Artificial Nutrition and Hydration for Infants with Life-Terminating Conditions: Rethinking the Catholic Position

Infants with life-terminating conditions (ILTCs) are those whose conditions prevent them from living more than two years. When these infants have difficulty assimilating food and fluids orally, doctors can provide nutrition and hydration through artificial means. While artificial nutrition and hydration (ANH) can provide benefits, it can also result in complications leading to pain and/or distress in addition to that which an ILTC may already be experiencing from one or more underlying conditions. Many medical experts maintain that withholding or withdrawing ANH can help a patient’s body produce its own analgesics. I consider four categories of ILTCs: 1) infants who receive prognoses of two weeks or less; 2) infants who will live longer than two weeks but no more than two years and who are not suffering or in distress; 3) infants who are not dying, but are in distress from the use of ANH; and 4) infants who are not dying, but are in distress from their conditions and/or ANH. I argue that in addition to providing natural analgesics, withholding or withdrawing ANH is a form of comfort care that prevents the occurrence of further complications requiring additional medical treatments and keeps ILTCs content. Under certain circumstances, the withholding or withdrawing of ANH should be obligatory. As it stands, the whole of Catholic teaching on ANH is inconsistent. Operating from the sanctity-of-life ethic, the Church teaches that ANH is an ordinary, therefore obligatory, form of care. But this position contradicts the view that any form of care presenting a grave burden to a patient and/or his family is extraordinary and therefore optional. In addition, by making ANH obligatory, the Catholic Church causes families to undergo heroic suffering (i.e., enduring more than what can be expected or asked of anyone), which the Church says is not required of everyone. I argue that rethinking the Catholic position on ANH will enable the Church to offer practical moral guidance for families to comfort ILTCs, help ILTCs and their families avoid heroic suffering, and provide spiritual care families of ILTCs need, all while still respecting the sanctity of life of every person

Shots Fired, Shots Refused: Scientific, Ethical & Legal Challenges Surrounding the U.S. Military\u27s COVID-19 Vaccine Mandate

The COVID-19 pandemic provided uncertain and challenging circumstances under which to lead a nation and the military that protects it. Those in charge and in command faced unique challenges—scientific, ethical, and legal—at our various levels of government to both keep people safe while keeping government and society functioning. While there were many successes to celebrate, there are also many criticisms for how this “whole-of-government approach” may have degraded some of our most cherished liberties along the way. The authors focus on the U.S. military’s vaccine mandate and propose military leaders may have failed to fully consider the evolving science, weigh the prevailing ethics, and appropriately apply the relevant law regarding exemptions, and instead adopted a more uniform approach that aligned with other federal agencies and not to the military’s unique population. And along the way, military leaders lost some of the trust and the faith of those they were seeking to protect, prompting the other two branches of government, the Judiciary and Congress, to intervene. Drawing from our diverse experiences as both practitioners and academics, this Article not only seeks to document the past but also provides some suggestions for the future should we face another such pandemic

Shots Fired, Shots Refused: Scientific, Ethical & Legal Challenges Surrounding the U.S. Military\u27s COVID-19 Vaccine Mandate

The COVID-19 pandemic provided uncertain and challenging circumstances under which to lead a nation and the military that protects it. Those in charge and in command faced unique challenges—scientific, ethical, and legal—at our various levels of government to both keep people safe while keeping government and society functioning. While there were many successes to celebrate, there are also many criticisms for how this “whole-of-government approach” may have degraded some of our most cherished liberties along the way. The authors focus on the U.S. military’s vaccine mandate and propose military leaders may have failed to fully consider the evolving science, weigh the prevailing ethics, and appropriately apply the relevant law regarding exemptions, and instead adopted a more uniform approach that aligned with other federal agencies and not to the military’s unique population. And along the way, military leaders lost some of the trust and the faith of those they were seeking to protect, prompting the other two branches of government, the Judiciary and Congress, to intervene. Drawing from our diverse experiences as both practitioners and academics, this Article not only seeks to document the past but also provides some suggestions for the future should we face another such pandemic

Increasing Ball Velocity in the Overhead Athlete: A Meta-Analysis of Randomized Controlled Trials

Overhead athletes routinely search for ways to improve sport performance, and one component of performance is ball velocity. The purpose of this meta-analysis was to investigate the effect of different strengthening interventions on ball and serve velocity. A comprehensive literature search with pre-set inclusion and exclusion criteria from 1970 to 2014 was conducted. Eligible studies were randomized control trials including the mean and SDs of both pretest and posttest ball velocities in both the experimental and the control groups. The outcome of interest was ball/serve velocity in baseball, tennis, or softball athletes. Level 2 evidence or higher was investigated to determine the effect different training interventions had on velocity. Pretest and posttest data were extracted to calculate Hedges\u27s g effect sizes with 95% confidence intervals (CIs). Methodological qualities of the final 13 articles within the analysis were assessed using the Physiotherapy Evidence Database scale. The majority of the articles included in this analysis had an effect on velocity with the strongest effect sizes found in periodized training (Hedges\u27s g = 3.445; 95% CI = 1.976-4.914). Six studies had CI that crossed zero, indicating that those specific interventions should be interpreted with caution. Consistent and high-quality evidence exists that specific resistance training interventions have an effect on velocity. These findings suggest that interventions consisting of isokinetic training, multimodal training, and periodization training are clinically beneficial at increasing velocity in the overhead athlete over different windows of time

More Elevated Fastballs Associated with Placement on the Injured List Due to Shoulder Injury

Purpose To evaluate whether impending shoulder injury was associated with changes in pitch location or velocity immediately preceding injury. Methods Pitchers placed on the injured list (IL) due to a shoulder injury between 2015 and 2020 were identified in the Major League Baseball transactions database. Four-seam fastball velocity and frequency of pitch location for each pitch type was collected for each player in the season before placement on the IL and within 1 month of placement on the IL with a minimum of 55 pitches thrown of 1 type. Pitch locations were collected as identified by Baseball Savant’s Game-Day Zones. Game-Day Zones were consolidated into high (above the strike zone midpoint) versus low, arm side (closer to the pitcher’s arm side of the plate) versus opposite side, and within the strike zone versus out of zone. Repeated measures analysis of variance determined differences in four-seam velocity and the location distribution of 4-seam fastballs, change-ups, and breaking balls among each group. Results In total, 267 pitchers were placed on the IL for a shoulder injury with the majority diagnosed with inflammation (89/267) followed by strain or sprain (69/267). Four-seam fastball locations significantly increased above the mid-point of the zone (45.9% vs 42.4%, P = .008) and out of the strike zone (48.5% vs 46.5%, P = .011) within a month before IL placement. There was no significant change in 4-seam fastball velocity immediately before IL placement. Conclusions Pitchers threw more elevated 4-seam fastballs and out-of-zone 4-seam fastballs in the month before IL placement for shoulder injury. These findings suggest that a loss of 4-seam fastball command decreases with impending shoulder injury. Level of Evidence IV, prognostic case series

Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.

Chronic kidney disease (CKD), which can ultimately progress to kidney failure, is influenced by genetics and the environment. Genes identified in human genome wide association studies (GWAS) explain only a small proportion of the heritable variation and lack functional validation, indicating the need for additional model systems. Outbred heterogeneous stock (HS) rats have been used for genetic fine-mapping of complex traits, but have not previously been used for CKD traits. We performed GWAS for urinary protein excretion (UPE) and CKD related serum biochemistries in 245 male HS rats. Quantitative trait loci (QTL) were identified using a linear mixed effect model that tested for association with imputed genotypes. Candidate genes were identified using bioinformatics tools and targeted RNAseq followed by testing in a novel in vitro model of human tubule, hypoxia-induced damage. We identified two QTL for UPE and five for serum biochemistries. Protein modeling identified a missense variant within Septin 8 (Sept8) as a candidate for UPE. Sept8/SEPTIN8 expression increased in HS rats with elevated UPE and tubulointerstitial injury and in the in vitro hypoxia model. SEPTIN8 is detected within proximal tubule cells in human kidney samples and localizes with acetyl-alpha tubulin in the culture system. After hypoxia, SEPTIN8 staining becomes diffuse and appears to relocalize with actin. These data suggest a role of SEPTIN8 in cellular organization and structure in response to environmental stress. This study demonstrates that integration of a rat genetic model with an environmentally induced tubule damage system identifies Sept8/SEPTIN8 and informs novel aspects of the complex gene by environmental interactions contributing to CKD risk

Association between Regulator of G Protein Signaling 9–2 and Body Weight

Regulator of G protein signaling 9–2 (RGS9–2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9–2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9–2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9–2 as a factor in regulating body weight.National Institute of Mental Health (U.S.) (R41MH78570 award)National Center for Research Resources (U.S.) (Rhode Island IDeA Network of Biomedical Research Excellence (RI-INBRE) Award P20RR016457-10

Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone

During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.</p

Ethnic Related Selection for an ADH Class I Variant within East Asia

The alcohol dehydrogenases (ADH) are widely studied enzymes and the evolution of the mammalian gene cluster encoding these enzymes is also well studied. Previous studies have shown that the ADH1B*47His allele at one of the seven genes in humans is associated with a decrease in the risk of alcoholism and the core molecular region with this allele has been selected for in some East Asian populations. As the frequency of ADH1B*47His is highest in East Asia, and very low in most of the rest of the world, we have undertaken more detailed investigation in this geographic region.Here we report new data on 30 SNPs in the ADH7 and Class I ADH region in samples of 24 populations from China and Laos. These populations cover a wide geographic region and diverse ethnicities. Combined with our previously published East Asian data for these SNPs in 8 populations, we have typed populations from all of the 6 major linguistic phyla (Altaic including Korean-Japanese and inland Altaic, Sino-Tibetan, Hmong-Mien, Austro-Asiatic, Daic, and Austronesian). The ADH1B genotyping data are strongly related to ethnicity. Only some eastern ethnic phyla or subphyla (Korean-Japanese, Han Chinese, Hmong-Mien, Daic, and Austronesian) have a high frequency of ADH1B*47His. ADH1B haplotype data clustered the populations into linguistic subphyla, and divided the subphyla into eastern and western parts. In the Hmong-Mien and Altaic populations, the extended haplotype homozygosity (EHH) and relative EHH (REHH) tests for the ADH1B core were consistent with selection for the haplotype with derived SNP alleles. In the other ethnic phyla, the core showed only a weak signal of selection at best.The selection distribution is more significantly correlated with the frequency of the derived ADH1B regulatory region polymorphism than the derived amino-acid altering allele ADH1B*47His. Thus, the real focus of selection may be the regulatory region. The obvious ethnicity-related distributions of ADH1B diversities suggest the existence of some culture-related selective forces that have acted on the ADH1B region