Attention-deficit/hyperactivity disorder and other neurodevelopmental disorders in offspring of parents with depression and bipolar disorder.

BACKGROUND: Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls. METHOD: We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder. RESULTS: Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23-4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03-3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring. CONCLUSIONS: Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.

Effect of hysterectomy on pain in women with endometriosis: a population-based registry study.

OBJECTIVE: To assess pain symptoms before and after hysterectomy in women with endometriosis. DESIGN: A population-based registry study. SETTING: Sweden. POPULATION: Women aged 18-45 years who underwent hysterectomy for endometriosis between 2010 and 2015. METHODS: Pain symptoms before hysterectomy and 12 months after surgery were collected from the Swedish National Quality Register for Gynaecological Surgery (GynOp). Pain symptoms were also assessed by follow-up surveys after a median follow-up period of 63 months. MAIN OUTCOME MEASURES: Pelvic or lower abdominal pain after hysterectomy. RESULTS: The study included 137 women. The proportion of women experiencing pain of any severity decreased by 28% after hysterectomy (P < 0.001). The proportion of women with severe pain symptoms decreased by 76% after hysterectomy (P < 0.001). The majority of women (84%) were satisfied with the surgical result. Presence of severe pain symptoms after the hysterectomy was associated with less satisfaction (P < 0.001). Pain symptoms after surgery, patient satisfaction and the patient's perceived improvement were not significantly different between women whose ovarian tissue was preserved and women who underwent bilateral oophorectomy. CONCLUSIONS: We observed a significant, long-lasting reduction in pain symptoms after hysterectomy among women with endometriosis. Hysterectomy, with the possibility of ovarian preservation, may be a valuable option for women with endometriosis who suffer from severe pain symptoms. TWEETABLE ABSTRACT: Hysterectomy is a valuable option for women with endometriosis and severe pain symptoms.

Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

BACKGROUND: Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state. METHODS: Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders. RESULTS: Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia. CONCLUSIONS: Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

Altered cerebral pain processing of noxious stimuli from inflamed joints in rheumatoid arthritis: An event-related fMRI study.

OBJECTIVE: To our knowledge, this is the first study assessing brain activation in response to painful stimulation over disease-relevant (finger joint) vs. neutral area (thumb nail) in patients suffering from rheumatoid arthritis (RA) compared to healthy controls (HC). METHOD: Thirty-one RA patients and 23 HC underwent functional magnetic resonance imaging (fMRI) while stimulated with subjectively calibrated painful pressures corresponding to a pain sensation of 50 mm on a 100 mm VAS scale (P50) at disease-affected finger joint and thumbnail (left hand), and corresponding sites in HC. RESULTS: Compared to controls, RA patients had significantly increased pain sensitivity (lower P50) at the inflamed joints but not at the thumbnail. RA patients exhibited significantly less activation in regions related to pain- and somatosensory processing (S1, M1, anterior insula, S2, SMG and MCC) during painful joint stimulation, compared to HC. No group difference in cerebral pain processing was found for the non-affected thumbnail. Within RA patients, significantly less brain activation was found in response to painful stimulation over disease-affected joint compared to non-affected thumbnail in bilateral S1, bilateral S2, and anterior insula. Further, RA patients exhibited a right-sided dlPFC deactivation, psycho-physiologically interacting (PPI) with the left dlPFC in response to painful stimulation at disease-affected joints. CONCLUSION: The results indicate normal pain sensitivity and cerebral pain processing in RA for non-affected sites, while the increased sensitivity at inflamed joints indicate peripheral/spinal sensitization. Brain imaging data suggest that disease-relevant pain processing in RA is marked by aberrations and a failed initiation of cortical top-down regulation.

Durations of second stage of labor and pushing, and adverse neonatal outcomes: a population-based cohort study.

OBJECTIVE: The associations between duration of second stage of labor, pushing time and risk of adverse neonatal outcomes are not fully established. Therefore, we aimed to examine such relationships. STUDY DESIGN: A population-based cohort study including 42 539 nulliparous women with singleton infants born in cephalic presentation at ⩾37 gestational weeks, using the Stockholm-Gotland Obstetric Cohort, Sweden, and the Swedish Neonatal Quality Register, 2008 to 2013. Poisson regression was used to analyze estimated adjusted relative risks (RRs), with 95% confidence intervals (CIs). Outcome measures were umbilical artery acidosis (pH <7.05 and base excess <-12), birth asphyxia-related complications (including any of the following conditions: hypoxic ischemic encephalopathy, hypothermia treatment, neonatal seizures, meconium aspiration syndrome or advanced resuscitation after birth) and admission to neonatal intensive care unit (NICU). RESULTS: Overall rates of umbilical artery acidosis, birth asphyxia-related complications and admission to NICU were 1.08, 0.63 and 6.42%, respectively. Rate of birth asphyxia-related complications gradually increased with duration of second stage: from 0.42% at <1 h to 1.29% at ≥4 h (adjusted RR 2.46 (95% CI 1.66 to 3.66)). For admission to NICU, corresponding rates were 4.97 and 9.45%, and adjusted RR (95% CI) was 1.80 (95% CI 1.58 to 2.04). Compared with duration of pushing <15 min, a duration of pushing ⩾60 min increased rates of acidosis from 0.57 to 1.69% (adjusted RR 2.55 (95% CI 1.51 to 4.30)). CONCLUSION: Prolonged durations of second stage of labor and pushing are associated with increased RRs of adverse neonatal outcomes. Clinical assessment of fetal well-being is essential when durations of second stage and pushing increases.

Prolonged second stage of labour, maternal infectious disease, urinary retention and other complications in the early postpartum period.

OBJECTIVE: To study the association between duration of second stage of labour and risks of maternal complications (infection, urinary retention, haematoma or ruptured sutures) in the early postpartum period. DESIGN: Population-based cohort study. SETTING AND SAMPLE: We included 72 593 mothers with singleton vaginal deliveries at ≥37 weeks of gestation in cephalic presentation, using the obstetric database from the Stockholm-Gotland region in Sweden, 2008-12. METHODS: Logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated and adjustments were made for maternal age, body mass index, height, smoking, cohabitation, gestational age, labour induction, epidural analgesia and oxytocin augmentation. RESULTS: Rates of any complication varied by parity from 7.3% in parous women with previous caesarean section, 4.8% in primiparas and 1.7% in parous women with no previous caesarean section. Compared with a second stage <1 hour, the adjusted ORs for any complication (95% CI) in primiparas were for 1 to <2 hours 1.28 (1.11-1.47); 2 to <3 hours 1.54 (1.32-1.79), 3 to <4 hours 1.63 (1.38-1.93) and ≥4 hours 2.08 (1.74-2.49). The corresponding adjusted ORs for parous women without previous caesarean were 2.27 (1.78-2.90), 2.97 (2.09-4.22), 3.65 (2.25-5.94) and 3.16 (1.44-6.94), respectively. The adjusted ORs for women with previous caesarean were for 1 to <2 hours 1.62 (1.13-2.32); 2 to <3 hours 1.56 (1.00-2.43), 3 to <4 hours 2.42 (1.52-3.87), and ≥4 hours 2.31 (1.25-4.24). CONCLUSIONS: Risks of maternal complications in the postpartum period increase with duration of second stage of labour also after accounting for maternal, pregnancy and delivery characteristics. Special attention has to be given to parous women with previous caesarean deliveries.

The Swedish CArdioPulmonary BioImage Study: objectives and design.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

Small constrained SP1-7 analogs bind to a unique site and promote anti-allodynic effects following systemic injection in mice.

Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect.

Labour dystocia--risk of recurrence and instrumental delivery in following labour--a population-based cohort study.

OBJECTIVE: To investigate risk of recurrence of labour dystocia and mode of delivery in second labour after taking first labour and fetal and maternal characteristics into account. DESIGN: A population-based cohort study. SETTING: The Swedish Medical Birth Register from 1992 to 2006. POPULATION: A total of 239 953 women who gave birth to their first and second singleton infants in cephalic presentation at ≥ 37 weeks of gestation with spontaneous onset of labour. METHODS: We used logistic regression analysis to estimate crude and adjusted odds ratios. MAIN OUTCOME MEASURES: Labour dystocia and mode of delivery in second labour. RESULTS: Overall labour dystocia affected only 12% of women with previous dystocia. Regardless of mode of first delivery, rates of dystocia in the second labour were higher in women with than without previous dystocia, but were more pronounced in women with previous caesarean section (34%). Analyses with risk score groups for dystocia (risk factors were long interpregnancy interval, maternal age ≥ 35 years, obesity, short maternal stature, not cohabiting and post-term pregnancy) showed that risk of instrumental delivery in second labour increased with previous dystocia and increasing risk score. Among women with trial of labour after caesarean section with previous dystocia and a risk score of 3 or more, 66% had a vaginal instrumental or caesarean delivery (17 and 49%, respectively). In women with trial of labour after caesarean section without previous dystocia and a risk score of 0, corresponding risk was 32% (14 and 18%, respectively). CONCLUSION: Previous labour dystocia increases the risk of dystocia in subsequent delivery. Taking first labour and fetal and maternal characteristics into account is important in the risk assessments for dystocia and instrumental delivery in second labour.

Effect of bacterial vaginosis on the pharmacokinetics of misoprostol in early pregnancy.

BACKGROUND: Misoprostol has been shown to be an effective agent for cervical ripening and termination of early pregnancy especially when administered vaginally. Our objective was to evaluate whether bacterial vaginosis (BV) affected the pharmacokinetics of vaginally administered misoprostol during early pregnancy. METHODS: Ten women with BV and 10 healthy women requesting medical abortion up to 9 weeks of pregnancy were administered 200 mg mifepristone followed 24-48 h later by a single dose of 800 µg misoprostol vaginally. Blood samples were taken before (0 h) and 0.5, 1, 2, 3 and 4 h after misoprostol administration. Misoprostol acid was determined in serum samples using liquid chromatography/tandem mass spectrometry. RESULTS: All women with BV had a vaginal pH > 4.7. The mean bioavailability measured as the area under the curve (AUC) and maximum concentration (C(max)) appeared higher in the control than in the BV group (1458.7 versus 878.1 pg h/ml) and (630.7 versus 342.5 pg/ml), respectively, but did not achieve statistical significance and there was no other significant difference in the pharmacokinetics between the two groups. However, if two women with vaginal pH > 4.7 were excluded from the control group the difference in AUC240 (1359 versus 878.1 pgh/ml) reached statistical significance (P = 0.048). CONCLUSIONS: BV had an effect on pharmacokinetics of vaginally administered misoprostol in early pregnancy. However, the results should be interpreted with caution due to the small sample size and marked individual variations.

Child and parental surveys about pre-hospitalization information provision.

BACKGROUND: There is little available information about what children and parents would like to know about a forthcoming hospitalization and what they currently receive. METHODS: The current study was a survey of 102 children between the ages of 6 and 10 years and their parents recruited either from the Recovery Unit following day surgery or from the wards following overnight admissions at Sydney Children's Hospital, Australia. Information was obtained about each child's experience in hospital, the nature and format of information that they had received prior to the admission, and what information the child/parent thought would be helpful to receive. RESULTS: Parents recorded a total of 163 questions asked by children prior to their admission. Questions related to timing (e.g. duration of admission, length of procedure), pain, procedural information, anaesthesia, needles, whether parents can be present, activities to do in hospital, seeking explanations ('Why' questions), hospital environment, seeking reassurance and miscellaneous questions. Children who were satisfied with the amount of information they received before coming to hospital subsequently reported that they would be significantly less scared should they need to come back to hospital for a future procedure. A total of 46.7% of children received information about their hospitalization from their parent(s) and a further 12% from a doctor and parent. CONCLUSIONS: Children were found to have many questions about a forthcoming hospitalization. Parents were found to have a major role as information providers. Further research is needed to assess parental confidence and competence to meet their child's information needs.

Survival among motherless children in rural and urban areas in Guinea-Bissau.

AIM: With the increasing incidence of HIV and TB, motherless children are becoming a rapidly growing problem in Africa. However, few studies describe the survival patterns of these children. The aim of this study was to investigate the mortality of motherless children in urban and rural areas of Guinea-Bissau. METHODS: A historical cohort study was set up in urban and rural areas in Guinea-Bissau. Motherless children were selected from two study cohorts under demographic surveillance since 1990. The relatives of 128 motherless children from the rural cohort and 192 from the urban area, as well as a total of 807 controls, were examined and interviewed. RESULTS: Controlling for significant background factors revealed that motherless children had a markedly higher mortality than that of controls in both urban (mortality rate ratio (MR) 2.32 (95% confidence interval 1.11-4.84)) and rural areas (MR = 4.16 (2.79-6.22)). Virtually all the excess mortality occurred among children under 2 y of age when their mother died. Few motherless children had been provided with surrogate breastfeeding. CONCLUSIONS: Since nearly all children in Guinea are breastfed until 2 y of age, premature weaning may be one of the major causes of the higher mortality rates observed among motherless children.

Prospects for cleaning ash in the acidic effluent from bioleaching of sulfidic concentrates.

Leaching of ashes in sulfuric acid (pH 1.0, liquid-to-solid (L/S) ratio 10:1, 25 degrees C) has been characterized with respect to the neutralizing capacity and the dissolution of dominant ions and trace elements. The conditions mimic the oxidation stage of a biohydrometallurgical process for base metal production from sulfidic mineral concentrates. Direct acid leaching of ash, integrated with this metallurgical process, offers a feasible route to the sustainable handling of metal-rich ashes. The treated ash will be deposited together with the inert mineral residue. Cd, Co, Cu, Ni and Zn are effectively leached and can be recovered utilizing existing hydrometallurgical technology, but the recovery of other readily dissolved metals, notably Mn, U and V, requires that additional steps are implemented. We make two recommendations for industrial processes. The first is to replace limestone with ash from biofuels, except peat, for pH control in biohydrometallurgical processing. This requires a modest increase of fresh alkali compared with limestone. The second is to implement sulfuric acid leaching of fly ash from the combustion of solid waste and other metal-rich fuels (used wood, tires), thereby avoiding costly ash-deposits. There is a significant economic incentive for these changes, since no costly ash-deposits and less limestone will be needed.

Factors associated with maternal mortality in rural Guinea-Bissau. A longitudinal population-based study.

OBJECTIVE: To assess demographic and obstetric risk factors for pregnancy-related death in a multiethnic rural population in a developing country. DESIGN: A prospective survey of women in the fertile age-range. SETTING: Rural Guinea-Bissau. POPULATION: More than 15,000 women living in 100 clusters were visited at six-monthly intervals over a period of more than six years. A total of 10,931 pregnancies were registered prospectively; 85 of these pregnancies resulted in maternal or late maternal death. MAIN OUTCOME MEASURE: Maternal mortality ratio. METHOD: In the rural areas of Guinea-Bissau, we conducted a prospective survey of women in the fertile age range. More than 15,000 women living in 100 clusters were visited at 6-monthly intervals over a period of more than six years. An analysis of demographic, environmental and obstetric risk factors for maternal death was performed based on 10,931 prospectively registered pregnancies; 85 of these pregnancies resulted in maternal or late maternal death. RESULTS: In the adjusted model maternal mortality ratio increased with increasing distance from the regional hospital (OR>25 km = 7.4 [95% CI: 1.6-132]). Multiple pregnancy was found to increase the risk of maternal death (OR = 3.4 [95% CI: 1.3-7.5]). The risk of subsequent maternal death was increased if the fetus was stillborn (OR = 5.3 [95% CI: 2.8-9.4]). Women living in the region of Gabu had higher mortality than those living in Biombo (OR = 2.5 [95% CI: 1.3-5.1]). No category of age or parity were associated with an increased risk of maternal mortality. Predictive values did not exceed 3% for any of the significant risk factors. CONCLUSIONS: For the purpose of reducing maternal mortality, the screening approach of antenatal care is of limited value. Age and parity should not be used routinely as selection criteria for transfer of otherwise healthy pregnant women to higher-level health institutions. Twin pregnancy seems to be the only operational risk factor identified in this study. Stillbirth is associated with an increased risk of maternal death. Regional differences must be studied further. The distance to emergency obstetric care (EOC) may determine the outcome of a complicated delivery.

Tacrine and rate of progression in Alzheimer's disease--relation to ApoE allele genotype.

Today, cognitive impairment can be successfully treated with acetylcholine esterase inhibitors (AChE-I) in many, but not all, patients with Alzheimer's disease (AD). To investigate the relation between tacrine treatment, inheritance of ApoE epsilon4 alleles, and rate of progression, the differences in MMSE and CIBIC scores (efficacy parameters) after 6 and 12 months of tacrine (an AChE-I) treatment were investigated in 145 AD patients. Of these, 84 were ApoE epsilon4-positive (ApoE4) and 61 were ApoE epsilon4-negative (ApoE2-3). No differences were found after 6 months of treatment, but after 12 months the CIBIC scores revealed that the ApoE4 patients had declined more than the ApoE2-3 patients (p < 0.05). No differences were found for the last 6 months of treatment. The results primarily suggest a faster rate of decline in the ApoE4 AD compared to the ApoE2-3, but may also reflect that ApoE epsilon4 genotype inheritance is a negative predictor of treatment effect of tacrine in AD patients.

Prevalences of HTLV-1 infection and associated risk determinants in an urban population in Guinea-Bissau, West Africa.

OBJECTIVE: To assess the prevalence and modes of transmission of HTLV-1 infection in an adult population in Bissau, and to evaluate possible interactions between the pattern of spread of HTLV-1 and HIV-1/HIV-2. DESIGN AND METHODS: Univariate and multivariate analyses were used to evaluate gender-and age-specific HTLV-1 prevalences as well as associated risk determinants in an adult population based on a serosurvey comprising 2127 individuals from 304 randomly selected houses in Bissau. RESULTS: Using stringent Western blot criteria, the overall seroprevalence of HTLV-1 was 3.6%, 2.2% among men and 4.7% among women, respectively. One individual was seropositive to HTLV-2. The prevalence of HTLV-1, which increased with age in both genders, however more markedly among women, was >4 times higher (9.4%) among older individuals (>44 years of age) than among younger individuals (2.4%). Blood transfusion and HIV-2 seropositivity were independently associated with HTLV-1 seropositivity in men. Among women, both HIV-2 seropositivity and HIV-1 seropositivity were significant risk determinants. Having had sexual partners was associated with a fivefold increased risk among women but did not reach significance. CONCLUSION: The adult population of Guinea-Bissau has a higher prevalence of HTLV-1 than reported from most other countries in West Africa. The gender-and age-specific pattern of spread of HTLV-1 closely resembles that observed for HIV-2, another retrovirus prevalent to the region. The close correlation between HTLV-1 and HIV-2 most likely reflects the shared risk factors related to sexual behavior. The implication of the high percentage of double infections in this population needs to be determined.

Class 1 integron-borne, multiple-antibiotic resistance encoded by a 150-kilobase conjugative plasmid in epidemic vibrio cholerae O1 strains isolated in Guinea-Bissau.

In the 1996-1997 cholera epidemic in Guinea-Bissau, surveillance for antimicrobial resistance showed the emergence of a multidrug-resistant strain of Vibrio cholerae O1 during the course of the epidemic. The strain was resistant to ampicillin, erythromycin, tetracycline, furazolidone, aminoglycosides, trimethoprim, and sulfamethoxazole. Concomitant with the emergence of this strain, we observed a resurgence in the number of registered cholera cases as well as an increase in the case fatality rate from 1.0% before the emergence of the multiple-drug-resistant strain to 5.3% after the emergence of the strain. Our study shows that the strain contained a 150-kb conjugative multiple-antibiotic resistance plasmid with class 1 integron-borne gene cassettes encoding resistance to trimethoprim (dhfrXII) and aminoglycosides [ant(3")-1a]). The finding of transferable resistance to almost all of the antibiotics commonly used to treat cholera is of great public health concern. Studies should be carried out to determine to what extent the strain or its resistance genes have been spread to other areas where cholera is endemic.

NMR structure of oxidized glutaredoxin 3 from Escherichia coli.

A high precision NMR structure of oxidized glutaredoxin 3 [C65Y] from Escherichia coli has been determined. The conformation of the active site including the disulphide bridge is highly similar to those in glutaredoxins from pig liver and T4 phage. A comparison with the previously determined structure of glutaredoxin 3 [C14S, C65Y] in a complex with glutathione reveals conformational changes between the free and substrate-bound form which includes the sidechain of the conserved, active site tyrosine residue. In the oxidized form this tyrosine is solvent exposed, while it adopts a less exposed conformation, stabilized by hydrogen bonds, in the mixed disulfide with glutathione. The structures further suggest that the formation of a covalent linkage between glutathione and glutaredoxin 3 is necessary in order to induce these structural changes upon binding of the glutathione peptide. This could explain the observed low affinity of glutaredoxins for S-blocked glutathione analogues, in spite of the fact that glutaredoxins are highly specific reductants of glutathione mixed disulfides.

Protection from cholera by adding lime juice to food - results from community and laboratory studies in Guinea-Bissau, West Africa.

Epidemiological studies have shown that food plays an important role in the transmission of Vibrio cholerae, and different foods have been incriminated in many epidemic outbreaks of cholera. Storing contaminated meals at ambient temperatures allows growth of V. cholerae. Some ingredients such as lime juice may inhibit the survival of V. cholerae in foods. During an epidemic caused by V. cholerae O1 in Guinea-Bissau in 1996, a case control study was conducted in the capital Bissau, the main affected region with an attack rate of 7.4%. Cases were hospitalized patients and controls were matched for area, gender and age. Lime juice in the sauce eaten with rice gave a strong protective effect (odds ratio [OR] = 0.31, 95% confidence interval [CI] = 0.17-0.56), and tomato sauce was also protective (OR = 0.36, 95% CI = 0.24-0.54). On the other hand, use of a bucket for storage of water in the house was associated with increased risk (OR = 4.4, CI = 2.21-8.74). Laboratory experiments to elucidate the inhibitory effect of different concentrations of lime juice on survival of V. cholerae in meals showed that V. cholerae thrives in rice with peanut sauce, but lime juice inhibited its growth. Since lime juice is a common ingredient of sauces, its use should be further encouraged to prevent foodborne transmission in the household during cholera outbreaks.