Management of Lambdoid Craniosynostosis: A Comprehensive and Systematic Review.

Background: Craniosynostosis is a condition characterized by the premature fusion of 2 or more skull bones. Craniosynostosis of the lambdoid suture is one of the rarest forms, accounting for 1-4% of all craniosynostoses. Documented cases are separated into simple (single suture), complex (bilateral), and associated with adjacent synostoses ("Mercedes Benz" Pattern) or syndromes (i.

Reduced Endothelin-2 and Hypoxic Signaling Pathways in Granulosa-Lutein Cells of PCOS Women.

Granulosa-lutein cells (GLCs) from PCOS women display reduced and levels, suggesting their role in PCOS etiology. Here, we investigated the mechanisms involved in aberrant expression in PCOS, and its association with . Various -dependent factors were studied in GLCs from PCOS and compared to normally ovulating women.

Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease.

Astrocyte reactivity is a hallmark of neuroinflammation that arises with Alzheimer's disease (AD) and nearly every other neurodegenerative condition. While astrocytes certainly contribute to classic inflammatory processes (e.g.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day.

Tricyclic antipsychotics promote adipogenic gene expression to potentiate preadipocyte differentiation in vitro.

Antipsychotic-induced weight gain is a well-established but poorly understood clinical phenomenon. New mechanistic insights into how antipsychotics modulate adipose physiology are sorely needed, in hopes of either devising a therapeutic intervention to ameliorate weight gain or contributing to improved design of future agents. In this study, we have hypothesized that the weight gain-associated tricyclic antipsychotics clozapine and chlorpromazine directly impact adipose tissue by potentiating adipogenic differentiation of preadipocytes.

Stroke as the initial presentation of Takayasu's arteritis: A case report.

In this study, we report the case of a pediatric neurology stroke patient who was ultimately diagnosed with Takayasu's Arteritis. Our case describes a 14-year-old Hispanic female with no significant past medical history who presented to an outside hospital for acute onset of confusion and right sided weakness. She was given tissue plasminogen activator (TPA) at the outside hospital and transferred as a stroke alert.

Mono-institutional phase 2 study of innovative Stereotactic Body RadioTherapy targeting PArtial Tumor HYpoxic (SBRT-PATHY) clonogenic cells in unresectable bulky non-small cell lung cancer: profound non-targeted effects by sparing peri-tumoral immune microenvironment.

Background: Radiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC.

OleD Loki as a Catalyst for Hydroxamate Glycosylation.

Herein we describe the ability of the permissive glycosyltransferase (GT) OleD Loki to convert a diverse set of >15 histone deacetylase (HDAC) inhibitors (HDACis) into their corresponding hydroxamate glycosyl esters. Representative glycosyl esters were subsequently evaluated in assays for cancer cell line cytotoxicity, chemical and enzymatic stability, and axolotl embryo tail regeneration. Computational substrate docking models were predictive of enzyme-catalyzed turnover and suggest certain HDACis may form unproductive, potentially inhibitory, complexes with GTs.

Rapid Induction and Maintenance of Remission in Refractory Ulcerative Colitis with Ustekinumab.

Ulcerative colitis is a chronic debilitating disease characterized by relapsing in intestinal inflammation and ulcers with no available cure. This is a clinical case report of a 52-year-old female patient with 30 years history of left-sided chronic ulcerative colitis controlled with standard of care (mesalamine and azathioprine) which subsequently relapsed and developed into active refractory ulcerative colitis. The patient became unresponsive to her medications including different forms of mesalamines and did not respond favorably to any of the other current therapies.

Optimal Ethanol-Ethiodol Emulsion Ratio in Renal Angiomyolipoma Embolization: A Question that Remains Unanswered.

The authors, a case series of five cases of angiomyolipomas (AMLs), embolized with a high ethanol:ethiodol ratio of 6:1 emulsion at a single tertiary center. Although ethanol as an embolic agent has been reported in the past for AMLs, much higher ratios of ethiodol were used, and administration is typically performed using an occlusion balloon. Two of the patients were incidentally diagnosed, while the other four were diagnosed after hematuria workup.

Sex-related responses after traumatic brain injury: Considerations for preclinical modeling.

Traumatic brain injury (TBI) has historically been viewed as a primarily male problem, since men are more likely to experience a TBI because of more frequent participation in activities that increase risk of head injuries. This male bias is also reflected in preclinical research where mostly male animals have been used in basic and translational science. However, with an aging population in which TBI incidence is increasingly sex-independent due to falls, and increasing female participation in high-risk activities, the attention to potential sex differences in TBI responses and outcomes will become more important.

Computational modeling of amylin-induced calcium dysregulation in rat ventricular cardiomyocytes.

Hyperamylinemia is a condition that accompanies obesity and precedes type II diabetes, and it is characterized by above-normal blood levels of amylin, the pancreas-derived peptide. Human amylin oligomerizes easily and can deposit in the pancreas [1], brain [2], and heart [3], where they have been associated with calcium dysregulation. In the heart, accumulating evidence suggests that human amylin oligomers form moderately cation-selective [4,5] channels that embed in the cell sarcolemma (SL).

Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions.

Transcriptome and phenotyping analyses support a role for chloroplast sigma factor 2 in red-light-dependent regulation of growth, stress, and photosynthesis.

Sigma factor (SIG) proteins contribute to promoter specificity of the plastid-encoded RNA polymerase during chloroplast genome transcription. All six members of the SIG family, that is, SIG1-SIG6, are nuclear-encoded proteins targeted to chloroplasts. Sigma factor 2 (SIG2) is a phytochrome-regulated protein important for stoichiometric control of the expression of plastid- and nuclear-encoded genes that impact plastid development and plant growth and development.

Reducing Cardiovascular Disparities Through Community-Engaged Implementation Research: A National Heart, Lung, and Blood Institute Workshop Report.

Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography.

Acceptability of intervention materials to decrease risk for alcohol and medication interactions among older adults.

Background: The majority of older adults take prescription or over-the-counter medications and about half consume alcohol regularly. Despite high risk for alcohol medication interactions (AMI), few community-level interventions exist to prevent AMI. The current study assessed the acceptability of educational materials created for use in a brief intervention to prevent AMI among older adults.

Dementia for the Primary Care Provider.

Dementia represents one of the most important and growing public health issues facing society today. Primary care clinics serve a crucial role as the first line of defense in the recognition and treatment of dementia. Increased awareness and treatment of risk factors for dementia are important for lessening disease burden in the population.

Community to clinic navigation to improve diabetes outcomes.

Rural residents experience rates of Type 2 Diabetes Mellitus (T2DM) that are considerably higher than their urban or suburban counterparts. Two primary modifiable factors, self-management and formal clinical management, have potential to greatly improve diabetes outcomes. "Community to Clinic Navigation to Improve Diabetes Outcomes," is the first known randomized clinical trial pilot study to test a hybrid model of diabetes self-management education plus clinical navigation among rural residents with T2DM.

The foot of Homo naledi.

Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot.

Caudal vertebral body articular surface morphology correlates with functional tail use in anthropoid primates.

Prehensile tails, capable of suspending the entire body weight of an animal, have evolved in parallel in New World monkeys (Platyrrhini): once in the Atelinae (Alouatta, Ateles, Brachyteles, Lagothrix), and once in the Cebinae (Cebus, Sapajus). Structurally, the prehensile tails of atelines and cebines share morphological features that distinguish them from nonprehensile tails, including longer proximal tail regions, well-developed hemal processes, robust caudal vertebrae resistant to higher torsional and bending stresses, and caudal musculature capable of producing higher contractile forces. The functional significance of shape variation in the articular surfaces of caudal vertebral bodies, however, is relatively less well understood.