Fine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairs

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

Eating habits and psychopathology: translation, adaptation, reliability of the Nutrition Behavior Inventory to Portuguese and relation to psychopathology

Objective: The Nutrition-Behavior Inventory (NBI) is a self-administered instrument that allows eating habits to be correlated with psychopathological symptoms. The objective was to translate and adapt the NBI to Portuguese, and test the Portuguese NBI’s reliability. The second aim was to verify its sensitivity for identification of risk factors in terms of behavior/eating habits in children and adolescents. Methods: The NBI was translated, adapted, and back-translated. The Portuguese version of the NBI was then applied (N = 96; 9-12 years). In order to verify the internal consistency, Cronbach’s alpha was used. The psychopathological indicators of the participants were accessed using the Child Behavior Checklist (CBCL). The mean CBCL scores were analyzed in relation to the NBI data (cutoff point: ≥ 30 with indicators, and < 30 without). Results: Internal consistency was high (Cronbach’s alpha = 0.89) for the NBI. The CBCL scores correlated significantly with NBI (> 30) on the following: anxiety and depression (p = 0.041), social difficulties (p = 0.028), attention problems (p = 0.001), aggressive behavior (p = 0.015); ADHD (p < 0.001), and conduct problems (p = 0.032). Conclusion: The present results indicate that the NBI is a reliable instrument. The NBI can be useful for evaluating psychopathological symptoms related to the eating habits and behaviors of children and adolescents.

Long-term prognosis of geriatric major depression in relation to cognition and white matter integrity: follow up of two cases

INTRODUCTION: The geriatric depression (GD) represents one of the most frequent psychiatric disorders in outpatient services specialized in old-age treatment. OBJECTIVE: The course of two illustrative cases of GD is discussed, highlighting its clinical picture after antidepressant treatment and underlining variables related to disease prognosis, treatment effectiveness and conversion to major cognitive disorders such as vascular dementia (VD). METHODS: The cognitive performance, depressive symptoms, autonomy and brain structural measurements as white matter hyperintensities (WMH) and hippocampal size, and microstructural integrity of WM with diffusion tensor imaging were followed during four years. RESULTS: Case 1, with a severe degree of WMH, was associated with worsening cognition and increasing functional disability. Case 2, with mild WMH, an improvement of cognitive functioning could be seen. CONCLUSIONS: The existence of different subtypes of GD, as presented in this report, points a pathophysiological heterogeneity of GD, and suggests a possible continuum vascular depression (VaDp) and vascular cognitive impairment (VCI).

A genetic perspective on African prehistory

The various genetic systems (mitochondrial DNA, the Y-chromosome and the genome-wide autosomes) indicate that Africa is the most genetically diverse continent in the world and the most likely place of origin for anatomically modern humans. However, where in Africa modern humans arose and how the current genetic makeup within the continent was shaped is still open to debate. Here, we summarize the debate and focus especially on the maternally inherited mitochondrial DNA (mtDNA) and a recently revised chronology for the African mtDNA tree. We discuss the possible origin of modern humans in southern, eastern or Central Africa; the possibility of a migration from southern to eastern Africa more than 100 ka, carrying lineages within mtDNA haplogroup L0; the evidence for a climate-change-mediated population expansion in eastern Africa involving mtDNA haplogroup L3, leading to the “out-of-Africa” migration around 70–60 ka; the re-population of North Africa from the Near East around 40–30 ka suggested by mtDNA haplogroups U6 and M1; the evidence for population expansions and dispersals across the continent at the onset of the Holocene ; and the impact of the Bantu dispersals in Central, eastern and southern Africa within the last few millennia.

Recurrence of atrial septal defect in three generations

Beginning with a patient presenting with an atrial septal defect (ASD) of the secundum type, the genealogy was identified in four affected individuals who belonged to three successive generations of the same family. The defects were visually confirmed in all individuals and were found to be anatomically similar. No other congenital malformations were present in these individuals. The genealogy was identified in 1972, when ASD recurred in two generations, and it was concluded that the mechanism of transmission was autosomal recessive. The fifth individual, identified 21 years later, and having an anomaly identical to that of the others, was the child of a couple who had no consaguinity and whose mother was a member of the previously studied genealogy. Considering the absence of phenotype in the parents and the rarity of the ASD gene in the general population, the occurrence of the uniparental disomy for this family nucleus, and the same autosomal recessive mechanism of transmission by this affected individual is possible. This study reports the familial occurrence of ASD by genetic mechanisms of transmission, emphasizing the necessity for genetic-clinical studies in members of the familial nucleus in order to detect new carriers, who usually are asymptomatic, thereby allowing for early and adequate treatment of individuals who may be affected.

Exercise and heart failure. Relation of the severity of the disease to the anaerobic threshold and the respiratory compensation point

OBJECTIVE - To identify, the anaerobic threshold and respiratory compensation point in patients with heart failure. METHODS - The study comprised 42 Men,divided according to the functional class (FC) as follows: group I (GI) - 15 patients in FC I; group II (GII) - 15 patients in FC II; and group III (GIII) - 12 patients in FC III. Patients underwent a treadmill cardiopulmonary exercise test, where the expired gases were analyzed. RESULTS - The values for the heart rate (in bpm) at the anaerobic threshold were the following: GI, 122±27; GII, 117±17; GIII, 114±22. At the respiratory compensation point, the heart rates (in bpm) were as follows: GI, 145±33; GII, 133±14; GIII 123±22. The values for the heart rates at the respiratory compensation point in GI and GIII showed statistical difference. The values of oxygen consumption (VO2) at the anaerobic threshold were the following (in ml/kg/min): GI, 13.6±3.25; GII, 10.77±1.89; GIII, 8.7±1.44 and, at the respiratory compensation point, they were as follows: GI, 19.1±2.2; GII, 14.22±2.63; GIII, 10.27±1.85. CONCLUSION - Patients with stable functional class I, II, and III heart failure reached the anaerobic threshold and the respiratory compensation point at different levels of oxygen consumption and heart rate. The role played by these thresholds in physical activity for this group of patients needs to be better clarified.

Myocardial infarction and subsequent pregnancy

We report the case of a 40-year-old woman with 2 previous myocardial infarctions, revascularization surgery, and an ongoing pregnancy complicated with preeclampsia and fetal hypoxia. Her follow-up performed by a multidisciplinary team made possible the birth through cesarean section of a premature infant of the female sex with a very low birth weight, but without severe respiratory distress of the hyaline membrane disease type. Three months after the delivery, mother and daughter were healthy.

End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the "transient arterial hypertension protocol" (TAH), and a quick and 10 min sustained elevation, the "sustained arterial hypertension protocol"(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it "transitory" or "sustained", did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

Genetic regulatory mechanisms by means of extended interactive Petri nets

In our work we have chosen to integrate formalism for knowledge representation with formalism for process representation as a way to specify and regulate the overall activity of a multi-cellular agent. The result of this approach is XP,N, another formalism, wherein a distributed system can be modeled as a collection of interrelated sub-nets sharing a common explicit control structure. Each sub-net represents a system of asynchronous concurrent threads modeled by a set of transitions. XP,N combines local state and control with interaction and hierarchy to achieve a high-level abstraction and to model the complex relationships between all the components of a distributed system. Viewed as a tool XP,N provides a carefully devised conflict resolution strategy that intentionally mimics the genetic regulatory mechanism used in an organic cell to select the next genes to process.

The alarm distress baby scale in a longitudinal Portuguese study reanalyzed with attachment data

Article first published online: 13 NOV 2013

Mother's anxiety and depression during the third pregnancy trimester and neonate's mother versus stranger's face/voice visual preference

Background: Neonates show visual preference for their mother's face/voice and shift their attention from their mother to a stranger's face/voice after habituation. Aim: To assess neonate's mother versus stranger's face/voice visual preference, namely mother's anxiety and depression during the third pregnancy trimester and neonate's: 1) visual preference for the mother versus the stranger's face/voice (pretest visual preference), 2) habituation to the mother's face/voice and 3) visual preference for the stranger versus the mother's face/voice (posttest visual preference). Method: Mothers (N=100) filled out the Edinburgh Postnatal Depression Scale (EPDS) and the State Anxiety Inventory (STAI) both at the third pregnancy trimester and childbirth, and the “preference and habituation to the mother's face/voice versus stranger” paradigm was administered to their newborn 1 to 5 days after childbirth. Results: Neonates of anxious/depressed mothers during the third pregnancy trimester contrarily to neonates of non-anxious/non-depressed mothers did not look 1) longer at their mother's than at the stranger's face/voice at the pretest visual preference (showing no visual preference for the mother), nor 2) longer at the stranger's face/voice in the posttest than in the pretest visual preference (not improving their attention to the stranger's after habituation). Conclusion: Infants exposed to mother's anxiety/depression at the third gestational trimester exhibit less perceptual/social competencies at birth.

Mother's stress, mood and emotional involvement with the infant: 3 months before and 3 months after childbirth

Adverse effects of maternal anxiety and depression are well documented, namely on the foetus/child behaviour and development, but not as much attention has been given to the mother's emotional involvement with the offspring. To study mother's prenatal and postpartum stress, mood and emotional involvement with the infant, the State-Trait Anxiety Inventory, the Edinburgh Postnatal Depression Scale and the Mother-to-Infant Bonding Scale were filled in and cortisol levels were measured, 3 months before and 3 months after childbirth, in a sample of 91 Portuguese women. From pregnancy to the postpartum period, mother's cortisol levels, anxiety and emotional involvement toward the child decrease. No significant change was observed regarding mother's depression. Mother's depression predicted a worse emotional involvement before childbirth, while mother's anxiety predicted a worse emotional involvement with the infant after childbirth. Additionally, pregnant women with a worse emotional involvement with the offspring are at risk of poorer emotional involvement with the infant and higher anxiety and depression at 3 months postpartum. It should be given more attention to mother's poor emotional involvement with the offspring during pregnancy, as it interferes with her emotional involvement with the infant and her psychological adjustment 3 months after childbirth.

Mother-to-infant emotional involvement at birth

Objectives. To study mother-to-infant emotional involvement at birth, namely factors (socio-demographics, previous life events, type of delivery, pain at childbirth, support from partner, infant characteristics, early experiences with the newborn, and mother’s mood) that interfere with the mother’s positive, negative and not clear emotions toward the newborn. Methods. The Bonding Scale (an extended Portuguese version of the ‘New Mother-to-Infant Bonding Scale’) and the Edinburgh Postnatal Depression Scale were administrated during the first after delivery days to 315 mothers recruited at Ju´lio Dinis Maternity Hospital (MJD, Porto, Portugal). Results. A worse emotional involvement with the newborn was observed when the mother was unemployed, unmarried, had less than grade 9, previous obstetrical/psychological problems or was depressed, as well as when the infant was female, had neonatal problems or was admitted in the intensive care unit. Lower total bonding results were significantly predicted when the mother was depressed and had a lower educational level; being depressed, unemployed and single predicted more negative emotions toward the infant as well. No significant differences in the mother-to-infant emotional involvement were obtained for events related to childbirth, such as type of delivery, pain and partner support, or early experiences with the newborn; these events do not predict mother’s bonding results either. Conclusion. The study results support the need for screening and supporting depressed, unemployed and single mothers, in order to prevent bonding difficulties with the newborn at birth.