Essential role of local antibody distribution in mediating bone-resorbing effects.

The link between antibodies and bone mass is debated. Activated IgG, which interacts directly with Fc gamma receptors, stimulates osteoclastogenesis in vitro, and local injection in immune-activated mice leads to bone loss. Multiple myeloma patients with high serum IgG levels have induced osteoclast activation and display bone loss. In addition, bone loss has been linked to serum autoantibodies in autoimmune diseases, including anti-citrullinated protein antibodies (ACPA) in individuals with rheumatoid arthritis (RA). Whether serum IgG or autoantibodies regulate bone mass under healthy conditions is poorly studied. In elderly men, neither serum levels of polyclonal IgG nor autoantibody were associated with areal bone mineral density in the MrOS Sweden study. Repetitive systemic injections of high-dose polyclonal IgG complexes in mice did not exert any discernible impact on bone mineral density. However, repetitive local intra-articular injection of the same IgG complexes led to a localized reduction of trabecular bone density. These results indicate antibodies may only impact bone density when close to the bone, such as within the synovial joint.

Strengthening research capacity of early-mid career researchers: Implementation and evaluation of the Excellence in Non-COmmunicable disease REsearch (ENCORE) program.

High-quality training and networking are pivotal for enhancing the research capacity of early- to mid-career researchers in the prevention and control of non-communicable diseases. Beyond building research skills, these professionals gain valuable insights from interdisciplinary mentorship, networking opportunities, and exposure to diverse cultures and health systems. Despite the significance of such initiatives, their implementation remains underexplored. Here, we describe the implementation and evaluation of the Excellence in Non-COommunicable disease REsearch (ENCORE) program, a collaborative initiative between Australia and India that was launched in 2016 and spanned a duration of 3 years. Led by a consortium that included the University of Melbourne and leading Indian research and medical institutions, ENCORE involved 15 faculty members and 20 early-mid career researchers. The program comprised various elements, including face-to-face forums, masterclasses, webinars, a health-technology conference, and roundtable events. ENCORE successfully trained the early-career researchers, resulting in over 30 peer-reviewed articles, 36 conference presentations, and the submission of seven grant applications, three of which received funding. Beyond individual achievements, ENCORE fostered robust research collaboration between Australian and Indian institutions, showcasing its broader impact on strengthening research capacities across borders.

Chitosan nanocomposite for tissue engineering and regenerative medicine: A review.

Regenerative medicine and tissue engineering have emerged as a multidisciplinary promising field in the quest to address the limitations of traditional medical approaches. One of the key aspects of these fields is the development of such types of biomaterials that can mimic the extracellular matrix and provide a conducive environment for tissue regeneration. In this regard, chitosan has played a vital role which is a naturally derived linear bi-poly-aminosaccharide, and has gained significant attention due to its biocompatibility and unique properties. Chitosan possesses many unique physicochemical properties, making it a significant polysaccharide for different applications such as agriculture, nutraceutical, biomedical, food, nutraceutical, packaging, etc. as well as significant material for developing next-generation hydrogel and bio-scaffolds for regenerative medicinal applications. Moreover, chitosan can be easily modified to incorporate desirable properties, such as improved mechanical strength, enhanced biodegradability, and controlled release of bioactive molecules. Blending chitosan with other polymers or incorporating nanoparticles into its matrix further expands its potential in tissue engineering applications. This review summarizes the most recent studies of the last 10 years based on chitosan, blends, and nanocomposites and their application in bone tissue engineering, hard tissue engineering, dental implants, dental tissue engineering, dental fillers, and cartilage tissue engineering.

Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause.

Introduction: The glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation. Purpose: In this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations. Methods: Mice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies. Results: Using a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells. Conclusion: The study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.

Multimorbidity clusters and associated health care cost among patients attending psychiatric clinics in Odisha, India.

Introduction: There is a dearth of data on common multimorbidity clusters and the healthcare costs for individuals with mental health disorders. This study aimed to identify clinically meaningful physical-mental multimorbidity clusters, frequently occurring clusters of conditions, and healthcare utilization patterns and expenditure among patients attending a psychiatric outpatient clinic. Materials and Methods: Data were collected in the psychiatric outpatient department among patients aged 18 years and above in February-July 2019 (n = 500); follow-up data on non-communicable disease incidence were collected after 18 months. For analysis, morbidity clusters were defined using two approaches: 1) agglomerative hierarchical clustering method to identify clusters of diseases; and 2) non-hierarchical cluster k mean analysis to identify clusters of patients. Self-reported healthcare costs in these clusters were also calculated. Result: Two disease clusters were identified: using the 1st approach were; 1) hypertension, diabetes, and mood disorder; 2) Neurotic, stress-related, and somatoform disorders, and acid peptic disease. Three clusters of patients identified using the 2nd approach were identified: 1) those with mood disorders and cardiometabolic, musculoskeletal, and thyroid diseases; 2) those with neurotic, substance use, and organic mental disorders, cancer, and epilepsy; and 3) those with Schizophrenia. Patients in Cluster 1 were taking more than six medicines and had more hospital visits. Within 18 months, 41 participants developed either one or two chronic conditions, most commonly diabetes, hypertension, or thyroid disease. Conclusion: Cardiometabolic diseases are most commonly clustered with mood disorders. There is a need for blood pressure and sugar measurement in psychiatric clinics and mood disorder screening in cardiac, endocrinology, and primary care clinics.

Membrane estrogen receptor α signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner.

Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 µg/mouse/day (low); 0.6 µg/mouse/day (medium)) or supraphysiological (6 µg/mouse/day (high)) doses of E2 (17ß-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (- 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (- 34% and - 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mERα signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.

Bazedoxifene does not share estrogens effects on IgG sialylation.

The incidence of rheumatoid arthritis (RA) increases at the same time as menopause when estrogen level decreases. Estrogen treatment is known to reduce the IgG pathogenicity by increasing the sialylation grade on the terminal glycan chain of the Fc domain, inhibiting the binding ability to the Fc gamma receptor. Therefore, treatment with estrogen may be beneficial in pre-RA patients who have autoantibodies and are prone to get an autoimmune disease. However, estrogen treatment is associated with negative side effects, therefore selective estrogen receptor modulators (SERMs) have been developed that have estrogenic protective effects with minimal side effects. In the present study, we investigated the impact of the SERM bazedoxifene on IgG sialylation as well as on total serum protein sialylation. C57BL6 mice were ovariectomized to simulate postmenopausal status, followed by ovalbumin immunization, and then treated with estrogen (estradiol), bazedoxifene, or vehicle. We found that estrogen treatment enhanced IgG levels and had a limited effect on IgG sialylation. Treatment with bazedoxifene increased the sialic acids in plasma cells in a similar manner to E2 but did not reach statistical significance. However, we did not detect any alteration in IgG-sialylation with bazedoxifene treatment. Neither estrogen nor bazedoxifene showed any significant alteration in serum protein sialylation but had a minor effect on mRNA expression of glycosyltransferase in the bone marrow, gonadal fat, and liver.

The role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy.

Immunotherapy has revolutionized cancer treatment and revitalized efforts to harness the power of the immune system to combat a variety of cancer types more effectively. However, low clinical response rates and differences in outcomes due to variations in the immune landscape among patients with cancer continue to be major limitations to immunotherapy. Recent efforts to improve responses to immunotherapy have focused on targeting cellular metabolism, as the metabolic characteristics of cancer cells can directly influence the activity and metabolism of immune cells, particularly T cells. Although the metabolic pathways of various cancer cells and T cells have been extensively reviewed, the intersections among these pathways, and their potential use as targets for improving responses to immune-checkpoint blockade therapies, are not completely understood. This review focuses on the interplay between tumor metabolites and T-cell dysfunction as well as the relationship between several T-cell metabolic patterns and T-cell activity/function in tumor immunology. Understanding these relationships could offer new avenues for improving responses to immunotherapy on a metabolic basis.

The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice.

Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2-/--young, and TLR2-/--old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2-/- mice, whereas IgG response was impaired in both aged and TLR2-/- mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2-/- mice. Both aging and TLR2-/- increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2-/- mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.

The Impact of Aging and Toll-like Receptor 2 Deficiency on the Clinical Outcomes of Staphylococcus aureus Bacteremia.

Staphylococcus aureus (S. aureus) causes a broad range of infections. Toll-like receptor (TLR) 2 senses the S. aureus lipoproteins in S. aureus infections. Aging raises the risk of infection. Our aim was to understand how aging and TLR2 affect the clinical outcomes of S. aureus bacteremia. Four groups of mice (wild type/young, wild type/old, TLR2-/-/young, and TLR2-/-/old) were intravenously infected with S. aureus, and the infection course was followed. Both TLR2 deficiency and aging enhanced the susceptibility to disease. Increased age was the main contributing factor for increased mortality rates and changes in spleen weight, whereas other clinical parameters, such as weight loss and kidney abscess formation, were more TLR2 dependent. Importantly, aging increased mortality rates without relying on TLR2. In vitro, both aging and TLR2 deficiency down-regulated cytokine/chemokine production of immune cells with distinct patterns. In summary, we demonstrate that aging and TLR2 deficiency impair the immune response to S. aureus bacteremia in distinct ways.

Recalibration of the Framingham risk score for predicting 10-year risk of cardiovascular events: A non-concurrent rural cohort study from Tamil Nadu.

OBJECTIVE: To recalibrate the Framingham Risk Score-cardiovascular diseases (FRS-CVD) using 10-year mortality data and baseline risk factor data for a rural cohort and assess the effect of recalibration on proportion categorised as high risk. METHODS: Participants of a cardiovascular risk factor survey aged 30-64 years in 2011-12, from 9 villages of a rural block in Vellore, Tamil Nadu, were followed up for mortality till 2021, as part of an established demographic surveillance system. We calculated both lipid-based and Body Mass Index-based FRS-CVD risk scores, as well as recalibrated scores using risk factor data from the baseline survey and CVD mortality observed over 10 years. RESULTS: Based on original lipid-based FRS-CVD scores, 8.48% (109) of 1285 males had a 10-year CVD risk ≥30%, compared to 11.60% (149) with recalibrated scores. Among 1737 females, 1.50% (26) had a 10-year CVD risk of ≥30%, using original FRS-CVD scores, and 3.22% (56) using recalibrated scores. Similarly, for BMI based FRS-CVD scores, overall, 3.63% (110/3028) had a 10-year risk of ≥30%, compared to 6.64% (201) using recalibrated scores. The median 10-year FRS-CVD original score in males was 7.57 (IQR: 3.67-15.83), and 2.53 (IQR: 1.28-5.32) in females, compared to 8.95 (IQR: 4.35-18.52) and 3.79 (IQR: 1.92-7.93) respectively, for the recalibrated FRS-CVD risk scores. CONCLUSION: The recalibrated Framingham models showed a greater proportion of the population at risk of CVDs compared to the original FRS scores, with males having 2-3 times greater CVD risk scores compared to females.

Vulnerability of facial attractiveness perception to early and multi-year visual deprivation.

Judgments of facial attractiveness invariably accompany our perception of faces. Even neonates appear to be capable of making such judgments in a manner consistent with adults. This suggests that the processes supporting facial attractiveness require little, if any, visual experience to manifest. Here we investigate the resilience of these processes to several years of early-onset visual deprivation. Specifically, we study whether congenitally blind children treated several years after birth possess the ability to rate facial attractiveness in a manner congruent to normally sighted individuals. The data reveal significant individual variability in the way each newly sighted child perceives attractiveness. This is in marked contrast to data from normally sighted controls who exhibit strong across-subject agreement in facial attractiveness ratings. This variability may be attributable, in part, to atypical facial encoding strategies used by the newly sighted children. Overall, our results suggest that the development of facial attractiveness perception is likely to be vulnerable to early visual deprivation, pointing to the existence of a possible sensitive period early in the developmental trajectory.

Provision of immobilization or ice by paramedics in Southwestern Ontario.

OBJECTIVES: Pain is the most common reason for prehospital transport. As emergency wait times increase, timely pain management is essential. In children, there is abundant evidence that prehospital pharmacologic analgesia is suboptimal, but little is known about non-pharmacologic therapies. We sought to characterize documentation by paramedics of non-pharmacologic (immobilization and ice) and pharmacologic analgesia in children with musculoskeletal injuries. METHODS: We reviewed all ambulance call reports for children 0-17 years transported to Southwestern Ontario regional hospitals from January 1, 2017, to December 31, 2019, with a musculoskeletal injury (Ontario Ministry of Health and Long-Term Care problem codes 66 and 67). Primary and secondary outcomes were documented immobilization or ice and pharmacologic analgesia, respectively. In a multivariable analysis, we explored the relationship between immobilization or ice and the following a priori covariates: age, sex, visible deformity, crew type, pain severity, and analgesia. RESULTS: Of 40,692 ambulance call reports reviewed, 4445 met inclusion criteria. There were 2584/4441 (58.2%) males, with a median (IQR) age of 14 (10, 16) years. In ambulance call reports with documented pain scores, 2106/3048 (69.1%) ambulance call reports reported "moderate or severe" pain. Immobilization or ice were documented in 1605/4445 (36.1%) and 385/4445 (8.7%) of ambulance call reports. Pharmacologic analgesia was documented in 275/1983 (13.9%) and 125/991 (12.6%) of ambulance call reports for primary care paramedics and advanced care paramedics, respectively. An increased odds of documented immobilization or ice was associated with moderate or severe pain [OR: 2.4; 95% CI 1.84-3.17; p < 0.01] and visible deformity [OR: 2.5; 95% CI 1.97-3.12; p < 0.01]. CONCLUSIONS: Documented immobilization and ice and pharmacologic analgesia to children by paramedics is suboptimal. Our findings underscore an important need for enhanced education surrounding the benefits of non-pharmacologic options for children with musculoskeletal injuries.

RéSUMé: OBJECTIFS: La douleur est le motif le plus fréquent de transport préhospitalier. À mesure que les temps d'attente aux urgences augmentent, la gestion de la douleur en temps opportun est essentielle. Chez les enfants, il existe de nombreuses preuves que l'analgésie pharmacologique préhospitalière est sous-optimale, mais on sait peu de choses sur les thérapies non pharmacologiques. Nous avons cherché à caractériser la documentation par les ambulanciers paramédicaux de l'analgésie non pharmacologique (immobilisation et glace) et pharmacologique chez les enfants souffrant de lésions musculo-squelettiques. MéTHODES: Nous avons examiné tous les rapports d'appels d'ambulance pour les enfants de 0 à 17 ans transportés vers les hôpitaux régionaux du Sud-Ouest de l'Ontario du 1er janvier 2017 au 31 décembre 2019, avec une blessure musculo-squelettique (codes de problèmes 66 et 67 du ministère de la Santé et des Soins de longue durée de l'Ontario). Les résultats primaires et secondaires étaient l'immobilisation documentée ou la glace et l'analgésie pharmacologique, respectivement. Dans une analyse multivariable, nous avons exploré la relation entre l'immobilisation ou la glace et les covariables a priori suivantes: âge, sexe, déformation visible, type d'équipage, intensité de la douleur et analgésie. RéSULTATS: Sur les 40 692 rapports d'appels d'ambulance examinés, 4 445 répondaient aux critères d'inclusion. Il y avait 2584/4441 (58,2 %) hommes, avec un âge médian (IQR) de 14 (10,16) ans. Dans les rapports d'appel d'ambulance avec des scores de douleur documentés, 2106/3048 (69,1 %) rapports d'appel d'ambulance ont signalé une douleur "modérée ou sévère". L'immobilisation ou la glace ont été documentées dans 1605/4445 (36,1 %) et 385/4445 (8,7 %) des rapports d'appel d'ambulance. L'analgésie pharmacologique a été documentée dans 275/1983 (13,9 %) et 125/991 (12,6 %) des rapports d'appel d'ambulance pour les ambulanciers de soins primaires et les ambulanciers de soins avancés, respectivement. Une probabilité accrue d'immobilisation documentée ou de glace était associée à une douleur modérée ou intense [OR: 2,4; IC à 95 %: 1,84-3,17; p < 0,01] et déformation visible [OR: 2,5; IC à 95 %: 1,97-3,12; p < 0,01]. CONCLUSIONS: L'immobilisation documentée et l'administration de glace et d'analgésie pharmacologique aux enfants par les ambulanciers est sous-optimale. Nos résultats soulignent le besoin important de renforcer l'éducation concernant les avantages des options non pharmacologiques pour les enfants souffrant de blessures musculo-squelettiques.

Comparison of three exercise interventions with and without gemcitabine treatment on pancreatic tumor growth in mice: No impact on tumor infiltrating lymphocytes.

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran at 12 m/min for 45 min and LVCE for 15 min, 5 days/week. HIIT ran 1-min at 20 m/min, followed by 1-min walking at 8 m/min for 20 total intervals, 3 days/week. SED did not run. Additional sets of inoculated mice were assigned to the exercise interventions but did not receive gemcitabine. Tumor volume was measured every other day for 2 weeks; tumor-infiltrating lymphocytes were assessed by flow cytometry 3-week post-inoculation. Results: Tumor growth did not differ between groups that received gemcitabine (F(3, 34) = 1.487; p = 0.235; η2 = 0.116). In contrast, tumor growth differed between groups not provided gemcitabine (F(3,14) = 3.364; p = 0.049, η2 = 0.419), with trends for slower growth in LVCE than SED (p = 0.088) and HIIT (p = 0.084). Groups did not differ in tumor infiltrating lymphocytes. Conclusion: Contrary to our hypotheses, the exercise interventions compared here did not further reduce pancreatic tumor growth beyond that provided by gemcitabine. However, in mice not receiving gemcitabine, there was a trend for reduced tumor growth in LVCE.

Reduction of Mature B Cells and Immunoglobulins Results in Increased Trabecular Bone.

Inflammation has a significant effect on bone remodeling and can result in bone loss via increased stimulation of osteoclasts. Activated immunoglobulins, especially autoantibodies, can increase osteoclastogenesis and are associated with pathological bone loss. Whether immunoglobulins and mature B lymphocytes are important for general bone architecture has not been completely determined. Here we demonstrate, using a transgenic mouse model, that reduction of mature B cells and immunoglobulins leads to increased trabecular bone mass compared to wild-type (WT) littermate controls. This bone effect is associated with a decrease in the number of osteoclasts and reduced bone resorption, despite decreased expression of osteoprotegerin. We also demonstrate that the reduction of mature B cells and immunoglobulins do not prevent bone loss caused by estrogen deficiency or arthritis compared to WT littermate controls. In conclusion, the reduction of mature B cells and immunoglobulins results in disturbed regulation of trabecular bone turnover in healthy conditions but is dispensable for pathological bone loss. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Burden, patterns, and impact of multimorbidity in North India: findings from a rural population-based study.

AIM: To estimate the prevalence, socio-demographic determinants, common disease combinations, and health impact of multimorbidity among a young rural population. METHODS: We conducted a cross-sectional survey among participants aged ≥30 years in rural Punjab, North India, from Jan 2019 to April 2019. Multimorbidity was defined as the coexistence of ≥two conditions using a 14-condition tool validated in India. We also calculated a multimorbidity-weighted index (MWI), which provides a weight to each disease based on its impact on physical functioning. Logistic regression was conducted to evaluate the association with sociodemographic variables, mental health (PHQ-9), physical functioning (ADL scale), and self-rated health (SRH). RESULTS: We analyzed data from 3213 adults [Mean age 51.5 (±13), 54% women]. Prevalence of single chronic condition, multimorbidity, and MWI was 28.6, 18% and - 1.9 respectively. Age, higher wealth index and ever use alcohol were significantly associated with multimorbidity. Overall, 2.8% of respondents had limited physical functioning, 2.1% had depression, and 61.5% reported low SRH. Poorer health outcomes were more prevalent among the elderly, women, less educated, and those having lower wealth index and multimorbidity, were found to be significantly associated with poor health outcomes. CONCLUSIONS: The burden of multimorbidity was high in this young rural population, which portends significant adverse effects on their health and quality of life. The Indian health system should be reconfigured to address this emerging health priority holistically, by adopting a more integrated and sustainable model of care.

Human (but not animal) motion can be recognized at first sight - After treatment for congenital blindness.

The long-standing nativist vs. empiricist debate asks a foundational question in epistemology - does our knowledge arise through experience or is it available innately? Studies that probe the sensitivity of newborns and patients recovering from congenital blindness are central in informing this dialogue. One of the most robust sensitivities our visual system possesses is to 'biological motion' - the movement patterns of humans and other vertebrates. Various biological motion perception skills (such as distinguishing between movement of human and non-human animals, or between upright and inverted human movement) become evident within the first months of life. The mechanisms of acquiring these capabilities, and specifically the contribution of visual experience to their development, are still under debate. We had the opportunity to directly examine the role of visual experience in biological motion perception, by testing what level of sensitivity is present immediately upon onset of sight following years of congenital visual deprivation. Two congenitally blind patients who underwent sight-restorative cataract-removal surgery late in life (at the ages of 7 and 20 years) were tested before and after sight restoration. The patients were shown displays of walking humans, pigeons, and cats, and asked to describe what they saw. Visual recognition of movement patterns emerged immediately upon eye-opening following surgery, when the patients spontaneously began to identify human, but not animal, biological motion. This recognition ability was evident contemporaneously for upright and inverted human displays. These findings suggest that visual recognition of human motion patterns may not critically depend on visual experience, as it was evident upon first exposure to un-obstructed sight in patients with very limited prior visual exposure, and furthermore, was not limited to the typical (upright) orientation of humans in real-life settings.

Emerging multimorbidity patterns and their links with selected health outcomes in a working-age population group.

Background: The study aims to identify recurrent multimorbidity pattern among individuals in the age-group 15-64 years. Further, the study examines the association of these identified patterns with sociodemographic variables and selected health outcomes. Methods: The study utilized data on 2912 individuals in the age-group 15-64 years collected under the burden of diseases study among patients attending public health care settings of Odisha. A latent class analysis was used to identify commonly occurring disease clusters. Results: The findings suggested that 2.4% of the individuals were multimorbid. Two latent disease clusters were identified, low co-morbidity and Hypertension-Diabetes-Arthritis. Findings highlighted that age, belonging to a non-aboriginal ethnicity and urban area increased the risk of being in the 'Hypertension-Diabetes-Arthritis' group. Furthermore, 50% of the individual in the 'Hypertension-Diabetes-Arthritis' group reported poor quality of life, whereas 30% reported poor self-rated health compared to only 11% by their counterparts. Additionally, the mean health score reported by the individuals in the 'Hypertension-Diabetes-Arthritis' group was 39.9 compared to 46.9 by their counterparts. Conclusions: The study findings hint towards increasing burden of multimorbidity among the working age population, which depicts a shift in causation of diseases as a result of which preventive measures also need to be taken much prior.

Development of Visual Memory Capacity Following Early-Onset and Extended Blindness.

It is unknown whether visual memory capacity can develop if onset of pattern vision is delayed for several years following birth. We had an opportunity to address this question through our work with an unusual population of 12 congenitally blind individuals ranging in age from 8 to 22 years. After providing them with sight surgery, we longitudinally evaluated their visual memory capacity using an image-memorization task. Our findings revealed poor visual memory capacity soon after surgery but significant improvement in subsequent months. Although there may be limits to this improvement, performance 1 year after surgery was found to be comparable with that of control participants with matched visual acuity. These findings provide evidence for plasticity of visual memory mechanisms into late childhood but do not rule out vulnerability to early deprivation. Our computational simulations suggest that a potential mechanism to account for changes in memory performance may be progressive representational elaboration in image encoding.