Scalpel and strife: Assessing the impact of Sudan's ongoing civil war on surgical practice and healthcare delivery.

BACKGROUND: This study aims to shed light on the profound ramifications of the military conflict that started in April 2023 on surgical practice in Sudan. METHODS: This is a survey-based study. The survey link was disseminated to Sudanese medical practitioners via various social media (WhatsApp, Telegram, X (previously twitter) and Facebook) channels. We included only responses from medical practitioners working in the surgical specialities. RESULTS: A total of 90 responses have been collected. All participants were working in surgical service provision institutes. Sixty per cent of the responses were from the age group 25-35 years old, and two-thirds of the total cohort either left Sudan or was internally displaced because of the conflict. Moreover, 51% are no longer practising because they had to flee the conflict area (75%) or because the hospital is out of service (20%). There was a significant drop in the average number of emergency and elective lists. CONCLUSION: The military conflict affected Sudan's already strained health system. There was a significant drop in the average number of emergency and elective lists with surgeons out of practice because they had to flee the conflict area and hospitals were out of service.

Four years after the implementation of antimicrobial stewardship program in Jordan: evaluation of program's core elements.

Objectives: To combat antimicrobial resistance, the World Health Organization (WHO) urged healthcare organizations in Low- and Middle-Income Countries (LMICs) to implement the core elements of the antimicrobial stewardship (AMS) programs. In response, Jordan took action and developed a national antimicrobial resistance action plan (NAP) in 2017 and commenced the AMS program in all healthcare facilities. It is paramount to evaluate the efforts to implement the AMS programs and understand the challenges of implementing a sustainable and effective program, in Low-Middle Income Country (LMIC) contexts. Therefore, the aim of this study was to appraise the compliance of public hospitals in Jordan to the WHO core elements of effective AMS programs after 4 years of commencement. Methods: A cross-sectional study in public hospitals in Jordan, using the WHO AMS program core elements for LMICs was carried out. The questionnaire comprised 30 questions that covered the program's six core elements: leadership commitment, accountability and responsibility, AMS actions, education and training, monitoring, and evaluation, and reporting and feedback. A five-point Likert scale was employed for each question. Results: A total of 27 public hospitals participated, with a response rate of 84.4%. Adherence to core elements ranged from (53%) in the leadership commitment domain to (72%) for AMS procedure application (actions). Based on the mean score, there was no significant difference between hospitals according to location, size, and specialty. The most neglected core elements that emerged as top priority areas were the provision of financial support, collaboration, access, as well as monitoring and evaluation. Conclusion: The current results revealed significant shortcomings in the AMS program in public hospitals despite 4 years of implementation and policy support. Most of the core elements of the AMS program were below average, which requires hospital leadership commitment, and multifaceted collaborative actions from the concerned stakeholders in Jordan.

Hypercalcemia as a rare presentation of hyaline fibromatosis syndrome from different Sudanese families: two case reports.

BACKGROUND: Hyaline fibromatosis syndrome is a rare progressive autosomal recessive connective tissue disorder caused by a mutation in the ANTXR2/CMG2 gene. According to its severity, patients may present with skin nodules or visceral infiltration, which carries a poor prognosis. Hypercalcemia has not been reported as a presenting feature of this syndrome. Stimulation of osteoclasts by inflammatory factors and immobilization--induced hypercalcemia have played role in the pathophysiology. To our knowledge, this is the first report of hypercalcemia-associated hyaline fibromatosis syndrome. CASE PRESENTATION: Here, we describe cases of two Sudanese patients, a boy aged 9 months and a girl aged 3.5 years with hypercalcemia as an associated presenting feature of hyaline fibromatosis syndrome. Other features include gingival hypertrophy, painful joint swellings, and restriction of movement, which was misdiagnosed as juvenile rheumatoid arthritis. Workup showed normal phosphate, normal to mildly elevated parathyroid hormone, low vitamin D 25. Genetic testing confirmed the mutation of the ANTXR2/CMG2 gene. Both patients responded well to medical therapy for hypercalcemia, but one of them with the severe form of juvenile hyaline fibromatosis died due to sepsis, while the other one has maintained normocalcemic status. CONCLUSIONS: These cases highlight the rare presentation of this syndrome and reflect the importance of biopsy and genetic testing in reaching the diagnosis, especially when the clinical presentation can mimic other inflammatory bone disorders. Calcium levels should be checked in such cases.

Characterization of Hashimoto´s thyroiditis in Sudanese children: a cross-sectional study at Gaafar Ibnauf Hospital, Khartoum.

Introduction: literature on Hashimoto´s thyroiditis, the common thyroid illness in the young populations, in Sudan and Africa is scarce. We aimed to study its clinical profile and outcome among Sudanese children and adolescents. Methods: records of 73 patients were reviewed. Data related to demographics, presenting features, family history and coexistence of autoimmune diseases, physical examination findings, and biochemical progression over time were obtained. Results: patients´ mean age at the diagnosis was 10.6 ± 2.9 years, 80.8% (n = 59) of them were female and 83.6% (n = 61) were residing in iodine-sufficient areas. The commonest presenting features were thyromegaly and fatigability (79.5%, n = 58 and 43.8%, n = 32, respectively) after an illness duration of 0.5-48 months. Autoimmune comorbidities were documented in 8.2% (n = 6) of our series and more than half (53.4%, n = 39) of them were pre-pubertal at the diagnosis. Sixty point three percent (60.3%) (n = 44), 20.5% (n = 15), 13.7% (n = 10) and 5.5% (n = 4) of patients presented with overt hypothyroidism, sub-clinical hypothyroidism, euthyroidism and hyperthyroidism respectively, and there were no significant differences in the clinical profile between them. In patients' continued follow-up, 94.1% (n = 32/34) of those presented with overt hypothyroidism required levothyroxine therapy to maintain euthyroidism for 0.5-13 years, while 85.7% (n = 6/7) of those with euthyroidism remained so for 0.5-6 years. Remission was reported in all hyperthyroid patients and in only 5.9% (n = 2/34) of those with overt hypothyroidism at diagnosis. The majority of our patients with subclinical hypothyroidism were treated with levothyroxine and continued to be euthyroid for 10 months to 13 years. Conclusion: goiter was the commonest presenting feature of Hashimoto´s thyroiditis. The majority of patients had overt or subclinical hypothyroidism and almost all of them required long-term levothyroxine therapy.

Upholding Quality and Patient Safety during COVID-19 Pandemic-A Jordanian Case Study.

BACKGROUND: The advent of the COVID-19 pandemic caused a rapid increase in demand for healthcare services over a prolonged period, and the hospital emergency preparedness system has been essential. Therefore, this study aimed to explore Jordanian hospitals' response to emergency situations and examine the underlying role and effect of accreditation programs as a "Quality and Patient Safety" tool to deal with emergency situations during the pandemic. METHODS: An online survey for a cross-sectional study was conducted in Jordan between 1 March and 30 May 2022, to examine the opinions of hospitals' top, senior, and middle managers using a validated questionnaire. RESULTS: A total of 200 healthcare providers from 30 hospitals participated in the study. From the areas within accreditation standards that were investigated, capacity building on emergency preparedness and communication abilities received the least scores (2.46 and 2.48, respectively). Additionally, hospitals with mature quality and patient safety culture (>3 accreditation cycles) demonstrated a statistically significant difference in score in two domains-emergency preparedness (p = 0.027) and infection prevention and control (p = 0.024). CONCLUSIONS: During outbreaks, hospitals that are required to comply with accreditation standards that address all emergency preparedness aspects will fare better in quality performance.

Assessment of Hospital Readiness to Respond to COVID-19 Pandemic in Jordan-A Cross Sectional Study.

During the global COVID-19 pandemic, hospitals faced tremendous pressure to cope with the emergency preparedness situations needed to cater for the influx of patients while maintaining their essential services. This study aimed to assess the level of readiness of hospitals in Jordan to respond to the COVID-19 pandemic using the WHO hospital readiness checklist. A cross-sectional survey using the modified and validated checklist was conducted in Jordan between 15 May and 15 June 2021. The checklist entailed ten key response functions with a total of 60 activities. Data from 22 hospitals were collected through a structured survey process by two surveyors for each hospital. The overall readiness score of hospitals was 1.77 ± 0.20, with a lower overall score in the northern region (1.65 ± 0.24) than the middle (1.86 ± 0.07) or southern (1.84 ± 0.14) regions. The diagnosis response function scored highest (1.95); but despite efforts, contingency plan development was not met by most hospitals, with a total score ≤ 1.45. Provision of psychological support and occupational health support to ensure the wellbeing of staff scored below average. Outcomes from this survey exposed gaps while offering a framework for upcoming endeavors to improve hospital readiness for any potential pandemic.

A Novel Splice-Site Deletion in the POU1F1 Gene Causes Combined Pituitary Hormone Deficiency in Multiple Sudanese Pedigrees.

Pathogenic variants within the gene encoding the pituitary-specific transcription factor, POU class 1 homeobox 1 (POU1F1), are associated with combined pituitary hormone deficiency (CPHD), including growth hormone, prolactin, and thyrotropin stimulating hormone deficiencies. The aim of the study was to identify genetic aetiology in 10 subjects with CPHD from four consanguineous Sudanese families. Medical history, as well as hormonal and radiological information, was obtained from participants' medical records. Targeted genetic analysis of the POU1F1 gene was performed in two pedigrees with a typical combination of pituitary deficiencies, using Sanger sequencing, and whole-exome sequencing was performed in the other two pedigrees, where hypocortisolism and additional neurologic phenotypes were also initially diagnosed. In POU1F1 gene (NM_001122757.2) a novel homozygous splice-site deletion-namely, c.744-5_749del-was identified in all 10 tested affected family members as a cause of CPHD. Apart from typical pituitary hormonal deficiencies, most patients had delayed but spontaneous puberty; however, one female had precocious puberty. Severe post-meningitis neurologic impairment was observed in three patients, of whom two siblings had Dyke-Davidoff-Masson syndrome, and an additional distantly related patient suffered from cerebral infarction. Our report adds to the previously reported POU1F1 gene variants causing CPHD and emphasises the importance of genetic testing in countries with high rates of consanguineous marriage such as Sudan. Genetic diagnostics elucidated that the aetiologies of hypopituitarism and brain abnormalities, identified in a subset of affected members, were separate. Additionally, as central hypocortisolism is not characteristic of POU1F1 deficiency, hydrocortisone replacement therapy could be discontinued. Elucidation of a genetic cause, therefore, contributed to the more rational clinical management of hypopituitarism in affected family members.

Ameliorate impacts of scopoletin against vancomycin-induced intoxication in rat model through modulation of Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK signaling pathways: Molecular study, molecular docking evidence and network pharmacology analysis.

Nephrotoxicity is an indication for the damage of kidney-specific detoxification and excretion mechanisms by exogenous or endogenous toxicants. Exposure to vancomycin predominantly results in renal damage and losing the control of body homeostasis. Vancomycin-treated rats (200 mg/kg/once daily, for seven consecutive days, i.p.) revealed significant increase in serum pivotal kidney function, oxidative stress, and inflammatory biomarkers. Histologically, vancomycin showed diffuse acute tubular necrosis, denudation of epithelium and infiltration of inflammatory cells in the lining tubular epithelium in cortical portion. In the existing study, the conservative consequences of scopoletin against vancomycin nephrotoxicity was investigated centering on its capacity to alleviate oxidative strain and inflammation through streamlining nuclear factor (erythroid-derived-2) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and prohibiting the nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (p38 MAPK) pathway. With respect to vancomycin group, scopoletin pretreatment (50 mg/kg/once daily, i.p.) efficiently reduced kidney function, oxidative stress biomarkers and inflammatory mediators. Moreover, histological and immunohistochemical examination of scopoletin-treated group showed remarkable improvement in histological structure and reduced vancomycin-induced renal expression of iNOS, NF-κB and p38 MAPK. In addition, scopoletin downregulated (Kelch Like ECH Associated Protein1) Keap1, P38MAPK and NF-κB expression levels while upregulated renal expression levels of regulatory protein (IκBα), Nrf2 and HO-1. Furthermore, molecular docking and network approach were constructed to study the prospect interaction between scopoletin and the targeted proteins that streamline oxidative stress and inflammatory pathways. The present investigations elucidated that scopoletin co-treatment with vancomycin may be a rational curative protocol for mitigation of vancomycin-induced renal intoxication.

Clinical profile, etiology, and diagnostic challenges of primary adrenal insufficiency in Sudanese children: 14-years' experience from a resource limited setting.

OBJECTIVES: Primary adrenal insufficiency (PAI) in children is an uncommon condition. Congenital adrenal hyperplasia (CAH) is the commonest cause followed by autoimmune disorders. Diagnosis and management are challenging especially in resource-limited settings. Studies from Africa are scanty and here we describe for the first time the clinical presentation, possible etiologies, and challenges in diagnosis and management of PAI in a large cohort of Sudanese children. METHODS: This was a descriptive hospital-based study where all patients diagnosed with PAI between 2006 and 2020 were reviewed. The diagnosis was based on clinical presentation, low morning cortisol ± high adrenocorticotropic hormone (ACTH), or inadequate response of cortisol to synacthen stimulation. Challenges faced in diagnosis and management were identified. RESULTS: From 422 PAI suspected patients, 309 (73.2%) had CAH, and 33 (7.8%) had PAI-like symptoms and were not furtherly discussed. Eighty patients (19%) had fulfilled the study criteria: 29 had Allgrove syndrome, nine auto-immune polyendocrinopathy syndrome, seven adrenoleukodystrophy, and one had an adrenal hemorrhage. Hyperpigmentation was the cardinal feature in 75 (93.8%) while the adrenal crisis was not uncommon. Lack of diagnostic facilities has obscured the etiology in 34 (42.5%) patients. CONCLUSIONS: PAI is not uncommon in Sudanese children where genetic causes outweigh the autoimmune ones. Many cases were missed due to nonspecific presentation, lack of awareness, and difficult access to tertiary health care facilities. In addition to the clinical findings, early morning cortisol ± ACTH levels can be used in diagnosis where facilities are limited particularly synacthen stimulation test.

Challenges in diagnosis and management of neonatal hyperparathyroidism in a resource-limited country: a case series from a Sudanese family.

Neonatal hyperparathyroidism is a rare disease caused by a homozygous inactivating mutation in the calcium sensing receptor gene. It presents early in life with life threatening manifestations of hypercalcemia, if left untreated the condition may be lethal. This is the first case series reported from Sudan. Three Sudanese siblings presented with severe symptoms of hypercalcemia in the form of polyuria, failure to thrive and multiple bone fractures. Serum calcium and parathyroid hormone levels were very high with low phosphate and normal alkaline phosphatase levels. Ultrasonography and sestamibi scan were normal and did not assist in diagnosing their condition. Medical management was a great challenge due to unavailability of medications such as parentral bisphosphonates and calcimimetics. Parathyroidectomy was inevitable. Tissue biopsies revealed parathyroid hyperplasia and no adenoma. Gene sequencing revealed a homozygous missense mutation: c 2038 C T p (Arg680Cys) in two siblings, both parents were heterozygous for the same missense mutation. Our report reflects the challenges in diagnosis and management of neonatal hyperparathyroidism in resource limited countries. We also highlight the importance of genetic testing in the diagnosis and management of such cases in countries with high rates of consanguineous marriage.

Assessment of Perceived Compliance and Barriers to Personal Protective Equipment Use Among Healthcare Workers During the COVID-19 Pandemic's Second Wave Surge: "Walk to Talk" Cross-Sectional Correlational Study.

OBJECTIVE: This study aimed at investigating HCWs' perceptions of PPE compliance and barriers, as well as influencing factors, in order to develop methods to combat the rise in their infection rates. METHODS: During the 'second wave' surge, a cross-sectional correlational analysis was conducted over a 1-month period. It consists of HCWs from various hospital sectors that admit COVID-19 patients using an online self-administered predesigned tool. RESULTS: Out of the 285 recruited participants, 36.1% had previously been diagnosed with COVID-19. Around 71% received training on PPE use. The perceived compliance was good for (PPE) usage (mean 2.60 ± 1.10). A significant higher compliance level was correlated with previous diagnosis with COVID-19, working with patients diagnosed with COVID-19, and having a direct contact with a family member older than 45 years old (P < 0.01). The main perceived barriers to the use of PPEs were unavailability of full PPEs (35%), interference with their ability to provide patient care (29%), not enough time to comply with the rigors of PPEs (23.2%) and working in emergency situations (22.5%). With regards to perceived barriers, those working with patients diagnosed with COVID-19 and those who reported having a direct contact with a family member older than 45 years old showed significantly higher level of barriers. CONCLUSION: A series of measures, including prioritization of PPE acquisition, training, and monitoring to guarantee appropriate resources for IPC, are necessary to reduce transmission.

Adipsic hypernatremia in a young Sudanese child, challenges in a limited-resource setting: a case report.

Adipsia is a rare condition characterized by a lack of thirst due to a defect in specific osmoreceptors located in the hypothalamus. The disorder is characterized by failure to maintain the body's normal plasma osmolality (POSM), resulting in chronic or recurrent severe hypernatremia and dehydration. Adipsia is usually accompanied by central diabetes insipidus (DI). Isolated adipsia (without DI) is very rare, with causes ranging from congenital central nervous system malformations to acquired anterior hypothalamic lesions. The diagnosis and management of the condition are considerably challenging for both clinicians and patients/parents, especially in a resource-limited setting. We here in present the first case report of adipsia from Sudan; a young child with isolated adipsia, diagnosed after recurrent severe hypernatemic dehydration episodes. The report portrays the unique challenges in suspecting, diagnosing, and managing the condition in a limited-resource setting.

Aetiologies and clinical patterns of hypopituitarism in Sudanese children.

There is paucity of reported information regarding aetiology and clinical profile of hypopituitarism from resource-limited countries particularly in populations with high rates of consanguineous marriages. Here, we are reporting the first data on this aspect from Sudan. This is a descriptive, retrospective, hospital-based study, carried out in the two main paediatric endocrinology centres in Sudan (Gafaar Ibn Auf Paediatric Tertiary Hospital and Soba University Hospital, Khartoum) from January 2006 up to December 2014. Patients' records were reviewed for relevant demographical, clinical, hormonal and radiological data using pretested study forms. The study included 156 patients. One hundred and one patients were males (M: F = 1.8:1). The commonest age groups were adolescents (57.7%). Consanguinity was found in 77.8% of patients overall and 91% of patients with congenital aetiologies. The commonest clinical presentation was short stature (93.5%). Congenital causes (86.5%) were more prevalent than acquired causes (13.5%). There were six family clusters with multiple pituitary hormone deficiencies (MPHD) and three families with isolated growth hormone (GH) deficiency (IGHD). Most of the congenital cases with MPHD were phenotypic for PROP1 gene mutation (77.5% of sporadic cases and 50% of familial cases). Craniopharyngioma was the commonest of the acquired causes (10.2%). GH was the most frequent hormone deficient (89.7%). Abnormal Magnetic resonance imaging brain findings were significantly seen more in MPHD in comparison to IGHD. The genetic forms of hypopituitarism in populations with high rates of consanguineous marriage like Sudan may be higher than those reported internationally. Molecular genetic studies are, therefore, highly recommended.

Fanconi Bickel syndrome: clinical phenotypes and genetics in a cohort of Sudanese children.

BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by the SLC2A2 gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate. PATIENTS & METHODS: Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients. RESULTS: Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD. Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenic SLC2A2 variants in our patients, one of whom had a novel mutation. CONCLUSIONS: FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals' awareness. This is the first series to describe this condition from Sub-Saharan Africa.

Cobalt Oxide Nanoparticles/Graphene/Ionic Liquid Crystal Modified Carbon Paste Electrochemical Sensor for Ultra-sensitive Determination of a Narcotic Drug.

Purpose: Drug-abuse, namely morphine (MO) affects the metabolism of neurotransmitters such as dopamine (DA). Therefore, it is crucial to devise a sensitive sensing technique to simultaneously determine both compounds in real samples. Methods: The fabrication of the sensor is based on in situ modification of a carbon paste (CP) electrode with cobalt oxide nanoparticles, graphene, and ionic liquid crystal in presence of sodium dodecyl sulfate; CoGILCCP-SDS. The modified sensor is characterized using scanning electron microscopy, electrochemical impedance spectroscopy and voltammetry measurements. Results: Electron transfer kinetics and analytical performance of the proposed sensor were enhanced due to the synergistic role of all the modifiers. The simultaneous determination of MO and DA achieved low detection limits of 0.54 nmol L-1 and 0.25 nmol L-1, respectively. Besides, a carbon-based electrochemical sensor is fabricated for the nano-molar determination of MO in real samples and formulations. The sensor showed fouling resistance and anti-interference ability in presence of other species in human fluids. The real sample analysis of MO was successfully achieved with good recovery results in urine samples and pharmaceutical tablets. Linear dynamic range, sensitivity, detection limit and quantification limit of MO in urine were 5 nmol L-1 to 0.6 µmol L-1, 6.19 µA/µmol L-1, 0.484 nmol L-1 and 1.61 nmol L-1, respectively. Conclusion: This sensor has great ability to be extended for electrochemical applications in assaying of many drugs.

Follicular aspiration versus coasting for ovarian hyper-stimulation syndrome prevention.

OBJECTIVE: To compare follicular reduction prior to human chorionic gonadotropin (HCG) trigger and coasting in terms of ovarian hyper-stimulation syndrome (OHSS) reduction, pregnancy, and cancellation rates in in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS:  This study was designed as a prospective study. The setting was the IVF unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. A total of 39 patients undergoing IVF/ICSI cycles, who were at risk of OHSS, 20 were put into a coasting group and 19 had follicular reduction instead. This occurred between October 2010 and January 2011. Our main outcome was OHSS reduction. RESULTS: Six (30%) women developed OHSS in the coasting group and 2 (10.5%) women developed OHSS in the follicular group (p-value=0.235). The pregnancy rates in the cycles were similar for both groups: 4/20 (20%) in the coasting group and 3/19 (15.8%) in the follicular group (p-value=1.000). The cancellation rate of the cycles was similar for both groups, 6/20 (30%) in the coasting group and 1/19 (5.3%) in the follicular group (p-value=0.09). The median number of punctured follicles was significantly lower in the follicular group (16 follicles, interquartile range (IQR)=21-12) compared to the coasting group (29 follicles, IQR=37.8-19.8, p-value=0.001). The retrieved, fertilized, and cleaved oocytes, as well as the number of embryos transferred, were similar amongst both groups. CONCLUSION: There was no difference between follicular reduction prior to HCG and coasting, in terms of OHSS reduction, pregnancy, and cancellation rates in both the IVF and ICSI cycles.

Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice.

CONTEXT: Currently, the outcomes of the use of cisplatin in cancer therapy is limited by nephrotoxicity. OBJECTIVE: This study aims to investigate the nephroprotective role of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. MATERIALS AND METHODS: Adult female Wistar Albino mice were divided into eight groups (n = 8). Group I served as normal control. Groups II, III and IV received apigenin (3 mg/kg, i.p.), myricetin (3 mg/kg, i.p.) or their combination respectively, for seven days. Group V served as positive control group, received vehicles for seven days and cisplatin (7.5 mg/kg, i.p.) for three days starting at day five. Groups VI, VII and VIII received apigenin, myricetin or their combination, respectively for seven days as well as cisplatin injection for three days starting at day five. by the end of the experimental period, a biochemical study involving, nephrotoxicity markers [serum creatinine (Cr) and blood urea nitrogen (BUN)], apoptotic marker [caspase 3], inflammatory mediators [tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase I and II (COXI, COXII)] and oxidative stress biomarkers [malondialdehyde (MDA), reduced glutathione (GSH) and catalase] was conducted. In addition, renal histopathological alterations were evaluated. RESULTS: Apigenin, myricetin and their combination significantly reduced blood BUN, serum Cr, caspase-3TNF-α, IL-6, COXI and COXII, MDA levels and significantly increased GSH level and catalase activity parallel to, histopathological improvement in kidney tissues. DISCUSSION AND CONCLUSION: Apigenin and myricetin exhibited a protective and promising preventive strategy against cisplatin-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

Preoperative ripening of the cervix before operative hysteroscopy.

BACKGROUND: Hysteroscopy is an operation in which the gynaecologist examines the uterine cavity using a small telescopic instrument (hysteroscope) inserted via the vagina and the cervix. Almost 50% of hysteroscopic complications are related to difficulty with cervical entry. Potential complications include cervical tears, creation of a false passage, perforation, bleeding, or simply difficulty in entering the internal os (between the cervix and the uterus) with the hysteroscope. These complications may possibly be reduced with adequate preparation of the cervix (cervical ripening) prior to hysteroscopy. Cervical ripening agents include oral or vaginal prostaglandin, which can be synthetic (e.g misoprostol) or natural (e.g. dinoprostone) and vaginal osmotic dilators, which can be naturally occurring (e.g. laminaria) or synthetic. OBJECTIVES: To determine whether preoperative cervical preparation facilitates cervical dilatation and reduces the complications of operative hysteroscopy in women undergoing the procedure for any condition. SEARCH METHODS: In August 2014 we searched sources including the Menstrual Disorders and Subfertility Group (MDSG) Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and reference lists of relevant articles. We searched for published and unpublished studies in any language. SELECTION CRITERIA: Two review authors independently selected randomised controlled trials (RCTs) of cervical ripening agents used before operative hysteroscopy in pre- and postmenopausal women. Cervical ripening agents could be compared to each other, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were conducted independently by two review authors. The primary review outcomes were effectiveness of cervical dilatation (defined as the proportion of women requiring mechanical cervical dilatation) and intraoperative complications. Secondary outcomes were mean time required to dilate the cervix, preoperative pain, cervical width, abandonment of the procedure, side effects of dilating agents and duration of surgery. We calculated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with 95% confidence intervals ( CIs). Data were statistically pooled where appropriate. Heterogeneity was assessed using the I(2) statistic. The overall quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Nineteen RCTs with a total of 1870 participants were included. They compared misoprostol with no treatment or placebo, dinoprostone or osmotic dilators.Misoprostol was more effective for cervical dilatation than placebo or no intervention, with fewer women requiring mechanical dilatation (OR 0.08, 95% CI 0.04 to 0.16, five RCTs, 441 participants, I(2)=0%, moderate quality evidence). This suggests that in a population in which 80% of women undergoing hysteroscopy require mechanical dilatation without use of preoperative ripening agents, use of misoprostol will reduce the need for mechanical dilatation to between 14% and 39%. Misoprostol was associated with fewer intraoperative complications (OR 0.37, 95% CI 0.18 to 0.77, 12 RCTs, 901 participants, I(2)=0%, moderate quality evidence). This suggests that in a population in which 3% of women undergoing hysteroscopy experience intraoperative complications without use of preoperative ripening agents, use of misoprostol will reduce the risk of complications to 2% or less.When specific complications were considered, the misoprostol group had a lower rate of cervical laceration or tearing (OR 0.25, 95% CI 0.11 to 0.57, nine RCTS, 669 women, I(2)=0%, moderate quality evidence) or false track formation (OR 0.34, 95% CI 0.12 to 0.97, seven RCTs, 560 participants, I(2)=0%, moderate quality evidence). There was no evidence of a difference between the groups in rates of uterine perforation (0.42, 95% CI 0.13 to 1.38, seven RCTs, 455 participants, I(2)=0%, low quality evidence) or uterine bleeding (OR 0.51, 95% CI 0.10 to 2.49, four RCTs, 340 participants, I(2)=0%, low quality evidence). Some treatment side effects (mild abdominal pain, vaginal bleeding, and increased body temperature) were more common in the misoprostol group.Compared with dinoprostone, misoprostol was associated with more effective cervical dilatation, with fewer women requiring mechanical dilatation (OR 0.58; 95% CI 0.34 to 0.98; one RCT, 310 participants, low quality evidence) and with fewer intraoperative complications (OR 0.32; 95% CI 0.12 to 0.83, one RCT, 310 participants, low quality evidence). However treatment side effects were more common in the misoprostol arm.Compared to osmotic dilatation (laminaria), misoprostol was associated with less effective cervical dilatation, with more women in the misoprostol group requiring mechanical dilatation (OR 5.96, 95% CI 2.61 to 13.59, one RCT, 110 participants, low quality evidence). There was no evidence of a difference between misoprostol and osmotic dilators in intraoperative complication rates (OR 5.14, 95% CI 0.24 to 109.01, three RCTs, 354 participants, low quality evidence), with only two events reported altogether.The overall quality of the evidence ranged from low to moderate. The main limitations in the evidence were imprecision and poor reporting of study methods. AUTHORS' CONCLUSIONS: There is moderate quality evidence that use of misoprostol for preoperative ripening of the cervix before operative hysteroscopy is more effective than placebo or no treatment and is associated with fewer intraoperative complications such as lacerations and false tracks. However misoprostol is associated with more side effects, including preoperative pain and vaginal bleeding. There is low quality evidence to suggest that misoprostol has fewer intraoperative complications and is more effective than dinoprostone.There is also low quality evidence to suggest that laminaria may be more effective than misoprostol, with uncertain effects for complication rates. However the possible benefits of laminaria need to be weighed against the inconvenience of its insertion and retention for one to two days.

Plasminogen activator inhibitor-1 (PAI-1) in children and adolescents with type 1 diabetes mellitus: relation to diabetic micro-vascular complications and carotid intima media thickness.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a fast-acting inhibitor of fibrinolysis that has been linked to increase risk of thrombosis. We determined PAI-1 levels in 80 children and adolescents with type 1 diabetes (T1DM) compared with 40 healthy controls as a potential marker for micro-vascular complications and assessed the relation to carotid intima media thickness (CIMT) as a synergistic risk factor for development of atherosclerosis. METHODS: Patients were divided into 2 groups according to micro-vascular complications. Hemoglobin A1c (HbA1c), urinary albumin excretion, fasting serum lipid profile and PAI-1 levels were measured. CIMT of the common carotid artery was assessed using high resolution ultrasonography. RESULTS: PAI-1 levels were significantly elevated in the group with diabetes compared with control group (p<0.001). PAI-1 levels were also increased in patients with micro-vascular complications compared with those without (p<0.001). CIMT was significantly higher in patients, particularly those with micro-vascular complications than patients without complications or controls (p<0.001). Positive correlations were found between PAI-1 levels and random blood glucose, HbA1c, triglycerides, total cholesterol and CIMT (p<0.05). CONCLUSIONS: Increased plasma PAI-1 may be involved in the state of hypofibrinolysis in patients with T1DM leading to the occurrence of micro-vascular complications and increased risk of atherosclerosis.

Knowledge, attitude, and practices of infertility among Saudi couples.

INTRODUCTION: Infertility places a huge psychological burden on infertile couples, especially for women. Greater knowledge of the factors affecting fertility may help to decrease the incidence of infertility by allowing couples to avoid certain risk factors. The aim of our study was (1) to assess the knowledge and attitudes of infertile and fertile Saudi participants on infertility, possible risk factors, and social consequences; and (2) to determine the practices of infertile Saudi couples to promote their fertility before having them attend an in vitro fertilization (IVF) clinic. METHODS AND MATERIALS: We conducted a cross-sectional study on 277 fertile participants from outpatient clinics and 104 infertile patients from the IVF clinic at King Abdulaziz Medical City between June 24, 2012 and July 4, 2012, using a previously validated interview questionnaire. Descriptive and analytical statistics were applied with a significance threshold of P ≤ 0.05. RESULTS: A generally poor level of knowledge (59%) and a neutral attitude (76%) toward infertility were reported by participants. Mistaken beliefs commonly held by the study participants regarding the causes of infertility were Djinns and supernatural causes (58.8%), black magic (67.5%), intrauterine devices (71.3%), and contraceptive pills (42.9%). The healer/Sheikh was reported as the primary and secondary preference for infertility treatment by 6.7% and 44.2% of IVF patients, respectively. Compared with fertile patients, IVF patients were significantly less likely to favor divorce (38.5% versus 57.6%; P = 0.001) or marriage to a second wife (62.5% versus 86.2%; P < 0.001), if the woman could not have a baby. The patients with infertility had more favorable attitudes toward fertility drugs (87.5% versus 68.4%; P = 0.003) and having a test tube baby (92.4% versus 70.3%; P < 0.001). Child adoption was accepted as an option for treatment by the majority of IVF patients (60.6%) and fertile outpatients (71.5%). Alternative treatments previously practiced by the IVF patients to improve fertility include practicing Ruqia (61%), using alternative medicine (42%), engaging in physical exercise (39%), eating certain foods (22%), and quitting smoking (12%). CONCLUSION: These findings have implications for health care providers regarding the reluctance that couples experiencing fertility problems may have, at least initially, to accept some interventions required for the couple to conceive.