A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers.

An Extensive Case of Aplasia Cutis Congenita.

Aplasia cutis congenita (ACC) is a rare connective tissue disorder that affects the epidermis, dermis, and subcutaneous tissue. Lesions can be small and benign or, in some cases, large and extensive. The lesions can be covered by a thin membrane, and depending on their location, they can make the underlying tissue vulnerable to damage or infection.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generated single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers.

Is low-molecular-weight heparin superior to aspirin for VTE prophylaxis?

Aspirin demonstrated a significantly higher rate of postoperative venous thromboembolic events compared with enoxaparin in this noninferiority study.

Two closely related ureotelic fish species of the genus Alcolapia express different levels of ammonium transporters in gills.

Most fish excrete their nitrogenous waste across the gills as ammonia through the activity of the Rhesus glycoprotein ammonium transporters. In contrast, fish of the subgenus Alcolapia (Oreochromis) are the only vertebrates that survive the extreme conditions of the soda lakes of Natron and Magadi in East Africa and have evolved adaptations to the highly alkaline waters including the ability to excrete their nitrogenous waste as urea. Nevertheless, Alcolapia retain the Rhesus glycoprotein genes in their genomes and using two heterologous expression systems, we demonstrate that Alcolapia Rhbg is capable of moving ammonia.

How has the COVID Pandemic Impacted the Clinical Volume and Variety of an Academic Oral and Maxillofacial Surgery Program?

Purpose: Attempts to mitigate the coronavirus disease of 2019 (COVID) have disrupted the delivery of non-pandemic care. The purpose of this study was to evaluate the effects of the COVID pandemic on surgical volume and variety at an academic oral and maxillofacial surgery program.

Materials And Methods: A retrospective cohort study was conducted using the surgical logs of the University of Pennsylvania, Department of Oral and Maxillofacial Surgery from January 2012 through January 2021.

Epidemiologic Patterns of Maxillofacial Trauma in a Metropolitan Area: A Retrospective Analysis.

Purpose: To illuminate epidemiologic trends of maxillofacial trauma in an urban setting over an 11-year period.

Materials And Methods: We performed an exhaustive database search at the University of Pennsylvania. The data were collected from 11 years of attending oral and maxillofacial surgery clinician and resident operating room logs and was conducted from 2011 to 2021.

Do Mandatory Face Shields Reduce the Number of Craniomaxillofacial Injuries in the National Hockey League?

Purpose: The purpose of this study was to analyze the effectiveness of the National Hockey League's (NHL) mandatory visor policy on the number and type of craniomaxillofacial (CMF) injuries.

Materials And Methods: A cross-sectional study was designed using the 2 databases: the NHL Injury Viz and the Pro Sports Transactions. CMF injuries and player characteristics from the NHL's 2009-2010 through the 2016-2017 seasons were obtained.

The molecular basis of thioalcohol production in human body odour.

Body odour is a characteristic trait of Homo sapiens, however its role in human behaviour and evolution is poorly understood. Remarkably, body odour is linked to the presence of a few species of commensal microbes. Herein we discover a bacterial enzyme, limited to odour-forming staphylococci that are able to cleave odourless precursors of thioalcohols, the most pungent components of body odour.

Adherence to guidelines across different specialties to prevent infections in patients undergoing immunosuppressive therapies.

Background: Substantial numbers of patients are now receiving either immunosuppressive therapies or chemotherapy. There are significant risks in such patients of developing opportunistic infections or re-activation of latent infections, with higher associated morbidity and mortality. The aim of this quality improvement project was to determine how effective 5 different specialties were in assessing and mitigating risks of developing opportunistic infections or re-activation of latent infections in patients undergoing immunosuppressive therapies.

Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons.

In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial motor neurons (CrMN) are spared until late stages of the disease. Using a rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) to SpMNs and CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time. ESC-derived CrMNs have higher proteasome activity to degrade misfolded proteins and are intrinsically more resistant to chemically-induced proteostatic stress than SpMNs.

Staphylococcus aureus adaptation to aerobic low-redox-potential environments: implications for an intracellular lifestyle.

Methicillin-resistant Staphylococcus aureus is a 'superbug' that is responsible for extensive death and morbidity. Chronic S. aureus infections are associated with the presence of intracellular bacteria and the host cytosol is an aerobic low-redox-potential (Eh) environment.

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function.

An evaluation of the Florence Nightingale Foundation scholarships.

The Florence Nightingale Foundation (FNF) is a charity that awards scholarships in leadership, travel and research to nurses, midwives and other healthcare professionals to promote excellence in practice. The FNF offers mentoring support to scholars, and provides support with career development and writing articles for publication, in addition to the financial award. The leadership scholarships are bespoke: leadership scholars can access a range of development opportunities that are specially commissioned for them, and select their programme of study and experiences, based on their individual needs.

ARID1A and TERT promoter mutations in dedifferentiated meningioma.

Unlike patients with World Health Organization (WHO) grade I meningiomas, which are considered benign, patients with WHO grade III meningiomas have very high mortality rates. The principles underlying tumor progression in meningioma are largely unknown, yet a detailed understanding of these mechanisms will be required for effective management of patients with these high grade lethal tumors. We present a case of an intraventricular meningioma that at first presentation displayed remarkable morphologic heterogeneity-composed of distinct regions independently fulfilling histopathologic criteria for WHO grade I, II, and III designations.

Atypical presentation of cerebral schistosomiasis four years after exposure to Schistosoma mansoni.

Schistosomiasis is the second most socioeconomically devastating parasitic disease worldwide, affecting over 240 million people in 77 countries on 5 continents and killing 300,000 people annually in sub-Saharan Africa alone. Neuroschistosomiasis is caused by granuloma formation around eggs that lodge in the CNS, with Schistosoma mansoni and Schistosoma haematobium usually affecting the spinal cord and Schistosoma japonicum causing most reported cerebral disease. We report a case of a previously healthy 25-year-old woman native to the United States who presented with a single generalized tonic-clonic seizure without other neurologic symptoms four years after spending a semester in Ghana where she went swimming once in a river.

Embryonic Expression and Function of the Ink4d Cyclin D-Dependent Kinase Inhibitor.

Here we report the cloning and functional characterization of the cyclin D-dependent kinase 4 and 6 (Cdk4/6) inhibitory protein Cdkn2d/p19 of (-Ink4d). - is the only family gene highly expressed during development and its transcripts were detected maternally and during neurulation. The -Ink4d protein has 63% identity to mouse and human Cdkn2d/p19 and its function as a negative regulator of cell cycle traverse is evolutionary conserved.

New insights into the development of infantile intraocular medulloepithelioma.

Purpose: To define the maturational sequence of 3 infantile intraocular medulloepitheliomas.

Design: Retrospective clinicohistopathologic and immunohistochemical study.

Methods: Immunoreactivity of paraffin sections for CRX (cone-rod homebox transcription factor) and NeuN (biomarker for neuronal differentiation) were investigated together with other biomarkers, including S100, glial fibrillary acidic protein, epithelial membrane antigen, and various cytokeratins.

Bilirubin labeling of borderzone and anterior cerebral artery territory infarction.

A 50-year-old woman developed multiorgan system failure secondary to sepsis. She became obtunded during a period of hypotension, and cranial CT demonstrated diffuse borderzone infarction. Brain autopsy revealed green pigmentation in areas of infarction due to vascular leakage of bilirubin at sites of blood–brain barrier disruption, mapping the borderzone regions and bilateral anterior cerebral artery territories with this endogenous label (total bilirubin at time of death was 24 mg/dL; direct bilirubin 19 mg/dL) (figure).

Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres.

Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol.

The Atoh1-lineage gives rise to hair cells and supporting cells within the mammalian cochlea.

The organ of Corti, located within the mammalian cochlea, contains a precise mosaic of hair cells (HC) and supporting cells (SC), the patterning of which is critical for auditory function. Progenitors of HCs and SCs are found in the same post-mitotic region of the cochlear duct during early stages of cochlear development, and both HCs and SCs are absent in mice lacking the transcription factor Atoh1. Based on existing data, Atoh1 is thought to be the earliest determinant of HC fate, and to have a cell-autonomous role in HC differentiation, but the lineage of Atoh1-positive cells within the cochlear duct remains unclear.