Marked reduction in fertility among African women with urogenital infections: A prospective cohort study.

BACKGROUND: There is paucity of data on risk factors for reduced fertility in low-income countries. OBJECTIVE: To investigate factors associated with fertility among women in rural north eastern Tanzania. SUBJECTS AND METHODS: A cohort of 1248 non-pregnant women was followed with urine pregnancy testing every third month or more regularly if they reported a missed menstrual period. Pregnancy was confirmed with trans-abdominal ultrasound. Information regarding general health, socioeconomic status and obstetric-gynaecological history was collected. Factors associated with conceiving within 180 days were identified using multivariate logistic regression analyses. RESULTS: Among the 1248 women, 736 were followed for 180 days and 209 of these had an ultrasound confirmed pregnancy. During the follow-up period, 169/736 women were diagnosed with urogenital infections, including suspected sexually transmitted or reproductive tract infections, urinary tract infection, and vaginal candidiasis. Urogenital infections were significantly associated with reduced odds of conceiving within 180 days (adjusted OR (AOR) 0.21, 95% CI 0.11-0.36). Being above 30 years of age was also negatively associated with odds of conceiving (AOR 0.45, 95% CI 0.26-0.77). In contrast, women who recently stopped using hormonal contraceptives (AOR 2.86, 95% CI 1.45-5.70) and women with low socioeconomic status (AOR 1.56, 95% CI 1.04-2.33) were significantly more likely to become pregnant within 180 days. CONCLUSION: Urogenital infection seems to be a major health factor associated with reduced chances of conceiving. Considering the availability of effective treatment options for these diseases, public health authorities should increase awareness of diagnostic tools in settings with limited resources in order to improve fertility.

Effect of locally tailored labour management guidelines on intrahospital stillbirths and birth asphyxia at the referral hospital of Zanzibar: a quasi-experimental pre-post study (The PartoMa study).

OBJECTIVE: To evaluate effect of locally tailored labour management guidelines (PartoMa guidelines) on intrahospital stillbirths and birth asphyxia. DESIGN: Quasi-experimental pre-post study investigating the causal pathway through changes in clinical practice. SETTING: Tanzanian low-resource referral hospital, Mnazi Mmoja Hospital. POPULATION: Facility deliveries during baseline (1 October 2014 until 31 January 2015) and the 9th to 12th intervention month (1 October 2015 until 31 January 2016) [corrected]. METHODS: Birth outcome was extracted from all cases of labouring women during baseline (n = 3690) and intervention months (n = 3087). Background characteristics and quality of care were assessed in quasi-randomly selected subgroups (n = 283 and n = 264, respectively). MAIN OUTCOME MEASURES: Stillbirths and neonates with 5-minute Apgar score ≤5. RESULTS: Stillbirth rate fell from 59 to 39 per 1000 total births (RR 0.66, 95% CI 0.53-0.82), and subanalyses suggest that this was primarily due to reduction in intrahospital stillbirths. Apgar scores between 1 and 5 fell from 52 to 28 per 1000 live births (RR 0.53, 95% CI 0.41-0.69). Median time from last fetal heart assessment till delivery (or fetal death diagnosis) fell from 120 minutes (IQR 60-240) to 74 minutes (IQR 30-130) (Mann-Whitney test for difference, P < 0.01). Oxytocin augmentation declined from 22% to 12% (RR 0.54, 95% CI 0.37-0.81) and timely use improved. CONCLUSION: Although low human resources and substandard care remain major challenges, PartoMa guidelines were associated with improvements in care, leading to reductions in stillbirths and birth asphyxia. Findings furthermore emphasise the central role of improved fetal surveillance and restricted intrapartum oxytocin use in safety at birth. TWEETABLE ABSTRACT: #PartoMa guidelines aided in reducing stillbirths and birth asphyxia at a Tanzanian low-resource hospital PLAIN LANGUAGE SUMMARY: PartoMa guidelines help birth attendants in Tanzania to save lives Every year, 3 million babies die on the day of birth. The vast majority of these deaths occur in the poorest countries. If their mothers had received better care during birth, most babies would have survived. At Mnazi Mmoja Hospital, an East African referral hospital, the PartoMa study shows that use of locally developed guidelines helps birth attendants to deliver better quality of care, which has led to improved survival at birth. At the hospital studied, resources are scarce. Each birth attendant assists four to six birthing women simultaneously, and many have less than 1 year of professional experience. International guidelines are available, but they are often unachievable and seldom applied. The PartoMa guidelines were developed in close collaboration with the birth attendants and approved by seven international experts. The result is an 8-page pocket booklet providing locally achievable and simple decision support for care during birth. Use of the PartoMa guidelines began in February 2015. As the staff group frequently changes, quarterly seminars are conducted where birth attendants are welcomed after working hours to learn about the guidelines. The guidelines have been positively received, and seminar attendance remains high. Use of the PartoMa guidelines is associated with: A decrease by one-third in stillbirths (59 to 39 per 1000 total births) A nearly halving in the number of babies born in immediate poor medical condition (52 to 28 per 1000 live births) The results presented here derive from a comparison of births before using the PartoMa guidelines and during the 9th-12th month of use. Such a 'before-after' study cannot exclude the possibility of other causes of better survival at birth. However, the improved survival is consistent with improved care during birth, which is in line with the PartoMa guidelines.

Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar: a cluster-randomised controlled trial.

OBJECTIVE: To examine the association between a mobile phone intervention and skilled delivery attendance in a resource-limited setting. DESIGN: Pragmatic cluster-randomised controlled trial with primary healthcare facilities as the unit of randomisation. SETTING: Primary healthcare facilities in Zanzibar. POPULATION: Two thousand, five hundred and fifty pregnant women (1311 interventions and 1239 controls) who attended antenatal care at one of the selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery. All pregnant women were eligible for study participation. METHODS: Twenty-four primary healthcare facilities in six districts in Zanzibar were allocated by simple randomisation to either mobile phone intervention (n = 12) or standard care (n = 12). The intervention consisted of a short messaging service (SMS) and mobile phone voucher component. MAIN OUTCOME MEASURES: Skilled delivery attendance. RESULTS: The mobile phone intervention was associated with an increase in skilled delivery attendance: 60% of the women in the intervention group versus 47% in the control group delivered with skilled attendance. The intervention produced a significant increase in skilled delivery attendance amongst urban women (odds ratio, 5.73; 95% confidence interval, 1.51-21.81), but did not reach rural women. CONCLUSIONS: The mobile phone intervention significantly increased skilled delivery attendance amongst women of urban residence. Mobile phone solutions may contribute to the saving of lives of women and their newborns and the achievement of Millennium Development Goals 4 and 5, and should be considered by maternal and child health policy makers in developing countries.

Acupuncture for the induction of labour: a double-blind randomised controlled study.

OBJECTIVE: To investigate whether acupuncture is effective for the induction of labour in post-term pregnancies. DESIGN: A double-blind multicentre randomised controlled study. SETTINGS: Aarhus University Hospital and Herning Regional Hospital, Denmark. POPULATION: One hundred and twenty-five healthy women with uneventful pregnancies at gestational week 41(+6) were randomised into two groups. METHODS: The intervention group was given acupuncture twice on the same day at acupuncture point GV20 and bilaterally at points BL67, LI4 and SP6. The control group received sham acupuncture at the same points. MAIN OUTCOME MEASURES: At effect evaluation, which was carried out 24 hours after randomisation, the primary endpoint was labour or delivery. RESULTS: The primary endpoint was achieved in seven women (12%) in the acupuncture group and eight women (14%) in the control group (P = 0.79). Stratification for parity and fetal gender did not alter the results. CONCLUSION: Under the treatment regimen investigated in this study, acupuncture for the induction of labour in post-term women at gestational age 41(+6) weeks may not be effective.

[A controlled trial of training in knee arthritis]. / En kontrolleret undersøgelse af traening af knaeartrose.

INTRODUCTION: The aim was to investigate the effectiveness and safety of a physical training programme in patients with severe osteoarthritis of the knees. MATERIAL AND METHODS: Twenty-five patients participated in this randomised clinical trial with a blind observer. Intervention consisted in training twice a week for three months and focused on general fitness, balance, co-ordination, and muscle strength. Follow-up was performed at 3 and 12 months. The recorded parameters were muscle strength, algofunctional index, pain, walking speed, and clinical findings. RESULTS: At three months follow-up, muscle strength had improved in the intervention group. By one year, pain at night had decreased, but the number of palpable knee joint effusions had increased. CONCLUSION: A general physical training programme appears to be beneficial to patients with osteoarthritis of the knees, but further investigation of the safety of such a programme is called for.

Characteristics of antenatal care attenders in a rural population in Tamil Nadu, South India: a community-based cross-sectional study.

The objectives of the study were to identify factors associated with utilisation of antenatal care facilities in a rural population in South India. A community-based, cross-sectional questionnaire study of 30 randomly selected areas was used. A total of 1254 women (95%) had at least one antenatal care visit. The median number of visits was four. High utilisation of antenatal care facilities was associated with low parity and adverse obstetrical history, short distance to healthcare facilities and literacy. It was concluded that antenatal care coverage was high. Information about the above few aspects can be used to target women who are at risk of getting inadequate antenatal care.

The Children's Global Assessment Scale (CGAS) and Global Assessment of Psychosocial Disability (GAPD) in clinical practice--substance and reliability as judged by intraclass correlations.

Studies on the inter-rater reliability on the Children's Global Assessment Scale (CGAS) and the Global Assessment of Psychosocial Disability (GAPD) involving different subgroups of 145 outpatients from 4 to 16 years of age showed fair to substantial intraclass correlations of 0.59 to 0.90. Raters of different training levels participated. Interrater reliability was dependent on number of ratings per rater, training, available data sources and experience. A more detailed description of anchor points resulted in higher inter-rater agreement by psychiatrists training in child and adolescent psychiatry, but did not influence the inter-rater reliability among more (widely) experienced raters. Both the CGAS and the GAPD seem to be sufficiently reliable tools in clinical practice. The CGAS seems to be more sensitive to inter-rater variation than the GAPD.

Crystallization and molecular-replacement solution of a truncated form of human recombinant tetranectin.

The two C-terminal domains, TN23 (residues 17-181), of human recombinant tetranectin, a plasminogen kringle 4 binding C-type lectin, have been crystallized in two different space groups. Using PEG 8000 as precipitant and at a pH of 8.5, crystals belonging to the monoclinic space group C2 are obtained, with unit-cell parameters a = 160.4, b = 44.7, c = 107.5 A, beta = 127.6 degrees. Using sodium formate as precipitant and at a pH of 5.0, TN23 crystallizes in a rhombohedral space group, with unit-cell parameters a = b = c = 107.4 A, alpha = beta = gamma = 78.3 degrees. A full data set to 4.5 A has been collected from the monoclinic crystals. Using the structure of full-length tetranectin, a molecular-replacement solution has been obtained. The crystal packing shows that TN23 crystallizes as a trimer, with one trimer in the asymmetric unit.

[From valium to the happy pill?]. / Fra valium til lykkepille?

The National Health Insurance started to refund expenditure on selective serotonin reuptake inhibitors in 1994. Questions have been raised if a significant portion of benzodiazepine users would transfer to these new drugs when they were described in the literature as also being used for light anxiety, but not carrying the addiction risk associated with benzodiazepines. The study looks at changes over a four-year period in the prescription of benzodiazepines and selective serotonin reuptake inhibitors dispensed from two pharmacies in Vest-Agder County with a total customer base of 17,800. For four years we also followed the prescription of drugs in these two groups to 1,125 patients who had been prescribed benzodiazepines in 1994. Our data show that only 5% of those receiving benzodiazepines in 1994, whom we were able to track, changed to a selective serotonin reuptake inhibitor-only therapy. 18% used a combination of the two groups of drugs and 77% continued to use benzodiazepines as before. The increase in the number of patients receiving selective serotonin reuptake inhibitors during the study period is far greater than the increase measured by number of daily doses. Selective serotonin reuptake inhibitors seem to have little influence on the use of benzodiazepines in our pharmacies' area. Our findings indicate that instead of "from Valium to Prozac" the change during the years 1994-97 can be described as "from Valium to Valium and Prozac".

Structure of the C-type lectin carbohydrate recognition domain of human tetranectin.

Tetranectin (TN) is a C-type lectin involved in fibrinolysis, being the only endogenous ligand known to bind specifically to the kringle 4 domain of plasminogen. TN was originally isolated from plasma, but shows a wide tissue distribution. Furthermore, TN has been found in the extracellular matrix of certain human carcinomas, whereas none or little is present in the corresponding normal tissue. The crystal structure of full-length trimeric TN (2.8 A resolution) has recently been published [Nielsen et al. (1997). FEBS Lett. 412, 388-396]. The crystal structure of the carbohydrate recognition domain (CRD) of human TN (TN3) has been determined separately at 2.0 A resolution in order to obtain detailed information on the two calcium binding sites. This information is essential for the elucidation of the specificity of TN towards oligosaccharides. TN3 crystallizes as a dimer, whereas it appears as a monomer in solution. The overall fold of TN3 is similar to other known CRDs. Each monomer is built of two distinct regions, one region consisting of six beta-strands and two alpha-helices, and the other region is composed of four loops harboring two calcium ions. The calcium ion at site 1 forms an eightfold coordinated complex and has Asp116, Glu120, Gly147, Glu150, Asn151, and one water molecule as ligands. The calcium ion at site 2, which is believed to be involved in recognition and binding of oligosaccharides, is sevenfold coordinated with ligands Gln143, Asp145, Glu150, Asp165, and two water molecules. One sulfate ion has been located at the surface of TN3, forming contacts to Glu120, Lys148, Asn106 of a symmetry-related molecule, and to an ethanol molecule.

Crystal structure of tetranectin, a trimeric plasminogen-binding protein with an alpha-helical coiled coil.

Tetranectin is a plasminogen kringle 4-binding protein. The crystal structure has been determined at 2.8 A resolution using molecular replacement. Human tetranectin is a homotrimer forming a triple alpha-helical coiled coil. Each monomer consists of a carbohydrate recognition domain (CRD) connected to a long alpha-helix. Tetranectin has been classified in a distinct group of the C-type lectin superfamily but has structural similarity to the proteins in the group of collectins. Tetranectin has three intramolecular disulfide bridges. Two of these are conserved in the C-type lectin superfamily, whereas the third is present only in long-form CRDs. Tetranectin represents the first structure of a long-form CRD with intact calcium-binding sites. In tetranectin, the third disulfide bridge tethers the CRD to the long helix in the coiled coil. The trimerization of tetranectin as well as the fixation of the CRDs relative to the helices in the coiled coil indicate a demand for high specificity in the recognition and binding of ligands.

Reproductive pattern, perinatal mortality, and sex preference in rural Tamil Nadu, south India: community based, cross sectional study.

OBJECTIVES: To study reproductive pattern and perinatal mortality in rural Tamil Nadu, South India. DESIGN: Community based, cross sectional questionnaire study of 30 randomly selected areas served by health subcentres. SETTING: Rural parts of Salem District, Tamil Nadu, South India. SUBJECTS: 1321 women and their offspring delivered in the 6 months before the interview. MAIN OUTCOME MEASURES: Number of pregnancies, pregnancy outcome, spacing of pregnancies, sex of offspring, perinatal and neonatal mortality rates. RESULTS: 41% of the women (535) were primiparous; 7 women (0.5%) were grand multiparous (> 6 births). The women had a mean age of 22 years and a mean of 2.3 pregnancies and 1.8 live children. The sex ratio at birth of the index children was 107 boys per 100 girls. The stillbirth rate was 13.5/1000 births, the neonatal mortality rate was 35.3/1000, and the perinatal mortality rate was 42.0/1000. Girls had an excess neonatal mortality (rate ratio 3.42%; 95% confidence interval 1.68 to 6.98; this was most pronounced among girls born to multiparous women with no living sons (rate ratio 15.48 (2.04 to 177.73) v 1.87 (0.63 to 5.58) in multiparous women with at least one son alive). CONCLUSIONS: In this rural part of Tamil Nadu, women had a controlled reproductive pattern. The excess neonatal mortality among girls constitutes about one third of the perinatal mortality rate. It seems to be linked to a preference for sons and should therefore be addressed through a holistic societal approach rather than through specific healthcare measures.

PIP: This study examines patterns of neonatal mortality among rural mothers in Salem district, Tamil Nadu state, India. Data were collected during August-September 1995 in a catchment area of 30 health subcenters. The sample includes 1321 women who had delivered within the preceding 6 months. The aim was to determine the extent of excess female neonatal mortality. The instrument was pretested, and other reliability checks were made. Findings indicate that 20% (261) of the mothers had experienced the death of one or more children. The mean age of the women was 22 years, the average number of pregnancies was 2.3, and the average number of live-born children was 1.8. The mean age of first-time mothers was 20.2 years. The mean age of multiparous women was 23.9 years. There were 268 live-born babies, 68 stillbirths, 275 postnatal deaths, 280 spontaneous abortions, and 60 induced abortions. The stillbirth rate was 13.5/1000 births. The perinatal mortality rate was 42.0/1000. The early neonatal mortality rate was 28.9/1000. The late neonatal mortality rate was 6.6/1000. Of the 1321 deliveries in the prior 6 months, 99% were singleton births. 51.7% were boys, and 48.3% were girls. 98.6% were live-born, and 1.4% were stillbirths. 4.0% of live-born infants died postnatally, of which 64% died in the first 7 days and 13% died between 8 and 28 days. 23% died 1 month or more following birth. There were 11 sets of twins, of which one each died in the early and late neonatal period. In the one set of quadruplets, all infants died in the early neonatal period. The relative risk of death among daughters was 4.36 compared to sons. Primiparous women did not experience excess female neonatal mortality. Risk of female neonatal death was higher among multiparous women with no living sons compared to women with at least one son. This study did not find a shorter birth interval after the birth of a girl. The preference for sons should be addressed through a holistic societal approach.

Dilution rate increases production of plant cell-wall degrading enzymes by anaerobic fungi in continuous-flow culture.

The gut anaerobic fungi,Neocallimastix hurleyensis and aOrpinomyces sp., were grown in 100 mL batch and continuous-flow cultures on wheat straw at a concentration of 80 g dry matter/L of culture liquid. In batch cultures,N. hurleyensis and Orpinomyces sp. degraded only ca. 9% and 5% of the wheat straw, respectively. In continuous-flow cultures, however, the two fungi degraded 52-56% of the apparent dry matter of wheat straw. Both fungi were able to produce greater quantities (up to x 30) of cell-wall degrading enzymes (CMCase, xylanase, beta-glucosidase and beta-xylosidase) in continuous-flow cultures than in the corresponding batch cultures. Increasing the dilution rate in continuous-flow culture resulted in the production of increased enzyme activity for all the measured cell-wall degrading enzymes, with proportional relationships between dilution rate and the cumulative activities of beta-glucosidase and beta-xylosidase. Dilution rates, however, had no consistent effect on the cumulative production of the fermentation end-products, acetate, formate, D- and L-lactate from both fungi. In addition to acetate and formate,N. hurleyens is produced D- and L-lactate in both batch and continuous-flow cultures, whereas only trace amounts of L-lactate were detected in the Orpinomyces sp. cultures.

Human plasminogen binding protein tetranectin: crystallization and preliminary X-ray analysis of the C-type lectin CRD and the full-length protein.

The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals diffract X-rays to at least 2.0 A resolution. A complete diffraction data set has been collected to 2.7 A resolution. The crystals of TN, obtained by the vapour-diffusion reverse salting-in method at 280 K, are rhombohedral, space group R3, with the hexagonal axes a = b = 89.1, c = 75.8 A, and diffract to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates that trimers of TN are formed in accordance with the observation of trimerization in solution.

The three-dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site than Escherichia coli R2.

The three-dimensional structure of mouse ribonucleotide reductase R2 has been determined at 2.3 A resolution using molecular replacement and refined to an R-value of 19.1% (Rfree = 25%) with good stereo-chemistry. The overall tertiary structure architecture of mouse R2 is similar to that from Escherichia coli R2. However, several important structural differences are observed. Unlike the E. coli protein, the mouse dimer is completely devoid of beta-strands. The sequences differ significantly between the mouse and E. coli R2s, but there is high sequence identity among the eukaryotic R2 proteins, and the identities are localized over the whole sequence. Therefore, the three-dimensional structures of other mammalian ribonucleotide reductase R2 proteins are expected to be very similar to that of the mouse enzyme. In mouse R2 a narrow hydrophobic channel leads to the proposed binding site for molecular oxygen near to the iron-radical site in the interior of the protein. In E. coli R2 this channel is blocked by the phenyl ring of a tyrosine residue, which in mouse R2 is a serine. These structural variations may explain the observed differences in sensitivity to radical scavengers. The structure determination is based on diffraction data from crystals grown at pH 4.7. Unexpectedly, the protein is not iron-free, but contains one iron ion bound at one of the dinuclear iron sites. This ferric ion is bound with partial occupancy and is coordinated by three glutamic acids (one bidentate) and one histidine in a bipyramidal coordination that has a free apical coordination position. Soaking of crystals in a solution of ferrous salt at pH 4.7 increased the occupancy on the already occupied site, but without any detectable binding at the second site.

Crystallization and crystallographic investigations of the small subunit of mouse ribonucleotide reductase.

The R2 protein component of mouse ribonucleotide reductase has been obtained from overproducing Escherichia coli bacteria. It has been crystallized using NaCl as precipitant. The crystals are orthorhombic, space group C222(1), with cell dimensions a = 76.9 A, b = 108.9 A, c = 92.7 A and diffract to at least 2.5 A. The asymmetric unit of the crystals contains one monomer. Rotation and translation function searches using a model based on the weakly homologous E. coli R2 gave one significant peak. Rotation about a crystallographic 2-fold axis parallel to the a-axis produces an R2 dimer with dimer interactions very similar to those found for E. coli R2.

Perceptions of the mammography experience.

The 1993 projections for breast cancer indicate a morbidity of 183,000 women with a mortality rate of 18%. Mammography is one of three approaches available for the early detection of breast cancer. However, underutilization has been reported and attributed to pain associated with the procedure, the expense to the consumer, and lack of referral by physicians. Other reasons for the low utilization rates include fears on the part of the woman of a positive diagnosis, radiation, and a possible mastectomy. This study provides an analysis of the responses of a convenience sample of 272 women, aged 30-90 years, to two open-ended questions about the mammography experience. The words and phrases women used to describe the mammography experience and the sensations experienced in their breasts during mammography were subjected to content analysis. The results of this study suggest that the word descriptors women use to describe their experience during mammography are highly individualistic and may not be totally captured by numeric or descriptive rating scales of pain intensity.

[Salmonella dublin]. / Salmonella dublin.

Salmonella dublin's natural host is cattle; it may cause acute disease in calves, while adult animals may be asymptomatic carriers. In humans S. dublin is the most invasive of the zoonotic Salmonella-bacteria found in Denmark. It is much more frequently isolated from the blood than from the faeces and may give rise to serous metastatic infections in practically all organs. The number of registered human infections rose from zero to 46 per year during the period 1980-1988, but has now stabilized at a level of about 20 per year. Outbreaks have been described abroad as being caused by unpasteurised milk and cheese; in Denmark beef and cow's liver must be viewed as the dominant source of infection. The direct routes of infection are, however, unknown. Tightening of regulations for the slaughtering of animals from S. dublin infected herds, optimal hygiene in the slaughterhouses and increased cooperation between the veterinary and medical professions concerning investigation of routes of infection are necessary measures to be taken in order to reduce the number of human S. dublin infections.