The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature.

Metabolic syndrome (MetS) is a prevalent and intricate health condition affecting a significant global population, characterized by a cluster of metabolic and hormonal disorders disrupting lipid and glucose metabolism pathways. Clinical manifestations encompass obesity, dyslipidemia, insulin resistance, and hypertension, contributing to heightened risks of diabetes and cardiovascular diseases. Existing medications often fall short in addressing the syndrome's multifaceted nature, leading to suboptimal treatment outcomes and potential long-term health risks. This scenario underscores the pressing need for innovative therapeutic approaches in MetS management. RNA-based treatments, employing small interfering RNAs (siRNAs), microRNAs (miRNAs), and antisense oligonucleotides (ASOs), emerge as promising strategies to target underlying biological abnormalities. However, a summary of research available on the role of RNA-based therapeutics in MetS and related co-morbidities is limited. Murine models and human studies have been separately interrogated to determine whether there have been recent advancements in RNA-based therapeutics to offer a comprehensive understanding of treatment available for MetS. In a narrative fashion, we searched for relevant articles pertaining to MetS co-morbidities such as cardiovascular disease, fatty liver disease, dementia, colorectal cancer, and endocrine abnormalities. We emphasize the urgency of exploring novel therapeutic avenues to address the intricate pathophysiology of MetS and underscore the potential of RNA-based treatments, coupled with advanced delivery systems, as a transformative approach for achieving more comprehensive and efficacious outcomes in MetS patients.

Total laparoscopic hysterectomy and bilateral salpingo-oophrectomy for stage 1 endometrial carcinoma under regional anaesthesia.

Total Laparoscopic hysterectomy is most commonly performed under general anesthesia. In elderly patients with severe medical co-morbidities and endometrial malignancy, laparoscopic surgery under general anesthesia can be hazardous. In such patients, regional anesthesia is safe, and can be the only option. We present a case of 75-year old women with severe lung fibrosis, chronic obstructive airway disease and heart failure who presented with severe post-menopausal bleeding and was diagnosed with endometrial carcinoma. She was considered unfit for general anesthesia. After multidisciplinary team meeting, the patient underwent total laparoscopic hysterectomy, bilateral salpingo-oophrectomy and peritoneal washings under regional anaesthesia. The procedure was successful and the patient was discharged 24 h later. In this case report, we demonstrate the anesthetic and surgical techniques for total laparoscopic hysterectomy under regional anesthesia. In the presence of dedicated multidisciplinary team, laparoscopic hysterectomy for endometrial carcinoma under regional anesthesia is safe and feasible.

Nurses' perceptions of the influence of leadership behaviours and organisational culture on patient safety incident reporting practices.

BACKGROUND: Patient safety is a priority for all healthcare organisations. Enhancing patient safety incident reporting practices requires effective leadership behaviours at all levels in healthcare organisations. AIM: To explore nurses' perceptions of the influence of nurse managers' leadership behaviours and organisational culture on patient safety incident reporting practices. METHOD: A descriptive, cross-sectional, correlational design was adopted with a convenience sample of 325 nurses from 15 Jordanian hospitals. RESULTS: Respondents had positive perceptions of their nurse managers' leadership behaviours and organisational culture. There was a significant positive relationship between leadership behaviours and organisational culture (r=0.423, P<0.001) and between leadership behaviours and actual incident-reporting practices (r=0.131, P<0.001). Additionally, there was a significant positive relationship between organisational culture and incident-reporting practices (r=0.250, P<0.001). CONCLUSION: Healthcare organisations must develop leaders who will foster a supportive and just culture that will enhance nurses' practice with regards to reporting patient safety incidents.

A Case Report of Hirschsprung's Disease in a Neonate: Early Detection and Review of Management.

Hirschsprung's disease is a rare disease characterized by the complete absence of ganglionic cells in the colon, thereby causing loss of peristalsis movement of the bowel. Most cases are diagnosed before the age of one. Here, we present a case of a newborn baby boy who was not feeding well and then developed a distended abdomen and began bilious vomiting. Blood mucoid stools were also observed. The diagnosis of Hirschsprung's disease was confirmed through a full-thickness rectal biopsy, and the Duhamel surgical procedure was performed as a course of treatment all within the first few days of birth. No complications were reported, and the baby was safely discharged after seven days. This case demonstrates the importance of timely treatment after prompt diagnosis due to the early recognition of the severe symptoms. Even though this disease is rare, pediatricians should be trained to recognize and treat the child to prevent further detrimental outcomes.

Efficiency analysis of primary healthcare facilities in Afghanistan.

BACKGROUND: Afghanistan's health system is unique in that primary healthcare is delivered by non-governmental organizations funded by multilateral or bilateral donors, not the government. Given the wide range of implementers providing the basic package of health services, there may be performance differences in service delivery. This study assessed the relative technical efficiency of different levels of primary healthcare services and explored its determinants. METHOD: Data envelopment analysis was used to assess the relative technical efficiency of three levels of primary healthcare facilities (comprehensive, basic, and sub-health centers). The inputs included personnel and capital expenditure, while the outputs were measured by the number of facility visits. Data on inputs and outputs were obtained from national health information databases for 1263 healthcare facilities in 31 provinces. Bivariate analysis was conducted to assess the correlation of various elements with efficiency scores. Regression models were used to identify potential factors associated with efficiency scores at the health facility level. RESULTS: The average efficiency score of health facilities was 0.74 when pooling all 1,263 health facilities, with 102 health facilities (8.1%) having efficiency scores of 1 (100% efficient). The lowest quintile of health facilities had an average efficiency score of 0.36, while the highest quintile had a score of 0.96. On average, efficiency scores of comprehensive health centers were higher than basic and sub-health centers by 0.11 and .07, respectively. In addition, the difference between efficiency scores of facilities in the highest and lowest quintiles was highest in facilities that offer fewer services. Thus, they have the largest room for improvement. CONCLUSIONS: Our findings show that public health facilities in Afghanistan that provide more comprehensive primary health services use their resources more efficiently and that smaller facilities have more room for improvement. A more integrated delivery model would help improve the efficiency of providing primary healthcare in Afghanistan.

Meckel's diverticulum causing acute intestinal obstruction: A case report and comprehensive review of the literature.

Introduction: Meckel's diverticulum is a congenital anomaly that is often detected incidentally. When it presents symptomatically, it causes painless gastrointestinal bleeding. Nevertheless, in rare instances, it can cause acute intestinal obstruction, often obscuring the true clinical picture. Case presentation: A 31-year-old male presented to the emergency department with a 24-h history of unremitting nausea, biliary emesis, abdominal distension, and absolute constipation. After ruling out the most common etiologies of acute bowel obstruction, radiological imaging was obtained and was suggestive of meckel's diverticulum. Laparoscopic meckel's diverticulectomy was performed, with the subsequent histopathological analysis confirming ectopic gastric tissue. Discussion: Meckel's diverticulum occurs consequent to incomplete obliteration of the vitelline or omphalomesenteric duct, which connects the developing intestines to the yolk sac. It is found in roughly 2% of the population, of which only about 4% may become symptomatic due to any number of complications. Specifically, small bowel obstruction (SBO) and diverticulitis secondary to ectopic gastric or pancreatic tissue are the most common presentations of symptomatic MD. Conclusion: Although relatively rare in adults, MD should be considered in the list of differentials in patients with intussusception leading to SBO, especially on a background history unremarkable for the most common etiologies causing SBO including post-operative adhesions and hernias.

Measurement and determinants of financial protection in health in Afghanistan.

BACKGROUND: Out of pocket (OOP) payments for health are significant health financing challenges in Afghanistan as it is a source of incurrence of catastrophic health expenditure (CHE) and impoverishment. Measuring and understanding the drivers and impacts of this financial health hardship is an economic and public health priority, particularly in the time of COVID-19. This is the first study that measures the financial hardship and determines associated factors in Afghanistan. METHODS: Afghanistan Living Conditions Survey data for 2016-2017 was used for this study. We calculated incidence and intensity of catastrophic health expenditure by using different thresholds ranging from 5 to 40% of total and nonfood consumption and subsequent impoverishment due to OOPs. Logistic regression was used to assess the degree to which Afghan households are protected from the catastrophic household expenditure. RESULTS: Results revealed that 32% of the population in Afghanistan incurred catastrophic health expenditure (as 10% of total consumption) and when healthcare payments are netted out of household consumption, the Afghan population live in extreme poverty ($1.9 in 2011 PPP), increased from 29 to 36%. Based on our findings from logistic regression in Afghanistan, having an educated head or being employed are protective factors from financial hardship while having a female head, an elderly member, a disabled, or a sick member are the risk factors of facing catastrophic health expenditure. Moreover, the people living in rural/nomadic areas or facing an economic shock are more likely to face catastrophic health expenditure and hence to be impoverished due to direct OOPs on health. CONCLUSIONS: The high rate of poverty and catastrophic health expenditure in Afghanistan emphasizes the need to strengthen the health financing system. Although Afghanistan has made great efforts to support households against health expenditure burden during the pandemic, households are at higher risk of poverty and financial hardship due to OOPs. Therefore, there is need for more financial and supportive response policies by providing a better and easier access to primary health services, extending to all entitlement to health services particularly in the public sector, eliminating user fees for COVID-19 health services and suspending fees for other essential health services, expanding coverage of income support, and strengthening the overall health financing system.

High plasma guanidinoacetate-to-homoarginine ratio is associated with high all-cause and cardiovascular mortality rate in adult renal transplant recipients.

L-Arginine:glycine amidinotransferase (AGAT) is the main producer of the creatine precursor, guanidinoacetate (GAA), and L-homoarginine (hArg). We and others previously reported lower levels of circulating and urinary hArg in renal transplant recipients (RTR) compared to healthy subjects. In adults, hArg emerged as a novel risk factor for renal and cardiovascular adverse outcome. Urinary GAA was found to be lower in children and adolescents with kidney transplants compared to healthy controls. Whether GAA is also a risk factor in the renal and cardiovascular systems of adults, is not yet known. In the present study, we aimed to investigate the significance of circulating GAA and the GAA-to-hArg molar ratio (GAA/hArg) in adult RTR. We hypothesized that GAA/hArg represents a measure of the balanced state of the AGAT activity in the kidneys, and would prospectively allow assessing a potential association between GAA/hArg and long-term outcome in RTR. The median follow-up period was 5.4 years. Confounders and potential mediators of GAA/hArg associations were evaluated with multivariate linear regression analyses, and the association with all-cause and cardiovascular mortality or death-censored graft loss was studied with Cox regression analyses. The study cohort consisted of 686 stable RTR and 140 healthy kidney donors. Median plasma GAA concentration was significantly lower in the RTR compared to the kidney donors before kidney donation: 2.19 [1.77-2.70] µM vs. 2.78 [2.89-3.35] µM (P < 0.001). In cross-sectional multivariable analyses in RTR, HDL cholesterol showed the strongest association with GAA/hArg. In prospective analyses in RTR, GAA/hArg was associated with a higher risk for all-cause mortality (hazard ratio (HR): 1.35 [95% CI 1.19-1.53]) and cardiovascular mortality (HR: 1.46 [95% CI 1.24-1.73]), independent of potential confounders. GAA but not GAA/hArg was associated with death-censored graft loss in crude survival and Cox regression analyses. The association of GAA and death-censored graft loss was lost after adjustment for eGFR. Our study suggests that in the kidneys of RTR, the AGAT-catalyzed biosynthesis of GAA is decreased. That high GAA/hArg is associated with a higher risk for all-cause and cardiovascular mortality may suggest that low plasma hArg is a stronger contributor to these adverse outcomes in RTR than GAA.

Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis.

Raynaud's phenomenon (RP) is often the first sign of systemic sclerosis (SSc). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SSc. Free thiol groups play a protective role against oxidative stress and may represent an attractive therapeutic target. We aimed to investigate the effects of hypothermia-induced vasoconstriction on the responsiveness of redox-related markers. Thirty participants (n = 10/group [SSc, primary Raynaud's phenomenon (PRP), healthy controls (HC)]) were included in this study. Fingertip photoelectric plethysmography was performed during a standardized cooling and recovery experiment. Venous blood was collected at four predetermined time points. Free thiols, NO-derived species (nitros(yl)ated species, nitrite, nitrate), sulfate and endothelin-1 were measured. Lower baseline concentrations of free thiols were observed in PRP and SSc patients (HC: 5.87 [5.41-5.99] µmol/g; PRP: 5.17 [4.74-5.61]; SSc 5.28 [4.75-5.80], P = 0.04). Redox-related markers remained unchanged during cooling. However, an unexpected increase in systemic free thiol concentrations was observed in all groups during the recovery phase. The response of this marker differed between groups, with a higher increase found in SSc patients (HC Δ = 1.30 [1.48-1.17]; PRP Δ = 1.04 [1.06-1.03]; SSc Δ = 1.72 [1.13-1.49], P = 0.04). NO-derived species, sulfate and endothelin-1 levels remained unchanged throughout the recovery phase. This exploratory study sheds light on the rapid responsiveness of systemic free thiol concentrations following reperfusion, which may reflect overall redox balance. The robust response to reperfusion in SSc patients suggests that reductive systems involved in this response are functionally intact in these patients.

Image-guided ureteral reconstruction using rendezvous technique for complex ureteric transection after gunshot injuries.

Management of complex ureteric transection poses a significant clinical challenge, particularly after gunshot injuries due to marked distortion of anatomy and associated tissue loss. We report two cases of total ureteric transection due to gunshot injury successfully repaired using fluoroscopy-guided rendezvous procedure and double J stent placement. This minimally invasive approach may offer a safe and effective technique to repair complete ureteral transection and obviate the need for complex surgical procedures.

Scroto-perineal hidradenitis suppurativa complicated by giant scrotal elephantiasis.

Scrotal elephantiasis has been a recognized complication of inguinal node irradiation, filarial infection, tumor involvement and surgical lymphatic destruction, but has rarely been reported in association with hidradenitis suppurativa (HS). HS, also known as acne inversa, is a chronic and often debilitating disease primarily affecting the axillae, inframammary regions and perineum. The location of the lesions may lead to social embarrassment and failure to seek medical treatment. Scroto-preineal HS complicated by scrotal elephantiasis is a distressing disease. Excisional surgery with reconstruction is the recommended treatment with a high likelihood of good outcome. We present a 38-year-old male patient with long-standing scroto-perineal HS complicated by giant scrotal elephantiasis.

Iatrogenic brain foreign body.

We describe a case of an adult patient admitted following severe head injury. His condition necessitated the insertion of intracranial pressure monitoring catheter for brain protection management. When the initial crisis was settled, the ICP catheter was gently removed. However after extracting the catheter it was noted that a considerable part of the tip was missing. Plain X-ray of skull confirmed the presence of radio-opaque fragment inside the brain tissue. The patient needed drainage operation within one week of the episode when the catheter fragment was removed with complete recovery. The aim of this paper is to review the literature and to present warning notes on the untoward effects of iatrogenic brain foreign body.

Evaluation of aetiology and efficacy of management protocol of epistaxis.

BACKGROUND: Epistaxis is one of the commonest medical emergencies. It affects all age groups and both sexes. The cause may be local or systemic but in majority it is spontaneous and idiopathic. Trauma is considered to be a major aetiological factor. Various treatment protocols are utilized to control epistaxis derpending upon the type, severity and cause of bleeding. METHODS: This descriptive study was designed to evaluate the aetiology and efficacy of management protocol of epistaxis in a tertiary care setting. 313 patients underwent prospective evaluation by consultant and non-consultant doctors with considerable experience in Ear, Nose & Throat (ENT) emergencies management. Standard principles were followed in the management. RESULTS: This study demonstrated a bimodal distribution with incidence peaks in below 25 years & above 50 years of age. Males were affected twice more than the females (2.15:1.04). Anterior nasal bleeding was noted in majority of the patients. Anterior nasal packing was the most effective method of controlling anterior epistaxis. While posterior bleeding was controlled by posterior nasal packing with Foley's catheter. The most common cause was found to be trauma, followed by hypertension. CONCLUSION: It may be concluded from this study that epistaxis is the most common ENT emergency, affecting all age groups. It has a bimodal age presentation and affects males twice more than females. Anterior bleeding is more common than posterior bleeding. Epistaxis may be controlled with chemical/electro-cautery if the bleeding point is visible. In case of failure to localize or access a bleeding point or profuse bleeding, anterior nasal packing can effectively control majority of epistaxis. Foley's catheter is a good option that can be used for posterior nasal packing. Gelfoam may be used for controlling epistaxis in cases of bleeding disorders, when there is mucosal ooze.

Intravesical immunotherapy for superficial bladder cancer.

OBJECTIVE: To compare and evaluate the efficacy and tolerance of intravesical instillation of Bacillus Calmette-Guerin (BCG) and interferon alpha-2b immunotherapy for superficial transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Thirty-five patients with superficial TCC of the urinary bladder, primary and recurrent tumors, stage Ta, T1, and grade 1 and 2, were prospectively enrolled for intravesical immunotherapy at the Armed Forces Hospital, Riyadh, Kingdom of Saudi Arabia between January 1992 and December 2000. The treatment regimes used were either 120 mg of BCG weekly for 6 weeks followed by a 2nd 6 week course given only on first tumor recurrence, or 50 million i.u. of interferon alpha-2b weekly for 3 months, bi-weekly for the next 3 months and monthly for 6 months. Twenty-two patients received BCG and 13 received interferon alpha-2b. Adequate blood counts, renal and hepatic function profiles, and informed consent were required. Cystoscopy was repeated every 3 months for the first 2 years, then 6 monthly for another 2 years and then yearly. RESULTS: The follow-up period ranged from 9-96 months (median 31.33 months). Twenty patients attended the follow-up and were evaluable in the BCG group and 13 in the interferon alpha-2b group. In the BCG versus interferon alpha-2b group, the rates of complete response were 80% and 41.6%, partial response were 5% and 33.3%, and progression were 15% and 8.3%. Mild side effects occurred in 5 patients and all of them completed their treatments. There was only one cancer related death in each group after 6 and 7 years of starting the treatment. CONCLUSION: Bacillus Calmette-Guerin was confirmed as a more effective intravesical immunotherapy for superficial TCC of the urinary bladder as compared to interferon alpha-2b. Both agents' treatments are well tolerated.