Online spatial normalization for real-time FMRI.
Real-time functional magnetic resonance imaging (rtfMRI) is a recently emerged technique that demands fast data processing within a single repetition time (TR), such as a TR of 2 seconds. Data preprocessing in rtfMRI has rarely involved spatial normalization, which can not be accomplished in a short time period. However, spatial normalization may be critical for accurate functional localization in a stereotactic space and is an essential procedure for some emerging applications of rtfMRI. In this study, we introduced an online spatial normalization method that adopts a novel affine registration (AFR) procedure based on principal axes registration (PA) and Gauss-Newton optimization (GN) using the self-adaptive β parameter, termed PA-GN(β) AFR and nonlinear registration (NLR) based on discrete cosine transform (DCT). In AFR, PA provides an appropriate initial estimate of GN to induce the rapid convergence of GN. In addition, the β parameter, which relies on the change rate of cost function, is employed to self-adaptively adjust the iteration step of GN. The accuracy and performance of PA-GN(β) AFR were confirmed using both simulation and real data and compared with the traditional AFR. The appropriate cutoff frequency of the DCT basis function in NLR was determined to balance the accuracy and calculation load of the online spatial normalization. Finally, the validity of the online spatial normalization method was further demonstrated by brain activation in the rtfMRI data.


The beneficial effect of electro-acupuncture given at PC6 (Neiguan-point) by the increase in cardiac transient outward K+ current channel which depends on the gene and protein expressions in artificially induced myocardial ischemia rats.
This study explored the mechanism of electro-acupuncture (EA) at PC6 to improve the heart function by regulating the cardiac transient outward potassium current (= Ito) channel in myocardial ischemia (MI). Kv1.4 is the main component of the slow Ito (Ito.s) channel. Kv4.2 and Kv4.3 are the main components of the fast Ito (Ito.f) channel. KChIP2 is a compound protein of Ito channel. In this experiment, MI was induced by injecting isoproterenol in rats, and the gene and protein expressions of Kv1.4, Kv4.2, Kv4.3 and KChIP2 were lower [The gene and protein decreased (42.8 ± 4.3)% and (37.2 ± 4.7)% respectively.] than the control rats significantly (p < 0.05). After MI induction, the MI rats were divided into three groups, including PC6, LU7 (Lieque-point) and Non-acupoint group which were acupunctured at once a day for 7 days respectively. After EA at PC6 and LU7, the gene and protein expressions showed obvious increased [EA at PC6: the gene and protein increased (50.24 ± 5.4)% and (39.14 ± 5.3)% respectively. EA at LU7: the gene and protein increased (24.6 ± 2.8)% and (22.04 ± 5.5)% respectively] and they are all higher than MI rats significantly (p < 0.05). EA at PC6 and LU7 showed the same variation, and the effects of EA at PC6 and LU7 were better than Non-acupuncture-point (p < 0.05). The effects of EA at PC6 were significantly better [The gene and protein increased (19.74 ± 2.7)% and (14.14 ± 4.4)% respectively] than LU7 (p < 0.05). PC6 is an acupoint of the pericardium meridian, and the pericardium meridian which corresponds to adrenal gland according to Omura Y's research, can affect the heart function directly LU7 belong to the lung meridian, and the lung plays an important factor in blood circulation according to TCM. So PC6 is more effective than LU7 on heart function regulation. The results suggested that PC6 showed the target effect of meridian specificity on regulating the Kv channel in MI.


Botrytis cinerea induces local hypoxia in Arabidopsis leaves.
Low oxygen availability often is associated with soil waterlogging or submergence, but may occur also as hypoxic niches in otherwise aerobic tissues. Experimental evidence assigns a role in Botrytis cinerea resistance to a group of oxygen-unstable Ethylene Response Factors (ERF-VII). Given that infection by B. cinerea often occurs in aerobic organs such as leaves, where ERF-VII stability should be compromised, we explored the possibility of local leaf hypoxia at the site of infection. We analyzed the expression of hypoxia-responsive genes in infected leaves. Confocal microscopy was utilized to verify the localization of the ERF-VII protein RAP2.12. Oxygen concentration was measured to evaluate the availability of oxygen (O2 ). We discovered that infection by B. cinerea induces increased respiration, leading to a drastic drop in the O2 concentration in an otherwise fully aerobic leaf. The establishment of a local hypoxic area results in stabilization and nuclear relocalization of RAP2.12. The possible roles of defence elicitors, ABA and ethylene were evaluated. Local hypoxia at the site of B. cinerea infection allows the stabilization of ERF-VII proteins. Hypoxia at the site of pathogen infection generates a nearly O2 -free environment that may affect the stability of other N-degron-regulated proteins as well as the metabolism of elicitors.


Caspase-2 is resistant to inhibition by inhibitor of apoptosis proteins (IAPs) and can activate caspase-7.
Caspases are a family of cysteine proteases with roles in cytokine maturation or apoptosis. Caspase-2 was the first pro-apoptotic caspase identified, but its functions in apoptotic signal transduction are still being elucidated. This study examined the regulation of the activity of caspase-2 using recombinant proteins and a yeast-based system. Our data suggest that for human caspase-2 to be active its large and small subunits must be separated. For maximal activity its prodomain must also be removed. Consistent with its proposed identity as an upstream caspase, caspase-2 could provoke the activation of caspase-7. Caspase-2 was not subject to inhibition by members of the IAP family of apoptosis inhibitors.


[Persistent hyperinsulinemic hypoglycemia of infancy: case report]
OBJECTIVE: To report a case of Persistent Hyperinsulinemic Hypoglycemia in twins which is a situation not yet reported in the literature. METHODS: Report of seizures in identical twins, from consanguineous parents, with persistent hypoglycemia as cause of the seizures. Laboratory tests, performed for etiological investigation of the hypoglycemia, included thyroid hormones (T4/TSH), insulin, cortisol, growth hormone, stimulation test with glucagon (to evaluate the insulin/glucose relation), and histopathological study of the pancreas. RESULTS: Laboratorial investigation revealed a persistent hypoglycemia with hyperinsulinism which were confirmed with the stimulation test with glucagon. The histopathological exam showed a persistence of first generation pancreatic islet, confirming the diagnosis of Persistent Hyperinsulinemic Hypoglycemia in Infancy (the new denomination of Nesidioblastosis). CONCLUSION: Although rare, this condition must be early suspected early in the evaluation of hypoglycemia of the young infant, even out of the neonatal period, specially if the parents are consanguineous. The adequate therapy must be quickly initiated in order to prevent neurological damage.


3R optical regeneration: an all-optical solution with BER improvement.
We demonstrate that an optical regenerator architecture providing re-amplification, re-shaping, and re-timing based on the principle of spectral shift followed by filtering can lead to bit error ratio improvement of the signal passing through it. This is in contrast with typical regenerators based on the usual principle of power conversion from a transfer function, which are unable to improve the bit error ratio. At first, we provide the theoretical basis that explains this improvement. Then we present the regenerator architecture based on spectral shift followed by filtering and provide experimental evidence of bit error ratio improvement of a noisy signal from 3x10(-6) without regenerator to 2x10(-10) with regenerator.


The value of nucleolar organizer regions in uveal melanoma. The Collaborative Ocular Melanoma Study Group.
Silver staining of nucleolar organizer regions is an objective method for evaluating the malignancy of a variety of tumors. We studied 126 ciliochoroidal melanomas, three coincidental nevi that occurred in eyes with melanomas, and one magnocellular nevus collected from the Collaborative Ocular Melanoma Study to determine the effectiveness of the silver-stained nucleolar organizer region technique in assessing the malignant potential of these tumors. Malignant lesions demonstrated higher mean silver-stained nucleolar organizer region counts (4.347) than benign nevi (1.855) (P less than or equal to .0001). Among malignant melanomas, mixed-cell melanomas had slightly higher counts than spindle-cell melanomas (P less than or equal to .0001), but this difference was not important clinically. Results were also compared to other histopathologic variables, which disclosed correlation of silver-stained nucleolar organizer regions with mitoses and tumor size. Comparison with computerized cytomorphometric analyses of prognosis also disclosed significant correlation. This technique may prove to be a useful adjunct in the assessment of malignancy and treatment response of uveal melanomas.


Functional differences in trophic structure of offshore wind farm communities: A stable isotope study.
The proliferation of offshore wind energy installations causes a local change in biodiversity because these structures become heavily colonised by large quantities of fouling fauna, attract large mobile crustaceans and fish, and alter the macrofaunal communities in the soft sediments surrounding the wind turbines. Here, we analysed the stable isotope signals (δ13C and δ15N) of the faunal communities associated with a wind turbine, its scour protection layer (SPL) and the surrounding soft sediments. We hypothesised that structural differences in community composition would be reflected in food web complexity and that resource partitioning could be one of the mechanisms contributing to the co-existence of such dense communities. Sampling was conducted at a gravity-based foundation in the Belgian part of the North Sea, where both sessile and mobile organisms were collected along the depth gradient of the turbine, the SPL and the surrounding soft substrate. The results indicated that the structural differences of the communities are reflected in the food web complexity as indicated by the trophic niche size, the trophic diversity and the redundancy of the communities along the depth gradient. Higher food web complexity was associated with zones where high accumulation of organic matter occurs (soft substrate and SPL). Low food web complexity was observed in depth zones that are dominated by sessile suspension-feeding organisms (intertidal and Mytilus zone). The high trophic diversity and low redundancy observed within the trophic clusters of the soft substrate and the Metridium zone indicated that resource partitioning can be a mechanism allowing the co-existence of large densities of a wide variety of species.


Sequencing and analysis of the gene-rich space of cowpea.
Cowpea, Vigna unguiculata (L.) Walp., is one of the most important food and forage legumes in the semi-arid tropics because of its drought tolerance and ability to grow on poor quality soils. Approximately 80% of cowpea production takes place in the dry savannahs of tropical West and Central Africa, mostly by poor subsistence farmers. Despite its economic and social importance in the developing world, cowpea remains to a large extent an underexploited crop. Among the major goals of cowpea breeding and improvement programs is the stacking of desirable agronomic traits, such as disease and pest resistance and response to abiotic stresses. Implementation of marker-assisted selection and breeding programs is severely limited by a paucity of trait-linked markers and a general lack of information on gene structure and organization. With a nuclear genome size estimated at ~620 Mb, the cowpea genome is an ideal target for reduced representation sequencing. We report here the sequencing and analysis of the gene-rich, hypomethylated portion of the cowpea genome selectively cloned by methylation filtration (MF) technology. Over 250,000 gene-space sequence reads (GSRs) with an average length of 610 bp were generated, yielding ~160 Mb of sequence information. The GSRs were assembled, annotated by BLAST homology searches of four public protein annotation databases and four plant proteomes (A. thaliana, M. truncatula, O. sativa, and P. trichocarpa), and analyzed using various domain and gene modeling tools. A total of 41,260 GSR assemblies and singletons were annotated, of which 19,786 have unique GenBank accession numbers. Within the GSR dataset, 29% of the sequences were annotated using the Arabidopsis Gene Ontology (GO) with the largest categories of assigned function being catalytic activity and metabolic processes, groups that include the majority of cellular enzymes and components of amino acid, carbohydrate and lipid metabolism. A total of 5,888 GSRs had homology to genes encoding transcription factors (TFs) and transcription associated factors (TAFs) representing about 5% of the total annotated sequences in the dataset. Sixty-two (62) of the 64 well-characterized plant transcription factor (TF) gene families are represented in the cowpea GSRs, and these families are of similar size and phylogenetic organization to those characterized in other plants. The cowpea GSRs also provides a rich source of genes involved in photoperiodic control, symbiosis, and defense-related responses. Comparisons to available databases revealed that about 74% of cowpea ESTs and 70% of all legume ESTs were represented in the GSR dataset. As approximately 12% of all GSRs contain an identifiable simple-sequence repeat, the dataset is a powerful resource for the design of microsatellite markers. The availability of extensive publicly available genomic data for cowpea, a non-model legume with significant importance in the developing world, represents a significant step forward in legume research. Not only does the gene space sequence enable the detailed analysis of gene structure, gene family organization and phylogenetic relationships within cowpea, but it also facilitates the characterization of syntenic relationships with other cultivated and model legumes, and will contribute to determining patterns of chromosomal evolution in the Leguminosae. The micro and macrosyntenic relationships detected between cowpea and other cultivated and model legumes should simplify the identification of informative markers for marker-assisted trait selection and map-based gene isolation necessary for cowpea improvement.


Role of anti-vimentin antibodies in allograft rejection.
Production of anti-vimentin antibodies (AVA) after solid organ transplantation are common. Although classically thought to be expressed mainly within the cytosol, recent evidence demonstrates that extracellular or cell surface expression of vimentin is not unusual. This review examines the evidence to assess whether AVA contribute to allograft pathology. Clinical studies suggest that AVA are associated with cardiac allograft vasculopathy in heart transplant recipients. Studies in non-human primates confirm that production of AVA after renal and heart transplantation are not inhibited by Cyclosporine. Experimental studies have demonstrated that mice pre-immunised with vimentin undergo accelerated acute rejection and vascular intimal occlusion of cardiac allografts. Adoptive transfer of hyperimmune sera containing AVA into B-cell-knock-out mice caused accelerated rejection of allografted hearts, this is clear evidence that antibodies to vimentin accelerate rejection. AVA act in concert with the alloimmune response and AVA do not damage syngeneic or native heart allografts. Confocal microscopy of allografted organs in vimentin immunised mice shows extensive expression of vimentin on endothelial cells, apoptotic leukocytes and platelet/leukocyte conjugates, co-localising with C4d. One explanation for the ability of AVA to accelerate rejection would be fixation of complement within the graft and subsequent pro-inflammatory effects; there may also be interactions with platelets within the vasculature.


Clinical potential of bevacizumab in the treatment of metastatic and locally advanced cervical cancer: current evidence.
The addition of bevacizumab to established therapies for metastatic and locally advanced cervical cancer is an area of evolving research and a potential strategy toward improving historically suboptimal outcomes for women with advanced disease. Bevacizumab, when added to first-line chemotherapy, has now been shown to improve overall survival among women with metastatic cervical cancer, and recent Phase II data suggests it is safe and effective for patients with locally advanced disease treated with curative intent. Here we review the rationale and current evidence for bevacizumab in clinical practice, with an emphasis on the emerging role of bevacizumab in the treatment of metastatic and locally advanced cervical cancer.


[Quality of life in elderly patients living with HIV/AIDS].
This study's objective was to evaluate quality of life in older adults living with HIV/AIDS and the associations with socio-demographic, economic, and clinical characteristics, using a cross-sectional design. Data were collected on demographics, disease history, and economic status according to the Brazilian Economic Classification Criterion and Targeted Quality of Life Instrument (HAT-QoL). A total of 201 elderly participated, with the following characteristics: males (63.7%), single or divorced (51.3%), economic classes C, D, or E (61.7%), and low schooling (53.7%). Nearly two-thirds (130, or 64.7%) had been infected by the sexual route. The following were significantly correlated with two or up to seven domains in the HAT-QoL: age, individual and family income, and time since diagnosis. Quality of life in elderly living with HIV/AIDS showed the lowest scores in the domains related to concern over disclosure of their diagnosis, sexual activity, and financial concerns. Age, income, and time since diagnosis were the variables that most accounted for altered quality of life.


Circulating angiotensin converting enzyme levels are increased in concentric, but not eccentric, left ventricular hypertrophy in elderly men.
To study the cross-sectional relationship between circulating angiotensin converting enzyme (ACE) activity and echocardiographically determined left ventricular geometry in a study of 380 70-year-old men participating in a health-survey reexamination and 50 patients with hypertension. Two-dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of serum ACE activity. The serum ACE activity was higher in the elderly men with left ventricular concentric hypertrophy than it was in men with normal geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l, respectively, P < 0.01 for both comparisons before and after adjustment for the 24 h mean arterial pressure, body mass index, and use of antihypertensive medication). The serum ACE activity correlated with the thickness of the left ventricular interventricular septum (r = 0.12, P = 0.0095), the left ventricular relative wall thickness (r = 0.13, P = 0.0053 ), and the total peripheral resistance (r = 0.16, P = 0.0034), but not with the left ventricular mass (r = -0.039, P = 0.45) of these elderly men. The serum ACE activity in the hypertensive patients also correlated with the left ventricular interventricular septum thickness (r = 0.34, P = 0.020) independently of the 24 h mean arterial blood pressure, age, sex, body mass index, and insulin sensitivity. Levels of serum ACE activity are associated with left ventricular geometry.


Optimizing Survey Response Rates in Graduate Medical Education Research Studies.
Survey response rates of 70% or higher are needed if findings are to be considered generalizable. Unfortunately, survey studies of health professionals have declining response rates. We have conducted survey research with residents and residency directors for over 13 years. Here we describe the strategies we used to obtain optimal response rates in residency training research collaboratives. We administered over 6,000 surveys between 2007 and 2019 to evaluate the Preparing the Personal Physician for Practice and Length of Training Pilot studies, both of which involved redesigning residency training. Survey recipients included program directors, clinic managers, residents, graduates, as well as supervising physicians and clinic staff members. We logged and analyzed survey administration efforts and approaches to optimize strategies. Overall, we obtained response rates of 100% for program director surveys, 98% for resident surveys, 97% for continuity clinic surveys, 81% for graduates surveys, and 48% for the supervising physician and 43% for the clinic staff. Response rates were highest when the relationships between the evaluation team and survey recipients were closest. Strategies for optimizing response rates included (1) building relationships with all participants whenever possible, (2) sensitivity to survey timing and fatigue, and (3) using creative and persistent follow-up measures to encourage survey completion. High response rates are achievable, though they require an investment in time, resources, and ingenuity in connecting with study populations. Investigators conducting survey research must consider administrative efforts needed to achieve target response rates, including planning for funds accordingly.


High efficacy of clonal growth and expansion of adult neural stem cells.
Neural stem cells (NSCs) from the adult central nervous system are currently being investigated for their potential use in autologous cell replacement strategies. High expansion rates of NSCs in culture are crucial for the generation of a sufficient amount of cells needed for transplantation. Here, we describe efficient growth of adult NSCs in Neurobasal medium containing B27 supplement under clonal and low-density conditions in the absence of serum or conditioned medium. Expansion of up to 15-fold within 1 week was achieved on low-density NSC cultures derived from the lateral ventricle wall, the hippocampal formation, and the spinal cord of adult rats. A 27% single-cell cloning efficiency in Neurobasal/B27 combination further demonstrates its growth-promoting ability. Multipotency and nontumorgenicity of NSCs were retained despite the high rate of culture expansion. In addition, increased cell survival was obtained when Accutase, instead of trypsin, was used for enzymatic dissociation of NSC cultures. This work provides an important step toward the development of standardized protocols for highly efficient in vitro expansion of NSCs from the adult central nervous system to move more closely to the clinical use of NSCs.


Limited versus full sternotomy for aortic valve replacement.
Aortic valve disease is a common condition easily treatable with cardiac surgery. This is conventionally performed by opening the sternum ('median sternotomy') and replacing the valve under cardiopulmonary bypass. Median sternotomy is well tolerated, but as less invasive options become available, the efficacy of limited incisions has been called into question. In particular, the effects of reducing the visibility and surgical access have raised safety concerns with regard to the placement of cannulae, venting of the heart, epicardial wire placement, and de-airing of the heart at the end of the procedure. These difficulties may increase operating times, affecting outcome. The benefits of smaller incisions are thought to include decreased pain; improved respiratory mechanics; reductions in wound infections, bleeding, and need for transfusion; shorter intensive care stay; better cosmesis; and a quicker return to normal activity. This is an update of a Cochrane review first published in 2017, with seven new studies. To assess the effects of minimally invasive aortic valve replacement via a limited sternotomy versus conventional aortic valve replacement via median sternotomy in people with aortic valve disease requiring surgical replacement. We performed searches of CENTRAL, MEDLINE and Embase from inception to August 2021, with no language limitations. We also searched two clinical trials registries and manufacturers' websites. We reviewed references of primary studies to identify any further studies of relevance. We included randomised controlled trials comparing aortic valve replacement via a median sternotomy versus aortic valve replacement via a limited sternotomy. We excluded trials that performed other minimally invasive incisions such as mini-thoracotomies, port access, transapical, transfemoral or robotic procedures. Although some well-conducted prospective and retrospective case-control and cohort studies exist, these were not included in this review. Two review authors independently assessed trial papers to extract data, assess quality, and identify risk of bias. A third review author provided arbitration where required. We determined the certainty of evidence using the GRADE methodology and summarised results of patient-relevant outcomes in a summary of findings table. The review included 14 trials with 1395 participants. Most studies had at least two domains at high risk of bias. We analysed 14 outcomes investigating the effects of minimally invasive limited upper hemi-sternotomy on aortic valve replacement as compared to surgery performed via full median sternotomy. Upper hemi-sternotomy may have little to no effect on mortality versus full median sternotomy (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.45 to 1.94; 10 studies, 985 participants; low-certainty evidence). Upper hemi-sternotomy for aortic valve replacement may increase cardiopulmonary bypass time slightly, although the evidence is very uncertain (mean difference (MD) 10.63 minutes, 95% CI 3.39 to 17.88; 10 studies, 1043 participants; very low-certainty evidence) and may increase aortic cross-clamp time slightly (MD 6.07 minutes, 95% CI 0.79 to 11.35; 12 studies, 1235 participants; very low-certainty evidence), although the evidence is very uncertain. Most studies had at least two domains at high risk of bias. Postoperative blood loss was probably lower in the upper hemi-sternotomy group (MD -153 mL, 95% CI -246 to -60; 8 studies, 767 participants; moderate-certainty evidence). Low-certainty evidence suggested that there may be no change in pain scores by upper hemi-sternotomy (standardised mean difference (SMD) -0.19, 95% CI -0.43 to 0.04; 5 studies, 649 participants). Upper hemi-sternotomy may result in little to no difference in quality of life (MD 0.03 higher, 95% CI 0 to 0.06 higher; 4 studies, 624 participants; low-certainty evidence). Two studies reporting index admission costs concluded that limited sternotomy may be more costly at index admission in the UK National Health Service (MD 1190 GBP more, 95% CI 420 GBP to 1970 GBP, 2 studies, 492 participants; low-certainty evidence). The evidence was of very low to moderate certainty. Sample sizes were small and underpowered to demonstrate differences in some outcomes. Clinical heterogeneity was also noted. Considering these limitations, there may be little to no effect on mortality. Differences in extracorporeal support times are uncertain, comparing upper hemi-sternotomy to full sternotomy for aortic valve replacement. Before widespread adoption of the minimally invasive approach can be recommended, there is a need for a well-designed and adequately powered prospective randomised controlled trial. Such a study would benefit from also performing a robust cost analysis. Growing patient preference for minimally invasive techniques merits thorough quality of life analyses to be included as end points, as well as quantitative measures of physiological reserve.


Oral-nasal membranes are not the major route for fetal absorption of amniotic fluid arginine vasopressin.
Intraamniotically injected substances such as arginine vasopressin and digoxin have been found to rapidly appear in the ovine fetal circulation, irrespective of whether the fetal esophagus has been ligated or occluded. To determine if the ovine fetal oral-nasal membrane plays a significant role in this fetal absorption of amniotic substances, we used two groups of chronically catheterized fetal sheep with a surgical glove sewed over the fetal head to prevent access of the head to amniotic fluid. In the first group 22.5 micrograms of arginine vasopressin was injected into the amniotic cavity; in the second group 22.5 micrograms was injected into the glove over the fetal head. We found that, after injection into the amniotic cavity, there were rapid and highly significant increases in amniotic fluid arginine vasopressin concentrations, from 6.1 +/- 1.3 to 51,249 +/- 18,182 pg/ml (mean +/- SE) (p less than 0.00001). Concurrently there was a rapid increase in fetal plasma arginine vasopressin concentrations from 4.5 +/- 1.3 to 93.8 +/- 18.9 pg/ml (p less than 0.00001). The increase was significant within 15 minutes and reached a maximum at 60 minutes after the injection. Fetal arterial pressure increased by 10 +/- 2 mm Hg, whereas heart rate decreased by 30 +/- 5 beats/min (p less than 0.00001). In contrast, after the injection into the glove covering the fetal head, there were no significant changes in any of the measured parameters. This suggests that the ovine fetal oral-nasal membrane is not a significant route of absorption of amniotic fluid arginine vasopressin and that the most likely route of absorption is the vascularized fetal surface of the placenta and vascularized fetal membranes, i.e., the intramembranous pathway.


What Could Explain the Lower COVID-19 Burden in Africa despite Considerable Circulation of the SARS-CoV-2 Virus?
The differential spread and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing Coronavirus Disease 2019 (COVID-19), across regions is a major focus for researchers and policy makers. Africa has attracted tremendous attention, due to predictions of catastrophic impacts that have not yet materialized. Early in the pandemic, the seemingly low African case count was largely attributed to low testing and case reporting. However, there is reason to consider that many African countries attenuated the spread and impacts early on. Factors explaining low spread include early government community-wide actions, population distribution, social contacts, and ecology of human habitation. While recent data from seroprevalence studies posit more extensive circulation of the virus, continuing low COVID-19 burden may be explained by the demographic pyramid, prevalence of pre-existing conditions, trained immunity, genetics, and broader sociocultural dynamics. Though all these prongs contribute to the observed profile of COVID-19 in Africa, some provide stronger evidence than others. This review is important to expand what is known about the differential impacts of pandemics, enhancing scientific understanding and gearing appropriate public health responses. Furthermore, it highlights potential lessons to draw from Africa for global health on assumptions regarding deadly viral pandemics, given its long experience with infectious diseases.


Thermodynamics of the dimer-decamer transition of reduced human and plant 2-cys peroxiredoxin.
Isothermal titration calorimetry (ITC) is a powerful technique for investigating self-association processes of protein complexes and was expected to reveal quantitative data on peroxiredoxin oligomerization by directly measuring the thermodynamic parameters of dimer-dimer interaction. Recombinant classical 2-cysteine peroxoredoxins from Homo sapiens, Arabidopsis thaliana, and Pisum sativum as well as a carboxy-terminally truncated variant were subjected to ITC analysis by stepwise injection into the reaction vessel under various redox conditions. The direct measurement of the decamer-dimer equilibrium of reduced peroxiredoxin revealed a critical concentration in the very low micromolar range. The data suggest a cooperative assembly above this critical transition concentration where a nucleus facilitates assembly. The rather abrupt transition indicates that assembly processes do not occur below the critical transition concentration while oligomerization is efficiently triggered above it. The magnitude of the measured enthalpy confirmed the endothermic nature of the peroxiredoxin oligomerization. Heterocomplexes between peroxiredoxin polypeptides from different species were not formed. We conclude that a functional constraint conserved the dimer-decamer transition with highly similar critical transition concentrations despite emerging sequence variation during evolution.


Identification of potential functions of polo-like kinase 1 in male reproductive development of the oriental river prawn (Macrobrachium nipponense) by RNA interference analysis.
Polo-like kinase 1 (Plk1) has multiple functions in the cell cycle, including in the maturation of centrosomes during the G2/M transition, the separation of centrosomes, and the activation of cyclin-dependent kinase 1 expression and spindle assembly. In this study, we investigated the potential regulatory roles of Plk1 in the reproductive development of the male oriental river prawn (Machrobrachium nipponense). The full cDNA sequence of Mn-Plk1 was 2360 base pairs long, with an open reading frame of 1836 base pairs encoding 611 amino acids. Protein sequence alignment identified a conserved serine/threonine kinase domain and two Polo-boxes. Phylogenetic tree analysis revealed that Mn-Plk1 had the closest evolutionary distance with Plk1s of freshwater prawns and then with those of crustacean species, whereas the evolutionary distance with mollusks was much more distant. Quantitative PCR analysis predicted that Mn-Plk1 plays essential roles in the regulation of gonad development. RNA interference analysis and histological observations showed that expression of insulin-like androgenic gland hormone decreased as the expression of Mn-Plk1 decreased, and fewer than 5% of cells were sperm cells at day 14 in the dsPlk1 injected prawns. This result indicated that Plk1 positively regulated testis development in M. nipponense by affecting the expression of this hormone. Our results highlight the functions of Plk1 in M. nipponense and provide valuable information that can be applied to establish artificial techniques to regulate testis development in this species.


Proteomic analysis of a PDEF Ets transcription factor-interacting protein complex.
Ets proteins are a family of transcription factors that share an 85 amino acid conserved DNA binding domain, the ETS domain. The 27 known human Ets transcription factors control multiple biological processes, including cellular proliferation, differentiation, apoptosis, angiogenesis, transformation, and invasion. Overexpression of some Ets genes has been linked to numerous malignancies, including breast cancers. The prostate derived Ets transcription factor (PDEF) is reported to be a breast and prostate tumor-associated Ets factor. To understand the roles of PDEF in breast cancers, we transiently overexpressed PDEF in MDA-MB-231 human breast cancer cells by adenoviral-mediated gene delivery. PDEF binding protein complexes were isolated by immunoprecipitation and PDEF-interacting proteins were analyzed by LC-MS/MS. After subtracting the proteins binding nonspecifically to antibody-bead complexes, we identified 286 proteins in the PDEF-associated protein complex. By comparison to published protein-protein interactions, we selected 121 proteins for further analysis. PDEF interactors distribute not only in the nucleus, but also in the cytoplasm, as well as other subcellular compartments. Our data reveals that PDEF interacts with a variety of proteins involved in cell cycle, DNA repair, cytoskeleton organization, mRNA processing, tRNA biosynthesis, protein folding, and cell signaling. Furthermore, the EGFR1- (Erbb1) and Erbb2- (HER2) related proteins erbin, an ERBB2 interacting protein, catenin delta-1 (which interacts with Erbin), and EGFR (a HER2-homology receptor) were associated with PDEF. These findings indicate that PDEF may be regulated by Erbb2 or EGFR-activated signaling pathways in breast cancer cells. Further analysis of these proteins will identify the roles of PDEF-interacting proteins in breast tumorigenesis.


[Encephalomyocarditis in hamadryas baboons].
In 1978--1979, four cases of encephalomyocarditis were recorded in baboons in a simian preserve of the USSR AMS Research Institute of Experimental Pathology and Therapy located in the Zapadnyaya Gumista river valley. The diagnosis was made on the basis of virological and pathomorphological examinations. The isolate recovered from the dead monkeys was identical with the prototype strain of encephalomyocarditis virus (EMC) and the EMC-70 strain previously isolated by us from M. rhesus monkeys. The infection of monkeys caused by the EMC-78/79 virus involved a severe affection of the myocardium of the type of parenchymatous-interstitial myocarditis, moderate encephalitis in the central nervous system, inflammatory changes in the brown fat and cross-striated muscles. An experimental infection in guinea pigs and mice exhibited similar features.


Left Circumflexus Coronary Artery Total Occlusion with Clinical Presentation as NSTEMI and Acute Pulmonary Oedema.
Current guidelines for the management of patients with acute coronary syndromes (ACSs) focus on the electrocardiogram to divide patients into ST-elevation acute myocardial infarction (STEMI) or non-ST-elevation acute myocardial infarction (NSTEMI)/unstable angina (UA). Patients with STEMI in the earliest time will receive reperfusion therapy to destruct occlusive thrombus. An ST segment elevation is the 'sine qua non' for diagnosing acute total coronary occlusion causing transmural myocardial infarction. Left circumflex coronary artery (LCx) occlusion is often categorized as NSTEMI because of the absence of significant ST-elevation on the 12 lead standard electrocardiogram. An ST segment elevation is presented in fewer than 50% of patients with LCx total occlusion, such that the reperfusion therapy is delayed. We reported a 77 years old woman whom being diagnosed with NSTEMI because a 12 lead electrocardiogram showed ST segment depression in lead V2-V5. On coronary angiography, we found a total occlusion in the LCx artery as the culprit lession.


Practical use of a word processor in a histopathology laboratory.
Some of the facilities available with a commercially purchased word processing program, linked to a DEC PDP 11/23 computer are described, together with an account of the practical histopathological use. The system is based on a share of the computer with a Clinical Chemistry Department. Development was time-consuming and required the constant availability of the Department of Physics. However, once working, considerable saving in secretarial time has resulted and a number of projects have been started which would not have been contemplated without the use of the word processor and its linked computer.


Efficiency improvements of public hospitals under a capitation payment scheme.
In a context of cost containment and demands for better quality in public health care, payment systems are used as an instrument to promote efficiency improvements in service providers. Andalusia has adopted an original type of risk-adjusted capitation payment mechanism to reimburse public hospitals. This paper presents the main characteristics of the reimbursement mechanism of the Andalusian Health Service highlighting some differences with the mechanisms adopted in other parts of Europe. The paper also explores the evolution of the efficiency and quality of the hospitals after its implementation using the Malmquist index. Results indicate that hospitals have slightly improved their efficiency, particularly urban hospitals, and these improvements are not significantly related to a negative evolution of quality. However, it is not possible to assert to what extent, improvements are the consequence of the new payment system. The organisation of the Servicio Andaluz de Salud and the limited competition between hospitals reduce the effectiveness of the reform.


Outcomes of directional branches using self-expandable or balloon-expandable stent grafts during endovascular repair of thoracoabdominal aortic aneurysms.
The objective of this study was to evaluate outcomes of directional branches using self-expandable stent grafts (SESGs) or balloon-expandable stent grafts (BESGs) during fenestrated-branched endovascular aneurysm repair of thoracoabdominal aortic aneurysms. Patients treated by fenestrated-branched endovascular aneurysm repair were enrolled in a prospective study from 2014 to 2018. We included in the analysis patients who had target vessels incorporated by directional branches using either SESG (Fluency [Bard, Covington Ga] or Gore Viabahn [W. L. Gore & Associates, Flagstaff, Ariz]) or BESG (Gore VBX). Target artery instability (TAI) was defined by a composite of any stent stenosis, separation, or type IC or type IIIC endoleak requiring reintervention and stent occlusion, aneurysm rupture, or death due to target artery complication. End points included technical success, target artery patency, freedom from TAI, freedom from type IC or type IIIC endoleak, and freedom from target artery reintervention. There were 126 patients (61% male; mean age, 73 ± 8 years) included in the study. A total of 335 renal-mesenteric arteries were targeted by directional branches using SESGs in 62 patients and 176 arteries or BESGs in 54 patients and 159 arteries. Patients in both groups had similar thoracoabdominal aortic aneurysm classification and aneurysm and target artery diameter, but SESG patients had significantly (P < .05) shorter stent length (-7 mm) and larger stent diameter (+1 mm) and more often had adjunctive bare-metal stents (72% vs 15%). Technical success was achieved in 99% of patients, with one 30-day death (0.7%). Mean follow-up was significantly longer among patients treated by SESGs compared with BESGs (23 ± 12 months vs 8±8 months; P < .0001). TAI occurred in 27 directional branches (8%), including 11 type IC endoleaks (2 SESGs, 9 BESGs), 10 stenoses (3 SESGs, 7 BESGs), 4 occlusions (3 SESGs, 1 BESGs), 4 type IIIC endoleaks (2 SESGs, 2 BESGs), and 1 stent separation (SESG), resulting in 20 target artery reinterventions in 16 patients (5 SESGs and 11 BESGs). At 1 year, SESGs had higher primary patency (97% ± 2% vs 96% ± 2%; P = .004), freedom from TAI (96% ± 2% vs 88% ± 3%; P < .0001), freedom from type IC or type IIIC endoleaks (98% ± 1% vs 92% ± 3%; P = .0004), and freedom from target artery reinterventions (98% ± 1% vs 88% ± 4%; P < .0001) compared with BESGs. There was no difference in secondary patency for SESGs and BESGs (98% ± 1% vs 99% ± 1%; P = .75). Factors associated with TAI were large stent diameter (odds ratio, 0.6; P < .0001) and use of VBX stent graft (odds ratio, 6.5; P < .0001). Directional branches were associated with high technical success and low rates of stent occlusion, independent of stent type. However, primary patency, freedom from TAI, and freedom from type IC or type IIIC endoleaks was lower for BESGs compared with SESGs.


[Ischemic preconditioning and exogenous L-arginine reduce infarct size in rabbit heart].
The effects of NO donor--L-arginine (L-arg) and ischemic preconditioning (IP) on the hemodynamics and myocardial infarct size were examined in the anesthetized rabbit subjected to myocardial ischemia-repefusion to define whether exogenous L-arg could exert a beneficial effect in this pathological model, and whether the L-arg-NO pathway was involved in the cardioprotection provided by IP. The results obtained were as follows: (1) During the course of ischemia (30 min)-reperfusion (180 min), blood pressure, heart rate and myocardial oxygen consumption decreased progressively, and the myocardial infarct size occupied 33.9 +/- 2.4% of the whole left ventricle. (2) The myocardial infarct size could be reduced to 20.1 +/- 2.2% (P < 0.01) by pretreatment with L-arg (300 mg/kg). This myocardial protective effect of L-arg was abolished by NO synthesis inhibitor--Nitro-L-arginine (L-NNA), thereby indicating the involvement of L-arg-NO pathway. (3) IP significantly reduced the infarct size to 21.9 +/- 2.1% (P < 0.01), indicating the prominent cardioprotective effect of such an intervention. Since L-NNA showed no effect on the cardioprotection afforded by IP, it was implied that the L-arg-NO pathway was not involved in the cardioprotective mechanism of IP. (4) Exogenous L-arg might markedly augment cardioprotection provided by IP. The above results strongly suggested that the cardioprotective effect of L-arg on ischemia-reperfused myocardium was mediated by L-arg-NO pathway, which, however, was not involved in the cardioprotection provided by IP.


Proteolytic degradation of vimentin and glial fibrillary acidic protein in rat astrocytes in primary culture.
Vimentin and glial fibrillary acidic (GFA) protein in rat astrocytes in primary culture were identified with their respective specific antisera on electroblots of one-dimensional and two-dimensional polyacrylamide gels. Each antiserum revealed respectively vimentin (58 kDa, pI 5.3), GFA protein (50 kDa, pI 6-5.8) and several more acidic, lower molecular mass vimentin-immunoreactive and GFA protein-immunoreactive polypeptides. These were more apparent when astrocyte proteins were extracted in the absence of EGTA and in the presence of Ca2+ ions suggesting that the lower immunoreactive polypeptides result from a Ca2+-sensitive proteolytic degradation of vimentin and GFA protein. The extent of proteolysis of GFA protein was higher when the differentiation of astrocytes was induced with 1,N6-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP). In contrast, the proteolysis of vimentin was not affected by the state of differentiation of astrocytes. The results indicate the existence of at least two distinct degradative pathways for intermediate filament proteins in astrocytes in primary culture and suggest that in differentiated astrocytes the activity of proteinase(s) involved in the degradation of GFA protein increases.


What to do when a competent ICU patient does not want to live anymore but is dependent on life-sustaining treatment? Experience from The Netherlands.
If patients on the intensive care unit (ICU) are awake and life-sustaining treatment is suspended because of the patients' request, because of recovering from the disease, or because independence from organ function supportive or replacement therapy outside the ICU can no longer be achieved, these patients can suffer before they inevitably die. In The Netherlands, two scenarios are possible for these patients: (1) deep palliative (terminal) sedation through ongoing administration of barbiturates or benzodiazepines before withdrawal of treatment, or (2) deliberate termination of life (euthanasia) before termination of treatment. In this article we describe two awake patients who asked for withdrawal of life-sustaining measures, but who were dependent on mechanical ventilation. We discuss the doctrine of double effect in relation to palliative sedation on the ICU. Administration of sedatives and analgesics before withdrawal of treatment is seen as normal palliative care. We conclude that the doctrine of the double effect is not applicable in this situation, and mentioning it criminalised the practice unnecessarily and wrongfully.


Coherence requirements for partially coherent optical processing.
The mutual intensity function for a partially coherent light is used to develop an expression for the output intensity distribution for a broadband optical information processor. The coherence requirement for smeared image deblurring and image subtraction is then determined using the intensity distribution. We also quantitatively show the dependence of coherence criteria on the spectral bandwidth, the source size, deblurring width, spatial frequency, and the separation of input object transparencies.


Progression and enhancement of metastatic potential after exposure of tumor cells to chemotherapeutic agents.
Data presented in this report indicate short-term in vitro treatment of nonmetastatic MCF-7 breast carcinoma cells with the chemotherapeutic agents-, Adriamycin and/or 5-fluoro-2'-deoxyuridine (FUdR), induced changes in the expressed phenotype. Cells treated sequentially with Adriamycin and FUdR expressed a metastatic phenotype. The results also show short-term exposure of MCF-7 cells to either Adriamycin or FUdR rapidly increases, in a dose-dependent manner, the release of the angiogenic cytokine, interleukin-8(IL-8), which is released at consistently higher levels in metastatic cell lines. Cell populations surviving a single treatment with either one or both of these chemotherapeutic agents continue to stably release IL-8. Survivors of sequential treatment with Adriamycin and FUdR (MCF-7 A/F) release the most IL-8 and express the greatest phenotypic variance from the parental, MCF-7 cells. Parental MCF-7 cells and MCF-7 A/F cells both form primary tumors when used in an orthotopic tumor model; however, the MCF-7 A/F tumors have a more rapid initial growth phase in situ and give rise to spontaneous lung metastases within 10 weeks. A cell line that is established from lung metastases releases more IL-8, has a higher cloning efficiency, and forms looser colonies in monolayer than do their parental cells. These experiments indicate the in vitro exposure of tumor cells to chemotherapeutic agents either selects more aggressive cells or enhances the metastatic potential of the surviving cells.


Simultaneous Engagement of Tumor and Stroma Targeting Antibodies by Engineered NK-92 Cells Expressing CD64 Controls Prostate Cancer Growth.
Metastatic castration-resistant prostate cancer (mCRPC) has been largely resistant to immunotherapy. Natural killer (NK) cells are cytotoxic lymphocytes that detect and kill transformed cells without prior sensitization, and their infiltration into prostate tumors corresponds with an increased overall survival among patients with mCRPC. We sought to harness this knowledge to develop an approach to NK-cell based immunotherapy for mCRPC. We engineered an NK cell line (NK-92MI) to express CD64, the sole human high-affinity IgG Fcγ receptor (FcγR1), and bound these cells with antibodies to provide interchangeable tumor-targeting elements. NK-92MICD64 cells were evaluated for cell-activation mechanisms and antibody-dependent cell-mediated cytotoxicity (ADCC). A combination of mAbs was used to target the prostate tumor antigen tumor-associated calcium signal transducer 2 (TROP2) and the cancer-associated fibroblast marker fibroblast activation protein alpha (FAP). We found that CD64, which is normally expressed by myeloid cells and associates with the adaptor molecule FcRγ, can be expressed by NK-92MI cells and mediate ADCC through an association with CD3ζ. Cytotoxicity from the combination approach was two-fold higher compared to treatment with NK-92MICD64 cells and either mAb alone, and seven-fold higher than NK-92MICD64 cells alone at an effector-target cell ratio of 20:1. The cytotoxic effect was lost when using isotype control antibodies, indicating a selective targeting mechanism. The combination approach demonstrated efficacy in vivo as well and significantly reduced tumor growth compared with the saline control. This combination therapy presents a potential approach for treating mCRPC and could improve immunotherapy response.


Effects of continuous visual feedback during sitting balance training in chronic stroke survivors.
Postural control deficits are common in stroke survivors and often the rehabilitation programs include balance training based on visual feedback to improve the control of body position or of the voluntary shift of body weight in space. In the present work, a group of chronic stroke survivors, while sitting on a force plate, exercised the ability to control their Center of Pressure with a training based on continuous visual feedback. The goal of this study was to test if and to what extent chronic stroke survivors were able to learn the task and transfer the learned ability to a condition without visual feedback and to directions and displacement amplitudes different from those experienced during training. Eleven chronic stroke survivors (5 Male - 6 Female, age: 59.72 ± 12.84 years) participated in this study. Subjects were seated on a stool positioned on top of a custom-built force platform. Their Center of Pressure positions were mapped to the coordinate of a cursor on a computer monitor. During training, the cursor position was always displayed and the subjects were to reach targets by shifting their Center of Pressure by moving their trunk. Pre and post-training subjects were required to reach without visual feedback of the cursor the training targets as well as other targets positioned in different directions and displacement amplitudes. During training, most stroke survivors were able to perform the required task and to improve their performance in terms of duration, smoothness, and movement extent, although not in terms of movement direction. However, when we removed the visual feedback, most of them had no improvement with respect to their pre-training performance. This study suggests that postural training based exclusively on continuous visual feedback can provide limited benefits for stroke survivors, if administered alone. However, the positive gains observed during training justify the integration of this technology-based protocol in a well-structured and personalized physiotherapy training, where the combination of the two approaches may lead to functional recovery.


Performance of three microimmunofluorescence assays for detection of Chlamydia pneumoniae immunoglobulin M, G, and A antibodies.
The microimmunofluorescence (MIF) test is considered the "gold standard" for laboratory diagnosis of acute and chronic Chlamydia pneumoniae infection. The performance of a MIF test based on C. pneumoniae antigen from Washington Research Foundation (WRF) was compared with those of assays from Labsystems (LAB) and MRL Diagnostics (MRL) by investigation of sera from three groups of patients: group I, 83 sera from 28 patients with atypical pneumonia; group II, 37 sera from 16 patients with acute C. pneumoniae or Chlamydia psittaci respiratory tract infection confirmed by PCR or culture; group III, 100 sera from 100 persons enrolled in the Copenhagen City Heart Study. The accordance among the results of the WRF assay and the two commercial assays was excellent for the immunoglobulin M (IgM) antibody detection rate (98%). The accordance in detection rates for IgG and IgA antibodies in sera from patients with acute infections was acceptable (87 and 88%), and in sera from group III, it was excellent (95 and 97%). The determinations of endpoint titers were reproducible with <1 dilution step difference for all three methods, except that the mean IgM antibody titer found by the LAB assay was almost 2 dilution steps higher than that found by the other two methods. Although the three assays use different C. pneumoniae strains as antigens, the detection rates and IgG and IgA endpoint titers were similar. The difference in endpoint titers of IgM antibodies is of no major concern, as the diagnosis of acute C. pneumoniae infection rests on the presence of IgM antibodies, not on their level.


[Food consumption of children and adolescents living in an area of invasion in Maceio, Alagoas, Brazil].
To assess the food intake of energy, macronutrients and micronutrients related to growth and development in individuals under 16 years of age living in a consolidated invasion settlement in Maceió, Alagoas. The assessment of food intake was carried out by the 24-hour recall method, using a food picture album. Nutritional composition of diets was analysed using the Virtual Nutri-1.0 software. The estimated prevalence of inadequate intake was based on the Dietary Reference (DRIs), adjusted to account for intra-individual variability. The Statistical Package for Social Science (SPSS) version 11.5 was used for data analysis. 5.6% of the subjects studied presented excessive energy intake and for 3.7% it was inadequate. The frequency of excessive energy intake was higher in the 1 to 3 year-old age group (p <0.05), which also showed higher rates of inadequate intake of vitamin A, vitamin E and zinc, and it was the only group in which average consumption of calcium was higher than the adequate intake. Data show that dietary patterns of the individuals studied need adjustments.


New bone formation with teriparatide [human parathyroid hormone-(1-34)] is not retarded by long-term pretreatment with alendronate, estrogen, or raloxifene in ovariectomized rats.
With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1-34)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17 alpha-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 microg/kg, twice weekly), EE (0.1 mg/kg per d), or Ral (1 mg/kg per d) for 10 months before switching to teriparatide 30 microg/kg per d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.


pH-sensitive immunoliposomes as an efficient and target-specific carrier for antitumor drugs.
pH-sensitive immunoliposomes composed of dioleoylphosphatidyl-ethanolamine and oleic acid (8:2) significantly enhanced the cytotoxic effect of the entrapped drug 1-beta-D-arabinofuranosylcytosine (ara-C) to target L-929 cells, as compared to free drug, drug encapsulated in antibody-free liposomes, or in pH-insensitive immunoliposomes. These pH-sensitive immunoliposomes were ineffective against nontarget A-31 cells. The enhanced cytotoxic effect could be blocked by excess free antibody or excess drug-free immunoliposomes. Pretreatment of target cells with the weak bases chloroquine or NH4Cl, which raise the internal pH of cellular acidic organelles such as endosomes and lysosomes, inhibited the cell killing activity of ara-C encapsulated in the pH-sensitive immunoliposomes. Since it is known that ara-C is rapidly inactivated in the lysosomes, our results suggest that the release of ara-C from the pH-sensitive immunoliposomes occurs in a prelysosomal compartment, i.e., the endosome. Parallel experiments using methotrexate as a cytotoxic drug confirm the enhanced ability of the pH-sensitive liposomes for cytoplasmic drug delivery over that of free drug. These results indicate that pH-sensitive immunoliposomes can be used as an efficient and target-specific carrier for antitumor drugs.


Effect of consuming fiber from corn bran, soy hulls, or apple powder on glucose tolerance and plasma lipids in type II diabetes.
The effects of consuming corn bran, soy hulls, or apple powder on glucose and lipid metabolism were investigated in two studies of persons with type II diabetes. Fiber sources, completely or partially added to bread, were incorporated into subjects' self-selected diets. Low fiber white bread served as a control. In study A, 10 subjects consumed 26 g fiber source daily; in study B, eight subjects consumed 52 g fiber source. Biochemical tests, including a 2-h postprandial glucose test using a low fiber formula meal, were scheduled after 2 and 4 wk of each dietary treatment. Soy hull consumption slightly improved some measures of glucose tolerance, with results varying between the studies. Consumption of 52 g corn bran decreased very low-density lipoprotein cholesterol, triglycerides, and glycosylated Hb, but subject tolerance was poor with the particle size used. Consumption of 52 g apple powder increased low-density lipoprotein and total cholesterol levels.


Investigating the effect of obsessive-compulsive disorder on clinical symptoms of temporomandibular joint disorders.
Temporomandibular disorders (TMD) are a group of clinical conditions involving muscles of mastication, temporomandibular joint (TMJ), and related structures or both. TMD is characterized by facial pain in TMJ and muscles of mastication, limitation or deviation of jaw movement, and TMJ sounds during jaw movement and function. The highest risk of TMD prevalence is between 18 and 24 years, and a relationship is between chronic TMD and psychological disorders such as stress and depression. The knowledge of the function of this joint and those with TMD symptoms when visiting the dentist will help to provide an ideal treatment plan for the patient. Therefore, if the therapist is familiar with the various etiological factors of this disorder, he will provide better treatment, especially if the simultaneous effect of psychological factors such as stress and obsessive-compulsive disorder (OCD) along with occlusal factors such as posterior cross-bite, overjet, and overbite is measured, it can be a valuable guide for clinicians. In this study, 385 patients were examined by DASS42 and Maudsley's test and classified into normal, with stress, and stress plus OCD groups. TMJ was examined for each of them by the TMD-RDC test. The presence or absence of TMD was noted in their file. The prevalence of TMD was 20.7% in the normal group, 30.70% in the stress group, and 44.68% in the stress and OCD group. After analyzing the data by SPSS 24 and performing analysis of variance and Duncan tests, no significant difference was found between the probability of TMD in normal and stressed groups, but the stress and OCD group has a higher chance of TMD. Although the co-occurrence of stress and OCD is associated with the prevalence of TMD, it cannot be considered a cause of TMD.


Graft-versus-leukemia reactivity involves cluster formation between superantigen-reactive donor T lymphocytes and host macrophages.
T-cell-mediated antitumor effects play an important role clinically in allogeneic graft-versus-leukemia (GvL) reactivity, whereas T-cell-mediated antihost effects are associated with a risk of developing graft-versus-host (GvH) disease. GvL and GvH were compared in an animal tumor model system after the systemic transfer of allogeneic antitumor immune T lymphocytes from B10.D2 [H-2d; minor lymphocyte-stimulating antigen (Mls)b] mice into ESb-MP tumor-bearing or normal DBA/2 (H-2d; Mls(a)) mice. Here we demonstrate that this T-cell-mediated therapy involves the formation of clusters of donor CD4 and CD8 T cells with host macrophages, in particular, with a subpopulation expressing the lymphocyte adhesion molecule sialoadhesin. DBA/2 mice and the derived tumor ESb-MP express viral superantigen 7 (Mls(a)), an endogenous viral superantigen that is absent from B10.D2 mice. To test the contribution of viral superantigen 7-reactive Vbeta6 donor T cells in the GvL-mediated eradication of liver metastases, we performed immunohistological and transmission electron microscopy studies. Vbeta6+ CD4 and CD8 T cells from B10.D2 donors formed tight clusters with host sialoadhesin-positive macrophages, and transmission electron microscopy pictures revealed direct membrane-membrane interactions between T cells and macrophages. Clusters were more abundant and consisted of more cells in tumor-bearing hosts (GvL model) than in non-tumor-bearing hosts (GvH model). In addition, Vbeta6 T cells within the clusters showed a strong proliferation activity, indicating stimulation. Moreover, in an in vitro tumor cytostasis assay, primed as well as nonprimed purified Vbeta6 T cells from donor mice were able to inhibit the proliferation of superantigen-expressing ESb-MP lymphoma cells. This suggests that the transferred superantigen-reactive Vbeta6 T cells contribute to the eradication of metastases. The observed cell clusters might be sites for antigen presentation and the activation of tumor-reactive T cells.


Diagnostic echocardiographic features of the sinus venosus defect.
To establish the diagnostic criteria for a sinus venosus atrial septal defect cross sectional echocardiograms, cineangiograms, and surgical notes of all patients with this diagnosis seen at the Children's Hospital of Pittsburgh between 1986 and 1988 were reviewed. Seven patients were identified. In each the extent of the atrial septum and the nature of the junction of the superior vena cava with the atria were evaluated echocardiographically from the subcostal position. All had overriding of the superior vena cava and abnormally connected right pulmonary veins. Six patients had undergone cardiac catheterisation and cineangiography. Five patients underwent surgical repair. The operative findings were consistent with the expected morphology in all five, and these features were additionally confirmed in a specimen from the cardiopathological museum. Therefore, the basic anatomical feature of a superior sinus venosus interatrial communication is a biatrial connection of the superior vena cava. This, together with anomalous drainage of the right sided pulmonary veins, results in an interatrial communication outside the confines of the true atrial septum. Overriding of the superior vena cava across the upper rim of the oval fossa is suggested as the pathognomonic diagnostic feature that can clearly be demonstrated echocardiographically from the subcostal position. In essence the lesion is an interatrial communication rather than an atrial septal defect.


Extracellular vesicles promote transkingdom nutrient transfer during viral-bacterial co-infection.
Extracellular vesicles (EVs) are increasingly appreciated as a mechanism of communication among cells that contribute to many physiological processes. Although EVs can promote either antiviral or proviral effects during viral infections, the role of EVs in virus-associated polymicrobial infections remains poorly defined. We report that EVs secreted from airway epithelial cells during respiratory viral infection promote secondary bacterial growth, including biofilm biogenesis, by Pseudomonas aeruginosa. Respiratory syncytial virus (RSV) increases the release of the host iron-binding protein transferrin on the extravesicular face of EVs, which interact with P. aeruginosa biofilms to transfer the nutrient iron and promote bacterial biofilm growth. Vesicular delivery of iron by transferrin more efficiently promotes P. aeruginosa biofilm growth than soluble holo-transferrin delivered alone. Our findings indicate that EVs are a nutrient source for secondary bacterial infections in the airways during viral infection and offer evidence of transkingdom communication in the setting of polymicrobial infections.


Surface feature based classification of plant organs from 3D laserscanned point clouds for plant phenotyping.
Laserscanning recently has become a powerful and common method for plant parameterization and plant growth observation on nearly every scale range. However, 3D measurements with high accuracy, spatial resolution and speed result in a multitude of points that require processing and analysis. The primary objective of this research has been to establish a reliable and fast technique for high throughput phenotyping using differentiation, segmentation and classification of single plants by a fully automated system. In this report, we introduce a technique for automated classification of point clouds of plants and present the applicability for plant parameterization. A surface feature histogram based approach from the field of robotics was adapted to close-up laserscans of plants. Local geometric point features describe class characteristics, which were used to distinguish among different plant organs. This approach has been proven and tested on several plant species. Grapevine stems and leaves were classified with an accuracy of up to 98%. The proposed method was successfully transferred to 3D-laserscans of wheat plants for yield estimation. Wheat ears were separated with an accuracy of 96% from other plant organs. Subsequently, the ear volume was calculated and correlated to the ear weight, the kernel weights and the number of kernels. Furthermore the impact of the data resolution was evaluated considering point to point distances between 0.3 and 4.0 mm with respect to the classification accuracy. We introduced an approach using surface feature histograms for automated plant organ parameterization. Highly reliable classification results of about 96% for the separation of grapevine and wheat organs have been obtained. This approach was found to be independent of the point to point distance and applicable to multiple plant species. Its reliability, flexibility and its high order of automation make this method well suited for the demands of high throughput phenotyping. • Automatic classification of plant organs using geometrical surface information• Transfer of analysis methods for low resolution point clouds to close-up laser measurements of plants• Analysis of 3D-data requirements for automated plant organ classification.


Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.
Timothy syndrome (TS) is a multisystem disorder that causes syncope and sudden death from cardiac arrhythmias. Prominent features include congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. All TS individuals have syndactyly (webbing of fingers and toes). We discovered that TS resulted from a recurrent, de novo cardiac L-type calcium channel (CaV1.2) mutation, G406R. G406 is located in alternatively spliced exon 8A, encoding transmembrane segment S6 of domain I. Here, we describe two individuals with a severe variant of TS (TS2). Neither child had syndactyly. Both individuals had extreme prolongation of the QT interval on electrocardiogram, with a QT interval corrected for heart rate ranging from 620 to 730 ms, causing multiple arrhythmias and sudden death. One individual had severe mental retardation and nemaline rod skeletal myopathy. We identified de novo missense mutations in exon 8 of CaV1.2 in both individuals. One was an analogous mutation to that found in exon 8A in classic TS, G406R. The other mutation was G402S. Exon 8 encodes the same region as exon 8A, and the two are mutually exclusive. The spliced form of CaV1.2 containing exon 8 is highly expressed in heart and brain, accounting for approximately 80% of CaV1.2 mRNAs. G406R and G402S cause reduced channel inactivation, resulting in maintained depolarizing L-type calcium currents. Computer modeling showed prolongation of cardiomyocyte action potentials and delayed afterdepolarizations, factors that increase risk of arrhythmia. These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS.


Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas.
Mutations in isocitrate dehydrogenase (IDH) genes occur in multiple cancer types, lead to global changes in the epigenome, and drive tumorigenesis. Yet, effective strategies targeting solid tumors harboring IDH mutations remain elusive. Here, we demonstrate that IDH-mutant gliomas and cholangiocarcinomas display elevated DNA damage. Using multiple in vitro and preclinical animal models of glioma and cholangiocarcinoma, we developed treatment strategies that use a synthetic lethality approach targeting the reduced DNA damage repair conferred by mutant IDH using poly(adenosine 5'-diphosphate) ribose polymerase inhibitors (PARPis). The therapeutic effects are markedly enhanced by cotreatment with concurrent, localized radiation therapy. PARPi-buttressed multimodality therapies may represent a readily applicable approach that is selective for IDH-mutant tumor cells and has potential to improve outcomes in multiple cancers.


Short-Term Immobilization Promotes a Rapid Loss of Motor Evoked Potentials and Strength That Is Not Rescued by rTMS Treatment.
Short-term limb immobilization results in skeletal muscle decline, but the underlying mechanisms are incompletely understood. This study aimed to determine the neurophysiologic basis of immobilization-induced skeletal muscle decline, and whether repetitive Transcranial Magnetic Stimulation (rTMS) could prevent any decline. Twenty-four healthy young males (20 ± 0.5 years) underwent unilateral limb immobilization for 72 h. Subjects were randomized between daily rTMS (n = 12) using six 20 Hz pulse trains of 1.5 s duration with a 60 s inter-train-interval delivered at 90% resting Motor Threshold (rMT), or Sham rTMS (n = 12) throughout immobilization. Maximal grip strength, EMG activity, arm volume, and composition were determined at 0 and 72 h. Motor Evoked Potentials (MEPs) were determined daily throughout immobilization to index motor excitability. Immobilization induced a significant reduction in motor excitability across time (-30% at 72 h; p < 0.05). The rTMS intervention increased motor excitability at 0 h (+13%, p < 0.05). Despite daily rTMS treatment, there was still a significant reduction in motor excitability (-33% at 72 h, p < 0.05), loss in EMG activity (-23.5% at 72 h; p < 0.05), and a loss of maximal grip strength (-22%, p < 0.001) after immobilization. Interestingly, the increase in biceps (Sham vs. rTMS) (+0.8 vs. +0.1 mm, p < 0.01) and posterior forearm (+0.3 vs. +0.0 mm, p < 0.05) skinfold thickness with immobilization in Sham treatment was not observed following rTMS treatment. Reduced MEPs drive the loss of strength with immobilization. Repetitive Transcranial Magnetic Stimulation cannot prevent this loss of strength but further investigation and optimization of neuroplasticity protocols may have therapeutic benefit.


The ring current model of the pentaprismane molecule.
Three-dimensional models of the quantum-mechanical current density J(B) , induced in the electron cloud of the C(10)H(10) pentaprismane molecule by a magnetic field B applied along the C(5) (a C(2)) symmetry axis, orthogonal to the pentagonal (a rectangular) face, and denoted by B(‖) (B(⊥)), have been constructed. Predictions of near Hartree-Fock quality are reported for the diagonal components of magnetic tensors, magnetizability (ξ), nuclear shielding of carbon (σ(C)) and hydrogen (σ(H)), and virtual shielding at the center of mass (σ(CM)). The complicated spatial features of the induced electronic current-density field have been rationalized and compactly described via stagnation graphs that elucidate the details of its topological structure. A representation of J(B) is obtained by three-dimensional perspective plots and by planar maps visualizing phase portraits of electron flow in a series of molecular domains. Both streamline J(B) /|J(B) | and modulus |J(B) | are analyzed. These graphic tools illustrate the competition between diatropic and paratropic regimes which determine the magnitude of various components of magnetizability and magnetic shielding of hydrogen and carbon nuclei. Shielding density maps show that the differential Biot-Savart law explains magnetic shielding at hydrogen and carbon nuclei, and virtual shielding at ring and cage centers. Similarities and/or contrasting ring current effects on magnetotropicity are discussed by a comparison with triprismane C(6)H(6) and cubane C(8)H(8) .


Calling song recognition in female crickets: temporal tuning of identified brain neurons matches behavior.
Phonotactic orientation of female crickets is tuned to the temporal pattern of the male calling song. We analyzed the phonotactic selectivity of female crickets to varying temporal features of calling song patterns and compared it with the auditory response properties of the ascending interneuron AN1 (herein referred to as TH1-AC1) and four newly identified local brain neurons. The neurites of all brain neurons formed a ring-like branching pattern in the anterior protocerebrum that overlapped with the axonal arborizations of TH1-AC1. All brain neurons responded phasically to the sound pulses of a species-specific chirp. The spike activity of TH1-AC1 and the local interneuron, B-LI2, copied different auditory patterns regardless of their temporal structure. Two other neurons, B-LI3 and B-LC3, matched the temporal selectivity of the phonotactic responses but also responded to some nonattractive patterns. Neuron B-LC3 linked the bilateral auditory areas in the protocerebrum. One local brain neuron, B-LI4, received inhibitory as well as excitatory synaptic inputs. Inhibition was particularly pronounced for nonattractive pulse patterns, reducing its spike activity. When tested with different temporal patterns, B-LI4 exhibited bandpass response properties; its different auditory response functions significantly matched the tuning of phonotaxis. Temporal selectivity was established already for the second of two sound pulses separated by one species-specific pulse interval. Temporal pattern recognition in the cricket brain occurs within the anterior protocerebrum at the first stage of auditory processing. It is crucially linked to a change in auditory responsiveness during pulse intervals and based on fast interactions of inhibition and excitation.


CHD1 and CHD2 are positive regulators of HIV-1 gene expression.
Retroviruses encode a very limited number of proteins and therefore must exploit a wide variety of host proteins for completion of their lifecycle. We performed an insertional mutagenesis screen to identify novel cellular regulators of retroviral replication. This approach identified the ATP-dependent chromatin remodeler, chromodomain helicase DNA-binding protein 2 (CHD2), as well as the highly related CHD1 protein, as positive regulators of both MLV and HIV-1 replication in rodent and human cells. RNAi knockdown of either CHD2 or the related CHD1 protein, in human cells resulted in a block to infection by HIV-1, specifically at the level of transcription. These results demonstrate that CHD1 and CHD2 can act as positive regulators of HIV-1 gene expression.


[Inhibitor participation in the regulation of serum RNAse activity in the formation of immunity against influenza].
It was shown that parenteral administration of lead ions caused in the blood serum of albino mice a significant decrease in the amount of the bound RNA-ase 1 inhibitor and a simultaneous increase in the activity of this enzyme. Consequently, this inhibitor served as a regulator of the serum RNA-ase 1 activity. A considerable increase in the amount of the bound and free RNA-ase 1 inhibitor was noted in the serum in the process of triple immunization of persons with live influenza vaccine; this was accompanied by a significant reduction of the free RNA-ase 1 activity. This indicated that along with other mechanisms the inhibitor apparently participated in the processes of formation of immunity against influenza.


A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Pericarp Color1 (P1) encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize (Zea mays) silks and red phlobaphene pigments in pericarps and other floral tissues, which makes P1 an important visual marker. Using genome-wide expression analyses (RNA sequencing) in pericarps and silks of plants with contrasting P1 alleles combined with chromatin immunoprecipitation coupled with high-throughput sequencing, we show here that the regulatory functions of P1 are much broader than the activation of genes corresponding to enzymes in a branch of flavonoid biosynthesis. P1 modulates the expression of several thousand genes, and ∼1500 of them were identified as putative direct targets of P1. Among them, we identified F2H1, corresponding to a P450 enzyme that converts naringenin into 2-hydroxynaringenin, a key branch point in the P1-controlled pathway and the first step in the formation of insecticidal C-glycosyl flavones. Unexpectedly, the binding of P1 to gene regulatory regions can result in both gene activation and repression. Our results indicate that P1 is the major regulator for a set of genes involved in flavonoid biosynthesis and a minor modulator of the expression of a much larger gene set that includes genes involved in primary metabolism and production of other specialized compounds.


Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats.
Exogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague-Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats. Male 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed. We reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted β-very-low-density lipoprotein (β-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the β-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats. Low production of liver TAG and secretion of CE-rich, TAG-poor β-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.


Transcriptional and post-transcriptional regulation of soybean seed protein mRNA levels.
We investigated soybean seed protein gene transcription during development. We found that seed protein genes are transcriptionally activated and then repressed during embryogenesis and that these genes are either inactive or transcribed at low levels in the mature plant. We further observed that genes encoding mRNAs with vastly different prevalences are transcribed at similar rates. DNA gel blot studies showed that transcriptionally active and inactive seed protein genes have indistinguishable methylation patterns. We conclude that both transcriptional and posttranscriptional processes regulate seed protein mRNA levels in the absence of detectable DNA methylation changes.


Activation of the human transient receptor potential vanilloid subtype 1 by essential oils.
Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel activated by capsaicin. TRPV1 is expressed not only on human sensory neurons but also on human epidermal and hair follicle keratinocytes. Therefore, TRPV1 could have the potential to be a therapeutic target for skin disorders. To search for novel TRPV1 agonists, we screened 31 essential oils by using human TRPV1-expressing HEK293 cells. TRPV1 was activated by 4 essential oils: rose, thyme geraniol, palmarosa, and tolu balsam. The dose-response curves for TRPV1 activation by the essential oils revealed a rank order potency [the half-maximal effective concentration (EC(50))] of rose>palmarosa>thyme geraniol>tolu balsam, and rank order efficiency (% activity in response to 1 microM capsaicin) of tolu balsam>rose>palmarosa>thyme geraniol. Moreover, the dose-response curves for TRPV1 activation by citronellol (main constituent of rose oil) and geraniol (main constituent of thyme geraniol and palmarosa oils) were consistent with the potency and efficiency of each essential oil. In contrast, benzyl cinnamate and benzyl benzoate (main constituent of tolu balsam oil) and geranyl acetate (main constituent of thyme geraniol oil) did not show TRPV1 activity. In this first-of-its-kind study, we successfully investigated the role of some essential oils in promoting human TRPV1 activation, and also identified two monoterpenes, citronellol and geraniol, as new human TRPV1 agonists.


Modelling the factor structure of the Child Depression Inventory in a population of apparently healthy adolescents in Nigeria.
Childhood and adolescent depression is common and often persists into adulthood with negative implications for school performances, peer relationship and behavioural functioning. The Child Depression Inventory (CDI) has been used to assess depression among adolescents in many countries including Nigeria but it is uncertain if the theoretical structure of CDI appropriately fits the experiences of adolescents in Nigeria. This study assessed varying theoretical modelling structure of the CDI in a population of apparently healthy adolescents in Benue state, Nigeria. Data was extracted on CDI scale and demographic information from a total of 1, 963 adolescents (aged 10-19 years), who participated in a state wide study assessing adolescent psychosocial functioning. In addition to descriptive statistics and reliability tests, Exploratory Factor Analysis (EFA) and Confirmatory Factor analysis (CFA) were used to model the underlying factor structure and its adequacy. The suggested new model was compared with existing CDI models as well as the CDI's original theoretical model. A model is considered better, if it has minimum Root Mean Square Error of Approximation (RMSEA<0.05), Minimum value of Discrepancy (CMIN/DF<3.0) and Akaike information criteria. All analyses were performed at 95% confidence level, using the version 21 of AMOS and the R software. Participants were 14.7±2.1 years and mostly male (54.3%), from Monogamous homes (67.9%) and lived in urban areas (52.2%). The measure of the overall internal consistency of the 2-factor CDI was α = 0.84. The 2-factor model had the minimum RMSEA (0.044), CMIN/DF (2.87) and least AIC (1037.996) compared to the other five CDI models. The child depression inventory has a 2-factor structure in a non-clinical general population of adolescents in Nigeria. Future use of the CDI in related setting may consider the 2-factor model.


[Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure].
The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.


Possible contributions of skin pigmentation and vitamin D in a polyfactorial model of seasonal affective disorder.
Seasonal affective disorder (SAD) is a polyfactorial and polygenetic disorder that involves biological and psychological sub-mechanisms that differentially involve depression, seasonality, circadian rhythms, retinal sensitivity, iris pigmentation, sleep factors, and the neurotransmitters involved with these systems. Within the framework of the polyfactorial conceptualization of SAD, we review the possible contributions of vitamin D3 with respect to the aforementioned sub-mechanisms. We hypothesize that rather than functioning primarily as a proximal or direct sub-mechanism in the etiology of SAD, vitamin D likely functions in a more foundational and regulative role in potentiating the sub-mechanisms associated with the depressive and seasonality factors. There are several reasons for this position: 1. vitamin D levels fluctuate in the body seasonally, with a lag, in direct relation to seasonally-available sunlight; 2. lower vitamin D levels have been observed in depressed patients (as well as in patients with other psychiatric disorders) compared to controls; 3. vitamin D levels in the central nervous system affect the production of both serotonin and dopamine; and 4. vitamin D and vitamin D responsive elements are found throughout the midbrain regions and are especially concentrated in the hypothalamus, a region that encompasses the circadian timing systems and much of its neural circuitry. We also consider the variable of skin pigmentation as this may affect levels of vitamin D in the body. We hypothesize that people with darker skin pigmentation may experience greater risks for lower vitamin D levels that, especially following their migration to regions of higher latitude, could contribute to the emergence of SAD and other psychiatric and physical health problems.


Immune modulation properties of herbal plant leaves: Phyllanthus niruri aqueous extract on immune cells of tuberculosis patient - in vitro study.
Disease progression in Tuberculosis (TB) is dependent on host's immune system. Phyllanthus niruri, a traditional herb, has long been used to boost immune system in Indonesian society. This study aimed to observe the potential role of P. niruri in inducing immune cells activity in TB patients by in vitro approach. Peripheral blood mononuclear cells (PBMCs) and macrophages were collected from active pulmonary TB patients. After stimulation with graded doses of P. niruri aqueous extract, cell proliferation, phagocytic activity and nitric oxide (NO) release were analysed. P. niruri aqueous extract induced proliferation of PBMCs, increased NO release, and improved macrophages phagocytic activity. These effects were observed in a dose-dependent manner. This may lead to further research for the potential role of P. niruri as immunomodulatory adjuvant therapy for TB patients.


Encouraging psychological outcomes after altruistic donation to a stranger.
In a growing number of transplant centers worldwide, altruistic donors are accepted to anonymously donate a kidney to a stranger. An important hesitation to expand these transplantation programs is the fear of evoking psychological distress in the altruistic donor after donation. To what extent this fear is justified has not yet been systematically investigated. In this study, 24 altruistic donors were interviewed on average 2 years after donation. Lifetime mental health history, current psychological complaints, satisfaction with and impact of the donation on well-being, motives for donation, communication with recipient and donation experience were assessed. Altruistic donors report a considerable positive impact of donation on psychological well-being, whereas negative impact was limited. Satisfaction with donation was very high. Although a history of a psychiatric diagnosis was ascertained in almost half of the donors, psychological complaints before and after donation were comparable to national average norm scores. Motives for donation were genuine and the experience of donation generally conformed to their expectations. In conclusion, living kidney donation to a stranger does not appear to exacerbate psychological complaints. Moreover, altruistic donors report considerable satisfaction and personal benefit. The exceptional gift of altruistic donors can contribute toward solving the current organ shortage issue.


Why do adults with spina bifida and hydrocephalus die? A clinic-based study.
To establish the death rate and factors contributing to death among attenders at a clinic for adults with spina bifida and hydrocephalus (CASBAH). Due to improvements in medical care in the past 40 years, increasing numbers of spina bifida patients go on to prosper in adult life. Despite this, levels of morbidity are high and services for such patients are uneven and unpredictable. Since 1990 there has been a CASBAH service in Belfast operating on a regional basis. Led by a consultant in rehabilitation medicine, it provides a multidisciplinary approach to patient care. Between 1990 and 1999 there have been 280 referrals to the clinic. Charts were reviewed regarding current health status and mode of death where relevant. There have been 18 deaths during the term of the clinic (6.4%). There were four deaths due to renal failure and two due to cardiac failure. Two deaths occurred following surgery for a Chiari/hydrosyringomyelia complex and one patient died due to shunt malfunction. Three deaths were presumed related to infection. Two deaths were attributable to malignancy (carcinoma of a renal conduit and transitional cell carcinoma of the kidney) and other terminal events in one patient each were: basilar artery aneurysm rupture, post-partum pulmonary embolism, peptic ulcer disease, myocardial infarction and status epilepticus. Although certain deaths were unpredictable during the period of review and not directly attributable to spina bifida, the majority reflect many of the related secondary health issues of the condition and indicate the need for organised, medically co-ordinated follow-up of adult patients.