Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa

Background: The mortality of severe dengue infections is approximately 23%. In the management of dengue shock syndrome (DSS), aggressive fluid resuscitation is recommended. The primary objective of our study was to assess the factors associated with 30-day mortality in DSS patients. Methods: Adult patients >18 years old, who were admitted with DSS were included. DSS was diagnosed in patients who required vasopressors or had lactic acidosis >4 mmol/L. Patients were divided into three different groups based on cumulative fluid balance at death or extubation: group I (<3.5 L), group II (3.5–8.0 L), and group III (>8.0 L). Results: A total of 135 patients with DSS was included, with an overall 30-day mortality of 74.8%. The average Sequential Organ Failure Assessment (SOFA) score on intensive care unit admission was 12.2. Mechanical ventilation was required in 112 patients (83.0%), with 61 patients (45.2%) being intubated without a noninvasive ventilation trial. Respiratory failure was the most common reason for requiring intubation (65 patients, 48.2%). In survivors, the median cumulative fluid balance was 1,493 ml (interquartile range [IQR], 0–4,501 ml), whereas that in the mortality group was 7,797 ml (IQR, 3,700–13,600 ml). On multivariate analysis, SOFA score (odds ratio [OR], 1.220; 95% CI, 1.011–1.472; P=0.038) and having received >8.0 L cumulative fluid balance (OR, 6.682; 95% CI, 1.808–24.689; P=0.004) were associated with increased risk of mortality. Conclusions DSS patients have high mortality rates. High SOFA scores and >8.0 L cumulative fluid balance may indicate worse outcomes.

Purpose: Limited data exist regarding outcome and morbidity associated with portosystemic shunts in the pediatric transplant population. Our study assesses the outcomes of pediatric patients who underwent a portosystemic shunt procedure, both with and without liver transplantation (LT). Methods: This study retrospectively reviewed the medical records of pediatric patients aged 0–19 years who underwent shunt placement between 2003 and 2017 at a tertiary care center.The analysis included cases of shunt placement with or without LT. Results: A total of 13 pediatric patients were included in the study with median age of 8.8 years. Among the cases, 11 out of 13 (84.6%) underwent splenorenal shunt, 1 (7.7%) underwent a mesocaval shunt, and another 1 (7.7%) underwent a Modified Rex (mesoportal) shunt. Additionally, 5 out of 13 (38.5%) patients had LT, with 4 out of 5 (80.0%) receiving the transplant before shunt placement, and 1 out of 5 (20.0%) receiving it after shunt placement.Gastrointestinal bleeding resulting from portal hypertension was the indication in all cases.A total of 10 complications were reported in 5 patients; the most common complication was anemia in 3 (23.1%) patients. At the most recent follow-up visit, the shunts were functional without encephalopathy, and no deaths were reported. Conclusion Shunt placement plays a crucial role in the management of patients with portal hypertension. Our study demonstrates favorable long-term outcomes in pediatric patients who underwent shunt placement. Long term shunt outcomes were similar and unremarkable in patients with LT and without LT.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.
Humans ; Male ; Consanguinity ; Pakistan ; Infertility, Male/metabolism* ; Semen/metabolism* ; Sperm Tail/metabolism* ; Spermatozoa/metabolism* ; Flagella/pathology* ; Mutation

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
Asthenozoospermia/pathology* ; Dyneins/genetics* ; Homozygote ; Humans ; Male ; Microtubule-Associated Proteins ; Mutation ; Mutation, Missense ; Sperm Tail/metabolism*

BACKGROUND: Lancashire Fire and Rescue Service (LFRS), the subject of this evaluative research document employs 1400 people. 80% of employees are operational firefighters and officers whom operate across a range of duty systems and support functions, providing prevention, protection and emergency response to the communities of Lancashire. METHODS: The overarching purpose of this epidemiological study is to assess the prevalence of post-traumatic stress disorder (PTSD) amongst operational LFRS personnel and to analyse the effects upon those who may be suffering from it, whether brought about by a single traumatic event or by repeated exposure to traumatic occurrences over a period of time. A combination of primary and secondary research was carried out. Primary data was collated using two recognised clinical questionnaires and statistical analysis was conducted with the aid of the software package SPSS. RESULTS: The findings and statistical analysis showed that out of the 100 people surveyed, 30% of respondents had signs of probable distress. Of this quota, 4% showed symptoms of PTSD. The study considers how an organisation can recognise and manage PTSD and provides recommendations to assist in better recognising and managing the associated risks. CONCLUSION: Based upon the findings, the authors conclude that the level of PTSD within LFRS is slightly lower than those found in other studies undertaken within the Fire and Rescue Service sector. The paper provides recommendations for future studies and a series of actions for consideration by LFRS senior management to improve PTSD support services for employees.
Emergencies ; Epidemiologic Studies ; Firefighters ; Fires* ; Humans ; Prevalence ; Stress Disorders, Post-Traumatic* ; Surveys and Questionnaires

Objective To evaluate the antihyperglycemic potential of Tamarix aphylla (T. aphylla) leaves in STZ–NIC induced diabetes in Wister Albino rats. Methods Acute toxicity study was done to check the toxicity of T. aphylla (L. Karst) methanol extract. T. aphylla leaves extract was administered intraperitoneally (100 mg, 250 mg and 400 mg/kg body weight per day) to diabetic Wister rats for 21 days. The various parameters were studied including fasting blood glucose levels, haemoglobin and glycosylated haemoglobin. Results The treatment groups with the extract at three dose levels expressively abridged the intensities of blood glucose and Glycosylated Haemoglobin. The earlier detected reduced level of plasma haemoglobin of the diabetic rats was raised to near normalcy with treatment of extract. Conclusions The results of the current study confirm that the leaves extract of T. aphylla are nontoxic and have antidiabetic nature.

BACKGROUND: Spinal anesthesia with bupivacaine, typically used for elective and emergency cesarean section, is associated with a significant incidence of hypotension resulting from sympathetic blockade. A variety of dosing regimens have been used to administer spinal anesthesia for cesarean section. The objective of this study was to compare the incidence of hypotension following two different fixed dosing regimens. METHODS: This was a randomized double-blind clinical trial with a two-sided design, 5% significance level and 80% power. After approval of the hospital ethics review committee, 60 patients were divided randomly into two groups. In one group, the local anesthetic dose was adjusted according to height and weight, and in the other, the dose was adjusted according to height only. RESULTS: Sixty women with a singleton pregnancy were included. Of the factors that could affect dose and blood pressure, including age, weight, height, and dose, only height differed between the groups. Mean heart rate was similar between the groups. Hypotension was significantly more frequent with dosage based on height alone than with two-factor dose calculation (56.7% vs. 26.7%; P = 0.018). CONCLUSIONS: Adjusting the dose of isobaric bupivacaine to a patient's height and weight provides adequate anesthesia for elective cesarean section and is associated with a decreased incidence and severity of maternal hypotension and less use of ephedrine.
Advisory Committees ; Anesthesia ; Anesthesia, Spinal* ; Anesthetics, Local ; Blood Pressure ; Body Height ; Body Weight ; Bupivacaine ; Cesarean Section* ; Emergencies ; Ephedrine ; Ethics, Institutional ; Female ; Heart Rate ; Humans ; Hypotension ; Incidence ; Pregnancy

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.
Adult ; Antioxidants ; metabolism ; Biomarkers ; blood ; China ; Dengue ; classification ; diagnosis ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin M ; metabolism ; Male ; Middle Aged ; Young Adult

BACKGROUND/AIMS: Approximately one-third of non-erosive reflux disease (NERD) patients are refractory to proton pump inhibitors (PPI) and face a therapeutic challenge. Therefore, it is important to differentiate between pathological and non-pathological reflux utilizing multichannel intraluminal impedance-pH (MII-pH) to analyze symptom-reflux association and diagnose true NERD versus hyper-sensitive esophagus (HE) and functional heartburn (FH). Herein, we evaluated the diagnostic yield of MII-pH in refractory NERD and sub-classified it based on quantity and quality of acid/non-acid reflux and reflux-symptom association. METHODS: Sixty symptomatic NERD patients on twice daily PPI for > 2 months were prospectively evaluated by MII-pH. Distal and proximal refluxes, bolus exposure time (BET), esophageal acid exposure time, symptom index (SI) and symptom association probability (SAP) were measured. RESULTS: Thirty-two (53%) patients had BET > 1.4% (MII-pH positive-true NERD), while 28 (47%) had BET < 1.4% (MII-pH negative NERD) where SI and SAP were negative in 15/60 (25%; categorized as FH) and SI or SAP were positive in 13/60 (22%; identified as HE). Thirty-eight (63%) patients reported significant SI or SAP parameters where > 80% of symptoms were associated with non-acid reflux. The number of distal refluxes in true NERD versus FH or HE were significantly different, but not between FH and HE. CONCLUSIONS: Approximately 60% of refractory PPI NERD patients had positive reflux-symptom association, primarily due to non-acid reflux. Nearly half of NERD patients on PPI had normal MII-pH monitoring, sub-divided further into FH and HE equally.
Esophagus ; Heartburn ; Humans ; Prospective Studies ; Proton Pump Inhibitors