Nature of the antigenic complex recognized by T lymphocytes. VIII. Specific inhibition of the stimulatory capacity of antigen-pulsed hapten-modified peritoneal exudate cells by anti-hapten antibody.
When macrophages which were pulsed with soluble protein antigens and then modified with 2,4,6-trinitrobenzenesulfonic acid (TNBS) were cultured with primed T cells in the presence of anti-2,4,6-trinitrophenyl (TNP) antiserum, a marked inhibition of the T cell proliferative response specific for the soluble protein antigen under study was observed. Inhibition of the proliferative response required that the protein antigen under study be easily susceptible to conjugation with TNBS. A lag period of 1-3 h must elapse following pulse exposure to the protein antigen and prior to TNP modification for anti-TNP antibody to exert an inhibitory effect, which suggests that processing of antigen in an intracellular site might occur with subsequent reexpression of antigen on the macrophage surface. It was hypothesized that anti-TNP antibody inhibits T cell proliferation by capping and shedding of TNP-modified determinants of the nominal antigen as well as TNP-modified cell surface proteins from the macrophage membrane. The failure of others to demonstrate an effect of anti-antigen antibody on T cell activation can best be explained as secondary to the low density of antigenic determinants on the macrophage membrane with resultant low-affinity binding of antibody to antigen.


Genetic structure of farmer-managed varieties in clonally-propagated crops.
The relative role of sexual reproduction and mutation in shaping the diversity of clonally propagated crops is largely unknown. We analyzed the genetic diversity of yam-a vegetatively-propagated crop-to gain insight into how these two factors shape its diversity in relation with farmers' classifications. Using 15 microsatellite loci, we analyzed 485 samples of 10 different yam varieties. We identified 33 different genotypes organized in lineages supported by high bootstrap values. We computed the probability that these genotypes appeared by sexual reproduction or mutation within and between each lineage. This allowed us to interpret each lineage as a product of sexual reproduction that has evolved by mutation. Moreover, we clearly noted a similarity between the genetic structure and farmers' classifications. Each variety could thus be interpreted as being the product of sexual reproduction having evolved by mutation. This highly structured diversity of farmer-managed varieties has consequences for the preservation of yam diversity.


[The EAA-ergic modulation of the brain dopaminergic system as a basis for creating new nootropic agents with stress-protective activity].
The paper provides theoretical evidence for and practical confirmation of the possible use of three lipophilic derivatives of N-acetyl-aspartic acid (EAA-AKF-94; AKF-92-10, and PIR-87-6-0). These compounds were shown to display pronounced nootropic activity to correct behavioral, memory, and cognitive disorders in rats exposed to emotional stress. Evidence is provided for the fact that modulation of monoaminergic brain activity mediated by heterosynaptic activation of EAA receptors.


Synthesis and charge-transfer properties of two acth analogues containing pentamethylphenylalanine in position 9.
In order to investigate the possible role of the Trp residue in ACTH as a change-transfer donor in the activation of ACTH receptors, two ACTH analogues (beta-corticotrophins (I-24) with L-Ser1 and D-Ser1, respectively) containing pentamethylphenylalanine instead of Trp have been synthesized. In these syntheses a new, alkaline-labile, amino-protecting group, the methylsulphonylethyloxycarbonyl group, was employed. The association constants of ACTH (I-24) and (Pmp9)-ACTH (I-24) with the water-soluble acceptor paraquat, were nearly equal.


Subcellular fractionation of human neutrophils and analysis of subcellular markers.
The neutrophil has long been recognized for its impressive number of cytoplasmic granules that harbor proteins indispensable for innate immunity. Analysis of isolated granules has provided important information on how the neutrophil grades its response to match the challenges it meets on its passage from blood to tissues. Nitrogen cavitation was developed as a method for disruption of cells on the assumption that sudden reduction of the partial pressure of nitrogen would lead to aeration of nitrogen dissolved in the lipid bilayer of plasma membranes. We find that cells are broken by the shear stress that is associated with passage through the outlet valve under high pressure, and that this results in disruption of neutrophils while leaving granules intact. The unique properties of Percoll as a sedimentable density medium with no inherent tonicity or viscosity are exploited for the creation of continuous density gradients with shoulders in the density profile created to optimize the physical separation of granule subsets and light membranes. Immunological methods (sandwich enzyme-linked immunosorbent assays) are used for quantitation of proteins that are characteristic constituents of the granule subsets of neutrophils.


Higher estimated net endogenous acid production with lower intake of fruits and vegetables based on a dietary survey is associated with the progression of chronic kidney disease.
Dietary acid load has been suggested to mediate the progression of chronic kidney disease (CKD). However, it is unclear what kinds of foods are actually associated with dietary acid load in patients with CKD. The self-administered diet history questionnaire (DHQ), which semi-quantitatively assesses the dietary habits of Japanese individuals through 150 question items, can estimate average daily intake of various foods and nutrients during the previous month. Using the DHQ, we investigated the association of dietary acid load with CKD progression. We also analyzed the kinds of food that significantly affect dietary acid load. Subjects were 96 outpatients with CKD (average estimated glomerular filtration rate [eGFR], 53.0 ± 18.1 ml/min/1.73 m2) at Niigata University Hospital, who had completed the DHQ in 2011. We calculated net endogenous acid production (NEAP) from potassium and protein intake evaluated by the DHQ in order to assess dietary acid load. CKD progression was assessed by comparing eGFR between 2008 and 2014. NEAP was not correlated with protein intake (r = 0.088, p = 0.398), but was negatively correlated with potassium intake (r = - 0.748, p < 0.001). Reduction in eGFR from 2008 to 2014 was estimated to be significantly greater in patients with higher NEAP (NEAP > 50.1 mEq/day, n = 45) than in those with lower NEAP (NEAP ≤50.1 mEq/day, n = 50) by 5.9 (95% confidence interval [95%CI], 0.1 to 11.6) ml/min/1.73 m2. According to multiple logistic regression analysis, higher NEAP was significantly associated with lower intake of fruits (odds ratio [OR], 6.454; 95%CI, 2.19 to 19.00), green and yellow vegetables (OR, 5.18; 95%CI, 1.83 to14.66), and other vegetables (OR, 3.87; 95%CI, 1.29 to 11.62). Elevated NEAP could be a risk factor for CKD progression. Low intake of fruits and vegetables would increase dietary acid load and might affect the progression of renal dysfunction in Japanese CKD patients.


Early predictors of severe COVID-19 among hospitalized patients.
Limited research has been conducted on early laboratory biomarkers to identify patients with severe coronavirus disease (COVID-19). This study fills this gap to ensure appropriate treatment delivery and optimal resource utilization. In this retrospective, multicentre, cohort study, 52 and 64 participants with severe and mild cases of COVID-19, respectively, were enrolled during January-March 2020. Least absolute shrinkage and selection operator and binary forward stepwise logistic regression were used to construct a predictive risk score. A prediction model was then developed and verified using data from four hospitals. Of the 50 variables assessed, eight were independent predictors of COVID-19 and used to calculate risk scores for severe COVID-19: age (odds ratio (OR = 14.01, 95% confidence interval (CI) 2.1-22.7), number of comorbidities (OR = 7.8, 95% CI 1.4-15.5), abnormal bilateral chest computed tomography images (OR = 8.5, 95% CI 4.5-10), neutrophil count (OR = 10.1, 95% CI 1.88-21.1), lactate dehydrogenase (OR = 4.6, 95% CI 1.2-19.2), C-reactive protein OR = 16.7, 95% CI 2.9-18.9), haemoglobin (OR = 16.8, 95% CI 2.4-19.1) and D-dimer levels (OR = 5.2, 95% CI 1.2-23.1). The model was effective, with an area under the receiver-operating characteristic curve of 0.944 (95% CI 0.89-0.99, p < 0.001) in the derived cohort and 0.8152 (95% CI 0.803-0.97; p < 0.001) in the validation cohort. Predictors based on the characteristics of patients with COVID-19 at hospital admission may help predict the risk of subsequent critical illness.


Suppressive effect of novel aromatic diamine compound on nuclear factor-kappaB-dependent expression of inducible nitric oxide synthase in macrophages.
N1-benzyl-4-methylbenzene-1,2-diamine (BMD) is a novel synthetic compound. In the present study, BMD compound was discovered to inhibit nitric oxide (NO) production in macrophages RAW 264.7. BMD compound attenuated lipopolysaccharide (LPS)-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), and inhibited LPS-induced iNOS promoter activity, indicating that the aromatic diamine compound could down-regulate iNOS expression at the transcription level. As a mechanism of the anti-inflammatory action, suppression of BMD compound on nuclear factor (NF)-kappaB activation has been documented. BMD compound exhibited dose-dependent inhibitory effect on LPS-mediated NF-kappaB transcriptional activity in the macrophages. Further, the compound inhibited LPS-mediated nuclear translocation of NF-kappaB p65 and DNA binding activity of NF-kappaB complex, in parallel, but did not affect LPS-mediated degradation of inhibitory kappaBalpha protein (IkappaBalpha). These results indicate that BMD compound could inhibit nuclear localization step of NF-kappaB p65 without affecting IkappaBalpha degradation. Finally, BMD compound could provide an invaluable tool to investigate NF-kappaB-dependent iNOS expression, in addition to its therapeutic potential in NO-associated inflammatory diseases.


Catalogue of topological electronic materials.
Topological electronic materials such as bismuth selenide, tantalum arsenide and sodium bismuthide show unconventional linear response in the bulk, as well as anomalous gapless states at their boundaries. They are of both fundamental and applied interest, with the potential for use in high-performance electronics and quantum computing. But their detection has so far been hindered by the difficulty of calculating topological invariant properties (or topological nodes), which requires both experience with materials and expertise with advanced theoretical tools. Here we introduce an effective, efficient and fully automated algorithm that diagnoses the nontrivial band topology in a large fraction of nonmagnetic materials. Our algorithm is based on recently developed exhaustive mappings between the symmetry representations of occupied bands and topological invariants. We sweep through a total of 39,519 materials available in a crystal database, and find that as many as 8,056 of them are topologically nontrivial. All results are available and searchable in a database with an interactive user interface.


Simple method for reduction of autofluorescence in fluorescence microscopy.
Autofluorescence of aldehyde-fixed neural tissue often complicates the use of fluorescence microscopy. Background fluorescence can be notably reduced or eliminated by irradiation with light before treatment with fluorescence probes, resulting in a higher contrast without adversely affecting the staining probabilities.


Emerging drugs for non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma. To discuss therapeutic management of NAFLD. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. Differentiation between steatosis and NASH currently requires a liver biopsy. We discuss different therapeutic approaches proposed in literature for patients with NAFLD. The treatment of associated conditions leads to an improvement of NAFLD and NASH. No specific drug is actually present to treat liver steatosis or NASH. The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Future research will discover possible specific liver drugs.


Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions.
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-β1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1β and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients' chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.


Multidetector row computed tomography in bowel obstruction. Part 2. Large bowel obstruction.
Large bowel obstruction may present as an emergency as high-grade colonic obstruction and can result in perforation. Perforated large bowel obstruction causes faecal peritonitis, which can result in high morbidity and mortality. Multidetector row computed tomography (MDCT) has the potential of providing an accurate diagnosis of large bowel obstruction. The rapid acquisition of images within one breath-hold reduces misregistration artefacts than can occur in critically ill or uncooperative patients. The following is a review of the various causes of large bowel obstruction with emphasis on important pathogenic factors, CT appearances and the use of multiplanar reformatted images in the diagnostic workup.


Mortality and length of stay in a veterans affairs hospital and private sector hospitals serving a common market.
To compare severity-adjusted in-hospital mortality and length of stay (LOS) in a Veterans Administration (VA) hospital and private sector hospitals serving the same health care market. Retrospective cohort study. A large VA hospital and 27 private sector hospitals in the same metropolitan area. Consecutive VA (N = 1,960) and private sector (N = 157,147) admissions in 1994 to 1995 with 9 high-volume diagnoses. Severity of illness was measured using validated multivariable models that were based on data abstracted from medical records. Outcomes were adjusted for severity and compared in VA and private sector patients using multiple logistic or linear regression analysis. Unadjusted mortality was similar in VA and private sector patients (5.0% vs 5.6%, respectively; P =.26), although mean LOS was longer in VA patients (12.7 vs 7.0 days; P <.001). Adjusting for severity, the odds of death in VA patients was similar (odds ratio [OR] 1.07; 95% confidence interval [95% CI], 0.74 to 1.54; P =.73). However, a larger proportion of deaths in VA patients occurred later during hospitalization (P <.001), and the odds of death in VA patients were actually lower (P <.05) in analyses limited to deaths during the first 7 (OR, 0.56) or 14 (OR, 0.63) days. Adjusted LOS was longer (P <.001) in VA patients for all 9 diagnoses. If the current findings generalizable to other markets, hospital mortality, a widely used performance measure, may be similar or lower in VA and private sector hospitals serving the same markets. The longer LOS of VA patients may reflect differences in practice patterns and may be an important source of bias in comparisons of VA and private sector hospitals.


Tibetan medicine Liuwei Muxiang pills (LWMX pills) effectively protects mice from chronic non-atrophic gastritis.
Chronic non-atrophic gastritis (CNG) is the most common type of chronic gastritis. If not actively treated, it may induce gastric cancer (GC). Western medicine is effective in CNG, but there are more adverse reactions after long-term medication, and it is easy to relapse after treatment, which affects patients' health and life. Tibetan medicine Liuwei Muxiang Pills (LWMX pills) is a traditional Tibetan medicine compound, which has a unique curative effect in the treatment of gastric inflammation, especially chronic non-atrophic gastritis. However, the mechanisms of LWMX pills for treatment CNG still remain poor known. The aim of this study was to evaluate the therapeutic intervention potential of Tibetan medicine LWMX pills on CNG and explore its potential mechanisms in mice models. The mice models was established to evaluate the therapeutic effect of LWMX pills on CNG. The main components of LWMX pills were analyzed by GC-MS. HE staining, immunohistochemistry, proteomics and Western Blot were used to analyze the potential mechanism of LWMX pills for CNG treatment. In the present study, LWMX pills containing costunolide, dehydrocostuslactone and antioxidants were found. IF results showed that the expression of ALDH1B1 in the control group was significantly lower than that in the model group in the gastric mucosa tissue, and the expression of ALDH1B1 was significantly lower in the 25 mg/ml LWMX Pills group (one month) and 25 mg/ml LWMX Pills group (two months) than in the model group. IHC revealed that model group samples expressed higher levels of Furin than 25 mg/ml LWMX Pills group samples, as evidenced by very strong staining of Furin in gastric mucosal cells. However, AMY2 staining in gastric mucosal cells did not differ significantly between the treated and control groups. the protein expression levels of these proteins were decreased in 25 mg/mL LWMX pills. Meanwhile, we found that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths).Western blotting showed that the protein expression levels of Furin, AMY2A, CPA3, ALDH1B1, Cam1, COXII, IL-6, IL-1β were decreased in 25 mg/mL LWMX pills. Meanwhile, that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths). 25mg/ml LWMX pill treatment for one month had better therapeutic effect on mice CNG. Further proteomic results showed that LWMX pills maintain gastric function by inhibiting inflammation and oxidative stress, and we also found that LWMX pills regulate the expression of proteins associated with cancer development (Amy2, Furin).


Congenital absence of the fourth metacarpal bone (congenital dysplasia of the ring finger).
Review of the related literature shows no reports of congenital absence of the fourth metacarpal or congenital dysplasia of the ring finger. I describe the clinical features, hand pattern profiles, and dermatogyphics of three patients with displastic floating ring finger. The surgical treatment is outlined.


Adenoma detection rate influences the risk of metachronous advanced colorectal neoplasia in low-risk patients.
In individuals with either no or 1 to 2 nonadvanced adenomas, future risks of advanced colorectal neoplasia (AN) vary according to clinical risk factors. However, little is known about the association between the adenoma detection rate (ADR) and the risk for metachronous AN in patients with low-risk adenomas. We identified 7171 participants with no or 1 to 2 nonadvanced adenomas at first-time screening colonoscopy. The risk of metachronous AN was investigated at surveillance colonoscopy, according to clinical characteristics and the ADR. In multivariate analysis the risk for metachronous AN was strongly associated with increasing age, male sex, increasing number of adenomas, and the ADR of the endoscopist. With the ADR modeled as a continuous variable, each 1.0% increase in the rate of ADR predicted a 3.0% decrease in the risk of metachronous AN (adjusted odds ratio [OR], .97; 95% confidence interval [CI], .95-.99). With the ADR modeled using a binary cut-off (32%), the risk of metachronous AN was reduced in patients of endoscopists with an ADR ≥32% (adjusted OR, .53; 95% CI, .35-.83). Moreover, the risk of metachronous AN was reduced (adjusted OR, .66; 95% CI, .46-.95) in patients of endoscopists with an ADR in the highest tertile, compared with patients of endoscopists with ADRs in the lowest tertile. The impact of ADR on metachronous AN was significant for patients with low-risk adenomas rather than patients with no adenoma. In patients with low-risk adenomas, the ADR of the endoscopist was inversely associated with the risk of metachronous AN.


Persisting volcanic ash particles impact stratospheric SO2 lifetime and aerosol optical properties.
Volcanic ash is often neglected in climate simulations because ash particles are assumed to have a short atmospheric lifetime, and to not participate in sulfur chemistry. After the Mt. Kelut eruption in 2014, stratospheric ash-rich aerosols were observed for months. Here we show that the persistence of super-micron ash is consistent with a density near 0.5 g cm-3, close to pumice. Ash-rich particles dominate the volcanic cloud optical properties for the first 60 days. We also find that the initial SO2 lifetime is determined by SO2 uptake on ash, rather than by reaction with OH as commonly assumed. About 43% more volcanic sulfur is removed from the stratosphere in 2 months with the SO2 heterogeneous chemistry on ash particles than without. This research suggests the need for re-evaluation of factors controlling SO2 lifetime in climate model simulations, and of the impact of volcanic ash on stratospheric chemistry and radiation.


Amyloid PET ordering practices in a memory disorders clinic.
This study assessed the ordering of amyloid positron emission tomography (PET) scans in a Veterans Affairs (VA) memory disorders clinic as part of routine clinical care, with possible implications for the extent to which ordering may occur outside of the VA in the future if covered by insurance. Clinical features predictive of ordering amyloid PET scans were retrospectively assessed; the percentage of patients who met appropriate use criteria were evaluated. Among 565 veterans, 34.9% of received an amyloid PET scan and 98.0% of these were consistent with appropriate use criteria. Patients with a PET were younger and more likely to have an initial diagnosis of Alzheimer's disease (AD). Of patients without an amyloid PET scan ordered, 64.4% would have met appropriate use criteria for amyloid PET. The majority of scans ordered were consistent with appropriate use criteria and more patients were eligible than received a scan. The current study's findings that approximately one-third of patients in a memory disorders clinic received an amyloid PET scan has implications for memory disorders clinics inside and outside of the US Veterans Health Administration.


Global progress in abortion advocacy and policy: an assessment of the decade since ICPD.
The 1994 International Conference on Population and Development (ICPD) Programme of Action represented a positive step toward legitimising abortion as a component of basic reproductive health services. This paper reviews how the ICPD principles and recommendations have been applied in the past decade toward increasing women's access to affordable, safe and legal abortion services. It examines advocacy efforts to increase understanding of abortion among policymakers and the public, policy and action at the global level, progress made in national-level policies and services, and obstacles encountered. Research and advocacy are helping to break the silence globally about unsafe abortion, and there is an emerging global movement supporting women's right to safe abortion. A great deal has been accomplished in the ten short years since ICPD, in spite of serious setbacks in some countries and continuing obstacles. A synthesis of public health and rights-based approaches, and strategic partnerships with other social justice movements are called for, as a foundation for effective legal reform efforts and to ensure that women have access to safe abortion services.


Epigenetic regulation of lung cancer cell proliferation and migration by the chromatin remodeling protein BRG1.
Malignant lung cancer cells are characterized by uncontrolled proliferation and migration. Aberrant lung cancer cell proliferation and migration are programmed by altered cancer transcriptome. The underlying epigenetic mechanism is unclear. Here we report that expression levels of BRG1, a chromatin remodeling protein, were significantly up-regulated in human lung cancer biopsy specimens of higher malignancy grades compared to those of lower grades. Small interfering RNA mediated depletion or pharmaceutical inhibition of BRG1 suppressed proliferation and migration of lung cancer cells. BRG1 depletion or inhibition was paralleled by down-regulation of cyclin B1 (CCNB1) and latent TGF-β binding protein 2 (LTBP2) in lung cancer cells. Further analysis revealed that BRG1 directly bound to the CCNB1 promoter to activate transcription in response to hypoxia stimulation by interacting with E2F1. On the other hand, BRG1 interacted with Sp1 to activate LTBP2 transcription. Mechanistically, BRG1 regulated CCNB1 and LTBP2 transcription by altering histone modifications on target promoters. Specifically, BRG1 recruited KDM3A, a histone H3K9 demethylase, to remove dimethyl H3K9 from target gene promoters thereby activating transcription. KDM3A knockdown achieved equivalent effects as BRG1 silencing by diminishing lung cancer proliferation and migration. Of interest, BRG1 directly activated KDM3A transcription by forming a complex with HIF-1α. In conclusion, our data unveil a novel epigenetic mechanism whereby malignant lung cancer cells acquired heightened ability to proliferate and migrate. Targeting BRG1 may yield effective interventional strategies against malignant lung cancers.


Effect of Denonvilliers' Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results of Chinese PUF-01 Randomized Clinical Trial.
To compare the outcomes of laparoscopic total mesorectal excision (L-TME) with Denonvilliers' fascia (DVF) preservation versus resection on urogenital function of male patients with rectal cancer. The protective effect of DVF during L-TME on pelvic autonomic nerves and postoperative urogenital function remains controversial. Between August 26, 2015 and July 18, 2019, 253 male patients with cT1-4 (T1-2 for anterior wall) N0-2M0 rectal cancer from 11 institutions were enrolled, and randomly assigned to L-TME with DVF preservation (Exp-group, n = 123) or resection procedures (Con-group, n = 130). Urinary function was assessed by residual urine volume, maximal flow rate, and International Prostate Symptom Score; sexual function was assessed by 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading. The Exp-group patients showed a lower urinary dysfunction rate (6.8% vs 25.4%, P = 0.003), higher maximal flow rate (16.25 ± 8.02 vs 12.40 ± 7.05 mL/s, P = 0.007), and lower International Prostate Symptom Score (6.55 ± 5.86 vs 8.57 ± 5.85, P = 0.026) than the Con-group patients at 2 weeks after surgery. The incidence of erectile dysfunction (IIEF-5 ≤ 11) at 12 months after surgery was lower in the Exp-group than in the Con-group (12.5% vs 34.2%, P = 0.023); Exp-group manifested superior IIEF-5 (16.63 ± 6.28 vs 12.26 ± 6.83, P = 0.018). The incidence of ejaculation dysfunction was lower in the Exp-group than in the Con-group at 12 months after surgery (10.0% vs 29.4%, P = 0.034). DVF preservation during L-TME revealed protective effects on postoperative urogenital function, and could be a better choice for male rectal cancer patients with specific staging and location. NCT02435758.


Biopsy of cervical lymph node.
This report examines 60 non-cancer patients who underwent a cervical lymph node biopsy, and discusses the value of the cervical lymph node biopsy as a diagnostic tool. Sixty patients with cervical lymph node enlargement who had lymph node biopsies at the Juntendo University between 2004 and 2007 were examined. The clinical parameters including age, size of the lymph node, white blood cell (WBC), C reactive protein (CRP), lactate dehydrase (LDH), soluble interleukin-2 receptor (sIL-2r) were measured at initial examination. Fine needle aspiration cytology was carried out in all patients. The patients were divided into 2 groups, including the malignant lymphoma (ML) group and the benign disease group. These groups were compared based on the patient's clinical parameters. Serum levels of LDH, sIL-2r, age and lymph node size in the ML group were significantly higher than in the benign group. WBC and CRP showed no significant differences. Simple regression analysis showed that there are correlation between the size of enlargement lymph node and serum levels of LDH and sIL-2r in ML group. The results of this study suggest that a biopsy should be considered early to patients with an advanced age, large swollen lymph nodes or high levels of serum sIL-2r or LDH.


Alzheimer's disease: the size of the problem, clinical manifestation and heterogeneity.
Age is the major demographic risk factor for the development of Alzheimer's disease (AD) and the ageing of our society has contributed to the growing importance of AD. The problem of AD has been tackled from numerous clinical and scientific angles. The traditional clinico-pathological disease concept, which relies on the manifestation of a dementia syndrome and the elimination of other relevant systemic and brain diseases for a diagnosis of AD, accommodates a number of genetically and clinically heterogeneous conditions, but cannot promote our understanding of the preclinical pathogenetic processes and their interaction. If new molecular biological discoveries cannot be integrated with this traditional clinico-pathological model, it may have outlived its usefulness.


A research program in medical physics for remote students.
The University of Adelaide in co-operation with the Royal Adelaide Hospital offers a degree of Master of Science (Medical Physics) which is available both to students resident in Adelaide and to remote students employed in hospitals in Australia or New Zealand. The program comprises research carried out in the work place, and courses delivered from Adelaide. The courses Radiation Biology, Protection and Epidemiology and Radiotherapy Physics are currently delivered on-line. A project has commenced to modify the presentation of all courses so that remote students can interact with their fellow students in weekly tutorials and engage in informal discussions through a discussion forum.


The United States experience with oral controlled-release morphine (MS Contin tablets). Parts I and II. Review of nine dose titration studies and clinical pharmacology of 15-mg, 30-mg, 60-mg, and 100-mg tablet strengths in normal subjects.
The results of nine US multicenter, sequential crossover, dose titration studies of controlled-release oral morphine (MS Contin 30 mg tablets [MSC], Purdue Frederick, Norwalk, CT) are reviewed in Part I. The studies demonstrated the prolonged analgesic efficacy of the preparation in the treatment of patients with moderate to severe cancer-related pain. Approximately 93% of the patients achieved satisfactory to excellent analgesia on a 12-hour regimen when appropriate dose titration was allowed. The remaining patients were successfully maintained on an 8-hour regimen. The preparation was well-tolerated and comparable in safety to immediate-release oral morphine. In global evaluations, MSC was judged to be significantly (P less than 0.05) more effective, and with significantly (P less than 0.05) fewer side effects than both the prestudy opioid analgesics and 4-hour immediate-release oral morphine. Patients had a broad range of morphine requirements (mean daily MSC dose, 240 mg; range, 60 mg/day to 1800 mg/day); therefore various MSC tablet strengths were developed. Part II presents three studies in which the MSC formulations (15-mg, 60-mg, and 100-mg tablets) were compared to the 30-mg tablet within three randomized, single-dose, two-way crossover, analytically blinded bioavailability protocols, to determine bioequivalence and dose proportionality. The maximum morphine concentration, time of maximum morphine concentration, and area under the plasma morphine versus 12-hour and 24-hour time curve (AUC 0.12; AUC 0.24) were determined in each study. There were no significant differences between the values associated with MSC 1 X 30 mg tablet and 2 X 15 mg tablets (study 1), MSC 2 X 30 mg tablets and 1 X 60 mg tablet (study 2), and MSC 3 X 30 mg tablets and 1 X 100 mg tablet (study 3, values adjusted to dose of 90 mg), except for one marginally significant difference in study 3 (AUC 0.24; P = 0.04) which was not clinically or biopharmaceutically significant. The results showed that MSC 15-mg, 30-mg, 60-mg, and 100-mg dosage strengths are bioequivalent and dose proportional, and, therefore, therapeutically interchangeable. It was concluded that with routine assessment of the patient and adherence to the principles of analgesic dosing, MSC can be successfully used to control cancer-related pain. Furthermore, the availability of various MSC tablet strengths can be expected to facilitate the analgesic management of a patient population with widely differing opioid requirements.


Leptin replacement therapy does not improve the abnormal lipid kinetics of hypoleptinemic patients with HIV-associated lipodystrophy syndrome.
Patients with HIV-associated dyslipidemic lipodystrophy (HADL) have characteristic lipid kinetic defects: accelerated lipolysis, blunted fat oxidation and increased hepatic fatty acid reesterification. HADL patients with lipoatrophy also have leptin deficiency. Small or non-randomized studies have suggested that leptin replacement improves glucose metabolism in HADL, with very limited data regarding its effects on the lipid kinetic abnormalities. We performed a randomized, double-blind, placebo-controlled, dose-escalating (0.02 mg/kg/d for two months; 0.04 mg/kg/d for a further two months) study of the effects of metreleptin on lipid kinetics in 17 adults with HADL, hypertriglyceridemia and hypoleptinemia. Rates of lipolysis, intra-adipocyte and intrahepatic reesterification and fatty acid oxidation were measured using infusions of (13)C(1)-palmitate and (2)H(5)-glycerol, and indirect calorimetry. Fasting lipid profiles and glucose and insulin responses to oral glucose challenge were also measured. Metreleptin treatment induced significant, dose-dependent increases in fasting plasma leptin levels. There was no significant change in total lipolysis, net lipolysis, adipocyte or hepatic re-esterification or fatty acid oxidation, or in fasting triglyceride or HDL-C concentrations, with metreleptin treatment. Metreleptin decreased fasting non-HDL-C levels (P<.01) and area-under-the-curve for glucose (P<.05). In hypoleptinemic HADL patients, treatment with metreleptin at 0.02 or 0.04 mg/kg/d does not improve abnormal fasting lipid kinetics, or triglyceride or HDL-C levels. Metreleptin does, however, improve glycemia and non-HDL-C in these patients. These results suggest a dissociation between leptin's effects on glucose metabolism compared to those on lipid kinetics in HADL.


A case report of exophytic nasal papilloma with acute dacryocystitis as the first symptom.
This study aims to explore a case of exophytic nasal papilloma with acute dacryocystitis as the first symptom. A 72-year-old male patient complaining of "a 10-year history of tearing and purulent discharge from the right eye, with subsequent redness and pain in the inner canthus for three days" was initially diagnosed with acute dacryocystitis of the right eye. The patient was treated with anti-inflammatory therapy. However, the redness and swelling of the inner canthus continued to increase. An endoscopic dacryocystorhinostomy of the right eye was performed under general anesthesia. A large amount of purulent secretion was drained during the operation. As a result, the swelling of the inner canthus was significantly reduced. A routine intra-operative biopsy of the wall of the lacrimal sac revealed an exophytic nasal papilloma. A second biopsy, 1 week after the surgery, revealed the same result. The patient was advised to undergo a dacryocystectomy once the swelling had subsided. However, the patient was reluctant to undergo this surgery and remains under clinical observation. It is rare for an exophytic nasal papilloma, which is a benign tumor in the lacrimal sac, which has the potential for recurrence and malignant transformation, to manifest with acute dacryocystitis as the first symptom. Therefore, this case report could provide a reference for the future clinical diagnosis of this disease.


Tracheostomy is associated with increased survival in Multiple System Atrophy patients with stridor.
Stridor treatment in multiple system atrophy (MSA) mainly comprises tracheostomy or continuous positive airway pressure (CPAP), but guidelines for the use of these treatments are lacking. The aim of the study was to evaluate the predictive value of stridor treatment in an MSA cohort. This is a retrospective and prospective monocentric cohort study including MSA patients evaluated at least once a year during the disease course. Stridor was video-polysomnography confirmed. The time of stridor treatment (CPAP or tracheostomy) and latency from stridor onset were collected. Survival and predictors of survival were calculated. A total of 182 (107 males, mean age at disease onset 57.3 ± 8.4 years) MSA patients were included in the study; 141 were deceased at the time of study. Of the total sample, 75 patients were diagnosed with stridor: 22 patients were treated with tracheostomy and 29 with CPAP, whilst 24 patients did not receive treatment. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment (incidence rate of death 12 vs. 21 vs. 23 per 100 person-years, respectively). Tracheostomy remained an independent factor associated with longer survival (hazard ratio 0.38, p = 0.029), also after adjustment for other confounders and latency for stridor treatment. This is the largest monocentric and long-term follow-up study comparing survival between tracheostomy and CPAP in MSA patients with stridor. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment. A careful multidisciplinary approach is required for the management of MSA patients with stridor.


Role of dyslipidemia in impairment of energy metabolism, oxidative stress, inflammation and cardiovascular disease in chronic kidney disease.
Advanced chronic kidney disease (CKD) results in a constellation of dysregulation of lipid metabolism, oxidative stress, and inflammation which are causally interconnected and participate in a vicious cycle. The CKD-associated lipid disorders are marked by impaired clearance of very low density lipoprotein and chylomicrons, hypertriglyceridemia, formation of small dense low-density lipoprotein (LDL), oxidative modification of LDL, intermediate density lipoprotein and chylomicron remnants, and high-density lipoprotein deficiency and dysfunction. This review provides a brief overview of the role of CKD-induced lipid disorders in the pathogenesis of oxidative stress, inflammation, cardiovascular disease, impaired exercise capacity, cachexia and wasting syndrome.


Parity violation and chiral symmetry breaking of a racemic mixture.
The chiral symmetry breaking of a racemic mixture by the parity violating weak interaction is considered. Particular attention is given to a mechanism recently proposed by Mason and Tranter whereby the weak neutral current interaction in chiral molecules leads to the differential absorption of unpolarized light by D vs. L enantiomers. After extending the usual theory of optical activity to include weak neutral currents, it is found that for spin-allowed transitions in typical organic molecules the weak photoabsorption asymmetry is much smaller than the value obtained using the reasoning of Mason and Tranter. Upon making a comparison with other mechanisms, it is concluded that differential radiolysis by beta electrons is likely to produce the largest symmetry breaking effect by the weak interaction.


Phase-wise analysis of the COVID-19 lockdown impact on aerosol, radiation and trace gases and associated chemistry in a tropical rural environment.
Phase-wise variations in different aerosol (BC, AOD, PM1, PM2.5 and PM10), radiation (direct and diffused) and trace gases (NO, NO2, CO, O3, SO2, CO2 and CH4) and their associated chemistry during the COVID-19 lockdown have been investigated over a tropical rural site Gadanki (13.5° N, 79.2° E), India. Unlike most of the other reported studies on COVID-19 lockdown, this study provides variations over a unique tropical rural environment located at a scientifically strategic location in the Southern Indian peninsula. Striking differences in the time series and diurnal variability have been observed in different phases of the lockdown. The levels of most species that are primarily emitted from anthropogenic activities reduced significantly during the lockdown which also impacted the levels and diurnal variability of secondary species like O3. When compared with the same periods in 2019, short-lived trace gas species such as NO, NO2, SO2 which have direct anthropogenic emission influence have shown the reduction over 50%, whereas species like CO and O3 which have direct as well as indirect impacts of anthropogenic emissions have shown reductions up to 10%. Long-lived species (CO2 and CH4) have shown negligible difference (<1%). BC and AOD have shown reductions over 20%. Particulate Matter (1, 2.5 and 10) reductions have been in the range of 40 to 50% when compared to the pre-lockdown period. The changes in shortwave downward radiation at the surface, diffuse component due to the scattering and diffuse fraction have been +2.2%, -4.1% and -2.4%, respectively, in comparison with 2019. In contrast with the studies over urban environments, air quality category over the rural environment remained same during the lockdown despite reduction in pollutants level. All the variations observed for different species and their associated chemistry provides an excellent demonstration of rural atmospheric chemistry and its intrinsic links with the precursor concentrations and dynamics.


[Application of mineral facets by optimization of the binding by silicoating and ceramic covering].
The binding technology of the mineral facet with the metal frame had been optimized by experimental examinations of the strainability of phantom facet crowns, by analyses of the adherence and light-microscopical representation of various combinations of material. Facet crowns equipped with ceramic covers exhibited the best results. The technology of manufacture can be modified by a holder for the adhesive-opaker mixture.


Assessing Two Different Aerial Toxin Treatments for the Management of Invasive Rats.
Aotearoa-New Zealand has embarked on an ambitious goal: to completely eradicate key invasive mammals by 2050. This will require novel tools capable of eliminating pests on a large scale. In New Zealand, large-scale pest suppression is typically carried out using aerial application of the toxin sodium fluoroacetate (1080). However, as currently applied, this tool does not remove all individuals. A novel application method, dubbed '1080-to-zero', aims to change this and reduce the abundances of target pests to zero or near-zero. One such target is black rats (Rattus rattus), an invasive species challenging to control using ground-based methods. This study monitored and compared the response of black rats to a 1080-to-zero operation and a standard suppression 1080 operation. No difference in the efficacy of rat removal was found between the two treatments. The 1080-to-zero operation did not achieve its goal of rat elimination or reduction to near-zero levels, with an estimated 1540 rats surviving across the 2200 ha treatment area. However, 1080 operations can produce variable responses, and the results observed here differ from the only other reported 1080-to-zero operation. We encourage further research into this tool, including how factors such as ecosystem type, mast fruiting and operational timing influence success.


Predictive testing for Huntington's disease: ten years' experience in two Italian centres.
Pre-symptomatic testing for Huntington's disease (HD) has been available as a clinical service in the medical centres of Rome and Genoa since December 1987, initially by DNA-linkage and since mid-1993 by direct mutation analysis. A multidisciplinary approach and a protocol which follows the Ethical Issue Policy Statement on Huntington's Disease Molecular Genetics Predictive Test has been used. In the period under study, 332 subjects requested the test, 288 were enrolled in the protocol and nearly half of these completed it. One hundred and forty-eight people withdrew from the testing procedure for various reasons but most frequently due to a more realistic evaluation of all possible consequences of test results, induced by psychological counselling. Therefore, 140 people completed the test. The overall gene-carrier/non-carrier ratio was 0.46:1. None of the identified gene carriers had catastrophic reactions such as suicide, suicide attempts or major psychiatric disorders. All appear to have had a similar pattern of reactions to an adverse result and none expressed regret for undergoing the test. In conclusion, presymptomatic testing for HD can be considered a safe procedure without adverse consequences when framed in an integrated protocol at qualified genetic centres.


Unilateral ligature-induced periodontitis influences the expression of neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats.
Expression of neuronal neuropeptides in inflammatory conditions is altered. The changes in expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in ipsilateral and contralateral trigeminal ganglion (TG) neurons were investigated by immunohistochemistry one week after unilateral ligature-induced periodontitis in rats. A retrograde nerve tracer Fluorogold (FG) was applied into the gingival sulcus of the second maxillary molar to identify the neurons in TG that specifically innervate the inflamed gingivomucosa. In addition, neurons from the corresponding maxillary and the adjacent mandibular-ophthalmic regions in TG were analysed. Statistically significantly higher frequencies of CGRP-positive neurons, regardless of their size, were found in TG ipsilateral to the periodontitis (83% and 73% in FG-labelled and maxillary regions, respectively) than in the control group without periodontitis (52% and 42% in FG-labelled and maxillary regions, respectively). The frequency of small FG-labelled SP-positive neurons in the ipsilateral TG (60%) was significantly higher than in the control TG (25%). In the contralateral TG the frequency of CGRP-positive neurons in maxillary region (66%) was significantly higher than in the control group. Surprisingly, the number of SP-positive neurons in all regions of contralateral TG decreased when compared to control and ipsilateral TGs. Taken together, these results implicate a role of neurogenic component in the pathogenesis of periodontitis. The contralateral response in the TG could be mediated through the transmedian neurological pathways crossing in the trigeminal nuclear complex or through the systemic inflammatory reaction and the activation of the so called "neuro-immune axis".


Younger females are at greater risk of vasodilation-related adverse symptoms caused by dihydropyridine calcium channel blockers: results of a study of 11,918 Japanese patients.
Adequate control of blood pressure in younger females is of crucial importance, because they are at higher risk of hypertensive target organ damage compared with males of similar age. In addition, female sex is a risk factor for adverse effects of antihypertensive drugs, especially dihydropyridines. This study set out to assess the incidence of adverse reactions during dihydropyridine use in a real-life clinical setting, focusing on the influence of female sex and age. The incidence of adverse reactions to dihydropyridine calcium channel blockers were investigated in 11,918 Japanese patients who participated in the Drug Event Monitoring project of the Japan Pharmaceutical Association conducted in Kumamoto prefecture. A multiple logistic regression analysis was used to determine the association between the incidence of adverse symptoms and female sex, with adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Vasodilation-related adverse symptoms occurred significantly more often in females than in males (OR 1.87, 95% CI 1.28-2.71, p=0.001). Furthermore, among females only, the younger age group (<50 years) complained of vasodilation-related symptoms more frequently (OR 2.39, 95% CI 1.02-5.59, p=0.045) and the older age group (≥80 years) complained of vasodilation-related symptoms less frequently (OR 0.56, 95% CI 0.33-0.95, p=0.030) than the middle age group (50-79 years). To the best of our knowledge, this is the first report showing that younger females are at high risk for vasodilation-related adverse symptoms during dihydropyridine use in a real-life clinical setting. These results should be verified in clinical studies using larger samples of young patients and more parameters.


International Workshop at the Nobel Forum, Karolinska Institutet on G protein-coupled receptors: finding the words to describe monomers, oligomers, and their molecular mechanisms and defining their meaning. Can a consensus be reached?
A meeting was held May 19, 2010 at the Karolinski Institute on Nomenclature in Pharmacology. This meeting occurred in conjunction with the Symposium The Changing World of G Protein Coupled Receptors: From Monomers to Dimers and Receptor Mosaics (Higher-order Oligomers) held the previous day at the Royal Swedish Academy of Science. Two broad topics of nomenclature were discussed; ligand nomenclature and the definition of 'receptor-receptor' interactions. This paper summarizes discussions on these topics along with a consensus definition of the term 'receptor-receptor' interaction.


Association between the prognostic nutritional index and severe headache or migraine: a population-based study.
Migraine is a highly prevalent headache disorder, and intake of various nutrients and special diets may improve migraine symptoms. We aimed to clarify the association between nutritional status and migraine. We collected the data of 1838/8953 (migraineurs/all participants) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 cycle. We used weighted multivariable linear or logistic regression analyses to study the association between the prognostic nutritional index (PNI) and the occurrence of severe headache or migraine. After adjusting for confounding variables, we found that mild (PNI 45-50) or moderate to severe (PNI <45) malnutrition were associated with higher prevalence of severe headache or migraine (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00-1.12, P = 0.004; OR 1.07, 95% CI 1.03-1.12, P < 0.001). In addition, we found that those with severe headache or migraine consumed less alcohol, dietary fiber, cholesterol, total folate, vitamin A, riboflavin, vitamin B6, vitamin B12, vitamin C, vitamin K, selenium, potassium, magnesium, and copper, and consumed more caffeine and theobromine than did those without severe headache or migraine. The PNI is associated with migraine prevalence, and may thus serve as a predictor of migraine risk and highlights the potential of nutrition-based strategies for migraine prevention and treatment.


Pathway of nerves with vasoactive intestinal polypeptide-like immunoreactivity to the major cerebral arteries of the rat.
The pathway of nerves with vasoactive intestinal polypeptide (VIP)-like immunoreactivity to the major cerebral arteries was studied in rats by means of the indirect immunofluorescent method. The fibers are densely distributed in the ethmoidal nerves and in the adventitia of both the external and internal ethmoidal arteries. Section of both ethmoidal nerves and external ethmoidal arteries before they enter the cranial cavity induced a marked reduction of VIP-like immunoreactive fibers in the walls of the vessels of the circle of Willis and its major branches. However, section of the external ethmoidal artery alone did not result in visible changes of the nerves around major cerebral arteries. The present study suggests that VIP-like immunoreactive fibers surrounding major cerebral arteries of the rat arise from fibers in the ethmoidal nerve showing immunoreactivity to VIP.


Bremsstrahlung imaging after 32P treatment for residual suprasellar cyst.
A patient with residual suprasellar cystic neoplasm was treated by direct instillation of the 32P colloid. The incidental bremsstrahlung images on a conventional gamma camera helped to localize the pharmaceutical within and outside of the lesion. Advantages of bremsstrahlung imaging and the dosimetry results of phantom studies carried out are described.


The influence of different registration techniques on condyle displacement and electromyographic activity in stomatognathically healthy subjects: a prospective study.
It is unclear whether different intermaxillary registration techniques are related to a physiological condylar position that permits neuromuscular equilibrium. This study analyzes and quantifies the effects of different registration techniques on the condyle position and how the registration technique modulates bilateral masseter and anterior temporalis muscle electromyographic activity. Three-dimensional electronic condylar position analysis (EPA) with an ultrasound-based jaw-tracking system and surface electromyographic activity (sEMG) was recorded during the registration of a manually guided centric relation (CR), maximal intercuspation (MI), and Gothic arch tracing guided centric relation (DIR method). Participants were 26 stomatognathically healthy volunteers (mean age, 30.6 ±9.5 years). Data were analyzed by 1-way ANOVA and post hoc Bonferroni correction (α=.05). EPA showed significant differences (P<.001) for CR, MI, and DIR in the vertical, sagittal, and horizontal axes. The condyle position during DIR was found to be significantly more anteriorly and inferiorly located than with CR (P<.001) and MI (P<.04). There were no significant differences in the mean muscle activity among CR, MI, and DIR. Muscular symmetry ranged from 63.87 to 81.47%. Significantly higher symmetry for the anterior temporalis (P=.03) and the masseter (P=.03) was found during the DIR than with CR. Torque coefficients (potential laterodeviating effect) were between 88.02% (CR) and 89.94% (MI). Registration technique significantly influenced the condyle position, while mean muscular activity was minimally affected. With respect to muscular balance and activation, the DIR position proved to be capable of inducing the greatest motor unit activity when compared with manually guided CR and MI.


Phenanthrene sorption studies on coffee waste- and diatomaceous earth-based adsorbents, and adsorbent regeneration with cold atmospheric plasma.
Phenanthrene (PHE) is a polycyclic aromatic hydrocarbon categorized as a high priority organic pollutant being toxic for the ecosystem and human health, and its sorption on natural organic or inorganic substances seems a well-promising method for its removal from water streams. The goals of the present work are (i) to assess the capacity of low-cost adsorbents fabricated by treating coffee wastes and diatomaceous earth to remove PHE from water; (ii) to elucidate the role of the pore structure on PHE sorption dynamics; and (iii) to assess the potential to regenerate adsorbents loaded with PHE, by using the novel technology of cold atmospheric plasma (CAP). Diatomaceous earth (DE) and DE pre-treated with sodium hydroxide (NaOH) or phosphoric acid (H3PO4) were chosen as inorganic adsorbents. Coffee waste (CW) and activated carbons (AC) produced from its pyrolysis at 800 °C (CWAC), either untreated (CWAC-800) or pre-treated with NaOH (CWAC-NaOH-800) and H3PO4 (CWAC-H3PO4-800), were chosen as organic adsorbents. The adsorbents were characterized with nitrogen adsorption-desorption isotherms, attenuated total reflectance-Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and mercury intrusion porosimetry. Based on the PHE sorption capacity and pore structure/surface characteristics, the CWAC-NaOH-800 was chosen as the most efficient adsorbent for further equilibrium and kinetic sorption studies. The multi-compartment model was used to describe the PHE sorption dynamics in CWAC-NaOH-800 by accounting for the pore/surface diffusion and instantaneous sorption. The CWAC-NaOH-800 exhibited remarkable values for (i) the specific surface area (SBET = 676.5 m2/g) and meso- and micro-pore volume determined by nitrogen sorption (VLN2 = 0.415 cm3/g); (ii) the macro- and meso-pore volume determined by mercury intrusion porosimetry (VMIP = 3.134 cm3/g); and (iii) the maximum PHE sorption capacity (qmax = 142 mg/g). The percentage of adsorbent recovery after its regeneration with CAP was found to be ~ 35%. From the simulation of sorption dynamics, it was found that at early times, the sorption kinetics is governed by the film diffusion towards the external surface of grains, but at late times, most of the adsorbed mass is transferred primarily to meso-/macro-pores via diffusion, and secondarily to micro-porosity via surface diffusion. Based on the adsorbent characteristics, effect of pH on sorption efficiency, and numerical analysis of sorption dynamics, it was concluded that probably the dominant adsorption mechanism is the π-π interactions between hydrophobic PHE aromatic rings and CWAC-NaOH-800 graphene layers. The high PHE removal efficiency of CWAC-NaOH-800, the successful interpretation of sorption dynamics with the multi-compartment model, and the potential to regenerate PHE-loaded adsorbents with the green and economic technology of CAP motivate a strategy for testing CWACs towards the adsorption of other PAHs, application of adsorbents to real wastewaters, and scaling-up to pilot units.


Clinical laboratory evaluation of a PCR assay for the detection of HCMV.
In limited laboratory space and consonant with limited opportunities for contamination, to implement and incorporate into our diagnostic virology laboratory, a polymerase chain reaction assay for human cytomegalovirus detection with maximum sensitivity. Polymerase chain reaction, adapted for use with the enzyme uracil-n-glycosylase to avoid the potential for false positive reactions due to amplicon carryover was developed, optimized using two primer pairs, and performed on 361 specimens, i.e., body fluids and tissues submitted to the viral laboratory for detection of human cytomegalovirus. Polymerase chain reaction results were compared to shell vial assay. Louisiana State University Health Sciences Center, Shreveport LA. Using the shell vial assay as the reference, analytical sensitivity (lower limit of detection) as well as laboratory sensitivity and specificity of both primer pairs. The lower limit of detection of our polymerase chain reaction assay was determined to be one focus-forming unit. Using the shell vial assay as the reference test, the sensitivity and specificity of both primer pairs were 96.5% and 94.3%, respectively. Polymerase chain reaction detected human cytomegalovirus in 6% of our culture-negative specimens. Based upon this study, our recommendations include the following: 1) a housekeeping gene amplification control is required for diagnostic polymerase chain reaction; 2) a single primer pair can be utilized for clinical work without sacrificing too much sensitivity; and 3) the laboratory should maintain close contact with clinicians to discuss polymerase chain reaction interpretation.


Experimental evidence challenges the presumed defensive function of a "slow toxin" in cycads.
[Formula: see text]-methylamino-L-alanine (BMAA) is a neurotoxic non-protein amino acid found in the tissues of cycad plants. The demonstrated toxicity of BMAA to diverse organisms, including humans, is widely assumed to imply a defensive function of BMAA against herbivores; however, this hypothesis has not previously been tested in an ecologically relevant system. We investigated the effects of dietary BMAA, across a range of dosages matching and exceeding levels typically present in cycad leaves, on the feeding preferences and performance of a generalist lepidopteran herbivore (Spodoptera littoralis).We observed no effects of dietary BMAA on the survival or development of S. littoralis larvae, nor any larval preference between BMAA-laced and control diets. These findings suggest that BMAA in cycad tissues does not deter feeding by insect herbivores, raising questions about other potential physiological or ecological functions of this compound.


[Experience for reconstruction of defects of abdominal wall with Gore-tex].
To evaluate the outcome of prevention of abdominal hernia in reconstruction of defect of abdominal wall with Gore-tex clinically. Six cases of the large defects of abdominal wall were repaired with Gore-tex after surgical removal of abdominal wall tumor. The reconstructed cases were followed up six months to three years and there was no postoperative complication. Gore-tex is a reliable and effective biomaterial for reconstruction of the large defect of abdominal wall.


Suicide Mortality Rate as a Sustainable Development Goal (SDG): A Bibliometric Analysis.
Suicidal behaviors are a serious but potentially preventable cause of premature death. Increased awareness of the importance of mental health for global health has led to new initiatives, supported by the World Health Organization (WHO) and the United Nations (UN). The suicide mortality rate is one of the indicators covered in the UN's Sustainable Development Goal (SDG) 3. The aim of this study is to identify the scientific production and its temporal evolution related to the suicide mortality rate indicator in the context of mental disorders and as one of the SDG. A bibliometric analysis was performed in Scopus to assess the related research on suicide mortality rate, including on the context of the third SDG, from inception to September 2, 2020. The set of articles were analyzed for bibliometric measures. A total of 3126 documents about mental health and suicide mortality rate on the context of SDG were collected. Articles were the predominant type of literature on this area (78.3%), with significant expression on the last years, more evident around 2015, the year of adoption of SDGs. Despite a large volume of evidence, the debate about suicide mortality rate as an indicator of SDG is still very sparse suggesting a need for better consensus on its evaluation methods. This study presents useful characteristics for the formulation of new studies and provides specific targets for the construction or improvement of public policies on the context of the SDGs for further discussion on this strategy proposed by the UN.


The role of dendritic cells in the initiation of immune responses to contact sensitizers. II. Studies in nude mice.
Twenty-four hours after skin painting nude mice with picryl chloride, there was an increase in the number of dendritic cells (DC) isolated from the draining lymph nodes. This increased inflow or retention of DC in lymph nodes following skin painting is therefore unlikely to depend on interaction of DC with T cells. The DC obtained initiated primary proliferative responses in vitro in lymph node cells from congenic euthymic mice. Contact sensitivity developed in congenic mice when they received footpad injections of 60,000 DC from the lymph nodes of nude mice skin sensitized 1 day previously with picryl chloride or oxazolone. The initiation of delayed hypersensitivity was therefore independent of T-cell contamination within the donor DC.


Biochemical responses, feeding and survival in the solitary bee Osmia bicornis following exposure to an insecticide and a fungicide alone and in combination.
In agricultural ecosystems, bees are exposed to combinations of pesticides that may have been applied at different times. For example, bees visiting a flowering crop may be chronically exposed to low concentrations of systemic insecticides applied before bloom and then to a pulse of fungicide, considered safe for bees, applied during bloom. In this study, we simulate this scenario under laboratory conditions with females of the solitary bee, Osmia bicornis L. We studied the effects of chronic exposure to the neonicotinoid insecticide, Confidor® (imidacloprid) at a realistic concentration, and of a pulse (1 day) exposure of the fungicide Folicur® SE (tebuconazole) at field application rate. Syrup consumption, survival, and four biomarkers: acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione S-transferase (GST), and alkaline phosphatase (ALP) were evaluated at two different time points. An integrated biological response (IBRv2) index was elaborated with the biomarker results. The fungicide pulse had no impact on survival but temporarily reduced syrup consumption and increased the IBRv2 index, indicating potential molecular alterations. The neonicotinoid significantly reduced syrup consumption, survival, and the neurological activity of the enzymes. The co-exposure neonicotinoid-fungicide did not increase toxicity at the tested concentrations. AChE proved to be an efficient biomarker for the detection of early effects for both the insecticide and the fungicide. Our results highlight the importance of assessing individual and sub-individual endpoints to better understand pesticide effects on bees.


[Routine subclavian revascularisation employing regional anaesthesia].
The increasing incidence of endovascular surgery on the thoracic aorta (TEVAR) is leading to an increased rate of subclavian-carotid transposition (SCT). Intentional overstenting of the left subclavian artery extends the proximal landing zone. If overstenting leads to a subclavian steal syndrome, vertebrobasilar insufficiency or if the risk of spinal ischaemia is present, SCT can safely be carried out with regional anaesthesia by means of a cervical block. Since January 2010 regional anaesthesia was employed in 13 consecutive patients receiving an SCT in our clinic. Subclavian revascularisation was performed either as adjunct procedure for TEVAR or in patients with occlusive disease of the aortic arch. The clinical course was prospectively observed. In 62 % of the cases (n = 8) a transposition of the subclavian artery onto the common carotid artery was carried out. In 38 % of the cases (n = 5) an intraoperative decision was made to construct a carotid-subclavian bypass. In 30 % (n = 4) of the cases a conversion from cervical block to general anaesthesia was necessary. All reconstructions proved to be patent at follow-up. Subclavian-carotid transposition under regional anaesthesia is safe and technically feasible if occlusion of the subclavian artery by thoracic stentgraft or stenosis has occurred. The technique employing regional anaesthesia can, therefore, also be offered to patients with increased risk for complications due to general anaesthesia.


Cannabis use breaks in young adults: The highs and lows of tolerance breaks.
Cannabis tolerance breaks, or T-breaks, are believed to benefit persons who use cannabis (PUCs) by decreasing tolerance levels to cannabis. However, no prior research, to our knowledge, has compared the effects of T-breaks and other use breaks on cannabis use patterns and outcomes. The current study examined whether the occurrence of cannabis use breaks (tolerance and other use breaks), or the duration of these breaks, is associated with changes in hazardous cannabis use (CUDIT-R), CUD severity, cannabis use frequency, and withdrawal symptoms over a 6-month follow-up. Young adults, who recreationally use cannabis, (N=170, 55.9% female, Mean age=21 yo) completed baseline and on-time 6-month assessments of hazardous cannabis use (CUDIT-R), CUD severity, cannabis use frequency, and withdrawal symptoms. The occurrence of cannabis use breaks and the duration of these breaks during the intervening period was assessed at 6 months. Taking a T-break was associated with an increase in hazardous cannabis use and CUD severity at 6 months. When considering cannabis use breaks for other reasons, a longer break was associated with a significant decrease in hazardous cannabis use (CUDIT-R), CUD severity, and cannabis use frequency at 6 months. Findings from our study suggest recreational PUCs who take a T-break may be at greater risk for problematic cannabis use. In addition, taking a longer cannabis use break for other reasons may have beneficial effects on cannabis-related outcomes. The ability to abstain from cannabis for other reasons may be protective while individuals who take T-breaks may be important targets for intervention and prevention.


[Development and evaluation of a double antigen sandwich ELISA for the detection of total antibodies against hemorrhagic fever with renal syndrome virus].
To develop and evaluate a method for detection of the total antibodies against hemorrhagic fever with renal syndrome (HFRS) virus with improved sensitivity and simplified operation procedure. The nucleic proteins of hantavirus were used as coating antigens as well as detection antigens labeled with horse radish peroxidase (HRP). The operation protocol was established, optimized and compared with indirect fluorescence assay (IFA). The specificity of this method was 100 percent in the test of different human sera and 4-8 times more sensitive than IFA. And, it is simpler without requiring any change of the reagents, different sources of samples did not affect the results of the test. This method is specific, sensitive and simple for detection of the total antibodies in sera against hantavirus, could be used for the screening of Hantavirus infection in human and host rodent animals.


Evaluation of crestal sinus floor elevations using versah burs with simultaneous implant placement, at residual bone height ≥ 2.0 _ < 6.0 mm. A prospective clinical study.
To evaluate the efficacy of Versah drills in breaching the maxillary sinus floor while keeping the membrane intact, as well as measure the implant stability (primary stability at the time of implant placement by the osseous densification of the residual bone height (RBH) of ≥ 2.0 _ < 6.0 mm, and secondary stability after 6 months of osseous healing period). This prospective clinical study, which included twenty crestal sinus floor elevations, was conducted on 17 patients (10 males and 7 females, ages 29 to 70 years). The sinus membrane integrity was clinically checked at the time of osseodensification sinus lifting and confirmed by CBCT after sinus augmentation and implant insertion. Time of operation has been recorded from the first drill to implant installation. Primary implant stability was measured using an Osstell beacon at the time of implant placement, and secondary stability was measured after 6 months of osseous healing. The mean of secondary stability in the current study is significantly higher than the mean of primary stability (P ≤ 0.011), which was 74.22 ± 8.11 and 69.85 ± 9.74, respectively, in RBH 3.81 mm as a mean. There was no clinical evidence of membrane perforation or complication reports, and the average operation time was 11.2 ± 1.85 min. The current study found that at highly atrophic posterior maxilla with a residual bone height of ≥ 2.0 _ < 6.0 mm, osseodensification using Versah drills was effective in crestal sinus elevation with no membrane perforation, which was confirmed by cone-beam CT scan postoperatively, and showed higher primary and secondary implant stability.


Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells.
Intestinal microflora (IM) is able to produce toxic and carcinogenic metabolites and induce more potent cytotoxicity against cells than non-metabolites. This study was performed to investigate the cytotoxic responses of geniposide (GS) and its metabolite and to determine the role of metabolism by IM in GS-induced cytotoxicity. Genipin (GP), a GS metabolite, increased cytotoxic effects in cells, but GS did not. Following GS incubation with IM for metabolic activation, increased cytotoxicity was detected compared to GS. Western blot analysis revealed that the activated GS inhibited Bcl-2 expression with a subsequent increase in Bax expression. Likewise, GS activation by IM stimulated caspase-3 and the production of reactive oxygen species (ROS). In addition, activated GS-induced apoptosis was confirmed by apoptosis and ROS assays; N-acetyl-l-cysteine (NAC) suppressed ROS production and apoptotic cell death. Activated GS induced sustained JNK phosphorylation. Moreover, activated GS-induced cell death was reversed by SP600125. Taken together, these findings suggest that human IM is able to metabolize GS into GP, and the related biological activities induce apoptosis through ROS/JNK signaling.


Histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits anti-inflammatory activities through induction of mitochondrial damage and apoptosis in activated lymphocytes.
Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been proven to be an anti-cancer agent. Its anti-inflammatory activities have recently been observed both in in vitro and in vivo models. Yet its action on lymphocytes and the underlying mechanism are still not well known. In this study, in order to evaluate the anti-inflammatory function of SAHA, we analyzed the effects of SAHA on the proliferation, activation, cytokines secretion, cell cycle distribution and apoptosis of murine lymphocytes activated with concanavalin A (Con A). Our results demonstrated that SAHA inhibited the proliferation of Con A-activated lymphocytes in a dose-dependent manner. The expression of CD69 on CD3(+) T lymphocytes was significantly inhibited by SAHA. Intracellular cytokine staining analysis showed that SAHA could downregulate the expression of pro-inflammatory cytokines TNF-α, IL-6 and IFN-γ in T lymphocytes. Furthermore, analysis of sub-G(0)/G(1) peaks and annexin V binding populations revealed that SAHA induced apoptotic cell death in Con A-activated lymphocytes. Consistent with these results, SAHA treatment also induced a decrease of mitochondrial membrane potential and cleavage of caspase-3 and PARP in these cells. Moreover, SAHA caused an accumulation of phosphorylated histone H2A.X, indicating increased double strand DNA breaks. These findings suggest that induction of apoptosis through the mitochondrial pathway may contribute to the anti-inflammatory activities of SAHA on activated lymphocytes.


Possible mutagenic properties and carcinogenic action of the irritant gaseous pollutants NO2, O3, and SO2.
Carcinogenic or cocarcinogenic effects of NO2, O3, and SO2 have not been proven to date with sufficient reliability. However, nitrosamine formation after exposure to NO2- or O3-induced decrease in benzpyrene hydroxylase are potential hazards. A final revaluation of a possible cocarcinogenic action of SO2 requires further experimental studies.


Glass transition of deoxymyoglobin probed by optical absorption spectroscopy.
We have measured the absorption spectrum of horse deoxymyoglobin in glycerol-water mixture around 430 nm in the 130 - 320 K temperature range. The observed asymmetric spectral shape of the Soret band was analyzed using a configuration-coordinate model. The results support the idea that myoglobin is liquid-like at physiological temperatures, but is glass-like below about 250 K. The equilibrium position of the iron atom in the heme group in the electronic excited state was estimated from the determined parameter values.


Carcinoid tumors of the alimentary tract. I. Radiographic diagnosis.
This paper is based on a retrospective analysis of the radiographic findings in 18 new proven cases of carcinoids of the gastrointestinal tract. Examples of lesions involving different segments together with a detailed review of the pertinent literature are provided. Background information regarding the malignant potential of all carcinoids with particular reference to invasiveness, size, site, and symptomatology is discussed. Depending on the time of the examination during their development, carcinoids present either as smoothly defined, mostly small intramural nodules, or as large infiltrating and ulcerating malignant looking tumors. When mesenteric infiltration is present, a more specific combination of findings composed of submucosal nodules, separation of loops, and localized kinking may be seen. The demonstration of an isolated, sharply contoured defect does not exclude malignancy. The less common radiographic manifestations of tumoral calcifications and bony metastases are reviewed and illustrated.


Left ventricular tachycardia originating near the left main coronary artery.
Eight patients with idiopathic ventricular tachycardia (VT) underwent mapping and radiofrequency ablation. Mapping showed VT originating in the high posterolateral left ventricular outflow tract in proximity to the left main and proximal circumflex coronary arteries. Ablation was not attempted due to this proximity to the left main and proximal circumflex coronary arteries. Ablation was not attempted due to this proximity in 2 patients and limited in 1 patient. It was successful in VT suppression in 5 of 6 patients.


Unravelling Cryptosporidium and Giardia epidemiology.
Molecular biology has provided insights into the taxonomy and epidemiology of Cryptosporidium and Giardia, which are major causes of protozoal diarrhoea in humans worldwide. For both genera, previously unrecognized differences in disease, symptomatology, zoonotic potential, risk factors and environmental contamination have been identified using molecular tools that are appropriate for species, genotype and subtype analysis. In this article, to improve understanding of the epidemiology of cryptosporidiosis and giardiasis, we consider specific requirements for the development of more-effective molecular identification and genotyping systems that should be applicable to both clinical and environmental samples.


The feasibility and acceptability of administering a telemedicine objective structured clinical exam as a solution for providing equivalent education to remote and rural learners.
Although many medical schools incorporate distance learning into their curricula, assessing students at a distance can be challenging. While some assessments are relatively simple to administer to remote students, other assessments, such as objective structured clinical exams (OSCEs) are not. This article describes a means to more effectively and efficiently assess distance learners and evaluate the feasibility and acceptability of the assessment. We developed a teleOSCE, administered online in real time, to two cohorts of students on a rural clerkship rotation and assessed the feasibility and acceptability of using such an approach to assess medical students' clinical skills at rural locations. Project feasibility was defined as having development and implementation costs of less than $5000. Project acceptability was determined by analyzing student interview transcripts. A qualitative case study design framework was chosen due to the novel nature of the activity. The implementation cost of the teleOSCE was approximately US$1577.20, making it a feasible educational endeavor. Interview data indicated the teleOSCE was also acceptable to students. The teleOSCE format may be useful to other institutions as a method to centrally administer clinical skills exams for assessment of distance medical students.


Promoted liquid-phase hydrodechlorination of chlorophenol over Raney Ni via controlling base: Performance, mechanism, and application.
The potential effect of base on Raney Ni-catalyzed hydrodechlorination (HDC) of chlorophenol was studied. Compared to weak inorganic bases, strong inorganic bases (NaOH and KOH) and triethylamine (Et3N) were more favorable to promote Raney Ni-catalyzed HDC reaction. Moreover, a stoichiometric amount of NaOH/Et3N was found to be optimal for the HDC reaction, and up to 100% conversion of 4-chlorophenol was achieved within 30 min. Catalyst characterization (SEM, EDXS, and XRD) combined with ICP-OES analysis were introduced to better understand the mechanism for the promoted effect of base on the HDC reaction. The results showed that the optimal amount of strong inorganic bases and Et3N efficiently eliminated HCl corrosion to Raney Ni, greatly reduced the active phase Ni and Al leaching, and avoided collapse of the catalyst framework. Based on the mechanism, the best bases and their optimal amount were developed for further disposal of polychlorinated phenols, and excellently stepwise HDC of polychlorinated phenols was achieved. Recycling tests showed that Raney Ni could be reused at least 5 times for the HDC reaction with the stoichiometric amount of NaOH, which was a promising option for the HDC of wastewater containing chlorophenols over Raney Ni.


Quantitative aspects of the E2 receptor assay for human breast tumour cytosol using dextran-coated charcoal.
Misclassification of the oestrogen status of a human breast tumour cytosol, arising from different sources and magnitudes of error in the dextran-coated charcoal (DCC) method, have been investigated using both practical and computer simulated data analysed by Scatchard and Mass Action models. The minimum detectable receptor site concentration, relative or absolute numerical bias and imprecision which are complex and integral functions of misclassification, have been calculated from practical data and for a range of experimental conditions likely to be encountered in practice. The Mass Action model was found to be superior and the computer program, designed to investigate the effects of methodological errors on quantitative aspects of the assay, may be a useful aid for analytical design and internal quality control of the receptor assay.


Pre- and postsynaptic localization of central muscarinic receptors.
3H-Quinuclidinyl benzylate and dimethyl 14C-d-tubocurarine were used to localize muscarinic and nicotinic receptors in synaptosomal membranes of the rat cerebral cortex. The results obtained, after the action of different concentrations of Triton X-100, suggest that, while nicotinic receptors are postsynaptic, the muscarinic ones are both pre- and postsynaptic.


What does the future hold for diabetic dyslipidaemia?
Preliminary evidence from trials with the HMG-CoA reductase inhibitors (statins), simvastatin and pravastatin, suggests that aggressive treatment of diabetic dyslipidaemia will reduce coronary events. Questions regarding the prevention of cardiovascular events in diabetic patients are now being addressed in prospectively designed trials. The first question is, can aggressive treatment of dyslipidaemia lead to primary prevention of cardiovascular events in patients with type 2 diabetes? This is being addressed in the ongoing Atorvastatin Study for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and the Collaborative AtoRvastatin Diabetes Study (CARDS). These trials will randomize over 4000 patients with type 2 diabetes and no previous myocardial infarction to either atorvastatin or placebo for 4 years. The second question is, are there benefits for aggressive lipid lowering to levels below those recommended in current treatment guidelines, i.e. is lower better? Results from the recent Atorvastatin VErsus Revascularization Treatment (AVERT) trial suggest this to be the case. AVERT showed that, in stable coronary heart disease patients who had been referred for revascularization, aggressive lowering of low density lipoprotein (LDL) cholesterol with atorvastatin 80 mg/day (to a mean level of 2.0 mmol/L [77 mg/dL]) reduced the incidence of ischaemic events by 36% compared with angioplasty and usual care (which reduced LDL cholesterol to 3.1 mmol/L [119 mg/dL]). The 36% reduction in events with atorvastatin versus angioplasty and usual care trended towards significance (p=0.048). The benefits of aggressive lipid-lowering therapy are also being investigated in the ongoing Treating to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trials. These studies will more closely examine the benefits of treating diabetic dyslipidaemia, and will determine how aggressively this abnormal lipid profile should be treated.


Spatial Patterns and Determinants of Diabetes Mellitus in Indian Adult Population: a Secondary Data Analysis from Nationally Representative Surveys.
Diabetes mellitus (DM) is a major public health challenge around the world. It is crucial to understand the geographic distribution of the disease in order to pinpoint high-priority locations and focus intervention on the target populations. Hence, this study was carried out to determine the spatial pattern and determinants of type-2 DM in an Indian population using National Family Health Survey-4 (NFHS-4) and Longitudinal Aging Survey in India (LASI). We have adopted an ecological approach, wherein geospatial analysis was performed using aggregated district-level data from NFHS-4 (613 districts) and LASI survey datasets (632 districts). Moran's I statistic was determined and Local Indicators of Spatial Association (LISA) maps were created to understand the spatial clustering pattern of DM. Spatial regression models were run to determine the spatial factors associated with DM. Prevalence of self-reported DM among males (15-50 years) and females (15-49 years) was 2.1% [95% confidence interval (CI) 2.0-2.3%] and 1.7% (95% CI 1.6-1.8%), respectively. Prevalence of self-reported DM among males and females aged 45 years and above was 12.5% (95% CI 11.5-13.5%) and 10.9% (95% CI 9.8-12%). Positive spatial autocorrelation with significant Moran's I was found for both males and females in both NFHS-4 and LASI data. High-prevalence clustering (hotspots) was maximum among the districts belonging to southern states such as Kerala, Tamil Nadu, Karnataka, and Andhra Pradesh. Northern and central states like Madhya Pradesh, Chhattisgarh, and Haryana mostly had clustering of cold spots (i.e., lower prevalence clustered in the neighboring regions). DM burden in India is spatially clustered. Southern states had the highest level of spatial clustering. Targeted interventions with intersectoral coordination are necessary across the geographically clustered hotspots of DM.


Runx1 expression defines a subpopulation of displaced amacrine cells in the developing mouse retina.
AML1/Runx1 (Runx1) is a mammalian transcription factor that plays critical roles in regulating the differentiation of a number of different cell types. In the present study, we have utilized mice expressing beta-galactosidase (beta-gal) under the control of the Runx1 promoter to characterize the spatiotemporal expression pattern of Runx1 during retinogenesis. Expression of beta-gal was first detected at embryonic day 13.5 in post-mitotic cells located in the inner retina and overlapped with expression of the early amacrine and ganglion cell marker protein Islet1. During subsequent developmental stages, the number of beta-gal-positive cells increased in a central-to-peripheral gradient until late embryogenesis but then decreased in the early post-natal retina. beta-gal-positive cells were located primarily in the ganglion cell layer by late embryonic/early post-natal stages and were identified as a subpopulation of displaced amacrine cells by the continued expression of Islet1, as well as Pax6, and the coexpression of the amacrine cell subtype-specific markers choline acetyltransferase, calretinin and the 65-kDa isoform of glutamic acid decarboxylase. These findings identify Runx1 as a novel marker for a restricted amacrine cell subtype and suggest a role for this gene in regulating the post-mitotic development of these cells.


Type-II Weyl semimetals.
Fermions--elementary particles such as electrons--are classified as Dirac, Majorana or Weyl. Majorana and Weyl fermions had not been observed experimentally until the recent discovery of condensed matter systems such as topological superconductors and semimetals, in which they arise as low-energy excitations. Here we propose the existence of a previously overlooked type of Weyl fermion that emerges at the boundary between electron and hole pockets in a new phase of matter. This particle was missed by Weyl because it breaks the stringent Lorentz symmetry in high-energy physics. Lorentz invariance, however, is not present in condensed matter physics, and by generalizing the Dirac equation, we find the new type of Weyl fermion. In particular, whereas Weyl semimetals--materials hosting Weyl fermions--were previously thought to have standard Weyl points with a point-like Fermi surface (which we refer to as type-I), we discover a type-II Weyl point, which is still a protected crossing, but appears at the contact of electron and hole pockets in type-II Weyl semimetals. We predict that WTe2 is an example of a topological semimetal hosting the new particle as a low-energy excitation around such a type-II Weyl point. The existence of type-II Weyl points in WTe2 means that many of its physical properties are very different to those of standard Weyl semimetals with point-like Fermi surfaces.


Long-term performance of porcine heart valve bioprostheses.
To assess the results after long-term implantation of porcine bioprosthetic heart valves, 320 patients with 381 valves were retrospectively reviewed. This group included all patients receiving one such xenograft in the mitral or aortic position (or both) in our institution between June 1974 and December 1976. The patients had a follow-up of 9-11.5 years. Actuarial patient survival rats (hospital mortality excluded) were 85%-90% at 6 years and 68%-79% at 11.5 years. Thromboembolic episodes did not show any significant clustering over the first weeks or months, in fact, they appeared at a constant rate. Actuarial rates of freedom from thromboembolism were greater than 90% for aortic patients at 11.5 years and greater than 80% for mitral and mitroaortic patients at 11.5 years. The linearized rate of anticoagulant-related haemorrhage for the whole group of patients was 0.4 events/100 patient years with a related mortality of 0.2 events/100 patient years. Prosthetic valve endocarditis and paravalvular leak appeared at linearized rates of 0.6 (0.1 of related mortality) and 0.4 (0.1 of related mortality) events/100 patient years. Primary tissue valve failure constituted the most prevalent complication (82 cases) in the long term but did not significantly worsen patient survival. Actuarial rates of freedom from primary tissue failure were 91% +/- 2% at 6, and 40% +/- 14% at 11.5 years for mitral valves, and 95% +/- 4% at 6 and 64% +/- 6% at 11.5 years for aortic valves.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunology of corneal allograft rejection: HLA-DR antigens on human corneal cells.
Human stromal and endothelial cultures were established from corneas obtained from the Maryland Eye Bank. Cultures were incubated in the presence of human gamma interferon for 4 days, trypsinized, washed, and then stained with a monoclonal reagent specific for human Class II (HLA-DR) antigens. Under these conditions, 100% of human corneal endothelial cells and 40 to 70% human corneal stromal cells expressed HLA-DR antigens.


Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection.
Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.


The potential involvement of MRP5 pump in urethral dysfunction in streptozotocin-induced diabetic rats.
To examine the effects of i.v. administration of MK-571, a MRP4/5 pump inhibitor, on urethral function in the urethane-anesthetized rat, and the changes of urethral multidrug resistance protein 5 (MRP5) pump in streptozotocin (STZ)-induced diabetes mellitus (DM) rats. Isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were carried out in normal control (NC) group and 8week DM groups under urethane anesthesia. When stable rhythmic bladder contractions were showed, UPP parameters were recorded after successive administration of various dose of MK-571. Additionally, urethral cyclic guanosine monophosphate (cGMP) protein level was evaluated by ELISA, and changes of MRP5 pump and neurogenic nitric oxide synthase (nNOs) in the urethra were examined with immunohistochemical staining and Western blot analysis. In NC group, UPPnadir was significantly decreased but UPP change increased after administration of MK-571, while no significant differences in UPP parameters were observed in 8-week DM group. Furthermore, urethral MRP5 protein level was up-regulated, whereas urethral cGMP and nNOS protein levels were down-regulated in 8-week DM group. MK-571 could not restore NO-mediated urethral relaxation dysfunction in DM rats, which may be attributed to the up-regulation of urethral MRP5 pump, and thus decrease of intracellular cGMP concentration in the urethra. These novel results would be useful for a better understanding of DM-related lower urinary tract dysfunction LUT (LUTD). Also, they could be helpful to study the importance of MRP pumps in the control of urethral relaxation mechanisms under physiological and pathological states.


HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma.
Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) are two rare histologic variants of uterine carcinoma, with distinct molecular profiles and aggressive metastatic potential. As the effectivity of traditional platinum-based chemotherapy for USC and UCS is low, and there are high rates of resistance and recurrence, the development of novel targeted therapeutics is needed. Human epidermal growth factor receptor 2 (HER2) has proven to be an oncogene of increasing interest in these cancers, as HER2 protein overexpression and/or c-ERBB2 gene amplification ranges from ~30 to 35% in USC, and between ~15 and 20% in UCS. This review summarizes the existing clinical and preclinical evidence, as well as ongoing clinical trials of HER2-targeting therapeutics, and identifies potential areas of further development and inquiry.