Postnatal Exposure to Exogenous progesterone Exacerbates the Prenatally-Induced Abnormal Sperms Production and Function in Rats / La exposición Posnatal a la Progesterona Exógena Exacerba la Producción y Función Anormales de Espermatozoides Inducidas Prenatalmente en Ratas

SUMMARY: This study aimed at clarifying the impact of long-term prenatal and postnatal exposure to exogenous progesterone on sperm production and function, relative sex organs weights, and the levels of the relevant hormones in rats. Sixty male Wistar rats were included and classified into three groups (n=20 in each). A test I group had mature rats born to dams treated with progesterone prenatally. A test II group included rats exposed to progesterone during prenatal as well as postnatal periods, and a control group had rats treated with a placebo (olive oil). The test groups revealed a significant reduction in sperm count, motility, and viability with higher abnormal forms than the control group (P< 0.05). Similarly, the test groups revealed significantly lower serum testosterone and higher FSH and LH levels (P< 0.001). Interestingly, the test II group showed pronounced sperm abnormalities, an alarming decrease in sperm viability and motility, and a significant accretion in the relative testicular weight compared to the test I group (p <0.001). Long-term (prenatal and early postnatal) treatment with synthetic progesterone hurts sperm quantity and quality, adversely affecting future male fertility.

Este estudio tuvo como objetivo aclarar el impacto de la exposición prenatal y posnatal a largo plazo a la progesterona exógena en la producción y función de los espermatozoides, el peso relativo de los órganos sexuales y los niveles de las hormonas relevantes en ratas. Sesenta ratas macho Wistar fueron incluidas y clasificadas en tres grupos (n=20 en cada uno). Un grupo de prueba I tenía ratas maduras nacidas de madres tratadas con progesterona prenatalmente. Un grupo de prueba II incluyó ratas expuestas a progesterona durante los períodos prenatal y posnatal, y un grupo de control tenía ratas tratadas con un placebo (aceite de oliva). Los grupos de prueba revelaron una reducción significativa en el recuento, la motilidad y la viabilidad de los espermatozoides con formas anormales más altas que el grupo de control (P < 0,05). De manera similar, los grupos de prueba revelaron niveles significativamente más bajos de testosterona sérica y niveles más altos de FSH y LH (P < 0.001). Curiosamente, el grupo de prueba II mostró anormalidades espermáticas pronunciadas, una disminución alarmante en la viabilidad y motilidad de los espermatozoides y una acumulación significativa en el peso testicular relativo en comparación con el grupo de prueba I (p <0.001). El tratamiento a largo plazo (prenatal y posnatal temprano) con progesterona sintética daña la cantidad y la calidad del esperma, lo que afecta negativamente la futura fertilidad masculina.

Variations of Arterial Supply of the Liver: C.T. Angiographic Study Among Sudanese Adults

Hepatobiliary surgery through laparoscopic approach is becoming a routine. Knowledge of extrahepatic arterial tree is essential for surgical and imaging procedures. Anatomical complexity is expected since the liver is developed by mergingof lobules with its separate blood supply. This makes a wide range of variations in the pattern of vascular arrangement and so reinforces the need for an accurate understanding of full spectrum of variations. This study aimed to investigate the variations in origin and distribution of extrahepatic arterial supply. Fifty volunteers (32 males and 18 females) aged 20­70 years were randomly recruited from the department of CT scan in Al Amal Hospital, Khartoum North, Sudan. The patients were already candidates for CT angiography with contrast for conditions other than hepatobiliary diseases. The reported data is related to those who accepted to participate in the study. Patients with history of hepatobiliary disease were excluded. 3D views of the scans were treated and the extrahepatic arterial tree was traced in a computer-based software. Key findings suggest that Michel's classification was considered the standard template for description ­ 76% of them showed Michel's type I classification. Types III and V constituted about 2%. About 4% of the cases were represented by types VI and IX. Other types of variations constituted about 12%. To conclude, although type I classification which describes the textbook pattern of hepatic artery distribution was significantly detected among the Sudanese population, other variants were to be considered since they are related to major arteries like aorta and superior mesenteric.

Seroprevalence of SARS-CoV-2 antibodies in the general population of Oman: results from four successive nationwide sero-epidemiological surveys.

OBJECTIVE: To assess the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Oman and longitudinal changes in antibody levels over time within the first 11 months of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This nationwide cross-sectional study was conducted as a four-cycle serosurvey using a multi-stage stratified sampling method from July to November 2020. A questionnaire was used and included demographics, history of acute respiratory infection and list of symptoms, COVID-19 contact, previous diagnosis or admission, travel history and risk factors. RESULTS: In total, 17,457 participants were surveyed. Thirty percent were female and 66.3% were Omani. There was a significant increase in seroprevalence throughout the study cycles, from 5.5% (4.8-6.2%) in Cycle 1 to 22% (19.6-24.6%) in Cycle 4. There was no difference in seroprevalence between genders, but significant differences were found between age groups. There was a transition of seroprevalence from being higher in non-Omanis than Omanis in Cycle 1 [9.1% (7.6-10.9%) vs 3.2% (2.6-3.9%)] to being higher in Omanis than non-Omanis in Cycle 4 [24.3% (21.0-27.9%) vs 16.8% (14.9-18.9%)]. There was remarkable variation in the seroprevalence of SARS-CoV-2 according to governorate. Close contacts of people with COVID-19 had a 96% higher risk of having the disease [adjusted odds ratio (AOR) 1.96, 95% confidence intervals (CI) 1.64-2.34]. Labourers had 58% higher risk of infection compared with office workers (AOR 1.58, 95% CI 1.04-2.35). CONCLUSION: This study showed a wide variation in the spread of SARS-CoV-2 across governorates in Oman, with higher estimated seroprevalence in migrants in the first two cycles. Prevalence estimates remain low and are insufficient to provide herd immunity.

Independent of Calorie Intake, Short-term Alternate-day Fasting Alleviates NASH, With Modulation of Markers of Lipogenesis, Autophagy, Apoptosis, and Inflammation in Rats.

Non-alcoholic steatohepatitis (NASH) is a worldwide health problem. Alternate-day fasting (ADF), although thought to be aggressive, has proven safety and efficacy. We aimed to evaluate the effect of short-term ADF against already established high-fat-fructose (HFF)-induced NASH, independent of the amount of calorie intake, and to study the effect of ADF on lipogenesis, apoptosis, and hepatic inflammation. Male Sprague Dawley rats were divided into two groups: (1) negative control and (2) NASH group fed on HFF for 9 weeks, and then randomized into two subgroups of either HFF alone or with ADF protocol for 3 weeks. The ADF could improve HFF-related elevation in serum lactate dehydrogenase and could decrease the mRNA expression of lipogenesis genes; acetyl CoA carboxylase, peroxisome proliferator-activated receptor γ, and peroxisome proliferator-activated receptor α; apoptotic genes caspase-3, p53, and inflammatory cyclo-oxygenase 2; and immunohistochemical staining for their proteins in liver with upregulation of LC3 and downregulation of P62 immunoexpression. Moreover, ADF ameliorated HFF-induced steatosis, inflammation, ballooning, and fibrosis through hematoxylin and eosin, Oil Red O, and Sirius Red staining, confirmed by morphometric analysis, without significant weight loss. Significant correlation of morphometric parameters with levels of gene expression was found. These findings suggest ADF to be a safe effective therapeutic agent in the management of NASH.

Can Dasatinib Ameliorate the Hepatic changes, Induced by Long Term Western Diet, in Mice?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a worldwide disease that progresses into steatohepatitis (NASH) that has no current effective treatment. This study aimed, for the first time, to investigate the effect of Dasatinib; a tyrosine kinase inhibitor showing anti-PDGFR activity with a macrophage modulating efficacy, on NASH. METHODS: NASH was induced, in C57BL/6 mice by western diet (WD). Control groups received either DMSO or Dasatinib. After 12 weeks, WD-fed mice received DMSO, Dasatinib (4 mg/kg) or Dasatinib (8 mg/kg) once daily, for four weeks. Serum was examined for ALT and lipid profile. Immunohistochemical staining for SREBP1 (lipogenesis marker), iNOS, arginase-1, CD68, CD163 (macrophage polarization markers), TGF-ß (fibrosis marker) and ASMA (a marker for activated hepatic stellate cell), hepatic mRNA expression for SREBP-1, iNOS, arginase-1, TGF-ß and PDGFA genes; and western blotting for phosphorylated PDGFR α and ß, SREBP1, iNOS, arginase-1, IL1α, COX2, TGF-ß and ASMA were performed. Liver sections were stained also for H & E, Oil red O and Sirius red. RESULTS: Dasatinib could ameliorate the WD-induced disturbance of serum ALT, lipid profile and significantly reduced hepatic expression of PDGFA, phosphorylated PDGFR α and ß, IL1α, COX2, SREBP-1, iNOS, CD68, TGF-ß and ASMA but increased expression for arginase-1 and CD163 (M2 macrophage markers). Moreover, Dasatinib reduced the steatosis, inflammation, hepatocellular ballooning, hepatic fibrosis and the high NAFLD activity scoring induced by WD. CONCLUSION: Dasatinib can prevent the progression of WD-induced NASH by attenuating lipogenesis, and inducing M2 macrophage polarization with antifibrotic activity.

Traumatic brain injury in patients screened for blood alcohol concentration based on the mechanism of injury.

INTRODUCTION: We aimed to investigate in-hospital outcomes of traumatic brain injury (TBI) based on blood alcohol concentration (BAC) and mechanism of injury (MOI). METHODS: We conducted a retrospective study for patients admitted with TBI between 2010 and 2014. Based on BAC, patients were classified into [negative (-BAC) and positive (+BAC) group]. Data were analyzed and compared according to the MOI. RESULTS: Out of 8141 trauma patients, 946 (11.6%) were diagnosed with TBI and 681 (72%) were subjected to BAC screening. One out of seven TBI was related to alcohol consumption with a mean age of 32 years. Gender, age, and Injury Severity Scores (ISS) were comparable in the two groups. However, the proportion of patients with polytrauma was significantly higher in -BAC than +BAC group regardless of the MOI except for the fall-related TBI. The median BAC was higher in fall-related followed by pedestrians and MVC victims [55 mmol/L (10-101), 49(9-71), and 31(1-69), respectively], p = 0.001. Overall hospital mortality was comparable between the two groups except for the pedestrian-related TBIs in which (+BAC) had significantly fewer mortality. CONCLUSIONS: Screening for BAC among patients with TBI increases substantially regardless of the MOI. The high BAC value in Fall-related TBI needs more attention to set appropriate preventive measures.

Functional Outcomes in Moderate-to-Severe Traumatic Brain Injury Survivors.

INTRODUCTION: We aimed to analyze the functional outcomes based on the admission characteristics in individuals with moderate-to-severe traumatic brain injury (TBI) over a 5-year period. METHODS: A retrospective cohort study was conducted to assess the cognitive, physical, and functional outcomes based on traditional and novel metrics used in potential outcome prediction. RESULTS: A total of 201 participants were enrolled with a mean age of 31.9 ± 11.9 years. Glasgow Coma Score (GCS) at emergency department did not correlate with the functional independence measure (FIM) score or Ranchos Los Amigos (RLA) scores at discharge. The absolute functional gain was significantly higher in individuals who sustained TBI with RLA 4-5 (34.7 ± 18.8 vs. 26.5 ± 15.9, P = 0.006). Participants with RLA 4-5 on admission to rehabilitation showed good correlation with the absolute FIM gain. On multivariate regression analysis, only age (odds ratio 0.96; 95% confidence interval: 0.93-0.98; P = 0.005) was found to be the independent predictor of good functional outcome. CONCLUSIONS: Initial GCS is not a predictor of functional outcome in individuals who sustained TBI. Consideration of age and development of novel functional measures might be promising to predict the outcomes in individuals with moderate-to-severe TBI.

Efficacy of prehospital administration of tranexamic acid in trauma patients: A meta-analysis of the randomized controlled trials.

OBJECTIVE: Antifibrinolytic agent tranexamic acid (TXA) has a potential clinical benefit for in-hospital patients with severe bleeding but its effectiveness in pre-hospital settings remains unclear. We conducted a systematic review and meta-analysis to evaluate whether pre-hospital administration of TXA compared to placebo improve patients' outcomes? METHODS: PubMed, MEDLINE, Cochrane Library, WHO International Clinical Trials Registry Platform, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and Google scholar databases were searched for a retrospective, prospective and randomized (RCT) or quasi-RCT studies that assessed the effect of prehospital administration of TXA versus placebo on the outcomes of trauma patients with significant hemorrhage. The main outcomes of interest were 24hour 30-day mortality and in-hospital thromboembolic complications. Two authors independently abstracted the data using a data collection form. Results from different studies were pooled for the analysis, when appropriate. RESULTS: Out of 92 references identified through the search, two analytical studies met the inclusion criteria. The effect of TXA on 24-hour mortality had a pooled odds ratio (OR) of 0.49 (95% CI 0.28-0.85), 30-day mortality OR of 0.86 (95% CI, 0.56-1.32), and thromboembolic events OR of 0.74 (95% CI, 0.27-2.07). CONCLUSION: Prehospital TXA appears to reduce early mortality in trauma patients. The pooled analysis also shows a trend toward lower 30-day mortality and reduced risk of thromboembolic events. Additional randomized controlled clinical trials are needed to determine the significance of these trends.

Clinical and Radiological Presentations and Management of Blunt Splenic Trauma: A Single Tertiary Hospital Experience.

BACKGROUND Splenic injury is the leading cause of major bleeding after blunt abdominal trauma. We examined the clinical and radiological presentations, management, and outcome of blunt splenic injuries (BSI) in our institution. MATERIAL AND METHODS A retrospective study of BSI patients between 2011 and 2014 was conducted. We analyzed and compared management and outcome of different splenic injury grades in trauma patients. RESULTS A total of 191 BSI patients were identified with a mean (SD) age of 26.9 years (13.1); 164 (85.9%) were males. Traffic-related accident was the main mechanism of injury. Splenic contusion and hematoma (77.2%) was the most frequent finding on initial computerized tomography (CT) scans, followed by shattered spleen (11.1%), blush (11.1%), and devascularization (0.6%). Repeated CT scan revealed 3 patients with pseudoaneurysm who underwent angioembolization. Nearly a quarter of patients were managed surgically. Non-operative management failed in 1 patient who underwent splenectomy. Patients with grade V injury presented with higher mean ISS and abdominal AIS, required frequent blood transfusion, and were more likely to be FAST-positive (p=0.001). The majority of low-grade (I-III) splenic injuries were treated conservatively, while patients with high-grade (IV and V) BSI frequently required splenectomy (p=0.001). Adults were more likely to have grade I, II, and V BSI, blood transfusion, and prolonged ICU stay as compared to pediatric BSI patients. The overall mortality rate was 7.9%, which is mainly association with traumatic brain injury and hemorrhagic shock; half of the deaths occurred within the first day after injury. CONCLUSIONS Most BSI patients had grade I-III injuries that were successfully treated non-operatively, with a low failure rate. The severity of injury and presence of associated lesions should be carefully considered in developing the management plan. Thorough clinical assessment and CT scan evaluation are crucial for appropriate management of BSI.

A morphological study of the dorsum sellae in human skull / Estudio morfológico del dorsum sellae en el cráneo humano

Anatomical variations in the shape and dimension of the dorsum sellae and posterior clinoid process are common. Most textbooks describe its shape as a median rectangular plate, a square plate, or a transverse ledge on a slope behind the sella turcica (hypophyseal fossa). This work aims to study the dorsum sellae of human skull. One hundred and twenty five dried adult human skulls, irrespective of age, were used for the study. Detailed features of the dorsum sellae were noted and classified into five types: crest like, thin plate, frail quadrilateral plate, heavy square plate, thick elongated plate. Fusion of the posterior and middle clinoid processes in one (unilateral) and all the clinoid processes (anterior, middle, and posterior) in three skulls (unilateral in one, bilateral in two) were also noticed. Findings are discussed in the light of the literature.

Son frecuentes las variaciones anatómicas de la forma y dimensión de dorsum sellae y de los procesos clinoides posteriores. La mayoría de los textos describen su forma como una placa rectangular mediana, una placa cuadrada, o un plano transversal en una pendiente detrás de la sella turcica (fosa hipofisaria). Este trabajo tiene como objetivo estudiar el dorsum sellae en cráneo humano. Para el estudio se utilizaron 125 cráneos humanos adultos secos, de diferentes edades. Se observaron características detalladas de dorsum sellae y se clasificaron en cinco tipos: cresta, al igual que la placa delgada, lámina cuadrilátera, placa cuadrada gruesa, placa alargada gruesa. En tres cráneos se observó fusión de la parte posterior y los procesos clinoides intermedios (unilateral) y los procesos clinoides (anterior, medio y posterior) (unilateral en uno de ellos, bilateral en dos). Los resultados se discuten en consideracion de la literatura.

Early high ratio platelet transfusion in trauma resuscitation and its outcomes.

INTRODUCTION: The optimal ratio of platelets (PLTs) to packed red blood cell (PRBC) in trauma patients requiring massive transfusion protocol (MTP) is still controversial. This report aims to describe the effect of attaining a high PLT:PRBC ratio (≥1:1.5) within 4 h postinjury on the outcomes of trauma patients receiving MTP. METHODS: Over a 24-month period, records of all adult patients with traumatic injury who received MTP were retrospectively reviewed. Data were analyzed with respect to PLT:PRBC ratio ([high-MTP ≥1:1.5] [HMTP] vs. [low-MTP <1:1.5] [LMTP]) given within the first 4 h postinjury and also between (>4 and 24 h). Baseline demographic, clinical characteristics, complications, and outcomes were compared according to HMTP and LMTP. RESULTS: Of the total 3244 trauma patients, PLT:PRBC ratio was attainable in 58 (1.2%) patients who fulfilled the inclusion criteria. The mean age was 32.3 ± 10.7 years; the majority were males (89.6%) with high mean Injury Severity Score (ISS): 31.9 ± 11.5 and Revise Trauma Score (RTS): 5.1 ± 2.2. There was no significant association between age, gender, type of injury, presenting hemoglobin, International Normalized Ratio, ISS, and RTS. The rate of ventilator-associated pneumonia (38.9% vs. 10.8%; P = 0.02) and wound infection (50% vs. 10.8%; P = 0.002) were significantly higher in the HMTP group. However, HMTP was associated with lower rate of multiple organ failure (MOF) (42.1% vs. 87.2%, P = 0.001) and mortality (36.8% vs. 84.6%, P = 0.001) within the first 30 days postinjury. CONCLUSIONS: Our study revealed that early attainment of high PLT/PRBC ratio within 4 h postinjury is significantly associated with lower MOF and mortality in trauma patients.

Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo.

Tumor necrosis factor-related apoptosis-inducing-ligand (TRAIL/Apo-2 ligand) induces apoptosis in the majority of cancer cells without appreciable effect in normal cells. Here, we report the effects of TRAIL on apoptosis in several human breast cancer cell lines, primary memory epithelial cells, and immortalized nontransformed cell lines, and we examine whether chemotherapeutic agents augment TRAIL-induced cytotoxicity in breast cancer cells in vitro and in vivo. TRAIL induced apoptosis with different sensitivities, and the majority of cancer cell lines were resistant to TRAIL. The chemotherapeutic drugs (paclitaxel, vincristine, vinblastine, etoposide, camptothecin, and Adriamycin) induced death receptors (DRs) TRAIL receptor 1/DR4 and TRAIL receptor 2/DR5, and successive treatment with TRAIL resulted in apoptosis of both TRAIL-sensitive and -resistant cells. Actinomycin D sensitized TRAIL-resistant cells through up-regulation of caspases (caspase-3, -9, and -8). TRAIL induces apoptosis in Adriamycin-resistant MCF7 cells already expressing high levels of death receptors DR4 and DR5. The pretreatment of breast cancer cells with chemotherapeutic drugs followed by TRAIL reversed their resistance by triggering caspase-3, -9, and -8 activation. The sequential treatment of nude mice with chemotherapeutic drugs followed by TRAIL induced caspase-3 activity and apoptosis in xenografted tumors. Complete eradication of established tumors and survival of mice were achieved without detectable toxicity. Thus, the sequential administration of chemotherapeutic drugs followed by TRAIL may be used as a new therapeutic approach for cancer therapy.