Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles.

Extracellular vesicles (EVs), or exosomes, play important roles in physiological and pathological cellular communication and have gained substantial traction as biological drug carriers. EVs contain both short and long non-coding RNAs that regulate gene expression and epigenetic processes. To fully capitalize on the potential of EVs as drug carriers, it is important to study and understand the intricacies of EV function and EV RNA-based communication. Here we developed a genetically encodable RNA-based biomaterial, termed EXO-Probe, for tracking EV RNAs. The EXO-Probe comprises an EV-loading RNA sequence (EXO-Code), fused to a fluorogenic RNA Mango aptamer for RNA imaging. This fusion construct allowed the visualization and tracking of EV RNA and colocalization with markers of multivesicular bodies; imaging RNA within EVs, and non-destructive quantification of EVs. Overall, the new RNA-based biomaterial provides a useful and versatile means to interrogate the role of EVs in cellular communication via RNA trafficking to EVs and to study cellular sorting decisions. The system will also help lay the foundation to further improve the therapeutic efficacy of EVs as drug carriers.

Rubella immunity among pregnant women and the burden of congenital rubella syndrome (CRS) in India, 2022.

BACKGROUND: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. METHODS: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. RESULTS: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. CONCLUSION: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella.

Chronic nonspecific multiple-sites pain [CNMSP] of unknown etiology: Biopsychosocial method of evaluation for the primary care level.

Background: Understanding and dealing with chronic nonspecific pain (CNP) is the important entity at primary care hospital. Chronic nonspecific multiple-site pain [CNMSP] of unknown etiology creates diagnostic and therapeutic challenges for primary care physicians due to lack of guidance regarding evaluation and treatment. Aims and Objectives: To classify and formulate the evaluation, treatment strategies, and prediction of prognosis of patients with CNMSP of unknown etiology. Methods: Patients present with CNMSP of more than 3-month duration without any obvious medical cause. The biopsychosocial [BPS] model with 3P model was applied to see the biological, psychological, and social factors behind persistence. Finally, patients were classified into four groups for evaluation response to treatment and relapse rates in 12-month follow-up. Results: Of the total 243 patients of CNMSP, 243 [96.3%] were females. Sixty [24.7%] patients had short duration, and 183 [75.3%] had long duration. Headache was in 115 [47%], low back pain ± leg pain in 96 [39.4%], cervical pain ± shoulder/arm pain in 83 [34.1%], and diffuse body pain in 50 [20.5%] in various combinations. A total of 155 [63.8%] patients had high somatization-sensitization index (SSI), and 144 [59.3%] had low ferritin level. Group 1 [high SSI and low ferritin] had 37.9% of patients, group 2 [high SSI and normal ferritin] had 25.9% of patients, group 3 [low to medium SSI with low ferritin] had 21.4% of patients, and group 4 [low to medium SSI with normal ferritin] had 14.8% of patients. Response to pain symptoms was better in group 1, and relapse rate was higher in group 2. Conclusion: CNMSP of unknown etiology itself is a heterogeneous entity, and assessment based on the BPS model can be very useful to understand the treatment plan and outcome of these patients.

Biomolecular Condensates Can Enhance Pathological RNA Clustering.

Intracellular aggregation of repeat expanded RNA has been implicated in many neurological disorders. Here, we study the role of biomolecular condensates on irreversible RNA clustering. We find that physiologically relevant and disease-associated repeat RNAs spontaneously undergo an age-dependent percolation transition inside multi-component protein-nucleic acid condensates to form nanoscale clusters. Homotypic RNA clusters drive the emergence of multiphasic condensate structures with an RNA-rich solid core surrounded by an RNA-depleted fluid shell. The timescale of the RNA clustering, which drives a liquid-to-solid transition of biomolecular condensates, is determined by the sequence features, stability of RNA secondary structure, and repeat length. Importantly, G3BP1, the core scaffold of stress granules, introduces heterotypic buffering to homotypic RNA-RNA interactions and impedes intra-condensate RNA clustering in an ATP-independent manner. Our work suggests that biomolecular condensates can act as sites for RNA aggregation. It also highlights the functional role of RNA-binding proteins in suppressing aberrant RNA phase transitions.

Zinc-exchanged montmorillonite clay: A promising slow-release nanofertilizer for rice (Oryza sativa L.).

This study is to examine zinc exchanged montmorillonite (Zn-MMT) as a potential slow release nanofertilizer for rice crop. The effective intercalation of zinc within the montmorillonite inter layers was firmly established via analytical techniques including Zeta potential, FE-SEM (Field Emission Scanning Electron Microscopy) with Energy Dispersive X-ray Analysis (EDAX), Transmission Electron Microscope (TEM), X-Ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR). The efficacy of Zn-MMT was examined by evaluating its ability to facilitate controlled zinc release, as confirmed through an incubation study. Subsequently, the kinetics of zinc release was analyzed by different mathematical models such as Zero-order kinetics, First-order kinetics, the Higuchi model, and the Korsmeyer-Peppas model. From the pot culture study spanning 90 days the results indicated that Zn-MMT had significantly high plant height, Leaf Area Index (LAI), Dry Matter Production (DMP), number of tillers per hill, panicles length, increased grain and straw yield, in comparison with conventional zinc sulphate (ZnSO4). Total phenol, total protein and total chlorophyll content were significantly at higher levels with Zn-MMT treated rice crops as compared to conventional fertilizers and control. A similar trend was seen with phytochemicals such as Indole Acetic Acid (IAA), Superoxide Dismutase (SOD) and Carbonic Anhydrase (CA). Notably, rice grains harvested from Zn-MMTtreated crops exhibited significantly higher zinc content than those using other treatments. This Zn-MMT can be confirmed as a better alternative to conventional zinc sulphate fertilizers owing to its slow-release of nutrient into the soil and thus increased zinc use efficiency.

Direct computations of viscoelastic moduli of biomolecular condensates.

In vitro facsimiles of biomolecular condensates are formed by different types of intrinsically disordered proteins including prion-like low complexity domains (PLCDs). PLCD condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model and information regarding intra- and inter-chain contacts that is extracted from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations. The key ingredient of the generalized Rouse model is the Zimm matrix that we compute from equilibrium MMC simulations. We compute two flavors of Zimm matrices, one referred to as the single-chain model that accounts only for intra-chain contacts, and the other referred to as a collective model, that accounts for inter-chain interactions. The single-chain model systematically overestimates the storage and loss moduli, whereas the collective model reproduces the measured moduli with greater fidelity. However, in the long time, low-frequency domain, a mixture of the two models proves to be most accurate. In line with the theory of Rouse, we find that a continuous distribution of relaxation times exists in condensates. The single crossover frequency between dominantly elastic versus dominantly viscous behaviors is influenced by the totality of the relaxation modes. Hence, our analysis suggests that viscoelastic fluid-like condensates are best described as generalized Maxwell fluids. Finally, we show that the complex shear moduli can be used to solve an inverse problem to obtain distributions of relaxation times that underlie the dynamics within condensates.

Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.

Vegetation change detection and recovery assessment based on post-fire satellite imagery using deep learning.

Wildfires are uncontrolled fires fuelled by dry conditions, high winds, and flammable materials that profoundly impact vegetation, leading to significant consequences including noteworthy changes to ecosystems. In this study, we provide a novel methodology to understand and evaluate post-fire effects on vegetation. In regions affected by wildfires, earth-observation data from various satellite sources can be vital in monitoring vegetation and assessing its impact. These effects can be understood by detecting vegetation change over the years using a novel unsupervised method termed Deep Embedded Clustering (DEC), which enables us to classify regions based on whether there has been a change in vegetation after the fire. Our model achieves an impressive accuracy of 96.17%. Appropriate vegetation indices can be used to evaluate the evolution of vegetation patterns over the years; for this study, we utilized Enhanced Vegetation Index (EVI) based trend analysis showing the greening fraction, which ranges from 0.1 to 22.4 km2 while the browning fraction ranges from 0.1 to 18.1 km2 over the years. Vegetation recovery maps can be created to assess re-vegetation in regions affected by the fire, which is performed via a deep learning-based unsupervised method, Adaptive Generative Adversarial Neural Network Model (AdaptiGAN) on post-fire data collected from various regions affected by wildfire with a training error of 0.075 proving its capability. Based on the results obtained from the study, our approach tends to have notable merits when compared to pre-existing works.

Imaging for Early Detection of Pancreatic Ductal Adenocarcinoma: Updates and Challenges in the Implementation of Screening and Surveillance Programs.

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive cancers. It has a poor 5-year survival rate of 12%, partly because most cases are diagnosed at advanced stages, precluding curative surgical resection. Early-stage PDA has significantly better prognoses due to increased potential for curative interventions, making early detection of PDA critically important to improved patient outcomes. We examine current and evolving early detection concepts, screening strategies, diagnostic yields among high-risk individuals, controversies, and limitations of standard-of-care imaging.

Evaluating a New Digital App-Based Program for Heart Health: Feasibility and Acceptability Pilot Study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the United States, affecting a significant proportion of adults. Digital health lifestyle change programs have emerged as a promising method of CVD prevention, offering benefits such as on-demand support, lower cost, and increased scalability. Prior research has shown the effectiveness of digital health interventions in reducing negative CVD outcomes. This pilot study focuses on the Lark Heart Health program, a fully digital artificial intelligence (AI)-powered smartphone app, providing synchronous CVD risk counseling, educational content, and personalized coaching. OBJECTIVE: This pilot study evaluated the feasibility and acceptability of a fully digital AI-powered lifestyle change program called Lark Heart Health. Primary analyses assessed (1) participant satisfaction, (2) engagement with the program, and (3) the submission of health screeners. Secondary analyses were conducted to evaluate weight loss outcomes, given that a major focus of the Heart Health program is weight management. METHODS: This study enrolled 509 participants in the 90-day real-world single-arm pilot study of the Heart Health app. Participants engaged with the app by participating in coaching conversations, logging meals, tracking weight, and completing educational lessons. The study outcomes included participant satisfaction, app engagement, the completion of screeners, and weight loss. RESULTS: On average, Heart Health study participants were aged 60.9 (SD 10.3; range 40-75) years, with average BMI indicating class I obesity. Of the 509 participants, 489 (96.1%) stayed enrolled until the end of the study (dropout rate: 3.9%). Study retention, based on providing a weight measurement during month 3, was 80% (407/509; 95% CI 76.2%-83.4%). Participant satisfaction scores indicated high satisfaction with the overall app experience, with an average score of ≥4 out of 5 for all satisfaction indicators. Participants also showed high engagement with the app, with 83.4% (408/489; 95% CI 80.1%-86.7%) of the sample engaging in ≥5 coaching conversations in month 3. The results indicated that participants were successfully able to submit health screeners within the app, with 90% (440/489; 95% CI 87%-92.5%) submitting all 3 screeners measured in the study. Finally, secondary analyses showed that participants lost weight during the program, with analyses showing an average weight nadir of 3.8% (SD 2.9%; 95% CI 3.5%-4.1%). CONCLUSIONS: The study results indicate that participants in this study were satisfied with their experience using the Heart Health app, highly engaged with the app features, and willing and able to complete health screening surveys in the app. These acceptability and feasibility results provide a key first step in the process of evidence generation for a new AI-powered digital program for heart health. Future work can expand these results to test outcomes with a commercial version of the Heart Health app in a diverse real-world sample.

A case of secondary multiple evanescent white dot syndrome in a patient with preexisting wet age-related macular degeneration.

Purpose: To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration. Observation: A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1 meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula. Conclusion and importance: Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.

Conservative Management of a Case of Peripartum Cardiomyopathy in a Young Multigravida.

Peripartum cardiomyopathy (PPCM) is a rare disorder that generally affects the elderly multigravida females. It is a type of dilated cardiomyopathy that generally affects the last trimester of pregnancy or early postpartum period. Several risk factors are associated with the development of PPCM. Even though PPCM has greater morbidity, if managed promptly, it can be reverted with minimal morbidity or mortality. We present a case of a young woman, multigravida, with moderate anemia corrected, who was taken for emergency lower segment cesarean section, without previous cardiac evaluation, and ended up with pulmonary edema intraoperatively. Later on, her evaluation was done which came out to be PPCM. She was managed conservatively thereafter with no significant morbidity and a good maternal and perinatal outcome. We should be alert in diagnosing a case of PPCM with prompt treatment to reduce mortality. Cardiovascular conditions cause approximately 26 percent of pregnancy-related deaths which include valvular heart disease and congenital heart disease. Appropriate diagnosis and management are necessary for preventing mishaps.

An Unusual Presentation of Villoglandular Papillary Adenocarcinoma in a Perimenopausal Woman.

Villoglandular papillary adenocarcinoma (VPA) or villoglandular adenocarcinoma (VGA) is a rare but well-recognized subtype of cervical carcinoma. It exhibits a favorable prognosis, particularly within the childbearing age group, and is considered a rare manifestation of mucinous adenocarcinoma typically observed in individuals of reproductive age. In comparison to other adenocarcinomas, VPA generally demonstrates a more optimistic prognosis. This report details the case of a 46-year-old perimenopausal woman who presented with complaints of irregular menses and a protruding mass from the vagina. Upon examination, an exophytic growth was identified, replacing the cervix. A biopsy confirmed the diagnosis of VPA. Subsequently, the patient underwent a radical hysterectomy, followed by post-operative radiation therapy.

Mortality in patients with normal left ventricular function requiring emergency VA-ECMO for postcardiotomy cardiogenic shock due to coronary malperfusion.

OBJECTIVES: To analyze outcomes in patients with normal preoperative left ventricular ejection fraction (LVEF) undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy due to postcardiotomy cardiogenic shock (PCCS) related to coronary malperfusion. METHODS: Retrospective single-center analysis in patients with normal preoperative LVEF treated with VA-ECMO for coronary malperfusion-related PCCS between May 1998 and May 2018. The primary outcome was 30-day mortality, which was compared using the Kaplan-Meier method and the log-rank test. Multivariable logistic regression was performed to identify predictors of mortality. RESULTS: During the study period, a total of 62,125 patients underwent cardiac surgery at our institution. Amongst them, 59 patients (0.1%) with normal preoperative LVEF required VA-ECMO support due to coronary malperfusion-related PCCS. The mean duration of VA-ECMO support was 6 days (interquartile range 4-7 days). The 30-day mortality was 50.8%. Under VA-ECMO therapy, a complication composite outcome of bleeding, re-exploration for bleeding, acute renal failure, acute liver failure, and sepsis occurred in 51 (86.4%) patients. Independent predictors of 30-day mortality were lactate levels > 9.9 mmol/l before VA-ECMO implantation (odds ratio [OR]: 3.3; 95% confidence interval [CI] 1.5-7.0; p = 0.002), delay until revascularization > 278 minutes (OR: 2.9; 95% CI 1.3-6.4; p = 0.008) and peripheral arterial artery disease (OR: 3.3; 95% 1.6-7.5; p = 0.001). CONCLUSIONS: Mortality rates are high in patients with normal preoperative LVEF who develop PCCS due to coronary malperfusion. The early implantation of VA-ECMO before the development of profound tissue hypoxia and early coronary revascularization increases the likelihood of survival. Lactate levels are useful to define optimal timing for the VA-ECMO initiation.

Determinants of viscoelasticity and flow activation energy in biomolecular condensates.

The form and function of biomolecular condensates are intimately linked to their material properties. Here, we integrate microrheology with molecular simulations to dissect the physical determinants of condensate fluid phase dynamics. By quantifying the timescales and energetics of network relaxation in a series of heterotypic viscoelastic condensates, we uncover distinctive roles of sticker motifs, binding energy, and chain length in dictating condensate dynamical properties. We find that the mechanical relaxation times of condensate-spanning networks are determined by both intermolecular interactions and chain length. We demonstrate, however, that the energy barrier for network reconfiguration, termed flow activation energy, is independent of chain length and only varies with the strengths of intermolecular interactions. Biomolecular diffusion in the dense phase depends on a complex interplay between viscoelasticity and flow activation energy. Our results illuminate distinctive roles of chain length and sequence-specific multivalent interactions underlying the complex material and transport properties of biomolecular condensates.

Heterotypic interactions can drive selective co-condensation of prion-like low-complexity domains of FET proteins and mammalian SWI/SNF complex.

Prion-like domains (PLDs) are low-complexity protein sequences enriched within nucleic acid-binding proteins including those involved in transcription and RNA processing. PLDs of FUS and EWSR1 play key roles in recruiting chromatin remodeler mammalian SWI/SNF (mSWI/SNF) complex to oncogenic FET fusion protein condensates. Here, we show that disordered low-complexity domains of multiple SWI/SNF subunits are prion-like with a strong propensity to undergo intracellular phase separation. These PLDs engage in sequence-specific heterotypic interactions with the PLD of FUS in the dilute phase at sub-saturation conditions, leading to the formation of PLD co-condensates. In the dense phase, homotypic and heterotypic PLD interactions are highly cooperative, resulting in the co-mixing of individual PLD phases and forming spatially homogeneous condensates. Heterotypic PLD-mediated positive cooperativity in protein-protein interaction networks is likely to play key roles in the co-phase separation of mSWI/SNF complex with transcription factors containing homologous low-complexity domains.

Experimental and numerical analysis of the thermal performance of pebble solar thermal collector.

In this work, pebbles of higher specific heat than the conventional absorber materials like aluminium or copper are proposed as a absorber in the solar flat plate collector. The proposed collector are integrated into the building design and constructed with masonry. Tests were conducted by varying the operating parameters which influence its performance, like the flow rate of the heat-absorbing medium, and the tilt of the collector using both coated and uncoated pebbles. The maximum temperature difference that could be measured for a conventional absorber was approximately 8 °C for a flow rate of 0.6 L/min. While for a coated and uncoated absorber, it was 7 °C and 5.5 °C respectively. This difference decreased with an increase in flow rates from 0.6 L/min to 1.2 L/min. For all the flow rates, it was observed that the average difference in efficiency between the coated and the conventional absorber collector is 5.82 %, while the difference between the coated and uncoated absorber collector is 15.68 %. Thus, it is very much evident that by replacing the conventional absorber with the proposed coated pebble absorber, the overall loss in efficiency is just 5.82 %, but the advantages are enormous. Along with the experimental study, numerical analysis was also carried out with CFD modeling. The numerical results agreed well with experimental results with the least error. Therefore, CFD simulation can be further used to optimize the design of the collector.

Late Presentation of ß-Thalassemia Major Patient With Left Hemiparesis: A Case Report.

Thalassemia is a hereditary autosomal recessive disorder that is distinguished by a diminished rate of hemoglobin (Hb) synthesis arising from an anomaly in the synthesis of α or ß globin chains. Classical symptoms of ß-thalassemia are frequently observed in patients who present late for blood transfusion (BT), which is typical among South Asian countries in light of their limited resources. This case report is an uncommon instance of a typical occurrence that has been infrequently reported in the South Asian region. The reporting of this case will assist healthcare workers in managing cases appropriately. We present a 12-year-old female child diagnosed with ß-thalassemia major with a late presentation than usual accompanied by an unusual finding of left hemiparesis at a young age of five years. The patient had been lost to follow-up, presented with easy fatiguability, poor weight gain, and growth restriction, all of which are classic symptoms of ß-thalassemia. The patient was treated with a BT and continued to be monitored for transfusion and iron overload management.

Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.

BACKGROUND: The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9-14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE. METHODS: In the DoRIS trial, 930 girls aged 9-14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15-20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50. FINDINGS: Month 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72-1·14) for HPV16 and 1·02 (0·78-1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14-1·82) and 1·47 (1·13-1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines. INTERPRETATION: HPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination. FUNDING: The UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section.