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Objectives. To examine gun violence with respect to hospital visits for treatment of intentional assault gunshot wounds (IGWs). Methods. IGW-coded visits among residents of Cook County, Illinois, were matched to census zip code tabulation areas (ZCTAs) to map changes in IGW visit frequencies between 2018 and 2020. Patient characteristics were compared across years, and Poisson regression models for the likelihood of an inpatient admission or in-hospital death were estimated. Results. Over the study period, Cook County residents made 7122 IGW-coded hospital visits to 89 Illinois hospitals, resulting in $342 million in charges and 24 894 hospital days. The number of visits almost doubled between 2018 and 2020, from 1553 to 3031; 6 ZCTAs had increases of more than 60 visits. Approximately one third of patients with a visit were admitted, and 6.5% died. Conclusions. Hospital statistics do not include the full toll of nonfatal gun injuries or the costs of related community-level trauma. The health care system remains crucial in implementing epidemiological approaches to violence prevention. Addressing the national spike in shootings will require large investments in community economic development and a professional public safety workforce. (Am J Public Health. 2022;112(5):795–802. https://doi.org/10.2105/AJPH.2022.306747 )

We characterized the evolution of neurologic symptoms and self-perceived recovery of non-hospitalized COVID-19 "long haulers" 6-9 months after their initial Neuro-COVID-19 clinic evaluation.In this follow-up study on the first 100 patients, 50 SARS-CoV-2 laboratory-positive (SARS-CoV-2Of 52 patients who completed the study (27 SARS-CoV-2Non-hospitalized COVID-19 "long haulers" continue to experience neurologic symptoms, fatigue, and compromised quality of life 14.8 months after initial infection.

Objective: The purpose of this study was to investigate factors related to treatment attendance for patients seeking gender-affirming voice therapy (GAVT). Method: We completed retrospective chart reviews of 50 patients (43 transgender women, three transgender men, four nonbinary patients; aged 18–67 years, M = 34.92 years, SD = 12.32 years) referred for GAVT at a Midwest outpatient center from 2016 to 2021. Data extraction included patient demographics, therapy visit specifics (e.g., number of sessions attended, treatment completion status, and in-person vs. virtual visits) and treatment timing (in relation to the onset of the COVID-19 pandemic), and psychosocial and socioeconomic information. Results: There was no impact of treatment-timing relative to the onset of the pandemic on any attendance measure; however, patients were 1.9 times more likely to complete therapy with each virtual telehealth session attended. Individual factors of outside social support and hormone replacement therapy were positively related to the number of therapy sessions attended, whereas insurance provider and employment status were related to therapy completion. Conclusions: Telehealth attendance during the COVID-19 pandemic was positively associated with GAVT completion. Future research should investigate psychosocial and socioeconomic factors to understand how to identify patients at risk for poor treatment adherence and facilitate access to clinical care.

Surgery, radiation, chemotherapy, and targeted therapy were the four basic kinds of cancer treatment until recently. Immuno-oncology (IO), or the cancer cells were damaged by engaging the body's of their own self immune system, has emerged and explained as a unique and crucial method to different cancers and their treatment over the last decade. The US Food and Drug Administration and the European Medicines Agency both advanced approvals of this newly recognised way of treating cancer in 2020. Within IO, different therapeutic classes have arisen, which are the subject of this same article. Immune checkpoint inhibitors have demonstrated extraordinary it will show efficacy in a different variety of tumors and they are the most well-known therapeutic class of Immuno-Oncology drugs until now. Biomarker and their testing for different tumors like Gastrointestinal cancer, whole Head, lower and upper part Neck cancer and too cervical cancer by programmed death-ligand 1 (PD-L1) checking point and their targets were innovated and is currently utilising prior to treatment by using Pembrolizumab. However, the significance of PD-L1 exhibition for immune checking point reticence therapy in other/different onco-cancer types remains unclear. Homogenized immune-oncology drugs with regular therapy were recently studied and clinical efficacy outcomes have shown to be significantly improved. While Immuno-oncology agents are fast transforming the marketed treatment for cancer patients, there are still number of obstacles to get those get the better of in their conditions of associating those side effects and confirming those different healthcare and their systems, such as finance these expensive therapies. In addition to cancer vaccines and chimeric antigen receptor T-cell treatments, the Immuno-Oncology drugs are in pipeline contains chimeric antigen receptor T-cell therapies, both of which have their own set of toxicity and cost-effectiveness challenges.

Metal coordination chemistry is common in biology, with many proteins containing metal ion-based structural motifs or catalytic centers. An interesting example of nature’s use of coordinate bonding to create a proteinaceous structural material is found in the Alitta virens marine worm jaw. Inspired by Zn+2 cross-linked polymers in A. virens, we have extended coordination cross-linking to preceramic polymers. Commercially available Si-based backbones functionalized with pyridyl-moieties were introduced to metal ions to initiate cross-linking. Metal coordination offered a single knob to tune multiple characteristics of the material before and after pyrolysis. The loading of the metal ions into the polymer impacted the viscoelastic properties, thermal stability, and ceramic yield. Pyrolysis yielded a ceramic representative of the metal ion cross-linker (e.g., forming TiC/SiC nanocomposites).

OBJECTIVES/HYPOTHESIS We investigated speech acoustics and self-reported vocal symptoms in mask-wearing healthcare professionals. We hypothesized that there would be an attenuation of spectral energies and increase in vocal effort during masked speech compared to unmasked speech. STUDY DESIGN Within and between subject quasi-experimental design. METHODS We prospectively enrolled 21 healthcare providers (13 cisgender female, 8 cisgender male; M = 32.9 years; SD = 7.9 years) and assessed acoustics and perceptual measures with and without a face mask in place. Measurements included: 1) acoustic Vowel Articulation Index (VAI); 2) cepstral and spectral acoustic measures; 3) traditional vocal measures (e.g., fundamental frequency, intensity); 4) relative fundamental frequency (RFF); and 5) self-reported ratings of vocal effort and dyspnea. RESULTS During masked speech, there was a significant reduction in VAI, high-frequency information (>4 kHz), and RFF offset 10, as well as a significant increase in cepstral peak prominence and perceived vocal effort. Further analysis showed that high-frequency attenuation was more pronounced when wearing an N95 mask compared to a simple mask. CONCLUSIONS Face masks pose an additional barrier to effective communication that primarily impacts spectral characteristics, vowel space measures, and vocal effort. Future work should evaluate how long-term mask use impacts vocal health and may contribute to vocal problems. LEVEL OF EVIDENCE 3 Laryngoscope, 2021.

Aging is accompanied by major changes in body composition that can negatively affect functional status in older adults, including a progressive decrease in muscle mass, strength, and quality. The prevalence of sarcopenia has varied considerably, depending on the definition used and the population surveyed-a 2014 meta-analysis across several countries found estimates ranging from 1% to 29% for people aged 60 years or older, who live independently. The potentially relevant studies were retrieved from the ScienceDirect/Medline/PubMed/Public library of science/Mendeley/Springer link and Google Scholar. Multiple keywords were used for the literature search both alone and in combination. Some of the important keywords used for literature search were as follows: "Epidemiology of muscle weakness/muscle disorders," "Pathogenesis of RAAS in muscle weakness," "Role of Angiotensin 1-7/ACE-2/Mas R axis in muscle weakness," and "Correction pathophysiology of muscle weakness via ACE2." The renin-angiotensin system (RAAS), a major blood pressure regulatory system, is a candidate mediator that may promote aging-associated muscle weakness. Previously, studies explored the proof concept for RAAS inhibition as a therapeutic target. Furthermore, in RAAS, angiotensin II, and angiotensin-converting enzyme 2 (ACE2) have been reported to induce endoplasmic reticulum (ER) stress via glucose-regulated protein 78/eukaryotic translation initiation factor 2α (eIF2α)/activating transcription factor 4 (ATF4)/CHOP axis in the liver. In addition, other mitochondria and ER physical interactions contribute to skeletal muscle dysfunction. However, very few studies have investigated the relationship between RAAS and ER stress-associated pathophysiological events and ACE2-mediated biological consequences in muscle weakness. Thus, the study has been designed to investigate the RAAS-independent beneficial role of ACE2 in muscle weakness.

Missense variants ABI3_rs616338-T and PLCG2_rs72824905-G were previously associated with elevated or reduced risk of Alzheimer’s disease (AD), respectively. Despite reports of associations with other neurodegenerative diseases, there are few studies of these variants in purely neuropathologically diagnosed cohorts. Further, the effect of these mutations on neurodegenerative disease pathologies is unknown. In this study, we tested the effects of ABI3_rs616338-T and PLCG2_rs72824905-G on disease risk in autopsy cohorts comprised of 973 patients diagnosed neuropathologically with Lewy body disease (LBD-NP) and 1040 with progressive supranuclear palsy (PSP), compared to 3351 controls. LBD-NP patients were further categorized as high, intermediate and low likelihood of clinical dementia with Lewy bodies (DLB-CL) based on DLB Consortium criteria. We also tested for association with both Braak neurofibrillary tau tangle (nTotal = 2008, nPSP = 1037, nLBD-NP = 971) and Thal phase amyloid plaque scores (nTotal = 1786, nPSP = 1018, nLBD-NP = 768). Additionally, 841 PSP patients had quantitative tau neuropathology measures that were assessed for genetic associations. There was no statistically significant association with disease risk for either LBD-NP or PSP in our study. LBD intermediate category disease risk was significantly associated with ABI3_rs616338-T (OR = 2.65, 95% CI 1.46–4.83, p = 0.001). PLCG2_rs72824905-G was associated with lower Braak stage (ß = − 0.822, 95% CI − 1.439 to − 0.204, p = 0.009). This effect was more pronounced in the PSP (ß = − 0.995, 95% CI − 1.773 to − 0.218, p = 0.012) than LBD-NP patients (ß = − 0.292, 95% CI − 1.283 to 0.698, p = 0.563). PLCG2_rs72824905-G also showed association with reduced quantitative tau pathology for each lesion type and overall tau burden in PSP (ß = − 0.638, 95% CI − 1.139 to − 0.136, p = 0.013). These findings support a role for PLCG2_rs72824905-G in suppressing tau neuropathology. ABI3_rs616338-T may influence disease risk specifically in the LBD-NP intermediate category comprised of patients with diffuse neocortical or limbic LB, concurrently with moderate or high AD neuropathology, respectively. Our study provides a potential mechanism of action for the missense PLCG2 variant and suggests a differential disease risk effect for ABI3 in a distinct LBD-NP neuropathologic category.

The self-assembly of block copolymers offers opportunities for the facile organization and templating of inorganic nanomaterials. Here, we describe a morphology map for a poly(methyl methacrylate)-...

Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer’s disease (AD), however these findings can be confounded by cellular composition changes in bulk-tissue. To identify cell intrinsic gene expression alterations of individual cell types, we designed a bioinformatics pipeline and analyzed three AD and control bulk-RNAseq datasets of temporal and dorsolateral prefrontal cortex from 685 brain samples. We detected cell-proportion changes in AD brains that are robustly replicable across the three independently assessed cohorts. We applied three different algorithms including our in-house algorithm to identify cell intrinsic differentially expressed genes in individual cell types (CI-DEGs). We assessed the performance of all algorithms by comparison to single nucleus RNAseq data. We identified consensus CI-DEGs that are common to multiple brain regions. Despite significant overlap between consensus CI-DEGs and bulk-DEGs, many CI-DEGs were absent from bulk-DEGs. Consensus CI-DEGs and their enriched GO terms include genes and pathways previously implicated in AD or neurodegeneration, as well as novel ones. We demonstrated that the detection of CI-DEGs through computational deconvolution methods is promising and highlight remaining challenges. These findings provide novel insights into cell-intrinsic transcriptional changes of individual cell types in AD and may refine discovery and modeling of molecular targets that drive this complex disease.

BACKGROUND Compared with adults, children may be at greater risk of medication errors and potential adverse effects. The American Academy of Pediatrics recommends developing mechanisms for proactively identifying patients at risk for medication-related adverse events and failed reconciliation. This study's primary purpose was to evaluate pediatric patients admitted to identify risk factors requiring pharmacist intervention during medication reconciliation (MedRec). METHODS This prospective study included pediatric patients admitted during the study time frame until the target population of 500 patient encounters was achieved. During each admission, pharmacy staff completed a medication history, after which a pediatric pharmacist completed a MedRec, as is standard hospital practice. The primary outcome was identification of factors for high-risk transitions of care during pediatric admissions based on the need for pharmacist interventions during the MedRec process. RESULTS In total, 331 interventions were made for 127 patients (median 2; range, 1–12). Of the 331 interventions, 196 (59.2%) were classified as being of moderate or significant severity. Although patients with at least 2 home medications were significantly more likely to require any intervention (p < 0.0001), patients with 5 or more home medications were more likely to have a significant intervention. CONCLUSION Identifying patients with home medications could allow for focused efforts to intervene. Also, patients admitted to the PICU or those with cardiology- or endocrinology-related diagnoses should be prioritized for MedRec process, because of the likelihood of requiring multiple home medications. This strategy should be tailored to individual pediatric institutions based on internal quality control assessments and available resources.

Persistent viral RNA shedding of SARS-CoV-2 following COVID-19 has increasingly been recognized, with limited understanding of its implications on outcomes in hospitalized COVID-19 patients.We retrospectively assessed for persistent viral shedding across Northwestern Medicine Healthcare (NMHC) patients between March and August 2020. We assessed for predictors of persistent viral shedding, in-hospital delirium, and six-month mortality using binary logistic regression.Of the 2,518 hospitalized patients with an RT-PCR-confirmed diagnosis of COVID-19, 959 underwent repeat SARS-CoV-2 RT-PCR at least fourteen days from initial positive testing. Of those, 405 (42.2%) patients were found to have persistent viral shedding. Persistent viral shedding was associated with male sex, increased BMI, diabetes mellitus, chronic kidney disease, and exposure to corticosteroids during initial COVID-19 hospitalization. Persistent viral shedding was independently associated with incidence of in-hospital delirium after adjusting for factors including severity of respiratory dysfunction (OR 2.45; 95% CI 1.75, 3.45). Even after adjusting for age, severity of respiratory dysfunction, and occurrence of in-hospital delirium, persistent viral shedding remained significantly associated with increased six-month mortality (OR 2.43; 95% CI 1.42, 4.29).Persistent viral shedding occurs frequently in hospitalized COVID-19 patients and is associated with in-hospital delirium and increased six-month mortality.

Blood-brain barrier (BBB) dysfunction is well-known in Alzheimer’s disease (AD), but the precise molecular changes contributing to its pathophysiology are unclear. To understand the transcriptional changes in brain vascular cells, we performed single nucleus RNA sequencing (snRNAseq) of temporal cortex tissue in 24 AD and control brains resulting in 79,751 nuclei, 4,604 of which formed three distinct vascular clusters characterized as activated pericytes, endothelia and resting pericytes. We identified differentially expressed genes (DEGs) and their enriched pathways in these clusters and detected the most transcriptional changes within activated pericytes. Using our data and a knowledge-based predictive algorithm, we discovered and prioritized molecular interactions between vascular and astrocyte clusters, the main cell types of the gliovascular unit (GVU) of the BBB. Vascular targets predicted to interact with astrocytic ligands have biological functions in signalling, angiogenesis, amyloid ß metabolism and cytoskeletal structure. Top astrocytic and vascular interacting molecules include both novel and known AD risk genes such as APOE, APP and ECE1. Our findings provide information on transcriptional changes in predicted vascular-astrocytic partners at the GVU, bringing insights to the molecular mechanisms of BBB breakdown in AD.Graphical AbstractPericytes (yellow), endothelia (salmon) and astrocytes (purple) that form the gliovascular unit (GVU) at the blood brain barrier (BBB) were interrogated for their differentially expressed genes (DEG) and vascular cell (pericyte or endothelia) to astrocyte interactions using single nucleus RNA sequencing (RNAseq) transcriptome obtained from brains of Alzheimer’s disease (AD) patients and controls. We identified many upregulated (red) or downregulated (blue) DEGs in AD brains in these cell types. These genes have known biological functions in amyloid ß (Aß) clearance, immune modulation, astrogliosis and neuronal death. Novel predicted interactions were identified between vascular cells and astrocytic DEGs. Collectively, our findings highlight the vast transcriptome changes that occur at the GVU and provide mechanistic insights into BBB dysfunction in AD. This figure was created with Biorender.com.

Frustrated Lewis pair (FLP) chemistry is an alternative strategy in the area of metal-free organic catalysis. This study reports adamantane as FLP molecular scaffold used to design new FLP (ambiphilic molecule) for the metal-free catalytic reduction of CO

Recent efforts have demonstrated that the morphology of ceramics can be manipulated to control both their deformation mechanism and mechanical performance. However, precise control of the ceramic nanostructure is still difficult to achieve. Biotemplating, leading to biomorphic materials, provides a facile route to manipulate the nanostructure of the resulting materials, and the use of melanin as a coating provides a new route to biotemplated materials. Melanin is underutilized for structural materials partly due to the cost of procuring it from natural sources and the inability to control the shape and sizes of melanin particles. Taking a combined synthetic biology and chemical synthesis approach, we report the melanization of Escherichia coli and its subsequent silanization and functionalization with preceramic polymers to make novel biomorphic silicon-based ceramic materials. Graft-to and graft-from reactions were used to append preceramic polymers to the melanin, followed by pyrolysis under argon. Samples were analyzed by FTIR, XRD, XPS, and TEM and found to retain the shape and size of the original cells with high fidelity. The homogeneity of coverage and yield of the resulting ceramic materials depended on the type of grafting reaction. This work provides a promising proof-of-concept that bacterial-templated ceramics can be readily made and opens a host of possibilities for further studies and applications.

Summary Objective We evaluated voice acoustics and self-perceptual ratings in healthcare workers required to wear face masks throughout their workday. Methods Eighteen subjects (11 cisgender female, 7 cisgender male; M = 33.72 years, SD = 8.30) completed self-perceptual ratings and acoustic recordings before and after a typical workday. Chosen measures were specific to vocal effort, dysphonia, and laryngeal tension. Mixed effects models were calculated to determine the impact of session, mask type, sex, and their interactions on the set of perceptual and acoustic measures. Results The subjects self-reported a significant increase in vocal effort following the workday. These perceptual changes coincided with an increase in vocal intensity and harmonics-to-noise ratio, but decrease in relative fundamental frequency offset 10. As expected, men and women differed in measures related to fundamental frequency and vocal tract length. Conclusion Healthcare professionals wearing masks reported greater vocal symptoms post-workday compared to pre-workday. These symptoms coincided with acoustic changes previously related to vocal effort; however, the degree of change was considered mild. Further research is needed to determine whether vocal hygiene strategies may reduce vocal symptoms in mask-wearing workers.

Microglia have fundamental roles in health and disease, however effects of age, sex and genetic factors on human microglia have not been fully explored. We applied bulk and single cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2 and BIN1. Meta-analyses with published bulk and single cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource; and highlight age, sex and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.

Cerebral amyloid angiopathy (CAA) contributes to accelerated cognitive decline in Alzheimer’s disease (AD) dementia and is a common finding at autopsy. The APOEε4 allele and male sex have previously been reported to associate with increased CAA in AD. To inform biomarker and therapeutic target discovery, we aimed to identify additional genetic risk factors and biological pathways involved in this vascular component of AD etiology. We present a genome-wide association study of CAA pathology in AD cases and report sex- and APOE-stratified assessment of this phenotype. Genome-wide genotypes were collected from 853 neuropathology-confirmed AD cases scored for CAA across five brain regions, and imputed to the Haplotype Reference Consortium panel. Key variables and genome-wide genotypes were tested for association with CAA in all individuals and in sex and APOEε4 stratified subsets. Pathway enrichment was run for each of the genetic analyses. Implicated loci were further investigated for functional consequences using brain transcriptome data from 1,186 samples representing seven brain regions profiled as part of the AMP-AD consortium. We confirmed association of male sex, AD neuropathology and APOEε4 with increased CAA, and identified a novel locus, LINC-PINT, associated with lower CAA amongst APOEε4-negative individuals (rs10234094-C, beta = −3.70 [95% CI −0.49—−0.24]; p = 1.63E-08). Transcriptome profiling revealed higher LINC-PINT expression levels in AD cases, and association of rs10234094-C with altered LINC-PINT splicing. Pathway analysis indicates variation in genes involved in neuronal health and function are linked to CAA in AD patients. Further studies in additional and diverse cohorts are needed to assess broader translation of our findings.

Additional file 1.

SummarySelective vulnerability is a central concept to the myriad of devastating neurodegenerative disorders. Although hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), the degree of involvement lies along a spectrum that we previously defined as AD subtypes revealing distinct clinical correlates. To operationalize heterogeneity of disease spectrum, we classified corticolimbic patterns of neurofibrillary tangles to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. Using a multidisciplinary approach, we uncovered disease-relevant hippocampal gene expression changes. Biological relevance was prioritized using machine learning and several levels of human validation. This resulted in five genes highly predictive of neuropathologically diagnosed AD:SERPINA5, RYBP, SLC38A2, FEM1B, andPYDC1. Deeper investigation revealed SERPINA5 to be a novel tau binding partner that may represent a “tipping point” in the dynamic maturity of neurofibrillary tangles. Our study highlights the importance of embracing heterogeneity of the human brain to yield promising gene candidates as exampled bySERPINA5.

Background and ObjectivesAlthough patients hospitalized with COVID-19 frequently present with encephalopathy, those with mild initial COVID-19 disease who never required hospitalization also often develop neurologic symptoms as part of postacute sequelae of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection (neuro-PASC). The pathogenic mechanisms of COVID-19 encephalopathy and neuro-PASC are unknown. We sought to establish biochemical evidence of CNS injury in those patients and their association with neuropsychiatric manifestations and SARS-CoV-2 antigenemia.MethodsWe recruited hospitalized, posthospitalized, and nonhospitalized patients with confirmed diagnosis of COVID-19 with neurologic symptoms in addition to healthy control (HC) subjects. Plasma neurofilament light chain (pNfL), plasma glial fibrillary acidic protein (pGFAP), and plasma SARS-CoV-2 Nucleocapsid antigen (pN Ag) were measured by HD-X Simoa analyzer (Quanterix) and compared with neuropsychiatric symptoms, patient-reported quality-of-life measures, and standardized cognitive assessments. Neuroglial scores (pGFAP/pNfL) were calculated to estimate the relative contribution of astroglial and neuronal involvement.ResultsWe enrolled a total of 64 study participants, including 9 hospitalized patients with COVID-19 encephalopathy (CE), 9 posthospitalization neuro-PASC (PNP) patients, 38 nonhospitalized neuro-PASC (NNP) patients, and 8 HC subjects. Patients with CE were older, had higher pNfL and pGFAP concentrations, and more frequent pN Ag detection than all neuro-PASC groups. PNP and NNP patients exhibited similar PASC symptoms, decreased quality-of-life measures, and cognitive dysfunction, and 1 of the 38 (2.6%) NNP patients had pN Ag detectable 3 weeks postsymptoms onset. Patients with neuro-PASC presenting with anxiety/depression had higher neuroglial scores, which were correlated with increased anxiety on quality-of-life measures.DiscussionpNfL, pGFAP, and pN Ag measurements indicate neuronal dysfunction and systemic involvement in hospitalized COVID-19 patients with encephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.

An amendment to this paper has been published and can be accessed via the original article.

Mycobacteriophages Darionha, Salz, and ThreeRngTarjay are mycobacteriophages isolated using the host Mycobacterium smegmatis mc2155. Following isolation from soil samples, all three siphoviridae phages were characterized, and their genomes were sequenced and annotated.

Additional file 1: Supplementary Text This file includes detailed methods on the acquisition of the neuropathology phenotypes

Additional file 1.

Space, it is the area provided for particular purpose. Space can be two dimensional, three dimensional or multi. The perception of a space is known by its functionality and quality. Space does not define the use or behavior. Space can be identified as interior, exterior, common, transition; public, personal etc. 90 percent of our daily lives are spent inside. That is our experience of the city – moving from one interior to another. So our remit is to improve the quality of life for citizen, focusing on the quality of interior spaces.

Nebraska Supreme Court Rules a Minor in Foster Care Seeking an Abortion Must Obtain Foster Parents Consent - In re Anonymous 51 - In a per curiam decision, the Nebraska Supreme Court held that for the purposes of Nebraska's Abortion Consent Law, a sixteen -year-old female must obtain consent from her foster parents before she can choose to obtain an abortion, despite her legal status as a ward of the State of Nebraska.2Nebraska's Abortion Parental Consent Law requires minors seeking an abortion to obtain the written consent of one of her parents or a legal guardian. 3 While the United States Supreme Court has upheld the rights of states to pass such parental consent laws, they have also required the laws to include certain exceptions. 4 For example, in Belotti v Baird, the Court held that a state must include a judicial bypass whereby a minor can seek judicial permission to forgo par ental consent.5 When granting permission, a judge must consider and determine whether the minor is sufficiently mature to obtain an abortion, or that an abortion would be in her best interest.6Nebraska's Parental Consent Law seemingly satisfies this const itutional standard by providing three types of "judicial bypass." 7 These include "medical emergency," "victim of abuse," and "mature minor" exceptions to the parental consent requirement.8 In this case, the Petitioner contended that she does not need to obtain consent because she is a victim of abuse from her biological parents and that she is sufficiently mature to proceed with the abortion without parental consent. 9The Petitioner is a sixteen-year-old female who was placed in the custody of Nebraska's Department of Health and Human Services (DHHS) in 2011.10 Subsequently, the DHHS placed her and her two younger siblings in a foster care home.11 In May 2013, a juvenile court terminated the parental rights of the Petitioner's parents.12 The Nebraska Supreme Court found that the Petitioner did not qualify for any judicial bypass because she did not establish by clear and convincing evidence that she was a victim of abuse by her foster parents who were acting as her guardian when she filed the petition, or tha t she was "sufficiently mature and well - informed to decide whether to have an abortion ."13 Ultimately, the Court reaffirmed that the Petitioner's foster parent's consent is needed under the Abortion Parental Consent law.14The crux of this case turned on the court's determination of who could provide proper consent for a minor. In its decision, the court found that Nebraska's Administrative Code, which states that if a ward of the state decides to have an abortion the consent of her parents or the DHHS is not required, did not apply in this case.15 The court came to this conclusion mainly on jurisdictional grounds, 16 as the regulation's applicability was not substantively raised in the lower court and the Petitioner only sought review for the "victim of abuse" a nd "sufficiently mature" judicial bypass determinations.17The court only briefly discussed the Petitioner's proper legal guardian. Specifically, the court stated that the DHHS was the legal guardian of all children committed to it; however, the court also avoided characterizing the legal status of the Petitioner's foster parents, claiming it was outside the scope of the "special proceeding."18 Ultimately, the court upheld the lower court's decision that for purposes of the Nebraska Abortion Parental Consent law, the Petitioner needed her foster parents' consent in order to obtain an abortion. 19As the dissenting j ustice noted, Nebraska's Parental Consent Law raises serious federal constitutional concerns because it may impose a strict prohibition against obtaining an abortion for wards of the State of Nebraska. 20 As discussed above, laws requiring parental consent for abortions are constitutional only if they include a process by which judge can determine if the minor in question is sufficiently mature, or it would be in her best interest to have an abortion. …

Background: Warfarin is still the most commonly used anticoagulant for the treatment of venous thromboembolism and other hypercoagulable states. Warfarin metabolism is affected by multiple factors, including diet, medications, and individual patient characteristics. As both underdosing and overdosing can increase risks to patients, several studies have attempted to develop dosing protocols. However, few have investigated how patient weight and body mass index (BMI) affect warfarin dosing. Objective: The objective of this study was to determine the association between BMI and the total weekly dose (TWD) of warfarin. Methods: In this retrospective study, we identified patients taking warfarin who had an international normalized ratio (INR) within the therapeutic range to assess if there was a significant correlation between TWD, that is, maintenance warfarin dosing, and BMI in obese and nonobese patients. Results: A total of 831 patients were studied, with a BMI range between 13.4 and 63.1 kg/m2. We found that BMI is positively correlated with the total weekly warfarin dose. Our study showed that for each 1-point increase in BMI, the weekly warfarin dose increased by 0.69 mg. We found that the average warfarin weekly dose in this population can be estimated using the formula: 12.34 + 0.69 × BMI. Conclusion: There is an association between BMI and the TWD of warfarin. This could have dosing implications for both patients and prescribers, as patients with a high BMI will be expected to require higher doses of warfarin to maintain a therapeutic INR.

Graphics was a two dimensional notion till the nineteenth century. It was only in the twentieth century, during the modern movement, that graphics emerged as a three dimensional tool. During the same time architecture also had a change in its definition and there was a breakthrough in the design industry. Colour which was earlier used as a superficial element for decoration now started being used as a design element of third dimension in architecture. Designing with colour therefore it must be considered in all its aspects of which are related to one another, so that virtually in any work in which colour plays a role all must be taken into accent. Colours have a profound effect on mind and emotion and influence our mood and feelings. Colour can reinforce ideas of form and material; express its divisions and proportions. Colour can underline an architectural statement, it can punctuate, direct and focus attention and compensate in a way unlike any other abstract element”. How graphical use of colour can create a statement in architecture.

Graphics was a two dimensional notion till the nineteenth century. It was only in the twentieth century, during the modern movement, that graphics emerged as a three dimensional tool. During the same time architecture also had a change in its definition and there was a breakthrough in the design industry. Colour which was earlier used as a superficial element for decoration now started being used as a design element of third dimension in architecture. Designing with colour therefore it must be considered in all its aspects of which are related to one another, so that virtually in any work in which colour plays a role all must be taken into accent. Colours have a profound effect on mind and emotion and influence our mood and feelings. Colour can reinforce ideas of form and material; express its divisions and proportions. Colour can underline an architectural statement, it can punctuate, direct and focus attention and compensate in a way unlike any other abstract element”. How graphical use of colour can create a statement in architecture.

Polymodal neurons of the trigeminal nerve innervate the nasal cavity, nasopharynx, oral cavity and cornea. Trigeminal nociceptive fibers express a diverse collection of receptors and are stimulated by a wide variety of chemicals. However, the mechanism of stimulation is known only for relatively few of these compounds. Capsaicin, for example, activates transient receptor potential vanilloid 1 (TRPV1) channels. In the present study, wildtype (C57Bl/6J) and TRPV1 knockout mice were tested in three behavioral assays for irritation to determine if TRPV1 is necessary to detect trigeminal irritants in addition to capsaicin. In one assay mice were presented with a chemical via a cotton swab and their response scored on a 5 level scale. In another assay, a modified two bottle preference test, which avoids the confound of mixing irritants with the animal’s drinking water, was used to assess aversion. In the final assay, an air dilution olfactometer was used to administer volatile compounds to mice restrained in a double-chambered plethysmograph where respiratory reflexes were monitored. TRPV1 knockouts showed deficiencies in the detection of benzaldehyde, cyclohexanone and eugenol in at least one assay. However, cyclohexanone was the only substance tested that appears to act solely through TRPV1.