Major depressive disorder and generalized anxiety disorder and response to treatment in hepatitis C patients in Egypt.
The aim of the study was to estimate the prevalence and associated correlates of major depressive disorder and generalized anxiety disorder in hepatitis C virus patients before and after treatment and to investigate the relationship between major depressive disorder and generalized anxiety disorder and treatment response. A total of 116 consecutive hepatitis C virus patients from hepatitis C virus treatment center in Zagazig city, Egypt, were included in the study and divided into treated group (N = 58) and untreated group (N = 58). All hepatitis C virus patients were screened for major depressive disorder and generalized anxiety disorder using hospital anxiety and depression scale, and those who screened positive were interviewed to confirm the diagnosis of major depressive disorder and generalized anxiety disorder using DSM-IV-TR diagnostic criteria. These measures were done at baseline and after 12 weeks of treatment or observation. At baseline, 3.5% and 12.1% of hepatitis C virus patients (treated group) had major depressive disorder and generalized anxiety disorder, respectively. After 12 weeks of treatment 37.9% of hepatitis C virus patients (treated group) had major depressive disorder and 46.6% had generalized anxiety disorder. There was a significant statistical difference between hospital anxiety and depression scale scores for depression (3.3 ± 2.3 vs. 6.4 ± 3.2, t = 9.6, p = 0.001) and for anxiety (4.6 ± 2.4 vs. 7.3 ± 3.0, t = 10.2, p = 0.001) before and after treatment. There was also significant statistical difference between treated group and untreated group regarding hospital anxiety and depression scale scores after treatment and observation (depression, treated group 6.4 ± 3.2 vs. untreated group 4.0 ± 2.4, t = 3.7, p = 0.001; anxiety, treated group 7.3 ± 3.0 vs. untreated group 4.5 ± 2.3, t = 4.4, p = 0.001). There was no association between major depressive disorder and generalized anxiety disorder and treatment response. Major depressive disorder and generalized anxiety disorder are common in hepatitis C virus patients after treatment with interferon and ribavirin and were not related to treatment response.


Reaction kinetics of diffusing particles injected into a reactive substrate.
We analyze the kinetics of trapping (A+B-->B) and annihilation (A+B-->0) processes on a one-dimensional substrate with homogeneous distribution of immobile B particles while the A particles are supplied by a localized source. For the imperfect reaction case, we analyze both problems by means of a stochastic model and compare the results with numerical simulations. In addition, we present the exact analytical results of the stochastic model for the case of perfect trapping.


Branch retinal vein occlusion associated with the 20210 G-to-A prothrombin variant.
To describe a case of branch retinal vein occlusion (BRVO) in a patient who tested positive for the 20210 A allele of the prothrombin (PT) gene. A 48-year-old man had visual loss in the right eye secondary to BRVO confirmed by ophthalmoscopy and fluorescein angiography. His medical history was not remarkable for common risk factors for retinal occlusive diseases. Laboratory tests for hypercoagulability were positive for PT 20210 A variant. The patient's family tested negative for the PT variant. Laboratory tests for coagulopathy, including the PT 20210 A variant, should be added to the examination of patients with central or BRVO, especially if most common risk factors for thrombosis have been excluded.


The role of the cylooxygenase pathway in nociception and pain.
Cycloxygenase (COX) pathways have long been targeted for the treatment of inflammatory pain, initially through the use of NSAIDs. With the demonstration of two major COX isoforms, COX-1 and COX-2, involved in the production of prostanoids, but with different distribution and regulation, selective COX-2 inhibitors have been developed. This review covers factors influencing COX enzyme activity, the role of their products in the development and maintenance of pain and discusses recent safety concerns of COX-2 inhibitors.


[Preoperative abstinence from smoking. An outdated dogma in anaesthesia?].
For decades it has been assumed, that smoking within 6 hours of anesthesia and surgery raises the incidence of perioperative cardiopulmonary complications (PPC) including aspiration. Therefore, every patient is advised to stop smoking at the day before surgery, and not to smoke at all at the day of surgery. If the patient does not follow this advice, this will result in a postponement of anesthesia and surgery. The present article aims at re-investigating the scientific basis of this dogma in anesthesia, which virtually forbids smoking at short-term prior to surgery. The influence of short-term (6 h) abstinence from smoking on the perioperative pulmonary morbidity has not been systematically investigated. Interestingly, giving up smoking less than two months prior to surgery does not significantly decrease, but rather may increase the incidence of PPC. With respect to the risk of aspiration, smoking does not increase either the volume or the acidity of gastric juices. A short-lived reduction in the tone of the lower esophageal sphincter is reversible within minutes after termination of smoking. While the emptying of liquid gastric juices is not influenced by smoking, there is a certain delay in the propulgation of solid food. This effect, however, is probably of no clinical relevance in patients, who had their last solid meal the evening before surgery. Hence, we conclude that the anesthesia dogma, which rules out smoking shortly prior to anesthesia, cannot be based on an otherwise increased incidence of pulmonary aspiration or other pulmonary morbidity. However, acute smoking (probably by an increase in COHb) may increase the incidence of myocardial ischemia during exercise and anesthesia. With reference to this possible cardiac complication it still seems reasonable to discourage smoking at least 12 to 48 hours prior to surgery in patients with elevated cardiac risk.


Analysing Cytochrome c Aggregation and Fibrillation upon Interaction with Acetonitrile: an in Vitro Study.
The propensity of native state to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. Our study was focused at analyzing the aggregation and fibrillation tendency of cytochrome c in presence of an organic solvent i.e. acetonitrile. In vitro analysis revealed that the interaction of cytochrome c with acetonitrile facilitated the oligomerization of cytochrome c via the passage through an intermediate state which was obtained at 20 % v/v concentration of acetonitrile featured by a sharp hike in the ANS fluorescence intensity with a blue shift of 20 nm compared to the native state. Oligomers and fibrils were formed at 40 and 50 % v/v concentration respectively as indicated by a significant hike in the ThT fluorescence intensity, red shift of 55 nm in congo red binding assay and an increase in absorbance at 350 nm. They possess β-sheet structure as evident from appearance of peak at 217 nm. Finally, authenticity of oligomeric and fibrillar species was confirmed by TEM imaging which revealed bead like aggregates and a meshwork of thread like fibrils respectively. It could be suggested that the fibrillation of bovine cytchrome c could serve as a model protein to unravel the general aggregation and fibrillation pattern of heme proteins. Graphical abstract .


Neuropathic pain in a cancer patient responding to subcutaneously administered lignocaine.
To demonstrate difficulties encountered in alleviating neuropathic pain in a terminally ill cancer patient, with the very tentative diagnosis of postherpetic neuralgia. A multidisciplinary pain department in a university hospital. A patient with Hodgkin's lymphoma and leiomyosarcoma in the liver developed an unusual manifestation of neuropathic pain. Oral drug treatment with morphine associated with amitriptyline, valproic acid, mexilitine, flufenazine, and methylprednisolone failed to suppress pain attacks. Only the subcutaneous instillation of lidocaine (2 mg/kg/h) could partially suppress pain. A dorsal root entry zone lesion intervention could only temporary stop the pain attacks. Infiltration and nervous stimulation techniques were not helpful. In determining pain control, the visual analog scale rating scale and the number of attacks per hour were considered. Only the subcutaneous administration of lignocaine could partially suppress pain. Because of the patient's poor hepatic circulation, variable lidocaine plasma concentrations were responsible for intolerable side effects. Subcutaneous lignocaine administration remains a useful method in treating neuropathic cancer pain. The poor metabolic condition of the patient can lead to deleterious high plasma levels. A dorsal root entry zone lesion could only temporarily stop the pain.


The health of children looked after by local authorities.
There are some 40,000 children 'in care' in England and Wales, i.e. being 'looked after' by local authorities and living in foster and residential homes. These children come from highly disadvantaged social backgrounds and are likely to experience more serious health problems than the wider population. Despite this, there is evidence to suggest that their health needs are frequently neglected. This is reflected in the dearth of research information. Health professionals play a key role in combating child abuse and are particularly concerned about future mental health, self-injury and high levels of pregnancy in this group of children. Health promotion is therefore vital, but is complicated by the fact that this group of children often do not attend school. The Department of Health has introduced a major initiative which has a strong health dimension to help promote better care planning and monitoring for children who have been separated from their parents.


Host recognition and integration of filamentous phage phiRSM in the phytopathogen, Ralstonia solanacearum.
Two prophages, called varphiRSM3 and varphiRSM4, that are closely related to, but differ from, filamentous phage varphiRSM1, have been detected in strains of the Ralstonia solanacearum species complex. The prophage varphiRSM3, found in host strain MAFF730139, could be converted to infectious phage by means of PCR and transfection. The nucleotide sequence of varphiRSM3 is highly conserved relative to varphiRSM1 except for open reading frame 2 (ORF2), encoding an unknown protein, and ORF9 encoding the presumed adsorption protein that determines host range. The two host ranges differ dramatically and correlate closely with different gel electrophoresis banding patterns for cell surface fimbriae. Infections by varphiRSM1 and varphiRSM3 enhance bacterial cell aggregation and reduce the bacterial host virulence in tomato plants. Database searches in the R. solanacearum strains of known genomic sequence revealed two inovirus prophages, one designated varphiRSM4 that is homologous to varphiRSM1 and varphiRSM3, and one homologues to RSS1, in the genome of strain UW551.


Structural and functional analysis of the rcsA gene from Erwinia stewartii.
RcsA is a positive regulator of genes for extracellular polysaccharide biosynthesis in the Enterobacteriaceae. The nucleotide sequence of the rcsA gene from Erwinia stewartii was determined and compared to rcsA sequences from E. amylovora, Escherichia coli, and Klebsiella pneumoniae. Three highly conserved regions of the gene were identified. The C-terminal end of the open reading frame (ORF) shared significant amino acid homology to the LuxR class of bacterial activator proteins. Insertion and deletion mutagenesis of the 5' non-coding region indicated that maximal expression of rcsA was dependent upon cis-acting regulatory sequences located more than 300 bp upstream of the translational start site.


Antibiotic policy.
Antibiotics are often effective in curing a patient of his infection even when used in a suboptimal manner. In this situation it is often difficult for the prescriber to accept that he/she is using antibiotics "badly" when he can point to the majority of his infections responding well--either to the antibiotic or the patient's own immune response. Many attempts have been made to limit antibiotic use by selective laboratory reporting, by restricting the antibiotics available, by producing guidelines for initial therapy of infection or prophylaxis, by involvement of infectious disease specialists in all antibiotic use and by several other systems. It appears, however, that antibiotic use is still heavily criticised and is a continuing source of conflict in medicine. Consensus on antibiotic indications is still difficult to obtain and is likely to be achieved very slowly. It is clear that polemic is not sufficient and that consensus practices can only be based upon firm scientifically acquired data and detailed discussion of the options by those most intimately involved.


New-onset cluster headache in middle-age and elderly women.
Cluster headache is usually considered to affect young men. We hereby report on new-onset cluster headache in middle-aged and elderly women. We performed a retrospective chart review of female patients diagnosed with cluster headache (IHS criteria), and studied the charts of women in whom the headache started after the age of 50 years. Out of 168 patients (26 women, 15%) diagnosed with cluster headache, the headache started after the age of 50 years in seven women, of whom three reported past tension-type or migraine headaches. The mean age at the beginning of the headache was 61 +/- 8 years (range 52--72 years). In all cases, the pain was severe, strictly unilateral, and accompanied by at least one autonomic symptom. The average duration of the pain was 70 min (range 20 min--3 h), recurring daily for an average period of 7 weeks (range 1--16 weeks). Five patients had 1--2 pain attacks each day, while the other two experienced up to eight episodes of pain in 1 day. In two patients the periodicity of the pain was currently undetermined. In the remainder, the headache periods recurred every 1--4 years. Cluster headache is commonly considered to be a young-male disorder, but middle-aged and elderly women may also be affected. The characteristics of the pain and its manner of occurrence were similar in our cases to those reported in the young-male population.


Patterns of ecosystem services supply across farm properties: Implications for ecosystem services-based policy incentives.
In developing countries, the protection of biodiversity and ecosystem services (ES) rests on the hands of millions of small landowners that coexist with large properties, in a reality of highly unequal land distribution. Guiding the effective allocation of ES-based incentives in such contexts requires researchers and practitioners to tackle a largely overlooked question: for a given targeted area, will single large farms or several small ones provide the most ES supply? The answer to this question has important implications for conservation planning and rural development alike, which transcend efficiency to involve equity issues. We address this question by proposing and testing ES supply-area relations (ESSARs) around three basic hypothesized models, characterized by constant (model 1), increasing (model 2), and decreasing increments (model 3) of ES supply per unit of area or ES "productivity". Data to explore ESSARs came from 3384 private landholdings located in southern Chile ranging from 0.5ha to over 30,000ha and indicators of four ES (forage, timber, recreation opportunities, and water supply). Forage provision best fit model 3, which suggests that targeting several small farms to provide this ES should be a preferred choice, as compared to a single large farm. Timber provision best fit model 2, suggesting that in this case targeting a single large farm would be a more effective choice. Recreation opportunities best fit model 1, which indicates that several small or a single large farm of a comparable size would be equally effective in delivering this ES. Water provision fit model 1 or model 2 depending on the study site. The results corroborate that ES provision is not independent from property area and therefore understanding ESSARs is a necessary condition for setting conservation incentives that are both efficient (deliver the highest conservation outcome at the least cost) and fair for landowners.


Taraxacum-like Mg-Al-Si@porous carbon nanoclusters for electrochemical rutin detection.
The authors describe a method for synthesis of a nanomaterial consisting of porous carbon encapsulated Mg-Al-Si alloy (denoted as Mg-Al-Si@PC) nanocluster. The nanocluster was synthesis by a solvothermal reaction, followed by high-temperature annealing. The nanoclusters were used as a novel immobilization platform for electrochemical sensing of rutin. The electrochemical behavior of rutin at a modified electrode was investigated by cyclic voltammetry and differential pulse voltammetry. The modified electrode demonstrates a high electrocatalytic activity toward rutin oxidation at a relatively low working potential (0.6 vs. Ag/AgCl). Under optimal conditions, the sensor has a linear response in the 1-10 μM rutin concentration range, and a 0.01 μM lower detection limit (at an S/N ratio of 3). It was successfully applied to the quantification of rutin in pharmaceutical tablets, and satisfactory results were obtained. Furthermore, the results correspond with those with the standard method and with the amounts indicated by the producer, respectively. Graphical abstract Schematic diagram of the Mg-Al-Si@PC nanocluster preparation process and electroanalysis mechanism.


Activation of the nuclear receptor PPARγ by metabolites isolated from sage (Salvia officinalis L.).
Salvia officinalis has been used as a traditional remedy against diabetes in many countries and its glucose-lowering effects have been demonstrated in animal studies. The active compounds and their possible mode of action are still unknown although it has been suggested that diterpenes may be responsible for the anti-diabetic effect of Salvia officinalis. To investigate whether the reported anti-diabetic effects of Salvia officinalis are related to activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ and to identify the bioactive constituents. From a dichloromethane extract of Salvia officinalis able to activate PPARγ several major metabolites were isolated by chromatographic techniques. To assess bioactivity of the isolated metabolites a PPARγ transactivation assay was used. Eight diterpenes were isolated and identified including a new abietane diterpene being the epirosmanol ester of 12-O-methyl carnosic acid and 20-hydroxyferruginol, which was isolated from Salvia officinalis for the first time, as well as viridiflorol, oleanolic acid, and α-linolenic acid. 12-O-methyl carnosic acid and α-linolenic acid were able to significantly activate PPARγ whereas the remaining metabolites were either unable to activate PPARγ or yielded insignificant activation. Selected metabolites from Salvia officinalis were able to activate PPARγ and hence, the anti-diabetic activity of this plant could in part be mediated through this nuclear receptor.


Maximizing anti-HBs seroresponsiveness in kidney transplant waitlist patients: A tertiary-center perspective .
Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.


The pharmacokinetics of recombinant human erythropoietin in Balkan endemic nephropathy patients.
Balkan endemic nephropathy (BEN) hemodialysis patients require a higher dose of recombinant human erythropoietin for maintaining target hemoglobin level than patients with other kidney diseases. Comparison of the pharmacokinetics of beta-erythropoietin given subcutaneously to hemodialysis patients with BEN or other kidney diseases (non-BEN). Recombinant human erythropoietin (75 U/kg) was administered subcutaneously to 10 BEN and 14 non-BEN hemodialysis patients. The predose plasma level of erythropoietin (Epo) was subtracted from all postdose levels. The relevant pharmacokinetic parameters were calculated after noncompartmental pharmacokinetic analysis using Kinetica software (Thermo Scientific, ver.5.0). Although basal plasma Epo concentration was similar in BEN (20.1 ± 10.3 U/L) and non-BEN (15.1 ± 8.1 U/L; p=.1964) patients, there were significant differences between the groups for elimination rate constant (0.016 ± 0.006 vs 0.026 ± 0.011 hr⁻¹; p=.020) and elimination half-life (50.24 ± 19.12 vs 33.79 ± 18.91 hr, p=.048). These differences remained significant after adjustment for patient characteristics (age, sex, hemodialysis duration, ferritin, PTH and ACEI use). No significant differences between groups were found in maximal Epo concentration, time to maximum Epo concentration, area under the curve from time of dosing extrapolated to infinity, clearance, mean residence time of Epo between groups both before and after adjustment. Pharmacokinetic analysis of beta-erythropoietin detected a significantly longer elimination half-life in BEN than in non BEN patients. This finding needs to be confirmed in a well-controlled study with a larger sample size.


Mitomycin C trabeculectomy in eyes with cicatricial conjunctiva.
To demonstrate favorable outcome of mitomycin C-augmented trabeculectomy in eyes with broad cicatricial conjunctiva created by previous surgeries. Forty-six eyes (40 patients) with extensive conjunctival scarring that had undergone mitomycin C trabeculectomy were reviewed retrospectively. After a mean follow-up +/- SD of 13.7 +/- 7.8 months (range, 6 to 36 months), intraocular pressure was well controlled, below or equal to 16 mm Hg and 21 mm Hg, respectively, in 33 (72%) and 44 (96%) of the 46 eyes. In all eyes, a functional filtering bleb was present during the follow-up periods. Mitomycin C trabeculectomy after dissection of conjunctival scar tissue may be useful for treating refractory glaucoma.


Intensity-modulated radiation therapy (IMRT): the radiation oncologist's perspective.
Intensity-modulated radiation therapy (IMRT) is a new and evolving technological advance in high-precision radiation therapy. It is an extension of 3-dimensional conformal radiotherapy (3D-CRT) that allows the delivery of highly complex isodose profiles to the target while minimizing radiation exposure to surrounding normal tissues. Clinical data on IMRT are emerging and being collected, as more institutions are implementing or expanding the use of IMRT. However, the currently available IMRT and its applications are far from being well understood and established. In some circumstances, it remains impractical and too costly. This article discusses some practical issues from the radiation oncologist's perspective.


Methyl parathion induces the formation of symplasts by round spermatid fusion and alters the biochemical parameters in the testis.
Methyl parathion (MP: O,O-dimethyl-O-4-nitrophenyl phosphorothioate) is an organophosphate pesticide used in agriculture to protect a variety of crops. Food stuffs such as fruits and vegetables could be contaminated with MP, which may be a potential route of exposure. Previous studies have shown that MP is a reproductive toxicant in animal models. The present study was designed to investigate the mechanism of symplast formation and biochemical changes that occur in the testis, following MP exposure. MP was treated to adult male Wistar rats (N=5/dose/sample time) as follows. Experiment 1 - 0, 0.75 or 1.5mg/kg/d i.p. for 25 days and experiment 2 - 0 or 3.5mg/kg/d p.o. for 25 days and sacrificed on Day 17, after the last exposure. Light microscopic examination of testis was made to evaluate the structural changes and also to establish a process of symplast formation and destruction. Quantitative biochemical estimations were made in the testis for acid phosphatase (ACP), cholesterol, total protein, uric acid, and lactate dehydrogenase (LDH). MP induced structural changes in the testis in consensus with the previous studies. The symplasts were found in the testes in experiment 1. Those cells were formed due to the cell fusion of round spermatids. The symplasts were degenerated by nuclear fragmentation. The nuclear fragments were extruded from the symplasts leaving behind only the eosinophilic cytoplasm. The cell fusion and multinucleated giant cell formation was the reason for MP induced tubular atrophy. Number of tubules with symplasts increased in experiment 1 in a dose-dependent pattern. Johnsen's scores also decreased in a dose-dependent manner in experiment 1 indicating a dose-dependent tubular destruction. The ACP, cholesterol, total protein, and LDH levels decreased in both experiments against their respective controls, whereas the uric acid level decreased in experiment 1 and increased in experiment 2 (P<0.01-0.001). The effects in experiment 1 were dose-dependent. In conclusion, MP induces the formation of symplasts by cell fusion of round spermatids, which is a process involved in tubular atrophy and also induces biochemical changes in the testis.


Preparation and partial characterisation of a multilamellar body fraction from Schistosoma mansoni.
Multilaminate vesicles were purified, from homogenised whole Schistosoma mansoni adults, by differential density centrifugation on sucrose gradients, following methods previously employed for isolating multilamellar bodies (MLB) from mammalian lung. Morphometric analysis, on electron micrographs, of the pelleted fraction revealed that the pellet contained at least 56% MLB (by volume of solid material). An apparent projection core was described in both fixed MLB from our fraction and in unfixed MLB from a freeze thaw preparation of whole worms. The phospholipid-protein ratio of the MLB fraction was 1.6:1. The major phospholipid classes were separated and identified by quantitative, two dimensional, thin layer chromatography on silica gel. Phosphatidylcholine was the predominant phospholipid in the MLB fraction, comprising 57% of the total phospholipids. Phosphatidic acid phosphatase, previously reported from lung MLB but not schistosomes, was detected in the fraction. The high activity of this enzyme suggests a more active role for schistosome MLB than that of a mere reservoir of preformed membrane precursors.


[Antagonistic activity as 1 of the properties of hospital strains of Staphylococcus aureus].
The frequency of antagonistic activity in S. aureus strains depended on the source from which the strains had been isolated. Antagonistic strains were most frequently detected in the departments of traumatology and orthopedy, as well as in the departments of routine and urgent surgery.


Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia.
To investigate the efficacy and safety of thalidomide in patients with thalassemia intermedia (TI). Patients with a confirmed diagnosis of TI who met the trial criteria and signed consent forms were prescribed oral thalidomide 50 mg qn for 3 months from February 2017. Complete blood counts, Hb analysis, and liver and kidney functions were monitored monthly during treatment and any differences were compared before and after treatment. Patients with Hb increments > 2.0 g/dL were termed main responders (MaR), and those with Hb increments between 1.0 and 2.0 g/dL as minor responders (MiR), otherwise they were termed non-responders. Relevance analysis was performed to explore parameters predicting Hb increments after treatment. Adverse effects during treatment were carefully recorded. The overall response rate (ORR = MaR + MiR) and MaR rates were 78.6 and 50% after 1 month of treatment, respectively, and 85.7 and 71.4% after 3 months treatment. At the end of the treatment period, Hb and HbF increased by 2.5 ± 1.8 g/dL and 2.5 ± 1.6 g/dL, while bilirubin, lactate dehydrogenase, and the nucleated red blood cell count (NRBC) were significantly decreased, while the reticulocyte count significantly increased. Correlation analysis showed that the Hb increments correlated significantly with the ratio of HbF before treatment (r = 0.683, P = 0.007) rather than age, Hb, reticulocyte count, and NRBC before treatment. Adverse events during treatment were mild, and drug reduction or withdrawal from the trial was not required. Thalidomide had rapid and significant effects in patients with TI, and also, it is safe and convenient. But larger scale clinical trials will be required to confirm our conclusions. NCT02995707, https://www.clinicaltrials.gov/ct2/show/NCT03184844?term=thalidomide+thalassemia&rank=1 .


An unusual cause of carpal tunnel syndrome. Case report.
A 38 year old woman with carpal tunnel syndrome of the right hand was treated with operative decompression, initially successfully. Subsequently, she developed a compartment syndrome after an injury. On re-exploration, an accessory palmaris longus muscle was encasing the median nerve at the distal forearm and passing through the flexor sheath, underneath the flexor retinaculum, inserted into the deep palmar fascia.


Global emergency medicine: a review of the literature from 2014.
The Global Emergency Medicine Literature Review (GEMLR) conducts an annual search of peer-reviewed and gray literature relevant to global emergency medicine (EM) to identify, review, and disseminate the most important new research in this field to a worldwide audience of academics and clinical practitioners. This year 6,376 articles written in six languages were identified by our search. These articles were distributed among 20 reviewers for initial screening based on their relevance to the field of global EM. An additional two reviewers searched the gray literature. A total of 477 articles were deemed appropriate by at least one reviewer and approved by the editor for formal scoring of overall quality and importance. Of the 477 articles that met our predetermined inclusion criteria, 63% were categorized as emergency care in resource-limited settings, 13% as EM development, and 23% as disaster and humanitarian response. Twenty-five articles received scores of 17.5 or higher and were selected for formal summary and critique. Inter-rater reliability for two reviewers using our scoring system was good, with an intraclass correlation coefficient of 0.657 (95% confidence interval = 0.589 to 0.713). Studies and reviews focusing on infectious diseases, trauma, and the diagnosis and treatment of diseases common in resource-limited settings represented the majority of articles selected for final review. In 2014, there were fewer total articles, but a slightly higher absolute number of articles screening in for formal scoring, when compared to the 2013 review. The number of EM development articles decreased, while the number of disaster and humanitarian response articles increased. As in prior years, the majority of articles focused on infectious diseases and trauma.


Synergistic efficacy of γ-radiation together with gallium trichloride and/or doxorubicin against Ehrlich carcinoma in female mice.
Combining chemotherapy with radiotherapy represents a key oncology strategy for a more comprehensive attack toward cancers and improves treatment outcome for various solid tumor malignancies. The present study aims to evaluate the synergistic antitumor effect of γ-radiation together with gallium trichloride (GaCl3) and/or doxorubicin (DOX) against solid Ehrlich carcinoma (EC) in female mice. GaCl3 (300 mg/kg body weight (b.w.)) was administered by gavages daily on the seventh day after tumor inoculation, while the cytotoxic drug DOX (4 mg/kg b.w.) was administered intraperitoneally once a week. Whole-body γ-radiation was carried out at a dose 2 Gy once a week. Biochemical analysis showed that solid EC induced a significant increase in malondialdehyde (MDA) content with a significant decrease in the antioxidant state (glutathione peroxidase (GPx) and catalase (CAT) activities) and depleted serum iron concentration compared to normal control. Moreover, a significant increase was observed in calcium level and caspase-3 concentrations in both serum and tumor homogenate respectively associated with a significant alteration in heart, liver, and kidney functions, as compared to control. Treatment of EC-bearing mice with GaCl3and/or DOX combined with γ-radiation exposure significantly reduced tumor volume and displayed a significant improvement in most studied markers which may indicate a synergistic effect of this combination against organ dysfunction and cellular injury. The histopathologically investigation showed that treatment of animals bearing EC with GaCl3and/or DOX with γ-radiation exposure showed shrinkage in tumor lesions and wide zones of apoptotic cells with signs of regenerations. It was concluded that the combination of GaCl3and/or DOX with γ-radiation exposure resulted in super-additive cytotoxic effects on treatment of cancer cells.


Timing of ventriculoperitoneal shunt insertion following spina bifida closure in Kenya.
In Western medical centers, emphasis has been placed on simultaneous myelomeningocele closure and ventriculoperitoneal shunting for children with spina bifida (SB) and co-morbid hydrocephalus (HC). This is not practical in developing countries where patients present in a delayed fashion, many with open, dirty myelomeningoceles. The purpose of this study was to evaluate whether timing of shunting in relation to myelomeningocele closure affected shunt-related complications such as SB wound infection, shunt infection, and shunt malfunction. A retrospective analysis was undertaken of all SB patients undergoing ventriculoperitoneal shunting within 11 days following myelomeningocele closure at Kijabe Hospital between 1997 and August 2007. Data were collected from hospital records and analyzed in SPSS. Over the study period there were 276 patients included. Eighteen patients were shunted prior to SB closure and 13 patients had simultaneous shunting and SB closure. Patients shunted prior to, simultaneously, or within the first 4 days after SB closure had a fivefold higher shunt infection rate (23%) than those shunted 5-10 days following SB closure (4.7%) (p < 0.0001). Shunt malfunctions were also significantly higher in the group shunted prior to back closure (33.3%) vs. those shunted simultaneously (15.4%) or within the first 10 days following SB closure (13.9%) (p = 0.0001). No difference was seen in these groups with regard to wound infections. No difference in shunt-related complications was observed between those shunted 5 to 10 days following back closure. This study indicates that in developing countries, patients with SB who present in a delayed fashion but require shunting and have sterile CSF, should have their shunts inserted 5-10 days after SB closure.


[Periapical odontogenic processes of inflammatory origin. Enzyme activity].
A histoenzymological study was carried out on 40 tissues specimens removed at biopsy and for surgical operations of the following lesions: 5 normal oral mucosa, 5 periapical granulomas, and 30 periapical inflammatory cysts. The purpose of this study was to study some possibly significant variations in levels o activities of oxidative enzymes, and hydrolaxes enzymes. In inflammatory cysts, enzymatic activities were similar to normal epithelium. There was high levels of acid phosphatase LDH and G6PDH activity in the central cells of apical granulomas and in the exfoliating epithelial cells of periapical inflammatory cysts. There were differency in the glycosaminoglicans activity on the different epitelial pattern.


Activation of C-H / H-H bonds by rhodium(II) porphyrin bimetalloradicals.
Reactivity, kinetic, and thermodynamic studies are reported for reactions of a rhodium(II) bimetalloradical with H(2), and with the methyl C-H bonds for a series of substrates CH(3)R (R = H, CH(3), OH, C(6)H(5)) using a m-xylyl diether tethered diporphyrin ligand. Bimolecular substrate reactions involving the intramolecular use of two metalloradical centers and preorganization of the four-centered transition state (M*...X...Y*...M) result in large rate enhancements as compared to termolecular reactions of monometalloradicals. Activation parameters and deuterium kinetic isotope effects for the substrate reactions are reported. The C-H bond reactions become less thermodynamically favorable as the substrate steric requirements increase, and the activation free energy (DeltaG++) decreases regularly as DeltaG degrees becomes more favorable. An absolute Rh-H bond dissociation enthalpy of 61.1 +/- 0.4 kcal mol(-1) is directly determined, and the derived Rh-CH(2)R BDE values increase regularly with the increase in the C-H BDE.


Induced expression of p16 and p21 proteins in UVB-irradiated human epidermis and cultured keratinocytes.
It has been suggested that p16INK4a, the product of the cyclin-dependent kinase inhibitor 2 or multiple tumor suppressor 1 gene, prevents phosphorylation of the retinoblastoma gene product, and thus acts as a negative cell cycle regulator. To elucidate an effect of ultraviolet B (UVB) radiation on p16 expression and its relation to p21, and proliferating cell nuclear antigen (PCNA), immunohistochemical and western blot analyses were performed on UVB-irradiated normal human epidermis and cultured keratinocytes, respectively. Little p16 protein was seen in the control epidermis or keratinocytes. Increases in the levels of p16 protein in both UVB-irradiated epidermis and keratinocytes occurred in a similar manner, in which p16 was induced at 24-48 h and peaked at 72-120 h after irradiation. The induced expression of p21 was observed relatively earlier than that of p16, with peaked expression at 24-48 h and a return to control level by 168 h. PCNA expression was increased slightly until 48 h but significantly increased during 48-168 h of post-irradiation with peak expression at 72 h. These results indicate that together with p21, p16 protein may play an important role for protective or adaptive response to UVB exposure of human skin.


[Dopamine-induced up-regulation of alpha 2-adrenoceptors in crude synaptic membranes of rat brain].
After cerebral cortical membranes were incubated with 0.1-100 microM of dopamine (DA) in 50 mM Tris-HCl buffer (pH 7.7) at 37 degrees C for 30 min, [3H] clonidine binding to alpha 2-receptors was increased in a concentration-dependent manner without changing [3H] WB4101 and [3H] DHA binding to alpha 1- and beta-receptors, respectively. Scatchard analysis of [3H] clonidine binding to cortical membranes showed that DA increased the Bmax in both high- and low-affinity components. The increasing effect of DA on [3H] clonidine was dependent on incubation time and temperature, and it was antagonized by pimozide and cis-flupenthixol. The addition of GTP produced a reduction in DA-induced elevation in [3H] clonidine binding, while that of cyclic AMP did not affect the effect of DA. DA and Mn2+, though both of them increased [3H] clonidine binding, appeared to act at a different site in the membrane. Furthermore, the DA-induced increase in [3H] clonidine was found uniformly in membranes prepared from 7 other regions of the rat brain. These results suggested that DA regulates specifically alpha 2-receptor density by stimulating D1-receptors and/or via other mechanism(s).


Cervical spine mobilisation forces applied by physiotherapy students.
Postero-anterior (PA) mobilisation is commonly used in cervical spine treatment and included in physiotherapy curricula. The manual forces that students apply while learning cervical mobilisation are not known. Quantifying these forces informs the development of strategies for learning to apply cervical mobilisation effectively and safely. This study describes the mechanical properties of cervical PA mobilisation techniques applied by students, and investigates factors associated with force application. Physiotherapy students (n=120) mobilised one of 32 asymptomatic subjects. Students applied Grades I to IV central and unilateral PA mobilisation to C2 and C7 of one asymptomatic subject. Manual forces were measured in three directions using an instrumented treatment table. Spinal stiffness of mobilised subjects was measured at C2 and C7 using a device that applied a standard oscillating force while measuring this force and its concurrent displacement. Analysis of variance was used to determine differences between techniques and grades, intraclass correlation coefficients (ICC) were used to calculate the inter- and intrastudent repeatability of forces, and linear regression was used to determine the associations between applied forces and characteristics of students and mobilised subjects. Mobilisation forces increased from Grades I to IV (highest mean peak force, Grade IV C7 central PA technique: 63.7N). Interstudent reliability was poor [ICC(2,1)=0.23, 95% confidence interval (CI) 0.14 to 0.43], but intrastudent repeatability of forces was somewhat better (0.83, 95% CI 0.81 to 0.86). Higher applied force was associated with greater C7 stiffness, increased frequency of thumb pain, male gender of the student or mobilised subject, and a student being earlier in their learning process. Lower forces were associated with greater C2 stiffness. This study describes the cervical mobilisation forces applied by students, and the characteristics of the student and mobilised subject associated with these forces. These results form a basis for the development of strategies to provide objective feedback to students learning to apply cervical mobilisation.


5-Methylflavasperone and rhamnetin from Guiera senegalensis and their antioxidative and 5-lipoxygenase inhibitory activity.
From the methylene chloride extract of the leaves of Guiera senegalensis a novel naphthopyran, 5-methylflavasperone (5,8,10-trimethoxy-2-methyl-4 H-naphtho[1,2-b]pyran-4-one), as well as rhamnetin were isolated. Rhamnetin showed a strong inhibitory activity on 5-lipoxygenase from porcine leucocytes with an IC50 value of 0.7 microM whereas 5-methylflavasperone revealed only a weak inhibitory activity (IC50 > 200 microM). In the deoxyribose assay both compounds exerted similar antiradicalar effects (IC50 15.8 and 16.7 microM, respectively). In another assay only rhamnetin inhibited peroxidation of phospholipid liposomes (IC50 = 2.4 microM). For 5-methylflavasperone no dose dependent inhibition could be observed.


Effects of flower size and number on pollinator visitation to wild radish, Raphanus raphanistrum.
Plant traits that increase pollinator visitation should be under strong selection. However, few studies have demonstrated a causal link between natural variation in attractive traits and natural variation in visitation to whole plants. Here we examine the effects of flower number and size on visitation to wild radish by two taxa of pollinators over 3 years, using a combination of multiple regression and experimental reductions in both traits. We found strong, consistent evidence that increases in both flower number and size cause increased visitation by syrphid flies. The results for small bees were harder to interpret, because the multiple regression and experimental manipulation results did not agree. It is likely that increased flower size causes a weak increase in small-bee visitation, but strong relationships between flower number and small-bee visitation seen in 2 years of observational studies were not corroborated by experimental manipulation of this trait. Small bees may actually have responded to an unmeasured trait correlated with flower number, or lower small-bee abundances when the flower number manipulation was conducted may have reduced our ability to detect a causal relationship. We conclude that studies using only 1 year, one method, or measuring only one trait may not provide an adequate understanding of the effects of plant traits on pollinator attraction.


Factors associated with late post-partum depression in Japan.
Postnatal depression is one of the life-threatening events faced by women. As the factors associated with postnatal depression have not been investigated fully in Japan, we studied the factors associated with postnatal depression. One-hundred-and-sixty-nine women who visited the health center of a city in Aomori Prefecture, Japan, at 4 months after childbirth for regular examination fulfilled the selection criteria and completed self-reporting questionnaires on postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) and a life and social events scale. The primiparas showed a significantly higher EPDS score than the multiparas. The EPDS score decreased with the frequency of delivery in the groups of mothers in their twenties and thirties. For the multiparas, the number of participants who suffered obstetric events was lower, the number of participants who went back to their home was higher, and the number of participants who were taken care of by their mother was lower than for the primiparas. General health abnormalities, sociability, and worries about baby care were significantly associated with the EPDS for both the primiparas and multiparas. The cooperation of the husband was associated with a decreased EPDS score, both for the primiparas and multiparas, irrespective of the family structure. The EPDS score decreased with an increased frequency of delivery, suggesting that the experience of delivery would impact on postnatal depression, partly because of decreased obstetric events. However, a social assistance system is needed for women with general health abnormalities, less sociability, worries about baby care, and limited cooperation of the husband for both primiparas and multiparas.


Medication Adherence in Children and Adolescents with Acne Vulgaris in Medicaid: A Retrospective Study Analysis.
The objectives of the study were to evaluate and compare medication adherence associated with acne drugs in children and adolescents with acne vulgaris. Data from MarketScan Medicaid enrollees with acne vulgaris were included if patients were ages 6 to 17 years on the index date, had at least one acne-related medication claim, and were enrolled in Medicaid during January 2004 to December 2007. The adherence rate was measured using the medication possession ratio. The medication possession ratio was dichotomized to categorize patients as adherent (≥0.8) or nonadherent (<0.8). Multivariate logistic regressions were used for analyses of the medication possession ratio. Of 20,039 eligible patients, 2,860 patients were children and 17,179 patients were adolescent. Approximately 6.96% of children and 16.75% of adolescents had at least one acne-related medication refill. The mean adherence rate to acne medication was significantly different between children (0.22) and adolescents (0.32). In addition, only 3.71% of children were adherent to acne medication while 13.38% of adolescents were adherent. After controlling for covariates, adolescents were 2.06 times more likely to get an acne-related medication refilled and were 2.40 times more likely to be adherent to acne-related medication. The analyses also showed that acne-related medication adherence was associated with the patient's characteristics and acne medication type. Neither patient population was considered adherent to acne-related medications, nor was there a significant difference between the two patient populations. This study also revealed that medication type is a contributing factor towards adherence. Health care providers should strive to educate patients on the importance of medication adherence.


Video assessment of finger tapping for Parkinson's disease and other movement disorders.
Functional motor impairment due to Parkinson's disease and other movement disorders are currently assessed with visual rating scales such as the Unified Parkinson's Disease Rating Scale (UPDRS). These methods rely on the subjective judgment of a rater to assign scores representing the extent of impairment while subjects perform prescribed activities. We describe a new model-based framework that uses statistical video processing to automatically track movement during prescribed activities. This approach has many advantages over traditional clinical rating scales. It can completely characterize movement during prescribed tasks over time objectively and precisely using hardware that is inexpensive and readily available. We demonstrate the potential of this framework with a simple statistical model applied to a paced finger tapping test. This technology could be deployed in a natural home environment for frequent assessments. This technology could ultimately improve both clinical practice and clinical trials.


During afterdischarges in the young rat in vivo extracellular potassium is not elevated above adult levels.
Studies have suggested that in the immature brain an unusually high ceiling level for potassium may lead to an increased propensity for seizures. In these experiments, the peak levels of extracellular potassium in the hippocampus in vivo were recorded in immature rats 10-27 days old and compared to levels reached in adults. There was no difference in the peak level of potassium attained during an afterdischarge in any of the age groups tested.


Preventable hazard of soft lens wear.
Recurrent pseudomonal conjunctivitis, caused by poor soft contact lens care and the use of contaminated saline, is described. This problem can easily be avoided by proper sterilization, with boiling being the method of choice.


Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice.
Pain pathways terminate in discrete brain areas that monitor the sensory and affective qualities of the initiating stimulus and show remarkable plasticity. Here, we found that chronic pain by sciatic nerve ligation caused a dramatic increase in glial fibrillary acidic protein (GFAP)-like immunoreactivity (IR), which is located in the dendritic astrocytes, with its expanding distribution in the cingulate cortex (CG) of mice. The branched GFAP-like IR in the CG of nerve-ligated mice was overlapped with S100beta-like IR, which is highly limited to the cell body of astrocytes, whereas there was no difference of S100beta-like IR between sham-operated and nerve-ligated mice. The number of BrdU-positive cells on the CG was not changed by sciatic nerve ligation. Furthermore, subventricular zone (SVZ)-derived neural stem cells marked by pEGFP-C1 did not migrate toward the CG after sciatic nerve ligation. In the behavioral assay, the thermal hyperalgesia observed on the ipsirateral side in nerve-ligated mice was significantly suppressed by a single pre-microinjection of a glial-modulating agent propentofylline into the CG 24 h before nerve ligation. These results suggest that chronic painful stimuli induces astrocyte activation in the CG, whereas they do not affect the cell proliferation/differentiation from neural stem cells in the CG and the migration of neural stem cells from the SVZ area. The astrocyte activation in the CG may, at least in part, contribute to the development of a chronic pain-like state following sciatic nerve ligation in mice.


Downregulation of intestinal cytochrome p450 in chronic renal failure.
Chronic renal failure (CRF) is associated with a decrease in intestinal drug metabolism. The mechanisms remain poorly understood, but one hypothesis involves a reduction in cytochrome P450 levels. This study aimed to investigate the effects of CRF on intestinal cytochrome P450. Two groups of rats were defined, i.e., rats with CRF (induced by 5/6 nephrectomy) and control pair-fed rats. Total cytochrome P450 levels and protein and mRNA expression of cytochrome P450 isoforms, as well as in vitro N-demethylation of erythromycin (a probe for CYP3A activity) and 7-ethoxyresorufin o-deethylase activity (a probe for CYP1A), were assessed in intestinal microsomes. Body weights were similar in the two groups. Creatinine clearance was reduced by 77% (P < 0.001) in CRF rats, compared with control pair-fed animals. Total intestinal cytochrome P450 activity was reduced by 32% (P < 0.001) in CRF rats. CYP1A1 and CYP3A2 protein expression was considerably reduced (>40%, P < 0.001) in rats with CRF. CYP2B1, CYP2C6, and CYP2C11 levels were the same in the two groups. RT-PCR assays revealed marked downregulation of CYP1A1 and CYP3A2 gene expression in CRF rats (P < 0.001). Although intestinal cytochrome P450 levels were reduced in CRF, induction by dexamethasone was present. N-Demethylation of erythromycin and 7-ethoxyresorufin o-deethylase activity were decreased by 25% (P < 0.05) in CRF rats, compared with control rats. In conclusion, CRF in rats is associated with decreases in intestinal cytochrome P450 activity (mainly CYP1A1 and CYP3A2) secondary to reduced gene expression.


Bacterial degradation of nitrophenols and their derivatives.
This review intends to provide an overview of bacterial degradation of nitrophenols (NPs) and their derivatives. The main scientific focus is on biochemical and genetic characterization of bacterial degradation of NPs. Other aspects such as bioremediation and chemotaxis correlated with biodegradation of NPs are also discussed. This review will increase our current understanding of bacterial degradation of NPs and their derivatives.


Chytrid infecting the bloom-forming marine diatom Skeletonema sp.: Morphology, phylogeny and distribution of a novel species within the Rhizophydiales.
Chytrids have long been recognised as important parasites of microalgae in freshwater systems, able to shape the dynamics of blooms, the gene pool of their host and phytoplankton succession. In the sea however, where the presence of these organisms is erratic and ephemeral, studies concerning chytrids are sparse and confined to metabarcoding surveys or microscopy observations. Despite the scarcity of data, chytrid epidemics are supposed to play an important role in marine biogeochemical cycles, being one of the drivers of phytoplankton dynamics. Here we combine microscopy observations and in silico mining of a single-cell whole genome to molecularly and morphologically characterise a novel chytrid parasite of the dominant diatom genus Skeletonema. Morphological observations highlight features of the thallus and ascertain the parasitic nature of the interaction whilst the genetic markers obtained allows for a phylogenetic reconstruction, placing the new species in the order Rhizophydiales. Thanks to the molecular data obtained we are also able to provide a first investigation of the global distribution of this organism by screening the Ocean Sampling Day (OSD) dataset, highlighting a northern transatlantic dissemination.


Interaction against different environmental dynamics during a leg extension task is controlled by temporal rather than amplitude scaling of muscular activity.
Force exertion against different mechanical environments can affect motor control strategies in order to account for the altered environmental dynamics and to maintain the ability to produce force. Here, we investigated the change of muscular activity of selected muscles of the lower extremities while the participants interacted with an external mechanical device of variable stability. Twenty-five healthy participants exerted force against the device by performing a unilateral ballistic leg extension task under 1 or 3 degrees of freedom (DoF). Directional force data and electromyographic responses from four leg muscles (TA, VM, GM, PL) were recorded. Muscle responses to the altered experimental conditions were analyzed by calculating time to peak electrical activity (TTP), peak electrical activity (PEA), slope of EMG-signal and muscle activity. It was found that neuromuscular system adjustments to the task are expressed mainly by temporal (TTP) rather than amplitude (PEA) scaling of muscular activity. This change was specific for the investigated muscles. Moreover, a selective increase of muscle activity occurred while increasing external DoF. This scheme was accompanied by a significant reduction of applicable force against the device in the unstable 3 DoF condition. The findings suggest that orchestration of movement control is linked to environmental dynamics also affecting the ability to produce force under dynamic conditions. The adjustments of the neuromuscular system are rather temporal in nature being consistent with the impulse timing hypothesis of motor control.


Estimation of economic values for milk coagulation properties in Italian Holstein-Friesian cattle.
The economic values (EV) of production traits, rennet coagulation time (RCT, min), and curd firmness (a30, mm) were derived for Italian Holstein-Friesian dairy cattle, based on the Grana Padano cheese industry. Three different sets of EV for RCT and a30 were estimated, assuming +2.5% (scenario 1), +5% (scenario 2), and +10% (scenario 3) increment in cheese yield due to the effect of milk coagulation properties (MCP). A model was developed to simulate the transformation of milk into Grana Padano cheese. The EV of RCT and a30 were -€2.213, -€4.426, and -€8.852/min, and €0.877, €1.755, and €3.509/mm for scenarios 1, 2, and 3, respectively. Relative emphasis of traits in the breeding objectives of the Italian Holstein-Friesian dairy cattle population should account for the effect of MCP on cheese yield. Economic values for milk components and MCP were affected by changes of dairy products, whereas variations of feed prices did not influence EV of RCT and a30.


One-step green synthesis of β-cyclodextrin/iron oxide-reduced graphene oxide nanocomposite with high supramolecular recognition capability: Application for vortex-assisted magnetic solid phase extraction of organochlorine pesticides residue from honey samples.
In this research, β-cyclodextrin/iron oxide reduced graphene oxide hybrid nanostructure (β-CD/MRGO) with high water dispersability, excellent magnetic responsivity and molecular selectivity was prepared via a facile one step green strategy. The obtained nanomaterial was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and vibrating sample magnetometry (VSM), which confirmed the modification of GO with β-CD and magnetic nanoparticles. The formation mechanism of β-CD/MRGO was also discussed. The prepared magnetic nanocomposite was then applied as adsorbent in the vortex-assisted magnetic solid phase extraction (MSPE) of 16 organochlorine pesticides (OCPs) from honey samples prior to gas chromatography-electron capture detection (GC-ECD) analysis. Optimum extraction conditions have been assessed with respect to vortex time, sample pH, adsorbent amount, and salt concentration as well as desorption conditions (type and volume of desorption solvent and desorption time). A good level of linearity (2-10,000ngkg-1) with satisfactory determination coefficients (R2>0.9966) and suitable precision (%RSDs less than 7.8) was obtained for OCPs under the optimal conditions. The limits of detection and quantification of the method were obtained in the sub-parts per trillion (ppt) to parts per trillion range (LOD: 0.52-3.21ngkg-1; LOQ: 1.73-10.72ngkg-1) based on 3 and 10 signal to noise ratios, respectively. The MSPE method was successfully applied to analysis of OCPs in honey samples with recoveries in the range of 78.8% to 116.2% and RSDs (n=3) below 8.1%. The results demonstrated that β-CD/MRGO could exhibit good supramolecular recognition, enrichment capability and high extraction recoveries toward OCPs.


Clutter filters adapted to tissue motion in ultrasound color flow imaging.
The quality of ultrasound color flow images is highly dependent on sufficient attenuation of the clutter signals originating from stationary and slowly moving tissue. Without sufficient clutter rejection, the detection of low velocity blood flow will be poor, and the velocity estimates will have a large bias. In some situations, e.g., when imaging the coronary arteries or when the operator moves the probe in search for small vessels, there is considerable movement of tissue. It has been suggested that clutter rejection can be improved by mixing down the signal with an estimate of the mean frequency prior to high pass filtering. In this paper, we compare this algorithm with several other adaptive clutter filtering algorithms using both experimental data and simulations. We found that realistic accelerations of the tissue have a large effect on the clutter rejection. The best results were obtained by mixing down the signal with non-constant phase increments estimated from the signal. This adapted the filter to a possibly accelerated tissue motion and produced a significant improvement in clutter rejection.


In-line holography and phase-contrast microtomography with high energy x-rays.
Holography with high energy x-rays is now feasible due to the coherence properties of third generation synchrotron sources. Simple in-line holographic techniques can be used to generate edge-enhanced images which for many samples can be interpreted without direct phase retrieval. The coherence properties of such sources and their exploitation for phase-contrast microimaging are demonstrated. The technique can easily be combined with computed microtomography (CMT) data collection and reconstruction strategies for three-dimensional imaging. A dramatically improved image contrast, as compared with absorption CMT, was obtained when imaging a wet human coronary artery specimen. In the tomograms, previously invisible detail could be visualized with absorbed doses below the level where radiation damage impedes the imaging. The results indicate the considerable potential of the in-line holographic CMT method in three-dimensional biomedical microscopy.


Influence of chemical microstructure of single-ion polymeric electrolyte membranes on performance of lithium-ion batteries.
A novel protocol to generate and control porosity in polymeric structures is presented for fabrication of single ion polymer electrolyte (SIPE) membranes for lithium ion batteries. A series of SIPEs with varying ratios of aliphatic and aromatic segments was successfully synthesized and subsequently blended with PVDF-HFP to fabricate membranes of various sizes of pores. The membranes were characterized using techniques including SEM, solvent uptake capacity measurement and ionic conductivity. We demonstrate that appropriate membrane porosity enhances ionic conductivity, reduces interfacial resistance between electrodes and electrolyte and ultimately boosts performance of Li-ion batteries. The implication of the structure-performance relationship for battery design is discussed.


Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal.
• Not only has a precise characterization of libido and sexual arousal in men as a central neural process been lacking, but the interactive role of gonadal hormones and sexual orientation in such processes has never been investigated. We investigate the relationships among sexual hormones, sexual arousal, and sexual orientation in men by comparing the self-reported sexual response of heterosexual and homosexual men with locally advanced prostate neoplasm, receiving the non-steroidal anti-androgen bicalutamide as monotherapy. • 29 Romanian men participated in this study: 17 heterosexual and 12 homosexual. Patients were undergoing treatment for prostate cancer consisting of a standard daily dose of 50 mg bicalutamide, a fast acting non-steroidal anti-androgen with action comparable to other anti-androgen drugs but with reportedly fewer sexual side effects. • Patients retrospectively provided information regarding their sexual functioning measured by the IIEF prior to commencing bicalutamide treatment. • Then, about five weeks later, patients were asked to prospectively provide information regarding their current sexual functioning while undergoing bicalutamide treatment. • Overall IIEF scores as well as the Erectile Function, Orgasmic Function, Sexual Desire, and Overall Satisfaction subscales showed group, treatment, and group by treatment effects. • The Intercourse Satisfaction subscale showed group and group by treatment effects. • On most subscales, homosexual men showed lower functioning than heterosexual men, primarily in response to treatment with bicalutamide. • Treatment with an anti-androgen in a clinical population of men undergoing therapy for prostate cancer affected homosexual men more than heterosexual men, although not all heterosexual men were unaffected. • These results are discussed in the context of dual sexual natures, a concept recently developed in the sexual literature. • Furthermore, these findings reiterate the importance of incorporating such variables as sexual orientation into studies investigating medical treatments on sexual response.


In vitro analysis of cell salvage blood collection with a laparoscopic suction device.
To determine whether cell salvage blood collection with a laparoscopic suction device is inferior to use of a traditional Yankauer suction device. Prospective, in vitro study. Academic teaching hospital. Individual units of donated packed red blood cells were diluted with normal saline solution to a hematocrit level of 21%. The blood was divided into 2 equal parts and then suctioned with either a laparoscopic suction device or a Yankauer plastic suction catheter tip connected to double-lumen cell salvage tubing with a diluted heparin drip and a vacuum pressure of 100 mm Hg. Collected blood was processed with a cell salvage device. Red blood cell volume was calculated by multiplying the hematocrit level by the total volume of blood product at the time of testing. Mean hemolysis indexes were compared between the laparoscopic and Yankauer method of blood collection by use of a 2-sample t test. Assuming a clinically acceptable limit of loss to be 7%, percent loss in red blood cell volume was tested with a 95% one-sided confidence limit to assess noninferiority. The mean hemolysis index was 43.33 with laparoscopic suction method and 34.67 with the Yankauer suction method. The mean difference was 8.67 and was not considered significant (p = .074). The percent loss in red blood cell volume after collection and cell salvage processing was 33.2% with the laparoscopic suction method and 29.57% with the Yankauer method. The mean difference was 3.63% and was within the acceptable 7% loss limit for noninferiority (p = .0278). Laparoscopic blood collection is not inferior to the standard Yankauer method for cell salvage collection.


Simultaneous determination of four secoiridoid and iridoid glycosides in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a comparative pharmacokinetic study.
A simple, reliable and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of four secoiridoid (gentiopicroside, swertiamarin, sweroside) and iridoid glycosides (loganic acid), the bio-active ingredients in rat plasma. After liquid-liquid extraction, chromatographic separation was accomplished on a Shim-pack XR-ODS column with a mobile phase consisting of methanol and 0.1% formic acid in water. A triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating both in positive and negative ionization mode and operated by multiple-reaction monitoring scanning. The lower limits of quantitation were 0.25-30 ng/mL for all the analytes. Both intra-day and inter-day precision and accuracy of analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard (amygdalin) from rat plasma were all >71.4%. The validated method was successfully applied to a comparative pharmacokinetic study of four analytes in rat plasma between normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan and Gentiana macrophylla extract, respectively. Results showed significant differences in pharmacokinetic properties of the analytes among the different groups.


Women's Understanding of the Term 'Pap smear': A Comparison of Spanish-Speaking Versus English-Speaking Women.
Objective To compare the understanding of the term 'Pap smear' among Spanish-speaking women, as compared to their English-speaking counterparts. Methods Surveys were distributed to English and Spanish speaking female patients in an urban Obstetrics and Gynecology clinic. Patients were at least 18 years old or they were less than 18 years old and pregnant. Results A majority of participants (77.3 % English-speaking vs. 74.1 % Spanish-speaking, respectively) were able to identify at least one correct descriptor for the term Pap smear. However, Spanish-speaking women were significantly less likely to choose incorrect descriptors. Spanish-speaking women were much less likely to say that a Pap smear was the same as a Pelvic exam (45.7 vs. 78.8 %; p = 0.001), or a test for a sexually transmitted disease (25 vs. 60.6 %; p = 0.001). Conclusions for Practice Compared to English-speaking women, Spanish-speaking women are much less likely to conflate a pelvic exam with a Pap smear. Overall understanding was suboptimal, regardless of primary language, indicating that major efforts are still needed to improve functional health literacy with respect to cervical cancer screening.


Recurrent inguinal hernias in infants and children.
The objective of this study was to analyze the etiologic factors possibly associated with the development of recurrent groin hernias in infants and children. For this purpose we analyzed the records of 2754 pediatric patients operated on for primary hernias between 1966 and 1990 at our department who have not had recurrences. They were compared with 28 boys and 4 girls we treated for recurrent hernias during the same period. We found an indirect hernia in 29 cases, a direct hernia in 4 patients, and a femoral hernia in 1 child at the time of reoperation. A significantly high recurrence rate was found to be associated with incarceration (21.9% versus 7.6%), postoperative complications (9.4% versus 1.8%), concomitant diseases (31.2% versus 5.7%), and premature birth. Day case treatment was closely related to concomitant diseases. No impact on the development of recurrences was seen for the surgeons' educational level and the time of day the surgery was performed. Knowledge of the factors contributing to hernia recurrence and perfect surgical technique with reduction of incarcerated hernias and early elective operation may result in fewer recurrences in infants and children.


Role of Murraya koenigii (curry leaf) and Brassica juncea (Mustard) in lipid peroxidation.
The status of lipid peroxidation was investigated in rats fed M. Koenigii (curry leaf) and B. juncea (Mustard). Concentration of malondialdehyde showed a significant decrease, while hydroperoxides and conjugated dienes were significantly increased in liver and heart of both the experimental groups. SOD and catalase activity was found to be increased in liver and heart of both the spices administered groups. Glutathione levels in liver, heart and kidney were lowered in rats administered these spices. Glutathione reductase, glutathione peroxidase and glutathione S-transferase activity showed a sharp increase in the experimental groups compared to the controls.


Primary malignant melanoma of the esophagus: report of two cases.
Two cases of primary esophageal malignant melanoma diagnosed at the Columbia-Presbyterian Medical Center are reported. One patient who received 3800 rads and had subsequent surgery lived for 18 months. The other had surgery and subsequent chemotherapy and is still alive three years later. Forty other cases reported in the literature are briefly analyzed.


Naturalistic comparative study of outcome and cognitive effects of unmodified electro-convulsive therapy in schizophrenia, mania and severe depression in Nigeria.
Although unmodified electro-convulsive therapy (ECT) is widely used in Nigeria for schizophrenia, mania and severe depression failing to respond to adequate pharmacotherapy in the short-term, there are no prospective studies on its efficacy and side effects. To compare the efficacy of electro-convulsive therapy and standard pharmacotherapy in the treatment of schizophrenia, mania and severe depression. A prospective open label study. Seventy subjects (mean age, 29.4) with mean duration of illness, 50.6 months, and diagnosis of schizophrenia (37.1%), mania (28.6%), severe depression (30%) and schizo-affective disorder (4.3%), were assessed pre-ECT and at seven other intervals in six months, using the Brief Psychiatric Rating Scale (BPRS), the Mini-Mental State Examination (MMSE) and other cognitive test batteries. They were compared with a matched group of patients who received only pharmacotherapy. Although the ECT group had suffered more treatment resistant disorders, there was full clinical recovery in two months, when all were discharged. The group had significantly shortened duration of hospitalisation, after commencement of ECT. Hence ECT facilitated recovery in this potentially drug treatment resistant psychotic subjects. Although frequency of complaints of subjective memory difficulty increased during ECT and normalised at follow up, objective tests showed steady cognitive improvement with clinical recovery. Complaints of muscle pain (31.4%), post-ECT confusion (15.7%) and post-ECT headache (20%) in the first week of treatment, were not evident at follow up. Unmodified ECT combined with pharmacotherapy was safe and effective with non-enduring subjective memory difficulty for this potentially drug treatment resistant group of psychotic patients.


Social capital is associated with decreased risk of hunger.
This article explores whether social capital-a measure of trust, reciprocity and social networks-is positively associated with household food security, independent of household-level socioeconomic factors. Interviews were conducted in 330 low-income households from Hartford, Connecticut. Social capital was measured using a 7-item Likert scale and was analyzed using household- and community-level scores. Household food security and hunger were measured using the US Household Food Security Module. chi2 tests were used to examine associations between social capital, food security and household demographic characteristics. Logistic regression was used to examine whether household- and community-level social capital decreases the odds of household hunger, and to estimate which household characteristics increase the likelihood of having social capital. Consistent with our hypotheses, social capital, at both the household and community levels, is significantly associated with household food security in these data. Community-level social capital is significantly associated with decreased odds of experiencing hunger (adjusted odds ratio (AOR)=0.47 [95% CI 0.28, 0.81], P<0.01), while controlling for household socioeconomic status. Results show that households with an elderly member are over two and a half times as likely to have high social capital (AOR=2.68 [1.22, 5.87], P<0.01) than are non-elderly households, after controlling for socioeconomic status. Having a household member who participates in a social or civic organization is also significantly associated with having higher levels of social capital. Social capital, particularly in terms of reciprocity among neighbors, contributes to household food security. Households may have similarly limited financial or food resources, but households with higher levels of social capital are less likely to experience hunger.


Increase in number of functional release sites by cyclic AMP-dependent protein kinase in cultured neurons isolated from hippocampal dentate gyrus.
The enhancement of synaptic exocytosis is one form of long-term potentiation (LTP) of synaptic transmission. As possible mechanisms underlying this enhancement, increases in the release probability and/or the number of release sites are suggested. To obtain direct evidence for the increase in the number of functional release sites induced by protein kinase A (PKA) cascade, we attempted to visualize functional release sites using styryl dyes, FM4-64 and FM1-43, and investigated the effects of PKA on the release sites. A PKA activator FSK increased the number of active release sites by approximately 20-30%. A direct PKA activator, Sp-cAMPS, showed the same effect, which was blocked by a PKA inhibitor, KT5720, suggesting that this effect was mediated by PKA. This PKA-dependent increase in the number of release sites requires Ca(2+) in the bath solution, and Sr(2+) can not be a substitute for Ca(2+). Since the number of functional release sites is approximately half the total number of synaptophysin-immunoreactive sites, the PKA dependent activation of silent release sites of DG neuron terminals is suggested.


Toll-like receptor-4 Asp299Gly polymorphism does not influence progression of atherosclerosis in patients with familial hypercholesterolaemia.
Toll-like receptor-4 (TLR4) is a major receptor for inflammatory stimuli potentially involved in the pathogenesis of atherosclerosis, such as lipopolysaccharide (LPS) and heat-shock proteins. The Asp299Gly polymorphism of the TLR4 gene has been associated with a reduced intima-media thickness (IMT) of the common carotid artery in healthy individuals. We have investigated whether the presence of the Asp299Gly polymorphism in patients with familial hypercholesterolaemia (FH) has a similar protective effect, and whether it influences the effects of HMG-CoA reductase treatment. A cohort of 293 FH patients and 200 healthy volunteers were genotyped for the presence of the Asp299Gly allele using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Intima-media thickness measurements, inflammatory parameters and the effect of HMG-CoA reductase inhibitors were compared between the patients with and without Asp299Gly allele. The Asp299Gly allele was present in 10.6% of the FH patients and 11.0% of the healthy individuals. Whereas the FH patients carrying the Asp299Gly allele displayed a reduced absolute IMT value compared with the FH patients carrying the wild-type allelle, the difference did not reach statistical significance. In addition, the effect of treatment with HMG-CoA reductase inhibitors was not influenced by the presence of Asp299Gly allele. The presence of the Asp299Gly allele of the TLR4 gene does not seem to exert a major influence on the progression of atherosclerosis in patients with FH.


Introduction of an innovative day surgery pathway for unicompartmental knee replacement: no need for early knee flexion.
To evaluate the introduction of an innovative rehabilitation protocol, delaying knee flexion, for patients receiving unicompartmental knee replacement. Longitudinal cohort. Specialist Orthopaedic Unit within an NHS Foundation Trust. 669 consecutive patients undergoing unicompartmental knee replacement. An innovative rehabilitation protocol, delaying knee flexion. Length of stay, range of movement, Surgical Satisfaction Questionnaire. There were 669 consecutive primary unilateral unicompartmental knee replacements from September 2016 to February 2018. In total 264 patients (39%) went home on the day of surgery, 253 (38%) on day 1 and 152 (23%) stayed in 2 or more days (range 2 to 28 days). The mean length of stay reduced from 2.6 to 1.2days (median 1day). Mean flexion was 110° (range 30 to 140) at 6 weeks. The surgical satisfaction questionnaire showed that 90% of patients discharged on day 0 were very satisfied with the results of surgery. Many components of traditional care were altered to introduce this protocol. The most important factors were delayed knee flexion providing benefits in terms of early mobilisation with no short term detriment, physiotherapists working late shifts, a consistent message and patient education. It was safe, effective and patient satisfaction was high.


Chequerboard effects on spurious currents in the lattice Boltzmann equation for two-phase flows.
Spurious currents near an interface between different phases are a common undesirable feature of the lattice Boltzmann equation (LBE) method for two-phase systems. In this paper, we show that the spurious currents of a kinetic theory-based LBE have a significant dependence on the parity of the grid number of the underlying lattice, which can be attributed to the chequerboard effect. A technique that uses a Lax-Wendroff streaming is proposed to overcome this anomaly, and its performance is verified numerically.


Body dysmorphic disorder: a cognitive behavioural model and pilot randomised controlled trial.
A cognitive behavioural model of body image is presented with specific reference to body dysmorphic disorder (BDD). We make specific hypotheses from the model for testing BDD patients in comparison with: (i) patients with "real" disfigurements who seek cosmetic surgery; (ii) subjects with "real" disfigurements who are emotionally well adjusted; and (iii) healthy controls without any defect. There have been no randomised controlled trials of treatment for BDD and therefore the model has clear implications for the development of cognitive behavioural therapy. This was evaluated in a pilot controlled trial. Nineteen patients were randomly allocated to either cognitive behaviour therapy or a waiting list control group over 12 weeks. There were no significant pre-post differences on any of the measures in the waiting list group. There were significant changes in the treated group on specific measures of BDD and depressed mood. Cognitive behaviour therapy should be further evaluated in a larger controlled trial in comparison with another psychological treatment such as interpersonal therapy and pharmacotherapy.


Evaluating nuclear protein-coding genes for phylogenetic utility in beetles.
Although nuclear protein-coding genes have proven broadly useful for phylogenetic inference, relatively few such genes are regularly employed in studies of Coleoptera, the most diverse insect order. We increase the number of loci available for beetle systematics by developing protocols for three genes previously unused in beetles (alpha-spectrin, RNA polymerase II and topoisomerase I) and by refining protocols for five genes already in use (arginine kinase, CAD, enolase, PEPCK and wingless). We evaluate the phylogenetic performance of each gene in a Bayesian framework against a presumably known test phylogeny. The test phylogeny covers 31 beetle specimens and two outgroup taxa of varying age, including three of the four extant beetle suborders and a denser sampling in Adephaga and in the carabid genus Bembidion. All eight genes perform well for Cenozoic divergences and accurately separate closely related species within Bembidion, but individual genes differ markedly in accuracy over the older Mesozoic and Permian divergences. The concatenated data reconstruct the test phylogeny with high support in both Bayesian and parsimony analyses, indicating that combining data from multiple nuclear loci will be a fruitful approach for assembling the beetle tree of life.


Non-exposure simple suturing endoscopic full-thickness resection (NESS-EFTR) versus laparoscopic wedge resection: a randomized controlled trial in a porcine model.
Current endoscopic full-thickness resection (EFTR) methods produce transmural communication and expose the tumor to the peritoneum. An EFTR method with a simple suturing technique that does not expose the gastric mucosa to the peritoneum (non-exposure simple suturing, NESS) was recently developed. To date, there have been no prospective studies that compare EFTR with laparoscopic wedge resection in human or animal. The aim of this study was to compare outcomes between NESS-EFTR and laparoscopic wedge resection (LWR) using the linear staplers in a randomized animal study. NESS-EFTR includes steps of laparoscopic seromuscular suturing, EFTR of the inverted stomach wall, and endoscopic mucosal suturing with endoloops and clips. Sixteen pigs underwent NESS-EFTR (n = 8) or LWR (n = 8). The resected locations were the cardia, fundus, upper body anterior and greater curvature, antrum lesser and greater curvature side. The pigs were killed 3 weeks after surgery. Rates of successful complete resection (en-bloc resection with clear margins), successful closure, and complications were evaluated. The complete resection rates in the NESS-EFTR and LWR groups were 100 and 75%, respectively (P = 0.467). All wounds were successfully closed in both groups. Resected tissues were significantly larger in the LWR group (mean ± SD: 8.0 ± 0.8 cm vs. 4.4 ± 0.5 cm, P < 0.001). Procedure time was significantly shorter in the LWR group (31.7 ± 10.0 min vs. 118.1 ± 23.4 min, P < 0.001). Early deaths due to complications only occurred in the LWR group (a leakage at cardia and a stenosis at the antrum lesser curvature side). Incomplete resection and complications were occurred in only LWR group. NESS-EFTR was feasible and safe in animal.


Metallothionein in the liver of the small lizard Podarcis muralis.
A cysteine-rich protein presenting optical and biochemical features typical of metallothionein and a similar amino acid composition was found in the liver of the small lizard Podarcis muralis. Animals were given either CdCl2 (0.8 mg Cd2+/kg body wt) or saline (NaCl 0.9%) by i.p. injection for 3 days. A second group of animals were injected with a single dose of [35S]cysteine plus CdCl2 or saline. Lizard MT contained Zn and Cu when injected with saline and also Cd when injected with CdCl2. Metallothionein induction by cadmium was demonstrated by radioactive labelling.


Circadian patterns of locomotor activity and body temperature in blind mole-rats, Spalax ehrenbergi.
A wide variety of organisms exhibit circadian rhythms, regulated by internal clocks that are entrained primarily by the alternating cycle of light and darkness. There have been few studies of circadian rhythms in fossorial species that inhabit a microenvironment where day-night variations in most environmental parameters are minimized and where exposure to light occurs only infrequently. In this study, daily patterns of locomotor activity and body temperature (Tb) were examined in adult blind mole-rats (Spalax ehrenbergi). These fossorial rodents lack external eyes but possess rudimentary ocular structures that are embedded in the Harderian glands and covered by skin and fur. Most individual mole-rats exhibited circadian rhythms of locomotor activity, but some animals were arrhythmic. Individuals that did exhibit robust rhythms of locomotor activity also showed rhythms of Tb. In most cases, Tb was highest during the phase of intense locomotor activity. Locomotor activity rhythms could be entrained to light:dark cycles, and several mole-rats exhibited entrainment to non-24-h light cycles (T-cycles) with period lengths ranging from T = 23 h to T = 25 h. Some individuals also showed entrainment to daily cycles of ambient temperature. There was considerable interindividual variation in the daily patterns of locomotor activity among mole-rats in virtually all the conditions of environmental lighting and temperature employed in this study. Thus, whereas it appears likely that photic cues have a significant role in the entrainment of circadian rhythms in mole-rats, the amount of variability in rhythm patterns among individuals appears to be much greater than for most species that have been studied.


Caffeine as an intensifier of stress-induced hormonal and pathophysiologic changes in mice.
Psychosocially stressed male mice competing in a Henry-Stephens complex population cage develop hypertension, cardiovascular damage, and chronic interstitial nephritis. Their plasma renin, noradrenaline, corticosterone, and adrenal-catecholamine synthetic enzymes are increased and they die prematurely. Adding 3.3 mg of caffeine a day per kilogram of mouse body weight (the equivalent of 20 micrograms/ml decaffeinated coffee) to their drinking water significantly intensifies most of these changes. A dose of 90 mg/kg of caffeine (the equivalent of 560 micrograms/ml, i.e., brewed tea or coffee) further increases the effects. The drug-induced enhancement of competitive social stimulation of the neuroendocrine system resulted in a further increase of plasma renin and corticosterone levels as well as blood pressure and adrenal weight. These effects together with accelerated mortality and increased pathology indicate that chronic consumption of caffeinated liquids adds to the risks of psychosocial stress.


Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh.
Poor vitamin B12 (B12) status is associated with adverse outcomes in pregnancy and infancy. Little is known about effects of B12 supplementation on immune function. The present study aimed to evaluate effects of pre- and postnatal B12 supplementation on biomarkers of B12 status and vaccine-specific responses in mothers and infants. In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, age 18-35 years, hemoglobin <110 g/L, 11-14 weeks pregnant) were randomized to receive 250 μg/day B12 or a placebo throughout pregnancy and 3-month postpartum along with 60 mg iron + 400 μg folate. Women were immunized with pandemic influenza A (H1N1) vaccine at 26- to 28-week gestation. Blood from mothers (baseline, 72-h post-delivery, 3-month postpartum), newborns and infants (3-month) was analyzed for hemoglobin, B12, methylmalonic acid (MMA), total homocysteine (tHcy), ferritin and serum transferrin receptor, C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP). Vitamin B12 was also assessed in breast milk. H1N1-specific antibodies were determined in plasma and colostrum/breast milk. At baseline, 26% women were B12 deficient (<150 pmol/L), 40% had marginal status (150-220 pmol/L), 43% had elevated MMA (>271 nmol/L), and 31% had elevated tHcy (>10 μmol/L). Supplementation increased B12 in plasma, colostrums and breast milk (p < 0.05) and lowered MMA in neonates, mothers and infants at 3 months (p < 0.05). B12 supplementation significantly increased H1N1-specific IgA responses in plasma and colostrums in mothers and reduced proportion of infants with elevated AGP and CRP compared with placebo. Supplementation with 250 μg/day B12 during pregnancy and lactation substantially improved maternal, infant and breast milk B12 status. Maternal supplementation improved H1N1 vaccine-specific responses in mothers only and may alleviate inflammatory responses in infants.


Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission.
The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci.


Tea drinking and microcytic anemia in infants.
To evaluate the effect of tea drinking on the occurrence of microcytic anemia in infants, we studied 122 healthy infants who underwent routine blood counts at the age of 6-12 months. An overall high frequency of anemia (Hb less than 11 gm/dl-48.4%), microcytosis (MCV less than 70 Mm3-21.3%) and microcytic anemia (19%) was found in the whole group. The percentage of tea drinking infants with microcytic anemia (32.6%) was significantly higher than that of the non-tea drinkers (3.5%). The daily amount of tea drinking was 50-750 ml (median 250 ml). The tea drinkers had significantly lower mean levels of hemoglobin than that of the non-tea drinkers (10.5 +/- 1.2 gm/dl vs 11.2 +/- 0.8 gm/dl, respectively) and significantly lower mean levels of mean corpuscular volume than that of the non-tea drinkers (71.5 +/- 7.1 micron 3 vs 76.1 +/- 4.6 micron 3). There were no significant differences between the two groups in their sex distribution and in the duration of breast feeding. The two groups differed with regard to their ages and social class but a multivariate analysis had excluded the possible confounding effect of these differences on the hematological results. Based on our finding we do not recommend giving tea to infants whose main source of iron is from milk, grains, vegetables or medicinal sources.


Prolonged salivary cortisol recovery in second-trimester pregnant women and attenuated salivary alpha-amylase responses to psychosocial stress in human pregnancy.
The underlying biological mechanisms of stress-related pregnancy complications in humans are still poorly understood. Recent research on pharmacological or physical provocation procedures in pregnant women has resulted in inhomogeneous findings. Furthermore, no studies conducted so far have used a psychosocial stress paradigm at different stages of pregnancy. The aim of this study was to identify endocrine, autonomic, and psychological responses to standardized psychosocial stress at different stages of pregnancy. Ninety healthy women (aged 21-37 yr), including 30 pregnant women at the beginning of the second trimester and 30 women at the beginning of the third trimester, as well as 30 nonpregnant women in the follicular phase of their menstrual cycle, underwent a psychosocial stress test. Salivary free cortisol, alpha-amylase, heart rate, and psychological parameters were repeatedly measured. Salivary cortisol recovery was significantly prolonged in second-trimester pregnant women (P = 0.04). Cortisol and heart rate increases of both pregnant groups were shown to be comparable with those of the controls. alpha-Amylase increases of both pregnant groups were markedly attenuated compared with nonpregnant women (P = 0.008). From these data, we conclude that, in contrast to pregnancy in rats, pregnancy in women does not result in a restraint of the hypothalamic-pituitary-adrenal axis to psychosocial stress. Furthermore, attenuated alpha-amylase stress response might reflect protective processes within the autonomic nervous system during pregnancy, whereas prolonged cortisol recovery during the beginning of second-trimester pregnancy might be associated with the vulnerability to stress-related pregnancy complications during this period of time.


Chiral enrichment of serine via formation, dissociation, and soft-landing of octameric cluster ions.
Chiral enrichment of serine is achieved in experiments that involve formation of serine octamers starting from non-racemic serine solutions. Serine octamers were generated by means of electrospray and sonic spray ionization of aqueous solutions of d(3)-L-serine (108 Da) and D-serine (105 Da) having different molar ratios of enantiomers. A cyclic process involving the formation of chirally-enriched octameric cluster ions and their dissociation, viz. Ser(1) --> Ser(8) --> Ser(1), allows serine monomers to be regenerated with increased enantiomeric excess as shown in two types of experiments: (1) Chiral enrichment in serine was observed in MS/MS/MS experiments in a quadrupole ion trap in which the entire distribution of serine octamers formed from non-racemic solutions was isolated, collisionally activated, and fragmented. Monomeric serine was regenerated with increased enantiomeric excess upon dissociation of octamers when compared with the enantiomeric composition of the original solution. (2) Chiral enrichment was observed in the products of soft-landing of mass-selected protonated serine octamers. These ions were generated by means of electrospray or sonic spray ionization, mass selected, and collected on a gold surface using ion soft-landing. Chiral enrichment of the soft-landed serine was established by redissolving the recovered material and comparing the intensities of protonated molecular ions of d(3)-L-serine and D-serine after APCI-MS analysis. Both of these experiments showed comparable results, suggesting that formation of serine octamers depends only on the enantiomeric composition of the serine solution and that the magnitude of the chiral preference is intrinsic to octamers formed from solutions of given chiral composition.