Micro-RNAs With Prognostic Significance in Gallbladder Cancer: A Systematic Review and Meta-Analysis.

Gallbladder cancer (GBC) stands out as one of the most widespread malignancies impacting the biliary tract globally. Despite increasing interest, to the best of our knowledge, no meta-analysis has been undertaken to amalgamate the existing data concerning the prognostic significance of micro-RNAs (miRNAs) in GBC in comparison to studies on miRNAs in other cancers. Hence, this systematic review and meta-analysis aimed at determining the prognostic significance of miRNAs in GBC patients. Comprehensive literature searches were conducted across PubMed, Cochrane Library, Ovid, Scopus, and Science Direct databases. Studies that evaluated the association between miRNAs and overall survival in GBC patients were included. Random-effect meta-analysis was employed to pool hazard ratios (HRs) and their 95% confidence intervals (CIs) across studies. A total of 15 studies, encompassing 16 miRs, were included for our analysis. The pooled analysis revealed that a high expression of miR-204, miR-7-2-3p, miR-29c-3p, miR-125b, miR-20a, miR-139-5p, miR-141, miR-92b-3p, miR-335, and miR-372 was significantly associated with poor prognosis and increased risk (HR>1 and the upper bound of the 95% CI>1). Additionally, these miRNAs were associated with the overall survival (HR = 1.56, 95% CI = 0.91-2.20, I2 = 91.82%). Significant heterogeneity was observed and could be attributed to the limited number of studies available on the GBC and significant reliance on quantitative real-time PCR for the detection of miRNAs. In conclusion, specific miRNAs exhibit prognostic significance in GBC, with potential implications for patient stratification and targeted therapeutic interventions. However, due to the heterogeneity among studies, these findings should be interpreted cautiously and validated in larger cohorts.

Laparoscopic Management of Auto-Amputated Ovarian Cyst in an Infant.

ABSTRACT: The routine schedule of antenatal ultrasound scans has led to an increased frequency of detection of foetal ovarian cysts. Although most of them regress spontaneously, some may grow into large cysts and undergo torsion followed by auto-amputation. However, pre- and post-natal scans may fail to identify this event. We report a case of a prenatally diagnosed ovarian cyst that failed to resolve conservatively and was increasing in size in post-natal ultrasounds. Pre-operative ultrasound and magnetic resonance imaging failed to detect the auto-amputation. The diagnosis was confirmed on laparoscopy which offers a safe and effective method for the removal of ovarian cysts in neonates and infants.

Indocyanine green fluorescent cholangiography: The new standard practice to perform laparoscopic cholecystectomy in pediatric patients. A comparative study with conventional laparoscopic technique.

BACKGROUND: This study aimed to compare outcomes of standard laparoscopic cholecystectomy and indocyanine green fluorescent cholangiography laparoscopic cholecystectomy over a 10-year period. METHODS: From 2013 to 2023, 173 laparoscopic cholecystectomies were performed in 2 pediatric surgery units: 83 using standard technique (G1) and 90 using indocyanine green fluorescent cholangiography (G2). Patients included 96 girls and 77 boys, with a median age of 12.3 years (range 4-17) and a median weight of 51 kg (range 19-114). The 2 groups were compared regarding the following: (1) perioperative complications rate; (2) overall length of surgery (T1); (3) length of cystic duct isolation, clipping, and sectioning (T2); (4) time of gallbladder removal (T3); (5) degree of visualization of biliary tree; (6) safety and feasibility of indocyanine green fluorescent cholangiography; (7) incidence of anatomical anomalies detected intraoperatively. RESULTS: All laparoscopic cholecystectomies were accomplished without conversion to open. The perioperative complications rate was significantly higher in G1 compared with G2 (12% vs 0%; P = .0007). Median T1, T2, and T3 were significantly longer in G1 (90, 37, 35 minutes) compared with G2 (55, 17, 19 minutes) (P = .0001), respectively. The visualization rate of the complete biliary tree was significantly higher in G2 (98.8%) than in G1 (80.7%) (P = .0001). No adverse reactions to indocyanine green were recorded. The incidence of biliary anomalies detected intraoperatively was significantly higher in G2 (7.8%) than in G1 (1.2%) (P = .03). CONCLUSION: Indocyanine green fluorescent cholangiography can be considered the new standard practice to perform laparoscopic cholecystectomy in pediatrics. Indocyanine green fluorescence provided superior visualization of biliary anatomy, increased detection of anatomic variants, faster procedure, and fewer complications compared with conventional technique. Indocyanine green fluorescent cholangiography was safe, feasible, simple, inexpensive, and a timesaving tool.

Efficacy of jackfruit components in prevention and control of human disease: A scoping review.

The jackfruit (Artocarpus heterophyllus) is one of the natural remedies significantly used in folk medicine. The ethnopharmacological applications of jackfruit are mainly concerned with the management of inflammation, diarrhea, and diabetes mellitus. Flavonoids, stilbenoids, aryl benzofurans, and lectin jacalin are abundant in jackfruit species. Jacalin is a good indicator for evaluating the immunological state of HIV-1 patients. The extracts and metabolites of jackfruit, particularly those from the leaves, bark, stem, and fruit, contain several beneficial bioactive mixtures. New studies are focused on exploring these bioactive compounds used in various biological activities such as antiviral, antiplatelet, anticancer, antiatherosclerotic, immunomodulatory effects, inhibitors of 5-alpha reductase activity, and the formulation of fast-dissolving tablets (orodispersible, rapid melts porous). Multidisciplinary programs that integrate traditional and modern technology play a crucial role in the lies ahead expansion of jackfruit as the prospective inception of therapeutic compounds. This review aims to highlight significant results on the identification, production, and bioactivity of metabolites found in jackfruit, with current developments in jackfruit research in the control and prevention of human diseases.

Next generation sequencing uncovers multiple miRNAs associated molecular targets in gallbladder cancer patients.

Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.

Determining the Clinical Value of Routine Post Operative follow up in Common Paediatric Surgical Conditions: A Prospective Observational Study.

Background: The traditional postoperative visit consists of an in-person hospital visit at a predetermined date which requires the investment of time and resources. This implies a need to prioritize visits rather than mandating them, which can be assessed by the requirement of clinical intervention at the time of follow-up. The purpose of this study is to determine the clinical value of routine postoperative physical follow-up in common pediatric surgery conditions, to identify factors determining follow-up, and to estimate the cost of routine follow-up. Materials and Methods: Surgical data of 226 patients admitted for routine pediatric surgical procedures were collected. The postoperative period was documented in detail and interventions done either physically or telephonically at the time of follow-up were used as a proxy measure of clinical value. Results: There were 226 patients enrolled, of which 64.60% followed up physically in outpatient department and 35.40% followed up telephonically. Maximum percentage of patients with postoperative complications belonged to the group of laparotomy at 22.22%, followed by complicated appendicitis at 15.62%. 13.27% of patients required clinical intervention at the time of follow-up. Conclusion: Patients undergoing simpler procedures such as inguinal hernia, hydrocele, and orchidopexy have lesser rate of complications which translates to requirement of fewer clinic visits, whereas those undergoing procedures such as appendectomy and laparotomy require a physical visit after discharge since they are more susceptible to develop complications requiring interventions. By selecting patients for physical visit, we can potentially eliminate unnecessary visits in patients who have low chance of developing complications.

Bilirubin in wound healing: A double-edged sword.

The impact of bilirubin levels on wound healing remains a topic of controversy. The present study is a literature review that examines the impact of increased levels of bilirubin in the bloodstream on the process of wound healing. The physiological pathways and their interrelationships, as well as the relevant research publications, were comprehensively addressed in our discussion. The present study undertook a comprehensive review of the extant literature pertaining to the impact of bilirubin concentration on the process of wound healing, with particular emphasis on its association with reactive oxygen species. This scholarly article provides an overview of several studies that elucidate the mechanisms and correlation between bilirubin and the process of wound healing. The impact of bilirubin on wound healing has been observed, and it appears to function as a modulator. This review demonstrates that there exists a spectrum of bilirubin concentrations that can function as precise regulators, although this range falls under pathological hyperbilirubinemia. Further research is required to determine the precise boundary of this range. Within a certain range, bilirubin serves as a positive regulator in the process of wound healing. Beyond this range, it has the potential to function as a negative regulator.

Non-coding RNAs, cancer treatment and cardiotoxicity: A triad of new hope.

The global health landscape has experienced a shift towards non-communicable diseases, with cardiovascular diseases and cancer as leading causes of mortality. Although advancements in healthcare have led to an increase in life expectancy, they have concurrently resulted in a greater burden of chronic health conditions. Unintended consequences of anticancer therapies on various tissues, particularly the cardiovascular system, contribute to elevated morbidity and mortality rates that are not directly attributable to cancer. Consequently, the field of cardio-oncology has emerged to address the prevalence of CVD in cancer survivors and the cardiovascular toxicity associated with cancer therapies. Non-coding RNAs (ncRNAs) have been found to play a crucial role in early diagnosis, prognosis, and therapeutics within the realm of cardio-oncology. This comprehensive review evaluates the risk assessment of cancer survivors concerning the acquisition of adverse cardiovascular consequences, investigates the association of ncRNAs with CVD in patients undergoing cancer treatment, and delves into the role of ncRNAs in the diagnosis, treatment, and prevention of CVD in patients with a history of anti-cancer therapy. A thorough understanding of the pathogenesis of cancer therapy-related cardiovascular disease and the involvement of ncRNAs in cardio-oncology will enable healthcare professionals to provide anticancer treatment with minimized cardiovascular side effects, thereby improving patient outcomes. Ultimately, this comprehensive analysis aims to provide valuable insights into the complex interplay between cancer and cardiovascular diseases, facilitating the development of more effective diagnostic, therapeutic, and preventive strategies in the burgeoning field of cardio-oncology.

Conjoined thoracopagus twins: A systematic review of the anomalies and outcome of surgical separation.

Introduction: Conjoined twin is an extremely rare condition and requires a thorough knowledge of anatomy, and a multidisciplinary approach is essential to successfully separate the twins. Thoracopagus twins lie face to face and are attached from chest to upper abdomen. They are the most common among all the varieties but have a poor survival rate. Materials and Methods: This study is a review of literature from 2019 to the oldest via PubMed and Google Scholar using keywords: Conjoined twins, Thoracopagus twins, Thoracoomphalopagus and Thoraco-omphalopagus twins. The articles were reviewed for the description of the anatomy of shared organs, management and outcome of these twins. Results: One hundred and fifty-eight sets of thoracopagus and thoraco-omphalopagus twins including our twins were included in this study. Out of 158 reported thoracopagus twin sets in literature, with M: F ratio of 1:2.3, 71 sets were found to be non-operable and all of them subsequently expired; 82 sets were operated upon, out of which 83 babies survived, suggesting an overall surgical success rate of about 50%. Conclusion: Thoracopagus twins have a dismal prognosis. The most important decisive parameter for successful separation is the extent of sharing of organs between twins. The role of a motivated multidisciplinary team is also indispensable and cannot be overemphasised.

Giardiasis in an Infant With Fibrosarcoma: A Case Report.

INTRODUCTION: Giardia lamblia is a neglected parasitic infection that typically affects the developing nations of the world. It is a microscopic intestinal parasite that is known to cause stomach cramps, bloating, nausea and bouts of diarrhoea. CASE PRESENTATION: Here, we are presenting the case of a 1.5 years-old-baby with an immunocompromised condition who got infected by Giardia lamblia. The baby with fibrosarcoma was receiving treatment in our tertiary care centre, and later developed abdominal and minor systemic complaints. Stool samples were collected, which showed trophozoites and cysts of Giardia. DISCUSSION: To the best of our knowledge, this is the first case of Giardia lamblia infection in a paediatric patient with fibrosarcoma. The patient improved after taking metronidazole for ten days. CONCLUSION: It is critical to keep a watch out for this neglected parasite, and suggested samples, particularly stool samples, must be sent for investigation in order to diagnose and manage these cases properly.

Congenital Diaphragmatic Hernia With Intra Thoracic Gastric Volvulus: A Rare, Life-Threatening Combination.

Congenital diaphragmatic hernia (CDH) is a known cause of secondary gastric volvulus (GV). Both entities are life-threatening, either alone or in exceedingly rare instances when they occur in combination. Here, we describe one such rare combination of CDH and secondary GV in a nine-year-old boy, who presented to us with recurrent episodes of abdominal pain. Urgent laparotomy was done after radiological evaluation (X-ray of chest and abdomen and contrast-enhanced CT chest and abdomen), which revealed mesenterico-axial volvulus of the stomach, secondary to an underlying diaphragmatic defect in the left hemidiaphragm, thus establishing the cause (diaphragmatic defect) and effect (GV), and resulting in a favourable outcome.

Retrospective Analysis of the Outcome of Stoma Closure in Children without Preoperative Mechanical Bowel Preparation.

Introduction: Stoma closure is one of the most frequently performed surgical procedures by pediatric surgeons worldwide. In this study, we studied the outcome of children undergoing stoma closures without mechanical bowel preparation (MBP) in our department. Materials and Methods: This is a retrospective observational study of children <18 years undergoing stoma closure from 2017 to 2021. The primary endpoints were surgical site infection (SSI), incisional hernia, anastomotic leak, and mortalities. The categorical data are expressed in percentages and the continuous data are in medians and interquartile ranges. The postoperative complications were classified according to the Clavien-Dindo system. Results: A total of 89 patients underwent stoma closure without bowel preparation during the study. The anastomosis leak and incisional hernia were seen in one patient each. The SSIs occurred in 23 patients (25.9%), which were superficial in 21 and deep in 2 patients. The Clavien-Dindo Grade III complications occurred in 2 (2.2%) patients. The median duration to start feeds and pass first stools was significantly longer in patients with ileostomy closure (P = 0.04 and 0.001, respectively). Conclusion: The outcome of stoma closures without MBP was favorable in our study and hence it can be suggested that the use of MBP in colostomy closures can be safely avoided in children.

Effect of Multimedia Teaching Tools in Parental Anxiety and Comprehension of Informed Consent Procedure in Pediatric Surgical Procedures: A Single Centre Randomized Control Trial.

INTRODUCTION: Informed consent is an essential component of medical ethics. In children, the parent or legally authorized guardian must consent to any medical or surgical intervention. A number of adjuncts have been developed to supplement the consent process including multimedia tools. Unfortunately, there is little information regarding the use of Multimedia teaching tools (MMT) in pediatric settings in developing countries with diversities in language, socioeconomic and educational status. OBJECTIVES: The objectives of the study were to compare the parental comprehension of the surgery through the informed consent obtained either by conventional method or by multimedia tool and the effect of MMT in alleviating parental anxiety against the conventional method and to assess their overall satisfaction. METHODS: A randomized control trial was conducted between 2018 and 2020, including MMT and conventional groups. A novel Multimedia tool with a Microsoft PowerPoint presentation was created. A 5-Question knowledge-based test, State-Trait Anxiety Inventory (STAI) tool, and a Likert-based questionnaire were used to assess the comprehension, anxiety, and satisfaction of parents. RESULTS: Among 122 randomized cohorts, the mean value of percentage fall in anxiety STAI score in the MMT group was 44.64 ± 10.14 whereas in the Conventional group it was 26.6 ± 11.91 (p < 0.05). MMT cohort scored higher in the knowledge-based test (p < 0.05) and recorded higher parental satisfaction. CONCLUSION: The Multimedia tool aided consent procedure is effective in reducing parental anxiety and improving their comprehension and overall satisfaction. Thus, they can be used as an effective supplement in preoperative surgical education and consent procedure. LEVEL OF EVIDENCE: Level I.

Effect of Cytomegalovirus Infection on Initial Presentation and Overall Prognosis of Biliary Atresia Patients.

Background and Aim: Biliary atresia is known to have a multifactorial etiology and perinatal infection with hepatotropic viruses such as cytomegalovirus (CMV) is a probable trigger in a subset of patients. The aim of the current study is to evaluate the effects of CMV association of biliary atresia on the initial presentation of patients and their response to Kasai portoenterostomy. Patients and Methods: We conducted a retrospective, single-center study on 20 patients of biliary atresia and classified them into two groups based on their CMV immunoglobulin M (IgM) positivity. We compared the age of initial presentation, the liver biochemistry at presentation, immediate and delayed follow-up, rate of jaundice clearance following Kasai portoenterostomy, and histopathology of liver between the two groups. Data were reported in terms of means, and P < 0.05 was considered significant. Results: Out of 20 cases of biliary atresia, 60% (n = 12) were CMV IgM positive. Infants with CMV-positive status were noted to be older at presentation (88.5 days [65-150 days] vs. 83 days [45-160 days] P < 0.05) were more jaundiced at presentation (total bilirubin - 13.51 mg/dl [9.09-15.99 mg/dl] vs. 11.83 mg/dl [6.5-13.5 mg/dl] P < 0.05), had higher alkaline phosphatase (751.2 IU/L [387-1951 IU/L] vs. 621.75 IU/L [172-857 IU/L] P < 0.05), higher gamma-glutamyl transferase levels (505.58 IU/L [376-1127 IU/L] vs. 376.75 IU/L [186-624 IU/L] P < 0.05), and had higher incidence of splenomegaly. The rate of resolution of jaundice postKasai portoenterostomy was also evidently less in CMV-positive patients. Four out of 12 patients have bilirubin >2 mg/dl at a 6-month follow-up. Conclusion: CMV-associated biliary atresia patients have delayed initial presentation and impaired jaundice clearance postKasai portoenterostomy. The role of antiviral therapy should be studied in this subset of patients.

Clinical, Biochemical, and Radiological Correlation in the Severity of Acute Pancreatitis: A Retrospective Study.

OBJECTIVES: To analyze the etiologies and the varying clinical presentations and to validate the clinical, biochemical, and radiological signs with severity and prognosis of acute pancreatitis. METHODS: A retrospective study of 1316 patients diagnosed with acute pancreatitis in an industrial hospital in Jamshedpur, Jharkhand, was conducted, and their clinicoradiological profiles, etiological factors, and outcomes were studied. RESULT: A total of 1316 cases were enrolled, out of which maximum cases (411 [31.23%]) were from the age group of 30-44 years, and the mean and median age were 44.54 and 47 years, respectively. A total of 731 (55.45%) patients had social habits (i.e., alcohol and smoking), and 585 (44.45%) patients did not have any social habits. Based on the etiology of acute pancreatitis (AP), the majority of cases were due to alcoholism (710 [53.95%]) followed by gallstone (343 [26.06%]) and idiopathic pancreatitis (217 [16.48%]). As per the severity of AP, most patients showed mild pancreatitis (937 [71.20%]) followed by moderate (312 [23.71%]) and severe pancreatitis (67 [05.09%]). Mild and moderate pancreatitis patients were shown in 85 and 28 cases, respectively, suggestive of chronic pancreatitis after repeated episodes of AP. But severe pancreatitis shown in 19 cases had hypocalcemia + shock + multi-organ dysfunction syndrome (MODS). In mild, moderate, and severe AP, the mortality rates were 19 (02.03%), 44 (14.10%), and 21 (31.34%), respectively. Overall, 1232 (93.62%) of AP cases recovered and were discharged in stable condition, but 84 (06.38%) cases expired. CONCLUSION: AP is a common cause of acute abdomen in patients presenting to the surgical emergency department. The management is mainly conservative with surgery limited to only a few selected cases, depending upon the severity of the disease.

The understated issue of caregiver anxiety for pediatric surgical hospital admissions: opening the blindfolds.

KEY MESSAGE: Hospitalization is a nerve-wrecking experience for patients and their families (Lam et al. in Int J Nurs Stud 43:535-545, 2006). The financial burden of hospitalization is the prime perpetrator, however, multiple other factors also contribute significantly to the underlying problem which can be eliminated by efforts of the doctors and other healthcare workers and by modifying the hospital policies (Bassett et al. in J Hosp Med 15:652-658, 2020). We can reduce the number of outpatient visits and switch to telemedicine for rescheduling the cases. The pre-anaesthetic clearance and all the relevant investigations can be done on a single OPD visit thereby reducing the requirement of repeated commutes to the hospital. The free of charge category of the hospital can be extended to the patient requiring prolonged hospital stay or for solid tumor patients who require repeated hospital admissions for chemotherapy. Association with child welfare Non-government organizations (NGO's) can also solve major monetary issues for parents of patients suffering from complex congenital anomalies and solid tumors. The pre-operative NPO period can be shortened to 2-4 h, antibiotic use can be completely avoided or minimized in clean elective cases, children living in the same city requiring dressing/catheter removal after a few days (e.g. hypospadias, posterior sagittal anorectoplasty) can be discharged and called for a OPD visit after 5-7 days if the parents are willing to take care of the child at home. Patients undergoing minor elective surgeries can be followed up on telemedicine visits only. Parents of patients suffering from complex congenital anomalies should be referred to a clinical psychologist and receive periodic counseling sessions. A child psychologist should also be included in the management of cases which have social stigma attached as bladder exstrophy, anorectal malformations, spina bifida requiring lifelong follow-up and bowel washes or repeated clean intermittent catheterisation. Anxiety assessment questionnaires must be incorporated in the management of chronic patients and high-risk parents must be identified (Tiedeman in J Pediatr Nurs 12:110-119, 1997). We hereby propose adoption of family centric approach during the management of a patient as this may minimize the overall burden of the hospitalization of the family. BACKGROUND: Hospital admission of a child leads to a myriad responses in the parents. Thus, we conducted a hospital-based cross-sectional study to determine the prevalence of anxiety and depression among the primary caregivers of hospitalized children and the factors causing it. METHODS: Parents of 228 children admitted in the pediatric surgery ward at a tertiary care hospital were interviewed using the HADS-A and Hamilton Anxiety Questionnaire to assess the prevalence of anxiety and depression during hospital admission. They were also subjected to a questionnaire comprising of 52 questions spread over 5 segments-demographic details, monetary burden, effect on siblings and other family members, practical problems faced, and surgery-specific concerns. FINDINGS: Thirty percent of the parents had severe anxiety and 20% developed depression due to the hospitalization of their child. We tested the association of this depression and anxiety against 56 variables in this study. Exorbitant loan amounts (ra - 0.449, rd- 0.557), repeated commute to the hospital (ra - 0.274, rd - 0.231), monetary burden (ra - 0.193, rd - 0.186), repetitive sampling (ra - 0.248, rd - 0.203), prolonged absence from work (ra - 0.440, rd - 0.424) were found to be the chief perpetrators of this anxiety and depression. INTERPRETATION: The burden of anxiety and depression in the primary caregivers of pediatric surgical patients is enormous. Identification of the implicating factors is essential. Simple reforms such as reduction in the number of OPD visits, extension of free of charge category, association with non-governmental organizations and involvement of a clinical psychologist can significantly meliorate the hospital journey of both the patients and their parents. (rd-correlation coefficient of for depression, ra-correlation coefficient of for anxiety).

Pattern of Preoperative Uroflowmetry in Hypospadias Patients and Age-matched Control Patients.

Aim: Patients with hypospadias often present with voiding difficulties after successful repairs. We sought to analyze the degree of uroflowmetric anomalies that may be present in children with hypospadias before a surgical repair. We, thus, undertook this study to compare the pattern of preoperative uroflowmetry study in hypospadias patients and a comparable age-matched control group. Materials and Methods: A total of 90 children underwent preoperative uroflowmetry in the Department of Pediatric Surgery at All India Institute of Medical Sciences (AIIMS), Jodhpur, India, between January 2019 and December 2020. Thirty patients with hypospadias and sixty age-matched controls who presented to the outpatient department without any associated urological or neurological anomalies were included in the study. Uroflowmetry parameters such as maximum urine flow rate (Qmax), average urine flow rate (Qavg), voided volume (VV), urination duration, duration of reaching maximum speed, and urine flow curves of the cases and the control group were measured and compared. Results: The median age of patients at the time of uroflowmetry in the hypospadias group was 7 years, while the same for the control group was 7.5 years. Median maximum urinary flow rates (Qmax) (10.7 vs. 14.45 mL/s, P = 0.01278), average urinary flow rates (Qavg) (6.5 vs. 8.5 mL/s, P = 0.0124), the ratio of maximum urinary flow rates with VV (Qmax/VV) (0.043 vs. 0.053, P = 0.0264) was found to be significant (P < 0.05). These values were significantly lower in the hypospadias group (P < 0.05). The voiding time (43.5 vs. 30 s, P = 0.0285) was significantly higher in the hypospadias group. However, there was no difference in the VV per micturition (219.5 vs. 270.0 mL, P = 0.40) and time to maximum flow rate (10 vs. 10, P = 0.43). Flow curve pattern analysis revealed plateau-shaped curves in 60% of the hypospadias group compared to 27% in the control group, while bell-shaped curve was seen in 37% of the hypospadias group as compared to 65% in the control group which were statistically significant (P = 0.003415). No statistically significant association was found between meatal localization and the uroflowmetry parameters. Conclusion: Children with hypospadias have abnormal uroflowmetry even before surgical correction and have a significantly low maximum urine flow rate. These uroflow anomalies may be due to meatal stenosis or hypoplastic proximal urethra. We postulate that these preoperative abnormal uroflow patterns in patients with hypospadias may contribute to voiding difficulties in repaired hypospadias cases. A greater understanding of the factors behind these uroflowmetric anomalies may allow surgeons to proactively tackle these intraoperatively, leading to better outcomes for patients with hypospadias.

The linker domain of the initiator DnaA contributes to its ATP binding and membrane association in E. coli chromosomal replication.

DnaA, the initiator of Escherichia coli chromosomal replication, has in its adenosine triphosphatase (ATPase) domain residues required for adenosine 5'-triphosphate (ATP) binding and membrane attachment. Here, we show that D118Q substitution in the DnaA linker domain, a domain known to be without major regulatory functions, influences ATP binding of DnaA and replication initiation in vivo. Although initiation defective by itself, overexpression of DnaA(D118Q) caused overinitiation of replication in dnaA46ts cells and prevented cell growth. The growth defect was rescued by overexpressing the initiation inhibitor, SeqA, indicating that the growth inhibition resulted from overinitiation. Small deletions within the linker showed another unexpected phenotype: cellular growth without requiring normal levels of anionic membrane lipids, a property found in DnaA mutated in its ATPase domain. The deleted proteins were defective in association with anionic membrane vesicles. These results show that changes in the linker domain can alter DnaA functions similarly to the previously shown changes in the ATPase domain.