Therapeutic enhancing potential of piracetam with diethylstilbestrol in prevention of grand-mal seizures in rats: inhibition of PI3K/Akt/mTOR signaling pathway and IL-1ß, IL-6, TNF-α cytokines levels.

OBJECTIVE: Epilepsy, a neurodegenerative disorder, continues to throw challenges in the therapeutic management. The current study sought to ascertain if the therapeutic interactions between piracetam and diethylstilbestrol may prevent grand-mal seizures in rats. MATERIALS AND METHODS: Piracetam (PIR; 10 and 20 mg/kg) and diethylstilbestrol (DES; 10 and 20 mg/kg) alone as a low-dose combination were administered to rats for 14 days. The electroshock (MES; 180 mA, 220 V for 0.20 s) was delivered via auricular electrodes on the last day of treatment and rats were monitored for convulsive behavior. To elucidate the mechanism, hippocampal mechanistic target of rapamycin (mTOR) and interleukin (IL)-1ß, IL-6 and tumor necrotic factor-alpha (TNF-α) levels were quantified. Hippocampal histopathology was conducted to study the neuroprotective effect of drug/s. In vitro studies and in silico studies were conducted in parallel. RESULTS: To our surprise, the low dose of the combination regimen of PIR (10 mg/kg) and DES (10 mg/kg) unfolded synergistic anti-seizure potential, with brimming neuroprotective properties. The mechanism could be related to a significant reduction in the levels of hippocampal mTOR and proinflammatory cytokines. The docking scores revealed higher affinities for phosphatidylinositol 3-kinase (PI3K) in co-bound complex, and when docking DES first, while better affinities for protein kinase B (Akt) were revealed when docking PIR first (both drugs bind cooperatively as well). This indicated that the entire PI3K/Akt/mTOR signaling pathway is intercepted by the said combination. In addition, the % of cell viability of HEK-293 cells [pre-exposed to pentylenetetrazol (PTZ)] was increased by 327.29% compared to PTZ-treated cells (toxic control; 85.16%). CONCLUSIONS: We are the first to report the promising efficacy of the combination (PIR 10 mg/kg + DES 10 mg/kg) to restrain seizures and epileptogenic changes induced by electroshock by a novel mechanism involving inhibiting the PI3K/Akt/mTOR signaling.

The effects of probiotic Lactobacillus acidophilus and/or prebiotic mannan oligosaccharides on growth performance, nutrient utilization, blood metabolites, faecal bacteria, and economics of crossbred calves.

Background: The ban on antibiotics as growth promoters paved the way for probiotics and prebiotics as growth promoters in animal production. Aims: The present study was conducted to evaluate the effect of probiotic Lactobacillus acidophilus and/or prebiotic Mannan oligosaccharides on growth performance, blood biochemical variables, and faecal bacterial count in crossbred calves. Methods: Fifteen-day-old crossbred calves (n=24) were divided into four groups, each consisting of six calves, and subjected to different experimental diets. The control group (T0) received a basal diet without any additives. The T1 and T2 groups received the basal diet and the probiotic (L. acidophilus, 2 × 1010 cfu/g) @ 1 g/calf per day and prebiotic (Mannan oligosaccharide) @ 4 g/calf per day, respectively. Calves of the T3 group were offered a basal diet and synbiotic (L. acidophilus, 0.5 g + Mannan oligosaccharide, 2 g/calf per day). The feed additives were mixed in milk. Results: The results of 90 days feeding trial showed that calves of the T3 and T1 groups had higher (P<0.05) body weight (BW) gain and dry matter digestibility than the control. Feeding the probiotic showed a positive effect (P<0.05) on body length at the first, second, and third months, compared to the control. The blood serum total protein and globulin concentrations in the T1 group, on days 30 and 90, and T3 group, on day 90, were higher (P<0.05) than those of the control. All the treatment groups (T1, T2, and T3) showed a reduction (P<0.05) in faecal coliform and E. coli count, compared to the control, on the 15th and 30th days of the study. Additionally, the T2 group showed a significant coliform count reduction on days 45 and 60 of the study. Conclusion: The dietary addition of L. acidophilus, 2 × 1010 cfu/g @ 1 g/calf per day and the combination of L. acidophilus, 0.5 g + Mannan oligosaccharide, 2 g/calf per day improved growth performance, serum biochemical values, and favourable gut microbiota.

Identifying individuals with multiple non-communicable disease risk factors in Kenya: a latent class analysis.

OBJECTIVES: Non-communicable diseases (NCDs) are the leading causes of death globally. In Kenya, the number of deaths resulting from NCDs is projected to surpass malaria and tuberculosis by 2030. Studies in Kenya show increasing NCDs; the aim of the present study is to examine the clustering of NCDs and risk factors in Kenya. STUDY DESIGN: This is a cross-sectional study using data from the 2015 Kenya STEPwise Survey. METHODS: This study examined relationships between NCDs (e.g. obesity, hypertension and diabetes) and health behaviours (e.g. sedentary activity, and fruit and vegetable consumption). Survey probability weights, which estimated the sampling design effect, were applied to consider the sampling units, and stratifications were used during sampling so that the results could be generalisable to the national adult Kenyan population. In total, 4350 adults were included in the study sample. RESULTS: Overall, 24.43% of participants were classified as having hypertension, 1.88% as having type 2 diabetes, and 27.94% were classified as being overweight or obese. The best-fit model was a four-class solution. Class 1 is best described as 'young with high NCD risk' and had the highest sedentary activity. Class 2 is best described as 'poor rural with lower NCD risk' with a high chance of smoking and alcohol consumption. Class 3 is best described as 'rural with high NCD risk' and had the highest fruit and vegetable consumption. Class 4 is best described as 'wealthy young urban dwellers with high NCD risk' with a high chance of alcohol consumption and smoking. Individuals in Class 4 had the highest chance (40%) of being overweight/obese, a 2% chance of type 2 diabetes and a 23% chance of having hypertension. CONCLUSIONS: NCDs are clustered in groups with high-risk behaviours. The group with the highest chance of having NCDs also had the highest chance of engaging in high-risk behaviours. The findings of this study suggest that smoking and alcohol consumption increase NCD risk in rural areas. Tailored and targeted interventions are needed to curb the increasing NCD prevalence in Kenya.

Mathematical modelling on COVID-19 transmission impacts with preventive measures: a case study of Tanzania.

The outbreak of COVID-19 was first experienced in Wuhan City, China, during December 2019 before it rapidly spread over globally. This paper has proposed a mathematical model for studying its transmission dynamics in the presence of face mask wearing and hospitalization services of human population in Tanzania. Disease-free and endemic equilibria were determined and subsequently their local and global stabilities were carried out. The trace-determinant approach was used in the local stability of disease-free equilibrium point while Lyapunov function technique was used to determine the global stability of both disease-free and endemic equilibrium points. Basic reproduction number, R0 , was determined in which its numerical results revealed that, in the presence of face masks wearing and medication services or hospitalization as preventive measure for its transmission, R0=0.698 while in their absence R0=3.8 . This supports its analytical solution that the disease-free equilibrium point E0 is asymptotically stable whenever R0<1 , while endemic equilibrium point E∗ is globally asymptotically stable for R0>1 . Therefore, this paper proves the necessity of face masks wearing and hospitalization services to COVID-19 patients to contain the disease spread to the population.

Initial Mapping of the New York City Wastewater Virome.

Bacteriophages are abundant members of all microbiomes studied to date, influencing microbial communities through interactions with their bacterial hosts. Despite their functional importance and ubiquity, phages have been underexplored in urban environments compared to their bacterial counterparts. We profiled the viral communities in New York City (NYC) wastewater using metagenomic data collected in November 2014 from 14 wastewater treatment plants. We show that phages accounted for the largest viral component of the sewage samples and that specific virus communities were associated with local environmental conditions within boroughs. The vast majority of the virus sequences had no homology matches in public databases, forming an average of 1,700 unique virus clusters (putative genera). These new clusters contribute to elucidating the overwhelming proportion of data that frequently goes unidentified in viral metagenomic studies. We assigned potential hosts to these phages, which appear to infect a wide range of bacterial genera, often outside their presumed host. We determined that infection networks form a modular-nested pattern, indicating that phages include a range of host specificities, from generalists to specialists, with most interactions organized into distinct groups. We identified genes in viral contigs involved in carbon and sulfur cycling, suggesting functional importance of viruses in circulating pathways and gene functions in the wastewater environment. In addition, we identified virophage genes as well as a nearly complete novel virophage genome. These findings provide an understanding of phage abundance and diversity in NYC wastewater, previously uncharacterized, and further examine geographic patterns of phage-host association in urban environments.IMPORTANCE Wastewater is a rich source of microbial life and contains bacteria, viruses, and other microbes found in human waste as well as environmental runoff sources. As part of an effort to characterize the New York City wastewater metagenome, we profiled the viral community of sewage samples across all five boroughs of NYC and found that local sampling sites have unique sets of viruses. We focused on bacteriophages, or viruses of bacteria, to understand how they may influence the microbial ecology of this system. We identified several new clusters of phages and successfully associated them with bacterial hosts, providing insight into virus-host interactions in urban wastewater. This study provides a first look into the viral communities present across the wastewater system in NYC and points to their functional importance in this environment.

Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer.

BACKGROUND: A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. METHODS: Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. RESULTS: PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. CONCLUSIONS: This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.

Awareness, treatment, and control of diabetes in Bangladesh: a nationwide population-based study.

OBJECTIVES: To examine awareness, treatment, and control of diabetes mellitus among the adult population in Bangladesh. METHODS: The study used data from the 2011 nationally representative Bangladesh Demographic and Health Survey (BDHS). The BDHS sample is comprised of 7,786 adults aged 35 years or older. The primary outcome variables were fasting blood glucose, diagnosis, treatment, and control of diabetes. Multilevel logistic regression models were used to identify the risk factors for diabetes awareness. RESULTS: Overall, age-standardized prevalence of diabetes was 9.2%. Among subjects with diabetes, 41.2% were aware of their condition, 36.9% were treated, and 14.2% controlled their condition. A significant inequality in diabetes management was found from poor to wealthy households: 18.2% to 63.2% (awareness), 15.8% to 56.6% (treatment), and 8.2% to 18.4% (control). Multilevel models suggested that participants who had a lower education and lower economic condition were less likely to be aware of their diabetes. Poor management was observed among non-educated, low-income groups, and those who lived in the northwestern region. CONCLUSIONS: Diabetes has become a national health concern in Bangladesh; however, treatment and control are quite low. Improving detection, awareness, and treatment strategies is urgently needed to prevent the growing burden associated with diabetes.

A Case of Recurrent Respiratory Papillomatosis Successfully Removed Via Endoscopic Argon Plasma Coagulation (APC) With No Evidence of Recurrence.

Recurrent respiratory papillomatosis (RRP) is a benign disease caused by the human papilloma virus (HPV), characterized by the formation of recurrent, epithelial neoplastic lesions in the airways. While benign, they can cause significant airway obstruction in some cases. Difficulties in treatment arise from the recurrent nature of the lesions despite repeated procedures. Other known procedures that result in deep tissue damage also cause unacceptable collateral damage to the underlying airway mucosa. We describe a case of recurrent papillomatosis that was successfully treated with argon plasma coagulation ( APC) when laser and electrocautery ablation had failed in the past. After the papillomatasis was treated with APC, there is no recurrence on repeat scope at 4 months and 9 months after the initial procedure. The procedure was done as a day case and there is no complication from the procedure. The property of the APC that allows it to cause only superficial thermal damage to the tissue makes it a suitable adjunct therapy to the treatment of papillomas, which are usually superficial lesions.

Revision cartilage cell transplantation for failed autologous chondrocyte transplantation in chronic osteochondral defects of the knee.

The management of failed autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI) for the treatment of symptomatic osteochondral defects in the knee represents a major challenge. Patients are young, active and usually unsuitable for prosthetic replacement. This study reports the results in patients who underwent revision cartilage transplantation of their original ACI/MACI graft for clinical or graft-related failure. We assessed 22 patients (12 men and 10 women) with a mean age of 37.4 years (18 to 48) at a mean of 5.4 years (1.3 to 10.9). The mean period between primary and revision grafting was 46.1 months (7 to 89). The mean defect size was 446.6 mm(2) (150 to 875) and they were located on 11 medial and two lateral femoral condyles, eight patellae and one trochlea. The mean modified Cincinnati knee score improved from 40.5 (16 to 77) pre-operatively to 64.9 (8 to 94) at their most recent review (p < 0.001). The visual analogue pain score improved from 6.1 (3 to 9) to 4.7 (0 to 10) (p = 0.042). A total of 14 patients (63%) reported an 'excellent' (n = 6) or 'good' (n = 8) clinical outcome, 5 'fair' and one 'poor' outcome. Two patients underwent patellofemoral joint replacement. This study demonstrates that revision cartilage transplantation after primary ACI and MACI can yield acceptable functional results and continue to preserve the joint.

Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy.

BACKGROUND: The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia. METHODS: This cross-sectional study included 53 paediatric patients aged 3-12 years old, who were diagnosed with either acute lymphoblastic leukaemia or acute myelogenous leukaemia and were undergoing chemotherapy treatments (induction or consolidation phase). Patients were matched for sex, age (±6 months) and ethnicity with healthy children as controls. Weight, height, body mass index, waist circumference, mid-upper arm circumference, triceps skinfold thickness, mid-upper arm muscle area and fat area were determined. Dietary intake was assessed using 3-day food records. RESULTS: Anthropometric variables were generally higher among patients compared to controls, although the differences were not statistically significant (P > 0.05). The prevalence of overnutrition among patients according to body mass index-for-age, waist circumference-for-age, mid-upper arm circumference-for-age and triceps skinfold-for-age were 24.5%, 29.1%, 17.0% and 30.2%, respectively. Mean energy [5732 ± 1958 kJ (1370 ± 468 kcal) versus 6945 ± 1970 kJ (1660 ± 471 kcal), P < 0.01], protein (50.0 ± 19.7 g versus 62.3 ± 22.3 g, P < 0.01) and fat (43.6 ± 18.9 g versus 58.3 ± 16.7, P < 0.001) intakes of patients were significantly lower than controls. CONCLUSIONS: The prevalence of being overweight and obesity in children with acute leukaemia was higher despite lower energy intake compared to controls. Studies assessing physical activity, the complex interaction and the effects of treatment drugs are warranted to better manage malnutrition among paediatric patients.

An unusual cause of confusion and hyponatraemia in an elderly patient.

A large proportion of patients presenting on the acute medical take are frail and elderly and a significant proportion of these will have symptoms such as confusion, reduced mobility and electrolyte disturbances. These symptoms are typically attributed either to the iatrogenic effects of prescribed medications, disturbances in fluid balance and possible infective causes. We describe the case of a gentleman who presented with delirium, reduced mobility and hyponatraemia who was subsequently found to have pituitary failure secondary to pituitary apoplexy.

Predominance of G to A codon 12 mutation K-ras gene in Dukes' B colorectal cancer.

INTRODUCTION: K-ras gene mutations in codons 12 and 13 are one of the earliest events in colon carcinogenesis. METHODS: DNA was extracted from 25 mg of tumour tissue (n = 70) that were taken from tumour mass and pairs with normal epithelial tissue distant from the tumour of colorectal cancer patients. Exon 1 and exon 2 of the K-ras gene were amplified. Hotspot mutations were detected using polymerase chain reaction-based single-strand conformation polymorphism method and confirmed by direct DNA sequencing analysis. RESULTS: Mutations were identified in 14 out of the 70 (20%) colorectal carcinoma tissues. Single-base transition from GGT to GAT (glycine to aspartate) in codon 12 was detected in nine samples, while three samples presented with GGC to GAC transition in codon 13. Patients with large adenoma had a 12-fold higher likelihood of K-ras mutations (odds ratios [OR] 12.31; 95% confidence intervals [CI] 1.81-83.76). Tumours located at the left colon were more likely to present with K-ras mutations (OR 4.54; 95% CI 0.96-21.54). CONCLUSION: Our study showed a high frequency of G to A transition of codon 12 mutation of the K-ras gene, with significant correlation with tumour size and tumour location.

Parenting Stress in Childhood Leukaemia

Parenting stress is the stress level experienced within the role of a parent (HoekstraWeebers et al. 1998). The source of stressors is variable and dependent on the phase of disease and chemotherapy (Sawyer et al. 2000). Failure to cope with these stressors may in turn affect the child’s emotional and social adjustment towards the diagnosis of cancer in addition to poor medical treatment adherence behaviour(Sawyer et al. 1993). The objectives of this study are to determine the level of parenting stress, the risk factors contributing to high parenting stress, and the coping mechanisms used to handle the stress. This single centred, cross-sectional study was done amongst 117 parents at the Paediatric Haematology and Oncology Unit, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) over two years duration. Self-administered questionnaires comprising the Parenting Stress Index/Short Form (PSI/SF) and Coping Inventory for Stressful Situation (CISS) were distributed to parents of children who were 12 years old and below. The mean total parenting stress score amongst parents of children diagnosed with acute leukaemia was 91.5±21.1(95%CI). A total of 27.3% of parents experienced a high total parenting stress score(defined as total PSI score ≥ 75th centile, ie ≥ 103). Task-oriented coping mechanism was used by the majority of parents. Emotion-oriented coping mechanism was the only identifiable risk factor for high parenting stress score following multiple logistic regression analysis. A parent who used emotion-oriented coping mechanism was 7.1 times (95% Confidence Interval 1.2 to 41.4) more likely to have a high parenting stress score compared to a parent who used other coping mechanisms. By identifying these at-risk parents, appropriate counselling and psychological support may be offered early to alleviate the stress as well as assist in the coping and adjustment mechanisms of these parents.

Contrecoup injury in patients with traumatic temporal bone fracture.

OBJECTIVE: To study the prevalence and patterns of contrecoup injury in traumatic temporal bone fracture cases. METHOD: A prospective, cohort study was undertaken of all patients with traumatic head injury admitted to a tertiary referral hospital in Malaysia within an 18-month period. High resolution computed tomography scans of the brain and skull base were performed in indicated cases, based on clinical findings and Glasgow coma score. Patients with a one-sided temporal bone fracture were selected and subsequent magnetic resonance imaging performed in all cases. Contrecoup injury incidence, type, severity and outcome were recorded. RESULTS: Of 1579 head injury cases, 81 (5.1 per cent) met the inclusion criteria and were enrolled in the study. Temporal bone fractures were significantly associated with intracranial injuries (p < 0.001). The incidence of a contrecoup injury in cases with temporal bone fracture was 13.6 per cent. Contrecoup injury was significantly associated with petrous temporal bone fracture (p < 0.01). The commonest contrecoup injury was cerebral contusion, followed by extradural haematoma and subdural haematoma. CONCLUSION: Contrecoup injury is not uncommon in cases of temporal bone fracture, and is significantly associated with petrous temporal bone fracture.

The influence of birth spacing on child survival in Bangladesh: a life table approach.

In this paper we have attempted to demonstrate the relationship between birth spacing and child survival in Bangladesh using data from the 2004 Bangladesh Demographic Health Survey (BDHS). We used standard life table techniques to estimate the probability of child survival and appropriate spacing of births. Logistic regression models were used to investigate the covariates, along with the birth interval that has significant influence on child survival. Study results showed that the probability of child survival was much lower when the preceding birth interval was less than 12 months, and it may be also impeded by a higher birth interval. Child survival probability was highest for a preceding birth interval of 5 years; thereafter, the probability declined. Results of the logistic regression model clearly showed that preceding birth interval was an important and strongly significant factor in explaining infant and child mortality. While education, current age, breastfeeding status and birth order were substantial and highly significant factors both in infant and child mortality, socio-economic factors such as occupation and socio-economic status showed a significant effect only on child mortality. Postponing another child (for a birth interval of 5 years and above) and proper spacing of births would have a noticeable effect in reducing the level of mortality.

Coronary artery to pulmonary artery fistulae with multiple aneurysms: radiological features on dual-source 64-slice CT angiography.

Coronary artery fistula is a rare vascular anomaly in which there is abnormal communication between the coronary artery and the great vessels or cardiac chambers. We report the case of a 66-year-old man with two separate coronary artery to pulmonary artery fistulas (one of which demonstrated multiple aneurysms), which were diagnosed on dual-source 64-slice coronary CT and reconfirmed by coronary catheter angiography.

Overexpression of WNT2 and TSG101 genes in colorectal carcinoma.

Colorectal carcinoma (CRC) arises as a result of mutational activation of oncogenes coupled with inactivation of tumour suppressor genes. Mutations in APC, K-ras and p53 have been commonly reported. In a previous study by our group, the tumour susceptibility gene 101 (TSG101) were found to be persistently upregulated in CRC cases. TSG101 was reported to be closely related to cancers of the breast, brain and colon, and its overexpression in human papillary thyroid carcinomas and ovarian carcinomas had previously been reported. The wingless-type MMTV integration site family member 2 (WNT2) is potentially important in the Wnt/beta-catenin pathway and upregulation of WNT2 is not uncommon in human cancers. In this study, we report the investigation for mutation(s) and expression pattern(s) of WNT2 and TSG101, in an effort to further understand their role(s) in CRC tumourigenesis. Our results revealed no mutation in these genes, despite their persistent upregulation in CRC cases studied.

Emergency obstetric hysterectomy in a university hospital: A 25-year review.

Over the past 25 years, 43 peripartum hysterectomies were performed at the authors' institution, an incidence of 0.64/1,000 deliveries; 31 procedures followed caesarean section and 12 were performed for haemorrhage following vaginal delivery. The common indications for hysterectomy were abnormal placentation (39.5%), uterine atony (23.3%), uterine rupture (23.3%), and haemorrhage during caesarean section (11.6%). The risk factors for hysterectomy included advancing maternal age and parity, previous caesarean section scars and abnormal placentation. Subtotal hysterectomy was performed in 72.1% cases which appeared a quicker and safer procedure than total hysterectomy in desperately ill patients. Five (11.6%) maternal deaths occurred in the series. Mortality was associated with massive haemorrhage. With rising caesarean section rates worldwide, MRI and colour Doppler sonography is useful to diagnose antepartum placenta accreta/bladder involvement in order to plan elective surgery that is associated with reduced maternal morbidity and mortality. Early decision to perform an emergency hysterectomy is essential before the patient's condition deteriorates, besides availability of an experienced obstetrician to undertake a technically demanding operation.