Nicotine addiction and the influence of life adversity and acute stress on PYY: Prediction of early smoking relapse.

Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi-experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19-73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow-up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24-h post-cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.

BlpU is a broad-spectrum bacteriocin in Streptococcus thermophilus.

Streptococcus thermophilus strain B59671 naturally produces thermophilin 110, a broad-spectrum bacteriocin encoded within the bacteriocin-like peptide (blp) gene cluster, and thermophilin 13 from a separate chromosomal locus. Analysis of the blp gene cluster revealed two genes, blpU and blpK, as potentially encoding bacteriocins. Deletion of blpK from the B59671 chromosome did not result in a loss of antimicrobial activity against either S. thermophilus ST113 or Pediococcus acidilactici F. A deletion mutant of blpU could not be generated in B59671, but the mature BlpU peptide obtained through overexpression in E. coli BL21 or chemical synthesis inhibited the growth of S. thermophilus strains, Streptococcus mutans UA159, P. acidilactici F, and Listeria innocua GV9 L-S, evidencing as a broad-spectrum bacteriocin that does not require modification for activity. This study also showed that the transcription of blpU was approximately 16-fold higher in B59671 than in an induced culture of S. thermophilus LMD-9, which produces a blp-encoded bacteriocin. The increased expression of BlpU in B59671 may explain the unique antimicrobial spectrum associated with this strain. Additionally, it was shown that a blpC deletion mutant of B59671, which prevents expression of BlpU and BlpK, inhibited the growth of other S. thermophilus strains and Bacillus cereus, suggesting that thermophilin 13 produced by B59671 possessed both intra- and interspecies antimicrobial activity. While this study confirmed that BlpU can function as an independent antimicrobial peptide, further studies are required to determine if BlpK can function independently as a broad-spectrum antimicrobial.

Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease.

Background: Peripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD. Objective: We sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise. Methods: Eleven PAD patients (52-80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1-2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured. Results: Although peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen's d = 0.56). Conclusion: Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

The Scratch-Collapse Test: Are Electrodiagnostic Changes Measurable?

INTRODUCTION: Carpal tunnel syndrome is commonly managed by hand and upper extremity surgeons. Though electrodiagnostics are considered the gold standard diagnosis, the scratch collapse test (SCT) was introduced to address uncertainty, despite remains controversial. To address this, we sought to identify if the SCT can correlate with EDS studies if the SCT can identify actual changes in measures of nerves. METHODS: We reviewed patients who underwent electrodiagnostic studies (EDX) and SCT for carpal tunnel syndrome (CTS). Demographic data as well as sensorimotor amplitudes, latencies, and velocities on nerve conduction and electromyography were collected. Analogous values based on SCT findings were analyzed for statistical significance. RESULTS: Three hundred fifty patients with CTS were included. Sensory and motor velocities and amplitudes were significantly lower in patients with a positive SCT. Motor values were independent of age, though younger patients had larger measured changes. Obese patients did not show any motor EDX changes with the scratch collapse test, though thinner patients did. All changes were seen in nerve conduction only. CONCLUSIONS: Carpal tunnel can be a difficult problem to diagnose as one study does not singularly determine the condition. The SCT was introduced to facilitate easier diagnosis. We demonstrate that the SCT correlates with changes on nerve conduction studies, especially in relation to decreased amplitudes and velocities, suggesting that it does identify changes in nerve with compression, specifically axonal, and myelin damage. These findings support the use of the SCT maneuver to evaluate and diagnose in appropriate patients.

Examining associations between mental health and Chronic Non-Communicable Diseases (C-NCDs) among older adults in Wakiso, Uganda.

BACKGROUND: Globally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda. METHODS: Between 2021-2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of <5 scores for minimal/no and 5+ for mild to severe symptomology) and anxiety (GAD-7 using a cutoff of 5+ scores for mild to severe symptomology). Bivariate analysis and multivariable logistic regression models were built using STATA software version 16.0 to examine associations between mental health disorders and having at least one C-NCD. Our exposures of interest were depressive and anxiety symptoms and our outcomes of interest was presence of C-NCDs. RESULTS: Majority of participants were females (63.6%), median age was 46 (IQR: 39-54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10-1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21-3.70). CONCLUSION: C-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda.

Women's access to family planning and experiences of reproductive coercion during the COVID-19 lockdown in two districts of Uganda.

Background: In March 2020, Uganda enforced country-wide restrictions to control the spread of SARS-CoV-2, categorizing some health services, including family planning (FP), as non-essential. Globally, similar COVID-19 restrictions have been associated with increased vulnerability to reproductive coercion (RC) among women, due to changes in FP service availability and restricted access by partners. This study aims to investigate these dynamics in Uganda, specifically examining the impact of the COVID-19 lockdown on women's access to FP, their experiences of RC, and the relationship between RC and intimate partner violence (IPV). Methods: We conducted a cross-sectional analysis of data from 960 women participating in the AMBSO Population Health Surveillance Study (APHS) between August 2020 and March 2021 across Wakiso (N = 164) and Hoima (N = 796) districts in Uganda. Our analysis focused on women who were sexually active in the past month, using bivariate analyses to explore the associations between RC and recent experiences of sexual, physical, and verbal IPV. Findings: The most commonly reported FP methods were injectables (36.8 %) and implants (16 %). Despite the COVID-19 lockdown, less than one percent of participants reported an inability to access their preferred FP method. Notably, 3 % of the women experienced RC in the past 12 months. There was a significant association between RC and sexual IPV (p < 0.0001), as well as physical IPV (p < 0.0001). Instances of verbal IPV were observed to have tripled during the lockdown period. Interpretation: An increase in verbal IPV was found among women during the COVID-19 lockdown. Additionally, a notable association emerged between other forms of IPV and an increased risk of RC. Despite the lockdown, access to FP remained high, which could be attributed to the prevalent use of long-acting FP methods.

Participant perspectives on incentives for TB preventative therapy adherence and reduced alcohol use: A qualitative study.

Economic incentives to promote health behavior change are highly efficacious for substance use disorders as well as increased medication adherence. Knowledge about participants' experiences with and perceptions of incentives is needed to understand their mechanisms of action and optimize future incentive-based interventions. The Drinkers' Intervention to Prevent Tuberculosis (DIPT) trial enrolled people with HIV (PWH) in Uganda with latent tuberculosis and unhealthy alcohol use in a 2x2 factorial trial that incentivized recent alcohol abstinence and isoniazid (INH) adherence on monthly urine testing while on INH preventive therapy. We interviewed 32 DIPT study participants across trial arms to explore their perspectives on this intervention. Participants described 1) satisfaction with incentives of sufficient size that allowed them to purchase items that improved their quality of life, 2) multiple ways in which incentives were motivating, from gamification of "winning" through support of pre-existing desire to improve health to suggesting variable effects of extrinsic and intrinsic motivation, and 3) finding value in learning results of increased clinical monitoring. To build effective incentive programs to support both reduced substance use and increased antimicrobial adherence, we recommend carefully selecting incentive magnitude as well as harnessing both intrinsic motivation to improve health and extrinsic reward of target behavior. In addition to these participant-described strengths, incorporating results of clinical monitoring related to the incentive program that provide participants more information about their health may also contribute to health-related empowerment.

"So that's why I found PrEP to be safest way to protect yourself": exploring IPV experiences and impact on HIV prevention among pregnant and postpartum women in Cape Town, South Africa.

Intimate partner violence (IPV) occurs at alarmingly high rates towards pregnant women in South Africa. Experiences of emotional, physical, and sexual IPV in pregnancy can adversely impact the health and safety of mother and fetus. Furthermore, IPV is associated with increased risk of HIV, exacerbating the public health impact of violence among pregnant women in this HIV endemic setting. In-depth understanding of cultural and contextual drivers of experiences of IPV is a critical precursor to development of interventions effectively addressing this issue among pregnant women in South Africa. The present study examines factors contributing to IPV among pregnant women to identify potential points of intervention. We conducted twenty in-depth interviews with postpartum women who used oral pre-exposure prophylaxis (PrEP) in pregnancy and reported recent experiences of IPV and/or ongoing alcohol use in a township near Cape Town, South Africa that experiences a heavy burden of both HIV and IPV. Interpretive thematic analysis was used. Several patterns of IPV during pregnancy were identified and violence was frequently described as co-occurring with male partner alcohol use. A majority of women referenced oral PrEP as their preferred method for HIV prevention, highlighting the agency and discretion it provided as beneficial attributes for women experiencing IPV. Fear of judgement from peers for remaining with an abusive partner and a lack of clear community messaging around IPV were identified as barriers to disclosure and support-seeking. Addressing the lack of social support received by women experiencing IPV during pregnancy in South Africa is essential to comprehensive IPV programming.

A Qualitative Exploration of Intimate Partner Violence Among HIV/TB Coinfected Persons With Problematic Alcohol Use Participating in an Incentive-Based Alcohol/Medication Adherence Intervention in Uganda During COVID-19.

In Uganda, four in ten women report experiencing intimate partner violence (IPV) in the past year. Salient drivers of IPV in sub-Saharan Africa include stress related to household finances, alcohol use, and partner infidelity. We conducted 42 interviews with participants (n = 32) in the Drinkers' Intervention to Prevent Tuberculosis (DIPT) study which included economic incentives, and their partners (n = 10) to understand how participating in DIPT during COVID-19 lockdown restrictions impacted relationship dynamics in intimate partnerships. Our findings highlight the need to develop policies to address root causes of IPV and to ensure continuity of IPV services in future pandemics. Policy and programming recommendations based on study results are presented.

Bacteriocin production by lactic acid bacteria using ice cream co-product as the fermentation substrate.

Ice cream manufacture commonly results in the accumulation of wasted product that contains valuable food-grade quality components, including fat, carbohydrates, and protein. Methods have been developed for recovering the fat from this waste stream, but this results in the generation of a co-product rich in fermentable carbohydrates. This study aimed to investigate the potential for using this co-product as a fermentation substrate for production of antimicrobial peptides, called bacteriocins, by dairy starter cultures. Results showed that Streptococcus thermophilus B59671 and Lactococcus lactis 11454 produced the broad-spectrum bacteriocins thermophilin 110 and nisin, respectively, when the fermentation substrate was melted ice cream, or a co-product generated by a modified butter churning technique. Bacteriocin production varied depending on the brand and variety of vanilla ice cream used in this study. When an alternate enzyme-assisted fat extraction technique was used, S. thermophilus metabolism was impaired within the resulting co-product, and thermophilin 110 production was not observed. Lactococcus lactis was still able to grow in this co-product, but antimicrobial activity was not observed. Results from this study suggest the co-product generated when using the churning technique is a better choice to use as a base medium for future studies to optimize bacteriocin production.

Substance Use and Associated Experiences of Intimate Partner Violence Among MSM in Los Angeles, California.

This study examined the prevalence and correlates of intimate partner violence (IPV) among a cohort of racial/ethnically diverse men who have sex with men (MSM) in Los Angeles. An ongoing longitudinal cohort study of MSM in Los Angeles, constructed by design so half of the participants use substances (SU) and half are persons living with HIV, provided data. Data collection occured between 2014 and 2020. At semiannual study visits, participants completed a computer-assisted self-interview which included questions on substance use (past 6 months) and experiences of IPV (past 12 months). The criterion variable was reported physical and sexual IPV. Multivariable models generalized estimating equations (GEE) estimated associations between reported SU and physical and sexual IPV, adjusting for repeated measurement and confounders. In total, 557 persons (2,962 visits) contributed to the analysis; the median baseline age was 30 years (interquartile range: 28.0-39.0). The prevalence of IPV in the past 12 months was 22.3%, with 18.3% reporting physical and 10.2% reporting sexual IPV across study visits. Stimulant use prevalence was higher among those who reported IPV compared to those who did not (68% vs. 42.1%; p < .001); cannabis use prevalence was lower among those reporting IPV (42.3% vs. 49% respectively; p < .001). Adjusted analysis showed reported stimulant use associated with greater odds of physical IPV (adjusted odds ratio [aOR] = 2.0; 95% confidence interval [CI] [1.4, 2.8], p < .001) but not sexual IPV (aOR = 1.3; 95% CI [0.8, 2.0], p = .332). Models stratified by HIV status yielded similar results. Findings showed a high prevalence of past-year IPV experiences among MSM in Los Angeles. Findings highlight links between SU and IPV and underscore a significantly increased likelihood of IPV for MSM in Los Angeles who report current methamphetamine use. This study provides evidence to support universal IPV screening and to make available safety resources at all points where MSM seek healthcare.

Fascial Lengthening at the Time of Surgical Release for de Quervain's Tenosynovitis to Prevent Postsurgical Tendon Subluxation.

BACKGROUND: De Quervain's tenosynovitis is a relatively common, painful condition. Although commonly managed nonoperatively, some patients have recalcitrant disease, necessitating surgical release. Traditional surgical release for de Quervain's tenosynovitis with simple retinacular release can leave patients susceptible to first dorsal extensor compartment tendon subluxation. We present a stair-step flap technique that releases the first dorsal compartment while simultaneously preventing postoperative tendon subluxation via fascial lengthening. METHODS: All patients over the past decade who underwent surgical release with this technique were collected. Preoperative characteristics, surgical details, and postoperative outcomes were reviewed and aggregated as summary statistics. RESULTS: A total of 101 patients were found. Of these, 35 patients had isolated first dorsal compartment release. Tourniquet time for the total group was 1 hour and that for the isolated first dorsal compartment release subgroup was 20 minutes. The average follow-up was 590 days for the total group and only 440 days for the isolated first dorsal compartment release subgroup. No patients who underwent our novel technique experienced subluxation of the tendons postoperatively. One patient required oral antibiotics for a superficial cellulitis, and 1 patient had recurrent symptoms due to excessive scarring that resolved with scar massage and steroid injection. No patient required repeat operations. CONCLUSION: Our study demonstrates that first dorsal compartment release with a stair-step incision allows for closure of the compartment with a very loose sheath without subluxation and simultaneously provides satisfactory decompression. This procedure is safe and efficacious and can be considered a useful modification to traditional retinacular release alone. LEVEL OF EVIDENCE: Level III.

Same-Day Discharge for Immediate Breast Reconstruction: A National Surgical Quality Improvement Program Study.

BACKGROUND: Patients undergoing immediate breast reconstruction with tissue expanders are frequently admitted after surgery for monitoring and pain control, which introduces additional costs and risks of nosocomial infection. Same-day discharge could conserve resources, mitigate risk, and return patients home for faster recovery. The authors used large data sets to investigate the safety of same-day discharge after mastectomy with immediate postoperative expander placement. METHODS: A retrospective review was performed of patients in the National Surgical Quality Improvement Program database who underwent breast reconstruction using tissue expanders between 2005 and 2019. Patients were grouped based on date of discharge. Demographic information, medical comorbidities, and outcomes were recorded. Statistical analysis was performed to determine efficacy of same-day discharge and identify factors that predict safety. RESULTS: Of the 14,387 included patients, 10% were discharged the same day, 70% on postoperative day 1, and 20% later than postoperative day 1. The most common complications were infection, reoperation, and readmission, which trended upward with length of stay (6.4% versus 9.3% versus 16.8%), but were statistically equivalent between same-day and next-day discharge. The complication rate for later-day discharge was statistically higher. Patients discharged later had significantly more comorbidities than same or next-day discharge counterparts. Predictors of complications included hypertension, smoking, diabetes, and obesity. CONCLUSIONS: Patients undergoing mastectomy with immediate tissue expander reconstruction are usually admitted overnight. However, same-day discharge was demonstrated to have an equivalent risk of perioperative complications as next-day discharge. For the otherwise healthy patient, going home the day of surgery is a safe and cost-effective option, although the decision should be made based on the individual patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Stakeholder perspectives on the Kisoboka intervention: A behavioral and structural intervention to reduce hazardous alcohol use and improve HIV care engagement among men living with HIV in Ugandan fishing communities.

BACKGROUND: East Africa's fishing communities experience a high burden of two interrelated and frequently co-occurring health issues: HIV and hazardous alcohol use. Nearly two-thirds of Ugandan fisherfolk men meet the criteria for harmful alcohol use. We developed a multilevel intervention to reduce hazardous alcohol use and improve HIV care engagement among fisherfolk men living with HIV (LWHIV) in Wakiso district, Uganda. METHODS: This is a qualitative study of stakeholder perspectives on the appropriateness, acceptability, and feasibility of a multilevel intervention for fisherfolk men LWHIV. The proposed intervention, Kisoboka ("It is possible!"), combines a structural component [changing the mode of work payments from cash to mobile money] with a behavioral component [motivational interviewing-based counseling combined with content using behavioral economic principles to promote behavior change]. We conducted one focus group (n=7) and eight in-depth interviews with fisherfolk men LWHIV and 19 key informant (KI) interviews with health workers, employers, and community leaders. These explored the appropriateness, acceptability, and feasibility of specific key intervention components. RESULTS: Overall, stakeholders' perspectives supported high intervention acceptability and perceived appropriateness of the proposed intervention. It was perceived to be feasible with some caveats of recommendations for overcoming potential implementation challenges identified (e.g., having a friend assist with documenting savings and alcohol use if an individual was unable to write themselves) which are discussed. CONCLUSION: This work highlights the potential of the Kisoboka intervention and the importance of early engagement of key stakeholders in the intervention development process to ensure appropriateness, acceptability, feasibility, and socio-cultural fit.

Nipple-Sparing Mastectomies in Patients over the Age of 60 Years: Factors Associated with Surgical Outcomes.

BACKGROUND: Nipple-sparing mastectomy (NSM) outcomes in the elderly have not been well characterized. The goal of this study was to evaluate NSM outcomes in patients over age 60. PATIENTS AND METHODS: A single-institution retrospective cohort study was performed for NSM patients over the age of 60 from January 2004 to January 2022. Demographic, intraoperative, and postoperative variables were collected. RESULTS: We identified 136 women who underwent a total of 200 NSMs at a mean age 65.2 years and with mean body mass index of 25. Most (56%) had invasive breast cancer, requiring neoadjuvant chemotherapy in 15%, and 17.5% had radiation prior to NSM. A total of 91% had immediate tissue expander placement. The infection rate was 19%, with 11.5% requiring expander explantation in the follow-up period. In binomial logistic regression analysis, prior radiation increased the odds of any complication by 2.9 (OR 2.93, CI 1.30-6.58, p = 0.009) and increased the odds of infection by 5.7 (OR 5.70, CI 1.95-16.66, p = 0.001), but no associations were seen for other covariates including age, comorbidities, prior chemotherapy, or presence of invasive disease. Diabetes increased the odds of wound breakdown specifically by 9.0 (OR 8.97, CI 2.01-39.92, p = 0.004). Local recurrence was 3% in mean 3.4-year follow-up. CONCLUSIONS: Our data support NSM in patients over the age of 60 years with acceptable outcomes within the standard of care. Locoregional recurrence was within the cited range of 0-5%, and only diabetes and prior radiation were associated with reconstructive complications. NSM should thus be offered when appropriate regardless of increased age to achieve oncologic and reconstructive goals.

Nigella sativa oil mitigates xerostomia and preserves salivary function in radiotherapy-treated mice.

Objective: This study aimed to assess if Nigella sativa oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage. Methods: Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + H2O gavage (control) (N = 4); 15 Gy RT + H2O gavage (N = 12); sham RT + NSO gavage (N = 12); and 15 Gy RT + NSO gavage (N = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment. Results: All mice in the sham RT + H2O gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + H2O compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g (p < .001). Salivary output showed significant decline in RT + H2O gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + H2O gavage group did not recover as effectively. Conclusion: NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells. Level of evidence: Not applicable.

Antimicrobial activity of thermophilin 110 against the opportunistic pathogen Cutibacterium acnes.

OBJECTIVE: Thermophilin 110, a bacteriocin produced by Streptococcus thermophilus B59671, inhibited planktonic growth and biofilm formation of Cutibacterium acnes, a commensal skin bacterium associated with the inflammatory disease, acne vulgaris, and more invasive deep tissue infections. RESULTS: Thermophilin 110 prevented planktonic growth of C. acnes at a concentration ≥ 160 AU mL-1; while concentrations ≥ 640 AU mL-1 resulted in a > 5 log reduction in viable planktonic cell counts and inhibited biofilm formation. Arabinoxylan (AX) and sodium alginate (SA) hydrogels were shown to encapsulate thermophilin 110, but as currently formulated, the encapsulated bacteriocin was unable to diffuse out of the gel and inhibit the growth of C. acnes. Hydrogels were also used to encapsulate S. thermophilus B59671, and inhibition zones were observed against C. acnes around intact SA gels, or S. thermophilus colonies that were released from AX gels. CONCLUSIONS: Thermophilin 110 has potential as an antimicrobial for preventing C. acnes infections and further optimization of SA and AX gel formulations could allow them to serve as delivery systems for bacteriocins or bacteriocin-producing probiotics.

Variant Characterization of a Representative Large Pedigree Suggests "Variant Risk Clusters" Convey Varying Predisposition of Risk to Lynch Syndrome.

Recently, worldwide incidences of young adult aggressive colorectal cancer (CRC) have rapidly increased. Of these incidences diagnosed as familial Lynch syndrome (LS) CRC, outcomes are extremely poor. In this study, we seek novel familial germline variants from a large pedigree Tunisian family with 12 LS-affected individuals to identify putative germline variants associated with varying risk of LS. Whole-genome sequencing analysis was performed to identify known and novel germline variants shared between affected and non-affected pedigree members. SNPs, indels, and structural variants (SVs) were computationally identified, and their oncological influence was predicted using the Genetic Association of Complex Diseases and Disorders, OncoKB, and My Cancer Genome databases. Of 94 germline familial variants identified with predicted functional impact, 37 SNPs/indels were detected in 28 genes, 2 of which (MLH1 and PRH1-TAS2R14) have known association with CRC and 4 others (PPP1R13B, LAMA5, FTO, and NLRP14) have known association with non-CRC cancers. In addition, 48 of 57 identified SVs overlap with 43 genes. Three of these genes (RELN, IRS2, and FOXP1) have a known association with non-CRC digestive cancers and one (RRAS2) has a known association with non-CRC cancer. Our study identified 83 novel, predicted functionally impactful germline variants grouped in three "variant risk clusters" shared in three familiarly associated LS groups (high, intermediate and low risk). This variant characterization study demonstrates that large pedigree investigations provide important evidence supporting the hypothesis that different "variant risk clusters" can convey different mechanisms of risk and oncogenesis of LS-CRC even within the same pedigree.

Is neighborhood deprivation index a risk factor for Staphylococcus aureus infections?

BACKGROUND: We assessed the association between neighborhood area deprivation index (ADI) and community-onset (co) and hospital-onset (ho) Staphylococcus aureus infection. METHODS: Demographic and clinical characteristics of patients admitted to 5 adult hospitals in the mid-Atlantic between 2016 and 2018 were obtained. The association of ADI with methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) S aureus infections was assessed using logistic regression models adjusting for severity of illness and days of admission. RESULTS: Overall, increasing ADI was associated with higher odds of co- and ho-MRSA and MSSA infection. In univariate analysis, Black race was associated with 44% greater odds of ho-MRSA infection (odds ratio [OR] 1.44; 95% CI 1.18-1.76) and Asian race (co-MRSA OR 0.355; Confidence Interval (CI) 0.240-0.525; co-MSSA OR 0.718; CI 0.557-0.928) and unknown race (co-MRSA OR 0.470; CI 0.365-0.606; co-MSSA OR 0.699; CI 0.577-0.848) was associated with lower odds of co-MSSA and co-MRSA infections. When both race and ADI were included in the model, Black race was no longer associated with ho-MRSA infections whereas Asian and unknown race remained associated with lower odds of co-MRSA and co-MSSA infection. In the multivariable logistic regression, ADI was consistently associated with increased odds of S aureus infection (co-MRSA OR 1.132; CI 1.064-1.205; co-MSSA OR 1.089; CI 1.030-1.15; ho-MRSA OR 1.29; CI 1.16-1.43: ho-MSSA OR 1.215; CI 1.096-1.346). CONCLUSIONS: The area deprivation index is associated with community and hospital-onset MRSA and MSSA infections.