Dynamic response of sandwich functionally graded nanoplate under thermal environments and elastic foundations using dynamic stiffness method.

The present paper introduces the development of dynamic stiffness method for analyzing small-scale sandwich functionally graded nanoplates resting on elastic foundation in thermal environments. The mathematical formulation is based on classical plate theory in conjunction with nonlocal elasticity theory. The governing equation is derived using Hamilton's principle. The dynamic stiffness matrix is obtained through the application of the Levy displacement approach and assembled to form the global stiffness matrix. The final matrix is solved for natural frequency of the plates using the Wittrick-Williams algorithm. The proposed methodology is validated against existing literature, demonstrating a strong agreement. Various parametric studies explore the effects of thermal environments, volume fraction index, sandwich configurations, elastic foundation characteristics, nonlocal parameter and boundary conditions. The results show the versatility of the proposed approach in addressing small scaled complex engineering structures. This research significantly contributes to the understanding and analysis of sandwich functionally graded nanoplates, providing valuable insights for applications in aerospace, structural systems, sensors, actuators, and energy harvesting devices.

Comparative study of thulium fiber laser versus holmium:yttrium-aluminum-garnet laser for ureteric stone management with semi-rigid ureteroscopy: A prospective, single-center study.

Objective: To compare the efficacy and safety of thulium fiber laser (TFL) and holmium:yttrium-aluminum-garnet (Ho:YAG) laser for ureteric stone management with semi-rigid ureteroscopy. Methods: In a prospective study from January 2020 to December 2021, we compared 40 patients in each group who underwent semi-rigid ureteroscopic lithotripsy with TFL and that with Ho:YAG laser. Stone volume, stone density, stone fragmentation rates, total lasing time, total operative time, endoscopic vision, retropulsion and stone free rates were analyzed in both groups and compared. Results: Mean stone volume was comparable in the TFL group and the Ho:YAG laser group (282.45 [standard deviation, SD 139.79] mm3 vs. 279.49 [SD 312.52] mm3; p=0.964). Mean stone density was also comparable in the TFL group and the Ho:YAG laser group (1135.30 [SD 317.04] Hounsfield unit vs. 1131.75 [SD 283.03] Hounsfield unit; p=0.959). The mean stone fragmentation rates calculated as stone volume divided by lasing time were 25.85 (SD 10.61) mm3/min and 21.37 (SD 14.13) mm3/min in the TFL group and the Ho:YAG laser group, respectively (p=0.113). The mean total lasing time (10.15 [SD] 4.69 min vs. 11.43 [SD 4.56] min; p=0.222), mean operative time (25.13 [SD 9.51] min vs. 25.54 [SD 10.32] min; p=0.866), and mean total hospital stay (2.62 [SD 0.77] days vs. 2.61 [SD 0.84] days; p=0.893) were comparable in the TFL group and in the Ho:YAG group. The vision was better and retropulsion was less in the TFL group. The stone-free rate at 1 month postoperatively was slightly better in the TFL group (100% vs. 90%; p=0.095). Conclusion: TFL technology was associated with the comparable total surgical time, total lasing time, and stone fragmentation rate with Ho:YAG laser. However, TFL had better endoscopic vision, lesser stone retropulsion, and slightly better stone-free rates.

Improving sepsis prediction in intensive care with SepsisAI: A clinical decision support system with a focus on minimizing false alarms.

Prediction of sepsis using machine-learning approaches has recently gained traction. However, the lack of translation of these algorithms into clinical routine remains a major issue. Existing early sepsis detection methods are either based on the older definition of sepsis or do not accurately detect sepsis leading to the high frequency of false-positive alarms. This results in a well-known issue of clinicians' "alarm fatigue", leading to decreased responsiveness and identification, ultimately resulting in delayed clinical intervention. Hence, there is a fundamental, unmet need for a clinical decision system capable of accurate and timely sepsis diagnosis, running at the point of need. In this work, SepsisAI-a deep-learning algorithm based on long short-term memory (LSTM) networks was developed to predict the early onset of hospital-acquired sepsis in real-time for patients admitted to the ICU. The models are trained and validated with data from the PhysioNet Challenge, consisting of 40,336 patient data files from two healthcare systems: Beth Israel Deaconess Medical Center and Emory University Hospital. In the short term, the algorithm tracks frequently measured vital signs, sparsely available lab parameters, demographic features, and certain derived features for making predictions. A real-time alert system, which monitors the trajectory of the predictions, is developed on top of the deep-learning framework to minimize false alarms. On a balanced test dataset, the model achieves an AUROC, AUPRC, sensitivity, and specificity of 0.95, 0.96, 88.19%, and 96.75%, respectively at the patient level. In terms of lookahead time, the model issues a warning at a median of 6 hours (IQR 6 to 20 hours) and raises an alert at a median of 4 hours (IQR 2 to 5 hours) ahead of sepsis onset. Most importantly, the model achieves a false-alarm ratio of 3.18% for alerts, which is significantly less than other sepsis alarm systems. Additionally, on a disease prevalence-based test set, the algorithm reported similar outcomes with AUROC and AUPRC of 0.94 and 0.87, respectively, with sensitivity, and specificity of 97.05%, and 96.75%, respectively. The proposed algorithm might serve as a clinical decision support system to assist clinicians in the accurate and timely diagnosis of sepsis. With exceptionally high specificity and low false-alarm rate, this algorithm also helps mitigate the well-known issue of clinician alert fatigue arising from currently proposed sepsis alarm systems. Consequently, the algorithm partially addresses the challenges of successfully integrating machine-learning algorithms into routine clinical care.

Anti-windup strategies for biomolecular control systems facilitated by model reduction theory for sequestration networks.

Robust perfect adaptation, a system property whereby a variable adapts to persistent perturbations at steady state, has been recently realized in living cells using genetic integral controllers. In certain scenarios, such controllers may lead to "integral windup," an adverse condition caused by saturating control elements, which manifests as error accumulation, poor dynamic performance, or instabilities. To mitigate this effect, we here introduce several biomolecular anti-windup topologies and link them to control-theoretic anti-windup strategies. This is achieved using a novel model reduction theory that we develop for reaction networks with fast sequestration reactions. We then show how the anti-windup topologies can be realized as reaction networks and propose intein-based genetic designs for their implementation. We validate our designs through simulations on various biological systems, including models of patients with type I diabetes and advanced biomolecular proportional-integral-derivative (PID) controllers, demonstrating their efficacy in mitigating windup effects and ensuring safety.

Plasmodium falciparum CLAG Paralogs All Traffic to the Host Membrane but Knockouts Have Distinct Phenotypes.

Malaria parasites increase their host erythrocyte's permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human Plasmodium falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, a protein integral to the host erythrocyte membrane and encoded by a member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also insert at the host membrane is unknown; their contributions to PSAC formation and other roles served are also unexplored. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog is colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular proteases, but CLAG8 and CLAG9 are protease resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with higher physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in the transcription of the remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake for specific solutes. We also report on the distinct transport properties of these knockout lines. Similar membrane topologies at the host membrane are consistent with each CLAG paralog contributing to PSAC, but other roles require further examination.

The Surprise Question and clinician-predicted prognosis: systematic review and meta-analysis.

BACKGROUND: The Surprise Question, 'Would you be surprised if this person died within the next year?' is a simple tool that can be used by clinicians to identify people within the last year of life. This review aimed to determine the accuracy of this assessment, across different healthcare settings, specialties, follow-up periods and respondents. METHODS: Searches were conducted of Medline, Embase, AMED, PubMed and the Cochrane Central Register of Controlled Trials, from inception until 01 January 2024. Studies were included if they reported original data on the ability of the Surprise Question to predict survival. For each study (including subgroups), sensitivity, specificity, positive and negative predictive values and accuracy were determined. RESULTS: Our dataset comprised 56 distinct cohorts, including 68 829 patients. In a pooled analysis, the sensitivity of the Surprise Question was 0.69 ((0.64 to 0.74) I2=97.2%), specificity 0.69 ((0.63 to 0.74) I2=99.7%), positive predictive value 0.40 ((0.35 to 0.45) I2=99.4%), negative predictive value 0.89 ((0.87 to 0.91) I2=99.7%) and accuracy 0.71 ((0.68 to 0.75) I2=99.3%). The prompt performed best in populations with high event rates, shorter timeframes and when posed to more experienced respondents. CONCLUSIONS: The Surprise Question demonstrated modest accuracy with considerable heterogeneity across the population to which it was applied and to whom it was posed. Prospective studies should test whether the prompt can facilitate timely access to palliative care services, as originally envisioned. PROSPERO REGISTRATION NUMBER: CRD32022298236.

Recombinant YopE and LcrV vaccine candidates protect mice against plague and yersiniosis.

No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1ß from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.

Successful Management of Anomalous Lipton R-III Right Coronary Artery Chronic Total Occlusion.

Chronic total occlusion (CTO) of the coronary artery is a subset where cardiologists confront technical challenges most of the time during percutaneous coronary intervention (PCI). A congenital coronary anomaly is considered a critical challenge, especially when accompanied by CTO lesions. We report a case of a 64-year-old hypertensive and chronic smoker male who presented to our tertiary care center with chief complaints of Canadian Cardiovascular Society II angina. Coronary angiography revealed proximal right coronary artery CTO in a patient with an anomalous origin of coronary arteries arising from the right single sinus "Lipton R-III" which was managed successfully through PCI.

Advanced methods for gene network identification and noise decomposition from single-cell data.

Central to analyzing noisy gene expression systems is solving the Chemical Master Equation (CME), which characterizes the probability evolution of the reacting species' copy numbers. Solving CMEs for high-dimensional systems suffers from the curse of dimensionality. Here, we propose a computational method for improved scalability through a divide-and-conquer strategy that optimally decomposes the whole system into a leader system and several conditionally independent follower subsystems. The CME is solved by combining Monte Carlo estimation for the leader system with stochastic filtering procedures for the follower subsystems. We demonstrate this method with high-dimensional numerical examples and apply it to identify a yeast transcription system at the single-cell resolution, leveraging mRNA time-course experimental data. The identification results enable an accurate examination of the heterogeneity in rate parameters among isogenic cells. To validate this result, we develop a noise decomposition technique exploiting time-course data but requiring no supplementary components, e.g., dual-reporters.

Vaginal pessary: a culprit for intraperitoneal bladder perforation.

Vaginal pessaries are widely considered to be a safe and effective non-surgical management option for women with pelvic organ prolapse. Complications may occur, and are more frequent with improper care and certain device designs and materials. It is imperative to provide information to patients about potential complications. We present the case of a woman in her 70s who presented to the Emergency Department with increasing groin and abdominal pain following a vaginal pessary insertion 2 days prior for grade 3 vaginal vault prolapse. On presentation, her abdomen was markedly distended with guarding. Laboratory investigations showed a significant acute kidney injury with a metabolic acidosis. An initial non-contrast CT showed fluid and inflammatory changes surrounding the bladder, and bladder perforation was suspected. A subsequent CT cystogram showed extravasation of contrast from the bladder into the peritoneal cavity, in keeping with an intraperitoneal bladder rupture. The patient underwent an emergency bladder repair in theatre.

Red in the face: Approach to diagnosis of red rashes on the face.

BACKGROUND: A red rash on the face in an adult patient is a common presentation to general practice in Australia. Rashes on the face significantly affect quality of life because this is a cosmetically sensitive site. Ascertaining the correct diagnosis is therefore of utmost importance so that appropriate treatment can be initiated. OBJECTIVE: This article discusses the assessment of red rashes on the face in an adult patient. DISCUSSION: Diagnosing a red rash on the face requires assessment of symptomology, age of onset, rash morphology and 'clinical clues' that help delineate between differentials. Although the list of differential diagnoses is wide, many of the common diagnoses can be made clinically without the need for investigations. Investigations such as skin biopsy are useful if the diagnosis is unclear, if the rash is not responding to initial treatment and/or a referral to a dermatologist is being considered.

Controlling CAR-T cell activity and specificity with synthetic SparX adapters.

While conventional chimeric antigen-receptor (CAR)-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-domain-containing proteins (soluble protein antigen-receptor X-linker [SparX]) bind one or more tumor antigens and mark those cells for elimination by genetically modified T cells (antigen-receptor complex [ARC]-T). The chimeric antigen receptor was engineered with a D-domain that specifically binds to the SparX protein via a unique TAG, derived from human alpha-fetoprotein. The interaction is mediated through an epitope on the TAG that is occluded in the native alpha-fetoprotein molecule. In vitro and in vivo data demonstrate that the activation and cytolytic activity of ARC-T cells is dependent on the dose of SparX protein and only occurs when ARC-T cells are engaged with SparX proteins bound to antigen-positive cells. ARC-T cell specificity was also redirected in vivo by changing SparX proteins that recognized different tumor antigens to combat inherent or acquired tumor heterogeneity. The ARC-SparX platform is designed to expand patient and physician access to cell therapy by controlling potential toxicities through SparX dosing regimens and enhancing tumor elimination through sequential or simultaneous administration of SparX proteins engineered to bind different tumor antigens.

A DNA aptamer-based assay for the detection of soluble ST2, a prognostic biomarker for monitoring heart failure.

Heart failure (HF) is emerging as a leading cause of death worldwide. Estimation of BNP levels is a routine diagnosis in these patients. However, in patients having high body-mass index (BMI), renal disease or in geriatric patients, BNP level is reported to be noisy and leads to incongruous conclusion. Thus, for better risk stratification among heart failure patients, it is imperative to look for a superior biomarker. In recent times, sST2 has shown promise as a biomarker. Identifying such biomarkers in peripheral blood of HF patients, need an affine and selective molecular recognition element. Thus, in the current study an aptamer (sS9_P) against sST2 was identified from an aptamer library. Systematic Evolution of Ligands through Exponential enrichment (SELEX) derived aptamer evinced role of its primer binding domains in maintaining its selectivity. This aptamer candidate demonstrated dissociation constant (Kd) in low nanomolar range, and the Limit of Detection (LOD) was ~4 ng. Circular dichroism confirms the formation of complex stem-loop like structure. The well characterized sS9_P aptamer was used in an Aptamer Linked Immobilized Sorbent Assay (ALISA) to detect sST2 level in patients' serum (n = 99). Aptamer sS9_P has shown significant discrimination to differentiate HF patients and healthy volunteers with a reasonable specificity (~83 %) with a modest sensitivity of ~64 %. While sST-2 antibody has shown poor specificity of ~44% but good sensitivity (~87%). The insight obtained from this study indicates that a combination of aptamer and antibody-based assay can be used to design a point-of-care assay for the rapid detection of HF patients in emergency settings.

Approach to red, scaly eruptions in the older patient.

BACKGROUND: Older patients with a red scaly eruption often present first to a primary care practitioner. A thorough clinical assessment can help delineate between common causes and assist the clinician with the next steps in management. OBJECTIVE: This article discusses the assessment of acute- to subacute-onset erythematous and scaly plaques that are present on multiple body sites in a patient aged >65 years. DISCUSSION: The differential diagnosis of a red, scaly rash in an older patient includes atopic dermatitis, psoriasis, generalised drug eruption, tinea, scabies and non-bullous pemphigoid. Less common causes include subacute cutaneous lupus and mycosis fungoides. If the diagnosis is unclear after clinical assessment, a skin biopsy sent for histopathology, and/or direct immunofluorescence can be very useful. Management requires consideration of physical impairments, carer availability and cost.

Outcomes following cardiac resynchronisation therapy in older people.

INTRODUCTION: Older patients may be less likely to receive cardiac resynchronisation therapy (CRT) for the management of heart failure. We aimed to describe the differences in clinical response, complications, and subsequent outcomes following CRT implantation compared to younger patients. METHODS: We conducted a retrospective cohort study of unselected, consecutive patients implanted with CRT devices between March 2008 and July 2017. We recorded complications, symptomatic and echocardiographic response, hospitalisation for heart failure, and all-cause mortality comparing patients aged <70, 70-79 and ≥ 80 years. RESULTS: Five hundred and seventy-four patients (median age 76 years [interquartile range 68-81], 73.3% male) received CRT. At baseline, patients aged ≥80 years had worse symptoms, were more likely to have co-morbidities, and less likely to be receiving comprehensive medical therapy, although left ventricular function was similar. Older patients were less likely to receive CRT-defibrillators compared to CRT-pacemakers. Complications were infrequent and not more common in older patients. Age was not a predictor of symptomatic or echocardiographic response to CRT (67.2%, 71.2% and 62.6% responders in patients aged <70, 70-79 and ≥ 80 years, respectively; P = 0.43), and time to first heart failure hospitalisation was similar across age groups (P = 0.28). Ten-year survival was lower for older patients (49.9%, 23.9% and 6.8% in patients aged <70, 70-79 and ≥ 80 years, respectively; P < 0.001). CONCLUSIONS: The benefits of CRT on symptoms and left ventricular function were not different in older patients despite a greater burden of co-morbidities and less optimal medical therapy. These findings support the use of CRT in an ageing population.

Clinical and Radiological End Points to Stop Anti-Tubercular Treatment in Central Nervous System Tuberculoma and Predictors of Poor Outcome: A Retrospective Study.

The clinical and radiological end points to stop anti-tubercular treatment in central nervous system (CNS) tuberculoma are not known. This retrospective study was done to determine end points to stop anti-tubercular treatment and find the predictors of poor outcome in patients with CNS tuberculoma. Patients who were admitted with a diagnosis of brain/spine tuberculoma between January 2015 and December 2019 and who completed a minimum of 1-year follow-up were enrolled. Clinical and radiological end points to stop anti-tubercular treatment and predictors of death and poor outcome (modified Rankin scale > 2) were analyzed. One hundred and eight patients (male-to-female ratio, 47 [43.5%]:61 [56.5%]; brain tuberculoma, 102; spinal cord tuberculoma, 14; brain and spinal cord tuberculoma, 8) were included in the study. Median duration of anti-tubercular treatment was 24 months. Radiological resolution of tuberculoma (resolution of gadolinium-enhancing lesion, gliosis, calcification, cord atrophy, or syrinx formation) and radiological halt (no increase in size/number of tuberculoma on magnetic resonance imaging scans done 6 months apart) were used as end points to stop anti-tubercular treatment in 69 and 7 patients, respectively. Seven patients stopped their treatment by themselves, and 25 patients died. Altered sensorium, motor weakness, infarcts, hydrocephalus, and constitutional symptoms of tuberculous meningitis were predictors of poor outcome or death in CNS tuberculoma patients. Radiological resolution or radiological halt of brain/spinal cord tuberculoma was a reasonable end point to stop anti-tubercular treatment. However, this may require 24 months or more of anti-tubercular treatment. Associated tuberculous meningitis and its complications portend a poor prognosis.

Effectiveness of Eupatorium perfoliatum 30C in Prevention of Dengue Fever and Acute Febrile Illness during 2017 Dengue Outbreak in Urban Slums of Delhi: A Prospective, Open-Label, Community-Based, Parallel Cohort Study.

OBJECTIVE: This study was undertaken to assess the effectiveness of Eupatorium perfoliatum (EP) 30C on the incidence of dengue fever and acute febrile illness (AFI) during the 2017 dengue outbreak. METHODS: We conducted a prospective, open-label, community-based parallel cohort study involving apparently healthy individuals residing in 06 urban slums (JJ colony) of Delhi. The participants were enrolled in two cohorts - the medicine cohort (MC) and the control cohort (CC). Participants in MC were given weekly one dose of EP 30C for 10 weeks along with Information, Education and Communication (IEC) material regarding dengue. Participants in the CC were provided with the IEC material only. The primary outcome measure was the incidence of dengue fever as per case definitions notified in the national guidelines for clinical management of dengue fever by the Government of India during the 10 weeks follow-up period. The secondary outcome measures were the incidence of AFI and the hospitalization of confirmed dengue cases. RESULTS: The analysis included 40,769 participants residing in 06 slum clusters of Delhi out of which 28,321 participants were in MC and 12,448 participants were in CC. The incidence of laboratory-confirmed dengue in the MC was 2.57 per 10,000 person-weeks (95% confidence interval [CI], 2.02-3.22) in comparison with 7.55 per 10,000 person-weeks (95% CI, 6.12-9.21) in the CC. The incidence of AFI in the MC was 19.66 per 10,000 person-weeks (95% CI, 18.07-21.36) in comparison with 40.96 per 10,000 person-weeks (95% CI, 37.48-44.67) in the CC. The overall protective effect of EP against laboratory-confirmed dengue was 65.77% (95% CI, 53.37-74.87; p = 0.0001) and against AFI was 52.58% (95% CI, 46.37-58.07; p = 0.0001). Hospitalization reported in the MC was nil as against 4.35% in the CC. No dengue-related case fatalities were reported from either cohort. None of the participants from the MC reported any adverse events owing to the prophylactic intervention. CONCLUSION: The study concludes that EP 30C was able to prevent dengue significantly. Randomized controlled trials are needed to confirm or refute our findings.Das Ziel dieser Studie war die Beurteilung der Wirksamkeit von Eupatorium perfoliatum (EP) 30C auf die Inzidenz von Dengue-Fieber und akuter fiebriger Erkrankung (AFE) während des Dengue-Ausbruchs 2017.Wir führten eine prospektive, unverblindete, Bevölkerungs-Parallelgruppen-Kohortenstudie mit augenscheinlich gesunden Bewohnern von 6 städtischen Slums (JJ-Kolonie) in Delhi durch. Die Teilnehmer wurden in 2 Kohorten aufgenommen, einer Medizinkohorte (MK) und einer Kontrollkohorte (KK). Die Teilnehmer in der MK erhielten 10 Wochen lang wöchentlich eine Dosis EP 30C und dazu Aufklärungsmaterialien über Dengue. Die Teilnehmer in der KK erhielten nur die Aufklärungsmaterialien. Die primäre Zielgröße war die Dengue-Fieber-Inzidenz laut der in den nationalen Leitlinien für das klinische Management des Dengue-Fiebers von der indischen Regierung bekannt gegebenen Falldefinition in dem zehnwöchigen Beobachtungszeitraum. Die sekundären Zielgrößen waren die Inzidenz von AFE und die Anzahl hospitalisierter bestätigter Dengue-Fälle.In die Analyse wurden 40,769 Bewohner von 6 Slum-Clustern in Delhi einbezogen, davon wurden 28,321 Teilnehmer in die MK aufgenommen und 12,448 Teilnehmer in die KK. Die Inzidenz von im Labor bestätigter Dengue betrug in der MK 2,57 pro 10,000 Personen/Woche (95%-Konfidenzintervall [KI]: 2,02­3,22), verglichen mit 7,55 pro 10,000 Personen/Woche (95%-KI: 6,12­9,21) in der KK. Die Inzidenz von AFI betrug in der MK 19,66 pro 10,000 Personen/Woche (95%-Konfidenzintervall [KI]: 18,07­21,36), verglichen mit 40,96 pro 10,000 Personen/Woche (95%-KI: 37,48­44,67) in der KK. Der Schutzeffekt (SE) von EP betrug gegen im Labor bestätigte Dengue 65,77% (95%-KI: 53,37­74,87; p = 0,0001) und gegen AFI 52,58% (95%-KI: 46,37­58,07; p = 0,0001). Die Hospitalisierungsrate war in der MK gleich Null versus 4,35% in der KK. In keiner Kohorte waren Dengue-bedingte Todesfälle zu verzeichnen. Bei keinem der Teilnehmer in der MK traten jegliche unerwünschten Ereignisse infolge der prophylaktischen Maßnahme auf.Die Studie gelangt zu dem Schluss, dass Eupatorium perfoliatum 30C in signifikantem Maße Dengue vorbeugen konnte. Randomisierte kontrollierte Studien sind erforderlich, um unsere Ergebnisse zu bestätigen bzw. zu widerlegen.

A systematic review exploring the mechanisms by which citrus bioflavonoid supplementation benefits blood glucose levels and metabolic complications in type 2 diabetes mellitus.

BACKGROUND: Citrus bioflavonoids are polyphenolic compounds that are derived from citrus fruits and vegetables. Although they are well known for their powerful antioxidant properties, their effects on glycemic control are not well understood. This review aims to highlight the potential benefits of using citrus bioflavonoids in patients with type 2 diabetes mellitus and its metabolic complications, as well as the medicinal effects of known subclasses of naturally occurring citrus bioflavonoids. METHODS: In this systematic review, a survey of studies was conducted from January 2012 to February 2023 using various databases (PubMed, Medline, Google Scholar, and Scopus) to determine the effects of citrus bioflavonoid supplementation on reducing oxidative stress, improving lipid profiles, and glycemic index in patients with diabetes mellitus, as well as the proposed mechanisms of action. RESULTS: The results of the survey indicate that citrus bioflavonoids may have a positive impact on reducing oxidative stress levels in patients with type 2 diabetes mellitus. In addition to reducing oxidative stress, citrus bioflavonoids may also have a positive impact on other markers of diabetes. For example, studies have shown that they can reduce non-enzymatic protein glycation, which is a process that occurs when glucose molecules bind to proteins in the body. CONCLUSION: The reduction in oxidative stress that can be achieved using citrus bioflavonoids may help to maintain antioxidant levels in the body, thereby reducing the severity of diabetes and its complications. These findings suggest that citrus bioflavonoids may be a useful complementary therapy for patients with diabetes.

Left-sided cholecystitis in a patient with situs inversus totalis, complicated by portal venous malformations.

Situs inversus totalis (SIT) is a rare autosomal recessive anomaly in which the thoracoabdominal viscerae are laterally transposed, introducing unique challenges in surgical scenarios. Only a few reports have demonstrated the treatment of cholecystitis in situs inversus, much less so in the context of portal vascular anomalies. We present the case of a 41-year-old female presenting to the emergency department with right upper quadrant pain, and subsequently found to have left-sided cholecystitis complicated by SIT with portal venous malformations on magnetic resonance cholangiopancreatography and abdominal computed tomography. Initially, she was referred for open cholecystectomy however due to the lack of symptoms and the presence of a tortuous recanalized portal vein presenting multiple thrombotic complications, an expectant approach was adopted. Thus, imaging remains the gold-standard to diagnose SIT and consideration of all congenital risk factors to cholecystectomy is crucial to avoid post-operative complications.