Anticonvulsant and procognitive properties of Novel Histamine H3 Receptor Antagonists in male adult rats

To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic and procognitive drugs, aromatic ether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models in male adult rats having phenytoin (PHT) and valproic acid (VPA) as the reference antiepileptic drugs, pitolisant (PIT) as the standard H3R antagonist/inverse agonist, and donepezil (DOZ) as a reference procognitive drug. Among the H3R ligands (1-12) tested in the current project, H3R antagonist 4 showed significant and dose dependent reduction in the duration of tonic hind limb extension (THLE) subsequent to acute systemic administration (5, 10, and 15 mg/kg, i.p.). Importantly, the protective action observed for H3R antagonist 4 in MES-induced seizure was comparable to that of the reference antiepileptic drug phenytoin (PHT), and was also reversed when rats were pretreated with the CNS penetrant pyrilamine (PYR) (10 mg/kg, i.p.), or with the selective H3R agonist R-(α)-methylhistamine (RAMH) (10 mg/kg, i.p.). Furthermore, the procognitive studies indicate that acute pre-training systemic administration of H3R antagonist 4 (2.5 mg/kg, i.p.) facilitated acquisition, whereas pre-testing acute administration of 4 (5 and 10 mg/kg, i.p.) improved retrieval. Interestingly, the procognitive effect of 4 on retrieval was completely abrogated when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL) but not the centrally acting H1R antagonist PYR, indicating that histaminergic pathways through activation of H2Rs appear to be participating in neuronal circuits involved in the retrieval processes. Taken together, our results show that H3R antagonist 4 demonstrates anticonvulsant properties in the MES-induced seizure model and improves cognitive performance through actions on different memory stages. Therefore, H3Rs may have implications for the treatment of degenerative disorders associated with impaired memory function and may represent a novel therapeutic pharmacological target to tackle cognitive problems associated with the chronic use of antiepileptic drugs

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Unveiling the unseen toll: exploring the impact of the Lebanese economic crisis on the health-seeking behaviors in a sample of patients with diabetes and hypertension

Abstract Background Against the backdrop of Lebanon’s escalating multifaceted crisis which resulted in medication shortages for chronic diseases and unaffordable healthcare services, the current study endeavors to shed light on a critical yet overlooked facet of the Lebanese economic crisis– its profound impact on the health-seeking behaviors of patients with hypertension and diabetes mellitus. Methods An exploratory cross-sectional study based on an online questionnaire was conducted on 156 adult Lebanese citizens diagnosed medically with either hypertension or diabetes. We gathered sociodemographic characteristics and healthcare-related challenges faced during the economic crisis. We also assessed stress levels using the Depression Anxiety Stress Scale (DASS-21). Descriptive and bivariate analyses were done using SPSS version 26. Results The mean age of the population was 49.8 ± 17.7 years old, 51.6% were females and 48.4% were males, 29.7% had diabetes, 51.3% had hypertension and 19.0% had both diseases. Among all, 84.2% reported dissatisfaction with the current healthcare system, 31.6% reported changing their physician mainly because of unaffordable consultation fees (66%) or immigration of the physician (32%). Of those with hypertension and/or diabetes, less than 20% reported finding all their prescribed medications and 47% either modified or discontinued their treatment without seeking medical advice. In case of drug shortage, patients relied on stocked reserves (26%), alternative/generic medications (10%) and external sources for medication procurement such as relatives living abroad (41.7%), outsourcing suppliers (19.9%), dispensaries (19.6%) and NGOs (20.3%). All participants reported a high stress level (5.03/7) with a mean total DASS-21 score of 38.7 ± 35.8 that were attributed to August 4th Beirut port explosion (81.0%), global pandemic (81%), unstable political conditions (90.5%), economic crisis (96.8%), medication shortage (91.8%) and inability to access healthcare (74.1%). Higher sub-scores for anxiety, depression and total stress were insignificantly noted in participants with both hypertension and diabetes (p > 0.05). Conclusion Our findings explore how the economic crisis has taken its toll on almost all aspects of healthcare in a sample of patients with diabetes and hypertension in Lebanon. The drug shortage as well as disruptions in affordable healthcare access imposed several barriers to adequate adherence to treatment regimens and acted as important mental health stressors

Additional file 1 of Unveiling the unseen toll: exploring the impact of the Lebanese economic crisis on the health-seeking behaviors in a sample of patients with diabetes and hypertension

Supplementary Material

Informal Cairo: Between Islamist Insurgency & the Neglectful State?

From the late 1980s, Islamist militants established a ‘state within the state’ in the Egyptian capital Cairo, situated in ‘informal’ neighbourhoods developed without official authorization, planning or public services. After government security forces in late 1992 crushed these efforts in the neighbourhood of Munira Gharbiyya, informal Cairo became pathologized in public discourse as ashwa’iyyat (‘random’ or ‘haphazard’ areas), a zone of socio-spatial disorder threatening Egypt as a whole and demanding state intervention. However, this securitizing move did not lead to heavy-handed intervention against informal Cairo more generally. Following the suppression of the militants, the Mubarak government instead returned to long-term patterns of indifference and neglect that had allowed informal neighbourhoods to flourish since the 1960s. In part, the absence of intervention can be explained in terms of resource constraints and risk avoidance. More profoundly, however, it reflects numerous linkages between informal urbanization and the Egyptian state. The ashwa’iyyat are, to a significant degree, both a consequence of an authoritarian political order and embedded in the informal control stratagems used by Egyptian governments to bolster their rule. Informal Cairo should thus not be understood as a disorderly zone of subaltern dissidence. Rather, the Egyptian state is best seen as facing its own oblique reflection

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

Students' participation in collaborative research should be recognised

Letter to the editor