Amikacin sulphate loaded chitosan-diopside nanoparticles composite scaffold for infectious wound healing.

A wound dressing material should inhibit infections that may occur at the wound site, and at the same time, it should enhance the healing process. In this study, we developed an amikacin sulphate (AK) incorporated chitosan (Ch) and Diopside nanoparticles composite dressing (Ch-nDE-AK) for controlling wound infection and healing. The diopside nanoparticles (nDE) were prepared using sol-gel synthesis and characterized using XRD, FT-IR, and FESEM. nDE shows a size range of 142 ± 31 nm through FESEM analysis. Later, the developed composite dressing was characterized using SEM, EDS, and FT-IR analysis. Ch-nDE-AK dressing possesses a porous nature that will aid in easy cell infiltration and proliferation. The swelling studies indicated the expansion capability of the scaffold when applied to the injured site. Ch-nDE-AK scaffold showed a 69.6 ± 8.2 % amikacin sulphate release up to 7 days, which indicates the sustained release of the drug from Ch-nDE-AK scaffold. The drug release data was subjected to various kinetics models and was observed to follow the Higuchi model. The scaffold showed antibacterial activity against ATCC strains of S. aureus and E. coli for 7 days by in vitro. Ch-nDE-AK scaffold also showed antibacterial activity against S. aureus and E. coli clinical strains in vitro. The ex vivo antibacterial study confirmed the antibacterial ability of Ch-nDE-AK scaffold against S. aureus and E. coli. Ch-nDE-AK scaffold also exhibits anti-biofilm activity against S. aureus and E. coli. The Ch-nDE-AK scaffold showed cytocompatibility and cell attachment to fibroblast cells. Additionally, the scratch assay using fibroblast cells confirmed the role of the nDE in the scaffold, helping in cell migration. Thus, the developed Ch-nDE-AK dressing can potentially be used to treat infectious wound healing.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

Antiseptic Chitosan-Poly(hexamethylene) Biguanide Hydrogel for the Treatment of Infectious Wounds.

Topical wound infections create the ideal conditions for microbial colonization and growth in terms of moisture, temperature, and nutrients. When they are not protected, numerous types of bacteria from the internal microbiota and the external environment may colonize them, creating a polymicrobial population. Treatment of these wounds often necessitates the use of antibiotics that may have systemic harmful effects. Unlike antibiotics, topical antiseptics exhibit a wider range of activity and reduced systemic toxicity and resistance. In order to address this issue, we developed an antiseptic Chitosan-Poly (hexamethylene) Biguanide (CS-PHMB) hydrogel. The prepared hydrogel was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). SEM images showed the smooth morphology and characteristic FTIR peaks of PHMB and confirmed the incorporation of the antiseptic into the chitosan (CS) hydrogel. A Water Vapor Permeation Rate study confirms the moisture retention ability of the CS-PHMB hydrogel. Rheological studies proved the gel strength and temperature stability. The prepared hydrogel inhibited the growth of S. aureus, P. aeruginosa, E. coli, methicillin-resistant Staphylococcus aureus (MRSA), and K. pneumoniae, which confirms its antibacterial properties. It also inhibited biofilm formation for S. aureus and E. coli. CS-PHMB hydrogel is also found to be hemo- and cytocompatible in nature. Thus, the developed CS-PHMB hydrogel is a very potent candidate to be used for treating infectious topical wounds with low systemic toxicity.

Nutrition-Focused Physical Examination for Detecting Protein Energy Wasting in Children with Chronic Kidney Disease.

Introduction: There is a need to explore less laborious point-of-care assessment tools to diagnose protein energy wasting (PEW) in children with chronic kidney disease (CKD). This cross-sectional study was undertaken to assess the profile of specific nutrition-focused physical examination (NFPE) and mid-arm muscle area (MAMA) in children with CKD and determine their role in the diagnosis of PEW. Methods: PEW criterion was applied to all eligible children and MAMA was derived from mid-arm circumference and triceps skin fold thickness. NFPE signs examined were muscle wasting (MW) and subcutaneous fat loss (FL). Results: One hundred and twenty-six children with CKD (86 in CKD stages 2-4 and 40 on dialysis) were studied. PEW was prevalent in 41.8% children with CKD2-4 and in 72.5% on dialysis. In children with CKD 2-4, low MAMA, MW, and FL were significantly associated with PEW with an odd's ratio of 5.3 (1.55,18.30), 10.6 (3.8,29.8), and 10.5 (3.7,29.2) respectively (P = <0.001). Similarly, in children on dialysis, low MAMA, MW, and FL were more likely to be associated with PEW with an odd's ratio of 17 (2.2,127.7); P = 0.017, 16.6 (3,90.8); P = 0.001 and 19 (2.1,170.3); and P = 0.009, respectively. MW demonstrated high sensitivity and specificity [80.6 and 72%, respectively, with a positive predictive value (PPV) of 67.4%] to diagnose PEW in the CKD 2-4 group and in those on dialysis [86.2 and 72.1%, respectively, with PPV of 89.3%]. Conclusion: Clinical signs based on NFPE are useful in detecting PEW in children with CKD2-4 and in those on dialysis.

Aerosol-CCN characteristics and dynamics associated with a pre-monsoon dust storm over a high-altitude site in Western Ghats, India.

Aerosol-CCN characteristics and dynamics during a pre-monsoon dust storm (April 6-11, 2015) over a high-altitude site ((17.92°N, 73.66°E, and 1348 m above mean sea level (MSL)) in Western Ghats, India, has been studied using ground-based observations, satellite, and reanalysis datasets. Spatial distribution of dust surface mass concentration along with the back trajectory analysis showed the Arabian Desert area (Rub-Al-khali desert) as the source region and strong westerly winds transported the dust particles toward the Indian subcontinent. High values noticed in the surface PM10 (PM2.5), i.e., ~ 450 (~ 130) µg m-3, MODIS AOD550nm (0.6), and MERRA 2 dust surface mass concentration (5 × 10-7 kg m-3) along MODIS true color images confirmed the dust storm event on April 6, 2015 over the observational site. Size-segregated aerosol number concentration measured from ground-based observations showed the dominance of Aitken, accumulation, and coarse mode particles during dust period. CCN concentrations at 0.1, 0.3, 0.5, 0.7, and 0.9% SS were analyzed. A low value of CCN concentration and activation fraction (~ 0.3) near surface was noticed during dust storm day, suggesting insoluble mineral dust particle being transported. Analyzed vertical velocity during pre-dust period showed downdraft between 900 and 750 hPa, suggesting dust transport from upper altitudes toward the observational site. WRF-Chem model simulation also captured the dust storm event, and the results are in good agreement with the observation with a significance of 95% confidence level.

Investigation of the current situation regarding diagnosis and treatment of Alport syndrome in Asian countries: results of survey of the Asian Paediatric Nephrology association (AsPNA) tubular and inherited working group.

BACKGROUND: Alport syndrome is one of the most common inherited kidney diseases worldwide. A genetic test or kidney biopsy is necessary for a definite diagnosis of this disease, and an accurate diagnosis system for this disease is highly desired in each country. However, the current situation in Asian countries is not clear. Therefore, the tubular and inherited disease working group of the Asian Pediatric Nephrology Association (AsPNA) aimed to assess the current situation of diagnosis and treatment for Alport syndrome in Asia. METHODS: The group conducted an online survey among the members of AsPNA in 2021-2022. Collected data included the number of patients for each inheritance mode, availability of gene tests or kidney biopsy, and treatment strategies for Alport syndrome. RESULTS: A total of 165 pediatric nephrologists from 22 countries in Asia participated. Gene test was available in 129 institutes (78%), but the cost was still expensive in most countries. Kidney biopsy was available in 87 institutes (53%); however, only 70 can access electron microscopy, and 42 can conduct type IV collagen α5 chain staining. Regarding treatment, 140 centers use renin-angiotensin system (RAS) inhibitors (85%) for Alport syndrome patients. CONCLUSIONS: This study result might suggest that the system is underdeveloped enough to diagnose all Alport syndrome patients in most Asian countries. However, once diagnosed with Alport syndrome, most of them were treated with RAS inhibitors. These survey results can be used to address knowledge, diagnostic system, and treatment strategy gaps and improve the Alport patients' outcomes in Asian countries.

CRISPR Screen Reveals BRD2/4 Molecular Glue-like Degrader via Recruitment of DCAF16.

Molecular glues (MGs) are monovalent small molecules that induce an interaction between proteins (native or non-native partners) by altering the protein-protein interaction (PPI) interface toward a higher-affinity state. Enhancing the PPI between a protein and E3 ubiquitin ligase can lead to degradation of the partnering protein. Over the past decade, retrospective studies of clinical drugs identified that immunomodulatory drugs (e.g., thalidomide and analogues) and indisulam exhibit a molecular glue effect by driving the interaction between non-native substrates to CRBN and DCAF15 ligases, respectively. Ensuing reports of phenotypic screens focused on MG discovery have suggested that these molecules may be more common than initially anticipated. However, prospective discovery of MGs remains challenging. Thus, expanding the repertoire of MGs will enhance our understanding of principles for prospective design. Herein, we report the results of a CRISPR/Cas9 knockout screen of over 1000 ligases and ubiquitin proteasome system components in a BRD4 degradation assay with a JQ1-based monovalent degrader, compound 1a. We identified DCAF16, a substrate recognition component of the Cul4 ligase complex, as essential for compound activity, and we demonstrate that compound 1a drives the interaction between DCAF16 and BRD2/4 to promote target degradation. Taken together, our data suggest that compound 1a functions as an MG degrader between BRD2/4 and DCAF16 and provides a foundation for further mechanistic dissection to advance prospective MG discovery.

Familial hypomagnesemia with hypocalcemia: a rare cause of infantile seizures.

Magnesium is one of the most abundant electrolytes in the human body but is often forgotten when it comes to the evaluation of an infant presenting with hypocalcemia. Its deficiency can present as neurological, cardiac and skeletal symptoms. Familial hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive genetic disease caused by a transient receptor potential melastatin 6 gene pathogenic variant (TRMP6). The underlying defect lies in the intestinal absorption of magnesium. A delay in diagnosis and lack of timely initiation of treatment can lead to long term irreversible neurological complications and even death. We describe a case of an infant presenting with seizures and severe hypomagnesemia and hypocalcemia. Genetic analysis subsequently identified the abnormality as a frameshift mutation in the TRMP6 gene confirming the diagnosis of Familial hypomagnesemia with secondary hypocalcemia. With fewer than a hundred cases reported in the literature, we aim to highlight the importance of early diagnosis and treatment initiation and create a deeper understanding of the disease.

Sustained Low Efficiency Dialysis in Critically Ill Children With Acute Kidney Injury: Single-Center Observational Cohort in a Resource-Limited Setting.

OBJECTIVES: To evaluate use of sustained low efficiency dialysis (SLED) in critically ill children with acute kidney injury in a resource-limited setting. DESIGN: Observational database cohort study (December 2016 to January 2020). SETTING: PICU of a tertiary hospital in India. PATIENTS: Critically ill children undergoing SLED were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data, prescription variables, hemodynamic status, complications, kidney, and patient outcomes of all children undergoing SLED in the PICU were analyzed. A total of 33 children received 103 sessions of SLED. The median (interquartile range, IQR) age and weight of children who received SLED were 9 years (4.5-12.8 yr) and 26 kg (15.2-34 kg), respectively. The most common diagnosis was sepsis with septic shock in 17 patients, and the mean (± sd ) Pediatric Risk of Mortality III score at admission was 11.8 (±6.4). The median (IQR) number and mean (± sd ) duration of inotropes per session were 3 hours (2-4 hr) and 96 (±82) hours, respectively. Of 103 sessions, the most common indication for SLED was oligoanuria with fluid overload and the need for creating space for fluid and nutritional support in 45 sessions (44%). The mean (± sd ) duration of SLED was 6.4 (±1.3) hours with 72 of 103 sessions requiring priming. The mean (± sd ) ultrafiltration rate per session achieved was 4.6 (±3) mL/kg/hr. There was significant decrease in urea and creatinine by end of SLED compared with the start, with mean change in urea and serum creatinine being 32.36 mg/dL (95% CI, 18.53-46.18 mg/dL) ( p < 0.001) and 0.70 mg/dL (95% CI, 0.35-1.06 mg/dL) ( p < 0.001), respectively. Complications were observed in 44 of 103 sessions, most common being intradialytic hypotension (21/103) and bleeding at the catheter site (21/103). Despite complications in one third of the sessions, only nine sessions were prematurely stopped, and 23 of 33 patients receiving SLED survived. CONCLUSION: In critically ill children, our experience with SLED is that it is feasible and provides a viable form of kidney replacement therapy in a resource-limited setting.

A novel combination of OHVIRA syndrome and likely causal variant in UMOD gene.

OHVIRA syndrome (or Herlyn-Werner-Wunderlich syndrome) is a rare condition, consisting classically of obstructed hemi-vagina with ipsilateral renal agenesis. It may be associated with complex uterine malformations and more rarely with lower urinary tract anomalies. The contralateral kidney usually has normal function. A genetic etiology of this syndrome has not yet been confirmed. We report a patient who was diagnosed to have unilateral renal agenesis in early childhood, and then presented after menarche with features of OHVIRA syndrome. The contralateral kidney was relatively small and echogenic, and serum creatinine and uric acid were raised. A likely causal variant of the UMOD gene was detected on whole exome sequencing. Genetic studies in more patients with OHVIRA syndrome may elucidate further, whether the association with UMOD gene is causal in nature.

Prevalence of and Factors Associated With High Blood Pressure Among Adolescents in India.

Importance: High blood pressure (BP) in children and adolescents is becoming one of the most common health conditions worldwide and is much more widely prevalent than previously thought. Objective: To estimate the prevalence of high BP in adolescents in India and identify associated factors. Design, Setting, and Participants: This cross-sectional study is a secondary analysis of data from the Comprehensive National Nutrition Survey (CNNS, 2016-2018), which used a multistage, stratified, probability proportion to size cluster sampling design to enroll a nationally representative sample of households and individuals aged 10 to 19 years across all states and union territories of India. Adolescents with acute or chronic illness, physical deformity, mental illness, or cognitive disability were excluded from the survey. Because BP was measured only in children between 10 and 19 years of age, only data from children within this age group were included for secondary analyses. Data analysis was performed from March 2021 to April 2022. Exposures: Anthropometry. Main Outcomes and Measures: On the basis of the 2017 American Academy of Pediatrics guidelines, high BP was defined as stage 1 and 2 hypertension, with BP above the 95th percentile in children younger than 13 years and greater than 130/80 mm Hg in children 13 years or older. The association of age, sex, region, socioeconomic status, body mass index, fasting blood glucose, hemoglobin A1c, and lipid profile with high BP were examined using log binomial regression. Results: Among 16 182 eligible children aged 10 to 19 years (mean [SD] age, 14.2 [2.8] years; 7849 [48.5%] female and 8333 [51.5%] male), 11 718 had valid BP data with 3 repeated readings. the prevalence of high BP was 35.1% (95% CI, 31.5%-38.9%) in children aged 10 to 12 years and 25.1% (95% CI, 22.5%-28.0%) in children 13 years or older. Overweight and obesity were associated with a higher risk of high BP in both younger (prevalence ratio, 1.17; 95% CI, 1.04-1.34) and older children (prevalence ratio, 1.33; 95% CI, 1.18-1.49). The prevalence of high BP in younger children with stunting was high at 40.1% (95% CI, 31.9%-48.9%) and was 21.9% (95% CI, 18.2%-26.1%) among older children with stunting. In both age groups, high BP coexisted with other cardiovascular disease risk factors, such that adolescents with high fasting blood glucose, high hemoglobin A1c, high triglyceride, and high low-density lipoprotein cholesterol levels had a higher risk of high BP. Conclusions and Relevance: In this cross-sectional study, the prevalence of high BP, along with cardiovascular risk factors, was substantial in Indian adolescents. There is a need to screen and identify adolescents who have high BP and initiate interventions to control the burden of hypertension and its consequences in India.

Subjective Global Nutritional Assessment [SGNA] in Children on Chronic Dialysis- A Prospective Observational Study.

Introduction: Nutritional assessment in children undergoing chronic dialysis is challenging as no single objective reference tool is available. There is a need to explore the application of the subjective global nutritional assessment (SGNA) tool in these children. This study assessed the nutritional status of children on chronic dialysis using SGNA, evaluated the utility of SGNA parameters in the longitudinal assessment of nutrition, and compared the SGNA tool with other nutritional measures. Methods: Children 2-18 years of age on chronic dialysis for at least 1 month were prospectively studied over a period of 18 months with two follow-up visits at least 3 months apart. Malnutrition was diagnosed by SGNA (well-nourished, moderately, and severely malnourished), mid-arm circumference <5th centile for age and gender, and serum albumin <3.8 g/l at baseline and follow-up. Results: In 41 children on dialysis (age: 124.8 ± 32 months), 73% had moderate or severe malnutrition by SGNA. Height for age (P = 0.008), weight for height (P = 0.004), dietary intake (P = 0.025) functional capacity (P = 0.001), loss of subcutaneous fat (P < 0.001), and muscle wasting (P < 0.001) were significantly associated with the presence and severity of malnutrition. SGNA showed a poor agreement with MUAC and serum albumin. On follow-up, there was no significant change in the category of nutritional status (P = 0.63) and no individual SGNA parameter was associated with the presence or severity of malnutrition. Conclusion: Two-thirds of the children on chronic dialysis were diagnosed with moderate to severe malnutrition by SGNA, while the majority remained in the same category of nutritional status on follow-up. Only half of the parameters used for assessment were strongly associated with the presence and severity of malnutrition. SGNA showed a poor agreement with objective nutritional measures and was not responsive in identifying a change in the nutritional status on follow-up.

Identification and structure-based drug design of cell-active inhibitors of interleukin 17A at a novel C-terminal site.

Anti-IL17A therapies have proven effective for numerous inflammatory diseases including psoriasis, axial spondylitis and psoriatic arthritis. Modulating and/or antagonizing protein-protein interactions of IL17A cytokine binding to its cell surface receptors with oral therapies offers the promise to bring forward biologics-like efficacy in a pill to patients. We used an NMR-based fragment screen of recombinant IL17A to uncover starting points for small molecule IL17A antagonist discovery. By examining chemical shift perturbations in 2D [1H, 13C-HSQC] spectra of isotopically labeled IL17A, we discovered fragments binding the cytokine at a previously undescribed site near the IL17A C-terminal region, albeit with weak affinity (> 250 µM). Importantly this binding location was distinct from previously known chemical matter modulating cytokine responses. Subsequently through analog screening, we identified related compounds that bound symmetrically in this novel site with two copies. From this observation we employed a linking strategy via structure-based drug design and obtained compounds with increased binding affinity (< 50 nM) and showed functional inhibition of IL17A-induced cellular signaling (IC50~1 µM). We also describe a fluorescence-based probe molecule suitable to discern/screen for additional molecules binding in this C-terminal site.

Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5-20% of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic profile of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT. METHODS: Customized targeted panel sequencing was performed to identify pathogenic variants in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed. RESULTS: The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). No pathogenic or likely pathogenic variants were identified in the study. Most of our variants (n = 39, 60%) were variants of unknown significance with 25.6% (10/39) of them were identified as potentially damaging but were novel variants. CONCLUSIONS: The present study did not identify any disease-causing monogenic variants in the cohort. The absence of genetic cause may be due to limitations of panel-based testing and also due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical, larger targeted panel or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT.

A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe syndrome.

Human brain development is a complex process where multiple cellular and developmental events are coordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS) is an X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1, which encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a 'disease-in-a-dish' model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development. This article has an associated First Person interview with the first author of the paper.

Protective efficacy of Alum adjuvanted Amidase protein vaccine against Staphylococcus aureus infection in multiple mouse models.

AIMS: Staphylococcus aureus is an opportunistic pathogen of humans. No commercial vaccine is available to combat S. aureus infections. In this study, we have investigated the protective immune response generated by S. aureus non-covalently associated cell wall surface protein N-acetylmuramoyl-L-alanine amidase (AM) in combination with Alum (Al) and heat-killed S. aureus (hkSA) using murine models. METHODS AND RESULTS: BALB/c mice were immunized with increasing concentrations of AM antigen or hkSA to determine their optimum concentration for vaccination. Fifty micrograms of AM and hkSA each were found to generate maximum anti-AM IgG antibody production. BALB/c mice were immunized next with 50 µg of AM, 50 µg of hKSA and 1 mg Al vaccine formulation. Vaccine efficacy was validated by challenging immunized BALB/c mice with S. aureus Newman and three clinical methicillin-resistant S. aureus strains. AM-hkSA-Al-immunized mice generated high anti-AM IgG antibody response with IgG1 and IgG2b as the predominant immunoglobulin subtypes. Increased survival (60%-90%) with decreased clinical disease symptoms was observed in the vaccinated BALB/c mice group. A significantly lower bacterial load and decreased kidney abscess formation was observed following the challenge with S. aureus in the vaccinated BALB/c mice group. Furthermore, the efficacy of AM-hkSA-Al vaccine was also validated using C57 BL/6 and Swiss albino mice. CONCLUSIONS: Using murine infection models, we have demonstrated that AM-hkSA-Al vaccine would be effective in preventing S. aureus infections. SIGNIFICANCE AND IMPACT OF STUDY: AM-hkSA-Al vaccine elicited strong immune response and may be considered for future vaccine design against S. aureus infections.

Clinical Profile and Outcome of Emergencies in Pediatric Chronic Kidney Disease.

OBJECTIVE: To describe the clinical profile and outcome of emergencies in children with chronic kidney disease (CKD). METHODS: This retrospective analysis studied children with CKD presenting with acute emergencies. The clinical profile, renal and patient outcomes were compared between incidentally diagnosed - iCKD, previously diagnosed not on dialysis - pCKD and those on maintenance dialysis - dCKD groups. RESULTS: 82 children (67 boys, median age - 8 years) with 99 visits were included. Uremic encephalopathy was the most common emergency in iCKD (64.7%) and pCKD (38.4 %), and access-related infections (32.1%) in dCKD group. Children with iCKD had higher Pediatric Risk of Mortality score (P<0.001), emergent initiation of dialysis (P=0.03) and discontinuation of treatment (P<0.001) when compared to the pCKD group. CONCLUSION: Uremic encephalopathy and access-related infections were the most common emergencies in children with CKD. Incidentally diagnosed CKD had a worse clinical profile and outcome.

What is in Our Kit? An Analysis of Building Blocks Used in Medicinal Chemistry Parallel Libraries.

Building blocks are the molecular foundations for drug molecule design. The building block is one of the determining factors of final compound qualities in any given medicinal chemistry campaign. Herein, we describe our analysis of the building blocks used in parallel library synthesis at AbbVie. The results gave insights into the synthetic tractability and accessibilities of building blocks used in medicinal chemistry. Furthermore, our analysis showed that opportunities still exist for the identification and future incorporation of underrepresented building blocks, even for commonly used reactions, to obtain intellectual and competitive advantages in drug discovery.