Whole-genome sequencing of two captive black soldier fly populations: Implications for commercial production.

Black soldier fly (BSF; Hermetia illucens) is a promising insect species for food and feed production as its larvae can convert different organic waste to high-value protein. Selective breeding is one way to optimize production, but the potential of breeding is only starting to be explored and not yet utilized for BSF. To assist in monitoring a captive population and implementing a breeding program, genomics tools are imperative. We conducted whole genome sequencing of two captive populations separated by geographical distance - Denmark (DK) and Texas, USA (TX). Various population genetics analyses revealed a moderate genetic differentiation between two populations. Moreover, we observed higher inbreeding in the DK population, and the detection of a subpopulation within DK population aligned well with the recent foundation of the DK population from two captive populations. Additionally, we generated gene ontology annotation and variants annotation for wider potential applications. Our findings establish a robust marker set for research in population genetics, facilitating the monitoring of inbreeding and laying the groundwork for practical breeding programs for BSF.

Two weeks of acarbose treatment show no effect on gut microbiome composition in patients with type 2 diabetes: a randomised, placebo-controlled, double-blind, crossover study.

AIMS: The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and absorption of ingested carbohydrates. This reduces postprandial blood glucose concentration and increases the content of carbohydrates in the distal parts of the intestine potentially influencing gut microbiome (GM) composition and thereby possibly impacting the gut microbiome (GM) dysbiosis associated with T2D. Here, we investigated the effect of acarbose on GM composition in patients with T2D. METHODS: Faecal samples collected in a previously conducted randomised, placebo-controlled, double-blind, crossover study in which 15 individuals with metformin-treated T2D (age 57-85 years, HbA1c 40-74 mmol/mol, BMI 23.6 - 34.6 kg/m2) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a six-week wash-out period. Faecal samples were collected before and by the end of each treatment period. The GM profiles were evaluated by 16S rRNA gene amplicon sequencing. RESULTS: The GM profiles after the treatment periods with acarbose or placebo remained unaffected (P > 0.7) when compared with the GM profiles before treatment. This applied to both the analysis of within-sample diversity (α-diversity) and between-sample bacterial composition diversity (ß-diversity). Additionally, no dominant bacterial species differentiated the treatment groups, and only minor increases in the relative abundances of Klebsiella spp and Escherichia coli were observed after acarbose treatment (P < 0.05). CONCLUSIONS: In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only physiologically unimportant effects on GM.

The Development of CDC25A-Derived Phosphoseryl Peptides That Bind 14-3-3ε with High Affinities.

Overexpression of the 14-3-3ε protein is associated with suppression of apoptosis in cutaneous squamous cell carcinoma (cSCC). This antiapoptotic activity of 14-3-3ε is dependent on its binding to CDC25A; thus, inhibiting 14-3-3ε - CDC25A interaction is an attractive therapeutic approach to promote apoptosis in cSCC. In this regard, designing peptide inhibitors of 14-3-3ε - CDC25A interactions is of great interest. This work reports the rational design of peptide analogs of pS, a CDC25A-derived peptide that has been shown to inhibit 14-3-3ε-CDC25A interaction and promote apoptosis in cSCC with micromolar IC50. We designed new peptide analogs in silico by shortening the parent pS peptide from 14 to 9 amino acid residues; then, based on binding motifs of 14-3-3 proteins, we introduced modifications in the pS(174-182) peptide. We studied the binding of the peptides using conventional molecular dynamics (MD) and steered MD simulations, as well as biophysical methods. Our results showed that shortening the pS peptide from 14 to 9 amino acids reduced the affinity of the peptide. However, substituting Gln176 with either Phe or Tyr amino acids rescued the binding of the peptide. The optimized peptides obtained in this work can be candidates for inhibition of 14-3-3ε - CDC25A interactions in cSCC.

Estimation of genetic parameters for the implementation of selective breeding in commercial insect production.

BACKGROUND: There is a burgeoning interest in using insects as a sustainable source of food and feed, particularly by capitalising on various waste materials and by-products that are typically considered of low value. Enhancing the commercial production of insects can be achieved through two main approaches: optimising environmental conditions and implementing selective breeding strategies. In order to successfully target desirable traits through selective breeding, having a thorough understanding of the genetic parameters pertaining to those traits is essential. In this study, a full-sib half-sib mating design was used to estimate variance components and heritabilities for larval size and survival at day seven of development, development time and survival from egg to adult, and to estimate correlations between these traits, within an outbred population of house flies (Musca domestica), using high-throughput phenotyping for data collection. RESULTS: The results revealed low to intermediate heritabilities and positive genetic correlations between all traits except development time and survival to day seven of development and from egg to adulthood. Surprisingly, larval size at day seven exhibited a comparatively low heritability (0.10) in contrast to development time (0.25), a trait that is believed to have a stronger association with overall fitness. A decline in family numbers resulting from low mating success and high overall mortality reduced the amount of available data which resulted in large standard errors for the estimated parameters. Environmental factors made a substantial contribution to the phenotypic variation, which was overall high for all traits. CONCLUSIONS: There is potential for genetic improvement in all studied traits and estimates of genetic correlations indicate a partly shared genetic architecture among the traits. All estimates have large standard errors. Implementing high-throughput phenotyping is imperative for the estimation of genetic parameters in fast developing insects, and facilitates age synchronisation, which is vital in a breeding population. In spite of endeavours to minimise non-genetic sources of variation, all traits demonstrated substantial influences from environmental components. This emphasises the necessity of thorough attention to the experimental design before breeding is initiated in insect populations.

PKCµ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.

Downregulation of intercellular communication through suppression of gap junctional conductance is necessary during wound healing. Connexin 43 (Cx43), a prominent gap junction protein in skin, is downregulated following wounding to restrict communication between keratinocytes. Previous studies found that PKCµ, a novel PKC isozyme, regulates efficient cutaneous wound healing. However, the molecular mechanism by which PKCµ regulates wound healing remains unknown. We have identified that PKCµ suppresses intercellular communication and enhances cell migration in an in vitro wound healing model by regulating Cx43 containing gap junctions. PKCµ can directly interact with and phosphorylate Cx43 at S368, which leads to Cx43 internalization and downregulation. Finally, utilizing phosphomimetic and non-phosphorylatable S368 substitutions and gap junction inhibitors, we confirmed that PKCµ regulates intercellular communication and in vitro wound healing by controlling Cx43-S368 phosphorylation. These results define PKCµ as a critical regulator of Cx43 phosphorylation to control cell migration and wound healing in keratinocytes.

Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.

14-3-3ε is involved in various types of malignancies by increasing cell proliferation, promoting cell invasion, or inhibiting apoptosis. In cutaneous squamous cell carcinoma (cSCC), 14-3-3ε is overexpressed and mislocalized from the nucleus to the cytoplasm where it interacts with the cell division cycle 25 A (CDC25A) and suppresses apoptosis. Hence, inhibition of the 14-3-3ε-CDC25A interaction is an attractive target for promoting apoptosis in cSCC. In this work, we optimized the structure of our previously designed inhibitor of the 14-3-3ε-CDC25A interaction, pT, a phosphopeptide fragment corresponding to one of the two binding regions of CDC25A to 14-3-3ε. Starting from pT, we developed peptide analogs that bind 14-3-3ε with nanomolar affinities. Peptide analogs were designed by shortening the pT peptide and introducing modifications at position 510 of the pT(502-510) analog. Both molecular dynamics (MD) simulations and biophysical methods were used to determine peptide binding to 14-3-3ε. Shortening the pT peptide from 14 to 9 amino acid residues resulted in a peptide (pT(502-510)) that binds 14-3-3ε with a KD value of 45.2 nM. Gly to Phe substitution in position 510 of pT(502-510) led to further improvement in affinity (KD: 22.0 nM) of the peptide for 14-3-3ε. Our results suggest that the designed peptide analogs are potential candidates for inhibiting 14-3-3ε-CDC25A interactions in cSCC cells and thus inducing their apoptosis.

Effects of Exogenous GIP and GLP-2 on Bone Turnover in Individuals With Type 2 Diabetes.

CONTEXT: Individuals with type 2 diabetes (T2D) have an increased risk of bone fractures despite normal or increased bone mineral density. The underlying causes are not well understood but may include disturbances in the gut-bone axis, in which both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are regulators of bone turnover. Thus, in healthy fasting participants, both exogenous GIP and GLP-2 acutely reduce bone resorption. OBJECTIVE: The objective of this study was to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D. METHODS: We included 10 men with T2D. Participants met fasting in the morning on 3 separate test days and were injected subcutaneously with GIP, GLP-2, or placebo in a randomized crossover design. Blood samples were drawn at baseline and regularly after injections. Bone turnover was estimated by circulating levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and PTH. RESULTS: GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after placebo (P = .001). In addition, P1NP and sclerostin increased acutely after GIP whereas a decrease in P1NP was seen after GLP-2. PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP. CONCLUSION: Subcutaneous GIP and GLP-2 affect CTX and P1NP in individuals with T2D to the same extent as previously demonstrated in healthy individuals.

Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.

14-3-3ε is involved in various types of malignancies by increasing cell proliferation, promoting cell invasion or inhibiting apoptosis. In cutaneous squamous cell carcinoma (cSCC), 14-3-3ε is over expressed and mislocalized from the nucleus to the cytoplasm where it interacts with the cell division cycle 25 A (CDC25A) and suppresses apoptosis. Hence inhibition of the 14-3-3ε - CDC25A interaction is an attractive target for promoting apoptosis in cSCC. In this work, we optimized the structure of our previously designed inhibitor of 14-3-3ε - CDC25A interaction, pT, a phosphopeptide fragment corresponding to one of the two binding regions of CDC25A to 14-3-3ε. Starting from pT, we developed peptide analogs that bind 14-3-3ε with nanomolar affinities. Peptide analogs were designed by shortening the pT peptide, and introducing modifications at position 510 of the pT(502-510) analog. Both molecular dynamics (MD) simulations and biophysical methods were used to determine peptides binding to 14-3-3ε. Shortening the pT peptide from 14 to 9 amino acid residues resulted in a peptide (pT(502-510)) that binds 14-3-3ε with a KD value of 45.2 nM. Gly to Phe substitution in position 510 of pT(502-510) led to further improvement in affinity (KD: 22.0 nM) of the peptide for 14-3-3ε. Our results suggest that the designed peptide analogs are potential candidates for inhibiting 14-3-3ε -CDC25A interactions in cSCC cells; thus, inducing their apoptosis.

Surgical Rehabilitation for Research Residents: A Pilot Program to Offset Surgical Skill Decay.

OBJECTIVE: Select general surgery residents in the surgeon-scientist pipeline dedicate time away from clinical residency to conduct research. However, these research residents (RR) are vulnerable to operative skill decay. The aim of this study is to assess the feasibility of implementation and impact of an organized intervention designed to combat skill decay experienced by RR. DESIGN: RR were enrolled in a pilot Surgical Rehabilitation Program (SRP). The SRP is comprised of 12 cadaver-based simulation sessions and supplemented with Fundamentals of Laparoscopic Surgery-based simulation workouts. The RR were integrated with the clinical residents (CR) during the cadaver sessions and were subsequently performance tested, surveyed, and interviewed. SETTING: One academic general surgery residency program graduating 8 chief residents yearly in New York. PARTICIPANTS: General surgery CR and residents on dedicated research years. RESULTS: Data were collected for all local RR (n = 8) and 77% (n = 37) of CR. Local RR conducted research within the same health system that sponsors the residency. RR experienced gaps in training ranging from 2 to 4 years. All RR were permitted to moonlight on surgical services, however performed 0 operations and only 0.88 procedures on average per shift. Although RR performed similarly to level-matched CR on basic laparoscopic tasks, they required significantly more time on laparoscopic suturing-based skills than CR (p < 0.001). RR had significantly lower confidence levels precadaver sessions but gained confidence postcadaver sessions (p < 0.05), whereas CR confidence was unchanged. Regarding the SRP, qualitative interviews revealed major themes emphasizing the integration of RR, exposure to CR and faculty, technical skill development, maintenance of surgical know-how, and improved confidence for RR. CONCLUSIONS: The implementation of such structured interventions, like our SRP, aimed at supporting RR over gap years is essential to help residents maintain skills and confidence needed to achieve their goals of becoming surgeon scientists.

Indocyanine green angiography in oncoplastic breast surgery, a prospective study.

INTRODUCTION: The use of Indocyanine green angiography (ICG-A) in oncoplastic breast-conserving surgery (OBCS) has not yet been investigated. This prospective trial applied ICG-A in volume displacement and replacement OBCS to localize perforators and determine tissue supplied by the perforator. Furthermore, to investigate and correlate the intraoperative ICG-A to postoperative surgical site infection, skin necrosis, epidermolysis, and timely onset of adjuvant therapy. METHODS: ICG-A was performed at three pre-set timepoints during surgery; after lumpectomy, upon dissection of possible perforators, and after wound closure. All patients were followed with clinical evaluations before surgery, 4 weeks, 4-6 months, and 12 months postoperatively. RESULTS: Eleven patients were included: seven volume displacement and four volume replacement OBCS. ICG-A located the tissue supplied by the perforator and demonstrated sufficient perfusion in all cases. The ICG-A corresponded to the surgeons' clinical assessment. One patient developed a postoperative infection and seroma and was treated conservatively. No patients had postoperative necrosis, loss of reconstruction, or lymphedema of the arm. Edema of the breast occurred in four patients (36.4%). Scar assessments were significantly worse at 4-weeks and 4-6 months. The quality of life improved significantly during follow-up. Adjuvant treatment was administered timely in all cases. CONCLUSION: ICG-A was feasible for OBCS in assessing intraoperative perfusion. Perfusion was sufficient in all patients and corresponded to the surgeon's clinical evaluation. No patients developed postoperative necrosis. Though edema of the breast occurred in 36.4%, a larger sample size is needed to investigate a possible correlation with ICG-A. Further studies, which includes patients requiring extensive tissue replacement challenging the borders of perfusion, are needed.

A randomized control trial of a combined community health worker and re-entry intervention for people with HIV recently released from jail who use substances.

INTRODUCTION: People with human immunodeficiency virus (HIV; PWH) who use substances are disproportionately involved in the criminal justice system. While HIV viral suppression typically improves during incarceration, these gains are frequently lost after release. We evaluated the impact of a combined intervention (formerly incarcerated community health workers [CHW] plus a re-entry organization; CHW+) on postrelease HIV- and substance use-related outcomes. METHODS: We conducted a pilot randomized controlled trial of a CHW+ for PWH who use substances, within 30 days of release from a large southern, urban jail. Between February 2019 and August 2021, participants were recruited, enrolled, and randomized to treatment as usual (TAU; passive referral to care) or CHW+. Follow up study visits occurred at 3, 6, and 12 months. The primary outcome was HIV VL at 6 months; secondary outcomes included 6-month urinary toxicology and high-risk substance use at 12 months. RESULTS: A total of 31 participants were enrolled who were primarily male (n = 24; 77 %), Black (n = 22; 71 %), unemployed (n = 23; 74.2 %), had unstable housing (n = 18; 58 %), had food insecurity (n = 14; 45 %), and reported their drug of choice was stimulants (n = 24; 77 %). The study identified no significant difference in HIV VL suppression at 6 months (20 % v. 37 %; [CHW+ v. TAU], p = 0.61). We observed improved substance use outcomes in CHW+ v. TAU, including fewer positive urinary toxicology screens for stimulants (40 % v. 100 %; p = 0.01) and a trend toward less high-risk substance use (30 % v. 43 %). The CHW+ group met more basic needs, such as food security [+32 % v. +11 %], housing security [+52 % v. -7 %] and full-time employment [+20 % v. +5 %] compared to TAU. CONCLUSIONS: PWH who use substances assigned to a combined intervention of CHW+ after jail release did not achieve higher rates of HIV VL suppression than TAU; however, they had improved substance use outcomes and met more basic subsistence needs. Results highlight the potential of culturally informed interventions to address the competing needs of PWH who use substances after release from jail and call for further development of innovative solutions to successfully bridge to HIV care in the community.

Membrane structure and internalization dynamics of human Flower isoforms hFWE3 and hFWE4 indicate a conserved endocytic role for hFWE4.

Human Flower (hFWE) isoforms hFWE1-4 are putative transmembrane (TM) proteins that reportedly mediate fitness comparisons during cell competition through extracellular display of their C-terminal tails. Isoform topology, subcellular localization, and duration of plasma membrane presentation are essential to this function. However, disagreement persists regarding the structure of orthologous fly and mouse FWEs, and experimental evidence for hFWE isoform subcellular localization or membrane structure is lacking. Here, we used AlphaFold2 and subsequent molecular dynamics-based structural predictions to construct epitope-tagged hFWE3 and hFWE4, the most abundant human isoforms, for experimental determination of their structure and internalization dynamics. We demonstrate that hFWE3 resides in the membrane of the endoplasmic reticulum (ER), while hFWE4 partially colocalizes with Rab4-, Rab5-, and Rab11-positive vesicles as well as with the plasma membrane. An array of imaging techniques revealed that hFWE4 positions both N- and C-terminal tails and a loop between second and third TM segments within the cytosol, while small (4-12aa) loops between the first and second and the third and fourth TM segments are either exposed to the extracellular space or within the lumen of cytoplasmic vesicles. Similarly, we found hFWE3 positions both N- and C-terminal tails in the cytosol, while a short loop between TM domains extends into the ER lumen. Finally, we demonstrate that hFWE4 exists only transiently at the cell surface and is rapidly internalized in an AP-2- and dynamin-1-dependent manner. Collectively, these data are consistent with a conserved role for hFWE4 in endocytic processes.

The effect of early follow-up after open cardiac surgery in a student clinic.

Objectives. Readmission rates following open cardiac surgery are high, affecting patients and the cost of care. This study aimed to investigate the effect of early additional follow-up after open cardiac surgery when 5th-year medical students conducted follow-ups under the supervision of physicians. The primary endpoint was unplanned cardiac-related readmissions within one year. The secondary outcomes were the detection of impending complications and health-related quality of life (HRQOL). Methods. Patients undergoing open cardiac surgery were prospectively included. For intervention, additional follow-up visits, including point-of-care ultrasound, were conducted by supervised 5th-year medical students on postoperative days 3, 14 and 25. Unplanned cardiac-related readmissions, including emergency department visits, were registered within the first year of surgery. Danish National Health Survey 2010 questionnaire was used for HRQOL. In standard follow-up, all patients were seen 4-6 weeks postoperative. Results. For data analysis, 100 of 124 patients in the intervention group and 319 of 335 patients in the control group were included. The 1-year unplanned readmission rates did not differ; 32% and 30% in the intervention and control groups, respectively (p = 0.71). After discharge, 1% of patients underwent pericardiocentesis. The additional follow-up initiated scheduled drainage, contrary to more unscheduled/acute drainages in the control group. Pleurocentesis was more common in the intervention group (17% (n = 17) vs 8% (n = 25), p = 0.01) and performed earlier. There was no difference between groups on HRQOL. Conclusion. Supervised student-led follow-up of newly cardiac-operated patients did not alter readmission rates or HRQOL but may detect complications earlier and initiate non-emergent treatment of complications.

Social Media, Misinformation, and Online Patient Education in Emergency General Surgical Procedures.

INTRODUCTION: Patients use the internet to learn about diagnoses and treatment options. These sources vary in quality and accuracy of medical information. Thus, utilization of social media may lead to misinformation regarding treatment for patients in need of emergent general surgery procedures. METHODS: YouTube was searched with keywords "cholecystectomy," "cholecystitis," and "gallbladder surgery" and "appendectomy," "appendicitis," and "appendix surgery." For each procedure, the 100 videos with the greatest views were reviewed. Videos were assessed by four surgical trainees using validated instruments, DISCERN and the Patient Education Materials Assessment Tool (PEMAT), and Likert scales for patient education and misinformation. After appendectomy or cholecystectomy, patients completed a survey assessing use of social media preoperatively. RESULTS: The median DISCERN score was 28.0 of 75. The median PEMAT scores were 66.7% for understandability and 0% for actionability. Nearly half (49%) of videos provided no patient education and only 22% provided moderate or more. More than a third (35%) of videos contained misinformation. Doctors, medical education, and healthcare systems published videos with less misinformation, whereas patients, health/wellness groups published more misinformation (P < 0.001). Videos discoverable with colloquial terms "appendix surgery" and "gallbladder surgery" were more likely to contain misinformation (45.3%) compared to 20.5% of videos with misinformation discoverable using medical search terms only (P < 0.001). CONCLUSIONS: There is a range of video quality online with most videos of poor quality and provide little patient education. Understanding information available to patients online can tailor surgeon-patient discussions to combat misinformation and improve the informed consent process for patients.

Acarbose diminishes postprandial suppression of bone resorption in patients with type 2 diabetes.

AIMS: The alpha-glucosidase inhibitor acarbose is an antidiabetic drug delaying assimilation of carbohydrates and, thus, increasing the amount of carbohydrates in the distal parts of the intestines, which in turn increases circulating levels of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1). As GLP-1 may suppress bone resorption, acarbose has been proposed to potentiate meal-induced suppression of bone resorption. We investigated the effect of acarbose treatment on postprandial bone resorption in patients with type 2 diabetes and used the GLP-1 receptor antagonist exendin(9-39)NH2 to disclose contributory effect of acarbose-induced GLP-1 secretion. METHODS: In a randomised, placebo-controlled, double-blind, crossover study, 15 participants with metformin-treated type 2 diabetes (2 women/13 men, age 71 (57-85 years), BMI 29.7 (23.6-34.6 kg/m2), HbA1c 48 (40-74 mmol/mol)/6.5 (5.8-11.6 %) (median and range)) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a six-week wash-out period. At the end of each period, circulating bone formation and resorption markers were assessed during two randomised 4-h liquid mixed meal tests (MMT) with infusions of exendin(9-39)NH2 and saline, respectively. Glucagon-like peptide 2 (GLP-2) was also assessed. RESULTS: Compared to placebo, acarbose impaired the MMT-induced suppression of CTX as assessed by baseline-subtracted area under curve (P = 0.0037) and nadir of CTX (P = 0.0128). During acarbose treatment, exendin(9-39)NH2 infusion lowered nadir of CTX compared to saline (P = 0.0344). Neither parathyroid hormone or the bone formation marker procollagen 1 intact N-terminal propeptide were affected by acarbose or GLP-1 receptor antagonism. Acarbose treatment induced a greater postprandial GLP-2 response than placebo treatment (P = 0.0479) and exendin(9-39)NH2 infusion exacerbated this (P = 0.0002). CONCLUSIONS: In patients with type 2 diabetes, treatment with acarbose reduced postprandial suppression of bone resorption. Acarbose-induced GLP-1 secretion may contribute to this phenomenon as the impairment was partially reversed by GLP-1 receptor antagonism. Also, acarbose-induced reductions in other factors reducing bone resorption, e.g. glucose-dependent insulinotropic polypeptide, may contribute.

Self-Reported Asthma Is Associated with Reduced Sperm Count-A Cross-Sectional Study of More than 6000 Young Men from the General Population.

Asthma is driven by an inflammatory response that may impact testicular function. In this cross-sectional study, we investigated the association between self-reported asthma and testicular function (semen parameters, reproductive hormone levels), and determined whether potential further inflammation due to self-reported allergy modified this association. A total of 6177 men from the general population completed a questionnaire including information on doctor-diagnosed asthma or allergy, had a physical examination, delivered a semen sample, and had a blood sample drawn. Multiple linear regression analyses were performed. A total of 656 (10.6%) men reported having ever been diagnosed with asthma. Generally, self-reported asthma was consistently associated with a poorer testicular function; however, few estimates were statistically significant. Specifically, self-reported asthma was associated with statistically significant lower total sperm count [median: 133 vs. 145 million; adjusted ß (95% CI): -0.18 (-0.33 to -0.04) million on cubic-root-transformed scale] and borderline statistically significant lower sperm concentration compared with no self-reported asthma. The association between asthma and total sperm count was of similar magnitude among men with and without allergy. In conclusion, men with self-reported asthma had poorer testicular function than men without asthma. However, the cross-sectional design of the study limits ascertainment of causality.

Testicular function is associated with cardiometabolic health markers: A cross-sectional study of 2289 young men.

BACKGROUND: Testicular function, including compensated Leydig cell function, has been indicated to be an early marker of morbidity. OBJECTIVE: To study the association of testicular function and markers of metabolic and cardiovascular health in a population of young men. MATERIALS AND METHODS: A cross-sectional study of 2289 men (median age 19 years, 5-95 percentile 18.4-22.2) from the general population examined between 2012 and 2019. Participants answered a questionnaire, had a blood sample drawn for assessment of reproductive hormone levels and health markers (lipids, glycosylated hemoglobin), delivered a semen sample, underwent physical examination including blood pressure measurements, and dual-energy X-ray absorptiometry scan for assessment of body composition. Associations were assessed in both crude and adjusted linear regression analyses. RESULTS: The men were within the normal reference intervals of their age for reproductive and health biomarkers. Compared to the lowest quartile, having luteinizing hormone levels in the highest quartile was associated with higher mean arterial pressure (1.6 [95% confidence interval: 0.8; 2.5] mmHg), cholesterol (0.1 [95% confidence interval: 0.02; 0.18] mmol/L), and total body fat percentage (1.1 [95% confidence interval: 0.4; 1.8] %-points). Higher serum testosterone levels were associated with more advantageous cardiometabolic health markers and higher total sperm count with a healthier body composition and lower glycosylated hemoglobin. DISCUSSION AND CONCLUSION: In this study of young men, unselected regarding reproductive hormones and semen quality, higher luteinizing hormone was associated with cardiovascular risk factors. Higher testosterone and total sperm count were associated with more favorable cardiometabolic indices. Thus, serum reproductive hormones and semen quality may be early appearing biomarkers of cardiovascular health even among young healthy men, which could potentially be useful for preventive initiatives to reduce the excess mortality and morbidity risk among infertile men. However, our study was cross-sectional and cannot determine causation. Future longitudinal studies of reproductive health in young men are warranted.

[Advanced locoregional chest wall recurrence of breast cancer].

Locoregional recurrence of breast cancer continues to be a significant clinical issue involving extensive examination programmes, modified oncologic therapy and advanced surgery. The latter includes tumour resection followed by reconstruction of the thoracic wall. The type of reconstruction depends on tumour location, depth, aetiology and whether the resection involves the stabilising osseous structures as summarised in this review. The treatment strategy is planned at multidisciplinary team conferences with the presence of relevant specialists to ensure evidence-based treatment of consistent quality.

Deep Learning-Based Total Kidney Volume Segmentation in Autosomal Dominant Polycystic Kidney Disease Using Attention, Cosine Loss, and Sharpness Aware Minimization.

Early detection of the autosomal dominant polycystic kidney disease (ADPKD) is crucial as it is one of the most common causes of end-stage renal disease (ESRD) and kidney failure. The total kidney volume (TKV) can be used as a biomarker to quantify disease progression. The TKV calculation requires accurate delineation of kidney volumes, which is usually performed manually by an expert physician. However, this is time-consuming and automated segmentation is warranted. Furthermore, the scarcity of large annotated datasets hinders the development of deep learning solutions. In this work, we address this problem by implementing three attention mechanisms into the U-Net to improve TKV estimation. Additionally, we implement a cosine loss function that works well on image classification tasks with small datasets. Lastly, we apply a technique called sharpness aware minimization (SAM) that helps improve the generalizability of networks. Our results show significant improvements (p-value < 0.05) over the reference kidney segmentation U-Net. We show that the attention mechanisms and/or the cosine loss with SAM can achieve a dice score (DSC) of 0.918, a mean symmetric surface distance (MSSD) of 1.20 mm with the mean TKV difference of −1.72%, and R2 of 0.96 while using only 100 MRI datasets for training and testing. Furthermore, we tested four ensembles and obtained improvements over the best individual network, achieving a DSC and MSSD of 0.922 and 1.09 mm, respectively.

Predictors of linkage to hepatitis C virus care among people living with HIV with hepatitis C infection and the impact of loss to HIV follow-up.

Objective: Half of the people living with HIV (PLWH) with hepatitis C virus (HCV) remain untreated for HCV. We examined predictors of HCV linkage to care among PLWH and the impact of HIV lost to care. Design and methods: We conducted a retrospective review of PLWH/HCV from our HIV clinics between 2014 and 2017, and examined predictors of HCV linkage to care. We used the Kaplan-Meier method to estimate the probability of HIV retention and HCV linkage over time. Results: Of 615 PLWH/HCV, 34% linked to HCV care and 21% were cured. Higher odds of linkage to HCV care were among blacks (adjusted odds ratio [aOR]: 2.95, 95% confidence interval [CI]: 1.59, 5.47), prior injection drug users (IDUs; aOR: 2.89, 95% CI: 1.39, 6.01), Medicare (aOR: 3.09, 95% CI: 1.56, 6.11), and cirrhotics (aOR: 2.80, 95% CI: 1.52, 5.14). Reduced odds for linkage were in active IDU (aOR: 0.16, 95% CI: 0.05, 0.45) and those seen by an advanced practice provider (aOR: 0.53, 95% CI: 0.30, 0.92). The main reason for failure to link to HCV care was lost to HIV care. At 3 years, the overall probability of being retained in HIV care was 53%; among those who had an HCV evaluation visit, it was 75% vs. 41% with no HCV evaluation visit. Accounting for loss to follow-up, PLWH/HCV had a 65% probability of having an HCV evaluation at 3 years.