Niosomas encapsulados en praziquantel contra Schistosoma mansoni con sensibilidad reducida al praziquantel

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. Objectives: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni (S. mansoni) isolate with reduced sensitivity to the drug during the intramolluscan phase. Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/week, followed by an interval of one week, and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ-encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen’s sensitivity to PZQ, as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. A remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56% respectively) was obtained associated with a massive increase in dead eggs and complete absence of immature stages. Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory-induced S. mansoni adult worms with reduced sensitivity to PZQ.Introducción. El praziquantel (PZQ) es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos eficaces y la falta de medidas preventivas eficaces aumentan su valor. El aumento de la prevalencia de la resistencia al PZQ bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia a PZQ mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni (S. mansoni) con sensibilidad reducida al fármaco durante la fase intramolusca. Material y métodos. Los caracoles que liberaban cercarias se trataron con dosis de PZQ de 200 mg / kg dos veces por semana, seguido de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. El éxito de inducir una sensibilidad reducida se confirmó in vitro mediante la reducción de la respuesta de las cercarias al PZQ con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. Resultados. El tratamiento oral con una dosis única de PZQ de 500 mg / kg en ratones infectados con cercarias con sensibilidad reducida a PZQ reveló una reducción no significativa (35,1%) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en PZQ inoculados por vía oral contra S. mansoni con sensibilidad reducida a PZQ permitieron reestablecer con éxito la sensibilidad del patógeno a PZQ, como lo demuestra la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a PZQ. La carga media total de gusanos fue de 1,33 ± 0,52 con una reducción estadísticamente significativa del 94,09% y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en tejido en el hígado y el intestino (97,68% y 98,56% respectivamente) asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en PZQ restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni inducidos en laboratorio con sensibilidad reducida a PZQ

Diagnostic value of ascitic fluid homocysteine and calprotectin in cirrhotic patients with spontaneous bacterial peritonitis

Background and study aim: Spontaneous bacterial peritonitis (SBP) is mainly diagnosed by ascitic polymorphonuclear (PMNL) leukocyte greater than 250/mm3. We intended to assess ascitic homocysteine and calprotectin for SBP diagnosis.Materials and methods: In our study, we collected ascitic fluids from 70 patients with liver cirrhosis (46 SBP plus 24 non-SBP according to PMNL>250 cells/mm3). Complete blood count, alanine aminotransferase, aspartate aminotransferase, serum albumin, total bilirubin, prothrombin time, INR, and serum creatinine were measured. Ascitic fluid sample was taken for chemical analysis, homocysteine was calculated in ascites by human homocysteine enzyme-linked immunosorbent assays (ELISA) kits and calprotectin was measured in the ascitic fluids using available human calprotectin enzyme-linked immunosorbent assays (ELISA) kits.Results: SBP patients had considerably greater ascitic homocysteine levels than non-SBP (5.66± 7.15 vs. 2.97±.61 μmol/l) P=0.001. Homocysteine at a cut-off of 3.6 μmol/l had 91.7% specificity, 69.9% sensitivity, PPV 94.1% and NPV 61.1% for SBP diagnosis (area under the curve: 0. 754). SBP patients had considerably greater ascitic calprotectin than the non-SBP (182.98± 76.27 vs. 118.1± 27 ng/mL) P=0.000. Using a cut-off 142 ng/mL, calprotectin had 91.7% specificity, 71.7% sensitivity, PPV 94.2% and NPV 62.9% for SBP diagnosis (area under the curve: 0.768).Conclusion: We found that ascitic homocysteine and calprotectin can be suitable diagnostic markers for SBP diagnosis

Oral diclofenac potassium versus hyoscine-N-butyl bromide for pain relief during copper intrauterine device insertion: randomized clinical trial

Background: Present study was carried out to compare the analgesic effect of oral diclofenac potassium versus hyoscine-N-butyl bromide (HBB) for pain relief during copper intrauterine device (IUD) insertion.Methods: It was a a randomized clinical trial carried out at Assiut University Hospital, Assiut, Egypt. Parous women eligible for Copper IUD insertion were recruited and randomized in a 1:1 ratio to diclofenac potassium or HBB. The participants were asked to take 2 tablets of the study medications 30 minutes before IUD insertion. The primary outcome was the participant's self-rated pain perception using a 10-cm Visual Analogue Scale (VAS) during IUD insertion. We considered a 1.5 cm difference in VAS scores between study groups as clinically significant.Results: One hundred eight women were enrolled (n=54 in each group). Diclofenac significantly has lower mean pain score during speculum placement (1.73 vs. 2.13) and tenaculum placement (1.85 vs. 2.3) than HBB with p<0.001. No statistical significant differences between both groups in other steps of IUD insertion. Additionally, the duration of IUD insertion was significantly lower in the diclofenac group (5.34±0.76 vs. 5.74±1.23 minutes, p=0.045). No women reported side effects in both groups.Conclusions: The use of oral diclofenac potassium 30 minutes prior to copper IUD insertion slightly reduce the insertional pain and duration than oral HBB with no adverse effects

Fahmy's four quadrant sutures: a new technique for control of blood loss during cesarean delivery for placenta previa

Background: The objective of this study is to assess the efficacy and safety of Fahmy's four quadrant suture technique (FFQS) in controlling blood loss during cesarean delivery for placenta previa (PP).Methods: The study was carried out in a tertiary University Hospital between January 2017 to December 2017 involved 12 women with heavy bleeding occurred after removal of the placenta from the lower section during cesarean delivery for PP. The FFQS technique consisted of two sutures to ligate the uterine branches on both sides and two sutures on the anterior and posterior wall of the lower uterine segment. Details regarding the management and maternal outcomes were recorded.Results: The mean age of the study participants was 29.58±5.29 years and the mean parity was 2.25±1.14. The mean gestational age at termination of pregnancy was 36.91±1.38 weeks.  The mean duration of the whole surgery was 78.75±43.28 minutes, while the mean duration of FFQS technique was only 10±2.09 minutes. The technique was exclusively effective in 8 out of 12 cases (66.67%) while 2 cases needed bilateral internal iliac artery ligation and 2 cases needed hysterectomy. The mean amount of blood loss in all cases was 2433.33±833.76 ml. the mean amount of transfused packed RBCs was 3.92±1.68 units and fresh frozen plasma (FFP) was 3.42±1.44 units. All cases had uneventful postoperative course and no mortality cases in present series.Conclusions: The new technique; FFQS represents a rapid, effective, and inexpensive opportunity for women with bleeding from the lower segment of uterus due to PP. This simple procedure should be attempted before other complex measures to achieve good hemostasis

Machine Learning to Quantitate Neutrophil NETosis

We introduce machine learning (ML) to perform classifcation and quantitation of images of nuclei from human blood neutrophils. Here we assessed the use of convolutional neural networks (CNNs) using free, open source software to accurately quantitate neutrophil NETosis, a recently discovered process involved in multiple human diseases. CNNs achieved \u3e94% in performance accuracy in diferentiating NETotic from non-NETotic cells and vastly facilitated dose-response analysis and screening of the NETotic response in neutrophils from patients. Using only features learned from nuclear morphology, CNNs can distinguish between NETosis and necrosis and between distinct NETosis signaling pathways, making them a precise tool for NETosis detection. Furthermore, by using CNNs and tools to determine object dispersion, we uncovered diferences in NETotic nuclei clustering between major NETosis pathways that is useful in understanding NETosis signaling events. Our study also shows that neutrophils from patients with sickle cell disease were unresponsive to one of two major NETosis pathways. Thus, we demonstrate the design, performance, and implementation of ML tools for rapid quantitative and qualitative cell analysis in basic science

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat