Pathological and molecular studies on elephant endotheliotropic herpesvirus haemorrhagic disease among captive and free-range Asian elephants in India.

In the present research pathology and molecular diagnosis of elephant endotheliotropic herpes virus-haemorrhagic disease (EEHV-HD) among Asian elephants was studied. Out of 76 cases, 20 were positive for EEHV infection in PANPOL and POL1 based semi-nested PCR. Out of 20 samples, 10 samples were fatal cases of EEHV-HD while 10 were of either subclinical or latent infection. Acute onset haemorrhagic disease with EEHV-HD had anorexia, facial and neck swelling, cyanotic buccal mucosa and tongue, nasal and ocular discharge, and colic. The hallmark of gross finding in all cases were severe haemorrhagic lesions in the internal organs viz. cyanosis of tongue with multifocal petechial haemorrhages, diffuse epicardial and endocardial haemorrhages, swollen liver (rounded edges) with parenchymal haemorrhages, serosal and mucosal haemorrhages in gastrointestinal tract, congested kidneys with corticomedullary haemorrhages, highly congested meninges, and brain capillaries with haemorrhages. Microscopic findings in all the cases had severe vascular changes in the visceral organs. Microthrombi was present in the vasculature of tongue, heart, lung, liver, kidney, and brain. The endothelial lining of most of the blood vessels were swollen with apoptotic changes. Amphophilic to basophilic intranuclear inclusion bodies were observed in the endothelial cells. Immunostaining using anti-EEHV DNAPOL hyperimmune sera revealed intense positive signals in the endothelium of blood vessels and their walls. Quantification of viral load in necropsy tissue samples revealed highest in the heart (7.4 × 106/µg of sample) and least in the brain (9 × 103/µg of sample). The PCR amplicons from EEHV1 specific genes (POL1(U38) and TER were subjected to partial genome sequencing which had 99.9% similarity with the EEHV1A subtype. It was concluded that Asian elephants in India are latently infected for EEHV1 and in all the fatal EEHV-HD cases, EEHV1A subtype was the causative agent with characteristic pathomorphological changes in visceral organs.

The effectiveness of prenatal and postnatal home visits by paramedical professionals and women's group meetings in improving maternal and child health outcomes in low and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of prenatal and postnatal home visits (HVs) and women group meetings (WGMs) by paramedical professionals to improve maternal and child health outcomes in low- and middle-income countries (LMICs). STUDY DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic review of trials published till December 2020, as per registered protocol in The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42018091968). Outcomes were neonatal mortality rate (NMR), maternal mortality ratio (MMR), the incidence of low birth weight, and still birth rate (SBR). The Cochrane Pregnancy and Childbirth Group's Trials Register, Cochrane Central Register of Controlled Trials, PubMed, and Excerpta Medica Database (EMBASE) were searched. Pooled results were estimated using random-effects meta-analysis in RevMan version 5.2. RESULTS: Twenty-five trials met the inclusion criteria. HVs were the key intervention in 12, WGMs in 11, and both interventions in 2 trials. The pooled estimates have shown that NMR was significantly reduced by HVs (OR 0.77, confidence interval [CI]: 0.67-0.90, P = 0.0007, I2 = 77%) and WGMs (OR 0.76, CI: 0.65-0.90, P = 0.001, I2 = 71%). SBR was significantly reduced by HVs (OR 0.77, CI: 0.70-0.85; P < 0.001, I2 = 0%). Subgroup analysis of studies in which more than 10% of pregnant women participated in the WGMs showed significant reduction in NMR (OR 0.67, CI 0.58-0.77, P = 0.00001, I2 = 31%) and MMR (OR 0.55, CI 0.36-0.84, P = 0.005, I2 = 27%). Two studies reported improvement in birth weight by HVs. CONCLUSIONS: HVs and WGMs (with >10% pregnant women) by paramedical professionals are effective strategies in reducing the NMR and MMR in LMICs. HVs were also effective in reducing SBR.

Effect of membrane stabilizers on semen quality and sperm membrane protein expression during cryopreservation of goat semen.

BACKGROUND: Semen cryopreservation is a complex process during which there is alteration in the expression of sperm and seminal plasma proteins, molecular weight of protein or loss of membrane proteins during the process. In order to compensate for these changes, different membrane stabilizers are used in freezing semen extenders. However, there is scarcity of such studies during cryopreservation of goat semen. OBJECTIVE: To investigate the effect of membrane stabilizers on sperm membrane protein expression during cryopreservation of goat semen. MATERIALS AND METHODS: A total of 36 semen ejaculates from nine Assam Hill Goat bucks aged 2 to 2.5 years was collected by artificial vagina method. Three membrane stabilizers, each at two different concentrations viz. 50 and 80 mM sucrose, 50 and 100 mM trehalose, and 100 and 150 ng per mL IGF-1 (insulin-like growth factor 1 protein) were added to Tris-citric acid fructose egg yolk glycerol (TCFEYG) extender and semen samples were cryopreserved. The sperm membrane protein profile was studied in fresh and cryopreserved semen by SDS-PAGE. RESULTS: SDS- PAGE of sperm membrane extract of fresh semen revealed the presence of 24 protein bands with molecular weights ranging from 10 kDa to 240 kDa. Samples supplemented with 50 mM sucrose and 80 mM sucrose revealed 21 protein bands with molecular weights ranging from 10 kDa to 240 kDa. All the 21 protein bands were same as those observed in the sperm membrane of fresh spermatozoa, except that the 23 kDa, 29 kDa and 42 kDa bands were absent in frozen semen. Similarly, frozen semen extended with 50 mM trehalose and 100 mM trehalose revealed 22 protein bands with molecular weights ranging from 10 kDa to 240 kDa, but lacking the 29 kDa and 42 kDa bands. Proteins with molecular weights of 29 kDa, 130 kDa and 240 kDa were absent in frozen semen supplemented with 100 ng per mL IGF-1 and 150 ng per mL IGF-1. CONCLUSION: The present study revealed that supplementation of tris basic extender with trehalose at 100 mM and or IGF-1 at 100 ng/mL or 150 ng per mL improves the post-thaw semen characteristics and protects certain fertility related sperm membrane proteins. Doi.org/10.54680/fr23510110612.

THE IMPACT OF CLIMATE CHANGE ON INFECTIOUS DISEASES: A COMPREHENSIVE ANALYSIS OF VECTOR-BORNE DISEASES, WATER-BORNE DISEASES, AND PUBLIC HEALTH STRATEGIES.

Climate change is long-term modifications to weather patterns and a rise in extreme weather events. It might modify the hazard to human health and exacerbate current problems. The article explores the scientific data in a description of the effects of Infectious diseases in humans and climate change. It identifies scientific advancements and gaps in potential responses from human civilization and how it might prepare for the changes that come with it by adjusting to them. The impact reflects three aspects, such as climate variables, selected infectious diseases, and infectious disease components. This study demonstrates how vulnerable people are to any ill consequences that climate change may have on their health. Humans can actively influence controllable correlated health impacts by taking proactive measures, such as increasing our understanding of the detrimental effects associated with specific diseases and the patterns in climate change. We can also carefully distribute technology and resources, encouraging exercise and public awareness. It is advised to take the following adaption measures: Considering how infectious diseases and climate change are not the only things that science has discovered and create locally efficient early warning systems for those effects to produce more scientific justifications and go beyond scientific reports. Improve prediction of the spatiotemporal processes behind climate change and changes in infectious illnesses connected at different temporal and spatial scales.

ANXIETY SYNDROMES IN ADOLESCENTS WITH OPERATIONAL RESPIRATORY CONDITIONS: A PROSPECTIVE STUDY.

Aim - determining the prevalence of anxiety disorders and their effect on disease progression and quality of life in adults with organic illnesses and functional disorders of the respiratory system treated in a pulmonology environment. A total of 135 young adults between the ages of 13 and 17 were analyzed. There were a total of 46 adolescents diagnosed with somatoform respiratory disorders (SRD), 45 adolescents diagnosed with bronchial asthma (BA), and 44 adolescents diagnosed with pneumonia. The Spielberger-Khanin anxiety questionnaire and the Nijmegen hyperventilation syndrome (HVS) scale were used for the research and diagnosis, respectively. The quality of life was measured using the asthma quality of life questionnaire (AQLQ). In comparison to adults with asthma (33.2%) and pneumonia (32.3%), adults with SRD (34.5%). There were mild immediate associations between the Spielberger scale and the Nijmegen HVS questionnaire for both trait and state anxiety, and mild inverse correlations between the Spielberger scale and the AQLQ for both state and trait anxiety. Adolescents with anxiety had a higher prevalence of trauma, pain, and social issues than their non-anxious counterparts who were referred to psychiatry. In adolescents, 5.1% had severe trait anxiety, and 19.3% had severe condition anxiety. Adolescents with SRD were twice as likely to suffer from extreme state and trait anxiety as the general population. It is hypothesized that anxiety problems are at the root of HVS and contribute to adults' dissatisfaction with their quality of life due to lung ailments. Although certain adolescents with anxiety disorders were referred for anxiety, this data nevertheless lends credence to the idea that using standardized and structured instruments regularly might help increase accuracy and detection rates in the clinic, regardless of the reason for referral. Complete evaluations are essential for this patient population due to the intricacy of their symptoms.

Interface morphology driven exchange interaction and magnetization reversal in a Gd/Co multilayer.

Rare-earth (RE)/transition metal (TM) ferromagnetic heterostructures with competing interfacial coupling and Zeeman energy provide a rich ground to study different phase states as a function of magnetic field and temperature. The interface morphology as a knob in these RE/TM heterostructures provides an excellent opportunity to engineer the macroscopic magnetic response by tuning the interface dependent microscopic interactions between the layers. We have investigated the interface morphology driven structure and magnetic properties of a Gd/Co multilayer. The interface morphology of the multilayer was controlled by annealing the multilayer at a relatively low temperature of 573 K under vacuum conditions. Combining the different experimental techniques and a simple one-dimensional spin-based model calculation, we studied the detailed magnetic structure and magnetization reversal mechanism in this system across compensation temperature (Tcomp), which suggested a strong interface dependent coupling in the system. We showed that changes in the interface morphology of the Gd/Co multilayer strongly influence the macroscopic magnetic properties of the system. The calculation also confirms the formation of a helical magnetic structure with a 2π domain wall in this system below Tcomp. The experimental finding and the simulation of this technologically important system will help to understand the physics of all-optical switching and related applications.

Laser processing of sapphire and fabrication of diffractive optical elements.

Sapphire is a high-temperature optical material with a melting temperature of over 2000ºC, high strength, good thermal conductivity, and low thermal expansion, and it exhibits chemical inertness and is optically transparent over a wavelength range of 0.15 µm to 5.5 µm. We report the detailed results of the laser processing of sapphire, fabrication of diffraction gratings, and the photon sieve, which have applications in the infrared spectrum using a nanosecond pulsed laser of 355 nm wavelength. Laser removal rates and surface roughness were studied. The fabricated gratings and photon sieve were characterized in terms of diffracted beam profile, optical diffraction efficiency, surface morphology, and depth profile.

Diagnosis of osteoarticular tuberculosis by immuno-PCR assay based on mycobacterial antigen 85 complex detection.

Diagnosis of osteoarticular tuberculosis (OATB) exhibits serious challenges owing to paucibacillary nature of specimens and localization of disease at sites that are difficult to access. We recently developed indirect immuno-PCR (I-PCR) and real-time I-PCR (RT-I-PCR) assays for the detection of mycobacterial antigen 85 complex (Ag85) in OATB patients. Detection limits for the purified Ag85 protein were found to be 1 and 41 fg ml-1 by I-PCR and RT-I-PCR, respectively, which were at least 105 -fold lower than respective ELISA. While spiking synovial fluids of non-TB control subjects with the purified Ag85 protein, LODs of 100 and 120 fg ml-1 were obtained by I-PCR and RT-I-PCR, respectively, thus demonstrating the sample matrix effect. Sensitivities of 87·5 and 70·5% were observed in bodily fluids of confirmed (n = 8) and clinically suspected (n = 51) OATB cases, respectively, by I-PCR, with a specificity of 93·9% (n = 33). Markedly, the sensitivities obtained by I-PCR/RT-I-PCR were significantly higher (P < 0·05-0·01) than ELISA and GeneXpert assay (n = 30). However, no substantial difference in sensitivity was observed between the I-PCR and RT-I-PCR assays. After further improving the accuracy of I-PCR, this test may lead to development of an attractive diagnostic kit.

Asymptomatic infection and transmission of COVID-19 among clusters: systematic review and meta-analysis.

OBJECTIVES: Countries throughout the world are experiencing COVID-19 viral load in their populations, leading to potential transmission and infectivity of asymptomatic COVID-19 cases. The current systematic review and meta-analysis aims to investigate the role of asymptomatic infection and transmission reported in family clusters, adults, children and health care workers, globally. STUDY DESIGN: Systematic review and meta-analysis. METHODS: An online literature search of PubMed, Google Scholar, medRixv and BioRixv was performed using standard Boolean operators and included studies published up to 17 August 2021. For the systematic review, case reports, short communications and retrospective studies were included to ensure sufficient asymptomatic COVID-19 transmission data were reported. For the quantitative synthesis (meta-analysis), participant data from a collection of cohort studies focusing on groups of familial clusters, adults, children and health care workers were included. Inconsistency among studies was assessed using I2 statistics. The data synthesis was computed using the STATA 16.0 software. RESULTS: This study showed asymptomatic transmission among familial clusters, adults, children and health care workers of 15.72%, 29.48%, 24.09% and 0%, respectively. Overall, asymptomatic transmission was 24.51% (95% confidence interval [CI]: 14.38, 36.02) among all studied population groups, with a heterogeneity of I2 = 95.30% (P < 0.001). No heterogeneity was seen in the population subgroups of children and health care workers. The risk of bias in all included studies was assessed using the Newcastle Ottawa Scale. CONCLUSIONS: For minimising the spread of COVID-19 within the community, this study found that following the screening of asymptomatic cases and their close contacts for chest CT scan (for symptomatic patients), even after negative nucleic acid testing, it is essential to perform a rigorous epidemiological history, early isolation, social distancing and an increased quarantine period (a minimum of 14-28 days). This systematic review and meta-analysis supports the notion of asymptomatic COVID-19 infection and person-to-person transmission and suggests that this is dependent on the varying viral incubation period among individuals. Children, especially those of school age (i.e. <18 years), need to be monitored carefully and follow mitigation strategies (e.g. social distancing, hand hygiene, wearing face masks) to prevent asymptomatic community transmission of COVID-19.

Integrin-mediated interactions with a laminin-presenting substrate modulate biosynthesis and phenotypic expression for cells of the human nucleus pulposus.

With aging and pathology, cells of the nucleus pulposus (NP) de-differentiate towards a fibroblast-like phenotype, a change that contributes to degeneration of the intervertebral disc (IVD). Laminin isoforms are a component of the NP extracellular matrix during development but largely disappear in the adult NP tissue. Exposing human adult NP cells to hydrogels made from PEGylated-laminin-111 (PEGLM) has been shown to regulate NP cell behaviors and promote cells to assume a biosynthetically active state with gene/protein expression and morphology consistent with those observed in juvenile NP cells. However, the mechanism regulating this effect has remained unknown. In the present study, the integrin subunits that promote adult degenerative NP cell interactions with laminin-111 are identified by performing integrin blocking studies along with assays of intracellular signaling and cell phenotype. The findings indicate that integrin α3 is a primary regulator of cell attachment to laminin and is associated with phosphorylation of signaling molecules downstream of integrin engagement (ERK 1/2 and GSK3ß). Sustained effects of blocking integrin α3 were also demonstrated including decreased expression of phenotypic markers, reduced biosynthesis, and altered cytoskeletal organization. Furthermore, blocking both integrin α3 and additional integrin subunits elicited changes in cell clustering, but did not alter the phenotype of single cells. These findings reveal that integrin- mediated interactions through integrin α3 are critical in the process by which NP cells sense and alter phenotype in response to culture upon laminin and further suggest that targeting integrin α3 has potential for reversing or slowing degenerative changes to the NP cell.

Role of α- and ß-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and ß-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and ß-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract.

Geographical variation in case fatality rate and doubling time during the COVID-19 pandemic.

Case fatality rate (CFR) and doubling time are important characteristics of any epidemic. For coronavirus disease 2019 (COVID-19), wide variations in the CFR and doubling time have been noted among various countries. Early in the epidemic, CFR calculations involving all patients as denominator do not account for the hospitalised patients who are ill and will die in the future. Hence, we calculated cumulative CFR (cCFR) using only patients whose final clinical outcomes were known at a certain time point. We also estimated the daily average doubling time. Calculating CFR using this method leads to temporal stability in the fatality rates, the cCFR stabilises at different values for different countries. The possible reasons for this are an improved outcome rate by the end of the epidemic and a wider testing strategy. The United States, France, Turkey and China had high cCFR at the start due to low outcome rate. By 22 April, Germany, China and South Korea had a low cCFR. China and South Korea controlled the epidemic and achieved high doubling times. The doubling time in Russia did not cross 10 days during the study period.

Opportunities for gender transformative approaches in a community-based drowning reduction program in Bangladesh.

BACKGROUND: Community-based programs in rural low-and middle-income country settings are well-placed to conduct gender transformative activities that aid program sustainability and catalyse wider social change, such as reducing gender inequities that in turn improve health outcomes. The Anchal program is a drowning prevention intervention for children aged 1-5 years old in rural Bangladesh. It provides community crèche-based supervision delivered by local trained paid-female volunteers. We aimed to identify the influence of the Anchal program on gender norms and behaviours in the community context, and the effects these had on program delivery and men and women's outcomes. METHODS: Qualitative in-depth interviews, focus group discussions and observations were conducted with program beneficiaries and providers. Gender outcomes were analysed using FHI 360's Gender Integration Framework. RESULTS: The Anchal program was found to be a gender accommodating program as it catered for communities' gender-based roles and constraints but did not actively seek to change underlying beliefs, perceptions and norms that led to these. The program in some cases enhanced the independence and status of female community staff. This changed perceptions of communities towards acceptable levels of physical mobility and community involvement for women. Conversely, gender affected program delivery by reducing the ability of female supervisory staff to engage with male community leaders. The double burden of wage and household labour carried by local female staff also limited performance and progression. Gender-based constraints on staff performance, attrition and community engagement affected efficiency of program delivery and sustainability. CONCLUSIONS: The Anchal program both adapted to and shaped community gender norms and roles. The program has well-established relationships in the community and can be leveraged to implement gender transformative activities to improve gender-based equity. Health programs can broaden their impacts and target social determinants of health like gender equity to increase program sustainability and promote equitable health outcomes.

Evolution of structural and magnetic properties of FePtCu alloy films on annealing of FePt/Cu multilayers.

Thin films of ternary (FePt)100-xCux alloys were obtained by annealing of FePt (100 Å)/Cu (d Å) multilayers with d = 50 and 100 Å deposited by sputtering at room temperature on Si substrates. The evolution of structural and magnetic properties of these multilayers induced by isochronal and isothermal annealing in a vacuum has been studied using depth dependent characterization techniques. Isochronal annealing for 0.5 h at different temperatures (300 to 600 °C) showed very low interdiffusion at the interfaces with no signature of alloy phase formation. However, isothermal annealing of multilayers at 600 °C for longer times (1.5-6.5 h) showed significantly large interdiffusion accompanied by the formation of polycrystalline ternary alloy and iron silicide phases. The iron silicide formed at the substrate-film interface assists the growth of the L10 ordered ternary alloy phase, which showed different stoichiometry for different multilayers. The L10 phase formed with higher Cu content showed drastically different magnetic properties with a reduction in saturation magnetization and an increase in coercivity (∼6 kOe) at room temperature. The iron silicide formed on high temperature annealing showed ferromagnetic nature with a magnetization of ∼140 emu cm-3 at room temperature.

Opportunities for the development of drowning interventions in West Bengal, India: a review of policy and government programs.

BACKGROUND: Four million people living in the Indian Sundarbans region in the state of West Bengal face a particularly high risk of drowning due to rurality, presence of open water, lack of accessible health systems and poor infrastructure. Although the World Health Organization has identified several interventions that may prevent drowning in rural low-and middle-income country contexts, none are currently implemented in this region. This study aims to conduct contextual policy analysis for the development of a drowning program. Implementation of a drowning program should consider leveraging existing structures and resources, as interventions that build on policy targets or government programs are more likely to be sustainable and scalable. METHODS: A detailed content review of national and state policy (West Bengal) was conducted to identify policy principles and/or specific government programs that may be leveraged for drowning interventions. The enablers and barriers of these programs as well as their implementation reach were assessed through a systematic literature review. Identified policies and programs were also assessed to understand how they catered for underserved groups and their implications for equity. RESULTS: Three programs were identified that may be leveraged for the implementation of drowning interventions such as supervised childcare, provision of home-based barriers, swim and rescue skills training and community first responder training: the Integrated Child Development Scheme (ICDS), Self-Help Group (SHG) and Accredited Social Health Activist (ASHA) programs. All three had high coverage in West Bengal and considered underserved groups such as women and rural populations. Possible barriers to using these programs were poor government monitoring, inadequate resource provision and overburdening of community-based workers. CONCLUSIONS: This is the first systematic analysis of both policy content and execution of government programs to provide comprehensive insights into possible implementation strategies for a health intervention, in this case drowning. Programs targeting specific health outcomes should consider interventions outside of the health sector that address social determinants of health. This may enable the program to better align with relevant government agendas and increase sustainability.

Reduced risk of suicidal behaviours associated with the treatment of hidradenitis suppurativa with tumour necrosis factor alpha antagonists: results from the US FDA Adverse Events Reporting System pharmacovigilance database.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent condition that presents as painful, suppurating lesions in the apocrine gland-bearing skin regions. HS has been associated with increased suicidal behaviours (SB), independent of any treatment. TNF-alpha antagonists are used to treat moderate-to-severe HS and have also been associated with SB, a factor that could confound the decision to use the TNF-α antagonists in the moderately to severely affected HS patients, who may already be experiencing increased SB risk. OBJECTIVES: To determine presence or absence of a safety signal for SB when HS is treated with TNF-α antagonists. METHODS: We calculated the reporting odds ratios (ROR) with 95% CI of SB associated with treatment for HS with TNF-α antagonists vs. the reference group of all other treatments for HS in the US Food and Drug Administration pharmacovigilance database from 1 January 2004 to 31 March 2019. A second analysis excluded isotretinoin (which has been used to treat HS and has also been associated with SB) from the reference group. RESULTS: There was a signal for decreased risk of SB with TNF-α antagonists (ROR = 0.1959, 95% CI 0.1247-0.3079; z = 7.071, P < 0.0001] vs. all other HS treatments; the ROR did not change significantly after isotretinoin was excluded from the reference group. CONCLUSIONS: Treatment of HS with TNF-α antagonists is associated with a decreased risk of SB.

An outlook on procedures of conjugating folate to (co)polymers and drugs for effective cancer targeting.

Folate receptors (FRs) are expressed in vast majority of cancers. Selective targeting of the FRs is, therefore, one of the most popular and sought-after strategies for improving the efficacy of cancer therapeutics. Variety of approaches involving folate conjugation to several well-known and novel, nontoxic, biodegradable, and biocompatible (co)polymers have been attempted and successfully applied to a large number of nanoparticulate drug delivery systems (micelles, liposomes, nanoparticles, quantum dots, mesoporous silica-based materials, and others) in the last decade-and-a-half. Standard and novel synthetic approaches were utilized for the conjugation, followed by the formulation of the drug delivery modality. In most of the cases, the targeted system lived up to its reputation, validating its usefulness in targeted cancer therapeutics. The present review summarizes the progress and state-of-the-art synthetic methodologies for folate conjugation to (co)polymers, drugs, and nucleic acids. The limitations of the FR targeting are discussed in brief to give the reader the other side of the story. Finally, the information on marketed folic acid conjugates highlight their industrial applications.

Clinical outcome and predictors of severity in scrub typhus patients at a tertiary care hospital in Chandigarh, India.

BACKGROUND & OBJECTIVES: Scrub typhus is an under-reported rickettsial illness caused by Orientia tsutsugamushi which is transmitted by trombiculid mites. Serious complications are not uncommon and multiorgan dysfunction may develop leading to death. Paucity of data on the clinical spectrum and determinants of aftermath may be contributing to higher mortality in the region. A prospective study was done to describe the spectrum of organ dysfunction in serologically confirmed cases of scrub typhus and document predictors of adverse outcomes. METHODS: This prospective study was carried out in patients diagnosed to have scrub typhus by IgM ELISA. The clinical features, investigations and complications among survivors were statistically compared to those in the deceased. Fisher's exact test, t-test and logistic regression have been applied where appropriate. RESULTS: The study population comprised of 123 patients. Majority of patients (62%) had one or more organ dysfunction. Ten patients (8.1%) did not survive. Complications documented were acute kidney injury (AKI) in 35%, hepatitis in 29.2%, acute respiratory distress syndrome (ARDS) in 26%, shock in 13%, meningitis in 5.7%, disseminated intravascular coagulation (DIC) in 2.6%, pancreatitis in 2.6% and myocarditis in 1.6%. Certain clinical features, biochemical parameters and complications had statistically significant correlation with the outcome. The mean SOFA score was considerably higher in those who did not survive. Interpretation &conclusion: Patients developing hepatic dysfunction, acute kidney injury and respiratory distress should be identified early and intensively monitored. The SOFA score can be utilized to assess the severity at admission and rapidly triage the sicker patients.

The kidney allocation system does not appropriately stratify risk of pediatric donor kidneys: Implications for pediatric recipients.

Kidney Allocation System (KAS) was enacted in 2014 to improve graft utility, while facilitating transplantation of highly-sensitized patients and preserving pediatric access to high-quality kidneys. Central to this system is the Kidney Donor Profile Index (KDPI), a metric intended to predict transplant outcomes based on donor characteristics but derived using only adult donors. We posited that KAS had inadvertently altered the profile and quantity of kidneys made available to pediatric recipients. This question arose from our observation that most pediatric donors carry a KDPI over 35 and have therefore been rendered relatively inaccessible to pediatric recipients under KAS. Here we explore early trends in pediatric transplantation following KAS, including: (i) use of pediatric donors, (ii) use of Public Health System (PHS) high infectious risk donors, (iii) wait time, and (iv) living donor transplantation. We note some concerning preliminary changes following KAS implementation, including the allocation of fewer deceased donor pediatric kidneys to children and stagnation in pediatric wait times. Moreover, the poor predictive power of the KDPI for adult donors appears to be even worse when applied to pediatric donors. These early trends warrant further observation and consideration of changes in pediatric kidney allocation if they persist.

Rush Fracture Liaison Service for capturing "missed opportunities" to treat osteoporosis in patients with fragility fractures.

In spite of being a public health problem of pandemic proportions, osteoporosis continues to be underdiagnosed and undertreated especially in older adults with fragility fractures. Confirmation of this hypothesis resulted in the development of a novel Fracture Liaison Service (Rush FLS). Results of the first 12 months of operation revealed that patients with confirmed fragility fracture do not have a timely diagnosis at fracture occurrence or treatment of their disease. The Rush FLS is an effective fracture liaison model. INTRODUCTION: Determining the prevalence of undiagnosed and untreated osteoporosis in fragility fracture patients, either admitted to an academic tertiary care center or treated and discharged from the center's emergency department to be followed in the endocrinology bone clinic, using an innovative, educational, low-cost, physician-run Fracture Liaison Service (FLS). METHODS: An automated alert was integrated into the electronic medical record at Rush University Medical Center (RUMC), triggered by historical and/or acute fracture(s) in patients 50 years or older, in patients that were either admitted to the hospital or in patients evaluated in the emergency department and discharged to be followed in the endocrinology bone clinic. We report the results of the first 12 months of operation in patients admitted to the hospital. RESULTS: First acute fragility fracture(s) were identified in 36% (80/223), only historical fragility fracture(s) in 28% (63/223) and both acute and historical fragility fracture(s) in 36% (80/223). The cumulative subgroup with historical fragility fractures with/without new fractures included 67% (96/143) without a previous diagnosis of osteoporosis. First acute fragility fracture group included 83.8% (67/80) without a previous diagnosis of osteoporosis. Rush FLS "captured missed opportunities" in 73.1% (163/223) of previously undiagnosed and 77.1% (172/223) of previously untreated osteoporosis patients. Dual-energy x-ray absorptiometry (DXA) prior to FLS consult was confirmed in 30% (67/223). Vitamin D deficiency (25-hydroxy vitamin D < 20 ng/ml) in 41.9% (78/186) including undetectable levels in 16.6% (31/186) and secondary hyperparathyroidism in 43.3% (78/180) were the most common laboratory confirmed secondary etiologies for bone loss. CONCLUSIONS: This study reported undiagnosed, uninvestigated, and untreated osteoporosis in the majority of fragility fracture patients seen by the Rush FLS in the first 12 months of operation.