis of tumoral calcinosis complicating hemodialysis.


Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): occurrence in an allogeneic donor of peripheral blood stem cells.
Granulocyte colony-stimulating factor (G-CSF) has been used to improve granulocyte count in chronic neutropenia and myelodysplasia, to minimize the incidence and duration of neutropenia during conventional chemotherapy, and to mobilize peripheral blood stem cells prior to leukapheresis for use in autologous and allogeneic marrow transplantation. The most common toxicity is bone pain, and other reactions such as inflammation at the site of injection have also occurred. In patients with chronic neutropenia, splenomegaly has been described with long-term use, and extramedullary hematopoiesis has also been reported. However, thus far, no life-threatening sequelae of these effects are found in the literature. We now describe a case of spontaneous splenic rupture four days following a six-day course of G-CSF therapy in an allogeneic donor of peripheral blood stem cells.


PDE5 inhibitors in the treatment of LUTS.
Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a negative impact on patients' quality of life. The co-prescription of two active agents for these conditions will improve each condition and the addition of one drug to the other may potentiate the primary response of the first treatment and thereby improve the QoL of patients. Several epidemiological studies have indicated that the association between LUTS and ED is more than a co-incidence of age, with a possible cause and effect relationship. LUTS is more common in men with ED and there is a strong relationship between the severity of LUTS and the degree of erectile difficulty. Four pathophysiologies have been suggested to explain the relationship between LUTS and ED. There is a complex interaction between these mechanisms and there may be additional processes involved. These are: (1) alteration in nitric oxide levels; (2) autonomic hyperactivity; (3) changes in the Rho-kinase/endothelin pathway; and (4) pelvic vasculature atherosclerosis. Studies of all three easily available PDE-5 inhibitors have shown improvements in both LUTS and ED in men with significant problems in both areas without any substantial increase in side effect profile. Studies have also shown that the greatest improvements occurred with the combination of an alpha blocker and PDE-5 inhibitor when compared with either drug alone. Whilst significant improvements were seen in LUTS symptom scores, there was no significant improvement in flow rates with PDE-5 inhibitors when compared with placebo. High quality basic science studies of PDE-5 inhibitors on bladder muscle and alpha blocker agents on penile cavernosal tissue have provided several explanations for their modes of action. Even so, the mechanism of action of PDE-5 inhibitors in LUTS remains far from certain. More well-designed, placebo-controlled studies are needed to confirm the impact of these drugs, alone or in combination, on both ED and LUTS. However combination therapy appears appropriate for patients with both LUTS and ED. At present though, we should not routinely offer a combination of PDE-5 inhibitors and alpha blocker for the treatment of LUTS alone.


Peanut shell colitis.
A 40-year-old physician experienced abdominal pain, loose stools, hematochezia, and anal discomfort with defecation associated with the daily consumption of 15 to 30 whole peanuts, including the shells. Thorough evaluation revealed only nonspecific colitis of the distal portion of the sigmoid colon and inflamed hemorrhoids. Discontinuation of whole peanut ingestion was associated with symptomatic, endoscopic, and histological resolution. In this patient, undigested peanut shells seem to have caused a nonspecific colitis, perhaps as the result of mechanical abrasion of the colonic mucosa.


Incidence, Etiology and Outcome of Ventilator-Associated Pneumonia in Patients with Percutaneous Tracheotomy
Although the incidence of ventilator-associated pneumonia (VAP) is very high, there are still many uncertainties about clinical course of VAP among tracheotomized patients. The goal of the present study was to determine the impact of tracheotomy on VAP incidence and etiology, as well as outcome of VAP patients with tracheotomy. The study was conducted in a 15-bed Surgical and Neurosurgical Intensive Care Unit (ICU), Sestre milosrdnice University Hospital Center in Zagreb, Croatia. The study included all patients undergoing only percutaneous tracheotomy during the study period. According to our data, the incidence of VAP among percutaneous tracheotomized patients was 42%, not considering the time between tracheotomy and VAP onset. However, when only patients developing VAP after tracheotomy were taken into account, the incidence of VAP among tracheotomized patients dropped to 8% only. The most commonly isolated bacterium was Staphylococcus aureus, accounting for 17 (37%) isolates, followed by Haemophilus influenzae, accounting for another 10 (22%) isolates. The development of VAP among percutaneously tracheotomized patients was associated with longer total ICU stay (regardless of whether VAP developed before or after tracheotomy), while total duration of mechanical ventilation and mortality rate remained unaffected.


Long-distance inter-hydrogen bond coupling effects in the polarized IR spectra of succinic acid crystals.
The spectral properties of four different crystalline succinic acid (HOOC-(CH2)2-COOH) (SAC) isotopomer systems, h6, d2, d4 and d6, were examined by means of the IR spectroscopy in polarized light aided by numerical simulations of the νO-H and νO-D band contour shapes on utilizing the "strong-coupling" model. The abnormal IR spectral properties of SAC crystals in relation to the corresponding properties of glutaric, pimelic and adipic acid crystals were ascribed to the hyperconjugation electronic effects in the acid associated molecules. A vibronic coupling mechanism involving the proton stretching vibrations in the (COOH)2 cycles and the electronic motions in the molecular skeletons, the isotopic "H/D self-organization" mechanisms and a long-distance vibrational exciton coupling between the adjacent (COOH)2 cycles in the molecular chains are mainly responsible for the generation of the temperature effects in the crystalline IR spectra.


Effects of continuous passive motion on reversing the adapted spinal circuit in humans with chronic spinal cord injury.
To investigate the possibility of restoring the adapted spinal circuit after spinal cord injury (SCI) by means of long-term continuous passive motion (CPM) of the ankle joint. Randomized controlled trial with repeated measures. Research laboratory in a general hospital. Individuals with motor complete SCI (N=14) were recruited from a community. CPM of the ankle joint for 1 hour a day, 5 days a week for 4 weeks. Modified Ashworth Scale (MAS) scores for evaluation of spasticity and postactivation depression (PAD) were documented prior to and after intervention. MAS scores improved after 4 weeks of CPM intervention, indicating a reduction in spasticity of the ankle joint. PAD was restored after 4 weeks of training. Passive motion of the ankle joint alone was sufficient in reversing the adapted spinal circuit, and therefore indicates that spasticity after SCI could possibly be managed by CPM intervention. The results of this study support the use of the passive mode of robot-assisted therapy for humans with complete SCI who cannot exercise actively.


Shift from depolarizing to hyperpolarizing glycine action occurs at different perinatal ages in superior olivary complex nuclei.
The inhibitory transmitters glycine and GABA undergo a developmental shift from depolarizing to hyperpolarizing action (D/H-shift). To analyse this shift in functionally related nuclei of the rat superior olivary complex (SOC), we employed voltage-sensitive dye recordings in auditory brainstem slices. Complementarily, we analysed single neurons in gramicidin perforated-patch recordings. Our results show a differential timing of the D/H-shift in the four SOC nuclei analysed. In the medial superior olive (MSO), the shift occurred at postnatal day (P) 5-9. In the superior paraolivary nucleus (SPN), it occurred between embryonic day (E) 18 and P1. No D/H-shift was observed in the medial nucleus of the trapezoid body (MNTB) until P10. This is in line with the finding that most of the patched MNTB neurons displayed glycine-induced depolarizations between P0-9. While no regional differences regarding the D/H-shift were found within the MSO, SPN, and MNTB, we observed such differences in the lateral superior olive (LSO). All LSO regions showed a D/H-shift at P4-5. However, in the high-frequency regions, hyperpolarizations were large already at P6, yet amplitudes of this size were not present until P8 in the low-frequency regions, suggesting a delayed development in the latter regions. Our physiological results demonstrate that D/H-shifts in SOC nuclei are staggered in time and occur over a period of almost two weeks. Membrane-associated immunoreactivity of the Cl- outward transporter KCC2 was found in every SOC nucleus already at times when glycine was still depolarizing. This implies that the mere presence of KCC2 does not correlate with functional Cl- outward transport.


Dosing practices of physicians for anticoagulation with warfarin during inpatient rehabilitation.
To determine the percentage of international normalized ratios (INRs) maintained within the therapeutic range for patients receiving chronic anticoagulation treatment with warfarin during inpatient rehabilitation. A consecutive, 4-month, retrospective chart review of all patients receiving oral anticoagulation treatment was conducted in a large academic rehabilitation center. The percentage of INRs within and out of the therapeutic range, frequency of blood samples, length of therapy, and warfarin dose prescribed by physicians were calculated. A total of 181 patients receiving chronic anticoagulation treatment were identified. A total of 3,709 blood samples were analyzed. In 74 patients, the primary physician recommended a therapeutic range (Group 1). In the remaining 107 patients, no therapeutic range was specified, and a target INR range of 2.0-3.0 was assumed (Group 2). In Group 1, the INRs were in the recommended range in 38.2% of all blood samples. In Group 2, 37.6% of all blood drawn was within an INR range of 2.0-3.0. Statistical analysis showed that no better accuracy was obtained when the INR range was predefined by a physician (Group 1) or assumed to be in the 2.0-3.0 range (Group 2; P = 0.839). Despite frequent physician monitoring, this study demonstrates the difficulty in maintaining INRs within therapeutic ranges for patients receiving oral anticoagulation. An overall tendency for underdosing is observed. Improvement is necessary, given the high morbidity and mortality associated with insufficient anticoagulation in rehabilitation inpatients.


Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants.
Single nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown. To study GC genotype-related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants. In this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined. 25OHD measured in cord blood at birth and at 12 and 24 months during intervention. A total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention. In infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.


[Causes and prevention of sudden arrest of circulation in surgical treatment of rheumatic mitral defect].
Analysis of case histories of patients operated on in 1965-1995 is presented. Ventricular fibrillation or asystole was observed in 3.34ë 1.1% of 480 patients subjected to closed mitral commissurotomy and in 6.25ë 1.1% of 98 ones subjected to cardiopulmonary bypass surgery for replacing mitral valves. The incidence of complications directly correlated with the stage of mitral valvular disease and reoperations and inversely with monitoring of hemodynamics, blood gases, etc. Examination of the myocardium before the development of ventricular fibrillation or asystole most often revealed 1) myocardial ischemia of different degree and localization; 2) changed stimulation and conduction of the myocardium; 3) total myocardial hypoxia; 4) electric current action in cases with diathermal coagulation of vessels and/or poor grounding of devices; 5) injection of potent drugs, etc. Electromechanical dissociation of ventricular myocardium was observed in 6 patients. Sudden heart arrest was not caused by blocking of the bloodflow in any of the cases. Thus, some signs can be regarded as predicting the risk of sudden arrest of circulation. Monitoring of the functions of the body helps timely detect these signs. If ventricular fibrillation developed, defibrillation was carried out immediately.


Lack of association between mortality and timing of surgical fixation in elderly patients with hip fracture: results of a retrospective population-based cohort study.
Conventional wisdom suggests high-quality care for most patients with hip fractures is surgical fixation within 24 hours to reduce mortality and complications, although there is little evidence to support this standard. We sought to determine the relationship between timing of hip fracture surgery and early mortality. This was a retrospective population-based cohort study of 3981 patients with hip fractures>60 years of age that were admitted to hospitals in one Canadian health region from 1994-2000. We collected sociodemographic, prefracture comorbidity, and postoperative complication data. Timing of surgery was classified as within 24 hours ("early surgery," the referent group for all analyses), 24-48 hours, and beyond 48 hours. Main outcome was in-hospital mortality. We used multivariable logistic regression methods, including adjustments with propensity scores and a validated hip fracture-specific mortality index, to determine the independent association between early versus later surgery and mortality. Median age of patients was 82 years, 71% were women, and 26% had >4 prefracture comorbidities. Unadjusted in-hospital mortality was 6%; it was 5% for those who had surgery within 24 hours or from 24 to 48 hours, 10% for surgery beyond 48 hours, and 21% for patients that did not have surgery. Compared with those who had surgery within 24 hours, there was no independent association between timing of surgery and in-hospital mortality (24-48 hours, adjusted odds ratio 0.89, 95% confidence interval 0.62-1.30, P=0.55; beyond 48 hours 1.30, 95% confidence interval 0.86-2.00], P=0.21). The timing of surgical fixation of hip fracture was not associated with early mortality in carefully adjusted analyses, and the use of "surgery within 24 hours" as a measure of high quality care may be inappropriate.


Synergistic effect of interleukin 1 and soluble CD23 on the growth of human CD4+ bone marrow-derived T cells.
Low-affinity Fc epsilon receptor (Fc epsilon RII/CD23) is expressed by various human cells and known to be cleaved into soluble fragments (sCD23). Several biological activities were ascribed to these molecules. In this study, we have assessed the effect of recombinant 25-kDa sCD23 (rsCD23) on human bone marrow-derived T cells. Our results show that rsCD23 in synergy with recombinant interleukin 1 enhances mitogenic responsiveness of CD4+ T cells but does not affect CD8+ cell growth. Furthermore, rsCD23 synergizes autologous marrow cells in enhancement of CD4+ cell growth while CD23 monoclonal antibodies decrease accessory cell effect. Together, these data confirm cytokine-like activity of sCD23 on human T cell lineage.


The characterisation of thawed semen, and the timing and route of insemination associated with conception in the human.
The temporal and qualitative aspects of the conceptual process of a small number of pregnancies achieved by donor insemination have been analysed to understand the semen values required and the optimal insemination timing and route.


Effects of epilepsy on women's reproductive health.
Reproductive dysfunctions are common and wide-ranging in women with epilepsy. Menstrual cycle disruption, anovulatory cycles, disturbances in hypothalamic and/or pituitary hormones, and disturbances in gonadal steroids are more common among women with epilepsy. Sexual dysfunction can present as either disorders of desire or physiologic arousal, but the most common dysfunction appears to be an inadequate initial physiologic arousal response. Reproductive dysfunctions may be due to psychologic, pharmacologic, or physiologic factors. Physicians should routinely question all women with epilepsy regarding their reproductive and sexual health. A full history, a complete physical, and laboratory evaluations with endocrinologic work-up should be performed in any woman who reports a reproductive dysfunction. Treatment and/or referral to a gynecologist or endocrinologist should be initiated as appropriate.


Neuropraxia of the cutaneous nerve of the cervical plexus after shoulder arthroscopy.
This article presents uncommon cases of neuropraxia of the lesser occipital nerve and the greater auricular nerve after arthroscopic surgery of the shoulder in the beach-chair position under general anesthesia. The lesser occipital nerve and the greater auricular nerve are superficial ascending branches of the cervical plexus. These 2 superficial nerves may be easily vulnerable because of their superficial anatomic locations. We assumed that the severity of the neuropraxia of superficial branches of the cervical plexus was related to the degree of rotation and deviation of the head and neck, the duration of the procedure, and compression by head strap and elastic bandage used for fixing the head to the rectangular-shaped headrest of the beach-chair device. We recommend that during surgery in the beach-chair position, the auricle be protected and covered with cotton and gauze to avoid direct compression and the position of the head and neck be checked and corrected frequently. We hope for a new design of the headrest of the beach-chair device to prevent neuropraxia and to attach the head firmly and safely.


Propranolol reduces emotional distraction in working memory: a partial mediating role of propranolol-induced cortisol increases?
Noradrenalin modulates prefrontal function, such as working memory (WM), and is associated with enhanced distractibility, and enhanced memory for emotional events and stimuli. The beta-blocker propranolol has been shown to reduce memory for emotional stimuli. Herein we describe investigations aimed at assessing whether the administration of propranolol would reduce the interference by emotional distractions during WM performance. In a between-subjects design, 48 young, healthy men received 80 mg propranolol (n=25) or placebo (n=23), before performing an "emotional Sternberg task" with neutral and negatively arousing distracters. Compared to placebo, propranolol impaired WM at low load, however, it also reduced the interference by emotional distracters at high load. Furthermore, an explorative moderated-mediation analysis indicated that the observed propranolol effects on emotional distraction were partially mediated by cortisol. In future non-clinical and clinical memory studies using propranolol administration, cortisol elevations should be monitored to further investigate the potential mediating role of cortisol.


Helminth infection alters mood and short-term memory as well as levels of neurotransmitters and cytokines in the mouse hippocampus.
Helminthic infections are important causes of morbidity and mortality in many developing countries, where children bear the greatest health burden. The ability of parasites to cause behavioral changes in the host has been observed in a variety of host-parasite systems, including the Taenia crassiceps-mouse model. In murine cysticercosis, mice exhibit a disruption in the sexual, aggressive and avoidance predator behaviors. The present study was conducted to characterize short-term memory and depression-like behavior, as well as levels of neurotransmitters and cytokines in the hippocampus of cysticercotic male and female mice. Cytokines were detected by RT-PCR and neurotransmitters were quantified by HPLC. Chronic cysticercosis infection induced a decrease in short-term memory in both male and female mice, having a more pronounced effect in females. Infected females showed a significant increase in forced swimming tests with a decrease in immobility. In contrast, male mice showed an increment in total activity and ambulation tests. Serotonin levels decreased by 30% in the hippocampus of infected females whereas noradrenaline levels significantly increased in infected males. The hippocampal expression of IL-4 increased in infected female mice, but decreased in infected male mice. Our study suggests that intraperitoneal chronic infection with cysticerci in mice leads to persistent deficits in tasks dependent on the animal's hippocampal function. Our findings are a first approach to elucidating the role of the neuroimmune network in controlling short-term memory and mood in T. crassiceps-infected mice.


RhoA regulation of NF-kappaB activation is mediated by COX-2-dependent feedback inhibition of IKK in kidney epithelial cells.
Numerous studies have demonstrated a central role of renal tubular epithelial cells in the etiology of kidney injury and disease through the elaboration of inflammatory mediators. However, little is known about the cellular signaling mechanisms involved in this process. In this study we employed normal rat kidney epithelial (NRK52E) cells to identify a novel LPS-induced signaling pathway in which RhoA-mediated AP-1 activity promotes expression of cyclooxygenase-2 (COX-2) with consequent feedback inhibition of NF-kappaB activation through IKKbeta. Inhibition of RhoA signaling using either the RhoA kinase inhibitor Y-27632 or a dominant negative mutant of RhoA (RhoA-DN) dramatically extended the duration of p65-DNA binding, IkappaBalpha phosphorylation, and IKKbeta activity following LPS treatment. Prolongation of events associated with NF-kappaB activation was also observed in cells pretreated and/or cotransfected with the JNK inhibitor SP600125 or deletion mutants of MEKK1 (MEKK1-KD) or Jun (Jun-DN). Conversely, constitutive expression of RhoA prevented NF-kappaB activation by LPS, and this effect was reversed by cotransfection with MEKK1-KD. In addition, we found that the RhoA/AP-1 signaling axis plays a necessary role in COX-2 expression by LPS and that this effect is independent of NF-kappaB activation. Moreover, inhibition of COX-2 activity results in persistent p65-DNA binding, IkappaBalpha phosphorylation, and IKKbeta activity, similar to that observed after prevention of RhoA/AP-1 axis signaling. These findings suggest that COX-2 links the RhoA/AP-1 signaling cascade to NF-kappaB activation, thereby defining a novel integrated model for regulation of the inflammatory response of kidney epithelial cells to LPS and potentially other external stimuli.


Can physical activity prevent physical and cognitive decline in postmenopausal women? A systematic review of the literature.
Participation in regular physical activity is among the most promising and cost effective strategies to reduce physical and cognitive decline and premature death. However, confusion remains about the amount, frequency, and duration of physical activity that is likely to provide maximum benefit as well as the way in which interventions should be delivered. This paper aimed to review research on the impact of leisure-time and general physical activity levels on physical and cognitive decline in postmenopausal women. In a systematic review of the literature, empirical literature from 2009 to 2013 is reviewed to explore the potential impact of either commencing or sustaining physical activity on older women's health. All studies found that physical activity was associated with lower rates of cognitive and physical decline and a significant reduction in all-cause mortality. In this review we found that exercise interventions (or lifestyle activities) that improved cardiorespiratory exercise capacity showed the most positive impact on physical health. Findings suggest that programs should facilitate and support women to participate in regular exercise by embedding physical activity programs in public health initiatives, by developing home-based exercise programs that require few resources and by creating interventions that can incorporate physical activity within a healthy lifestyle. The review also suggests that clinicians should consider prescribing exercise in a tailored manner for older women to ensure that it is of a high enough intensity to obtain the positive sustained effects of exercise.


Elucidating early mechanisms of developmental psychopathology: the case of prenatal smoking and disruptive behavior.
There is a robust association between prenatal smoking and disruptive behavior disorders, but little is known about the emergence of such behaviors in early development. The association of prenatal smoking and hypothesized behavioral precursors to disruptive behavior in toddlers (N=93) was tested. Exposed toddlers demonstrated atypical behavioral patterns, including (1) escalating externalizing problems from 18 to 24 months and (2) observed difficulty modulating behavior in response to social cues. Specification of exposure-related behaviors is a first step toward generating testable hypotheses about putative mechanisms of effect. While it remains unclear whether prenatal exposure plays an etiologic role in the emergence of disruptive behavior, atypical exposure-related behavioral patterns are evident in the first years of life and demonstrate developmental coherence.


Depression Treatment by Bedford East Community Mental Health Team an Audit to assess how many patients in a Bedfordshire Community Mental Health Team might safely be transferred to Primary Care.
Recently there has been pressure on Secondary Psychiatric services to discharge patients back into Primary care. This project is to show what depression treatments are used by Bedford East Community Mental Health Team (BECMHT) and therefore identify whether some of these patients could be appropriately managed in Primary care. We identified, using an anonymised database, patients being treated with different anti-depressant regimens in BECMHT. We compared these treatments with the steps described in NICE Guidelines, and other evidence based treatment modalities which we found on literature search. Based on this data, we attempted to predict which patients it might be safe to discharge to primary care for ongoing treatment. Many different combinations of medications were found. Many patients had other intercurrent mental health diagnoses. There are many possible evidence based treatments for depression which can be employed once those listed by NICE are exhausted. We review all of these. Some patients are, accordingly, on combinations of medication as augmentation strategies.It is responsible to only discharge patients into Primary care when their symptoms are controlled. We identified groups of patients who might be transferred back to primary care for maintenance treatment, provided that shared care protocols are in Place, and there is easy access to secondary care services should the need arise.


Risperidone (depot) for schizophrenia.
Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation. To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia. We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies. Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapineRelapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychoticsOutcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence). Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.


Successful outcomes for the ventilator-dependent patient.
The challenges of working with the ongoing ventilator-dependent population are many. All have survived some element of critical illness to arrive at the point of step-down care. The team challenge is to craft a plan of care unique to their needs. Working through patients' pain of loss of control, the team helps patients and their families accept what is ahead--finding meaning in the smallest accomplishments and making peace. If the patient is to return home, achieving quality of life for whatever time is left is important. The ventilator dependent individual is the outlier, the variance, and the exception. Such is the challenge for the team caring for the ventilator-dependent population. It is our opportunity to make a difference.


[Transbronchial cryobiopsy in diffuse interstitial lung diseases].
In the diagnostic approach to interstitial lung disease (ILD), the use of transbronchial cryobiopsy (TBC) may offer an alternative to surgical lung biopsy (SLB). We report the diagnostic effectiveness and the safety of TBC in ILD based on the preliminary experience in two French university centers. Twenty four patients underwent TBC for the diagnosis of ILD in the operating room between 2014 and 2017. All the histological diagnoses obtained were then reviewed and validated during multidisciplinary discussions (MDD). Patients had an average of 3 TBC.TBC samples were analyzable in 22/24 (91.7%) patients. In these, samples allowed a histological diagnosis to be made in 14/22 (63.6%) patients and a diagnosis with certainty in 13/22 (59%) after MDD. The overall diagnostic yield from TBC was 13/24 (54.2%). Nine (37.5%) patients had a pneumothorax. Five (20.8%) patients had a bleeding. There were no deaths. Taking into account a possible initial learning curve and considering only the 15 patients who had their TBC after 2015, we note that a diagnosis could be made after MDD for 12 of them, that is, 80%. A prospective randomized study is needed to evaluate the technique in France in order to specify its diagnostic performance and its safety profile in comparison to SLB.


Beneficial autoimmunity to proinflammatory mediators restrains the consequences of self-destructive immunity.
Therapies that neutralize the function of TNF-alpha suppress rheumatoid arthritis (RA) but not osteoarthritis (OA). We show that patients suffering from RA but not OA have significant levels of autoantibodies directed to TNF-alpha. Thus, the immune system can selectively generate autoimmunity to proinflammatory mediators when such a response is beneficial for the host. A well-defined model of RA was used to elaborate the contribution of beneficial autoimmunity to the regulation of disease. We show that during the disease autoantibody production is elicited against few inflammatory, but not regulatory, mediators. Selective amplification of these beneficial antibodies by targeted DNA vaccines provided protective immunity. Epitope mapping revealed that anti-TNF-alpha immunity is highly restricted and excretes no crossreactivity to other known gene products. Its selective exclusion substantially exacerbated the disease. Administration of anti-TNF-alpha antibodies could then override this aggravation. This substantiates the significance of beneficial autoimmunity in restraining self-destructive immunity.


Baclofen in the treatment of intractable hiccups.
Availability of a large number of drugs/remedies for the management of hiccups suggests that all the available drugs are not effective in all the patients. Baclofen was successful in relieving the intractable hiccups where all other known drugs of hiccup were unable to provide relief.


Regiodivergent synthesis of functionalized indene derivatives via Pt-catalyzed Rautenstrauch reaction of propargyl carbonates.
A regiodivergent synthesis of functionalized indene derivatives from a Pt-catalyzed Rautenstrauch reaction of propargyl carbonate is described. A one-pot Rautenstrauch/Tsuji-Trost reaction delivering 2-indanones was realized efficiently using this methodology.


Urodynamics and lower urinary tract symptoms.
In a retrospective study four questions concerning urodynamics and lower urinary tract symptoms (LUTS) were answered: Do obstructive symptoms correlate with bladder outlet obstruction? Does the symptom urgency correlate with bladder instability? What is the value of a free uroflow study in men with LUTS? Should all men with LUTS have pressure-flow studies before surgery? The authors state that urodynamic investigation is very important before surgery in patients with LUTS.