Maternal health and human rights

In Malawi the maternal mortality ratio is extremely high. Since almost all maternal deaths are avoidable, maternal mortality is also an issue of human rights. This paper examines the root causes of high maternal mortality in Malawi and applies a human rights-based approach to the reduction of maternal mortality. It recommends roles for the various duty-bearers.It describes indicators to monitor and evaluate the strategy and suggests how transparency and accountability should be ensured. In conclusion, full and effective implementation of the strategy is indispensable for achieving the fifth Millennium Development Goal that calls for the reduction of maternal mortality

<i>In</i> <i>vitro </i>regulation of fibroblast growth factor 23 by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D synthesized by osteocyte-like MC3T3-E1 cells

Fibroblast growth factor 23 (FGF23) is produced and secreted by osteocytes and is essential for maintaining phosphate homeostasis. One of the main regulators of FGF23, 1,25-dihydroxyvitamin D (1,25(OH)2D3), is primarily synthesized in the kidney from 25-hydroxyvitamin D (25(OH)D) by 1α-hydroxylase (encoded by CYP27B1). Hitherto, it is unclear whether osteocytes can convert 25(OH)D and thereby allow for 1,25(OH)2D3 to induce FGF23 production and secretion locally. Here, we differentiated MC3T3-E1 cells toward osteocyte-like cells expressing and secreting FGF23. Treatment with 10-6 M 25(OH)D resulted in conversion of 25(OH)D to 150 pmol/L 1,25(OH)2D3 and increased FGF23 expression and secretion, but the converted amount of 1,25(OH)2D3 was insufficient to trigger an FGF23 response, so the effect on FGF23 was most likely directly caused by 25(OH)D. Interestingly, combining phosphate with 25(OH)D resulted in a synergistic increase in FGF23 expression and secretion, likely due to activation of additional signaling pathways by phosphate. Blockage of the vitamin D receptor (VDR) only partially abolished the effects of 25(OH)D or 25(OH)D combined with phosphate on Fgf23, while completely inhibiting the upregulation of cytochrome P450 family 24 subfamily A member 1 (Cyp24a1), encoding for 24-hydroxylase. RNA sequencing and in silico analyses showed that this could potentially be mediated by the nuclear receptors Retinoic Acid Receptor β (RARB) and Estrogen Receptor 2 (ESR2). Taken together, we demonstrate that osteocytes are able to convert 25(OH)D to 1,25(OH)2D3, but this is insufficient for FGF23 activation, implicating a direct effect of 25(OH)D in the regulation of FGF23, which occurs at least partially independent from its cognate VDR. Moreover, phosphate and 25(OH)D synergistically increase expression and secretion of FGF23, which warrants investigating consequences in patients receiving a combination of vitamin D analogues and phosphate supplements. These observations help us to further understand the complex relations between phosphate, vitamin D, and FGF23.</p

Postoperative outcome of caesarean sections and other major emergency obstetric surgery by clinical officers and medical officers in Malawi

<p>Abstract</p> <p>Background</p> <p>Clinical officers perform much of major emergency surgery in Malawi, in the absence of medical officers. The aim of this study was to validate the advantages and disadvantages of delegation of major obstetric surgery to non-doctors.</p> <p>Methods</p> <p>During a three month period, data from 2131 consecutive obstetric surgeries in 38 district hospitals in Malawi were collected prospectively. The interventions included caesarean sections alone and those that were combined with other interventions such as subtotal and total hysterectomy repair of uterine rupture and tubal ligation. All these surgeries were conducted either by clinical officers or by medical officers.</p> <p>Results</p> <p>During the study period, clinical officers performed 90% of all straight caesarean sections, 70% of those combined with subtotal hysterectomy, 60% of those combined with total hysterectomy and 89% of those combined with repair of uterine rupture. A comparable profile of patients was operated on by clinical officers and medical officers, respectively. Postoperative outcomes were almost identical in the two groups in terms of maternal general condition – both immediately and 24 hours postoperatively – and regarding occurrence of pyrexia, wound infection, wound dehiscence, need for re-operation, neonatal outcome or maternal death.</p> <p>Conclusion</p> <p>Clinical officers perform the bulk of emergency obstetric operations at district hospitals in Malawi. The postoperative outcomes of their procedures are comparable to those of medical officers. Clinical officers constitute a crucial component of the health care team in Malawi for saving maternal and neonatal lives given the scarcity of physicians.</p

The difficulties of conducting maternal death reviews in Malawi

<p>Abstract</p> <p>Background</p> <p>Maternal death reviews is a tool widely recommended to improve the quality of obstetric care and reduce maternal mortality. Our aim was to explore the challenges encountered in the process of facility-based maternal death review in Malawi, and to suggest sustainable and logically sound solutions to these challenges.</p> <p>Methods</p> <p>SWOT (strengths, weaknesses, opportunities and threats) analysis of the process of maternal death review during a workshop in Malawi.</p> <p>Results</p> <p><it>Strengths</it>: Availability of data from case notes, support from hospital management, and having maternal death review forms. <it>Weaknesses</it>: fear of blame, lack of knowledge and skills to properly conduct death reviews, inadequate resources and missing documentation. <it>Opportunities</it>: technical assistance from expatriates, support from the Ministry of Health, national protocols and high maternal mortality which serves as motivation factor. <it>Threats</it>: Cultural practices, potential lawsuit, demotivation due to the high maternal mortality and poor planning at the district level. <it>Solutions</it>: proper documentation, conducting maternal death review in a blame-free manner, good leadership, motivation of staff, using guidelines, proper stock inventory and community involvement.</p> <p>Conclusion</p> <p>Challenges encountered during facility-based maternal death review are provider-related, administrative, client related and community related. Countries with similar socioeconomic profiles to Malawi will have similar 'pull-and-push' factors on the process of facility-based maternal death reviews, and therefore we will expect these countries to have similar potential solutions.</p

Dopamine Increases a Value-Independent Gambling Propensity

Although the impact of dopamine on reward learning is well documented, its influence on other aspects of behavior remains the subject of much ongoing work. Dopaminergic drugs are known to increase risk-taking behavior, but the underlying mechanisms for this effect are not clear. We probed dopamine’s role by examining the effect of its precursor L-DOPA on the choices of healthy human participants in an experimental paradigm that allowed particular components of risk to be distinguished. We show that choice behavior depended on a baseline (ie, value-independent) gambling propensity, a gambling preference scaling with the amount/variance, and a value normalization factor. Boosting dopamine levels specifically increased just the value-independent baseline gambling propensity, leaving the other components unaffected. Our results indicate that the influence of dopamine on choice behavior involves a specific modulation of the attractiveness of risky options—a finding with implications for understanding a range of reward-related psychopathologies including addiction

A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?

Addiction to a wide range of substances of abuse has been suggested to reflect a ‘Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D(2) receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30–40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity

Season of Birth and Dopamine Receptor Gene Associations with Impulsivity, Sensation Seeking and Reproductive Behaviors

Season of birth (SOB) has been associated with many physiological and psychological traits including novelty seeking and sensation seeking. Similar traits have been associated with genetic polymorphisms in the dopamine system. SOB and dopamine receptor genetic polymorphisms may independently and interactively influence similar behaviors through their common effects on the dopaminergic system.Based on a sample of 195 subjects, we examined whether SOB was associated with impulsivity, sensation seeking and reproductive behaviors. Additionally we examined potential interactions of dopamine receptor genes with SOB for the same set of traits. Phenotypes were evaluated using the Sociosexual Orientation Inventory, the Barratt Impulsivity Scale, the Eysenck Impulsivity Questionnaire, the Sensation Seeking Scale, and the Delay Discounting Task. Subjects were also asked about their age at first sex as well as their desired age at the birth of their first child. The dopamine gene polymorphisms examined were Dopamine Receptor D2 (DRD2) TaqI A and D4 (DRD4) 48 bp VNTR. Primary analyses included factorial genderxSOB ANOVAs or binary logistic regression models for each dependent trait. Secondary analysis extended the factorial models by also including DRD2 and DRD4 genotypes as independent variables. Winter-born males were more sensation seeking than non-winter born males. In factorial models including both genotype and season of birth as variables, two previously unobserved effects were discovered: (1) a SOBxDRD4 interaction effect on venturesomeness and (2) a DRD2xDRD4 interaction effect on sensation seeking.These results are consistent with past findings that SOB is related to sensation seeking. Additionally, these results provide tentative support for the hypothesis that SOB modifies the behavioral expression of dopaminergic genetic polymorphism. These findings suggest that SOB should be included in future studies of risky behaviors and behavioral genetic studies of the dopamine system

Suicidal Behavior and Alcohol Abuse

Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates