Direct costs of managing in-ward dengue patients in Sri Lanka: A prospective study

Introduction The cost in managing hospitalised dengue patients varies across countries depending on access to healthcare, management guidelines, and state sponsored subsidies. For health budget planning, locally relevant, accurate costing data from prospective studies, is essential. Objective To characterise the direct costs of managing hospitalised patients with suspected dengue infection in Sri Lanka. Methods Colombo Dengue Study is a prospective single centre cohort study in Sri Lanka recruiting suspected hospitalised dengue fever patients in the first three days of fever and following them up until discharge. The diagnosis of dengue is retrospectively confirmed and the cohort therefore has a group of non-dengue fever patients with a phenotypically similar illness, managed as dengue while in hospital. The direct costs of hospital admission (base and investigation costs, excluding medication) were calculated for all recruited patients and compared between dengue and non-dengue categories as well as across subgroups (demographic, clinical or temporal) within each of these categories. We also explored if excluding dengue upfront, would lead to an overall cost saving in several hypothetical scenarios. Results From October 2017 to February 2020, 431 adult dengue patients and 256 non-dengue fever patients were recruited. The hospitalisation costs were USD 18.02 (SD: 4.42) and USD 17.55 (SD: 4.09) per patient per day for dengue and non-dengue patients respectively (p>0.05). Laboratory investigations (haematological, biochemical and imaging) accounted for more than 50% of the total cost. The costs were largely homogenous in all subgroups within or across dengue and non-dengue categories. Excluding dengue upfront by subsidised viral genomic testing may yield overall cost savings for non-dengue patients. Conclusion As non-dengue patients incur a similar cost per day as the dengue patients, confirming dengue diagnosis using subsidised tests for patients presenting in the first three days of fever may be cost-efficient

Effects of 3 Topical Plant Extracts on Wound Healing in Beef Cattle

Eleven heifers of the Purunã cattle breed were used to evaluate wound healing by second intention. An experimental wound excision model in bovines was created by means of a skin punch of diameter 2cm. The animals were topically treated for 17 days with a saline control or decoctions of Schinus terebinthifolius Raddi (Aroeira mansa), Tabebuia avellanedae Lorentz ex Griseb (Ipê Roxo), and Casearia sylvestris Sw.(Guaçatonga) mixed with carboxymethyl cellulose. Centripetal retraction, clinical, and histological aspects of the wounds were observed until complete healing. Decoctions of T. avellanedae and S. terebinthifolius, but not C. sylvestris, had a beneficial effect on wound healing by second intention

Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals

Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction

Restrictions and extensions of semibounded operators

We study restriction and extension theory for semibounded Hermitian operators in the Hardy space of analytic functions on the disk D. Starting with the operator zd/dz, we show that, for every choice of a closed subset F in T=bd(D) of measure zero, there is a densely defined Hermitian restriction of zd/dz corresponding to boundary functions vanishing on F. For every such restriction operator, we classify all its selfadjoint extension, and for each we present a complete spectral picture. We prove that different sets F with the same cardinality can lead to quite different boundary-value problems, inequivalent selfadjoint extension operators, and quite different spectral configurations. As a tool in our analysis, we prove that the von Neumann deficiency spaces, for a fixed set F, have a natural presentation as reproducing kernel Hilbert spaces, with a Hurwitz zeta-function, restricted to FxF, as reproducing kernel.Comment: 63 pages, 11 figure

Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil

In the context of universal access to antiretroviral therapy, the surveillance of human immunodeficiency virus type 1 (HIV-1) genetic diversity and resistance becomes pivotal. In this work our purpose was to describe the genetic variability; prevalence of drug-resistance mutations; and genotypic resistance profiles in HIV-1 infected individuals under antiretroviral treatment, from the Federal District, Brasília, Central Brazil. The entire viral protease and codons 19 to 234 of the reverse transcriptase gene from 45 HIV-1 isolates were amplified and sequenced for subtyping and genotyping. By phylogenetic analysis, 96% of the samples clustered with subtype B and the remaining 4% with HIV-1 subtype F sequences. One major protease inhibitor resistance-associated mutation, I50V, was detected in 38% of the samples. Minor mutations were also found at the protease gene: L10I/V (7%), K20M (2%), M36I (11%), L63P (20%), A71T (2%), and V77I (7%). Many mutations associated with reduced susceptibility to nucleoside or non-nucleoside reverse transcriptase inhibitors were detected: M41L (11%), E44D (4%), D67N (11%), T69D (2%), K70R (11%), L74V (2%), L100I (4%), K103N (18%), V118I (9%), Y181C (11%), M184V (18%), G190A (4%), T215Y (4%), and K219E (4%). This study has shown that 84% of the studied population from the Federal District, showing evidences of therapy failure, presented viral genomic mutations associated with drug resistance. The main antiretrovirals to which this population showed resistance were the PI amprenavir (38%), the NNRTIs delavirdine, nevirapine (31%), and efavirenz (24%), and the NRTIs lamivudine (18%), abacavir, and zidovudine (13%)

Maternal and neonatal factors related to prematurity

ABSTRACT OBJECTIVE To identify maternal and neonatal factors associated with prematurity in the municipality of Porto Alegre. METHOD This was a population-based case-control study. The cases were newborns under 37 weeks of gestation and the controls were newborns over 37 weeks. The data came from the records of 19,457 births in the city of Porto Alegre in the year 2012 from the Information System on Live Births of the Municipal Health Department. The analysis was carried outand adjusted by a Logistic Regression according to a hierarchical model. The variables studied were allocated into three hierarchy levels: sociodemographic variables; reproductive history; and gestational and birth factors. RESULTS There were 767 cases allocated and 1,534 controls in a design of a case for two controls (1:2) by simple randomization. In the final model, a statistically significant association was found for prematurity for the following variables: mother's age under 19 years old (OR=1.32; CI 95%: 1.02-1.71) or over 34 years old (OR=1.39; CI 95%: 1.12-1.72); inadequate maternal schooling for age (OR=2.11; CI 95%: 1.22-3.65); multiple pregnancies (OR=1.14; CI 95%: 1.01-1.29); C-section (OR=1.15; CI 95%: 1.03-1.29); birth weights under 2,500g (OR=4.04; CI 95%: 3.64-4.49); Apgar score at five minutes between zero and three (OR=1.47; CI 95%: 1.12-1.91); and inadequate prenatal care (OR=1.18; CI 95%: 1.02-1.36). CONCLUSION The present study showed the most immediate consequence of prematurity for newborns by evidencing its association with worse Apgar scores and low birth weight. The following factors were also shown as possible more distal determinants of prematurity: mother's age; inadequate maternal education; multiple gestation; inadequate prenatal care; and C-section