[Study on clinical manifestation, genotype and genetic characteristics of two Kennedy disease pedigrees].
To investigate the clinical manifestations, genotypes, and genetic characteristics of two pedigrees with Kennedy disease. The clinical data of the patients from two Kennedy disease families were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis. Family A was composed of 58 individuals in 4 generations. The proband had onset at 39 years old. There were two Kennedy disease patients in family B which included 61 individuals in 5 generations. The two patients had onset at 39 and 41 years old, respectively. All the three patients displayed limbs and bulbar muscular weakness because of the damage of lower motor neurons. They had androgen insensitivity syndrome in common, and showed mild or moderate increase in serum creatine kinase level. The electromyogram showed wild damage in anterior horn of spinal cord. Muscle biopsy displayed neurogenic muscular atrophy. The numbers of the CAG repeat expansion in the androgen receptor gene of the three patients were 49, 48, and 47, respectively. X-linked recessive mode of inheritance was demonstrated by pedigree analysis in the two families. Kennedy disease usually occurs in mid-adulthood man. The clinical features are the weakness and wasting of limbs and bulbar muscles. Genetic analysis contributes to diagnosis and identification of carriers, and is beneficial to genetic counseling and prenatal diagnosis.


Assessment of urinary gonadotropin and steroid hormone profiles of female cynomolgus monkeys after treatment with Pueraria mirifica.
This study investigated the changes in the urinary hormone levels of female monkeys (Macaca fascicularis) after single-dose and long-term treatments with Pueraria mirifica (PM). The monkeys were separated into 3 groups (n=3) and orally treated with 10, 100, or 1,000 mg of PM in each group. Two series of experiments were performed. In the first series of experiments, the monkeys were orally treated with a single dose of PM. The experimental schedule was divided into a one menstrual cycle pretreatment period and a two menstrual cycle post-treatment period. In the second series of experiments, the monkeys were orally treated daily with PM for 90 days. The experiment schedule was divided into a one menstrual cycle pretreatment period, a three menstrual cycle treatment period, and a two menstrual cycle post-treatment period. Urinary samples were collected daily and assayed for the FSH, LH, estradiol, and progesterone levels. The results showed that there were no changes in the FSH, LH, estradiol, and progesterone levels after treatment with a single dose of 10, 100, or 1,000 mg of PM or after daily treatment with 10 mg of PM for 90 days compared with the levels observed during the pretreatment period. Daily treatment with 100 mg and 1,000 mg of PM for 90 days only produced a clear reduction in the urinary FSH levels. This suggests that changes of urinary FSH levels can be considered an indicator for study of estrogenic effects on hormonal levels in female monkeys.


Steroid-dependent pericarditis following anti-PD1 immunotherapy in a metastatic melanoma patient: a case report.
Immune-related adverse events are increasingly prevalent in the oncologist's practice. Cardiac adverse events are rare but can be life-threatening. Case reports of immune checkpoint inhibitor (ICI)-related pericarditis are scarce and so is the scientific evidence for its management. This is the first report of a steroid-dependent pericarditis. We present a case of a woman with lung metastatic melanoma who developed pericarditis after two infusions of pembrolizumab. The initial response to steroids and colchicine was favourable, and steroids were successfully tapered, after which the immunotherapy was reintroduced. A complete metabolic remission was achieved after six cycles of pembrolizumab, but pericarditis symptoms recur each time the steroid dose is lowered below 10 mg. After introduction of azathioprine, steroids were successfully tapered over the course of 6 months. Because of the chronicity of the pericarditis, it was hypothesized that an underlying auto-immune pericarditis was triggered by the checkpoint inhibitor and the general guidelines for recurrent idiopathic pericarditis were followed, successfully adding azathioprine to taper steroids to stop.


Use of a multinational survey to provide clinical guidelines for upper gastrointestinal bleeding in developing countries.
The OMGE multinational survey of patients with upper gastrointestinal bleeding demonstrated that it was possible to predict patient outcome, using a computer and a database of information from many centres. It remained to be seen whether this database could be used in specific remote areas of the world. To answer this question, two areas have been studied, Sikkim and China. In Sikkim, when the computer-aided prognostic system was used, 69% of patients put into a high-risk group for rebleeding actually did so; and 54% died. By contrast, only 2% of patients placed into a low-risk group for rebleeding did so. As there is little computer technology in Sikkim, a simplified scoring system was developed which gave the same predictive accuracy as the computer system. In China there was a slightly lower accuracy with both systems. Hence a new database and scoring system were created, using only information from Chinese patients. This database improved the results. From the studies it is suggested that these types of systems can be of value to patients in remote areas by targeting patients at high risk rebleeding or dying, so that the scarce resources available can be best used.


Extrauterine Growth Restriction in Very Low Birth Weight Infants: Concordance Between Fenton 2013 and INTERGROWTH-21st Growth Charts.
Postnatal growth restriction has high prevalence in very low birth weight (VLBW) preterm neonates, and this could affect their long-term prognosis. Nowadays, there is no consensus on how to monitor growth in these neonates. Objective: This study aimed to compare prevalence of intra- and extrauterine growth restriction (IUGR and EUGR) in a sample of VLBW infants according to the Fenton 2013 charts and INTERGROWTH-21st (IW-21) standards and to analyze concordance between both in the different EUGR definitions criteria (cross-sectional, dynamic, and true). Patients and Methods: An observational retrospective study of 635 VLBW preterm was performed. The study was carried out in Central University Hospital of Asturias. Body measurements (weight, length, and head circumference) were collected at birth and at hospital discharge and expressed in z-scores for the two references (Fenton 2010 and IW-21). Kappa concordance was calculated. Results: Kappa concordance between Fenton and IW-21 was 0.887 for IUGR and 0.580 for static EUGR. Prevalence was higher according to Fenton in IUGR (36.5 vs. 35.1%), in static EUGR (73.8 vs. 59.3%), and in dynamic EUGR (44.3 vs. 29.3%). Despite observing low prevalence of EUGR when IW-21 was used to define EUGR, a statistical association between neonatal morbidity and diagnosis of EUGR was observed. Conclusion: The Fenton and IW-21 concordance for IUGR is good. IW-21 is more restrictive than Fenton in EUGR. Patients diagnosed by IW-21 as EUGR are more likely to have neonatal morbidity, especially if we use EUGR dynamic definition. In our study, we cannot conclude that one graph is better than the other.


Cardiac patients' perception of patient-centred care: a qualitative study.
The aim of this study was to explore cardiac patients' perception of patient-centred care. Despite patient's importance in the process of care, less attention has been paid to experiences and expectations of patients in definitions of patient-centred care. As patients are an important element in process of patient-centred care, organizing care programs according to their perceptions and expectations will lead to enhanced quality of care and greater patient satisfaction. This study is a descriptive qualitative study. Content analysis approach was performed for data analysis. Participants were 18 cardiac patients (10 women and 8 men) hospitalized in coronary care units of teaching hospitals affiliated to Tehran University of Medical Sciences. We collected the study data through conducting personal face-to-face semi-structured interviews. The participants' perceptions of patient-centred care fell into three main themes including managing patients uncertainty, providing care with more flexibility and establishing a therapeutic communication. The second theme consisted of two sub-themes: empathizing with patients and having the right to make independent decisions. Receiving patient-centred care is essential for cardiac patients. Attention to priorities and preferences of cardiac patients and making decisions accordingly is among effective strategies for achieving patient-centred care. Cardiac care unit nurses ought to be aware that in spite of technological developments and advances, it is still important to pay attention to patients' needs and expectations in order to achieve patient satisfaction. In planning care programs, they should consider accountability towards patients' needs, flexibility in process of care and establishing medical interactions as an effective strategy for improving quality of care.


Angiopoietin-like protein 8/betatrophin as a new determinant of type 2 diabetes remission after bariatric surgery.
This work aimed to explore the link between angiopoietin-like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross-sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow-up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow-up.


Lipidomic profile of human nasal mucosa and associations with circulating fatty acids and olfactory deficiency.
The nasal mucosa (NM) contains olfactory mucosa which contributes to the detection of odorant molecules and the transmission of olfactory information to the brain. To date, the lipid composition of the human NM has not been adequately characterized. Using gas chromatography, liquid chromatography coupled to mass spectrometry and thin layer chromatography, we analyzed the fatty acids and the phospholipid and ceramide molecular species in adult human nasal and blood biopsies. Saturated and polyunsaturated fatty acids (PUFAs) accounted for 45% and 29% of the nasal total fatty acids, respectively. Fatty acids of the n-6 family were predominant in the PUFA subgroup. Linoleic acid and arachidonic acid (AA) were incorporated in the main nasal phospholipid classes. Correlation analysis revealed that the nasal AA level might be positively associated with olfactory deficiency. In addition, a strong positive association between the AA levels in the NM and in plasma cholesteryl esters suggested that this blood fraction might be used as an indicator of the nasal AA level. The most abundant species of ceramides and their glycosylated derivatives detected in NM contained palmitic acid and long-chain fatty acids. Overall, this study provides new insight into lipid species that potentially contribute to the maintenance of NM homeostasis and demonstrates that circulating biomarkers might be used to predict nasal fatty acid content.


Living Cell-Target Responsive Accessibility Profiling Reveals Silibinin Targeting ACSL4 for Combating Ferroptosis.
We report a living cell-target responsive accessibility profiling (LC-TRAP) approach to identify the targetome of silibinin (SIL), a well-established hepatoprotective natural product (NP), in HepG2 cells. Proteins showing accessibility changes, probed by covalent lysine labeling reagents and leveraged by multiplexed quantitative proteomics, following the administration of SIL to the living cells were assigned as potential targets. Among the assigned targetome, ACSL4, an enzyme essential for ferroptosis induction, might be involved in the hepatoprotective effects of SIL and hence was intensively validated. We first demonstrated that SIL protected HepG2 cells from ferroptosis dependent on ACSL4. Then, we used biophysical assays and a SIL-derivatized chemical probe to corroborate that SIL can bind to ACSL4. The ensuing enzymatic assays showed that SIL inhibited ACSL4 enzymatic activity, thereby mitigating the ACSL4-mediated ferroptosis. As such, we revealed that ACSL4 inhibition, using SIL as a model compound, represents a promising hepatoprotective strategy. Further, since TRAP probes the accessibility changes of reactive proteinaceous lysines, it can pinpoint the proximal regions where the ligand engagement may occur. Thus, the LC-TRAP analysis of SIL, the newly discovered ligand of ACSL4, and arachidonic acid (AA), the substrate, intriguingly showed that SIL and AA both affected the conformation of the K536-proximal region of ACSL4, albeit through distinct binding patterns. Collectively, we describe a straightforward LC-TRAP workflow that does not involve ligand-derived probe synthesis and is widely applicable to target discovery of NPs.


[Sex education in Tunisia: students' expectations and teachers' conceptions].
Health education, as defined by the World Health Organization (WHO 1983), includes sex education. In Tunisia, there is a growing interest in sexuality issues, in contrast with the reigning conservative culture, challenging the taboos and restrictions imposed by religion. A global sex education strategy is therefore required in Tunisian in schools to help students understand their body and its biological functions, construct a real sexual identity and adopt behaviours that promote a healthy and low-risk lifestyle. In this study, we wonder whether the objectives defined by official programmes and conveyed by biology teachers are consistent with the expectations of their students in terms of sex education. This questionnaire-based survey, conducted among 95 biology teachers and 735 students, with an average age of 18 years, shows to what extent the objectives of biology teachers differ from the expectations of students, illustrating to what extent sex education needs to be adapted.


[The perspectives of adjuvant chemotherapy of urethral stricture].
A review of preclinical, clinical and postclinical (comparative) studies dedicated to adjuvant therapy for urethral strictures in the form of injections and instillations is presented in the article. The focus is on studies, carried out over the past decade. An information on new antifibrotic drugs used in other areas of medicine that could potentially be used in urology is also provided.


Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation.
Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organism's physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS.


Flow-through multianalyte chemiluminescent immunosensing system with designed substrate zone-resolved technique for sequential detection of tumor markers.
A novel flow-through immunosensing system for performing a multianalyte chemiluminescent determination in a single run was designed. A new analytical strategy of substrate zone-resolved technique was proposed. Using carcinoma antigen 125 (CA 125) and carcinoembryonic antigen (CEA) as model analytes, the capture antibodies for CA 125 and CEA were immobilized on an UltraBind aldehyde-activated membrane to act as an immunoreactor, to which the mixture of CA 125, CEA, and their corresponding tracers, horseradish peroxidase (HRP)-labeled anti-CA 125 and alkaline phosphatase (ALP)-labeled anti-CEA, was introduced for on-line incubation. The substrates for HRP and ALP were then delivered into the detection cell sequentially to perform substrate zone-resolved immunoassay by a sandwich format. Under optimal conditions, CA 125 and CEA could be assayed in the ranges of 5.0-100 units/mL and 1.0-120 ng/mL, respectively. The whole assay process including incubation, wash, detection, and regeneration could be completed in 35 min. The serum samples from the clinic were assayed with the proposed method, and the results were in acceptable agreement with the reference values. This method and the strategy of substrate zone-resolved technique could be further developed for high-throughput multianalyte immunoassay.


Impact of Monovalent Rotavirus Vaccine on Rotavirus Hospitalizations among Children Younger Than 5 Years of Age in the Ouest and Artibonite Departments, Haiti, 2013 to 2019.
Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.


Reconstructing embryonic development.
Novel approaches to bio-imaging and automated computational image processing allow the design of truly quantitative studies in developmental biology. Cell behavior, cell fate decisions, cell interactions during tissue morphogenesis, and gene expression dynamics can be analyzed in vivo for entire complex organisms and throughout embryonic development. We review state-of-the-art technology for live imaging, focusing on fluorescence light microscopy techniques for system-level investigations of animal development, and discuss computational approaches to image segmentation, cell tracking, automated data annotation, and biophysical modeling. We argue that the substantial increase in data complexity and size requires sophisticated new strategies to data analysis to exploit the enormous potential of these new resources.


Inhibitor of Apoptosis Protein (IAP) Antagonists in Anticancer Agent Discovery: Current Status and Perspectives.
Apoptosis, an important form of programmed cell death (PCD), is a tightly regulated cellular process to eliminate unwanted or damaged cells. Resistance of apoptosis is a hallmark of cancer cells. Inhibitor of apoptosis proteins (IAPs) is a class of key apoptosis regulators that promote cancer cell resistant to apoptosis, particularly in cancer treatment. Disrupting the binding of IAPs with their functional partners therefore is a promising strategy to restore the apoptotic response to proapoptotic stimuli, particularly those introduced by standard cancer therapies. The most successful example is the use of small molecules to mimic the IAP-binding motif of an endogenous IAP antagonist, second mitochondria-derived activator of caspase (SMAC). Here we will review the functions of IAPs, the structural interactions of IAPs with SMAC, four generations of SMAC-mimetic IAP antagonists, and representative antagonists in clinical evaluations, focusing on research articles over the past 15 years. Outlooks and perspectives on the associated challenges are provided as well.


[Impact of thymic function in age-related immune deterioration].
Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline.


CC-122 immunomodulatory effects in refractory patients with diffuse large B-cell lymphoma.
In the three patients included in a phase I clinical trial (NCT01421524), we report the immunomodulatory effects and efficacy of CC-122, a novel pleiotropic pathway modifier compound originally developed for broad diffuse large B-cell lymphoma (DLBCL). The chemical structure of CC-122 includes the glutarimide moiety that is known to modulate the immune response. The immunomodulatory agents including lenalidomide represent a promising therapeutic strategy targeting tumors in B-cell lymphoid malignancies. We observed that CC-122 might regulate the NK phenotype and its activity due to the reduced accumulation of myeloid-derived suppressor cell and eventually decrease the Tregs subsets. Finally, the activation of T cells through co-stimulatory molecule (CD28) was detected as a delayed CC-122 effect. In this context, CC-122 arises as an alternative option for DLBCL patients refractory to the traditional chemotherapeutic agents.


Interaction between serum neutrophil gelatinase associated lipocalin and visceral fat area on cardiovascular health in a cohort of community-based individuals.
We assessed the predictive values of neutrophil gelatinase-associated lipocalin (NGAL), fat distribution, and their interaction on the development of major adverse cardiovascular events (MACE) in a community-based cohort of middle-aged and older individuals. This prospective study involved 1349 adults (43.2% men) aged 50-80 y, without baseline cardiovascular diseases, from communities in 2013-2014. All participants were followed up for a mean of 7.6 y via phone calls and medical records. Serum NGAL concentrations were analyzed at baseline. Fat distribution, including subcutaneous fat area and visceral fat area (VFA), was assessed by magnetic resonance imaging. In fully-adjusted Cox regression models, baseline high NGAL concentrations were related to an increased risk of MACE in women [HR 1.75, 95% CI 1.03-2.99], compared with low NGAL concentrations. After stratification by VFA concentrations, the observed association was more predominant in women with baseline low VFA (HR 1.24, 95% CI 1.11-1.38). Moreover, the association between NGAL and MACE was interacted by VFA, strengthening the association at low VFA concentrations (Pinteraction < 0.05). Serum NGAL determined at baseline predicts the development of MACE, and the association is modified by VFA in women.


Mass loss and chemical structures of wheat and maize straws in response to ultraviolet-B radiation and soil contact.
The role of photodegradation, an abiotic process, has been largely overlooked during straw decomposition in mesic ecosystems. We investigated the mass loss and chemical structures of straw decomposition in response to elevated UV-B radiation with or without soil contact over a 12-month litterbag experiment. Wheat and maize straw samples with and without soil contact were exposed to three radiation levels: a no-sunlight control, ambient solar UV-B, and artificially elevated UV-B radiation. A block control with soil contact was not included. Compared with the no-sunlight control, UV-B radiation increased the mass loss by 14-19% and the ambient radiation by 9-16% for wheat and maize straws without soil contact after 12 months. Elevated UV-B exposure decreased the decomposition rates of both wheat and maize straws when in contact with soil. Light exposure resulted in decreased O-alkyl carbons and increased alkyl carbons for both the wheat and maize straws compared with no-sunlight control. The difference in soil contact may influence the contribution of photodegradation to the overall straw decomposition process. These results indicate that we must take into account the effects of photodegradation when explaining the mechanisms of straw decomposition in mesic ecosystems.


A Systematic Review of Interventions That Integrate Perinatal Mental Health Care Into Routine Maternal Care in Low- and Middle-Income Countries.
Women in low- and middle-income countries (LMICs) are disproportionally affected by perinatal depression and anxiety and lack access to mental health care. Integrating perinatal mental health care into routine maternal care is recommended to address gaps in access to mental health care in such under-resourced settings. Understanding the effectiveness of interventions that integrate perinatal mental health care into routine maternal care in LMICs is critical to inform ongoing intervention development, implementation, and scale-up. This systematic review aims to assess the effectiveness of interventions that integrate perinatal mental health care into routine maternal care to improve maternal mental health and infant health outcomes in LMICs. In accordance with the PRISMA guidelines, an electronic database search was conducted seeking publications of controlled trials examining interventions that aimed to integrate perinatal mental health care into routine maternal care in LMICs. Abstracts and full text articles were independently reviewed by two authors for inclusion utilizing Covidence Review Software. Data was extracted and narrative synthesis was conducted. Twenty studies met eligibility criteria from the initial search results of 2,382 unique citations. There was substantial heterogeneity between the study samples, intervention designs, and outcome assessments. Less than half of the studies focused on women with active depression or anxiety. Most studies (85%) implemented single intervention designs involving psychological, psychosocial, psychoeducational, or adjuvant emotion/stress management. There were few interventions utilizing multicomponent approaches, pharmacotherapy, or referral to mental health specialists. Outcome measures and assessment timing were highly variable. Eighteen studies demonstrated significantly greater improvement on depression and/or anxiety measures in the intervention group(s) as compared to control. Integrated interventions can be effective in LMICs. The findings provide a critical understanding of current interventions design gaps. This includes the lack of comprehensive intervention designs that incorporate increasing intensity of treatment for more severe illness, pharmacotherapy, mental health specialist referrals, and non-mental health professional training and supervision. The findings also provide strategies to overcome design and implementation barriers in LMICs. Study findings provide a foundation for future evidence-based adaptation, implementation, and scale-up of interventions that integrate perinatal mental health care into routine maternal care in LMICs. [https://www.crd.york.ac.uk/prospero/display_ record.php?ID=CRD42021259092], identifier [CRD42021259092].


Thermodynamic relations in a driven lattice gas: numerical experiments.
We explore thermodynamic relations in nonequilibrium steady states with numerical experiments on a driven lattice gas. After operationally defining the pressure and chemical potential in the driven lattice gas, we confirm numerically the validity of the integrability condition (the Maxwell relation) for the two quantities whose values differ from those for an equilibrium system. This implies that a free-energy function can be constructed for the nonequilibrium steady state that we consider. We also investigate a fluctuation relation associated with this free-energy function. Our result suggests that the compressibility can be expressed in terms of density fluctuations even in nonequilibrium steady states.


Stereoselective synthesis of tri-substituted tetrahydrothiophenes and their in silico binding against mycobacterial protein tyrosine phosphatase B.
A facile approach to tri-substituted tetrahydrothiophenes via thia-Michael/aldol has been developed. The cascade reaction was carried out in the presence of 5 mol% of DABCO in ethyl acetate to afford diversely functionalized tetrahydrothiophenes (THTs) with excellent diastereoselectivity. The present methodology has broad substrate tolerance. Gram-scale reaction proceeds with equal efficiency. Functional group transformations further highlight the synthetic potential of the THTs. An asymmetric version of the cascade reaction has also been investigated and a maximum of 72% ee was observed with cinchonidine derived squaramide. Moreover, in silico based molecular docking followed by deep learning based affinity prediction and molecular dynamics simulation analysis indicate the synthesized THT derivatives can act as potent competitive inhibitors of MptpB at low micromolar to nanomolar concentrations. In silico ADME analysis further suggests the plausibility of these compounds to act as future anti-mycobacterial therapeutic leads.


Quadrupolar NMR Relaxation from ab Initio Molecular Dynamics: Improved Sampling and Cluster Models versus Periodic Calculations.
Quadrupolar NMR relaxation rates are computed for 17O and 2H nuclei of liquid water, and of 23Na+, and 35Cl- in aqueous solution via Kohn-Sham (KS) density functional theory ab initio molecular dynamics (aiMD) and subsequent KS electric field gradient (EFG) calculations along the trajectories. The calculated relaxation rates are within about a factor of 2 of experimental results and improved over previous aiMD simulations. The relaxation rates are assessed with regard to the lengths of the simulations as well as configurational sampling. The latter is found to be the more limiting factor in obtaining good statistical sampling and is improved by averaging over many equivalent nuclei of a system or over several independent trajectories. Further, full periodic plane-wave basis calculations of the EFGs are compared with molecular-cluster atomic-orbital basis calculations. The two methods deliver comparable results with nonhybrid functionals. With the molecular-cluster approach, a larger variety of electronic structure methods is available. For chloride, the EFG computations benefit from using a hybrid KS functional.


Functional dynamics of deuterated β2 -adrenergic receptor in lipid bilayers revealed by NMR spectroscopy.
G-protein-coupled receptors (GPCRs) exist in conformational equilibrium between active and inactive states, and the former population determines the efficacy of signaling. However, the conformational equilibrium of GPCRs in lipid bilayers is unknown owing to the low sensitivities of their NMR signals. To increase the signal intensities, a deuteration method was developed for GPCRs expressed in an insect cell/baculovirus expression system. The NMR sensitivities of the methionine methyl resonances from the β2 -adrenergic receptor (β2 AR) in lipid bilayers of reconstituted high-density lipoprotein (rHDL) increased by approximately 5-fold upon deuteration. NMR analyses revealed that the exchange rates for the conformational equilibrium of β2 AR in rHDLs were remarkably different from those measured in detergents. The timescales of GPCR signaling, calculated from the exchange rates, are faster than those of receptor tyrosine kinases and thus enable rapid neurotransmission and sensory perception.


A Genetic Lung Cancer Susceptibility Test may have a Positive Effect on Smoking Cessation.
Smoking increases the risk of developing lung cancer. Genetic loci have been identified which could form the basis of a lung cancer susceptibility test; but little is known whether such a test would interest or motivate those trying to quit smoking. To address this, we investigated the attitudes of people trying to quit smoking towards genetic susceptibility testing for lung cancer. Participant's attitudes to topics associated with lung cancer susceptibility testing were assessed; were they interested in genetic testing? What impact would a hypothetical high- or low- risk result have on smoking cessation? 680 self-completion questionnaires were given to individuals attending National Health Service stop smoking clinics in three different areas of the United Kingdom between 2011 and 2012. 139 questionnaires were returned, giving a 20 % response rate. Participants expressed an interest in a genetic susceptibility test for lung cancer and almost all reported that a high-risk result would increase their motivation to stop smoking. However, many participants had a neutral attitude towards a low-risk result. Most participants agreed their smoking habit could lead to lung cancer. Lung cancer susceptibility testing may be a useful incentive to help people quit smoking. This study suggests the need for genetic services to work with smoking cessation teams if routine testing becomes available in the future.


Nursing in Switzerland: struggling to maintain quality and ideals.
After an edited transcript of an interview with a nurse leader, Teodora Duarte, RN; MA, on nursing in Switzerland, the author further discusses the challenges and opportunities facing nursing in that country from a global perspective. Also discussed are some of the advantages and problems of international nursing, in particular nurses who migrate to work in other countries or commute across national borders.


Update on endometriosis pathogenesis.
Endometriosis is a chronic, inflammatory, condition of high incidence and serious reproductive and general health consequences. Understanding the pathogenesis of endometriosis is crucial for proper diagnostic and ordering the most effective treatment. Even though there is a large body of data regarding this pathology our understanding of the pathogenesis of this disease remains incomplete. The aim of this review is to summarize contemporary data regarding pathogenesis of endometriosis. Current data regarding endometrial origin, metaplastic and Mullerian embryonic rests theory will be reviewed here. Also genetic, epigenetic, environmental factors and immunological dysfunction role in endometriosis will be summarized. To conclude, a lot of effort must be put to integrate the abundant data from genetic, epigenetic and immunological studies to propose one coherent theory for the pathogenesis of endometriosis.


Unusual Presentations of Primary and Metastatic Adenoid Cystic Carcinoma Involving the Skin.
Adenoid cystic carcinoma (ACC) is most commonly seen in the salivary glands but may occur at other sites. Primary or metastatic involvement of the skin is unusual. We report 2 cases of ACC with unusual presentation. In the first case, a 55-year-old woman presented with a cutaneous lesion on the right shin, and final pathology showed ACC. An extracutaneous origin was excluded by clinical and imaging studies. In the second case, a 49-year-old woman presented with a nodule on the breast, and biopsy confirmed high-grade ACC (>30% solid areas). She underwent lumpectomy and subsequent mastectomy after recurrence. Sixteen months after the initial diagnosis of ACC of the breast, distant metastases at multiple sites, including the skin, were identified. This report will increase awareness of these rare presentations of cutaneous ACC and allow correct diagnosis and appropriate management of such cases.


[Hemoglobin abnormalities diagnosis in the clinical laboratory (author's transl)].
For routine detection of hemoglobin abnormalities, a number of tests are necessary including hemoglobin electrophoresis at alkaline pH, the study of hemoglobin molecular stability, possibly assay for hemoglobin A2 and hemoglobin F, as well as tests for reduced hemoglobin solubility in cases where hemoglobin S is suspected. Among the complementary techniques required for identification of abnormal hemoglobin or electrophoretically "silent" mutants, isoelectrofocalization is the method of choice and is easily set up in the clinical laboratory.


A case of air-bag associated severe ocular injury.
Air-bags have received widespread support as an effective means of enhancing automotive safety, and they are becoming more common as standard automobile equipment on many cars. Although air-bag induced ocular injuries are rare, they present a serious concern because of the possibility of permanent damage or visual impairment. To date, most reports have investigated ocular injury from high velocity motor vehicle accidents and reports of ocular injury from low speed motor vehicle accidents have been rare. We describe a patient who sustained severe ocular injury, including periorbital fracture, hyphema, vitreous hemorrhage, and choroidal rupture of the macular area, due to an inflated air-bag in a low speed motor vehicle accident.


Differential effects of two period genes on the physiology and proteomic profiles of mouse anterior tibialis muscles.
The molecular components that generate and maintain circadian rhythms of physiology and behavior in mammals are present both in the brain (suprachiasmatic nucleus; SCN) and in peripheral tissues. Examination of mice with targeted disruptions of either mPer1 or mPer2 has shown that these two genes have key roles in the SCN circadian clock. Here we show that loss of the clock gene mPer2 affects forced locomotor performance in mice without altering muscle contractility. A proteomic analysis revealed that the anterior tibialis muscles of the mPer2 knockout mice had higher levels of glycolytic enzymes such as triose phosphate isomerase and enolase than those of either the wild type or mPer1 knockout mice. In addition, the level of expression of HSP90 in the mPer2 mutant mice was also significantly higher than in wildtype mice. These results suggest that the reduced locomotor endurance of the mPer2 knockout mice reflects a greater dependence on anaerobic metabolism under stress conditions, and that the two canonical clock genes, mPer1 and mPer2, play distinct roles in the physiology of skeletal muscle.


Plasmapheresis as immunotherapeutic modality in the treatment of the canine venereal tumor.
Plasmapheresis was evaluated as a treatment modality for the transmissible venereal tumor (TVT) of the dog. The TVT is a unique tumor because of its capability for transplantation as a homograft between untreated randomly bred dogs and is characterized by the presence of dog leukocyte antigen (DLA) determinants on its tumor cells and reactivity in the mixed leukocyte tumor cell culture (MLTC). In the progressing phase, high titers of blocking antibodies measurable in the MLTC were noted. The purpose of this study was to evaluate the influence of plasmapheresis on the growth of established TVT and to correlate tumor response with the removal of blocking factors. Six pairs of DLA-identical dogs were used as experimental and control animals. Plasmapheresis was performed by discontinuous centrifugation using the Hemonetics model 30. An average of 1100 +/- 120 ml of plasma was exchanged on consecutive days during the third week after tumor injection. Consistently lower growth rates were observed in 2 experimental dogs, but there was no early rejection. Sera taken at day 14 of tumor growth contained significant blocking activity in all 12 dogs. Sera obtained post-plasmapheresis showed a decrease of blocking activity in all 6 experimental dogs, P less than 0.001. The TVT appears to be a suitable model for preclinical studies of plasmapheresis alone and in combination with other modalities.


Characterization and expression analysis of a fiber differentially expressed Fasciclin-like arabinogalactan protein gene in Sea Island cotton fibers.
Fasciclin-like arabinogalactan (FLA) protein is a cell-wall-associated protein playing crucial roles in regulating plant growth and development, and it was characterized in different plants including Upland cotton (Gossypium hirsutum L.). In cDNA-AFLP analysis of 25 DPA (days post anthesis) fiber mRNA, two FLA gene-related transcripts exhibit differential expression between Sea Island cotton (G. barbadense L.) and Upland cotton. Based on the transcript-derived fragment, RACE-PCR and realtime PCR technique, GbFLA5 full-length cDNA was isolated and its expression profiles were characterized in both cotton plant tissues and secondary cell wall (SCW) fibers in this study. The 1154 bp GbFLA5 cDNA contains an ORF of 720 bp, encoding GbFLA5 protein of 239 amino acids residues in length with an estimated molecular mass of 25.41 kDa and isoelectric point of 8.63. The deduced GbFLA5 protein contains an N-terminal signal sequence, two AGP-like domains, a single fasciclin-like domain, and a GPI anchor signal sequence. Phylogenetic analysis shows that GbFLA5 protein is homologous to some known SCW-specific expressed FLAs of plant developing xylem, tension wood and cotton fibers. In the SCW deposition stage from 15 to 45 DPA detected, FLA5 maintains a significantly higher expression level in Sea Island cotton fibers than in Upland cotton fibers. The increasing FLA5 transcript abundance coincided with the SCW deposition process and the expression intensity differences coincided with their fiber strength differences between Sea Island cotton and Upland cotton. These expression profile features of GbFLA5 in cotton fibers revealed its tissue-specific and SCW developmental stage-specific expression characters. Further analysis suggested that GbFLA5 is a crucial SCW-specific protein which may contribute to fiber strength by affecting cellulose synthesis and microfibril deposition orientation.


Effect of Molecular Crowding on Complexation of Metal Ions and 8-Quinolinol-5-Sulfonic Acid.
The effect of molecular crowding on macromolecular reactions has been revealed by many researchers. In this study, we investigate the complexation of metal ions (Zn, Co, and Cd) with 8-quinolinol-5-sulfonic acid as a model of small-molecular reactions in molecular crowding. The complexation constants for 1:1, 1:2, and total complexation in the presence of polyethylene glycol (PEG, a molecular crowding reagent) are evaluated based on the increase in the reactant activity by volume exclusion and the decrease in the water activity due to the change in osmotic pressure. All complexation constants are enhanced by increasing the concentration of PEG. Its mechanisms differ for 1:1, 1:2, and total complexation. The 1:1 complexation is promoted only by the influence of the water activity, while the reactant and water activities influence the increase in the 1:2 complexation constant. Increasing the molecular weight of PEG further increases the complexation constants, as dehydration of the complex is promoted by a higher hydration number of PEG. Because this study gives the fundamental knowledge for the protein-metal interaction, in which solvation is an important factor, in molecular crowding, it provides new insights into molecular crowding studies and should attract the attention of a broad spectrum of biochemistry researchers.


A new tiazofurin pronucleotide: synthesis and biological evaluation of cyclosaligenyl-tiazofurin monophosphate.
Synthesis and biological activities of cyclosaligenyl-tiazofurin monophosphate (CycloSal-TRMP), a new tiazofurin pronucleotide, are reported. CycloSal-TRMP proved to be active in vitro against human myelogenous leukemia K562 cell line and as A1 adenosine receptor agonist.


Conditioning history and the reinforcing effects of drugs: comment on Alessi, Roll, Reilly, and Johanson (2002).
Drug reinforcement plays a central role in drug abuse. Drugs of abuse are unconditioned reinforcers whose functional effects are mediated through neuropharmacological mechanisms. The role of conditioning has received attention, but the focus has been on associations between environmental cues and unconditioned drug stimuli. Recent studies by C.-E. Johanson, A. Mattox, and C. R. Schuster (1995) and S. M. Alessi, J. M. Roll, M. P. Reilly, and C.-E. Johanson (2002) have demonstrated that drugs can also acquire functional control over human behavior through conditioning processes. Given the potent effects that conditioned reinforcers (e.g., money) can have on human behavior, studies by Johanson et al. and Alessi et al. should engender further examination of conditioning processes and drug reinforcement.


Pneumomediastinum as first manifestation of emphysematous pyelonephritis in a patient who is non-diabetic.
Emphysematous pyelonephritis (EPN) is a rare but life-threatening acute suppurative infection of the kidney, characterised by production of gas within the renal parenchyma, collecting system or perirenal tissue. It has a high mortality rate (70% to 90%), and the majority of patients have diabetes mellitus. The left kidney is most common involved and Escherichia coli is the most common pathogen. EPN complicated with pneumomediastinum (PM) has been reported in only four cases previously. Here, a case of PM as first manifestation of EPN in a non-diabetic 81-year-old man is reported. He had experienced back pain and abdominal fullness for 1 week. A plain radiograph, CT aortography and MRI confirmed the diagnosis of EPN complicated with PM. The patient died on the 22nd day of treatment with antibiotics of cefmetazole, gentamycin and metronidazole.


Cost Analysis and Rational Use of Anti-Glaucoma Therapy in a Tertiary Hospital in Ghana.
Glaucoma is the leading cause of irreversible blindness worldwide. In Ghana, 19.4% of all blindness recorded is due to glaucoma. Reducing intraocular pressure medically (using eye drops) is the evidence-based therapeutic option. To determine the rational use and undertake cost analysis of anti-glaucoma drugs among patients attending clinic at the Lions International Eye Centre (LIEC), Korle-Bu Teaching Hospital. In this cross-sectional study, we reviewed all prescriptions presented to the pharmacy unit from 01/12/2015 to 31/03/2016. The dispensed drops were classified, and all anti-glaucoma drugs were identified. This was followed by cost analysis. A total of 588 prescriptions were captured, 27.3% (161/588) contained an anti-glaucoma medication. The mean number of anti-glaucoma medications was 1.71 of which 52.7% was prescribed to females. Prostaglandin analogs (PGA) were the most prescribed (37% (102/276)), followed by beta blockers (25.4% (70/276)), carbonic anhydrase group of medicines (16.3% (45/276)), combined beta blockers (11.2% (31/276)), alpha agonists (8.7% (24/276)) and miotics (1.4% (4/276)). The median (IQR) cost of anti-glaucoma therapy per prescription per month was GHC 65.00 (GHC38.5-GHC140) about [US$16.25 (US$ 9.6-US$35)]. Azopt (Brimonidine) was the most expensive with daily treatment cost of GHC 5.8 (about US$ 1.45), whilst the least expensive drug with a daily treatment cost of GHC 0.14 (about US$ 0.035) was timolol eye drops. Prostaglandin analogs though expensive remain the most preferred treatment for managing glaucoma at the Korle-Bu Eye Centre in Ghana. This may adversely affect treatment among the poor since prostaglandins analogs are currently not covered by insurance.


Revisiting Alkoxysilane Assembly on Silica Surfaces: Grafting versus Homo-Condensation in Solution.
Silica surface functionalization is often done through the condensation of functional silanes on silanols, silica surfaces' terminal groups. APTES, aminopropyltriethoxysilane, is widely used due to its assumed high reactivity with silanols, kinetically promoted by the catalytic action of the terminal amine function. Here, we revisit, based on a quantitative analysis by solid-state 29Si NMR, the assembly of this silane on silica surfaces to investigate whether its presence results from grafting, i.e., hetero-condensation with silanol groups or from homo-condensation of silane molecules in solution leading to polycondensates physisorbed on silica. We investigate the interaction of APTES with a crystalline layered silicate, ilerite, and with amorphous nonporous silica. We also studied a second silane, cyanopropyltrichlorosilane (CPTCS), terminated with a nitrile group. Our results undoubtedly prove that while CPTCS is grafted on the silica surface, the presence of APTES on silica and silicate materials is only marginally associated with silanol consumption. The analysis of the signal related to silicon atoms from silanes (Tn species) and those from silica (Qn species) allowed for the accurate estimation of the extent of homo-condensation vs grafting based on the ratio of T-O-T/Q-O-T siloxane bridges. These findings deeply question the well-established certainties on APTES assembly on silica that should no longer be seen as grafting of alkoxysilane by hetero-condensation with silanol groups but more accurately as a homo-condensed network of silanes, predominantly physisorbed on the surface but including some sparse anchoring points to the surface involving less than 6% of the overall silanol groups.


Molecular actions of two synthetic brassinosteroids, iso-carbaBL and 6-deoxoBL, which cause altered physiological activities between Arabidopsis and rice.
Brassinosteroid (BR) is an important plant hormone that is perceived by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor. BRI1 is conserved among dicot and monocot species; however, the molecular mechanism underlying BR perception in monocots is not fully understood. We synthesised two BRs, iso-carbabrassinolide (iso-carbaBL) and 6-deoxoBL, which have different BR activities in Arabidopsis thaliana (Arabidopsis) and rice. Our bioassay indicated that iso-carbaBL has relatively strong BR activity in Arabidopsis, but is inactive in rice and competitively inhibits BR activity. The bioactivity of 6-deoxoBL was similar to that of BL in Arabidopsis, but was much lower in rice. Binding experiments using recombinant Arabidopsis and rice BRI1 protein fragments suggested that iso-carbaBL and 6-deoxoBL bind to both receptors. These results showed that iso-carbaBL and 6-deoxoBL act as an antagonist and agonist, respectively, of BRs in rice. A docking simulation analysis suggested that iso-carbaBL fits deeper in the binding pocket to block the binding of active BR to rice BRI1. The simulated binding energy of 6-deoxoBL with rice BRI1 is much lower than that with Arabidopsis BRI1. The possible structural characteristics of rice BRI1 were determined based on the difference in the BR activities of iso-carbaBL and 6-deoxoBL in Arabidopsis and rice.


Biobehavioral composite of social aspects of anxiety in young adults with fragile X syndrome contrasted to autism spectrum disorder.
Social anxiety is a common disorder that has negative impacts across multiple domains of function. Several clinical groups are at elevated risk for social anxiety, including those with fragile X syndrome and those with autism spectrum disorder. Measuring social anxiety in these clinical subgroups is fraught with challenge, however, given the complexity of social anxiety and measurement limitations that are particularly acute in persons with neurodevelopmental disorders. The over-arching aim of this study was to contribute to our understanding of the nature of social anxiety in fragile X syndrome and its association with autism spectrum disorder. To address this aim, we created a multi-faceted composite representing behavioral and biological aspects of social anxiety and examined differences in two adolescent and young adult-aged groups: 59 males with fragile X syndrome and 18 males with autism spectrum disorder. Results indicated a lower score on the multivariate composite for the males with fragile X syndrome relative to autism spectrum disorder but with evidence that traits of autism and social anxiety overlap. We conclude that measuring anxiety and autism traits in fragile X syndrome and autism spectrum disorder is complex with features that overlap and interact in a dynamic manner.


Can Tracheostomy Improve Outcome and Lower Resource Utilization for Patients with Prolonged Mechanical Ventilation?
It is not clear whether the benefits of tracheostomy remain the same in the population. This study aimed to better examine the effect of tracheostomy on clinical outcome among prolonged ventilator patients. Data were from the medical claims data in Taiwan. A total of 3880 patients with ventilator use for more than 14 days between 2005 and 2009 were identified. Among them, 645 patients with tracheostomy conducted within 30 days of ventilator use were compared to 2715 patients without tracheostomy on death during hospitalization and study period, and successful weaning and medical utilization during hospitalization. Cox proportional hazards and linear regression models were used to examine the associations between tracheostomy and the main outcomes. The tracheostomy rate was 30%, and 55% of tracheostomies were performed within 30 days of mechanical ventilation. After adjustments, patients with tracheostomy were at a lower risk of death during hospitalization (hazard ratio [HR] =0.51; 95% confidence interval [CI] =0.43-0.61) and 5-year observation (HR = 0.73; 95% CI = 0.66-0.81), and a lower probability of successful weaning (HR = 0.88; 95% CI = 0.79-0.99). Higher medical use was also observed in patients with tracheostomy. The beneficial effect for tracheostomy observed in our data was the reduction of death. However, patients with tracheostomy were less likely to wean and more likely to consume medical resources.


A cross-sectional analysis of green space prevalence and mental wellbeing in England.
With urbanisation increasing, it is important to understand how to design changing environments to promote mental wellbeing. Evidence suggests that local-area proportions of green space may be associated with happiness and life satisfaction; however, the available evidence on such associations with more broadly defined mental wellbeing in still very scarce. This study aimed to establish whether the amount of neighbourhood green space was associated with mental wellbeing. Data were drawn from Understanding Society, a national survey of 30,900 individuals across 11,096 Census Lower-Layer Super Output Areas (LSOAs) in England, over the period 2009-2010. Measures included the multi-dimensional Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) and LSOA proportion of green space, which was derived from the General Land Use Database (GLUD), and were analysed using linear regression, while controlling for individual, household and area-level factors. Those living in areas with greater proportions of green space had significantly higher mental wellbeing scores in unadjusted analyses (an expected increase of 0.17 points (95% CI 0.11, 0.23) in the SWEMWBS score for a standard deviation increase of green space). However, after adjustment for confounding by respondent sociodemographic characteristics and urban/rural location, the association was attenuated to the null (regression coefficient B = - 0.01, 95% CI -0.08, 0.05, p = 0.712). While the green space in an individual's local area has been shown through other research to be related to aspects of mental health such as happiness and life satisfaction, the association with multidimensional mental wellbeing is much less clear from our results. While we did not find a statistically significant association between the amount of green space in residents' local areas and mental wellbeing, further research is needed to understand whether other features of green space, such as accessibility, aesthetics or use, are important for mental wellbeing.


Reproducibility of serial creatinine excretion measurements in peritoneal dialysis.
To test whether muscle mass evaluated by creatinine excretion (EXCr) is maintained in patients with end-stage kidney disease (ESKD) treated by peritoneal dialysis (PD), we evaluated repeated measurements of EXCr in a PD population. One hundred and sixty-six PD patients (94 male, 72 female) receiving the same PD dose for the duration of the study (up to approximately 2.5 years) had repeated determinations of total (in urine plus spent dialysate) 24-h EXCr (EXCr T) to assess the adequacy of PD by creatinine clearance. All 166 patients had two EXCr T determinations, 84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements. EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times. In patients who were studied twice, with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EXCr T did not differ between the first and second study. In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD, EXCr T did not differ between the first and second study, but was significantly lower in the third study compared to the first study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EXCr T did not differ between any of the studies. The average EXCr T value did not change significantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EXCr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more. The average value of EXCr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule. However, repeated individual EXCr T values vary considerably in a large proportion of the patients. Further studies are needed to evaluate the clinical significance of varying EXCr T values and the stability of EXCr T beyond 2.5 years of PD follow-up.


Frequency, intensity and localization of pain as risk factors for frailty in older adults.
the association between pain characteristics and frailty risk is uncertain. to investigate the separate impact of the frequency, intensity and location of pain on frailty risk and its possible mechanisms. prospective cohort of 1505 individuals ≥63 years followed between 2012 and 2015 in Spain. In 2012, pain was classified into: lowest pain (Score 0), middle pain (Score 1-4) and highest pain (Score 5-6). Incident frailty was assessed in 2015 as having ≥3 Fried criteria or a Frailty Index (FI) ≥0.30. in multivariate analyses, the risk of frailty (measured with the Fried criteria or the FI) increased progressively with the frequency of pain, its intensity and the number of pain locations. Compared with those having the lowest pain score, the odds ratio (95% confidence interval) of Fried-based frailty was 1.24 (0.56-2.75) in the middle score and 2.39 (1.34-4.27; P-trend <0.01) in the highest score. Corresponding values for frailty as FI ≥0.30 were 1.39 (0.80-2.42) and 2.77 (1.81-4.24; P-trend <0.01). Odds ratios did not change after adjustment for alcohol intake, Mediterranean diet adherence or sedentary time, but were reduced with adjustment for pain-associated chronic diseases (cardiovascular disease, diabetes, chronic lung disease, osteomuscular disease and depression). A higher pain score was linked to higher risk of exhaustion and low physical activity (two out of five Fried criteria) and to a worse score in all FI domains. frequency, intensity and location of pain were associated with higher risk of frailty. Study associations were partly explained by pain-associated morbidity.


Is impingement the cause of jumper's knee? Dynamic and static magnetic resonance imaging of patellar tendinitis in an open-configuration system.
Chronic overload is considered the main cause of patellar tendinitis, but it has been postulated that impingement of the inferior patellar pole against the patellar tendon during knee flexion could be responsible. The role of the patellar pole in patellar tendinitis can be determined by dynamic magnetic resonance imaging. Case-control study. We compared 19 knees with patellar tendinitis and 32 asymptomatic knees of age-matched subjects using an open-configuration magnetic resonance imaging system. Dynamic sagittal images were obtained from full extension to 100 degrees of flexion with and without activation of the quadriceps muscle. The following measurements were made from the images: tendon-patella angle, anteroposterior diameter of the tendon, signal difference-to-noise ratio, the shape of the inferior patellar pole, and the location of the patellar tendon insertion. The tendon-patella angle was not significantly different between groups at any flexion angle, with or without quadriceps muscle activation. The insertion site of the patellar tendon differed significantly but not the shape of the inferior pole of the patella. The volume and the signal difference-to-noise ratio of zones of increased intratendinous signal as well as the anteroposterior diameter of the proximal patellar tendon were increased in symptomatic knees. The relationship between the patella and the patellar tendon was identical in both groups; therefore, chronic overload seems to be a major cause of patellar tendinitis.


Automated x-ray/light field congruence using the LINAC EPID panel.
X-ray/light field alignment is a test described in many guidelines for the routine quality control of clinical linear accelerators (LINAC). Currently, the gold standard method for measuring alignment is through utilization of radiographic film. However, many modern LINACs are equipped with an electronic portal imaging device (EPID) that may be used to perform this test and thus subsequently reducing overall cost, processing, and analysis time, removing operator dependency and the requirement to sustain the departmental film processor. This work describes a novel method of utilizing the EPID together with a custom inhouse designed jig and automatic image processing software allowing measurement of the light field size, x-ray field size, and congruence between them. The authors present results of testing the method for aS1000 and aS500 Varian EPID detectors for six LINACs at a range of energies (6, 10, and 15 MV) in comparison with the results obtained from the use of radiographic film. Reproducibility of the software in fully automatic operation under a range of operating conditions for a single image showed a congruence of 0.01 cm with a coefficient of variation of 0. Slight variation in congruence repeatability was noted through semiautomatic processing by four independent operators due to manual marking of positions on the jig. Testing of the methodology using the automatic method shows a high precision of 0.02 mm compared to a maximum of 0.06 mm determined by film processing. Intraindividual examination of operator measurements of congruence was shown to vary as much as 0.75 mm. Similar congruence measurements of 0.02 mm were also determined for a lower resolution EPID (aS500 model), after rescaling of the image to the aS1000 image size. The designed methodology was proven to be time efficient, cost effective, and at least as accurate as using the gold standard radiographic film. Additionally, congruence testing can be easily performed for all four cardinal gantry angles which can be difficult when using radiographic film. Therefore, the authors propose it can be used as an alternative to the radiographic film method allowing decommissioning of the film processor.


The anti-aging protein alpha-Klotho in systemic sclerosis patients: does a relationship to telangiectasia exist?
The anti-aging protein alpha-Klotho has been reported to have an emerging role in the pathogenesis of systemic sclerosis (SSc). More studies are needed to approach this issue. This study aimed to assess the serum levels of α‑Klotho in SSc patients compared to healthy controls, and to correlate them with the disease parameters. Forty-two SSc patients were included in this study. History taking, clinical examination, and related investigations were performed. The modified Rodnan skin score (mRss) was used to assess skin tightness in SSc patients. Twenty-seven age- and sex-matched healthy participants served as controls. Serum α‑Klotho was assessed in the two groups. SSc patients comprised 39 females and 3 males; mean age was 42.2 ± 12.1 years and mean disease duration 8.5 ± 6.3 years. Serum α‑Klotho levels were decreased in scleroderma patients in comparison to healthy controls (p < 0.001). Scleroderma patients who had higher frequencies of telangiectasias and digital ischemic lesions had higher serum α‑Klotho levels (p = 0.01 and p = 0.04, respectively). By simple regression, only telangiectasias were significantly associated with higher α‑Klotho levels (p = 0.01). No other significant relationships were found between serum α‑Klotho and SSc disease parameters. Scleroderma patients had significantly lower serum α‑Klotho levels than healthy controls. Higher α‑Klotho levels were significantly associated with telangiectasias. An imbalance in serum α‑Klotho levels may be involved in systemic sclerosis. Further longitudinal studies in a larger population of systemic sclerosis patients may provide a clearer clue for its role.


Metastatic melanoma of the tongue: a case report with immunohistochemical profile.
Melanoma of the skin is characterised by a high metastatic potential, but reports of metastasis to the tongue are rare. We report a case of skin melanoma with metastasis to the lymph nodes, tongue and brain. This report highlights the clinical and histological features of oral metastatic melanoma. A 72-year-old man was seen with a nodule on the tongue. The differential diagnosis included salivary gland tumour, lymphoma and metastatic melanoma. His medical history revealed treatment for melanoma in the periumbilical region and micrometastases in the inguinal lymph nodes. An incisional biopsy was obtained and histological analysis showed the presence of a solid, epithelioid malignant tumour of monotonous appearance infiltrating the skeletal musculature. Immunohistochemistry showed reactivity of neoplastic cells to anti-HMB45, anti-melan A and anti-S100 antibodies and negativity for anti-PAN cytokeratin, confirming the diagnosis of metastatic melanoma. The present findings highlight the importance of a complete medical evaluation of the patient by anamnesis to identify possible oral repercussions of primary diseases in other organs and/or systems.


TARP γ-2 Is Required for Inflammation-Associated AMPA Receptor Plasticity within Lamina II of the Spinal Cord Dorsal Horn.
In the brain, transmembrane AMPAR regulatory proteins (TARPs) critically influence the distribution, gating, and pharmacology of AMPARs, but the contribution of these auxiliary subunits to AMPAR-mediated signaling in the spinal cord remains unclear. We found that the Type I TARP γ-2 (stargazin) is present in lamina II of the superficial dorsal horn, an area involved in nociception. Consistent with the notion that γ-2 is associated with surface AMPARs, CNQX, a partial agonist at AMPARs associated with Type I TARPs, evoked whole-cell currents in lamina II neurons, but such currents were severely attenuated in γ-2-lacking stargazer (stg/stg) mice. Examination of EPSCs revealed the targeting of γ-2 to be synapse-specific; the amplitude of spontaneously occurring miniature EPSCs (mEPSCs) was reduced in neurons from stg/stg mice, but the amplitude of capsaicin-induced mEPSCs from C-fiber synapses was unaltered. This suggests that γ-2 is associated with AMPARs at synapses in lamina II but excluded from those at C-fiber inputs, a view supported by our immunohistochemical colabeling data. Following induction of peripheral inflammation, a model of hyperalgesia, there was a switch in the current-voltage relationships of capsaicin-induced mEPSCs, from linear to inwardly rectifying, indicating an increased prevalence of calcium-permeable (CP) AMPARs. This effect was abolished in stg/stg mice. Our results establish that, although γ-2 is not typically associated with calcium-impermeable AMPARs at C-fiber synapses, it is required for the translocation of CP-AMPARs to these synapses following peripheral inflammation.SIGNIFICANCE STATEMENT In the brain, transmembrane AMPAR regulatory proteins (TARPs) critically determine the functional properties of AMPARs, but the contribution of these auxiliary subunits to AMPAR-mediated signaling in the spinal cord remains unclear. An increase in the excitability of neurons within the superficial dorsal horn (SDH) of the spinal cord is thought to underlie heighted pain sensitivity. One mechanism considered to contribute to such long-lived changes is the remodeling of the ionotropic AMPA-type glutamate receptors that underlie fast excitatory synaptic transmission in the SDH. Here we show that the TARP γ-2 (stargazin) is present in SDH neurons and is necessary in a form of inflammatory pain-induced plasticity, which involves an increase in the prevalence of synaptic calcium-permeable AMPARs.


Synthesis and structures of novel 1-methylcytosinato-bridged (ethylenediamine)platinum(II) and platinum(III) dinuclear complexes.
The reaction of [Pt(en)(H(2)O)(2)](2+) with 1 equivalent of 1-methylcytosine at an initial pH of 6 ultimately led to the 1-methylcytosinato-bridged (ethylenediamine)platinum(II) dimer, [(en)Pt(MetCyt-H)(2)Pt(en)](NO(3))(2) (1). The species during the reactions prior to formation of 1 have been investigated by using (195)Pt NMR spectroscopy. From the reaction mixture the [Pt(en)(MetCyt)(2)](NO(3))(2) complex (3) could be isolated and structurally characterized. A rational synthesis of 1 was also achieved by dimerization of [Pt(en)(MetCyt)(H(2)O)](NO(3))(2). According to X-ray structure analysis, the Pt-Pt distance of 2.9816(3) A in 1 is well comparable with the corresponding value found in the cis-diammineplatinum(II) analog (2.981(2) A). Oxidation of 1 with K(2)S(2)O(8) led to the symmetrically sulfate-capped diplatinum(III) complex with two ethylenediamine ligands equatorially bound to the two Pt atoms ht-[(SO(4))(en)Pt(MeCyt-H)(2)Pt(en)(SO(4))] (5), as established by X-ray crystallography. When the oxidation was carried out in the presence of HClO(4), the formation of the hydroxido/aqua ht-1-methylcytosinato bridged (en)Pt(III) dimer ht-[H(2)O(en)Pt(MetCyt-H)(2)Pt(en)OH](ClO(4))(3) (6) was observed, as supported by elemental and X-ray structure analysis. In the structure of 6, two ethylenediamine ligands are differently bound to the two Pt centers: one of them equatorially while the second one caps the opposite axial site of the diplatinum(III) core. The Pt-Pt distances in the platinum(iii) dimers are 2.5982(4) in 5 and 2.5569(3) A in 6.


Direct comparison of optical frequency combs using a comb-injection-lock technique.
This paper demonstrates a direct comparison of optical frequency combs (OFCs) with different repetition rates without a stable intermediate laser using a single-mode comb-injection-lock technique. Two OFCs based on Ti:Sapphire mode-locked lasers were compared utilizing a single-mode diode laser for the selection and the amplification of one mode of an OFC by comb-injection, which makes the direct comb comparison possible. The frequencies of the two combs were found to agree within 0.019 Hz at 352 THz with the uncertainty of 0.25 Hz (7.1 x 10(-16) ). This is one of the best results among the comparisons of combs referenced to a microwave frequency. This technique simplifies the comb comparison utilities and can be applied even when repetition rates differ.


Inner nuclear membrane and signal transduction.
Recent research has shown that the inner nuclear membrane is a site for regulation of signal transduction from the plasma membrane to the nucleus. This has coincided with discoveries showing that mutations in extrinsic and intrinsic inner nuclear membrane proteins cause a variety of inherited diseases. In most instances, the mechanisms by which mutations in inner nuclear membrane proteins cause disease are not understood. In at least one case, however, an alteration in signal transduction appears to underlie disease pathogenesis.


Angiotensin II AT1 receptor blockade prevents gastric ulcers during cold-restraint stress.
Cold-restraint stress reduces gastric blood flow and produces acute gastric ulcers. We studied the role of Angiotensin II (Ang II) on gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated for 14 days with the AT(1) receptor antagonist candesartan before cold-restraint stress. AT(1) blockade increased gastric blood flow 40% to 50%; prevented gastric ulcer formation by 70% to 80%; reduced the increase in adrenomedullary epinephrine and TH mRNA without preventing the stress-induced increase in adrenal corticosterone; decreased the stress-induced expression of tumor necrosis factor alpha (TNF-alpha) and adhesion protein ICAM-1 in arterial endothelium, and neutrophil infiltration in the gastric mucosa; and decreased PGE(2) content. AT(1) receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, anti-inflammatory effects with reduction in TNF-alpha, and ICAM-1 expression, leading to reduced neutrophil infiltration while maintaining the protective glucocorticoid effects and PGE(2) release. Ang II has a crucial role, through stimulation of AT(1) receptors, in the production and progression of stress-induced gastric injury, and AT(1) receptor antagonists could be of therapeutic benefit.


Direct and indirect costs of refractory epilepsy in a tertiary epilepsy center in Germany.
There are only few studies on the costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate the direct and indirect costs of refractory epilepsy in a German epilepsy center. A "prevalence-based," cross-sectional convenience sample of adults with active epilepsy attending the outpatient clinic of our tertiary epilepsy center was evaluated. Seizure-free patients and patients presenting with their first seizure were excluded. Direct and indirect costs were prospectively recorded over a three-month period using questionnaires and a patient diary. Cost driving factors were identified. One hundred one patients were included (40.7+/-15.2 years; disease duration: 18.1+/-15.3 years; 6 patients had focal epilepsy with simple partial seizures only, 28 with complex partial seizures, 43 with secondarily generalized tonic-clonic seizures; 20 had idiopathic generalized epilepsy with generalized tonic-clonic seizures). The total costs of epilepsy per patient were in average euro 2610+/-4200 over the three-month period. Direct cost contributed 39% to the total costs. Costs of anticonvulsant medication were the main contributor to the direct costs while indirect costs were caused mainly by losses due to early retirement. Cost driving factors included higher seizure frequency, longer disease duration, ictal falls, and situationally inappropriate complex behavior during or after the seizure. Indirect costs were higher than direct costs in adult patients with active epilepsy attending a German epilepsy center. Medication contributed the most to the direct costs and early retirement was the main factor for the indirect costs. The costs of poorly controlled epilepsy in this German study were above average of the European costs of epilepsy.


[Pancreatic groove carcinoma in a young adult].
A 26-year-old woman was admitted to our hospital with jaundice. Under a diagnosis of biliary and duodenal stenosis due to so called "groove pancreatitis", prednisolone (30 mg/day, 2 weeks) was administered. But these stenosis did not improve after the treatment, and pancreaticoduodenectomy was performed. Histologically, poorly differentiated adenocarcinoma was found in the "groove" between the duodenum and the pancreatic head. We should be kept of "pancreatic groove carcinoma" in mind when making a diagnosis of "groove pancreatitis".


Cloning, expression, characterisation and three-dimensional structure determination of Caenorhabditis elegans spermidine synthase.
The polyamine synthesis enzyme spermidine synthase (SPDS) has been cloned from the model nematode Caenorhabditis elegans. Biochemical characterisation of the recombinantly expressed protein revealed a high degree of similarity to other eukaryotic SPDS with the exception of a low affinity towards the substrate decarboxylated S-adenosylmethionine (Km = 110 microM) and a less pronounced feedback inhibition by the second reaction product 5'-methylthioadenosine (IC50 = 430 microM). The C. elegans protein that carries a nematode-specific insertion of 27 amino acids close to its N-terminus was crystallized, leading to the first X-ray structure of a dimeric eukaryotic SPDS.


Involvement of redox state in the aging of Drosophila melanogaster.
The main objective of this review was to provide an exposition of investigations, conducted in Drosophila melanogaster, on the role of reactive oxygen species and redox state in the aging process. While early transgenic studies did not clearly support the validity of the oxidative stress hypothesis of aging, predicated on the accumulation of structural damage, they spawned a broader search for redox-related effects that might impact the aging process. Initial evidence implicating the thiol redox state as a possible causative factor in aging has been obtained in Drosophila. Overexpression of genes, such as GCL, G6PD, Prx2, and Prx5, which are involved in the maintenance of thiol redox homeostasis, has strong positive effects on longevity. Further, the depletion of peroxiredoxin activity in the mitochondria through the double knockdown of Prx5 and Prx3 not only results in a redox crisis but also elicits a rapid aging phenotype. Herein, we summarize the present status of knowledge about the main components of the machinery controlling thiol redox homeostasis and describe how age-related redox fluctuations might impact aging more acutely through disruption of the redox-sensitive signaling mechanisms rather than via the simple accumulation of structural damage. Based on these initial insights into the plausible impact of redox fluctuations on redox signaling, future studies should focus on the pathways that have been explicitly implicated in aging, such as insulin signaling, TOR, and JNK/FOXO, with particular attention to elements that are redox sensitive.


Comorbid auditory processing disorder in developmental dyslexia.
The primary objective of this study was to investigate the extent of comorbid auditory processing disorder (APD) in a group of adults with developmental dyslexia. An additional objective was to compare performance on auditory tasks to results from standardized tests of reading in an attempt to generate a clinically useful profile of developmental dyslexics with comorbid APD. A group of eleven persons with developmental dyslexia and 14 age- and intelligence-matched controls participated in the study. Behavioral audiograms, 226-Hz tympanograms, and word recognition scores were obtained binaurally from all subjects. Both groups were administered the frequency-pattern test (FPT) and duration-pattern test (DPT) monaurally (30 items per ear) in both the left and right ear. Gap detection results were obtained in both groups (binaural presentation) using narrowband noise centered at 1 kHz in an adaptive two-alternative forced-choice (2-AFC) paradigm. The FPT, DPT, and gap detection results were analyzed for interaural (where applicable), intergroup, and intragroup differences. Correlations between performance on the auditory tasks and the standardized tests of reading were examined. Additive logistic regression models were fit to the data to determine which auditory tests proved to be the best predictors of group membership. The persons with developmental dyslexia as a group performed significantly poorer than controls on both the FPT and DPT. Furthermore, the group differences were significant in both monaural conditions. On the FPT and DPT, five of the eleven participants with dyslexia performed below the widely used clinical criterion for APD of 70% correct in either ear. All five of these participants performed below criterion on the FPT, whereas four of the five additionally performed below 70% on the DPT. The data also were analyzed by fitting a series of stepwise logistic regression models, which indicated that gap detection did not significantly predict group membership, whereas the FPT and DPT were significant predictors. The addition of the FPT score after the DPT did not result in a significant change in the residual deviance. Approximately half of the participants with developmental dyslexia showed clinically significant diminished performance on the FPT and DPT indicative of APD. These results indicate that the percentage of persons with developmental dyslexia and comorbid APD may be substantial enough to warrant serious clinical considerations.


Active sensing and its application to sensor node reconfiguration.
This paper presents a perturbation/correlation-based active sensing method and its application to sensor node configuration for environment monitoring. Sensor networks are widely used as data measurement tools, especially in dangerous environments. For large scale environment monitoring, a large number of nodes is required. For optimal measurements, the placement of nodes is very important. Nonlinear spring force-based configuration is introduced. Perturbation/correlation-based estimation of the gradient is developed and it is much more robust because it does not require any differentiation. An algorithm for tuning the stiffness using the estimated gradient for node reconfiguration is presented. The performance of the proposed algorithm is discussed with simulation results.


Serology of Neisseria gonorrhoeae: W-antigen serogrouping by coagglutination and protein I serotyping by enzyme-linked immunosorbent assay both detect protein I antigens.
A total of 224 strains were serogrouped by coagglutination (COA) and serotyped by protein I enzyme-linked immunosorbent assay (ELISA). Of these strains, 61 were from patients with disseminated gonococcal infection, 21 were from patients with pelvic inflammatory disease, and 115 were from patients with uncomplicated gonococcal infection in Singapore, the Philippines, and Denmark. Twenty-seven were laboratory reference strains. Of the patient strains, 102 belonged to COA serogroup WI, and all of the 100 strains that typed with protein I serotypes 1, 2, or 3 were in this group. Most of the strains of gonococci from the 61 patients with disseminated gonococcal infection were within this group (COA WI, 53 or 87%; protein I serotypes 1, 2, or 3, 51 or 84%). All 46 strains that were protein I serotypes 4 through 7 were also COA serogroup WII. Protein I serotypes 8 and 9 accounted for 49 (25%) of the 197 patient strains. Twenty-eight of these strains typed as COA serogroup WII, 20 typed as serogroup WIII, and 1 typed as serogroups WII and WIII. COA W serogrouping and protein I ELISA both appeared to detect antigens on the protein I molecule of the outer membrane of Neisseria gonorrhoeae. Protein I serotyping, which uses unboiled organisms, may generally recognize more variable and surface-exposed antigenic determinants. In contrast, COA W serogrouping, which uses boiled organisms, may recognize less exposed shared antigenic determinants in addition to variable protein I antigenic determinants. Both methods may prove useful for further studies of the epidemiology and pathogenesis of gonorrhea.


Deoxynivalenol in Fusarium graminearum: Evaluation of Cyproconazole Stereoisomers In Vitro and In Planta.
Cyproconazole (CPZ), a representative chiral triazole fungicide, is widely used to control Fusarium head blight (FHB). In this study, the stereoselective efficiency of CPZ was investigated in vitro and in planta. Consistent results were observed between the in vitro bioassay and the in planta visual disease rating, with the control efficacy ordered RS-CPZ > RR-CPZ > SR-CPZ > SS-CPZ. Unexpectedly, the in planta deoxynivalenol level was in the order RR-CPZ > RS-CPZ > SS-CPZ > SR-CPZ, while RS-CPZ inhibited the deoxynivalenol production and ergosterol biosynthesis in Fusarium graminearum. We further investigated that the Tri genes were upregulated in Fusarium graminearum of the RS-CPZ group, and SR-CPZ preferentially degraded in wheat. An extra action mode of CPZ was inferred to stimulate the production of deoxynivalenol. These findings revealed the stereoselective efficiency of CPZ stereoisomers against FHB and provided new insights into the mechanism of action of triazole fungicides against FHB and deoxynivalenol.


Painless thyroiditis presenting as apathetic hyperthyroidism in a young male.
Apathetic hyperthyroidism is an uncommon presentation of thyrotoxicosis that is most commonly observed in elderly individuals. A small number of cases, however, have been observed in young adults-all of whom were female. We describe a case of apathetic hyperthyroidism due to painless thyroiditis in a 23-year-old active duty male, who presented with a 1-month history of change in behavior characterized by poverty of speech and disinterest in his surrounding environment. Initial evaluation for neuropsychological disorders was negative. Thyroid function tests showed a thyrotoxic state. Results of thyroid antibody testing and a thyroid uptake and scan supported the diagnosis of painless thyroiditis. The patient's presenting symptoms were attributed to apathetic thyrotoxicosis and he was treated supportively. His speech and social involvement slowly improved. Although uncommon in young adults, we recommend that apathetic hyperthyroidism be considered in the differential diagnosis of withdrawn social behavior and subsequently investigated with thyroid function tests.


Sex-differences of face coding: evidence from larger right hemispheric M170 in men and dipole source modelling.
The processing of faces relies on a specialized neural system comprising bilateral cortical structures with a dominance of the right hemisphere. However, due to inconsistencies of earlier findings as well as more recent results such functional lateralization has become a topic of discussion. In particular, studies employing behavioural tasks and electrophysiological methods indicate a dominance of the right hemisphere during face perception only in men whereas women exhibit symmetric and bilateral face processing. The aim of this study was to further investigate such sex differences in hemispheric processing of personally familiar and opposite-sex faces using whole-head magnetoencephalography (MEG). We found a right-lateralized M170-component in occipito-temporal sensor clusters in men as opposed to a bilateral response in women. Furthermore, the same pattern was obtained in performing dipole localization and determining dipole strength in the M170-timewindow. These results suggest asymmetric involvement of face-responsive neural structures in men and allow to ascribe this asymmetry to the fusiform gyrus. This specifies findings from previous investigations employing event-related potentials (ERP) and LORETA reconstruction methods yielding rather extended bilateral activations showing left asymmetry in women and right lateralization in men. We discuss our finding of an asymmetric fusiform activation pattern in men in terms of holistic face processing during face evaluation and sex differences with regard to visual strategies in general and interest for opposite faces in special. Taken together the pattern of hemispheric specialization observed here yields new insights into sex differences in face perception and entails further questions about interactions between biological sex, psychological gender and influences that might be stimulus-driven or task dependent.


Secondary structure of the leader transcript from the Escherichia coli S10 ribosomal protein operon.
Genetic analysis of the autogenous control of the S10 ribosomal protein operon of Escherichia coli has suggested that the secondary or tertiary structure of the leader transcript is important for this regulation. We have therefore determined the secondary structure of the leader by enzyme digestion and chemical modification. Our results suggest that the 172 base leader exists in two forms, differing only immediately upstream of the Shine-Dalgarno sequence of the first gene. We discuss the possibility that the equilibrium between these alternate structures is important for the L4-mediated regulation of translation of the S10 operon. We have also determined the structure of several mutant transcripts. Correlation of these structures with the regulatory phenotypes suggest that a hairpin about 50 bases upstream of the first gene is essential for the control of translation of the operon. Finally, our results show that a two base substitution in an eight base loop destabilizes the attached stem.


Effects of Binahong (Anredera cordifolia (Tenore) Steenis) Extracts on the Levels of Malondialdehyde (MDA) in Cataract Goat Lenses.
Cataracts are one of the most causes of blindness in the world. Oxidative stress can form pathological conditions such as cataracts. This oxidative stress ability can be measured by the malondialdehyde (MDA) biomarker. Binahong leaves (Anredera cordifolia (Tenore) Steenis) are native plants from Indonesia that are used to treat various diseases including cataract treatment. Binahong leaf (Anredera cordifolia (Tenore) Steenis) has a high amount of flavonoids and is rich in antioxidants that can be used to treat cataracts. Objective. The purpose of this study was to assess the effect of binahong leaf extract on the levels of MDA in a goat lens with cataract-induced material. Method. As many as possible, 40 goat eye lenses were divided into several groups, namely, group I normal lenses as controls (glucose 5.5 mM), group II lenses were cataract induced with glucose concentration of 55 mM, group III lenses with glucose 55 mM + binahong leaf extract (100 μg/ml), group IV lens with glucose 55 mM + binahong leaf extract (200 μg/ml), and group V lens with glucose 55 mM + quercetin (positive control). Biochemical parameters measured in the lens homogenate are malondialdehyde lens morphology in all groups' observations and comparisons made. Results. The results of the study found that the lens group with the addition of binahong extract showed more results transparency compared to lens groups induced by glucose concentrations of 55 mM). This shows that the diabetic cataract group experienced high oxidative stress due to the accumulation of sorbitol compounds derived from glucose which caused turbidity in the goat eye lens and increased levels of lens MDA. Binahong levels at concentrations of 100 or 200 can inhibit MDA production. Conclusion. Binahong (Anredera cordifolia (Tenore) Steenis) extract has the ability to inhibit the production of MDA levels. In glucose-induced goat lenses, binahong extract and quercetin show antioxidant and anticataract properties.


Using spectral-domain optical coherence tomography to detect optic neuropathy in patients with craniosynostosis.
Detecting and monitoring optic neuropathy in patients with craniosynostosis is a clinical challenge due to limited cooperation, and subjective measures of visual function. The purpose of this study was to appraise the correlation of peripapillary retinal nerve fiber layer (RNFL) thickness measured by spectral-domain ocular coherence tomography (SD-OCT) with indication of optic neuropathy based on fundus examination. The medical records of all patients with craniosynostosis presenting for ophthalmic evaluation during 2013 were retrospectively reviewed. The following data were abstracted from the record: diagnosis, historical evidence of elevated intracranial pressure, current ophthalmic evaluation and visual field results, and current peripapillary RNFL thickness. A total of 54 patients were included (mean age, 10.6 years [range, 2.4-33.8 years]). Thirteen (24%) had evidence of optic neuropathy based on current fundus examination. Of these, 10 (77%) demonstrated either peripapillary RNFL elevation and papilledema or depression with optic atrophy. Sensitivity for detecting optic atrophy was 88%; for papilledema, 60%; and for either form of optic neuropathy, 77%. Specificity was 94%, 90%, and 83%, respectively. Kappa agreement was substantial for optic atrophy (κ = 0.73) and moderate for papilledema (κ = 0.39) and for either form of optic neuropathy (κ = 0.54). Logistic regression indicated that peripapillary RNFL thickness was predictive of optic neuropathy (P < 0.001). Multivariable analysis demonstrated that RNFL thickness measurements were more sensitive at detecting optic neuropathy than visual field testing (likelihood ratio = 10.02; P = 0.002). Sensitivity and specificity of logMAR visual acuity in detecting optic neuropathy were 15% and 95%, respectively. Peripapillary RNFL thickness measured by SD-OCT provides adjunctive evidence for identifying optic neuropathy in patients with craniosynostosis and appears more sensitive at detecting optic atrophy than papilledema.


Effects of melatonin and gonadal androgens on cell proliferation in the pituitary of viscachas (Lagostomus maximus maximus).
Melatonin and androgens are involved in the regulation of cell proliferation. However, effects of these hormones on pituitary pars distalis (PD) of male viscachas is not fully understood. In the present study, we analysed melatonin and gonadal androgens' effects on proliferating cell nuclear antigen (PCNA) expression. Pituitary glands from foetuses, immature individuals, prepubertal individuals and adult viscachas during their reproductive cycle, after melatonin administration and after castration, were used. PCNA-ir cells were detected by immunocytochemistry and morphometrically quantified using image analysis. Total percentage of PCNA-ir cells varied seasonally in the adult pituitary, with maximum values during the reproductive period and minima during gonadal regression periods. Percentages of PCNA-ir cells increased after melatonin administration, whereas it decreased after castration. Caudal end and ventral regions were the PD zones which were most affected by seasonal variations and castration. PCNA expression was highest in foetal pituitary from midpregnancy. Numbers of PCNA-ir cells decreased during sexual maturity. Our results demonstrate the effect of gonadal androgens on cell proliferation during the reproductive period and sexual maturity of these animals. Exogenous melatonin increased PD cell proliferation in adults. Thus, these hormones seem to be involved in different mechanisms that regulate cell renewal of PD in this seasonally breeding rodent.