Description and analysis of patients and outcomes following third-time heart transplantation: An analysis of the United Network for Organ Sharing database from 1985 to 2017.

BACKGROUND: Following second heart transplantation (HTx), some patients experience graft failure and require third-time heart transplantation. Little data exist to guide decision-making with regard to repeat retransplantation in older patients. METHODS: We performed a retrospective cohort analysis of patients receiving a third HTx, as identified in the United Network for Organ Sharing (UNOS) database from 1985 to 2017. RESULTS: The study cohort consisted of N = 60 patients, with an average age of 29 with a standard deviation of ±18 years. Overall survival for the cohort at 1, 5, and 10 years is 83%, 64%, and 44%, respectively. The rate of third-time HTxs has steadily increased in all age groups. Patients older than 50 years now account for 18.3% of all third-time HTxs. Although this group demonstrated longer average previous graft survival, after third HTx they demonstrate significantly poorer survival outcomes compared to third-time HTx recipients younger than 21 (P = 0.05). Age over 50, BMI over 30, and diabetes were all found to be independent risk factors for decreased survival following third HTx. CONCLUSIONS: We describe trends in patients undergoing third HTx. We highlight subsets of such recipients who exhibit decreased survival.

Exploring the relationship between changes in weight and utterances in an online weight loss forum: a content and correlational analysis study.

BACKGROUND: There is increasing interest in the use of online forums as a component of eHealth weight loss interventions. Although the research is mixed on the utility of online forums in general, results suggest that there is promise to this, particularly if the systems can be designed well to support healthful interactions that foster weight loss and continued engagement. OBJECTIVE: The purpose of this study was to examine the relationship between the styles of utterances individuals make on an online weight loss forum and week-to-week fluctuations in weight. This analysis was conducted to generate hypotheses on possible strategies that could be used to improve the overall design of online support groups to facilitate more healthful interactions. METHODS: A convenience sample of individuals using an online weight loss forum (N=4132) included data both on online forum use and weight check-in data. All interactions were coded utilizing the Linguistic Inquiry and Word Count (LIWC) system. Mixed model analyses were conducted to examine the relationship between these LIWC variables and weight over time. RESULTS: Results suggested that increased use of past-tense verbs (P=.05) and motion (P=.02) were associated with lower weekly weights whereas increased use of conjunctions (eg, and, but, whereas; P=.001) and exclusion words (eg, but, without, exclude; P=.07) were both associated with higher weight during the weeks when these utterances were used more. CONCLUSIONS: These results provide some insights on the styles of interactions that appear to be associated with weight fluctuations. Future work should explore the stability of these findings and also explore possibilities for fostering these types of interactions more explicitly within online weight loss forums.

Fetal Ultrasound Segmentation and Measurements Using Appearance and Shape Prior Based Density Regression with Deep CNN and Robust Ellipse Fitting.

Accurately segmenting the structure of the fetal head (FH) and performing biometry measurements, including head circumference (HC) estimation, stands as a vital requirement for addressing abnormal fetal growth during pregnancy under the expertise of experienced radiologists using ultrasound (US) images. However, accurate segmentation and measurement is a challenging task due to image artifact, incomplete ellipse fitting, and fluctuations due to FH dimensions over different trimesters. Also, it is highly time-consuming due to the absence of specialized features, which leads to low segmentation accuracy. To address these challenging tasks, we propose an automatic density regression approach to incorporate appearance and shape priors into the deep learning-based network model (DR-ASPnet) with robust ellipse fitting using fetal US images. Initially, we employed multiple pre-processing steps to remove unwanted distortions, variable fluctuations, and a clear view of significant features from the US images. Then some form of augmentation operation is applied to increase the diversity of the dataset. Next, we proposed the hierarchical density regression deep convolutional neural network (HDR-DCNN) model, which involves three network models to determine the complex location of FH for accurate segmentation during the training and testing processes. Then, we used post-processing operations using contrast enhancement filtering with a morphological operation model to smooth the region and remove unnecessary artifacts from the segmentation results. After post-processing, we applied the smoothed segmented result to the robust ellipse fitting-based least square (REFLS) method for HC estimation. Experimental results of the DR-ASPnet model obtain 98.86% dice similarity coefficient (DSC) as segmentation accuracy, and it also obtains 1.67 mm absolute distance (AD) as measurement accuracy compared to other state-of-the-art methods. Finally, we achieved a 0.99 correlation coefficient (CC) in estimating the measured and predicted HC values on the HC18 dataset.

Emerging roles of SnoRNAs in the pathogenesis and treatment of autoimmune disorders.

SnoRNAs (small non-coding RNAs) have recently gained prominence in autoimmune diseases, revealing their crucial role in modulating the immune response and contributing to disease pathogenesis. Initially known for their involvement in ribosomal RNA processing and modification, molecular biology and genomics advancements have uncovered their broader impact on cellular function, especially in autoimmune disorders. Autoimmune diseases represent conditions characterized by the immune system's erroneous attacks on self-tissues, encompassing disorders like systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The complex etiology of these conditions involves a delicate interplay of genetic and environmental factors. Emerging evidence suggests that snoRNAs initially recognized for their housekeeping roles, extend their influence on immune regulation through diverse mechanisms. SnoRNAs have been implicated in epigenetic modification, directly affecting the gene expression profiles of immune cells. Their ability to guide site-specific changes on ribosomal RNAs and other non-coding RNAs can significantly influence the translation of proteins involved in immune response pathways. Moreover, snoRNAs interact with key immune-related proteins, modulating their functions and subsequently impacting immune cell development, activation, and tolerance. Dysregulation of snoRNA expression has been observed in various autoimmune diseases, underscoring their potential as biomarkers for disease diagnosis, prognosis, and therapeutic targets. Manipulating snoRNA expression or activity is a promising therapeutic intervention avenue, offering the potential for personalized treatment strategies in autoimmune diseases. However, there remains a need for comprehensive research efforts to elucidate the precise molecular mechanisms underlying snoRNA-mediated immune modulation. Further investigations in this domain are essential to unravel the potential of snoRNAs in autoimmune disorders.

Navigating Complexity in Mandibular Condyle Aplasia and Temporomandibular Joint Ankylosis in a Five-Year-Old Child: A Case Report.

Mandibular condyle aplasia and temporomandibular joint (TMJ) ankylosis represent complex challenges in diagnosis and management, affecting jaw function and facial aesthetics. This case report presents a five-year-old female child with a right-sided small jaw and facial asymmetry due to left-sided TMJ ankylosis. The coexistence of mandibular condyle aplasia and TMJ ankylosis underscores the need for comprehensive evaluation and tailored treatment approaches. Syndromic associations, such as Goldenhar syndrome and Treacher Collins syndrome, further complicate diagnosis and management. Surgical intervention involving left-side gap arthroplasty and reconstruction using a costochondral graft/temporalis fascia was performed under general anesthesia. However, postoperative complications, including decreased mouth opening and left-sided lower motor neuron facial palsy, necessitated further surgical debridement and drainage of an abscess. The case emphasizes the importance of a multidisciplinary approach in addressing complex craniofacial anomalies, with treatment strategies such as bone grafting and tailored surgical interventions offering promising outcomes. Understanding the multifaceted etiology of mandibular condyle aplasia and TMJ ankylosis is crucial for optimal management, highlighting the collaborative efforts required for achieving favorable patient outcomes.

Unravelling the role of long non-coding RNAs in modulating the Hedgehog pathway in cancer.

Cancer is a multifactorial pathological condition characterized by uncontrolled cellular proliferation, genomic instability, and evasion of regulatory mechanisms. It arises from the accumulation of genetic mutations confer selective growth advantages, leading to malignant transformation and tumor formation. The intricate interplay between LncRNAs and the Hedgehog pathway has emerged as a captivating frontier in cancer research. The Hedgehog pathway, known for its fundamental roles in embryonic development and tissue homeostasis, is frequently dysregulated in various cancers, contributing to aberrant cellular proliferation, survival, and differentiation. The Hh pathway is crucial in organizing growth and maturation processes in multicellular organisms. It plays a pivotal role in the initiation of tumors as well as in conferring resistance to conventional therapeutic approaches. The crosstalk among the Hh pathway and lncRNAs affects the expression of Hh signaling components through various transcriptional and post-transcriptional processes. Numerous pathogenic processes, including both non-malignant and malignant illnesses, have been identified to be induced by this interaction. The dysregulation of lncRNAs has been associated with the activation or inhibition of the Hh pathway, making it a potential therapeutic target against tumorigenesis. Insights into the functional significance of LncRNAs in Hedgehog pathway modulation provide promising avenues for diagnostic and therapeutic interventions. The dysregulation of LncRNAs in various cancer types underscores their potential as biomarkers for early detection and prognostication. Additionally, targeting LncRNAs associated with the Hedgehog pathway presents an innovative strategy for developing precision therapeutics to restore pathway homeostasis and impede cancer progression. This review aims to elucidate the complex regulatory network orchestrated by LncRNAs, unravelling their pivotal roles in modulating the Hedgehog pathway and influencing cancer progression.

MicroRNA-21's role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology.

MicroRNA-21 (miR-21) was recognized as a key figure in the intricate web of tumor biology, with a prominent role in regulating the PTEN tumor suppressor gene and the PI3K/AKT cascade. This review elucidates the multifaceted interactions between miR-21, PTEN, and the PI3K/AKT signaling, shedding light on their profound implications in cancer initiation, progression, and therapeutic strategies. The core of this review delves into the mechanical intricacies of miR-21-mediated PTEN suppression and its consequent impact on PI3K/AKT pathway activation. It explores how miR-21, as an oncogenic miRNA, targets PTEN directly or indirectly, resulting in uncontrolled activation of PI3K/AKT, fostering cancerous cell survival, proliferation, and evasion of apoptosis. Furthermore, the abstract emphasizes the clinical relevance of these molecular interactions, discussing their implications in various cancer types, prognostic significance, and potential as therapeutic targets. The review provides insights into ongoing research efforts to develop miR-21 inhibitors and strategies to restore PTEN function, offering new avenues for cancer treatment. This article illuminates the critical function of miR-21 in PTEN suppression and PI3K/AKT activation, offering profound insights into its implications for cancer biology and the potential for targeted interventions.

Prevalence of chronic pulmonary aspergillosis in fibrocavitary pulmonary tuberculosis patients.

Background: Tuberculosis (TB) is still a global health issue. While the lungs are the most commonly affected, infections can also affect other organs. Because of the rise in immunocompromised hosts, the number of opportunistic infections has skyrocketed. In instances of aspergilloma and chronic pulmonary aspergillosis (CPA), pulmonary tuberculosis (PTB) is the most usually linked condition. Material and Methods: The current cross-sectional study was conducted on 42 study participants from January 2018 to June 2019. Results: Aspergilloma was observed in two participants (4.8%) of the study population. Candida growth was observed in five participants (11.9%) of the study population on sputum fungal culture. Aspergillus growth and Candida growth was observed in three (7.1%) and two (4.8%) participants of the study population, respectively, on bronchoalveolar lavage (BAL) fungal culture. Aspergillus IgG antibody was positive in four particpants (9.5%) of study population. Out of the 42 participants, four were diagnosed with CPA. Conclusion: Since CPA and PTB patients present similar symptoms, it is virtually impossible to distinguish between the two unless serological test is performed. There has been a significant burden of patients with CPA, especially in post tuberculosis fibro-cavitation. CPA patients requires long-term anti-fungal therapy; hence an improved case detection should be undertaken.

Unlocking new approaches to Urolithiasis management via Nutraceutical.

Urolithiasis, commonly known as kidney stones, is characterized by the formation of hard deposits in the urinary tract. These stones can cause severe pain and discomfort, and their management typically involves a combination of medical interventions and lifestyle modifications. According to the literature, 30% and 50% of urolithiasis cases recur. Between 9 and 12% of persons in industrialised countries are predicted to have urolithiasis at some time. Due to the high frequency of stone formation, recurrent nature, and prevalence in adults, it has a significant impact on society, the person, and the health care system. Adopting the best prophylactic measures is crucial in light of these developments to decrease the impact of urolithiasis on individuals and society. In recent years, there has been growing interest in the potential role of nutraceuticals in the management of urolithiasis. Nutraceuticals, such as herbal extracts, vitamins, minerals, and probiotics, have gained recognition for their potential in promoting urinary health and reducing the risk of urolithiasis. These compounds can aid in various ways, including inhibiting crystal formation, enhancing urine pH balance, reducing urinary calcium excretion, and supporting kidney function. Additionally, nutraceuticals can help alleviate symptoms associated with urolithiasis, such as pain and inflammation. While medical interventions remain crucial, incorporating nutraceuticals into a comprehensive management plan can offer a holistic approach to urolithiasis, improving patient outcomes and quality of life. Therefore, nutraceuticals may be a desirable choice for treating and avoiding recurring urolithiasis for patients and medical professionals. Therefore, the present study has focused on nutraceuticals' role in preventing urolithiasis.

Restarting LDLT During COVID-19: Early Results After Restructuring.

INTRODUCTION: Living-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic. MATERIALS AND METHODS: The changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months). RESULTS: Nineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected. CONCLUSION: This study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.

Post-operative hypertension, a surrogate marker of the graft function and predictor of survival in living donor liver transplant recipients: A retrospective study.

BACKGROUND AND AIMS: De novo hypertension (HTN) in liver transplantation recipients is a known entity. We investigated haemodynamic behaviour after a liver transplant to see if it can predict survival to discharge from the hospital. METHODS: electronic records of Haemodynamic parameters and laboratory investigations of 95 patients of living donor liver transplant (LDLT) were retrospectively analysed. RESULTS: Twenty-three patients were operated for acute liver failure (ALF) and 72 patients for chronic liver disease (CLD). Eight patients of CLD and four of ALF did not survive. CLD patients had statistically significant rise in systolic blood pressure from the post-operative day (POD) 1 to POD 4 and diastolic blood pressure (DBP) from POD 3 to POD 6. Heart rate (HR) significantly decreased from POD 3 to POD 5. Haemodynamic parameters returned to baseline values within 20 days. Diastolic HTN had a positive predictive value of 100% for survival with 100% sensitivity and specificity. Systolic HTN had a positive predictive value of 100% for survival (sensitivity-89%, specificity-100%). ALF patients had a significant decrease in HR from POD 2 to POD 10. Bradycardia (HR ≤60/min) had a positive predictive value of 100% for survival with a sensitivity of 45% and 58% in CLD and ALF, respectively, with a specificity of 100% in both the groups. Non-survivors had no significant change in haemodynamics. In CLD group, International Normalised Ratio had statistically significant, strong negative correlation with DBP. CONCLUSION: Haemodynamic pattern of recovery may be used for predicting survival to discharge after LDLT.

Addition of sub-anaesthetic dose of ketamine reduces gag reflex during propofol based sedation for upper gastrointestinal endoscopy: A prospective randomised double-blind study.

BACKGROUND AND AIMS: Gag reflex is unwanted during upper gastrointestinal endoscopy (UGIE). Experimental studies have demonstrated that N-methyl-D-aspartate receptor antagonism prevents gag reflex. We conducted a study to determine if sub-anaesthetic doses of ketamine, added to propofol, reduce the incidence of gag reflex. METHODS: This prospective, randomised, double-blind and placebo-controlled study was done in a tertiary care hospital. A total of 270 patients undergoing UGIE, were randomised to propofol (P) group (n = 135) or propofol plus ketamine (PK) group (n = 135). All patients received propofol boluses titrated to Ramsay sedation score of not <4. Patients in PK group in addition received ketamine, 0.15 mg/kg immediately before the first-propofol dose. Top-up doses of propofol were given as required. Stata 11 software (StataCorp.) was used to calculate the proportion of patients with gag reflex and the corresponding relative risk. Propofol consumed and time to recovery in the two groups was compared using Student's t-test and Cox proportional hazards regression respectively. RESULTS: Significantly, fewer patients in the PK group had gag reflex compared to the P group (3 vs. 23, risk ratio = 0.214, 95% confidence interval [CI], 0.07-0.62; P = 0.005). The incidence of hypotension (6 vs. 16, risk ratio = 0.519, 95% CI = 0.25-1.038; P = 0.06), number of required airway manoeuvres (4 vs. 19, risk ratio = 0.32, 95% CI = 0.13-0.74; P = 0.014), median time to recovery (4 min vs. 5 min, hazard ratio = 1.311, 95% CI = 1.029-1.671; P = 0.028) and propofol dose administered (152 mg vs. 167 mg, 95% CI = 4.74-24.55; P = 0.004) was also less in the PK group compared to the P group. CONCLUSION: Ketamine in sub-anaesthetic dose decreases gag reflex during UGIE.

Derivation of autism spectrum disorder-specific induced pluripotent stem cells from peripheral blood mononuclear cells.

Induced pluripotent stem cells (iPSCs) hold tremendous potential both as a biological tool to uncover the pathophysiology of disease by creating relevant cell models and as a source of stem cells for cell-based therapeutic applications. Typically, iPSCs have been derived by the transgenic overexpression of transcription factors associated with progenitor cell or stem cell function in fibroblasts derived from skin biopsies. However, the need for skin punch biopsies to derive fibroblasts for reprogramming can present a barrier to study participation among certain populations of individuals, including children with autism spectrum disorders (ASDs). In addition, the acquisition of skin punch biopsies in non-clinic settings presents a challenge. One potential mechanism to avoid these limitations would be the use of peripheral blood mononuclear cells (PBMCs) as the source of the cells for reprogramming. In this article we describe, for the first time, the derivation of iPSC lines from PBMCs isolated from the whole blood of autistic children, and their subsequent differentiation in GABAergic neurons.