The Burden of OASIS Increases along with Socioeconomic Position – Register-Based Analysis of 980,733 Births in Finland

Background

Obstetric anal sphincter injury (OASIS) has been identified as a major preventable risk factor for anal incontinence.

Objective

Aim was to measure national variation in incidence of OASIS by socioeconomic status (SES).

Methods

A retrospective population based case-control study using the data derived from the Finnish Medical Birth Register for the years 1991–2010. A total population of singleton vaginal births was reviewed. We calculated unadjusted incidences of OASIS stratified by SES and vaginal parity, and adjusted risks for OASIS in each social class, after controlling for parity, birthweight, mode of delivery, maternal age and maternal smoking. SES was recorded into five categories based on mother’s occupation at time of birth; upper white-collar workers such as physicians, lower white-collar workers such as nurses, blue-collar workers such as cleaners, others such as students, and cases with missing information.

Results

Seven per thousand (6,404 of 980,733) singleton births were affected by OASIS. In nulliparae the incidence of OASIS was 18% higher (adjusted OR 1.18 95% CI 1.04−1.34) for upper white-collar workers and 12% higher (adjusted OR 1.12 95% CI 1.02−1.24) for lower white-collar workers compared with blue-collar workers. Among women in these higher SES groups, 40% of the excess OASIS risk was explained by age, non-smoking, birthweight and mode of delivery. Despite the large effect of SES on OASIS, inclusion of SES in multivariable models caused only small changes in estimated adjusted effects for other established risk factors.

Conclusions

OASIS at the first vaginal delivery demonstrates a strong positive social gradient. Higher SES is associated with a number of risk factors for OASIS, including higher birthweight and non-smoking, but only 40% of the excess incidence is explained by these known risk factors. Further research should address other underlying causes including differences in lifestyle or environmental factors, and inequalities in healthcare provision.     

Are Women Deciding against Home Births in Low and Middle Income Countries?

Background

Although there is evidence to tracking progress towards facility births within the UN Millennium Development Goals framework, we do not know whether women are deciding against home birth over their reproductive lives. Using Demographic and Health Surveys (DHS) data from 44 countries, this study aims to investigate the patterns and shifts in childbirth locations and to determine whether these shifts are in favour of home or health settings.

Methods and Findings

The analyses considered 108,777 women who had at least two births in the five years preceding the most recent DHS over the period 2000–2010. The vast majority of women opted for the same place of childbirth for their successive births. However, about 14% did switch their place and not all these decisions favoured health facility over home setting. In 24 of the 44 countries analysed, a higher proportion of women switched from a health facility to home. Multilevel regression analyses show significantly higher odds of switching from home to a facility for high parity women, those with frequent antenatal visits and more wealth. However, in countries with high infant mortality rates, low parity women had an increased probability of switching from home to a health facility.

Conclusions

There is clear evidence that women do change their childbirth locations over successive births in low and middle income countries. After two decades of efforts to improve maternal health, it might be expected that a higher proportion of women will be deciding against home births in favour of facility births. The results from this analysis show that is not the case.     

Can Community Health Workers Report Accurately on Births and Deaths? Results of Field Assessments in Ethiopia,Malawi and Mali

Introduction

Most low-income countries lack complete and accurate vital registration systems. As a result, measures of under-five mortality rates rely mostly on household surveys. In collaboration with partners in Ethiopia, Ghana, Malawi, and Mali, we assessed the completeness and accuracy of reporting of births and deaths by community-based health workers, and the accuracy of annualized under-five mortality rate estimates derived from these data. Here we report on results from Ethiopia, Malawi and Mali.

Method

In all three countries, community health workers (CHWs) were trained, equipped and supported to report pregnancies, births and deaths within defined geographic areas over a period of at least fifteen months. In-country institutions collected these data every month. At each study site, we administered a full birth history (FBH) or full pregnancy history (FPH), to women of reproductive age via a census of households in Mali and via household surveys in Ethiopia and Malawi. Using these FBHs/FPHs as a validation data source, we assessed the completeness of the counts of births and deaths and the accuracy of under-five, infant, and neonatal mortality rates from the community-based method against the retrospective FBH/FPH for rolling twelve-month periods. For each method we calculated total cost, average annual cost per 1,000 population, and average cost per vital event reported.

Results

On average, CHWs submitted monthly vital event reports for over 95 percent of catchment areas in Ethiopia and Malawi, and for 100 percent of catchment areas in Mali. The completeness of vital events reporting by CHWs varied: we estimated that 30%-90% of annualized expected births (i.e. the number of births estimated using a FPH) were documented by CHWs and 22%-91% of annualized expected under-five deaths were documented by CHWs. Resulting annualized under-five mortality rates based on the CHW vital events reporting were, on average, under-estimated by 28% in Ethiopia, 32% in Malawi, and 9% in Mali relative to comparable FPHs. Costs per vital event reported ranged from $21 in Malawi to $149 in Mali.

Discussion

Our findings in Mali suggest that CHWs can collect complete and high-quality vital events data useful for monitoring annual changes in under-five mortality rates. Both the supervision of CHWs in Mali and the rigor of the associated field-based data quality checks were of a high standard, and the size of the pilot area in Mali was small (comprising of approximately 53,205 residents in 4,200 households). Hence, there are remaining questions about whether this level of vital events reporting completeness and data quality could be maintained if the approach was implemented at scale. Our experience in Malawi and Ethiopia suggests that, in some settings, establishing and maintaining the completeness and quality of vital events reporting by CHWs over time is challenging. In this sense, our evaluation in Mali falls closer to that of an efficacy study, whereas our evaluations in Ethiopia and Malawi are more akin to an effectiveness study. Our overall findings suggest that no one-size-fits-all approach will be successful in guaranteeing complete and accurate reporting of vital events by CHWs.     

Births during 7 years after the translocation of a pair of black-and-gold howler monkeys (<Emphasis Type="Italic">Alouatta caraya</Emphasis>) to a forest fragment in southeast Brazil

Fecundity in female primates is influenced by the nutritional condition. If when translocated howler monkeys exhibit the same breeding patterns as non-translocated members of the same genus, it is an indication that the translocated monkeys have become well adapted to their release site and that they are likely in good nutritional condition. The objective of this study was therefore to investigate this pattern by recording copulations (over 5 years) and births (over 7 years) after the translocation of a pair of black-and-gold howler monkeys (Alouatta caraya) and to evaluate their gestation period, seasonality of births, and intervals between births. The pair was released in November 2009 on the campus of the University of São Paulo in Ribeirão Preto, São Paulo State, Brazil. Data on copulations were collected from January 2010 to March 2011 and from January 2012 to December 2014. Births were collected from January 2010 to December 2016. During the 5-year observation period, 25 copulations were recorded. Seven births were recorded over a period of 7 years, which included reproduction of the offspring of the translocated pair. Births occurred in the dry season between April and August. The interval between births was approximately 1 year. Our data provide insight into the reproduction of howler monkeys that have been translocated to a new habitat. Translocation can provide a valuable approach for rescuing or restoring Alouatta, whose populations have been detrimentally impacted by long-term habitat fragmentation.     

A comparative analysis of karyotypes of three species of Macleaya—producers of a complex of isoquinoline alkaloids

Using a set of methods (C-banding, DAPI-staining, fluorescence hybridization in situ (FISH) with probes of 26S and 5S rDNA, and analysis of meiosis), the first comparative cytogenetic study of three species of Macleaya, producers of complex isoquinoline alkaloids, cordate Macleaya cordata (Willd.) R. Br. (2n = 20), small-fruited Macleaya microcarpa (Maxim.) Fedde (2n = 20) and Macleaya kewensis Turrill (2n = 20), was first carried out. On the basis of morphometric analysis, formulas of karyotypes were made for each species. Species ideograms for M. cordata, M. microcarpa, and M. kewensis were constructed taking into account the polymorphic variants of the C-banding patterns and indicating the location of 26S and 5S rDNA sites. A comparative study revealed that the karyotypes of M. microcarpa and M. kewensis have more in common with each other than with M. cordata. Analysis of meiotic chromosomes suggests of genetic stability of Macleaya genomes. The results of chromosome analysis were used to confirm the close relationship of Macleaya and to clarify their phylogenetic relationships.     

Effect of γ-Irradiation on Development of Lachrymator of Onion

A thermosensitive uracil requiring mutant of Bacillus subtilis Marburg 168 thy trp₂ ts42 was examined as to the colony forming ability at the permissive and nonpermissive temperatures. The viability of the mutant cells decreased rapidly at the restrictive temperature in the modified Woese’s (MW) medium. However, the cells retained viability when sodium succinate or potassium chloride was added to the medium at that temperature although uracil deficiency was unchanged. A little but significant incorporation of adenine-8-¹⁴C into RNA still continued even after the incorporation of N-acetyl-³H-d-glucosamine into acid insoluble fraction of the cells terminated in the MW medium at 48°C. Both incorporations as well as increase of absorbance were slowed down in the presence of sodium succinate at 48°C. This mutant, ts42, was more sensitive to deoxycholate (DOC) than the parent strain. The restoration of colony forming ability after the temperature shift back from 48 to 37°C was suppressed by the addition of DOC to the medium. However, the cell became resistant to DOC when uracil was added to the medium prior to the temperature shift.     

Mechanisms of action of the α-amylase of Micromonospora melanosporea

The -amylase of Micromonospora melanosporea was produced extracellularly during batch fermentation in a 5.0-1 fermentor. The absence of an organic nitrogen source in its growth medium facilitated subsequent purification of the enzyme by ammonium sulphate fractionation and two consecutive Superose-12 gel-filtration steps. The enzyme exhibited maxima for activity at pH 7.0 and 55° C and was 72% stable at pH 6.0–12.0 for 30 min at 40° C. It had a relative molecular mass of 45 000 and an isoelectric point at pH 7.6. The enzyme catalyses the conversion of starch to maltose (53%, w/w) as the predominant final end-product. Initial hydrolysis of this substrate, however, gave rise to the formation of maltooligosaccharides in the range maltotriose to maltohexaose. Maximum yields of these intermediate sugars accumulated to between 31 and 42% (w/w) as the reaction proceeded. The action of the M. melanosporea amylase on high concentrations of saccharides larger than maltotriose resulted in the formation of mainly maltose and maltotriose without concomitant glucose production. A combination of hydrolytic and transfer events is postulated to be responsible for this phenomenon and for the high maltose levels achieved. Correspondence to: C. T. Kelly     

Selection of optimal variants of Gō-like models of proteins through studies of stretching

The Gō-like models of proteins are constructed based on the knowledge of the native conformation. However, there are many possible choices of a Hamiltonian for which the ground state coincides with the native state. Here, we propose to use experimental data on protein stretching to determine what choices are most adequate physically. This criterion is motivated by the fact that stretching processes usually start with the native structure, in the vicinity of which the Gō-like models should work the best. Our selection procedure is applied to 62 different versions of the Gō model and is based on 28 proteins. We consider different potentials, contact maps, local stiffness energies, and energy scales—uniform and nonuniform. In the latter case, the strength of the nonuniformity was governed either by specificity or by properties related to positioning of the side groups. Among them is the simplest variant: uniform couplings with no i, i + 2 contacts. This choice also leads to good folding properties in most cases. We elucidate relationship between the local stiffness described by a potential which involves local chirality and the one which involves dihedral and bond angles. The latter stiffness improves folding but there is little difference between them when it comes to stretching.     

Mechanism of action of α-galactosidase

The effect ofpH on K_m and V_max values of coconut α-galactosidase indicates the involvement of two ionizing groups with pK_a values of 3.5 and 6.5 in catalysis. Chemical modification has indicated the presence of two carboxyl groups, a tryptophan and a tyrosine, at or near the active site of α-galactosidase. Based on these facts a new mechanism of action for α-galactosidase is proposed in which the ionizing group with a pK_a of 3.5 is a carboxyl group involved in stabilizing a carbonium ion intermediate and the ionizing group with a pK_a of 6.5 is a carboxyl group perturbed due to the presence of a hydrophobic residues in its vicinity which donates a H⁺ ion in catalysis.     

Chemistry of the “molecular trap” of protease-catalyzed splicing reaction of complementary segments of α-subunit of hemoglobin A

The complementary fragments of human Hb α, α_1–30, and α_31–141 are spliced together by V8 protease in the presence of 30%n-propanol to generate the full-length molecule (Hb α-semisynthetic reaction). Unlike the other protease-catalyzed protein/peptide splicing reactions of fragment complementing systems, the enzymic condensation of nonassociating segments of Hb α is facilitated by the organic cosolvent induced α-helical conformation of product acting as the “molecular trap” of the splicing reaction. The segments α_24–30 and α_31–40 are the shortest complementary segments that can be spliced by V8 protease. In the present study, the chemistry of the contiguous segment (product) α_24–40 has been manipulated by engineering the amino acid replacements to the positions α²⁷ and α³¹ to delineate the structural basis of the molecular trap. The location of Glu²⁷ and Arg³¹ residues in the contiguous segment α_24–40 (as well as in other larger segments) is ideal to generate (i, i+4) side-chain carboxylate-guanidino interaction in its α-helical conformation. The amino acid residue replacement studies have confirmed that the side chains at α²⁷ and α³¹ facilitate the semisynthetic reaction. The relative influence of the substitute at these sites on the splicing reaction depends on the chemical nature of the side chain and the location. The γ-carboxylate guanidino side-chain interaction appears to contribute up to a maximum of 85% of the thermodynamic stability of the molecular trap. The studies also demonstrate that the thermodynamic stability of the molecular trap is determined by two interdependent conformational aspects of the peptide. One is an amino acid-sequence-specific event that facilitates the induction of an α-helical conformation to the contiguous segment in the presence of organic cosolvent that imparts some amount of protease resistance to Glu³⁰-Arg³¹ peptide bond. The second structural aspect is a site-specific event, ani, i+4 side-chain interaction in the α-helical conformation of the peptide which imparts an additional thermodynamic stability to the molecular trap. The results suggest that conformationally driven “molecular traps” of protease-mediated ligation reactions of peptides could be designed into products to facilitate the modular assembly of peptides/proteins.     

Association of the subunits of the calcium-independent receptor of α-latrotoxin

CIRL-1 also called latrophilin 1 or CL belongs to the family of adhesion G protein-coupled receptors (GPCRs). As all members of adhesion GPSR family CIRL-1 consists of two heterologous subunits, extracellular hydrophilic p120 and heptahelical membrane protein p85. Both CIRL-1 subunits are encoded by one gene but as a result of intracellular proteolysis of precursor, mature receptor has two-subunit structure. It was also shown that a minor portion of the CIRL-1 receptor complexes dissociates, producing the soluble receptor ectodomain, and this dissociation is due to the second cleavage at the site between the site of primary proteolysis and the first transmembrane domain. Recently model of independent localization p120 and p85 on the cell surface was proposed. In this article we evaluated the amount of p120-p85 complex still presented on the cellular membrane and confirmed that on cell surface major amount of mature CIRL-1 presented as a p120-p85 subunit complex.     

Kinetics of renaturation and self-assembly of intermediates on the pathway of folding of the β2-subunit of Escherichia coli tryptophan-synthetase

The kinetics of renaturation of the β₂-subunit of Escherichia coli tryptophan-synthetase (l-serine hydrolyase (adding indole) E.C. 4.2.1.20) and those of its two proteolytic fragments F₁ and F₂ are studied and compared. Steps corresponding to the refolding of F₁, to the association of the folded F₁ and F₂ fragments, and to an isomerization of the associated protein are identified. These steps are ordered on the pathway of renaturation and some of their kinetic parameters are determined. This leads to a tentative kinetic model for the renaturation of nicked-β₂ starting from the denatured F₁ and F₂ fragments.The step corresponding to the refolding of the F₁ domain, as well as that corresponding to the last rate-limiting isomerization leading to the native protein, is shown to be the same in the refolding of the entire, uncleaved β₂-protein. It is concluded that the refolded F₁ fragment corresponds to a folding intermediate on the pathway of renaturation of the β₂-subunit.     

Determination of the number of degrees of freedom of the trapeziometacarpal joint–An in vitro study

ObjectiveMost of the studies about trapeziometacarpal joint assume that it exhibits only two independent degrees of freedom, but the experimental or theoretical support for considering a two-degrees of freedom model is not always clear.Materials and methodsTherefore, an in vitro kinematic study has been designed to demonstrate, from experimental data, that only two of the trapeziometacarpal degrees of freedom (i.e., flexion/extension and adduction/abduction) are non-null and independent. Several movements of maximal amplitude in flexion, abduction and circumduction have been realized and the relative position and orientation of the segment coordinate system embedded on the first metacarpal with respect to that embedded on the trapezium have been collected using electromagnetic sensors. The trapeziometacarpal rotations have been described using a joint coordinate system and the joint displacements have been evaluated on the axes of this coordinate system.ResultsThe root mean square (RMS) values of the joint displacement components have been found small enough to assume that the trapeziometacarpal joint has no translation degrees of freedom. A paraboloid coupling equation has been found between the internal/external rotation angle and the two other, flexion/extension and adduction/abduction, angles.ConclusionThus, this study demonstrates that the trapeziometacarpal joint has only two independent rotational degrees of freedom, and further, the described methodology could also be used to determine the coupling laws between degrees of freedom of various joints.     

Some aspects of mechanism of inhibition of cholesterol absorption by β-sitosterol

(1) Mixed bile salt micelle solubilized either cholesterol or β-sitosterol to a comparable extent. When added simultaneously, β-sitosterol restricted the micellar solubility of cholesterol. (2) β-Sitosterol also reduced the cholesterol content in the aqueous (micellar) phase of the intestinal contents of rats, the extent of reduction being comparable with that observed in vitro. The intestinal uptake of cholesterol in vivo was equivalent to the micellar incorporation of cholesterol both in vitro and in vivo. (3) β-Sitosterol had no inhibitory effect on cholesterol absorption from the micellar solution in jejunal loops in situ, whereas the rate of β-sitosterol uptake was only about one-fifth that of cholesterol. (4) The intestinal uptake of β-sitosterol intubated into the stomach of rats was about one-fifth that of cholesterol. The intestinal brush-border membrane discriminated these sterols. These results suggest that the restriction of the micellar solubility of cholesterol, rather than the inhibition of uptake from brush-border membrane, is the major determinant for the interference of β-sitosterol with cholesterol absorption.     

Inhibition of colony-spreading activity of Staphylococcus aureus by secretion of δ-hemolysin

Staphylococcus aureus spreads on the surface of soft agar, a phenomenon we termed "colony spreading." Here, we found that S. aureus culture supernatant inhibited colony spreading. We purified δ-hemolysin (Hld, δ-toxin), a major protein secreted from S. aureus, as a compound that inhibits colony spreading. The culture supernatants of hld-disrupted mutants had 30-fold lower colony-spreading inhibitory activity than those of the parent strain. Furthermore, hld-disrupted mutants had higher colony-spreading ability than the parent strain. These results suggest that S. aureus negatively regulates colony spreading by secreting δ-hemolysin.     

Diagnostic Utility of the Impact of Event Scale–Revised in Two Samples of Survivors of War

The study aimed at examining the diagnostic utility of the Impact of Event Scale-Revised (IES-R) as a screening tool for post-traumatic stress disorder (PTSD) in survivors of war. The IES-R was completed by two independent samples that had survived the war in the Balkans: a sample of randomly selected people who had stayed in the area of former conflict (n = 3,313) and a sample of refugees to Western European countries (n = 854). PTSD was diagnosed using the MINI International Neuropsychiatric Interview. Prevalence of PTSD was 20.1% in the Balkan sample and 33.1% in the refugee sample. Results revealed that when considering a minimum value of specificity of 0.80, the optimally sensitive cut-off score for screening for PTSD in the Balkan sample was 34. In both the Balkan sample and the refugee sample, this cut-off score provided good values on sensitivity (0.86 and 0.89, respectively) and overall efficiency (0.81 and 0.79, respectively). Further, the kappa coefficients for sensitivity for the cut-off of 34 were 0.80 in both samples. Findings of this study support the clinical utility of the IES-R as a screening tool for PTSD in large-scale research studies and intervention studies if structured diagnostic interviews are regarded as too labor-intensive and too costly.     

Quantitative assessment of the association of the α-I fragment of spectrin with oligomers of intact spectrin

• 1.1. The α-I fragment of human spectrin that carries the binding site on the α-chain of spectrin for the β -chain has been purified from limited trypsin digests of spectrin by means of FPLC.
• 2.2. The self-association of spectrin and the binding of the α-I fragment to spectrin heterodimers and to tetramers have been quantified through the use of gel electrophoresis, staining with Coomassie Blue, and quantification of the bound dye following elution with pyridine.
• 3.3. The parameters of self-association were found to be consistent with those estimated from sedimentation equilibrium analysis.
• 4.4. The data were consistent with a model in which both self-association and the binding of the α-I fragment are considered to occur through an intermediate in which the α-β interface is initially dissociated. The α-β interface in the heterodimer was found to be less stable than that of higher oligomers by approx. 3 kJ/mol.