Morbidity profile of children from birth to 18 years of age referred for intervention to the district early intervention centre in a District Hospital, Andhra Pradesh.

BACKGROUND: The "Child Health Screening and Early Intervention Services" program aims at early detection and management of the four dimensions prevalent in children-defects at birth, diseases in children, deficiency conditions, and developmental delays, including disabilities. OBJECTIVE: The objective of the study was to assess the morbidity profile of children from birth to 18 years of age screened in the district early intervention center (DEIC). METHODS: A record-based descriptive study was done in the DEIC in Chittoor, Andhra Pradesh. The data were retrieved for 1-year from April 2017 to March 2018 into the excel sheet, and the combined master sheet was prepared for analysis. The analysis was done with SPSS 21.0 Version. RESULTS: A total of 10571 children were screened and referred to the DEIC during the period. Out of them, 5679 (53.7%) were male and 4892 (46.3%) were female. Among all the four types of morbidities screened, majority 4847 (45.9%) were having the childhood diseases, 4177 (39.5%) had developmental delays including disabilities, 1067 (10.1%) had different deficiencies, and 361 (3.4%) had birth defects. Among the adolescent health issues, 119 (1.1%) were screened and sent for the early intervention to the district hospital. CONCLUSIONS: A huge number of children were screened and referred to the DEIC every year for intervention. The health sector has to focus more on the resources like workforce, training of peripheral health workers at regular intervals about the different morbidities screened, that would help in identifying the morbidities at the earliest possible time and receive the intervention at the best center.

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists.

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.

Early versus later onset childhood-onset systemic lupus erythematosus: Clinical features, treatment and outcome.

The objective of the study was to compare clinical features, treatment and disease outcome in patients with early versus later onset of childhood-onset systemic lupus erythematosus (cSLE). A retrospective matched cohort study of cSLE patients diagnosed between 1988 and 2008 and followed for a minimum of one year was conducted. Thirty-four pre-pubertal cSLE patients with disease onset prior to their 12th birthday were matched by ethnicity and year of diagnosis to 34 pubertal cSLE patients. The most common criteria at diagnosis in both groups were malar rash, arthritis, hematologic manifestations, and renal disease. After a mean follow-up of more than six years, a similar proportion of patients in the two groups were still prescribed corticosteroids (47% and 41%); patients in the early onset group required a significantly higher daily dose (0.6 mg/kg prednisone-equivalent versus 0.2 mg/kg, p < 0.05). There were no significant differences in organ involvement, disease activity and disease damage between the two groups, and severe complications occurred at similar rates. There were a greater number of admissions to the pediatric intensive care unit (PICU) in the early onset group (18 versus 5, p = 0.01), with time-to-event analysis demonstrating a significantly shorter disease duration from diagnosis to first PICU admission in the early onset group (p < 0.001). While a similar proportion of patients in the early and later onset groups required treatment with cyclophosphamide, patients in the early onset group received treatment earlier in their disease course (mean 13.7 versus 19.9 months, p < 0.001). Early onset cSLE leads to earlier and more frequent PICU admission, earlier use of cyclophosphamide, and higher corticosteroid dose at long-term follow-up.

Vascular surgical emergencies: how will future surgeons be trained?

INTRODUCTION: We wished to assess whether pattern and impact of emergency vascular surgical referrals has altered since a previous study in 1990. Following introduction of shift working patterns, we wished to assess how these changes may affect vascular training and vascular on-call cover. PATIENTS AND METHODS: Prospective survey of emergency vascular referrals at two district general hospitals (DGH-R and DGH-L) in 2003. DGH-R received only regional referrals whereas DGH-L also received 'next day' referrals from a smaller hospital. Results were compared between centres and with a previous study undertaken at DGH-R in 1990. RESULTS: From 1990 to 2003 emergency vascular referrals at DGH-R increased by 51% (53 to 80). The number seen at DGH-R and DGH-L were similar in 2003. There were significantly more out-of-hours referrals in DGH-R than DGH-L (59% versus 35%; P = 0.0123). Referrals were more likely to be seen initially by the vascular team at DGH-L than DGH-R (80% versus 47%, P < 0.0001). CONCLUSIONS: Vascular emergency referrals have increased. A trainee was likely to see more emergency referrals at DGH-L than DGH-R. This may impact on future training.

Unfolding and refolding of bovine serum albumin at acid pH: ultrasound and structural studies.

Serum albumin is the most abundant protein in the circulatory system. The ability of albumins to undergo a reversible conformational transition, observed with changes in pH, is conserved in distantly related species, suggesting for it a major physiological role possibly related to the transport of small molecules including drugs. We have followed changes of bovine serum albumin (BSA) in volume by densimetry and in adiabatic compressibility during its conformational transition from pH 7-2, using ultrasound measurements. In parallel, circular dichroism was measured. The volume and adiabatic compressibility decrease from pH 4 to 2. The change in ellipticity shows a decrease over the same pH range from 70% to 40% of its alpha-helix content. Sorbitol, at concentrations from 0 to 2 M, led to the progressive restoration of BSA volume and compressibility values, as well as a substantial recovery of its original alpha-helix content. This finding implies that the compressibility variation observed reflects the conformational changes during the transition. The mutual interactions of the mechanical properties and structural features of BSA reported here are important in biotechnology for research in material sciences and for the design and the development of new, tailor-made drug carriers.

Surgery in severe factor XIII deficiency: report of a case of epilepsy neurosurgery and review.

Factor XIII (FXIII) deficiency is a rare autosomal recessive congenital disorder of haemostasis, associated with a high risk of intracranial haemorrhage. Intracranial haemorrhage can result in neurological sequelae including seizure disorders. In some cases, medically intractable epilepsy led to epilepsy surgery. Little has been reported on the management of FXIII deficiency during surgery, and there is only a few data on the management, safety and efficacy of epilepsy surgery in the patients with haemostatic disorder. We report here an epilepsy neurosurgery in a case of severe FXIII deficiency.

Environmentally induced reversible conformational switching in the yeast cell adhesion protein alpha-agglutinin.

The yeast cell adhesion protein alpha-agglutinin is expressed on the surface of a free-living organism and is subjected to a variety of environmental conditions. Circular dichroism (CD) spectroscopy shows that the binding region of alpha-agglutinin has a beta-sheet-rich structure, with only approximately 2% alpha-helix under native conditions (15-40 degrees C at pH 5.5). This region is predicted to fold into three immunoglobulin-like domains, and models are consistent with the CD spectra as well as with peptide mapping and site-specific mutagenesis. However, secondary structure prediction algorithms show that segments comprising approximately 17% of the residues have high alpha-helical and low beta-sheet potential. Two model peptides of such segments had helical tendencies, and one of these peptides showed pH-dependent conformational switching. Similarly, CD spectroscopy of the binding region of alpha-agglutinin showed reversible conversion from beta-rich to mixed alpha/beta structure at elevated temperatures or when the pH was changed. The reversibility of these changes implied that there is a small energy difference between the all-beta and the alpha/beta states. Similar changes followed cleavage of peptide or disulfide bonds. Together, these observations imply that short sequences of high helical propensity are constrained to a beta-rich state by covalent and local charge interactions under native conditions, but form helices under non-native conditions.

Interaction of alpha-agglutinin and a-agglutinin, Saccharomyces cerevisiae sexual cell adhesion molecules.

alpha-Agglutinin and a-agglutinin are complementary cell adhesion glycoproteins active during mating in the yeast Saccharomyces cerevisiae. They bind with high affinity and high specificity: cells of opposite mating types are irreversibly bound by a few pairs of agglutinins. Equilibrium and surface plasmon resonance kinetic analyses showed that the purified binding region of alpha-agglutinin interacted similarly with purified a-agglutinin and with a-agglutinin expressed on cell surfaces. At 20 degrees C, the K(D) for the interaction was 2 x 10(-9) to 5 x 10(-9) M. This high affinity was a result of a very low dissociation rate ( approximately 2.6 x 10(-4) s(-1)) coupled with a low association rate (= 5 x 10(4) M(-1) s(-1)). Circular-dichroism spectroscopy showed that binding of the proteins was accompanied by measurable changes in secondary structure. Furthermore, when binding was assessed at 10 degrees C, the association kinetics were sigmoidal, with a very low initial rate. An induced-fit model of binding with substantial apposition of hydrophobic surfaces on the two ligands can explain the observed affinity, kinetics, and specificity and the conformational effects of the binding reaction.

Buried charged surface in proteins.

BACKGROUND: The traditional picture of charged amino acids in globular proteins is that they are almost exclusively on the outside exposed to the solvent. Buried charges, when they do occur, are assumed to play an essential role in catalysis and ligand binding, or in stabilizing structure as, for instance, helix caps. RESULTS: By analyzing the amount and distribution of buried charged surface and charges in proteins over a broad range of protein sizes, we show that buried charge is much more common than is generally believed. We also show that the amount of buried charge rises with protein size in a manner which differs from other types of surfaces, especially aromatic and polar uncharged surfaces. In large proteins such as hemocyanin, 35% of all charges are greater than 75% buried. Furthermore, at all sizes few charged groups are fully exposed. As an experimental test, we show that replacement of the buried D178 of muconate lactonizing enzyme by N stabilizes the enzyme by 4.2 degrees C without any change in crystallographic structure. In addition, free energy calculations of stability support the experimental results. CONCLUSIONS: Nature may use charge burial to reduce protein stability; not all buried charges are fully stabilized by a prearranged protein environment. Consistent with this view, thermophilic proteins often have less buried charge. Modifying the amount of buried charge at carefully chosen sites may thus provide a general route for changing the thermophilicity or psychrophilicity of proteins.

A CD2-based model of yeast alpha-agglutinin elucidates solution properties and binding characteristics.

We have previously shown that the Saccharomyces cerevisiae cell adhesion protein alpha-agglutinin has sequence characteristics of immunoglobulin-like proteins and have successfully modeled residues 200-325, based on the structure of immunoglobulin variable-type domains. Alignments matching residues 20-200 of alpha-agglutinin with domains I and II of members of the CD2/CD4 subfamily of the immunoglobulin superfamily showed > 80% conservation of key residues despite low sequence similarity overall. Three-dimensional models of two alpha-agglutinin domains constructed on the basis of these alignments were shown to conform to peptide mapping data and biophysical properties of alpha-agglutinin. In addition, the residue volume and surface accessibility characteristics of these models resembled those of the well-packed structures of related proteins. Residue-by-residue analysis showed that packing and accessibility anomalies were largely confined to glycosylated and protease-susceptible loop regions of the domains. Surface accessibility of hydrophobic residues was typical of proteins with extensive domain interactions, a finding compatible with the hydrodynamic properties of alpha -agglutinin and the hydrophobic nature of binding to its peptide ligand alpha-agglutinin. The procedures used to align the alpha-agglutinin sequence and test the quality of the model may be applicable to other proteins, especially those that resist crystallization because of extensive glycosylation.

A short synthesis of troglitazone: an antidiabetic drug for treating insulin resistance.

Troglitazone was obtained in 5 steps from 4-bromo-1,1-dimethoxy-3-methylbut-2-ene with an overall yield of 7.5%. The formation of the chromane ring was achieved by condensing an unsaturated acetal with trimethylhydroquinone in the presence of bis(trifluoromethylsulfonyl)imide.

Incidence of arrhythmias after thoracic surgery: thoracotomy versus video-assisted thoracoscopy.

PURPOSE: Atrial arrhythmias, especially supraventricular tachycardia (SVT) and atrial fibrillation, are common after thoracotomy and lung surgery. There are few existing data on the incidence of postoperative arrhythmias after video-assisted thoracoscopy (VAT). The purpose of the present investigation was to retrospectively determine the incidence of postoperative arrhythmias in patients who underwent VAT compared with those who underwent thoracotomy, and which factors are associated with an increased risk for arrhythmias in both groups. DESIGN: A retrospective investigation. SETTING: A metropolitan university hospital. PARTICIPANTS: The medical records of 124 patients who underwent thoracotomy and 81 patients who underwent VAT over a 2-year period were reviewed. MEASUREMENTS AND MAIN RESULTS: There was a 17% incidence of atrial arrhythmias after thoracotomy and 10% after VAT, but the difference was not statistically significant. In both groups, atrial fibrillation was the most common atrial arrhythmia. CONCLUSION: Patients receiving digoxin were at higher risk for postoperative arrhythmias. Patients older than 65 years were at risk for arrhythmias after thoracotomy and patients older than 80 years were at risk for arrhythmias after VAT. Patients who had postoperative arrhythmias had prolonged hospital stays compared with patients who did not have arrhythmias.

Thermodynamic volume cycles for electron transfer in the cytochrome c oxidase and for the binding of cytochrome c to cytochrome c oxidase.

Dilatometry is a sensitive technique for measuring volume changes occurring during a chemical reaction. We applied it to the reduction-oxidation cycle of cytochrome c oxidase, and to the binding of cytochrome c to the oxidase. We measured the volume changes that occur during the interconversion of oxidase intermediates. The numerical values of these volume changes have allowed the construction of a thermodynamic cycle that includes many of the redox intermediates. The system volume for each of the intermediates is different. We suggest that these differences arise by two mechanisms that are not mutually exclusive: intermediates in the catalytic cycle could be hydrated to different extents, and/or small voids in the protein could open and close. Based on our experience with osmotic stress, we believe that at least a portion of the volume changes represent the obligatory movement of solvent into and out of the oxidase during the combined electron and proton transfer process. The volume changes associated with the binding of cytochrome c to cytochrome c oxidase have been studied as a function of the redox state of the two proteins. The volume changes determined by dilatometry are large and negative. The data indicate quite clearly that there are structural alterations in the two proteins that occur on complex formation.

Children's moral and ecological reasoning about the Prince William Sound oil spill.

Sixty 2nd, 5th, and 8th graders were interviewed on their moral and ecological reasoning about the 1990 Exxon Valdez oil spill that occurred in Prince William Sound, Alaska. Results showed that children understood that the oil spill negatively affected the local Alaskan shoreline, marine life, fishermen, recreationists, and the oil company. Children cared that harm occurred to the shoreline and marine life and conceived of both types of harm as violating a moral obligation. Fifth and 8th graders, compared with 2nd graders, used a greater proportion of anthropocentric reasoning (e.g., that nature ought to be protected to protect human welfare) and biocentric reasoning (e.g., that nature has intrinsic value, rights, or a teleology). Discussion focuses on how studying children's reasoning about nature not only extends the bounds of what counts as moral--to include a relationship with the natural world--but also provides a unique means by which to conduct basic research on children's moral development.

Impact of childhood brain injury on work and family finances.

Parents of children who suffer brain injuries are often surprised by the extent to which work and family finances are disrupted. In this paper, work and financial problems are described, predictors are identified, and ways to minimize problems are discussed. Eighty-two children treated at two Massachusetts trauma centres were given an extensive battery of medical, functional, and psychosocial tests during hospitalization. At 1 and 6 months post-discharge they were retested and their parents were surveyed about work and financial difficulties. Trouble maintaining regular work schedules and injury-related financial problems were common. At highest risk for work and financial problems were families of children with severe injuries who had four to nine impairments, along with children hospitalized > 2 weeks who were not discharged to home. Surprisingly, families with HMO coverage reported significantly fewer financial problems, and this relationship was not due to differences in socioeconomic status or injury severity. Health-care providers need to pay more attention to the potential impact of injury on work and family finances. Providers can help at-risk families muster child-care services, deal effectively with employers and insurance companies, and plan for the future.