Chlorogenic Acid Enhances the Chaperone Potential of BSA at Physiological Concentrations on Model Protein Cytochrome c.

Neurodegenerative disorders are associated with the accumulation of disease-related proteins intracellularly and extracellularly. Extracellular chaperones play a crucial role in clearing the extracellularly accumulated proteins. In this study, we observed the extracellular chaperone-like potential of BSA at physiological concentrations on model protein cytochrome c (cyt c). Kinetics of heat-induced aggregation of cyt c suggest the nucleation independent first order aggregation kinetics. Aggregation of cyt c was studied in the presence of varying concentrations of BSA to assess its chaperone nature. At lower concentrations of BSA when the sub molar ratio of cyt c:BSA are 1:0.6 and 1:1.2, heat-induced unfolded cyt c promotes the aggregation of BSA. However, as the ratio of cyt c:BSA increases to 1:1.8, the aggregation of cyt c is reduced. When the concentration of BSA reaches physiological levels, yielding a cyt c:BSA ratio of 1:2.4, the rate of aggregation drastically decreases reflecting its chaperone potential. These observations indicate that under physiological conditions, macromolecular crowding stabilizes the native structure of both proteins and enhances their interaction that results in the reduced aggregation of cyt c. Additionally, the presence of the phytochemical chlorogenic acid at a sub-molar ratio of 1:1 stabilizes cyt c and prevents its unfolding and facilitates the binding of cyt c to BSA at physiological concentrations. This interaction further decreases the overall aggregation of cyt c and stabilizes its native fold.

Common pediatric surgical conditions and associated health-seeking behaviors in Pakistan: An urban and rural comparative assessment.

Approximately five billion people do not have access to necessary surgical treatment globally and up to 85% of children in LMICs are affected with conditions requiring surgical care by the age of 15 years. It is crucial to identify common surgical conditions in children in Pakistan to inform healthcare professionals and policymakers for effective resource allocation. This representative cross-sectional household survey conducted on children aged 5-10 years assessed existing surgical diseases and healthcare-seeking behaviors in the two largest provinces (Sindh and Punjab) of Pakistan. The data was collected through a validated cross-sectional survey tool [Surgeons OverSeas Assessment of Surgical Need (SOSAS)]. Caregivers were asked about their child's recent and past surgical conditions in six distinct anatomical regions and pictures were taken of identified conditions after appropriate consent for further diagnosis. Health-seeking behaviors including the kind of treatment sought, the nature of care received, and the reasons for not receiving care were noted. 13.5% of children surveyed reported a surgical condition, with a similar distribution across urban (13.2%) and rural (13.7) areas and the most common cause was trauma. The greatest number of surgical conditions were found to be on the head and neck region (57.7%), while the back accounted for the least number of conditions (1.7%). Our results outline a need for organizing all entities (governmental, non-governmental, and private) involved in child health to ensure efficient resource allocation to cater to existing surgical problems.

Ligation of intersphincteric fistula tract: A retrospective, single centre, individual surgeons' experience for the management of complex fistula in ano.

Objectives: To identify early treatment outcomes among patients having undergone ligation of intersphincteric fistula tract for complex fistula-in-ano in a tertiary care setting. METHODS: The single-centre retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2016 to January 2021 of adult complex fistula-in-ano patients who underwent ligation of intersphincteric fistula tract procedure. All surgeries were done by a single surgeon. Pre- and post-operative Wexner continence scores were measured, and various factors, including change in continence, complete wound healing, postoperative infection and recurrence, were assessed. Data was analysed using SPSS 23. RESULTS: Of the 20 patients, 15(75%) were females and 5(25.0%) were males. The overall mean age was 38.4±13.8 years. The median duration of surgery was 65 minutes (interquartile range: 57-99 minutes). There were 2(10%) patients who showed a change in continence after surgery to flatus alone. Complete healing was noted in 11(55%) patients. Recurrence was noted in 8(40%) patients; trans-sphincteric fistula-in-ano in 2(10%) patients, and inter-sphincteric fistula in 6(30%). Body mass index had a significant association with the change in continence (p=0.028). CONCLUSIONS: There was a comparable risk of recurrence after ligation of intersphincteric fistula tract surgery, but among those without recurrence, the post-operative outcomes were optimal and no faecal incontinence was noted.

Correction: A new extended gumbel distribution: Properties and application.

[This corrects the article DOI: 10.1371/journal.pone.0267142.].

Association between achieving adequate antenatal care and health-seeking behaviors: A study of Demographic and Health Surveys in 47 low- and middle-income countries.

BACKGROUND: Antenatal care (ANC) is essential for ensuring the well-being of pregnant women and their fetuses. This study models the association between achieving adequate ANC and various health and health-seeking indicators across wealth quintiles in low- and middle-income countries (LMICs). METHODS AND FINDINGS: We analyzed data from 638,265 women across 47 LMICs using available Demographic and Health Surveys from 2010 to 2022. Via multilevel logistic regression analyses adjusted for a series of confounding variables and country and wealth quintile fixed effects, we estimated the projected impact of achieving adequate ANC utilization and quality on a series of health and health care indicators: facility birth, postnatal care, childhood immunizations, and childhood stunting and wasting. Achieving adequate levels of ANC utilization and quality (defined as at least 4 visits, blood pressure monitoring, and blood and urine testing) was positively associated with health-seeking behavior across the majority of countries. The strongest association was observed for facility birth, followed by postnatal care and child immunization. The strength of the associations varied across countries and wealth quintiles, with more significant ones observed in countries with lower baseline ANC utilization levels and among the lower wealth quintiles. The associations of ANC with childhood stunting and wasting were notably less statistically significant compared to other indicators. Despite rigorous adjustments for potential confounders, a limitation to the methodology is that it is possible that unobserved variables may still impact outcomes. CONCLUSIONS: Strengthening ANC is associated with improved use of other health care in LMICs. ANC could serve as a critical platform for improving health outcomes for mothers and their children, emphasizing its importance beyond direct impact on maternal and neonatal mortality.

Barriers and Facilitators to Collecting Surgical Outcome Data in Low- and Middle-Income Countries: An International Survey.

Background: Perioperative data are essential to improve the safety of surgical care. However, surgical outcome research (SOR) from low- and middle-income countries (LMICs) is disproportionately sparse. We aimed to assess practices, barriers, facilitators, and perceptions influencing the collection and use of surgical outcome data (SOD) in LMICs. Methods: An internet-based survey was developed and disseminated to stakeholders involved in the care of surgical patients in LMICs. The Performance of Routine Information Systems Management framework was used to explore the frequency and relative importance of organizational, technical, and behavioral barriers. Associations were determined using χ 2 and ANOVA analyses. Results: Final analysis included 229 surgeons, anesthesia providers, nurses, and administrators from 36 separate LMICs. A total of 58.1% of individuals reported that their institution had experience with collection of SOD and 73% of these reported a positive impact on patient care. Mentorship and research training was available in <50% of respondent's institutions; however, those who had these were more likely to publish SOD (P = 0.02). Sixteen barriers met the threshold for significance of which the top 3 were the burden of clinical responsibility, research costs, and accuracy of medical documentation. The most frequently proposed solutions were the availability of an electronic data collection platform (95.3%), dedicated research personnel (93.2%), and access to research training (93.2%). Conclusions: There are several barriers and facilitators to collection of SOD that are common across LMICs. Most of these can be addressed through targeted interventions and are highlighted in this study. We provide a path towards advancing SOR in LMICs.

Modeling COVID-19 data with a novel neutrosophic Burr-III distribution.

In this study, we have presented a novel probabilistic model called the neutrosophic Burr-III distribution, designed for applications in neutrosophic surface analysis. Neutrosophic analysis allows for the incorporation of vague and imprecise information, reflecting the reality that many real-world problems involve ambiguous data. This ability to handle vagueness can lead to more robust and realistic models especially in situation where classical models fall short. We have also explored the neutrosophic Burr-III distribution in order to deal with the ambiguity and vagueness in the data where the classical Burr-III distribution falls short. This distribution offers valuable insights into various reliability properties, moment expressions, order statistics, and entropy measures, making it a versatile tool for analyzing complex data. To assess the practical relevance of our proposed distribution, we applied it to real-world data sets and compared its performance against the classical Burr-III distribution. The findings revealed that the neutrosophic Burr-III distribution outperformed than the classical Burr-III distribution in capturing the underlying data characteristics, highlighting its potential as a superior modeling toolin various fields.

A Journey of Innovation: 40 years of Pioneering Medical Education at the Aga Khan University Medical College in Karachi, Pakistan.

This article presents an overview of Aga Khan University's (AKU) pioneering medical education initiatives over the past 40 years, exploring its impact on healthcare in the region and its commitment to advancing medical education and research in the developing world. Established in 1983 as the first private university in Pakistan, AKU has evolved into a global institution with a focus on improving healthcare standards and addressing healthcare needs in the developing world. The article also discusses the undergraduate and postgraduate medical education programs at AKU Medical College, Pakistan, highlighting their unique features and pioneering approaches to medical education. The institution's journey highlights its ability to adapt to the evolving healthcare landscape while maintaining a focus on quality and excellence, offering a model for other institutions striving to meet healthcare needs in low- and middle-income countries.

Perceived progress toward scale of 14 maternal, newborn, child health, and nutrition (MNCHN) assets at subnational level in Burkina Faso, Ethiopia, India, Kenya, and Nigeria.

Inequitable coverage of evidence-based MNCHN interventions is particularly pronounced in low and middle income countries where access and delivery of these interventions can vary dramatically at the subnational level. We conducted health system assessments in nine subnational geographies in five countries (Burkina Faso, Ethiopia, India, Kenya and Nigeria) to explore progress toward scale of 14 evidence-based MNCHN interventions (iron-folic acid, oxytocin, magnesium sulfate, misoprostol; 7.1% chlorhexidine for umbilical cord care, neonatal resuscitation, kangaroo mother care, community regimen for the treatment of possible severe bacterial infection; amoxicillin dispersible tablets, multiple micronutrient supplements, balanced energy protein supplementation, early and exclusive breastfeeding, feeding of small and sick newborns, and management of severe and moderate acute malnutrition in children less than five years old). Between March and October 2021, we conducted key informant interviews with a purposive sample of 275 healthcare providers and 94 district health management (DHMT) staff to better understand bottlenecks, facilitators and uptake of the interventions across varied subnational settings. Across all interventions and geographies, providers and DHMT staff perceived lack of robust HMIS data as the most significant barrier to scale followed by weak facility infrastructure. DHMT staff viewed limited budget allocation and training as a much larger barrier than healthcare providers, most likely given their purview as subnational managers. Healthcare providers were focused on supply chain and staffing, which affect workflows and service provision. Understanding provider and health facility management views of why interventions do or do not advance towards effective coverage can assist in creating enabling environments for the scale of best practices. These types of data are most helpful when collected at the subnational level, which allows for comparisons both within and between countries to show health disparities. Importantly, this strategic data collection can provide a starting point for improvement efforts to address existing health system gaps.

Achieving Surgical, Obstetric, Trauma, and Anesthesia (SOTA) care for all in South Asia.

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions-initiatives and innovations-toward addressing these challenges. Local partnerships, sustained research and advocacy efforts, and politics can be aligned with evidence-based policymaking and health planning to achieve equitable SOTA care access in the South Asian region under the South Asian Association for Regional Cooperation (SAARC).

Development and content validation of a financial and functional outcomes tool for diabetes-related foot disease in patients undergoing major lower limb amputation: a prospective observational study from Pakistan.

OBJECTIVE: To develop and content validate a questionnaire to assess the financial and functional impact of major lower limb amputation in patients with diabetes-related foot disease. DESIGN: Prospective observational study. SETTING: This study was conducted at a tertiary care centre in Pakistan. PARTICIPANTS: We conducted a thorough literature review and a group interview with 10 participants, resulting in domain identification and item generation. The group included seven patients with diabetes-related foot disease who underwent major lower limb amputation and three caregivers. Subsequently, a focused group discussion was held to assess overlap and duplication among the items, and two rounds of content validation were carried out by five content and five lay experts in both English and Urdu. Question items with a Content Validity Index (CVI) score of >0.79 were retained, items with a CVI score between 0.70 and 0.79 were revised and items with a CVI score of <0.70 were excluded. RESULTS: The initial literature review and group interview resulted in 61 items in the financial and functional domains. After the focused group discussion, the questionnaire was reduced to 37 items. Following two rounds of content validation, the English questionnaire achieved the Scale-Content Validity Index/Average (S-CVI/Ave) of 0.92 and 0.89 on relevance and clarity, respectively. Similarly, the Urdu questionnaire achieved the S-CVI-Ave of 0.92 and 0.95, respectively. CONCLUSION: A 37-item multidimensional questionnaire was developed and rigorously content-validated to assess the financial and functional impact of major lower limb amputation in patients with diabetes-related foot disease. The questionnaire used in this study has shown robust content validity specifically for our population.

Photocatalytic degradation of parabens: A comprehensive meta-analysis investigating the environmental remediation potential of emerging pollutant.

The increasing prevalence of paraben compounds in the environment has given rise to concerns regarding their detrimental impacts on both ecosystems and human health. Over the past few decades, photocatalytic reactions have drawn significant attention as a method to accelerate the otherwise slow degradation of these pollutants. The current study aims to evaluate the current efficacy of the photocatalytic method for degrading parabens in aqueous solutions. An extensive literature review and bibliometric analysis were conducted to identify key research trends and influential areas in the field of photocatalytic paraben degradation. Studies were screened based on the predetermined inclusion and exclusion criteria, which led to 13 studies that were identified as being appropriate for the meta-analysis using the random effects model. Furthermore, experimental parameters such as pH, paraben initial concentration, catalyst dosage, light intensity, and contact time have been reported to have key impacts on the performance of the photocatalytic degradation process. A comprehensive quantitative assessment of these parameters was carried out in this work. Overall, photocatalytic techniques could eliminate parabens with an average degradation efficiency of >80 %. The findings of the Egger's test and the Begg's test were statistically not significant suggesting potential publication bias was not observed. This review provides a holistic understanding of the photocatalytic degradation of parabens and is anticipated to encourage more widespread adoption of photocatalytic procedures as a suitable method for the elimination of parabens from aqueous solutions, opening new avenues for future research in this direction.

Protective role of chlorogenic acid in preserving cytochrome-c stability against HFIP-induced molten globule state at physiological pH.

Numerous neurodegenerative disorders are characterized by protein misfolding and aggregation. The mechanism of protein aggregation is intricate, and it is very challenging to study at cellular level. Inhibition of protein aggregation by interfering with its pathway is one of the ways to prevent neurodegenerative diseases. In the present work, we have evaluated the protective effect of a polyphenol compound chlorogenic acid (CGA) on the native and molten globule state of horse heart cytochrome c (cyt c). A molten globule state of this heme protein was achieved in the presence of fluorinated alcohol 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) at physiological pH, as studied by UV-Vis absorption, circular dichroism, intrinsic and ANS fluorescence. We found that at 50 % (v/v) HFIP, the native cyt c transformed into a molten globule state. The same techniques were also used to analyze the protective effect of CGA on the molten globule state of cyt c, and the results show that the CGA prevented the molten globular state and retained the protein close to the native state at 1:1 protein:CGA sub molar ratio. Molecular dynamics study also revealed that CGA retains the stability of cyt c in HFIP medium by preserving it in an intermediate state close to native conformation.

Oxidative stress in polycystic ovary syndrome: a case-control study.

OBJECTIVE: To compare the serum levels of biochemical and oxidative stress markers i.e., malondialdehyde (MDA) and paraoxonase-1(PON1) in polycystic ovary syndrome (PCOS) patients and healthy female individuals of reproductive age group (18-40 years). METHODS: This case-control study was conducted in Dow University of Health Sciences (DUHS), Karachi from June 2019 to October 2020. Seventy Subjects including 35 PCOS patients that have primary subfertility problem (cases) and 35 healthy and fertile females (controls) were recruited. Serum samples were collected for analysis of insulin, sex hormone-binding globulin, testosterone, fasting blood glucose and lipid profile. PON 1 and MDA levels were estimated by ELISA. Comparison between the two groups was done using independent t-test. RESULTS: The patients had significantly increased mean body mass index (28.5+4.6 kg/m2 vs 25.7+4.5 kg/m2, p=0.014), systolic (129.6±13.9 mm of Hg vs 113±7.7 mm of Hg, p<0.001) and diastolic (78.7±8.8 mm of Hg vs 74.6±6.7 mm of Hg, p=0.032) blood pressures compared to controls. The high-density lipoprotein cholesterol levels were significantly lower in PCOS (42.2±8.6mg/dl) than controls (48.8±11.8mg/dl, p=0.009, p=0.009). Serum insulin (14.3±5.8 uIU/mL) vs (10.0±5.2 uIU/mL), p=0.002 and testosterone levels (1.3±0.9 nmol/L) vs (0.82±0.3 nmol/L), p<0.001 were significantly higher whereas sex hormone binding globulin (SHBG) levels (35.2±19.7nmol/L vs 58.8±31.0 nmol/L) were significantly lower in patients than healthy controls (p<0.001). Both oxidative stress markers, paraoxonase 1 (7.7±2.4 vs 6.4±2.6 µg/mL, p=0.04) and malondialdehyde (2.5±1.0 vs 1.9+0.51µg/mL, p=0.034) levels were significantly elevated in PCOS patients than controls. No significant correlation was found between dietary habits and life style between cases and controls. CONCLUSIONS: The study reported significantly elevated levels of oxidative stress markers in PCOS patients.

Bovine serum albumin prevents human hemoglobin aggregation and retains its chaperone-like activity.

This study investigates the ability of bovine serum albumin (BSA) to act as an extracellular chaperone (EC) on human hemoglobin (Hb) at a pH of 7.4. The best temperature for studying this behavior was determined by analyzing Hb's aggregation kinetics at multiple temperatures. 55 °C was chosen as the optimal temperature for forming Hb amyloids. BSA was then tested at various concentrations (20-100 µM) to assess its chaperone-like activity on Hb at 55 °C. At a concentration of 100 µM, BSA exhibits chaperone-like activity with a client protein:BSA ratio of 1:10. The high ratio implies that the chaperone activity of BSA is favored by the effects of macromolecular crowding. The results showed that BSA has the potential to inhibit Hb's dissociation into alpha and beta subunits and protein aggregation by inhibiting secondary nucleation. BSA also causes the depolymerization of fibrils over time. The results were validated using molecular docking and all-atom molecular dynamics simulations. MD analysis such as RMSD, RMSF, Rg, SASA, Hydrogen bond, PCA, Free energy landscape (FEL) revealed that the stability of hemoglobin is greater when it is bound to BSA compared to unbound state. The study suggests that BSA can potentially bind to Hb dimers and reduce excitonic interactions, which reduces Hb aggregation. These results are consistent with the aggregation kinetics experiments.Communicated by Ramaswamy H. Sarma.

Emergence of Rapid-Onset Ototoxicity Following Three Doses of Vancomycin: A Unique Case Report in the Context of Normal Renal Function and Therapeutic Dosing.

Vancomycin, a potent glycopeptide antibiotic renowned for its efficacy against methicillin-resistant Staphylococcus aureus, also harbors the potential for adverse reactions. While its use is often associated with infusion-related events and nephrotoxicity, ototoxicity has emerged as a noteworthy but rare concern. This adverse effect, characterized by a spectrum of transient to permanent hearing loss or damage, typically surfaces in patients receiving excessive doses, those undergoing concomitant therapy with other ototoxic agents such as aminoglycosides, or individuals with baseline hearing impairment or renal dysfunction. This report highlights the possibility of ototoxicity in the setting of normal renal function and therapeutic dosing. We report a case of a 58-year-old male patient with a complex medical history, who presented with sepsis, respiratory failure, and a constellation of underlying conditions. His treatment regimen encompassed intravenous vancomycin administration, which led to an unexpected development-severe-to-profound bilateral conductive and sensorineural hearing loss after three doses. The absence of concurrent ototoxic agents and Bayesian dosing software predicting an acceptable AUC/MIC ratio complicates the understanding of this adverse event. Amid this complex scenario, the case underscores the evolving landscape of vancomycin-induced ototoxicity, encouraging heightened vigilance, thorough audiometric monitoring, and an in-depth exploration of potential mechanisms underlying this adverse reaction. Early audiometric testing and referral to otolaryngology may allow for early intervention with high-dose steroids to mitigate the ototoxicity.

Oxidative Stress in Beta-thalassemia Patients: Role of Enzymatic and Non-enzymatic Modulators.

BACKGROUND: Oxidative stress is a pathophysiological state that arises due to an imbalance created between ROS generation and the antioxidant potential of the host cell. Transfusion- dependent beta-thalassemia major patients are at high risk of cellular and molecular damages induced by ROS mainly due to iron overload caused by repetitive blood transfusion. OBJECTIVES: To analyze oxidative stress status levels in ß-thalassemia patients. To analyze the expression profile of enzymatic (NOS2, OGG1, HuR, SOD2) and non-enzymatic (VDR) redox regulators in ß-thalassemia patients. To assess polymorphism in VDR (rs2228570) and NOS2 (rs944725) in ß-thalassemia patients. To analyze serum vitamin D levels of ß-TM patients compared to healthy individuals. METHODS: The present case-control study aimed to identify Vitamin D levels in the serum of ß-thalassemia patients and compared it with healthy subjects. The study further analyzed VDR FOKI (rs2228570) polymorphism through ARMS-PCR. Expression profiling of VDR, anti-oxidant enzyme (SOD2 and GPx), and their respective regulator (HuR and NrF2) transcripts was done by the 2-ΔΔCt method. RESULTS: The study reports that there is no a significant difference between the Vitamin D levels among healthy and patients. VDR polymorphism analysis (rs2228570) demonstrates that although the C allele is prevalent in the study cohort, the frequency of the T allele is comparatively higher in ß-thalassemia patients as compared to healthy subjects. Furthermore, patients express lower levels of anti-oxidant enzymes despite having increased oxidative stress. CONCLUSION: The study reports that ß-thalassemia patients are at higher risk of cellular and molecular damages induced by oxidative stress and their associated pathologies inefficient enzymatic and non-enzymatic anti-oxidant defense systems.

Much room for change: access to surgical care for stateless individuals in Pakistan.

BACKGROUND: As developing countries take steps towards providing universal essential surgery, ensuring the equitable distribution of such care for underrepresented populations is a vital function of the global surgery community. Unfortunately, in the context of the global "stateless", there remains much room for improvement. KEY ISSUES: Inherent structural deficiencies, such as lack of adequate population data on stateless communities, absent health coverage policies for stateless individuals, and minimal patient-reported qualitative data on barriers to surgical service delivery prevent stateless individuals from receiving the care they require - even when healthcare infrastructure to provide such care exists. The authors therefore propose more research and targeted interventions to address the systemic issues that prevent stateless individuals from accessing surgical care. CONCLUSION: It is essential to address the aforementioned barriers in order to improve stateless populations' access to surgical care. Rigorous empirical and qualitative research provides an important avenue through which these structural issues may be addressed.

Promising New Horizons in Medicine: Medical Advancements with Nanocomposite Manufacturing via 3D Printing.

Three-dimensional printing technology has fundamentally revolutionized the product development processes in several industries. Three-dimensional printing enables the creation of tailored prostheses and other medical equipment, anatomical models for surgical planning and training, and even innovative means of directly giving drugs to patients. Polymers and their composites have found broad usage in the healthcare business due to their many beneficial properties. As a result, the application of 3D printing technology in the medical area has transformed the design and manufacturing of medical devices and prosthetics. Polymers and their composites have become attractive materials in this industry because of their unique mechanical, thermal, electrical, and optical qualities. This review article presents a comprehensive analysis of the current state-of-the-art applications of polymer and its composites in the medical field using 3D printing technology. It covers the latest research developments in the design and manufacturing of patient-specific medical devices, prostheses, and anatomical models for surgical planning and training. The article also discusses the use of 3D printing technology for drug delivery systems (DDS) and tissue engineering. Various 3D printing techniques, such as stereolithography, fused deposition modeling (FDM), and selective laser sintering (SLS), are reviewed, along with their benefits and drawbacks. Legal and regulatory issues related to the use of 3D printing technology in the medical field are also addressed. The article concludes with an outlook on the future potential of polymer and its composites in 3D printing technology for the medical field. The research findings indicate that 3D printing technology has enormous potential to revolutionize the development and manufacture of medical devices, leading to improved patient outcomes and better healthcare services.

Value profile for respiratory syncytial virus vaccines and monoclonal antibodies.

Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.