Advancing Transcription Factor Binding Site Prediction Using DNA Breathing Dynamics and Sequence Transformers via Cross Attention.

Understanding the impact of genomic variants on transcription factor binding and gene regulation remains a key area of research, with implications for unraveling the complex mechanisms underlying various functional effects. Our study delves into the role of DNA's biophysical properties, including thermodynamic stability, shape, and flexibility in transcription factor (TF) binding. We developed a multi-modal deep learning model integrating these properties with DNA sequence data. Trained on ChIP-Seq (chromatin immunoprecipitation sequencing) data in vivo involving 690 TF-DNA binding events in human genome, our model significantly improves prediction performance in over 660 binding events, with up to 9.6% increase in AUROC metric compared to the baseline model when using no DNA biophysical properties explicitly. Further, we expanded our analysis to in vitro high-throughput Systematic Evolution of Ligands by Exponential enrichment (SELEX) and Protein Binding Microarray (PBM) datasets, comparing our model with established frameworks. The inclusion of DNA breathing features consistently improved TF binding predictions across different cell lines in these datasets. Notably, for complex ChIP-Seq datasets, integrating DNABERT2 with a cross-attention mechanism provided greater predictive capabilities and insights into the mechanisms of disease-related non-coding variants found in genome-wide association studies. This work highlights the importance of DNA biophysical characteristics in TF binding and the effectiveness of multi-modal deep learning models in gene regulation studies.

Parathyroid carcinoma: Imaging features of initial presentation and recurrence. A single center experience.

BACKGROUND AND PURPOSE: Parathyroid carcinoma is the rarest endocrine neoplasm with very few published data discussing its imaging appearance with primary focus on ultrasound imaging features. We present our 23 years institutional experience to highlight multimodality imaging evaluation at presentation and at recurrence. MATERIAL AND METHODS: Retrospective chart review of clinical and pathological diagnosis of parathyroid carcinoma patients presented for initial or recurrent disease management at M.D. Anderson Cancer Center between the period of January 2000 and February 2023 was performed. Imaging findings on US, CT, PET/CT, and technetium-99m sestamibi were analyzed for initial and local recurrent parathyroid carcinoma. We further assess patterns of distant recurrence and its location. RESULTS: Twenty three patients with pathological and clinical diagnosis of initial (14 patients) or recurrent parathyroid carcinoma (14 patients) were included in this study. US findings of parathyroid carcinoma were larger lesions, increased/irregular vascularity, and non-circumscribed margins. Multiphasic CT findings of parathyroid carcinoma included an arterially enhancing lesion that is hypoenhancing relative to the thyroid and demonstrates no washout on delayed imaging. Highly suggestive findings for recurrent disease included a hypoechoic solid nodule (91.67%) with increased vascularity on ultrasound (81.8%) with corresponding enhancement on CT. CONCLUSION: Parathyroid carcinoma is a rare malignancy often diagnosed after surgical resection. We provided CT and US imaging features that are helpful in suggesting the diagnosis of parathyroid carcinoma and detection of early local recurrence.

Examining DNA breathing with pyDNA-EPBD.

MOTIVATION: The two strands of the DNA double helix locally and spontaneously separate and recombine in living cells due to the inherent thermal DNA motion. This dynamics results in transient openings in the double helix and is referred to as "DNA breathing" or "DNA bubbles." The propensity to form local transient openings is important in a wide range of biological processes, such as transcription, replication, and transcription factors binding. However, the modeling and computer simulation of these phenomena, have remained a challenge due to the complex interplay of numerous factors, such as, temperature, salt content, DNA sequence, hydrogen bonding, base stacking, and others. RESULTS: We present pyDNA-EPBD, a parallel software implementation of the Extended Peyrard-Bishop-Dauxois (EPBD) nonlinear DNA model that allows us to describe some features of DNA dynamics in detail. The pyDNA-EPBD generates genomic scale profiles of average base-pair openings, base flipping probability, DNA bubble probability, and calculations of the characteristically dynamic length indicating the number of base pairs statistically significantly affected by a single point mutation using the Markov Chain Monte Carlo algorithm. AVAILABILITY AND IMPLEMENTATION: pyDNA-EPBD is supported across most operating systems and is freely available at https://github.com/lanl/pyDNA_EPBD. Extensive documentation can be found at https://lanl.github.io/pyDNA_EPBD/.

Examining DNA Breathing with pyDNA-EPBD.

Motivation: The two strands of the DNA double helix locally and spontaneously separate and recombine in living cells due to the inherent thermal DNA motion.This dynamics results in transient openings in the double helix and is referred to as "DNA breathing" or "DNA bubbles." The propensity to form local transient openings is important in a wide range of biological processes, such as transcription, replication, and transcription factors binding. However, the modeling and computer simulation of these phenomena, have remained a challenge due to the complex interplay of numerous factors, such as, temperature, salt content, DNA sequence, hydrogen bonding, base stacking, and others. Results: We present pyDNA-EPBD, a parallel software implementation of the Extended Peyrard-Bishop- Dauxois (EPBD) nonlinear DNA model that allows us to describe some features of DNA dynamics in detail. The pyDNA-EPBD generates genomic scale profiles of average base-pair openings, base flipping probability, DNA bubble probability, and calculations of the characteristically dynamic length indicating the number of base pairs statistically significantly affected by a single point mutation using the Markov Chain Monte Carlo (MCMC) algorithm.

Isolation of Brucella inopinata from a White's tree frog (Litoria caerulea): pose exotic frogs a potential risk to human health?

Introduction: Cold-blooded hosts, particularly exotic frogs, have become a newly recognized reservoir for atypical Brucella species and strains worldwide, but their pathogenicity to humans remains largely unknown. Here we report the isolation and molecular characterization of a B. inopinata strain (FO700662) cultured from clinical samples taken from a captive diseased White's Tree Frog (Litoria caerulea) in Switzerland. The isolation of B. inopinata from a frog along with other reports of human infection by atypical Brucella raises the question of whether atypical Brucella could pose a risk to human health and deserves further attention. Methods: The investigations included histopathological analysis of the frog, bacterial culture and in-depth molecular characterization of strain FO700662 based on genome sequencing data. Results and Discussion: Originally identified as Ochrobactrum based on its rapid growth and biochemical profile, strain FO700622 was positive for the Brucella- specific markers bcsp31 and IS711. It showed the specific banding pattern of B. inopinata in conventional Bruce-ladder multiplex PCR and also had identical 16S rRNA and recA gene sequences as B. inopinata. Subsequent genome sequencing followed by core genome-based MLST (cgMLST) analysis using 2704 targets (74% of the total chromosome) revealed only 173 allelic differences compared to the type strain of B. inopinata BO1T, while previously considered the closest related strain BO2 differed in 2046 alleles. The overall average nucleotide identity (ANI) between the type strain BO1T and FO700622 was 99,89%, confirming that both strains were almost identical. In silico MLST-21 and MLVA-16 also identified strain FO700662 as B. inopinata. The nucleotide and amino acid-based phylogenetic reconstruction and comparative genome analysis again placed the isolate together with B. inopinata with 100% support. In conclusion, our data unequivocally classified strain FO700622, isolated from an exotic frog, as belonging to B. inopinata.

Increased risk of stress urinary incontinence surgery after hysterectomy for benign indication-a population-based cohort study.

BACKGROUND: Hysterectomy is a common procedure used to treat different gynecologic conditions. The association between hysterectomy for benign indication and stress urinary incontinence has previously been established. Stress urinary incontinence can be treated surgically, and options have improved after introduction of the midurethral sling procedure in 1998. OBJECTIVE: This study aimed to estimate the risk of stress urinary incontinence surgery after hysterectomy for benign indication. STUDY DESIGN: The study was carried out as a matched register-based cohort study including Danish women born from 1947 to 2000. Women who underwent hysterectomy for benign indication were matched to nonhysterectomized women in a 1:5 ratio on the basis of age and calendar year of hysterectomy. The risk of stress urinary incontinence surgery after hysterectomy was estimated. We adjusted for income, educational level, and parity. The risk of stress urinary incontinence surgery was further estimated in a subcohort excluding all vaginal hysterectomies. The joint effect of hysterectomy and parity was estimated in the main cohort, and the joint effect of hysterectomy and vaginal birth or cesarean delivery on stress urinary incontinence surgery was explored in a subgroup of women who only had 1 mode of delivery. All analyses were made using the Cox proportional hazards model. RESULTS: We included 83,370 women who underwent hysterectomy and 413,969 reference women. The overall risk of stress urinary incontinence surgery was more than doubled for women who underwent hysterectomy (adjusted hazard ratio, 2.6; 95% confidence interval, 2.4-2.8). The adjusted hazard ratio decreased slightly to 2.4 (95% confidence interval, 2.3-2.6) when excluding all vaginal hysterectomies. We found a trend of increasing risk of stress urinary incontinence surgery with increased parity among both women who underwent hysterectomy and the reference group. In the subgroup of women who only had 1 mode of delivery, we found the risk of stress urinary incontinence surgery to be particularly increased for women with a history of ≥1 vaginal births. The hazard ratio was 15.1 (95% confidence interval, 10.3-22.1) for women with a history of 1 vaginal birth who underwent hysterectomy, whereas the hazard ratio for women in the reference group with 1 vaginal birth was 5.1 (95% confidence interval, 3.8-8.1). Overall, women who underwent hysterectomy had a 3 times higher risk of stress urinary incontinence surgery than the reference group, irrespective of the number of vaginal births. CONCLUSION: This study indicates, in accordance with previous studies, that hysterectomy increases the risk of subsequent stress urinary incontinence surgery. Women should be informed and gynecologists include this knowledge in decision-making. Further precautions should be taken when treating parous women, particularly those with a history of ≥1 vaginal births.

[Nutrition and adipose tissue distribution in low cardiovascular risk individuals, depending on the central obesity].

The low cardiovascular risk group according to SCORE in relation to the clinical and laboratory characteristics of patients is very heterogeneous, which leads to the presence of a residual risk of cardiovascular events. This category may include individuals with a family history of cardiovascular disease at a young age, with abdominal obesity (AO), endothelial dysfunction, and high levels of triglyceride-rich lipoproteins. In this regard, an active search is underway for new metabolic markers within the low cardiovascular risk group. The purpose of the study was to compare the nutrition, the adipose tissue distribution in low cardiovascular risk individuals, depending on the AO. Material and methods. The study included 86 healthy low risk (SCORE<1%) patients (mean age 42.6±2 years), who were divided into 2 groups: with AO [waist circumference (WC) >=94 cm in men and >=80 cm in women] - 44 patients (32% of men) and without AO - 42 patients (38% of men). The body composition was carried out using the bioimpedance analyzer. The distribution of ectopic fat deposits in the liver, pancreas and epicardial region was studied using ultrasound methods. A frequency questionnaire (Diet Risk Score) was used to assess nutrition. Results. In low risk patients with AO, signs of unhealthy diet are statistically significantly more common (in 52 in the main group vs 2% in the control group, p<0.01), ectopic deposition of adipose tissue in the liver (53 vs 9%, p<0.001), pancreas (56% in the main group, absent in the control group, p<0.001), epicardia l region (the epicardial fat thickness median is 4.24 mm in the main group vs 2.15 mm in the control group) compared with a control group. Conclusion. The low cardiovascular risk group is very heterogeneous. One of the markers of heterogeneity is central obesity - a marker of unhealthy diet, subclinical ectopic fat deposition and hypertriglyceridemia. Patients with AO of the low cardiovascular risk group require a more thorough examination with the obligatory determination of waist circumference, ultrasound assessment of the liver and pancreas parenchyma, and determination of the epicardial fat thickness. Using a short nutrition questionnaire allows you to quickly identify signs of unhealthy diet and discuss them with the patient.

Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAFV600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study.

Background: The aim of this study was to describe the oncologic outcomes of patients with BRAFV600E-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy. Methods: This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAFV600E-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Results: All patients had stage IVB (35%) or IVC (65%) ATC. Approximately 70% of patients treated with BRAF-directed therapy ultimately had surgical resection of residual disease. Patients who had neoadjuvant BRAF-directed therapy followed by surgery (n = 32) had 12-month OS of 93.6% [confidence interval (CI) 84.9-100] and PFS of 84.4% [CI 71.8-96.7]. Patients who had surgery before BRAF-directed therapy (n = 12) had 12-month OS of 74.1% [CI 48.7-99.5] and PFS of 50% [CI 21.7-78.3]. Finally, patients who did not receive surgery after BRAF-directed therapy (n = 13) had 12-month OS of 38.5% [CI 12.1-64.9] and PFS of 15.4% [CI 0-35.0]. Neoadjuvant BRAF-directed therapy reduced tumor size, extent of surgery, and surgical morbidity score. Subgroup analysis suggested that any residual ATC in the surgical specimen was associated with significantly worse 12-month OS and PFS (OS = 83.3% [CI 62.6-100], PFS = 61.5% [CI 35.1-88]) compared with patients with pathologic ATC complete response (OS = 100%, PFS = 100%). Conclusions: We observed that neoadjuvant BRAF-directed therapy reduced extent of surgery and surgical morbidity. While acknowledging potential selection bias, the 12-month OS rate appeared higher in patients who had BRAF-directed therapy followed by surgery as compared with BRAF-directed therapy without surgery; yet, it was not significantly different from surgery followed by BRAF-directed therapy. PFS appeared higher in patients treated with neoadjuvant BRAF-directed therapy relative to patients in the other groups. These promising results of neoadjuvant BRAF-directed therapy followed by surgery for BRAF-mutated ATC should be confirmed in prospective clinical trials.

Cervical cancer after the Manchester procedure: a nationwide cohort study.

INTRODUCTION AND HYPOTHESIS: The Manchester procedure is a successful operation to treat uterine prolapse. However, the influence on cervical cancer remains unknown. We hypothesized a lower risk of cervical cancer after the Manchester procedure. METHODS: We included all Danish women undergoing the Manchester procedure during 1977-2018 (N = 23,935). Women undergoing anterior colporrhaphy (N = 51,008) were included as references due to comparable health-seeking behaviors. The study cohort is as previously described. We assessed the risk of cervical cancer mortality after the Manchester procedure versus anterior colporrhaphy using cumulated incidence plots and Cox hazard regressions. We applied Fisher's exact test to compare the distribution of histological subtypes after the operations. RESULTS: Generally, few women were diagnosed with cervical cancer (0.1% after Manchester procedure and 0.2% after anterior colporrhaphy). After the Manchester procedure, the risk of cervical cancer was reduced (HR 0.60 [95% CI 0.39-0.94]). Furthermore, we found a slightly reduced risk of overall death (HR 0.96 [95% 0.94-0.99]), but no association regarding death due to cervical cancer (HR 0.66 [95% 0.34-1.25]). The distribution of histological subtypes was not changed. CONCLUSIONS: Women undergoing the Manchester procedure are at lower risk of being diagnosed with cervical cancer, while the risk of cancer specific mortality is unchanged compared to women undergoing anterior colporrhaphy. Based on this study, we cannot recommend that women exit ordinary screening programs for human papillomavirus/cervical dysplasia after a Manchester procedure.

Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. PATIENTS AND METHODS: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. RESULTS: Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size = -0.33; all P≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P≤.05). CONCLUSIONS: A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.

Stress Urinary Incontinence After Operations for Uterine Prolapse: A Nationwide Cohort Study.

IMPORTANCE: Concomitant surgery for stress urinary incontinence (SUI) during pelvic organ prolapse (POP) operations are debated. OBJECTIVES: We aimed to assess the risk of an SUI operation after a uterine prolapse operation and compare the risk after the Manchester procedure versus vaginal hysterectomy. STUDY DESIGN: We performed a nationwide historical cohort study including women with no history of hysterectomy undergoing the Manchester procedure (n = 6065) or vaginal hysterectomy (n = 9,767) for POP during 1998 to 2018. We excluded women with previous surgery for SUI and POP, concomitant surgery for SUI (n = 34, 0.2%), and diagnosed with gynecological cancer before or within 90 days from surgery. Women were followed up until SUI operation/death/emigration/diagnosis of gynecological cancer/December 31, 2018, whichever came first. Women undergoing the Manchester procedure were censored if they had undergone hysterectomy.We assessed the rate of SUI surgery with cumulative incidence plots. We performed Cox Regression to analyze the risk of SUI surgery, adjusting for age, calendar year, income level, concomitant surgery in anterior and posterior compartments, and diagnosis of SUI before POP operation. RESULTS: We found that 12.4% women with and 1.6% without SUI diagnosed before the POP surgery who underwent SUI surgery within 10 years.During follow-up (median, 8.5 years), 129 (2.1%) underwent SUI surgery after the Manchester procedure and 175 (1.8%) after vaginal hysterectomy (adjusted hazard ratio, 1.06 [0.84-1.35]). CONCLUSIONS: Of women diagnosed with SUI before POP operation 1 in 8 subsequently underwent SUI surgery. Few women not diagnosed with SUI subsequently underwent SUI surgery. There was no difference in risk of SUI after the Manchester procedure and vaginal hysterectomy.

The Learning Curve of an Absorbable Subcuticular Stapling Device in Plastic and Reconstructive Surgery.

Background: Learning curves can reflect a surgical trainee's rate of progress and competence in acquiring new skills. The INSORB subdermal staple device has been well established to facilitate decreased closure time across various surgical procedures, with similar cosmesis, healing, and consistency as those of standard subdermal sutures. This study is unique, as it demonstrated an observable learning curve with this device when used by a junior surgeon. Methods: Sixty-six patients underwent a cosmetic procedure during the second half of 2019 under the care of a single plastic surgeon in Melbourne, Australia. This corresponded to 254 unique linear incisions. Subdermal closure was done either with interrupted 3-0 Monocryl sutures or with the INSORB device. The consultant closed the incisions on one side, with the contralateral incision closed by the assistant using the same closure method. Data were then compared retrospectively, and closure times were compared over the ensuing 6 months. Results: Overall, consultant closure speed is 25% faster than assistant speed. When using 3-0 Monocryl, the difference is 33%, whereas the difference is reduced to 21% when using the INSORB. Furthermore, a mild learning curve could be appreciated with the assistant's use of the INSORB over the comparatively short 6-month study period. Conclusions: In addition to improved speed, cost, outcome, and ergonomics, subdermal absorbable staples may also garner a faster learning curve than standard closure with 3-0 Monocryl. This study supported the learning curve of a surgical device as another innovative benefit and an important aspect of developing surgical technology.

Bacteremia With Anaerobic Bacteria and Association With Colorectal Cancer: A Population-based Cohort Study.

BACKGROUND: There is a well-described association between bacteremia with bovis group streptococci or Clostridium septicum and an increased probability of a colorectal cancer (CRC) diagnosis. We wanted to investigate the existence of a similar association between CRC and bacteremia with other bacteria belonging to the gut microbiota.. METHODS: A population based cohort study in a population about 2 million people including 45 774 bacteremia episodes and 231 387 blood culture negative cases was performed in the Region of Southern Denmark and Region Zealand from 2007-2016. Episodes of bacteremia were combined with the Danish central register for CRC. We performed Cox's regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The study results confirmed previous findings of an increased risk of a CRC diagnosis after bacteremia with the bovis group streptococci (risk within a year: 4.3%; HR [95% CI]: 8.46 [3.51-20.4]) or C. septicum (20.8%; 76.2 [42.0-138]). Furthermore, Bacteroides ovatus (6.7%; 20.3 [5.04-81.8]), Bacteroides uniformis (5.4%; 16.2 [4.02-65.7]), Clostridium tertium (3.6 %; 13.9 [1.96-99.4]), Fusobacterium spp. (excluding F. necrophorum) (3.0 %; 8.51 [2.73-26.5]), and Gram-positive anaerobic cocci (3.6 %; 10.9 [4.50-26.3]) were also associated with an increased risk of a CRC diagnosis compared to patients with negative blood cultures (0.4%). CONCLUSIONS: Bacteremia with specific gut microbiota anaerobic bacteria is associated with a high risk of a diagnosis of CRC, indicating the need for colorectal workup. Importantly, this strategy also holds the possible additional benefit of detecting adenomas or other premalignant conditions, which were not included in the present study.

Endometrial cancer after the Manchester procedure: a nationwide cohort study.

INTRODUCTION AND HYPOTHESIS: We aimed to investigate whether the Manchester procedure affects the risk and prognosis of endometrial cancer. METHODS: All Danish residents have a personal number permitting linkage of nationwide registers on the individual level enabling epidemiological studies with lifelong follow-up. We performed a nationwide historical cohort study including Danish women born before 2000 undergoing the Manchester procedure (N = 23,935) during 1977-2018. We included women undergoing anterior colporrhaphy as a reference group (N = 51,008) because of comparable inclination to consult a doctor and clinical similarities. Main outcomes were the number of women diagnosed with endometrial cancer, the stage of endometrial cancer at time of diagnosis, and cancer-specific and overall mortality. We followed the cohort until endometrial cancer/death/emigration/hysterectomy/31 December 2018. We performed chi-square test for trend to compare the diagnostic stage and Cox regressions to analyze the risk of endometrial cancer and mortality. The models were adjusted for age, calendar year, income level, and parity. RESULTS: During follow-up (median 13 years), 271 (1.13%) women were diagnosed with endometrial cancer after the Manchester procedure and 520 (1.05%) after anterior colporrhaphy. The adjusted hazard ratio (HR) for endometrial cancer was 1.00 [95% confidence interval (CI) 0.86-1.16]. No difference in stage of cancer was found (p = 0.18) nor when stratifying for calendar year. The HR for cancer-specific mortality and overall mortality after the Manchester procedure was 0.87 (95% CI 0.65-1.16) and 0.93 (95% CI 0.77-1.12), respectively. CONCLUSIONS: The Manchester procedure does not affect the risk or prognosis of endometrial cancer.

Pelvic organ prolapse following hysterectomy on benign indication: a nationwide, nulliparous cohort study.

BACKGROUND: Hysterectomy is commonly performed and may increase the risk of pelvic organ prolapse. Previous studies in parous women have shown an increased risk of pelvic organ prolapse surgery after hysterectomy. Parity is a strong risk factor for pelvic organ prolapse and may confuse the true relation between hysterectomy and pelvic organ prolapse. OBJECTIVE: This study aimed to investigate whether hysterectomy performed for benign conditions other than pelvic organ prolapse leads to an increased risk of pelvic organ prolapse surgery in a cohort of nulliparous women. STUDY DESIGN: We conducted a historical matched cohort study based on a nationwide population of nulliparous women born in 1947 to 2000 and living in Denmark during 1977 to 2018 (N=549,197). The data were obtained from the Danish Civil Registration System, the Danish National Patient Registry, the Fertility Register, and Statistics Denmark. Women who had a hysterectomy performed in 1977 to 2018 were included in the study (n=9535). For each of these women we randomly retrieved five nonhysterectomized women matched on age and calendar year to constitute the reference group (n=47,370). Cox proportional hazard regression analyses were performed to compare the risk of pelvic organ prolapse surgery in the 2 groups of women. RESULTS: The study included 56,905 women whom we observed for up to 42 years, entailing 809,435 person-years in risk. Overall, 9535 women who underwent a hysterectomy were matched individually with 47,370 reference women. Subsequently, a total of 29 women (30.4%) who underwent a hysterectomy and 85 reference women (17.9%) had a pelvic organ prolapse surgery performed, corresponding to incidence rates of 20.5 and 12.7 per 100,000 risk years, respectively. In addition, the risk of pelvic organ prolapse surgery increased by 60% in women who underwent a hysterectomy compared with women in the reference group (crude hazard ratio, 1.6; 95% confidence interval, 1.0-2.5; P=.04; adjusted hazard ratio, 1.6; 95% confidence interval, 1.0-2.5; P=.04). After the exclusion of women who underwent vaginal hysterectomy and their matches, the results were significantly the same (crude hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P=.05). Furthermore, we found higher rates of pelvic organ prolapse surgery in women who had a subtotal hysterectomy, total hysterectomy, or vaginal and laparoscopic-assisted vaginal hysterectomies than in women in the reference group. CONCLUSION: Hysterectomy increased the risk of pelvic organ prolapse surgery for nulliparous women by 60%. Previous studies of multiparous women have similarly shown an increased risk of prolapse after hysterectomy. As the most common risk factor for pelvic organ prolapse-vaginal birth-was not included and women were >72 years of age in this study, the numbers of pelvic organ prolapse surgeries were low. Despite the low absolute risk of pelvic organ prolapse surgery in nulliparous women, they were important in investigating the association between hysterectomy and pelvic organ prolapse, excluding vaginal birth, which is the most common risk factor for pelvic organ prolapse. As this cohort study of nulliparous women found an increased risk of pelvic organ prolapse surgery after hysterectomy, it is implied that the uterus per se protects against pelvic organ prolapse. As such, gynecologists should be aware of the risks associated with hysterectomy, and alternative uterus-sparing treatments should be considered when possible. Furthermore, women should be informed about the risks before being offered a hysterectomy.

Parameters of cutaneous microvasculature in men of working age with newly diagnosed arterial hypertension.

OBJECTIVE: To investigate structural and functional features of cutaneous microvasculature in men of working age with newly diagnosed arterial hypertension (AH). MATERIALS AND METHODS: The study included 161 apparently healthy men from 30 to 60 years, who underwent a comprehensive examination of cardiovascular system "from the heart to the capillaries". Control group (CG) included 60 normotensive men. AH group included 101 men with elevated BP. RESULTS: There is no rarefaction of the capillary bed and latent fluid retention in the interstitial space in the skin in men with AH. No data were obtained for increased endothelial, neurogenic and myogenic tone of resistive cutaneous precapillary arterioles in AH group, but a decrease in the perfusion efficiency of the endothelial and myogenic mechanisms of tissue perfusion modulation was noted. CONCLUSION: Obtained results allow making the assumption that metabolic disorders at the level of capillaries that are of a systemic nature prevail in men with the onset of AH.

Jaboticaba (Myrciaria jaboticaba) powder consumption improves the metabolic profile and regulates gut microbiome composition in high-fat diet-fed mice.

The consumption of a high-fat diet can cause metabolic syndrome and induces host gut microbial dysbiosis and non-alcoholic fatty liver disease (NAFLD). We evaluated the effect of polyphenol-rich jaboticaba peel and seed powder (JPSP) on the gut microbial community composition and liver health in a mouse model of NAFLD. Three-month-old C57BL/6 J male mice, received either a control (C, 10% of lipids as energy, n = 16) or high-fat (HF, 50% of lipids as energy, n = 64) diet for nine weeks. The HF mice were randomly subdivided into four groups (n = 16 in each group), three of which (HF-J5, HF-J10, and HF-J15) were supplemented with dietary JPSP for four weeks (5%, 10%, and 15%, respectively). In addition to attenuating weight gain, JPSP consumption improved dyslipidemia and insulin resistance. In a dose-dependent manner, JPSP consumption ameliorated the expression of hepatic lipogenesis genes (AMPK, SREBP-1, HGMCoA, and ABCG8). The effects on the microbial community structure were determined in all JPSP-supplemented groups; however, the HF-J10 and HF-J15 diets led to a drastic depletion in the species of numerous bacterial families (Bifidobacteriaceae, Mogibacteriaceae, Christensenellaceae, Clostridiaceae, Dehalobacteriaceae, Peptococcaceae, Peptostreptococcaceae, and Ruminococcaceae) compared to the HF diet, some of which represented a reversal of increases associated with HF. The Lachnospiraceae and Enterobacteriaceae families and the Parabacteroides, Sutterella, Allobaculum, and Akkermansia genera were enriched more in the HF-J10 and HF-J15 groups than in the HF group. In conclusion, JPSP consumption improved obesity-related metabolic profiles and had a strong impact on the microbial community structure, thereby reversing NAFLD and decreasing its severity.

Imaging of the Thyroid: Practical Approach.

Imaging evaluation of the thyroid gland spans a plethora of modalities, including ultrasound imaging, cross-sectional studies, and nuclear medicine techniques. The overlapping of clinical and imaging findings of benign and malignant thyroid disease can make interpretation a complex undertaking. We aim to review and simplify the vast current literature and provide a practical approach to the imaging of thyroid disease for application in daily practice. Our approach highlights the keys to differentiating and diagnosing common benign and malignant disease affecting the thyroid gland.