65 research outputs found
Condom tamponade in the management of atonic postpartum hemorrhage
Background: Postpartum hemorrhage (PPH) remains a leading direct cause of maternal death in both developed and developing countries. Millennium development goal of reducing maternal mortality rate cannot be achieved unless the prevention and treatment of PPH is prioritized. Objectives of the study were to study the efficacy of condom tamponade to arrest bleeding in cases of atonic PPH unresponsive to uterotonics.Methods: Prospective study conducted in the Kottayam Medical College where mothers who develop atonic PPH following childbirth unresponsive to uterotonics (after ruling out traumatic PPH) were included in study. Condom tamponade was applied in them and inflated with normal saline until the bleeding stops. Intrauterine drain was fitted with this to find out ongoing bleeding with tamponade in situ. The Condom tamponade was kept for 12-24 hrs and gradually deflated when bleeding ceased. Outcome measures were (1) Ability of condom catheter to stop bleeding; (2) Cases requiring further intervention; (3) Time required to stop bleeding and (4) Subsequent morbidity in terms of infection.Results: Of the 487 cases of atonic PPH, 61 required condom tamponade; bleeding controlled in 59 cases (96.7%); two patients (3.3%) needed further surgical intervention. No cases of maternal mortality due to PPH. No clinical evidence of intrauterine infection.Conclusions: The hydrostatic condom tamponade controls PPH quickly and effectively. It is simple, inexpensive, easily available, needs less expertise and life saving. Any healthcare provider may use this procedure as a timely measure to save the life of patients especially during referral to decrease ongoing loss
The bountiful and baffling baculovirus: the story of polyhedrin transcription
Baculoviruses are a unique group of eukaryotic viruses that parasitize insects. The prototype member of the family Baculoviridae is Autographa californica multiple nuclear polyhedrosis virus (AcMNPV). Global interest in baculovirus biology stems from two important uses of baculoviruses - as biopesticides and as a highly favoured eukaryotic expression system for the large-scale production of recombinant proteins in the laboratory. Of late, baculoviruses have invited renewed interest by virtue of their potential use as a delivery system in gene therapy. Although the baculovirus expression vector system (BEVS) is extensively used worldwide, the transcriptional regulation of the hyperactive promoters used to drive foreign gene expression still remains shrouded in mystery. It is clear, however, that this regulation involves an intricate interplay of both host and viral factors. This review provides an overview of what we do know about the mechanisms of transcription of baculoviral genes, with special emphasis on the polyhedrin promoter, the workhorse promoter of the BEVS, and the insect cell host factors involved in enhancing transcription from it
The homologous region sequence (hr1) of Autographa californica multinucleocapsid polyhedrosis virus can enhance transcription from non-baculoviral promoters in mammalian cells
The Autographa californica multinucleocapsid polyhedrosis virus homologous region sequence hr1 enhances transcription from the viral polyhedrin promoter in Spodoptera frugiperda insect cells and independently functions as an origin of replication (ori) sequence. The binding of the host nuclear protein, hr1-binding protein (hr1-BP), is crucial for the enhancer activity (Habib, S., Pandey, S., Chatterji, U., Burma, S., Ahmad, R., Jain, A., and Hasnain, S. E. (1996) DNA Cell Biol. 15, 737-747 and Habib, S., and Hasnain, S. E. (1996) J. Biol. Chem. 271, 28250-28258). We demonstrate that hr1 can also enhance transcription from non-baculoviral promoters like cytomegalovirus and hsp70 in mammalian cells but does not support ori activity in these cells. Unlike insect cells, hr1 can also function in mammalian cells as an enhancer when present in trans. hr1 DNA sequence binds with high affinity and specificity to nuclear factors in the mammalian cells. The insect hr1-BP- and the hr1-BP-like proteins from mammalian cells (mhr1-BP) have different properties with respect to ion requirements, DNA groove binding, and molecular size. When mammalian cells are infected with a recombinant baculovirus containing two promoters, the baculovirus polyhedrin and Drosophila hsp70 gene promoter, the hsp70 gene promoter alone is active in these cells, and this activity is further enhanced by the presence of an additional hr1 in the recombinant virus. hr1 may thus also have a role in baculovirus-mediated gene delivery in mammalian cells
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
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Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation
A Fractal Operator on Some Standard Spaces of Functions
Through appropriate choices of elements in the underlying iterated function system, the methodology of fractal interpolation enables us to associate a family of continuous self-referential functions with a prescribed real-valued continuous function on a real compact interval. This procedure elicits what is referred to as an α-fractal operator on , the space of all real-valued continuous functions defined on a compact interval I. With an eye towards connecting fractal functions with other branches of mathematics, in this paper we continue to investigate the fractal operator in more general spaces such as the space of all bounded functions and the Lebesgue space , and in some standard spaces of smooth functions such as the space of k-times continuously differentiable functions, Hölder spaces and Sobolev spaces . Using properties of the α-fractal operator, the existence of Schauder bases consisting of self-referential functions for these function spaces is established
Control of integrated task sequences shapes components of reaching
Reaching toward an object usually consists of a sequence of elemental actions. Using a reaching task sequence, the authors investigated how task elements of that sequence affected feedforward and feedback components of the reaching phase of the movement. Nine right-handed adults performed, with their dominant and nondominant hands, 4 tasks of different complexities: a simple reaching task; a reach-to-grasp task; a reach-to-grasp and lift object task; and a reach-to-grasp, lift, and place object task. Results showed that in the reach-to-grasp and lift object task more time was allocated to the feedforward component of the reach phase, while latency between the task elements decreased. We also found between-hand differences, supporting previous findings of increased efficiency of processing planning-related information in the preferred hand. The presence of task-related modifications supports the concept of contextual effects when planning a movement
An additional copy of the homologous region (hr1) sequence in the Autographa californica multinucleocapsid polyhedrosis virus genome promotes hyperexpression of foreign genes
The Autographa californica multinucleocapsid nuclear polyhedrosis virus genome contains nine homologous region (hr1, hr1a, hr2, hr2a, hr3, hr4a, hr4b, hr4c, and hr5) sequences that are thought to be involved in viral replication and activation of transcription. Our results show that the 750 bp hr1 sequence is capable of functioning as an enhancer of transcription of foreign genes from the homologous late polyhderin gene promoter and the heterologous Drosophila heat shock protein (hsp70) promoter in insect cells. Introduction of an additional copy of the complete hr1 element downstream to the polyhedrin locus in the viral genome, while not affecting the stability of the recombinant virus for at least 30 serial passages, led to hyperexpression of reporter genes. The enhancement in the expression levels of foreign genes varied from 40 to 90-fold depending on the promoter used
Children with developmental coordination disorder (DCD) can adapt to perceptible and subliminal rhythm changes but are more variable
Children with DCD demonstrate impairments in bimanual finger tapping during self-paced tapping and tapping in synchrony to different frequencies. In this study, we investigated the ability of children with DCD to adapt motorically to perceptible or subliminal changes of the auditory stimuli without a change in frequency, and compared their performance to typically developing controls (TDC). Nineteen children with DCD between ages 6–11 years (mean age ± SD = 114 ± 21 months) and 17 TDC (mean age ± SD = 113 ± 21 months) participated in this study. Auditory perceptual threshold was established. Children initially tapped bimanually to an antiphase beat and then to either a perceptible change in rhythm or to gradual subliminal changes in rhythm. Children with DCD were able to perceive changes in rhythm similar to TDC. They were also able to adapt to both perceptible and subliminal changes in rhythms similar to their age- and gender- matched TDC. However, these children were significantly more variable compared with TDC in all phasing conditions. The results suggest that the performance impairments in bilateral tapping are not a result of poor conscious or sub-conscious perception of the auditory cue. The increased motor variability may be associated with cerebellar dysfunction but further behavioral and neurophysiological studies are needed
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