ICU admission for solid cancer patients treated with immune checkpoint inhibitors.
Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered "likely" associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2-3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13-18.90, and OR = 3.66, 95% CI 1.33-10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19-9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission "likely" related to irAE. Three patients were subsequently treated with immunosuppressants. IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.


The biostimulating effects of viable microalgal cells applied to a calcareous soil: Increases in bacterial biomass, phosphorus scavenging, and precipitation of carbonates.
Microalgae used in wastewater treatment may be applied to soil as a biofertilizer - this is a novel strategy for recycling of nutrients in the circular economy. There is little information about how the application of large concentrations of unicellular algae to soil will affect soil biochemistry, particularly when they are living algal cells with the potential to form a soil biofilm, whereas soil biofilms are expected to influence plant-microbe interactions. Chlorophyte unicellular algae of the Chlorella genera are widely employed in algae-based water treatment systems, and Chlorella sorokiniana has proven to be highly adaptable for this purpose. We applied three filtrates of a Chlorella sorokiniana culture to soil microcosms, separating the microalgae from other microorganisms, as well as a sterile control filtrate without biological activity. Bacterial biomass in soils receiving the non-filtered (NF) slurry with viable algal cells was increased by 25% in the soil surface (0-8mm), and heterotrophic activity in those treatments increased as measured by CO2-C evolution. Total soil carbon concentrations were increased in the treatment with living algal cells (NF) by 0.4%, but no differences in organic carbon were measured; instead, it was found that inorganic carbon (CaCO3) concentrations increased by 0.6% in the NF treatment only. Soil phosphorus availability was also reduced in the surface of the NF treatment, indicating an increased biological demand. The results show that, when applied to soil, microalgae and associated biofilms will have relevant direct and indirect effects on soil quality and nutrients of agricultural importance.


Familial Aicardi-Goutières syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.
We report on two siblings doubly heterozygous for null mutations in the recently identified AGS5 gene SAMHD1. The older female child showed mild intellectual disability with microcephaly. Her brother demonstrated a significant spastic paraparesis with normal intellect and head size. Both children had an unclassified chronic inflammatory skin condition with chilblains, and recurrent mouth ulcers. One child had a chronic progressive deforming arthropathy of the small and large joints, with secondary contractures. This family illustrate the remarkable phenotypic diversity accruing from mutations in genes associated with Aicardi-Goutières syndrome (AGS). The association of arthropathy with SAMHD1 mutations highlights a phenotypic overlap of AGS with familial autoinflammatory disorders such as chronic infantile neurological cutaneous and articular syndrome (CINCA). This family therefore illustrate the need to consider mutation analysis of SAMHD1 in non-specific inflammatory phenotypes of childhood. We propose that arthropathy with progressive contractures should now be considered part of the spectrum of Aicardi-Goutières syndrome because of SAMHD1 mutations.


Noninvasive intracranial pressure monitoring methods: a critical review.
Intracranial pressure (ICP) monitoring has been used for decades in management of various neurological conditions. The gold standard for measuring ICP is a ventricular catheter connected to an external strain gauge, which is an invasive system associated with a number of complications. Despite its limitations, no noninvasive ICP monitoring (niICP) method fulfilling the technical requirements for replacing invasive techniques has yet been developed, not even in cases requiring only ICP monitoring without cerebrospinal fluid (CSF) drainage. Here, we review the current methods for niICP monitoring. The different methods and approaches were grouped according to the mechanism used for detecting elevated ICP or its associated consequences. The main approaches reviewed here were: physical examination, brain imaging (magnetic resonance imaging, computed tomography), indirect ICP estimation techniques (fundoscopy, tympanic membrane displacement, skull elasticity, optic nerve sheath ultrasound), cerebral blood flow evaluation (transcranial Doppler, ophthalmic artery Doppler), metabolic changes measurements (near-infrared spectroscopy) and neurophysiological studies (electroencephalogram, visual evoked potential, otoacoustic emissions). In terms of accuracy, reliability and therapeutic options, intraventricular catheter systems still remain the gold standard method. However, with advances in technology, noninvasive monitoring methods have become more relevant. Further evidence is needed before noninvasive methods for ICP monitoring or estimation become a more widespread alternative to invasive techniques.


Circulating immune complexes in pregnancy, preeclampsia, and autoimmune diseases: evaluation of Raji cell enzyme-linked immunosorbent assay and polyethylene glycol precipitation methods.
Sera from 86 individuals were tested for circulating immune complexes by the polyethylene glycol precipitation method and a Raji cell enzyme immunoassay (Raji-ELISA). These included normal nonpregnant control subjects, nonpregnant patients with autoimmune diseases, healthy women in the second and third trimesters of pregnancy, patients with preeclampsia, and women with pregnancies complicated by preexisting autoimmune diseases. Diseases such as systemic lupus erythematosus and rheumatoid arthritis were associated with increased levels of immune complexes in both pregnant and nonpregnant individuals. Circulating immune complexes were not observed in normal pregnancies or in preeclampsia. Although pregnancy itself is not an immune complex-associated state, the presence of immune complexes in autoimmune diseases may explain some of the complications observed during pregnancy in these patients.


Advanced Optical Materials: From Materials to Applications.
Optical materials interact significantly with electromagnetic radiation in the visible, ultraviolet, and infrared regions of the spectrum [...].


A comparative study of co-trimoxazole and amoxycillin in the treatment of acute bronchitis in general practice: a multicentre study.
One hundred and five patients with acute bronchitis were treated with co-trimoxazole, and amoxycillin, in a single-blind trial. The present study confirms that co-trimoxazole and amoxycillin are effective, and well tolerated agents, both suitable for the management of acute bronchitis.


Female CEO succession and corporate social disclosure in China: unveiling the significance of ownership status and firm performance.
This study intends to examine the effect of CEO succession with gender change from male to female (i.e., female CEO succession) on corporate social responsibility (CSR) reporting. Based on insights from upper echelons theory, it is proposed that female CEO successors are more likely than male CEO successors to improve the firm's CSR reporting level due to variations in their traits, values, and preferences regarding green issues, especially CSR. The study also explores the influence of the firm's ownership status (i.e., SOEs vs. non-SOEs) and performance (high-performance firms vs. low-performance firms) on the relationship between female CEO succession and CSR reporting. Using data from Chinese publicly traded firms from 2010 to 2020, this study employs the logistic regression technique to examine the proposed relationship between female CEO succession and CSR reporting and presents robust evidence that female CEO succession has a positive effect on firm CSR reporting, and that this effect is more prevalent in non-SOEs and high-performance firms than in SOEs and low-performance firms, respectively. The study adds fresh insights to the extant literature on CSR and corporate leadership and offers useful policy recommendations for corporate decision-makers and policymakers while considering women's involvement in succession plans for top leadership positions like CEO to tackle the strategic management of CSR disclosure in China.


Florida State Opioid Prescription Restriction Law: Impact on Opioid Utilization After Total Joint Arthroplasty.
In response to the opioid epidemic, Florida recently passed the opioid prescription limiting law, effective since July 1st, 2018. However, its impact on opioid prescription after total joint arthroplasty (TJA) has not been elucidated. Thus, our objective was to assess if this new law led to reduced opioid prescription after TJA and to determine its impact on perioperative clinical outcomes. A retrospective chart review was conducted on a consecutive series of 658 primary TJAs (618 patients), performed by four surgeons in a single institution [1/2/2018-10/23/2018]. Based on effective date of the law, cases were divided into: prelaw (327 cases; 168 hips/159 knees) and postlaw (331 cases; 191 hips/140 knees) phases. Baseline demographics and surgical characteristics were compared. The effect of the law on perioperative outcomes: length of stay, complications, emergency department/office visits, patient phone calls, reoperation or readmission (90 days), and total morphine equivalents prescribed was investigated. Independent sample t-tests and chi-square analyses were performed. Prelaw and postlaw phases had no significant difference in baseline demographics and characteristics. No difference was found in length of stay. Opioid law implementation led to significantly lower total oral morphine equivalents after TJAs [Prelaw: 1059.9 ± 825.4 vs postlaw: 942.8 ± 691.7; P = .04], but did not result in a significant increase in 90-day complications, patient visits (office or emergency) or phone calls, and reoperation or readmission. Our data suggest that Florida state opioid prescription limiting law has resulted in a marked decline in opioid prescription without any increase in rates of patient visits, phone calls, or readmission after TJA.


Growth and heavy metals removal efficiency of Nostoc muscorum and Anabaena subcylindrica in sewage and industrial wastewater effluents.
The growth of Nostoc muscorum and Anabaena subcylindrica in sterilized sewage wastewater and N. muscorum in sterilized wastewater of El-Soda Company was higher than those grown in Allen synthetic medium. Whereas, the growth of A. subcylindrica in El-Soda Company sterilized wastewater and N. muscorum as well as A. subcylindrica grown in Verta Company sterilized wastewater was slightly lower than that grown in the standard synthetic medium. The contents of chlorophyll a, carotenoids and protein of N. muscorum and A. subcylindrica grown in sterilized sewage wastewater were higher than those grown in the standard medium. Similarly, N. muscorum and the bio-mixture of N. muscorum and A. subcylindrica grown in the sterilized wastewater of El-Soda Company showed high pigments and protein contents more than those reared in Allen medium. On the other hand, the bio-mixture of N. muscorum and A. subcylindrica grown in the sterilized sewage wastewater, A. subcylindrica grown in El-Soda Company and Verta Company sterilized wastewater showed lower contents of pigments and protein compared to synthetic medium. Heavy metals, copper, cobalt, lead and manganese were removed by 12.5-81.8, 11.8-33.7, 26.4-100 and 32.7-100%, respectively, from wastewater by using cyanobacterial cultures. The metal sorption efficiency depended on the type of biosorbent, the physiological state of the cells, availability of heavy metal, concentration of heavy metal and chemical composition of wastewater. It was observed also that the single cultures in most cases was better than the mixed cultures in heavy metal removal, this may be due to the cyanobacterial competition for nutrients in mixed cultures.


Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies.
Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network.


Synthesis, in vitro biological evaluation and molecular modelling of new 2-chloro-3-hydrazinopyrazine derivatives as potent acetylcholinesterase inhibitors on PC12 cells.
The loss of cholinergic neurotransmission in Alzheimer's disease (AD) patients' brain is accompanied by a reduced concentration of Acetylcholine (ACh) within synaptic clefts. Thus, the use of acetylcholinesterase inhibitors (AChEIs) to block the cholinergic degradation of ACh is a promising approach for AD treatment. In the present study, a series of 2-chloro-3-hydrazinopyrazine derivatives (CHP1-5) were designed, synthesized, and biologically evaluated as potential multifunctional anti-AD agents. In addition, the chemical structures and purity of the synthesized compounds were elucidated through using IR, 1H and 13C NMR, and elemental analyses. Further, the intended compounds were assessed in vitro for their AChE inhibitory and neuroprotective effects. Furthermore, DPPH, FRAP and ABTS assays were utilized to determine their antioxidant activity. The statistical analysis was performed using one-way ANOVA. Based on the results, CHP4 and CHP5 exhibited strong AChE inhibitory effects with the IC50 values of 3.76 and 4.2 µM compared to the donepezil (0.53 µM), respectively. The study examined the effect and molecular mechanism of CHP4 on the Ab1-42-induced cytotoxicity in differentiated PC12 cells. At concentrations of 0-100 μM, CHP4 was non-toxic in PC12. Additionally, Ab1-42 significantly stimulated tau hyperphosphorylation and induced differentiated PC12 cell death. Further, CHP4 resulted in diminishing the Ab1-42-induced toxicity in PC12 cell significantly. CHP4 at 30 μM concentration significantly increased the Ab1-42-induced HSP70 expression and decreased tau hyperphosphorylation. According to the results of our studies CHP4 can be considered as safe and efficient AChEI and employed as a potential multifunctional anti-AD agent.


Emittance-exchange-based high harmonic generation scheme for a short-wavelength free electron laser.
Generation of short-wavelength radiation by a free-electron laser using up-frequency conversion of an electron bunch density modulation is currently an area of active research. We propose a new scheme for producing the longitudinal electron bunch density modulation similar to the recently proposed echo-enabled harmonic generation but based on an emittance exchange beam line and a multislit mask. Beam line analysis and start-to-end simulation are presented.


Diagnosis and management of intrahepatic cholangiocarcinoma: a comprehensive update for the radiologist.
There is increasing focus on intrahepatic cholangiocarcinoma (IHCC) due to its rising incidence worldwide and relatively poor prognosis, with the revised TNM classification (2009) introducing a separate staging system for IHCC for the first time. In this article, we comprehensively review the current role of the radiologist in the diagnosis and management of patients with IHCC.


Tcf1 preprograms the mobilization of glycolysis in central memory CD8+ T cells during recall responses.
The mechanisms underlying the heightened protection mediated by central memory CD8+ T (TCM) cells remain unclear. Here we show that the transcription factor Tcf1 was required in resting TCM cells to generate secondary effector CD8+ T cells and to clear pathogens during recall responses. Recall stimulation of CD8+ TCM cells caused extensive reprogramming of the transcriptome and chromatin accessibility, leading to rapid induction of glycolytic enzymes, cell cycle regulators and transcriptional regulators, including Id3. This cluster of genes did not require Tcf1 in resting CD8+ TCM cells, but depended on Tcf1 for optimal induction and chromatin opening in recall-stimulated CD8+ TCM cells. Tcf1 bound extensively to these recall-induced gene loci in resting CD8+ TCM cells and mediated chromatin interactions that positioned these genes in architectural proximity with poised enhancers. Thus, Tcf1 preprogramed a transcriptional program that supported the bioenergetic and proliferative needs of CD8+ TCM cells in case of a secondary challenge.


ADP-activated calcium ion exchange in sarcoplasmic reticulum vesicles.
(1) Ca2+ efflux from rabbit skeletal muscle sarcoplasmic reticulum vesicles pre-loaded with 45Ca2+ was studied in the presence and in the absence of external Ca2+. (2) In the absence of Ca2+ in the assay media, ADP activates the Ca2+ efflux. The increment of Ca2+ efflux requires Pi, is coupled to ATP synthesis, and is inhibited by external Ca2+ (Ki 0.1-0.2 muM). (3) When Ca2+ is added to the assay media, ADP alone activates the Ca2+ efflux, but this is coupled to a Ca2+ influx of the same magnitude. It is therefore an exchange of internal for external Ca2+ in a 1:1 ratio. (4) The ADP-activated Ca2+ exchange requires external Ca2+ with an apparent Km of 0.1-0.2 muM, does not require the addition of Pi or Mg2+, although 3-10 mM MgCl2 activates it. It is not inhibited by the removal of contaminating ATP with hexokinase plus glucose. (5) It seems likely that Ca2+ can be translocated across sarcoplasmic reticulum membrane without the formation of a phosphorylated intermediate.


Mass spectral study of the occurrence of tautomeric forms of thiohydantoins.
Mass spectrometry is used to evaluate the occurrence of thio-enol structures among the several possible tautomers of thiohydantoins and dithiohydantoins. Mass spectra of differently substituted thiohydantoins are examined looking for common mass spectral behaviors. Ion fragmentations from specific tautomers allow to predict the most stable thio-enol structure for both type of compounds. The mass spectrum of the alkylation product of 5,5- dimethyldithiohydantoin and the nuclear magnetic resonance spectra of the alkylation products of both 2- thiohydantoin and dithiohydantoin support the fact that the most likely thio-enolstructure is determined by the presence of one or two thio-carbonyl groups in the hydantoin molecule.


Memory and self-neuroscientific landscapes.
Relations between memory and the self are framed from a number of perspectives-developmental aspects, forms of memory, interrelations between memory and the brain, and interactions between the environment and memory. The self is seen as dividable into more rudimentary and more advanced aspects. Special emphasis is laid on memory systems and within them on episodic autobiographical memory which is seen as a pure human form of memory that is dependent on a proper ontogenetic development and shaped by the social environment, including culture. Self and episodic autobiographical memory are seen as interlocked in their development and later manifestation. Aside from content-based aspects of memory, time-based aspects are seen along two lines-the division between short-term and long-term memory and anterograde-future-oriented-and retrograde-past-oriented memory. The state dependency of episodic autobiographical is stressed and implications of it-for example, with respect to the occurrence of false memories and forensic aspects-are outlined. For the brain level, structural networks for encoding, consolidation, storage, and retrieval are discussed both by referring to patient data and to data obtained in normal participants with functional brain imaging methods. It is elaborated why descriptions from patients with functional or dissociative amnesia are particularly apt to demonstrate the facets in which memory, self, and personal temporality are interwoven.


Preparation for Pastoral Counseling and Spiritual Care: Strengthening Pastoral "Felt Knowledge" and Empathy through the Appreciation and Use of Contemporary Films.
Contemporary film offers something unique in the preparation and practice of pastoral counselors and spiritual caregivers by expanding both "felt knowledge" and strengthening empathic responses to care seekers. By experiencing well-chosen films, pastoral counselors and other spiritual caregivers will be better prepared to work with relevant feelings in various caregiving contexts, and clients will gain many rewards, as both their healing and growth will be enhanced. This will be especially true when pastoral and spiritual caregivers are working in areas of need where they have limited personal or professional experience.


Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy.
Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP). A total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131). Acylcarnitines, sialic acid and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by unibiomarker linear regression, sparse partial least squares discriminant analysis, random forest, and conditional random forest analyses. However, the absolute difference in the metabolic profile among groups was marginal. A decision-tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish patients with DCM and left ventricular reverse remodeling from symptomatic DCM (area under the curve 0.813 ± 0.138 vs 0.739 ± 0.114; P = 0.02). Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in nonischemic DCM.


Pain as an evolutionary necessity.
The proposed title "Pain as an evolutionary necessity" could lead to a broad debate with implications covering many chapters of the medicine and particularly of clinical neurology. In the present perspective, the discussion will focus on migraine and cluster headache chosen as elective examples of biological and not only clinical conditions, that unveil the bond between pain and necessity. Migraine, cluster headache, and perhaps other primary headaches begin to be depicted in terms of recurrent activation of innate bio-behavioral specific patterns, with a crucial and highly conserved evolutionarily adaptive significance. The pan-mammalian sickness behavior and the fight or flight response, selectively activated by different kinds of pain, are here proposed as paradigmatic of migraine and cluster headache attacks associated behaviors, allowing to reformulate these forms as the inappropriate recurrent presentation of coordinated allostatic processes, modeled along million of years of natural evolution. In this light, all the multifaceted characteristics of migraine and cluster headache attacks can be reinterpreted as complex and integrated allostatic defensive reactions to an inescapable or to an escapable pain, respectively aimed to the restoration of biologic homeostasis through a temporary disengagement from active interaction with environment (migraine associated sickness behavior) or, on the contrary, to promote the coordinated biological changes preparatory to emergency and defensive behaviors (cluster headache-related fight or flight response).


Latest Trends in Subpectoral Breast Reconstruction.
There has been a shift in recent years toward a growing popularity of implant-based breast reconstruction, especially in the setting of increased frequency of concurrent contralateral prophylactic mastectomy. Advancements in implant safety and technology have also allowed for an expanding implant reconstruction practice across the country. The traditional approach is immediate two-stage implant reconstruction with placement of a tissue expander within a subpectoral pocket. The introduction of acellular dermal matrix has revolutionized implant-based breast reconstruction, allowing surgeons the opportunity to minimize morbidity while maximizing aesthetic outcomes. There have also been advances in the management of postoperative pain control as well as secondary revision surgery.


Oral immunization with attenuated Salmonella carrying a co-expression plasmid encoding the core and E2 proteins of hepatitis C virus capable of inducing cellular immune responses and neutralizing antibodies in mice.
Hepatitis C virus (HCV) core protein has long been considered an attractive candidate for inclusion in a protective vaccine. However, this protein may hamper the development of systemic immune responses because of its immune suppressive properties. We previously reported that immune responses to HCV core protein could be efficiently induced by attenuated Salmonella carrying the HCV core protein, but not the HCV core DNA vaccine. To optimize the combination of the core protein and envelope protein 2 (E2) into a vaccine formulation to induce cellular immune responses and neutralizing antibodies, we constructed a plasmid containing two expression cassettes. One expression cassette was included to regulate the expression of HCV core protein by an inducible in vivo-activated Salmonella promoter, the other was included to regulate the expression of HCV E2 protein by the cytomegalovirus enhancer/promoter. Oral immunization of BALB/c mice with the attenuated Salmonella strain SL7207 carrying this plasmid efficiently induced HCV core and E2-specific cellular immune responses and antibodies. IgG purified from immunized mice could neutralize the infectivity of HCV pseudoparticles (HCVpp) of both the autologous Con 1 isolate and the heterologous H77 isolate, and cell culture produced HCV (HCVcc) of Con1-JFH1 chimera. These results indicated that this vaccine strategy can effectively deliver core and E2 protein to the immune system and provide a promising approach for the development of prophylactic and therapeutic vaccines against HCV infection.


Transport mechanism for succinate and phosphate localized in the plasma membrane of bovine spermatozoa.
Bovine spermatozoa accumulated a small amount of 32Pi during aerobic incubation in vitro. At least 50% of the acquired isotope rapidly entered cellular nucleotides. Both adenosine and guanosine di- and triphosphates were labeled, but contrary to expectations, the specific activity of ADP exceeded that of ATP. The uptake of phosphate and its incorporation into nucleotides were suppressed by respiratory inhibitors and were abolished by treatment with sulfhydryl-directed reagents at 10 to 20 nmol/mg of sperm protein. With fructose as an energy source for motility, glycolysis did not support phosphate uptake. Nucleotide labeling was increased 60 to 80-fold when the cells were treated with the polyene antibiotic filipin, and filipin was able to reverse the inhibition of phosphate (and succinate) entry produced by N-ethylmaleimide or mersalyl. Since filipin interacts specifically with the cholesterol-containing plasma membrane of bovine spermatozoa and increases its permeability, it is probable that the plasma membrane normally limits phosphate and succinate transport into these cells. This contention is further supported by the observation that high concentrations of extracellular Pi, the penetration of which was extremely limited under these conditions, protected against inactivation by N-ethylmaleimide. Phosphate uptake was increased 10 to 20-fold, but nucleotide labeling was inhibited, when calcium was present in the incubation medium. Ruthenium red, presumably acting extracellularly, prevented these effects of calcium. Thus, the entry of phosphate and succinate into spermatozoa is controlled by plasma membrane components that resemble the phosphate and succinate exchangers and calcium carrier found in mitochondria isolated from other sources.


Real-life efficacy and safety of secukinumab in elderly patients with psoriasis over a 2-year period.
The prevalence of psoriasis is increasing among older people. Elderly patients with psoriasis represent a challenge for dermatologists owing to multiple comorbidities, polypharmacy and immune senescence, which lead to an increased possibility of adverse events (AEs), drug interactions and susceptibility to cancers and infections. Therefore, conventional systemic therapies are often contraindicated, with biologics appearing as the mainstay for moderate-to-severe disease. However, the data on efficacy and safety of biologics in older people are scant. To evaluate the efficacy and safety of secukinumab in elderly patients with psoriasis over a 2-year period. A real-life retrospective observational study was performed on patients aged ≥ 65 years with moderate-to-severe plaque psoriasis who were treated with secukinumab at the Psoriasis Care Unit of the University of Naples Federico II, Italy from June 2016 to June 2019. Mean Psoriasis Area Severity Index (PASI) reduced from 11.4 ± 6.3 at baseline to 2.1 ± 1.7 at week 24 and 1.7 ± 1.9 at week 96 (P < 0.001 for all follow-up visits), with a final mean PASI reduction of 85.1%. A similar trend was noted for body surface area (BSA), with baseline value of 27.5 ± 15.7 decreasing to 6.8 ± 5.0 at week 24, and to 3.3 ± 2.5 at week 96 (P < 0.001 at all follow-up visits), with a final mean BSA score reduction of 88.0%. Registered AEs did not lead to secukinumab discontinuation, except in one patient (3.4%). Secukinumab seems to be a safe and effective treatment for elderly patients with psoriasis, who frequently have multiple comorbidities, polypharmacy and multiple failures with previous systemic treatments including biologics.


Risk Perceptions on Hurricanes: Evidence from the U.S. Stock Market.
This article examines the market reaction of the main Property and Casualty (P & C) insurance companies listed in the New York Stock Exchange (NYSE) to seven most recent hurricanes that hit the East Coast of the United States from 2005 to 2012. For this purpose, we run a standard short horizon event study in order to test the existence of abnormal returns around the landfalls. P & C companies are one of the most affected sectors by such events because of the huge losses to rebuild, help and compensate the inhabitants of the affected areas. From the financial investors' perception, this kind of events implies severe losses, which could influence the expected returns. Our research highlights the existence of significant cumulative abnormal returns around the landfall event window in most of the hurricanes analyzed, except for the Katrina and Sandy Hurricanes.


Arterial embolization in the treatment of Curling's ulcer bleeding in a burn patient.
Curling's ulcer bleeding is a well-known life-threatening complication of the severely thermally injured patient. This report describes a successful left gastric artery embolization in a 70 per cent total body area burn patient with severe gastric bleeding. We discuss the various non-surgical invasive modalities for treating such patients, and emphasize the advantages of arterial embolization over surgery.


GliPR1 knockdown by RNA interference exerts anti-glioma effects in vitro and in vivo.
In human glioblastomas, glioma pathogenesis-related protein1 (GliPR1) is overexpressed and appears to be an oncoprotein. We investigated whether GliPR1 knockdown in glioma cells by RNA interference exerts anti-glioma effects. Experiments used human glioblastoma cell lines transduced with GliPR1 shRNA (sh#301, sh#258). Transduction produced stringent doxycycline-dependent GliPR1 knockdown in clones (via lentiviral "all-in-one" TetOn-shRNA vector) or stable GliPR1 knockdown in polyclonal cells (via constitutive retroviral-shRNA vector). In vitro assessments included cellular proliferation and clonogenic survival. In vivo assessments in tumor-bearing nude mice included tumor growth and survival. Using doxycycline-dependent GliPR1 knockdown, shGliPR1-transduced U87-MG clones demonstrated reductions in cellular proliferation in the presence versus absence of doxycycline. Using stable GliPR1 knockdown, polyclonal shGliPR1-transduced U87-MG, A172, and U343-MG cells consistently showed decreased clonogenic survival and induced apoptosis (higher proportion of early apoptotic cells) compared to control shLuc-transduced cells. In tumor-bearing nude mice, using doxycycline-dependent GliPR1 knockdown, subcutaneous and cranial transplantation of the U87-MG clone 980-5 (transduced with GliPR1 sh#301) resulted in reduced subcutaneous tumor volume and cerebral tumor area in doxycycline-treated mice versus those left untreated. Using stable GliPR1 knockdown, nude mice cranially transplanted with polyclonal U87-MG cells transduced with GliPR1 sh#258 had significantly prolonged survival compared to mice cranially transplanted with control shLuc-transduced cells (41 versus 26 days; P < 0.001). GliPR1 knockdown in glioma cells decreased cellular proliferation, decreased clonogenic survival, and induced apoptosis in vitro, and reduced glioblastoma tumor growth and prolonged survival in vivo. These findings support that GliPR1 may have potential value as a therapeutic target.


WIMP detection and slow ion dynamics in carbon nanotube arrays.
Large arrays of aligned carbon nanotubes (CNTs), open at one end, could be used as target material for the directional detection of weakly interacting dark matter particles (WIMPs). As a result of a WIMP elastic scattering on a CNT, a carbon ion might be injected in the body of the array and propagate through multiple collisions within the lattice. The ion may eventually emerge from the surface with open end CNTs, provided that its longitudinal momentum is large enough to compensate energy losses and its transverse momentum approaches the channeling conditions in a single CNT. Therefore, the angle formed between the WIMP wind apparent orientation and the direction of parallel carbon nanotube axes must be properly chosen. We focus on very low ion recoil kinetic energies, related to low mass WIMPs ([Formula: see text] GeV) where most of the existing experiments have low sensitivity. Relying on some exact results on two-dimensional lattices of circular obstacles, we study the low energy ion motion in the transverse plane with respect to CNT directions. New constraints are obtained on how to devise the CNT arrays to maximize the target channeling efficiency.


Expression and localization of thrombomodulin in preneoplastic bronchial lesions and in lung cancer.
Thrombomodulin (TM) is an endothelial surface glycoprotein that acts as a natural anticoagulant. It inhibits thrombin and accelerates the activation of the anticoagulant protein C. TM has been detected in dermal keratinocytes, where it is associated with terminal differentiation. It can also be detected in various types of squamous malignant neoplasms and in malignancies of endothelial and mesothelial origin, such as Kaposi's sarcoma or malignant mesothelioma, but is absent in pulmonary adenocarcinomas (AC). Seventy-two lung tumour specimens [33 squamous cell carcinomas (SQCC), 23 AC, 1 large cell carcinoma, 8 small cell lung cancers (SCLC) and 7 multidifferentiated tumours (MT)] were analysed immunohistochemically by staining with an anti-TM antibody in order to assess TM expression. All of the SQCC stained positively for TM. In contrast, only 9 AC and 4 MT and none of the SCLC showed positive anti-TM staining. Seven hyperplastic bronchial epithelial specimens and eight preneoplastic bronchial lesions (five cases of moderate dysplasia, two cases of severe dysplasia and one case of carcinoma in situ) were used as controls. Normal or hyperplastic areas of bronchial epithelium revealed no positive reaction. However, a distinct positive anti-TM staining pattern related to the degree of keratiniziation of dysplastic lesions was seen. The present results suggest that anti-TM immunostaining is a useful marker for squamous cell carcinoma in the differential diagnosis of pulmonary carcinoma, also indicating keratinocyte differentiation in dysplastic bronchial epithelium.


Polygenic adaptation after a sudden change in environment.
Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.


Improving delirium screening and recognition in UK hospitals: results of a multi-centre quality improvement project.
delirium is an acute severe neuropsychiatric condition associated with adverse outcomes, particularly in older adults. However, it is frequently under-recognised. this multi-centre quality improvement project utilised a collaborative approach to implementation of changes at sites, with the aim to improve delirium screening, recognition and documentation on discharge summaries. Resources, including delirium guidelines and presentations, were shared between sites, and broad details of local interventions were collected. Three timepoints of data collection (14 March 2018, 14 September 2018 and 13 March 2019) were conducted to assess screening, recognition and documentation of delirium in unscheduled admissions of adults aged ≥65 years old. The impact of local interventions and site-specific factors was assessed using logistic regression analysis, adjusting for patient factors. a total of 3,013 patients (mean age 80.2, 53.8% females) were recruited across the three timepoints. Screening for delirium was associated with increased odds of recognition (aOR 4.75, CI 2.98-7.56; P < 0.001); this was not affected by grade/profession of screener. Rates of screening, recognition and discharge documentation improved across the three timepoints of data collection. The presence of a local delirium specialist team was associated with increased rates of screening for delirium (aOR 1.75, CI 1.41-2.18; P < 0.001), and the presence of a geriatric medicine team embedded into the admissions unit was associated with increased recognition rates (aOR 1.78, CI 1.09-2.92; P = 0.022). delirium screening is associated with improved recognition. Interventions that strive to improve screening within a culture of delirium awareness are encouraged.


Potential barriers to therapeutics utilizing pluripotent cell derivatives: intrinsic immunogenicity of in vitro maintained and matured populations.
The potential to develop into any tissue makes pluripotent stem cells (PSCs) one of the most promising sources for cellular therapeutics. However, numerous hurdles exist to their clinical applications, three of the most concerning include the inability to separate therapeutic population from heterogeneously differentiated cultures, the risk of teratoma formation from residual pluripotent cells, and immunologic rejection of engrafted cells. The recent development of induced PSCs has been proposed as a solution to the histocompatibility barrier. Theoretically, creation of patient-specific induced PSC lines would exhibit a complete histocompatibility antigen match. However, regardless of the PSC source, in vitro propagation and nonphysiologic differentiation may result in other, likely less powerful, mechanisms of immune rejection. In light of recent progress towards clinical application, this review focuses on two such potential immunologic mechanisms applicable to isogenic PSC derivates: namely, the immunogenicity of aberrant antigens resulting from long-term in vitro maintenance and alterations in immunologic properties due to rapid in vitro differentiation. These issues will be considered with attention to their relation to effector cells in the adult immune system. In addition, we highlight immunosuppressive approaches that could potentially address the immunogenicity of these proposed mechanisms.


Modeling simultaneous saccharification and fermentation of softwood.
Simultaneous saccharification and fermentation (SSF) of wood has been modeled for the past 15-20 years, but the substrates used for model evaluation have so far not included pretreated softwood. In the present study, data from lab-scale batch SSF of SO2-impregnated, steam-pretreated spruce chips were used to evaluate a model found in the literature. The model, which was somewhat modified, consists of a number of nonlinear, coupled ordinary differential equations, which were solved numerically. Some parameter values were fitted to data by use of least-squares minimization. A difficulty in parameter estimation was the lack of cellobiose measurements, something that was relieved by adding assumptions about parameter relations. The simulated concentration profiles agreed well with the measured concentrations of glucose and ethanol. It is therefore concluded that the basic model features apply to softwood SSF. The model predicts rate saturation with respect to enzyme concentration at concentrations above 60 FPU/g cellulose, although this was not observed in the experimental data, which only comprised enzyme concentrations up to 32 FPU/g cellulose.


Pasteurella multocida toxin facilitates inositol phosphate formation by bombesin through tyrosine phosphorylation of G alpha q.
The intracellularly acting Pasteurella multocida toxin (PMT) is a potent mitogen that stimulates Gq-dependent formation of inositol trisphosphate. We show that PMT, a nontoxic mutant of PMT (PMTC1165S), and bombesin each stimulate time-dependent phosphorylation of G alpha q at tyrosine 349. Although PMT and PMTC1165S each cause phosphorylation of G alpha q, only the wild-type toxin activates Gq. Pretreatment of cells with wild-type or mutant PMT potentiated the formation of inositol phosphates stimulated by bombesin equally. These data show that PMT potentiates bombesin receptor signaling through tyrosine phosphorylation of Gq and distinguishes between the two proposed models of Gq activation, showing that tyrosine phosphorylation is not linked to receptor uncoupling.


OpenSim Moco: Musculoskeletal optimal control.
Musculoskeletal simulations are used in many different applications, ranging from the design of wearable robots that interact with humans to the analysis of patients with impaired movement. Here, we introduce OpenSim Moco, a software toolkit for optimizing the motion and control of musculoskeletal models built in the OpenSim modeling and simulation package. OpenSim Moco uses the direct collocation method, which is often faster and can handle more diverse problems than other methods for musculoskeletal simulation. Moco frees researchers from implementing direct collocation themselves-which typically requires extensive technical expertise-and allows them to focus on their scientific questions. The software can handle a wide range of problems that interest biomechanists, including motion tracking, motion prediction, parameter optimization, model fitting, electromyography-driven simulation, and device design. Moco is the first musculoskeletal direct collocation tool to handle kinematic constraints, which enable modeling of kinematic loops (e.g., cycling models) and complex anatomy (e.g., patellar motion). To show the abilities of Moco, we first solved for muscle activity that produced an observed walking motion while minimizing squared muscle excitations and knee joint loading. Next, we predicted how muscle weakness may cause deviations from a normal walking motion. Lastly, we predicted a squat-to-stand motion and optimized the stiffness of an assistive device placed at the knee. We designed Moco to be easy to use, customizable, and extensible, thereby accelerating the use of simulations to understand the movement of humans and other animals.


Clinically suspected primary acquired nasolacrimal duct obstruction: clinicopathologic review of 150 patients.
The incidence of lacrimal sac pathology in patients with clinically suspected primary acquired nasolacrimal duct obstruction is unknown. This is an important issue when considering the potential risk of either conservative nonsurgical management or laser dacryocystorhinostomy, neither of which permits direct visualization and biopsy of the lacrimal outflow apparatus. A total of 162 lacrimal sac biopsy specimens were obtained in 150 consecutive patients undergoing external or endonasal dacryocystorhinostomy for clinical primary acquired nasolacrimal duct obstruction from January 1992 to October 1994. A total of 147 patients (98%) had histopathologic findings consistent with inflammation or fibrosis of the lacrimal sac or both. In the remaining three patients, abnormalities included sarcoid granuloma (one patient), oncocytoma (one patient), and lymphoma (one patient). The incidence of significant pathology of the lacrimal sac in clinically suspected primary acquired nasolacrimal duct obstruction is low. However, these cases can be identified correctly only by routine biopsy of the lacrimal sac during dacryocystorhinostomy.


The aberrant expression of HLA-DR in intrahepatic bile ducts in patients with biliary atresia: an immunohistochemistry and immune electron microscopy study.
Although the precise pathogenesis for the destruction of the intrahepatic biliary tract in a patient with biliary atresia (BA) is still unclear, it is known that progressive destruction of the intrahepatic biliary tract is responsible for poor long-term outcome after surgical treatment. In this study, the authors evaluated the expression of HLA-DR in liver tissue of patients with BA to explore its role in the pathogenesis of this disease. Liver biopsy specimens from patients with BA (n = 14) and normal liver biopsies (n = 12) were studied immunohistochemically and were assessed immune electron microscopically to detect the expression of HLA-DR. All patients underwent follow-up for at least 3 months after surgery evaluating the short-term postoperative outcome by monitoring the serum bilirubin level during jaundice persistency. The immunohistochemical examinations showed in 10 of 14 liver specimens in the BA group a positive expression of HLA-DR. This expression was mainly detected in bile ducts of the central portal area rather than in proliferated ones in more peripheral areas. None of the specimens from the control group showed positive expression. Eight of 14 specimens in the BA group showed immunoelectron microscopic depositions of colloidal gold in dull and swollen ductules microvilli. This was not observed in the control group. In patients with BA there was an inverse relationship between short-term postoperative outcome and expression of HLA-DR in intrahepatic ductules. Our findings show that there is an aberrant expression of HLA-DR in microvilli of the ductules in patients with BA, and this abnormal expression is inversely related to the short-term postoperative outcome. It is suggested that aberrant HLA-DR expression in bile ductules may play a pathogenic role in progressive damage to the intrahepatic bile ducts in BA.


Clinical predictors of scleral rupture after blunt ocular trauma.
We conducted a two-part study to define better the clinical predictors of scleral rupture after blunt trauma. In part 1 we ascertained the prevalence of scleral rupture among a population of patients examined in an ophthalmic emergency room with severe blunt ocular trauma over a six-month period. Scleral rupture was diagnosed in ten of 283 patients (3.5%). In part 2 we compared the clinical findings in 29 patients with scleral rupture to those of 273 patients with no scleral rupture after blunt trauma. We noted that eyes with visual acuity of light perception or less, an intraocular pressure of 5 mm Hg or less, an abnormally deep or shallow anterior chamber, or a media opacity preventing a view of fundus details by indirect ophthalmoscopy, should be considered ruptured when severe intra- or periocular hemorrhage is present. This diagnostic algorithm had a sensitivity of 100.0% (98.7% to 100.0%), specificity of 98.5% (97.1% to 99.9%), and a positive predictive value of 71.4% (66.3% to 76.5%).


N-Benzoyl-N',N''-dicyclo-hexyl-phospho-ric triamide.
In the title compound, C(19)H(30)N(3)O(2)P, the central P atom has a distorted tetra-hedral configuration. The N atoms in both cyclo-hexyl-amide moieties exhibit a slight deviation [0.32 (7) and 0.44 (6) Å] from planarity, while the benzoyl-amide N atom is planar [0.11 (3) Å]. In the crystal, mol-ecules are linked via N-H⋯O(P) and N-H⋯O(C) hydrogen bonds, forming R(2) (2)(10) rings within linear arrangements parallel to the b axis.


Alterations of locus coeruleus noradrenergic activity in relation to pituitary secretion after hemorrhage in cats.
Noradrenergic (NA) activity in the cat ventral locus coeruleus (vLC), measured either by voltammetry or by push-pull perfusion, increased in response to hemorrhage. This stimulus also elicited plasma adrenocorticotropin (ACTH) and vasopressin responses. Increased vLC NA activity following the initial hemorrhage (InHem) persisted even after plasma hormone levels returned toward prestimulus values. Upon stimulus repetition, the peak increase in vLC NA activity was similar to that observed during InHem while the hormone responses were of greater magnitude (i.e. potentiated). Hence, it is suggested that the LC may exert a modulatory role in the hemodynamic control of hypothalamic-pituitary axis function.


Polymorphisms of the TNF, LTA, and TNFRSF1B genes are associated with onsets of menarche and menopause in US women of European ancestry.
The TNF, LTA and TNFRSF1B genes have been implicated in various traits related to menarche and menopause. To analyse the TNF, LTA and TNFRSF1B genes for their association with ages at menarche (AM) and natural menopause (ANM). The study sample consisted of 314 unrelated females of European ancestry. Twenty SNPs located in and near the genes were analysed using various statistical methods. In addition, the functional significance of the loci associated with AM and ANM was analysed in silico. Locus rs2229094 of the LTA gene was associated with AM according to the additive (β = -0.295, pperm = 0.016) and recessive (β = -0.940, pperm = 0.016) genetic models. Haplotype GG rs1148459-rs590368 of the TNFRSF1B gene was associated with AM (β = 0.307, pperm = 0.023). Haplotype GCA rs2844484-rs2229094-rs1799964 was associated with ANM after adjustment for covariates (β = -1.020, pperm = 0.035). All studied loci were associated with ANM after adjustment for breastfeeding (raw p < 0.05). In addition, eight of the most significant models of interlocus interactions were associated with AM and five with ANM. The results of the present study suggest that the TNF, LTA and TNFRSF1B genes are associated with AM and ANM.


Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study.
Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.


A new fractal structural-mechanical theory of particle-filled colloidal networks with heterogeneous stress translation.
This work addresses the role of rigid inclusions in determining the elastic modulus of particle-filled colloidal networks by modifying an established fractal scaling model. The approach acknowledges the heterogeneous nature of stress distribution at length scales beyond the colloidal aggregates, while maintaining structural information at the level of individual clusters. This was achieved by introducing a scaling factor to account for system heterogeneity which contains intrinsic information about the network's capacity to form load-bearing links. Rigid fillers bound to the network induce stress concentration, but additionally serve as junction zones which introduce additional load-bearing pathways. This gives rise to the observed increase in the modulus with filler volume fraction. The proposed relationship between the load-bearing network connectivity and scaling behavior may have additional implications on the fractal dimension determined by rheological methods. Further, this model accommodates an experimentally observed correlation between the scaling behavior of the modulus associated with the addition of fillers and that arising from increasing structurant concentration. The modified fractal model thus provides an alternative view of how fillers contribute to the small- and large-deformation mechanical behavior of filled colloidal gels in a manner consistent with experimental observations.


Chronic arthritis increases tyrosine hydroxylase mRNA levels in the pontine noradrenergic cell groups.
In situ hybridization was used to examine the change of tyrosine hydroxylase(TH) mRNA levels in the pontine noradrenergic cell groups of chronic monoarthritic rats induced by adjuvant inoculation. The number of TH mRNA-expressing neurons and grains per labeled neuron in the A5,A6 and A7 cell groups on the ipsilateral and contralateral sides significantly increased 2 weeks after adjuvant inoculation into the left tibio-tarsal joint, compared to controls. These results suggest that noradrenalin in the pontine region may play a role in modulating chronic nociceptive stimuli.


Young children's exposure to phenols in the home: Associations between house dust, hand wipes, silicone wristbands, and urinary biomarkers.
Environmental phenols, such as parabens, bisphenol A, and triclosan, are ubiquitous in indoor environments because of their use in packaging, plastics, personal care products, and as anti-microbials. The primary pathways of exposure, as well as habits and behaviors that may lead to greater exposure, are still unclear. Herein, we investigate the relationships between phenols found in residential environments by comparing levels in paired samples of house dust and hand wipes with children's urine. In addition, phenols were analyzed in a novel exposure tool, the silicone wristbands, to investigate which external matrix best correlates with individual exposure based on urinary phenol biomarkers. Children aged 3-6 years in central North Carolina, United States, provided paired hand wipe (n = 202), wristband (n = 76), and spot urine samples (n = 180), while legal guardians completed questionnaires on habits and behaviors. House dust samples (n = 186) were collected from the main living area during home visits completed between 2014 and 2016. Environmental phenols were detected frequently in all matrices investigated. Ethyl, methyl, and propylparaben levels observed in hand wipes, dust, and on wristbands were significantly correlated to their associated urinary biomarkers. In addition, intra-paraben correlations were noted, with biomarkers of ethyl, methyl, and propylparabens generally positively and significantly correlated, which suggests co-application of parabens in products. Triclosan levels in dust were positive and significantly correlated with levels in hand wipes and wristbands and with urinary concentrations, suggesting non-personal care product sources may be important in children's overall triclosan exposure. Generally, chemicals on wristbands were more highly correlated with urinary biomarkers than with chemicals in hand wipes or house dust. In addition, more frequent lotion use was positively associated with urinary concentrations of paraben biomarkers. Our results suggest that the home environment is an important source of exposure which has been under-investigated for some environmental phenols (e.g., triclosan in house dust). Associations between wristbands and biomarkers of exposure, which were stronger than for hand wipes and house dust, suggest that silicone wristbands may provide a suitable exposure assessment tool for some phenols.


Sleep and rest-activity rhythms for women at different menopausal statuses: the role of mental health.
To examine how mental health interplays with menopausal status in relation to sleep patterns and rest-activity rhythms (RARs) among middle-aged women. This cross-sectional study recruited 87 women aged 45 to 60 years from community and a gynecology clinic in Taiwan. Participants wore actigraphy devices for 7 days and were also assessed with self-reported questionnaires. Hierarchical regression was used to examine the effects of menopausal status and mental health on sleep and RARs. Perimenopausal and postmenopausal women had higher relative amplitude and interdaily stability of RARs than premenopausal women. There were no differences in actigraphy-based sleep parameters across menopausal statuses. There was no difference in depressive symptoms or loneliness across menopausal statuses. Higher levels of depressive symptoms were significantly associated with longer sleep latency (β = 0.26, P = 0.022) and wake after sleep onset (β = 0.28, P = 0.012), and lower sleep efficiency (β = -0.30, P = 0.008) after adjusting for menopausal status and age. In addition, there was marginal significance of the positive association between loneliness and interdaily stability (β = 0.18, P = 0.079). A moderating effect (βmenopausal status*loneliness = -0.40, P = 0.025) showed that lonelier premenopausal women exhibited greater relative amplitude (RA) of rest-activity rhythms, but lonelier menopausal women had lower RA of RAR. Mental health plays an important role for middle-aged women with different menopausal statuses in relation to sleep patterns and RARs.


Chemotherapy for advanced gallbladder cancer (GBC): A systematic review and meta-analysis.
The benefit from chemotherapy, specifically for patients with gallbladder cancer (GBC), has been poorly explored since GBC is mostly studied jointly with other biliary tract cancers (BTC). Eligible studies reporting outcome of palliative systemic chemotherapy for advanced GBC were identified through MEDLINE, cross-referencing and conferences (PROSPERO-CRD42019155745). Meta-analysis of proportions and calculation of pooled weighted means were performed. 58 eligible studies (n = 1,986 patients); cisplatin/gemcitabine (33 % of patients), gemcitabine/oxaliplatin (14 %) or gemcitabine monotherapy (9%). Estimated pooled overall radiological response rate(ORR), and pooled weighted mean progression-free (PFS) and overall survivals (OS) were 23.2 % (95 %-CI 20.0-26.5) (I2: 52.5 % (p < 0.001)), 4.8 months (95 %-CI 4.3-5.2) and 8.3 months (95 %CI 7.6-8.9), respectively. Patients with non-GBC BTCs achieved a lower ORR than GBC [odds ratio 0.65 (95 % CI, 0.50-0.84)]. GBC benefit from chemotherapy differs from other BTCs, with shorter PFS/OS despite higher ORR; new treatment options are urgently required for management of advanced GBC.


Biliary-enteric reconstruction with hepaticoduodenostomy following laparoscopic excision of choledochal cyst is associated with better postoperative outcomes: a single-centre experience.
With the advent of laparoscopic surgery, more choledochal cysts are excised laparoscopically. In this study, we compared the outcomes from laparoscopic hepaticojejunostomy (HJ) and hepaticoduodenostomy (HD) for biliary-enteric reconstruction. A retrospective analysis of patients who had undergone laparoscopic choledochal cyst excision between February 2005 and January 2014 in a tertiary referral centre was performed. Demographics data, operative techniques and surgical outcomes were analysed according to the way of biliary-enteric reconstruction. A total of 31 patients were identified, 20 of whom underwent HJ and 11 underwent HD. There were no significant differences in terms of demographics. Median operative time was significantly shorter in HD group (211.0 ± 96.4 vs. 386.0 ± 90.4 min, p = 0.001). Although postoperative enteral feeding was initiated later in HD group (5.0 ± 0.8 vs. 4.0 ± 3.6 days, p = 0.036), postoperative stay in intensive care unit (ICU) (0.7 ± 1.0 vs. 2.4 ± 1.7 days, p = 0.007) and overall hospital stay (9.1 ± 1.0 vs. 14.4 ± 12.2 days, p = 0.157) favoured HD group. There was no perioperative mortality. Median follow-up duration was 24.0 (±11.0) months in HD group and 67.5 (±23.7) months in HJ group. One patient in HJ group had postoperative cholangitis related to anastomotic stricture whereas no cholangitis noted in HD group. In total, five patients in HJ group required second operation for complications and residual diseases whereas none in HD group required reoperation. Laparoscopic excision of choledochal cyst with hepaticoduodenostomy reconstruction is safe and feasible with shorter operative time, ICU stay and overall hospital stay. It is not inferior to HJ in terms of short-term postoperative outcomes.


Holistic manual therapy techniques.
This article focuses on three holistic manual therapy techniques: Myofascial Release, Trager Psychophysical Integration and Therapeutic Touch. The theories and principles of each technique, indications and contraindications for treatment, an overview of the actual approach, and case studies are outlined, and the principles that make them effective complementary therapies in health care are discussed.


ProNetView-ccRCC: A Web-Based Portal to Interactively Explore Clear Cell Renal Cell Carcinoma Proteogenomics Networks.
To better understand the molecular basis of cancer, the NCI's Clinical Proteomics Tumor Analysis Consortium (CPTAC) has been performing comprehensive large-scale proteogenomic characterizations of multiple cancer types. Gene and protein regulatory networks are subsequently being derived based on these proteogenomic profiles, which serve as tools to gain systems-level understanding of the molecular regulatory factories underlying these diseases. On the other hand, it remains a challenge to effectively visualize and navigate the resulting network models, which capture higher order structures in the proteogenomic profiles. There is a pressing need to have a new open community resource tool for intuitive visual exploration, interpretation, and communication of these gene/protein regulatory networks by the cancer research community. In this work, ProNetView-ccRCC (http://ccrcc.cptac-network-view.org/), an interactive web-based network exploration portal for investigating phosphopeptide co-expression network inferred based on the CPTAC clear cell renal cell carcinoma (ccRCC) phosphoproteomics data is introduced. ProNetView-ccRCC enables quick, user-intuitive visual interactions with the ccRCC tumor phosphoprotein co-expression network comprised of 3614 genes, as well as 30 functional pathway-enriched network modules. Users can interact with the network portal and can conveniently query for association between abundance of each phosphopeptide in the network and clinical variables such as tumor grade.


Structural basis for AMP binding to mammalian AMP-activated protein kinase.
AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound.


Development of plasmid and oligonucleotide nanometric particles.
Nucleic acids delivery vectors have shown promising therapeutic potential in model systems. However, comparable clinical success is delayed essentially because of their poor biodistribution and of their ineffective intracellular trafficking. The size of condensed DNA particles is a key determinant for in vivo diffusion, as well as for gene delivery to the cell nucleus. Towards this goal, we have developed cationic thiol-detergents that individually compact plasmid DNA molecules into anionic particles. These particles are then 'stabilized' by air-induced dimerization of the detergent into a disulfide lipid on the template DNA. The particles all measure approximately 30 nm, which corresponds to the volume of a single molecule of plasmid DNA. The gel electrophoretic mobility of the anionic particles was found to be higher than that of the plasmid DNA itself. Similarly, particles formed with a 31-mer oligonucleotide measured 19 nm. Improved in vivo diffusion, as well as improved intracellular trafficking may be inferred from the faster migration of the complexes. Moreover, the size of the particles remains compatible with nuclear pore crossing. Finally, in an attempt to improve the biodistribution of these particles, we have coated the monomolecular particles with a poly(ethylene glycol) corona.


Polyunsaturated fatty acids regulate Shiga toxin transport.
Shiga toxin (Stx) is internalized by receptor-mediated endocytosis and transported retrogradely to the endoplasmic reticulum from where the enzymatically active part of the toxin is translocated to the cytosol. In this study, we have investigated the effect of polyunsaturated fatty acids (PUFA) on intoxication and retrograde transport of Stx. In HEp-2 cells, PUFA treatment inhibited Stx intoxication by a factor of 10. Moreover, both Stx internalization and endosome-to-Golgi transport were reduced by PUFA and these reductions can together explain the reduced toxicity. Also cholera toxin internalization was reduced by PUFA treatment. Finally, ricin and Pseudomonas exotoxin 1 cytotoxicity were not reduced by PUFA, demonstrating that PUFA do not cause a general block in retrograde transport to the endoplasmic reticulum. In conclusion, these results clearly demonstrate the importance of PUFA for Stx and cholera toxin trafficking.


Effects of Medicaid managed care programs on health services access and use.
To estimate the effects of Medicaid managed care (MMC) programs on Medicaid enrollees' access to and use of health care services at the national level. 1991-1995 National Health Interview Surveys (NHIS) and a 1998 Urban Institute survey on state Medicaid managed care programs. Using multivariate regression models, we estimated the effect of living in a county with an MMC program on several access and use measures for nonelderly women who receive Medicaid through AFDC and child Medicaid recipients. We focus on mandatory programs and estimate separate effects for primary care case management (PCCM) programs, health maintenance organization (HMO) programs, and mixed PCCM/HMO programs, relative to fee-for-service (FFS) Medicaid. We control for individual and county characteristics, and state and year effects. This study uses pooled individual-level data from up to five years of the NHIS (1991-1995), linked to information on Medicaid managed care characteristics at the county level from the 1998 MMC survey. We find virtually no effects of mandatory PCCM programs. For women, mandatory HMO programs reduce some types of non-emergency room (ER) use, and increase reported unmet need for medical care. The PCCM/HMO programs increase access, but had no effects on use. For children, mandatory HMO programs reduce ER visits, and increase the use of specialists. The PCCM/HMO programs reduce ER visits, while increasing other types of use and access. Mandatory PCCM/HMO programs improved access and utilization relative to traditional FFS Medicaid, primarily for children. Mandatory HMO programs caused some access problems for women.


Educational needs related to elder abuse among undergraduate nursing students in Korea: An importance-performance analysis.
Elder abuse is a prominent social issue and is a particularly grave problem in increasingly aging societies. Provision of appropriate elder abuse education programs for undergraduate nursing students, who are the future healthcare providers, can aid the detection of elder abuse by strengthening their practical knowledge. The purpose of this study was to conduct an importance-performance analysis (IPA) on the educational content related to elder abuse among undergraduate nursing students in Korea. Cross-sectional design with a questionnaire survey. Nursing department in the Chungcheong region of South Korea. A total of 324 undergraduate nursing students participated. The IPA and Borich needs assessment of undergraduate nursing students' perceptions of elder abuse education were conducted. The IPA analysis indicated that quadrant I demonstrated high levels of both importance and performance. The results of the Borich needs assessment, which analyzed the order of priority of the educational needs, also indicated that the factors that ranked high in the order of priority belonged to quadrant 1 (strengthening maintenance) and quadrant 4 (concentrated investment), consistent with the IPA results. The results of the locus for focus model identified the elder abuse education topics' first and second priority groups. Educational themes such as "understanding of laws regarding elder abuse and ways of reporting it" were revealed to be the highest priority, and themes such as "human rights of the elderly" and "types and cases of elder abuse" received the second priority. Courses regrading elder abuse that include the educational needs, identified the by undergraduate nursing students, are required to improve the professional ability of nurses who care for the elderly.


Unsupervised domain adaptation of bearing fault diagnosis based on Join Sliced Wasserstein Distance.
Deep neural networks have been successfully utilized in the mechanical fault diagnosis, however, a large number of them have been based on the same assumption that training and test datasets followed the same distributions. Unfortunately, the mechanical systems are easily affected by environment noise interference, speed or load change. Consequently, the trained networks have poor generalization under various working conditions. Recently, unsupervised domain adaptation has been concentrated on more and more attention since it can handle different but related data. Sliced Wasserstein Distance has been successfully utilized in unsupervised domain adaptation and obtained excellent performances. However, most of the approaches have ignored the class conditional distribution. In this paper, a novel approach named Join Sliced Wasserstein Distance (JSWD) has been proposed to address the above issue. Four bearing datasets have been selected to validate the practicability and effectiveness of the JSWD framework. The experimental results have demonstrated that about 5% accuracy is improved by JSWD with consideration of the conditional probability than no the conditional probability, in addition, the other experimental results have indicated that JSWD could effectively capture the distinguishable and domain-invariant representations and have a has superior data distribution matching than the previous methods under various application scenarios.


Functional connectivity of the language area in migraine: a preliminary classification model.
Migraine is a complex disorder characterized by debilitating headaches. Despite its prevalence, its pathophysiology remains unknown, with subsequent gaps in diagnosis and treatment. We combined machine learning with connectivity analysis and applied a whole-brain network approach to identify potential targets for migraine diagnosis and treatment. Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI(rfMRI), and diffusion weighted scans were obtained from 31 patients with migraine, and 17 controls. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into diagnostic groups based on functional connectivity (FC) and derive networks and parcels contributing to the model. PageRank centrality analysis was also performed on the structural connectome to identify changes in hubness. Our model attained an area under the receiver operating characteristic curve (AUC-ROC) of 0.68, which rose to 0.86 following hyperparameter tuning. FC of the language network was most predictive of the model's classification, though patients with migraine also demonstrated differences in the accessory language, visual and medial temporal regions. Several analogous regions in the right hemisphere demonstrated changes in PageRank centrality, suggesting possible compensation. Although our small sample size demands caution, our preliminary findings demonstrate the utility of our method in providing a network-based perspective to diagnosis and treatment of migraine.


Saethre-Chotzen syndrome associated with defective neutrophil chemotaxis.
An 11-month-old male infant with Saethre-Chotzen syndrome and recurrent respiratory infections is described. Persistent extremely high leukocytosis warranted evaluation of neutrophil functions. It was found that the opsonophagocytic activity was normal, but neutrophil chemotaxis was markedly decreased. Further studies pointed to an intracellular neutrophil defect causing this motility dysfunction.


Attitudes towards suicide among Kurdish people in Iran.
Attitudes towards suicide represent a key stage in the pathway leading to suicide. A deeper understanding of the social, psychological and treatment-related factors influencing the development of attitudes towards suicide could guide suicide prevention strategies especially in a neglected population like Kurds. In a cross-sectional study in Iranian Kurdistan, 1,000 households participated in the investigation from April to May 2006 selected by a cluster random sampling process. A questionnaire on attitudes towards suicide (ATTS) was used to measure suicide related attitudes and thoughts. Suicide related experiences were more often reported from the wider social network (relative, friends, acquaintances) than from family members. There is a significant accumulation of suicide related experiences when a related event was reported in the close family. The level of suicide related attitudes is related to age, gender, marital status, level of education and employment status. Openness towards the topic of suicide as well as abilities to communicate about it should be improved by educating the public and additionally be promoted by changing conservative value systems.


Endogenous Retroviruses Walk a Fine Line between Priming and Silencing.
Endogenous retroviruses (ERVs) in mammals are closely related to infectious retroviruses and utilize host tRNAs as a primer for reverse transcription and replication, a hallmark of long terminal repeat (LTR) retroelements. Their dependency on tRNA makes these elements vulnerable to targeting by small RNAs derived from the 3'-end of mature tRNAs (3'-tRFs), which are highly expressed during epigenetic reprogramming and potentially protect many tissues in eukaryotes. Here, we review some key functions of ERV reprogramming during mouse and human development and discuss how small RNA-mediated silencing maintains genome stability when ERVs are temporarily released from heterochromatin repression. In particular, we take a closer look at the tRNA primer binding sites (PBS) of two highly active ERV families in mice and their sequence variation that is shaped by the conflict of successful tRNA priming for replication versus evasion of silencing by 3'-tRFs.


Correction: Prediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP).
[This corrects the article DOI: 10.1371/journal.pmed.1002883.].


Development and validation of an algorithm to determine the minimal factors needed for non-invasive measurement of the in vivo primary stability of cementless hip implants.
Aseptic loosening is a frequent cause for revision of endoprosthesis. X-ray examinations like Radio-Stereometry-Analysis (RSA) are among the most widely used in vivo methods for its detection. Nevertheless, this method is not used routinely because of bone marker and related radiation exposure. This work aims at creating a new in vivo concept to detect implant stability measuring micromotions without x-ray and to develop a corresponding algorithm. Based on the assumption of contactless measurement, the input parameters for the algorithm are the distances of each ultrasound sensor to the object (prosthesis and bone) and its position. First, the number of parameters necessary for a precise reconstruction and measurement of micromotions between objects had to be defined. Therefore, the algorithm has been tested with simulations of these parameters. Two experimental measurements, either using contact sensors or ultrasound, were used to prove the accuracy of the algorithm. Simulations indicate a high accuracy with three distances as initial parameters for each object. Contact measurements show precise representation of micromotion, and the contactless measurements show the possibility of detecting various materials with a high resolution. This work lays the foundations for non-invasive detection of micromotions between the implant-bone interface.


A new approach on synergistic effect and chemical stability of graphene oxide-magnetic nanocomposite in the heterogeneous Fenton degradation of caffeine.
Two compositions of graphene oxide-magnetite nanocomposites were studied as catalysts in the heterogeneous Fenton process. Transmission electron microscopy and X-ray diffraction revealed that the graphene oxide sheets were covered with nanoparticles of magnetite, with an average crystallite size of 7 nm. Infrared spectroscopy analysis indicated that the phases interacted through covalent Fe-O-C bonds. The composites presented significantly improved catalytic activity, compared to pure magnetite, with a synergistic effect of up to a factor of 17.1 for the Fenton degradation of caffeine, achieving total removal after 90 min. This synergistic effect was a consequence of the interaction between the phases, resulting in improved mass transfer of caffeine to the catalyst surface, adsorption and efficient degradation, with enhanced HO• generation. The surface reaction constant increased by up to three orders of magnitude, demonstrating the important role of graphene oxide in the degradation kinetics of the heterogeneous Fenton process. The surface-bonded hydroxyl radicals were responsible for caffeine degradation, achieving 9.4 μmol L-1. After five degradation cycles, a loss of Fe-O-C bonds and increase in oxygenated groups were associated with a small decrease of caffeine removal efficiency, from 98 to 82%, without significant iron leaching, in the dark, and with low consumption of hydrogen peroxide.


Functional adiponectin resistance and exercise intolerance in heart failure.
The contribution of skeletal muscle myopathy to the phenotype of patients with chronic heart failure (CHF) has become generally accepted. Besides the macro- and microscopic changes that develop during the progressive process of muscular wasting, functional abnormalities manifest in an earlier stage. Analogous to the failing heart, alterations in skeletal muscle energy metabolism, including insulin resistance, are increasingly recognized. In the search for factors causing this observed myopathy, adipokines receive growing attention. In particular, adiponectin is of special interest due to its fundamental role in skeletal muscle energy metabolism. In strong contrast with patients at risk for cardiovascular disease, circulating adiponectin levels are increased in patients with CHF, and this finding is associated with adverse outcome. Recently, the concept of functional skeletal muscle adiponectin resistance has been suggested to explain compensatory elevated adiponectin levels in CHF. Unraveling of adiponectin's complex downstream signalling pathways and insights into the concept of adiponectin resistance hopefully will disengage the road for targeted therapeutic interventions.


Cell-to-cell variability in Myc dynamics drives transcriptional heterogeneity in cancer cells.
Cell-to-cell heterogeneity is vital for tumor evolution and survival. How cancer cells achieve and exploit this heterogeneity remains an active area of research. Here, we identify c-Myc as a highly heterogeneously expressed transcription factor and an orchestrator of transcriptional and phenotypic diversity in cancer cells. By monitoring endogenous c-Myc protein in individual living cells, we report the surprising pulsatile nature of c-Myc expression and the extensive cell-to-cell variability in its dynamics. We further show that heterogeneity in c-Myc dynamics leads to variable target gene transcription and that timing of c-Myc expression predicts cell-cycle progression rates and drug sensitivities. Together, our data advocate for a model in which cancer cells increase the heterogeneity of functionally diverse transcription factors such as c-Myc to rapidly survey transcriptional landscapes and survive stress.


[Problems in the rehabilitation of chronic or frequently relapsing schizophrenic psychoses and their causes].
The rehabilitative difficulties in part of the patients with schizophrenia are connected with premorbid disablements which lead to faulty social developments. An attempt is made to show by the example of some courses of diseases that the problems of these patients are largely similar; they are related to the patients entering the phase of vocational life, the establishment of appropriate partner relations and disturbed relations with the generation of their parents.


Performance Metrics of Substance Use Disorder Care Among Medicaid Enrollees in New York, New York.
There is limited evaluation of the performance of Medicaid managed care (MMC) private plans in covering substance use disorder (SUD) treatment. To compare the performance of MMC plans across 19 indicators of access, quality, and outcomes of SUD treatment. This cross-sectional study used administrative claims and mandatory assignment to plans of up to 159 016 adult Medicaid recipients residing in 1 of the 5 counties (boroughs) of New York, New York, from January 2009 to December 2017 to identify differences in SUD treatment access, patterns, and outcomes among different types of MMC plans. Data from the latest years were received from the New York State Department of Health in October 2019, and analysis began soon thereafter. Approximately 17% did not make an active choice of plan, and a subset of these (approximately 4%) can be regarded as randomly assigned. Plan assignment. Percentage of the enrollees achieving performance measures across 19 indicators of access, process, and outcomes of SUD treatment. Medicaid claims data from 159 016 adults (mean [SD] age, 35.9 [12.7] years; 74 261 women [46.7%]; 8746 [5.5%] Asian, 73 783 [46.4%] Black, and 40 549 [25.5%] White individuals) who were auto assigned to an MMC plan were analyzed. Consistent with national patterns, all plans achieved less than 50% (range, 0%-62.1%) on most performance measures. Across all plans, there were low levels of treatment engagement for alcohol (range, 0%-0.4%) and tobacco treatment (range, 0.8%-7.2%), except for engagement for opioid disorder treatment (range, 41.5%-61.4%). For access measures, 4 of the 9 plans performed significantly higher than the mean on recognition of an SUD diagnosis, any service use for the first time, and tobacco use screening. Of the process measures, total monthly expenditures on SUD treatment was the only measure for which plans differed significantly from the mean. Outcome measures differed little across plans. The results of this cross-sectional study suggest the need for progress in engaging patients in SUD treatment and improvement in the low performance of SUD care and limited variation in MMC plans in New York, New York. Improvement in the overall performance of SUD treatment in Medicaid potentially depends on general program improvements, not moving recipients among plans.


Judging the sources of inferior groundwater quality and health risk problems through intake of groundwater nitrate and fluoride from a rural part of Telangana, India.
Evaluation of groundwater quality and related health hazards is a prerequisite for taking preventive measures. The rural region of Telangana, India, has been selected for the present study to assess the sources and origins of inferior groundwater quality and to understand the human health risk zones for adults and children due to the consumption of nitrate ([Formula: see text])- and fluoride (F-)-contaminated groundwater for drinking purposes. Groundwater samples collected from the study region were determined for various chemical parameters. Groundwater quality was dominated by Na+ and [Formula: see text] ions. Piper's diagram and bivariate plots indicated the carbonate water type and silicate weathering as a main factor and man-made contamination as a secondary factor controlling groundwater chemistry; hence, the groundwater quality in the study region is low. According to the Groundwater Quality Index (GQI) classification, 48.3% and 51.7% of the total study region are excellent (GQI: < 50) and good (GQI: 50 to 100) water quality types, respectively, for drinking purposes. However, [Formula: see text] ranged from 0.04 to 585 mg/L, exceeding the drinking water quality limit of 45 mg/L in 34% of the groundwater samples due to the effects of nitrogen fertilizers. This was supported by the relationship of [Formula: see text] with TDS, Na+, and Cl-. The F- content was from 0.22 to 5.41 mg/L, which exceeds the standard drinking water quality limit of 1.5 mg/L in 25% of the groundwater samples. The relationship of F- with pH, Ca2+, Na+, and [Formula: see text] supports the weathering and dissolution of fluoride-rich minerals for high F- content in groundwater. They were further supported by a principal component analysis. The Health Risk Index (HRI) values ranged from 0.20 to 20.10 and 0.36 to 30.90 with a mean of 2.82 and 4.34 for adults and children, respectively. The mean intensity of HRI (> 1.0) was 1.37 times higher in children (5.70) than in adults (4.16) due to the differences in weight size and exposure time. With an acceptable limit of more than 1.0, the study divided the region into Northern Safe Health Zone (33.3% for adults and 28.1% for children) and Southern Unsafe Health Zone (66.7% for adults and 71.9% for children) based on the intensity of agricultural activity. Therefore, effective strategic measures such as safe drinking water, denitrification, defluoridation, rainwater harvesting techniques, sanitary facilities, and chemical fertilizer restrictions are recommended to improve human health and protect groundwater resources.


Adaptation and implementation of family-based treatment enhanced with dialectical behavior therapy skills for anorexia nervosa in community-based specialist clinics.
Although family-based therapy (FBT) is a well-established treatment for anorexia nervosa, its implementation and effectiveness in clinical settings has been neglected. A group of seven therapists at a community-based eating disorders clinic were trained in skills-enhanced FBT and provided treatment to 11 youth with anorexia nervosa. Family-based skills training, which borrowed heavily from dialectical behavior therapy, was introduced in four additional sessions and then integrated throughout the remainder of FBT. FBT was perceived as appropriate and acceptable by all participants. Therapists reported high treatment fidelity. There was a large improvement in weight and moderate improvement in caregiver-reported eating disorder psychopathology but no clinically significant change by youth report. This study provides preliminary data on the implementation and effectiveness of FBT in the community.


Synthesis, decomposition studies and crystal structure of a three-dimensional CuCN network structure with protonated N-methylethanolamine as the guest cation.
The compound poly[2-hydroxy-N-methylethan-1-aminium [μ3-cyanido-κ3C:C:N-di-μ-cyanido-κ4C:N-dicuprate(I)]], {(C3H10NO)[Cu2(CN)3]}n or [meoenH]Cu2(CN)3, crystallizes in the tetragonal space group P43. The structure consists of a three-dimensional (3D) anionic CuICN network with noncoordinated protonated N-methylethanolamine cations providing charge neutrality. Pairs of cuprophilic Cu atoms are bridged by the C atoms of μ3-cyanide ligands, which link these units into a 43 spiral along the c axis. The spirals are linked together into a 3D anionic network by the two other cyanide groups. The cationic moieties are linked into their own 43 spiral via N-H...O and O-H...O hydrogen bonds, and the cations interact with the 3D network via an unusual pair of N-H...N hydrogen bonds to one of the μ2-cyanide groups. Thermogravimetric analysis indicates an initial loss of the base cation and one cyanide as HCN at temperatures in the range 130-250 °C to form CuCN. We show how loss of a specific cyanide group from the 3D CuCN structure could form the linear CuCN structure. Further heating leaves a residue of elemental copper, isolated as the oxide.


Body measurements of Chinese males in dynamic postures and application.
It is generally accepted that there is a relationship between body dimensions, body movement and clothing wearing ease design, and yet previous research in this area has been neither sufficient nor systematic. This paper proposes a method to measure the human body in the static state and in 17 dynamic postures, so as to understand dimensional changes of different body parts during dynamic movements. Experimental work is carried out to collect 30 measurements of 10 male Chinese subjects in both static and dynamic states. Factor analysis is used to analyse body measurement data in a static state, and such key measurements describe the characteristics of different body figures. Moreover, one-way ANOVA is used to analyse how dynamic postures affect these key body measurements. Finally, an application of the research results is suggested: a dynamic block patternmaking method for high-performance clothing design.


Same-different judgments of multiletter strings: insensitivity to positional bias and spacing.
Several recent studies of multiletter matching have included pairs of strings that have the same letters in different positions (rearranged pairs). The task can be defined such that these rearranged pairs are correctly classified as different (i.e., subjects respond "same" only if the strings have the same letters in the same positions--the order task) or as same (i.e., subjects respond "same" if the strings have the same letters regardless of their positions--the item task). The order task produces left-to-right serial-position effects, whereas the item task produces U-shaped serial-position effects. Because these differences suggest that subjects may be able to exert strategic control over the comparison process, two sets of experiments were designed to test whether or not subjects can change the relative weightings devoted to the respective serial positions. In Experiments 1 and 2, the probability that a mismatch occurred in the different positions was manipulated. In Experiments 3 and 4, the physical spacing between letters, as well as whether or not the spaces were filled with neutral noise characters, was varied. None of the manipulations had much influence on the serial-position effects. Thus, the distinct serial-position effects for the order and item tasks apparently are mandatory and not due to any voluntary comparison strategy.


Development of new-tools to investigate toxicological hazard due to endocrine disruptor organochlorines and emerging contaminants in Mediterranean cetaceans.
The possibility that certain Mediterranean cetaceans are subject to toxicological hazard due to organochlorines and emerging contaminants, such as polybrominated diphenyl ethers (PBDEs) with endocrine disrupting capacity, was investigated using non-lethal methods. The need for new biomarkers for EDCs and for a "cell model" to explore the different susceptibilities to several classes of ECDs, including emerging contaminants, led us to culture fibroblasts of different cetacean species ("dolphins in test tubes"). We then explored interspecies and gender susceptibility to OC-EDCs and PBDEs using qualitative and semi-quantitative evaluation of target proteins, such as CYP1A and CYP2B in cultured cetacean fibroblasts (Stenella coeruleoalba, Tursiops truncatus and Balaenoptera physalus), by western blot and immunofluorescence techniques.


Tris(ethyl-enediamine)-cobalt(III) diformatodioxalatoindate(III) dihydrate.
In the cation of the title compound, [Co(C(2)H(8)N(2))(3)][In(C(2)O(4))(2)(CHO(2))(2)]·2H(2)O, the Co-N bond lengths lie in the range 1.960 (5)-1.997 (5) Å. In the anion, the In(III) atom is coordin-ated by four O atoms from two oxalato ligands and two O atoms from two formato ligands in a distorted octa-hedral geometry. Inter-molecular O-H⋯O and N-H⋯O hydrogen bonds form an extensive hydrogen-bonding network, which link the cations, anions and water mol-ecules into three-dimensional structure.