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Esophageal perforation, a rare and serious condition, has seen a reduction in mortality from 30% to 15% over the last three decades due to advancements such as gastrointestinal stents, minimally invasive surgeries, and improved interventional radiology techniques. This review analyzes management strategies for esophageal perforation based on 14 English-language articles published from 2009 to 2024, primarily utilizing surveys and national database analyses. The management of esophageal perforation is complex, with challenges in diagnosis and treatment strategy. Despite surgery being the traditional treatment, the role of less invasive methods is growing. Effective management of esophageal perforation involves advanced imaging for diagnosis, hemodynamic stabilization, and a multidisciplinary approach to treatment, including surgical and non-surgical interventions. The evidence for different treatment outcomes remains limited, highlighting the need for comprehensive care involving thoracic surgery, interventional radiology, gastroenterology, and critical care in an intensive care unit setting.
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The proximal femoral fracture patients in particular fractures in the trochanteric region of the femur could have treatment under the title proximal femoral nailing (PFN)-this operation is a less invasive type. The proximal femoral nail, an osteosynthetic implant, has been investigated to produce positive heeling to ensure a better fixation, several advantages of PFN include such as bleeding time during operation which leads to the need to perform reaming on the femoral canal during surgery. MATERIAL AND METHODS: The study was carried out at three teaching Hospitals in Mosul City from the period of January 2022 to December 2022, fourteen nurses from orthopaedic wards were subjected to this study, all the nurses were evaluated by the checklist, and they attended the training program which was taken from the Iraqi Ministry of Health guide for organizing nursing operations and practices inside the hospitals and medical departments. RESULTS AND DISCUSSION: More than (50%) of the study sample had a poor score in the initial evaluation for post-operative steps and after submitting the training program, the performance and practices of the nursing staff have improved significantly where the poor score decreased to approximately (25%) at P value (0.0001). CONCLUSION: The study concluded that there is a significant and clear weakness in the performance and practices of the nursing staff towards patients with upper femoral fractures in the fracture wards and that the training program that was given to them improved their performance and practices significantly and effectively.
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Clavos Ortopédicos , Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/prevención & control , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Fracturas del Fémur/cirugía , Femenino , Masculino , AdultoRESUMEN
Blinding eye diseases are often related to changes in retinal structure, which can be detected by analysing retinal blood vessels in fundus images. However, existing techniques struggle to accurately segment these delicate vessels. Although deep learning has shown promise in medical image segmentation, its reliance on specific operations can limit its ability to capture crucial details such as the edges of the vessel. This paper introduces LMBiS-Net, a lightweight convolutional neural network designed for the segmentation of retinal vessels. LMBiS-Net achieves exceptional performance with a remarkably low number of learnable parameters (only 0.172 million). The network used multipath feature extraction blocks and incorporates bidirectional skip connections for the information flow between the encoder and decoder. In addition, we have optimised the efficiency of the model by carefully selecting the number of filters to avoid filter overlap. This optimisation significantly reduces training time and improves computational efficiency. To assess LMBiS-Net's robustness and ability to generalise to unseen data, we conducted comprehensive evaluations on four publicly available datasets: DRIVE, STARE, CHASE_DB1, and HRF The proposed LMBiS-Net achieves significant performance metrics in various datasets. It obtains sensitivity values of 83.60%, 84.37%, 86.05%, and 83.48%, specificity values of 98.83%, 98.77%, 98.96%, and 98.77%, accuracy (acc) scores of 97.08%, 97.69%, 97.75%, and 96.90%, and AUC values of 98.80%, 98.82%, 98.71%, and 88.77% on the DRIVE, STARE, CHEASE_DB, and HRF datasets, respectively. In addition, it records F1 scores of 83.43%, 84.44%, 83.54%, and 78.73% on the same datasets. Our evaluations demonstrate that LMBiS-Net achieves high segmentation accuracy (acc) while exhibiting both robustness and generalisability across various retinal image datasets. This combination of qualities makes LMBiS-Net a promising tool for various clinical applications.
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Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Vasos Retinianos , Vasos Retinianos/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , AlgoritmosRESUMEN
OBJECTIVES: To assess clinicians' adherence to fingolimod's effective use according to the prescribed recommendations to reduce safety risk, identify the consequences, and highlight areas for improvement to policy makers for the benefit of both patient and care-giver. METHODS: A retrospective observational study conducted at a tertiary hospital targeting multiple sclerosis patients on fingolimod from January 2017 to December 2021. The physicians' adherence to the manufacturer's instructions was assessed and categorized into good, moderate, and poor based on adherence to fingolimod instructions and monitoring measures. Four monitoring measures were assessed: bradycardia observation, ophthalmic examination, liver enzymes, and infections. In addition, the impact of adherence on patient safety was also assessed. RESULTS: A total of 140 patients were included. Seventy-twopatients (51.4%) had physician with poor adherence (followed only one instruction or none). Sixty-five patients (46.4%) had 2-3 manufacture recommendations where physician's adherence was moderate. Three patients (2.10%) had all manufacturer's recommendations. In terms of fingolimod complications, 18 patients found to have bradycardia after the first does, macular oedema and infections was reported in 4 patients, and the elevation in hepatic enzymes was reported in 6 patients. Poor physician's adherence has resulted in treatment incompleteness and highest fingolimod discontinuation or switching to other treatment options. CONCLUSION: Adherence to fingolimod instructions was poor among physicians which resulted in highest drug switching or discontinuing rate.
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Clorhidrato de Fingolimod , Inmunosupresores , Esclerosis Múltiple , Seguridad del Paciente , Humanos , Clorhidrato de Fingolimod/uso terapéutico , Clorhidrato de Fingolimod/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Persona de Mediana Edad , Adhesión a Directriz/estadística & datos numéricosRESUMEN
Background: Ulnar collateral ligament (UCL) injuries in youth pitchers continue to be concerning despite the institution of pitch count limits. Flexor-pronator mass fatigue can lead to diminished dynamic stability, resulting in greater stress on the UCL. Purpose/Hypothesis: To evaluate fatigue of the flexor-pronator mass by assessing changes in medial elbow laxity; noninvasively characterizing alterations in muscle glycogen; and identifying changes in subjective fatigue, strength, range of motion (ROM), pitching velocity, and accuracy with increasing pitches thrown by youth pitchers to their recommended 75-pitch count limit. It was hypothesized that, with increased pitches, medial elbow laxity would increase and that the glycogen content of the flexor-pronator mass would decrease. Study Design: Descriptive laboratory study. Methods: Healthy male pitchers aged 10 years (n = 22) threw 3 sets of 25 pitches with 12 minutes between sets (3 timepoints). Bilateral ulnohumeral joint gapping was measured by applying a standardized valgus force and utilizing ultrasound imaging. Relative changes in muscle glycogen in the bilateral flexor carpi radialis (FCR), and the flexor digitorum superficialis/flexor carpi ulnaris (FDS/FCU) muscles were measured with ultrasound software and recorded as fuel percentiles. Additional measures obtained included subjective fatigue, strength, ROM, velocity, and accuracy. Results: There were no differences in medial elbow joint-line gapping between the throwing and nonthrowing arms or between timepoints. The throwing arm demonstrated a significant decline in fuel percentile of the FCR from baseline to after 75 pitches (P = .05). There were no differences across timepoints for FDS/FCU fuel percentile values. Fatigue measurements for both arms were significantly higher at all timepoints compared with baseline (P≤ .03). Grip strength of the dominant arm after 75 pitches was decreased significantly compared with after 25 pitches (P = .02). Conclusion: Although an increase in medial elbow joint gapping was not demonstrated within the recommended 75 pitch count limit in 10-year-olds, a relative decrease in glycogen stores of the flexor-pronator mass did occur, as well as a decrease in grip strength, with increasing subjective fatigue. Clinical Relevance: This study provides a foundation for further objective testing of physiologic changes that occur with pitching to better guide pitch count limits and improve the safety of young athletes.
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The literature does not provide any "high-performance thin-layer chromatographic (HPTLC)" techniques for the determination of a novel antidiabetic medicine, ertugliflozin (ERZ). Additionally, there are not many environmentally friendly analytical methods for ERZ measurement in the literature. A rapid, sensitive, and eco-friendly reversed-phase-HPTLC (RP-HPTLC) method was designed and validated in an attempt to analyze ERZ in marketed pharmaceutical tablets more precisely, accurately, and sustainably over the traditional normal-phase HPTLC (NP-HPTLC) method. The stationary phases used in the NP- and RP-HPTLC procedures were silica gel 60 NP-18F254S and 60 RP-18F254S plates, respectively. For NP-HPTLC, a chloroform/methanol (85:15 v/v) mobile phase was used. However, ethanol-water (80:20 v/v) was the preferred method for RP-HPTLC. Four distinct methodologies, including the National Environmental Method Index (NEMI), Analytical Eco-Scale (AES), ChlorTox, and Analytical GREEnness (AGREE) approaches, were used to evaluate the greenness of both procedures. For both approaches, ERZ detection was carried out at 199 nm. Using the NP- and RP-HPTLC techniques, the ERZ measurement was linear in the 50-600 and 25-1200 ng/band ranges. The RP-HPTLC method was found to be more robust, accurate, precise, linear, sensitive, and eco-friendly compared to the NP-HPTLC approach. The results of four greenness tools demonstrated that the RP strategy was greener than the NP strategy and all other reported HPLC techniques. The fact that both techniques can assess ERZ when its degradation products are present implies that they both have characteristics that point to stability-indicating features. 87.41 and 99.28%, respectively, were the assay results for ERZ in commercial tablets when utilizing the NP and RP procedures. Based on several validation and greenness metrics, it was determined that the RP-HPTLC approach was better than the NP-HPTLC method. As a result, it is possible to determine ERZ in pharmaceutical products using the RP-HPTLC approach.
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The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol in individuals with asthma with and without post-COVID condition (PCC). The study was designed to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA. The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased (p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC. However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r = -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683), but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age, IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma. Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main influence of asthma on the overall inflammatory response. These findings reveal a complex interplay between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.
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Asma , COVID-19 , Calcifediol , Interleucina-10 , Interleucina-6 , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , Interleucina-6/sangre , Interleucina-10/sangre , Calcifediol/sangre , Persona de Mediana Edad , COVID-19/sangre , COVID-19/complicaciones , SARS-CoV-2 , Enfermedad CrónicaRESUMEN
A two-step simple and efficient ion-exchange chemical strategy is proposed to obtain nanostructured Bi2S3 electrodes of different surface morphologies from the Bi2O3. In the first step, nanoplates of the Bi2O3 are obtained on nickel-foam using successive ionic layer adsorption and reaction method at room-temperature (25 °C). In the second phase, as-obtained nanoplates of the Bi2O3 are transferred to the Bi2S3 using four autoclaves containing different sulfur precursor solutions at 120 °C for 8 h for phase change, structural conversion and surface morphological modification (i.e., walnuts, network-type, nanowires, and nanoflowers). Due to higher surface area and conductivity, lower charge transfer resistance, and reduced band gap caused by ionic and phase conversion, the Bi2S3 surpasses the Bi2O3 in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activities. The overpotential of 112-370 mV for the Bi2S3 network is much lower than that of the nanoplates of the Bi2O3 (275-543 mV), and walnuts (134-464 mV), nanowires (125-500 mV), and nanoflowers (194-520 mV) of the Bi2S3. The Bi2S3 network-type Bi2S3 electrode shows considerable chemical stability through cycling measurement, suggesting the importance of the present study in obtaining metal sulfides from metal oxide with better water splitting activities.
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Guideline-directed medical therapy utilization in patients with heart failure with reduced ejection fraction (HFrEF) remains low despite benefits in morbidity and mortality. The authors describe a unique quality improvement initiative designed to increase angiotensin receptor-neprilysin inhibitor (ARNI) and mineralocorticoid receptor antagonist (MRA) utilization in outpatients with HFrEF in a large cardiology practice, whereby eligible patients were identified in a standardized review process and medication utilization rates were linked to group quality metrics. Eligible HFrEF patients were defined as having a left ventricular ejection fraction (LVEF) ≤40% and NYHA functional class II to IV level of symptoms. Those with an LVEF >40%, no documented LVEF, or with NYHA functional class I symptoms were excluded. ARNI utilization was defined as any dose of sacubitril/valsartan prescribed, and MRA utilization was defined as any dose of either spironolactone or eplerenone prescribed. Group quality metric targets were set at >25% ARNI prescription and >60% MRA prescription in eligible patients. Following project implementation, ARNI utilization rose from 31% to 67% and MRA increased from 28% to 66%. Establishing clear quality metrics and formulating a proactive evaluation process was associated with a significant increase in prescription rates.
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Insuficiencia Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Neprilisina , Volumen Sistólico , Valsartán , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/fisiología , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Aminobutiratos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Neprilisina/antagonistas & inhibidores , Combinación de Medicamentos , Masculino , Femenino , Mejoramiento de la Calidad , Espironolactona/uso terapéutico , Anciano , Tetrazoles/uso terapéutico , Eplerenona/uso terapéutico , Persona de Mediana EdadRESUMEN
OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.
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COVID-19 , Educación a Distancia , Personal de Salud , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Personal de Salud/educación , Educación a Distancia/métodos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Competencia Clínica , SARS-CoV-2 , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of spike protein in the endoplasmic reticulum likely due to decreased N-glycan transfer, and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy.
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The scarcity of data on burn-related injuries in Pakistan prompted this study. The study is specifically aimed at assessing the burn patients who were admitted to a national burn care center (BCC) in Pakistan. This single-center retrospective analysis was conducted for 12 months from January to December 2021. During this time period, 14,069 patients visited BCC with burn injuries of diverse natures while 613 of them were admitted. The patients' information was abstracted from the hospital database. This information included age, sex, diagnosis, burn depth/degree, time of arrival, circumstances of burn injury, TBSA (total burn surface area), complications, outcome, and management plan. This information was shifted to Microsoft Office Excel Worksheet 2015 and then coded into the IBM Statistical Package for the Social Sciences (SPSS) version 24.0. Armonk, NY: IBM Corp. Of 14,069 patients, 613 were admitted to the burn care center, indicating an admission rate of 4.35%. Among these 613 patients, there was a high proportion of males (58.89%) and a mean age of 20.2±12.5 years. Most patients (40.4%) visited within the first hour after being burnt and flame burns were the most common (41.10%). Most patients were burnt due to accidents (97.7%). The mean length of hospital stay was 15.5 days. Flames were the main cause of burns among our cohort of patients. Most patients had a TBSA of >10% and generally had a second-degree burn, mostly in the pediatric population. An urgent appraisal of burn policies and related legislation is needed to halt the burn burden in the country.
Cette étude a été décidée en raison de la pauvreté des données épidémiologiques concernant les brûlures au Pakistan. Il s'agit d'une étude monocentrique rétrospective sur dossier conduite dans le CTB national d'Islamabad sur l'année 2021. Sur les 14 069 patients brûlés qui s'y sont présentés, 613 (4,35%) ont été hospitalisés. Nous avons recueilli l'âge, le sexe, la SCB, la profondeur, la cause, le délai de présentation, la stratégie thérapeutique, les complications et le devenir des patients. Les données ont été implantée dans Excel et analysées avec SSPS 24.0. Parmi les patients hospitalisés, 58,89% étaient des hommes âgés de 20,2±12,5 ans. Le délai de présentation était de moins de 1h dans 40,4% des cas et l'atteinte était quasiment toujours accidentelle (97,7%), majoritairement par flamme (41%). La DMS était de 15,5 j. L'atteinte était le plus souvent > 10% SCT, habituellement au 2ème degré en particulier en population pédiatrique. Une évaluation de la législation préventive est urgente, afin de mettre fin au fardeau que représentent les brûlures dans notre pays.
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To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.
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COVID-19 , SARS-CoV-2 , Animales , Ratones , Humanos , SARS-CoV-2/genética , Vacunas Combinadas , Anticuerpos Neutralizantes , Nanovacunas , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/prevención & control , ARN Mensajero/genética , Vacunas de ARNm , Lípidos , Anticuerpos AntiviralesRESUMEN
Significance: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). Aim: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. Approach: We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1). Results: A new LMO generated from this approach (LMO7) showed significantly stronger BL-driven opsin activation compared to previous and other new variants. We extensively benchmarked LMO7 against LMO3 (current standard) and found significantly stronger neuronal activity modulation ex vivo and in vivo, and efficient modulation of behavior. Conclusions: We report a robust new option for achieving multiple modes of control in a single actuator and a promising engineering strategy for continued improvement of BL-OG.
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Mosquitoes of the genera Aedes, Anopheles and Culex vector a wide range of pathogens seriously affecting humans and livestock on a global scale. Over-reliance on insecticides and repellents has driven research into alternative, naturally-derived compounds to fulfil the same objectives. Steam distilled extracts of four plants with strong, yet attractive, volatile profiles were initially assessed for repellency in a dual-port olfactometer using Aedes aegypti as the model species. Picea sitchensis was found to be the most repellent, proving comparable to leading products when applied at 100% (p = 1.000). Key components of conifer-derived volatile profiles were then screened via electroantennography before those components eliciting an electrophysiological response were assayed individually in the olfactometer; according to WHO protocol. The most promising 5 were selected for reductive analyses to produce an optimised semiochemical blend. This combination, and a further two variations of the blend, were then progressed to a multi-species analysis using the BG-test whereby bite-attempt frequency on hands was assessed under different repellent treatments; assays were compared between Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus. Efficacy was found against all three species, although it was found that Ae. aegypti was the most susceptible to the repellent, with An. gambiae being the least. Here, a novel, naturally-derived blend is presented with weak spatial repellency, as confirmed in laboratory assays. Further work will be required to assess the full extent of the potential of the products, both in terms of field application and species screening; however, the success of the products developed demonstrate that plant metabolites have great capacity for use in the repellent sector; both to improve upon known compounds and to reduce the usage of toxic products currently on the market.
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Aedes , Anopheles , Culex , Culicidae , Repelentes de Insectos , Insecticidas , Humanos , Animales , Mosquitos Vectores , Extractos Vegetales/farmacología , Repelentes de Insectos/farmacología , Insecticidas/farmacologíaRESUMEN
Parasitic diseases, notably babesiosis, exert a substantial impact on the global cattle industry, posing challenges to commerce, economies, and human health. This study, conducted in Southern Punjab, Pakistan, aimed to assess the prevalence of Babesia spp. across various livestock species using microscopic and PCR methods. A total of 180 blood samples (60 from each district) were systematically collected from apparently healthy animals, with 36 samples obtained from each domestic animal species, including camel, cattle, buffalo, goat, and sheep, noting that 12 samples were collected from each district for each animal species. Overall prevalence was determined to be 32.8% (59/180), with varying rates among species: 25.0% in cattle, 41.66% in buffalo, 30.55% in goats, 33.3% in sheep, and 33.3% in camels. Microscopic examination revealed slightly varied infection rates among large and small domestic animals (22.2%), while PCR results indicated a 32.8% overall infection rate in both large and small domestic animals, with no statistical significance. District-wise analysis showed regional variations, with Muzaffargarh recording a prevalence rate of 23.33% through microscopic examination, while Lodhran and Bahawalpur recorded 21.67%. PCR results revealed higher rates (38.33%, 26.67%, and 33.33%, respectively), underlining the importance of employing PCR for accurate detection. Examining ruminant types, large ruminants exhibited a 32.4% infection rate, while small domestic animals showed 33.3%, with no significant difference (p=0.897). District-wise prevalence showcased significant variation, with Muzaffargarh demonstrating a 25% prevalence, Lodhran 22%, and Bahawalpur 22%, through microscopic examination. PCR results displayed 38.33%, 27%, and 33.3%, respectively, with no statistical significance. Detailed analysis of individual districts highlighted variations in infection rates among camels, cattle, buffalo, goats, and sheep. The binomial test indicated significant differences through microscopic analysis (P=0.011) but non-significant variations through PCR (P=0.065), emphasizing the precision of PCR. Regional variations in prevalence, notably with Punjab exhibiting the highest frequency (33.87%) and KPK the lowest (13.24%), suggest potential influences from varying veterinary practices and environmental factors. This study underscores the pivotal role of PCR alongside microscopy for accurate babesiosis diagnosis. These findings contribute to the broader understanding of babesiosis prevalence, emphasizing the necessity of advanced molecular techniques for informed control measures.
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Babesia , Babesiosis , Humanos , Bovinos , Ovinos , Animales , Animales Domésticos , Babesia/genética , Babesiosis/epidemiología , Babesiosis/parasitología , Prevalencia , Búfalos , Pakistán/epidemiología , Camelus , CabrasRESUMEN
Olfactory systems are indispensable for insects as they, including Western Flower Thrips (Frankliniella occidentalis), use olfactory cues for ovipositing and feeding. F. occidentalis use odorant binding proteins (OBPs) to transport semiochemicals to odorant receptors to induce a behavioural response from the sensillum lymph of the insect's antennae. This study identifies four OBPs of F. occidentalis and analyses their expression at three stages of growth: larvae, adult males and adult females. Further, it investigates the presence of conserved motifs and their phylogenetic relationship to other insect species. Moreover, FoccOBP3 was in silico characterized to analyse its structure along with molecular docking and molecular dynamics simulations to understand its binding with semiochemicals of F. occidentalis. Molecular docking revealed the interactions of methyl isonicotinate, p-anisaldehyde and (S)-(-)-verbenone with FoccOBP3. Moreover, molecular dynamics simulations showed bonding stability of these ligands with FoccOBP3, and field trials validated that Lurem TR (commercial product) and p-anisaldehyde had greater attraction as compared to (S)-(-)-verbenone, given the compound's binding with FoccOBP3. The current study helps in understanding the tertiary structure and interaction of FoccOBP3 with lures using computational and field data and will help in the identification of novel lures of insects in the future, given the importance of binding with OBPs.Communicated by Ramaswamy H. Sarma.
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Type 1 diabetes (T1D) is characterized by the destruction of pancreatic ß-cells. Several observations have renewed the interest in ß-cell RNA sensors and editors. Here, we report that N6-methyladenosine (m6A) is an adaptive ß-cell safeguard mechanism that controls the amplitude and duration of the antiviral innate immune response at T1D onset. m6A writer methyltransferase 3 (METTL3) levels increase drastically in ß-cells at T1D onset but rapidly decline with disease progression. m6A sequencing revealed the m6A hypermethylation of several key innate immune mediators, including OAS1, OAS2, OAS3 and ADAR1 in human islets and EndoC-ßH1 cells at T1D onset. METTL3 silencing enhanced 2'-5'-oligoadenylate synthetase levels by increasing its mRNA stability. Consistently, in vivo gene therapy to prolong Mettl3 overexpression specifically in ß-cells delayed diabetes progression in the non-obese diabetic mouse model of T1D. Mechanistically, the accumulation of reactive oxygen species blocked upregulation of METTL3 in response to cytokines, while physiological levels of nitric oxide enhanced METTL3 levels and activity. Furthermore, we report that the cysteines in position C276 and C326 in the zinc finger domains of the METTL3 protein are sensitive to S-nitrosylation and are important to the METTL3-mediated regulation of oligoadenylate synthase mRNA stability in human ß-cells. Collectively, we report that m6A regulates the innate immune response at the ß-cell level during the onset of T1D in humans.
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Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Animales , Humanos , Ratones , Adenosina Desaminasa/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Inmunidad Innata , Células Secretoras de Insulina/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Oxidación-ReducciónRESUMEN
Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.
Asunto(s)
Muerte Celular Inmunogénica , Lisosomas , Péptidos , Polietileneimina , Protones , Lisosomas/metabolismo , Humanos , Péptidos/química , Muerte Celular Inmunogénica/efectos de los fármacos , Polietileneimina/química , Línea Celular Tumoral , Neoplasias/patología , Nanopartículas/química , Nanoestructuras/química , Supervivencia Celular/efectos de los fármacosRESUMEN
Regenerative endodontics represents a paradigm shift in dental therapy, with the potential to not only restore damaged dental tissues but also to preserve the vitality of teeth. At the heart of this innovative approach is cell homing, a technique that harnesses the body's own healing mechanisms by recruiting endogenous stem cells to the site of dental injury for effective tissue regeneration. This review delves into the intricate processes of cell homing in the context of regenerative endodontics, particularly focusing on its application in immature teeth with open apices. It examines the role of bioactive molecules, scaffolds, and growth factors in orchestrating cell migration and differentiation within the root canal space. In addition, the review addresses the current limitations in clinical practice, such as the challenges in completely regenerating the pulp-dentin complex and the unpredictability in long-term outcomes. It also explores future possibilities, including the potential for more refined and effective regenerative strategies. By providing a comprehensive overview of the current state of cell homing in regenerative endodontics, this article aims to contribute to the ongoing development of advanced therapeutic techniques that could revolutionize endodontic treatment and improve patient care.