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Fisetin has been shown to be beneficial for brain injury and age-related brain disease via different mechanisms. The purpose of this study was to determine the presence of senescent cells and the effects of fisetin on cellular senescence in the brain and other vital organs in old sheep, a more translational model. Female sheep 6–7 years old (N = 6) were treated with 100 mg/kg fisetin or vehicle alone on two consecutive days a week for 8 weeks. All vital organs were harvested at the time of sacrifice. Histology, immunofluorescence staining, and RT-Q-PCR were performed on different regions of brain tissues and other organs. Our results indicated that fisetin treatment at the current regimen did not affect the general morphology of the brain. The presence of senescent cells in both the cerebral brain cortex and cerebellum and non-Cornu Ammonis (CA) area of the hippocampus was detected by senescent-associated β-galactosidase (SA-β-Gal) staining and GL13 (lipofuscin) staining. The senescent cells detected were mainly neurons in both gray and white matter of either the cerebral brain cortex, cerebellum, or non-CA area of the hippocampus. Very few senescent cells were detected in the neurons of the CA1-4 area of the hippocampus, as revealed by GL13 staining and GLB1 colocalization with NEUN. Fisetin treatment significantly decreased the number of SA-β-Gal+ cells in brain cortex white matter and GL13+ cells in the non-CA area of the hippocampus, and showed a decreasing trend of SA-β-Gal+ cells in the gray matter of both the cerebral brain cortex and cerebellum. Furthermore, fisetin treatment significantly decreased P16+ and GLB1+ cells in neuronal nuclear protein (NEUN)+ neurons, glial fibrillary acidic protein (GFAP)+ astrocytes, and ionized calcium binding adaptor molecule 1 (IBA1)+ microglia cells in both gray and white matter of cerebral brain cortex. Fisetin treatment significantly decreased GLB1+ cells in microglia cells, astrocytes, and NEUN+ neurons in the non-CA area of the hippocampus. Fisetin treatment significantly decreased plasma S100B. At the mRNA level, fisetin significantly downregulated GLB1 in the liver, showed a decreasing trend in GLB1 in the lung, heart, and spleen tissues, and significantly decreased P21 expression in the liver and lung. Fisetin treatment significantly decreased TREM2 in the lung tissues and showed a trend of downregulation in the liver, spleen, and heart. A significant decrease in NRLP3 in the liver was observed after fisetin treatment. Finally, fisetin treatment significantly downregulated SOD1 in the liver and spleen while upregulating CAT in the spleen. In conclusion, we found that senescent cells were widely present in the cerebral brain cortex and cerebellum and non-CA area of the hippocampus of old sheep. Fisetin treatment significantly decreased senescent neurons, astrocytes, and microglia in both gray and white matter of the cerebral brain cortex and non-CA area of the hippocampus. In addition, fisetin treatment decreased senescent gene expressions and inflammasomes in other organs, such as the lung and the liver. Fisetin treatment represents a promising therapeutic strategy for age-related diseases.

Objective HIV-related stigma is a major public health concern compromising the rights and health outcomes of many people living with HIV (PLWH). Its reduction is said to be critical in strengthening the continuous efforts targeted at preventing and controlling HIV, as it directly impacts antiretroviral treatment adherence. This study examines the association between HIV-related stigma and adherence to antiretroviral therapy (ART) among PLWH in one of the 16 administrative regions of Ghana, Africa. Methods This descriptive cross-sectional study employed a survey to assess the factors affecting the utilization of ART among PLWH ( n  = 155) in the Volta region. The Center for Support Evaluation adherence index and internalized stigma of AIDS Tool were used to collect data on medication adherence and stigma, respectively. Data was analyzed using R statistical analysis software. Logistic regression models were performed to ascertain the predictors of ART utilization among PLWH. Results A greater proportion (70%) of the study’s participants reported adherence to ART. We found a positive association between HIV-related internalized stigma and medication adherence such that reporting high levels of stigma on average was associated with high levels of medication adherence [OR = 1.08, 95% CI:1.01, 1.15]. Older age was related to higher adherence while reporting more depressive symptoms was associated with low medication adherence. Conclusion Our findings show that stigma may serve as a facilitator instead of a barrier to adhering to antiretroviral medication. Although this contradicts common narratives about stigma’s destructive effect, it is possible to promote good health-seeking behavior when the fear component of stigma is considered. To encourage medication adherence towards meeting UNAIDS’ 95-95-95 agenda and better understand stigma’s role, further research is required.

Background: Posterior shoulder instability (PSI) is a multifactorial condition of atraumatic or traumatic onset that most frequently affects young male athletes. To address capsulolabral detachment, arthroscopic posterior capsulolabral repair with suture anchors can be performed. Purpose: To report patient-reported outcomes (PROs), failure rates, survivorship, and return-to-sport/activity rates after arthroscopic posterior capsulolabral repair with suture anchors at a minimum of 10 years after surgery. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent arthroscopic posterior capsulolabral repair for PSI by a single surgeon between November 2005 and September 2010 were included; patients with multidirectional instability and concomitant bony reconstruction were excluded. Demographic, surgical, and subjective data were collected prospectively and retrospectively reviewed. PROs that were collected included the American Shoulder and Elbow Surgeons (ASES); Single Assessment Numeric Evaluation (SANE); Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH); and 12-Item Short Form physical component summary (SF-12 PCS) scores. Recurrent instability, dislocations, and reoperations were recorded, and a survivorship analysis was performed. Results: Overall, 17 shoulders in 16 patients (all male; mean age, 31.4 years; age range, 19.2-51.2 years) were included. The onset of PSI was atraumatic in 11 shoulders (65%) and traumatic in 6 shoulders (35%). Three patient shoulders (17.6%) underwent revision surgery for instability or osteoarthritis at 6.3, 7.6, and 12.5 years postoperatively. A minimum 10-year follow-up was obtained in 12 of 14 remaining shoulders (86%), with a mean follow-up of 13.1 years. For patients not requiring revision surgery, pre- to postoperatively, the ASES score significantly improved (72.6 to 89.9; P = .016), as did the SF-12 PCS score (43.8 to 55.0; P = .002). The mean postoperative SANE score was 86.9, and the mean postoperative QuickDASH score was 6.6. Median satisfaction was 8 (range, 3-10). At follow-up, 67% of patients had returned to their original fitness program. Kaplan-Meier survivorship analysis showed an 86.7% survival rate at 10 years. Conclusion: Study findings indicated that arthroscopic posterior capsulolabral repair was an effective treatment for patients with PSI, albeit with a 17.6% revision rate. Patients who did not require revision had satisfactory PRO scores that were maintained at long-term follow-up.

Background Mental health is a global public good essential for human development. Yet there exist vast inequities in the distribution of and access to mental health resources within and between countries. To address these inequities, a non-governmental organization in Ghana, Psych Corps Ghana (PCG), leveraged the country’s National Service program to train psychology graduates to provide psychological first-aid. The objective of this study was to qualitatively evaluate the experiences of different stakeholders involved in PCG’s task-sharing intervention. Methods We conducted a qualitative study in Accra, Ghana. Convenience sampling was used to recruit a diverse sample of adults involved with the intervention: Psych Corps members (recent psychology graduates who delivered the intervention during their National Service placement), mental health professionals (supervisors and co-workers of Psych Corps members), community members, and PCG leadership. Data were collected through in-person and virtual in-depth interviews and focus group discussions. Reflexive thematic analysis was used. Results Forty individuals were interviewed (20 Psych Corps members, 10 mental health professionals, 5 community members, 5 PCG leaders). Most were female (67.5%), living/working in the Greater Accra region (80%), and had completed secondary school (97.5%). Participants had an overwhelmingly positive perception of the intervention, highlighting its usefulness in supporting clinicians and addressing the dearth of mental health professionals. They also emphasized its role in increasing community awareness of mental health services and helping to reduce mental health stigma. Important weaknesses were the lack of clarity on the specific tasks Psych Corps members were equipped to engage in and a lack of continued supervision and support from PCG leadership during their placements. Recommendations for improvement included (1) better integration into Ghana’s mental healthcare system (2), strengthening communication between PCG leadership and the mental health professionals with whom Psych Corps members worked during their placements, and (3) ensuring structured, consistent support of Psych Corps members during their placement. Conclusions PCG’s task-sharing intervention leverages an existing platform to provide an innovative solution to the shortage of mental health professionals in Ghana. Further evidence on its implementation and effectiveness are needed to inform its potential scale-up to address Ghana’s mental healthcare needs.

Background: Medial meniscal extrusion (MME) is a risk factor for osteoarthritis of the knee and is usually assessed using a supine, unloaded magnetic resonance imaging. However, protocols for examining meniscal extrusion with ultrasound in the literature vary regarding specific flexion angles and the extent of weightbearing during the examination, complicating interpretations of the influence of loading and position on meniscal extrusion. Hypothesis: The hypothesis was that loading and increased flexion angles would increase physiologic MME relative to supine and neutral positions. Study Design: Descriptive laboratory study. Methods: Asymptomatic volunteers with no history of knee pain, injury, or surgery were included. Real-time knee joint angles were obtained by a motion-capture system using retroreflective markers placed on the lower limbs. Ultrasound images of the medial meniscus of both knees were acquired in the coronal plane for supine, single-leg, and double-leg standing positions and with the knee in neutral (0°-5°), 20°, and 45° of flexion. MME was compared across legs, stances, and angles using a repeated-measures mixed-effects linear model, and pairwise comparisons were made using a post hoc Tukey test. Results: A total of 21 volunteers (age, 33 ± 12 years; body mass index, 23 ± 2.3 kg/m2; 9 women) participated in the study. MME was significantly lower in the supine position compared with single- and double-leg stances (P < .0001, estimated marginal mean MME: supine = 1.1, 1-leg = 1.3, 2-leg = 1.3), with no significant difference between weightbearing stances. Increasing knee flexion angles were associated with significantly lower extrusion (P < .0001, estimated marginal mean MME: neutral = 1.4; 20° = 1.3; 45° = 1), with extrusion greatest at neutral flexion and lowest at 45° of flexion. There was no significant difference in MME between right and left legs (estimated marginal mean MME = 1.2 for both left and right legs; P = .7255). Conclusion: Our study demonstrated that unloaded, supine examinations of MME may be of limited value. Also, including ultrasound assessment under loaded conditions may better reflect the biomechanical function of the meniscus during activities of daily life. Clinical Relevance: Examining physiologic meniscal behavior is important to provide context for altered meniscal function in the presence of pathology, which may help inform clinical decisions regarding the management of meniscal degeneration or tears.

Bacteriophages are an attractive tool for application in the therapy of bacterial infections, for biological control of bacterial contamination of foodstuffs in the alimentary industry, in plant protection, for control of water-borne pathogens, and control of environmental microflora. This review is mainly focused on structures governing phage recognition of host cell and mechanisms of phage adsorption and penetration into microbial cell.

Background: A labral injury contributes to glenohumeral instability. The Anterior Labral Circumferential Onlay Technique (ALCOT) reconstructs the labrum using the long head of the biceps tendon. Hypothesis: The ALCOT would restore glenohumeral joint stability in a cadaveric model without glenoid bone loss (1) comparable to the native state and (2) comparable to the Latarjet procedure. Study Design: Controlled laboratory study. Methods: A total of 10 fresh-frozen cadaveric shoulders were tested using a 6 degrees of freedom robotic arm in 5 consecutive states: (1) native, (2) capsular repair, (3) labral tear, (4) ALCOT, and (5) Latarjet procedure. Biomechanical testing consisted of 80 N of anteroinferior force and 50 N of compression in 90° of humerothoracic abduction. Lateral displacement of the humeral head and the force ratio during a dislocation were measured. Results: The mean lateral translation of the humeral head during a dislocation in the native state was 6.5 ± 2.2 mm and decreased to 5.4 ± 2.4 mm in the labral tear state (P < .001). The mean lateral translation of the humeral head was restored to 6.4 ± 2.2 mm (P > .99) with the ALCOT, showing no difference from the native state. The Latarjet procedure restored the mean force ratio during a dislocation to 1.3 ± 0.6 but failed to restore lateral translation, with a value of 5.6 ± 2.8 mm (P = .003 vs native; P = .94 vs labral tear). The mean force ratio was 1.8 ± 0.1 in the native state, decreased to 1.1 ± 0.4 in the labral tear state, and was 1.4 ± 0.4 (P < .27) with the ALCOT, showing no difference from the native state. Conclusion: The ALCOT is a novel technique for labral reconstruction that may have a role in the treatment of anterior glenohumeral instability in the setting of a deficient labrum without bone loss. In this study, the ALCOT restored the force ratio and lateral translation of the humeral head compared to the native state. The Latarjet procedure restored the force ratio but not lateral translation of the humeral head compared to the native state. Clinical Relevance: This study proposes and biomechanically validates the ALCOT as a surgical technique for labral reconstruction that may have a role in treating patients with chronic anterior shoulder instability in the setting of a deficient labrum.

Mathematical models have been developed to explore the population dynamics of viral diseases among wildlife. However, assessing the predictions stemming from these models with wildlife databases adequate in size and temporal duration is uncommon. An epizootic of raccoon rabies that began in the mid-Atlantic region of the United States in the late 1970s has developed into one of the largest and most extensive in the history of wildlife rabies. We analyzed the dynamics of local epizootics at the county level by examining a database spanning more than 20 years and including 35,387 rabid raccoons. The size, number, and periodicity of rabies epizootics among raccoons were compared with predictions derived from a susceptible, exposed, infectious, and recovered model of raccoon rabies [Coyne, J., Smith, G. & McAllister, F. E. (1989) Am. J. Vet. Res. 50, 2148-2154]. After our methods for defining epizootics were applied to solutions of the model, the time series revealed recurrent epizootics in some counties, with a median first epizootic period of 48 months. Successive epizootics declined in size and the epizootic period progressively decreased. Our reanalysis of the model predicted the initial-epizootic period of 4-5 years, with a progressive dampening of epizootic size and progressive decrease in epizootic period. The best quantitative agreement between data and model assumed low levels of immunity (1-5%) within raccoon populations, suggesting that raccoons develop little or no rabies immune class. These results encourage the use of data obtained through wildlife surveillance in assessing and refining epidemic models for wildlife diseases.

The hospital structural reform through the Hospital Treatment Remuneration Improvement Act (Krankenhausversorgungsverbesserungsgesetz, KHVVG) will fundamentally change the medical care landscape in Germany starting in 2025. Outpatient care and cross-sectoral care models will substantially influence advanced surgical training. In particular, comprehensive training networks between hospitals and outpatient facilities are being discussed as a core solution to ensure surgical training. The aim of this position paper is to highlight the wishes and demands of young surgeons regarding training alliances. These should serve as guidelines for the stakeholders involved for a successful implementation. The position paper is based on discussions of the Young Forums of surgical societies, analyses of current further training models and experiences from pilot projects. It describes measures that promote cross-sectoral structured further training with clear legal, financial and didactic framework conditions. Successful models, such as rotation in outpatient facilities, show a positive effect on further training and practical experience. Necessary steps include simplifications of labor legislation, transparent curricula, adequate financing and certified didactic qualifications for those providing surgical residency training. Pilot projects underline the potential of intersectoral cooperation, while inadequate legal and financial structures have been identified as the main obstacles. The introduction of mandatory continuous education networks is essential to ensure surgical residency training and improving the quality of surgical patient care. In addition to political action to finance and adapt the framework conditions, hospitals and outpatient facilities need to take the initiative. In the long term surgical continuing education in Germany should be of exceptional quality.

This study examined parents’ knowledge and attitudes about sexuality and sex education of their children with developmental disabilities (DD) in the Accra Metropolis of Ghana. Using a descriptive cross-sectional design, 46 conveniently sampled parents of children with DD responded to an online survey on knowledge of their children’s sexuality and their attitudes towards sex education. Findings from univariate analysis revealed that about 67% of parents have not given any form of sexual education to their children. However, 65% of parents in this study had good general knowledge about the sexuality of their children except for experiential topics (i.e., sexual feelings and experiences, including their sexual orientation (heterosexual/ gays and lesbians), and masturbation, but were generally positive about views of sex education for their children. Majority of the parents (82.6%) had not received any training on how to educate their children on sexuality matters to support and empower themselves and their children. These findings indicate that Ghanaian families rarely provide sex education for their children with DD, however, they perceive sex education as a positive and protective strategy for the reproductive and sexual health of their children with DD. Implications for the development of training programs that provides appropriate knowledge and skills related to sexual health are discussed.