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Dengue fever is the most prevalent arboviral disease worldwide. Dengue virus (DENV), the etiological agent, is known to have been circulating in Senegal since 1970, though for a long time, virus epidemiology was restricted to the circulation of sylvatic DENV−2 in south-eastern Senegal (the Kedougou region). In 2009 a major shift was noticed with the first urban epidemic, which occurred in the Dakar region and was caused by DENV−3. Following the notification by Senegal, many other West African countries reported DENV−3 epidemics. Despite these notifications, there are scarce studies and data about the genetic diversity and molecular evolution of DENV−3 in West Africa. Using nanopore sequencing, phylogenetic, and phylogeographic approaches on historic strains and 36 newly sequenced strains, we studied the molecular evolution of DENV−3 in Senegal between 2009 and 2022. We then assessed the impact of the observed genetic diversity on the efficacy of preventive countermeasures and vaccination by mapping amino acid changes against vaccine strains. The results showed that the DENV−3 strains circulating in Senegal belong to genotype III, similarly to strains from other West African countries, while belonging to different clades. Phylogeographic analysis based on nearly complete genomes revealed three independent introduction events from Asia and Burkina Faso. Comparison of the amino acids in the CprM-E regions of genomes from the Senegalese strains against the vaccine strains revealed the presence of 22 substitutions (7 within the PrM and 15 within the E gene) when compared to CYD-3, while 23 changes were observed when compared to TV003 (6 within the PrM and 17 within the E gene). Within the E gene, most of the changes compared to the vaccine strains were located in the ED-III domain, which is known to be crucial in neutralizing antibody production. Altogether, these data give up-to-date insight into DENV−3 genomic evolution in Senegal which needs to be taken into account in future vaccination strategies. Additionally, they highlight the importance of the genomic epidemiology of emerging pathogens in Africa and call for the implementation of a pan-African network for genomic surveillance of dengue virus.

Brucellosis is a widespread zoonotic disease of veterinary and public health importance with considerably higher prevalence in developing/underdeveloped countries. This study reports the prevalence and risk determinants of brucellosis in small ruminants of peri-urban and rural areas of district Multan, Southern Punjab, Pakistan. For this purpose, sera samples ( n  = 392) of small ruminants were collected and subjected to preliminary screening using commercially available RBPT reagents followed by serodetection of brucellosis using multispecies i-ELISA kit (ID.vet, France). All the ELISA positive samples were confirmed by PCR using genus-specific primers, and frequencies of Brucella species in positive samples were enumerated using species-specific primers. Results indicated seropositivity rates of 9.69, 9.95, and 10.20% in study population using RBPT reagents of IDEXX-USA, ID.Vet-France, and VRI-Pakistan, respectively, with a statistically nonsignificant difference ( p > 0.05). Results of ELISA showed an overall seroprevalence rate of 7.14% in target population with a slightly higher rate in sheep (7.65%) as compared to goat (6.63%) population ( p = 0.695; OR = 1.16, 95% CI = 0.53, 2.57). Results revealed that out of total positive samples, B. abortus was detected in 60.71% of seropositive samples and B. melitensis was detected in 14.28% of positive samples. It was revealed that risk factors including body condition scores, hygienic conditions of the housing facility, farming system, reproductive disorders, educational status of farmers, and awareness of farmers about brucellosis had significant association with brucellosis in small ruminants of study area ( p < 0.05). Conversely, farm/herd size, locality, gender, age, weight, and parity showed a nonsignificant association ( p > 0.05) with brucellosis. In conclusion, brucellosis is prevalent in small ruminants of Multan, Pakistan. It is recommended to devise and implement effective control strategies with a major focus on raising awareness about brucellosis in farmers for the containment of infection in the region., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2024 Mian Muhammad Awais et al.)

Background: Brucellosis is a zoonotic disease caused by a bacterial pathogen belonging to the genus Brucella. It is one of the most frequent bacterial zoonoses globally but unfortunately, it is still considered as a neglected disease in the developing world. Keeping in view, this study was conducted to determine the prevalence and risk determinants of brucellosis in large ruminants of peri-urban and rural areas of district Multan-Pakistan. For this purpose, blood samples (n = 490) were collected from the cattle (n = 245) and buffalo (n = 245) population of the study area and subjected to preliminary screening of brucellosis using local and imported RBPT reagents. All the samples were further analyzed using commercially available multi-specie indirect ELISA kit followed by their confirmation by PCR using genus and species-specific primers. Data obtained from lab analysis and questionnaires were subjected to statistical analysis for Pearson Chi-square, Odds Ratio and Confidence intervals (95%)., Results: The results showed that the maximum seropositivity was recorded with local RBPT reagent (VRI, Pakistan; 12.45%; 95%CI = 9.72-15.65%) followed by RBPT-IDEXX (12.24%; 95%CI = 9.52-15.45%) and RBPT-ID.vet (11.84%; 95%CI = 9.18-14.95%) however statistical difference was non-significant (P = 0.956). The ELISA results showed an overall seroprevalence rate of 11.22% (95%CI = 8.59-14.33%) with comparatively higher rate in cattle (12.65%; 95%CI = 8.82-17.44%) as compared to buffaloes (9.80%; 95%CI = 6.49-14.15%). The PCR analysis confirmed the presence of genus Brucella in all seropositive samples whereas frequency of B. abortus and B. melitensis in seropositive samples was 80% and 20%, respectively. The co-existence of both species was also observed in 5.45% samples. The statistical analysis showed a significant association of bovine brucellosis with herd size, breed, reproductive disorders, mode of insemination, educational status and farmers' awareness about brucellosis (P < 0.05). Conversely, locality, age, weight, gender, pregnancy status, parity and puberty status had no associations with brucellosis (P > 0.05)., Conclusion: In conclusion, brucellosis is prevalent in large ruminants of district Multan, Pakistan. It is suggested to devise and implement stringent policies for the effective control and prevention of brucellosis in the region. Further, the current situation also warrants the need to strengthen interdisciplinary coordination among veterinarians and physicians in one health perspective to ensure and strengthen the human and animal health care systems in the region., (© 2024. The Author(s).)

Background: The prognosis after rotational atherectomy of a side-branch ostium to treat bifurcation coronary lesions is unknown., Methods: This was a retrospective case-review study of 40 consecutive patients who underwent rotational atherectomy of the sidebranch ostium to treat symptomatic bifurcation coronary lesions meeting the Medina classification (1,1,1) at our institution between 2003 and 2007., Results: Twenty-two (55.0%) patients underwent rotational atherectomy of the side-branch ostium alone and 18 (45.0%) underwent rotational atherectomy of the both the main vessel and the sidebranch ostium. Most of the patients (n = 37, 92.5%) had a drug-eluting stent placed in the main vessel after rotational atherectomy. Only 8 patients (20.0%) required side-branch stents, and 2 patients (5.0%) underwent a final kissing-balloon technique. No acute closure of the side branch or coronary perforation were observed. Major adverse cardiac events included cardiac death (n = 1; 2.5%), nonfatal myocardial infarction (n = 1; 2.5%), target vessel revascularization (n = 2; 5.0%) and target lesion revascularization (n = 0; 0.0%) during the mean follow-up period of 21.3 +/- 18.5 months., Conclusions: The study demonstrated safety and feasibility of rotational atherectomy and provisional side-branch stenting to treat side-branch ostial lesions of true severe bifurcation coronary artery disease. The study results suggest that rotational atherectomy of a side-branch ostium prior to main-vessel stenting may be an option in selected patients undergoing complex bifurcation lesion angioplasty.

Renal artery stenosis is a common cause of secondary hypertension and ischemic nephropathy. Percutaneous angioplasty and stent placement has allowed select patients with renal artery stenosis to use fewer antihypertensive agents and improve or stabilize renal function. The associations of baseline systolic, diastolic, and pulse pressures (PPs) with outcomes of blood pressure (BP) and renal function were examined in 243 patients who underwent renal angioplasty and stent placement. The average PP before the procedure in patients with improvements or stabilizations in renal function was 53 +/- 20 mm Hg, compared to 107 +/- 18 mm Hg (p <0.05) in those with poorer outcomes. The average PPs before procedure were 47 +/- 15 mm Hg in those with improvements in BP, 82 +/- 10 mm Hg in those with stabilizations of BP, and 111 +/- 14 mm Hg in those with worsening BP. All findings were statistically significant (p <0.05). In conclusion, wide PP may reflect more advanced vascular stiffness and renal disease distinguishing patients less likely to benefit from revascularization.

Background: Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation., Methods: Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality., Results: The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality., Conclusion: Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.

Background: Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described., Methods: We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed., Results: Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses., Conclusion: Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.