Clinical importance of new-onset atrial fibrillation after cardiac resynchronization therapy.
Data on the occurrence and implications of new-onset atrial fibrillation (AF) following cardiac resynchronization therapy (CRT) are scarce. We studied the incidence of new onset AF in CRT-defibrillator (CRT-D) recipients. The influence of new-onset AF on echocardiographic response to CRT and the rate of adverse events also were evaluated. The purpose of this study was to assess the incidence and implications of new-onset AF following CRT. The study population consisted of 223 consecutive patients with no history of AF. New-onset AF was defined as atrial high-rate episodes >180 bpm for more than 10 minutes/day as detected by the device. Echocardiography was performed at baseline and after 6 months of biventricular pacing. Long-term events included implantable cardioverter-defibrillator therapy for ventricular arrhythmias, hospitalization for heart failure, and all-cause mortality. Fifty-five (25%) patients developed new-onset AF during mean follow-up of 32 +/- 16 months. When compared to the patients who maintained sinus rhythm during follow-up, patients who developed AF showed less left ventricular (LV) reverse remodeling (DeltaLV end-systolic volume 37 +/- 53 vs >19 +/- 37 mL, P <.05) and less improvement in LV function (DeltaLV ejection fraction 6.7% +/- 8.9% vs 3.5% +/- 10.3%, P <.05). Importantly, patients who developed AF experienced more appropriate ICD shocks for ventricular arrhythmias, more inappropriate shocks, and more hospitalizations for heart failure. Recipients of CRT-D who develop new-onset AF show less echocardiographic response to CRT and more cardiac adverse events during long-term follow-up.


Design and catalytic studies of structural and functional models of the catechol oxidase enzyme.
The catechol oxidase activity of three copper/bicompartmental salen derivatives has been studied. One mononuclear, [CuL] (1), one homometallic, [Cu2L(NO3)2] (2), and one heterometallic, [CuMnL(NO3)2] (3) complexes were obtained using the ligand H2L = N,N'-bis(3-methoxysalicylidene)-1,3-propanediamine through different synthetic methods (electrochemical, chemical and solid state reaction). The structural data indicate that the metal ion disposition models the active site of type-3 copper enzymes, such as catechol oxidase. In this way, their ability to act as functional models of the enzyme has been spectrophotometrically determined by monitorization of the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butyl-o-benzoquinone (3,5-DTBQ). All the complexes show significant catalytic activity with ratio constants (kobs) lying in the range (223-294) × 10-4 min-1. A thorough kinetic study was carried out for complexes 2 and 3, since they show structural similarities with the catechol oxidase enzyme. The greatest catalytic activity was found for the homonuclear dicopper compound (2) with a turnover value (kcat) of (3.89 ± 0.05) × 106 h-1, which it is the higher reported to date, comparable to the enzyme itself (8.25 × 106 h-1).


Deciphering transcriptional and functional heterogeneity in hematopoiesis with single-cell genomics.
Single-cell genomic approaches have uncovered cell fate biases and heterogeneity within hematopoietic subpopulations. However, standard single-cell transcriptomics suffers from high sampling noise, which particularly skews the distribution of lowly expressed genes, such as transcription factors (TFs). This might preclude the identification of rare transcripts that define cell identity and demarcate cell fate biases. Moreover, these studies need to go hand in hand with relevant functional assays to ensure that observed gene expression changes represent biologically meaningful alterations. Single-cell lineage tracing and functional validation studies have uncovered cell fate bias within transcriptionally distinct hematopoietic stem and progenitor subpopulations. Novel markers identified using these strategies have been proposed to prospectively isolate functionally distinct subpopulations, including long-term hematopoietic stem cells for ex vivo applications. Furthermore, the continuous nature of hematopoiesis has prompted the study of the relationship between stochastic transcriptional noise in hematopoietic TFs and cell fate determination. An understanding of the limitations of single-cell genomic approaches and follow-up functional assays is critical to discern the technical and biological contribution of noise in hematopoietic heterogeneity, to identify rare gene expression states, and to uncover functionally distinct subpopulations within hematopoiesis. http://links.lww.com/COH/A23.


A multiplex-NGS approach to identifying respiratory RNA viruses during the COVID-19 pandemic.
A methodological approach based on reverse transcription (RT)-multiplex PCR followed by next-generation sequencing (NGS) was implemented to identify multiple respiratory RNA viruses simultaneously. A convenience sampling from respiratory surveillance and SARS-CoV-2 diagnosis in 2020 and 2021 in Montevideo, Uruguay, was analyzed. The results revealed the cocirculation of SARS-CoV-2 with human rhinovirus (hRV) A, B and C, human respiratory syncytial virus (hRSV) B, influenza A virus, and metapneumovirus B1. SARS-CoV-2 coinfections with hRV or hRSV B and influenza A virus coinfections with hRV C were identified in adults and/or children. This methodology combines the benefits of multiplex genomic amplification with the sensitivity and information provided by NGS. An advantage is that additional viral targets can be incorporated, making it a helpful tool to investigate the cocirculation and coinfections of respiratory viruses in pandemic and post-pandemic contexts.


Investigating the blood-spinal cord barrier in preclinical models: a systematic review of in vivo imaging techniques.
This study is a systematic review. To evaluate current in vivo techniques used in the investigation of the blood-spinal cord barrier (BSCB). Search of English language literature for animal studies that investigated the BSCB in vivo. Data extraction included animal model/type, protocol for BSCB evaluation, and study outcomes. Descriptive syntheses are provided. A total of 40 studies were included, which mainly investigated rodent models of experimental autoimmune encephalomyelitis (EAE) or spinal cord injury (SCI). The main techniques used were magnetic resonance imaging (MRI) and intravital microscopy (IVM). MRI served as a reliable tool to longitudinally track BSCB permeability changes with dynamic contrast enhancement (DCE) using gadolinium, or assess inflammatory infiltrations with targeted alternative contrast agents. IVM provided high-resolution visualization of cellular and molecular interactions across the microvasculature, commonly with either epi-fluorescence or two-photon microscopy. MRI and IVM techniques enabled the evaluation of therapeutic interventions and mechanisms that drive spinal cord dysfunction in EAE and SCI. A small number of studies demonstrated the feasibility of DCE-computed tomography, ultrasound, bioluminescent, and fluorescent optical imaging methods to evaluate the BSCB. Technique-specific limitations and multiple protocols for image acquisition and data analyses are described for all techniques. There are few in vivo investigations of the BSCB. Additional studies are needed in less commonly studied spinal cord disorders, and to establish standardized protocols for data acquisition and analysis. Further development of techniques and multimodal approaches could overcome current imaging limitations to the spinal cord. These advancements might promote wider adoption of techniques, and can provide greater potential for clinical translation.


The Black Report and beyond: what are the issues?
This paper provides an overview of the Black Report, published in Britain in 1980. It outlines its place in the history of British concern about socio-economic differentials in death rates since the mid-19th century, and suggests continuities in suggested explanations for these, a particularly persistent thread being debates between environmentalists, hereditarians, and those emphasising personal ignorance or irresponsibility. It introduces a distinction between "hard" "soft" versions of the Black Report's four explanatory models for inequalities in health (artefact, selection, behavioural and materialist), points out that the working group rejected the "hard" rather than the "soft" versions of the first three and espoused the "soft" version of the last, and suggests that the rather polarised debate about these explanations that followed can be understood in the light of the contemporary political context and a tendency to confuse the "hard" and "soft" versions. Methodological and empirical developments since the report are summarised, attention being drawn to seven themes which raise important issues for future research: the ubiquity of socio-economic differentials across industrialised countries, continuing or increasing differentials, stepwise gradients, interest in psychosocial mechanisms, the hypothesis of biological programming in utero or infancy, controls for behaviour, and evaluations of interventions. The overall conclusion is that we need more detailed studies of the mechanisms which generate and maintain social inequalities in health, and of interventions to reduce such inequalities.


Apicobasal polarity controls lymphocyte adhesion to hepatic epithelial cells.
Loss of apicobasal polarity is a hallmark of epithelial pathologies. Leukocyte infiltration and crosstalk with dysfunctional epithelial barriers are crucial for the inflammatory response. Here, we show that apicobasal architecture regulates the adhesion between hepatic epithelial cells and lymphocytes. Polarized hepatocytes and epithelium from bile ducts segregate the intercellular adhesion molecule 1 (ICAM-1) adhesion receptor onto their apical, microvilli-rich membranes, which are less accessible by circulating immune cells. Upon cell depolarization, hepatic ICAM-1 becomes exposed and increases lymphocyte binding. Polarized hepatic cells prevent ICAM-1 exposure to lymphocytes by redirecting basolateral ICAM-1 to apical domains. Loss of ICAM-1 polarity occurs in human inflammatory liver diseases and can be induced by the inflammatory cytokine tumor necrosis factor alpha (TNF-α). We propose that adhesion receptor polarization is a parenchymal immune checkpoint that allows functional epithelium to hamper leukocyte binding. This contributes to the haptotactic guidance of leukocytes toward neighboring damaged or chronically inflamed epithelial cells that expose their adhesion machinery.


Ontogeny of insulin and glucagon receptors and the adenylate cyclase system in guinea pig liver.
To gain insight into the mechanisms responsible for the impaired glycogenolytic response to glucagon and the diminished ketogenic capacity of newborn guinea pig, we studied the ontogeny of insulin and glucagon receptors, and the responsiveness of the adenylate cyclase complex to glucagon, PGE1, NaF, and cholera toxin in liver plasma membrane from fetal (58 d, late gestation, and 65 d, term) and adult guinea pigs. The number of insulin receptors (x 10(-10) M/L) was least in 58-d fetus (3.0 +/- 0.4; mean +/- SEM) and increased 3-fold in 65 d fetus (8.8 +/- 0.6; P less than 0.01). In adult guinea pig, both insulin receptor number (6.0 +/- 0.7) and average affinity constant (1.20 +/- 0.08 x 10(8) M-1) were significantly lower (P less than 0.01) compared with 65-d fetus. The number of glucagon receptors remained unchanged between 58-d and 65-d fetuses, but both average and high affinity association constants were significantly higher at d 65. In contrast to the lower capacity and affinity of insulin receptors in the adult compared with term fetus, the total glucagon receptor number (x 10(-10) M/L) in adults (7.2 +/- 0.8) was twice that of the 58 d (3.2 +/- 0.2) and 65 d (3.2 +/- 1.0) fetuses. The average affinity constant (x 10(8) M-1) in adult (3.8 +/- 0.2) was, however, significantly lower than the two fetal groups (58 d, 5.0 +/- 0.3; P less than 0.05 and 65 d, 8.1 +/- 1.0; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetics (PK) of S/D treated anti-D immunoglobulin after intramuscular injection in healthy volunteers: gender differences in PK.
The aim of this study was to investigate the pharmacokinetic profile of the new solvent/detergent (S/D) formulation of an anti-D IgG preparation, and to evaluate gender differences. RhD-negative subjects (m/f=10/8) received a single i.m. injection of 250 microg anti-D (Partobulin SDF). There was a rapid increase in median anti-D titers over the first 2 days, followed by a plateau from days 2-7. Interestingly, women had a higher maximum concentration (Cmax) of anti-D and a lower volume of distribution at steady state (Vss) than men. The half-life calculated in this study was 23 days. Thus, results are comparable to published data of the non-S/D treated predecessor product. Because of the observed gender differences in the pharmacokinetics we recommend to pursue the evaluation of sex differences in the pharmacokinetics of other antibodies during early phase drug development.


Radial nerve palsy in humeral shaft fractures with internal fixation: analysis of management and outcome.
The incidence of radial nerve injury after humeral shaft fractures is on average 11.8% (Shao et al., J Bone Jt Surg Br 87(12):1647-1652, 2005) representing the most common peripheral nerve injury associated with long bone fractures (Korompilias et al., Injury, 2013). The purpose of this study was to analyze our current policy and long-term outcome, regarding surgically treated humeral shaft fractures in combination with radial nerve palsy. We retrospectively analyzed the data of patients with surgically treated humeral shaft fractures from 01/01/2003 to 28/02/2013. The analysis included fracture type, soft tissue injury regarding closed and open fractures, type of fixation, management, and outcome of radial nerve palsy. A total of 151 humeral shaft fractures were fixed in our hospital. In 20 (13%) cases, primary radial palsy was observed. Primary nerve exploration was performed in nine cases. Out of the 13 patients with follow-up, 10 showed a complete, 2 a partial, and 1 a minimal nerve recovery. Two of them underwent a revision procedure. Secondary radial nerve palsy occurred in 9 (6%) patients postoperatively. In five patients, the radial nerve was not exposed during the initial surgery and, therefore, underwent revision with nerve exploration. In all 5, a potential cause for the palsy was found and corrected as far as possible with full recovery in 3 and minimal recovery in one patient. In four patients with exposure of the nerve during the initial surgery, no revision was performed. All of these 4 showed a full recovery. Our study showed an overall rate of 19% radial nerve palsy in surgically treated humeral shaft fractures. Most of the primary palsies (13%) recovered spontaneously, and therefore, nerve exploration was only exceptionally needed. The incidence of secondary palsy after surgery (6%) was high and mainly seen after plate fixation. In these cases, we recommend early nerve exploration, to detect and treat potential curable neural lesions.


Glutamine Addiction In Gliomas.
Cancer cells develop and succeed by shifting to different metabolic programs compared with their normal cell counterparts. One of the classical hallmarks of cancer cells is their higher glycolysis rate and lactate production even in the presence of abundant O2 (Warburg effect). Another common metabolic feature of cancer cells is a high rate of glutamine (Gln) consumption normally exceeding their biosynthetic and energetic needs. The term Gln addiction is now widely used to reflect the strong dependence shown by most cancer cells for this essential nitrogen substrate after metabolic reprogramming. A Gln/glutamate (Glu) cycle occurs between host tissues and the tumor in order to maximize its growth and proliferation rates. The mechanistic basis for this deregulated tumor metabolism and how these changes are connected to oncogenic and tumor suppressor pathways are becoming increasingly understood. Based on these advances, new avenues of research have been initiated to find novel therapeutic targets and to explore strategies that interfere with glutamine metabolism as anticancer therapies. In this review, we provided an updated overview of glutamine addiction in glioma, the most prevalent type of brain tumor.


The substrate specificity of yeast hexokinase: reaction with D-arabinose oxime.
By chromatography, electrophoresis, n.m.r. spectroscopy, and spectrophotometric assay, it has been shown that D-arabinose oxime acts as a weak substrate for yeast hexokinase. The enzyme-catalysed phosphorylation of the oxime, which exists as a mixture of E (80%) and Z (20%) acyclic forms in solution at equilibrium, is proposed to proceed via the transient formation of a furanoid species. Weak substrate-activity was also observed with 4-deoxy-D-xylo-hexose, but not with 5-deoxy-D-xylohexose. The relation of these and previous results concerning the carbohydrate-substrate specificity of yeast hexokinase in solution to X-ray crystallographic studies is discussed.


Revisiting the issue of malignancy risk in systemic lupus erythematosus.
Certain cancers occur more frequently in systemic lupus erythematosus (SLE) as compared with the general population, as recent data substantiates. The risk appears to be most heightened for lymphoma. Several pathogenic mechanisms may explain these observations, although little is definitively known. One particular concern relates to whether cancer risk in SLE is increased by medication exposures. Cooperative efforts to evaluate this have been undertaken by the Systemic Lupus International Collaborating Clinics and the Canadian Network for Improved Outcomes in Systemic Lupus research groups. This and other works in progress will, it is hoped, considerably advance the knowledge regarding the association between autoimmune diseases and malignancy.


The fine structure of a parasitic ciliate Terebrospira during ingestion of the exoskeleton of a shrimp Palaemonetes.
The ciliated protozoan, Terebrospira chattoni, invades the exoskeleton of the shrimp, Palaemonetes pugio, eating out long galleries parallel to the surface of the exoskeleton. Solubilization of the exoskeleton occurs around an area of the elaborately infolded surface membrane at the anterior of the organism. Dissolved products of the digestion of the exoskeleton are taken into the body by the formation of coated vesicles at pores in the membrane. The surface membrane that is taken in by pinocytosis is apparently recycled by the introduction into the membrane of organelles implicated in membrane recycling in other ciliates. Acid phosphatase can be demonstrated on the surface membrane as well as in the endocuticle around the organism.


Clinical characteristics, outcome, and therapeutic effect of tafamidis in wild-type transthyretin amyloid cardiomyopathy.
Tafamidis improves prognosis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, real-world data on the therapeutic effect of tafamidis are lacking. This study aimed to evaluate the clinical course, outcomes, and effectivity monitoring of the therapeutic effect of tafamidis in patients with ATTR-CM. This is a single-centre, retrospective observational study. We evaluated the clinical characteristics and outcomes in 125 consecutive patients with wild-type ATTR-CM (ATTRwt-CM) treated with tafamidis (treatment group) and 55 untreated patients (treatment-naïve group). We monitored the therapeutic effect of tafamidis for 12 months by evaluating serial cardiac biomarker and imaging findings. The treatment group had significantly more favourable outcome in all-cause mortality and hospitalization due to heart failure than the treatment-naïve group in both the entire cohort (P < 0.01) and the propensity score-matched cohort (P < 0.05). Kaplan-Meier survival curves showed that tafamidis treatment significantly reduced all-cause mortality (P = 0.03, log-rank test), with the curves diverging after approximately 18 months of treatment in the propensity score-matched cohort. On inverse probability of treatment weighting analysis, tafamidis treatment showed a reduced all-cause mortality [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.11-0.93; P = 0.04]. High-sensitivity cardiac troponin T (hs-cTnT) > 0.05 ng/mL, B-type natriuretic peptide (BNP) > 250 pg/mL, and estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 scored 1 point each. Multivariate logistic regression analysis revealed that a high score (2-3 points) was a significantly poor prognostic factor of composite clinical outcomes, including all-cause death and hospitalization for heart failure (HR, 1.55; 95% CI, 1.22-1.98; P < 0.01) for patients in the treatment group. After 12 months of tafamidis treatment, hs-cTnT levels decreased significantly [0.054 (0.036-0.082) vs. 0.044 (0.033-0.076); P = 0.002], with no significant changes in BNP levels, echocardiographic parameters, native T1 value, and extracellular volume fraction on cardiac magnetic resonance imaging. The prognosis of patients with ATTRwt-CM treated with tafamidis was more favourable than that of untreated patients. Patient stratification combined with biomarkers (hs-cTnT, BNP, and eGFR) predicted clinical outcomes. hs-cTnT may be a useful biomarker for evaluating the therapeutic effect of tafamidis.


[Impact of frailty and other geriatric syndromes on the clinical management and prognosis of elderly ambulatory patients with heart failure. A prospective and multicentre study].
Heart failure (HF) is a chronic disease that is often associated with ageing. There are predictive models based on variables that associate it with a poor prognosis, although those do not include common conditions in the elderly, such as frailty or comorbidity. The aim of this study is to determine the clinical and epidemiological characteristics of a cohort of elderly outpatients with HF followed-up by cardiologists. This will include a study of the prevalence of frailty and other geriatric syndromes, as well as their impact on the prognosis, and to evaluate whether these may improve predictive ability of such predictive models. Observational, prospective, and multicentre study that will include 400 patients ≥75years old with chronic HF followed-up in Spanish tertiary hospitals by cardiology specialists in HF. Patients will undergo a comprehensive geriatric assessment, and prediction of events will be performed based on MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and Barcelona-Bio HF calculator scores. The primary endpoint is cardiovascular and overall mortality at 1 and 3years follow-up. This study will assess both the characteristics and prognosis of elderly patients with HF followed-up by cardiologists in Spain and the applicability in the elderly population of scores used in the general population with chronic HF. This is the first prospective study that will systematically assess frailty and other geriatric syndromes in the elderly outpatient with HF in Spain and followed-up by cardiologists, thus contributing to improve knowledge about both its prevalence and impact on our patients.


Operating without a safety net: gay male adolescents and emerging adults' experiences of marginalization and migration, and implications for theory of syndemic production of health disparities.
Health disparities among gay men (HIV, substance use, depression) have been described as a mutually occurring "syndemic" that is socially produced through two overarching dynamics: marginalization and migration. Although the syndemic theory proposes a developmental trajectory, it has been largely based on epidemiological studies of adult gay men and has not been examined using qualitative data from gay male adolescents and emerging adults describing their developmental experience. We conducted interviews with 54 HIV-positive gay and bisexual male adolescents and emerging adults at four sites in the United States. This study provides examples of developmental trajectories that help explain the early onset of socially produced health disparities among some gay male adolescents and emerging adults, but also the development of risk factors that may follow some gay men into adulthood.


The Dietary Inflammatory Index is positively associated with cardiometabolic risk parameters in atherosclerosis patients.
Inflammation is implicated in the development and progression of a variety of cardiovascular diseases. We hypothesized that the Dietary Inflammatory Index (DII) is associated with anthropometric indices and metabolic parameters in Iranian atherosclerosis patients. The present cross-sectional study was conducted on 320 Iranian atherosclerosis patients. The DII was estimated using a valid and reliable 168-item food frequency questionnaire. Odds ratios and 95% confidence intervals were evaluated for anthropometric indices and metabolic parameters according to the DII score. Linear regression was used to estimate the relationship between DII scores with atherosclerosis-related dependent variables. According to the continuous score of DII, there was no significant association between DII and odds of obesity, total cholesterol/high-density lipoprotein cholesterol ratio, and aspartate aminotransferase/alanine aminotransferase ratio in all 3 models (P ≥ .05). In linear regression analysis, we found a significant association between DII score and fasting blood sugar, lipid profile (except for high-density lipoprotein cholesterol), liver enzymes (except for alkaline phosphatase), and serum sodium in adjusted models (P < .05). In this study, patients with atherosclerosis consuming a pro-inflammatory diet was positively associated with fasting blood sugar, lipid, and liver enzymes measures. Future studies with prospective and interventional designs are required to clarify the association between this dietary index and cardiovascular disease risk factors among patients with atherosclerosis.


Monocyte-Derived Dendritic Cells (moDCs) Differentiate into Bcl6+ Mature moDCs to Promote Cyclic di-GMP Vaccine Adjuvant-Induced Memory TH Cells in the Lung.
Induction of lung mucosal immune responses is highly desirable for vaccines against respiratory infections. We recently showed that monocyte-derived dendritic cells (moDCs) are responsible for lung IgA induction. However, the dendritic cell subset inducing lung memory TH cells is unknown. In this study, using conditional knockout mice and adoptive cell transfer, we found that moDCs are essential for lung mucosal responses but are dispensable for systemic vaccine responses. Next, we showed that mucosal adjuvant cyclic di-GMP differentiated lung moDCs into Bcl6+ mature moDCs promoting lung memory TH cells, but they are dispensable for lung IgA production. Mechanistically, soluble TNF mediates the induction of lung Bcl6+ moDCs. Our study reveals the functional heterogeneity of lung moDCs during vaccination and paves the way for an moDC-targeting vaccine strategy to enhance immune responses on lung mucosa.


On the increasing role of older adolescents and younger adults during the SARS-CoV-2 epidemic in Mexico.
During the first months of the SARS-CoV-2 pandemic, Mexico implemented a national lockdown followed by post-lockdown mitigation. We used daily number of SARS-CoV-2-confirmed hospitalizations (by date of symptom onset) to assess the changes in the incidence of individuals between the age of 10-59 years during the epidemic in Mexico. For each age group g, we computed the proportion E(g) of individuals in that age group among all cases aged 10-59y during the early lockdown period (April 20-May 3, 2020), and the corresponding proportion L(g) during the late lockdown period (May 18-31, 2020) and post-lockdown mitigation (June 15-28, 2020). For each later period (late lockdown or post-lockdown), we computed the proportion ratios relative to the early lockdown period PR(g)=L(g)/E(g). For each pair of age groups g1,g2, PR(g1)> PR(g2) is interpreted as a relative increase in SARS-CoV-2 infections in the age group g1 compared to g2 for the late lockdown and post-lockdown periods vs. the early lockdown period. For the late lockdown period, the highest PR estimates belong to persons aged 15-19y (PR=1.69(95%CI(1.05, 2.72))) and 20-24y (PR=1.43(1.10,1.86)). For the post-lockdown period, the highest PR estimates were also in age groups 15-19y (PR=2.05(1.30, 3.24)) and 20-24y (PR=1.49(1.15,1.93)). These estimates were higher in persons 15-24y compared to those ≥30y. Our results suggest that adolescents and younger adults had an increased relative incidence during late lockdown and the post-lockdown mitigation periods. The role of these age groups during the epidemic should be considered when implementing future pandemic response efforts.


Obesity is associated with worse quality of life in women with gynecologic malignancies: an opportunity to improve patient-centered outcomes.
The objective of the current study was to evaluate the effect of obesity on pretreatment quality of life (QoL) in gynecologic oncology patients. The authors analyzed collected data from an institution-wide cohort study of women with gynecologic cancers enrolled from August 2012 to June 2013. The Functional Assessment of Cancer Therapy-General, site-specific symptom scales, and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) global mental and physical health tools were administered. Survey results were linked to clinical data abstracted from medical records (demographics and comorbid conditions). Bivariate tests and multivariate linear regression models were used to evaluate factors associated with QoL scores. A total of 182 women with ovarian, uterine, cervical, and vulvar/vaginal cancers were identified; of these, 152 (84%) were assessed before surgery. Mean body mass index was 33.5 kg/m(2) and race included white (120 patients [79%]), black (22 patients [15%]), and other (10 patients [6.5%]). A total of 98 patients (64.5%) were obese (body mass index ≥30). On multivariate analysis, subscales for functional (17 vs 19; P = .04), emotional (16 vs 19; P = .008), and social (22 vs 24; P = .02) well-being as well as overall Functional Assessment of Cancer Therapy-General scores (77 vs 86; P = .002) and Patient-Reported Outcomes Measurement Information System global physical health scores (45 vs 49; P = .003) were found to be significantly lower in obese versus nonobese patients. Before cancer treatment, obese patients with gynecologic malignancies appear to have worse baseline QoL than their normal-weight counterparts. Emerging models of QoL-based cancer outcome measures may disproportionately affect populations with a high obesity burden. The potential disparate impact of cancer therapy on longitudinal QoL in the obese versus nonobese patients needs to be evaluated.


Synthesis of 2-vinylbenzofurans via the copper-catalyzed multicomponent reactions involving an oxa-Michael/arylation/vinylation cascade.
2-Vinylbenzofurans have been synthesized via the copper-catalyzed one-pot, three-component reactions of o-iodophenols, in situ generated allenes, and dichloromethane. Cascade transformation of oxa-Michael addition, C-arylation, and sp(3)C-H/sp(3)C-Cl conversion-based vinylation has been involved in realizing the construction of this 2-vinylbenzofuran framework.


Influenza A H1N1 Virus 2009 Synthetic Hemagglutinin and Neuraminidase Peptides for Antibody Detection.
Influenza serologic diagnosis is mainly based on hemagglutination inhibition and microneutralization methods, both methods require handling living viruses under an enhanced biosafety level. The current study was performed for developing an ELISA using synthetic peptides to detect influenza A H1N1 virus 2009 specific antibodies in serum and saliva. Alignments were made with H1N1 hemagglutinin and neuraminidase (HA and NA, respectively) sequences; only conserved sites were used for antigenicity prediction. Two synthetic peptides were assayed; one of neuraminidase (NA15) and one of hemagglutinin (HA-15) and used in ELISA for detecting IgG and IgA antibodies. A cross-sectional study was performed in three municipalities of Mexico City, using negative samples collected before the 2009 influenza outbreak, samples of people who became ill during the outbreak, and samples of the participants in the epidemiological study with or without symptoms. The determination of serum IgG antibodies with both peptides allowed differentiating between the post outbreak groups with respect to all others. No differences were found in IgA determination in saliva against both peptides. The frequency of positive participants for NA-15 was 9.5 and 8.8% for HA-15 in serum IgG; whereas the frequency of positive participants for NA-15 was 11%, and for HA-15 was 8.6% for saliva IgA. Synthetic peptides of the neuraminidase and hemagglutinin proteins can be used in ELISA for the determination of IgG and IgA antibodies against the influenza A H1N1 virus 2009.


Erythrocyte sedimentation tests as an aid to diagnosis.
As part of a continuing series focusing on the way the work of clinical laboratories contributes to patient care, this article describes the ESR test, one of the oldest blood tests still performed in clinical laboratories. Consideration is given to the collection of blood for this commonly requested test and the way in which results are used in clinical practice.


Synovialization on second-look arthroscopy after anterior cruciate ligament reconstruction using Achilles allograft in active young men.
This study is to assess the relationship between clinical outcomes and the extent of synovialization through second-look arthroscopy for anterior cruciate ligament (ACL) reconstruction using Achilles allograft in active young men. Ninety-five subjects were diagnosed with ACL rupture and underwent reconstruction with Achilles allograft. Median age was 22 years old (range, 17-40). Mean period from injury to operation was 15.1 ± 18.2 weeks. Lysholm score, IKDC classification, range of motion (ROM) of knee, and side-to-side difference (SSD) in anterior instability were evaluated preoperatively and at the last follow-up. Tegner activity scale was evaluated before injury and at the final follow-up. The extent of synovialization of the graft was evaluated under second-look arthroscopy at least 1 year after surgery. Formation of the synovial membrane was divided into four groups-group 1 for 25% or less, group 2 for 25-50%, group 3 for 50-75%, and group 4 for more than 75%. Outcomes were compared between each group. Lysholm score and IKDC classification were improved after surgery (P < 0.05). Most subjects had full ROM at the final follow-up except three subjects that showed flexion deficit of 5 degrees or less. Mean SSD in anterior instability was 9.0 ± 2.1 mm preoperatively and 1.6 ± 2.0 mm at the final follow-up (P < 0.001). Median Tegner activity scale was 7 before injury and 7 at the final follow-up (P < 0.001). Twelve subjects were in group 1, 10 in group 2, 14 in group 3, and 59 in group 4. Clinical outcomes depending on the extent of synovialization of the grafts were different between each group (P < 0.05). The average period from injury to reconstruction in each group was significantly different (P < 0.001). Correlation coefficient between the period from injury to reconstruction and the extent of synovialization was -0.411 (P < 0.001). The extent of the synovialization is positively correlated with clinical outcomes and is negatively correlated with the period from injury to reconstruction.


Heterotopic triplet pregnancy: report of a patient with remnant tubal ectopic and intrauterine twin pregnancy after frozen-thawed embryo transfer.
A case of heterotopic triplet pregnancy after frozen-thawed embryo transfer is presented. The patient conceived after transfer of three frozen-thawed embryos at a fertility clinic where she had previously undergone laparoscopic left salpingectomy due to pyosalpinx. Approximately 4 weeks after the embryo transfer, she presented with a complaint of abnormal genital bleeding and was diagnosed by ultrasound as having a dichorionic twin pregnancy. One week later, she was referred to our hospital because of lower abdominal pain. Hematoperitoneum was suspected based on findings of low blood pressure and tachycardia. Diagnostic emergent laparoscopy demonstrated an ectopic pregnancy in the remnant isthmic portion of the left tube. Laparoscopic excision of the remnant fallopian tube was performed, but the procedure resulted in early-pregnancy loss of one of the twins. The risk of heterotopic pregnancy is not small under assisted reproductive technology. Attention should be paid to the risk of tubal pregnancy after transferring more than two embryos or controlled ovarian hyperstimulation, even after salpingectomy has been performed.


Comparison of PCR and serotyping of Group B Streptococcus in pregnant women: the Oslo GBS-study.
Streptococcus agalactiae (GBS) is a leading cause of invasive neonatal infection. Serotyping of GBS is important in following epidemiological trends and vaccine development. Capsular serotyping of GBS by latex agglutination has been the predominant typing method, but more recently capsular genotyping has been introduced as an alternative method. The purpose of this study was to compare the relative performance of these methods in a contemporary population of pregnant women. We typed isolates from an unselected population of 426 colonized women at delivery using latex agglutination and a combination of four PCR methods. Antibiotic resistance was tested in 449 isolates. Capsular genotyping gave a result in all except three of 426 isolates. Fifty-nine of 426 isolates could not be typed by latex agglutination. Agreement between serotyping and genotyping was shown in 303 (71.1%) of the isolates. 10.2% of the isolates were resistant to erythromycin, 9.6% to clindamycin, 76.6% to tetracycline and none to penicillin. In conclusion, a substantial proportion of the colonizing strains were non-typeable by serotyping, but typeable by genotyping. This suggests that a diagnostic genotyping strategy is preferable to serotyping of the GBS polysaccharide capsule in colonized, pregnant women.


Microfluidics-Based Blood Typing Devices: An In-Depth Overview.
Identification of correct blood types holds paramount importance in understanding the pathophysiological parameters of patients, therapeutic interventions, and blood transfusion. Considering the wide applications of blood typing, the requirement of centralized laboratory facilities is not well suited on many occasions. In this context, there has been a significant development of such blood typing devices on different microfluidic platforms. The advantages of these microfluidic devices offer easy, rapid test protocols, which could potentially be adapted in resource-limited settings and thereby can truly lead to the decentralization of testing facilities. The advantages of pump-free liquid transport (i.e., low power consumption) and biodegradability of paper substrates (e.g., reduction in medical wastes) make it a more preferred platform in comparison to other microfluidic devices. However, these devices are often coupled with some inherent challenges, which limit their potential to be used on a mass commercial scale. In this context, our Review offers a succinct summary of the recent development, especially to understand the importance of underlying facets for long-term sustainability. Our Review also delineates the role of integration with digital technologies to minimize errors in interpreting the readouts.


Microarray analysis of thioacetamide-treated type 1 diabetic rats.
It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.


Abiotic stress response in yeast and metal-binding ability of a type 2 metallothionein-like protein (PutMT2) from Puccinellia tenuiflora.
Metallothioneins are low-molecular weight and cysteine-rich metal-binding proteins that play predominant cellular roles in the scavenging of reactive oxygen species and in mediating metal metabolism. To evaluate the role of a type-2 metallothionein-like gene from Puccinellia tenuiflora (PutMT2), the gene was over-expressed in yeast, and growth was assessed under a variety of abiotic stress conditions including peroxide (H2O2), salinity (NaCl and NaHCO3), and metal stress. PutMT2 overexpression in yeast improved the tolerance of cells to H2O2, NaCl, NaHCO3, Zn(2+), Fe(2+), Fe(3+), Cd(2+), Cr(6+), and Ag(+), but increased the sensitivity of cells to Mn(2+), Co(2+), Cu(2+), and Ni(2+) compared with control cells. PutMT2 was then expressed in Escherichia coli BL21as a glutathione S-transferase (GST) fusion protein (GST-PutMT2), and the metal-binding ability of GST-PutMT2 was analyzed and compared with GST alone using inductively coupled plasma atomic emission spectroscopy. Results showed that PutMT2 could bind to Cr, Cd, Co, Ag, Ba, Pb, Mn, Zn, Fe, Cu, P, Al, and Mg, but not Ni and As. There was no evidence to suggest that PutMT2 exhibited a specific or selective binding tendency to any individual metal ion. PutMT2 protein bound to Zn, Na, and Cu in vivo, perhaps with the highest affinity for Cu. Taken together, our results suggest that PutMT2 protein could play an important role in improving metal tolerance by metal binding in yeast. However, additional studies are required to confirm these results and to clarify the function of PutMT2 in transgenic plants.


Serum nickel concentration in normal menstrual cycle and after combined contraceptive pill.
Serum nickel concentration in the different phases of the menstrual cycle and after use of a combined contraceptive pill (Anovlar) was determined by atomic absorption spectrophotometry. Twenty ovulating females had their serum nickel level measured on day 5 and on day 27 of their cycle. Forty females using Anovlar for 6 months and 40 females using it for more than 3 years had their serum nickel determined. The serum nickel concentration of the non-pill users was higher on day 5 (2.52 +/- 0.46 micrograms/L) than on day 27 (2.21 +/- 0.37 micrograms/L p less than 0.05). In long-term users, the serum nickel (0.98 +/- 0.38 microgram/L) was less than the short-term users (2.38 +/- 0.35 micrograms/L, p less than 0.01) and the non-users (p less than 0.01). There was a negative correlation between the duration of pill use and the serum nickel level (r = -0.44, p less than 0.01). The significance of the decreased serum nickel level with long-term pill use remains to be determined.


Assessing Private Sector Involvement in Health Care and Universal Health Coverage in Light of the Right to Health.
The goal of universal health coverage is to "ensure that all people obtain the health services they need without suffering financial hardship when paying for them." There are many connections between this goal and the state's legal obligation to realize the human right to health. In the context of this goal, it is important to assess private actors' involvement in the health sector. For example, private actors may not always have the incentives to deal with externalities that affect the availability, accessibility, acceptability, and quality of health care services; they may not be in a position to provide "public goods"; or they may operate under imperfect information. This paper sets out to answer the question, what legal human rights obligations do states have in terms of regulating private sector involvement in health care?


Estimation of genetic parameters for production and reproductive traits in Indian Karan-Fries cattle using multi-trait Bayesian approach.
Estimates of variance components are needed for implementing genetic selection. This study was conducted to genetic parameters for production and reproductive traits on Indian Karan-Fries cattle using multi-trait repeatability animal model. Data collected from ICAR-National Dairy Research Institute, Karnal, India (from 1988 to 2019) were used. Single-trait and multi-trait repeatability animal models were used for parameter estimation. The posterior mean of Heritability estimates for 305-day milk yield (305-DMY), lactation milk yield (LMY), lactation length (LL) were 0.20 ± 0.03, 0.19 ± 0.03 and 0.06 ± 0.02, respectively. For age at first calving (AFC), calving interval (CI), and days open (DO), the posterior mean of heritability estimates were 0.24 ± 0.08, 0.06 ± 0.01, and 0.07 ± 0.02, respectively. The repeatability estimates for 305-DMY, LMY, LL, CI, and DO were 0.37 ± 0.02, 0.34 ± 0.02, 0.15 ± 0.02, 0.09 ± 0.02, and 0.12 ± 0.02, respectively. Genetic correlation between milk production traits (305-DMY, LMY, and LL) was positive and strong (> 0.80). However, the genetic correlation between milk production trait and AFC ranges from - 0.31 to 0.12. Unfavorable strong genetic correlations were observed between production and reproductive traits (CI and DO) with values ranged from 0.5 to 0.7. Phenotypic correlations among 305-DMY, LMY, and LL were generally positive and high. The moderate heritability estimates and potential genetic variation for 305-DMY, TMY, and AFC suggested that genetic gain can be obtained for these traits through genetic selection. Low heritability estimates found for LL, CI and DO, indicating that the possibility of changing these traits through genetic selection is small. High genetic correlation observed between productive and fertility traits were unfavorable. The existed strong genetic and phenotypic correlation estimates between CI and DO indicates that recording only one of them would be sufficient in the herd. As the multi-trait model showed slight improvements in the h2 as well as r estimates for both productive and reproductive traits over univariate analysis, future selection with a multi-trait animal model applying Bayesian approach would be recommended.


Factors influencing murine embryo bioassay: effects of proteins, aging of medium, and surgical glove coatings.
The 2-cell murine embryo bioassay as quality control for human in vitro fertilization (IVF) was used to evaluate the effects of protein supplements, medium aging, and surgical glove coatings. Ham's F-10 medium (GIBCO, Grand Island, NY) without protein supplementation supported growth of the 2-cell embryos to blastocysts. Addition of bovine serum albumin (BSA), fetal cord serum (FCS), or maternal serum (MS) did not enhance or reduce the blastulation rates (medium alone, 89.4%; BSA, 86.4%; FCS, 90%; MS, 74.7%). Unsupplemented Ham's F-10 medium was found to contain three major peaks of approximately 50,000 daltons and several minor peaks, analyzed on high-performance liquid chromatography (HPLC) and sodium sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), suggesting the presence of protein(s) in the medium itself. The storing of medium up to 425 days at 4 degrees C affected neither the HPLC profile nor its ability to support embryo growth (blastulation rates: fresh, 84%; stored 150 to 425 days, 77.7%). The coating of surgical gloves affected embryo growth. Both talc-coated (TC) and "talc-free," starch-coated (SC) surgical gloves were found to be progressively embryotoxic when they touched the medium for increasing lengths of time, compared with uncoated latex (UL) gloves and untouched control medium. Quality control of medium preparation and handling in murine embryo bioassay is reemphasized, with requirements for protein supplementation, use of fresh medium, and possible contamination with even talc-free, SC surgical gloves reevaluated.


Simplified method for determination of protocollagen proline hydroxylase.
Preparation of (14C) Pro labeled protocollagen and requirements for its hydroxylation by PPH was investigated. Protocollagen can be prepared by centrifugation of the biological material at 15.000 X g. Substances in current use, viz catalase, bovine serum albumin and dithiothreitol were found unnecessary under the hydroxylation conditions used. A decrease in PPH in the testis and skin of rats with increasing age was demonstrated.


Endovascular aortic arch repair with chimney technique for pseudoaneurysm.
Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones. A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter. The median age of 32 patients was 68.0 years (range, 28-81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred. For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.


Investigating the dose-response effect in open-ended psychotherapy.
Findings from previous psychotherapy research suggest that the majority of improvement takes place in the initial phase of treatment with the relative effectiveness dropping at a negatively accelerating rate. However, the evidence for this pattern of change comes from investigations of short-term treatments and it is unclear whether this also holds for more flexible and long-term psychotherapy. We provided open-ended treatments under routine-care conditions for a representative sample of 362 patients, including a large proportion characterized by severe psychopathology. Patients attended 52 sessions on average (SD = 59, range = 1-364, Mdn = 36). Our results indicated that the degree of improvement was linearly associated with time spent in psychotherapy and contingent upon the severity of psychological problems at intake. The least severely afflicted received the shortest treatments, experienced the most rapid change but demonstrated smaller overall magnitudes of improvement. More severely suffering patients received longer treatments, had slower rates of change but in general received greater overall benefits. We argue that previous suggestions of psychotherapy dosage have been less appropriate for patients suffering from moderate to severe psychopathology.


Physiological characteristics of the primitive CO(2) concentrating mechanism in PEPC transgenic rice.
The relationship between carbon assimilation and high-level expression of the maize PEPC in PEPC transgenic rice was studied by comparison to that in the untransformed rice,japonica kitaake. Stomatal conductance and photosynthetic rates in PEPC transgenic rice were higher than those of untransformed rice, but the increase of stomatal conductance had no statistical correlation with that of photosynthetic rate. Under high levels of light intensity, the protein contents of PEPC and CA were increased significantly. Therefore the photosynthetic capacity was increased greatly (50%) with atmospheric CO(2) supply. While CO(2) release in leaf was reduced and the compensation point was lowered correspondingly under CO(2) free conditions. Treatment of the rice with the PEPC-specific inhibitor DCDP showed that overexpression of PEPC and enhancement of carbon assimilation were related to the stability of Fv/Fm. Labeling with(14)CO(2) for 20 s showed more(14)C was distributed to C(4) primary photosynthate asperate in PEPC transgenic rice, suggesting that there exists a limiting C(4) photosynthetic mechanism in leaves. These results suggest that the primitive CO(2) concentrating mechanism found in rice could be reproduced through metabolic engineering, and shed light on the physiological basis for transgenic breeding with high photosynthetic efficiency.


Multiple peer use of pivotal response training to increase social behaviors of classmates with autism: results from trained and untrained peers.
Two children with autism and 8 typical peers participated in a study designed to replicate an earlier finding of successful social-skills intervention for children with autism using peer-implemented pivotal response training (PRT) and to assess the effects of using multiple peer trainers on generalization of treatment effects. During training, peers were taught PRT strategies using didactic instruction, modeling, role playing, and feedback. After treatment, children with autism engaged in increased levels of social behavior.


Identification of knowledge gaps in neurosurgery through analysis of responses to the Self-Assessment in Neurological Surgery (SANS).
To examine the gaps in knowledge of neurosurgeons responding to the Self-Assessment in Neurological Surgery (SANS). From 2008-2010, 267 neurosurgery residents and 993 attending neurosurgeons completed the 245 available question in SANS. Mean scores were calculated and assessed according to 18 major neurosurgical knowledge disciplines. Statistical analysis was carried out to evaluate for knowledge gaps among all users and differences in performance between residents and practicing neurosurgeons. The mean overall score was 66% ± 12. Of the 18 major knowledge categories in SANS, respondents answered questions incorrectly ≥ 30% of the time in half of the categories. Mean scores in anatomy (76%) were the highest, and mean scores in vascular (60%) were the lowest (P < 0.001). The mean score per category was significantly higher for practicing neurosurgeons (71.5% ± 8.9) than residents (60.5% ± 12.6; P < 0.001). Residents answered questions incorrectly ≥ 30% of the time in all 18 categories versus 7 categories for attending neurosurgeons. Among residents, the highest mean scores were achieved in anatomy and the lowest were achieved in vascular (P < 0.001); this differential response was also reflected among attending neurosurgeons. SANS demonstrated areas of knowledge gaps in a broad group of neurosurgeons. There were also significant differences between residents and attending neurosurgeons. Identification of areas of deficiency could prove useful in future educational endeavors.


Low intensity ultrasound-mediated drug-loaded nanoparticles intravaginal drug delivery: an effective synergistic therapy scheme for treatment of vulvovaginal candidiasis.
Vulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC. Polymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm2, 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo. The prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels. US-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis.


Application of Novel Breast Biospecimen Cell-Type Adjustment Identifies Shared DNA Methylation Alterations in Breast Tissue and Milk with Breast Cancer-Risk Factors.
DNA methylation patterning is cell-type-specific and altered DNA methylation is well established to occur early in breast carcinogenesis, affecting non-cancerous, histopathologically normal breast tissue. Previous work assessing risk factor-associated alterations to DNA methylation in breast tissue has been limited, with even less published research in breast milk, a noninvasively obtained biospecimen containing sloughed mammary epithelial cells that may identify early alterations indicative of cancer risk. Here, we present a novel library for the estimation of the cellular composition of breast tissue and milk and subsequent assessment of cell-type-independent alterations to DNA methylation associated with established breast cancer-risk factors in solid breast tissue (n = 95) and breast milk (n = 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array. We identified 772 hypermethylated CpGs (P < 0.01) associated with age consistent between breast tissue and breast milk samples. Age-associated hypermethylated CpG loci were significantly enriched for CpG island shore regions known to be important for regulating gene expression. Among the overlapping hypermethylated loci mapping to genes, a differentially methylated region was identified in the promoter region of SFRP2, a gene observed to undergo promoter hypermethylation in breast cancer. Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens. This work demonstrates the potential of using breast milk as a noninvasive biomarker of breast cancer risk, improving our ability to detect early-stage disease and lowering the overall disease burden.


A retrospective study of drug related problems and contributing factors among type 2 diabetes mellitus patients on follow up at public health institutions of kemisse town, north east Ethiopia.
Drug related problems interfere with the desired treatment outcomes of type 2 Diabetes mellitus. This study was conducted to determine prevalence of drug related problems and associated factors among patients with type 2 Diabetes Mellitus in public health institutions of Kemisse town, northeast Ethiopia from May 01 to 30, 2019. Institution based retrospective cross sectional study was conducted among type 2 Diabetes Mellitus patents on follow up at public health institutions of Kemisse town, northeast Ethiopia. From the total of 156 patients included in the study, 126 (80.8%) patients have at least one drug related problem with a total of 149 drug related problems. The most prevalent drug related problems were need for additional drug therapy 60 (40.3%) followed by non-compliance 51 (34.2%) and unnecessary drug therapy 12 (8%). Identified causes of need for additional drug therapy were the need for prophylactic drug therapy (statins and antiplatelet), 83.3%; presence of untreated medical condition (Hypertension, diabetic nephropathy and diabetic foot ulcer), 11.7%; and the need for combination therapy for better efficacy, 5%. This study revealed that age ≥45 years (AOR = 5.59, 95% CI = 1.38-20.64, P = 0.016), presence of comorbid condition (AOR = 3.22, 95% CI = 1.75-13.47, P = 0.014 and emergency visit in the last one year (AOR = 5.08, 95% CI = 1.14-18.71, P = 0.033) were significantly associated with the occurrence of drug related problems. A total of 149 drug related problems were identified in 80.8% of type 2 diabetes mellitus patients. The three most prevalent drug related problems were need for additional drug therapy 60 (40.3%) followed by non-compliance 51 (34.2%) and unnecessary drug therapy 12 (8%). Additionally, age ≥45 years (AOR = 5.59, P = 0.016), presence of comorbidity (AOR = 3.22, P = 0.014) and emergency visit in the last one year (AOR = 5.08, P = 0.033) were significantly associated with the occurrence of drug related problem.


Is weight status associated with peripheral levels of oxytocin? A pilot study in healthy women.
The neuropeptide oxytocin is best known for its role during parturition and the milk-let down reflex. Recent evidence identifies a role for oxytocin in eating behaviour. After oxytocin administration, caloric intake is reduced with stronger inhibitory effects in individuals with obesity. Whether the experience of visual food cues affects secretion or circulating levels of oxytocin is unknown. This pilot study had three aims: 1) to measure fasting appetite hormones with a focus on plasma oxytocin concentrations; 2) determine whether healthy vs. hyperpalatable visual food cues differentially altered plasma oxytocin; and 3) assess whether appetite hormone responses to healthy vs. hyperpalatable food images depended on weight or food addiction status. Eighteen healthy women of varying weight status, with/without self-reported food addiction were recruited. Study participants completed a set of standardised questionnaires, including Yale Food Addiction Scale, and attended a one-off experimental session. Blood was collected before and after viewing two sets of food images (healthy and hyperpalatable foods). Participants were randomly allocated in a crossover design to view either healthy images or hyperpalatable foods first. A positive correlation between BMI and plasma oxytocin was found (r2 = 0.32, p = 0.021) at baseline. Oxytocin levels were higher, and cholecystokinin levels lower, in food addicted (n = 6) vs. non-food addicted females (p = 0.015 and p<0.001, respectively). There were no significant changes (p>0.05) in plasma oxytocin levels in response to either healthy or hyperpalatable food images. Given that endogenous oxytocin administration tends to suppress eating behaviour; these data indicate that oxytocin receptor desensitization or oxytocin resistance may be important factors in the pathogenesis of obesity and food addiction. However, further studies in larger samples are needed to determine if peripheral oxytocin is responsive to visual food cues.


Care of the Patient With IBD Requiring Hospitalisation During the COVID-19 Pandemic.
The management of IBD has been highly affected in the context of the COVID-19 pandemic, with restriction of hospitalisations and unprecedented redeployment of health care resources. Hospital admissions of IBD patients should be limited to reduce the risks of coronavirus transmission. However, delaying hospitalisation of IBD patients with severe or complicated disease may increase the risk of poor outcomes. Delaying surgery in some cases may increase the risk of disease progression, postoperative morbidity, and disease complications. IBD patients who are infected with SARS-CoV-2 may have a higher risk of poor outcomes than the general population, potentially related to concomitant medications, especially corticosteroids. There is no evidence today that IBD patients with COVID-19 have worse outcomes if they receive immunosuppressant medications including thiopurines, biologics, and novel small molecules. This article summarises recommendations by the international membership of IOIBD regarding hospitalisations of IBD patients, either for active or complicated IBD or for severe COVID-19, and for management of IBD patients according to SARS-CoV-2 infectious status.


Effect of docetaxel on mechanical properties of ovarian cancer cells.
Docetaxel could inhibit the proliferation of tumor cells by targeting microtubules. The extension of cellular microtubules plays an important role in the invasion and metastasis of tumor cells. This paper aims to study the distribution and mechanical properties of cytoskeletal proteins with low concentration of docetaxel. MTT assay was used to detect the minimum drug activity concentration of docetaxel on SKOV-3 cells, fluorescence staining was used to analyze the distribution of cytoskeleton proteins, scanning electron microscopy(SEM) was used to observe the morphology of single cells, and atomic force microscopy(AFM) was used to determine the microstructure and mechanical properties of cells. The results showed that the IC10 of docetaxel was 1 ng/ml. Docetaxel can effectively inhibit the formation of cell pseudopodia, hinder the indirectness between cells, reduce the cell extension area, and make the cells malformed. In addition, when AFM analyzes the effects of drugs on cell microstructure and mechanical properties, the average cell surface roughness and cell height are positively correlated with the concentration of docetaxel. Especially when the concentration was 100 ng/ml, the adhesion decreased by 37.04% and Young's modulus increased by 1.57 times compared with the control group. This may be because docetaxel leads to microtubule remodeling and membrane protein aggregation, which affects cell microstructure and increases cell strength, leading to significant changes in the mechanical properties of ovarian cells. This is of great significance to the study of the formation mechanism of tumor cell invasion and migration activities mediated by actin.


Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.
Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.


Can we define ecosystems? On the confusion between definition and description of ecological concepts.
Sound definitions of its basic concepts are fundamental to every scientific discipline. In some instances, like in the case of the ecosystem concept, the question arises if we can define such concepts at all. And if we can define them, how should we choose from the multiple definitions available? And what are the preconditions for a scientifically sound and useful definition? On the basis of the ecosystem concept, this paper illustrates a major, often neglected distinction in the definition of ecological concepts, namely that between defining criteria and additional descriptive statements connected to those definitions. As is demonstrated by examples from the literature, mixing up these categories leads to false inferences about the properties of physical objects (e.g. a particular forest) subsumed by the concept (e.g. the ecosystem). As a further consequence, this inference becomes problematic in terms of theory development and/or the application of ecological concepts for management decisions.


Adenocarcinoma in a Koff Urinary Ileal Diversion.
The use of an ileal conduit as a means of treatment for bladder cancer or dysfunction is widely used and understood. However, long term surveillance of that conduit has not been strongly established and set forth as a means of screening. We present a 76yo female with a history of neurogenic bladder secondary to paraplegia who underwent the formation of a "Koff" pouch as a conduit. Nineteen years later she presents with hematuria and was found to have adenocarcinoma originating in her conduit.


Management strategies and floristic diversity in agroforestry practices of northwestern Ethiopia.
Agroforestry has been recognized as an effective circa citum conservation strategy in Ethiopia. Despite progress in the recent past, there has been very little research characterizing the management strategies of farmers for agroforestry practices (AFP) and quantifying their contribution to biodiversity conservation. We (i) characterized the management strategies of farmers for agroforestry practices and (ii) assessed the floristic composition, diversity, and structure of woody species in agroforestry practices in Northwestern Ethiopia. We interviewed farm owners to gather information on the management strategies of agroforestry practices. We also collected biophysical data using quadrats established in 126 fields selected from homegardens (HG), coffee-based (CS), and Rhamnus prinoides (Locally Gesho)-based practices. A total of 83 trees and shrubs (76 % native and 24 % non-native) from 40 families and 47 genera recorded in the study area. The results indicate that AFPs represent diverse vertical and horizontal management strategies, and plant functions, which vary among AFPs and wealth status. The results suggest the potential of agroforestry practices for supporting livelihoods and biodiversity conservation. Farmers' management practices and strategies affect the species diversity of AFPs. The mean height (m), basal area (m2 ha-1), and diameter at breast height (cm) varied among AFPs. The average stem density ha-1 as well as species richness per farm significantly varied among AFPs and wealth status. Richness, Shannon, and Simpson's diversity varied among HGs in the study sites. In the Lay Armachiho district, species richness, Shannon, and Simpson's diversity significantly varied (P < 0.05) among agroforestry practices. Our study suggests management strategies and household wealth status that affect the diversity of woody plants in AFPs should be consider to improve biodiversity conservation in agricultural landscapes. Since AFPs play a vital role in biodiversity conservation that is part of a bigger conservation strategy, the suggestion of AFPs to apply in Ethiopia is proposed. To advance the overall contribution, further studies on the optimization of technical, socio-economic and environmental (including density and diversity) performance of agroforestry practices is needed.


In vitro and in vivo anthelmintic study of Sesbania sesban var. bicolor, a traditionally used medicinal plant of Santhal tribe in Assam, India.
The leaf decoction of Sesbania sesban var. bicolor is used traditionally by Santhal tribe of Assam, India, for the treatment of intestinal helminthic infections. This study was conducted to evaluate the in vitro and in vivo anthelmintic efficacy of methanolic extract of S. sesban var. bicolor leaves using Hymenolepis diminuta-rat (cestode) and Syphacia obvelata-mice (nematode) as test parasites and models. Praziquantel (PZQ) and albendazole (ABZ) were used as reference drugs. At the highest concentration of 30 mg/ml of the plant extract, H. diminuta and S. obvelata showed mortality at 0.81 ± 0.01 h and 15.17 ± 0.05 h, respectively. The in vivo results substantiated the in vitro findings, and the extract showed a better cestocidal efficacy in a dose-dependent manner, whereby treatment of rats with 400 mg/kg of the plant extract caused 65.10% reduction in eggs per gram (EPG) of faeces and 56% reduction in worm counts. S. obvelata-infected mice treated at the same dose showed 34.32% and 47.08% reduction in EPG and worm counts at necropsy, respectively. The methanolic extract was subjected to bioassay-guided fractionation using different solvents and the ethyl acetate fraction proved to be the most active. This active fraction was subjected to column chromatography using varying concentrations of hexane:ethyl acetate. Maximum efficacy was observed in 7:3 hexane:ethyl acetate, where H. diminuta and S. obvelata showed mortality at 3.56 ± 0.12 h and 9.21 ± 0.02 h, respectively. This indicates that the isolated fraction contained the active component responsible for its anthelmintic activity, which substantiates the medicinal usage in traditional practice.


Impact of age on long-term complications after biliopancreatic diversion.
The aim of the study is to evaluate the importance of age on the mid- and long-term results and complications after biliopancreatic diversion (BPD). Our study comprises 132 morbidly obese patients who underwent Scopinaro BPD from February 1995 to April 2001, with follow-up from 24 to 96 months. The patients, 53 males (40%) and 79 females (60%), with mean preoperative BMI 50.2 (35.4-81.5), and mean age 42 (20-65), were divided in 4 groups. Group A age 20-35, 43 patients; Group B age 36-45, 33 patients; Group C age 46-55, 31 patients and Group D age >55, 25 patients. Incidence of long-term specific complications after BPD were analyzed, including protein malnutrition, reversals, anastomotic ulcer, and incisional hernia. Mean postoperative BMI was similar in all Groups. After 60 months the following BMI values were observed. Group A 30.8, Group B 34.9, Group C 35.9, Group D 32. Incidence of long-term complications were not significantly different (chi(2)) in the 4 Groups, and were respectively: protein malnutrition 6.9%, 12.1%, 6.4%, 16.0%; anastomotic ulcer 11.6%, 9%, 6.4%, 16.0%; reversal 2.3%, 9.0%, 1.32%, 8.0%; ventral hernia 34.8%, 45.4%, 54.8%, 32.0%. From the preliminary results, it appeared that the incidence of the complications was higher in group D (>55 years old), whereas group C (46-55 years old) showed a lower complication rate. However, the prevalence of complications in all groups was not statistically different on chi(2) analysis. No age limit for bariatric surgery could be determined from the age ranges studied.


Shoulder Latarjet Surgery Shows Wide Variation in Reported Indications, Techniques, Perioperative Treatment, and Definition of Outcomes, Complications, and Failure: A Systematic Review.
To systematically review and compare the surgical indications, technique, perioperative treatment, outcomes measures, and how recurrence of instability was reported and defined after coracoid transfer procedures. A systematic review of the literature examining open coracoid transfer outcomes was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the Cochrane registry, MEDLINE, and EMBASE databases from 2010 to 2020. Inclusion criteria included open coracoid transfer techniques, including the Bristow or Latarjet technique, full text availability, human studies, and English language. A screen of 1,096 coracoid transfer studies yielded 72 studies, which met inclusion criteria with a total of 4,312 shoulders. One study was a randomized controlled trial, but the majority of them were retrospective. Of those, 65 studies reported on postoperative outcome scores, complication rates, revision rate, and recurrence rates. Forty-three reported on range of motion results. Thirty studies reported on primary coracoid transfer only, 7 on revision only, and 30 on both primary and revision, with 5 not reporting. Average follow-up was 26.9 months (range: 1-316.8 months). Indications for coracoid transfer, technique, perioperative care, complications, and how failure was reported varied greatly among studies. Latarjet and coracoid transfer surgery varies greatly in its indications, technique, and postoperative care. Further, there is great variation in reporting of complications, as well as recurrence and failure and how it is defined. Although coracoid transfer is a successful treatment with a long history, greater consistency regarding these factors is essential for appropriate patient education and surgeon knowledge. Level IV, systematic review of Level I-IV studies.


Prospects and Clinical Perspectives of Total-Body PET Imaging Using Plastic Scintillators.
Total-body PET opens a new diagnostic paradigm with prospects for personalized disease treatment, yet the high cost of the current crystal-based PET technology limits dissemination of total-body PET in hospitals and even in research clinics. The J-PET tomography system is based on axially arranged low-cost plastic scintillator strips. It constitutes a realistic cost-effective solution of a total-body PET for broad clinical applications. High sensitivity of total-body J-PET and triggerless data acquisition enable multiphoton imaging, opening possibilities for multitracer and positronium imaging, thus promising quantitative enhancement of specificity in cancer and inflammatory disease assessment.


Respiratory rhythm and pattern generation: Brainstem cellular and circuit mechanisms.
Breathing movements in mammals are driven by rhythmic neural activity automatically generated within spatially and functionally organized brainstem neural circuits comprising the respiratory central pattern generator (CPG). This chapter reviews up-to-date experimental information and theoretical studies of the cellular and circuit mechanisms of respiratory rhythm and pattern generation operating within critical components of this CPG in the lower brainstem. Over the past several decades, there have been substantial advances in delineating the spatial architecture of essential medullary regions and their regional cellular and circuit properties required to understand rhythm and pattern generation mechanisms. A fundamental concept is that the circuits in these regions have rhythm-generating capabilities at multiple cellular and circuit organization levels. The regional cellular properties, circuit organization, and control mechanisms allow flexible expression of neural activity patterns for a repertoire of respiratory behaviors under various physiologic conditions that are dictated by requirements for homeostatic regulation and behavioral integration. Many mechanistic insights have been provided by computational modeling studies driven by experimental results and have advanced understanding in the field. These conceptual and theoretical developments are discussed.


Biological synthesis, characterization of three metal-based nanoparticles and their anticancer activities against hepatocellular carcinoma HepG2 cells.
Treatment of liver cancer has always been a challenge for clinicians and development of appropriate drug against hepatocellular carcinoma is the major focus for researchers working in the field. The synthesis of metal-based nanoparticles (NPs) by green method for pharmacological uses has attained considerable attention recently. In current study three different NPs (AgO2, CeO2, CuO2) were synthesized by using Trianthima portulacastrum and Chinopodium quinoa leaf extracts. These biogenic NPs were analyzed by High-tech. approaches including Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray (EDX) spectroscope, SEM-EDS spot analysis, elemental mapping and X-ray diffraction (XRD). The anticancer potential of these nanoparticles was estimated using MTT assay, against hepatic cancer cell line (HepG2). SEM secondary electron images presented the nano size of prepared particles in agglomerated form with few porous forms. Average size of Ag-, Ce-, and CuNPs was observed 19-24 nm, 8-12 nm, 13-15 nm respectively. Elemental mapping and EDS-spot analysis ratifies the formation of AgNPs, CeNPs, and CuNPs. These NPs have shown good anticancer activity at different concentrations against HepG2 cell line. Further studies are however needed to identify the molecular mechanisms of these anticancer activities.


Value of CXCL8-CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study.
In this study we investigate the prediction and prognostic value of CXCL8-CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2- patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900-0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933-4.949; CXCR1/2++, HR 3.466, 95% CI 1.569-7.655, CXCR1/2- was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome. This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8-CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.


α2δ-1 protein promotes synaptic expression of Ca2+ permeable-AMPA receptors by inhibiting GluA1/GluA2 heteromeric assembly in the hypothalamus in hypertension.
Glutamate AMPA receptors (AMPARs) lacking GluA2 subunit are calcium permeable (CP-AMPARs), which are increased in the hypothalamic paraventricular nucleus (PVN) and maintain sympathetic outflow in hypertension. Here, we determined the role of α2δ-1, an NMDA receptor-interacting protein, in regulating synaptic CP-AMPARs in the hypothalamus in spontaneously hypertensive rats (SHR). Co-immunoprecipitation showed that levels of GluA1/GluA2, but not GluA2/GluA3, protein complexes in hypothalamic synaptosomes were reduced in SHR compared with Wistar-Kyoto rats (WKY). The level of GluA1/GluA2 heteromers in endoplasmic reticulum-enriched fractions of the hypothalamus was significantly lower in SHR than in WKY, which was restored by inhibiting α2δ-1 with gabapentin. Gabapentin also switched AMPAR-mediated excitatory postsynaptic currents (AMPAR-EPSCs) from inward rectifying to linear and attenuated the inhibitory effect of IEM-1460, a selective CP-AMPAR blocker, on AMPAR-EPSCs in spinally projecting PVN neurons in SHR. Furthermore, co-immunoprecipitation revealed that α2δ-1 directly interacted with GluA1 and GluA2 in the hypothalamus of rats and humans. Levels of α2δ-1/GluA1 and α2δ-1/GluA2 protein complexes in the hypothalamus were significantly greater in SHR than in WKY. Disrupting the α2δ-1-AMPAR interaction with an α2δ-1 C terminus peptide normalized GluA1/GluA2 heteromers in the endoplasmic reticulum of the hypothalamus diminished in SHR. In addition, α2δ-1 C terminus peptide diminished inward rectification of AMPAR-EPSCs and the inhibitory effect of IEM-1460 on AMPAR-EPSCs of PVN neurons in SHR. Thus, α2δ-1 augments synaptic CP-AMPARs by inhibiting GluA1/GluA2 heteromeric assembly in the hypothalamus in hypertension. These findings extend our understanding of the molecular basis of sustained sympathetic outflow in neurogenic hypertension.


Addressing voltage decay in Li-rich cathodes by broadening the gap between metallic and anionic bands.
Oxygen release and irreversible cation migration are the main causes of voltage fade in Li-rich transition metal oxide cathode. But their correlation is not very clear and voltage decay is still a bottleneck. Herein, we modulate the oxygen anionic redox chemistry by constructing Li2ZrO3 slabs into Li2MnO3 domain in Li1.21Ni0.28Mn0.51O2, which induces the lattice strain, tunes the chemical environment for redox-active oxygen and enlarges the gap between metallic and anionic bands. This modulation expands the region in which lattice oxygen contributes capacity by oxidation to oxygen holes and relieves the charge transfer from anionic band to antibonding metal-oxygen band under a deep delithiation. This restrains cation reduction, metal-oxygen bond fracture, and the formation of localized O2 molecule, which fundamentally inhibits lattice oxygen escape and cation migration. The modulated cathode demonstrates a low voltage decay rate (0.45 millivolt per cycle) and a long cyclic stability.


Using big data to gauge effectiveness of breast cancer awareness month.
Breast Cancer Awareness Month (BCAM) has been used for decades to increase awareness and screening for breast cancer, but its geographic reach and effectiveness is difficult to judge. Using Internet Search Interest (ISI) could allow for better evaluation of BCAM effects. Using Google Trends, we evaluated the ISI for "breast cancer" and "mammogram" for each state and metropolitan area from 2006 to 2019. The ISI represents population level Google internet searches relative to the highest number of searches for the United States over a given period, with a max number of 100. The ISI for each term in October (BCAM) was compared against all other months during this period, across states and across major metropolitan regions. ISI was 2.34 times higher (95% Confidence Interval [CI]: 2.10-2.61, P < .001) in BCAM than the average for all other months combined. Geographically categorized data revealed that there were significant differences in the ISI for "breast cancer" and for "mammogram" among the 50 states, and among major metropolitan areas (P < .001for each). ISI suggests that BCAM is effective at increasing breast cancer related internet searches, with significant heterogeneity across states and metro areas. Google Trends is a publicly available free tool that can be used to assess penetrance of awareness campaigns in a time sensitive and location specific manner for future targeting of populations with low breast cancer awareness. Future research is needed to assess relationships between preventive outcomes and ISI scores.


Responding to the "unknown assailant": A qualitative exploration with Australian health and aged care chaplains on the impact of COVID-19.
The global coronavirus pandemic (COVID-19) has brought about physical, psychological and spiritual challenges within health and aged care services across Australia. The aim of this study was to consider the impact of COVID-19 from the perspective of Australian chaplains. Semi-structured interviews were conducted with 17 chaplains. A grounded theory analysis identified three overarching themes: (1) a changing healthcare environment; (2) the impact of the virus; and (3) chaplains responding to the crisis. Increased healthcare restrictions in response to COVID-19 raised levels of fear and anxiety among patients, residents, family members and staff, and generated feelings of isolation and disconnection. Chaplains responded by providing a calm presence, being available, holding out hope, introducing creative ways to provide spiritual care and seeking spiritual nourishment themselves. The value of chaplaincy in health and aged care services is discussed in light of these findings.


Re-irradiation tolerance of rat spinal cord to fractionated X-ray doses.
Experiments were performed to assess the re-irradiation fractionation sensitivity in the rat cervical spinal cord. Animals were given initially three daily fractions of 9 Gy representing 75% of tolerance at the ED50 level. After an interval of 20 weeks, they were re-irradiated with graded doses of X-ray in single, 2, 5, 10 and 20 daily fractions, or a single retreatment top-up dose of 12.8 Gy (equivalent to 80% of retreatment tolerance) followed by doses in 1, 2, 4, 10 and 20 daily fractions. The end-point was paralysis of the forelimbs secondary to white matter necrosis. Latent periods to paralysis ranged from 188 to 245 days from initial irradiation, or from 48 to 105 days from re-irradiation. For a given fractionated retreatment schedule, shorter latent times were observed in animals re-irradiated to higher total doses. The re-irradiation ED50 values for single, 2, 5, 10 and 20 fractions were 14.0 (95% CI 13.3, 14.2), 20.5 (19.9, 21.2), 29.1 (28.0, 30.1), 36.3 (35.1, 37.4) and 47.8 Gy (46.2, 48.3), respectively. For re-irradiations with a 12.8 Gy top-up dose followed by doses in single, 2, 4 and 20 fractions, the retreatment ED50 values excluding the 12.8 Gy top-up dose were 4.5 (95% CI 3.0, 5.4), 6.5 (5.6, 7.3), 7.0 (5.0, 8.1) and 10.9 Gy (8.9, 12.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Percutaneous endoscopic stomas.
Percutaneous endoscopic gastrostomy was introduced in 1980 as a method for the creation of a feeding gastrostomy without the need for laparotomy or general anesthesia. The technique originally described, the pull method, involves puncturing the apposed gastric and abdominal walls under endoscopic control. A suture is then passed from the exterior into the gastric lumen and grasped with a snare. The suture is pulled out of the mouth, affixed to the end of a gastrostomy tube, and then pulled back down into the stomach. The gastrostomy tube is thus pulled into the stomach, and its end exits the abdominal wall. Modifications of this technique have included pushing the gastrostomy tube over a guidewire (the push method) and direct puncture of the stomach under endoscopic control with an introducer and outer peel-away sheath. All of these methods have been used with good results. Complications have included infection of the abdominal wall and intraperitoneal leakage. These may be minimized by attention to detail. The indications for the method have been expanded to include gastric decompression, administration of unpalatable medications in children, and creation of a conduit for bile replacement. Careful judgment in patient selection is crucial if good results are to obtained. This technique also introduces the concept of percutaneous endoscopic fixation of a loop of bowel to the abdominal wall. This concept may be employed in other areas of the gastrointestinal tract.


Pathomechanism of iris sphincter tear.
Traumatic iris sphincter tear has been thought to occur secondary to anteroposterior compression of the globe with defined forces lead to equatorial expansion and active pull along the corneoscleral junction and sphincter tear. However, here in this report, we elaborate the additional forces involved in the traumatic rupture of the sphincter pupillae muscle. During the anteroposterior compressive forces along the globe, the corneal deformation beyond certain limits leads to the development of sudden displacement forces within the anterior chamber. Aqueous within it which is incontinuous circulation with a posterior narrow pupillary aperture as its entrance, find the path of least resistance that is along the pupillary orifices leading to anexpulsive drive to displace the fluid through this small aperture. During this process, the horizontally oriented mechanical stretching forces appear to be the main cause ofpupillary sphincter tear.


An Iridium/Aluminum Cooperative Strategy for the β-C(sp3 )-H Borylation of Saturated Cyclic Amines.
Despite the widespread success in the functionalization of C(sp2 )-H bonds, the deliberate functionalization of C(sp3 )-H bonds in a highly site- and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the β-selective C-H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol-derived chiral aluminum catalysts to forge C-B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate-determining reductive elimination step.


White muscle disease of foals.
White muscle disease (nutritional myodegeneration) of foals is a peracute to subacute myodegenerative disease affecting skeletal and cardiac muscle. It is caused by a dietary deficiency of selenium and vitamin E, usually in association with predisposing factors such as a high intake of dietary unsaturated fats or unaccustomed exercise. White muscle disease has been observed in foals from birth to 1 year of age, particularly those foals born to dams fed selenium-deficient diets, during gestation. The disease in foals may present as an acute, fulminant syndrome, which is rapidly fatal, or a subacute syndrome characterized by profound muscular weakness. Failure of passive transfer, aspiration pneumonia, and stunting are frequent complications. Markedly increased muscle enzyme and low glutathione peroxidase activities are common findings in affected foals. Foals with the subacute form of the disease may survive if they are supplemented early with selenium; however, mortality rates ranging from 30% to 45% have been reported, even for this form of the disease.


Identification and characterization of a circulating tumor-associated oncofetal protein from a radiation-induced adenocarcinoma of the rat small bowel.
A tumor-associated protein from the cellular membranes of a radiation-induced rat small bowel adenocarcinoma was identified, found to be serologically unaltered in the circulatory system, and was observed to be susceptible to acid hydrolysis. The immunochemical reactivity was unchanged by heat, alkali, or neuraminidase digestion. The protein appeared to be a single immunologically active species, but it was structurally composed of a heterogeneous group of proteins.