Effectiveness of rVSV-ZEBOV vaccination during the 2018-20 Ebola virus disease epidemic in the Democratic Republic of the Congo: a retrospective test-negative study.

BACKGROUND: The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature. METHODS: We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018-20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times. FINDINGS: 1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70-92). INTERPRETATION: This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo. FUNDING: Médecins Sans Frontières. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Virtual Reality and Higher Education Sporting Events: Social Anxiety Perception as an Outcome of VR Simulation.

BACKGROUND: This study investigates the relationship between Virtual Reality Exposure Therapy (VRET) and social anxiety in sport environments. Social anxiety is a mental health condition that manifests people's intense fear of being watched and judged by others and worrying about humiliation It is important to research potential tools like VRET that could help to mitigate the impact of social anxiety as people with social anxiety often avoid attending live events due to the venue's sensory stimuli and the social encounters they anticipate. VR simulation could allow socially anxious individuals to fully experience a sporting event simulation minus the anxiety induced by potential social encounters. VR's therapeutic effects on social anxiety should be explored when considering several findings of VR intervention to mental health. AIM: The study aims to assess the impact of exposing socially anxious people to a virtual sporting game by measuring their levels of social anxiety, team identification, and intentions to attend a live sporting event before and after the VR exposure. Due to VR's positive experience, social anxiety is expected to decrease. However, team identification and intentions to attend live sporting events are expected to increase because of VR's ability to develop sport fanship. METHOD: Fourteen students with symptoms of social anxiety participated in the study. To create the VR simulation stimuli, the researchers used six 360° cameras to record an NCAA Division-I women's volleyball game. Participants experienced the sporting event via VR simulation. Data were analyzed via one-group pre- and post-comparison. RESULTS AND CONCLUSIONS: Significant results were found for behavioral intentions of participants after experiencing the simulation. Social anxiety's difference was negative 0.22, t(13) = 3.47, p < 0.01. After watching the game in VR, the respondents' social anxiety decreased significantly. Team identification's difference was 0.53, t(13) = -3.56, p < 0.01. Lastly, event visit intentions' difference was 0.24, t(13) = -2.35, p < 0.05. Team identification and intentions to visit a sporting event rose significantly after viewing the game in VR.

Olecranon Osteotomy Exposure for Distal Humeral Fracture Treatment.

Background: Olecranon osteotomy (OO) is commonly utilized to improve exposure when treating intra-articular distal humeral fractures. A chevron-shaped osteotomy facilitates reduction and increases surface area for healing1. Following distal humeral fracture reduction and fixation, the OO fragment is fixed with a precontoured plate. The OO technique yields comparable outcomes to alternative techniques1,2. Description: The technique is performed as follows. (1) Imaging is reviewed and preoperative planning is performed. (2) The patient is positioned in the lateral decubitus position with the operative extremity placed over a bolster. (3) A longitudinal posterior skin incision is centered just medial or lateral to the tip of the olecranon. Full-thickness skin flaps are raised medially and laterally. (4) The ulnar nerve is identified and mobilized for later anterior subcutaneous transposition. (5) An OO is performed at the non-articular "bare area" of the trochlear notch with an oscillating saw and completed with an osteotome. (6) Open reduction and internal fixation of the distal humerus is performed. (7) The osteotomy fragment is reduced, and a precontoured plate is applied. (8) A small longitudinal slit in the distal triceps over the proximal edge of the plate decreases plate prominence and is repaired with suture. (9) The subcutaneous tissues and skin are closed in the usual manner. Alternatives: Alterative techniques include extra-articular OO, triceps splitting, triceps reflecting, and lateral para-olecranon combined with a medial approach. Multiple drill holes and a thin osteotome can help mitigate the kerf created by the oscillating saw. Alternative fixation methods include a predrilled 6.5-mm intramedullary screw, a tension band construct, suture fixation, or a one-third tubular plate. Rationale: The OO technique provides improved exposure when compared with alternative techniques, enabling accurate reduction and fixation of distal humeral fractures1-3. Wilkinson and Stanley found that OO exposed the distal humeral articular surface to a greater degree than the triceps-splitting and triceps-reflecting approaches3. OO has not been associated with triceps weakness, unlike some of the alternative techniques2. Expected Outcomes: The incidence of good-to-excellent outcomes is similar when comparing the techniques for exposure of intra-articular distal humeral fractures4. Osteotomies united in all patients in 2 reported series, totaling 84 cases1,2. Removal of symptomatic hardware used in OO fragment fixation can occur in a small subset of patients1,2. Important Tips: Provisionally size a precontoured plate and fix it on the olecranon to aid in later reduction and fracture fixation.The bare area is the desired position for the OO because of its natural lack of cartilage5,6. This non-articular bare area is located just distal to the deepest portion of the trochlear notch, approximately 2 to 2.5 cm distal to the olecranon tip5,6.An (apex-distal) chevron osteotomy angle of ∼130° will help to keep the osteotomy within the non-articular bare area6.Beginning on the dorsal surface of the ulna, directly posterior to the bare area, an oscillating saw is utilized to create a chevron osteotomy to subchondral bone, perpendicular to the long axis of the ulna5,6.The OO is completed by fracturing through the osteochondral surface, which leaves an irregular chondral cancellous surface that can accurately interdigitate. This facilitates later reduction and stability of the osteotomy.Anatomic articular reduction of the OO is not solely judged on the dorsal cortical bone because of the kerf removed by the saw blade. Instead, examination of the articular surface of the trochlear notch is the primary assessment of reduction.Placement of suture through the proximal portion of the plate aids in the repair of the longitudinal split of the distal triceps.Successful treatment of distal humeral fractures requires accurate reduction and rigid fixation aided by adequate exposure achieved through OO. Acronyms and Abbreviations: ORIF = open reduction and internal fixationOT = occupational therapyHWR = hardware removalK-wire = Kirschner wireROM = range of motion.

Grasp Posture Variability Leads to Greater Ipsilateral Sensorimotor Beta Activation During Simulated Prosthesis Use.

Motor behaviour using upper-extremity prostheses of different levels is greatly variable, leading to challenges interpreting ideal rehabilitation strategies. Elucidating the underlying neural control mechanisms driving variability benefits our understanding of adaptation after limb loss. In this follow-up study, non-amputated participants completed simple and complex reach-to-grasp motor tasks using a body-powered transradial or partial-hand prosthesis simulator. We hypothesised that under complex task constraints, individuals employing variable grasp postures will show greater sensorimotor beta activation compared to individuals relying on uniform grasping, and activation will occur later in variable compared to uniform graspers. In the simple task, partial-hand variable and transradial users showed increased neural activation from the early to late phase of the reach, predominantly in the hemisphere ipsilateral to device use. In the complex task, only partial-hand variable graspers showed a significant increase in neural activation of the sensorimotor cortex from the early to the late phase of the reach. These results suggest that grasp variability may be a crucial component in the mechanism of neural adaptation to prosthesis use, and may be mediated by device level and task complexity, with implications for rehabilitation after amputation.

Vascular calcification in chronic kidney disease associated with pathogenic variants in ABCC6.

Vascular calcification is prevalent in chronic kidney disease (CKD). Genetic causes of CKD account for 10-20% of adult-onset disease. Vascular calcification is thought to be one of the most important risk factors for increased cardiovascular morbidity and mortality in CKD patients and is detectable in 80% of patients with end stage kidney disease (ESKD). Despite the high prevalence of vascular calcification in CKD, no single gene cause has been described. We hypothesized that variants in vascular calcification genes may contribute to disease pathogenesis in CKD, particularly in families who exhibit a predominant vascular calcification phenotype. We developed a list of eight genes that are hypothesized to play a role in vascular calcification due to their involvement in the ectopic calcification pathway: ABCC6, ALPL, ANK1, ENPP1, NT5E, SLC29A1, SLC20A2, and S100A12. With this, we assessed exome data from 77 CKD patients, who remained unsolved following evaluation for all known monogenic causes of CKD. We also analyzed an independent cohort (Ontario Neurodegenerative Disease Research Initiative (ONDRI), n = 520) who were screened for variants in ABCC6 and compared this to a control cohort of healthy adults (n = 52). We identified two CKD families with heterozygous pathogenic variants (R1141X and A667fs) in ABCC6. We identified 10 participants from the ONDRI cohort with heterozygous pathogenic or likely pathogenic variant in ABCC6. Replication in a healthy control cohort did not reveal any variants. Our study provides preliminary data supporting the hypothesis that ABCC6 may play a role in vascular calcification in CKD. By screening CKD patients for genetic causes early in the diagnostic pathway, patients with genetic causes associated with vascular calcification can potentially be preventatively treated with new therapeutics with aims to decrease mortality.

Distinct expression patterns of Hedgehog signaling components in mouse gustatory system during postnatal tongue development and adult homeostasis.

The Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae. HH signaling also mediates taste organ maintenance and regeneration in adults. However, there are knowledge gaps in HH pathway component expression during postnatal taste organ differentiation and maturation. Importantly, the HH transcriptional effectors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; the HH receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, also remain unexplored. Using lacZ reporter mouse models, we mapped expression of the HH ligand SHH, HH receptors, and GLI transcription factors in FP, CVP and FOP in early and late postnatal and adult stages. In adults we also studied the soft palate, and the geniculate and trigeminal ganglia, which extend afferent fibers to the anterior tongue. Shh and Gas1 are the only components that were consistently expressed within taste buds of all three papillae and the soft palate. In the first postnatal week, we observed broad expression of HH signaling components in FP and adjacent, non-taste filiform (FILIF) papillae in epithelium or stroma and tongue muscles. Notably, we observed elimination of Gli1 in FILIF and Gas1 in muscles, and downregulation of Ptch1 in lingual epithelium and of Cdon, Gas1 and Hhip in stroma from late postnatal stages. Further, HH receptor expression patterns in CVP and FOP epithelium differed from anterior FP. Among all the components, only known positive regulators of HH signaling, SHH, Ptch1, Gli1 and Gli2, were expressed in the ganglia. Our studies emphasize differential regulation of HH signaling in distinct postnatal developmental periods and in anterior versus posterior taste organs, and lay the foundation for functional studies to understand the roles of numerous HH signaling components in postnatal tongue development.

Baseline and end-of-treatment host serum biomarkers predict relapse in adults with pulmonary tuberculosis.

BACKGROUND: There is a need for new tools for monitoring of the response to TB treatment. Such tools may allow for tailored treatment regimens, and stratify patients initiating TB treatment into different risk groups. We evaluated combinations between previously published host biomarkers and new candidates, as tools for monitoring TB treatment response, and prediction of relapse. METHODS: Serum samples were collected at multiple time points, from patients initiating TB treatment at research sites situated in South Africa (ActionTB study), Brazil and Uganda (TBRU study). Using a multiplex immunoassay platform, we evaluated the concentrations of selected host inflammatory biomarkers in sera obtained from clinically cured patients with and without subsequent relapse within 2 years of TB treatment completion. RESULTS: A total of 130 TB patients, 30 (23%) of whom had confirmed relapse were included in the study. The median time to relapse was 9.7 months in the ActionTB study (n = 12 patients who relapsed), and 5 months (n = 18 patients who relapsed) in the TBRU study. Serum concentrations of several host biomarkers changed during TB treatment with IL-6, IP-10, IL-22 and complement C3 showing potential individually, in predicting relapse. A six-marker signature comprising of TTP, BMI, sICAM-1, IL-22, IL-1ß and complement C3, predicted relapse, prior to the onset of TB treatment with 89% sensitivity and 94% specificity. Furthermore, a 3-marker signature (Apo-CIII, IP-10 and sIL-6R) predicted relapse in samples collected at the end of TB treatment with sensitivity of 71% and specificity of 74%. A previously identified baseline relapse prediction signature (TTP, BMI, TNF-ß, sIL-6R, IL-12p40 and IP-10) also showed potential in the current study. CONCLUSION: Serum host inflammatory biomarkers may be useful in predicting relapse in TB patients prior to the initiation of treatment. Our findings have implications for tailored patient management and require prospective evaluation in larger studies.

Dual ß-lactam for treatment of pulmonary Mycobacterium abscessus in a child.

Treatment of Mycobacterium abscessus infection presents significant challenges, exacerbated by the emergence of macrolide-resistant strains that necessitate the use of multiple antimicrobials in combination and carry the potential for significant toxic effects. Select dual beta-lactam combinations, with or without beta-lactamase inhibitors, have been shown to be highly active in vitro. Herein, we describe a 6-year-old child with underlying mild bilateral lower lobe cylindrical bronchiectatic lung disease who developed pulmonary Mycobacterium abscessus infection and was treated with a multi-drug regimen including two ß-lactam antibiotics, achieving both early clinical and microbiological cure. This case highlights the potential benefit of dual ß-lactam therapy for the treatment of drug-resistant Mycobacterium abscessus infection.

Beyond prevention: Unveiling the benefits of triple vaccination on COVID-19 severity and resource utilization in solid organ transplant recipients.

OBJECTIVE: Despite the widespread reduction in COVID-19-related morbidity and mortality attributed to vaccination in the general population, vaccine efficacy in solid organ transplant recipients (SOTR) remains under-characterized. This study aimed to investigate clinically relevant outcomes on double and triple-vaccinated versus unvaccinated SOTR with COVID-19. STUDY DESIGN AND SETTING: A retrospective propensity score-matched cohort study was performed utilizing data from the US Collaborative Network Database within TriNetX (n = 117,905,631). We recruited vaccinated and unvaccinated (matched controls) SOTR with COVID-19 over two time periods to control for vaccine availability: December 2020 to October 2022 (bi-dose, double-dose vaccine effectiveness) and December 2020 to April 2023 (tri-dose, triple-dose vaccine effectiveness). A total of 42 factors associated with COVID-19 disease severity were controlled for including age, obesity, diabetes, and hypertension. We monitored 30-day outcomes including acute respiratory failure, intubation, and death following a diagnosis of COVID-19. RESULTS: Subjects were categorized into two cohorts based on the two time periods: bi-dose cohort (vaccinated, n = 462; unvaccinated, n = 20,998); tri-dose cohort (vaccinated, n = 517; unvaccinated, n = 23,061).Compared to unvaccinated SOTR, 30-day mortality was significantly lower for vaccinated subjects in both cohorts: tri-dose (2.0% vs 7.5%, HR = 0.22 [95% CI: 0.11, 0.46]); bi-dose (3.7% vs 8.2%, HR = 0.43 [95% CI: 0.24, 0.76]). Hospital admission rates were similar between bi-dose vaccinated and unvaccinated subjects (33.1% vs 28.6%, HR = 1.2 [95% CI: 0.95, 1.52]). In contrast, tri-dose vaccinated subjects had a significantly lower likelihood of hospital admission (29.4% vs 36.6%, HR = 0.74 [95% CI: 0.6, 0.91]). Intubation rates were significantly lower for triple-vaccinated- (2.3% vs 5.2%, p < 0.05), but not double-vaccinated subjects (3.0% vs 5.2%, p > 0.05). CONCLUSION: In solid organ transplant recipients with COVID-19, triple vaccination, but not double vaccination, against SARS-CoV-2 was associated with significantly less hospital resource utilization, decreased disease severity, and fewer short-term complications. These real-world data from extensively matched controls support the protective effects of COVID-19 vaccination with boosters in this vulnerable population.

Personal journeys to and in human genetics and dysmorphology.

Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.

Exclusive Enteral Nutrition Beneficially Modulates Gut Microbiome in a Preclinical Model of Crohn's-like Colitis.

Exclusive enteral nutrition (EEN) is an established dietary treatment for Crohn's disease (CD) by alleviating inflammation and inducing remission. However, the mechanisms of action of EEN are incompletely understood. As CD is associated with gut microbiome dysbiosis, we investigated the effect of EEN on the microbiome in a rat model of CD-like colitis. The rat model of CD-like colitis was established by an intracolonic instillation of TNBS at 65 mg/kg in 250 µL of 40% ethanol. Sham control rats were instilled with saline. Rats were fed ad libitum with either regular pellet food or EEN treatment with a clear liquid diet (Ensure). Rats were euthanized at 7 days. Fecal pellets were collected from the distal colon for 16S rRNA sequencing analysis of gut microbiota. In addition, colon tissues were taken for histological and molecular analyses in all the groups of rats. EEN administration to TNBS-induced CD rats significantly improved the body weight change, inflammation scores, and disease activity index. The mRNA expression of IL-17A and interferon-γ was significantly increased in the colonic tissue in TNBS rats when fed with regular food. However, EEN treatment significantly attenuated the increase in IL-17A and interferon-γ in TNBS rats. Our 16S rRNA sequencing analysis found that gut microbiota diversity and compositions were significantly altered in TNBS rats, compared to controls. However, EEN treatment improved alpha diversity and increased certain beneficial bacteria such as Lactobacillus and Dubosiella and decreased bacteria such as Bacteroides and Enterorhabdus in CD-like rats, compared to CD-like rats with the regular pellet diet. In conclusion, EEN treatment increases the diversity of gut microbiota and the composition of certain beneficial bacteria. These effects may contribute to the reduced inflammation by EEN in the rat model of CD-like colitis.

Analysis of sexual dysfunction development among male and female living kidney donors.

INTRODUCTION: Living kidney donations (LKDs) face a persistent demand for patients with end-stage renal disease, emphasizing the importance of LKDs' growth and success. Although living kidney donors generally exhibit excellent survival rates, little research has explored the development of long-term sexual dysfunction following LKD. OBJECTIVES: This study aimed to analyze differences in 5-year sexual dysfunction outcomes between male and female living kidney donors, utilizing the TriNetX database, a federated network of electronic medical records from multiple U.S. healthcare organizations. METHODS: A propensity score-matched cohort study compared 45-year sexual dysfunction outcomes in adult male and female living kidney donors from December 2013 to December 2022. Cohorts were matched on age; sex; race and ethnicity; diabetes, cardiovascular, genitourinary, and psychiatric comorbidities; lifestyle-related factors; and medications that may impact normal sexual functioning. Primary outcomes included hazard ratio (HR) for decreased libido, sexual dysfunction (composite of male erectile dysfunction, ejaculatory disorders, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders), and sexually transmitted diseases. Secondary outcomes assessed sex counseling and interpersonal relationship issues with spouses or partners. RESULTS: The matched cohorts included 2315 patients each (male, female), and the mean age was 42.3 ± 12.5 years. At 5 years, male donors had a significantly higher HR for sexual dysfunction (HR, 3.768; 95% confidence interval, 1.929-7.358). Erectile dysfunction occurred in 1% of male patients, while vaginismus/dyspareunia affected <1% of female patients. Other sexual disorders, decreased libido, sexually transmitted diseases, and incidences of sexual and interspousal counseling were not significantly different. CONCLUSION: Male living kidney donors faced a higher risk of developing sexual dysfunction 5 years after donation. While LKD remains a safe and viable alternative, clinicians and donors should be mindful of the potential association with sexual dysfunction postdonation. Further research may enhance support for the well-being of living kidney donors.

Gene coexpression networks reveal a broad role for lncRNAs in inflammatory bowel disease.

The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation of inflammation is increasingly appreciated. We addressed the extent of lncRNA involvement in inflammatory bowel disease (IBD) using biopsy-derived RNA-sequencing data from a large cohort of deeply phenotyped patients with IBD. Weighted gene correlation network analysis revealed gene modules of lncRNAs coexpressed with protein-coding genes enriched for biological pathways, correlated with epithelial and immune cell signatures, or correlated with distal colon expression. Correlation of modules with clinical features uncovered a module correlated with disease severity, with an enriched interferon response signature containing the hub lncRNA IRF1-AS1. Connecting genes to IBD-associated single nucleotide polymorphisms (SNPs) revealed an enrichment of SNP-adjacent lncRNAs in biologically relevant modules. Ulcerative colitis-specific SNPs were enriched in distal colon-related modules, suggesting that disease-specific mechanisms may result from altered lncRNA expression. The function of the IBD-associated SNP-adjacent lncRNA IRF1-AS1 was explored in human myeloid cells, and our results suggested IRF1-AS1 promoted optimal production of TNF-α, IL-6, and IL-23. A CRISPR/Cas9-mediated activation screen in THP-1 cells revealed several lncRNAs that modulated LPS-induced TNF-α responses. Overall, this study uncovered the expression patterns of lncRNAs in IBD that identify functional, disease-relevant lncRNAs.

A propensity score-matched analysis of intra- and postoperative penile prosthetic complications in the solid organ transplant population.

INTRODUCTION: Solid organ transplant (SOT) has an anticipated higher risk of penile prosthesis (PP) complications related to immunosuppression and surgical approach post-SOT. It is still not determined if PP surgery in the SOT population incurs these same higher risks. OBJECTIVES: To observe differences in intra- and postoperative PP complications between SOT and non-SOT cases from the TriNetX US Collaborative Network, a large real-world database of deidentified patient data from 56 health care organizations within the United States. METHODS: We used the TriNetX database to perform a propensity score-matched cohort study comparing 10-year outcomes between patients with and without a SOT (kidney, heart, lung, liver, pancreas, and intestine) who underwent a PP procedure. Cohorts were matched on age, race/ethnicity, history of pelvic and abdominal surgery, overweight and obesity status, type 2 diabetes mellitus, atherosclerosis, substance use disorders, socioeconomic difficulties, anticoagulant/antiplatelet medications, and spinal cord injury. Outcomes included intra- and perioperative complications as well as prosthetic complications (mechanical malfunction, fibrosis, displacement, hemorrhage, pain, stenosis, removal with or without replacement, and complex [all postoperative complications]). RESULTS: There were 233 patients in each group after matching (SOT and non-SOT). The mean ± SD age at the prosthesis procedure was 59.7 ± 9.89 years, and 44% of patients were White (P > .05). There was no significant difference for incidence of intra- and perioperative complications (2.62% vs 2.19%, P = .76). The SOT group did not have a higher 10-year incidence of complex complications (30.58% vs 27.51%, P = .11) or mechanical malfunction (10.35% vs 11.62%, P = .25) when compared with the non-SOT group. No difference was found for other prosthetic-related complications (P > .05). CONCLUSION: In our analysis, patients with a SOT were not more likely to experience long-term complications related to PP. Surgeons performing PP surgery in the SOT population may consider this procedure a potentially safe and viable option for restoring erectile function.

Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress-Induced Th17-Polarizing Cytokines in Crohn's-like Colitis.

BACKGROUND AND AIMS: Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. METHODS: A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. RESULTS: TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. CONCLUSIONS: Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.

Astrovirology: how viruses enhance our understanding of life in the Universe.

Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life. As viruses are the only replicators that span all known types of nucleic acids, an expanded experimental and theoretical toolbox built for Earth's viruses will be pivotal for detecting and understanding life on Earth and beyond. Only by filling in these knowledge and technical gaps we will obtain an inclusive assessment of how to distinguish and detect life on other planetary surfaces. Meanwhile, space exploration requires life-support systems for the needs of humans, plants and their microbial inhabitants. Viral effects on microbes and plants are essential for Earth's biosphere and human health, but virus-host interactions in spaceflight are poorly understood. Viral relationships with their hosts respond to environmental changes in complex ways which are difficult to predict by extrapolating from Earth-based proxies. These relationships should be studied in space to fully understand how spaceflight will modulate viral impacts on human health and life-support systems, including microbiomes. In this review, we address key questions that must be examined to incorporate viruses into Earth system models, life-support systems and life detection. Tackling these questions will benefit our efforts to develop planetary protection protocols and further our understanding of viruses in astrobiology.

Genetic continuity and change among the Indigenous peoples of California.

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.

Validation of machine vision and action sport cameras for 3D motion analysis model reconstruction.

The study investigated the feasibility of using action sport cameras for motion analysis research. Data acquired from two different marker-based motion capture systems and six different camera combinations were analyzed for motion reconstruction accuracy. Two different calibration procedures were used to determine the influence on marker position reconstruction. Static and dynamic calibration mean merit score differences between the reference and experimental camera systems were 0.4 mm and 1.3 mm, respectively. Angular displacement difference between the reference and experimental camera systems range between 0.1 and 2.0 degrees. A systematic bias (- 0.54 to 0.19 degrees) was determined between the reference and the experimental camera systems for range of motion. The mean of the multi-trial findings suggests the machine vision camera system calibrated with a dynamic procedure generated highly accurate three-dimensional reconstructed ROM data (0.5 degree) followed closely by the four action sport cameras implementing a static calibration procedure (0.5 degree). The overall findings suggest the selected machine vision and action sport camera systems produced comparable results to the reference motion analysis system. However, the combination of camera type, processing software, and calibration procedure can influence motion reconstruction accuracy.

Perceptions about and reasons for participation in research bronchoscopy in Uganda: A qualitative analysis.

This study sought to assess perceptions towards and reasons for participation in research bronchoscopy studies in a high TB burden urban setting. Additionally, the study aimed to identify areas of pre- and post-procedural concern among healthy adults approached to participate in research bronchoscopy. A cross sectional qualitative study was undertaken at the Uganda-Case Western Reserve University Collaboration Tuberculosis Research Project Clinic at Mulago National Referral Hospital in Kampala, Uganda. In-depth interviews were conducted with participants at their pre-bronchoscopy visit (n = 17) and after they had undergone bronchoscopy (n = 23) to examine their perceptions and experiences with the procedure. Following consent, all interviews were audio recorded and later transcribed and typed in MS WORD. Local language interviews were translated into English by the social science interviewers. Qualitative analysis was performed manually following an inductive and emergent approach typical in thematic analysis. This study was approved by the Makerere University School of Social Sciences Research Ethics Committee (MAKSS REC 09.18.220) and registered with the Uganda National Council for Science and Technology (UNCST SS4785). Overall willingness to participate in bronchoscopy was high as many participants viewed the study as primarily a means of getting free health checks and determining their health status. Notably, despite extensive face to face counseling for this study coupled with the fact that our participants had been involved in prior research at the site, therapeutic misconception still played a pivotal role in willingness to participate in research bronchoscopy. Therapeutic misconception has important ethical and research implications in clinical research, which requires strategies to tackle it, even among a pool of potential participants who are knowledgeable about a disease or clinical care procedures. Continuous awareness and knowledge building about the difference between being a trial participant and therapeutic misconception must become a mainstay in trials to improve the process of informed consent for future research bronchoscopy studies.