An insight into the mechanisms of action of selected bioactive compounds against epigenetic targets of prostate cancer: implications on histones modifications.

Prostate cancer is a leading cause of morbidity and mortality among men globally. In this study, we employed an in silico approach to predict the possible mechanisms of action of selected novel compounds reported against prostate cancer epigenetic targets and their derivatives, exhausting through ADMET profiling, drug-likeness, and molecular docking analyses. The selected compounds: sulforaphane, silibinin, 3, 3'-diindolylmethane (DIM), and genistein largely conformed to ADMET and drug-likeness rules including Lipinski's. Docking studies revealed strong binding energy of sulforaphane with HDAC6 (- 4.2 kcal/ mol), DIM versus HDAC2 (- 5.2 kcal/mol), genistein versus HDAC6 (- 4.1 kcal/mol), and silibinin against HDAC1 (- 7.0 kcal/mol) coupled with improved binding affinities and biochemical stabilities after derivatization. Findings from this study may provide insight into the potential epigenetic reprogramming mechanisms of these compounds against prostate cancer and could pave the way toward more success in prostate cancer phytotherapy.

Associations of circulating dimethylarginines with the metabolic syndrome in the Framingham Offspring study.

BACKGROUND: Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively. METHODS: We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study who attended a routine examination. RESULTS: Adjusting for age, sex, smoking, and eGFR, we observed significant associations of ADMA (direct) and ARG/ADMA (inverse) with odds of MetS (N = 1461 prevalent cases; Odds Ratio [OR] per SD increment 1.13, 95%CI 1.04-1.22; and 0.89, 95%CI 0.82-0.97 for ADMA and ARG/ADMA, respectively). Upon further adjustment for waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides, we observed a positive relation between SDMA and MetS (OR per SD increment 1.15, 95% CI 1.01-1.30) but the other associations were rendered statistically non-significant. We did not observe statistically significant associations between any of the methylarginines and the risk of new-onset MetS (752 incident events) over a median follow-up of 11 years. CONCLUSION: It is unclear whether dimethylarginines play an important role in the incidence of cardiometabolic risk in the community, notwithstanding cross-sectional associations. Further studies of larger samples are needed to replicate our findings.

Managing fecal incontinence in patients with myelomeningocele in Sub-Saharan Africa: Role of antegrade continence enema (ACE).

BACKGROUND: Neural tube defects (NTDs) are among the major causes of sphincter dysfunctions. Fecal incontinence (FI) because of myelomeningocele (MMC) leads to problems with social acceptability and decreased quality of life (QOL), life satisfaction in addition to other morbidities. This is a report of experience with antegrade continence enema (ACE) in the management of FI in patients with MMC in an African set-up. MATERIALS AND METHOD: A retrospective review of 23 children and young adults with FI because of MMC managed with ACE from October 2008 to September 2015 from African Specialist Hospital. The clinical outcomes have been analyzed. RESULTS: From October 2008 to September 2015, a total of thirty-two n=32 patients underwent ACE procedure after repair of MMC associated with FI. Available data of 23 (71.87%) patients were reviewed retrospectively. Mean age at which ACE was created was 6.43±3.83years, range (3.5-17.8) years, median 5years. Follow-up after ACE creation was (0.5-6.9) years, median 2.6years. There were full continence in 13 (56.52%), partial continence in 8 (34.78%) and failure in 2 (8.69%). There were 16 (69.56%) complications and 4 (17.39%) minor post ACE surgery revisions. Mean PedQOL(™) score before ACE and then 5, 10, and 15months after ACE were 47.86±13.83, range (20.4-66.0) vs 88.34±7.11, range (77.9-98.6); p=0.000, 88.9±6.44 range (76.9-98.5); p=0.000, 89.01±6.50, range (76.9-98.88) p=0.000 respectively. Mean parental/caregiver satisfaction score for 15 (65.21%) patients aged 6years and below using modified visual analogue scale (VAS) 1 to 10 before ACE and after were 3.06±0.79, range (2-4), median 3 vs 8.0±1.30, range (5-10), median 8; (p=0.000) while 8 (34.78%) patients aged above 6years were able to assess their satisfactions score before and after ACE creation with mean of 1.75±0.70, range (1-3), median 2 vs 7.75±1.03, range (6-9) median 8; (p=0.000). CONCLUSION: ACE has satisfactory outcomes in an African set-up in patients with MMC associated with FI. Multidisciplinary approach to neurogenic FI should be encouraged in such set-ups.

Open inguinal herniotomy: Analysis of variations.

BACKGROUND: Repair of congenital groin hernia/hydrocele is the most common surgical procedure performed by paediatric surgeons. There is dearth of literature comparing the outcomes of open herniotomy in children using various surgical approaches. This study was aimed at evaluating the efficacy of open herniotomy by comparing external ring incision, hernial sac twisting and whether or not double ligation has benefit over a single suture application. MATERIALS AND METHODS: A multi-centre prospective randomised clinical trial was conducted with a total of 428 patients having congenital inguinal hernia and/or hydrocele. Patients were randomly assigned into four groups: RO (had external ring opened, hernial sac twisted and doubly ligated), ST (had hernial sac twisted and doubly ligated without opening the ring), DL (had double ligation of hernial sac without ring opening nor twisted) while SL (had single ligation of hernial sac with neither ring opening nor sac twisting). RESULTS: A total of 458 repairs were done. Patients' age ranged from 0.25 years (3 months) to 21 years in group RO with mean of 4.87 × 4.07 (median, 4), 0.069 years (24 days) to 17 years in group ST with mean of 4.23 × 4.03 (median, 3), 0.5 years (6 months) to 16 years in group DL with mean of 4.59 × 3.87 (median, 4) and 1 year to 19 years in group SL with mean of 5.00 × 4.19 (median, 4). Operation time per repair was 26.50 × 5.46 min, range 16-40 min (median, 27 min) in group RO, 22.18 × 5.34 min, range 12-39 min (median, 21 min) in group ST while 17.98 × 3.40 min with range of 12-39 min (median, 17 min) in group DL and 15.27 × 4.18 min, range 7-40 min (median, 15 min) in group SL P < 0.0001. The mean paracetamol dose/patient was 3.96 × 1.43, 2.94 × 0.81, 2.18 × 0.69, 1.87 × 0.78 in group RO, ST, DL and SL, respectively, P < 0.0001. CONCLUSION: Congenital inguinal hernia repair with opening of the external ring, hernia sac twisting and double ligation of the processus vaginalis confers no advantage.

Menace of childhood non-accidental traumatic brain injuries: A single unit report.

BACKGROUND: Childhood traumatic brain injury (TBI) has high rate of mortality and morbidity worldwide. There are dearths of reports from developing countries with large paediatric population on trauma; neurosurgery trauma of nonaccidental origin is not an exemption. This study analysed menace of non-accidental TBI in the paediatric population from our center. MATERIALS AND METHODS: This is a single unit, retrospective study of the epidemiology of non-accidental TBI in children starting from September, 2008 to March, 2014. The management outcomes of the epidemiology of the non-accidental TBI were analysed. RESULTS: Total of 109 children age range from 0 (intra-natal) to 16 years with a mean of 5.8 ± 4.6 years (median, 5 years) were enrolled into the study. 34 (31.2%) were domestic violence, 26 (23.9%) street assaults, 16 (14.7%) were due to animal assaults and mishaps, 17 (15.6%) fall from heights. Seven (6.4%) cases of collapsed buildings were also seen during the period. Four (3.7%) industrial accidents and two (1.8%) were self-inflicted injuries. There were also three (2.8%) cases of iatrogenic TBI out of which two infants (1.8%) sustained TBI from cesarean section procedure while one patient (0.9%) under general anaesthesia felt from the operation bed resulting to severe TBI. CONCLUSION: Child abuse, unprotected child labour, parental/care-givers negligence are the main cause of nonaccidental TBI. Human right activists and government agents should be incorporated in curtailing the menace.

Herniotomy in resource-scarce environment: Comparison of incisions and techniques.

BACKGROUND: There are various methods for surgical treatment of hernia and hydrocele in children with variable cost-effectiveness, recovery and cosmetic outcomes. This study analyses our experience with mini-incision/invasive herniotomy in children in resource-limited centre. MATERIALS AND METHODS: Seven hundred and eighty-four n = 784 patients underwent herniotomy via conventional and mini-invasive methods were assigned into Group A and Group B. Three hundred and seventy-six n = 376 (47.95%) in Group A while four hundred and eight n = 408 (52.04%) in Group B. Eight hundred and seventeen (817) herniotomy was performed. Demographic data, hernia/hydrocele sides, volume of surgical suture used, surgery duration, and complications analysed. RESULTS: Right side hernia and/or hydrocele were 464 (59.18%). 287 (36.60%) had left sided while 33 (4.21%) had bilateral hernia and/or hydrocele. There were 14 bilateral hernia repair in Group A and 19 in Group B. The lengths of operation time for unilateral repair ranged from 14 to 54 min in Group A (median, 23 min) and 7-44 min in Group B (median, 15 min) with a mean surgical duration of 15.48 ± 4.16 min in Group B versus 23.41 ± 5.94 min in Group A (P < 0.001) while the range of the lengths of operation time for bilateral repair in Group A was 20-54 min (median, 36) and 12-30 min (median, 21) in Group B with a mean duration of 36.35 ± 9.89 min in Group A versus 20.42 ± 4.83 min in Group B P = 0.00563. 376 sachets of 45 cm suture material were used in Group A versus 137 in Group B. There were total of 87 (23.13%) complications in Group A versus 3 (1.47%) in Group B P = 0.000513. Superficial wound infection and abscess were 9 (2.36%) and 16 (4.25%) in Group A versus none (0) in Group B. CONCLUSION: Mini-incision/invasive herniotomy in children and adolescents is fast, cost-effective with satisfactory cosmetic outcome and limited complications.

TOBACCO ABUSE AND ITS HEALTH EFFECT.

Tobacco smoking is still one of the most important risk factor for Respiratory and cardiovascular diseases and an estimated 90% of causes of lung cancer are attributable toTobacco smocking and equally 90% of peripheral vascular disease in non-diabetic population is attributable to Tobacco smoking, despite the health effect there is disturbing figures of people who take up smoking habit daily and increase level of failed quit smoking attempts. Environment and genetics still plays major role, and various forms of tobacco is used worldwide and its health consequence has been highlighted. Monitoring tobacco use and prevention policies through effective tax laws is paramount to reduction of the tobacco health effects in our environments.

Burden of congenital inguinal hernia and hydrocele in northern and southern Nigeria: an opportunity for awareness creation.

BACKGROUND: Nigeria, with a population of >150 million people in which half of the population are children encounters challenges in paediatric surgery practice in rural areas. There are paediatric surgeons in Nigeria, but majority practice in tertiary health facilities in cities. The poor rural dwellers have little or no access to such highly trained specialists. Hence, children with congenital and acquired paediatric surgical pathologies including anterior abdominal wall defects not only grow up with these diseases to adulthood, they are also exposed to various health hazards posed by unqualified personnel. Therefore, we are evaluating the burden of congenital inguinal hernia/hydrocele in northern and southern Nigeria for awareness creation and the way forward. MATERIALS AND METHODS: Data obtained from organised free hernia missions to the rural populace from northern and southern Nigeria by the West African Collage of Surgeons in 2010 and Kano State Government in 2013 was analysed. RESULTS: A total of 811 patients aged from 3 months (0.25 years) to 35 years was screened and found to have congenital hernia and/or hydrocele from the two centres. 171 (21.1%) were successfully operated, while the remaining 640 (78.9%) could not benefit from a surgical procedure during the missions. There were n = 46 (26.9%) patients with various forms of genital mutilations/and or surgical mismanagements among the operated patients. CONCLUSION: The burden of congenital anterior abdominal wall defects among Nigerian children is high. A little effort could bring succor and create awareness among this group of people.

Single-layer closure of typhoid enteric perforation: Our experience.

BACKGROUND: Typhoid enteritis is rare in developed countries. The increasing prevalence of typhoid fever with enteric perforation in our environment is alarming. Peritonitis follows enteric perforation due to typhoid enteritis. Surgical treatments and repair of the perforated areas due to typhoid enteritis varies between institutions with high mortality and morbidity. MATERIALS AND METHODS: We retrospectively studied the effects of single versus double layer intestinal closure after typhoid enteric perforation with peritonitis in 902 pediatric patients from September 2007 to April 2012. All the patients underwent laparotomy after resuscitation and antibiotic cover. The patients were divided into two groups: group A (n = 454) double layer closure and group B (n = 448) single layer closure. RESULTS: There were 554 males and 348 females with male to female ratio 1.6:1. Ages of the patients were three years to 14 years with mean age at eight years and mode at nine years. The following clinical outcomes were recorded: burst abdomen 38 (8.3%) vs 3 (0.6%), enterocutaneous fistula formation 52 (11.4%) vs 8 (1.7%), superficial wound infection 215 (47.3%) vs 91 (20.3%), ligature fistula 13 (2.8%) vs 7 (1.5%), mean length of 29.4 ± 7.8 vs 45.3 ± 11.6. CONCLUSION: Our results showed that single layer closure of the perforated ileum due to typhoid enteric perforation with peritonitis in children was effective by reducing complication rates.

Lymphoepithelial cyst of the pancreas in female children--report of two cases.

Lymphoepithelial cyst (LEC) of the pancreas is almost always reported as a case report or in small series mostly in male adult patients with vague clinical manifestations and difficult pre-operative diagnosis. Between the years 2007 and 2012, two female children with LEC of the pancreas were operated on at the Children's Surgical Unit of Murtala Mohammad Specialist Hospital, Kano in northern Nigeria. Satisfactory outcomes were achieved after distal pancreatectomy and splenectomy in one and a Whipple procedure in the other. This benign lesion of the pancreas should be considered in the differential diagnosis of cystic lesions of the pancreas in children.