Toward determining amyloid fibril structures using experimental constraints from Raman spectroscopy.

We present structural models for three different amyloid fibril polymorphs prepared from amylin20-29 (sequence SNNFGAILSS) and amyloid-ß25-35 (Aß25-35) (sequence GSNKGAIIGLM) peptides. These models are based on the amide C=O bond and Ramachandran ψ-dihedral angle data from Raman spectroscopy, which were used as structural constraints to guide molecular dynamics (MD) simulations. The resulting structural models indicate that the basic structural motif of amylin20-29 and Aß25-35 fibrils is extended ß-strands. Our data indicate that amylin20-29 forms both antiparallel and parallel ß-sheet fibril polymorphs, while Aß25-35 forms a parallel ß-sheet fibril structure. Overall, our work lays the foundation for using Raman spectroscopy in conjunction with MD simulations to determine detailed molecular-level structural models of amyloid fibrils in a manner that complements gold-standard techniques, such as solid-state nuclear magnetic resonance and cryogenic electron microscopy.

Deadly Initiations: Characteristics of Hazing Deaths in the United States (1994-2019).

On American college campuses, numerous students have died as a result of hazing activities perpetrated in fraternities, sororities, and other student groups. Still, little is known about the common characteristics among these hazing deaths. This study aims to investigate the circumstances surrounding these fatal incidents by examining hazing deaths that occurred at institutions of higher education in the United States from 1994 to 2019. This analysis revealed common characteristics related to the victims, organizations, institutions, incidents, and outcomes of these deaths. The findings support past hazing research, as victims were predominantly males pledging social fraternities. Although hazing deaths were widespread, there was variation among institutional characteristics, region, and size. The perpetrators of these incidents faced legal ramifications, including criminal convictions and civil lawsuits. The recognition of these trends can improve our understanding of the conditions present when dangerous hazing activities occur and the best practices for prevention and response.

A randomized comparison of health-related quality of life outcomes of dolutegravir versus efavirenz-based antiretroviral treatment initiated in the third trimester of pregnancy.

INTRODUCTION: Evidence on health-related quality of life (HRQoL) outcomes is limited for new antiretroviral therapies (ART). Dolutegravir-based treatment is being rolled out as the preferred first-line treatment for HIV in many low- and middle-income countries. We compared HRQoL between treatment-naïve pregnant women randomized to dolutegravir- or efavirenz-based ART in a clinical trial in Uganda and South Africa. METHODS: We gathered HRQoL data from 203 pregnant women of mean age 28 years, randomized to either dolutegravir- or efavirenz-based ART. We used the medical outcomes study-HIV health survey at baseline, 24 and 48 weeks between years 2018 and 2019. Physical health summary (PHS) and mental health summary (MHS) scores were the primary study outcomes, while the 11 MOS-HIV subscales were secondary outcomes. We applied mixed model analysis to estimate differences within and between-treatment groups. Multivariate regression analysis was included to identify associations between primary outcomes and selected variables. RESULTS: At 24 weeks postpartum, HRQoL scores increased from baseline in both treatment arms: PHS (10.40, 95% CI 9.24, 11.55) and MHS (9.23, 95% CI 7.35, 11.10) for dolutegravir-based ART; PHS (10.24, 95% CI 9.10, 11.38) and MHS (7.54, 95% CI 5.66, 9.42) for efavirenz-based ART. Increased scores for all secondary outcomes were significant at p < 0.0001. At 48 weeks, improvements remained significant for primary outcomes within group comparison. Estimated difference in PHS were higher in the dolutegravir-based arm, while increases in MHS were more for women in the efavirenz-based armat 24 and 48 weeks. No significant differences were noted for corresponding PHS scores at these time points compared between groups. Differences between arms were observed in two secondary outcomes: role function (1.11, 95% CI 0.08, 2.13), p = 0.034 and physical function outcomes (2.97, 95% CI 1.20, 4.73), p = 0.001. In the multivariate analysis, internet access was associated with higher PHS scores while owning a bank account, using the internet and longer treatment duration were associated with an increase in MHS scores. CONCLUSION: We found no important differences in HRQoL outcomes among HIV-positive women started on dolutegravir relative to efavirenz in late pregnancy. Increases in HRQoL in the first year after delivery provide additional support for the initiation of ART in HIV-positive women presenting late in pregnancy. Trial Registration Clinical Trial Number: NCT03249181.

A Review of the Effects of the Violence Against Women Act on Law Enforcement.

One of the goals of the Violence Against Women Act (VAWA) was to improve law enforcement responses to sexual and domestic violence by providing funding to expand prevention, enhance investigations, and increase victim services. Since VAWA's enactment, police responses to these crimes have evolved, including officer responses to victims and offenders, and various agency operations. This article highlights some noteworthy changes in law enforcement related to facilitating victim reporting, enhancing victim advocacy and services, crime reduction and investigative tools, supplementing personnel and training, and encouraging multiagency collaborations as a result of VAWA.

The Immediate Impact of COVID-19 on Law Enforcement in the United States.

During pandemics, like COVID-19, law enforcement agencies are responsible for working with government and public health officials to contain spread, serve the local community, and maintain public order. Given the person-to-person spread of COVID-19 through respiratory droplets, law enforcement officers are also at a heightened risk of exposure due to their close contact with members of the public. To protect officers, the Centers for Disease Control and Prevention (CDC) and other agencies have made numerous recommendations for law enforcement agencies to protect officers and the public. Departments around the country have responded to the pandemic in various ways, such as reassigning personnel to high-traffic areas, suspending training, roll calls, and community outreach initiatives, only issuing citations for low-level crimes, implementing safety precautions for officers, and limiting access to department facilities. The COVID-19 pandemic also has exposed some key obstacles for law enforcement, related to communication, resource management, the enforcement of public health restrictions, and changes to crime and service patterns. Based on these early/initial responses and obstacles during the COVID-19 outbreak, the current paper highlights directions for future responses to pandemics to ensure the safety and security of police officers and the communities they serve.

Recovery from tympanic membrane perforation: Effects on membrane thickness, auditory thresholds, and middle ear transmission.

Sounds delivered to the ear move the tympanic membrane (TM), which drives the middle-ear (ME) ossicles and transfers the acoustic energy to the cochlea. Perforations of the TM result in hearing loss because of less efficient sound conduction through the ME. The patterns of TM motions, and thus ME sound transmission, vary with frequency and depend on many factors, including the TM thickness. In this study, we measured TM thickness, auditory brainstem responses (ABR), and ME transmission immediately following a controlled pars tensa perforation and after 4 weeks of spontaneous recovery in a gerbil model. It is found that after recovery, the hearing thresholds showed a sloping pattern across frequencies: almost back to normal levels at frequencies between 2 and 8 kHz, sloping loss in the low (<2 kHz) and mid-frequency (8-30 kHz) range, and little restoration at frequencies above 30 kHz. This pattern was confirmed by the measured ME pressure gains. The thickness of the healed TM did not return to normal but was 2-3 times thicker over a significant portion of the membrane. The increased thickness was not limited to the perforated area but expanded into intact regions adjacent to the perforation, which led to an increased thickness in general. Combined, these results suggest that TM thickness is an important factor in determining its vibration patterns and efficiency to transfer sounds to the ossicles and thus influencing ME sound transmission, especially for high-frequency sounds. The results provided both structural and functional observations to explain the conductive hearing loss seen in patients with abnormal TMs, e.g., caused by otitis media, spontaneously healed post-perforation, or repaired via tympanoplasty in the clinic.

Conduct Disorder and Neighborhood Effects.

There has been a considerable amount of scholarly attention to the relationship between neighborhood effects and conduct disorder, particularly in recent years. Having said this, it has been nearly two decades since a comprehensive synthesis of this literature has been conducted. Relying on a detailed and comprehensive search strategy and inclusion criteria, this article offers a systematic and interdisciplinary review of 47 empirical studies that have examined neighborhood effects and conduct disorder. Described results suggest that there are generally robust linkages between adverse neighborhood factors and conduct disorder and externalizing behavior problems, as 67 of the 93 (72.04%) effect sizes derived from these studies yielded statistically significant neighborhood effects. The review also identifies salient mediating and moderating influences. It discusses study limitations and directions for future research as well.

Adverse Childhood Experiences and Suicide Attempts: The Mediating Influence of Personality Development and Problem Behaviors.

Adverse childhood experiences, comprised of forms of maltreatment and certain dysfunctional household environments, can affect the development of a child in a variety of different ways. This multitude of developmental changes may subsequently produce compounding harmful effects on the child's life and increase acutely maladaptive outcomes, including adolescent suicidal behavior. This study uses data collected from 2007 to 2012 for 64,329 Florida Department of Juvenile Justice youth (21.67 % female, 42.88 % African American, and 15.37 % Hispanic) to examine the direct and indirect effects of adverse childhood experiences on suicide attempts. Using a generalized structural equation model, the effects of adverse childhood experience scores are estimated on suicidal behavior through pathways of certain aspects of a child's personality development (aggression and impulsivity), as well as adolescent problem behaviors (school difficulties and substance abuse). The results show that a large proportion of the relationship between childhood adversity and suicide is mediated by the aforementioned individual characteristics, specifically through the youth's maladaptive personality development. These results suggest that, if identified early enough, the developmental issues for these youth could potentially be addressed in order to thwart potential suicidal behavior.

Trauma changes everything: examining the relationship between adverse childhood experiences and serious, violent and chronic juvenile offenders.

Among juvenile offenders, those who commit the greatest number and the most violent offenses are referred to as serious, violent, and chronic (SVC) offenders. However, current practices typically identify SVC offenders only after they have committed their prolific and costly offenses. While several studies have examined risk factors of SVCs, no screening tool has been developed to identify children at risk of SVC offending. This study aims to examine how effective the adverse childhood experiences index, a childhood trauma-based screening tool developed in the medical field, is at identifying children at higher risk of SVC offending. Data on the history of childhood trauma, abuse, neglect, criminal behavior, and other criminological risk factors for offending among 22,575 delinquent youth referred to the Florida Department of Juvenile Justice are analyzed, with results suggesting that each additional adverse experience a child experiences increases the risk of becoming a serious, violent, and chronic juvenile offender by 35, when controlling for other risk factors for criminal behavior. These findings suggest that the ACE score could be used by practitioners as a first-line screening tool to identify children at risk of SVC offending before significant downstream wreckage occurs.