Influence of tuftsin-like synthetic peptides derived from C-reactive protein (CRP) on platelet behaviour.
C-reactive protein (CRP) is an acute-phase reactant that modifies platelet function differently, depending upon its physiochemical state. Aggregated and ligand-complexed forms of CRP initiate the activation of platelets, whereas naturally occurring CRP peptides inhibit platelet activation. The present study documents neutral proteases of the polymorphonuclear leucocyte (PMN) to cleave CRP into reaction products with the potential to inhibit platelet activation, and explore the structure-function relationships involved in the regulation of platelet activation by CRP using synthetic CRP peptides. Evidence was obtained that (i) a minimum of two linear functional domains exist within CRP that influence platelet activation; (ii) they reside in the mid-portion and at the C-terminus of the CRP molecule; (iii) the mid-portion domain inhibits platelet activation stimulated by adenosine diphosphate (ADP) or acid-soluble collagen, whereas the C-terminal domain initiates platelet activation; (iv) the functional expression of the C-terminal domain is maximized when the linear peptide is immobilized on latex; and (v) both CRP domains contain a homologue of the immunoregulatory signal peptide, tuftsin. These data suggest that the molecular mechanisms by which platelet processes are modulated by CRP may be related to the presence of tuftsin homologues in CRP.


Risk factors for developing transient neonatal cholestasis.
To describe the incidence and the characteristics of neonatal cholestasis in a cohort of patients with known risk factors and to investigate additional risk factors. A prospective observational study conducted between April 2008 and 2009 involved all neonates admitted in the neonatal ward. They were divided into high- and low-risk groups for cholestasis. The high-risk group included preterm birth <34 weeks of gestation, small for gestational age (SGA), parenteral nutrition (PN) >7 days, abdomino-pelvic or thoracic surgery. Bilirubinemia was weekly measured in the high-risk group. Of the 460 newborns studied, 234 were included in the high-risk group and 226 in the low-risk group. Cholestasis developed in 32 patients (13.7%) in the high-risk group at mean (SD) age of 14.7 (12.9) days; all were receiving PN. None of the patients in the low-risk group developed cholestasis. An analysis was carried out in the 207 patients in the high-risk group who received PN. The odds ratio (OR) for developing cholestasis was 2.3 [1.1-5.0] and 5.6 [2.5-12.5] for SGA or surgical patients, respectively. Cholestasis was associated with neonatal severe conditions, longer PN duration, and more intravenous macronutrients' intakes. In multivariate analysis, SGA and neonatal surgery were strong independent risk factors for cholestasis, with OR (95% confidence interval [95% CI]) of 4.4 [1.6-12.5] and 4.6 [1.7-12.3], respectively. Transient neonatal cholestasis is a complication of PN. SGA and neonatal surgery are additional risk factors. There is no evidence to limit intravenous protein intakes in preterm.


Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies.
The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft-versus-host disease (GvHD). We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin in order to expedite immune reconstitution after a CD3-depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3(+) T-cells, T-cell receptor (TCR) excision circle counts, TCRbeta repertoire diversity and natural killer (NK)-cells during the first 4 months post-transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.


Theoretical study on the tetranuclear endohedral vanadyl carboxylates with guest-switchable redox properties and large polarizability.
The polarizability and redox properties for the tetranuclear vanadium-oxide-carboxylates have been investigated using density functional theory (DFT). These so-called inorganic crown ethers possess large polarizabilities, which are equivalent to fullerene and generate large polarization on the guest anions into the host. The dipole-induced dipole interaction between the host and the guest anions induces charge transfer from the guest to the host, which is enhanced with the increasing polarization. Moreover, the redox potentials are sensitive to different guests inside the host bowl, and they shift negatively as compared to the isolated host bowl. In contrast, the modification of the methyl group by CH(2)tBu on the rim of the bowl has evoked higher polarizability (over 560 a.u.) with larger polarization on the guest anions and more negative redox potentials. The weak interaction energies in accord with the organic crown ether incorporating alkali metal ions indicate that the guest anions can move freely inside and outside the host bowl, so this kind of inorganic crown ether may exhibit potential guest-switchable redox properties based on reversible complexation-decomplexation and will be expected to find applications in ion recognition and selectivity studies based on the sensitivity to different guests.


[Development of a novel drug dilivery system based on calcium phosphate cement with methotrexate and its drug release test in vitro].
To develop a novel drug dilivery system based on calcium phosphate cement (CPC) with methotrexate (MTX) as a model drug and to study its drug release in vitro. Three MTX mass fractions (0.1%, 0.2%, and 0.5%) were tested after solidification, and the compound of CPC-MTX were put into the simulated body fluid at 37 degrees C. The concentration of MTX was tested by high-performance liquid chromatography at day 2, 5, 10, 16 hours, 1, 2, 3, 5, 8, 10, 15, 20, 25, 30, 35, 40, and 45 days. The drug dilivery curves were drawn and drug dilivery rules were analyzed. MTX was released slowly and stably from the compound of CPC-MTX. Remarked prophase of drug release was noted, which conformed with the Higuchi equation. The drug release rate and concentration was related with the concentration of MTX in compound but not with the thickness and shape of CPC. The releasing time was not affected by the concentration of MTX. A stable drug dilivery system can be developed by loading proper concentration of MTX into CPC.


No Geographic Distribution Change Among Residency Applicants in the Neurology Match During COVID-19.
Objectives The COVID-19 pandemic posed a novel challenge for the 2020-2021 Match cycle resulting in a virtual interview season. The advent of virtual interviews raised concerns for both programs and medical students. The possibility of an impact on the application strategies for medical students resulting in students being more likely to remain in the region or state of their medical school was considered. We investigated whether there was a change in the geographic distribution of residency applicants for the class of 2025 (matched in 2021) as compared to the previous three application cycles (classes of 2022-2024) across all 168 neurology residency programs within the United States. Methods Publicly available data from neurology program websites were compiled to record the location of resident medical schools and matched programs for the residency classes of 2022-2025. Missing or ambiguous information was cross-referenced to social media, (e.g. LinkedIn and Twitter). Statistical analyses were conducted utilizing SPSS 26 (IBM SPSS 26 Statistics for Windows, Armonk, NY). Results Across all four classes, regional retention (students matching in the same region) was 70.2% for the Northeast, 59.6% for the Midwest, 52.9% for the South, and 59.4% for the West. No significant change between the residency class of 2025 and the previous three classes was present. Discussion No significant change to the geographic trends for candidates was seen with the virtual interview process for the 2020-2021 neurology Match. As has been seen in other fields, a strong regional preference, with the majority of residents matching to programs in the same regions as their medical school, was seen for neurology.


The Global State of Helminth Control and Elimination in Children.
Helminth infections, including soil-transmitted helminths and schistosomiasis, remain one of the most common infections in the world with over 1 billion people infected. These infections cause significant morbidity, particularly in young children, that may last a lifetime, including growth and cognitive stunting. There is an urgent need for the control and elimination of helminth infections from areas of poverty to reduce morbidity in children. Mass drug administration programs were adopted by the World Health Assembly in 2001 and have evolved to provide coverage with multiple anthelmintic medications in a single rapid impact package and more extensive coverage within a community.


The gut bacterial community of mammals from marine and terrestrial habitats.
After birth, mammals acquire a community of bacteria in their gastro-intestinal tract, which harvests energy and provides nutrients for the host. Comparative studies of numerous terrestrial mammal hosts have identified host phylogeny, diet and gut morphology as primary drivers of the gut bacterial community composition. To date, marine mammals have been excluded from these comparative studies, yet they represent distinct examples of evolutionary history, diet and lifestyle traits. To provide an updated understanding of the gut bacterial community of mammals, we compared bacterial 16S rRNA gene sequence data generated from faecal material of 151 marine and terrestrial mammal hosts. This included 42 hosts from a marine habitat. When compared to terrestrial mammals, marine mammals clustered separately and displayed a significantly greater average relative abundance of the phylum Fusobacteria. The marine carnivores (Antarctic and Arctic seals) and the marine herbivore (dugong) possessed significantly richer gut bacterial community than terrestrial carnivores and terrestrial herbivores, respectively. This suggests that evolutionary history and dietary items specific to the marine environment may have resulted in a gut bacterial community distinct to that identified in terrestrial mammals. Finally we hypothesize that reduced marine trophic webs, whereby marine carnivores (and herbivores) feed directly on lower trophic levels, may expose this group to high levels of secondary metabolites and influence gut microbial community richness.


Efficacy and influence on quality of life of enalapril as a first step treatment of hypertension.
205 patients with mild to moderate uncomplicated hypertension participated in a six-month double-blind parallel study performed in a unique center. After a two-week single-blind placebo period, the patients were randomly allocated to receive either Enalapril 20 mg once-a-day or placebo as the first step treatment. They were then followed-up every two weeks and successive doses of hydrochlorothiazide, oxprenolol, and dihydralazine were added until the diastolic pressure was lower than 90 mmHg. After six months, the systolic and diastolic blood pressures were lower in the Enalapril than in the control group (129/82 +/- 12/6 mmHg versus 136/86 +/- 10/5 mmHg; p less than 0.001). Drug withdrawal was necessary for 8 patients in the Enalapril group and for 16 patients in the control group (p less than 0.05). The number of daily tablets was 2.7 +/- 1.8 in the Enalapril group and 4.4 +/- 2.4 in the control group (p less than 0.01). Therefore, a stepped-care program based on Enalapril appears significantly more effective than a stepped-care program based on a diuretic.


Identification and functional characterization of the hepatic stellate cell CD38 cell surface molecule.
The activation of hepatic stellate cells (HSCs) is a critical event in hepatic fibrosis, because these cells are the main producers of extracellular matrix proteins in the liver and contribute to the modulation of inflammatory responses via the secretion of several cytokines and the expression of adhesion molecules. The goal of the present study was to characterize cell surface proteins that regulate HSC activation. To this end, a panel of monoclonal antibodies (mAbs) was generated. mAb 14.27 recognized a protein of 45 kd that was highly expressed on HSCs. Affinity purification of this protein followed by sequencing revealed that protein to be CD38. We subsequently demonstrated that CD38 was constitutively expressed by HSCs and that its expression increased after in vitro and in vivo activation. mAb 14.27 induced an increase in cytosolic Ca2+ levels in HSCs, showing that it functions as an agonistic antibody. Moreover, the effects mediated by the CD38 mAb included induction of the proinflammatory cytokine interleukin-6 and up-regulation of the adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neural cell adhesion molecule. Collectively, our data suggest that CD38 can act as a regulator of HSC activation and effector functions.


Optical alignment of oval graphene flakes.
Patterned graphene, as an atomically thin layer, supports localized surface plasmon polaritons at mid-infrared or far-infrared frequencies. This provides a pronounced optical force/torque in addition to large optical cross sections and will make it an ideal candidate for optical manipulation. Here, we study the optical force and torque exerted by a linearly polarized plane wave on circular and oval graphene flakes (single layers of graphene). While the torque vanishes for circular flakes, the finite torque allows rotating and orienting oval flakes relative to the electric field polarization. Depending on the wavelength, the alignment is either parallel or perpendicular to the electric field vector. In our contribution, we rely on a full-wave numerical simulation and also on an analytical model that treats the graphene flakes in a dipole approximation. The presented results reveal a good level of control on the spatial alignment of graphene flakes subjected to far-infrared illumination.


Coronary Spasm: Ethnic and Sex Differences.
Coronary spasm (CS), which may occur at the epicardial (focal or diffuse spasm) and/or microvascular (microvascular spasm) level, is a well-established cause of myocardial ischaemia, in particular in patients with anginal chest pain despite unobstructed coronary arteries. The diagnosis of CS can be confirmed during coronary angiography by an additional provocation test with vasoactive substances such as acetylcholine. Due to partially inconsistent data from large clinical studies, especially between Asian and white CS patients, ethnic differences concerning the prevalence and angiographic patterns of CS seem to exist. Furthermore, several studies in patients with coronary vasomotor disorders pointed towards differences among male and female CS patients. This article gives an overview of ethnic- and sex-related differences in patients with CS.


Percutaneous aortic valve implantation: the anesthesiologist perspective.
Percutaneous aortic valve implantation is an emergent technique alternative to surgical aortic valve replacement in high risk patients with aortic stenosis. Percutaneous aortic valve implantation techniques are undergoing rapid development and currently represent a dynamic field of research. Perioperative optimal strategies keep on evolving too. At a review of the literature, only three previous papers on Pubmed focused specifically on anesthesiological challenges of percutaneous aortic valve implantation. In one of them our first 6 months experience was reported. In this new paper we describe the anesthesiological management of percutaneous aortic valve implantation at our Centre, reporting the results of our implantation program from November 2007 to February 2009.


Niche-directed therapy in acute myeloid leukemia: optimization of stem cell competition for niche occupancy.
Acute myeloid leukemia (AML) is an aggressive malignancy of stem cell origin that contributes to significant morbidity and mortality. The long-term prognosis remains dismal given the high likelihood for primary refractory or relapsed disease. An essential component of relapse is resurgence from the bone marrow. To date, the murine hematopoietic stem cell (HSC) niche has been clearly defined, but the human HSC niche is less well understood. The design of niche-based targeted therapies for AML must account for which cellular subsets compete for stem cell occupancy within respective bone marrow microenvironments. In this review, we highlight the principles of stem cell niche biology and discuss translational insights into the AML microenvironment as of 2021. Optimization of competition for niche occupancy is important for the elimination of measurable residual disease (MRD). Some of these novel therapeutics are in the pharmacologic pipeline for AML and may be especially useful in the setting of MRD.


The role of muramyl dipeptide in the therapy of established experimental bacterial infection.
Muramyl dipeptide (MDP) actively potentiates host defences and confers protection when given before a bacterial challenge. Experiments were undertaken to characterize its actions when used alone or in combination with cephaloridine in a manner analogous to clinical therapy, i.e. after initiation of bacterial infection. MDP, alone or in combination, significantly decreased the systemic manifestations of infection compared with placebo when administered up to 6 h following bacterial contamination. Its effect on the primary lesion was less marked, but it may potentiate host defences sufficiently to have an impact on the decisive period. Benefits observed in this study were of lesser magnitude than those observed following administration of the dipeptide before bacterial inoculation.


Asymmetric C-Alkylation by the S-Adenosylmethionine-Dependent Methyltransferase SgvM.
S-Adenosylmethionine-dependent methyltransferases (MTs) play a decisive role in the biosynthesis of natural products and in epigenetic processes. MTs catalyze the methylation of heteroatoms and even of carbon atoms, which, in many cases, is a challenging reaction in conventional synthesis. However, C-MTs are often highly substrate-specific. Herein, we show that SgvM from Streptomyces griseoviridis features an extended substrate scope with respect to the nucleophile as well as the electrophile. Aside from its physiological substrate 4-methyl-2-oxovalerate, SgvM catalyzes the (di)methylation of pyruvate, 2-oxobutyrate, 2-oxovalerate, and phenylpyruvate at the β-carbon atom. Chiral-phase HPLC analysis revealed that the methylation of 2-oxovalerate occurs with R selectivity while the ethylation of 2-oxobutyrate with S-adenosylethionine results in the S enantiomer of 3-methyl-2-oxovalerate. Thus SgvM could be a valuable tool for asymmetric biocatalytic C-alkylation reactions.


[A new classification of vulvar intraepithelial neoplasia (VIN)].
Vulvar cancer is a rare disease and its screening is depending on the quality and the relevance of our clinical examination. Incidence of vulvar cancer and especially precancerous lesions, vulvar intraepithelial neoplasias (VIN), increased during these last years. The new terminology of vulvar intraepithelial neoplasia will help us to identify high risk groups which could develop a cancer: usual and differentiated VIN. An early diagnosis is essential to propose an adequate treatment. Management is a major point according to the rising incidence of these lesions in younger women. Until we can observe a benefit from the vaccination against human papillomavirus, we must increase the quality of screening by a careful examination of the vulva.


Practice patterns in the management of acute intervertebral disc herniation in dogs.
Acute intervertebral disc herniation is commonly managed by veterinary neurologists and surgeons. Anecdote suggests that patterns of management vary considerably and there is controversy surrounding many aspects of treatment. The goal of this study was to document patterns in management of acute spinal cord injury caused by acute intervertebral disc herniation among these two groups to aid in future discussions on best practices. A survey querying diagnostic, medical and surgical practices for dogs with acute intervertebral disc herniation was distributed to diplomates on the databases of the American College of Veterinary Surgeons and the American College of Veterinary Internal Medicine (Neurology). Responses were received from 314 board-certified veterinary surgeons and neurologists. Both groups handled timing of decompression, surgical approach, and most postoperative recommendations in a similar fashion. Case volume differed between groups, with 77% of neurologists and 18% of surgeons managing ê50 cases of acute intervertebral disc herniation per year. MRI was used most frequently as a diagnostic tool by neurologists (75%), while CT was used most commonly by surgeons (58%). Corticosteroids were routinely administered as a neuroprotective strategy by 34% of surgeons and 11% of neurologists. Disc fenestration was performed "always" or "most of the time" by 69% of neurologists and 36% of surgeons. Understanding the common practices in the management of canine acute intervertebral disc herniation can provide a springboard for future discussions regarding the best practices in diagnosing and treating this disease.


A defense of fundamental principles and human rights: a reply to Robert Baker.
This article seeks to rebut Robert Baker's contention that attempts to ground international bioethics in fundamental principles cannot withstand the challenges posed by multiculturalism and postmodernism. First, several corrections are provided of Baker's account of the conclusions reached by the Advisory Committee on Human Radiation Experiments. Second, a rebuttal is offered to Baker's claim that an unbridgeable moral gap exists between Western individualism and non-Western communalism. In conclusion, this article argues that Baker's "nonnegotiable primary goods" cannot do the work of "classical human rights" and that the latter framework is preferable from both a practical and a theoretical standpoint.


Predicting visual resolution from detection thresholds.
Visual acuity is one of the most frequent health measures and is central to vision assessment in schools, industry, aviation, drivers' licensing, and ocular health examinations. There is a need for a rapid, simple, and interpretation-free measure of visual acuity which is amenable to automated and objective assessment. This study shows that a rapid (15 s) and simple contrast threshold measure for a 5 min arc spot correlates highly (r = 0.75) with letter acuity in 360 clinic patients. Assessments by optometrist and technician correlated highly (r = 0.88) as did repeated measures by the same examiner (r = 0.85). The instrumentation appears to be well suited for rapid, automated, and interpretation-free assessment of visual acuity and for visual acuity screening.


In vivo and in vitro methods for evaluating soil arsenic bioavailability: relevant to human health risk assessment.
Arsenic (As) is the most frequently occurring contaminant on the priority list of hazardous substances, which lists substances of greatest public health concern to people living at or near U.S. National Priorities List site. Accurate assessment of human health risks from exposure to As-contaminated soils depends on estimating its bioavailability, defined as the fraction of ingested As absorbed across the gastrointestinal barrier and available for systemic distribution and metabolism. Arsenic bioavailability varies among soils and is influenced by site-specific soil physical and chemical characteristics and internal biological factors. This review describes the state-of-the science that supports our understanding of oral bioavailability of soil As, the methods that are currently being explored for estimating soil As relative bioavailability (RBA), and future research areas that could improve our prediction of the oral RBA of soil As in humans. The following topics are addressed: (1) As soil geochemistry; (2) As toxicology; (3) in vivo models for estimating As RBA; (4) in vitro bioaccessibility methods; and (5) conclusions and research needs.


Comparison of fresh and post-mortem human arterial tissue: an analysis using FT-IR microspectroscopy and chemometrics.
Fourier transform infrared (FT-IR) microspectroscopy and chemometric methods have been applied to the study of fresh and simulated post-mortem human arterial tissue. The results have shown that although physical differences were observed using light microscopy, no spectroscopic distinction could be made between these groups. The presence of collagen throughout the artery wall results in characteristic absorptions which may mask any biochemical changes that could otherwise have been detected by the FT-IR technique. Because the structure of the artery is unique, these findings should be regarded as tissue specific.


DNA cytometry of osteosarcoma.
The relationship between cytochemical features and histomorphology in osteosarcoma, and the clinical significance of DNA content were investigated by microspectrophotometry (MSP) of tissue sections and flow cytophotometry (FCM) of cell suspensions. MSP of tissue sections entails the methodological error of determining the DNA content of sectioned cell nuclei. By analyzing 184 normal mesenchymal cell populations, an upper limit of diploidy (normal DNA content) was deduced. Applying this upper limit for 42 sarcomas, 6 were diploid and 36 hyperploid. Comparative analysis of the same lesions by MSP of imprint preparations and by FCM disclosed complete agreement in ploidy classification (diploid versus hyperploid). Retrospective MSP analysis of bone tumors is often impeded by previous demineralization in acid, which destroys DNA. EDTA as an alternative was found to slightly reduce Feulgen DNA stainability of osteosarcomas, but did not affect tumor ploidy determination. Hence, EDTA offers a means of retaining DNA stainability of bone tumors requiring demineralization. MSP analysis of different histologic areas, and comparative FCM analysis of biopsy and surgical specimens, dislosed that individual osteosarcomas are cytochemically uniform despite morphologic heterogeneity. Hence, a single tumor sample for DNA analysis can be relied upon as representative for the tumor as a whole. In a consecutive series of 83 osteosarcoma patients treated by surgery and adjuvant Interferon, the 7-year survival rate was 0.44. MSP DNA analysis gave no significant prognostic information. Multivariate analysis identified 3 risk factors for tumor related death, i.e., male sex, proximal tumor location, and histologic grade IV. In a prognostication model, the 7-year survival rates, for patients with 0, 1, 2, or 3 risk factors, were 0.80, 0.59, 0.42, and 0.13, respectively. Hence, it is possible to identify subgroups of high grade osteosarcoma patients with different prognosis. In a study of 166 primary bone tumors, the applicability of DNA analysis for differential diagnostic purposes was investigated. The series included high grade osteosarcomas, parosteal osteosarcomas and benign bone tumors, which may be mixed up histologically with osteosarcoma. Out of 166 tumors, 149 (90%) were histologically noncontroversial, whereas 17 (10%) posed diagnostic difficulties. In the diagnostically noncontroversial group, all benign tumors and parosteal osteosarcomas were diploid, whereas 97 of 102 osteosarcomas were hyperploid. Hence, hyperploidy seems to be a characteristic feature of high grade osteosarcoma.(ABSTRACT TRUNCATED AT 400 WORDS)


THE ROLE OF COURTSHIP SONGS IN REPRODUCTIVE ISOLATION AMONG POPULATIONS OF GREEN LACEWINGS OF THE GENUS CHRYSOPERLA (NEUROPTERA: CHRYSOPIDAE).
Male and female lacewings tremulate during courtship, establishing duets that always precede copulation. Three distinct courtship songs are found in populations of the green lacewing Chrysoperla plorabunda (P1, P2 and P3 song morphs). Analysis of five features of the songs for individuals collected from Connecticut, Idaho, Oregon and California showed few differences within song morphs, but sympatric song morphs differed significantly in temporal features of the songs and their mode of presentation. Playback experiments using recorded songs were performed on females with all possible sympatric and allopatric combinations of females and recorded songs. The results showed that females strongly prefer to duet with recordings of males of their own song type and usually showed no responses to songs of other types. Thus, song differences are effective barriers to reproduction between the sympatric morphs. Our results support the hypothesis that the three song morphs are true biological species.


Predictors of mental health and well-being in employed adults with autism spectrum disorder at 12-month follow-up.
People with Autism Spectrum Disorder (ASD) commonly experience poor outcomes in adulthood. Previous research on adult outcomes has focused on negative aspects of health and well-being, while positive well-being remains understudied. The current study charted 12-month change in daily living skills, job satisfaction, depression, anxiety, and positive well-being in 36 (32 male) newly employed adults with ASD aged 18 to 57 years who were participating in a supported employment program. There was a small increase in daily living skills, and a slight decrease in job satisfaction, with all other measures remaining stable over time. Regression analyses revealed that, controlling for baseline depression, positive well-being negatively predicted depression at follow-up. No significant predictors of anxiety were identified. Social support and depression at baseline were associated with positive well-being at follow-up; however, they were no longer significant predictors after the effects of baseline positive well-being were taken into account. The findings provide evidence that positive well-being may buffer against depression in people with ASD. Our finding of stability of mental health and well-being measures over time indicates more research is required to uncover the mechanisms underpinning mental health and well-being outcomes in employed adults with ASD. Autism Res 2019, 12: 482-494 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience poor outcomes in adulthood. We studied mental health and well-being in newly employed adults with autism who were participating in a supported employment program. Apart from a slight increase in daily living skills and a slight decrease in job satisfaction, other measures of mental health and well-being remained stable over time. Our findings suggest that positive well-being may protect against symptoms of depression in people with autism.


Salmonella Weltevreden food poisoning in a tea garden of Assam: An outbreak investigation.
Salmonella enterica serovar Weltevreden has been a rare cause of acute gastroenteritis occurring worldwide. Here, we report an outbreak of food poisoning in a tea garden. To determine the aetiological agent and risk factors responsible for the outbreak and to take necessary steps for prevention of future outbreaks. Affected area was visited by a team of microbiologists for collecting stool samples/rectal swabs from affected patients. Samples were processed by culture followed by confirmation of the isolates biochemically, automated bacterial identification system, conventional serotyping and molecular typing. Water samples were also processed for detection of faecal contamination. Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion technique according to the Clinical Laboratory Standard Institute guidelines. The isolates were confirmed as S. enterica subspecies enterica serovar Weltevreden. They were found sensitive to ampicillin, amoxycillin-clavulanic acid, ciprofloxacin, ofloxacin, norfloxacin, cefotaxime, ceftriaxone, co-trimoxazole and doxycycline. Water samples showed high-level faecal contamination. Source of outbreak was found to be drinking water contaminated with dead livestock. House to house visit was made for early diagnosis and treatment of the cases, awareness campaigning and chlorination of drinking water. This report emphasises the geographical distribution of this organism in Assam. As S. Weltevreden is widely distributed in domestic animals, people should be made aware of immediate reporting of any unusual death among the livestock and their safe disposal which can significantly reduce the incidence of non-typhoidal salmonellosis in the country.


Gender differences in vocal fold contact computed from electroglottographic signals: the influence of measurement criteria.
EGGW is a phonatory parameter that can be derived from electroglottographic (EGG) signals and used to infer the relative degree of vocal fold contact. Vocal fold models predict that men will exhibit medial bulging of their vocal folds during phonation but women will not. These models lead us to expect gender differences in the magnitude of EGGW. Nevertheless, significant gender differences in EGGW for adults with normal voices have not been documented in previous studies when EGGW was computed from criterion lines placed at 25%-40% of the amplitude of the uninverted EGG wave form. We hypothesized that EGGW would better reflect gender differences in vocal fold adductory patterns if EGGW was computed from portions of the wave form that were associated with more vocal fold contact. EGGW was measured for seven men and seven women with normal voices. When EGGW was computed from segments of the wave form that were associated with relatively greater vocal fold contact (i.e., using criterion levels of > or = 55%), findings were consistent with the gender-specific adductory patterns that have been proposed from vocal fold models. Guidelines for appropriate placement of criterion lines when computing EGGW are discussed.


Functional characterization of the clade B serine protease inhibitor SerpinB3 in the pacific white shrimp Litopenaeus vannamei.
The clade B serpins contain predominantly intracellular proteins and were reported to be involved in multiple biological functions, especially in inflammation and immune system function. However, studies about the role of the invertebrate intracellular serpins in immune responses were still deficient. Therefore, this paper focused on the functional characterization of LvserpinB3 in white shrimp Litopenaeus vannamei. The pAc5.1-LvserpinB3-EGFP vector was transfected into Drosophila Schneider 2 (S2) cells to analyze the subcellular localization of LvserpinB3, and fluorescent imaging showed that LvserpinB3 were mainly localized to the mitochondria. Knockdown LvserpinB3 significantly increased the mRNA expression of LvSpätzle4 (LvSpz4) and LvPenaeidin4 (LvPen4) upon Vibrio anguillarum infection. Moreover, GST-Pull down analysis showed that LvserpinB3 could interact with serine protease 1 (LvSP1). The recombinant LvserpinB3 (rLvserpinB3) protein exhibited inhibitory roles on the proteolytic activity of trypsin, whereas, mutation at the P1 residue led to the disfunction of the inhibitor. Furthermore, the LvserpinB3 and trypsin mixture were incubated with Anti-SERPINB3 antibodies, and a peptide band with an apparent molecular weight of 30 kDa were detected by western blot analysis. These findings might be valuable in understanding the potential role for LvserpinB3 in inhibiting the target proteases during shrimp immune defences.


Central Administration of Indomethacin Mitigates the Injury-Induced Upregulation of Aromatase Expression and Estradiol Content in the Zebra Finch Brain.
Injury to the vertebrate brain causes neuroinflammation, characterized in part by increases in prostaglandins. In rodents and songbirds, brain injury also induces the transcription and translation of aromatase in reactive astrocytes around the site of damage. Interestingly, this induction is more rapid in female zebra finches relative to males. Induced aromatization is neuroprotective, as inhibition of aromatase and estrogen replacement, increases and decreases the extent of damage, respectively. Although the consequences of induced astrocytic aromatization are intensely studied, little is known about what factors induce aromatase. Inflammation is sufficient to induce astrocytic aromatase suggesting that the link between inflammation and aromatase expression may be causal. To test this hypothesis, adult male and female zebra finches received bilateral mechanical injuries through which either the cyclooxygenase (COX)-1/2 inhibitor indomethacin or vehicle was administered into contralateral hemispheres. Subjects were killed either 6 or 24 hours after injury. In both sexes, an enzyme immunoassay for prostaglandin E2 (PGE2) revealed that indomethacin decreased PGE2 relative to the contralateral hemisphere at both time points, suggesting that the dose and mode of administration used were successful in affecting neuroinflammation locally. Indomethacin reduced aromatase expression and 17β-estradiol (E2) content at 6 hours but not 24 hours following injury in females. However, in males, the inhibitory effect of indomethacin on aromatase and E2 was apparent at 24 but not 6 hours after treatment. These data suggest that COX activity, perhaps via consequent prostaglandin secretion, may induce aromatase expression and central E2, an effect that is detectable in temporally distinct patterns between sexes.


Inflammatory Liver Tumor Caused by Fasciola hepatica Mimicking Intrahepatic Cholangiocarcinoma.
Human fascioliasis is a rare parasitic disease outside of countries in which it is endemic. The diagnosis of hepatic-phase fascioliasis by diagnostic imaging alone is challenging. A 69-year-old female was referred to our hospital for the treatment of a solitary solid cystic mass lesion, 6 cm in diameter, accompanied with mild symptoms and minimal changes in laboratory parameters. Intrahepatic cholangiocarcinoma was suspected, and she underwent extended posterior sectionectomy. Four months later, she was re-admitted because of fatigue, high fever, and epigastric pain. Her eosinophil fraction and immunoglobulin E levels were extremely elevated (49.1% and 6833 IU/ml, respectively). She was found to have two new reticular cystic hepatic tumors. Serum dot enzyme-linked immunosorbent assay for parasites revealed strong positivity for Fasciola hepatica. Praziquantel was ineffective, and multi-cystic tumors rapidly developed in the left lateral section, requiring emergency left lateral sectionectomy. An F. hepatica helminth, approximately 3 cm in size, was observed on the cut liver surface during hepatic resection. Prophylactic triclabendazole (1,000 mg/day) was administered twice. She has been well for over 10 years without relapse of fascioliasis. In patients with hepatic tumors accompanied by inflammatory changes and eosinophilia, detailed medical history and serological testing by dot enzyme-linked immunosorbent assay for parasites are strongly recommended.


Differentiating anti-lamina lucida and anti-sublamina densa anti-BMZ antibodies by indirect immunofluorescence on 1.0 M sodium chloride-separated skin.
Sixty-one bullous disease sera containing IgG anti-BMZ antibodies were examined by indirect immunofluorescence on intact skin and skin separated through the lamina lucida by incubation in 1.0 M NaCl. All sera produced an indistinguishable pattern of linear immunofluorescence on intact skin at dilutions of 1:10 or higher. On separated skin, antibodies bound to either the epidermal (epidermal pattern), dermal (dermal pattern), or epidermal and dermal (combined pattern) sides of the separation. The binding patterns were consistent on separated skin from several donors and titers of anti-basement membrane zone antibodies on separated skin were comparable to those on intact skin. Sera from 3 patients with herpes gestationis (HG), 36 patients with bullous pemphigoid (BP), and 1 patient with clinical and histologic features of epidermolysis bullosa acquisita (EBA) showed an epidermal pattern. Sera from 9 patients with BP showed a combined pattern and sera from 6 patients with EBA and 6 patients with clinical and histologic features of BP showed a dermal pattern. Indirect immunoelectron microscopy of selected sera showed antibodies producing the epidermal and combined patterns were anti-lamina lucida antibodies and those producing the dermal pattern were anti-sublamina densa antibodies. These results show indirect immunofluorescence on separated skin is a dependable method for differentiating bullous disease anti-lamina lucida and anti-sublamina densa antibodies and that differentiating between the antibodies is essential for accurate diagnosis in some patients. The results also suggest BP anti-lamina lucida antibodies may have more than one antigenic specificity.


The Association between COVID-19 and Reactive Arthritis: A Systematic Review of Case Reports and Case Series.
Reactive arthritis (ReA) is a joint inflammation that follows an infection at a distant site, often in the gastrointestinal or urogenital tract. Since the emergence of COVID-19 in January 2020, several case reports have suggested a relation between reactive arthritis and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), due to the novelty of the disease, most findings were reported in the form of case reports or case series, and a comprehensive overview is still lacking. We searched PubMed/Medline and Embase to identify studies addressing the association between ReA and COVID-19. The following terms were used: ("Reactive Arthritis" OR "Post-Infectious Arthritis" OR "Post Infectious Arthritis") AND ("COVID-19" OR "SARS-CoV-2" OR "2019-nCoV"). A total number of 35 reports published up to February 16th, 2022, were included in this study. A wide range of ages was affected (mean 41.0, min 4 max 78), with a higher prevalence of males (61.0%) from 16 countries. The number and location of the affected joints were different in included patients, with a higher prevalence of polyarthritis in 41.5% of all cases. Cutaneous manifestations and visual impairments were found as the most common associated symptoms. Most patients (95.1%) recovered, with a mean recovery time of 24 days. Moreover, arthritis induced by COVID-19 seems to relieve faster than ReA, followed by other infections. ReA can be a possible sequel of COVID-19 infection. Since musculoskeletal pain is a frequent symptom of COVID-19, ReA with rapid onset can easily be misdiagnosed. Therefore, clinicians should consider ReA a vital differential diagnosis in patients with post-COVID-19 joint swelling. Additional studies are required for further analysis and to corroborate these findings.


Predictive value of the red blood cell distribution width-to-platelet ratio for hepatic fibrosis.
The red blood cell distribution width-to-platelet ratio (RPR) has been reported to be an indicator of hepatic fibrosis in patients with chronic hepatitis B (HBV), nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (HCV). However, no research has explored the RPR in all patients with hepatic fibrosis. There is a recognized need to establish whether the RPR could assess hepatic fibrosis and reflect the severity of fibrosis, regardless of the patient's etiology. Quantitative data from 1282 patients who underwent liver biopsy between January 2010 and December 2014 at the Second Affiliated Hospital of Zhejiang University School of Medicine were included. The etiologies included HBV or HCV infection, NAFLD, schistosomiasis, granulomatous liver disease, and vascular abnormalities. Five noninvasive models were calculated for all patients based on laboratory parameters. The degrees of fibrosis severity were evaluated based on the Metavir scoring scale. The RPR demonstrated the best accuracy of predicting hepatic fibrosis among the selected five models (0.75, p < .001) regardless of etiology. In addition, the RPR values increased with advanced hepatic fibrosis progression. Furthermore, combining the RPR with the white blood cell (WBC) count improved the accuracy of grading hepatic fibrosis as reflected by the likelihood ratio (LR + 9.03, LR - 0.49). The RPR is a useful indicator for hepatic fibrosis, regardless of etiology, and can reflect the severity of fibrosis. This study supports further clinical development of the RPR both in a stepwise manner or in combination with inflammatory parameters to improve the accuracy of scoring hepatic fibrosis.


Survey of catalysts for oxidation of mercury in flue gas.
Methods for removing mercury from flue gas have received increased attention because of recent limitations placed on mercury emissions from coal-fired utility boilers by the U. S. Environmental Protection Agency and various states. A promising method for mercury removal is catalytic oxidation of elemental mercury (Hg0) to oxidized mercury (Hg2+), followed by wet flue gas desulfurization (FGD). FGD cannot remove Hg0, but easily removes Hg2+ because of its solubility in water. To date, research has focused on three broad catalyst areas: selective catalytic reduction catalysts, carbon-based materials, and metals and metal oxides. We review published results for each type of catalyst and also present a discussion on the possible reaction mechanisms in each case. One of the major sources of uncertainty in understanding catalytic mercury oxidation is a lack of knowledge of the reaction mechanisms and kinetics. Thus, we propose that future research in this area should focus on two major aspects: determining the reaction mechanism and kinetics and searching for more cost-effective catalyst and support materials.


Individually guided training prescription by heart rate variability and self-reported measure of stress tolerance in recreational runners: Effects on endurance performance.
The aim of this study was to determine the effect of endurance training individually guided by objective (Heart Rate Variability-HRV) or self-report measure of stress (DALDA-questionnaire) in comparison to predefined endurance training prescription for improving endurance performance in recreational runners. After a 2-week preliminary baseline period to establish resting HRV and self-reported measure of stress, thirty-six male recreational runners were randomly assigned to HRV-guided (GHRV; n = 12), DALDA-guided (GD; n = 12) or predefined training (GT; n = 12) prescription groups. Before and after 5-weeks of endurance training, participants performed a track field peak velocity (Vpeak_TF), time limit (Tlim) at 100% of Vpeak_TF and 5 km time-trial (5 km TT) tests. GD lead to higher improvements in Vpeak_TF (8.4 ± 1.8%; ES = 1.41) and 5 km TT (-12.8 ± 4.2%; ES = -1.97), than GHRV (6.6 ± 1.5% and -8.3 ± 2.8%; ES = -1.20; 1.24) and GT (4.9 ± 1.5% and -6.0 ± 3.3%; ES = -0.82; 0.68), respectively, with no differences for Tlim. Self-report measures of stress may be used to individualize endurance training prescription on a daily basis leading to better performance enhancement, which may be used with HRV for a holistic understanding of daily training-induce adaptations.


Raman observation of the interactions between NH4+, SO4(2-), and H2O in supersaturated (NH4)2SO4 droplets.
High signal-to-noise ratio (S/N) Raman spectra of (NH(4))(2)SO(4) droplets deposited on a quartz substrate were obtained from dilute to supersaturated states upon decreasing the relative humidity (RH). When the molar water-to-solute ratio (WSR) decreases from 16.8 to 3.2, the v(1)-SO(4)(2-) band changes very little, that is, showing a red-shift of only about 1 cm(-1) (from 979.9 to 978.8 cm(-1)) and an increase of its full width at half-maximum (fwhm) from 8.3 to 9.8 cm(-1). Other vibration modes such as v(2)- and v(4)-SO(4)(2-) bands appear almost constantly at 452 and 615 cm(-1). Such kind of a spectroscopic characteristic is different from previous observation on other cations, indicating that the interactions between SO(4)(2-) and NH(4)+ in supersaturated states are similar to those between SO(4)(2-) and H(2)O in dilute states. After fitting the Raman spectra with Gaussian functions in the spectral range of 2400-4000 cm(-1), we successfully extracted six components at positions of 2878.7, 3032.1, 3115.0, 3248.9, 3468.4, and 3628.8 cm(-1), respectively. The first three components are assigned to the second overtone of NH(4)+ umbrella bending, the combination band of NH(4)+ umbrella bending and rocking vibrations, and the NH(4)+ symmetric stretching vibration, while the latter three components are from the strongly, weakly, and slightly hydrogen-bonded components of water molecules, respectively. With a decrease of the RH, the proportion of the strongly hydrogen-bonded components increases, while that of the weakly hydrogen-bonded components decreases in the droplets. The coexistence of strongly, weakly, and slightly hydrogen-bonded water molecules must hint at a similar hydrogen-bonding network of NH(4)+, SO(4)(2-), and H(2)O to that of pure liquid water in supersaturated (NH(4))(2)SO(4) droplets.


African American Women's Reports of Racism during Hurricane Katrina: Variation by Interviewer Race.
This study investigated the effects of interviewer race on low-income African American female hurricane survivors' reports of racism during Hurricane Katrina and its aftermath (N = 41). Respondents were asked directly about the role of racism during the storm and evacuation by one of three interviewers (two White females and one African American female). Contrary to expectations, respondents were not significantly more likely to agree that racism played a role during the hurricane and its aftermath when with an African American interviewer compared to a White interviewer. However, when speaking to the White interviewers versus the African American interviewer, respondents were significantly more likely to use qualifying and contradictory statements and to make references to other races also being victims of the hurricane.


BSA-FITC-loaded microcapsules for in vivo delivery.
Here we describe the preparation of BSA-FITC-loaded microcapsules as a model protein system for in vivo delivery. BSA-FITC-loaded microcapsules were prepared using a mono-axial nozzle ultrasonic atomizer, varying a number of parameters to determine optimal conditions. The preparation method chosen resulted in a BSA-FITC encapsulation efficiency of approximately 60% and a particle size of approximately 50 microm. An analysis of the microcapsules showed a BSA-FITC core surrounded by a poly(D,L-lactic-co-glycolic acid) (PLGA) shell. Injection of BSA-FITC-loaded microcapsules into rats resulted in a sustained release of BSA-FITC that maintained increased concentrations of BSA-FITC in plasma for up to 2 weeks. In contrast, the concentration of BSA-FITC in plasma after injection of BSA-FITC-only solution reached near-zero levels within 3 days. Fluorescence images of microcapsules removed at various times after implantation showed a gradual decrease of BSA-FITC in BSA-FITC-loaded microcapsules, confirming a sustained in vivo release of BSA-FITC. The duration of in vivo release and plasma concentration of BSA-FITC was correlated with the initial dose of BSA-FITC. BSA-FITC-loaded microcapsules maintained their structure for at least 4 weeks in the rat. The inflammatory response observed initially after injection declined over time. In conclusion, BSA-FITC-loaded microcapsules achieved sustained release of BSA-FITC, suggesting that microcapsules manufactured as described may be useful for in vivo delivery of pharmacologically active proteins.


'It feels sometimes like my house has burnt down, but I can see the sky': A qualitative study exploring patients' views of cognitive behavioural therapy for chronic fatigue syndrome.
Cognitive behavioural therapy (CBT) is currently a first-line treatment for chronic fatigue syndrome (CFS). Even though the results from trials are promising, there is variability in patient outcomes. The aim of this study was to explore the experiences of patients with CFS who undertook CBT at a specialist service for CFS. This was a qualitative study. Thirteen patients with CFS, approaching the end of CBT, participated in semi-structured interviews. In addition, participants were asked to rate their satisfaction with CBT and perceived level of improvement. The data were analysed using inductive thematic analysis. The majority of participants were satisfied with treatment and reported marked improvements. This was evident from the ratings and corroborated by the qualitative data, yet recovery was in general incomplete. Participants often disclosed mixed feelings towards CBT prior to its start. Behavioural aspects of treatment were found useful, while participants were more ambivalent towards the cognitive aspects of treatment. The tailored nature of CBT and therapist contact were important components of treatment, which provided participants with support and validation. Engagement and motivation were crucial for participants to benefit from CBT, as well as the acceptance of a bio-psychosocial model of CFS. Illness beliefs around CFS were also discussed throughout the interviews, possibly impeding engagement with therapy. The results suggest that various factors may moderate the effectiveness of CBT, and a greater understanding of these factors may help to maximize benefits gained from CBT. Statement of contribution What is already known on this subject? CBT is effective in reducing CFS symptoms, but not all patients report marked improvements following treatment. Predictors of outcome have been explored in the literature. Few studies have looked at the experience of adult patients with CFS who have had CBT. What does this study add? Findings provide insights as to why variability in CBT-related improvements exists. Beliefs about CFS and CBT may shape engagement and consequently contribute to post-treatment outcomes. Flexibility and sensitivity are necessary from therapists throughout treatment to ensure full engagement.


A patient-centred approach to treatment with incretin-based agents in patients with type 2 diabetes.
The 2012 position statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommends a haemoglobin A1c level of <7% for most patients with type 2 diabetes (T2D). Initial therapy consists of lifestyle changes plus metformin, with an emphasis on a patient-centred approach to management. Addition of incretin-based therapy is recommended as an add-on after metformin failure, and later on in combination with basal insulin. Basal insulin is recommended from the onset in patients with A1c ≥10%. The possibility of incorporating incretin-based therapy in the patient-centred approach will be investigated both in the literature and clinical experience. Incretin-based therapy targets multiple dysfunctional organ systems in T2D and provides sustained glycaemic control, with extraglycaemic benefits and low risk of hypoglycaemia. To initiate an incretin-based therapy that best fits an individual patient's needs, the patient's A1c level, preference and comorbid conditions should be considered along with any drug safety and adherence-related issues. There is good evidence to support the patient-centred approach to T2D management. This approach allows patient treatment goals and personal preferences to be matched with the clinical profile(s) of one or more agents to formulate a treatment plan that can best achieve the goals. Incretin-based therapies are an important class of agents to consider after metformin monotherapy failure and later in combination with basal insulin. By matching patient needs with the clinical profiles of the various treatment options, pharmacists can actively engage in the practice of patient-centred care and management.


[Epidemiological and clinical profile of skin damages in black African patients on chronic hemodialysis].
Dermatologic manifestations are common among patients on chronic hemodialysis and may represent systemic involvement. Our study aims to determine the epidemiological and clinical profile of skin damages in black patients living in Yaounde, Cameroon. We conducted a cross sectional study including all patients receiving chronic haemodialysis treatment for at least 3 months in two hemodialysis centers in Yaounde from February to May 2014. Patients underwent an interview and a dermatological examination. Chi-squared tests and Student's t-test (or equivalents) were used for statistical analysis, with significance level at p <0.05. A total of 112 patients (78 (69.9%) men) with an average age of 48.6 ± 13 years and a mean duration of dialysis of 46,3 ± 37 months were included in the study. Skin lesions were present in 94 (83.9%) patients. Xerosis (63.3%), pruritus (37.5%), melanoderma (34.8%), acne (12.5%) and half and half nails (10.7%) were the most common dermatologic manifestations. Xerosis was associated with anuria (p = 0.0001) and advanced age (p = 0.032); melanoderma was associated with anuria (p = 0.042) and time spent on dialysis (p = 0.027) while half and half nails were associated with young age (p = 0.018) and biweekly dialysis (p = 0.01 ). Skin damages are frequent and dominated by xerosis, pruritus and melanoderma in patients on chronic hemodialysis living in Yaounde. Biweekly dialysis, advanced age, anuria and time spent on dialysis were associated factors.


A feminist analysis of the menopause discourse.
Menopause has been viewed as a medical condition which needs to be treated. The discourse surrounding the process reflects a positivist paradigm without acknowledgement of the lived experiences of women who have been given conflicitng information. In this paper we write about the dilemmas faced by peri menopausal, menopausal and post menopausal women as they grapple with the issues that focus on 'symptoms', rather than a natural phenomenon. We point out that the 'science' of menopause is class, race and gender biased as we present a feminist analysis of the concerns facing mid life women.


Distribution of tyrosinated and detyrosinated alpha-tubulin revealed by mouse anti-peptide polyclonal antibodies.
Mouse anti-peptide antibodies that specifically react (in competitive ELISA and immunoblotting) with the corresponding C-terminal hepta- and octapeptides of alpha-tubulin differing in the terminal tyrosine and that hence recognize the post-translationally modified forms of alpha-tubulin are described. At the light microscopic level tyrosinated tubulin was demonstrated practically in all structures containing microtubules with the exception of the flagella of the spermatozoa of several species. The presence of detyrosinated Glu tubulin was very limited; occasional interphase microtubules, midbody and flagella of the spermatozoa only exhibited the positive reaction. The results compared to the recently published findings indicate that the different arrangement of microtubules assembled mostly of Glu tubulin can be distinguished by polyclonal antibodies against detyrosinated tubulin.


Are patients with lichen planus really prone to urolithiasis? Lichen planus and urolithiasis.
to investigate whether patients with lichen planus (LP) are really prone to urolithiasis or not. We performed a prospective analysis of 40 patients diagnosed with lichen planus (LP) (group I), and 40 volunteers did not have LP before (group II). Participants were all checked for urolithiasis by radiological investigations. Blood samples were analyzed for biochemistry parameters including calcium and uric acid. 24-h urine samples were analyzed to investigate oxalate, citrate calcium, uric acid, magnesium, sodium and creatinine. Men/women ratio and mean age were similar between group I and II (p>0.05). A presence or history of urolithiasis was detected in 8 (20%) and 2 (%5) patients in group I and II, respectively (p<0.05). Hypocitraturia was the most common anomaly with 35% (n:14) in group I. The rate of hypocitraturia in group II was 12.5% (n:5) and the difference was statistically significantly different (p=0.036). In group I, hyperuricosuria and hyperoxaluria followed with rates of 27.5% (n:11) and 25% (n:10), respectively. The rate of hyperuricosuria and hyperoxaluria were both 5% (n:2) in group II and the differences were significant (p<0.05). Hyperuricemia was another importante finding in the patients with LP. It was detected in 13 (32.5%) patients in group I and in 1 (2.5%) participant in group II (p=0.001). According to our results, metabolic disorders of urolithiasis were highly detected in the patients with LP. However, similar to the etiology of LP, the exact reasons for these metabolic abnormalities in LP remain a mystery.


Modafinil: the unique properties of a new stimulant.
Modafinil, a novel stimulant which has several remarkable features that distinguish it from other stimulants, has been developed by Lafon, a French pharmaceutical company. Unlike the amphetamines, for example, modafinil is reported to have minimal peripheral side effects at therapeutic doses. It also appears to have a low abuse potential, does not interfere with normal sleep, and does not seem to produce tolerance. It improves vigilance especially in sleep-deprived subjects. It has been used clinically for up to 3 years in the treatment of narcolepsy and idiopathic hypersomnia. It could be an ideal replacement for amphetamine in short-term operations in which fatigue might threaten the successful completion of a mission. We recommend that military laboratories experienced in studying sustained performance include modafinil or perhaps a more selective alpha 1 receptor agonist in their investigations.


Education and decline in cognitive performance: compensatory but not protective.
The association between education and cognitive change was investigated in a large community sample of elderly people followed up after 3.6 years. Lower education was predictive of decline on the Mini-Mental State Examination (MMSE) and on tests of language and knowledge, but not on tests of cognitive speed, memory or reaction time. The effects of education were not attenuated when adjusted for health, disability or activity level. The findings suggest that education slows the rate of decline on crystallized intelligence, but not other cognitive abilities. Education may compensate for neurodegenerative changes rather than protect against them.


Optimization of fermentation conditions for P450 BM-3 monooxygenase production by hybrid design methodology.
Factorial design and response surface techniques were used to design and optimize increasing P450 BM-3 expression in E. coli. Operational conditions for maximum production were determined with twelve parameters under consideration: the concentration of FeCl(3), induction at OD(578) (optical density measured at 578 nm), induction time and inoculum concentration. Initially, Plackett-Burman (PB) design was used to evaluate the process variables relevant in relation to P450 BM-3 production. Four statistically significant parameters for response were selected and utilized in order to optimize the process. With the 416C model of hybrid design, response surfaces were generated, and P450 BM-3 production was improved to 57.90x10(-3) U/ml by the best combinations of the physicochemical parameters at optimum levels of 0.12 mg/L FeCl(3), inoculum concentration of 2.10%, induction at OD(578) equal to 1.07, and with 6.05 h of induction.


The use of perfluorochemical emulsion in the study of pulmonary microvascular permeability.
The perfluorochemical exchange transfused rat was used to examine whether the interaction of plasma proteins with the luminal surface of endothelial cells effects the permeability of pulmonary capillaries. Ultrastructural immunocytochemical techniques were used to localize albumin and IgG. The results indicated that the presence of plasma proteins localized solely within the glycocalyx was sufficient to render the underlying pulmonary capillary endothelium as impermeable to intravenously injected native ferritin (pI 4.7) as that of nonexchange transfused control rats. In further experiments it was observed that the removal of circulating plasma proteins by exchange transfusion resulted in the unmasking of anionic sites on the glycocalyx. This was determined by morphometry by counting the number of intravenously injected cationized ferritin particles (pI 8.5) bound to the luminal surface of the endothelium. There was no statistically significant difference in the amount of binding to the thick and thin sides of the capillaries. These observations support the fiber matrix model of capillary permeability as formulated by Curry and Michel.


The study of prevalence rate, and clinical characteristics of high altitude deterioration.
This study was aimed to investigate the prevalence rate and clinical characteristics of high altitude deterioration (HADT), which would provide a scientific basis for the diagnosis and prevention of HADT. A total of 175 subjects, who had migrated to a high altitude (4516 m) for more than 1 year, were investigated. A questionnaire survey based on the symptoms of HADT was conducted, and 117 subjects were determined to have HADT according to the diagnostic criteria of HADT. To explore the clinical characteristics of HADT, 117 HADT patients and 31 healthy individuals were assigned to HADT patient group and healthy control group, respectively. Their body mass indexes (BMIs), blood rheology, full blood count (including hemoglobin concentration, leukocyte count, neutrophil count, lymphocyte count and platelet count), blood pressure, heart rate, oxygen saturation as well as left ventricular ejection fraction (LVEF) and fraction shortening (LVFS) were assessed. The prevalence rate of HADT was 66.9% at a high altitude of 4516 m. Compared with those in healthy people at high altitude, some health indicators such as BMI, leukocyte count, neutrophil count, lymphocyte count, platelet count, systolic blood pressure, oxygen saturation, LVEF value and LVFS value were lower but other indicators including the blood viscosity, hematocrit, hemoglobin concentration and heart rate were higher in patients with HADT. The prevalence rate of HADT (66.9%) was high among people moving to a high altitude of 4516 m. Clinical characteristics of HADT were: (1) Impairment of left ventricular systolic function; (2) Immune depression; (3) Microcirculation disturbance; and (4) Decline of hemostasis and coagulation function.


Stimulation in vitro of lymphocytes for induction of uveoretinitis without any significant proliferation.
Experimental autoimmune uveoretinitis can be adoptively transferred into naive recipients by lymphocytes from rats immunized with uveitogenic Ag, provided these cells are activated in vitro before being injected. The activation of sensitized lymphocytes, by the immunizing Ag, or by cross-reacting Ag, is usually accompanied by vigorous proliferation. We report, however, on a complete dissociation between the capacity of a peptide to generate uveitogenicity and to stimulate proliferation in cultured lymphocytes. This peptide, which occupies sequence 579-591 of the bovine interphotoreceptor retinoid-binding protein (IRBP), is one of the three "repeats" that exhibit partial sequence homologies with the immunodominant and highly immunogenic peptide, 1179-1191. Peptide 579-591 is nonimmunogenic and nonuveitogenic in Lewis rats and does not stimulate any significant proliferation in lymphocytes sensitized against whole IRBP, peptide 1179-1191, or another "repeat" peptide, 271-283, which is immunogenic and uveitogenic. In contrast, peptide 579-591 effectively generates uveitogenicity in the lymphocytes sensitized against these three Ag. Unlike 579-591, peptides 271-283 and 1179-1191 stimulated both proliferation and uveitogenicity in these sensitized lymphocytes. A different pattern of activities was observed with the other "repeat" peptide, 880-892. This peptide did not have any effect on the lymphocytes sensitized against IRBP, 271-283 or 1179-1191, but did stimulate both proliferation and uveitogenicity in lymphocytes sensitized against itself. The data suggest that 579-591 selectively stimulates a lymphocyte subset that is uveitogenic, but is incapable of mounting proliferative responses.


Genetic (In)stability of 2,6-Dichlorobenzamide Catabolism in Aminobacter sp. Strain MSH1 Biofilms under Carbon Starvation Conditions.
Aminobacter sp. strain MSH1 grows on and mineralizes the groundwater micropollutant 2,6-dichlorobenzamide (BAM) and is of interest for BAM removal in drinking water treatment plants (DWTPs). The BAM-catabolic genes in MSH1 are located on plasmid pBAM1, carrying bbdA, which encodes the conversion of BAM to 2,6-dichlorobenzoic acid (2,6-DCBA) (BbdA+ phenotype), and plasmid pBAM2, carrying gene clusters encoding the conversion of 2,6-DCBA to tricarboxylic acid (TCA) cycle intermediates (Dcba+ phenotype). There are indications that MSH1 easily loses its BAM-catabolic phenotype. We obtained evidence that MSH1 rapidly develops a population that lacks the ability to mineralize BAM when grown on nonselective (R2B medium) and semiselective (R2B medium with BAM) media. Lack of mineralization was explained by loss of the Dcba+ phenotype and corresponding genes. The ecological significance of this instability for the use of MSH1 for BAM removal in the oligotrophic environment of DWTPs was explored in lab and pilot systems. A higher incidence of BbdA+ Dcba- MSH1 cells was also observed when MSH1 was grown as a biofilm in flow chambers under C and N starvation conditions due to growth on nonselective residual assimilable organic carbon. Similar observations were made in experiments with a pilot sand filter reactor bioaugmented with MSH1. BAM conversion to 2,6-DCBA was not affected by loss of the DCBA-catabolic genes. Our results show that MSH1 is prone to BAM-catabolic instability under the conditions occurring in a DWTP. While conversion of BAM to 2,6-DCBA remains unaffected, BAM mineralization activity is at risk, and monitoring of metabolites is warranted.IMPORTANCE Bioaugmentation of dedicated biofiltration units with bacterial strains that grow on and mineralize micropollutants was suggested as an alternative for treating micropollutant-contaminated water in drinking water treatment plants (DWTPs). Organic-pollutant-catabolic genes in bacteria are often easily lost, especially under nonselective conditions, which affects the bioaugmentation success. In this study, we provide evidence that Aminobacter sp. strain MSH1, which uses the common groundwater micropollutant 2,6-dichlorobenzamide (BAM) as a C source, shows a high frequency of loss of its BAM-mineralizing phenotype due to the loss of genes that convert 2,6-DCBA to Krebs cycle intermediates when nonselective conditions occur. Moreover, we show that catabolic-gene loss also occurs in the oligotrophic environment of DWTPs, where growth of MSH1 depends mainly on the high fluxes of low concentrations of assimilable organic carbon, and hence show the ecological relevance of catabolic instability for using strain MSH1 for BAM removal in DWTPs.


LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424.
Study has demonstrated the abnormal expression and role of lncRNA CASC15 in diabetes patients with chronic renal failure. However, its role in diabetes nephropathy (DN) is still unclear. This study aimed to investigate the potential mechanism and role of lncRNA CASC15 in DN. The relationship between miR-424 and CASC15/SP-A was predicted by Starbase software and verified by luciferase reporter assay. HK-2 cells were treated with 25 mM glucose (HG) for 24 h to establish DN cell model. MTT and flow cytometry analysis were carried out to test cell proliferation and apoptosis. Epithelial-to-mesenchymal transition (EMT) markers were analyzed by RT-qPCR and western blot assay. We proved that CASC15 could interact with miR-424, and SP-A was a target of miR-424. HG-treatment significantly enhanced lncRNA CASC15 level and decreased miR-424 level in HK-2 cells. LncRNA CASC15-siRNA significantly improved cell viability, repressed apoptosis, promoted E-cadherin expression, and inhibited N-cadherin expression in HG-treated HK-2 cells, and these effects were reversed by miR-424 inhibitor. SP-A was highly expressed in HG-treated HK-2 cells. The biological effects of miR-424 mimic on HG-treated HK-2 cells were reversed by SP-A-plasmid. In conclusion, lncRNA CASC15 inhibition relieved HG-induced HK-2 cell injury and EMT through miR-424/SP-A axis.


Poor tolerance of beta-blockers by elderly patients with heart failure.
Despite the well-understood importance of beta-blocker therapy in heart failure, it is sometimes not possible to use beta-blockers in elderly patients due to poor tolerance. In this report, we describe the case of an 83-year-old patient with severe systolic heart failure complicated by aortic valve stenosis and atrial fibrillation. A simple therapeutic approach involving discontinuation of beta-blockers remarkably alleviated the symptoms such as left ventricular ejection fraction, and improved the chest radiography and laboratory findings; further, atrial fibrillation converted to sinus rhythm. It is important to carefully administer beta-blocker therapy to elderly patients with heart failure, especially after considering cardiac output.


Plate-Based Phenotypic Screening for Pain Using Human iPSC-Derived Sensory Neurons.
Screening against a disease-relevant phenotype to identify compounds that change the outcome of biological pathways, rather than just the activity of specific targets, offers an alternative approach to find modulators of disease characteristics. However, in pain research, use of in vitro phenotypic screens has been impeded by the challenge of sourcing relevant neuronal cell types in sufficient quantity and developing functional end-point measurements with a direct disease link. To overcome these hurdles, we have generated human induced pluripotent stem cell (hiPSC)-derived sensory neurons at a robust production scale using the concept of cryopreserved "near-assay-ready" cells to decouple complex cell production from assay development and screening. hiPSC sensory neurons have then been used for development of a 384-well veratridine-evoked calcium flux assay. This functional assay of neuronal excitability was validated for phenotypic relevance to pain and other hyperexcitability disorders through screening a small targeted validation compound subset. A 2700-compound chemogenomics screen was then conducted to profile the range of target-based mechanisms able to inhibit veratridine-evoked excitability. This report presents the assay development, validation, and screening data. We conclude that high-throughput-compatible pain-relevant phenotypic screening with hiPSC sensory neurons is feasible and ready for application for the identification of new targets, pathways, mechanisms of action, and compounds for modulating neuronal excitability.


Anatomic and Molecular Imaging in Prostate Cancer.
Prostate cancer is characterized by a complex set of heterogeneous disease states. This review aims to describe how imaging has been studied within each specific state. As physicians transition into an era of precision medicine, multiparametric magnetic resonance imaging (mpMRI) is proving to be a powerful tool leading the way for a paradigm shift in the diagnosis and management of localized prostate cancer. With further research and development, molecular imaging modalities will likely change the way we approach recurrent and metastatic disease. Given the range of possible oncological progression patterns, a thorough understanding of the underlying carcinogenesis, as it relates to imaging, is a requisite if we are to appropriately manage prostate cancer in future decades.


Endoplasmic reticulum stress-mediated autophagy contributes to 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium-mediated photodynamic therapy via the PERK-eIF2α pathway.
5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium (EtNBSe) is a novel synthetic bipolar photosensitizer with many promising applications. This study investigated the impact of EtNBSe-mediated photodynamic therapy (EtNBSe-PDT) on the autophagy and endoplasmic reticulum (ER) stress of squamous carcinoma cells (A-431 cells), as well as the related molecular mechanisms. The potency of EtNBSe-PDT against squamous cell carcinoma was evaluated in BALB/c nude mice. Cell viability was evaluated using MTT. Western blotting and immunofluorescence were used to determine the expression levels of ER stress- and autophagy-related proteins. Both morphological and microscopic findings showed that the tumor on the xenograft mice exhibited an apparent reduction in volume and was replaced with fibrosis 20 days after EtNBSe-PDT. Additionally, in an in vitro study using A-431 cells, EtNBSe-PDT was found to inhibit A-431 cell survival in an EtNBSe concentration- and light dose- dependent manner, and to induce ER stress via the PERK-eIF2α signaling pathway. Additionally, EtNBSe-PDT could also induce autophagy of A-431 cells. Furthermore, the ER stress inhibitor 4-PBA and the eIF2α inhibitor salubrinal were found to inhibit the autophagy induced by EtNBSe-PDT. This study demonstrated that the PERK-eIF2α signaling pathway was involved in the ER stress induced by EtNBSe-PDT. Meanwhile, the ER stress via the PERK-eIF2α pathway promoted the occurrence of autophagy in A-431 cells.


Infusions of hFSH and hLH in normal men. II. Serum testosterone response to infused hLH and hFSH.
Standardized 4 h intravenous infusions of human follicle stimulating hormone (hFSH) and/or human luteinizing hormone (hLH) were given either separately or combined to 7 normal male volunteers. The infusions raised the serum gonadotrophin levels at least 10 (FSH) and 18 (LH) times above the basal ones. Serum testosterone (T) levels were measured serially before, during and after the infusions and, in 4 subjects, during a corresponding period of another normal day. During a normal or basal 24 h period fluctuations were seen and also a circadian rhythm with lower levels in the evening. The infusion of hFSH alone (3 subjects) did not alter the serum T levels. The infusion of hLH alone in 2 subjects raised serum T levels by 17% and 55% over those of the basal day. The combined FSH/LH infusion caused a significant rise (35-68%) in 4 subjects and greater rise in 2 of them than after infusion of the hLH alone. The serum T responses were gradual, reaching a maximum 7-8 h after the end of the infusion.


Aptamer Inhibits Tumor Growth by Leveraging Cellular Proteasomal Degradation System to Degrade c-Met in Mice.
Current action mechanisms for aptamer-based therapeutics depend on occupancy-driven pharmacology to mediate protein functions. We report a new mechanism where aptamers leverage cellular proteasomal degradation system to degrade proteins for cancer treatment. A DNA aptamer (hereinafter referred to as c-Met-Ap) binds to the extracellular domain of mesenchymal-epithelial transition factor (c-Met) and selectively induces c-Met phosphorylation at Y1003 and Y1349. The phosphorylation of Y1003 recruits E3 ubiquitin ligase casitas B-lineage lymphoma, causing c-Met ubiquitination and degradation in the proteasome. Furthermore, c-Met-Ap can induce a decrease in the heterodimeric partner proteins of c-Met and the downstream effector proteins in the c-Met signal axis, effectively inhibiting tumor growth in A549 tumor-bearing BALB/c mice. Our study uncovers a novel, actionable mechanism for aptamer therapeutics and opens a new avenue for developing highly efficient anticancer drugs.


A case of abdominal aortic aneurysm with short angulated proximal neck treated with the chimney graft technique.
Endovascular aneurysm repair (EVAR) using stent grafts has shown to be an effective alternative to surgical repair in treating an abdominal aortic aneurysm (AAA). EVAR is associated with shorter hospital stays, less blood loss, shorter operating times, and lower early morbidity and mortality compared to open surgical repair, although EVAR required a higher reintervention rate during a longer follow-up period. However, short or severely an angulated infrarenal proximal aortic neck is considered unsuitable for EVAR. The chimney graft technique is a modified procedure based on the deployment of a covered or bare-metal stent parallel to the main aortic endograft within the aneurysm, thereby creating a conduit that runs outside the aortic main endograft to preserve flow to the aortic branches. In this case report, we present a 78-year-old patient with an AAA with a short and severely angulated proximal neck who was successfully treated by EVAR using the chimney graft technique.


Geochemical aspects and contamination evaluation of major and trace elements in the sediments of Kallada river, southern Western Ghats, India.
The metal concentrations within the sediments of Kallada River Basin (KRB) draining the south-western flanks of Western Ghats in Kerala, India were examined using pollution indices and statistical analysis in order to inspect the level of contamination. This study includes a systematic analysis of sediment contamination by heavy metals and major oxides of the river Kallada draining the south-western flanks of Western Ghats in Kerala, India during pre-monsoon (May 2019), monsoon (September 2019) and post-monsoon (February 2020) seasons. Sediment samples were taken from 20 locations and the major investigations carried out in the sediment samples include geochemical analysis for the determination of major oxides and minor (trace) elements by using X-ray Fluorescence spectrometer (XRF) and textural analysis for the classification of sediment samples into different categories. To understand the pollution loads in the sediments of the area under study, the heavy metal and major element contamination of the samples were assessed based on crustal enrichment factor (EFc), geo accumulation index (Igeo), contamination factor (CF), degree of contamination (Cdeg) and pollution load index (PLI). From the analysis, it is seen that the coastal sediments of KRB were polluted mainly by Zirconium which exhibits high values in the pre-monsoon season. Among the major elements, Titanium is the only one which manifests slightly higher values in the pre-monsoon period. Based on the textural analysis, it is observed that these sediments predominantly come under sandy loam and loamy silt classifications during the three seasons of study. The concentrations of heavy metals and major ions in the surface sediments of Kallada river were studied to determine the extent of anthropogenic inputs in this tropical river system.


Food consumption, growth, and development of Dutch children fed on alternative diets.
A review of four studies examining food consumption growth and development of Dutch children fed on alternative diets is given. A literature study indicated that regarding child nutrition the three important movements in the Netherlands are the ecological movement, the anthroposophics, and the macrobiotics. A study on food consumption, height, and weight in preschool children fed these diets showed that the group of macrobiotic children were most at risk. Antropometric data collected in a cross-sectional study with 300 macrobiotic-fed children aged 0-8 y showed that the growth curves for boys and girls deviated from the Dutch standard curves after approximately 5 mo of age. There was no catch-up growth. In a selected sample of this latter group (43 children aged 4-6 y) mental development was measured by the Snijders-Oomen-Nonverbal intelligence test. The results of this test did not indicate an abnormal mental development for this age group of macrobiotic children.


Experimental and theoretical study of the ion-ion mutual neutralization reactions Ar(+)+SF(n)- (n=6, 5, and 4).
The ion-ion mutual neutralization reactions Ar(+)+SF(n) (-)-->Ar+SF(n) (n=6, 5, and 4) have been studied in a flowing afterglow-Langmuir probe (FALP) apparatus at 300 K and 1 Torr of He buffer gas. Electron concentrations and product ion fractions were measured, and neutralization rate constants of 4.0 x 10(-8), 3.8 x 10(-8), and 4 x 10(-8) cm(3) s(-1) for SF(6) (-), SF(5) (-), and SF(4) (-), respectively, were derived, with uncertainties of +/-25% (+/-35% for SF(4) (-)). During the neutralization process, excited neutrals are generated that are able to dissociate to neutral fragments. In the case of SF(6), the formation of SF(5) and SF(4), and similarly in the case of SF(5), the formation of SF(4) and SF(3) were observed and quantified. The mechanism of primary and secondary reaction was analyzed in detail, and rate constants for the dissociative electron attachments e(-)+SF(5)-->F(-)+SF(4) (k=3 x 10(-9) cm(3) s(-1),+/-40%) and e(-)+SF(3)-->F(-)+SF(2) (k=2 x 10(-8) cm(3) s(-1),+400%,-75%) were also derived. The experimental ion-ion neutralization rate constants were found to be in good agreement with estimates from an optimum two-state double-passage Landau-Zener model. It was also found that energy partitioning in the neutralization is related to the extent of electronic excitation of Ar generated by the electron transfer processes.


Identification of regulatory role of DNA methylation in colon cancer gene expression via systematic bioinformatics analysis.
Colon cancer arises from the accumulations of genetic and epigenetic changes. Currently, profiles of DNA methylation and gene expression of colon cancer have not been elucidated clearly. This articles aims to characterize the profile of DNA methylation and gene expression of colon cancer systemically, and acquire candidate genes potentially regulated by altered methylation for this disease.Data were downloaded from The Cancer Genome Atlas database. Differentially methylated CpG sites (DMCs) and differentially methylated regions (DMRs) were calculated via COHCAP. Differentially expressed genes (DEGs) were identified by DESeq2. Weighted gene co-expression network analysis (WGCNA) package in R was applied for WGCNA.Data of 275 solid tumor tissues and 19 adjacent tumor tissues of colon cancer were obtained. A total of 1828 DMCs, including 1390 hypermethylated and 438 hypomethylated CpG sites, were identified between tumor and normal groups. A total of 789 DEGs, containing 435 upregulated genes and 354 downregulated genes were observed. It revealed that 8 DMRs-DEGs and 95 DMCs-DEGs pairs were significantly correlated. Furthermore, genes of yellow and brown modules from WGCNA were significantly correlated with tumor/normal status, and significantly enriched in peroxisome proliferator activated receptor signaling pathway, glutamatergic synapse, and neuroactive ligand-receptor interaction. Genes in the above 2 modules were also significantly enriched in DMCs or DMRs-associated genes. Specifically, ADHFE1, HAND2, and GNAO1 were hypermethylated and downregulated in colon cancer, suggesting that the low expression levels of these genes may be regulated by DNA hypermethylation. In addition, the 3 genes were involved in brown module of WGCNA, indicating their important roles in colon cancer.The investigation of the relationship between DNA methylation and gene expression may help to understand the effect of DNA methylation alteration on genes expression, especially gene co-expression network in the development of colon cancer. Genes such as ADHFE1, HAND2, and GNAO1 may be served as potential candidates for diagnosis and therapy targets in colon cancer.


Effect of alternate nostril breathing on cardio respiratory parameters and muscle strength among rotating shift workers.
Night shifts at work is the most frequent reasons for circadian rhythm disruption and subsequent psychological and physiological disturbances, especially increased risk of cardiovascular and respiratory ailments compared to daytime workers. Alternate nostril breathing for about 15 minutes was known to have effect over cardiac, respiratory parameters and muscle strength. Hence aim is of interest to assess the effects of alternate nostril breathing (ANB) on cardio-respiratory parameters and muscle strength among the rotating shift workers in the tertiary care hospital. This observational study was carried out in the department of Physiology after getting institutional ethical committee clearance. Around 140 rotating night shift workers of both sex of age 25-40 years with normal BMI and 140 non-shift workers age, sex and BMI matched were selected as study and control group respectively. Heart rate, blood Pressure, respiratory rate, peak expiratory flow rate, respiratory endurance, respiratory burst test, muscle strength and fatigue were recorded before and after 15 minutes of ANB. Shift workers were found to have significantly altered systolic (P=0.000) and diastolic (P=0.002) blood pressure and heart rate (P=0.010) compared to non-shift workers. Fatigue is altered significantly (P< 0.05) after ANB between both shift and non- shift workers. ANB can be used as a therapeutic module among the shift workers, to maintain their sound health and to improve their performance in the night duty.


RagC GTPase regulates mTOR to promote chemoresistance in senescence-like HepG2 cells.
Radiotherapy and chemotherapy can arrest cancer cells in a senescence-like state, which can lead to therapy resistance and cancer relapse. mTOR is hyperactivated in senescent cells but the mechanisms remain unclear. In this study, we examine the roles of several mTOR-regulated GTPases in senescence-like liver cancer cells and the mechanisms in drug resistance. We show that although RagC, Rheb, Rab1A, Rab5 and Arf1 GTPases were required for optimal mTOR activation in proliferating HepG2 cells, only RagC and Rheb are required in the senescence-like counterparts. Consistently, the drug resistance of the senescence-like HepG2 can be reduced by knocking down RagC and Rheb but not the other GTPases. Autophagic and lysosomal activity were increased in senescence-like cells; pharmacological inhibition of autophagy-lysosome decreased mTOR activity and preferentially sensitized senescence-like HepG2 cells to chemotherapy drugs including trametinib, cisplatin, and doxorubicin. In liver cancer patients, expression of RagC and Rheb but not other GTPases examined was associated with unfavorable prognosis. Our study therefore has defined a key role of Rag-Rheb GTPase in mediating mTOR activation and drug resistance in senescence-like HepG2 cells, which could have important implications in developing second-line treatments for liver cancer patients.


Hypothalamic sydrome as an initial presentation of Wernicke encephalopathy: A case report.
Wernicke encephalopathy (WE) is a syndrome characterized by an acute or subacute onset of ataxia, ophthalmoplegia, and mental status changes. To our knowledge, hypothalamic syndrome is rare in WE. A 73-year-old female patient with acute cerebral infarct, who showed initial symptoms of vomiting, nausea, ataxia, and subsequent anorexia, was treated with parenteral nutritional supplement for 20 days. Nevertheless, the patient still developed refractory hyponatremia despite the appropriate sodium supplement given for a week following parenteral nutritional supplement. In fact, after 14 days of parenteral nutritional supplement, the patient gradually showed hypotension and apathy. Hyponatremia, hypotension, anorexia and apathy were signs of hypothalamic syndrome. Finally, the patient was diagnosed as WE by head magnetic resonance imaging, which showed symmetrical lesions in T2-weighted imaging images and FLAIR high signal intensity in the periaqueduct, hypothalamus, thalamus, mammiliary bodies, medulla oblongata, and vermis cerebelli. The patient was given thiamine supplementation. The patient regained consciousness within 3 days. The sings of hyponatremia, hypotension, and apathy were relieved subsequently. When patients develop unexplained hypothalamic syndrome, we should think of the possibility of WE. The concomitant presence of hyponatremia, hypotension, anorexia, and apathy in WE is rare. Therefore, this case is reported here for discussion.


A Langerhans' cell in mitosis within the epidermis of a case of lichen amyloidosus.
While studying skin specimens of lichen amyloidosus, we found an epidermal Langerhans' cell in mitosis. Since there are only two previous reports of Langerhans' cells in mitosis in the epidermis, a third instance is reported by us.


Pharmacological profile of the new anticonvulsant etazepine.
The pharmacological profile of the new anticonvulsant etazepine (5,6-dihydro-5-methyl-11H-11-ethoxy-dibenzo[b,e]azepin-6-one) was investigated. It protected mice and rats from a wide variety of convulsant agents (maximal electroshock, pentetrazol (metrazole), bicuculline, strychnine, 3-mercaptopropionic acid, nicotine, cefazoline and kainic acid) at doses about 16-45 times lower than those exerting neurotoxic effects (depending on the test used). The anticonvulsant effect of etazepine was long-acting (more than 24 h) and did not seem to develop tolerance. Moreover, etazepine did not prolong thiopental-induced sleeping time. Based on pharmacological studies etazepine seems to exert its anticonvulsant effects by activating the GABAergic system.


Epidemiological analysis of Salmonella enterica ssp. enterica serovars Hadar, Brancaster and Enteritidis from humans and broiler chickens in Senegal using pulsed-field gel electrophoresis and antibiotic susceptibility.
Salmonella Hadar, Salmonella Brancaster and Salmonella Enteritidis are the main Salmonella enterica ssp. enterica serovars isolated from poultry in Senegal. Our objective was to analyse the pulsed-field gel electrophoresis (PFGE) and antibioresistance patterns of strains belonging to these serovars and to assess the significance of broiler-chicken meat as a source of human infection. A total of 142 Salmonella isolates were analysed: 79 were isolated from Senegalese patients with sporadic diarrhoea (11 S. Hadar, nine S. Brancaster and 59 S. Enteritidis) and 63 from poultry (30 S. Hadar, 17 S. Brancaster and 16 S. Enteritidis). The PFGE of XbaI- and SpeI-digested chromosomal DNA gave 20 distinct profiles for S. Hadar, nine for S. Brancaster and 22 for S. Enteritidis. Each serovar was characterized by a major pulsotype which was X3S1 in 42% of S. Hadar, X8S1 in 53.8% of S. Brancaster and X1S2 in 43% of S. Enteritidis isolates. Human and poultry isolates of Salmonella had common PFGE patterns. Antibiosensitivity tests showed multiresistance (more than two drugs) was encountered in 14.5% of S. Hadar and in 5% of S. Enteritidis isolates. Resistance to quinolones was considered to be of particular importance and 14.5% of S. Hadar isolates were found to be resistant to nalidixic acid. CONLCUSIONS: The sharing of similar PFGE profiles among isolates from humans and poultry provided indirect evidence of Salmonella transmission from contaminated broiler meat. But most of the Salmonella isolates remained drug sensitive. Efforts are needed to eliminate Salmonella from poultry meat intended for human consumption. This study has also highlighted the importance of continuous surveillance to monitor antimicrobial resistance in bacteria associated with animals and humans.


Intestinal parasitism: a childhood problem in rural Bengal.
A study was undertaken to assess the parasitic infection rate in a rural community of West Bengal amongst children below four years of age suffering from gastrointestinal complaints. A total of 221 faecal samples were examined during November 1992 to April 1994. G. lamblia (17.2%) and E. histolytica (8.1%) were the predominant protozoas, whereas E. vermicularis (12.2%) and A. lumbricoides (8.1%) were found to be common amongst helminthic infection. A significantly lower infection rate was observed in children below one year (24.4 per cent) as compared to older age groups (66.4 per cent).


Developmental changes of sheep surfactant: in vivo function and in vitro subtype conversion.
Developmental differences in the intrinsic characteristics of surfactant have not been evaluated. Therefore, heavy-subtype surfactant was recovered from alveolar washes of 132-, 139-, and 148-day preterm lambs, 2- to 3-day-old newborn ventilated lambs, and adult sheep. The density of heavy-subtype surfactant and surfactant protein-A-to-saturated phosphatidylcholine ratios increased significantly with developmental age. In contrast, percent conversion from heavy to light surfactant forms was more rapid for surfactant from preterm animals than for surfactant from mature or adult animals. The function of the heavy-subtype surfactant was tested by treating ventilated 27-day gestational age preterm rabbits. The surfactant from the most immature animals was less effective at improving compliance or maintaining lung volumes on deflation than was surfactant from newborn or adult animals. These results demonstrate intrinsic and functional differences in surfactant from developing compared with mature sheep that correlated with the surfactant protein-A-content. The pattern of changes indicates that the preterm animal is at a disadvantage, because the surfactant is intrinsically abnormal relative to that of the adult.