Muslim perspectives on palliative care in perinatal and neonatal patients: a mini-review.

Muslims comprise nearly a quarter of the worldwide population, with significant populations in the United States, Canada, and Europe. As clinicians, it is important to be familiar with Islamic religious and cultural perspectives on medical treatment, life-prolonging measures and comfort and palliative care, but historically, this has been a gap in the literature. Recently, there have been multiple papers discussing Islamic bioethics, particularly in regards to end of life care in adults; however, there has been a lack of literature discussing the Islamic perspective on issues related to neonatal and perinatal end of life care. This paper uses clinical scenarios to review key relevant principles of Islamic law, discussing the primary and secondary sources used in formulating fatawa, including the Quran, hadith, qiyas, and 'urf, and the importance of preservation of life and upholding of human dignity (karamah). Neonatal and perinatal scenarios are used to specifically explore the Islamic perspective on withholding and withdrawal of life-sustaining measures and determining what constitutes an acceptable quality of life. In some Islamic cultures the expertise of the patient's physician is given significant weight in making these judgments, and as such, families may appreciate frank assessment of the situation by the clinical team. Because of the various factors involved in issuing religious ruling, or fatwa, there is a wide spectrum of opinions on these rulings, and physicians should be aware of these differences, seek counsel and guidance from local Islamic leaders, and support families in their decision-making process.

The protective effect of 7-hydroxycoumarin against cisplatin-induced liver injury is mediated via attenuation of oxidative stress and inflammation and upregulation of Nrf2/HO-1 pathway.

Cisplatin (CIS) is an effective chemotherapy against different solid cancers. However, the adverse effects, including hepatotoxicity, limit its clinical use. 7-hydroxycoumarin (7-HC) possesses antioxidant and hepatoprotective activities, but its protective effect against CIS hepatotoxicity has not been investigated. This study evaluated the effect of 7-HC on liver injury, oxidative stress (OS), and inflammation provoked by CIS. Rats received 7-HC (25, 50, and 100 mg/kg) orally for 2 weeks followed by intraperitoneal injection of CIS (7 mg/kg) at day 15. CIS increased serum transaminases, alkaline phosphatase (ALP), and bilirubin and provoked tissue injury accompanied by elevated reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO). Liver nuclear factor (NF)-κB p65, inducible NO synthase (iNOS), pro-inflammatory cytokines, Bax, and caspase-3 were upregulated, and antioxidant defenses and Bcl-2 were decreased in CIS-treated rats, while 7-HC prevented liver injury and ameliorated OS, inflammatory and apoptosis markers. In addition, 7-HC enhanced nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase (HO)-1 in CIS-administered rats and in silico studies revealed its binding affinity toward HO-1. In conclusion, 7-HC protected against CIS hepatotoxicity by mitigating OS and inflammatory response and modulating Nrf2/HO-1 pathway.

Apigenin Attenuates Hippocampal Microglial Activation and Restores Cognitive Function in Methotrexate-Treated Rats: Targeting the miR-15a/ROCK-1/ERK1/2 Pathway.

Microglial activation underpins the methotrexate (MTX)-induced neurotoxicity; however, the precise mechanism remains unclear. This study appraised the potential impact of apigenin (Api), a neuroprotective flavonoid, in MTX-induced neurotoxicity in rats in terms of microglial activation through targeting the miR-15a/Rho-associated protein kinase-1 (ROCK-1)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Male Sprague Dawley rats were randomly divided into 4 groups: Normal control (saline i.p. daily and i.v. on days 8 and 15); Api control (20 mg/kg, p.o.) daily for 30 days; MTX-alone (75 mg/kg, i.v.) on days 8 and 15, then four i.p. injections of leucovorin (LCV): 6 mg/kg after 18 h, then three doses (3 mg/kg) every 8 h post-MTX; and Api co-treated (20 mg/kg/day, p.o.) throughout the model for 30 days, with administration of MTX and LCV as in group 3. MTX administration elevated hippocampal ionized calcium-binding adaptor protein-1 (Iba-1) immunostaining, indicating microglial activation. This was accompanied by neuroinflammation, oxidative stress, and enhanced apoptosis manifested by elevated hippocampal interleukin-1ß, malondialdehyde, and caspase-3, and decreased reduced glutathione levels. Concurrently, abated miR-15a expression, overexpression of its target ROCK-1, diminished downstream ERK1/2 and cAMP response element-binding protein (CREB) phosphorylation, and decreased hippocampal brain-derived neurotrophic factor (BDNF) levels were observed. Api mitigated the MTX-induced neurotoxicity by reversing the biochemical, histopathological, and behavioral derangements tested by novel object recognition and Morris water maze tests. Conclusively, Api lessens MTX-induced neuroinflammation, oxidative stress, and apoptosis and boosts cognitive function through inhibiting microglial activation via modulating the miR-15a/ROCK-1/ERK1/2/CREB/BDNF pathway. Graphical abstract showing the effects of methotrexate and apigenin co-treatment in MTX-induced neurotoxicity model. On the left, methotrexate (MTX) administration to rats resulted in hippocampal miR-15a downregulation, which triggered an enhanced expression of its target ROCK-1, consequently inhibiting the downstream ERK1/2/CREB/BDNF pathway, instigating a state of microglial activation, neuroinflammation, oxidative stress, and apoptosis. On the other hand, apigenin (Api) co-treatment restored miR-15a, inhibited ROCK-1 expression, and activated the ERK1/2/CREB/BDNF pathway, leading to diminished hippocampal microglial activation, neuroinflammation, and apoptosis, and restoration of the redox balance, along with improvement in memory and cognitive function of the MTX-treated rats.

Association of Advanced Lipoprotein Subpopulation Profiles with Insulin Resistance and Inflammation in Patients with Type 2 Diabetes Mellitus.

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years; HbA1c, 8.66 ± 1.60%; mean body mass index, 35.15 ± 6.65 kg/m2). Plasma lipoprotein particles number and size were determined by nuclear magnetic resonance spectroscopy. Associations of different lipoprotein subpopulations with lipoprotein insulin resistance (LPIR) score and glycoprotein acetylation (GlycA) were assessed using multi-regression analysis. In stepwise regression analysis, VLDL and HDL large particle number and size showed the strongest associations with LPIR (R2 = 0.960; p = 0.0001), whereas the concentrations of the small VLDL and HDL particles were associated with GlycA (R2 = 0.190; p = 0.008 and p = 0.049, respectively). In adjusted multi-regression analysis, small and large VLDL particles and all sizes of lipoproteins independently predicted LPIR, whereas only the number of small LDL particles predicted GlycA. Conventional markers HbA1c and Hs-CRP did not exhibit any significant association with lipoprotein subpopulations. Our data suggest that monitoring insulin resistance-induced changes in lipoprotein subpopulations in T2DM might help to identify novel biomarkers that can be useful for effective clinical intervention.

7-hydroxycoumarin modulates Nrf2/HO-1 and microRNA-34a/SIRT1 signaling and prevents cisplatin-induced oxidative stress, inflammation, and kidney injury in rats.

The kidneys are vulnerable to toxicity and acute kidney injury (AKI) is the main adverse effect associated with the clinical use of the chemotherapeutic agent cisplatin (CIS). Oxidative stress and inflammation are implicated in CIS nephrotoxicity. In this study, the effect of the antioxidant 7-hydroxycoumarin (7-HC) against CIS-induced renal intoxication was evaluated. Rats received 7-HC (25, 50, and 100 mg/kg) orally for 14 days and CIS (7 mg/kg) at day 15, and samples were collected 3 days after CIS administration. CIS increased serum urea, creatinine and kidney injury molecule (Kim)-1, caused multiple histopathological changes and increased renal reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO), NF-κB p65, iNOS, and pro-inflammatory cytokines. 7-HC dose-dependently prevented kidney dysfunction and tissue injury and suppressed ROS and inflammatory mediators. 7-HC boosted renal antioxidants and Bcl-2 while decreased Bax and caspase-3 expression in CIS-administered rats. In addition, 7-HC downregulated Keap-1 and microRNA-34a and upregulated Nrf2, NQO-1, HO-1, and SIRT1. Molecular docking revealed the binding affinity of 7-HC towards NF-κB, Keap-1, and SIRT1. In Conclusion, 7-HC prevented CIS nephrotoxicity by attenuating tissue injury, oxidative stress, inflammation, and apoptotic cell death. The protective efficacy of 7-HC was associated with inhibiting NF-κB and Keap-1, and modulating Nrf2/HO-1 and microRNA34a/Sirt1 signaling.

The potential use of urinary transferrin, urinary adiponectin, urinary Retinol Binding Protein, and serum zinc alpha 2 glycoprotein levels as novel biomarkers for early diagnosis of diabetic nephropathy: A case-control study.

BACKGROUND AND AIMS: The level of albuminuria is used to evaluate diabetic nephropathy (DN). However, to detect or predict the early stages of DN, better biomarkers are needed. METHODS: This study is a case-control observational study. 80 Egyptians participated in the study: 60 patients with type 2 diabetes mellitus (T2DM) were divided into three groups (20 patients each), and 20 healthy subjects with matched age and gender were used as controls. Demographic and laboratory data were analyzed. An enzyme-linked immunosorbent assay was used to determine the levels of four biomarkers of DN; urinary adiponectin (ADP), urinary transferrin, serum Zinc Alpha 2 Glycoprotein (ZAG), and urinary Retinol Binding Protein (RBP). RESULTS: The levels of DN biomarkers urinary ADP, transferrin, RBP, and serum, ZAG were significantly higher in patients with T2DM than in controls. The ROC curve of the validity of the simultaneous use of all four biomarkers in predicting albuminuria indicates a sensitivity of 90% and a specificity of 90%. The Area Under the Curve (AUC) was 0.948, the 95% confidence interval was 0.998-0.897, and the p-value was 0.001. CONCLUSIONS: In patients with T2DM, urine adiponectin, transferrin, RBP, and serum ZAG concentration may be useful biomarkers in the early diagnosis of DN. A further longitudinal prospective study is required to explore the potential utility of these biomarkers.

Necrostatin-1 mitigates renal ischaemia-reperfusion injury - time dependent - via aborting the interacting protein kinase (RIPK-1)-induced inflammatory immune response.

The recently defined necroptosis process participates in the pathophysiology of several tissue injuries. Targeting the necroptosis mediator receptor-interacting protein kinase (RIPK1) by necrostatin-1 in different phases of ischaemia-reperfusion injury (IRI) may provide new insight into the protection against renal IRI. The rat groups included (n = 8 in each group): 1) Sham; 2) Renal IRI; 3) Necrostatin-1 treatment 20 min before ischaemia induction in a dose of 1.65 mg/kg/intravenous; 4) Necrostatin-1 injection just before reperfusion; 5) Necrostatin-1 injection 20 min after reperfusion establishment; and 6) drug injection at both the pre-ischaemia and at reperfusion time in the same dose. Timing dependent, necrostatin-1 diminished RIPK1 (p < 0.001), and aborted the necroptosis-induced renal cell injury. Necrostatin-1 decreased the renal chemokine (CXCL1), interleukin-6, intercellular adhesion molecule (ICAM-1), myeloperoxidase, and the nuclear factor (NFκB), concomitant with reduced inducible nitric oxide synthase (iNOS), inflammatory cell infiltration, and diminished cell death represented by apoptotic cell count and the BAX/Bcl2 protein ratio. In group 6, the cell injury was minimal and the renal functions (creatinine, BUN and creatinine clearance) were almost normalised. The inflammatory markers were diminished (p < 0.001) compared to the IRI group. The results were confirmed by histopathological examination. In conclusion, RIPK1 inhibition ameliorates the inflammatory immune response induced by renal IRI. The use of two doses was more beneficial as the pathophysiology of cell injury is characterised.

Effects of bee venom and dopamine-loaded nanoparticles on reserpine-induced Parkinson's disease rat model.

Parkinson's disease (PD) is a progressive chronic neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. Current PD therapeutic strategies are mainly symptomatic and can lead to motor complications overtime. As a result, alternative medicine may provide an effective adjuvant treatment for PD as an addition to or as a replacement of the conventional therapies. The aim of this work was to evaluate the effects of Bee Venom (BV) and dopamine (DA)-loaded nanoparticles in a reserpine-induced animal model of PD. After inducing PD with reserpine injection, different groups of male rats were treated with L-Dopa, BV, DA-nanoparticles. Our findings showed that BV and DA-nanoparticles administration restored monoamines, balanced glutamate/GABA levels, halted DNA fragmentation, decreased pro-inflammatory mediators (IL-1ß and TNF-α), and elevated anti-inflammatory mediators (PON1) and neurotropic factor (BDNF) levels in comparison with conventional therapy of PD. Furthermore, in a reserpine-induced PD rat model, the ameliorative effects of BV were significantly superior to that of DA-nanoparticles. These findings imply that BV and DA-nanoparticles could be useful as adjuvant treatments for PD.

Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer.

miRNAs, a group of short noncoding RNAs, are key regulators of fundamental cellular processes and signaling pathways. Dysregulation of miRNA expression with known oncogenic or tumor suppressor functions has been associated with neoplastic transformation. Numerous studies have reported dysregulation of miRNA-141, miR-181b1, and miR-23b in a wide range of malignancies, including breast cancer. To the best of our knowledge, no previous study had demonstrated the expression of miR-141-3p, miR-181b1-5p, and miR-23b-3p in different histological grades and molecular subtypes of breast cancer. Here, we identified differential expression of these three miRNAs in breast cancer tissues compared with benign breast fibroadenomas. In addition, high expression levels of miR-141-3p and miR-181b1-5p are strongly associated with aggressive breast carcinomas. We also confirmed the clinical potential of using the three miRNAs individually or combined as diagnostic and prognostic markers in breast cancer. Using bioinformatics analyses, we identified 23 hub genes of these three miRNAs which are involved in key signaling pathways in breast cancer. Furthermore, the KM plotter online database analysis demonstrates the association between elevated expression of miR-141 and miR-181b and shorter overall survival of breast cancer patients. Together, our data suggest an oncogenic role of the studied miRNAs and highlight their molecular roles and potential clinical applications in breast cancer.

Thoracic esophageal rupture during sleeve gastrectomy: a case report with successful laparoscopic transhiatal repair.

While laparoscopic sleeve gastrectomy (LSG) is one of the most common bariatric procedures for morbid obesity, the rate of complications is decreasing. These complications include hemorrhage and gastric leak that are considered life threatening. The esophageal complications in the form of perforation or rupture during LSG are rare and mainly because of iatrogenic reasons, such as blind, unguided instrumentation, which include the bougie (commonly used for gastric calibration during LSG). These complications are potential life threatening. The detection and management of these complications can affect the outcome and minimize the morbidity and avoid the incidence of mortality. We report a case of 38-year-old female, with a body mass index of 42 with iatrogenic rupture of distal and thoracic part of esophagus for >10-cm length during LSG and the immediate full laparoscopic transhiatal primary repair.

Bochdalek hernia with retrocardiac spleen - Diagnostic dilemma for emergency care physicians-A case report.

INTRODUCTION: Physicians working as first-level responders in emergency departments (ED) often encounter patients, of any age group with shortness of breath (SOB). Definitive diagnosis is quite challenging once the underlying pathology is rare and unusual and/or the ED physicians recommend and rely on non-specific investigations. PRESENTATION OF CASE: A 29-year-old female presented to the emergency department with sudden onset of shortness of breath and upper abdominal pain radiating to the left shoulder. Diagnosis of Bochdalek hernia was made clinically coupled with radiological findings of CXR and computed tomography (CT) by the surgeon on-call, while it was missed by an emergency care physician on her first visit. DISCUSSION: Herniation of the abdominal contents into the thoracic cavity via the Bochdalek opening, commonly known as Bochdalek hernia is seen and diagnosed most commonly accidentally in early life. Adult cases of symptomatic Bochdalek hernia has been reported in the literature. These patients usually present with non-specific symptoms, thus pose a diagnostic challenge for an emergency care physician. CONCLUSION: The report of this case highlights the notion that such rare causes of acute onset dyspnea and upper abdominal pain pose a diagnostic challenge for novice emergency care physicians especially in situations where he/she does not ask for second-line help in general and recommend and rely on a non-specific investigation in specific.

Chlorhexidine-alcohol versus povidone-iodine for skin preparation before elective cesarean section: a prospective observational study.

Introduction: The ideal antiseptic agent for skin preparation before elective cesarean section (CS) is not yet determined. The aim of the study was to assess the impact of skin preparation by chlorhexidine-alcohol compared with povidone-iodine before elective CS on the rate of surgical site infection (SSI).Materials and methods: This prospective observational study included a total of 1424 pregnant women at term who were candidates for the elective CS and were divided into two equal groups of 712 patients in each, group 1 (chlorhexidine-alcohol group) and group 2 (povidone-iodine group). Patients were followed up at 1 week and 1 month postoperative to determine the rate of SSI.Results: The rate of SSI was 3.7% (26 patients) in the chlorhexidine-alcohol group compared with 4.6% (33 patients) in the povidone-iodine group (odds ratio: 0.7798, 95% CI: 0.46-1.3, p = .35), nine patients in the chlorhexidine-alcohol group, and 10 patients in the povidone-iodine group required resuturing (odds ratio: 0.9, 95% CI: 0.36-2.2, p = .82). Four patients (0.56%) in the chlorhexidine-alcohol group and five patients (0.7%) in the povidone-iodine group developed endometritis (p = .74). The rate or readmission because of SSI was 2.7% (19 patients) in the chlorhexidine-alcohol group and 2.9% (21 patients) in the povidone-iodine group (p = .75).Conclusions: Skin preparation with either chlorhexidine-alcohol or povidone-iodine resulted in comparable rates of SSIs. Accordingly, both are suitable antiseptic agents for skin preparation before elective CS.

Myocardial infarction due to coronary steal caused by a congenital unilateral absence of the right pulmonary artery: a rare case.

A 27-year-old male patient presented with symptoms that mimic an acute coronary syndrome and associated with significant myocardial perfusion ischaemic defects. The latter was detected by adenosine stress Tc-99m estamibi single photon emission CT. However, subsequently the CT angiogram revealed a normal coronary arteries outline and calibre with prominent coronary artery collaterals filling the distal branches of the absent right pulmonary artery.

Variables affecting initial stability of impaction grafting for hip revision.

Impaction grafting allows restoration of bone stock in hip revision, but there are reports of massive early subsidence. The aim of this study was to determine prognostic factors for stem and cup migration in a group of 56 consecutive patients followed up from 1 to 5 years. Cup and stem migration was correlated with 13 predictors including stem design, stem positioning, femoral anatomy, patient characteristics, and bone graft density. All migration occurred mainly during the first 3 months after surgery. Stem alignment changed by an average of 4.8 degrees . Fifty percent of the change in stem alignment was explained by four variables: age, femoral diameter, stem design, and density of the graft at the tip of the stem. Stem subsidence averaged 2.7 mm, and cup migration averaged 3.0 mm. None of the predictors explained the wide variation of migration of the cup or distal migration of the stem. It may be necessary to determine implant stability at the time of surgery.