Comparison of the effects of nitric oxide synthase, guanylate cyclase and potassium channel inhibition on vascular contractions in vitro in the rat

1. We have investigated the differences between the nitric oxide synthase inhibitor L-NMMA, the guanylate cyclase inhibitor methylene blue and the potassium channel blockers apamin and charybdotoxin or apamin and iberiotoxin, in their abilities to increase vasoconstrictor responses in rat small mesenteric arterial rings. 2. When administered during the maintained contraction to PGF2alpha (10 microM), L-NMMA (100 microM) or the combination of apamin (0.7 microM) and charybdotoxin (0.1 microM) significantly increased the contractile response. Methylene blue (10 microM) increased the contraction, but this did not reach significance. However, apamin (0.7 microM) and iberiotoxin (0.1 microM) also significantly increased the contractile response. 3. The combination of L-NMMA or methylene blue with apamin/charybdotoxin produced significantly greater increases in the contractile response to PGF2alpha than achieved individually. 4. Relaxations to acetylcholine (10 microM) were significantly reduced by L-NMMA or methylene blue but not by apamin in combination with charybdotoxin or iberiotoxin. 5. Since apamin/iberiotoxin had similar effects to apamin/charybdotoxin, it is likely that the actions of these agents involve direct actions on smooth muscle potassium channels rather than inhibition of endothelium-derived hyperpolarising factor (EDHF). These results suggest that endothelium-derived nitric oxide but not EDHF has a major role in modulating vascular tone under these conditions.     

Menstrual, psychosexual, psychological and somatic sequelae following postpartum sterilisation.

This study was designed to investigate the menstrual, psychosexual, psychological and somatic sequelae in a group of women who may be more prone to express regret following sterilisation. They were at a younger age, and all underwent postpartum sterilisation. The follow-up was conducted by a questionnaire between 6 months and 5 years following the procedure. Data were available from 242 patients with 76.8% before age 30, and 23.2% age 30 or older. Of all the patients, 21.9% regretted their choice of sterilisation. About one-third had various menstrual cycle disturbances. In general, patients rated their sex life more enjoyable in many aspects. The two most common psychological symptoms were irritability, nervousness and depression. The common somatic symptoms were pelvic/ abdominal pain, backache and tiredness. A complete assessment of the patient's postoperative condition, including menstrual cycle history, sexual history, psychological and somatic complaints if any, is warranted during presterilisation counselling in addition to a routine informed consent. This is especially important for those patients who are known to be more prone to express regret following the procedure.     

Segmental myoclonus as the presenting symptom of an acute disseminated encephalomyelitis: a case report.

Segmental myoclonus is described as the involuntary contractions of contiguous muscles innerved by the brain stem or by spinal cord. The underlying causes of segmental myoclonus in children are demyelinating diseases and intrinsic tumors. Here, we report a case who was presented with segmental myoclonus on his left arm and later diagnosed as atypical monosymptomatic presentation of acute disseminated encephalomyelitis (ADEM). The case represents the first in the literature in which ADEM is considered as the possible cause of segmental myoclonus. Our findings demonstrate that: (i) in focal movement disorders such as segmental myoclonus, a careful neuroradiological examination of the neuroanatomical region for the possible presence of organic lesions might be rewarding, (ii) ADEM might be one of the potentially reversible causes of myoclonus.     

Precoronary stenosis after stage I palliation for hypoplastic left heart syndrome

We report a patient with stenosis of the native ascending aorta after palliation of hypoplastic left heart syndrome and aortic atresia. We describe the approach to diagnosis, temporary support with extracorporeal membrane oxygenation, and successful surgical reintervention. Stenosis of the native ascending aorta is an important, potentially reversible cause of acute, early postoperative ventricular dysfunction.     

Ginkgo biloba extract ameliorates ischemia reperfusion-induced renal injury in rats.

There is increasing evidence to suggest that reactive oxygen metabolites (ROMs) play a role in the pathogenesis of ischemia/reperfusion injury (I/R) in the kidney. This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Ginkgo biloba extract (EGb) (50 mg kg(-1) day(-1)) or saline was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the treatment period, all rats were decapitated. Kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence (CL) assay. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Ischemia/reperfusion caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH and TNF-alpha, were elevated in the I/R group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by I/R. The findings imply that ROMs play a causal role in I/R-induced renal injury and EGb exerts renoprotective effects probably by the radical scavenging and antioxidant activities.     

Temperature-Mediated Effects on Mayaro Virus Vector Competency of Florida Aedes aegypti Mosquito Vectors

Mayaro virus (MAYV) is an emerging mosquito-borne arbovirus and public health concern. We evaluated the influence of temperature on Aedes aegypti responses to MAYV oral infection and transmission at two constant temperatures (20 °C and 30 °C). Infection of mosquito tissues (bodies and legs) and salivary secretions with MAYV was determined at 3, 9, 15, 21, and 27 days post ingestion. At both temperatures, we observed a trend of increase in progression of MAYV infection and replication kinetics over time, followed by a decline during later periods. Peaks of MAYV infection, titer, and dissemination from the midgut were detected at 15 and 21 days post ingestion at 30 °C and 20 °C, respectively. Mosquitoes were able to transmit MAYV as early as day 3 at 30 °C, but MAYV was not detectable in salivary secretions until day 15 at 20 °C. Low rates of MAYV in salivary secretions collected from infected mosquitoes provided evidence supporting the notion that a substantial salivary gland barrier(s) in Florida Ae. aegypti can limit the risk of MAYV transmission. Our results provide insights into the effects of temperature and time on the progression of infection and replication of MAYV in Ae. aegypti vectors.     

Gemcitabine and Cisplatin as Neo-Adjuvant for Cholangiocarcinoma Patients Prior to Liver Transplantation: Case-Series

Background: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. Methods: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. Results: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02–71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120–250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813–967). Overall survival was 100% (95% CI 100–100%) at both years one and two; 75% (95% CI 13–96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. Conclusions: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.     

Hyaluronic acid augmentation pharyngoplasty complicated by retropharyngeal abscess and grisel syndrome: Case report and literature review

Augmentation pharyngoplasty, in which tissue filler or grafts are used to augment the posterior nasopharynx, is an accepted option to treat velopharyngeal insufficiency. It is generally well tolerated and safe with limited side effects. In this study, we describe a case of a retropharyngeal abscess and Grisel syndrome following hyaluronic acid augmentation pharyngoplasty. Grisel syndrome is a serious condition that requires early diagnosis and prompt intervention to prevent further complications.     

Whole exome sequencing identified a novel single base pair insertion mutation in the EYS gene in a six generation family with retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) and is characterized by photoreceptor degeneration. RP is clinically and genetically heterogeneous disorder. More than 70 genes are known and, thus, identification of causative genes and mutations in known genes is challenging. This study was designed to identify the underlying genetic defect in a large extended Saudi family with multiple RP affected members. Fundus photography, Optical Coherence Tomography (OCT) and visual field perimetry were performed for affected individuals. Whole exome sequencing was used to detect the underlying genetic defect in a large family with 12 affected individuals showing autosomal recessive isolated RP. WES data analysis identified a novel insertion mutation in the EYS (eyes shut homolog) gene (c.910_911insT; p.Trp304LeufsTer8). Sanger sequencing validates the variant discovered through exome in all 12 affected individuals and showed that this mutation is segregating with RP phenotype in an autosomal recessive manner in 51 individuals of the family tested here. Our study expands the mutation spectrum of EYS gene in RP patients and extends the body of evidence that supports the importance of EYS gene in eye development.     

Forecasting the Post-Pandemic Effects of the SARS-CoV-2 Virus Using the Bullwhip Phenomenon Alongside Use of Nanosensors for Disease Containment and Cure

The COVID-19 pandemic has the tendency to affect various organizational paradigm alterations, which civilization hasyet to fully comprehend. Personal to professional, individual to corporate, and across most industries, the spectrum of transformations is vast. Economically, the globe has never been more intertwined, and it has never been subjected to such widespread disruption. While many people have felt and acknowledged the pandemic’s short-term repercussions, the resultant paradigm alterations will certainly have long-term consequences with an unknown range and severity. This review paper aims at acknowledging various approaches for the prevention, detection, and diagnosis of the SARS-CoV-2 virus using nanomaterials as a base material. A nanostructure is a material classification based on dimensionality, in proportion to the characteristic diameter and surface area. Nanoparticles, quantum dots, nanowires (NW), carbon nanotubes (CNT), thin films, and nanocomposites are some examples of various dimensions, each acting as a single unit, in terms of transport capacities. Top-down and bottom-up techniques are used to fabricate nanomaterials. The large surface-to-volume ratio of nanomaterials allows one to create extremely sensitive charge or field sensors (electrical sensors, chemical sensors, explosives detection, optical sensors, and gas sensing applications). Nanowires have potential applications in information and communication technologies, low-energy lightning, and medical sensors. Carbon nanotubes have the best environmental stability, electrical characteristics, and surface-to-volume ratio of any nanomaterial, making them ideal for bio-sensing applications. Traditional commercially available techniques have focused on clinical manifestations, as well as molecular and serological detection equipment that can identify the SARS-CoV-2 virus. Scientists are expressing a lot of interest in developing a portable and easy-to-use COVID-19 detection tool. Several unique methodologies and approaches are being investigated as feasible advanced systems capable of meeting the demands. This review article attempts to emphasize the pandemic’s aftereffects, utilising the notion of the bullwhip phenomenon’s short-term and long-term effects, and it specifies the use of nanomaterials and nanosensors for detection, prevention, diagnosis, and therapy in connection to the SARS-CoV-2.