Does arterial hypotension due to cardiogenic shock in older patients lead to functional oliguria or to acute renal failure?
Reports indicate some differences in the outcome of prolonged arterial hypotension due to cardiogenic shock: acute renal failure in older and more often functional oliguria in younger patients. The aim of the study is to analyze prolonged hypotension due to acute myocardial infarction in older and younger patients and to answer the question: does prolonged hypotension, due to acute myocardial infarction, lead to acute renal failure or to functional oliguria in older patients. During a 10-year observation, a study of 11 older (> 65 years) and 7 younger patients (< 65 years), suffering from acute myocardial infarction and cardiogenic shock, is presented: clinical data and laboratory: diuresis, sodium in urine, creatinine urine/plasma ratio, urine osmolality, osmolality urine/plasma ratio, renal failure index and fractional excretion of filtered sodium. In 7 older and 5 younger patients, natriuresis indicated acute renal failure. The ratio of creatinine in urine and plasma in 3 older and 5 younger indicated functional oliguria; in 3 older and 1 younger, acute renal failure; and in 5 older and 1 younger, borderline values. In 7 older and 2 younger, the values of urine osmolality were in the range of functional oliguria and, in 4 older and 5 younger, borderline values between those two parameters, as the osmolality quotient in urine and plasma. The values of the renal failure index in all older and younger patients was lower than 3.0 (in 6 older and 3 younger, lower than 1.0) indicated functional oliguria, as the fractional excretion of filtered sodium Of 9 older patients who died, 5 were examined by autopsy, and 3 out of 4 younger who died. All had myocardial fibrosis and scars, apart from recent myocardial infarction and coronary atherosclerosis. In 2 older, acute tubular necrosis was found while in 2 no renal changes were found. In 2 younger, no renal changes were found and in 1 showed disseminated intravascular coagulation. Acute renal failure due to cardiogenic shock in older patients is functional, or is rare renal.


Fuel-hormone metabolism during exercise and after physical training.
In this review the metabolic changes encountered in response to exercise in normal humans are considered in the context of the following categories: (1) fuel utilization and production, (2) hormone secretion, (3) the post-exercise recovery period, (4) effects of physical training on fuels and hormone secretion, and (5) effects of exercise on lipoprotein metabolism.


Induction of the human gene for p44, a hepatitis-C-associated microtubular aggregate protein, by interferon-alpha/beta.
A hepatitis-C-associated microtubular aggregate protein, referred to as p44, has been identified as a cytoplasmic antigen in the hepatocytes of chimpanzees infected with hepatitis C virus. The production of p44 mRNA is markedly induced in the liver of chimpanzees infected with hepatitis C or hepatitis D virus. To examine the mechanism of this induction, we isolated a genomic clone for the human p44 protein and analyzed its structure. The human p44 gene spans approximately 14 kbp of DNA and consists of nine exons separated by eight introns. An interferon-stimulated response element, which confers inducibility by interferon-alpha/beta, was found in the promoter region of the gene. Northern-blot analysis revealed that the human p44 gene is inducible by interferon-alpha/beta, but not by interferon-gamma. Functional analysis demonstrated that the interferon-stimulated response element in the promoter region of the gene mediates the inducibility of the gene by interferon-alpha/beta. Thus, the human p44 gene is a member of the family of interferon-alpha/beta inducible genes. The protein p44 may be one of the mediators involved in the antiviral action of interferon.


Pharmacologic management of seizures in organ transplant.
Seizures in a transplant candidate or recipient raise complicated management issues, but there are no results from controlled drug trials to guide their pharmacologic treatment. Most seizures in the transplant population are isolated events that do not require long-term antiseizure therapy. Short-term therapy, however, can reduce seizure recurrence. This review focuses on the pharmacologic management issues associated with acute and short-term therapy of seizures in this population. Phenytoin, fosphenytoin, and phenobarbital are current first-line therapies. The interactions between immunosuppressants and these antiepileptic drugs (AEDs) are of particular importance because the latter may reduce immunosuppressant blood levels. Other, newer agents are not subject to this interaction, and further studies are needed to define their role in the management of seizures in transplant patients.


Proteome approach to characterize the methylmalonate-semialdehyde dehydrogenase that is regulated by gibberellin.
Proteins regulated by gibberellin (GA) in rice were determined by proteome analysis. Proteins extracted from suspension culture cells of slr1, a constitutive GA response mutant of rice, were separated by two-dimensional polyacrylamide gel electrophoresis, and three proteins were greatly accumulated in the mutant. The most up-regulated protein was methylmalonate-semialdehyde dehydrogenase (MMSDH), and the amount of protein was 7-fold that of wild type. In this study, the function of MMSDH in rice was analyzed. MMSDH gene expression in suspension culture cells, roots, and leaf sheaths ofslr1 was higher than that in its wild-type. MMSDH expression in wild-type roots was increased by exogenous GA(3). Analyzed by in situ hybridization, MMSDH mRNA was expressed in root primordia of slr1, where cells are undergoing growth. MMSDH gene expression in the root zone of tissue differentiation was higher than in the elongation zone or meristem. Transgenic rice expressing antisense MMSDH showed that its seminal roots were thinner than that of control, and that the leaf sheath elongation was slightly inhibited compared to control. Concentrations of TCA cycle metabolites were decreased in the antisense plants as compared with the control plants, suggesting that acetyl-CoA was reduced in the antisense plants. These results suggest that one of the regulations by GA signal transduction including SLR1 is the expression of MMSDH, and that MMSDH may play a role in root development and leaf sheath elongation in rice.


Introduction of a citrus blight-associated gene into Carrizo citrange [Citrus sinensis (L.) Osbc. x Poncirus trifoliata (L.) Raf.] by Agrobacterium-mediated transformation.
The protein p12 accumulates in leaves of trees with citrus blight (CB), a serious decline of unknown cause. The function of p12 is not known, but sequence analysis indicates it may be related to expansins. In studies to determine the function of p12, sense and antisense constructs were used to make transgenic Carrizo citrange using an Agrobacterium-mediated transformation system. Homogeneous beta-glucuronidase+ (GUS+) sense and antisense transgenic shoots were regenerated using kanamycin as a selective agent. Twenty-five sense and 45 antisense transgenic shoots were in vivo grafted onto Carrizo citrange for further analyses. In addition, 20 sense and 18 antisense shoots were rooted. The homogeneous GUS+ plants contained either the p12 sense or antisense gene (without the intron associated with the gene in untransformed citrus) as shown by PCR and Southern blotting. Northern blots showed the expected RNA in the sense and antisense plants. A protein of identical size and immunoreactivity was observed in seven of nine sense plants but not in nine antisense or non-transgenic plants. At the current stage of growth, there are no visual phenotypic differences between the transgenic and non-transgenic plants. Selected plants will be budded with sweet orange for field evaluation for resistance or susceptibility to CB and general rootstock performance.


Serum levels of interleukins 8 and 10, interferon gamma, granulocyte-macrophage colony stimulating factor and soluble CD23 in patients with primary sclerosing cholangitis.
The presence of auto-antibodies and hypergammaglobulinaemia in patients with primary sclerosing cholangitis (PSC) suggest an overactive humoral immune system. Serum cytokines, measured using in-house double monoclonal sandwich ELISA, were used to assess the state of cellular and humoral immunity in this condition by comparison with sex and age matched normal controls and patients with alcoholic cirrhosis (AC). Soluble CD23 (sCD23) as a marker of humoral immunity was significantly elevated in PSC (N = 31) relative to patients with AC (N = 12) and the control group (N = 20) (P < 0.0001 and P < 0.001 respectively). Serum interleukin (IL) 10, as an anti-inflammatory cytokine and IL8, as a marker of neutrophil activation were significantly elevated in patients with PSC relative to those with AC and the controls (P < 0.001 and P < 0.05 respectively). Interferon gamma, as a marker of cellular immunity, and granulocyte-macrophage colony stimulating factor, a marker of monocyte/macrophage function were similar in all the groups. Cytokines and sCD23 were no different between patients with AC and the control group. While more than two thirds of the patients with PSC were positive for ANCA, there was no correlation between the presence of ANCA or ANCA titre and serum levels of either IL8, IL10 and sCD23. These results suggest exaggerated humoral immunity in PSC. The raised levels of IL10 and IL8 in PSC are discussed in the context of inflammatory bowel disease and liver dysfunction.


The use of angiotensin II receptor antagonists to increase the efficacy of radiotherapy in cancer treatment.
Angiotensin II receptor antagonists inhibit various signaling pathways involved in the regulation of inflammation, apoptosis and angiogenesis. Radiation-induced activation of a proinflammatory cytokine network has been shown to mediate normal tissue injury induced by ionizing radiation in cancer patients, resulting in serious side effects. Hence, not only do angiotensin II receptor antagonists block inflammatory signaling both in cancer cells and in normal cells, but they are also effective in the treatment of cancer by inhibiting tumor progression, vascularization and metastasis. This review addresses the role of angiotensin II inhibitors in cancer therapy, and their potential to increase therapeutical index by protecting normal cells and sensitizing tumor cells to radiotherapy.


Quantifying antimicrobial use on Canadian dairy farms using garbage can audits.
Antimicrobial resistance in pathogenic bacteria is one of the preeminent concerns for the future of global health. There is a dose-dependent relationship between antimicrobial use (AMU) and the prevalence of antimicrobial-resistant pathogens. As most AMU in Canada is related to animal agriculture, there is a need to reduce overall AMU, which could be accomplished through surveillance of AMU in animal agriculture, including the dairy industry. The objective of this study was to quantify AMU on dairy farms across Canada. This study had two parts: a description of data collected in 2019-2020, and a meta-analysis comparing this data to previous estimates of AMU in the Canadian dairy industry. The first included a garbage can audit (GCA) on 107 farms in four Canadian provinces (British Columbia, Alberta, Ontario, and Nova Scotia) in 2020; AMU data were converted to the dose-based metrics of defined course doses (DCD) and defined daily doses (DDD). Mixed-effect linear models were fit to determine the relationship between province and use of different classes of antimicrobials. On average, for every 100 animals on the farm, 117 DCD of antimicrobials were administered per year (IQR: 55, 158). These treatments amounted to 623 DDD / 100 animal-yr (IQR: 302, 677 DDD/100 animal-years). Penicillins were the most used class of antimicrobials, followed by first-and third-generation cephalosporins. Farms in Ontario used more third-generation cephalosporins than other provinces. The second part of this study compared AMU in 2020 to previously reported Canadian studies through a meta-analysis. A GCA was conducted in 2007-2008 in Alberta, Ontario, Québec, and the Maritime provinces (Prince Edward Island, New Brunswick and Nova Scotia); another GCA was conducted in Québec in 2018. Overall, AMU was lower in 2018-2020 than in 2007-2008, with the exception of third-generation cephalosporin use, which increased.


Traumatic bilateral lumbosacral facet dislocation without fracture: illustrative case.
Traumatic bilateral lumbosacral facet dislocations without fractures are extremely rare. Only 7 cases have been documented since the first description by Watson-Jones in 1974. Although various treatment strategies have been reported, no consensus has been reached regarding the best surgical approach. A 35-year-old female presented for medical attention following a high-speed motor vehicle collision. She sustained multiple injuries, including an abdominal aortic injury requiring emergent thoracic endovascular aortic repair. She was found to have bilateral lumbosacral dislocation without fracture (L5-S1) and was noted to be neurologically intact. Once medically stabilized, the patient was taken to the operating room for minimally invasive reduction and stabilization of her lumbosacral spine. Postoperatively, the patient was neurologically intact and remained stable with no deficits and appropriate lumbosacral alignment throughout her 2-year follow-up. The authors report a minimally invasive approach to the management of bilateral lumbosacral facet dislocation without fracture. Although conventional open approaches have been described previously, consideration should be given to minimally invasive strategies in select patients to facilitate their rehabilitative postoperative course.


The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response.
The long noncoding RNA (lncRNA) NEAT1 (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases. NEAT1 and paraspeckle formation are increased in cells upon exposure to a variety of environmental stressors and believed to play an important role in cell survival. The present study was undertaken to further investigate the role of NEAT1 in cellular stress response pathways. We show that NEAT1 is a novel target gene of heat shock transcription factor 1 (HSF1) and is up-regulated when the heat shock response pathway is activated by sulforaphane (SFN) or elevated temperature. HSF1 binds specifically to a newly identified conserved heat shock element in the NEAT1 promoter. In line with this, SFN induced the formation of NEAT1-containing paraspeckles via an HSF1-dependent mechanism. HSF1 plays a key role in the cellular response to proteotoxic stress by promoting the expression of a series of genes, including those encoding molecular chaperones. We have found that the expression of HSP70, HSP90, and HSP27 is amplified and sustained during heat shock in NEAT1-depleted cells compared with control cells, indicating that NEAT1 feeds back via an unknown mechanism to regulate HSF1 activity. This interrelationship is potentially significant in human diseases such as cancer and neurodegenerative disorders.


The importance of genetic variants in TNFα for periodontal disease in a cohort of coronary patients.
The aim of this analysis was to evaluate the importance of genetic variants of TNFα for the severity of periodontal disease and periodontal risk factors with respect to periodontal risk factors in a cohort of coronary patients. A total of 942 consecutive patients with angiographic proven coronary heart disease were prospectively included in the study entitled "Periodontitis and Its Microbiological Agents as Prognostic Factors in Patients With Coronary Heart Disease" (ClinicalTrials.gov identifier:NCT01045070). After including of patients, an extensive periodontal examination also involving PCR-sampling for 11 periodontal bacteria was performed. In this subanalysis, single nucleotide polymorphisms (SNPs) c.-308G>A, c.-238G>A and haplotypes for TNFα were analysed by CTS-PCR-SSP Tray kit (Heidelberg, Germany). The AG+AA genotype of SNP c.-238G>A of TNFα gene was associated with the amount of clinical attachment loss in patients with coronary heart disease in multivariate regression analysis. Moreover, Prevotella intermedia occurred more frequently in carriers who were positive for the AG+AA genotype and A-allele of SNP c.-308G>A in bivariate and multivariate analyses. Furthermore, only in bivariate analyses significant associations of genetic variants of TNFα with intensified bleeding on probing and with higher plasma level of interleukin 6 could be shown. Genetic variants of TNFα gene, namely c.-308G>A and c.-238G>A, are associated with periodontal conditions in patients with coronary heart disease.


ASSESSMENT OF MEASURES OF ADIPOSITY THAT CORRELATE WITH BLOOD PRESSURE AMONG HYPERTENSIVE AFRICANS.
Studies differ on which anthropometric measure of adiposity shows good correlation with cardiovascular diseases. In this study, we evaluated the effects of common epidemiological measures of adiposity as a correlate of elevated blood pressure in an African population. The study was carried out between June 2009 and December 2011 at the medical out-patient department of a tertiary healthcare center in Nigeria. Correlation analysis was used to assess the relationship between blood pressure and body mass index (BMI), waist to height ratio (WHtR), and waist circumference (WC). A total of 1,416 Hypertensives comprising 1090 (77%) adult females recruited over two and half years. Women were significantly older (49.2±8.1 vs. 48.0±10.0 years, p=0.039) and shorter (1.6±6.3 vs 1.7±6.8 meters, p<0.0001) when compared with men. Blood pressure parameters were comparable between women and men. Approximately 1 out of 5 participants had good blood pressure control with no gender difference. Anthropometric measurements showed that 446(32%) were overweight, 404(29%) obese and 40(3%) were morbidly obese. Compared with their male counterparts, females were significantly more likely to be obese (P<0.0001). Similarly, 51.6% of the subjects had abdominal obesity, with female preponderance (P<0.0001). Likewise, a greater proportion of women had substantially higher measured waist circumference risk. Compared with other measures of adiposity, body mass index correlated best with diastolic blood pressure in both gender (P< 0.05). This study adds to the evidence that obesity is a major cardiovascular risk factor. BMI, as a measure of adiposity, was found to correlate best with blood pressure. These findings support other observations in other populations that BMI rather than waist to height ratio (WHtR), and waist circumference (WC) is a better correlate of hypertension.


Genome-wide Loci linked to non-obstructive azoospermia susceptibility may be independent of reduced sperm production in males with normozoospermia.
Non-obstructive azoospermia (NOA) is a complex, multifactorial disease. Recent genome-wide association studies (GWAS) have identified eight NOA susceptibility loci at genome-wide significance of P < 5.0 × 10(-8) in Han Chinese from southeastern, northern, and central China. To better understand the role of the variants in conferring NOA risk, we selected four GWAS loci (HLA-DRA rs3129878, PRMT6 rs12097821, SOX5 rs10842262, and PEX10 rs2477686) that were reported before 2014 to investigate their association with NOA and their potential effects on sperm production in 1177 Han males from southwest China, including 545 patients with idiopathic NOA and 632 controls with normozoospermia. The results confirmed that the HLA-DRA rs3129878 was an NOA susceptibility locus in the present population. Along with our data, meta-analyses supported the association of the four GWAS-linked loci with NOA, whereas an additive effect of the four loci on NOA susceptibility was not found. Interestingly, the normozoospermic males with the risk genotypes of rs12097821 and rs3129878 + rs10842262 + rs12097821 were observed to have higher total sperm counts relative to non-risk genotypes, suggesting that the risk alleles of the genetic loci may not be via impairing spermatogenic ability to express susceptibility to NOA. These findings may advance our understanding of the role of the NOA susceptibility loci, although the results need to be confirmed in larger samples.


Mycophenolate mofetil treatment in resistant myositis.
To assess the efficacy and tolerability of mycophenolate mofetil (MMF) in six patients with myositis refractory to conventional immunosuppressive therapy. Six patients were identified from hospital notes. All had previously failed to respond to other immunosuppressive treatments. Efficacy was measured as changes in muscle strength, creatine kinase (CK) levels and prednisolone dose. The mean age of the group was 49.8 +/- 9.1 yrs, 6 (100%) were female and Caucasian. Patients had failed to respond to a median of 3 (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/- 18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9 mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6 +/- 555.8 IU/l (P = 0.03). Our data demonstrate that MMF may be effective in myositis, previously unresponsive to conventional immunosuppressive drugs.


Is Interstitial Cells of Cajal‒opathy Present in Gastroparesis?
Gastroparesis (GP), defined as delayed gastric emptying in the absence of any mechanical obstruction, is a challenging clinical condition, mainly because of limited treatment options. Studies in animal models of delayed gastric emptying as well as patients with gastroparesis revealed depletion or ultrastructural changes of interstitial cells of Cajal (ICC) in the gastric tissue, recently termed ICC-opathy. ICC are the pacemakers of the gastrointestinal tract and are involved in the transmission of the neuronal signaling to the smooth muscles. Therefore, lack of ICC could be one explanation of delayed gastric emptying in gastroparetic patients. How frequently ICC changes are observed in gastroparesis is not yet clear. In this review, the data on gastric ICC counts and morphology in animal models and patients with gastroparesis are discussed.


[Diagnostic utility of pleural fluid eosinophilia].
Diagnostic utility of eosinophilic pleural effusion (EPE) is still the matter of controversy. Some earlier studies have showed that pleural fluid eosinophilia considerably reduces the probability of malignancy, while some later analyses were not able to confirm such an observation. To evaluate the diagnostic significance of EPE the retrospective study of all patients with pleural effusion (PE) managed in our hospital between 1995 and 2001 has been undertaken. We analyzed 915 patients with PE and 1086 pleural effusions subjected to a biochemical, cytological and bacteriological examinations. We identified 72 (7,9%) patients with EPE and 82 EPEs liquid (7,5%) among them. The group of patients with EPE consisted of 41 (57%) males and 31 (43%) females; average age 62.2 year (range 21.0-94.0). Etiologic distribution showed the largest subgroup were patients with malignant EPE (n=28, 38.9%) followed by idiopathic EPE (n=12, 16.7%) and parapneumonic EPE (n=11, 15.3%). Looking for predictors of malignancy in EPE we found some differences between malignant and nonmalignant EPE: patients with malignant EPE were older (67.9+/-13.6) then patients with nonmalignant EPE (58.7+/-15.6; p<0.015), and have higher percentage of lymphocytes in PE (47.9+/-16.9 vs. 37.9+/-18.9; p<0.03). Similarly we noticed some differences between two largest groups (malignant and idiopathic PE). Patients with malignant PE were older (67.9+/-13.6 vs. 53.9+/-13.6 yrs; p=0.005), had lower pleural fluid eosinophilia (25.2+/-15.3% vs. 41.4+/-21.0%; p=0.01) and higher percentage of lymphocyte in PE (47.9+/-16.9 vs. 29.6+/-19.1%; p=0.004). We conclude that pleural fluid eosinophilia cannot be considered as predictor of nonmalignant etiology. The older age and the higher number of lymphocytes in EPE might suggest malignant etiology of pleural effusion.


The migration process as a stress factor in pregnant immigrant women in Spain.
Spain has seen a significant increase of the immigrant population in the past two decades. There are 5.6 million registered immigrants in this country, and 63% of them range in age between 16 and 41 years; 47% of the immigrant population are women. This situation requires additional health care, particularly as it pertains to the sexual and reproductive health of female immigrants. The objective of our study was to determine if there were differences between women of Spanish origin and immigrant women in terms of obstetric outcomes (obstetric history, gestational age at end of gestation, and at delivery) and various psychological variables during the immediate postpartum period. This was a cross-sectional study-we evaluated 30 women of Spanish origin and 30 immigrant women during the immediate postpartum period. During the 4 months after delivery, we proceeded to gather perinatal data for the study participants from their health records, partograms, and nursing assessment notes. Additionally, and following the immediate postpartum period, participants filled out the Stress Perception and Stress Vulnerability Questionnaires, as well as the Optimism Scale. Immigrant women have greater perception of stress (p = .00) and vulnerability to stress (p = .001) than do Spanish women. However, no group differences were found in obstetric variables.


Cortisone in coccidioidomycosis.
Cortisone administered orally, in low dosages for brief periods, promptly suppressed the allergic manifestations accompanying primary pulmonary coccidioidomycosis in 19 cases. There was no interference with the coccidioidin skin test reaction or with the usual serologic pattern. Dissemination of the disease as a sequel to the administration of cortisone and/or corticotropin has not been reported. A survey of physicians and of the known instances of disseminated coccidioidomycosis in Kern County failed to reveal any such episode. In none of the cases in which the authors gave cortisone in the presence of coccidioidomycosis was there any complication or undesirable sequel-specifically, no subsequent dissemination of the disease. The data presented are not to be interpreted as a therapeutic recommendation, but as a contribution to the information available concerning the effects of these drugs in infectious diseases.


Laparoscopic Splenopexy Due to Wandering Spleen: Feasible Technique.
Wandering spleen (WS) is a rare disease caused by the looseness of the splenic ligaments. A 29-year-old female patient presented to the emergency department with complaints of abdominal pain and a palpable mass in the abdomen. A diagnosis of WS was made as a result of preoperative imaging. We performed urgent laparoscopic splenopexy with non-absorbable mesh in a patient with torsioned WS. WS is a disease that must be operated on urgently because it causes ischemia and necrosis in cases where it causes torsion in the splenic pedicle. Many researchers also recommend surgery in asymptomatic patients. While splenectomy was previously recommended for WS, current recommendations advocate for splenopexy. As a result, the only and definite treatment option in the case of WS is surgery. Splenopexy with minimally invasive techniques should be the first choice if possible. Splenopexy with non-absorbable mesh is an inexpensive and feasible method to prevent re-torsion. The use of non-absorbable mesh in laparoscopic splenopexy has not been shared before in the literature.


A zomepirac reaction mimicking ectopic pregnancy.
A case is presented of a 29-year old woman who developed sudden onset of abdominal pain, vomiting, near syncope, abdominal tenderness, profound hypotension, and a late menstrual period. The patient was in good health and her only medication was zomepirac for musculoskeletal discomfort. An exploratory mini-laparotomy was performed for the suspicion of a ruptured ectopic pregnancy, but no evidence of hemoperitoneum or of ectopic pregnancy was found. A subsequent pregnancy test was negative, and the episode was attributed to a zomepirac reaction. A review of zomepirac and zomepirac reactions is included.


Downfolded Configuration Interaction for Chemically Accurate Electron Correlation.
A model subspace configuration interaction method is developed to obtain chemically accurate electron correlations by diagonalizing a very compact effective Hamiltonian of a realistic molecule. The construction of the effective Hamiltonian is deterministic and implemented by iteratively building a sufficiently small model subspace comprising local clusters of a small number of Slater determinants. Through the low-rank reciprocal of interaction Hamiltonian, important determinants can be incrementally identified to couple with selected local pairwise clusters and then downfolded into the model subspace. This method avoids direct ordering and selection of the configurations in the entire space. We demonstrate the efficiency and accuracy of this theory for obtaining the near-FCI ground- and excited-state potential energies by benchmarking the C2 molecule and illustrate its application potential in computing accurate excitation energies of organometallic [Cu(NHC)2(pyridine)2]x+ complexes and other organic molecules of various excitation character.


Increased 68Ga-FAPI Uptake in the Pulmonary Cryptococcus and the Postradiotherapy Inflammation.
A 51-year-old man, previously treated for nasopharyngeal carcinoma, presented a newly detected pulmonary nodule. This patient underwent 18F-FDG and 68Ga-FAPI PET/CT to detect tumor recurrence under the prospective study NCT04416165. Both 18F-FDG and 68Ga-FAPI PET/CT showed intense uptake in a pulmonary nodule in the right lower lobe. In addition, 68Ga-FAPI PET/CT demonstrated increased uptake in the nasopharynx that previously treated with radiotherapy. The pulmonary nodule was found to be cryptococcus by the CT-guided biopsy, and the increased 68Ga-FAPI uptake in the nasopharynx was interpreted as false-positive finding due to a stable Epstein-Barr virus level and no progression on follow-up imaging.


Progress and prospects: gene therapy clinical trials (part 1).
Over the last two decades gene therapy has moved from preclinical to clinical studies for many diseases ranging from single gene disorders such as cystic fibrosis and Duchenne muscular dystrophy, to more complex diseases such as cancer and cardiovascular disorders. Gene therapy for severe combined immunodeficiency (SCID) is the most significant success story to date, but progress in many other areas has been significant. We asked 20 leaders in the field succinctly to summarize and comment on clinical gene therapy research in their respective areas of expertise and these are published in two parts in the Progress and Prospect series.


B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes.
Purpose: The immune checkpoint PD-1 and its receptor B7-H1 (PD-L1) are successful therapeutic targets in cancer but less is known about other B7 family members. Here, we determined the expression level of B7-H3 protein in non-small cell lung cancer (NSCLC) and evaluated its association with tumor-infiltrating lymphocytes (TIL), PD-L1, B7-H4, and major clinicopathologic characteristics is in 3 NSCLC cohorts.Experimental design: We used multiplexed automated quantitative immunofluorescence (QIF) to assess the levels of B7-H3, PD-L1, B7-H4, and TILs in 634 NSCLC cases with validated antibodies. Associations between the marker levels, major clinicopathologic variables and survival were analyzed.Results: Expression of B7-H3 protein was found in 80.4% (510/634) of the cases. High B7-H3 protein level (top 10 percentile) was associated with poor overall survival (P < 0.05). Elevated B7-H3 was consistently associated with smoking history across the 3 cohorts, but not with sex, age, clinical stage, and histology. Coexpression of B7-H3 and PD-L1 was found in 17.6% of the cases (112/634) and with B7-H4 in 10% (63/634). B7-H4 and PD-L1 were simultaneously detected only in 1.8% of NSCLCs (12/634). The expression of B7-H3 was not associated with the levels of CD3-, CD8-, and CD20-positive TILs.Conclusions: B7-H3 protein is expressed in the majority of NSCLCs and is associated with smoking history. High levels of B7-H3 protein have a negative prognostic impact in lung carcinomas. Coexpression of B7-H3 with PD-L1 and B7-H4 is relatively low, suggesting a nonredundant biological role of these targets. Clin Cancer Res; 23(17); 5202-9. ©2017 AACR.


Web-based classroom data collection in ADHD: a best practices case study.
Best practices research identifies and disseminates effective clinical strategies developed and refined by clinicians for their practices. As opposed to the content of health care, medical students and residents are typically not trained in the process of its provision. This paper illustrates a best practices approach to development of a Web-based classroom data collection method to improve medication management in attention deficit hyperactivity disorder (ADHD). 1) To increase Primary Care Physician (PCP) awareness of the process of best practices research, and; 2) to highlight the use of the World Wide Web as a tool for integration of care of children with ADHD. Based on the review of a large national study in ADHD, the key ingredients for the best pharmacotherapy practices were identified. The lessons from the literature were adapted for local practice using the framework and steps for best practices outlined by Mold and Gregory. A conceptual model of managing information provided by parents/caregivers and teachers to PCPs was developed. Several steps were identified, including Web-based classroom behavioral data collection by a care manager and feedback reports to PCPs from a child psychiatrist based on the data collected. This model is currently being tested. Our preliminary experience suggests that a best practices approach has potential applications to a variety of primary care settings in South Dakota. We encourage PCPs to consider best practice strategies for their own practices. The practice-based research network (Rush Net) being developed by the Center for Rural Health Improvement of the University of South Dakota School of Medicine's Department of Family Medicine can be helpful in this regard.


Effect of Nursing Intervention on Promoting Healing of RW in Patients with Diabetic Foot: A Systematic Review and Meta-Analysis.
To systematically assess the effect of nursing intervention on promoting the healing of refractory wounds (RW) in patients with diabetic foot (DF). A computer search of PubMed, EMBASE, ScienceDirect, CochraneLibrary, China knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database was conducted in a randomized controlled trial (RCT) of traditional Chinese and western medicine nursing intervention on patients with RW of DF. Retrieval time was limited to the period from the date the database was established to present. Separately, two researchers gathered the data. RevMan5.3 statistical software was used to analyze the collected data by meta-analysis according to Cochrane Handbook 5.3. Finally, 8 articles were included with a total sample size of 772 cases. The meta-analysis of the wound healing time after intervention indicated that the wound healing time of the study group was notably shorter, and the difference was statistically significant (P < 0.05). Qualitative, fixed-effect model analysis indicated that the nursing effective rate after treatment in the study group was notably higher, and the difference was statistically significant (P < 0.05). Fasting blood glucose level in the study group after treatment was notably lower, and the difference was statistically significant (P < 0.05). The life quality in the study group was notably higher, and the difference was statistically significant (P < 0.05). Further subgroup analysis indicated that the score of physical function (PF), emotional function (RE), social function (SF), physical pain (BP), general health (GH), vitality (VT), and mental health (MH) in the study group were higher, and the difference was statistically significant (P < 0.05). A publication bias analysis was conducted using the inverted funnel chart as the outcome indicator for this study. The results indicated that most of the funnel maps were symmetrical and a few were asymmetrical, suggesting that there exhibited a certain publication bias in the included literature. The application of traditional Chinese and western medicine nursing intervention when treating DF patients clinically can effectively promote the healing of foot ulcer wounds. Traditional Chinese and western medicine nursing can help patients heal wounds faster and enhance their life quality compared to simplistic western medicine nursing. According to the original literature, the conclusion deserves to be popularized in clinic.


ADAR1p150 Forms a Complex with Dicer to Promote miRNA-222 Activity and Regulate PTEN Expression in CVB3-Induced Viral Myocarditis.
Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene's 3'-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.


Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition.
We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) characterization of primary motor cortex (M1) excitability and inhibition. Motor response inhibition prevents unwanted actions and is abnormal in several neuropsychiatric conditions. TMS is a non-invasive technology that can quantify M1 excitability and inhibition using single- and paired-pulse protocols and can be precisely timed to study cortical physiology with high temporal resolution. We modified the original Slater-Hammel (S-H) stop signal task to create a "racecar" version with TMS pulses time-locked to intra-trial events. This task is self-paced, with each trial initiating after a button push to move the racecar towards the 800 ms target. GO trials require a finger-lift to stop the racecar just before this target. Interspersed randomly are STOP trials (25%) during which the dynamically adjusted stop signal prompts subjects to prevent finger-lift. For GO trials, TMS pulses were delivered at 650 ms after trial onset; whereas, for STOP trials, the TMS pulses occurred 150 ms after the stop signal. The timings of the TMS pulses were decided based on electroencephalography (EEG) studies showing event-related changes in these time ranges during stop signal tasks. This task was studied in 3 blocks at two study sites (n=38) and we recorded behavioral performance and event-related motor-evoked potentials (MEP). Regression modelling was used to analyze MEP amplitudes using age as a covariate with multiple independent variables (sex, study site, block, TMS pulse condition [single- vs. paired-pulse], trial condition [GO, successful STOP, failed STOP]). The analysis showed that TMS pulse condition (p<0.0001) and its interaction with trial condition (p=0.009) were significant. Future applications for this online S-H/TMS paradigm include the addition of simultaneous EEG acquisition to measure TMS-evoked EEG potentials. A potential limitation is that in children, the TMS pulse sound could affect behavioral task performance.


A novel anti-osteoporotic agent that protects against postmenopausal bone loss by regulating bone formation and bone resorption.
Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts. In vivo, OVX female mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses, histological analyses, and biomechanical testing. In vitro, RAW264.7 cell-derived osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone resorption, as well as on osteogenesis and mineralization. In this study, we demonstrated that TRX prevented cortical and trabecular bone loss in ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in vivo. In vitro, TRX inhibited the formation and activity of RAW264.7-derived osteoclasts and the expression of nuclear factor of activated T-cells 1 and cathepsin K. Meanwhile, TRX improved the osteogenesis and mineralization of MC3T3-E1 by enhancing the expression of Runt-related transcription factor 2, Osterix, and collagen type 1 alpha 1. Our data demonstrated that TRX could prevent OVX-induced osteoporosis and be used in a novel treatment for postmenopausal osteoporosis.


Oriented graphene nanoribbons embedded in hexagonal boron nitride trenches.
Graphene nanoribbons (GNRs) are ultra-narrow strips of graphene that have the potential to be used in high-performance graphene-based semiconductor electronics. However, controlled growth of GNRs on dielectric substrates remains a challenge. Here, we report the successful growth of GNRs directly on hexagonal boron nitride substrates with smooth edges and controllable widths using chemical vapour deposition. The approach is based on a type of template growth that allows for the in-plane epitaxy of mono-layered GNRs in nano-trenches on hexagonal boron nitride with edges following a zigzag direction. The embedded GNR channels show excellent electronic properties, even at room temperature. Such in-plane hetero-integration of GNRs, which is compatible with integrated circuit processing, creates a gapped channel with a width of a few benzene rings, enabling the development of digital integrated circuitry based on GNRs.


Therapeutic activity of intramuscular peramivir in mice infected with a recombinant influenza A/WSN/33 (H1N1) virus containing the H275Y neuraminidase mutation.
The therapeutic activity of intramuscular (IM) peramivir was evaluated in mice infected with a recombinant influenza A/WSN/33 virus containing the H275Y neuraminidase (NA) mutation known to confer oseltamivir resistance. Regimens consisted of single (90 mg/kg of body weight) or multiple (45 mg/kg daily for 5 days) IM peramivir doses that were initiated 24 h or 48 h postinfection (p.i.). An oral oseltamivir regimen (1 or 10 mg/kg daily for 5 days) was used for comparison. Untreated animals had a mortality rate of 75% and showed a mean weight loss of 16.9% on day 5 p.i. When started at 24 h p.i., both peramivir regimens prevented mortality and significantly reduced weight loss (P < 0.001) and lung viral titers (LVT) (P < 0.001). A high dose (10 mg/kg) of oseltamivir initiated at 24 h p.i. also prevented mortality and significantly decreased weight loss (P < 0.05) and LVT (P < 0.001) compared to the untreated group results. In contrast, a low dose (1 mg/kg) of oseltamivir did not show any benefits. When started at 48 h p.i., both peramivir regimens prevented mortality and significantly reduced weight loss (P < 0.01) and LVT (P < 0.001) whereas low-dose or high-dose oseltamivir regimens had no effect on mortality rates, body weight loss, and LVT. Our results show that single-dose and multiple-dose IM peramivir regimens retain clinical and virological activities against the A/H1N1 H275Y variant despite some reduction in susceptibility when assessed in vitro using enzymatic assays. IM peramivir could constitute an alternative for treatment of oseltamivir-resistant A/H1N1 infections, although additional studies are warranted to support such a recommendation.


Sleep Disturbance and Short Sleep as Risk Factors for Depression and Perceived Medical Errors in First-Year Residents.
While short and poor quality sleep among training physicians has long been recognized as problematic, the longitudinal relationships among sleep, work hours, mood, and work performance are not well understood. Here, we prospectively characterize the risk of depression and medical errors based on preinternship sleep disturbance, internship-related sleep duration, and duty hours. Survey data from 1215 nondepressed interns were collected at preinternship baseline, then 3 and 6 months into internship. We examined how preinternship sleep quality and internship sleep and work hours affected risk of depression at 3 months, per the Patient Health Questionnaire 9. We then examined the impact of sleep loss and work hours on depression persistence from 3 to 6 months. Finally, we compared self-reported errors among interns based on nightly sleep duration (≤6 hr vs. >6 hr), weekly work hours (<70 hr vs. ≥70 hr), and depression (non- vs. acutely vs. chronically depressed). Poorly sleeping trainees obtained less sleep and were at elevated risk of depression in the first months of internship. Short sleep (≤6 hr nightly) during internship mediated the relationship between sleep disturbance and depression risk, and sleep loss led to a chronic course for depression. Depression rates were highest among interns with both sleep disturbance and short sleep. Elevated medical error rates were reported by physicians sleeping ≤6 hr per night, working ≥ 70 weekly hours, and who were acutely or chronically depressed. Sleep disturbance and internship-enforced short sleep increase risk of depression development and chronicity and medical errors. Interventions targeting sleep problems prior to and during residency hold promise for curbing depression rates and improving patient care.


Computed tomography (CT) characteristics and pathologic basis of ciliated muconodular papillary tumors of the lung.
Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor with papillary architecture. Most studies have focused on the clinicopathological features of CMPT, while computed tomography (CT) characteristics have rarely been systematically described. A cohort of 27 patients with surgically resected CMPT were identified. Clinical and demographic features were recorded. Preoperative CT images of the CMPTs and the corresponding histopathological basis were also retrospectively analyzed. All of the tumors appeared as solitary nodules. Pure ground glass, part-solid nodules and solid nodules were detected in 2/27 (7.4%), 17/27 (63.0%), and 8/27 (29.6%) patients, respectively. Twenty-one tumors (77.8%) were located in the lower lobe. The average tumor size was 1.21±0.74 (range, 0.44-3.46) cm. Eighteen (66.7%) of the 27 patients had tumors with well-defined margins and lobulated contours. Fifteen patients (55.6%) had air bronchograms in the tumor, and 19 patients (70.4%) had air-containing space. There were two patients whose tumor size was enlarged and accompanied by an increase in solid components, and one patient simply had an increase in tumor size at the preoperative follow-up duration. Notably, one patient with solid tumor components was finally diagnosed with CMPT accompanied by adenocarcinoma. CMPTs of the lung mostly manifest as solitary, lobulated, well-defined tumors with air-containing spaces on CT and often occur in the periphery of the pulmonary lower lobe. When CT findings meet these criteria, the possibility of CMPT should be considered. Additionally, CMPT can coexist with adenocarcinoma. Further investigation will contribute significantly to the biological properties of CMPT and its relationship to the potential for malignant transformation.


Changes in Prevalence and Socioeconomic Factors of Psychiatric Disability among Children in China from 1987-2006: A Population Based Survey.
The prevalence and risk factors associated with psychiatric disability among Chinese children under 14 years of age has long been of interest. Data used in the study included two nationally representative population-based surveys from the first and second China National Sample Surveys on Disability, conducted in 1987 and 2006. Both surveys used multistage, stratified random cluster sampling, with probability proportion to size, to derive nationally representative samples. Age-standardized point prevalence of mental disability was estimated through direct standardization using the 2000 census-derived Chinese population as the standard. Associations between psychiatric disability in children and possible risk factors were examined by logistic regression. Age-standardized point prevalence of psychiatric disability in children increased sharply from 0.18% to 1.11% in the 20 years between surveys. In the logistic regression analysis, the children's age and household size presented inverse associations with psychiatric disability in both surveys, although these associations were not all significant in 1987. Residential area, minority group status and gender of children were consistently associated with psychiatric disability in both surveys. To face the challenge of rising prevalence rates of psychiatric disability among children in China, the government should adopt more vigorous strategies to prevent it, especially for minority ethnicity children and those living in rural areas.


[Effect of ablations by pulsed versus continuous high-intensity focused ultrasound on isolated perfused porcine liver].
To compare the effect of ablations with pulsed and continuous high-intensity focused ultrasound (HIFU) on the target area containing large blood vessels in isolated perfused porcine liver. An isolated perfused liver model was established by perfusing the isolated porcine liver with autologous blood through the portal vein and hepatic artery using an cardiopulmonary bypass machine. With B-mode ultrasound guidance, a blood vessel about 4 mm in diameter was selected, and pulsed and continuous HIFU ablation at the same dose was delivered along the blood vessel at 3 mm to the vascular wall. After the ablation, the damages of the blood vessels as the acoustic channel and the target area were inspected, and the tissues at the interface of target volume and blood vessels were sampled for pathological examination. Neither pulsed nor continuous HIFU caused noticeable injuries of the acoustic channel vessels, but the volume of necrotic tissues in the target area differed significantly between the two groups (P<0.05). HE staining and vessel staining did not show any injuries of the blood vessels in the pathway of ultrasound ablation in neither of the groups (P>0.05). When the target area contains large blood vessels in the pathway of ultrasound ablation, pulsed HIFU can have better therapeutic efficiency to effectively induce tissue damages without affecting the blood vessels.


Resident teaching versus the operating room schedule: an independent observer-based study of 1558 cases.
Efforts to improve operating room efficiency may threaten clinician training. Therefore, we designed a prospective, observational study to determine the actual time spent teaching anesthesiology residents during the interval from patient-on-table to skin incision and to determine whether anesthesia teaching in the peri-induction period increases the time to surgical incision. This study was conducted in an inpatient operating room suite of a tertiary academic medical center. Of 1558 cases examined, 75% had an element of teaching (mean percent teaching per case = 46.4). A 33% decrease in teaching occurs when the attending anesthesiologist concurrently directed care in 2 rooms (P < 0.001). The percent teaching significantly increased as a function of ASA physical status classification and time of day of surgical case (P = 0.001). Teaching accounted for a mean increase of time to incision of 4.5 +/- 3.2 min, but represented only 3% of the mean surgical case length (207 +/- 132 min). We conclude that teaching occurs in the majority of cases in the operating room and although it contributes to increased time to incision, this increase is insignificant compared with the time required to complete the surgical procedure.


Functionalized Ionic Microgel Sensor Array for Colorimetric Detection and Discrimination of Metal Ions.
A functional ionic microgel sensor array was developed by using 1-(2-pyridinylazo)-2-naphthaleno (PAN)- and bromothymol blue (BTB)-functionalized ionic microgels, which were designed and synthesized by quaternization reaction and anion-exchange reaction, respectively. The PAN microgels (PAN-MG) and BTB microgels (BTB-MG) were spherical in shape with a narrow size distribution and exhibited characteristic colors in aqueous solution in the presence of various trace-metal ions, which could be visually distinguished by the naked eye. Such microgels could be used for the colorimetric detection of various metal ions in aqueous solution at submicromolar levels, which were lower than the U.S. Environmental Protection Agency standard for the safety limit of metal ions in drinking water. A total of 10 species of metal ions in aqueous solution, Ba2+, Cr3+, Mn2+, Pb2+, Fe3+, Co2+, Zn2+, Ni2+, Cu2+, and Al3+, were successfully discriminated by the as-constructed microgel sensor array combined with discriminant analysis, agglomerative hierarchical clustering, and leave-one-out cross-validation analysis.


Interlocked benzenes in triangular π-architectures: anchoring groups dictate ion binding and transmission.
Macrocyclic compounds like crown ethers, calixarenes, etc. are well explored in the literature as receptors for alkali metal ions. In most of these studies, the size of the macrocyclic cavity has evolved as the prominent determining criterion for the selective binding of various ions. However, approaches to systematically tailor the ion transport properties via the interplay of topological as well as electronic properties of the hosts are rarely addressed. Herein, we investigate the performance of [2.2.2]PCPs ([2.2.2]paracyclophane and [2.2.2]paracyclophene) and cyclohexaphenylene (CHP) as receptors for the alkali ions, Li+, Na+ and K+. The three macrocycles differ in terms of the groups (ethylene, vinylene and phenylene) anchoring the three benzene rings into triangular three-dimensional architectures, thereby providing opportunities for controlling the topological and the electronic features of the cavities. Based on electronic structure calculations, we predict that PCPs and CHP could be used in conjunction with dehydrobenzoannulenes that possess similar triangular π-architectures in two-dimensions to achieve selective ion transmission. Furthermore, an extended network of CHP, graphenylene, is shown for the first time to be potentially useful in energy storage applications in lithium ion batteries akin to graphyne and graphdiyne. The ion binding properties of graphenylenes would be rather interesting to investigate experimentally for energy applications, particularly in the context of the recent successful synthesis of one of the members of the graphenylene family. Overall, we have attempted to provide a unified description of the cationic interactions with 2D and 3D triangular π-architectures, describing the utility of materials like graphyne, graphdiyne and graphenylene for ion sensing and separation and energy storage applications.


Characterizing Micromechanical Properties of Friction Welding Interface between TiAl Alloy and GH3039 Superalloy.
To explore the macro-fracture mechanism of a friction welded joint between TiAl alloy and GH3039 superalloy, the micromechanical properties of intermediate phases at the joint interface are characterized and the relationship between the macro-fracture and micro-fracture of the joint is established. The indentation technique has been employed to calculate the nano-hardness and fracture toughness of the intermediate phases. The dynamic in-situ tensile test in SEM has been applied to observe the initiation and propagation process of cracks at the interface. It has been found that Al3NiTi2 and AlNi2Ti have the highest nano-hardness and elastic recovery rates, while TiAl and GH3039 base metals have the lowest nano-hardness and elastic recovery rates. This indicates that the harder the materials, the more prone they are to elastic deformation. Nevertheless, the fracture toughness of Al3NiTi2 and AlNi2Ti are the two lowest, which were 1.7 MPa·m1/2 and 2.7 MPa·m1/2, respectively. The cracks sprouted from Al3NiTi2 and AlNi2Ti and then spread throughout the entire intermediate phase zone. In other words, the fracture mainly happened in these two phase layers. It has been concluded that Al3NiTi2 and AlNi2Ti were the two weakest phases at the interface and their poor fracture toughness results in low joint strength.


Validation and Clinical Applicability of Whole-Volume Automated Segmentation of Optical Coherence Tomography in Retinal Disease Using Deep Learning.
Quantitative volumetric measures of retinal disease in optical coherence tomography (OCT) scans are infeasible to perform owing to the time required for manual grading. Expert-level deep learning systems for automatic OCT segmentation have recently been developed. However, the potential clinical applicability of these systems is largely unknown. To evaluate a deep learning model for whole-volume segmentation of 4 clinically important pathological features and assess clinical applicability. This diagnostic study used OCT data from 173 patients with a total of 15 558 B-scans, treated at Moorfields Eye Hospital. The data set included 2 common OCT devices and 2 macular conditions: wet age-related macular degeneration (107 scans) and diabetic macular edema (66 scans), covering the full range of severity, and from 3 points during treatment. Two expert graders performed pixel-level segmentations of intraretinal fluid, subretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment, including all B-scans in each OCT volume, taking as long as 50 hours per scan. Quantitative evaluation of whole-volume model segmentations was performed. Qualitative evaluation of clinical applicability by 3 retinal experts was also conducted. Data were collected from June 1, 2012, to January 31, 2017, for set 1 and from January 1 to December 31, 2017, for set 2; graded between November 2018 and January 2020; and analyzed from February 2020 to November 2020. Rating and stack ranking for clinical applicability by retinal specialists, model-grader agreement for voxelwise segmentations, and total volume evaluated using Dice similarity coefficients, Bland-Altman plots, and intraclass correlation coefficients. Among the 173 patients included in the analysis (92 [53%] women), qualitative assessment found that automated whole-volume segmentation ranked better than or comparable to at least 1 expert grader in 127 scans (73%; 95% CI, 66%-79%). A neutral or positive rating was given to 135 model segmentations (78%; 95% CI, 71%-84%) and 309 expert gradings (2 per scan) (89%; 95% CI, 86%-92%). The model was rated neutrally or positively in 86% to 92% of diabetic macular edema scans and 53% to 87% of age-related macular degeneration scans. Intraclass correlations ranged from 0.33 (95% CI, 0.08-0.96) to 0.96 (95% CI, 0.90-0.99). Dice similarity coefficients ranged from 0.43 (95% CI, 0.29-0.66) to 0.78 (95% CI, 0.57-0.85). This deep learning-based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research.


Intestinal cancer induced by N-nitroso compounds.
Several N-nitroso compounds induce tumors of the colon, and some induce tumors in other parts of the intestinal tract as well. The nitrosamines that induce colon tumors are beta oxidized n-propyl-nitrosamines. These require metabolic activation, as do 1,2-dimethylhydrazine, azomethane, and azoxymethane, another group of colon carcinogens. Several nitrosoalkylureas induce tumors in rat colons after oral administration, although the monoalkylnitrosoureas are fairly unstable and might not be expected to reach the colon. However, monoalkylnitrosoureas are equally effective with the much more stable dialkylnitrosoureas. Although nitrosomethylurea did not induce colon tumors under these conditions, nitrosoethylurea did, together with nitrosodiethylurea and other nitrosoethylalkylureas. Nitroso-n-butyl-, n-amyl-, n-hexyl-urea, and nitrosohydroxyethylurea also induced colon tumors, but the last, like nitrosoethylurea, also induced tumors of the duodenum and ileum. In most of these experiments male rats were more susceptible to induction of intestinal tumors than female rats. An explanation for the differences between these compounds of similar structure might be found in variations in their ability to alkylate DNA in intestinal cells, or in differences in stability of the alkylated product between the compounds. The physical properties of the compounds might also modulate the process of carcinogenesis, however.


Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils.
Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.


Optical transitions and Rabi oscillations in waveguide arrays.
It is theoretically demonstrated that Rabi interband oscillations are possible in waveguide arrays. Such transitions can take place in optical lattices when the unit-cell is periodically modulated along the propagation direction. Under phase-matching conditions, direct power transfer between two Floquet-Bloch modes can occur. In the nonlinear domain, periodic oscillations between two different lattice solitons are also possible.


Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications.
Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. More recently, however, there has been a paradigm shift toward a neuroplasticity hypothesis of depression in which downstream effects of antidepressants, such as increased neurogenesis, contribute to improvements in cognition and mood. This review takes a top-down approach to assess how changes in behavior and hippocampal-dependent circuits may be attributed to abnormalities at the molecular, structural, and synaptic level. We conclude with a discussion of how antidepressant treatments share a common effect in modulating neuroplasticity and consider outstanding questions and future perspectives.


Clinical conditions and concentrations of MOPEG in the cerebrospinal fluid and urine of male alcoholic patients during withdrawal.
The levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG), the major noradrenaline metabolite in the central nervous system, were analyzed in lumbar cerebrospinal fluid (CSF) and urine from 74 male alcohol addicts during acute withdrawal and after 1 week of abstinence. The values obtained were compared to those of 21 healthy male volunteers. Clinical conditions were rated on the sampling days. Concentrations of MOPEG were elevated during early withdrawal and the levels decreased during detoxication. This pattern was found in both the CSF and urine, irrespective of type of drug treatment during withdrawal. The clinical symptoms improved during withdrawal and, in the beginning, there were significant positive correlations between MOPEG levels in the CSF and sleeping problems, tremors, restlessness, visual hallucinations, and elevated muscle tension. Changes in MOPEG levels correlated to changes of mood. A significant correlation was also found between low MOPEG level and craving for alcohol. Few correlations were found between MOPEG levels in the urine and clinical symptoms. The results indicate an elevated noradrenergic transmitter turnover rate in the early phase of alcohol withdrawal and a connection between noradrenaline metabolism and several clinical conditions during alcohol withdrawal.


Traumatic common peroneal nerve palsy: a retrospective study.
A retrospective analysis of 26 consecutive cases of traumatic common peroneal nerve palsy seen during a four-year period in the Department of Rehabilitation Medicine at New York Medical College was carried out. Fifteen were complete lesions, nine were incomplete lesions, and there were two cases of neurapraxia. Among the factors studied were etiology, age, sex, associated injuries, electrodiagnostic findings, and prognosis for recovery. The ultimate functional status of the patients was evaluated up to three years following injury. Of the patients, 19.2% recovered fully, and 26.9% showed partial recovery. The maximum time of recovery was achieved in 15.5 months in complete lesions and 9.5 months in incomplete lesions. The relationship of peronneal nerve injury to fractures of the femur is emphasized. The indications for medical, surgical and rehabilitative management are discussed.


Mutualism Between Fire Ants and Mealybugs Reduces Lady Beetle Predation.
Solenopsis invicta Buren is an important invasive pest that has a negative impact on biodiversity. However, current knowledge regarding the ecological effects of its interaction with honeydew-producing hemipteran insects is inadequate. To partially address this problem, we assessed whether the interaction between the two invasive species S. invicta and Phenacoccus solenopsis Tinsley mediated predation of P. solenopsis by Propylaea japonica Thunbery lady beetles using field investigations and indoor experiments. S. invicta tending significantly reduced predation by the Pr. japonica lady beetle, and this response was more pronounced for lady beetle larvae than for adults. A field investigation showed that the species richness and quantity of lady beetle species in plots with fire ants were much lower than in those without fire ants. In an olfaction bioassay, lady beetles preferred to move toward untended rather than tended mealybugs. Overall, these results suggest that mutualism between S. invicta and P. solenopsis may have a serious impact on predation of P. solenopsis by lady beetles, which could promote growth of P. solenopsis populations.


Analysis of Energy-Based Metrics for Laparoscopic Skills Assessment.
The complexity of minimally invasive surgery (MIS) requires that trainees practice MIS skills in numerous training sessions. The goal of these training sessions is to learn how to move the instruments smoothly without damaging the surrounding tissue and achieving operative tasks with accuracy. In order to enhance the efficiency of these training sessions, the proficiency of the trainees should be assessed using an objective assessment method. Several performance metrics have been proposed and analyzed for MIS tasks. The differentiation of various levels of expertise is limited without the presence of an external evaluator. In this study, novel objective performance metrics are proposed based on mechanical energy expenditure and work. The three components of these metrics are potential energy, kinetic energy, and work. These components are optimally combined through both one-step and two-step methods. Evaluation of these metrics is accomplished for suturing and knot-tying tasks based on the performance of 30 subjects across four levels of experience. The results of this study show that the one-step combined metric provides 47 and 60 accuracy in determining the level of expertise of subjects for the suturing and knot-tying tasks, respectively. The two-step combined metric provided 67 accuracy for both of the tasks studied. The results indicate that energy expenditure is a useful metric for developing objective and efficient assessment methods. These metrics can be used to evaluate and determine the proficiency levels of trainees, provide feedback and, consequently, enhance surgical simulators.


Building healthy and equitable societies: what Australia can contribute to and learn from the Commission on Social Determinants of Health.
The Commission on Social Determinants of Health (the Commission) was launched by the World Health Organization in 2005. It aims to support countries and global health partners to act on social factors leading to ill-health and health inequalities. Taking action on the social determinants of health is not new for Australia. This paper provides a description of the work of the first 18 months of the Commission and relevant Australian examples. Taking action on the social determinants of health is never simple or easy even in the most supportive of policy environments. The global focus of the Commission should ensure that knowledge and examples of successful action will be collected from a diverse range of country and policy environments, particularly low to middle-income countries. Given Australia's experience, we encourage practitioners to contribute to the deliberations of the Commission. It is also critical that Australian practitioners engage with the Commission's different actors and stakeholders, particularly knowledge networks, to derive important policy lessons from the knowledge generated by the Commission.


Diode laser lidar wind velocity sensor using a liquid-crystal retarder for non-mechanical beam-steering.
We extend the functionality of a low-cost CW diode laser coherent lidar from radial wind speed (scalar) sensing to wind velocity (vector) measurements. Both speed and horizontal direction of the wind at ~80 m remote distance are derived from two successive radial speed estimates by alternately steering the lidar probe beam in two different lines-of-sight (LOS) with a 60° angular separation. Dual-LOS beam-steering is implemented optically with no moving parts by means of a controllable liquid-crystal retarder (LCR). The LCR switches the polarization between two orthogonal linear states of the lidar beam so it either transmits through or reflects off a polarization splitter. The room-temperature switching time between the two LOS is measured to be in the order of 100 μs in one switch direction but 16 ms in the opposite transition. Radial wind speed measurement (at 33 Hz rate) while the lidar beam is repeatedly steered from one LOS to the other every half a second is experimentally demonstrated - resulting in 1 Hz rate estimates of wind velocity magnitude and direction at better than 0.1 m/s and 1° resolution, respectively.


Implementing a quality assurance program using a risk assessment tool on dairy operations.
Concerns and perceptions about antibiotic residues in milk prompted the dairy industry to develop a voluntary program to support rational antibiotic use on dairy farms. One deficiency of this program is the inability of producers to identify easily the weaknesses in antibiotic management in order to develop control plans. To overcome this deficiency, an educational approach was designed. The program centered on an on-farm risk assessment tool used by the producer and an industry educator to determine the current risk for residue violation. The risk assessment tool was tested by 25 field personnel working with northeastern milk receivers and 250 producers in seven states. The participants in the study identified a lack of adequate treatment records as being the highest risk factor for antibiotic residues, followed by deficiencies in understanding how to use antibiotics and poor relationships between veterinarians and their clients. When field representatives utilized the risk assessment tool, for most producers, risk of antibiotic residue decreased by approximately 19%. In particular, more farms kept written records or more complete records. Finally, producers with reported histories of antibiotic residues were less likely to implement management changes to reduce the risk of antibiotic residue.


Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease.
Cardiovascular disease is a major target for many experimental stem cell-based therapies and mesenchymal stem cells (MSCs) are widely used in these therapies. Transplantation of MSCs to treat cardiac disease has always been predicated on the hypothesis that these cells would engraft, differentiate and replace damaged cardiac tissues. However, experimental or clinical observations so far have failed to demonstrate a therapeutically relevant level of transplanted MSC engraftment or differentiation. Instead, they indicate that transplanted MSCs secrete factors to reduce tissue injury and/or enhance tissue repair. Here we review the evidences supporting this hypothesis including the recent identification of exosome as a therapeutic agent in MSC secretion. In particular, we will discuss the potential and practicality of using this relatively novel entity as a therapeutic modality for the treatment of cardiac disease, particularly acute myocardial infarction.


A quantitative trait locus on chr.4 regulates thymic involution.
The mechanisms underlying age-associated thymic involution are unknown. In mice, thymic involution shows mouse strain-dependent genetic variation. Identification of the underlying genes would provide mechanistic insight into this elusive process. We previously showed that responsiveness of hematopoietic stem and progenitor cells (HSPCs) to transforming growth factor-beta 2, a positive regulator of HSPC proliferation, is regulated by a quantitative trait locus (QTL) on chr. 4, Tb2r1. Interestingly, Tgfb2(+/-) mice have delayed thymic involution. Therefore, we tested the hypothesis that a QTL on chr. 4 might regulate thymic involution. Aged, but not young, B6.D2-chr.4 congenic mice, where the telomeric region of chr. 4 was introgressed from DBA/2 to C57BL/6 mice, had larger thymi, and better maintenance of early thymic precursors than C57BL/6 control mice. These observations unequivocally demonstrate that the telomeric region of chr. 4 contains a QTL, Ti1 (thymic involution 1) that regulates thymic involution, and suggest the possibility that Ti1 may be identical to Tb2r1.


Living with disfigurement.
Body-image disturbance, as a consequence of disfigurement, affects a large number of people in the UK, yet there is little research into the psychosocial consequences. There is evidence that many of the psychological difficulties can be likened to phobic behaviour, particularly in social situations. A fear-avoidance model of psychosocial difficulties following disfigurement is, therefore, potentially useful to nurses working in a variety of settings. The first of two articles on disfigurement explores some of the background to the fear-avoidance model.


[Traumatology in the elderly. Problems exemplified by femoral neck fractures].
The most frequent complications in response to a fracture of the femoral neck, a typical injury of the elderly, are necrosis of the head of femur and pseudoarthrosis of the femoral neck. Only the around dressed down fracture can be conveyed to conservative treatment. The classification of AO takes these problems into consideration. One possibility to preserve the femur head is by operative insertion of a dynamic hip screw (DHS). Specific problems of the diverse types of fracture and their surgical details are taken into special account.


Data analysis strategies for reducing the influence of the bias in cross-cultural research.
In cross-cultural research, researchers have to adjust the constructs and associated measurement instruments that have been developed in one culture and then imported for use in another culture. Importing concepts from other cultures is often simply reduced to language adjustment of the content in the items of the measurement instruments that define a certain (psychological) construct. In the context of cross-cultural research, test bias can be defined as a generic term for all nuisance factors that threaten the validity of cross-cultural comparisons. Bias can be an indicator that instrument scores based on the same items measure different traits and characteristics across different cultural groups. To reduce construct, method and item bias,the researcher can consider these strategies: (1) simply comparing average results in certain measuring instruments; (2) comparing only the reliability of certain dimensions of the measurement instruments, applied to the "target" and "source" samples of participants, i.e. from different cultures; (3) comparing the "framed" factor structure (fixed number of factors) of the measurement instruments, applied to the samples from the "target" and "source" cultures, using explorative factor analysis strategy on separate samples; (4) comparing the complete constructs ("unframed" factor analysis, i.e. unlimited number of factors) in relation to their best psychometric properties and the possibility of interpreting (best suited to certain cultures, applying explorative strategy of factor analysis); or (5) checking the similarity of the constructs in the samples from different cultures (using structural equation modeling approach). Each approach has its advantages and disadvantages. The advantages and lacks of each approach are discussed.


Two-dimensional electron-hole liquid in single Si quantum wells with large electronic and dielectric confinement.
We report a luminescence study of the electronic properties of the 2D electron-hole liquid in crystalline Si quantum wells with SiO2 dielectric barriers. The Fermi-Dirac condensation of e-h pairs into a metallic liquid is strongly enhanced by spatial localization. We present experimental evidence for the formation of liquid nanodroplets, with size increasing with e-h pair density. The quantum confined regime is observed for well width below 15 nm. The data are analyzed in a confinement model that takes account of the band-gap renormalization by 2D many-body effects and the increase of the Coulomb interactions due to the dielectric mismatch between the Si well and the SiO2 barriers.


Actigraphic and self-reported sleep quality in women: associations with ovarian hormones and mood.
Sleep and mood disturbances in women have often been linked to the menstrual cycle, implying an ovarian hormonal causation. However, most studies in this area have used self-reported menstrual cycle phase rather than direct measurement of ovarian hormone concentrations. Further, many studies have focused primarily on peri- and postmenopausal populations reporting clinical sleep difficulty. In this study, we examined the associations among sleep quality, mood, and ovarian hormone concentration in a random sample of community-dwelling, nonclinical women of reproductive age. Our sample consisted of 19 non-help-seeking women aged 18-43 years, each contributing an average of 39.5 nights of data. Over the 42 days of the study, we collected self-reported and actigraphic sleep-quality data, concentrations of urinary estrogen and progesterone metabolites (estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide [PdG], respectively), and daily mood ratings. Linear-mixed models were used to estimate associations, clustering longitudinal observations by the participant. We found a significant positive association between Sleep Efficiency and E1G, and a significant negative association between Sleep Efficiency and PdG. Otherwise, the self-reported and actigraphic sleep measures were not associated with ovarian hormone concentrations. Self-reported sleep was strongly associated with mood, whereas actigraphic sleep was associated with only two of the 11 individual mood items, "Feeling on Top of Things" and "Difficulty Coping." In this community sample of women of reproductive age, ovarian hormones play little, if any, role in day-to-day sleep quality. Our findings additionally highlight the different associations that self-reported and actigraphic sleep show with hormones and mood.


Expression of GLI1 correlates with expression of lymphangiogenesis proteins, vascular endothelial growth factor C and vascular endothelial growth factor receptor 3, in colorectal cancer.
Aberrant activation of the hedgehog (Hh) signaling pathway is associated with tumorigenesis in various tissues. In colorectal cancer (CRC), evidence for Hh activation is inconsistent, and the relationship between the Hh signaling pathway and lymphangiogenesis has not been studied. The aim of this study was to determine the relationship between Hh signaling and lymphangiogenesis and the association of this relationship with lymph node metastasis in CRC. We investigated 189 patients who underwent curative surgical resection for CRC between 2002 and 2004 at Korea University Guro Hospital. Paraffin-embedded specimens of colorectal adenocarcinoma and adjacent normal mucosa were evaluated. Immunohistochemical staining for Sonic hedgehog (Shh), Gli1, vascular endothelial growth factor C (VEGFC), and VEGF receptor 3 (VEGFR3) was performed for each specimen. Tumor specimen showed significantly strong staining of Shh, Gli1, VEGFC, and VEGFR3 compared with a normal specimen. Shh expression was not associated with Gli1 expression. Gli1 expression correlated positively with VEGFC and VEGFR3 expression (P < 0.05 in both) but not with lymph node metastasis. Activation of the Hh signaling pathway associated with Gli1 promotes expression of lymphangiogenesis proteins, VEGFC and VEGFR3, in CRC. Further studies are necessary to determine the association of this relationship with lymph node metastasis in CRC.


Self-assembly formation of lipid bilayer coatings on bare aluminum oxide: overcoming the force of interfacial water.
Widely used in catalysis and biosensing applications, aluminum oxide has become popular for surface functionalization with biological macromolecules, including lipid bilayer coatings. However, it is difficult to form supported lipid bilayers on aluminum oxide, and current methods require covalent surface modification, which masks the interfacial properties of aluminum oxide, and/or complex fabrication techniques with specific conditions. Herein, we addressed this issue by identifying simple and robust strategies to form fluidic lipid bilayers on aluminum oxide. The fabrication of a single lipid bilayer coating was achieved by two methods, vesicle fusion under acidic conditions and solvent-assisted lipid bilayer (SALB) formation under near-physiological pH conditions. Importantly, quartz crystal microbalance with dissipation (QCM-D) monitoring measurements determined that the hydration layer of a supported lipid bilayer on aluminum oxide is appreciably thicker than that of a bilayer on silicon oxide. Fluorescence recovery after photobleaching (FRAP) analysis indicated that the diffusion coefficient of lateral lipid mobility was up to 3-fold greater on silicon oxide than on aluminum oxide. In spite of this hydrodynamic coupling, the diffusion coefficient on aluminum oxide, but not silicon oxide, was sensitive to the ionic strength condition. Extended-DLVO model calculations estimated the thermodynamics of lipid-substrate interactions on aluminum oxide and silicon oxide, and predict that the range of the repulsive hydration force is greater on aluminum oxide, which in turn leads to an increased equilibrium separation distance. Hence, while a strong hydration force likely contributes to the difficulty of bilayer fabrication on aluminum oxide, it also confers advantages by stabilizing lipid bilayers with thicker hydration layers due to confined interfacial water. Such knowledge provides the basis for improved surface functionalization strategies on aluminum oxide, underscoring the practical importance of surface hydration.


Asymptomatic Cecal Perforation in a Renal Transplant Recipient After Sodium Polystyrene Sulfonate Administration.
Sodium polystyrene sulfonate (SPS) is a medication commonly used for the treatment of hyperkalemia. There have been many cases of colonic necrosis and perforation associated with administration of SPS. There are very few such cases reported in renal transplant patients. We present a case of renal transplant recipient who developed cecal perforation after a single oral dose of SPS. She had no signs or symptoms suggestive of intestinal perforation and was incidentally diagnosed with it on abdominal imaging performed to find cause of acute blood loss anemia. This case underlines the importance of recognizing this severe and potentially life-threatening complication associated with SPS. The clinicians should also consider renal/solid organ transplant and immunosuppression as potential risk factors.


Roger Carpenter.
Roger Carpenter is Reader in Oculomotor Physiology at the University of Cambridge. His main research interest is eye movements, and especially the neural decision mechanisms that determine where you look. He is the author of Movements of the Eyes as well as of the highly successful textbook Neurophysiology. In 2000 he was one of the inaugural winners of a national teaching prize.


Prevalence and correlates of weight gain attempts across five countries.
To determine the prevalence and correlates of weight gain attempts in a pooled sample of adults aged 18 and older from Canada, Australia, the United Kingdom, the United States, and Mexico. Data collected during 2 years (2018 and 2019) of the International Food Policy Study (N = 42,108) were analyzed. Unadjusted 12-month prevalence of weight gain attempts was estimated based on body mass index (BMI; kg/m2 ), weight perception, country, survey year, and sex. Logistic regression analyses were estimated to determine the sociodemographic correlates (age, race/ethnicity, education, BMI, weight perception, weight perception accuracy, and self-rated mental health) of weight gain attempts among the pooled sample stratified by sex. Men (10.4%) were significantly more likely than women (5.4%) to report weight gain attempts (p < .001). Nearly one in five (17.1%) men with a BMI in the "normal" range (≥18.5 to <25.0) reported weight gain attempts. Among both men and women, minority group identity was associated with higher odds, while older age and higher BMI category were associated with lower odds, of reporting weight gain attempts. Country differences over the two survey years showed the prevalence of weight gain attempts in 2019 (vs. 2018) was higher among women in Australia (p < .05) and men in the United States (p < .01). Weight gain attempts are more common among men, compared to women, across five countries, potentially reflecting the global salience of the pursuit of a muscular body.


Extranodal non-T-cell lymphoblastic lymphoma in adults. A report of two cases.
Typical adult cases of malignant lymphoma, diffuse, lymphoblastic type (MLLB), are of the T-cell immunophenotype and occur as mediastinal masses. The authors report two unusual adult cases with initial extranodal sites of involvement and non-T-cell immunophenotype that were originally misclassified. One patient presented with a right submaxillary salivary gland mass and the other presented with a T7-8 spinal cord compression resulting from a vertebral body tumor. A lymphoblastic leukemic phase developed in both patients after 15 months and 5 months, respectively. The bone marrow blasts of both patients had positive results for cluster designation (CD) 10, CD19, HLA-DR, and terminal deoxynucleotidyl transferase. Because both extranodal sites of presentation and non-T-cell immunophenotype are unusual in adult MLLB, these features may have contributed to the original misclassification of these lesions.


Shostakovich and ALS.
The life of the Russian composer Dmitri Dmitriyevich Shostakovich (25 September 1903 - 9 August 1975) was marked by chronic ill health. There is evidence that he suffered from a progressive asymmetric weakness of the limbs. The diagnosis of his condition eluded multiple physicians and was never conclusively identified. Despite enduring an insidious 20-year course, Shostakovich remained a prolific composer and performer. His remarkable cultural contributions, in the setting of such adversity, continue to inspire other people beset with chronic paralytic illnesses such as amyotrophic lateral sclerosis.


Jamming coverage in competitive random sequential adsorption of a binary mixture.
We propose a generalized car parking problem where cars of two different sizes are sequentially parked on a line with a given probability q. The free parameter q interpolates between the classical car parking problem of only one car size and the competitive random sequential adsorption (CRSA) of a binary mixture. We give an exact solution to the CRSA rate equations and find that the final coverage, the jamming limit of the line, is always larger for a binary mixture than for the unisized case. The analytical results are in good agreement with our direct numerical simulations of the problem.


Probing the magnocellular and parvocellular visual pathways in facial emotion perception in schizophrenia.
Schizophrenia patients have well-established deficits in facial emotion perception, which contribute to their poor social functioning. A number of studies have related these deficits to a differential dysfunction in the magnocellular (M) versus parvocellular (P) visual pathway. We assessed 35 schizophrenia patients and 35 healthy individuals on an emotion identification task, in which facial stimuli were either unaltered (broad spatial frequency, BSF) or manipulated to contain only high (HSF) or low (LSF) spatial frequencies, thereby respectively biasing the visual system toward the P- or M- pathways. As expected, patients were less accurate and slower in recognizing emotions across all conditions, relative to controls. Performance was best in the BSF condition followed by the HSF and finally the LSF condition, in both groups. A significant group by spatial frequency interaction reflected a smaller magnitude of impairment in the HSF condition, compared to the other two conditions that preferentially engage the M-system. These findings are consistent with studies showing a differential M-pathway abnormality in schizophrenia with a less pronounced impairment in P-function. The current study suggests that patients have less difficulty extracting emotional content from faces when LSFs are attenuated and supports the need to remediate basic visual processing deficits in schizophrenia.


Two distinct compartments of a ctenophore comb plate provide structural and functional integrity for the motility of giant multicilia.
Comb plates are large ciliary structures uniquely seen in comb jellies (ctenophores).1,2,3 A comb plate is constructed from tens of thousands of cilia that are bundled together by structures called compartmenting lamellae (CLs).4,5,6 We previously reported the first component of the CL, CTENO64, and found that it was specifically found in ctenophores and was essential for the determination of ciliary orientation.3 However, CTENO64 is localized only in the proximal region of the CL; therefore, the molecular architecture of the CL over the entire length of a comb plate has not been elucidated. Here, we identified a second CL component, CTENO189. This ctenophore-specific protein was present in the distal region of comb plates, with a localization clearly segregated from CTENO64. Knockdown of the CTENO189 gene using morpholino antisense oligonucleotides resulted in complete loss of CLs in the distal region of comb plates but did not affect the formation of comb plates or the orientation of each cilium. However, the hexagonal distribution of cilia was disarranged, and the metachronal coordination of comb plates along a comb row was lost in the CTENO189 morphants. The morphant comb plate showed asymmetric ciliary-type movement in normal seawater, and in a high-viscosity solution, it could not maintain the normal waveforms but showed a symmetric flagellar-type movement. Our findings demonstrated two distinct compartments of a comb plate: the proximal CL as the building foundation that rigidly fixes the ciliary orientation, and the distal CL that reinforces the elastic connection among cilia to overcome the hydrodynamic drag of giant multiciliary plates.


Inhibition of Human Class I vs Class III Phosphatidylinositol 3'-Kinases.
Most investigations of phosphatidylinositol 3'-kinase (PI3K) drug inhibition have been via assays based on ADP appearance or ATP consumption (e.g., Liu, Q., et al. ( 2011 ) J. Med. Chem. 54 , 1473 - 1480 ). However, at least some PI3K isoforms show basal ATPase activity in the absence of PI lipid substrate(s), which may complicate quantification of drug potency, isoform specificity of some drugs, and synergy for drug combinations. In this study, we probe the class I vs class III isoform specificity of a selected set of PI3K inhibitors using a simple, inexpensive, semi high-throughput assay that quantifies production of phosphatidylinositol 3'-phosphate (PI3P) from phosphatidylinositol. Results are compared to previous data largely generated using ATPase activity assays. Good agreement between EC50 values computed via ATPase assays vs the reported PI3P formation assay is found for most drugs, but with a few exceptions. Furthermore, for the first time, drug inhibition of class I vs class III enzymes is compared side-by-side with the same assay for the important class I-specific inhibitors GSK2126458 ("Omipalisib") and NVP-BGT226 ("BGT226") currently in clinical development for advanced solid tumors.


Intrinsic Properties of Suspended MoS2 on SiO2/Si Pillar Arrays for Nanomechanics and Optics.
Semiconducting two-dimensional (2D) materials, such as transition-metal dichalcogenides (TMDs), are emerging in nanomechanics, optoelectronics, and thermal transport. In each of these fields, perfect control over 2D material properties including strain, doping, and heating is necessary, especially on the nanoscale. Here, we study clean devices consisting of membranes of single-layer MoS2 suspended on pillar arrays. Using Raman and photoluminescence spectroscopy, we have been able to extract, separate, and simulate the different contributions on the nanoscale and to correlate these to the pillar array design. This control has been used to design a periodic MoS2 mechanical membrane with a high reproducibility and to perform optomechanical measurements on arrays of similar resonators with a high-quality factor of 600 at ambient temperature, hence opening the way to multiresonator applications with 2D materials. At the same time, this study constitutes a reference for the future development of well-controlled optical emissions within 2D materials on periodic arrays with reproducible behavior. We measured a strong reduction of the MoS2 band gap induced by the strain generated from the pillars. A transition from direct to indirect band gap was observed in isolated tent structures made of MoS2 and pinched by a pillar. In fully suspended devices, simulations were performed allowing both the extraction of the thermal conductance and doping of the layer. Using the correlation between the influences of strain and doping on the MoS2 Raman spectrum, we have developed a simple, elegant method to extract the local strain in suspended and nonsuspended parts of a membrane. This opens the way to experimenting with tunable coupling between light emission and vibration.