The study of association of Vitamin B12 deficiency in type 2 diabetes mellitus with and without diabetic nephropathy in North Indian Population.
Diabetic Mellitus is the chronic metabolic disorder associated with various complications of heart, eyes, nerves, kidney etc. Diabetic Nephropathy is one of the leading causes of death in diabetic patient. We hypothesized that decrease Vitamin B12 levels is associated with Diabetic Nephropathy. Aim of our study is to study the serum Vitamin B12 levels in type 2 diabetes mellitus patients with and without nephropathy. Our study population consist of 100 subjects out of which 50 cases of Diabetes Mellitus without Diabetic Nephropathy and 50 cases of Diabetes Mellitus with Diabetic Nephropathy. We measured various routine lab parameters, apart from it, we measured spot urinary albumin to creatinine ratio to assess diabetic nephropathy and in special investigation we measured serum Vitamin B12 by chemiluminesence based immunoassay. Serum Vitamin B12 level in the group with nephropathy (181.6±17.6pg/dl) was significantly lower than in the group without nephropathy (286±30.1pg/dl) (p=0.03). Our study points towards the decrease levels of serum Vitamin B12 levels associated with the complication of diabetic mellitus such as diabetic nephropathy. So treatment of Vitamin B12 deficiency by supplementing could prevent the development and progression of diabetic nephropathy and improves the overall management of diabetic patient.


Intrachromosomal insertion mimicking a pericentric inversion: molecular cytogenetic characterization of a three break rearrangement of chromosome 20.
Intrachromosomal insertions are uncommon rearrangements, in which a chromosomal segment is intercalated into another part of the same chromosome. The insertion may occur in the same arm (paracentric) or in the other arm (pericentric). The cytogenetic recognition of these structurally rearranged chromosomes can be difficult, and intrachromosomal insertions can be easily mistaken for inversions. We describe a case of a familial pericentric insertion of chromosome 20, initially misdiagnosed as a pericentric inversion in the healthy carrier and then reinterpreted as insertion in an abnormal child with a recombinant chromosome. Fluorescence in situ hybridization (FISH) allowed us to confirm the mechanism of recombinant formation and to locate the three breakpoints precisely. Our cytogenetically unbalanced epileptic patient carried a 20q deletion and 20p duplication, and the genes, CHRNA4 and KCNQ2 that have been implicated in autosomal dominant epilepsy, were deleted. The haplo-insufficiency of these two genes may contribute to the cause of epilepsy in patients with ring chromosome 20.


Transrectal stapling for colonic resection and anastomosis (10 cases).
The purpose of this retrospective study was to determine the feasibility of using the end-to-end anastomosis (EEA) stapling device transrectally for managing distal colonic disease in clinical veterinary cases. Ten animals met the criteria of having distal colonic or rectal resection and anastomosis with the EEA stapling device. The only complications seen after discharge from the hospital were colonic stricture at the anastomosis site in two animals and transient colitis in two animals. The stapled anastomosis has good success when properly applied, and the incidences of stricture formation, leakage, and other potential complications can be kept to a minimum.


Two cases of aberrant right subclavian artery and right vertebral artery that originated from the right common carotid artery.
We present here two patients that had an aberrant right subclavian artery and an anomalous origin of the right vertebral artery from the right common carotid artery. We review the previous literature and discuss herein the embryologic mechanism and clinical implications of this variation.


Hodological characterization of the medial amygdala in anuran amphibians.
Early studies in anuran amphibians defined the amygdala as a single unit that only later could be subdivided into medial and lateral parts with the achievement of sensitive immunohistochemical and tracing techniques. However, the terminology used was often misleading when comparing with "homologous" amygdaloid nuclei in amniotes. Recently, the basal telencephalon of anurans has been demonstrated to be more complex than previously thought, and distinct amygdaloid nuclei were proposed on the basis of immunohistochemistry. Moreover, developmental data are increasing that support this notion. In the present study, we analyzed the patterns of afferent and efferent connections of the medial amygdala (MeA; formerly amygdala pars lateralis), considered as the main target of the vomeronasal information from the accessory olfactory bulb, as in other vertebrates. By means of axonal transport of dextran amines, the afferent and efferent connections of the MeA were traced in Rana perezi and Xenopus laevis under in vivo and in vitro conditions. Largely similar results were found in both species. The results showed abundant intratelencephalic and extratelencephalic connections that were readily comparable to those of other tetrapods. Most of these connections were reciprocal and, in particular, the strong relation of the MeA with the hypothalamus, via the stria terminalis, was demonstrated. Immunohistochemical techniques showed staining patterns that revealed abundant peptidergic afferents to the MeA, as well as minor inputs containing other neurotransmitters such as catecholamines. Double-labeling experiments demonstrated that the peptidergic fibers that reach the MeA originate in the ventral hypothalamus, whereas the catecholaminergic innervation of the MeA arises in the caudal extent of the posterior tubercle. Taken together, the results about connectivity in our study support the comparison of the MeA in anurans with its counterparts (and similarly named) amygdaloid nuclei in amniotes. Most of the hodological features of the medial amygdala seem to be shared by those tetrapods with well-developed vomeronasal systems.


Marine Polysaccharides in Tailor-made Drug Delivery.
Marine sources have attracted much interest as an emerging source of biomaterials in drug delivery applications. Amongst all other marine biopolymers, polysaccharides have been the most investigated class of biomaterials. The low cytotoxic behavior, combined with the newly explored health benefits of marine polysaccharides, has made it one of the prime research areas in the pharmaceutical and biomedical fields. This review focused on all available marine polysaccharides, including their classification based on biological sources. The applications of several marine polysaccharides in recent years for tissue-specific novel drug delivery, including gastrointestinal, brain tissue, transdermal, ocular, liver, and lung, have also been discussed here. The abundant availability in nature, cost-effective extraction, and purification process, along with a favorable biodegradable profile, will encourage researchers to continue investigating marine polysaccharides to explore newer applications targeting the specific delivery of therapeutics.


Acoustically controlled enhancement of molecular sensing to assess oxidative stress in cells.
We demonstrate a microfluidic platform for the controlled aggregation of colloidal silver nanoparticles using surface acoustic waves (SAWs), enabling surface enhanced Raman scattering (SERS) analysis of oxidative damage in cells. We show that by varying the frequency and the power of the acoustic energy, it is possible to modulate the aggregation of the colloid within the sample and hence to optimise the SERS analysis.


Direct vesicoureteral scintigraphy: quantifying early outcome predictors in children with primary reflux.
This study quantifies some of the outcome predictors in a group of children with primary vesicoureteral reflux who were initially managed medically. We studied 133 patients with primary reflux for 7.1 +/- 2.2 yr. Direct vesicoureteral scintigraphy (DVS) was used to prospectively measure the absolute bladder volume at which reflux began and the maximum volume of urine refluxed into the ureters during the filling and voiding phases of their first two DVS studies. Findings were related to outcome as defined by spontaneous resolution or the eventual need for reconstructive surgery. Medical management eventually failed in 35% of this sample. Patients who did not begin to reflux until their bladders had been filled to more than 60% total bladder capacity had a substantially smaller risk of surgery than those who began to reflux at smaller bladder volumes. Patients who refluxed a volume of urine back into their ureters that was less than about 2% of their total bladder capacity had a substantially smaller risk of surgery than those who refluxed more than 2%. The difference between groups was significant for both DVS variables (p < 0.001). Quantitative DVS contributes to the assessment of prognosis in children with vesicoureteral reflux who are managed medically.


Wnt signalling mediates miR-133a nuclear re-localization for the transcriptional control of Dnmt3b in cardiac cells.
MiR-133a is a muscle-enriched miRNA, which plays a key role for proper skeletal and cardiac muscle function via regulation of transduction cascades, including the Wnt signalling. MiR-133a modulates its targets via canonical mRNA repression, a process that has been largely demonstrated to occur within the cytoplasm. However, recent evidence has shown that miRNAs play additional roles in other sub-cellular compartments, such as nuclei. Here, we show that miR-133a translocates to the nucleus of cardiac cells following inactivation of the canonical Wnt pathway. The nuclear miR-133a/AGO2 complex binds to a complementary miR-133a target site within the promoter of the de novo DNA methyltransferase 3B (Dnmt3b) gene, leading to its transcriptional repression, which is mediated by DNMT3B itself. Altogether, these data show an unconventional role of miR-133a that upon its relocalization to the nucleus is responsible for epigenetic repression of its target gene Dnmt3b via a DNMT3B self-regulatory negative feedback loop.


Strategies for community participation in diabetes prevention: a Detroit experience.
The African-American community has been disproportionately burdened by diabetes and its associated complications. Nearly 2.8 million African Americans have diabetes. It is essential to increase community participation in diabetes prevention and health promotion as a method to improve health disparities. To address these issues, the Center for Medical Treatment Programs in Diverse Populations (MedTEP) was developed at Henry Ford Health System. The community participatory strategies described in this paper give a framework, which health systems can use to develop community-based partnerships and improve participation of community members in diabetes prevention and diabetes-related research. The strategies include receiving guidance by community leaders, providing a service, establishing partnerships, and disseminating information to the community. It is the goal of the MedTEP Center to continue to further develop and test models of community outreach to determine the most effective approaches to improve health outcomes and sustain the gain in African-American communities.


The C-terminal domain of aminopeptidase A is an intramolecular chaperone required for the correct folding, cell surface expression, and activity of this monozinc aminopeptidase.
Aminopeptidase A (APA, EC 18.104.22.168) is a type II integral membrane glycoprotein responsible for the conversion of angiotensin II to angiotensin III in the brain. Previous site-directed mutagenesis studies and the recent molecular modeling of the APA zinc metallopeptidase domain have shown that all the amino acids involved in catalysis are located between residues 200 and 500. The APA ectodomain is cleaved in the kidney into an N-terminal fragment corresponding to the zinc metallopeptidase domain, and a C-terminal fragment of unknown function. We investigated the function of this C-terminal domain, by expressing truncated APAs in Chinese hamster ovary and AtT-20 cells. Deletion of the C-terminal domain abolished the maturation and enzymatic activity of the N-terminal domain, which was retained in the endoplasmic reticulum as an unfolded protein bound to calnexin. Expression in trans of the C-terminal domain resulted in association of the N- and C-terminal domains soon after biosynthesis, allowing folding rescue, maturation, cell surface expression, and activity of the N-terminal zinc metallopeptidase domain. We also show that the C-terminal domain is not required for the catalytic activity of APA but is essential for its activation. Moreover, we show that the C-terminal domain of aminopeptidase N (EC 188.8.131.52, APN) also promotes maturation and cell surface expression of the N-terminal domain of APN, suggesting a common role of the C-terminal domain in the monozinc aminopeptidase family. Our data provide the first demonstration that the C-terminal domain of an eukaryotic exopeptidase acts as an intramolecular chaperone.


The African American Heart Failure Trial: a clinical trial update.
Progressive vascular and myocardial remodeling in heart failure is effectively slowed by therapy with neurohormonal antagonists, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, and adrenergic-receptor blockers. These therapies, along with the correction of hemodynamic abnormalities, have dramatically reduced morbidity and mortality in patients with heart failure. Endothelial dysfunction, increased oxidative stress, and decreased bioavailability of nitric oxide (NO) also occur in heart failure. Data suggest that endothelial dysfunction and reduced NO bioavailability may be more prevalent in populations who self-identify as African Americans. Thus, differences observed in the African American population with respect to prevalence of heart failure, etiology, outcomes, and response to medication may in part be explained by differences in the relative contributions of neurohormonal activation and diminished NO bioavailability to the progression of heart failure. The African American Heart Failure Trial (A-HeFT) was designed to assess the benefit of fixed-dose combination isosorbide dinitrate-hydralazine (ISDN-HYD) in an African American population with advanced heart failure. The A-HeFT enrolled 1,050 African American patients with New York Heart Association (NYHA) class III-IV heart failure with dilated ventricles and low ejection fractions. Patients were randomized to receive either a fixed-dose combination of ISDN-HYD or placebo added to standard neurohormonal blockade. The primary end point was a composite score in which mortality, hospitalization, and quality of life were weighted. On July 19, 2004, the independent Data Safety Monitoring Committee recommended early termination of the trial because of a significant mortality benefit in the cohort receiving fixed-dose ISDN-HYD. The A-HeFT confirms the benefit of fixed-dose ISDN-HYD, which may enhance NO bioavailability in African American patients with NYHA class III-IV heart failure and suggests that NO-enhancing therapy is an effective new treatment strategy for heart failure. In addition, the A-HeFT affirms the critical importance of the inclusion of population subgroups in clinical trials both as a way to probe for pathophysiologic mechanisms of disease and to devise optimal treatment strategies. The rich and unique A-HeFT database will provide new opportunities to understand the pathophysiology and management of heart failure.


Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases.
Triazole resistance in Aspergillus fumigatus has been increasing. We explored the A. fumigatus azole resistance profiles in bronchoalveolar lavage (BAL) fluid samples from Danish patients examined for aspergillosis. A total of 94 BAL samples from 87 patients were evaluated by galactomannan (GM) test and A. fumigatus CYP51A profiling by PCR. Aspergillus spp. were isolated from 27/48 (56.3%) cultured samples, including 23 A. fumigatus with one resistant strain (4.3%). Samples were classified into GM-positive (≥3.0), GM-intermediate (0.5 to <3.0) and GM-negative (<0.5) groups, where the CYP51A PCR was positive in 81.8% (36/44), 56.3% (18/32) and 38.9% (7/18) of samples, respectively. Nine CYP51A PCR-positive samples (9/61, 14.8%) were found to have mutations resulting in amino acid substitutions. M220V was detected from a sample culture positive for susceptible A. fumigatus and P216L was found in a culture-negative BAL sample. Conversely, no mutation was found in one sample culture positive for azole-resistant A. fumigatus. The tandem repeat/L98H mutation was not detected. Our study shows that azole resistance in A. fumigatus can be cryptic and may go undiagnosed. The combination of improved culture/susceptibility tests and the direct molecular detection of resistance markers will facilitate prompt institution of appropriate antifungal therapy.


Comparison of 19 major infectious diseases during COVID-19 epidemic and previous years in Zhejiang, implications for prevention measures.
The global pandemic of coronavirus disease 2019 (COVID-19) has attracted great public health efforts across the world. Few studies, however, have described the potential impact of these measures on other important infectious diseases. The incidence of 19 major infectious diseases in Zhejiang Province was collected from the National Notifiable Infectious Disease Surveillance System from January 2017 to October 2020. The entire epidemic control phase was divided into three stages. The government deployed the first level response from 24 January to 2 March (the most rigorous measures). When the outbreak of COVID-19 was under control, the response level changed to the second level from 3 to 23 March, and then the third level response was implemented after 24 March. We compared the epidemiological characteristics of 19 major infectious diseases during different periods of the COVID-19 epidemic and previous years. A total of 1,814,881 cases of 19 infectious diseases were reported in Zhejiang from January 2017 to October 2020, resulting in an incidence rate of 8088.30 cases per 1,000,000 person-years. After the non-pharmaceutical intervention, the incidence of 19 infectious diseases dropped by 70.84%, from 9436.32 cases per 1,000,000 person-years to 2751.51 cases per 1,000,000 person-years, with the large decrease in the first response period of influenza. However, we observed that the daily incidence of severe fever with thrombocytopenia syndrome (SFTS) and leptospirosis increased slightly (from 1.11 cases per 1,000,000 person-years to 1.82 cases per 1,000,000 person-years for SFTS and 0.30 cases per 1,000,000 person-years to 1.24 cases per 1,000,000 person-years for leptospirosis). There was no significant difference in the distribution of epidemiological characteristic of most infectious diseases before and during the implementation of COVID-19 control measures. Our study summarizes the epidemiological characteristics of 19 infectious diseases and indicates that the rigorous control measures for COVID-19 are also effective for majority of infectious diseases.


New oral liposomal vitamin C formulation: properties and bioavailability.
Vitamin C is the exogenous compound necessary for a variety of metabolic processes; therefore, the efficient delivery is critical for the maintenance of body homeostasis. Vitamin C pharmacokinetics and low quantities in processed foodstuff, necessitates its continuous supplementation. In the paper, we present the new liposomal formulation of vitamin C free of harmful organic solvents. The formulation was quantitatively characterized with respect to its chemically composition and nano-structuring. The vitamin C accessibility to cells from the formulation was evaluated using evidence derived from experiments performed on cell cultures. Finally, the enhanced bioavailability of vitamin C from the formulation was demonstrated in the medical experiment.


Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study.
White matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear. We used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females). We found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [-18 46-14]), left limbic lobe uncus (peak coordinates [-18 2-22]), and right cerebellum posterior lobe (peak coordinates [26-34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores. We found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.


Spaced Apart: Autoethnographies of Access Throughout the COVID 19 Pandemic.
In this article, we present six autoethnographies of lives marked by crisis that reflect on the issues of access, very broadly defined, that the COVID 19 pandemic has raised or redefined for each of us. As the time of crisis has made access concerns more and more evident it also exposes how access is not an issue just for disabled people, but for all lives. Drawing on recent scholarship in disability studies that critically interrogates access through an intersectional lens, we take this unexpected unveiling as an occasion to further tease out the complexities, ambiguities, and messiness of access.


Role of the pre-hospital treatment team on the UK military exercise SAIF SAREEA 3.
The prehospital treatment team (PHTT) involves a small team working under the clinical supervision of a clinical lead. The clinical lead can be a general duties medical officer (Post Foundation Years Doctor), military nurse practitioner or more senior clinician. The team is mounted in vehicles appropriate to the environment they expect to operate in. A PHTT is closely located to the front line reducing transportation timelines from the point of wounding to more definitive care. The PHTT can provide medical support on the move or when time is available; a more permanent fully erected treatment facility can be established. Either configuration can provide both trauma and primary care. The size of the team allows for multiple trauma subteams enabling care to casualties that arrive simultaneously. The PHTT can move independently which could leave the team vulnerable as there is no integral force protection within the current structure. In such a small team, the right balance of medical and soldiering skills among team members is essential to success. Exercise SAIF SAREEA 3 represented a large-scale battlegroup exercise to the Middle East in the austere desert of Oman. This provided an ideal environment for employing the PHTT concept is a large deployed force undertaking dynamic activity.


Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses.
Viral oncogenes are responsible for oncogenesis resulting from persistent virus infection. Although different human tumor viruses express different viral oncogenes and induce different tumors, their oncoproteins often target similar sets of cellular tumor suppressors or signal pathways to immortalize and/or transform infected cells. Expression of the viral E6 and E7 oncogenes in papillomavirus, E1A and E1B oncogenes in adenovirus, large T and small t antigen in polyomavirus, and Tax oncogene in HTLV-1 are regulated by alternative RNA splicing. However, this regulation is only partially understood. DNA tumor viruses also encode noncoding RNAs, including viral microRNAs, that disturb normal cell functions. Among the determined viral microRNA precursors, EBV encodes 25 from two major clusters (BART and BHRF1), KSHV encodes 12 from a latent region, human polyomavirus MCV produce only one microRNA from the late region antisense to early transcripts, but HPVs appears to produce no viral microRNAs.


Urinary bladder epithelium antigen induces CD8+ T cell tolerance, activation, and autoimmune response.
The effort to explore the specific autoimmune mechanisms of urinary bladder has long been hindered due to a lack of proper animal models. To better elucidate this issue, we developed a novel line of transgenic (Tg) mice, designated as URO-OVA mice, that express the model Ag OVA as a "self"-Ag on the bladder epithelium. URO-OVA mice are naturally tolerant to OVA and show no response to OVA stimulation. Adoptive transfer of naive OVA-specific T cells showed cell proliferation, activation, and infiltration but no bladder histopathology. In contrast, adoptive transfer of activated OVA-specific T cells induced OVA-mediated histological bladder inflammation. Increased mast cells and up-regulated mRNA expressions of TNF-alpha, nerve growth factor, and substance P precursor were also observed in the inflamed bladder. To further facilitate bladder autoimmunity study, we crossbred URO-OVA mice with OVA-specific CD8(+) TCR Tg mice (OT-I mice) to generate a dual Tg line URO-OVA/OT-I mice. The latter mice naturally acquire clonal deletion for autoreactive OT-I CD8(+) T cells (partial deletion in the thymus and severe deletion in the periphery). Despite this clonal deletion, URO-OVA/OT-I mice spontaneously develop autoimmune cystitis at 10 wk of age. Further studies demonstrated that the inflamed bladder contained infiltrating OT-I CD8(+) T cells that had escaped clonal deletion and gained effector functions before developing histological bladder inflammation. Taken together, we demonstrate for the first time that the bladder epithelium actively presents self-Ag to the immune system and induces CD8(+) T cell tolerance, activation, and autoimmune response.


Functional organization of the hematopoietic stem cell compartment: implications for cancer and its therapy.
Recent discoveries indicate that hematopoietic stem cells have limits on their proliferative capacity and are unable to divide indefinitely. There is great heterogeneity within the compartment as to the extent of this proliferative limitation. At any given time it appears that hematopoiesis is maintained by the progeny of only a few stem cells. When these are exhausted the progeny from other stem cells take their place. The observations of proliferative limitation, heterogeneity, and clonal succession must be incorporated into any model of stem cell organization. These new discoveries and the models incorporating them have important clinical implications. They may explain the inability of normal tissues to develop drug resistance and they also offer a mechanism by which cell renewal systems decrease the development of malignancies. In the selection of chemotherapeutic agents not only the effectiveness of the drug upon the tumor must be considered, but also how specific agents affect the stem cell compartment. These data have important implications in the use of bone marrow transplantation for both malignant and nonmalignant disease.


In situ hybridization demonstrating coexpression of urotensins I, II-alpha, and II-gamma in the caudal neurosecretory neurons of the carp, Cyprinus carpio.
In order to examine the coexpression of different urotensins in the same caudal neurosecretory neurons, in situ hybridization with synthetic oligonucleotide probes specific for mRNAs for urotensins I, II-alpha, and II-gamma (UI, UII-alpha, and UII-gamma) was applied to the caudal neurosecretory system of the carp, Cyprinus carpio, together with immunohistochemistry. Almost all identifiable caudal neurosecretory neurons were labeled with the oligonucleotide and cDNA probes for UI mRNA. Further, any two of the probes for UI, UII-alpha, and UII-gamma mRNAs labeled the same neurons in serial sections. These results suggest that essentially all caudal neurosecretory neurons of the carp coexpress UI, UII-alpha, and UII-gamma. Although most neurons were densely labeled with oligonucleotide probes, only a small portion of the neurons were intensely immunoreactive. This suggests that most caudal neurosecretory neurons actively synthesize all three hormones, but that in some neurons, all or some of the hormones are rapidly transported to the urophysis, resulting in low or undetectable immunoreactivity in the perikarya.


Unaltered immunoglobulin expression in hybridoma cells modified by targeting of the heavy chain locus with an integration vector.
Chimeric antibodies against the murine T-cell antigen Thy-1.2 were generated in amounts sufficient for in vivo studies by substituting the constant gene segments via homologous recombination in the hybridoma cell. We show that an integration vector targets the heavy chain locus at high frequency even in a non-isogenic situation. Using this vector type, for the first time expression rates were obtained that were identical to the parental hybridoma. The use of the gpt selection marker seems to be crucial for efficient expression, and may overcome a recently claimed drawback of vector integration. A chimeric antibody produced by gene targeting was characterized in vitro and in vivo.


Synchronous endometrial and ovarian cancer: A case report.
Synchronous endometrial and ovarian cancer (SEOC) is a rare genital tract tumor. Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer (EC) or OC. In this review we present 2 cases of women who were diagnosed with SEOC, and discuss the clinical characteristic of SEOC, diagnostic and molecular profiling issues. Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples. In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC. They underwent surgical treatment and staging. Next-generation sequencing of 10 gene-panel identified CTNNB1, PIK3CA, and PTEN gene mutations in ovarian tissue in one case, while none of these genes were mutated in other case. Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage. Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.


Primary certification in vascular surgery: what does this really mean?
A primary certificate for vascular surgery has recently been approved by both the American Board of Medical Specialties and the Accreditation Council for Graduate Medical Education. This new training paradigm will allow training and certification in vascular surgery without first obtaining American Board of Surgery certification in general surgery. There are now several pathways ways to obtain vascular surgery certification, which are described in this article. All programs require an MD or DO degree from an institution accredited by the Liaison Committee of Medical Education or by the American Osteopathic Association. Graduates of schools of medicine from countries other than the United States or Canada must present evidence of final certification by the Education Commission for Foreign Medical Graduates.


Regulatory and functional divergence among members of Ibβfruct2, a sweet potato vacuolar invertase gene controlling starch and glucose content.
Sweet potato [Ipomoea batatas (L.) Lam.] is an important food and industrial crop. Its storage root is rich in starch, which is present in the form of granules and represents the principal storage carbohydrate in plants. Starch content is an important trait of sweet potato controlling the quality and yield of industrial products. Vacuolar invertase encoding gene Ibβfruct2 was supposed to be a key regulator of starch content in sweet potato, but its function and regulation were unclear. In this study, three Ibβfruct2 gene members were detected. Their promoters displayed differences in sequence, activity, and cis-regulatory elements and might interact with different transcription factors, indicating that the three Ibβfruct2 family members are governed by different regulatory mechanisms at the transcription level. Among them, we found that only Ibβfruct2-1 show a high expression level and promoter activity, and encodes a protein with invertase activity, and the conserved domains and three conserved motifs NDPNG, RDP, and WEC are critical to this activity. Only two and six amino acid residue variations were detected in sequences of proteins encoded by Ibβfruct2-2 and Ibβfruct2-3, respectively, compared with Ibβfruct2-1; although not within key motifs, these variations affected protein structure and affinities for the catalytic substrate, resulting in functional deficiency and low activity. Heterologous expression of Ibβfruct2-1 in Arabidopsis decreased starch content but increased glucose content in leaves, indicating Ibβfruct2-1 was a negative regulator of starch content. These findings represent an important advance in understanding the regulatory and functional divergence among duplicated genes in sweet potato, and provide critical information for functional studies and utilization of these genes in genetic improvement.


A Critical Review of MELD as a Reliable Tool for Transplant Prioritization.
In a context of global organ shortage, the Model for End-Stage Liver Disease (MELD) score seems to be a fair prioritization tool, with a paradigm: "sickest first." Since its introduction in the United States in 2002, it has been rapidly adopted by transplant centers and organ sharing agencies around the world. The MELD score showed its effectiveness with a 12% reduction in waiting list mortality in the United States. Its success is linked to its simplicity, the use of basic variables (serum creatinine, serum bilirubin, and international normalized ratio [INR]), and its ability to predict short-term mortality, particularly on the transplant waiting list. However, this score is not perfect: its variables may have disadvantages for some patients, especially women, with serum creatinine and interlaboratory variability of the INR. The MELD score does not take into account some variables associated with poor short-term prognosis in cirrhotic patients. In addition, it is currently capped at 40, which results in the exclusion of sicker patients who could greatly benefit from transplantation. Finally, the MELD score does not accurately reflect the prognosis of several conditions, requiring a MELD exception system. Some solutions have been suggested such as MELD-Na or MELD uncapping, but it has not yet been fully accepted by all transplant centers.


How Honeybees Defy Gravity with Royal Jelly to Raise Queens.
The female sex in honeybees (Apis spp.) comprises a reproductive queen and a sterile worker caste. Nurse bees feed all larvae progressively with a caste-specific food jelly until the prepupal stage. Only those larvae that are exclusively fed a large amount of royal jelly (RJ) develop into queens [1]. RJ is a composite secretion of two specialized head glands: the mandibular glands, which produce mainly fatty acids [2], and the hypopharyngeal glands, which contribute proteins, primarily belonging to the major royal jelly protein (MRJP) family [3]. Past research on RJ has focused on its nutritional function and overlooked its central role with regard to the orientation of the larva in the royal brood cell. Whereas workers are reared in the regular horizontal cells of the comb, the queen cells are specifically built outside of the normal comb area to accommodate for the larger queen [4, 5]. These cells hang freely along the bottom of the comb and are vertically oriented, opening downward [6]. Queen larvae are attached by their RJ diet to the cell ceiling. Thus, the physical properties of RJ are central to successful retention of larvae in the cell. Here, we show that the main protein of RJ (MRJP1) polymerizes in complex with another protein, apisimin, into long fibrous structures that build the basis for the high viscosity of RJ to hold queen larvae on the RJ surface.


In-vial dual extraction liquid chromatography coupled to mass spectrometry applied to streptozotocin-treated diabetic rats. Tips and pitfalls of the method.
The aim of metabolomics studies is the comprehensive and quantitative analysis of all metabolites in a cell, tissue or organism. This approach requires sample preparation methods to be fast, reproducible and able to extract a wide range of analytes with different polarities, as well as analytical platforms able to detect the extracted metabolites. Recently, we have developed a one-step extraction method consisting of a lipophilic and hydrophilic layer within a single vial insert, in-vial dual extraction (IVDE). In order to check possible application of this method to real biological case, analysis of plasma samples obtained from three streptozotocin-induced diabetic and three control rats was performed. Analytical validity of the method was proved by the calculation (in quality control samples) of relative standard deviation (RSD) for detected metabolites. The percentage of metabolites with RSD<30% was 93% for Fatty acyls, 80% for Glycerolipids, 93% for Glycerophospholipids, 68% for Sterol lipids, and 91% for Sphingolipids. IVDE allowed for selection of more than 600 different features discriminating two studied groups. For around 40% of these masses putative identification was possible. Adequate, with several considerations described within this paper, application of IVDE method enables wide metabolite coverage from a single 20μL plasma aliquot. Within the features putatively identified, glycerolipids and glycerophospholipids arose as the most important groups of compounds discriminating diabetic rats from controls. All discriminating metabolites give an idea of the large metabolic differences that can be present in non-controlled type 1 diabetes.


Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat thymocytes: a possibility of aspartame toxicity.
Aspartame is a widely used artificial sweetener added to many soft beverages and its usage is increasing in health-conscious societies. Upon ingestion, this artificial sweetener produces methanol as a metabolite. In order to examine the possibility of aspartame toxicity, the effects of methanol and its metabolites (formaldehyde and formate) on dissociated rat thymocytes were studied by flow cytometry. While methanol and formate did not affect cell viability in the physiological pH range, formaldehyde at 1-3 mmol/L started to induce cell death. Further increase in formaldehyde concentration produced a dose-dependent decrease in cell viability. Formaldehyde at 1 mmol/L or more greatly reduced cellular content of glutathione, possibly increasing cell vulnerability to oxidative stress. Furthermore, formaldehyde at 3 mmol/L or more significantly increased intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner. Threshold concentrations of formaldehyde, a metabolite of methanol, that affected the [Ca2+]i and cellular glutathione content were slightly higher than the blood concentrations of methanol previously reported in subjects administered abuse doses of aspartame. It is suggested that aspartame at abuse doses is harmless to humans.


An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup.
We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance. A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy. A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001). While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.


The interaction between ruthenium red and the isolated sarcoplasmic reticulum.
The multivalent anions, ATP and oxalate, present at 5mM concentrations in incubation mixtures with isolated sarcoplasmic reticulum (SR) preparations, reduce the binding of ruthenium red (RR) to the SR. When oxalate is omitted from the incubation mixture and ATP is used at reduced concentrations, it is possible to observe an inhibitory effect of RR on calcium uptake by the SR and on ATPase activity. However, this inhibition is only partial and it remains clear that calcium transport in the SR is much less susceptible to inhibition by RR than is calcium transport in mitochondria. The effect of multivalent anions in suppressing the effect of RR, a hexavalent cation, is probably due to the formation of soluble complexes with RR.


The BEETS (JACCRO CC-18) trial: an observational and translational study of BRAF-mutated metastatic colorectal cancer.
For BRAF V600E-mutated metastatic colorectal cancer (mCRC), the BEACON phase 3 trial showed survival benefit of triplet therapy with cetuximab (anti-EGFR antibody), encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor) as well as doublet therapy with cetuximab and encorafenib over irinotecan-based chemotherapy plus anti-EGFR antibody. Both regimens are standards of care in Japan, but definite biomarkers for predicting efficacy and selecting treatment remain lacking. The mechanisms underlying resistance to these regimens also warrant urgent exploration to further evolve treatment. This prospective observational/translational study evaluated real-word clinical outcomes with cetuximab and encorafenib with or without binimetinib for BRAF-mutated mCRC patients and investigated biomarkers for response and resistance by collecting blood samples before and after treatment. Clinical Trial Registration: UMIN000045530 (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051983).


High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1.
Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive, and have limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Although it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was recently identified in ocular tissues. In this article we examined the involvement of the GAPDH/Siah1 interaction in human retinal pericyte (hRP) apoptosis. HRP were cultured in 5 mm normal glucose, 25 mm l- or d-glucose for 48 h (osmotic control and high glucose treatments, respectively). Siah1 siRNA was used to down-regulate Siah1 expression. TAT-FLAG GAPDH and/or Siah1-directed peptides were used to block GAPDH and Siah1 interaction. Co-immunoprecipitation assays were conducted to analyze the effect of high glucose on the association of GAPDH and Siah1. Apoptosis was measured by Annexin V staining and caspase-3 enzymatic activity assay. High glucose increased Siah1 total protein levels, induced the association between GAPDH and Siah1, and led to GAPDH nuclear translocation. Our findings demonstrate that dissociation of the GAPDH/Siah1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of DR. Thus, the work presented in this article can provide a foundation to identify novel targets for early treatment of DR.


Impact of family history of diabetes and ethnicity on -cell function in obese, glucose-tolerant individuals.
The increased insulin secretion in response to reduced insulin sensitivity (SI) is heritable, but whether the genetic predisposition is restricted to members of high-risk Caucasian families is unknown. Furthermore, the relative importance of insulin resistance and defective beta-cell compensation in the increased prevalence of type 2 diabetes (T2DM) in African-American compared with Caucasian individuals is uncertain. We tested whether obese individuals with a family history of T2DM have decreased beta-cell compensation compared with obese controls without a family history of T2DM. In addition, we compared S(I) and insulin secretion measures in African-American and Caucasian individuals. SI, acute insulin response to iv glucose (AIRg), maximally potentiated insulin response to arginine (AIRmax), and disposition indexes (DIs) (DI = SI * AIRg; DImax = SI * AIRmax) were compared among nondiabetic Caucasian and African-American individuals with and without a family history of diabetes. This study was performed in an Ambulatory General Clinical Research Center. SUBJECTS were healthy, nondiabetic individuals with or without a family history of T2DM. There were no interventions. Comparison of SI, AIRg, AIRmax, DI, and DImax between Caucasians and African-Americans with or without a strong family history of T2DM were made. Obese subjects did not differ in SI, AIRg, or DI by family history of diabetes. African-Americans had 8% lower SI (P < 0.001), but 68% higher AIRg (P < 0.001) and 46% higher DI (P = 0.001) than age, gender, body mass index-matched Caucasian individuals. However, African-Americans had lower DImax compared with Caucasians. We found no reduction in insulin secretion in obese subjects with a family history of T2DM compared with controls, but in general, African-Americans were more insulin resistant and had lower maximal beta-cell response (DImax). The paradoxical increased DI could be explained by the reduced hepatic insulin extraction.


N-Terminal Cysteine Bioconjugation with (2-Cyanamidophenyl)boronic Acids Enables the Direct Formation of Benzodiazaborines on Peptides.
Benzodiazaborines (BDABs) have emerged as a valuable tool to produce stable and functional bioconjugates via a click-type transformation. However, the current available methods to install them on peptides lack bioorthogonality, limiting their applications. Here, we report a strategy to install BDABs directly on peptide chains using (2-cyanamidophenyl)boronic acids (2CyPBAs). The resulting BDAB is stabilized through the formation of a key intramolecular B-N bond. This technology was applied in the selective modification of N-terminal cysteine-containing functional peptides.


Tissue inhibitor of metalloproteinases-1 (TIMP-1) is differentially induced in neurons and astrocytes after seizures: evidence for developmental, immediate early gene, and lesion response.
We investigated in vivo the expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in the rat CNS after kainate (KA)-induced excitotoxic seizures. In situ hybridization revealed that TIMP-1 mRNA is induced rapidly and massively in most regions of the adult forebrain after KA treatment. Neuronal activity seems to be necessary but not sufficient to trigger TIMP-1 induction, because it is not observed in seizing 10-d-old pups, unlike what is observed in 21- and 35-d-old animals after seizures. The rapid induction of TIMP-1 is not prevented by the inhibitor of protein synthesis cycloheximide, suggesting that, after seizures, TIMP-1 is induced in neurons as an immediate early gene (IEG). The initial neuronal upregulation is followed by enhanced expression in astrocytes, as assessed by double-labeling experiments. In the hippocampus rapid increases in mRNA are followed by relatively delayed (8 hr after KA) increases in TIMP-1 immunoreactivity in the perisomatic and dendro-axonic areas, suggesting secretion of the protein. At 3 d after KA treatment, strong immunoreactivity is found in astrocytes and in the cell bodies and dendro-axonic projections of resistant neurons such as the dentate granule cells. Taken together, the results suggest that TIMP-1 may be instrumental for neurons and astrocytes in coupling early cellular events triggered by seizures with the regulation of long-lasting changes involved in tissue reorganization and/or neuroprotection.


Radial artery cannulation in 1,000 patients: precautions and complications.
A review of 1,000 radial artery cannulations performed over a 2-year period showed that, with careful selection of patients, by means of the Allen test and Doppler studies, and with the apparatus used, only two serious complications were encountered; embolectomy was necessary in one and arterial reconstruction in another. Twenty-four percent of patients had evidence of diminution of flow, but in none did it persist for more than 2 weeks. Critical factors in reducing complications were a short period of cannulation, use of a Teflon catheter, and a continuous arterial line flush system.


Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.
The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g · kg · day (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.


Qualitative proteomic analysis of Tipula oleracea nudivirus occlusion bodies.
Nudiviruses are arthropod-specific large double-stranded circular DNA viruses, related to baculoviruses, which replicate in the nucleus of the cells they infect. To date, six fully sequenced nudiviral genomes are available in databases, and the protein profile from nudivirus particles was mainly characterized by PAGE. However, only a few direct matches have been completed between genomic and proteomic data, with the exception of the major occlusion body protein from Penaeus monodon nudivirus and four nucleocapsid proteins from Helicoverpa zea nudivirus-2. The function of predicted nudiviral proteins is still inferred from what is known from baculoviruses or endogenous nudiviruses (i.e. bracoviruses). Tipula oleracea nudivirus (ToNV) is the causative agent of crane fly nucleopolyhedrosis. Along with Penaeus monodon nudivirus, ToNV is the second fully sequenced nudivirus to be described as forming occlusion bodies. The protein profile revealed by Coomassie-stained SDS-PAGE is very similar to those observed for other nudiviruses, with five major protein bands of about 75, 48, 35, 25 and 12 kDa. Proteomic analysis, using on-line nanoflow liquid chromatography in tandem with high-resolution mass spectrometry, revealed that ToNV occlusion bodies are composed of 52 viral proteins, the most abundant of which are the functional homologue of baculovirus polyhedrin/granulin and the homologues of three Helicoverpa zea nudivirus-2 predicted proteins: the two virion structural proteins 34K (Hz2V052, the baculovirus capsid protein VP39 homologue) and 11K (Hz2V025), and the hypothetical protein Hz2V079, a newly identified nudivirus core gene product.


The microwave spectrum of a two-top peptide mimetic: the N-acetyl alanine methyl ester molecule.
The rotational spectrum of N-acetyl alanine methyl ester, a derivative of the biomimetic, N-acetyl alanine N'-methyl amide or alanine dipeptide, has been measured using a mini Fourier transform spectrometer between 9 and 25 GHz as part of a project undertaken to determine the conformational structures of various peptide mimetics from the torsion-rotation parameters of low-barrier methyl tops. Torsion-rotation splittings from two of the three methyl tops capping the acetyl end of the -NH-C(=O)- and the methoxy end of -C(=O)-O- groups account for most of the observed lines. In addition to the AA state, two E states have been assigned and include an AE state having a torsional barrier of 396.45(7) cm(-1) (methoxy rotor) and an EA state having a barrier of 64.96(4) cm(-1) (acetyl rotor). The observed torsional barriers and rotational constants of alanine dipeptide and its methyl ester are compared with predictions from Möller-Plesset second-order perturbation theory (MP2) and density functional theory (DFT) in an effort to explore systematic errors at the two levels of theory. After accounting for zero-point energy differences, the torsional barriers at the MP2/cc-pVTZ level are in excellent agreement with experiment for the acetyl and methoxy groups while DFT predictions range from 8% to 80% too high or low. DFT is found to consistently overestimate the overall molecular size while MP2 methods give structures that are undersized. Structural discrepancies of similar magnitude are evident in previous DFT results of crystalline peptides.


Damage identification of piles based on vibration characteristics.
A method of damage identification of piles was established by using vibration characteristics. The approach focused on the application of the element strain energy and sensitive modals. A damage identification equation of piles was deduced using the structural vibration equation. The equation contained three major factors: change rate of element modal strain energy, damage factor of pile, and sensitivity factor of modal damage. The sensitive modals of damage identification were selected by using sensitivity factor of modal damage firstly. Subsequently, the indexes for early-warning of pile damage were established by applying the change rate of strain energy. Then the technology of computational analysis of wavelet transform was used to damage identification for pile. The identification of small damage of pile was completely achieved, including the location of damage and the extent of damage. In the process of identifying the extent of damage of pile, the equation of damage identification was used in many times. Finally, a stadium project was used as an example to demonstrate the effectiveness of the proposed method of damage identification for piles. The correctness and practicability of the proposed method were verified by comparing the results of damage identification with that of low strain test. The research provided a new way for damage identification of piles.


The copBL operon protects Staphylococcus aureus from copper toxicity: CopL is an extracellular membrane-associated copper-binding protein.
As complications associated with antibiotic resistance have intensified, copper (Cu) is attracting attention as an antimicrobial agent. Recent studies have shown that copper surfaces decrease microbial burden, and host macrophages use Cu to increase bacterial killing. Not surprisingly, microbes have evolved mechanisms to tightly control intracellular Cu pools and protect against Cu toxicity. Here, we identified two genes (copB and copL) encoded within the Staphylococcus aureus arginine-catabolic mobile element (ACME) that we hypothesized function in Cu homeostasis. Supporting this hypothesis, mutational inactivation of copB or copL increased copper sensitivity. We found that copBL are co-transcribed and that their transcription is increased during copper stress and in a strain in which csoR, encoding a Cu-responsive transcriptional repressor, was mutated. Moreover, copB displayed genetic synergy with copA, suggesting that CopB functions in Cu export. We further observed that CopL functions independently of CopB or CopA in Cu toxicity protection and that CopL from the S. aureus clone USA300 is a membrane-bound and surface-exposed lipoprotein that binds up to four Cu+ ions. Solution NMR structures of the homologous Bacillus subtilis CopL, together with phylogenetic analysis and chemical-shift perturbation experiments, identified conserved residues potentially involved in Cu+ coordination. The solution NMR structure also revealed a novel Cu-binding architecture. Of note, a CopL variant with defective Cu+ binding did not protect against Cu toxicity in vivo Taken together, these findings indicate that the ACME-encoded CopB and CopL proteins are additional factors utilized by the highly successful S. aureus USA300 clone to suppress copper toxicity.


A prospective cohort study on the intersectionality of obesity, chronic disease, social factors, and incident risk of COVID-19 in US low-income minority middle-age mothers.
Coronavirus disease 2019 (COVID-19) has disproportionally affected communities of color. We aimed to determine what factors are associated with COVID-19 testing and test positivity in an underrepresented, understudied, and underreported (U3) population of mothers. This study included 2996 middle-aged mothers of the Boston Birth Cohort (a sample of predominantly urban, low-income, Black and Hispanic mothers) who were enrolled shortly after they gave birth and followed onward at the Boston Medical Center. COVID-19 testing and test positivity were defined by the SARS-CoV-2 nucleic acid test. Two-probit Heckman selection models were performed to identify factors associated with test positivity while accounting for potential selection associated with COVID testing. The mean (SD) age of study mothers was 41.9 (±7.7) years. In the sample, 1741 (58.1%) and 667 (22.3%) mothers were self-identified as Black and Hispanic, respectively. A total of 396 mothers had COVID-19 testing and of those, 95 mothers tested positive from March 2020 to February 2021. Among a multitude of factors examined, factors associated with the probability of being tested were obesity (RR = 1.27; 95% confidence interval (CI): 1.08-1.49); and presence of preexisting chronic medical conditions including hypertension, asthma, stroke, and other comorbidities (coronary heart disease, chronic kidney disease, and sickle cell disease) with a corresponding RR = 1.40 (95% CI: 1.23-1.60); 1.29 (95% CI: 1.11-1.50); 1.44 (95% CI: 1.23-1.68); and 1.37 (95% CI: 1.12-1.67), respectively. Factors associated with higher incident risk of a positive COVID-19 test were body mass index, birthplace outside of the USA, and being without a college-level education. This study demonstrated the intersectionality of obesity and social factors in modulating incident risk of COVID-19 in this sample of US Black and Hispanic middle-aged mothers. Methodologically, our findings underscore the importance of accounting for potential selection bias in COVID-19 testing in order to obtain unbiased estimates of COVID-19 infection.


Contrasting processes drive ophiuroid phylodiversity across shallow and deep seafloors.
Our knowledge of the distribution and evolution of deep-sea life is limited, impeding our ability to identify priority areas for conservation1. Here we analyse large integrated phylogenomic and distributional datasets of seafloor fauna from the sea surface to the abyss and from equator to pole of the Southern Hemisphere for an entire class of invertebrates (Ophiuroidea). We find that latitudinal diversity gradients are assembled through contrasting evolutionary processes for shallow (0-200 m) and deep (>200 m) seas. The shallow-water tropical-temperate realm broadly reflects a tropical diversification-driven process that shows exchange of lineages in both directions. Diversification rates are reversed for the realm that contains the deep sea and Antarctica; the diversification rates are highest at polar and lowest at tropical latitudes, and net exchange occurs from high to low latitudes. The tropical upper bathyal (200-700 m deep), with its rich ancient phylodiversity, is characterized by relatively low diversification and moderate immigration rates. Conversely, the young, specialized Antarctic fauna is inferred to be rebounding from regional extinctions that are associated with the rapid cooling of polar waters during the mid-Cenozoic era.


In vitro evaluation of chemopreventive agents using cultured human prostate epithelial cells.
The effects of nine potential cancer chemopreventive agents on cell growth or clonogenic survival were evaluated in normal human prostate epithelial cells, an immortalized but non-tumorigenic human prostate epithelial cell line (267B1), a human benign prostatic hyperplasia (BPH) cell line (BRF-55T), and a human prostate cancer cell line (267B1/Ki-ras). Of the nine agents tested, 9-cis retinoic acid, liarozole fumarate, phenylenebis(methylene)-selenocyanate (p-XSC), and L-selenomethionine demonstrated much stronger growth inhibitory effects on prostate cancer cells than on the normal prostate epithelial cells, suggesting that these agents may be useful as prostate cancer chemopreventive agents. 9-cis retinoic acid, genistein, liarozole fumarate, p-XSC, L-selenomethionine and vitamin E also showed much stronger growth inhibitory effects on BRF-55T cells than on the normal prostate epithelial cells, indicating that these agents may also be useful for the prevention and treatment of BPH. Difluoromethylornithine (DFMO), DHEA analogue 8354 (fluasterone), and oltipraz did not show strong inhibitory effects on the growth or survival of normal prostate epithelial cells, 267B1 or 267B1/Ki-ras cells, suggesting that these agents may not be effective as prostate cancer preventive or therapeutic agents.


Correlations Between Macular, Skin, and Serum Carotenoids.
Ocular and systemic measurement and imaging of the macular carotenoids lutein and zeaxanthin have been employed extensively as potential biomarkers of AMD risk. In this study, we systematically compare dual wavelength retinal autofluorescence imaging (AFI) of macular pigment with skin resonance Raman spectroscopy (RRS) and serum carotenoid levels in a clinic-based population. Eighty-eight patients were recruited from retina and general ophthalmology practices from a tertiary referral center and excluded only if they did not have all three modalities tested, had a diagnosis of macular telangiectasia (MacTel) or Stargardt disease, or had poor AFI image quality. Skin, macular, and serum carotenoid levels were measured by RRS, AFI, and HPLC, respectively. Skin RRS measurements and serum zeaxanthin concentrations correlated most strongly with AFI macular pigment volume under the curve (MPVUC) measurements up to 9° eccentricity relative to MPVUC or rotationally averaged macular pigment optical density (MPOD) measurements at smaller eccentricities. These measurements were reproducible and not significantly affected by cataracts. We also found that these techniques could readily identify subjects taking oral carotenoid-containing supplements. Larger macular pigment volume AFI and skin RRS measurements are noninvasive, objective, and reliable methods to assess ocular and systemic carotenoid levels. They are an attractive alternative to psychophysical and optical methods that measure MPOD at a limited number of eccentricities. Consequently, skin RRS and MPVUC at 9° are both reasonable biomarkers of macular carotenoid status that could be readily adapted to research and clinical settings.


Emotion lies in the eye of the listener: Emotional arousal to novel sounds is reflected in the sympathetic contribution to the pupil dilation response and the P3.
Novel sounds in the auditory oddball paradigm elicit a biphasic dilation of the pupil (PDR) and P3a as well as novelty P3 event-related potentials (ERPs). The biphasic PDR has been hypothesized to reflect the relaxation of the iris sphincter muscle due to parasympathetic inhibition and the constriction of the iris dilator muscle due to sympathetic activation. We measured the PDR and the P3 to neutral and to emotionally arousing negative novels in dark and moderate lighting conditions. By means of principal component analysis (PCA) of the PDR data we extracted two components: the early one was absent in darkness and, thus, presumably reflects parasympathetic inhibition, whereas the late component occurred in darkness and light and presumably reflects sympathetic activation. Importantly, only this sympathetic late component was enhanced for emotionally arousing (as compared to neutral) sounds supporting the hypothesis that emotional arousal specifically activates the sympathetic nervous system. In the ERPs we observed P3a and novelty P3 in response to novel sounds. Both components were enhanced for emotionally arousing (as compared to neutral) novels. Our results demonstrate that sympathetic and parasympathetic contributions to the PDR can be separated and link emotional arousal to sympathetic nervous system activation.


[Experience of the Pharmacotherapy against Appendix and Sigmoid Colon Signet Ring Cell Carcinoma with the Peritoneal Dissemination].
We report 2 cases of signet ring cell carcinoma of the appendix and colon. Case 1: A 61-year-old man was admitted for lower abdominal pain. Colonoscopy revealed an elevated lesion in the orifice of the appendix. Signet ring cell carcinoma was diagnosed on biopsy. The surgical findings showed multiple peritoneal dissemination nodules, while the primary tumor was unresectable owing to extensive invasion into the retroperitoneum. The histopathological findings were signet ring cell carcinoma, T4b (retroperitoneum), NX, P3, Stage Ⅳ. Although the patient received 14 courses of treatment with S-1 as postoperative chemotherapy, he died of his illness at 32 postoperative months. Case 2: A 76-year-old man was admitted for abdominal pain. Perforation of the lower gastrointestinal tract was diagnosed on abdominal CT, and an emergency operation was performed. The surgical findings demonstrated a large number of peritoneal dissemination nodules, cecal invasion of a sigmoid tumor, and perforation of the ascending colon. The primary tumor was thought to be unresectable, and the perforated segment was resected. The histopathological findings were signet ring cell carcinoma, T4b (cecum), NX, P3, Stage Ⅳ. Although 11 courses of treatment using FOLFIRI+Bev were administered as postoperative chemotherapy, the patient died of his illness at 26 postoperative months.


ATM, KAP1 and the Epstein-Barr virus polymerase processivity factor direct traffic at the intersection of transcription and replication.
The timing of transcription and replication must be carefully regulated for heavily-transcribed genomes of double-stranded DNA viruses: transcription of immediate early/early genes must decline as replication ramps up from the same genome-ensuring efficient and timely replication of viral genomes followed by their packaging by structural proteins. To understand how the prototypic DNA virus Epstein-Barr virus tackles the logistical challenge of switching from transcription to DNA replication, we examined the proteome at viral replication forks. Specifically, to transition from transcription, the viral DNA polymerase-processivity factor EA-D is SUMOylated by the epigenetic regulator and E3 SUMO-ligase KAP1/TRIM28. KAP1's SUMO2-ligase function is triggered by phosphorylation via the PI3K-related kinase ATM and the RNA polymerase II-associated helicase RECQ5 at the transcription machinery. SUMO2-EA-D then recruits the histone loader CAF1 and the methyltransferase SETDB1 to silence the parental genome via H3K9 methylation, prioritizing replication. Thus, a key viral protein and host DNA repair, epigenetic and transcription-replication interference pathways orchestrate the handover from transcription-to-replication, a fundamental feature of DNA viruses.


Fatty acids attached to all-trans-astaxanthin alter its cis-trans equilibrium, and consequently its stability, upon light-accelerated autoxidation.
Fatty acid esterification, common in naturally occurring astaxanthin, has been suggested to influence both colour stability and degradation of all-trans-astaxanthin. Therefore, astaxanthin stability was studied as influenced by monoesterification and diesterification with palmitate. Increased esterification decelerated degradation of all-trans-astaxanthin (RP-UHPLC-PDA), whereas, it had no influence on colour loss over time (spectrophotometry). This difference might be explained by the observation that palmitate esterification influenced the cis-trans equilibrium. Free astaxanthin produced larger amounts of 9-cis isomer whereas monopalmitate esterification resulted in increased 13-cis isomerization. The molar ratios of 9-cis:13-cis after 60min were 1:1.7 (free), 1:4.8 (monopalmitate) and 1:2.6 (dipalmitate). The formation of 9-cis astaxanthin, with its higher molar extinction coefficient than that of all-trans-astaxanthin, might compensate for colour loss induced by conjugated double bond cleavage. As such, it was concluded that spectrophotometry is not an accurate measure of the degradation of the all-trans-astaxanthin molecule.


Work adjustment and readjustment of persons with mid-career onset traumatic brain injury.
This study investigated the effects of mid-career onset traumatic brain injury on work adjustment, as well as examining the utility of Hershenson's model of work adjustment. Ten clients in a head injury rehabilitation programme were intensively interviewed and completed questionnaires concerning the effect of their mid-career onset disability on their work adjustment. Information about post-traumatic work adjustment and coping was identified, collated and summarized. Results indicated that for this population work adjustment assumes a special meaning and career development becomes are development and planning process, rather than an unbroken, linear process. Results also suggested the utility of the Hershenson model for structuring studies on this specific topic and further emphasized that work adjustment development must be studied in the context of personal, family and social development.


The role of the nurse executive.
It is vital that the nurse executive critically examine her role conception and her role performance. She should take an activist's position in regard to her role, making it the sort of role it should be rather than merely filling the role as others expect or anticipate. Every role has much elasticity in it, and this enables the nurse executive to manipulate and alter the role if she tries. She also should learn to be sensitive to attempts to cast her in lesser roles than those which accord with her position in the organization. Role is an excellent concept by which to consider and link such various elements of management as managerial skills and abilities, managerial functions, organizational status, and strategies for management.


The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis.
Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients. Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed. Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years. Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.


Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals.
The risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and protease inhibitors (PIs) respectively. Thymidine associated mutations were identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2), 215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the changes associated with resistance to lamivudine (184V or 118I). No non nucleoside-RTI (NNRTI) mutations were present in the study period. Primary PIs mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note, mutations related to resistance to more than one class of antiretrovirals were present in one (1.5%). Among patients with chronic infection a large proportion (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4 patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). Primary mutations associated with substantial resistance to PIs were found in only 5/347 patients (1.4%); all the other patients carried only secondary mutations. Prevalence of mutations associated with high-level resistance to antiretroviral drugs is stable in recently infected individuals and low in patients with established HIV infection. The potential impact of transmitted mutations on the response to first regimen in individuals carrying transmitted mutations needs to be assessed by prospective studies.


Oral administration of radioactive sulfate to measure extracellular fluid space in man.
Radioactive sulfate-35 (35S) was administered to eight human subjects intravenously and orally, to compare respective kinetics of distribution. Intravenously administered 35S attained equilibration within 60-90 min. Orally administered 35S attained equilibration within 60-105 min and thereafter achieved plasma activity equivalent to the intravenously administered tracer. Eighty percent or greater of the 35S dose was recovered in the 24-h urine, following either intravenous or oral administration. The mean extracellular fluid space demonstrated less than 9% mean difference between routes of administration. It is concluded that 35S is completely absorbed at tracer doses, and may be administered orally as a reliable substitute for intravenously administered 35S for measuring extracellular fluid space.


Use of Quantitative Vertebral Bone Marrow Fat Fraction to Assess Disease Activity and Chronicity in Patients with Ankylosing Spondylitis.
We quantitatively measured the fat fraction (FF) in the vertebrae of patients with ankylosing spondylitis (AS) using magnetic resonance imaging (MRI) and investigated the role of FF as an indicator of both active inflammation and chronicity. A total of 52 patients with AS who underwent spinal MRI were retrospectively evaluated. The FF values of the anterosuperior and anteroinferior corners of the bone marrow in the L1-S1 spine were assessed using the modified Dixon technique. AS activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), AS Disease Activity Score (ASDAS), and serum inflammatory marker levels. AS disease chronicity was assessed by AS disease duration and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Univariable and multivariable regression analyses were conducted to investigate the correlation between FF and other clinical characteristics. The mean FF ± standard deviation of the total lumbar spine was 43.0% ± 11.3%. At univariable analysis, spinal FF showed significant negative correlation with BASDAI (β = -0.474, p = 0.002) and ASDAS with C-reactive protein (ASDAS-CRP; β = -0.478, p = 0.002) and a significant positive correlation with AS disease duration (β = 0.440, p = 0.001). After adjusting for patient age, sex, and total mSASSS score, spinal FF remained significantly negatively correlated with BASDAI (β = -0.543, p < 0.001), ASDAS-CRP (β = -0.568, p < 0.001), and ASDAS with erythrocyte sedimentation rate (β = -0.533, p = 0.001). Spinal FF was significantly lower in patients with very high disease activity (ASDAS-CRP > 3.5) than in those with only high disease activity (2.1 ≤ ASDAS-CRP ≤ 3.5) (p = 0.010). Spinal FF may help assess both AS disease activity and chronicity.


Wernicke's encephalopathy presenting with severe dysphagia: a case report.
A 62-year-old man developed dysphagia 4 weeks before the classic symptoms and signs of Wernicke's encephalopathy appeared. Adequate treatment with parenteral thiamine resulted in complete recovery of all symptoms, including his dysphagia. This extraordinary presentation with dysphagia, and the unusual course of the disease, encouraged us to present this case history.


Effect of elastic cavity wall and occlusal loading on microleakage and dentin bond strength.
This study evaluated the effect of an unfilled-adhesive resin (Adper Single Bond) and a filled-adhesive resin (Adper Single Bond 2) with and without a low viscosity resin (Filtek Flow) as an elastic cavity wall on marginal leakage and dentin microtensile bond strength in Class V composite restorations under unloaded and loaded conditions. V-shaped cavities were prepared on the buccal surfaces of 56 premolars lined with unfilled (Groups 1 and 3) or filled (Groups 2 and 4) adhesives with (Groups 3 and 4) and without (Groups 1 and 2) a low viscosity resin and restored with a resin composite. The restored teeth in each group were divided into two sub-groups for unloaded and loaded conditions with 50N loading force for 250,000 cycles parallel to the long-axis of the tooth. Five specimens from each group were cut bucco-lingually 0.7 mm thick and subjected to a dye leakage test for four hours using 2% methylene blue dye. The tested specimens were then trimmed into dumbbell shapes at the gingival margin and subjected to microtensile testing. The remaining two specimens were cut, embedded and observed for resin/dentin interfaces under a scanning electron microscope. For the microleakage test, there were no significant differences in microleakage among the groups on both the enamel and dentin margin. No statistically significant differences were found between microleakage of the loaded and unloaded groups on enamel margins for all materials. There were statistically significant differences between microleakage of the loaded and unloaded groups on the dentin margin for Groups 3 and 4. For the microtensile test, the significant difference was found between Groups 1 and 4 for the unloaded groups. For the loaded groups, there were no significant differences between Groups 1 and 2 and Groups 3 and 4. There were no statistically significant differences in microtensile bond strength between the loaded and unloaded groups except for Group 2. The application of filled adhesive or low viscosity resin had no influence on marginal leakage at both the enamel and dentin margin but it had an influence on the microtensile bond strength to dentin of Class V restorations. Occlusal loading significantly increased the degree of marginal leakage at the dentin margin when low viscosity was applied in combination with either unfilled or filled-adhesives, but it decreased dentin bond strength in the group treated with only filled adhesive.


Heart tissue repair and cardioprotection using drug delivery systems.
The capacity of the heart to heal after a myocardial infarction is not enough to restore normal cardiac function. Fortunately, delivery of therapeutics such as stem cells, growth factors, exosomes and small interfering ribonucleic acid (siRNA), among other bioactive molecules, has been shown to enhance heart repair and improve cardiac function. Furthermore, new delivery systems for these therapeutic agents have enhanced their regenerative and cardioprotective potential. In particular, nano- and microparticles (NPs and MPs) are promising. These systems may be administered directly in the infarcted myocardium or reach the heart after intravenous injection due to the enhanced permeability and retention effect or active targeting. Thus, NPs and MPs have made it possible to administer a wide range of potential drugs, including therapeutic molecules and/or stem cells, and evidence in favor of their use has been reported in several preclinical studies. Here, we review the studies done over the last 5 years using NPs and MPs loaded with therapeutics for repairing cardiac tissue after a myocardial infarction, and discuss some of the advances, challenges and future prospects in this field. In addition, we address the application of NPs and MPs for cardioprotective purposes.


Highly purified papain-solubilized HL-A antigens contain beta2-microglobulin.
HL-A antigens comprising 11 different antigenic specificities were isolated after papain solubilization of spleen-cell membrane constituents. During the entire purification procedure, beta(2)-microglobulin appeared together with the HL-A antigens. The highly purified antigens were composed of two polypeptide chains. The large subunit carried the antigenic specificity whereas the small polypeptide chain was very similar, if not identical, to beta(2)-microglobulin. The two HL-A antigen polypeptide chains were held together by noncovalent interactions only, and beta(2)-microglobulin, isolated from urine, could replace the small subunit in forming a complex with the large polypeptide chain. The topographical relationship in the cell membrane between beta(2)-microglobulin and the large HL-A antigen polypeptide chain is unknown. The two polypeptide chains may be fortuitously bound as a result of the solubilization procedure.


Meta-Analysis of a Web-Based Disease Forecast System for Control of Anthracnose and Botrytis Fruit Rots of Strawberry in Southeastern United States.
Strawberry production in Florida and South Carolina is affected by two major diseases, anthracnose fruit rot (AFR) and Botrytis fruit rot (BFR), caused by Colletotrichum acutatum and Botrytis cinerea, respectively. The effective management of both diseases traditionally relied on weekly fungicide applications. However, to improve timing and reduce the number of fungicide sprays, many growers follow the Strawberry Advisory System (StAS), a decision support system for forecasting fungicide applications based on environmental conditions and previously developed models. The objective of this study was to perform a meta-analysis to determine the effectiveness of the StAS for AFR and BFR management compared with a calendar-based spray program. Thirty-nine trials were conducted from 2009 to 2014 in Florida and South Carolina commercial strawberry fields. Meta-analysis was conducted to quantify the treatment effects on four effect sizes, all based on the difference in response variables for StAS and the calendar-based treatments in each trial. The mean difference in BFR incidence, AFR incidence, yield, and number of marketable fruit between the two treatments was not significantly different from 0 (P < 0.05). However, the number of fungicide applications per season was reduced by a median of seven when using the StAS, a 50% reduction in sprays compared with the calendar-based approach. Effect sizes were not influenced by location or the favorability of the environment for disease development. These findings indicate that use of StAS in commercial fields is effective in controlling fruit rot diseases with no reduction in yield while substantially reducing fungicide applications.


Increased upper airway collapsibility in children with obstructive sleep apnea during wakefulness.
Upper airway collapsibility (UAC) is increased in children with sleep-disordered breathing (SDB), but during wakefulness, active neural processes preserve upper airway patency, such that measurement of upper airway dynamics using acoustic pharyngometry may contribute to diagnostic accuracy in snoring children. Upper airway cross-sectional area obtained from acoustic pharyngometry measurements was assessed in 247 children referred for evaluation of suspected SDB and control subjects, before and after application of cetacaine 1% spray to the pharyngeal introitus under visual inspection. UAC was determined from the precentage change in cross-sectional area after topical anesthesia. UAC measurements were reproducible 1 week apart in both control subjects and patients with SDB (p < 0.005). A UAC less than or equal to -30% exhibited high sensitivity and specificity in identification of all children with obstructive apnea-hypopnea index greater than 5/hour total sleep time in a prospective initial sample of 54 children and in a subsequent post hoc sample of 94 snoring children. Thus, upper airway dynamic testing during wakefulness in response to a topical airway anesthetic may provide a useful clinical adjunct to the evaluation of snoring children, with more accurate identification of those children with SDB.


Methylophaga natronica sp. nov., a new alkaliphilic and moderately halophilic, restricted-facultatively methylotrophic bacterium from soda lake of the Southern Transbaikal region.
A new, moderately haloalkaliphilic and restricted-facultatively methylotrophic bacterium (strain Bur2T) with the ribulose monophosphate pathway of carbon assimilation is described. The isolate, which utilizes methanol, methylamine and fructose, is an aerobic, Gram-negative, asporogenous, motile short rod multiplying by binary fission. It is auxotrophic for vitamin B12, and requires NaHCO3 or NaCl for growth in alkaline medium. Cellular fatty acids profile consists primarily of straight-chain saturated C16:0, unsaturated C16:1 and C18:1 acids. The major ubiquinone is Q-8. The dominant phospholipids are phosphatidylethanolamine and phosphatidylglycerol. Diphosphatidylglycerol is also present. Optimal growth conditions are 25-29 degrees C, pH 8.5-9.0 and 2-3% (w/v) NaCl. Cells accumulate ectoine and glutamate as the main osmoprotectants. The G + C content of the DNA is 45.0 mol%. Based on 16S rDNA sequence analysis and DNA-DNA relatedness (25-35%) with type strains of marine and soda lake methylobacteria belonging to the genus Methylophaga, the novel isolate was classified as a new species of this genus and named Methylophaga natronica (VKM B-2288T).


Urinary stone disease burden is increased in patients with cognitive impairment.
Mental illness and brain disorders such as dementia are commonly encountered in patients with cognitive impairment in urology. In this cohort study, we assessed the prevalence and outcomes of inpatient admissions for stone disease in patients with cognitive impairment. Using the National Inpatient Sample database, we identified adults (>18 years) with stone disease between 2015 and 2019. The patients were dichotomized based on the presence or absence of cognitive impairment. The groups were compared for baseline differences in inpatient admissions and hospital complications. We evaluated the independent factors associated with urinary complications in the population using multivariate logistic regression. We identified 223,072 patients with stone disease. Patients with cognitive impairment were significantly (P<0.001) older (68 vs. 62 years), female (55.7% vs. 47.4%), had government-issued insurance (77.5% vs. 64.4%), and were discharged to a nursing facility (31.7% vs. 14.2%). Patients with cognitive impairment had significantly higher rates of urinary tract infection (29.7% vs. 21.5%, P<0.001), pneumonia (5.6% vs. 4.6%, P<0.001), systemic sepsis (4.3% vs. 3.8%, P<0.001), and acute renal failure (0.9% vs. 0.7%, P = 0.008). Female sex, low income, and cognitive impairment were all independently more likely to experience a urinary complication, with significant differences (P<0.001). Patients with cognitive impairment have a higher prevalence of stone disease and urinary complications associated with inpatient admissions than the rest of the population. Health care inequities among cognitively impaired patients should be a topic of further study.


Computational Inference of Synaptic Polarities in Neuronal Networks.
Synaptic polarity, that is, whether synapses are inhibitory (-) or excitatory (+), is challenging to map, despite being a key to understand brain function. Here, synaptic polarity is inferred computationally considering three experimental scenarios, depending on the nature of available input data, using the Caenorhabditis elegans connectome as an example. First, the inputs consist of detailed neurotransmitter (NT) and receptor (R) gene expression, integrated through the connectome model (CM). The CM formulates the problem through a wiring rule network that summarizes how NT-R pairs govern synaptic polarity, and resolves 356 synaptic polarities in addition to the 1752 known polarities. Second, known synaptic polarities are considered as an input, in addition to the NT and R gene expression data, but without wiring rules. These data train the spatial connectome model, which infers the polarity of 81% of the CM-resolved connections at >95$>95$ % precision, while also inferring 147 of the remaining unknown polarities. Last, without known expression or wiring rules, polarities are inferred through a network sign prediction problem. As an illustration of high performance in this case, the generalized CM is introduced. These results address imminent challenges in unveiling large-scale synaptic polarities, an essential step toward more realistic brain models.


[Clinical features of depression in adolescents with schizotypal disorder].
To study the clinical features of depressive disorders in adolescents with schizotypal disorder (STD). Were examined 87 adolescents with STD (F21), taken for outpatient or inpatient observation in 2018-2020. Of these, 26 patients were selected (12 males, 14 females, mean age 12.7±2.9 years) diagnosed with clinically significant depression (F32). To assess the severity of depression, the Hamilton Depression Rating Scales (HDRS) and the Beck Depression Self-Assessment Questionnaire (BDI) were used. The SPQ questionnaire was used to quantify the presence of STD symptoms. Depressive disorders were observed in 28% of all examined patients with STD. Signs of dysontogenesis were observed in 92% of the examined. The duration of depressive episodes before the start of treatment averaged 8.7 months, and until therapeutic remission was achieved, an average of 12.6 years. A mild depressive episode according to the HDRS scale corresponded in 23.1% of patients with a moderate degree in 61.5% and a severe one in 3.8%. At the same time, according to the BDI questionnaire, the results were different: there was no mild degree of depression during treatment, moderate-severe degree was detected in 8 (30.1%) patients, in the remaining 16 (61.5%) - extremely severe degree. Suicidal thoughts were noted in 76.9% of the surveyed, while the parents knew about their presence only in 27.0% of adolescents. A suicidal attempt was made by 3 patients (11.5%), one of them repeatedly. Non-suicidal self-injurious behavior was found in 38.5% of patients. Depressive episodes in adolescents with STD are noted chkasto, characterized by the duration and severity of symptoms. Subjective depressive experiences, primarily internal feelings of longing, ideas of failure and guilt, as well as the frequency of anti-vital thoughts and self-injurious behavior, are much more pronounced in adolescents than they demonstrate in everyday life.


Overview of clinical trials on endosseous implants.
Early history of clinical trials on endosseous implants revolved around anecdotal reports on predominantly blade implants in the U.S. The first criteria to define success or failure were established at the National Institutes of Health (NIH)-Harvard Conference in 1978. This was followed by the multi-center trials from the Branemark group which described round, metallic implants. At the 1988 NIH Conference, questions dealt with the following: 1) the effectiveness of dental implants for the long-term; 2) indications and contra-indications of various types of implants; 3) requirements for management of dental implants; 4) health risks of dental implants; and 5) future directions in research. In the ensuing 7 years since the second NIH Conference, most of the data generated have been from non-controlled case reports, which describe a 90% success rate in 5 years or more with many types of endosteal systems in both partially and fully edentulous patients. Therefore, it can be said that there is evidence that dental implants are effective for the long-term. The other questions posed at the 1988 NIH Conference have not been as well described and have led to many controversies and future research areas. Two areas which will have a special future impact are 1) the establishment of a standard of care and risk-benefit ratio for implants and 2) the use of various factors to accelerate bone formation to allow greater access to dental implants by patients.


Cytotoxic oxygenated triterpenoid saponins from Symplocos chinensis.
A n-butanol-soluble fraction of an ethanolic extract from the roots of Symplocos chinensis showed cytotoxic activity against several cancer cell lines. Bioassay-guided purification led to the isolation and characterization of eight new triterpenoid saponins, symplocososides L-S (1-8). The structures of 1-8 were elucidated as glycosides based on oxygenated aglycons by spectroscopic and chemical methods. These compounds and their hydrolytic products, along with some additional analogues obtained earlier from S. chinensis roots, were evaluated for cytotoxicity in a small cancer cell panel.


Relevance of synovial fluid chondroitin sulphate as a biomarker to monitor polo pony joints.
Osteoarthritis (OA) of the metacarpophalangeal joint is the most common articular disease in polo ponies leading to early retirement. A biomarker that would discriminate between pathological and physiological changes secondary to exercise could be helpful in OA prevention. The aim of this study was to investigate the effects of polo training on synovial fluid biomarkers of inflammation and cartilage turnover in polo ponies of different skill levels. Synovial fluid samples were collected from metacarpophalangeal joints of polo ponies before and during the polo season (320 d). Nucleated cells, soluble protein, prostaglandin E2 (PGE2), glycosaminoglycans (GAG), and urea were measured. The main synovial fluid GAG are chondroitin sulphate (CS, ~25 μg/mL) and hyaluronic acid (HA, ~400 μg/mL). After a polo match, a transitory increase in protein and PGE2, but not CS and HA, occurred (expressed as urea ratio), returning to basal levels in 24 h. During the polo season, the number of synovial fluid nucleated cells was always in the normal range. Increases in protein and HA occurred during the initial 40 to 80 d, returning to basal levels afterwards. In contrast, in polo prospects the concentration of CS steadily increased during the season. Long-term follow-up revealed that the synovial fluid CS was significantly higher in polo ponies that developed joint diseases within 24 months following our study. In conclusion, CS seems to be an early marker of articular cartilage damage.