Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

Polarization of atoms plays a substantial role in molecular interactions. Class I and II force fields mostly calculate with fixed atomic charges which can cause inadequate descriptions for highly charged molecules, for example, ion channels or metalloproteins. Changes in charge distributions can be included into molecular mechanics calculations by various methods. Here, we present a very fast computational quantum mechanical method, the Bond Polarization Theory (BPT). Atomic charges are obtained via a charge calculation method that depend on the 3D structure of the system in a similar way as atomic charges of ab initio calculations. Different methods of population analysis and charge calculation methods and their dependence on the basis set were investigated. A refined parameterization yielded excellent correlation of R=0.9967. The method was implemented in the force field COSMOS-NMR and applied to the histidine-tryptophan-complex of the transmembrane domain of the M2 protein channel of influenza A virus. Our calculations show that moderate changes of side chain torsion angle χ1 and small variations of χ2 of Trp-41 are necessary to switch from the inactivated into the activated state; and a rough two-side jump model of His-37 is supported for proton gating in accordance with a flipping mechanism

Association between Anaemia during Pregnancy and Blood Loss at and after Delivery among Women with Vaginal Births in Pemba Island, Zanzibar, Tanzania

The study sought to identify determinants of blood loss at childbirth and 24 hours postpartum. The study was nested in a community-based randomized trial of treatments for anaemia during pregnancy in Wete Town, Pemba Island, Zanzibar, United Republic of Tanzania. Status of anaemia during pregnancy, nutritional information, obstetric history, and socioeconomic status were assessed at enrollment during routine antenatal care. Pregnant women presented for spontaneous vaginal delivery, and nurse-midwives collected information on labour and delivery via partograph. Blood-stained sanitary napkins and pads from childbirth and 24 hours postpartum were quantified using the alkaline hematin method. Moderate-to-severe anaemia (Hb <90 g/L) at enrollment was strongly associated with blood loss at delivery and the immediate postpartum period, after adjusting for maternal covariates and variables of biological relevance to blood loss. Greater blood loss was associated (p<0.10) with duration of the first stage of labour, placental weight, receipt of oxytocin, preterm birth, and grand multiparity. The findings provide unique evidence of a previously-suspected link between maternal anaemia and greater blood loss at childbirth and postpartum. Further research is needed to confirm these findings on a larger sample of women to determine whether women with moderate-to-severe anaemia are more likely to experience postpartum haemorrhage and whether appropriate antenatal or peripartum care can affect the relationships described here

Prioritization of Biomarker Targets in Human Umbilical Cord Blood: Identification of Proteins in Infant Blood Serving as Validated Biomarkers in Adults

Background: Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped

Association between Anaemia during Pregnancy and Blood Loss at and after Delivery among Women with Vaginal Births in Pemba Island, Zanzibar, Tanzania

The study sought to identify determinants of blood loss at childbirth and 24 hours postpartum. The study was nested in a community-based randomized trial of treatments for anaemia during pregnancy in Wete Town, Pemba Island, Zanzibar, United Republic of Tanzania. Status of anaemia during pregnancy, nutritional information, obstetric history, and socioeconomic status were assessed at enrollment during routine antenatal care. Pregnant women presented for spontaneous vaginal delivery, and nurse-midwives collected information on labour and delivery via partograph. Blood-stained sanitary napkins and pads from childbirth and 24 hours postpartum were quantified using the alkaline hematin method. Moderateto-severe anaemia (Hb &lt;90 g/L) at enrollment was strongly associated with blood loss at delivery and the immediate postpartum period, after adjusting for maternal covariates and variables of biological relevance to blood loss. Greater blood loss was associated (p&lt;0.10) with duration of the first stage of labour, placental weight, receipt of oxytocin, preterm birth, and grand multiparity. The findings provide unique evidence of a previously-suspected link between maternal anaemia and greater blood loss at childbirth and postpartum. Further research is needed to confirm these findings on a larger sample of women to determine whether women with moderate-to-severe anaemia are more likely to experience postpartum haemorrhage and whether appropriate antenatal or peripartum care can affect the relationships described here

A home calendar and recall method of last menstrual period for estimating gestational age in rural Bangladesh: a validation study

Background: The best method of gestational age assessment is by ultrasound in the first trimester; however, this method is impractical in large field trials in rural areas. Our objective was to assess the validity of gestational age estimated from prospectively collected date of last menstrual period (LMP) using crown-rump length (CRL) measured in early pregnancy by ultrasound. Methods: As part of a large, cluster-randomized, controlled trial in rural Bangladesh, we collected dates of LMP by recall and as marked on a calendar every 5 weeks in women likely to become pregnant. Among those with a urinetest confirmed pregnancy, a subset with gestational age of &lt;15 weeks (n = 353) were enrolled for ultrasound follow-up to measure CRL. We compared interview-assessed LMP with CRL gestational age estimates and classification of preterm, term, and post-term births. Results: LMP-based gestational age was higher than CRL by a mean (SD) of 2.8 (10.7) days; differences varied by maternal education and preterm birth (P &lt; 0.05). Lin\u2019s concordance correlation coefficient was good at ultrasound [0.63 (95 % CI 0.56, 0.69)] and at birth [0.77 (95 % CI 0.73, 0.81)]. Validity of classifying preterm birth was high but post-term was lower, with specificity of 96 and 89 % and sensitivity of 86 and 67 %, respectively. Results were similar by parity. Conclusions: Prospectively collected LMP provided a valid estimate of gestational age and preterm birth in a rural, low-income setting and may be a suitable alternative to ultrasound in programmatic settings and large field trials. Trial registration: ClinicalTrials.gov NCT0086047

From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus

Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures) and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells). We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping), failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial) place learning into navigational performance

Outcomes with a posterior reduced dental arch: a randomised controlled trial

OBJECTIVE: To compare function, patient satisfaction and quality of life of patients with a posterior reduced mandibular arch with those who had all missing teeth replaced with removable partial dentures. METHODS: Patients with at least 3 and not more than 6 posterior occluding pairs of teeth were enrolled sequentially and randomized into one of two treatment groups: a denture and no denture group. A research assistant allocated interventions; concealment was ensured using opaque-sealed envelopes. Analysis of data was performed in stages, adding samples of 10 incrementally, and stopping when the relevant statistical tests indicated a clear conclusion as judged by the power set at 80% or above. Study outcomes included patient satisfaction, function and survival of remaining teeth at 3 and 12 months post-intervention, using a visual analogue scale and the Oral Impacts on Daily Performance) Statistical analysis was performed by the ‘intention-to-treat’ principle. RESULTS: Age range of included patients was 23-55 years (mean=42.3; SD=9.2), with 78% being females. Most patients (70%) belonged to the low- or no-income group. Nine patients left the study, for different reasons. Primary outcomes for the denture group: 10% of the patients were not satisfied and 20% were unhappy with their function; for the no-denture group: 85% of the patients (with 15% having left the study) were satisfied with both their function and their non-denture status. CONCLUSION: Patients with posterior reduced mandibular dental arches reported greater perceived satisfaction, function and quality of life compared to those who had received a cobalt-chrome clasp-retained partial removable prosthesis.University of the Western Cape and Stellenbosch University Research Fund