Ultrasound imaging of core muscles activity in multiparous women with vaginal laxity: a cross-sectional study.

Vaginal laxity (VL) is a common condition among multiparous women, especially those who have delivered vaginally. Since pelvic floor muscles (PFMs) work synergistically with other core muscles, physical therapy protocols that aim to treat VL should train the PFMs in combination with other core muscles. To investigate the activity of core muscles in multiparous women with and without VL, and its relation to sexual function. An observational, cross-sectional study. The study included 100 multiparous women, who were divided into two groups according to their scores on the vaginal laxity questionnaire (VLQ). Women who scored between 1 and 3 on the VLQ were categorized as having VL (n = 48), while those who scored between 5 and 7 were placed in the control group (n = 52). The primary outcomes were PFM displacement, diaphragmatic excursion, transversus abdominis activation ratio, and lumbar multifidus thickness measured by ultrasound imaging. The secondary outcome was sexual functioning, evaluated using the Arabic female sexual function index (ArFSFI). The VL group had significantly lower PFM displacement (mean difference (MD) - 0.42; 95% confidence interval (CI) - 0.49 to - 0.33; p = 0.001), diaphragmatic excursion (MD - 2.75; 95% CI - 2.95 to - 2.55; p = 0.001), lumbar multifidus thickness (MD - 10.08; 95% CI - 14.32 to - 5.82; p = 0.02), and ArFSFI scores (MD - 9.2; 95% CI - 10.59 to - 7.81; p = 0.001) in comparison to the control group (p < 0.05). Nevertheless, the transversus abdominis activation ratio demonstrated no significant difference between the two groups (MD 0.06; 95% CI - 0.05 to 0.17; p = 0.33). Multiparous women with VL had significantly lower PFM displacement, diaphragmatic excursion, lumbar multifidus thickness, and sexual function index scores than women in the control group. The only exception was transversus abdominis activation, which did not differ significantly between the VL and control groups.

Internal Hernia as a Rare Complication of Acute Appendicitis.

Appendicitis is a well-known and highly common surgical emergency disease, yet it presents with a wide variety of manifestations. This is a case report of a 47-year-old female who presented with a complaint of having constant crampy right lower abdominal pain for two weeks. The patient reported having a sudden onset of symptoms that went with the typical picture of acute appendicitis that occurred two weeks ago. Our pre-op workup was inconclusive; therefore, we planned to go for a diagnostic laparoscopy, where surprisingly, the appendix was long, inflamed, and attached to the posterior wall of the cecum. Thus, a ring-like structure was developed, in which 8 to 10 cm of the terminal ileum (the last part of the small bowel) was going through and causing an internal hernia. Although blood and radiology workups provide valuable assistance in diagnosing common cases, a highly suspicious sense and skillful surgeons with good clinical experience play a major role in managing such rare presentations.

Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette-Guérin Immunotherapy of Bladder Cancer.

The clinical management of bladder cancer continues to present significant challenges. Bacillus Calmette-Guérin (BCG) immunotherapy remains the gold standard of treatment for non-muscle invasive bladder cancer (NMIBC), but many patients develop recurrence and progression to muscle-invasive disease (MIBC), which is resistant to BCG. This review focuses on the immune mechanisms mobilized by BCG in bladder cancer tumor microenvironments (TME), mechanisms of BCG resistance, the dual role of the BCG-triggered NFkB/TNFα/PGE2 axis in the regulation of anti-tumor and tumor-promoting aspects of inflammation, and emerging strategies to modulate their balance. A better understanding of BCG resistance will help develop new treatments and predictive biomarkers, paving the way for improved clinical outcomes in bladder cancer patients.

Differentiation and characterization of healthy versus pathological tau using chemical exchange saturation transfer.

Neurofibrillary tangles of tau constitute one of the key biological hallmarks of Alzheimer's disease. Currently, the assessment of regional tau accumulation requires intravenous administration of radioactive tracers for PET imaging. A noninvasive MRI-based solution would have significant clinical implications. Herein, we utilized an MRI technique known as chemical exchange saturation transfer (CEST) to determine the imaging signature of tau in both its monomeric and pathologic fibrillated conformations. Three sets of purified recombinant full-length (4R) tau protein were prepared for collection of CEST spectra using a 9.4 T NMR spectrometer at varying temperatures (25, 37, and 42 °C) and RF intensities (0.7, 1.0, 1.5, and 2.2 µT). Monomeric and fibrillated tau were readily distinguished based on their Z-spectrum profiles. Fibrillated tau demonstrated a less prominent peak at 3.5 ppm with additional peaks near 0.5 and 1.5 ppm. No significant differences were identified between fibrillated tau prepared using heparin versus seed-competent tau. In conclusion, monomeric and fibrillated tau can be readily detected and distinguished based on their CEST-derived Z-spectra, pointing to the potential utility of CEST-MRI as a noninvasive biomarker of regional pathologic tau accumulation in the brain. Further testing and validation in vitro and in vivo will be necessary before this can be applied clinically.

Novel 2-Aminobenzothiazole Derivatives: Docking, Synthesis, and Biological Evaluation as Anticancer Agents.

Sixteen novel 2-aminobenzothiazole compounds with different amines or substituted piperazine moieties were designed, synthesized, and tested using various methods. Potential interactions were assessed by docking new compounds in the adenosine triphosphate (ATP) binding domain of the PI3Kγ enzyme (PDB code: 7JWE) by nucleophilic substitution or solvent-free/neat fusion for docked compound synthesis. Final 2-aminobenzothiazole compounds were characterized by direct probe gas chromatography-mass spectrometry (GC-MS), proton (1H-NMR), carbon-13 (13C-NMR), and attenuated total reflectance-infrared Fourier transform infrared (ATR FT-IR). The synthesized compounds were investigated for anticancer activities on lung cancer (A549) and breast cancer (MCF-7) cell lines. The compounds' PI3Kγ inhibition was evaluated at a 100 µM concentration. 4-Nitroaniline and piperazine-4-nitroaniline combination in OMS5 and OMS14 reduced lung and breast cancer cell line growth. IC50 values for OMS5 and OMS14, the strongest compounds, ranged from 22.13 to 61.03 µM. OMS1 and OMS2 inhibited PI3Kγ at the highest rates (47 and 48%, respectively) at a 100 µM concentration. Results show that the PI3Kγ enzyme suppression is not the main mechanism behind these OMS5 and OMS14 anticancer effects. CDK2, Akt, mTOR, and p42/44 MAPK are affected. EGF receptor suppression matters. AKT1, AKT3, CDK1/cyclin B, PDK1 direct, PIK3CA E542 K/PIK3R1 (p110 α/p85 α), PIK3CD/PIK3R1 (p110 δ/p85 α), and PKN inhibition were measured to evaluate the possible mechanism of compound OMS14. PIK3CD/PIK3R1 (p110 δ/p85 α) is the most, with 65% inhibition, suggesting a possible mechanism of anticancer properties. Furthermore, the NCI 60-cell line inhibition demonstrates promising broad anticancer inhibition against numerous cancer cell lines of OMS5 and OMS14, which could be good lead compounds for future development.

The genetic landscape of autism spectrum disorder in the Middle Eastern population.

Introduction: Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk. Methods: We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify de novo or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents). Results: Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel de novo variants in new candidate genes for ASD (DTX4, ARMC6, and B3GNT3). Also, we have identified 15 de novo variants in genes that were previously implicated in ASD or related neurodevelopmental disorders (PHF21A, WASF1, TCF20, DEAF1, MED13, CREBBP, KDM6B, SMURF1, ADNP, CACNA1G, MYT1L, KIF13B, GRIA2, CHM, and KCNK9). Additionally, we defined eight novel recessive variants (RYR2, DNAH3, TSPYL2, UPF3B KDM5C, LYST, and WNK3), four of which were X-linked. Conclusion: Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population.

Energy drink consumption among medical students in Jordan - prevalence, attitudes, and associated factors: a cross-sectional study.

Background: Energy drinks (ED) are popular beverages that contain high levels of caffeine, sugar, and other supplements, such as vitamins, which are marketed to enhance mental alertness and physical performance. Studies have shown that energy drink consumption is prevalent among medical students. Therefore, this study aimed to assess the prevalence, attitudes, and factors associated with energy drink consumption among medical students in Jordan. Materials and methods: A cross-sectional study was conducted among medical students from six public universities in Jordan. A total of 307 students were included in the study, and data were collected using an expert-validated questionnaire. The collected data were analyzed using SPSS version 25. Results: The study found that 50% of the sample had consumed ED, half of them started consuming them at the age of 16-18, and learned about them from friends. The primary reasons for consuming ED were to stay awake at night and the majority of them increase their consumption during exams to increase alertness. Regular energy drink consumption was significantly associated with being a student at the university located in the south governorate of Jordan (P=0.021), living alone (P=0.000), drinking alcohol (P=0.049), drinking coffee daily (P=0.043), and consuming more than 10 cans of soft drinks weekly (P=0.001). However, sex, age, academic achievement, and smoking status had no significant association with regular energy drink consumption. Students with regular energy drink consumption experienced daytime sleepiness, decreased concentration, fatigue, and reduced performance more than students with no regular energy drink consumption. Conclusion: The prevalence of energy drink consumption among medical students in Jordan is high, with factors such as social influences, lifestyle behaviors, and academic pressure being significant contributors. This study highlights the need for interventions to promote healthy behaviors and raise awareness about the potential harms of ED among medical students.

15-Year Analysis of Surgical Approaches and Outcomes for Coarctation in 132 Neonates and Infants.

A variety of surgical approaches exist to treat aortic coarctation in neonates and infants. Our institutional approach is designed to match the surgical approach to the individual anatomy of the patient. The objective of this study is to evaluate operative characteristics and outcomes of all neonates and infants who underwent surgical repair of coarctation of the aorta or hypoplastic aortic arch at University of Florida from 2006 to 2021, inclusive, either in isolation or with concomitant repair of atrial septal defect (ASD) and/or ventricular septal defect (VSD). A retrospective review was performed of 132 patients aged 0-1 year who underwent surgical repair of aortic coarctation or hypoplastic aortic arch between 2006 and 2021, inclusive, either in isolation or with concomitant repair of ASD and/or VSD. Patients were divided into two groups based on the surgical approach: Group 1 = Median Sternotomy and Group 2 = Left Lateral Thoracotomy. Continuous variables are presented as median (minimum-maximum); categorical variables are presented as N (%). The most common operative technique in Group 1 was end-to-side reconstruction with ligation of the aortic isthmus. The most common operative technique in Group 2 was extended end-to-end repair. Operative Mortality was one patient (1/132 = 0.76%). Transcatheter intervention for recurrent coarctation was performed in seven patients (7/132 = 5.3%). Surgical re-intervention for recurrent coarctation was performed in three patients (3/132 = 2.3%). From these data, one can conclude that a strategy of matching the surgical approach to the anatomy of neonates and infants who underwent surgical repair of aortic coarctation or hypoplastic aortic arch, either in isolation or with concomitant repair of ASD and/or VSD, is associated with less than 1% Operative Mortality and less than 3% recurrent coarctation requiring reoperation.

Outcomes of mechanical thrombectomy in patients with acute ischemic stroke and thrombocytopenia: systematic review and meta-analysis.

BACKGROUND: Mechanical Thrombectomy (MT) has improved outcomes in acute ischemic stroke (AIS) due to Large Vessel Obstruction (LVO). However, there is limited data on the safety and outcomes of MT in AIS patients with thrombocytopenia. This study aims to assess the efficacy and safety of MT in this population. METHODS: Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus. Studies meeting inclusion criteria underwent rigorous risk of bias assessment using the ROBINS-I tool. We compared outcomes between patients with and without thrombocytopenia undergoing MT. Using the R software version 4.3.1, meta-analyses were conducted employing random-effect models. RESULTS: This meta-analysis encompassed data from 5 studies. Thrombocytopenic AIS patients who underwent MT (n = 974) exhibited lower rates of functional independence (OR 0.83, 95% CI 0.71-0.98; p = 0.030) compared to patients with normal platelet counts (n = 2036). In addition, the thrombocytopenic group experienced higher mortality as compared to the group with normal platelet counts (OR 1.76, 95% CI 1.26-2.45; p < 0.001). Rates of sICH were found to be similar between groups (OR 1.20, 95% CI 0.74-1.93; p = 0.456), as were rates of successful recanalization (OR 0.94, 95% CI 0.47-1.87; p = 0.863). Lastly, no significant differences were observed in procedure times between thrombocytopenic and non-thrombocytopenic groups. CONCLUSION: As compared to patients without thrombocytopenia, thrombocytopenic AIS patients undergoing MT displayed lower functional independence and higher mortality rates, with no significant differences in sICH or successful recanalization.

Effect of Extracorporeal shock wave on upper trapezius trigger points in patients with cervicogenic headache: A Randomized Clinical Trial.

OBJECTIVE: A recent study was designed to ascertain the impact of extracorporeal shock wave therapy (ESWT) on upper trapezius trigger points in cervicogenic headaches patients. DESIGN: A double-blinded randomized controlled trial study, in which 50 participants (11 male and 39 female) aged between 20-40 with cervicogenic headache were subdivided with randomization to group (A), which received traditional physical therapy and sham shock wave therapy, and group (B), which received traditional physical therapy and actual shock wave therapy. All assessments were performed by a therapist before and after the treatment program (four weeks). RESULTS: Significant improvement of headache disability index, visual analogue scale scores, and upper trapezius electromyographic characteristics with p-value <.05 in both groups, in favor of the shock wave group. CONCLUSION: Extracorporeal shock wave therapy (ESWT) could be used for clinical and research concerns because it's positive effects on pain suppression, reduction of headache intensity, and restoration of muscle regular activity in cervicogenic headache patients.

Recurrent Localized Tenosynovial Giant Cell Tumor of the Left Ring Finger: A Case Report and Literature Review.

Here, we report the case of recurrent swelling and pain in the proximal interphalangeal joint of the left ring finger, which was later diagnosed as a localized tenosynovial giant cell tumor in a young adult female. The first presentation was at the same anatomical site four years prior. Examination at presentation showed a firm skin-colored nodule in the volar aspect of the left ring finger. The swelling was seen to be partly attached to underlying structures and was non-tender. After a careful physical examination and plain radiograph imaging of the hand, the two differential diagnoses considered were tenosynovial giant cell tumor and ganglion cyst. A surgical excision was performed, and histopathologic evaluation showed features consistent with a tenosynovial giant cell tumor, localized type. The resection margins were clear of tumor. The patient had no intraoperative or postoperative complications. Postoperative physiotherapy was recommended. No recurrence was seen after postoperative surgical follow-up for one year. This report highlights the importance of histopathologic evaluation and confirmation of clear surgical margins in the management of tenosynovial giant cell tumors. In recurrent cases, surgical re-excision with clear margins provides good clinical outcomes. Before surgical excision, patients should be informed about the biologic nature of the lesion and the high risk of recurrence. The management modalities to prevent recurrence and the need for long-term follow-up should also be discussed with the patient.

Simple and inexpensive microwave setup for industrial based applications: Quantification of flower honey adulteration as a case study.

A simple and inexpensive microwave measurement setup based on measurements of magnitudes of transmission properties ( | S 21 | dB ) is proposed for industrial-based microwave aquametry (moisture or water content) applications. An easy-to-apply calibration procedure based on normalization is implemented to eliminate systematic errors in the measurement system. As a case study, we applied this setup for the quantification of water-adulteration in flower honey. After validating this system by distilled water and pure flower honey measurements, | S 21 | dB measurements of the pure flower honey with various adulteration percentages ( δ ) up to 9% are conducted to examine the performance of the measurement setup for quantification of water adulteration. A multi-dimensional fitting procedure is implemented to predict δ using the proposed inexpensive microwave measurement setup. It is shown that it is possible to quantify an adulteration level with an accuracy better than ∓ 1 % by the proposed measurement setup and the applied multi-dimensional fitting procedure.

Examining the interplay between cardiovascular disease and cancer incidence: Data from NHANES III and continuous.

Introduction: This study aimed to investigate the relationship between risk factors of cancer among individuals with existing cardiovascular disease (CVD). Methods: The analysis included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors. Results: Females in NHANES-III had lower cancer risk (aHR 0.39, P = 0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P < 0.001) and current smoking (aHR 2.55, P = 0.001) also showed a significant association with developing cancer. No other factors investigated showed significant associations. Discussion: This study highlights the interplay between traditional risk factors and the elevated risk of cancer in CVD patients. Further research with larger samples and wider age ranges is needed to solidify these findings and inform intervention strategies.

A demonstration of incorporating discriminative stimuli into an AAC device during functional communication training.

Functional communication training (FCT) is an effective intervention for teaching communication responses and reducing challenging behavior. One limitation of FCT is that frequent reinforcement may be impractical or impossible in many situations. Recently, Mitteer et al. published a tutorial in the journal AAC that provided video models on how to implement an empirically supported strategy for thinning reinforcement during FCT, known as FCT with discriminative stimuli, when teaching with an augmentative and alternative communication (AAC) device. However, no study has empirically evaluated the approach described in that tutorial. This paper details a case study using several single-case experimental designs to teach a non-vocal autistic adult who did not use speech to communicate requests only when reinforcement was signaled to be available by the color of the AAC icons. We demonstrated the efficacy of this approach with unique pairs of discriminative stimuli for tangible and edible items, thinning reinforcement for each stimulus class independently. We then rapidly transferred stimulus control to new icons and integrated both classes of stimuli into a single AAC grid. This first demonstration of embedding discriminative stimuli into an AAC device represents a promising advancement for individuals who do not use speech and may not readily respond to delay or denial cues.

Patient-reported outcomes in Primary Spinal Intradural Tumours: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: Primary Spinal Intradural Tumours (PSITs) are rare pathologies that can significantly impact quality of life. This study aimed to review patient reported outcomes (PROs) in PSITs. METHODS: A systematic search of Pubmed and Embase was performed to identify studies measuring PROs in adults with PSITs. PRO results were categorised as relating to Global, Physical, Social, or Mental health. Outcomes were summarised descriptively. RESULTS: Following review of 2382 records, 11 studies were eligible for inclusion (737 patients). All studies assessed surgically treated patients. Schwannoma was the commonest pathology (n = 190). 7 studies measured PROs before and after surgery, the remainder assessed only post-operatively. For eight studies, PROs were obtained within 12 months of treatment. 21 PRO measurement tools were used across included studies, of which Euro-Qol-5D (n = 8) and the pain visual/numerical analogue scale (n = 5) were utilised most frequently. Although overall QoL is lower than healthy controls in PSITs, improvements following surgery were found in Extramedullary tumours (EMT) in overall physical, social, and mental health. Similar improvements were not significant across studies of Intramedullary tumours (IMT). Overall QoL and symptom burden was higher in IMT patients than in brain tumour patients. No studies evaluated the effect of chemotherapy or radiotherapy. CONCLUSION: Patients with PSITs suffer impaired PROs before and after surgery. This is particularly true for IMTs. PRO reporting in PSITs is hindered by a heterogeneity of reporting and varied measurement tools. This calls for the establishment of a standard set of PROs as well as the use of registries.

Patient-Led Skin Cancer Teledermatology without Dermoscopy during the Covid pandemic: Important lessons for the development of future patient-facing teledermatology & AI-assisted self-diagnosis.

MySkinSelfie was a mobile phone application for skin self-monitoring enabling secure sharing of patient-captured images with healthcare providers. This retrospective study assessed MySkinSelfie's role in remote skin cancer assessment at two centres for urgent (melanoma & squamous cell carcinoma) and non-urgent skin cancer referrals, investigating the feasibility of using patient-taken images without dermoscopy for remote diagnosis. Total number of lesions utilising MySkinSelfie was 814 with mean age of 63. Remote consultations reduced face-to-face appointments by 90% for basal cell carcinoma and 63% for two-week-wait referrals. Diagnostic concordance (consultant vs histological diagnosis) rates of 72% and 83% were observed for basal cell carcinoma (n=107) and urgent skin cancers (n=704), respectively. Challenges included image quality, workflow integration and lack of dermoscopy. Higher sensitivities have been observed in recent Artificial Intelligence (AI) algorithms employing dermoscopy. While patient-taken images proved useful during the pandemic, further research is needed to explore the feasibility of widespread patient-led dermoscopy to enable direct patient-to-AI diagnostic assessment.

The feasibility and outcomes of metabolic and bariatric surgery prior to neoplastic therapy.

BACKGROUND: Metabolic and bariatric surgery (MBS) is a potent intervention for addressing obesity-related medical conditions and achieving sustainable weight loss. Beyond its conventional role, MBS has demonstrated potential to serve as a transitional step for patients requiring various interventions. However, the implications of MBS in the context of neoplasia remain understudied. OBJECTIVES: To explore the feasibility of MBS as a possible attempt to reduce surgical and treatment risks in patients with benign tumors or low-grade cancers. SETTING: Multicenter review from twelve tertiary referral centers spanning 8 countries. METHODS: A retrospective review of patients with a diagnosis of primary neoplasia, deemed inoperable or high-risk due to obesity, and receiving primary MBS prior to neoplastic therapy. Data encompassed baseline characteristics, neoplasia characteristics, MBS outcomes, and neoplastic therapy outcomes. RESULTS: Thirty-seven patients (median age 52 years, 75.7% female, median BMI of 49.1 kg/m2) were included. There were 9 distinct organs of origin of primary neoplasia, with the endometrium (43.2%) being the most common, followed by the pancreas, colon, kidney and breast. Sleeve gastrectomy (SG) was the most commonly performed MBS procedure (78.4%), with no MBS-related complications or mortalities reported over an average of 4.3 ± 3.9 years. Thirty-one patients (83.8%) eventually underwent neoplastic surgery, with a mean BMI decrease from 49.9 kg/m2 to 39.7 kg/m2 at surgery over an average of 5.8 ± 4.8 months. There were 2 (6.7%) documented mortalities associated with neoplastic surgical intervention. CONCLUSIONS: This study highlights the potential feasibility of employing MBS prior to neoplastic therapy in patients with low-grade, less aggressive neoplasms in the context of obesity. This underscores the importance of providing a personalized, case-to-case multidisciplinary approach in the management of these patients.

The COVID-19 pandemic and OBGYN residency training: We have a problem and it's not just masks.

BACKGROUND: The COVID-19 pandemic has left no one untouched. Resident trainees have been driven to reconsider virtually every component of their daily lives. The purpose of this pilot study is to evaluate the impact of the COVID-19 pandemic on Obstetrics and Gynecology (OBGYN) residency training and education. METHODS: A cross-sectional pilot study was conducted between 2/2022 and 5/2022. A survey was created and distributed to OBGYN residents. The survey queried the effects of the pandemic on OBGYN residents' procedure skills training and mental health. RESULTS: A total of 95 OBGYN residents across programs affiliated with each American College of Obstetricians and Gynecologists (ACOG) district participated in the survey. Among them, just over half (n = 52, 55%) self-identified as under-represented minorities. A significant majority, 80% (n = 81), felt their gynecological training was inadequate, with 70% of fourth-year residents expressing a lack of confidence in their ability to independently practice gynecology after graduation. This lack of confidence among fourth-year residents suggests a notable disparity in readiness for independent gynecological practice, linked to meeting ACGME requirements before completing their residency (p = 0.013). Among the residents who reported a negative impact of the pandemic on their mental health (n = 76, 80%), about 40% (n = 31) had contemplated self-harm or knew a colleague who considered or attempted suicide (p < 0.001). This issue was especially pronounced in residents experiencing burnout (n = 44, 46%), as nearly half (n = 19, 43%) reported suicidal thoughts or knew someone in their program who had such thoughts or engaged in self-harm (p = 0.048). CONCLUSIONS: Residents expressed concerns about reduced hands-on gynecological training and doubts about their readiness for independent practice post-residency, highlighting the need for enhanced support through mentorship and revised training curriculums. Additionally, despite the availability of mental health resources to address pandemic-induced burnout, their underuse suggests a need for more accessible time for residents to use at their discretion and flexible training schedules that encourage mental health support resource utilization.

Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors.

Dialkyl/aryl aminophosphonates, 3a-g and 4a-e were synthesized using the LiClO4 catalyzed Kabachnic Fields-type reaction straightforwardly and efficiently. The synthesized phosphonates structures were characterized using elemental analyses, FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. The new compounds were subjected to in-silico molecular docking simulations to evaluate their potential inhibition against Influenza A Neuraminidase and RNA-dependent RNA polymerase of human coronavirus 229E. Subsequently, the compounds were further tested in vitro using a cytopathic inhibition assay to assess their antiviral activity against both human Influenza (H1N1) and human coronavirus (HCoV-229E). Diphenyl ((2-(5-cyano-6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl) hydrazinyl) (furan-2-yl) methyl) phosphonate (3f) and diethyl ((2-(5-cyano-6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl) hydrazinyl) (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) methyl) phosphonate (4e) were demonstrated direct inhibition activity against Influenza A Neuraminidase and RNA-dependent RNA polymerase. This was supported by their highly favorable binding energies in-silico, with top-ranked values of -12.5 kcal/mol and -14.2 kcal/mol for compound (3f), and -13.5 kcal/mol and -9.89 kcal/mol for compound (4e). Moreover, they also displayed notable antiviral efficacy in vitro against both viruses. These compounds demonstrated significant antiviral activity, as evidenced by selectivity indices (SI) of 101.7 and 51.8, respectively against H1N1, and 24.5 and 5.1 against HCoV-229E, respectively.

Characteristics and management of periprosthetic joint infections caused by rapidly growing mycobacteria: a retrospective study and a review of the literature.

Background: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are the predominant causative organisms, PJIs caused by rapidly growing mycobacteria (RGM) have been reported, albeit at a lower frequency. This study aimed to investigate the characteristics and management of PJI caused by RGM. Methods: A retrospective review was conducted using an institutional PJI database to identify patients diagnosed with PJI due to RGM from January 2010 to December 2021. Clinical data, including demographics, symptoms, comorbidity information, laboratory parameters, surgical procedures, medical treatment and outcomes, were collected and analyzed. Results: A total of eight patients were identified with PJI caused by RGM during the study period. The median age was 66 years old, and most cases occurred in patients with total knee arthroplasty (n=6). The isolated RGM species included Mycobacterium abscessus (three cases), M. fortuitum (three cases), and one case each of M. immunogenum and M. mageritense. Surgical debridement was performed in all cases, with six patients undergoing two-stage revision and two patients requiring amputation. Combination antimicrobial therapy was administered based on antimicrobial susceptibility testing, and the median duration of treatment was 7.5 months. Adverse events related to therapy occurred in 75 % of cases. No relapses were observed during the median follow-up period of 39.6 months. Conclusions: PJI caused by RGM is a rare complication of total joint arthroplasty. Surgical debridement and combination antimicrobial therapy are the mainstays of treatment. Although clinical cure rates are high, amputation may be required in severe cases.