Comparison of Various Therapeutic Approaches to Manage Infertility in Polycystic Ovarian Syndrome.

OBJECTIVE: To compare the efficacies of common therapeutic regimens and their combinations, used in polycystic ovarian syndrome (PCOS) to improve fertility in reproductive-age women. STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Obstetric Gynaecologist, Medicare Cardiac and General Hospital, Karachi, Pakistan, from November 2022 to July 2023. METHODOLOGY: Out of 300 patients with the symptoms of menstrual irregularities and infertility, 152 were diagnosed as PCOS patients based on the ultrasound and hormonal assays and selected for study purpose. They were divided according to their therapeutic regimen into four treatment groups, treated by different therapeutic agents. Group A received metformin 500 mg/day (n = 38); Group B received metformin + myo-inositol 1g (n = 49); Group C received metformin + letrozole 2.5 mg (n = 36), and Group D received metformin + letrozole + myo-inositol (n = 29), orally for three months. All continuous variables, such as body mass index (BMI), FSH, LH, FT4, and FSI were analysed by applying t-test to all therapeutic groups, keeping p ≤0.05 as the level of significance. RESULTS: HCG-positive was found as 86% (n = 33) in Group A, 63% (n = 31) in Group B, 52% (n = 19) in Group C, and 27% (n = 08) in Group D. There were statistically significant (p <0.001) changes in BMI, FSH, LH, FT4, and FSI as well. Metformin alone and metformin plus myo-inositol came out to be more effective than other regimens. CONCLUSION: Metformin alone and myo-inositol plus metformin are effective therapeutic options in PCOS-induced infertility problems. KEY WORDS: Polycystic ovarian syndrome, Infertility, Metformin, Myo-inositol, Letrozole, Menstrual irregularities.

Climate change and healthy ageing: An assessment of the impact of climate hazards on older people.

Background: Climate change not only directly impacts older people's longevity but also healthy ageing, which is the process of maintaining physical and mental capacities while optimising functional abilities. The urgency to address both population ageing and climate change necessitates a rethink and assessment of the impact of climate change on older people. This includes identifying what can be done to anticipate, mitigate and adapt to climate change and engage older persons. Methods: A review of climate change and healthy ageing forms the basis of evidence in this report. We developed a comprehensive search to assess current literature, combining terms related to ageing and climate change across four major data sets and assessing articles published up to the end of 2021. Results: We summarised the current and future impact of climate change on older people and developed a framework identifying climate change impacts on older persons, recognising social and environmental determinants of healthy ageing. Major hazards and some key exposure pathways include extreme temperatures, wildfire, drought, flooding, storm and sea level rise, air quality, climate-sensitive infectious diseases, food and water insecurities, health and social care system displacement, migration, and relocation. Strategies to address climate change require interventions to improve systems and infrastructure to reduce vulnerability and increase resilience. As a heterogeneous group, older people's perceptions of climate change should be integrated into climate activism. Increasing climate change literacy among older people and enabling them to promote intergenerational dialogue will drive the development and implementation of equitable solutions. Pathways may operate via direct or indirect exposures, requiring longitudinal studies that enable assessment of exposures and outcomes at multiple time points, and analyses of cumulative impacts of hazards across the life course. Conclusions: The lack of systematic reviews and primary research on the impact of most climate hazards, except for heat, on older people is apparent. Future research should include outcomes beyond mortality and morbidity and assess how older people interact with their environment by focusing on their capacities and optimising abilities for being and doing what they value.

Mental health and psychosocial interventions in the context of climate change: a scoping review.

The evidence on the impacts of climate change on mental health and wellbeing is growing rapidly. The objective of this scoping review is to understand the extent and type of existing mental health and psychosocial interventions aimed at addressing the mental health and psychosocial impacts of climate change. A scoping review methodology was followed. MEDLINE, PsycINFO, and Web of Science databases were searched from inception to May 2022. Comprehensive gray literature search, including expert consultation, was conducted to identify interventions for which peer-reviewed academic literature may not yet be available. Data on intervention type, setting, climate stressor, mental health outcome, evaluation, and any other available details were extracted, and results were summarized narratively. Academic literature search identified 16 records and gray literature search identified a further 24 records. Altogether, 37 unique interventions or packages of interventions were identified. The interventions act at the levels of microsystem, mesosystem, exosystem, and macrosystem through diverse mechanisms. While most interventions have not been formally evaluated, promising preliminary results support interventions in low- and middle-income-country settings disproportionately affected by climate disasters. Interventions from multidisciplinary fields are emerging to reduce psychological distress and enhance mental health and wellbeing in the context of climate change. This scoping review details existing evidence on the interventions and summarizes intervention gaps and lessons learned to inform continued intervention development and scale-up interventions.

A highly efficient transgene knock-in technology in clinically relevant cell types.

Inefficient knock-in of transgene cargos limits the potential of cell-based medicines. In this study, we used a CRISPR nuclease that targets a site within an exon of an essential gene and designed a cargo template so that correct knock-in would retain essential gene function while also integrating the transgene(s) of interest. Cells with non-productive insertions and deletions would undergo negative selection. This technology, called SLEEK (SeLection by Essential-gene Exon Knock-in), achieved knock-in efficiencies of more than 90% in clinically relevant cell types without impacting long-term viability or expansion. SLEEK knock-in rates in T cells are more efficient than state-of-the-art TRAC knock-in with AAV6 and surpass more than 90% efficiency even with non-viral DNA cargos. As a clinical application, natural killer cells generated from induced pluripotent stem cells containing SLEEK knock-in of CD16 and mbIL-15 show substantially improved tumor killing and persistence in vivo.

Experiences of loneliness in lower- and middle-income countries: A systematic review of qualitative studies.

Loneliness is understood as a subjective experience resulting from unmet social relationship expectations. As most loneliness research has been conducted in higher-income-countries, there is limited understanding of loneliness in relation to diverse cultural, economic, and socio-political factors. To address this gap, the present review systematically synthesises existing qualitative studies on the experience of loneliness and social relationship expectations in lower- and middle-income countries (LMICs). Between June and July 2022, six online databases (Embase, Ovid Medline, APA PsycINFO, Global Health, Web of Science, Google Scholar) were searched for peer-reviewed studies from LMICs on loneliness using qualitative methods. There were no restrictions on publication date, language, or study setting. Studies that solely focused on social isolation or were conducted with children (<16 years) were excluded. Risk of bias was assessed with the Critical Appraisal Skills Programme. After deduplication, a total of 7866 records were identified and screened for inclusion, resulting in 24 studies published between 2002 and 2022. The included studies represent data from 728 participants in 15 countries across West Africa (Ghana, Nigeria, Niger, Mali), East Africa (Uganda, Kenya), North Africa (Egypt), West Asia (Iran), South Asia (India, Pakistan, Sri Lanka) and Southeast Asia (Myanmar, Cambodia, Indonesia, Philippines). Data were analysed combining inductive and deductive coding, summarised using narrative synthesis, and examined by geographical region. Common features of loneliness included rejection, overthinking, and pain. Loneliness was related to depression across regions. Whereas loneliness tended to be distinguished from social isolation in studies from Africa, it tended to be related with being alone in studies from Asia. Poverty and stigma were common barriers to fulfilling social relationship expectations. This review illustrates how loneliness and expectations are contextually embedded, with some expectations possibly being specific to a certain culture or life stage, having implications for assessment of and interventions for loneliness worldwide.

Assessment of neuropharmacological consequences induced by dexamethasone administration in rats model of neurodegenerative diseases.

Stress is a well-known and frequently used term among present generation. It has been referred to the response of body to any challenge for a change. It is a natural process and our body is designed to cope with it. However, if stress becomes chronic, it can lead to mental health problems. Stress due to the prolonged administration of glucocorticoid is enabled to produce impressive alterations in rats model shoeing depressive like behavior. In this investigation; purpose was to study the impact of episodic treatment of dexamethasone with respect to behavioral changes in rats. It was hypothesized that repeated administration of dexamethasone could increase stress and thus, psychological stress leading to mood disorders and behavior deficits in rats. Rats were injected daily with DEX (10 mg/ml/kg, orally) and the different behavioral models of the animals were assessed. DEX-treated rats exhibited depressive behavior like greater time to start mobility in a novel environment and elevated anxiety-like behavior in elevated plus maze. However, time spent in light compartment was shorter with repeated administration of DEX. From results it is demonstrated that the administration of DXM for weeks induced stress and consequently, induced a depression-like behaviors in rats models.

A cost-free CURE: using bioinformatics to identify DNA-binding factors at a specific genomic locus.

Research experiences provide diverse benefits for undergraduates. Many academic institutions have adopted course-based undergraduate research experiences (CUREs) to improve student access to research opportunities. However, potential instructors of a CURE might still face financial or practical hurdles that prevent implementation. Bioinformatics research offers an alternative that is free, safe, compatible with remote learning, and may be more accessible for students with disabilities. Here, we describe a bioinformatics CURE that leverages publicly available datasets to discover novel proteins that target an instructor-determined genomic locus of interest. We use the free, user-friendly bioinformatics platform Galaxy to map ChIP-seq datasets to a genome, which removes the computing burden from students. Both faculty and students directly benefit from this CURE, as faculty can perform candidate screens and publish CURE results. Students gain not only basic bioinformatics knowledge, but also transferable skills, including scientific communication, database navigation, and primary literature experience. The CURE is flexible and can be expanded to analyze different types of high-throughput data or to investigate different genomic loci in any species.

Proportions of four distinct classes of sensory neurons are retained even when axon regeneration is enhanced following peripheral nerve injury.

Introduction: Recovery from peripheral nerve injuries is poor because axon regeneration is slow and inefficient. Experimental therapies that increase signaling of neuronal brain-derived neurotrophic factor (BDNF) through its TrkB receptor or through its downstream effectors enhance axon regeneration, increasing the number of motor and sensory neurons whose axons successfully regenerate and reinnervate muscle targets. The goal of this study was to compare the proportions of four different classes of sensory (dorsal root ganglion, DRG) neurons that successfully reinnervate two different muscle targets in control mice and mice treated pharmacologically to enhance axon regeneration. Methods: Following sciatic nerve transection and repair, C57BL/6 J mice were treated for 2 weeks, either with R13, a prodrug that releases the small molecule TrkB ligand, 7,8-dihydroxyflavone, with compound 11 (CP11), an inhibitor of asparaginyl endopeptidase (δ-secretase), or with a control vehicle. Four weeks after injury, different fluorescent retrograde tracers were injected into the gastrocnemius and tibialis anterior muscles to mark DRG neurons that had successfully reinnervated these muscles. Using immunofluorescence, retrogradely labeled DRG neurons also expressing markers of four different sensory neuronal classes were counted. Results and discussion: Treatments with R13 or CP11 resulted in muscle reinnervation by many more DRG neurons than vehicletreated controls, but neurons expressing proteins associated with the different classes of DRG neurons studied were largely in the same proportions found in intact mice.

Implementation of a Multidisciplinary Medication Refill Protocol.

Introduction: Primary care clinicians spend significant time managing nonvisit activities, including processing of requests for prescription renewal. Delays in processing refills may lead to patient dissatisfaction and impact provider productivity. Having nonclinicians process refills can be more efficient and time-saving. We aimed to evaluate the use of a multidisciplinary medication refill protocol to decrease the time to complete refill requests. Methods: We implemented nursing-driven management of refill requests within two family medicine residency clinics in Milwaukee, Wisconsin (Phase 1: single clinic implementation [March 2017-June 2019]; Phase 2: added second clinic prepandemic [June 2019-March 2020] and postpandemic [April 2020-December 2020]). The multidisciplinary refill protocol was created by faculty, residents, pharmacy, and nursing. Data were collected using electronic health record time stamps to determine when refill requests were initiated and filled by faculty, residents, and nurses. We used Mood's median test to compare the median time for medication refill completion. We used Levene's test to test for equal variance surrounding the median of each caregiver group. We used Fisher's exact test or χ2 test with Yates' correction for 2×2 contingency tables. Results: In both phases, we identified a significant reduction in median time to refill completion ( P<.001) and variability of time to refill completion ( P<.001). Notably, in Phase 1, reduction in median refill time was most apparent among residents (383 vs 79 min postimplementation); and in Phase 2, the percentage of refills completed within 48 hours significantly increased between the pre-COVID-19 and COVID-19 pandemic among faculty and nursing in Clinic 1 and residents and faculty in Clinic 2 (all P's<.001). Conclusions: Implementation of a multidisciplinary refill protocol significantly improved time and predictability of refill completion in both phases.

Identification of an APOE ε4-specific blood-based molecular pathway for Alzheimer's disease risk.

INTRODUCTION: The precise apolipoprotein E (APOE) ε4-specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear. METHODS: Plasma protein modules/cascades were analyzed using weighted gene co-expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), and brain glucose metabolism, stratified by APOE genotype. RESULTS: The Green Module was associated with AD diagnosis in APOE ε4 homozygotes. Three proteins from this module, C-reactive protein (CRP), complement C3, and complement factor H (CFH), had dose-dependent associations with CSF p-tau and cognitive impairment only in APOE ε4 homozygotes. The link among these three proteins and glucose hypometabolism was observed in brain regions of the default mode network (DMN) in APOE ε4 homozygotes. A Framingham Heart Study validation study supported the findings for AD. DISCUSSION: The study identifies the APOE ε4-specific CRP-C3-CFH inflammation pathway for AD, suggesting potential drug targets for the disease.Highlights: Identification of an APOE ε4 specific molecular pathway involving blood CRP, C3, and CFH for the risk of AD.CRP, C3, and CFH had dose-dependent associations with CSF p-Tau and brain glucose hypometabolism as well as with cognitive impairment only in APOE ε4 homozygotes.Targeting CRP, C3, and CFH may be protective and therapeutic for AD onset in APOE ε4 carriers.

A bioinformatics screen reveals hox and chromatin remodeling factors at the Drosophila histone locus.

BACKGROUND: Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. RESULTS: To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). CONCLUSIONS: Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

Treatments with the specific δ-secretase inhibitor, compound 11, promote the regeneration of motor and sensory axons after peripheral nerve injury.

Limited axon regeneration following peripheral nerve injury may be related to activation of the lysosomal protease, asparaginyl endopeptidase (AEP, δ-secretase) and its degradation of the microtubule associated protein, Tau. Activity of AEP was increased at the site of sciatic nerve transection and repair but blocked in mice treated systemically with a specific AEP inhibitor, compound 11 (CP11). Treatments with CP11 enhanced axon regeneration in vivo. Amplitudes of compound muscle action potentials recorded 4 weeks after nerve transection and repair and 2 weeks after daily treatments with CP11 were double those of vehicle-treated mice. At that time after injury, axons of significantly more motor and sensory neurons had regenerated successfully and reinnervated the tibialis anterior and gastrocnemius muscles in CP11-treated mice than vehicle-treated controls. In cultured adult dorsal root ganglion neurons derived from wild type mice that were treated in vitro for 24 h with CP11, neurites were nearly 50% longer than in vehicle-treated controls and similar to neurite lengths in cultures treated with the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF). Combined treatment with CP11 and 7,8-DHF did not enhance outgrowth more than treatments with either one alone. Enhanced neurite outgrowth produced by CP11 was found also in the presence of the TrkB inhibitor, ANA-12, indicating that the enhancement was independent of TrkB signalling. Longer neurites were found after CP11 treatment in both TrkB+ and TrkB- neurons. Delta secretase inhibition by CP11 is a treatment for peripheral nerve injury with great potential.

Effect Of Elastomeric Separator On Microbial Count In Gingival Crevicular Fluid.

BACKGROUND: The separators are a preliminary step for band insertion, but there is a potential risk of bacteraemia during their placement, particularly in susceptible patients. The objective of the study is to determine the effect of separators on the bacterial count in gingival crevicular fluid (GCF) and to assess the efficacy of chlorhexidine mouth rinse and saline irrigation in the reduction of the bacterial count. METHODS: This randomized controlled trial was conducted on 51 participants who were divided into three equal g roups randomly (brushing only/control, saline irrigation, and 2% chlorhexidine mouthwash rinse). The inclusion criteria were age between 18-25 years, good oral hygiene, gingival and plaque index <1, no previous orthodontic treatment, and healthy individuals. The bacterial count was obtained from GCF samples after two hours, on the third day, and on the seventh day. Kruskal Wallis test was used to compare the bacterial count among the three groups, and post hoc analysis was done using Dunn's test. Friedman test was applied to see the difference at three-time points in each group. RESULTS: In both saline and chlorhexidine groups the mean bacterial count decreased significantly from baseline to 3rd day and 7th day after separator placement (p<0.001). For the third day, a significant difference was found in control versus saline and control versus chlorhexidine. No significant difference was found between saline and chlorhexidine on the third day. Similar results were found on the 7 thday. For controls, the bacterial count increased with time and for both saline and chlorhexidine groups the bacterial count decreased. The highest decrease in the bacterial count was found for the chlorhexidine group. CONCLUSIONS: After the placement of separators, there was an increase in the bacterial count in GCF. Notably, chlorhexidine was found to be more effective than saline irrigation in reducing the bacterial count.

A bioinformatics screen reveals Hox and chromatin remodeling factors at the Drosophila histone locus.

Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets and 27 factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax, Abdominal-A and Abdominal-B, suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other transcription factors that target the histone gene array: JIL-1, Hr78, the long isoform of fs(1)h as well as the generalized transcription factors TAF-1, TFIIB, and TFIIF. Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

Blood levels of MCP-1 modulate the genetic risks of Alzheimer's disease mediated by HLA-DRB1 and APOE for Alzheimer's disease.

INTRODUCTION: C-Reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are both implicated in the peripheral proinflammatory cascade and blood-brain barrier (BBB) disruption. Since the blood CRP level increases Alzheimer's disease (AD) risk depending on the apolipoprotein E (APOE) genotype, we hypothesized that the blood MCP-1 level exerts different effects on the AD risk depending on the genotypes. METHODS: Using multiple regression analyses, data from the Framingham Heart Study (n = 2884) and Alzheimer's Disease Neuroimaging Initiative study (n = 231) were analyzed. RESULTS: An elevated blood MCP-1 level was associated with AD risk in major histocompatibility complex, Class II, DR beta 1 (HLA-DRB1) rs9271192-AC/CC (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.50-6.28, p = 0.002) and in APOE ε4 carriers (HR = 3.22, 95% CI = 1.59-6.53, p = 0.001). In contrast, among HLA-DRB1 rs9271192-AA and APOE ε4 noncarriers, blood MCP-1 levels were not associated with these phenotypes. DISCUSSION: Since HLA-DRB1 and APOE are expressed in the BBB, blood MCP-1 released in the peripheral inflammatory cascade may function as a mediator of the effects of HLA-DRB1 rs9271192-AC/CC and APOE ε4 genotypes on AD pathogenesis in the brain via the BBB pathways.

Caregiving, volunteering, and loneliness in middle-aged and older adults: a systematic review.

OBJECTIVES: Older adults contribute vast amounts of care to society, yet it remains unclear how unpaid productive activities relate to loneliness. The objective of this systematic review is to synthesise the evidence for associations between midlife and older people's unpaid productive activities (i.e., spousal and grandparental caregiving, volunteering) and loneliness. METHODS: Peer-reviewed observational articles that investigated the association between loneliness and caregiving or volunteering in later life (>50 years) were searched on electronic databases (Ovid MEDLINE, Embase, PsychInfo and Global Health) from inception until July 2021. Studies were analysed using narrative synthesis and assessed for methodological quality applying the Newcastle Ottawa Scale. RESULTS: A total of 28 articles from 21 countries with 191,652 participants were included (52.5% women). Results were separately discussed for the type of unpaid productive activity, namely, general caregiving (N = 10), spousal caregiving (N = 7), grandparental caregiving (N = 7), and volunteering (N = 6). Risk of bias assessments revealed a moderate to high quality of included studies. Loneliness was positively associated with spousal caregiving but negatively associated with caregiving to grandchildren and volunteering. CONCLUSIONS: Grandparental caregiving and volunteering may be promising avenues for reducing loneliness in older age. Future studies will need to distinguish between different types of caregiving and volunteering and explore more complex longitudinal designs with diverse samples to investigate causal relationships with loneliness.

Spousal caregiving is associated with more lonelinessGrandparental caregiving and volunteering are associated with less lonelinessThere is a lack of longitudinal evidence from lower- and middle-income countries.

Unpaid productive activities and loneliness in later life: Results from the Indonesian Family Life Survey (2000-2014).

INTRODUCTION: Contributing to society constitutes an essential part of healthy ageing. To date, however, it remains unclear how valuable contributions such as caregiving and volunteering, also described as unpaid productive activities, are related to older adults' loneliness. The present longitudinal study addresses this question in a lower-middle-income country, in Indonesia. METHODS: Using data from two waves of the nationally representative Indonesian Family Life Survey (2000-2014), logistic regression models were applied with caregiving (to non-resident children, siblings, and parents) and volunteering (1-99 h, >100 h per year) as predictors and loneliness as outcome. Participants who were <50 years old and felt lonely at baseline were excluded. Results are reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Of the 3,572 participants (52.8% women; Mean age: 60 years), 538 (15.1%) developed loneliness. In the unadjusted model, volunteering 1-99 h per year and caregiving to parents were each associated with a lower likelihood of feeling lonely later in life. For moderate volunteering (1-99 h), participating in the volunteer decision-making process was beneficial for loneliness. After adjusting for covariates, only the association between caregiving to parents and loneliness remained significant (OR=0.48, 95%CI: 0.27-0.81, p = 0.01). Specifically, providing care to parents who did not need help with daily activities was associated with lower loneliness. CONCLUSION: This longitudinal study addresses important research gaps in the literature on global healthy ageing, as it relates to the protective role of older adults' unpaid productive activities on loneliness in Indonesia.

Understanding and Addressing Older Adults' Loneliness: The Social Relationship Expectations Framework.

Loneliness is an experience resulting from a perceived discrepancy between expected and actual social relationships. Although this discrepancy is widely considered the "core mechanism" of loneliness, previous research and interventions have not sufficiently addressed what older adults specifically expect from their social relationships. To address this gap and to help situate research on older adults' loneliness within broader life span developmental theories, we propose a theoretical framework that outlines six key social relationship expectations of older adults based on research from psychology, gerontology, and anthropology: availability of social contacts, receiving care and support, intimacy and understanding, enjoyment and shared interests, generativity and contribution, and being respected and valued. We further argue that a complete understanding of loneliness across the life span requires attention to the powerful impacts of contextual factors (e.g., culture, functional limitations, social network changes) on the expression and fulfillment of older adults' universal and age-specific relationship expectations. The proposed Social Relationship Expectations Framework may fruitfully inform future loneliness research and interventions for a heterogeneous aging population.

Evaluation of CSF kappa free light chains for the diagnosis of multiple sclerosis (MS): a comparison with oligoclonal bands (OCB) detection via isoelectric focusing (IEF) coupled with immunoblotting.

This study was done to evaluate the diagnostic accuracy of cerebrospinal fluid kappa free light chain (KFLC) for diagnosis of multiple sclerosis, against isoelectrofocusing (IEF) to detect oligoclonal bands (OCB) as gold standard. 64 cases were divided into positive and negative based on the OCB results. Diagnostic accuracy was calculated for the 1 mg/L cut-off. The 1 mg/L cut-off yielded a percent agreement of 86.1% and Cohen's kappa value of 0.8. Youden's index, yielded a cut-off of 0.92 mg/L as optimal (90.3% specificity and 90.9% sensitivity). The analytical time was 3 hours and 55 min for IEF and 25 min for KFLC. The cost of a single OCB test was PKR12 000 (US$68.17) compared with PKR4150 (US$23.58) for KFLC. KFLC proved to be an accurate, cheaper and time-saving alternative and can be performed prior to the contemporary testing.