IsoScore: automated localization of biotransformations by mass spectrometry using product ion scoring of virtual regioisomers.
We describe a novel approach for the automated localization of biotransformations, which we term IsoScore. Accurate mass measurement spectra of a parent drug and its metabolites are acquired. All virtual regioisomers of a given biotransformation are generated in silico by iterating over all plausible sites of oxidation around the parent drug. Each is then fragmented virtually using an exhaustive approach supplemented with chemical intelligence. Each fragment is scored based on the likelihood that it can be formed from the precursor structure. The fragment library of each virtual isomer is then compared with the experimentally observed ions. The likelihood that a regioisomer explains the observed fragmentation data is contained in its cumulated score. We include additional weightings, which take into account the level of similarity between the mass spectra of the metabolite and the parent compound.This concept was tested on a variety of metabolites from different chemical platforms formed via single biotransformations. For a very large proportion of the metabolites, IsoScore correctly located the biotransformation to the expected position. All ions above a defined threshold in the spectrum are used to contribute to the score with no predisposition to ignore minor ions or to weight conclusions based on readily interpretable fragments. The approach is found to be most successful when differential scoring is observed between related ions in the parent and the metabolite. Further improvements in the scoring function will result in increased differentiation between likely and unlikely structures, even when the parent and the metabolite spectra show little similarity.


Estimation of minimum infection rates with Legionella pneumophila in an exposed population.
The distribution of antibody levels to Legionella (L.) pneumophila (serotypes 1-7) was compared between subjects who worked near the source of a large outbreak of Legionnaires' disease (n=668) and a population sample of comparable age (n=480). In a previous analysis of these data, it was estimated that 80% of those working near the source were infected with L. pneumophila. However, the estimation procedure implicitly assumes that the probability of infection does not depend on the antibody level of a person before exposure. This is questionable, as antibodies could protect against infection. We have now estimated the minimum value consistent with the data on the number of infected persons. We observed that a minimum of 40% [95% confidence interval (CI) 32-48] of those working near the source and 13% (95% CI 8-18) of those working further away were infected with L. pneumophila. Implications of these findings for design options in future research are discussed.


Improving CD4+ lymphocyte counts in HIV-infected hemophilia patients. A favorable prognostic indicator?
CD4+ lymphocyte counts of 91 HIV+ hemophilia patients were monitored for a mean of 4 years (range: 15-69 months). CD4+ lymphocytes decreased in 55 but increased in 36 patients over time. The CD4+ cell increases were persistent in 5 patients, whereas they fluctuated in 31. Of the 36 patients with increasing CD4+ counts 3 developed AIDS and 1 LAS. The other 32 patients were clinically asymptomatic (CDC II), but had immunological abnormalities, such as increased serum neopterin (N = 18) and impaired in vitro T cell responses to pooled allogenic stimulator cells (N = 15) or mitogens (N = 18). In contrast, of the 55 patients whose CD4+ cells decreased, 24 developed AIDS and 5 ARC (P less than 0.0005). Only 2 of these 55 patients had normal mitogen stimulation in vitro and normal serum neopterin levels.


Quality control of nonstop membrane proteins at the ER membrane and in the cytosol.
Since messenger RNAs without a stop codon (nonstop mRNAs) for organelle-targeted proteins and their translation products (nonstop proteins) generate clogged translocon channels as well as stalled ribosomes, cells have mechanisms to degrade nonstop mRNAs and nonstop proteins and to clear the translocons (e.g. the Sec61 complex) by release of nonstop proteins into the organellar lumen. Here we followed the fate of nonstop endoplasmic reticulum (ER) membrane proteins with different membrane topologies in yeast to evaluate the importance of the Ltn1-dependent cytosolic degradation and the Dom34-dependent release of the nonstop membrane proteins. Ltn1-dependent degradation differed for membrane proteins with different topologies and its failure did not affect ER protein import or cell growth. On the other hand, failure in the Dom34-dependent release of the nascent polypeptide from the ribosome led to the block of the Sec61 channel and resultant inhibition of other protein import into the ER caused cell growth defects. Therefore, the nascent chain release from the translation apparatus is more instrumental in clearance of the clogged ER translocon channel and thus maintenance of normal cellular functions.


The Resting-State Functional Magnetic Resonance Imaging Regional Homogeneity Metrics-Kendall's Coefficient of Concordance-Regional Homogeneity and Coherence-Regional Homogeneity-Are Valid Indicators of Tumor-Related Neurovascular Uncoupling.
The aim of this study is to determine whether regional homogeneity (ReHo) of resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (rsfMRI) data based on Kendall's coefficient of concordance (KCC-ReHo) and coherence (Cohe-ReHo) metrics may allow detection of brain tumor-induced neurovascular uncoupling (NVU) in the sensorimotor network similar to findings in standard motor task-based BOLD fMRI (tbfMRI) activation. Twelve de novo brain tumor patients undergoing clinical fMRI exams (tbfMRI and rsfMRI) were included in this Institutional Review Board (IRB)-approved study. Each patient displayed decreased/absent tbfMRI activation in the primary ipsilesional sensorimotor cortex in the absence of corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for motor tasks were obtained from the general linear model (GLM) analysis (reflecting motor activation vs. rest). KCC-ReHo and Cohe-ReHo maps were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and ipsilesional (IL) hemispheres were parcellated using an automated anatomical labeling (AAL) template for each patient. Similar region of interest (ROI) analysis was performed on tbfMRI, KCC-ReHo, and Cohe-ReHo maps to allow direct comparison of results. Voxel values in CL and IL ROIs of each map were divided by the corresponding global mean of KCC-ReHo and Cohe-ReHo in bihemispheric cortical brain tissue. Group analysis revealed significantly decreased IL mean KCC-ReHo (p = 0.02) and Cohe-ReHo (p = 0.04) metrics compared with respective values in the CL ROIs, consistent with similar findings of significantly decreased ipsilesional BOLD signal for tbfMRI (p = 0.0005). Ipsilesional abnormalities in ReHo derived from rsfMRI may serve as potential indicators of NVU in patients with brain tumors and other resectable brain lesions; as such, ReHo findings may complement findings on tbfMRI used for presurgical planning.


Development of an In-House TaqMan Real Time RT-PCR Assay to Quantify Hepatitis C Virus RNA in Serum and Peripheral Blood Mononuclear Cells in Patients With Chronic Hepatitis C Virus Infection.
Viral load measurements are commonly used to monitor HCV infection in patients with chronic diseases or determining the number of HCV-genomes in serum samples of patients after sustained virological response. However, in some patients, HCV viral load in serum samples is too low to be detected by PCR, especially after treatment. The aim of this study was to develop a highly specific, sensitive, and reproducible in-house quantitative PCR using specific primers and probe cited in highly conservative region of HCV genome that allows simultaneous detection of HCV genotypes 1 - 4. In this study, three sets of primer pairs and a TaqMan probe for amplification and detection of selected region within 5'-non-coding (5'NCR) of four HCV genotypes were used. Using plasmid containing 5'NCR region of HCV, standard curve, threshold, and threshold cycle (CT) values were determined. Real-time and nested PCR were performed on HCV genotypes 1 - 4 extracted from plasma and peripheral blood mononuclear cells (PBMCs) samples collected from patients with chronic HCV infection. The lower limit detection of this in-house HCV real-time RT-PCR was determined as 100 RNA copies/mL. Inter- and intra-assay coefficient of variation (CV) of this in-house HCV real-time RT-PCR ranged from 0.9% to 1.8% and 1.76% to 3.94%, respectively. The viral load of the genotyped samples ranged from 2.0 × 10(6) ± 0.31 to 2.7 × 10(5) ± 0.46 copies/mL in serum samples and 5 × 10(2) ± 0.36 to 4.0 × 10(3) ± 0.51 copies/10(6) cells/mL of PBMCs. The quite sensitive in-house TaqMan real time RT-PCR assay was able to detect and quantify all four main HCV genotypes prevailing around all geographical regions of Iran.


Sex-driven modifiers of Alzheimer risk: A multimodality brain imaging study.
To investigate sex differences in late-onset Alzheimer disease (AD) risks by means of multimodality brain biomarkers (β-amyloid load via 11C-Pittsburgh compound B [PiB] PET, neurodegeneration via 18F-fluorodeoxyglucose [FDG] PET and structural MRI). We examined 121 cognitively normal participants (85 women and 36 men) 40 to 65 years of age with clinical, laboratory, neuropsychological, lifestyle, MRI, FDG- and PiB-PET examinations. Several clinical (e.g., age, education, APOE status, family history), medical (e.g., depression, diabetes mellitus, hyperlipidemia), hormonal (e.g., thyroid disease, menopause), and lifestyle AD risk factors (e.g., smoking, diet, exercise, intellectual activity) were assessed. Statistical parametric mapping and least absolute shrinkage and selection operator regressions were used to compare AD biomarkers between men and women and to identify the risk factors associated with sex-related differences. Groups were comparable on clinical and cognitive measures. After adjustment for each modality-specific confounders, the female group showed higher PiB β-amyloid deposition, lower FDG glucose metabolism, and lower MRI gray and white matter volumes compared to the male group (p < 0.05, family-wise error corrected for multiple comparisons). The male group did not show biomarker abnormalities compared to the female group. Results were independent of age and remained significant with the use of age-matched groups. Second to female sex, menopausal status was the predictor most consistently and strongly associated with the observed brain biomarker differences, followed by hormone therapy, hysterectomy status, and thyroid disease. Hormonal risk factors, in particular menopause, predict AD endophenotype in middle-aged women. These findings suggest that the window of opportunity for AD preventive interventions in women is early in the endocrine aging process.


Simultaneous depth-profiling of electrical and elemental properties of ion-implanted arsenic in silicon by combining secondary-ion mass spectrometry with resistivity measurements.
A method is proposed to extract the electrical data for surface doping profiles of semiconductors in unison with the chemical profile acquired by secondary-ion mass spectrometry (SIMS)-a method we call SIMSAR (secondary-ion mass spectrometry and resistivity). The SIMSAR approach utilizes the inherent sputtering process of SIMS, combined with sequential four-point van der Pauw resistivity measurements, to surmise the active doping profile as a function of depth. The technique is demonstrated for the case of ion-implanted arsenic doping profiles in silicon. Complications of the method are identified, explained, and corrections for these are given. While several techniques already exist for chemical dopant profiling and numerous for electrical profiling, since there is no technique which can measure both electrical and chemical profiles in parallel, SIMSAR has significant promise as an extension of the conventional dynamic SIMS technique, particularly for applications in the semiconductor industry.


Recovery of a low mutant frequency after ionizing radiation-induced mutagenesis during spermatogenesis.
Humans are exposed to ionizing radiation (IR) under various circumstances, e.g. cosmic radiation, diagnostic X-rays and radiotherapy for cancer. It has been shown that IR can impair spermatogenesis and can cause mutations in germ cells. However, the mutagenic responses of germ cells exposed to IR at different stages of testicular maturation have not been examined by directly assessing the mutant frequency in defined spermatogenic cell types. This study was performed to address whether preadult exposure to IR can increase mutations in adult germ cells that could in turn have a major impact on adult reproductive function and the health of ensuing offspring. Male Lac I transgenic mice were irradiated with a single dose of 2.5 Gy of gamma-ray at different ages before adulthood, reflecting different stages of testicular maturation, and then mutant frequency (MF) was determined directly in spermatogenic cell types emanating from the irradiated precursor cells. The results showed that (1) preadult exposure to IR did not significantly increase MF in adult epididymal spermatozoa; (2) spermatogenic stages immediately following the irradiated stage(s) displayed an elevated mutant frequency; but (3) the mutant frequency was restored to unirradiated levels in later stages of spermatogenesis. These findings provide evidence that there is a mechanism(s) to prevent spermatogenic cells with elevated mutant frequencies from progressing through spermatogenesis.


Impacts of the COVID-19 pandemic on patients with chronic conditions in Vietnam: A cross-sectional study.
We assess the impact of the COVID-19 pandemic on health, treatment adherence and expectations of patients with chronic diseases in Vietnam. We conducted a national cross-sectional study using a questionnaire survey, distributed through social networks and presented on Google Forms. The survey was performed during two months of the most stringent social distancing in Vietnam (between 21 July and 21 September 2021). Most of the participants said that the COVID-19 epidemic had affected their daily activities (91.9%), health (53.6%), sleep behavior (52.3%), and mental health (79.8%). During social distancing in Vietnam, three-quarter could not go to hospitals for periodic health examination; nearly half of respondents did not do daily physical activity; a quarter of respondents did not adhere to recommended diet plan. Factors associated with the effect of the COVID-19 epidemic on patient's health included those living in Ho Chi Minh City (p = 0.015), lived alone (p = 0.027), uncontrolled chronic conditions (p < 0.001), treatment dissatisfaction or experienced anxiety/stress (p < 0.001). Factors associated with medication adherence included the elderly (p = 0.015), having periodic health examination (p = 0.012), direct consultation (p = 0.003), and telemedicine (p = 0.007). This study highlights the urgent need for better chronic management strategies for the new post-COVID era in the future.


Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers.
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway controls several important biological functions, such as cell growth regulation, apoptosis, and migration. However, the way in which PI3K/Akt controls androgen receptor (AR)-mediated prostate cancer cell growth remains unclear and controversial. Here, we demonstrate that the PI3K/Akt pathway regulates AR activity in a cell passage number-dependent manner. Specifically, PI3K/Akt pathway can suppress AR activity in androgen-dependent LNCaP cells with low passage numbers. In contrast, it can also enhance AR activity in LNCaP cells with high passage numbers. Furthermore, we also demonstrate that insulin-like growth factor-1 can activate the PI3K/Akt pathway that results in the phosphorylation of AR at Ser210 and Ser790. The consequence of these events may then change the stability of AR protein. Together, our results demonstrate that the PI3K/Akt pathway may have distinct mechanisms to modulate AR functions in various stages of prostate cancer cells and that a combined therapy of antiandrogens and anti-PI3K/Akt inhibitors may be worth considering as a future therapeutic approach to battle prostate cancer.


The effect of platelet-activating factor on histamine release from rat peritoneal mast cells.
The effect of platelet-activating factor (PAF) on histamine release from peritoneal mast cells of adult and young male rats was investigated. PAF alone tended to release histamine from the mast cells of adult and young rats, although very slightly. On the other hand, PAF significantly inhibited the histamine release induced by the Ca2+ ionophore A23187 in mast cells obtained from rats of either age group, but not that by compound 48/80. Such inhibition was not seen with lyso-PAF. CV-3988, a PAF antagonist, antagonized the inhibitory effect of PAF on the A23187-induced histamine release in mast cells from adult and young rats. These results suggest that PAF does not have a strong histamine-liberating action on mast cells, and that PAF inhibits the calcium influx into mast cells through the activation of PAF receptors.


Aggression in psychiatry: a qualitative study focusing on the characterization and perception of patient aggression by nurses working on psychiatric wards.
The present study focuses on the characterization and perception of patient aggression by nurses working in a psychiatric hospital in The Netherlands. Data have been collected by interviewing nurses working on open and closed wards. The results have been compared and related to the existing literature on aggression. An expert panel has collaborated in the assessment of part of the research findings. Nurses perceive and describe aggression in different ways. Since the descriptions of aggression varied considerably, it was not possible to formulate a general definition of aggression on the basis of the results of the study. Despite the fact that on the whole the general public have a negative view of aggression, the descriptions nurses gave were not always negative. Most of the nurses acknowledged positive as well as negative aspects of aggressive behaviour by patients. Interventions in cases of aggressive behaviour depend on different factors, e.g. the individual nurse's perception of the situation, the (mostly unwritten) rules, and the type of ward (open or closed). The same interventions are often used both to prevent aggression and to stop it. The difference lies in the moment of execution. Most interventions are aimed at stopping aggressive behaviour by acting in a non-restrictive way, e.g. by talking to the patient, touching the patient and giving unexpected responses. Nurses express the belief that aggression is mainly caused by a combination of patient-related, situational and interactional factors. This is not in accordance with the opinion of the North American Nursing Diagnosis Association, who relate aggressive behaviour mainly to patient characteristics.


Making trouble.
The United States is moving to tighten oversight of studies that could make viruses more dangerous. But how far should it go?


Thyroid-Friendly Soft Materials as 3D Cell Culture Tool for Stimulating Thyroid Cell Function.
The disruption of thyroid hormones because of chemical exposure is a significant societal problem. Chemical evaluations of environmental and human health risks are conventionally based on animal experiments. However, owing to recent breakthroughs in biotechnology, the potential toxicity of chemicals can now be evaluated using 3D cell cultures. In this study, the interactive effects of thyroid-friendly soft (TS) microspheres on thyroid cell aggregates are elucidated and their potential as a reliable toxicity assessment tool is evaluated. Using state-of-the-art characterization methods coupled with cell-based analysis and quadrupole time-of-flight mass spectrometry, it is shown that TS-microsphere-integrated thyroid cell aggregates exhibit improved thyroid function. Specifically, the responses of zebrafish embryos, which are used for thyroid toxicity analysis, and the TS-microsphere-integrated cell aggregates to methimazole (MMI), a known thyroid inhibitor, are compared. The results show that the thyroid hormone disruption response of the TS-microsphere-integrated thyroid cell aggregates to MMI is more sensitive compared with those of the zebrafish embryos and conventionally formed cell aggregates. This proof-of-concept approach can be used to control cellular function in the desired direction and hence evaluate thyroid function. Thus, the proposed TS-microsphere-integrated cell aggregates may yield new fundamental insights for advancing in vitro cell-based research.


A case of hut lung: scanning electron microscopy with energy dispersive x-ray spectroscopy analysis of a domestically acquired form of pneumoconiosis.
Hut lung is a pneumoconiosis caused by exposure to smoke derived from biomass fuels used for cooking in poorly ventilated huts. We report, to our knowledge, the first analysis of the dust deposited in the lungs in hut lung by scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM/EDS). A Bhutanese woman presented with shortness of breath and an abnormal chest radiograph. Chest CT scan showed innumerable tiny bilateral upper lobe centrilobular nodules. Transbronchial biopsy revealed mild interstitial fibrosis with heavy interstitial deposition of black dust. SEM/EDS showed that the dust was carbonaceous, with smaller yet substantial numbers of silica and silicate particles. Additional history revealed use of a wood/coal-fueled stove in a small, poorly ventilated hut for 45 years. The possibility of hut lung should be considered in women from countries where use of biomass-fueled stoves for cooking is common. Our findings support the classification of this condition as a mixed-dust pneumoconiosis.


National Estimates of Recovery-Remission From Serious Mental Illness.
A broad range of estimates of recovery among previously institutionalized persons has been reported, but no current, community-based national estimate of recovery from serious mental illness exists. This study reports recovery rate results, based on a remission definition, and explores related demographic factors. A national, geographically stratified, and random cross-sectional survey conducted from September 2014 to December 2015 resulted in responses from more than 41,000 individuals. Lifetime prevalence of serious mental illness was assessed by asking about receipt of a diagnosis (major depression, bipolar disorder, manic depression, and schizophrenia or schizoaffective disorder) and hospitalization and impairment associated with the diagnosis. Recovery was determined by asking about impairments over the past 12 months. Almost 17% reported receiving one of the diagnoses in their lifetime, 6% had a lifetime rate of a serious mental illness, and nearly 4% continued to experience interference associated with serious mental illness. One-third of those with a lifetime serious mental illness reported having been in remission for at least the past 12 months. Recovery rates were low until age 32 and then progressively increased. Lifetime estimates of diagnosed illness and current prevalence of serious mental illness are consistent with previous research. Results indicate that recovery is possible and is associated with age. Further research is needed to understand factors that promote recovery, and sustained evaluation efforts using similar parsimonious approaches may be useful in conducting timely assessments of national and local mental health policies.


Assessment of Risk Factors for Enteric Fistula and Intra-Abdominal Sepsis in Patients with Open Abdomen in Trauma: An Original Research.
In emergency surgeries, open abdomen or laparostomy, especially with perforated viscus, has been used primarily to prevent delayed ventral hernia, burst abdomen, and abdominal compartment syndrome. In the present study, the clinical and resuscitative factors that are linked with open abdomen morbidity are evaluated. A retrospective analysis was done for all the subjects who were admitted at the tertiary care center between May 2020 and May 2022 for the open abdomen surgeries. These patients were examined to see whether they needed more postoperative care than usual, including the need for resuscitative treatments and other critical clinical indicators. Patients were evaluated if they had any complications. The data that were collected were analysed for any variance using analysis of variance considering P <.05 as significant. A total of 100 subjects were analysed in this study. Forty nine patients had intra-abdominal sepsis of the 100 cases examined from historical case records and 1 had entero-cutaneous fistulas. These patients did not necessitate additional actions for intensive care unit care, resuscitation, an chest infection, extended hospital stay, or any disabilities compared to those who did not undergo laparotomy during the same period. In this group of patients with open abdomens, the immediate postoperative period was not linked to an increase in resuscitation efforts or a load on clinical staff. Once patients are stabilized, early definitive abdominal closure is advised to prevent problems associated to laparostomies. The quantity of initial fluid revival and the coagulation factors at the time of admission are not related to intra-abdominal sepsis and enteric fistula following laparostomy after significant abdominal injuries.


Social Media and Oncology: The Past, Present, and Future of Electronic Communication Between Physician and Patient.
The relationship between patient and physician is in flux with the advent of electronic media that are advancing and enhancing communication. We perform a retrospective, current, and forward-looking examination of the technologies by which information is exchanged within the healthcare community. The evolution from e-mail and listservs to blogs and the modern social networks is described, with emphasis on the advantages and pitfalls of each medium, especially in regard to maintaining the standards of privacy and professionalism to which doctors are held accountable. We support the use of contemporary platforms like Twitter and Facebook for physicians to establish themselves as trustworthy online sources of medical knowledge, and anticipate ongoing collaboration between researchers, patients, and their advocates in trial design and accrual.


Kidney cysts in patients with HOGA1 variants.
In an era of increased accessibility to genetic testing, nephrologists may be able to better understand pathophysiologic mechanisms by which their patients develop specific conditions. In this study, we describe clinical and genetic findings of two patients with kidney cysts, who were found to have variants in HOGA1, a mitochondrial 4-hydroxy-2-oxoglutarate aldolase enzyme associated with primary hyperoxaluria type 3 and the development of oxalate-containing kidney stones. We describe possible mechanisms by which mutations in this enzyme could result in the kidney cyst formation seen in our two patients. We propose that patients with mutations in HOGA1 are predisposed to crystal or stone deposition, tubule dilation, and inflammasome activation, which can result in kidney cyst formation.


Isolated Common Femoral Artery Injury Resulting from Blunt Military Trauma.
The incidence of an isolated femoral vessel injury in the absence of fractures or other organ injury is extremely rare. A 20-yr-old male Korean soldier was taken to the hospital with a common femoral artery (CFA) obstruction. Injured CFA segment was resected and replaced by using 7-mm PTFE (polytetrafluoroethylene) graft. Two months after the surgical treatment, the patient discharged from the hospital without any complaints or postoperative complications. We report an unusual case of isolated femoral artery injury due to blunt trauma during military service with following review of literature.


Spontaneous modification of the oxoglutarate translocator in vivo.
In studying the oxoglutarate translocator of rat-heart mitochondria over many years, we have observed an unexpected decrease in its efficiency. It has been divided by 2.48 +/- 0.07, (S.E.M.) for the exchange of external oxoglutarate for internal malate at 2 degrees C when the internal-malate concentration is 4 mM and is accompanied by an increase in its concentration (multiplied by 1.61 +/- 0.02, S.E.M.). The affinity of the external sites of the translocator for the external oxoglutarate is unchanged as well as the binding and kinetic cooperativities of the external oxoglutarate. This shows that the external side of the translocator has not been modified and suggests that its central part has not been modified either. The apparent Michaelis constant of the internal malate is increased (multiplied by 1.74 +/- 0.23, S.E.M.) suggesting that the translocator has been modified on its matricial side. Some control experiments show that a change in the diet of the rats, despite its effect on the fatty-acid content of the mitoplasts, is probably not responsible for the observed modification. As it is nevertheless very likely that changes of the oxoglutarate translocator have occurred in vivo, it is proposed that the observed modification has a genetic origin. The existence of two antagonist changes which are not directly related suggests that one of them is a response of the organism against the other; thus the oxoglutarate translocator may play a regulatory rôle in certain physiological conditions.


Four years later: Clara revisited.
The use of art therapy to treat post-traumatic response. To demonstrate through the use of a case presentation ways in which art therapy can be used to facilitate healing from post-traumatic response. The author's own clinical work. The healing process for individuals experiencing post-traumatic response does not end with the formal termination of therapy. It may need to be supplemented with support and follow-up, short-term therapy episodes. Healing can be facilitated by art therapy, which provides a useful medium for identifying and exploring changes in self-concept, behaviors, and feelings.


Maternal behavior influences development of a reflexive action pattern in the newborn rat.
This study examined the effect of maternal behavior on the expression and postnatal development of a reflexive behavior in rat pups. In neonatal rats, the leg extension response (LER) is a bilateral hyperextension of the hindlimbs in response to maternal anogenital licking (AGL). Past research has found that intranasal application of zinc sulfate (ZnSO4 ) to the dam induces hyponosmia, thereby reducing the incidence of AGL. In this study, pregnant dams received intranasal application of air (control), distilled water (control), or ZnSO4 on the day before birth and every other day thereafter until postnatal day 9 (P9). The LER was experimentally evoked in pups, using a vibrotactile device, at P1, P5, or P10. Pups born to ZnSO4 -treated dams showed significantly shorter bilateral LER durations and significantly smaller ankle angles than pups born to control dams. Reduction of overall maternal AGL approached significance, and afternoon AGL was significantly reduced. These data suggest that maternal behavior influenced development of the LER in rat pups, demonstrating the influence of maternal care on behavioral development during the perinatal period.


The glutamate carboxypeptidase gene II (C>T) polymorphism does not affect folate status in the Framingham Offspring cohort.
Glutamate carboxypeptidase II (GCPII) hydrolyzes polyglutamyl folates before their absorption. Recently, a 1561 C>T polymorphism in the GCPII gene was reported to be associated with lower folate and higher homocysteine plasma concentrations in a small (n = 75) selected elderly population. In this study, we examined the effect of this polymorphism in 680 men and 644 women attending the fifth examination of the Framingham Offspring Study. At the time of sample collection, subjects were not taking any supplements and were not exposed to food folate fortification. GCPII genotypes were determined by allelic discrimination using Taqman probes. In the population as a whole, this mutation was not associated with lower plasma folate level or with elevated plasma homocysteine. In men, plasma folate concentrations were higher in carriers of the T allele compared with those homozygotes of the wild-type allele (P < 0.05), whereas in women folate concentrations did not differ between genotypes (P = 0.8). In its relationship to plasma folate, this mutation exhibited a weak interaction with age and gender only in older women (P = 0.05). Overall, our data show that the GCPII C1561T polymorphism is not a determinant of plasma folate or total homocysteine concentrations in this large cohort of participants from the Framingham Offspring Study.


Mechanochemical synthesis of an organometallic compound: a high volume manufacturing method.
Chemical vapor deposition (CVD) precursor chemicals are held to some of the highest purity levels in industry. Many metal reagents form stable, unbreakable adducts with the coordinating solvents that are necessary for solvating highly polar reagents. These adducts are undesirable and must be removed prior to usage. Herein we describe a mechanochemical approach to the synthesis of bis(n-propyltetramethylcyclopentadienyl)strontium that eliminates the use of strongly coordinating solvents. This method overcomes the solubility problems of the two reagents without the formation of stable, unbreakable adducts. We utilize a unique reactor geometry that facilitates mechanochemical syntheses while simplifying handling and allowing for "one pot" production. The synthesis was scaled to five hundred gram lot sizes in a six liter reactor. This technique is applicable to many syntheses and is linearly scalable - limited only by reactor size.


Antimicrobial Use in Patients with Dementia: Current Concerns and Future Recommendations.
Infections are common in people with dementia, and antibiotic use is widespread, albeit highly variable, across healthcare settings and countries. The few studies conducted to date that consider the appropriateness of antibiotic prescribing specifically for people with dementia focus on people with advanced dementia and suggest that much of the prescribing of antibiotics for these patients may be potentially inappropriate. We suggest that clinicians must consider a number of factors to determine appropriateness of antimicrobial prescribing for people with dementia, including the risks and benefits of assessing and treating infections, the uncertainty regarding the effects of antibiotics on patient comfort, goals of care and treatment preferences, hydration status, dementia severity and patient prognosis. Future research should examine antibiotic prescribing and its appropriateness across the spectrum of common infections, dementia severities, care settings and countries, and should consider how antibiotic therapy should be considered in discussions regarding treatment preferences, goals of care and/or advance care planning between clinicians, patients and families.


Effect of Polymer Blends on the Properties of Foamed Wood-Polymer Composites.
The polypropylene (PP)/wood flour (WF) composites were prepared using a co-rotating twin-screw extruder followed by a single-screw extruder foaming system in this paper. Polymers, such as polyolefin elastomer (POE), high-density polyethylene (HDPE) or microcrystalline wax, were blended with PP in the preparation of composites to improve the melt strength. And a cavity transfer mixer was introduced to increase the distribution uniformity of components in composites. Meanwhile, the effect of the polymer blends on the microstructure and mechanical properties of samples was investigated. The experimental results show that the addition of POE and HDPE resulted in the second melting peak in the differential scanning calorimeter (DSC) curves and a great decrease in the cell size was caused by the added POE. However, due to the velocity difference of composites in the die, the shape of bubbles gradually became irregular. Moreover, the impact strength of samples significantly increased by 85% for the added POE and the apparent density decreased by 6.7%. And the minimum Vicat softening temperature of 133.7 °C was obtained when the mass ratio of HDPE to PP was 4/6.


Directed forgetting and aging: the role of retrieval processes, processing speed, and proactive interference.
The directed forgetting effect obtained with the item method is supposed to depend on both selective rehearsal of to-be-remembered (TBR) items and attentional inhibition of to-be-forgotten (TBF) items. In this study, we investigated the locus of the directed forgetting deficit in older adults by exploring the influence of recollection and familiarity-based retrieval processes on age-related differences in directed forgetting. Moreover, we explored the influence of processing speed, short-term memory capacity, thought suppression tendencies, and sensitivity to proactive interference on performance. The results indicated that older adults' directed forgetting difficulties are due to decreased recollection of TBR items, associated with increased automatic retrieval of TBF items. Moreover, processing speed and proactive interference appeared to be responsible for the decreased recall of TBR items.


Exploring the Alternative Model for Personality Disorders Using SCORS-G Ratings on Thematic Apperception Test Narratives.
The Alternative Model for Personality Disorders (AMPD) in Section III of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013) conceptualizes personality pathology as a combination of impairment (Criterion A) and traits (Criterion B). One measure used to develop Criterion A was the Social Cognition and Object Relations Scale - Global Rating Method (SCORS-G), which is a multidimensional, object-relational clinician-rated measure of personality functioning. Although there are conceptual links between the AMPD and SCORS-G dimensions, there exists no research examining the relationship. To address this, we examined associations between the SCORS-G dimensions and measures of the AMPD constructs in a large, archival dataset of outpatients and inpatients. More pathological scores on SCORS-G dimensions reflecting self- and interpersonal functioning were associated with greater pathological traits and impairment. Overall, results support further investigation into SCORS-G as a useful measure in AMPD research and assessment.


Observation of CH⋅⋅⋅π Interactions between Methyl and Carbonyl Groups in Proteins.
Protein structure and function is dependent on myriad noncovalent interactions. Direct detection and characterization of these weak interactions in large biomolecules, such as proteins, is experimentally challenging. Herein, we report the first observation and measurement of long-range "through-space" scalar couplings between methyl and backbone carbonyl groups in proteins. These J couplings are indicative of the presence of noncovalent C-H⋅⋅⋅π hydrogen-bond-like interactions involving the amide π network. Experimentally detected scalar couplings were corroborated by a natural bond orbital analysis, which revealed the orbital nature of the interaction and the origins of the through-space J couplings. The experimental observation of this type of CH⋅⋅⋅π interaction adds a new dimension to the study of protein structure, function, and dynamics by NMR spectroscopy.


Structural characterization of lignin during Pinus taeda wood treatment with Ceriporiopsis subvermispora.
Pinus taeda wood chips were biotreated with Ceriporiopsis subvermispora under solid-state fermentation for periods varying from 15 to 90 days. Milled wood lignins extracted from sound and biotreated wood samples were characterized by wet-chemical and spectroscopic techniques. Treatment of the lignins by derivatization followed by reductive cleavage (DFRC) made it possible to detect DFRC monomers and dimers that are diagnostic of the occurrence of arylglycerol-beta-O-aryl and beta-beta, beta-5, beta-1, and 4-O-5 units in the lignin structure. Quantification of these DFRC products indicated that beta-O-aryl cleavage was a significant route for lignin biodegradation but that beta-beta, beta-5, beta-1, and 4-O-5 linkages were more resistant to the biological attack. The amount of aromatic hydroxyls did not increase with the split of beta-O-4 linkages, suggesting that the beta-O-4 cleavage products remain as quinone-type structures as detected by UV and visible spectroscopy. Nuclear magnetic resonance techniques also indicated the formation of new substructures containing nonoxygenated, saturated aliphatic carbons (CH(2) and CH(3)) in the side chains of lignins extracted from biotreated wood samples.


Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules.
Skin biopsies and scale samples from nine infants and one fetus affected with harlequin ichthyosis (HI) were obtained from eight families. Epidermal differentiation was examined by morphologic and biochemical criteria and cell culture studies. Two striking abnormalities were identified; first, keratin and filaggrin expression were abnormal and varied between cases, and, second, in all cases lamellar granules were absent or abnormal, and intercellular lamellae within the stratum corneum were absent. Three HI phenotypes were distinguished by variable expression of epidermal structural proteins. Cases were classified by the absence (type 1) or presence (types 2 and 3) of keratins K6 and K16 ("hyperproliferative" keratins) and by the presence of profilaggrin in the interfollicular epidermis (types 1 and 2 only). Profilaggrin is apparently not converted to filaggrin, but it is retained in the scale. The block in profilaggrin processing may be due to an inactive phosphatase. Siblings in two families (presenting with types 1 and 2) showed the same type classification suggesting that expression of the phenotype is consistent within families but differs between families. Cultured HI keratinocytes were normal by phase microscopy, but abnormal by electron microscopy with no lamellar granules and extensive stacking of the upper layers. We conclude that harlequin ichthyosis is a genetically heterogeneous group of disorders with altered lamellar granules, intercellular lipids, and variation in expression and/or processing of structural protein markers of normal epidermal keratinization. Furthermore, the lamellar granule and structural protein defects may be indirectly related via a mechanism involving phosphorylation/dephosphorylation.


Spectrophotometric and computerized evaluation of tooth bleaching employing 10 different home-bleaching procedures: In-vitro study.
The aim of this in-vitro study was to evaluate the efficacy of bleaching products, determine the applicability and validation of the measurement methods. Freshly extracted 110 human incisor teeth were stained with whole blood and hemolysate solution prior to the application of 10 different home-bleaching products. Spectrophotometric measurements of the tooth shades were performed for each specimen before and after bleaching at the 1(st), 3(rd), 7(th), and 14 days. Differences in lightness (Δl), chroma (Δc), hue (Δh) values and shade changes were measured to evaluate process. Computerized digital imaging analyses to determine the color changes were performed with Photoshop CS4 software (Adobe, San Jose, CA, USA). Statistical analyses were performed with analysis of variance, Scheffe and Tukey tests. In all of the test groups regardless of the material used, a significant increase in lightness and hue, and decrease of chroma were observed, as compared to the control group. After recommended bleaching applications, Δl and Δh values respectively increased in group Zaris White and Brite (ZWB) and group Pola Night and Δc values showed significant decrease in groups ZWB and Rembrandt REM3 (P < 0.05). At the end of the procedure both spectrophotometric and digital imaging analysis showed ZWB was the most effective product among the others while Yotuel and Happy Smile were the least (P < 0.05). Home-bleaching systems showed slower but almost permanent bleaching effect likewise office-based methods. Both software and spectrophotometric analyses have advantages such as evaluating the results objectively and numerically, also treatment outcomes could be preserved.


Association of Sleep Duration, Midday Napping with Atrial Fibrillation in Patients with Hypertension.
This study aimed to assess the associations of sleep duration, midday napping and the risk of atrial fibrillation (AF) in patients with hypertension. We conducted a cross-sectional study enrolling 11,524 hypertensive participates from the Chinese Hypertension Registry Study. Information on sleep duration and midday napping were obtained by a self-administered questionnaire. Multivariate logistic regression analyses were performed to estimate odds ratio (OR) and 95% confidence intervals (CIs) for the risk of AF. Compared with sleeping 6 to ≤8 hours/night, those reporting shorter sleep duration (≤5 hours/night) had a greater risk of AF (OR 1.95; 95% CI 1.28-2.95) in the fully adjusted model, while longer sleep (≥9 hours/night) was not significantly associated with the risk of AF. Compared with nonhabitual nappers, nappers had a higher risk of AF (OR 1.28; 95% CI 1.03-1.60) in the fully adjusted model. Moreover, we observed significant joint effects of sleeping ≤5 hours/night and nap (OR 2.13; 95% CI 1.09-4.14) on the risk of AF after adjusting for confounding factors. Short sleep duration and midday napping were independently and jointly associated with higher risks of AF in patients with hypertension.


Higher-order electric multipole contributions to retarded non-additive three-body dispersion interaction energies between atoms: equilateral triangle and collinear configurations.
The theory of molecular quantum electrodynamics (QED) is used to calculate higher electric multipole contributions to the dispersion energy shift between three atoms or molecules arranged in a straight line or in an equilateral triangle configuration. As in two-body potentials, three-body dispersion interactions are viewed in the QED formalism to arise from exchange of virtual photons between coupled pairs of particles. By employing an interaction Hamiltonian that is quadratic in the electric displacement field means that third-order perturbation theory can be used to yield the energy shift for a particular combination of electric multipole polarizable species, with only six time-ordered diagrams needing to be summed over. Specific potentials evaluated include dipole-dipole-quadrupole (DDQ), dipole-quadrupole-quadrupole (DQQ), and dipole-dipole-octupole (DDO) terms. For the geometries of interest, near-zone limiting forms are found to exhibit an R(-11) dependence on separation distance for the DDQ interaction, and an R(-13) behaviour for DQQ and DDO shifts, agreeing with an earlier semi-classical computation. Retardation weakens the potential in each case by R(-1) in the far-zone. It is found that by decomposing the octupole moment into its irreducible components of weights-1 and -3 that the former contribution to the DDO potential may be taken to be a higher-order correction to the leading triple dipole energy shift.


Buscando la Calma Dentro de la Tormenta: A Brief Review of the Recent Literature on the Impact of Anti-Immigrant Rhetoric and Policies on Stress Among Latinx Immigrants.
The mental health burden associated with anti-immigrant rhetoric and ever-changing immigration policies is undeniable, though the psychological and emotional sequalae may remain invisible for years to come. Exclusionary immigration policies, as a form of structural racism, have also led to an epidemic of stress-related health within the Latinx community, particularly the Latinx immigrant community, across the United States. Recent examples of anti-Latinx and anti-immigrant rhetoric and policies include the 45th President's implementation of the Zero Tolerance policy, Migrant Protection Protocols, and Title 42. The recognition of previous and existing anti-immigrant policies, and the impact on Latinx immigrants, is critical in understanding the manifestation of psychological stress to prevent it from becoming chronic. For mental health providers, attention to existing policies that can be detrimental to the Latinx immigrant community is essential to understanding their mental health trajectory and applying frameworks that honor an individual's psychological stress to prevent pathologizing the immigrant experience and negative health outcomes. The objective of the present brief review is to shed light on recent research and offer recommendations for practice (eg, educating the Latinx community about the link between the immigrant experience and psychological stress) and policy (eg, drafting of legislation aimed at rescinding harmful immigration policies) regarding the relation between aggressive anti-immigration rhetoric and psychological stress among Latinx immigrants in the United States.


Fatigue and workload in short and long-haul train driving.
Little has been investigated regarding the role of shift schedule on fatigue and workload among Iranian train drivers. This study sought to compare train drivers' fatigue and workload between a long-haul and a short-haul train trips. One-hundred train drivers, in two routes of Tehran-Mashhad (long-haul) and Tehran-Semnan (short-haul), were asked to complete the Samn-Perelli Fatigue Scale prior to departure, immediately after ending driving duty on the way going, and immediately after ending driving on the way back. Moreover, they were asked to complete NASA-TLX at the end of their shift. Accordingly, understudy train drivers stated relatively similar levels of fatigue and workload for the two trips. Furthermore, fatigue scores were significantly higher at the end of shifts in both routes. Overall, train drivers in long-haul trips had longer rest hours between the ways going and coming back, which seems to compensate for the side effects of longer driving durations.


[Prevention of inter-human rabies transmission after corneal graft].
Transplantation, to a normal recipient, of a cornea taken from a donor who died of rabies encephalitis constitutes an extremely serious exposure. Four cases, up to now are known of human to human transmission of rabies virus. In these four cases, the diagnosis of rabies in the donor has been made afterwards when to the recipient developed fatal rabies. We report here the first case of this type of exposure where the diagnosis of rabies in the donor could be made on the day following the transplantation thus allowing application, without delay, the recipient of a prophylactic therapy for inactivated rabies vaccine administered. No signs or symptoms of rabies appeared and, more than three months after the transplantation, the recipient is well and alive.


The relationship between flowering time and growth responses to drought in the Arabidopsis Landsberg erecta x Antwerp-1 population.
Limited water availability is one of the most prominent abiotic constraints to plant survival and reproduction. Thus, plants have evolved different strategies to cope with water deficit, including modification of their growth and timing of developmental events such as flowering. In this work, we explore the link between flowering time and growth responses to moderate drought stress in Arabidopsis thaliana using natural variation for these traits found in the Landsberg erecta x Antwerp-1 recombinant inbred line population. We developed and phenotyped near isogenic lines containing different allelic combinations at three interacting quantitative trait loci (QTL) affecting both flowering time and growth in response to water deficit. We used these lines to confirm additive and epistatic effects of the three QTL and observed a strong association between late flowering and reduced sensitivity to drought. Analyses of growth responses to drought over time revealed that late flowering plants were able to recover their growth in the second half of their vegetative development. In contrast, early flowering, a common drought escape strategy that ensures plant survival under severe water deficit, was associated with strongly impaired plant fitness. The results presented here indicate that late flowering may be advantageous under continuous mild water deficit as it allows stress acclimatization over time.


Computerization of three-channel thrombelastograph.
A small-size and low-cost microcomputer using an Intel 8080 micro-processer is employed to provide real-time data collection and reduction of a three-channel electronic-readout thrombelastograph (TEG). Computed values of significant clotting parameters are obtained instantly allowing for rapid analysis and monitoring of many patients. Computer hardware was designed to optimize signal sampling rates, processing time and storage.


Genomic copy-number aberrations related to lymph-node metastasis of colon cancer.
Lymph-node metastasis is an important indicator in the diagnosis of colon cancer. In order to determine the genes involved in metastasis, genomic copy-number aberrations in the primary tumours and lymph-node metastases were analysed in 12 patients using comparative genomic hybridization. This method detects genomic copy-number changes at the chromosomal level and the identification of the regions of aberration on any chromosome. Copy-number gains at 6p12 and losses at 8p12 were observed in a greater number of the primary tumours than in the metastases. These aberrations appear to be involved in lymph-node metastasis of colon cancer, and may allow measurement of the risk of lymph-node metastasis from a given colon cancer.


Differential changes in dietary habits after gastric bypass versus gastric banding operations.
Reduction of food intake is an important mechanism by which bariatric procedures reduce body weight. However, only few studies have systematically assessed what patients actually eat after different types of bariatric operations. Dietary habits were assessed by a food frequency questionnaire in 121 bariatric patients (48 gastric bypass patients, 73 gastric banding patients) during follow-up visits in our interdisciplinary obesity center as well as in 45 severely obese (body mass index (BMI)>35 kg/m2) and 45 nonobese (BMI<27 kg/m2) control subjects. As compared with nonobese control subjects, obese control subjects consumed more meat, white bread, and diet soft drinks. Gastric bypass patients showed an enhanced consumption of foods rich in protein such as poultry, fish, and eggs as well as of cooked vegetables, while the consumption of fatty sweets like chocolate, cake, biscuits, and cookies was found to be distinctly reduced in this patient group. In contrast, gastric banding patients reported on a reduced intake of pasta, white bread, and fresh fruits and, just like gastric bypass patients, also on an enhanced intake of poultry and fish. Direct comparison of dietary habits between the two bariatric patient groups revealed that gastric bypass patients consumed more frequently fresh fruits, eggs, and diet soft drinks but strikingly less chocolate than gastric banding patients. Collectively, data clearly point to distinct changes in dietary habits after bariatric operations which markedly differ between gastric bypass and gastric banding patients. Overall, it is tempting to conclude that gastric bypass operations lead to a healthier and a more balanced diet than gastric band implantations.


Prevalence, Pattern and Functional Outcome of Post COVID-19 Syndrome in Older Adults.
Introduction COVID-19 pandemic has been shown to produce high infection rates, significant morbidity and mortality among older adults. A significant proportion of people who have recovered from acute COVID-19 illness seem to suffer from post COVID-19 syndrome. Post COVID-19 syndrome is thought to be a multisystem disease involving physical, functional, mental and psychological domains. This analysis tries to estimate the prevalence, pattern and functional outcomes of post COVID-19 syndrome in hospitalized older adults. Methods A prospective cohort study was done on 279 older adults who were discharged from our centre between August 1st, 2020 and November 30th 2020. Information was collected through a telephonic interview after 90 days of discharge from the hospital using a standard questionnaire by a trained physician. Collected data were analyzed with IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY). Results After 90 days of recovery, the most common symptoms prevalent in the study population were fatigue (8.9%) followed by cough (4.3%), breathlessness (1.8%), dizziness (1.4%), myalgia (1.1%), loss of smell and taste (0.8%) and chest discomfort (0.7%). The prevalence of risk of anxiety in the study population after 90 days of recovery was 7.5% while that of risk of depression was 12.2%. After 90 days of recovery, 66 (23.6%) patients reported the presence of at least one clinical feature while 9.3% had two or more clinical features. On comparing the mean activities of daily living (ADL) 5.58 (.795) and mean instrumental activities of daily living (IADL) 5.84 (1.49) before the illness and 90 days following recovery there was no statistical difference for the study population. Conclusion The prevalence of post COVID-19 syndrome in older adults is about 9.3%. The most common symptoms reported by older adults after 90 days following recovery were fatigue followed by cough and breathlessness. Most older adults retained their baseline functional status after 90 days of recovery from acute COVID-19.


Factors associated with work accidents in a rural area in Minas Gerais, Brazil.
Noise and pesticide exposure is frequent among Brazilian agricultural workers, however, few studies analyzed its association with work accidents. To investigate the association between self-reported noise and pesticide exposure and self-reported work accidents among rural workers. Cross-sectional study performed in Conceição das Pedras, southern Minas Gerais, Brazil. We administered a questionnaire to 170 rural workers from April through October 2014. We subjected the data to unconditional multiple logistic regression analysis by means of the stepwise method. The prevalence of work accidents was 11.8% (95%CI 7.3-17.6). Independent variables associated with occurrence of work accidents were: use of the fungicide Priori® (OR 11.8; p=0.007), use of hand-held power tools (OR 8.28; p=0.010), noise-induced hearing loss (OR 38.60; p=0.022) and length in the job (OR 1.04; p=0.034). We did not find association between work accidents and self-reported combined noise and pesticide exposure. The results, however, evidenced factors significantly related to the occurrence of work accidents, which identification might serve to ground preventive actions. We recommend performing additional studies likely to overcome detected limitations to establish the role of combined exposures in work accidents.


Identification of a six-gene prognostic signature for bladder cancer associated macrophage.
As major components of the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play an exceedingly complicated role in tumor progression and tumorigenesis. However, few studies have reported the specific TAM gene signature in bladder cancer. Herein, this study focused on developing a TAM-related prognostic model in bladder cancer patients based on The Cancer Genome Atlas (TCGA) data. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key genes related to TAM (M2 macrophage). Gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed the functional categories of the key genes. Simultaneously, we used the Least Absolute Shrinkage and Selection Operator (LASSO) and univariate and multivariate Cox regressions to establish a TMA-related prognostic model containing six key genes: TBXAS1, GYPC, HPGDS, GAB3, ADORA3, and FOLR2. Subsequently, single-cell sequencing data downloaded from Gene Expression Omnibus (GEO) suggested that the six genes in the prognostic model were expressed in TAM specifically and may be involved in TAM polarization. In summary, our research uncovered six-TAM related genes that may have an effect on risk stratification in bladder cancer patients and could be regarded as potential TAM-related biomarkers.


Directional Bloch surface wave coupling enabled by magnetic spin-momentum locking of light.
We study the magnetic spin-locking of optical surface waves. Through an angular spectrum approach and numerical simulations, we predict that a spinning magnetic dipole develops a directional coupling of light to transverse electric (TE) polarized Bloch surface waves (BSWs). A high-index nanoparticle as a magnetic dipole and nano-coupler is placed on top of a one-dimensional photonic crystal to couple light into BSWs. Upon circularly polarized illumination, it mimics the spinning magnetic dipole. We find that the helicity of the light impinging on the nano-coupler controls the directionality of emerging BSWs. Furthermore, identical silicon strip waveguides are configured on the two sides of the nano-coupler to confine and guide the BSWs. We achieve a directional nano-routing of BSWs with circularly polarized illumination. Such a directional coupling phenomenon is proved to be solely mediated by the optical magnetic field. This offers opportunities for directional switching and polarization sorting by controlling optical flows in ultra-compact architectures and enables the investigation of the magnetic polarization properties of light.


A continuum of hypnotherapeutic interactions: from formal hypnosis to hypnotic conversation.
Hypnotherapeutic interactions can be mapped on a continuum from formal hypnosis to hypnotic conversation. Unlike the structured forms of formal hypnosis, hypnotic conversation relies upon utilizing the client's responses, both verbal and non-verbal, to facilitate therapeutic process. In this paper, we illustrate this continuum with a series of anecdotal clinical examples starting with formal hypnosis and moving incrementally towards hypnotic conversation. Finally, we offer an example similar in appearance to formal hypnosis, but now described in the context of hypnotic conversation. We are neither putting forth a theory nor offering a new perspective for those who research hypnosis as a phenomenon. Rather, these ideas and metaphors serve to broaden the framework of what constitutes hypnotic interaction so as to evoke new opportunities for increasing therapeutic efficiency and efficacy.


Development of an UPLC-MS/MS method for quantification of Avitinib (AC0010) and its five metabolites in human cerebrospinal fluid: Application to a study of the blood-brain barrier penetration rate of non-small cell lung cancer patients.
Avitinib (AC0010) is a mutant-selective epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), designed to be a targeted therapeutic agent for non-small cell lung cancer (NSCLC) patients harboring EGFR active and T790M resistant mutations. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of Avitinib and its five metabolites (M1, M2, M4, M7, MII-6) in human cerebrospinal fluid (CSF). The samples were purified by protein precipitation and separated on a BEH C18 column (2.1×50mm, 1.7μm). Electrospray ionization (ESI) in positive ion mode and multiple reaction monitoring (MRM) were used to monitor the ion transitions at m/z 488/257, 474/403, 504/487, 434/377, 490/405, 476/391. The results indicated that the method had excellent sensitivity and specificity. The linear range covered from 0.05 to 50ng/mL for Avitinib, M1, M4, M7, and MII-6, and from 0.01 to 10ng/mL for M2. Intra-day and inter-day precisions (in terms of% RSD) were all <15% and the accuracies (in terms of% RE) were within the range of ±15%. The lower limit of quantification (LLOQ), matrix effect, extraction recovery, stability and dilution integrity were also validated and satisfied with the criteria of validation. Finally, the method was successfully applied to a blood-brain barrier (BBB) penetration rate research of NSCLC patients after an oral administration of Avitinib.


A family-based approach to preventing excessive weight gain.
Preventing weight gain in adults and excessive weight gain in children is a high priority. We evaluated the ability of a family-based program aimed at increasing steps and cereal consumption (for breakfast and snacks) to reduce weight gain in children and adults. Families (n = 105) with at least one 8- to 12-year-old child who was at-risk-for-overweight or overweight (designated as the target child) were recruited for the study. Eighty-two families were randomly assigned to receive the family-based intervention and 23 families to the control condition. The 13-week intervention consisted of specific increases in daily steps (an additional 2000 steps/d) and consumption of 2 servings/d of ready-to-eat cereal. The intervention was successful in increasing walking (steps) and cereal consumption. The intervention had positive, significant effects on percentage BMI-for-age and percentage body fat for target children and weight, BMI, and percentage body fat for parents. On further analysis, the positive effects of the intervention were seen largely in target girls and moms, rather than in target boys and dads. This family-based weight gain prevention program based on small changes holds promise for reducing excessive weight gain in families and especially in growing overweight children.


Toxicity, repellency and flushing out in Triatoma infestans (Hemiptera: Reduviidae) exposed to the repellents DEET and IR3535.
DEET and IR3535 are insect repellents present worldwide in commercial products; their efficacy has been mainly evaluated in mosquitoes. This study compares the toxicological effects and the behavioral responses induced by both repellents on the blood-sucking bug Triatoma infestans Klug (Hemiptera: Reduviidae), one of the main vectors of Chagas disease. When applied topically, the Median Lethal Dose (72 h) for DEET was 220.8 µg/insect. Using IR3535, topical application of 500 µg/insect killed no nymphs. The minimum concentration that produced repellency was the same for both compounds: 1,15 µg/cm2. The effect of a mixture DEET:IR3535 1:1 was similar to that of their pure components. Flushing out was assessed in a chamber with a shelter containing groups of ten nymphs. The repellents were aerosolized on the shelter and the number of insects leaving it was recorded for 60 min. During that time, 0.006 g/m3 of the positive control tetramethrin flushed out 76.7% of the nymphs, while 1.76 g/m3 of DEET or IR3535 flushed out 30 and 0%, respectively. The concentrations required for both compounds to produce toxicity or flushing out are too high to have any practical applications. However, they showed a promising repellency. Additional research should be done to evaluate their possible use for personal protection against T. infestans bites.


Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia.
Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. Autophagy plays an important role in neuronal apoptosis induced by ischemia. However, whether autophagy is involved in neuron apoptosis induced by cardiac arrest has been less studied. This study found that TRPML1 participates in cerebral ischemic reperfusion injury. Primary neurons were isolated and treated with mucolipin synthetic agonist 1 (ML-SA1), as well as infected with the recombinant lentivirus TRPML1 overexpression vector in vitro. ML-SA1 was delivered intracerebroventricularly in transient global ischemia model. Protein expression levels were determined by western blot. Neurological deficit score and the infarct volume were analyzed for the detection of neuronal damage. We found that TRPML1 was significantly downregulated in vivo and in vitro ischemic reperfusion model. We also observed that TRPML1 overexpression or treatment with the ML-SA1 attenuated neuronal death in primary neurons and ameliorated neurological dysfunction in vivo. Our findings suggested that autophagy and apoptosis were activated after transient global ischemia. Administration of ML-SA1 before transient global ischemia ameliorated neurological dysfunction possibly through the promotion of autophagy and the inhibition of apoptosis.


Switching Reaction Pathway of Medium-Concentration Ether Electrolytes to Achieve 4.5 V Lithium Metal Batteries.
Pursuing high-energy-density lithium metal batteries (LMBs) necessitates the advancement of electrolytes. Despite demonstrating high compatibility with lithium metal anodes (LMAs), ether-based electrolytes face challenges in achieving stable cycling at high voltages. Herein, we propose a strategy to enhance the high-voltage stability of medium-concentration (∼1 M) ether electrolytes by altering the reaction pathway of ether solvents. By employing a 1 M lithium difluoro(oxalato)borate in dimethoxyethane (LiDFOB/DME) electrolyte, we observed that LiDFOB displays a pronounced tendency for decomposition over DME, leading to a modification in the decomposition pathway of DME. This modification facilitates the formation of a stable organic-inorganic hybrid interface. Utilizing such an electrolyte, the Li-LCO cell demonstrates a discharge specific capacity of 146 mAh g-1 (5 C) and maintains retention of 86% over 1000 cycles at 2 C under a 4.5 V cutoff voltage. Additionally, the optimized ether electrolyte demonstrated outstanding cycling performance in Li-LCO full cells under practical conditions.


Identification of Potent DNA Gyrase Inhibitors Active against Mycobacterium tuberculosis.
Mycobacterium tuberculosis DNA gyrase manipulates the DNA topology using controlled breakage and religation of DNA driven by ATP hydrolysis. DNA gyrase has been validated as the enzyme target of fluoroquinolones (FQs), second-line antibiotics used for the treatment of multidrug-resistant tuberculosis. Mutations around the DNA gyrase DNA-binding site result in the emergence of FQ resistance in M. tuberculosis; inhibition of DNA gyrase ATPase activity is one strategy to overcome this. Here, virtual screening, subsequently validated by biological assays, was applied to select candidate inhibitors of the M. tuberculosis DNA gyrase ATPase activity from the Specs compound library (www.specs.net). Thirty compounds were identified and selected as hits for in vitro biological assays, of which two compounds, G24 and G26, inhibited the growth of M. tuberculosis H37Rv with a minimal inhibitory concentration of 12.5 μg/mL. The two compounds inhibited DNA gyrase ATPase activity with IC50 values of 2.69 and 2.46 μM, respectively, suggesting this to be the likely basis of their antitubercular activity. Models of complexes of compounds G24 and G26 bound to the M. tuberculosis DNA gyrase ATP-binding site, generated by molecular dynamics simulations followed by pharmacophore mapping analysis, showed hydrophobic interactions of inhibitor hydrophobic headgroups and electrostatic and hydrogen bond interactions of the polar tails, which are likely to be important for their inhibition. Decreasing compound lipophilicity by increasing the polarity of these tails then presents a likely route to improving the solubility and activity. Thus, compounds G24 and G26 provide attractive starting templates for the optimization of antitubercular agents that act by targeting DNA gyrase.


Survival after haemorrhage from the brachiocephalic truncus following tracheostomy.
A patient with two massive haemorrhages from the brachiocephalic truncus after tracheostomy is reported. An analysis of 6 previously reported long-term survivors following this complication shows that the initial care in controlling the haemorrhage is of major importance. The operation method of choice is permanent division of the brachiocephalic truncus. Transitory or no neurological postoperative complications were found.


Epidemiology of hypertension in a north Indian population. Based on rural-urban community surveys.
The epidemiology of hypertension was studied on the basis of total community surveys in defined urban (mostly non-agricultural) and rural (agricultural) populations of Haryana, using WHO criteria. A total of 4,068 subjects, comprising 95% of the eligible populations, were examined. Hypertension was found to be almost twice as common in the urban (64.3/1,000) as in the rural group (35.7/1,000). The prevalence of hypertension as well as the mean pressures were greater in men than in women in the 3rd and 4th decades, after which the pattern was reversed in all the subsequent age groups. The regression lines intersected at approximately 45 years of age. However, there was no appreciable sex difference in either group in the overall prevalence of hypertension. The mean systolic and diastolic pressures rose significantly with increasing age. These were generally lower in rural than in urban subjects and there was a difference of almost one decade group. Only one out of every four hypertensives detected during the survey was aware of his disease, and even among these three-fourths were either untreated or inadequately controlled. The lower prevalence of hypertension was associated with lesser mean pressures in the rural community, and both these observations are ascribed to a much larger proportion of rural people (compared to city dwellers) being thinner in size, engaging in hard physical activity, and belonging to a lower socio-economic group. The data have also been compared with other studies from India and abroad and the possible reasons for the observed differences discussed.


The increasing importance of percutaneous mechanical circulatory assist device therapy in heart failure management.
Advances in medical and surgical care have made it possible for an increasing number of patients with Congenital Heart disease (CHD) to live into adulthood. Transposition of the great vessels (TGV) is the most common cyanotic congenital cardiac disease where the right ventricle serves as systemic ventricle. It is not uncommon for these patients to have systemic ventricular failure requiring transplantation. Hemodynamic decompensation in these patients can be swift and difficult to manage. Increasingly percutaneous LVAD's such as the Impella (Abiomed, Mass, USA) are gaining popularity in these situations owing to their relative ease of placement, both in and outside of the operating room. In this paper we demonstrate that Impella (IMP) CP placement through the axillary artery approach shows to be suitable option for short term cardiac support and improvement of end organ perfusion in anticipation of cardiac transplantation.


Methylammonium-free co-evaporated perovskite absorbers with high radiation and UV tolerance: an option for in-space manufacturing of space-PV?
With a remarkable tolerance to high-energetic radiation and potential high power-to-weight ratios, halide perovskite-based solar cells are interesting for future space PV applications. In this work, we fabricate and test methylammonium-free, co-evaporated FA0.7Cs0.3Pb(I0.9Br0.1)3 perovskite solar cells that could potentially be fabricated in space or on the Moon by physical vapor deposition, making use of the available vacuum present. The absence of methylammonium hereby increased the UV-light stability significantly, an important factor considering the increased UV proportion in the extra-terrestrial solar spectrum. We then tested their radiation tolerance under high energetic proton irradiation and found that the PCE degraded to 0.79 of its initial value due to coloring of the glass substrate, a typical problem that often complicates analysis. To disentangle damage mechanisms and to assess whether the perovskite degraded, we employ injection-current-dependent electroluminescence (EL) and intensity-dependent VOC measurements to derive pseudo-JV curves that are independent of parasitic effects. This way we identify a high radiation tolerance with 0.96 of the initial PCE remaining after 1 × 1013 p+ cm-2 which is beyond today's space material systems (<0.8) and on par with those of previously tested solution-processed perovskite solar cells. Together our results render co-evaporated perovskites as highly interesting candidates for future space manufacturing, while the pseudo-JV methodology presents an important tool to disentangle parasitic effects.


Epidemiological study of antifungal-resistant dermatophytes isolated from Japanese patients.
An epidemiological study of antifungal drug-resistant dermatophytes was conducted as a follow-up to our 2020 survey. Dermatophytes were isolated in 2022 from the same dermatology clinics as in the previous study. In total, 288 Trichophyton interdigitale and Trichophyton rubrum clinical isolates were obtained from 288 human cases of dermatophytosis in Tokyo, Saitama, Shizuoka, and Kumamoto, Japan. Four strains were found to be resistant to terbinafine (TRF) and susceptible to itraconazole (ITZ), luliconazole (LCZ), and ravuconazole (RVZ), and three other strains were found to be resistant to ITZ and susceptible to TRF, LCZ, and RVZ. We determined the sequences of the squalene epoxidase (SQLE)-encoding gene in the three TRF-resistant T. rubrum strains, and found that two strains harbored L393F missense mutations, and one strain harbored a F397L missense mutation. The results of the present study indicated that the prevalence of TRF-resistant dermatophytes has not increased since 2020. However, TRF-resistant T. interdigitale (L393F mutation) was isolated for the first time, indicating that attention should be paid to the presence of TRF-resistant T. interdigitale in the future. We also examined for the first time the epidemiology of ITZ-resistant T. rubrum in Japanese patients. Although the number of ITZ-resistant strains was not large, the results confirmed that ITZ-resistant T. rubrum strains do exist in Japanese patients.


Managed care contracts. A guide for clinical case managers.
When healthcare executives speak of managed care, they often use the term generically to refer to any arrangement with a healthcare payer other than traditional fee-for-service reimbursement. All too often, the "management" aspect is missing from managed care, resulting in an arrangement that could more aptly be described as "discounted care." This lack of clinical representation is unfortunate, since there are numerous issues that have an impact on clinical care, including choice of referral providers, noncoverage of certain procedures or treatments, and similar issues that may influence the patient's plan of care. Organizations that approach managed care as a system that blends the resources of management, finance, and clinicians, will enjoy the greatest potential for success. With their practical experience and insight into the administrative and clinical issues that may be encountered, nurse case managers will ultimately be responsible for managing the care of the contracted population. As case managers are the vital link among payers, providers, patients, and families, it is essential that the case manager understand managed care concepts, be conversant in the terminology of managed care, function as a member of the team responsible for evaluating contracts, and periodically review existing arrangements. This article presents an overview of the managed care contract development process, and provides tools to enable the nurse case manager to participate in the contracting process.


The house economist and the eating paradox.
An important observation of the experiments of George Collier is that animals normally prefer to maintain their body weight by eating a large number of small meals each day. However, as the effort to obtain access to food increases, the animals adapt by changing to a schedule of eating a small number of large meals each day. A strong implication of this is that there is a hidden cost to eating large meals, and this is the basis of the eating paradox that states that although food is a necessary commodity, the act of ingesting it poses certain metabolic problems for animals. Experiments on cephalic insulin secretion, conditioned insulin secretion and meal feeding are discussed to make the point that the economy demonstrated by rats in Collier's paradigm is dictated in part by predictions of the eating paradox.


An analysis of the UNOS liver transplant registry: high serum alpha-fetoprotein does not justify an increase in MELD points for suspected hepatocellular carcinoma.
The current United Network for Organ Sharing (UNOS) criteria for liver transplantation gives priority to patients with elevated serum alpha-fetoprotein (AFP; > or = 500 ng/mL) in the absence of radiologic evidence of a hepatic mass. Reports have shown that an elevated serum AFP is a poor diagnostic indicator for hepatocellular carcinoma (HCC) in patients with cirrhosis. Our aim was to determine if an AFP level above 500 ng/mL, in the absence of a liver mass by imaging study, correlates with the presence of HCC. Using the UNOS database we identified all patients transplanted for HCC in the United States between February 2002 and October 2005 based on these criteria. The data collected included: patient demographics, clinical information, and pathological outcomes. The data was analyzed using a chi-squared t-test and confirmed by logistic regression modeling. A total of 22 patients received a cadaveric liver transplant, while 1 received a living donor transplant during the study period. HCC was confirmed posttransplantation in only 6 patients (26%). There was no difference in race, gender, etiology of liver disease, or AFP level between patients with and without HCC but a significant difference in age (59.8 yr for HCC patients vs. 51.3 yr for the non-HCC group; P = 0.01). In conclusion, the majority of the patients who received extra Model for End-Stage Liver Disease (MELD) points based on an elevated AFP did not have HCC. Older age was a significant predictor for the presence of HCC in patients with a serum AFP greater than 500 ng/mL. These results demonstrate the poor correlation of serum AFP with the presence of HCC in patients awaiting liver transplantation.


Patch-clamp recording of human retinal photoreceptors and bipolar cells.
Photoreceptors and retinal bipolar cells are considered as nonspiking neurons; however, we recently showed that human rod photoreceptors can generate sodium action potentials in response to membrane depolarization from membrane potentials of -60 or -70 mV (Kawai et al., Neuron 30 [2001] 451). We performed patch-clamp recording of human cone photoreceptors and retinal bipolar cells to examine whether functional voltage-gated sodium channels are expressed in these cells as well as rod photoreceptors. Under current-clamp conditions, the injection of depolarizing current steps into a cone photoreceptor-induced marked action potentials. These action potentials were blocked by 1 microM tetrodotoxin, a voltage-gated sodium channel blocker. Under voltage-clamp conditions, depolarizing voltage steps-induced a fast transient inward current in several bipolar cells (n = 4/78). This current was activated from -70 to + 20 mV (maximal at -10 mV) and inactivated within 5 ms. The 10-90% rise time of this current was shorter than another inward current (less than one-hundredth). These results indicate that human cones and bipolar cells express voltage-gated sodium channels as rod photoreceptors. Sodium channels may serve to amplify the release of a neurotransmitter and to accelerate the light-dark change in photosignals.


Sexuality, sexual abuse. Omissions in admissions?
The main focus of this paper is to highlight the evidence relating long-term effects of childhood sexual abuse to presenting complaints on acute admission wards and to explore how sexuality, as an aspect of nursing concern, is broached by mental health nurses. There are few nursing articles on sexual abuse issues which are research-based, this literature has to be drawn from a wider field. Several authors recognize this paucity highlighting the need for future research in this area. The evidence from the literature review (1985-1995) makes it clear that the environment, the perceived interpersonal skills of the nurse and a general lack of definition of the nurse's role has a large influence on whether or not these issues are addressed. Following discussion about these findings, recommendations are made for inclusion of teaching on sexuality and sexual abuse, interpersonal skills training and illumination of assessment practice, with space for personal growth and development, in pre- and post-registration nurse education. This theme is developed further by considering how these recommendations could be introduced on acute admission wards.


The study of health effects of vinyl chloride air pollution on population.
A series of indicators, including serum lysozyme activity, G-banding chromosome aberration (G-banding CA) analysis, sister chromatid exchanges (SCEs), chromosome aberration (CA), T-lymphocyte transformation rate (TcTR), gamma-GT, GPT and AKP, were employed in the present survey among occupationally vinyl chloride (VC) exposed workers and inhabitants living in VC polluted area in a polyvinyl chloride (PVC) factory. The results showed that the serum lysozyme (S-LZM) activities in Group 3 (adult inhabitants exposed to 0.20 mg/m3 VC for at least 8 years), Group 2 (workers exposed to 4.1 mg/m3 for at least 7 years occupationally), Group 1 (workers exposed to 25.7 mg/m3 for at least 2 years) were significantly higher than control. G-banding CA analysis showed that the total chromosome breakage rates in both Groups 1 and 2 were higher, but no difference existed between Group 3 and control. Only Group 1 was observed having higher SCEs, CA level and lower TcTR than control. AKP levels in Groups 1 and 2 were higher than control, but no gamm-GT and GPT differences were found among groups. The study also suggests that G-banding CA analysis is more sensitive than CA and SCEs.


Comparison of chemical cautery (AgNo3) and steroid spray against SMD (submucosal diathermy) in the treatment of symptomatic inferior turbinate hypertrophy (ITH).
To compare the efficacy of chemical cautery (AgNo3) and steroid nasal spray against SMD (submucosal diathermy) in the treatment of symptomatic Inferior Turbinate Hypertrophy (ITH). Patients attending OPD in the department of ENT &HNS at KMCTH with symptomatic Inferior turbinate Hypertrophy were taken with their approval included for the study. Patients were divided into 2 Groups: in the first Group 25 patients were included and treated with chemical cautery (AgNo3) under Local Anaesthesia (LA), followed by steroid nasal spray for 3 months; in the second Group 25 patients were included and were treated with SMD (submucosal diathermy) under General Anaesthesia (GA).They all had history of use of topical nasal decongestant for different time period. Patients were followed up for 6 months. In Group 1, 16 patients complain of burning sensation for first week and 8 patients complain of continuous nasal blockage for 6 weeks.1 patient complain about inosmia for 2 weeks. In Group 2, nasal pain was complained by 17 patient for 2 weeks. 3 patients complain of persistent nasal blockage for 4 weeks. 3 patients complain of anosmia for 4 weeks. After completion of 6 months in Group 1, 20 patient has recurrent nasal blockage, whereas in Group 2, 10 patient has recurrent nasal blockage. Besides these, other symptoms noticed during initial phase did not appear. Chemical cautery (AgNo3) and steroid nasal spray is easy to follow, has less complication ,but failure rate is high, whereas SMD is procedure with less failure rate, but has to carried out under GA and has more discomfort postoperatively. For symptomatic inferior turbinate hypertrophy, where topical nasal decongestant has little role SMD is the choice of treatment for longer relief.


Commentary: do medical schools have a responsibility to train physicians to meet the needs of the public? The case of persistent rural physician shortages.
Persistent shortages of rural physicians have plagued the U.S. health care system for much of the last century. Recent, sharp declines in the number and proportion of U.S. medical students entering primary care have exacerbated this chronic problem because primary care physicians are the foundation of rural health care systems. The article by Chen and colleagues in the current issue of this journal replicates findings of a study 15 years ago by the author of this commentary and his colleagues that demonstrated that a relatively small number of medical schools are responsible for a large share of all of the rural physicians in the country. The lack of progress in the ensuing 15 years is distressing because there is now excellent evidence that targeted rural tracks in medical schools-including selective admissions of students from rural backgrounds and supportive integrated curricula-yield dramatic increases in the number of students choosing rural careers. U.S. medical schools-supported in large part by public funds-have a responsibility to ensure that the specialty choices and practice locations of their graduates meet the needs of the nation at large, as well as the rural and underserved communities in the regions they serve.


Does physical therapy impact clinical outcomes after lumbar decompression surgery?
The objectives of our study were to (1) determine if physical therapy (PT) impacts patient-reported outcomes (PROMs) after lumbar decompression surgery and (2) determine if PT impacts postsurgical readmissions or reoperations after lumbar decompression surgery. Patients >18 years of age who underwent primary one- or two-level lumbar decompression at our institution were identified. Patient demographics, surgical characteristics, surgical outcomes (all-cause 90 days readmissions and 90 days surgical readmissions), and patient-reported outcomes (PROMs) were compared between the groups. Multivariate linear regression was utilized to determine the individual predictors of 90 days readmissions and PROMs at the 1-year postoperative point. Alpha was set at P < 0.05. Of the 1003 patients included, 421 attended PT postoperatively. On univariate analysis, PT attendance did not significantly impact 90-day surgical reoperations (P = 0.225). Although bivariate analysis suggests that attendance of PT is associated with worse improvement in physical function (P = 0.041), increased preoperative Visual Analogue Scale leg pain (0 = 0.004), and disability (P = 0.006), as measured by the Oswestry Disability Index, our multivariate analysis, which accounts for confounding variables found there was no difference in PROM improvement and PT was not an independent predictor of 90-day all-cause readmissions (P = 0.06). Instead, Charlson Comorbidity Index (P = 0.025) and discharge to a skilled nursing facility (P = 0.013) independently predicted greater 90-day all-cause readmissions. Postoperative lumbar decompression PT attendance does not significantly affect clinical improvement, as measured by PROMs or surgical outcomes including all-cause 90 days readmissions and 90-day surgical readmissions.


Involvement of complement components in renal disease.
The complement system is a critical element of innate immunity whose role in renal physiology and disease is illustrated by the following observations: (1) a deficiency or inhibition of a complement regulatory protein results in renal tissue damage; (2) inhibition of complement activation (with cobra venom factor or sCR1), or in C6-deficient rats, attenuates complement-mediated tissue destruction; and (3) ongoing glomerular disease has been associated with the deposition/expression of complement proteins in glomerular or tubular structures and the excretion of C5b-9 and CD59 proteins. Complement activation by cellulosic membranes results in the production of C5a, which has now been shown to provoke most of the same inflammatory responses observed during hemodialysis. Controlling the dose of C5a given during dialysis, by controlling blood flow rates or membrane types, may have an impact on patient health. Finally, lessons learned in the xenotransplant setting suggest that complement activation can be effectively controlled to limit inflammation (with sCR1 or anti-C5 monoclonal antibodies). Recent developments in this area may lead to new therapeutic approaches to deal with the complex etiology of renal disease.


Efficacy of orally administered prednisolone versus partial endodontic treatment on pain reduction in emergency care of acute irreversible pulpitis of mandibular molars: study protocol for a randomized controlled trial.
Irreversible pulpitis is a highly painful inflammatory condition of the dental pulp which represents a common dental emergency. Recommended care is partial endodontic treatment. The dental literature reports major difficulties in achieving adequate analgesia to perform this emergency treatment, especially in the case of mandibular molars. In current practice, short-course, orally administered corticotherapy is used for the management of oral pain of inflammatory origin. The efficacy of intraosseous local steroid injections for irreversible pulpitis in mandibular molars has already been demonstrated but resulted in local comorbidities. Oral administration of short-course prednisolone is simple and safe but its efficacy to manage pain caused by irreversible pulpitis has not yet been demonstrated. This trial aims to evaluate the noninferiority of short-course, orally administered corticotherapy versus partial endodontic treatment for the emergency care of irreversible pulpitis in mandibular molars. This study is a noninferiority, open-label, randomized controlled clinical trial conducted at the Bordeaux University Hospital. One hundred and twenty subjects will be randomized in two 1:1 parallel arms: the intervention arm will receive one oral dose of prednisolone (1 mg/kg) during the emergency visit, followed by one morning dose each day for 3 days and the reference arm will receive partial endodontic treatment. Both groups will receive planned complete endodontic treatment 72 h after enrollment. The primary outcome is the proportion of patients with pain intensity below 5 on a Numeric Scale 24 h after the emergency visit. Secondary outcomes include comfort during care, the number of injected anesthetic cartridges when performing complete endodontic treatment, the number of antalgic drugs and the number of patients coming back for consultation after 72 h. This randomized trial will assess the ability of short-term corticotherapy to reduce pain in irreversible pulpitis as a simple and rapid alternative to partial endodontic treatment and to enable planning of endodontic treatment in optimal analgesic conditions. ClinicalTrials.gov, identifier: NCT02629042 . Registered on 7 December 2015. (Version n°1.1 28 July 2015).


Importance of familial predisposition to heart failure to the risk of anthracycline-related cardiotoxicity: A nationwide study.
Anthracycline-based chemotherapy has improved the prognosis of various malignancies, but increases the long-term risk of heart failure (HF). Identification of patients at risk prior to treatment initiation is warranted. Therefore, the aim of this study was to evaluate if a familial predisposition to HF increases the risk of anthracycline related HF. Using nationwide Danish registries, all patients treated with anthracycline from 2004 to 16 were identified. The primary outcome was long-term HF risk. First-degree relatives were identified in the Danish Family Registry and exposure was defined as a first-degree biological relative with prior HF. Risk of HF was evaluated in a cumulative incidence function and the association in a multivariable Cox regression model. A total of 11,651 patients (median age 49.1 years (IQR: 43.6-53.7), 12.2% male) were included after exclusion of 46 with preanthracycline HF. Median follow-up was 3.8 years (IQR 1.9-6.4). In the group with a first-degree relative with HF (n = 1,608) 35 patients (2.2%) were diagnosed with HF vs 133 (1.3%) in the group without a first-degree relative with HF (n = 10,043), corresponding to incidence rates per 1,000 patient-years of 5.2 (CI:3.8-7.3) vs 3.0 (CI:2.5-3.5). The cumulative incidence of HF after 10 years was higher in the first-degree relative group (3.2% vs 2.0%, P = .004); adjusted hazard ratio 1.53 (CI:1.05-2.23, P = .03). In this nationwide register-based study having a first-degree relative with HF was associated with increased risk of anthracycline related HF, suggesting that attention towards family predisposition may be warranted when estimating the risk of anthracycline related cardiotoxicity.


Photoinduced Multicomponent Synthesis of α-Silyloxy Acrylamides, an Unexplored Class of Silyl Enol Ethers.
The photoinduced, multicomponent reaction of α-diazoketones, silanols, and isocyanides affords α-silyloxy acrylamides, formally derived from α-keto amides. The presence of a secondary amido group makes classic preparative methods for silyl enol ethers unfeasible in this case, while the mild conditions required by this photochemical approach allow their synthesis in good yields; moreover, the general structure can be easily modified by varying each component of the multicomponent reaction. Fine-tuning of the reaction conditions (i.e., solvents, radiation, additives) can be exploited to obtain complete Z selectivity. The reactivity of this overlooked class of silyl enol ethers has been investigated, and features that could pave the way to new applications have been found.