Access to continued-use medication among older adults, Brazil.
OBJECTIVE To determine the prevalence and associated access factors for all continued-use prescription drugs and the ways in which they can be obtained. METHODS Data was obtained from the 2008 Household National Survey. The sample comprised 27,333 individuals above 60 years who reported that they used continued-use prescription drugs. A descriptive analysis and binary and multiple multinomial logistic regressions were performed. RESULTS 86.0% of the older adults had access to all the medication they needed, and among them, 50.7% purchased said medication. Those who obtained medication from the public health system were younger (60-64 years), did not have health insurance plans, and belonged to the lower income groups. It is remarkable that 14.0% of the subjects still had no access to any continued-use medication, and for those with more than four chronic diseases, this amount reached 22.0%. Those with a greater number of chronic diseases ran a higher risk of not having access to all the medication they needed. CONCLUSIONS There are some groups of older adults with an increased risk of not obtaining all the medication they need and of purchasing it. The results of this study are expected to contribute to guide programs and plans for access to medication in Brazil.


The dual role of Smad7 in the control of cancer growth and metastasis.
Smad7 was initially identified as an inhibitor of Transforming growth factor (TGF)-β due mainly to its ability to bind TGF-β receptor type I and prevent TGF-β-associated Smad signaling. More recently, it has been demonstrated that Smad7 can interact with other intracellular proteins and regulate also TGF-β-independent signaling pathways thus making a valid contribution to the neoplastic processes in various organs. In particular, data emerging from experimental studies indicate that Smad7 may differently modulate the course of various tumors depending on the context analyzed. These observations, together with the demonstration that Smad7 expression is deregulated in many cancers, suggest that therapeutic interventions around Smad7 can help interfere with the development/progression of human cancers. In this article we review and discuss the available data supporting the role of Smad7 in the modulation of cancer growth and progression.


Contraception across transgender.
Sexual and reproductive issues are essential elements of well-being in cisgenders as well as for the transgender population. Gender-affirming hormonal treatments (GAHTs) aim to induce phenotypical changes congruent with the desired gender and subsequent reduction of gender dysphoria. While genital surgical procedures including hysterectomy and/or adenectomy cause permanent loss of ability to conceive, GAHT may induce a varying degree of reversible loss of fertility. For these reasons, transgender men and women need to be counseled concerning contraceptive options and potential effects of treatment on reproductive function before initiating GAHT. The literature reports that sexual activity with genital involvement is performed by less than half of transgender persons who have been sexually active with a partner in the past. Testosterone (T) is the most commonly used compound in transmen and usually leads to amenorrhea within 1-12 months from first administration, however cessation of menses does not mean anovulation. Some studies report cases of unintended pregnancies among transgender men under masculinizing therapy, therefore T treatment cannot be considered a contraceptive option. Currently available contraceptive options have pros and cons in transmen and scarce literature exists on their use. The effects of GAHT on fertility in transwomen are even less well known. Prolonged estrogen exposure induces sperm suppression and morphological changes of the spermatozoa, however the degree of resulting pregnancy protection is unclear. Further research to inform the contraceptive counseling in this population is mandatory.


31P Magnetic Resonance Spectroscopy Assessment of Muscle Bioenergetics as a Predictor of Gait Speed in the Baltimore Longitudinal Study of Aging.
Aerobic fitness and muscle bioenergetic capacity decline with age; whether such declines explain age-related slowing of walking speed is unclear. We hypothesized that muscle energetics and aerobic capacity are independent correlates of walking speed in simple and challenging performance tests and that they account for the observed age-related decline in walking speed in these same tests. Muscle bioenergetics was assessed as postexercise recovery rate of phosphocreatine (PCr), k PCr, using phosphorus magnetic resonance spectroscopy (31P-MRS) in 126 participants (53 men) of the Baltimore Longitudinal Study of Aging aged 26-91 years (mean = 72 years). Four walking tasks were administered-usual pace over 6 m and 150 seconds and fast pace over 6 m and 400 m. Separately, aerobic fitness was assessed as peak oxygen consumption (peak VO2) using a graded treadmill test. All gait speeds, k PCr, and peak VO2 were lower with older age. Independent of age, sex, height, and weight, both k PCr and peak VO2 were positively and significantly associated with fast pace and long distance walking but only peak VO2 and not k PCr was significantly associated with usual gait speed over 6 m. Both k PCr and peak VO2 substantially attenuated the association between age and gait speed for all but the least stressful walking task of 6 m at usual pace. Muscle bioenergetics assessed using 31P-MRS is highly correlated with walking speed and partially explains age-related poorer performance in fast and long walking tasks.


ANP32A and ANP32B are key factors in the Rev-dependent CRM1 pathway for nuclear export of HIV-1 unspliced mRNA.
The nuclear export receptor CRM1 is an important regulator involved in the shuttling of various cellular and viral RNAs between the nucleus and the cytoplasm. HIV-1 Rev interacts with CRM1 in the late phase of HIV-1 replication to promote nuclear export of unspliced and single spliced HIV-1 transcripts. However, other cellular factors involved in the CRM1-dependent viral RNA nuclear export remain largely unknown. Here, we demonstrate that ANP32A and ANP32B mediate the export of unspliced or partially spliced viral mRNA via interactions with Rev and CRM1. We found that a double, but not single, knockout of ANP32A and ANP32B significantly decreased the expression of gag protein. Reconstitution of either ANP32A or ANP32B restored the viral production equally. Disruption of both ANP32A and ANP32B expression led to a dramatic accumulation of unspliced viral mRNA in the nucleus. We further identified that ANP32A and ANP32B interact with both Rev and CRM1 to promote RNA transport. Our data strongly suggest that ANP32A and ANP32B play an important role in the Rev-CRM1 pathway, which is essential for HIV-1 replication, and our findings provide a candidate therapeutic target for host defense against retroviral infection.


Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study.
Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (-800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella™ enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.


Drug-Induced Itch Management.
Drugs may cause itching as a concomitant symptom of drug-induced skin reactions or in the form of pruritus without skin lesions. Drug-induced itch is defined as generalized itching without skin lesions, caused by a drug. Itching associated with drug-induced cholestasis is among the common dermatologic adverse events (dAEs) that induce itching. Some drugs such as opioids, antimalarials, and hydroxyethyl starch are known to induce itching without skin lesions. The clinical features and underlying proposed mechanisms of itching caused by these drugs have been specifically investigated. The recent application of targeted anticancer drugs has increased the survival rate of cancer patients. These new agents cause significant dAEs such as acneiform rashes, dry skin, hand-foot syndrome, paronychia, and itching. Itching is a common side effect of epidermal growth factor receptor inhibitors. Though not life-threatening, these dAEs have a negative impact on a patient's quality of life, leading to dose reduction and possibly less effective cancer therapy. It is important to provide an effective supportive antipruritic treatment without interruption of the administration of these drugs. This chapter concludes by describing basic measures to be taken for diagnosis and treatment of drug-induced itch. The principle of treatment is discontinuation of suspected causative drugs in general except for anticancer medications. In case itching lasts long after drug withdrawal or the causative drug cannot be stopped, vigorous symptomatic antipruritic treatment and specific therapies for different types of drug-induced itch should be undertaken.


Platelet anti-aggregating activity and tolerance of clopidogrel in atherosclerotic patients.
The anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trail of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50, 75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 microM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.


Current state of and need for enzyme engineering of 2-deoxy-D-ribose 5-phosphate aldolases and its impact.
Deoxyribose-5-phosphate aldolases (DERAs, EC 126.96.36.199) are acetaldehyde-dependent, Class I aldolases catalyzing in nature a reversible aldol reaction between an acetaldehyde donor (C2 compound) and glyceraldehyde-3-phosphate acceptor (C3 compound, C3P) to generate deoxyribose-5-phosphate (C5 compound, DR5P). DERA enzymes have been found to accept also other types of aldehydes as their donor, and in particular as acceptor molecules. Consequently, DERA enzymes can be applied in C-C bond formation reactions to produce novel compounds, thus offering a versatile biocatalytic alternative for synthesis. DERA enzymes, found in all kingdoms of life, share a common TIM barrel fold despite the low overall sequence identity. The catalytic mechanism is well-studied and involves formation of a covalent enzyme-substrate intermediate. A number of protein engineering studies to optimize substrate specificity, enzyme efficiency, and stability of DERA aldolases have been published. These have employed various engineering strategies including structure-based design, directed evolution, and recently also machine learning-guided protein engineering. For application purposes, enzyme immobilization and usage of whole cell catalysis are preferred methods as they improve the overall performance of the biocatalytic processes, including often also the stability of the enzyme. Besides single-step enzymatic reactions, DERA aldolases have also been applied in multi-enzyme cascade reactions both in vitro and in vivo. The DERA-based applications range from synthesis of commodity chemicals and flavours to more complicated and high-value pharmaceutical compounds. KEY POINTS: • DERA aldolases are versatile biocatalysts able to make new C-C bonds. • Synthetic utility of DERAs has been improved by protein engineering approaches. • Computational methods are expected to speed up the future DERA engineering efforts.


Infant iron deficiency, child affect, and maternal unresponsiveness: Testing the long-term effects of functional isolation.
Children who are iron deficient (ID) or iron-deficient anemic (IDA) have been shown to seek and receive less stimulation from their caregivers, contributing to functional isolation. Over time, the reduced interactions between child and caregiver are thought to interfere with the acquisition of normative social competencies and adversely affect the child's development. The current study examined functional isolation in children who were ID or IDA in infancy in relation to social difficulties in middle childhood and problem behaviors in adolescence. Using a sample of 873 Chilean children, 45% of whom were ID or IDA in infancy, structural equation modeling results indicated that infant IDA was associated with children's dull affect and social reticence at age 5, which were related to mothers' unresponsiveness and understimulation. Mothers' limited responsiveness and stimulation were, in turn, related to children's peer rejection at age 10, which further linked to problem behaviors and associating with deviant peers at adolescence. Findings support the functional isolation hypothesis and suggest that early limited caregiver responsiveness and stimulation contribute to long-term social difficulties in adolescents who were iron-deficient anemic in infancy. (PsycINFO Database Record


Combined approach for spontaneous rupture of hepatocellular carcinoma.
Ruptured hepatocellular carcinoma is a rare, emergency occurrence in western countries with high mortality risk. A number of hypotheses have been formulated in order to explain the precise mechanism that leads to hepatocellular carcinoma (HCC) rupture: sub-capsular location, dimensions, portal hypertension, tumour necrosis, local increase of venous pressure due to the outflow reduction caused by neoplastic invasion, and the presence of a previous vascular injury which might predispose to HCC rupture. There is still a debate in the literature concerning the best approach in cases of HCC rupture. Surgery is the first option for treatment of acute abdominal bleeding. However the advent of endovascular treatments widens the range of possible therapies for acute bleeding control and subsequent ablation purposes. We report a case of hemoperitoneum from spontaneous rupture of undiagnosed HCC, that was treated successfully by emergency surgical resection followed by transarterial chemo-embolization for local recurrence.


Clinal variation for amino acid polymorphisms at the Pgm locus in Drosophila melanogaster.
Clinal variation is common for enzymes in the glycolytic pathway for Drosophila melanogaster and is generally accepted as an adaptive response to different climates. Although the enzyme phosphoglucomutase (PGM) possesses several allozyme polymorphisms, it is unique in that it had been reported to show no clinal variation. Our recent DNA sequence investigation of Pgm found extensive cryptic amino acid polymorphism segregating with the allozyme alleles. In this study, we characterize the geographic variation of Pgm amino acid polymorphisms at the nucleotide level along a latitudinal cline in the eastern United States. A survey of 15 SNPs across the Pgm gene finds significant clinal differentiation for the allozyme polymorphisms as well as for many of the cryptic amino acid polymorphisms. A test of independence shows that pervasive linkage disequilibrium across this gene region can explain many of the amino acid clines. A single Pgm haplotype defined by two amino acid polymorphisms shows the strongest correlation with latitude and the steepest change in allele frequency across the cline. We propose that clinal selection at Pgm may in part explain the extensive amino acid polymorphism at this locus and is consistent with a multilocus response to selection in the glycolytic pathway.


Remote results of reconstructive operations in pathological deformity of the internal carotid artery.
to study remote results of surgical treatment of patients presenting with a pathological deformity of the internal carotid artery. the study was based on retrospectively analysing the findings of examination and the outcomes of surgical treatment of 142 patients presenting with an isolated pathological deformity of the internal carotid artery (ICA), who underwent a total of 166 reconstructive operations. 7% of patients were operated on at the asymptomatic stage, more than half (56%) of the patients were found to have transient (21%) or persistent neurological deficit (35%), 37% of patients had stage III cerebrovascular insufficiency. Twenty-five (15%) operations were performed for C- and S-shape tortuosity, ninety-seven (58%) procedures for kinking of the internal carotid artery, and forty-four (27%) interventions for coiling. The operation of choice was resection with redressation of the internal carotid artery and reimplantation into the old ostium (74%). Analysing the results of surgical treatment showed its high neurological efficiency in prevention of cerebral circulation impairments (93% of patients at terms up to 25 years had no such complications), as well as clinical efficacy (relief of cerebrovascular insufficiency symptoms in 91.1% of patients). The effect obtained appeared to preserve during 2 and 5 years in 96% and 92% of patients, respectively, and at terms up to 25 years in 83%. The 3-, 5- and up- to-25-year survival amounted to 95%, 92% and 75%, respectively. Restenosis of the internal carotid artery was significantly more often observed after prosthetic repair of the artery (p <0.05) as compared with other methods of reconstruction employed. Thromboses of the internal carotid artery were encountered with similar frequency (8%) only after prosthetic repair and resection of the internal carotid artery with an «end-to-end» anastomosis, which was significantly more often than in resection with redressation (p <0.05). Stroke incidence in the remote postoperative period amounted to 0.8% and the «stroke + stroke-related mortality» parameter equalled 1.6%. the remote results of surgical treatment for pathological deformity of the internal carotid artery are strongly suggestive of high efficacy of this method of prevention of impairments of cerebral circulation and treatment of cerebrovascular insufficiency in patients with the pathology concerned. The operation of choice in pathological deformity of the internal carotid artery is resection with redressation of the internal carotid artery and reimplantation into the original ostium.


Synthesis of coral-like tantalum oxide films via anodization in mixed organic-inorganic electrolytes.
We report a simple method to fabricate nano-porous tantalum oxide films via anodization with Ta foils as the anode at room temperature. A mixture of ethylene glycol, phosphoric acid, NH4F and H2O was used as the electrolyte where the nano-porous tantalum oxide could be synthesized by anodizing a tantalum foil for 1 h at 20 V in a two-electrode configuration. The as-prepared porous film exhibited a continuous, uniform and coral-like morphology. The diameters of pores ranged from 30 nm to 50 nm. The pores interlaced each other and the depth was about 150 nm. After calcination, the as-synthesized amorphous tantalum oxide could be crystallized to the orthorhombic crystal system. As observed in photocatalytic experiments, the coral-like tantalum oxide exhibited a higher photocatalytic activity for the degradation of phenol than that with a compact surface morphology, and the elimination rate of phenol increased by 66.7%.


Coregulation, dysregulation, self-regulation: an integrative analysis and empirical agenda for understanding adult attachment, separation, loss, and recovery.
An integrative framework is proposed for understanding how multiple biological and psychological systems are regulated in the context of adult attachment relationships, dysregulated by separation and loss experiences, and, potentially, re-regulated through individual recovery efforts. Evidence is reviewed for a coregulatory model of normative attachment, defined as a pattern of interwoven physiology between romantic partners that results from the conditioning of biological reward systems and the emergence of felt security within adult pair bonds. The loss of coregulation can portend a state of biobehavioral dysregulation, ranging from diffuse psychophysiological arousal and disorganization to a full-blown (and highly organized) stress response. The major task for successful recovery is adopting a self-regulatory strategy that attenuates the dysregulating effects of the attachment disruption. Research evidence is reviewed across multiple levels of analysis, and the article concludes with a series of testable research questions on the interconnected nature of attachment, loss, and recovery processes.


Serum protein electrophoretic pattern and angiotensin-converting enzyme in sarcoidosis.
S-angiotensin-converting enzyme (SACE), s-protein electrophoretic pattern and ESR were examined in 61 patients with sarcoidosis. Among 46 patients with active disease there was a significant elevation of ESR, alpha 2-globulin, and gamma-globulin, but the deviations from healthy controls were generally small and the pattern was unspecific, without correlation to clinical or roentgenographic features. Elevation of SACE was confined to active sarcoidosis, in which group elevation was noted in 59% of the patients. SACE was positively correlated to total protein and gamma-globulin. This correlation may not be causal but rather an expression of two different cellular activities in the disease, involving the macrophage-system and the B-lymphocytes, respectively.


Assessment of the relationship of spiritual well-being to depression and quality of life for persons with spinal cord injury.
This study sought to describe the association between spiritual well-being, demographic characteristics, quality of life (QOL) and depressive symptoms following spinal cord injury (SCI). We hypothesized QOL and depressed mood would both be explained by extent of spiritual well-being, and meaning-focused (M&P) spirituality would have a stronger impact than faith-focused spirituality. 210 individuals with SCI were screened as part of a randomized control trial of venlafaxine XR for major depressive disorder (MDD). 204 completed all measures: Patient Health Questionniare-9 (PHQ-9) assessed depression, the FACIT-Sp assessed spiritual well-being, the Neuro-QOL PAWB scale assessed QOL, and the PANAS assessed affect. Approximately 26% had major depression. Bivariate correlations of scores on PAWB and PANAS and FACIT-Sp showed that all four scales had strong associations with those on PAWB (p < 0.0005). As hypothesized, both the M&P and Faith scales of the FACIT-Sp were significant predictors of QOL (β = 0.544; p < 0.0005 and β = 0.151; p = 0.004), though only the M&P scale was an independently significant predictor of likely MDD. The findings support that spirituality, as measured by the FACIT-Sp, is strongly associated with QOL and likelihood of MDD. Assessment of spirituality should be included along with more traditional psychological measurements to better inform treatment. Implications for Rehabilitation Spiritual beliefs can contribute to quality of life and may help moderate depressive symptoms that accompany chronic illness and disability, suggesting that rehabilitation professionals should address spirituality in working with their patients with spinal cord injury (SCI). While spiritual issues are often deferred to pastoral counselors during hospitalization, it is clear that addressing these is not the domain of one discipline and does not end upon inpatient discharge. In addressing spirituality, clinicians should tap the spiritual strengths present in their clients, whether meaning/peace-focused or religious, understanding that spirituality involves more than religiosity and also that having a sense of meaning and peace appears to be of great importance.


Peripheral nerve injury: principles for repair and regeneration.
Peripheral Nerve Injuries are one of the most common causes of hand dysfunction caused by upper limb trauma but still current management has remained suboptimal. This review aims to explain the traditional view of pathophysiology of nerve repair and also describe why surgical management is still inadequate in using the new biological research that has documented the changes that occur after the nerve injury, which, could cause suboptimal clinical outcomes. Subsequently presentation and diagnosis will be described for peripheral nerve injuries. When traditional surgical repair using end-to-end anastomosis is not adequate nerve conduits are required with the gold standard being the autologous nerve. Due to associated donor site morbidity and poor functional outcome documented with autologous nerve repair several new advancements for alternatives to bridge the gap are being investigated. We will summarise the new and future advancements of non-biological and biological replacements as well as gene therapy, which are being considered as the alternatives for peripheral nerve repair.


X-ray irradiation induced Disabled-2 gene promoter de-methylation enhances radiosensitivity of non-small-cell lung carcinoma cells.
Disabled-2 (Dab2) is known as a tumor suppressor as well as a Wnt pathway inhibitor. We previously reported that Dab2 was down-regulated due to gene promoter hypermethylation in lung cancer. Here, we aim to study if X-ray irradiation can induce de-methylation of the Dab2 gene and subsequently up-regulate its expression, and also to attempt to suppress the malignant biological behavior of and enhance the radiosensitivity in lung cancer cells with hypermethylation of the Dab2 gene. Immunostaining was performed to investigate the relationship between Dab2 expression and lung cancer clinicopathological characteristics. Bisulfite sequencing PCR (BSP) was used to evaluate the methylation status of lung cancer cells with or without X-ray treatment. Real-time PCR and western Blot were performed to investigate the expression of Dab2, Wnt pathway factors, DNMTs and methyl CpG binding protein 2 (MeCP2). Colony Formation, matrigel invasion and xenograft experiment were performed to evaluate the malignant biological behavior of lung cancer cells with irradiation. The result of immunostaining of Dab2 in lung cancer tissues showed that decreased Dab2 expression was positively correlated with poor differentiation, lymph node metastasis, advanced TNM stage and poor prognosis. X-ray treatment significantly up-regulated Dab2 expression and inhibited Wnt factors in LK2 cells (with hypermethylation of the Dab2 gene promoter, P < 0.05), but not in SPC-A-1 cells (with hypomethylation of the Dab2 gene promoter); however, the effect could be reversed by Dab2 or Axin knockdown (P < 0.05). Decreased expression of DNMT1, DNMT3b and MeCP2 could be detected in both LK2 and SPC-A-1 cells compared to non-irradiated cells (P < 0.05). Both in vitro studies and in vivo xenograft tumor growth demonstrated that X-ray could significantly inhibit the proliferation and invasion of LK2 but not SPC-A-1 cells (P < 0.05). In general, X-ray-induced up-regulation of Dab2 and inhibition of the Wnt pathway may be mediated by de-methylation of a hypermethylated Dab2 gene promoter. X-ray treatment significantly inhibits proliferation and invasion of lung cancer cells with hypermethylation of the Dab2 gene promoter, but is less effective in lung cancer cells with hypomethylation of the Dab2 gene promoter. These results indicate that the methylation status of the Dab2 gene promoter might be a potential predictor of the radiosensitivity of lung cancer cells.


[The effect of the acidity of the medium and of the temperature on the growth and polysaccharide excretion of Bacillus subtilis under submerged cultivation].
Growth of Bacillus subtilis strains and excretion of polysaccharides have been studied under different environmental condition. These strains were studied as active antagonists of pathogenic microflora and were used for development of the biopreparation (probiotic), being efficient in treatment and prophylaxis of a number of bacterial infections of farm animals; the drug soon will be put into series production. The indices of accumulation of biomass of viable cells and exopolysaccharides (EPS) were used to study productivity of the strains. A possibility to increase yield in the production process was shown using the temperature factor and optimal pH of the culture medium under batch cultivation. The processes of the biomass and EPS accumulation were noncompetitive, almost coincided in time and were independent of the initial level of the pH of medium.


Facial growth after condylectomy or ostectomy in the mandibular ramus.
A study was conducted in six young and six adult monkeys to determine how the condyle influences growth of the mandible. Either an ostectomy in the ramus to decrease condylar height or a condylectomy was performed on each monkey. Similar morphologic changes were observed in the maxilla and the mandible of both groups, indicating that the changes resulted from ramal shortening and alterations in function rather than from loss of a condylar growth center.


Three-photon microscopy shows that somatic release can be a quantitatively significant component of serotonergic neurotransmission in the mammalian brain.
Recent experiments on monoaminergic neurons have shown that neurotransmission can originate from somatic release. However, little is known about the quantity of monoamine available to be released through this extrasynaptic pathway or about the intracellular dynamics that mediate such release. Using three-photon microscopy, we directly imaged serotonin autofluorescence and investigated the total serotonin content, release competence, and release kinetics of somatic serotonergic vesicles in the dorsal raphe neurons of the rat. We found that the somata of primary cultured neurons contain a large number of serotonin-filled vesicles arranged in a perinuclear fashion. A similar distribution is also observed in fresh tissue slice preparations obtained from the rat dorsal raphe. We estimate that the soma of a cultured neuron on an average contains about 9 fmoles of serotonin in about 450 vesicles (or vesicle clusters) of < or =370 nm average diameter. A substantial fraction (>30%) of this serotonin is released with a time scale of several minutes by K(+)-induced depolarization or by para-chloroamphetamine treatment. The amount of releasable serotonin stored in the somatic vesicles is comparable to the total serotonin content of all the synaptic vesicles in a raphe neuron, indicating that somatic release can potentially play a major role in serotonergic neurotransmission in the mammalian brain.


[Expression of chemokine like factor-like myelin and lymphocyte and related proteins for vesicle trafficking and membrane link transmembrane domain-containing protein 2 in rats with varicocele].
To investigate whether chemokine like factor (CKLF)-like myelin and lymphocyte and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain-containing protein 2 (CMTM2) is involved in spermatogenesis in varicocele induced subfertility rats and to discuss the possible mechanisms. Forty male SD rats (body weight: 220-330 g, age: 6-7 weeks) were randomly divided into 4 groups: varicocele for 4 weeks, varicocele for 12 weeks, sham operation for 4 weeks and sham operation for 12 weeks, with 10 rats in each group. These rats were introduced by partially ligating left kidney veins for the experimental groups, and the sham surgery groups as controls were executed with exactly the same surgery as in the experimental groups except for the ligation. The rats in control and experimental groups for 4 and 12 weeks were killed after laparotomy at the end of 4 and 12 weeks, respectively, the left testes and epididymis were taken out for counting the sperm, observing the seminiferous tubule change and immunochemistry for CMTM2. The changes included sperm density and motility, the outer diameter and inner diameter change and the changes of epithelium and the CMTM2 expression in immunochemistry. Compared with the control groups, the sperm density [(63.9±7.1)×106/mL vs.(74.3±5.0)×106/mL] and motility [(58.7%±7.9%) vs.(66.1%±4.3%)] were reduced slightly in group of varicoele for 4 weeks, respectively (t=1.432, 1.563; P=0.076, 0.059, respectively). Varicocele significantly caused a decrease in sperm concentration [(40.5±7.2) ×106/mL vs.(71.1±4.5)×106/mL] and motility [(35.2%±8.5%)vs. (63.4%±4.1%)] at 12 weeks, compared with the related sham groups (t=3.754, 3.933; P=0.004, 0.002, respectively). Additionally, testis CMTM2 exhibited the same disparity, that is, the CMTM2 protein expression in varicocele group was significantly reduced, with the ratio of sham group to varicocele group at the end of 12 weeks 2.3±0.4 (t=1.978; P=0.039). In the evaluation of seminiferous tubules diameter, the external [(198.2±10.2) μm vs. (255.8±12.7) μm, t=2.125, P=0.003] and epithelium diameter [(54.1±1.5) μm vs. (75.5±4.1) μm, t=2.246, P=0.021] were decreased compared with the sham-related groups and previous varicocele groups. In all the varicocele groups, all types of sperm motility decreased compared with the related sham-operated group (P<0.05). This study suggests varicocele has a detrimental effect on CMTM2 levels and decreases spermatogonia cell number, seminiferous tubules diameter, and sperm indices. CMTM2 is associated with sperm changes in rats with varicocele, and further studies are needed to study the mechanism.


Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease.
The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site.


Advances in G protein-coupled receptor allostery: from function to structure.
It is now widely accepted that G protein-coupled receptors (GPCRs) are highly dynamic proteins that adopt multiple active states linked to distinct functional outcomes. Furthermore, these states can be differentially stabilized not only by orthosteric ligands but also by allosteric ligands acting at spatially distinct binding sites. The key pharmacologic characteristics of GPCR allostery include improved selectivity due to either greater sequence divergence between receptor subtypes and/or subtype-selective cooperativity, a ceiling level to the effect, probe dependence (whereby the magnitude and direction of the allosteric effect change with the nature of the interacting ligands), and the potential for biased signaling. Recent chemical biology developments are beginning to demonstrate how the incorporation of analytical pharmacology and operational modeling into the experimental workflow can enrich structure-activity studies of allostery and bias, and have also led to the discovery of a new class of hybrid orthosteric/allosteric (bitopic) molecules. The potential for endogenous allosteric modulators to play a role in physiology and disease remains to be fully appreciated but will likely represent an important area for future studies. Finally, breakthroughs in structural and computational biology are beginning to unravel the mechanistic basis of GPCR allosteric modulation at the molecular level.


Biological activities of purified marennine, the blue pigment responsible for the greening of oysters.
Marennine, the blue pigment produced by the diatom Haslea ostrearia , exists in two different forms, the intra- and extracellular forms. We investigated the antibacterial, antiviral, and antiproliferative properties of both of these forms. Both forms of marennine inhibited the development of marine bacteria, in particular the pathogenic organism Vibrio aesturianus , at concentrations as low as 1 μg/mL, but they did not display any effect on a wide range of pathogenic bacteria that are relevant for food safety. Both forms of the pigment produced by H. ostrearia also exhibited antiviral activity against the HSV1 herpes virus, with intra- and extracellular marennine having EC(50) values of 24.0 and 27.0 μg/mL, respectively. These values are 2 orders of magnitude higher than the value for the reference drug, Zovirax. Moreover, both forms of marennine were effective in slowing or inhibiting the proliferation of cancer cells. This study confirms the potential of marennine as a biologically active organic molecule, which could have a protective effect on bivalves, which filter seawater and fix the pigment on their gills. Moreover, marennine could be used in food engineering and chemistry as a natural blue pigment. However, despite that it is eaten and possibly assimilated by green oyster consumers, it also deserves in depth evaluation before being considered for use as a nutraceutical.


Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.
Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET. Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis. Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168). ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET. • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.


The multi-country PROMOTE HIV antiretroviral treatment observational cohort in Sub-Saharan Africa: Objectives, design, and baseline findings.
The PROMOTE study aims to measure long-term antiretroviral treatment (ART) safety and adherence; compare HIV disease progression; assess subsequent adverse pregnancy outcomes; evaluate effect of ART exposure on growth and development in HIV-exposed uninfected children; and assess long-term survival of mothers and children. This report primarily describes cohort characteristics at baseline to better understand long-term outcomes. This is a prospective study. HIV-infected mothers and their children originally recruited in a multisite randomized clinical trial for prevention of perinatal HIV transmission were re-enrolled in PROMOTE. A total of 1987 mothers and 1784 children were enrolled from eight sites in Uganda, Malawi, Zimbabwe and South Africa. Most women (≥75%) reported being married in Malawi and Zimbabwe compared to low proportions in South Africa (4.4% in Durban and 15% in Soweto), and 43.5% in Uganda (p<0.001). There were variabilities in contraceptive practices: injectable contraceptive was the commonest reported method (40.9% overall); implant was the second commonest (15.7% overall); oral contraceptives were common in Zimbabwe; and tubal ligation was common in Malawi and South Africa. At baseline, 97.8% of women reported currently using ART; 96.4% were in WHO clinical class 1 or 2; median CD4 cell count was 825 cells per uL; and viral load was undetectable in 1637 (~85%) of the women. Approximately, 14% of women did not inform their primary partners of their own HIV status, 18% reported that they knew their partners were not HIV tested, and 9% did not know if partner was tested. Overall mean age of children at enrollment was 3.5 years; and 5.7% and 25.0% had weight-for-age and height-for-age z-scores <2 standard deviations, respectively. These baseline data show high adherence to ART use. However, issues of HIV disclosure and reproductive intentions remain important. In addition to ART and ensuring high adherence, other preventive measures should be included.


Direct observation of individual particle armored bubble interaction, stability, and coalescence dynamics.
The interactions between two individual particle-stabilized bubbles were investigated, in the absence of surfactant, using a combination of coalescence rig and high-speed video camera. This combination allows the visualization of bubble coalescence dynamics which provide information on bubble stability. Experimental data suggested that bubble stability is enhanced by both the adsorption of particles at the interface as indicated by the long induction time and the increase in damping coefficient at high surface coverage. The interaction between an armored bubble and a bare bubble (asymmetric interaction) can be destabilized through the addition of a small amount of salt, which suggested that electrostatic interactions play a significant role in bubble stability. Interestingly, the DLVO theory cannot be used to describe the bubble stability in the case of a symmetric interaction as coalescence was inhibited at 0.1 M KCl in both the absence and presence of particles at the interfaces. Furthermore, bubbles can also be destabilized by increasing the particle hydrophobicity. This behavior is due to thinner liquid films between bubbles and an increase in film drainage rate. The fraction of particles detached from the bubble surface after film rupture was found to be very similar within the range of solution ionic strength, surface coverage, and particle hydrophobicity studied. This lack of dependence implies that the kinetic energy generated by the coalescing bubbles is larger than the attachment energy of the particles and dominates the detachment process. This study illuminates the stability behavior of individual particle-stabilized bubbles and has potential impact on processes which involve their interaction.


The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands.
The long and complex Trypanosoma brucei development in the tsetse fly vector culminates when parasites gain mammalian infectivity in the salivary glands. A key step in this process is the establishment of monoallelic variant surface glycoprotein (VSG) expression and the formation of the VSG coat. The establishment of VSG monoallelic expression is complex and poorly understood, due to the multiple parasite stages present in the salivary glands. Therefore, we sought to further our understanding of this phenomenon by performing single-cell RNA-sequencing (scRNA-seq) on these trypanosome populations. We were able to capture the developmental program of trypanosomes in the salivary glands, identifying populations of epimastigote, gamete, pre-metacyclic and metacyclic cells. Our results show that parasite metabolism is dramatically remodeled during development in the salivary glands, with a shift in transcript abundance from tricarboxylic acid metabolism to glycolytic metabolism. Analysis of VSG gene expression in pre-metacyclic and metacyclic cells revealed a dynamic VSG gene activation program. Strikingly, we found that pre-metacyclic cells contain transcripts from multiple VSG genes, which resolves to singular VSG gene expression in mature metacyclic cells. Single molecule RNA fluorescence in situ hybridisation (smRNA-FISH) of VSG gene expression following in vitro metacyclogenesis confirmed this finding. Our data demonstrate that multiple VSG genes are transcribed before a single gene is chosen. We propose a transcriptional race model governs the initiation of monoallelic expression.


Darling, Come Lay with Me or Talk with Me: Perceived Mattering and the Complementary Association between Sex and Communication within Marital Relationships.
According to the theories on interpersonal mattering, reciprocal interactions and mutual engagements facilitate the formation of interpersonal mattering within relationships. However, the theoretical framework on mattering has rarely been applied to understand the roles of sexual and verbal exchanges within intimate relationships. To fill this research gap, the authors proposed that heightened perception of mattering captures the common mechanism through which both frequent sex and communication predict greater marital satisfaction. Building on this perspective, the study examined whether frequent sex and communication can compensate for the other in predicting marital satisfaction by sustaining the sense of mattering between spouses. Two survey studies were conducted using cross-cultural online samples (Study 1: Nkorean = 307 and NAmerican = 277) and a community sample of married dyads (Study 2: N = 286). Across these samples, the results demonstrated that the perceived sense of mattering to spouse mediated the effects of both sexual frequency and communication quantity on the couples' overall satisfaction with their marriage. Moreover, the results of the moderated mediation analyses supported the hypothesis that sexual frequency and communication quantity can moderate the effects of the other on marital satisfaction by providing a buffer on the couples' perceived sense of mattering to spouse.


Interaction of putative transmitters in central nervous pathways involved in the control of heart rate and arterial pressure.
As many putative transmitter substances have been shown to be co-localized in areas of the central nervous system involved in cardiovascular control, we have investigated the possibility that some of these substances may interact in eliciting changes in heart rate and arterial pressure in anesthetized rats. In a first set of experiments, interactions between atrial natriuretic factor and glutamate were investigated by microinjection into the nucleus of the tractus solitarius, the site of termination of baroreceptor fibers of the aortic depressor nerve. In addition, interactions between the transmitter released in the nucleus tractus solitarius by electrical stimulation of the aortic depressor nerve and atrial natriuretic factor microinjected into the nucleus tractus solitarius were investigated. Combined microinjection of atrial natriuretic factor and glutamate into the nucleus tractus solitarius, or stimulation of the aortic depressor nerve combined with atrial natriuretic factor in the nucleus tractus solitarius, elicited decreases in heart rate and arterial pressure which were greater than the responses to either substance or stimulation alone or their algebraic sum. In a second set of experiments, interactions between substance P and acetylcholine were investigated in the intermediolateral nucleus of the spinal cord, the location of sympathetic preganglionic neurons. Furthermore, we investigated the possibility that the cardiovascular responses to microinjection of substance P and acetylcholine into the intermediolateral nucleus could be potentiated by the transmitter released in the intermediolateral nucleus by microinjection of glutamate into the rostral ventrolateral medulla, a region with known sympatho-excitatory function.(ABSTRACT TRUNCATED AT 250 WORDS)


In Vivo Study of The Oestrogenic Activity of Milk.
Milk has been suggested to be a possible source of oestrogenically active compounds. In order to assess the health risk for milk consumers and ensure the safety of this staple part of the human diet, it is important to study the effect of xenooestrogen mixtures present in milk. This investigation used the available in vivo model to learn to what extent such compounds may be endocrine disruptors. The recommended immature golden hamster uterotrophic bioassay was chosen. A total of 132 animals were divided into nine groups of experimental animals and positive and negative control groups, each of 12 animals. The experimental females received ad libitum either one of five samples of raw cow's milk from individual animals or one of four samples of pasteurised or ultra-high temperature treated cow's milk as retail products. After 7 days, the animals were sacrificed and necropsied. Uterine weight increases were measured as the endpoint of oestrogenic activity in milk. The milk samples from individual cows and the retail milk samples did not show oestrogenic activity. However, in three groups, decreased uterine weights were observed. Considering that milk supplies are beneficial to health, contamination in this food should be avoided. There is a need for further animal experiments and epidemiological studies are warranted to evaluate any causative role of milk in human endocrinological disorders.


Population dynamics of Cosmoclopius nigroannulatus Stal (Hemiptera, Reduviidae) in tobacco culture.
The role of predators influencing populations of insects considered as pests is extremely important for agroecosystems. The population ecology of Cosmoclopius nigroannulatus, a predatory reduvid associated with the tobacco culture was investigated aiming to study the population dynamics of adults, along the culture cycle. In an experimental plot of approximately 300 m2, in Porto Alegre (30 degrees 0'S; 51 degrees 13'W), RS, Brazil, 270 tobacco plants were grown; each plant identified by alphanumeric coordinates. Using the mark-release-recapture method, daily samplings were done from August to December 1999, and three times a week from this date until April 2000. The adults were captured by hand, marked, sexed and released on the same plant they were captured. The individual number and plant coordinate were registered. Population estimates were analyzed by the Fisher-Ford method. In 107 sampling occasions, 604 individuals were marked, 273 males and 331 females. Three generations of C. nigroannulatus were registered during the culture cycle. The colonizing generation was represented by 14 males and 15 females (a sex ratio of 0.48), the first by 109 males and 137 females (0.44) and the second by 150 males and 179 females (0.46). The estimated daily survival rate varied between generations decreasing from 98% in the colonizing generation to 87% in the second. The observed longevity or permanence time in the experimental area varied significantly among generations, being at about 40 days in the colonizing generation, 13 days in the first and 5 days in the second. It was observed that as the population increases, the survival and/or permanence time in the area decreases, suggesting a relation between this and a decline in the available resources probably with an associated increase in intra-specific competition.


Histochemical localization of nitric oxide neurons in the hypothalamus: association with gonadotropin-releasing hormone neurons and co-localization with N-methyl-D-aspartate receptors.
The neurotransmitter glutamate plays an important role in the control of gonadotropin-releasing hormone (GnRH) secretion. Recent evidence suggests that the novel transmitter nitric oxide may also play a role in controlling GnRH release and may be an important mediator of glutamate effects. To explore the role of nitric oxide in these events, the present study determined the distribution of the enzyme which catalyzes nitric oxide production, nitric oxide synthase (NOS) in the hypothalamus, its association with GnRH neurons, and whether NOS neurons contain NMDA receptors. NOS was localized by staining hypothalamic sections from female rats for NADPH-diaphorase activity. Specific antibodies for GnRH and the NMDAR1 receptor subunit were used for double-staining to determine NOS association with GnRH neurons and the presence of NMDA R1 receptor subunits in hypothalamic NOS neurons. The studies showed intense NOS cell body and fiber staining in the organum vasculosum of the lamina terminalis (OVLT) where numerous GnRH cell bodies are located. Other major GnRH cell body sites such as the median preoptic nucleus (MPN) and medial preoptic area (MPOA) displayed moderate staining of NOS cell bodies and fibers. Intense NOS staining was also observed in the median eminence, ventromedial nucleus, paraventricular nucleus and supraoptic nucleus of the hypothalamus. While no GnRH neurons were found to double stain for NOS in the hypothalamus, GnRH neurons were frequently surrounded by NOS neurons in the OVLT, MPN and MPOA with potential contacts between NOS and GnRH neurons in these areas. In addition, there was significant overlap of GnRH and NOS fibers in the lateral portion of the internal zone of the median eminence where GnRH fibers and terminals converge. Double-staining studies for NADPH-diaphorase and NMDA R1 receptor subunit showed that many NOS neurons in the OVLT, MPOA, ventromedial nucleus, paraventricular nucleus and supraoptic nucleus co-localize the NMDA R1 receptor subunit. Localization of NMDA R1 receptor subunit immunoreactivity in B-NOS neurons in the hypothalamus was further confirmed by using combined immunohistochemistry-in situ hybridization. Finally, the functional importance of this co-localization was shown by the finding that central administration of a nitric oxide synthase inhibitor blocked the ability of NMDA to induce LH secretion. Taken as a whole, these studies provide evidence which support a role for nitric oxide as an important regulator of GnRH neurons in the female. They also suggest that hypothalamic NOS neurons are targets for glutamate regulation as evidenced by co-localization of the NMDA R1 receptor subunit.


Acoustic Change Responses to Amplitude Modulation in Cochlear Implant Users: Relationships to Speech Perception.
The ability to understand speech is highly variable in people with cochlear implants (CIs) and to date, there are no objective measures that identify the root of this discrepancy. However, behavioral measures of temporal processing such as the temporal modulation transfer function (TMTF) has previously found to be related to vowel and consonant identification in CI users. The acoustic change complex (ACC) is a cortical auditory-evoked potential response that can be elicited by a "change" in an ongoing stimulus. In this study, the ACC elicited by amplitude modulation (AM) change was related to measures of speech perception as well as the amplitude detection threshold in CI users. Ten CI users (mean age: 50 years old) participated in this study. All subjects participated in behavioral tests that included both speech and amplitude modulation detection to obtain a TMTF. CI users were categorized as "good" (n = 6) or "poor" (n = 4) based on their speech-in noise score (<50%). 64-channel electroencephalographic recordings were conducted while CI users passively listened to AM change sounds that were presented in a free field setting. The AM change stimulus was white noise with four different AM rates (4, 40, 100, and 300 Hz). Behavioral results show that AM detection thresholds in CI users were higher compared to the normal-hearing (NH) group for all AM rates. The electrophysiological data suggest that N1 responses were significantly decreased in amplitude and their latencies were increased in CI users compared to NH controls. In addition, the N1 latencies for the poor CI performers were delayed compared to the good CI performers. The N1 latency for 40 Hz AM was correlated with various speech perception measures. Our data suggest that the ACC to AM change provides an objective index of speech perception abilities that can be used to explain some of the variation in speech perception observed among CI users.


RHD gene polymorphism among RhD-negative Han Chinese.
To evaluate the status of eight RHD specific exons in 131 Han Chinese blood donors who were classified as RhD-negative by serological methods and explore the genomic structure of RHD gene among the Han Chinese. The Rh blood group system has the highest prevalence of polymorphisms among human blood group systems and is clinically significant in transfusion medicine. The Rh antigens are expressed on polypeptides encoded by two highly homologous genes, RHD and RHCE. Recent molecular studies have shown that the RhD-negative trait could be generated by multiple genetic mechanisms and is ethnic group-dependent. The polymerase chain reaction using-sequence specific primers (PCR-SSP) was used to amplify exons 2, 3, 4, 5, 6, 7, 9 and 10 of RHD gene and exons 1, 2 and 5 of RHCE gene, as well as intron 4 in each of them. The 131 cases of RhD-negative phenotypes consisted of 60 ccee, 58 Ccee, 5 ccEe, 5 CcEe and 3 CCee. Among them, 83 with the Rh ccee or ccEe phenotypes (63.4%) lacked the eight RHD exons indicated above, while 26 cases with the Rh Ccee, CCee, CcEe phenotypes (19.9%) had all the RHD exons examined. Twenty-two individuals with the Ccee, CCee, CcEe phenotypes (16.8%) carried at least one RHD exon. The phenotypes of the RhD negative individuals carrying the RHD gene were Rh CC or Cc, but not cc. Three classes of RhD-negative polymorphisms among a population of Han Chinese were observed. Antigen association analysis suggested the existence of a novel class of RhD-negative associated haplotype in Han Chinese. This haplotype consisted of a normal RHCE allele and a nonfunctional RHD gene. It may be beneficial to redefine the RhD-negative blood group among Chinese populations upon clarification of the mechanisms of RHD gene expression and RhD antigen immunization.


Pollution level in distillery effluent and its phytotoxic effect on seed germination and early growth of maize and rice.
The effluent from a Lucknow- based distillery (Mohan Meakin Distillery) was analyzed for physico-chemical and biological parameters of pollution and concentration of potentially toxic heavy metals (Cd, Cr, Ni and Zn) and the effect of the distillery effluent, as such and on 50% dilution with tap water was studied on seed germination and seedling growth of maize (Zea mays L.) and rice (Oryza sativa L.). The effluent was wine red in colour and highly acidic (pH approximately 55) and possessed decaying alcoholic smell. The effluent contained high values of different pollution parameters, particularly total solids, 3450 mgl(-1) (soluble plus suspended solids), alkalinity 1500 mgl(-1), biological oxygen demand (BOD, 1649 mgl(-1)) and chemical oxygen demand (COD, 2036 mgl(-1)). It had very low values of dissolved oxygen (DO, 0.34 mgl(-1)). The heavy metals (Cd, Cr, Ni and Zn) content, particularly the nickel concentration (0.029 mg l(-1)) was high. Use of the distillery effluent, even on 1:1 dilution with tap water inhibited germination and early seedling growth of maize and rice. In both maize and rice, more so in the former germination % of seeds, length of radicle and plumule and the fresh and dry weight of the seedlings were significantly reduced. The emerging leaves of the seedlings also developed visible effects of toxicity some of which resembled the symptoms of nickel toxicity. Our observations suggest that the effluent, as discharged from the distillery carry a heavy load of pollutants. Its discharge into the river Gomti poses a potential threat to the aquatic life, perticularly during the summer months when the water flow in the river is drastically reduced. The distillery effluentis also harmful for irrigating crops grown along the drain carrying it.


Sex Differences in Stress and Group Housing Effects on the Number of Newly Proliferated Cells and Neuroblasts in Middle-Aged Dentate Gyrus.
Sex differences in stress and coping responses have been frequently documented in aged people, while whether such differences in aged people may appear at the middle age are unknown. This study was undertaken to study the impact of acute stress and social interaction on early neurogenesis in the dentate gyrus (DG) and hippocampus-related memory in two sexes of middle-aged mice. The number of newly proliferated cells, neuroblasts in DG, the object recognition and location memory in 9-month-old male and female C57BL/6N mice were assessed under baseline conditions as well as following an acute stressor regimen and group housing. Three conspecific companions, serving as "the housing group," were used to model the social interaction throughout the stressor regimen. Males had lower numbers of newly proliferated cells and neuroblasts under baseline conditions as compared to females. The stressor regimen caused rapid decreases in the number of newly proliferated cells and neuroblasts in female DG but no obvious changes were observed in male DG. Group housing, regardless of companions' age, prevented the stress-induced decreases in the number of newly proliferated cells and neuroblasts in female DG. In contrast, the presence of young or age-matched companions potentiated the stress effect in males by decreasing the number of newly proliferated cells and neuroblasts. Finally, neither the stressor regimen nor group housing affected mouse performances in the object recognition and location memory in either sex. These findings, taken together, provide evidence to support a notion that middle-aged females appear to demonstrate more stress susceptibility on early neurogenesis in DG as compared to middle-aged males, although the hippocampus-related memory performances are comparable and not affected by stress in these males and females. Experiencing stress, middle-aged females are more prone to benefit from social interaction as compared to middle-aged males in this regard. We suggest, accordingly, that involving social interaction may afford a therapeutic advance in preventing stress-produced decreases in early neurogenesis in middle-aged females' DG.


POLYOMA VIRUS: PRODUCTION IN BACILLUS SUBTILIS.
Particles of complete polyoma virus are produced in competent Bacillus subtilis incubated with DNA isolated from purified, conventionally grown polyoma virus. The virus grown in B. subtilis is biologically identical to polyoma virus produced by animal cells. Quantitative parameters of the system have been established, and fluctuation tests indicate that viral replication occurs within the infected bacteria.


Near shot-noise limited time-resolved circular dichroism pump-probe spectrometer.
We describe an optical near shot-noise limited time-resolved circular dichroism (TRCD) pump-probe spectrometer capable of reliably measuring circular dichroism signals in the order of μdeg with nanosecond time resolution. Such sensitivity is achieved through a modification of existing TRCD designs and introduction of a new data processing protocol that eliminates approximations that have caused substantial nonlinearities in past measurements and allows the measurement of absorption and circular dichroism transients simultaneously with a single pump pulse. The exceptional signal-to-noise ratio of the described setup makes the TRCD technique applicable to a large range of non-biological and biological systems. The spectrometer was used to record, for the first time, weak TRCD kinetics associated with the triplet state energy transfer in the photosynthetic Fenna-Matthews-Olson antenna pigment-protein complex.


Role of innate immunity in triggering and tuning of autoimmune diabetes.
Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cells (APCs) to beta-cell antigens to almost total insulin deficiency due to islet destruction. Although it is established that the interaction of environmental factors with genetic traits plays a pivotal role in the pathogenesis of T1D, in most cases, the exact trigger of anti-islet autoimmunity and how genetic and environmental factors regulate its progression, ultimately leading to the development of T1D remain elusive. In this review, based on the recent advances in understanding the role of innate immunity in development of autoimmune diseases, we focus on the possibility that aberrant regulation of the innate immune system frequently observed in animal models and patients with T1D, induces T1D by triggering anti-islet autoimmunity in the context of the autoimmune-prone environment; this information might provide an insight into possibilities for therapeutic intervention modulating innate immunity to mitigate or prevent T1D.


Application of Data-Driven Decision Making Using Ayres Sensory Integration(®) With a Child With Autism.
Health care and educational legislation and policy require that clinicians demonstrate, using measurement and report of outcomes, accountability for services rendered. Clinical algorithms have been developed and are used by various health care professionals to assist with hypothesis generation and systematic clinical reasoning; however, they do not explicitly guide measurement of outcomes as part of the reasoning process. Schaaf and colleagues developed the Data-Driven Decision Making (DDDM) process to address the greater need for outcome measurement, systematically support decision making, target intervention more precisely, and measure and document outcomes. This article describes the application of the DDDM process with a child with ASD who received occupational therapy using Ayres Sensory Integration(®).


[Comparative antiplatelet efficacy of prasugrel and high-dose clopidogrel in patients with coronary heart disease including acute coronary syndrome].
A number of randomized double-blind studies have been conducted for comparative assessment of the pharmacodynamic properties of high loading and maintenance doses of clopidogrel (600-900 mg loading dose and 150 mg maintenance dose) and standard dose of prasugrel (60 mg loading dose and 10 mg maintenance dose) in patients with coronary heart disease, including those with acute coronary syndrome. This review briefly discusses the trials ACAPULCO and PRINCIPLE-TIMI 44. Compared with high dose clopidogrel, prasugrel inhibited P2Y12-mediated platelet aggregation faster and to a greater extent. A difference between effects of clopidogrel and prasugrel emerged as soon as at 30 minutes after the loading dose. Antiplatelet effects of prasugrel were greater than those of clopidogrel both during first 2-4 hours after administration of loading dose, and during maintenance dosing. This may have important clinical implications.


A comparative sequence analysis to revise the current taxonomy of the family Coronaviridae.
The Coronaviridae family, comprising the Coronavirus and Torovirus genera, is part of the Nidovirales order that also includes two other families, Arteriviridae and Roniviridae. Based on genetic and serological relationships, groups 1, 2 and 3 were previously recognized in the Coronavirus genus. In this report we present results of comparative sequence analysis of the spike (S), envelope (E), membrane (M), and nucleoprotein (N) structural proteins, and the two most conserved replicase domains, putative RNA-dependent RNA polymerase (RdRp) and RNA helicase (HEL), aimed at a revision of the Coronaviridae taxonomy. The results of pairwise comparisons involving structural and replicase proteins of the Coronavirus genus were consistent and produced percentages of sequence identities that were distributed in discontinuous clusters. Inter-group pairwise scores formed a single cluster in the lowest percentile. No homologs of the N and E proteins have been found outside coronaviruses, and the only (very) distant homologs of S and M proteins were identified in toroviruses. Intragroup sequence conservation was higher, although for some pairs, especially those from the most diverse group 1, scores were close or even overlapped with those from the intergroup comparisons. Phylogenetic analysis of six proteins using a neighbor-joining algorithm confirmed three coronavirus groups. Comparative sequence analysis of RdRp and HEL domains were extended to include arterivirus and ronivirus homologs. The pairwise scores between sequences of the genera Coronavirus and Torovirus (22-25% and 21-25%) were found to be very close to or overlapped with the value ranges (12 to 22% and 17 to 25%) obtained for interfamily pairwise comparisons, but were much smaller than values derived from pairwise comparisons within the Coronavirus genus (63-71% and 59-67%). Phylogenetic analysis confirmed toroviruses and coronaviruses to be separated by a large distance that is comparable to those between established nidovirus families. Based on comparison of these scores with those derived from analysis of separate ranks of several multi-genera virus families, like the Picornaviridae, a revision of the Coronaviridae taxonomy is proposed. We suggest the Coronavirus and Torovirus genera to be re-defined as two subfamilies within the Coronavirdae or two families within Nidovirales, and the current three informal coronavirus groups to be converted into three genera within the Coronaviridae.


Mapping the literature of respiratory therapy.
Little research has been conducted on the characteristics of the literature of respiratory care. The bibliometric method was used to identify the core journals in the discipline and the extent of indexing of those journals. This study was a part of Medical Library Association (MLA) Nursing and Allied Health Resources Section's project to map the literature of allied health. Findings indicate that the research writings of the discipline cite journal articles most heavily, with the majority of the citations published between 1980 and 1993. The literature has a small core of cited journals with a wide dispersion. MEDLINE and EMBASE provided the best indexing coverage of the literature, and minimal coverage was given by the Cumulative Index to Nursing and Allied Health Literature and HEALTH.


Sleepwalking in Italian operas: a window on popular and scientific knowledge on sleep disorders in the 19th century.
There is little knowledge on sleepwalking in ancient times even though it is a very common condition. The aim of this report is to describe the backgrounds of medical knowledge on somnambulism in the 19th century, a key period in the development of neurosciences, by analysing its representation in two famous Italian operas: La Sonnambula by Vincenzo Bellini and Macbeth by Giuseppe Verdi. The 19th-century operas may be considered as a crossing point between the popular and intellectual world because they mirror popular answers to phenomena that were still awaiting scientific explanations. Shakespeare's play Macbeth was also considered. In Shakespeare's play and in Verdi's Macbeth, sleepwalking is looked upon as a neuropsychiatric disorder, a manifestation of internal anxiety. In La Sonnambula by Bellini, this condition is considered as common disorder that anticipates scientific theories. The analysed Italian operas provide two different views on sleepwalking, probably because they are based on texts belonging to different periods. Their examination allows one to understand the gradual evolution of theories on sleepwalking, from demoniac possession to mental disorder and sleep disease. At the same time, this analysis throws some light on the history of psychological illnesses.


Ectopic ACTH-producing large cell neuroendocrine Pancoast tumour presenting as Horner syndrome.
We present an interesting case where a patient is presented with a droopy left eyelid (as part of Horner syndrome) and Cushingoid features which were a result of a Pancoast tumour (apical lung tumour in superior pulmonary sulcus) involving the left lung. This tumour was secreting ectopic adrenocorticotropic hormone (ACTH), a paraneoplastic endocrine phenomenon, which resulted in Cushing syndrome symptomatology. Though most ectopic ACTH-producing lung cancers are either small cell or carcinoid tumours, this was in fact a large cell neuroendocrine cancer (LCNEC). Patient underwent surgical resection and adjuvant/neoadjuvant chemotherapy with radiation; however, he succumbed to LCNEC given aggressive nature of the disease.


Genome annotation and comparative analyses of the odorant-binding proteins and chemosensory proteins in the pea aphid Acyrthosiphon pisum.
Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are two families of small water-soluble proteins, abundant in the aqueous fluid surrounding olfactory receptor neurons in insect antennae. OBPs are involved in the first step of olfactory signal transduction, carrying airborne semiochemicals to the odorant receptors and can be classified into three groups: Classic OBPs, Plus-C OBPs and Atypical OBPs. Here, we identified and annotated genes encoding putative OBPs and CSPs in the pea aphid Acyrthosiphon pisum using bioinformatics. This identified genes encoding 13 Classic and two Plus-C OBPs and 13 CSPs. Homologous OBP sequences were also identified in nine other aphid species, allowing us to compare OBPs across several aphid and non-aphid species. We show that, although OBP sequences are divergent within a species and between different orders, there is a high similarity between orthologs within a range of aphid species. Furthermore, the phylogenetic relationships between OBP orthologs reflect the divergence of aphid evolution lineages. Our results support the 'birth-and-death' model as the major mechanism explaining aphid OBP sequence evolution, with the main force acting on the evolution being purifying selection.


Diagnosis of pulmonary infection caused by Aspergillus: usefulness of respiratory cultures.
Aspergillus infection is often difficult to diagnose, and the usefulness of methods of culture for diagnosis has been questioned. We reviewed all respiratory cultures that yielded any species of Aspergillus and all surgical and autopsy materials suspected or diagnostic of infection with Aspergillus over a two-year period. Of 89 patients with one or more positive cultures of nonbiopsy respiratory tract specimens, eight had histologically proven disease (three had aspergillomas and five, invasive aspergillosis). All cases of disease were due to Aspergillus fumigatus or Aspergillus flavus, and eight of nine patients with two or more positive cultures of A. fumigatus or A. flavus had proven disease, versus one of 81 who were uninfected (P less than .001). Cultures from infected patients also had heavier growth and contained mixed Aspergillus species less often than did cultures from uninfected patients. We conclude that cultures of respiratory specimens are useful for diagnosis of pulmonary infection caused by Aspergillus.


Symptoms of migraine in the paediatric population by age group.
The revised criteria of the International Headache Society (IHS) for paediatric headache do not differentiate among age groups. This study aims to determine if different symptoms of migraine are specific or typical of different age groups of children. The files of 160 children (79 boys, 81 girls, mean age 10.39 +/- 3.71 years) with migraine treated at the paediatric headache clinic of a tertiary centre were reviewed. The diagnosis was based on the criteria of the IHS (ICHD-II). The patients were divided by age into three groups according to educational status, < or =6 years (preschool, group 1), >6 to < or =12 years (elementary school, group 2) and >12 to < or =18 years (secondary school, group 3), and compared by symptoms and signs. Symptoms of migraine with and without aura were also compared. There was no significant difference among the groups in rates of unilateral headache, phonophobia, photophobia, awakening pain, nausea or worsening of pain during physical activity. The parameters found to be statistically significant were dizziness and duration of migraine, and aura which increased with time. Frequency of attacks increased with age. The single statistically significant parameter found to be more frequent in younger age was vomiting. The statistically significant parameters of nausea and duration of migraine were more frequent in migraine with aura compared with migraine without aura. In conclusion, most of the migraine symptoms included in the 2004 recommendations of the IHS are not typical for specific paediatric age groups, probably because brain maturity is a continuous process. A familial history of migraine is a frequent finding among all age groups and should be considered in the paediatric criteria, especially in younger children in whom diagnosis is more difficult. Vomiting may help the diagnosis of migraine in young children with a familial history of migraine.


Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.
More than 850 million people worldwide suffer from acute and chronic kidney diseases (CKD) which are tremendous socioeconomic burdens for society. Currently, the treatment choices for CKD are limited. There is a great need to understand the underlying mechanisms of the development of CKD in order to develop potential therapeutic strategies. The alteration in cellular metabolism has emerged as an important common pathological mechanism in different kidney diseases. Metabolic intervening and reprogramming will yield new insights to prevent and slow the progression of kidney disease. As one essential component of cellular metabolisms in fuel-source preferences (glucose, fatty acids, or ketones), the polyamine compound metabolism comprising the metabolites (spermine, spermidine, and putrescine) and their biosynthetic and catabolic enzymes are an endogenous pathophysiological regulator that is arising as a potential therapeutic object for many diseases. This article aimed to review current knowledge on polyamine metabolism and physiological processes, and its potential regulatory and beneficial roles in immunoregulation, mitochondrial homeostasis, autophagy, DNA damage, and kidney diseases, and thus provide a novel therapeutic opportunity for kidney diseases.


Association of low 25-hydroxyvitamin D concentrations with elevated parathyroid hormone concentrations and low cortical bone density in early pubertal and prepubertal Finnish girls.
Very few studies have evaluated both parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] and their effects on bone mass in children. We studied the associations of serum 25(OH)D and intact PTH (iPTH) with bone mineral content (BMC) and bone mineral density (BMD) at different bone sites and the relation between serum 25(OH)D and iPTH in early pubertal and prepubertal Finnish girls. The subjects were 10-12-y-old girls (n = 193) at Tanner stage 1 or 2, who reported a mean (+/- SD) dietary calcium intake of 733 +/- 288 mg/d. 25(OH)D, iPTH, tartrate-resistant acid phosphatase 5b (TRAP 5b), urinary calcium excretion, BMC, areal BMD, and volumetric BMD were assessed by using different methods. Thirty-two percent of the girls were vitamin D deficient [serum 25(OH)D < or = 25 nmol/L], and 46% of the girls had an insufficient concentration (26-40 nmol/L). iPTH and TRAP 5b concentrations were significantly higher in the deficient group than in the insufficient and sufficient groups [iPTH: 43.9 +/- 15.7 compared with 38.6 +/- 11.2 pg/L (P = 0.049) and 32.7 +/- 12.1 pg/L (P < 0.001), respectively; TRAP 5b: 12.2 +/- 2.9 compared with 11.0 +/- 2.8 U/L (P = 0.009) and 10.9 +/- 1.9 U/L (P = 0.006), respectively]. The girls in the deficient group also had significantly lower cortical volumetric BMD of the distal radius (P < 0.001) and tibia shaft (P = 0.002). High iPTH concentrations were also associated with low total-body apparent mineral density and urinary calcium excretion (P < 0.007). Vitamin D-deficient girls have low cortical BMD and high iPTH concentrations, which are consistent with secondary hyperparathyroidism. A low vitamin D concentration accompanied by high bone resorption (TRAP 5b) may limit the accretion of bone mass in young girls.


Intra-arterial chemotherapy as a treatment for intraocular retinoblastoma: alternatives to direct ophthalmic artery catheterization.
Intra-arterial chemotherapy is a very effective treatment option for intraocular retinoblastoma. However, direct catheterization of the OA is not always possible. The purpose of this work was to report our initial results with intra-arterial chemotherapy for intraocular retinoblastoma when delivery of the drug was not via direct catheterization of the OA. Retrospective review of 110 eyes (89 patients) undergoing a total of 351 intra-arterial treatments at our institution between 2006 and 2010 identified 18 eyes (14 patients) that received at least 1 infusion via a vascular route other than direct OA catheterization. Alternatives included catheterization of the orbital branch of the MMA and temporary balloon occlusion of the ICA. Tumor control was observed in 17 of 18 eyes at a mean follow-up of 18.9 months (median, 17.5 months; range, 8-36 months). The mean number of intra-arterial infusions was 3.7 per eye (median, 3; range, 2-9). Treatment routes included the following: MMA only, 3 eyes; MMA + OA, 4 eyes; MMA + balloon, 2 eyes; balloon only, 1 eye; balloon + OA, 7 eyes; balloon + OA + MMA, 1 eye. Intra-arterial chemotherapies included melphalan, topotecan, and carboplatin. Complications were all transient. ERG readings were the following: stable, 10 eyes; improved, 3 eyes; reduced, 5 eyes. One patient died from a second malignancy (pinealoblastoma). This initial experience shows that when direct OA catheterization is not possible, using alternative routes of intra-arterial chemotherapy saves eyes and preserves vision with acceptable side effects.


The DNA sequence of human chromosome 7.
Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame.


Involvement of a single thiol group in the conversion of the NAD+-dependent activity of rat liver xanthine oxidoreductase to the O2-dependent activity.
The effects of 2-iodosobenzoic acid, 4-chloromercuribenzoate, 5,5'-dithiobis-(2-nitrobenzoic acid) and tetraethylthioperoxydicarbonic diamide (disulphiram) on the NAD+-dependent activity of xanthine oxidoreductase from rat liver were investigated. Only disulphiram converted the NAD+-dependent activity into the O2-dependent activity quantitatively, without changing the xanthine hydroxylation rate. The modification process was a first-order reaction with respect to time (min) and disulphiram concentration (microM). The kinetic data showed that modification of single thiol group is sufficient for loss of the enzymic activity towards NAD+ as electron acceptor. The complete protection afforded by NAD+ against the action of disulphiram suggests that the essential thiol group may be involved in binding of NAD+ to the xanthine oxidoreductase molecule.


Inhibition of apoptosis in rat mesangial cells by tissue inhibitor of metalloproteinase-1.
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an important inhibitor of extracellular matrix degradation. Recently, it was reported that TIMP-1 also could inhibit apoptosis in B type lymphocyte. This study was designed to examine the effects of TIMP-1 on mesangial cell apoptosis. The full-length cDNA of TIMP-1 was cloned and used to construct two recombinant vectors, TIMP-1S and TIMP-1AS, encoding sense TIMP-1 and antisense TIMP-1, respectively. The vectors were transfected into rat mesangial cells (RMC) and their expressions detected by Northern and Western blotting. Apoptosis was induced by serum deprivation, and was monitored for DNA fragmentation by TUNEL assay and DNA laddering. In addition, the expression of endogenous TIMP-1, matrix metalloprotein-2 (MMP-2), and MMP-9, as well as apoptosis-related genes Bcl-2 and Bax were investigated. TIMP-1AS transfection induced a suppression of TIMP-1 expression accompanied by an earlier onset of apoptosis, and TIMP-1S transfection induced TIMP-1 over-expression accompanied by a much later onset of apoptosis. A neutralizing antibody of TIMP-1 restored the sensitivity of TIMP-1S-transfected RMC to serum deprivation, but a synthetic matrix metalloproteinase inhibitor BB-94 did not influence the sensitivity of TIMP-1S-transfected RMC to serum deprivation. Finally, TIMP-1 over-expression inhibited the expression of Bax but with no effect on the expression of Bcl-2. TIMP-1 inhibits the serum deprivation-induced apoptosis in RMC, in which Bax might be involved.


Change in sexual behavior with provision of no-cost contraception.
To estimate whether providing no-cost contraception is associated with the number of sexual partners and frequency of intercourse over time. This was an analysis of the Contraceptive CHOICE Project, a prospective cohort study of 9,256 adolescents and women at risk for unintended pregnancy. Participants were provided reversible contraception of their choice at no cost and were followed-up with telephone interviews at 6 and 12 months. We examined the number of male sexual partners and coital frequency reported during the previous 30 days at baseline compared with 6-month and 12-month time points. From our total cohort, 7,751 (84%) women and adolescents completed both 6-month and 12-month surveys and were included in this analysis. We observed a statistically significant decrease in the fraction of women and adolescents who reported more than one sexual partner during the past 30 days from baseline to 12 months (5.2% to 3.3%; P<.01). Most participants (70-71%) reported no change in their number of sexual partners at 6 and 12 months, whereas 13% reported a decrease and 16% reported an increase (P<.01). More than 80% of participants who reported an increase in the number of partners experienced an increase from zero to one partner. Frequency of intercourse increased during the past 30 days from baseline (median, 4) to 6 and 12 months (median, 6; P<.01). However, greater coital frequency did not result in greater sexually transmitted infection incidence at 12 months. We found little evidence to support concerns of increased sexual risk-taking behavior subsequent to greater access to no-cost contraception.


[Differential diagnoses in leg ulcers].
In Germany about 0.7% of the adult population have a chronic leg ulcer. Although chronic venous insufficiency accounts for at least 80% of all chronic leg ulcers, knowledge of the relevant differential diagnostic considerations is of crucial importance, in particular for patients who are refractory to therapy. In addition to vascular disease, other causes include neuropathic, metabolic, hematologic and exogenous factors as well as neoplasias, infections, drugs, genetic defects and some primary skin disorders. For the long-term successful treatment of patients with chronic leg ulcers, it is necessary to identify all relevant factors, in order to enable a pathogenesis-oriented, interdisciplinary therapeutic approach.


Design and implementation of an m-health data model for improving health information access for reproductive and child health services in low resource settings using a participatory action research approach.
Information and Communication Technologies (ICTs) have been utilised globally for advancing social and economic development. As information becomes key to enlightening development initiatives, the role of mobile technology-based ICT services is becoming more significant. The aim of this study was to design and implement a mHealth data model with an intention of improving mothers' knowledge of Reproductive and Child Health (RCH) services in rural environments and to remind mothers who do not have access to mobile phones to attend antenatal care. The methodology adopted in this research was participatory action research. A phased approach was utilised to answer the research question. The phases were: diagnosis of the problem, action planning, action taking, evaluation and reflection. The study was conducted in Chamwino district of Dodoma region, Tanzania. Reproductive and Child Health sections of Buigiri dispensary and Chamwino health centre were purposively selected. Data were collected through key informant interviews, document review, focus group discussion and observation. Content analysis methods were utilised during analysis. Consequently, the data model was designed, implemented and evaluated. Challenges of information dissemination in low resource settings noted in this study are: mobile phone ownership and access of mothers, vertical coordination of health services and low staffing levels of health workers. Mothers who do not own mobile phones can leverage phone ownership of community leaders, TBAs, CHWs and relatives. This in turn facilitates communication of health messages to mothers. Although this study was conducted in a low resource setting, mobile network coverage was good and thus SMS technology could be used. Research should be conducted on how to disseminate similar information in remote areas without mobile coverage.


The environmental and social influences of HIV/AIDS in sub-Saharan Africa: a focus on rural communities.
The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) pandemic has caused far-reaching effects in sub-Saharan Africa. The pandemic has effectively diminished the workforce, increased poverty rates, reduced agricultural productivity, and transformed the structure of many rural households. HIV/AIDS further strains the already fragile relationship between livelihood and the natural and social environments of these regions. Therefore, the objective of this review is to characterize the impact of HIV/AIDS on the environment and the social infrastructure of rural sub-Saharan Africa. There are many aspects of rural life that contribute to disease transmission of HIV/AIDS and that pose unique challenges to the population dynamics in sub-Saharan Africa. Widespread AIDS-related mortality has caused a decrease in population growth for many African countries. In turn, these alterations in population dynamics have resulted in a decrease in the percentage of prime-age working adults, as well as a gender disparity, whereby, females carry a growing burden of household responsibilities. There is a rising proportion of older adults, often females, who assume the role of provider and caretaker for other dependent family members. These changing dynamics have caused many to exploit their natural surroundings, adopting less sustainable land use practices and utilizing protected resources as a primary means of generating revenue.


Early production of human neutrophils and platelets posttransplant is severely compromised by growth factor exposure.
The critical human cells that produce neutrophils and platelets within 3 weeks in recipients of hematopoietic transplants are thought to produce these mature blood cells with the same kinetics in sublethally irradiated immunodeficient mice. Quantification of their numbers indicates their relative underrepresentation in cord blood (CB), likely explaining the clinical inadequacy of single CB units in rescuing hematopoiesis in myelosuppressed adult patients. We here describe that exposure of CD34(+) CB cells ex vivo to growth factors that markedly expand their numbers and colony-forming cell content also rapidly (within 24 hours) produce a significant and sustained net loss of their original short-term repopulating activity. This loss of short-term in vivo repopulating activity affects early platelet production faster than early neutrophil output, consistent with their origin from distinct input populations. Moreover, this growth factor-mediated loss is not abrogated by published strategies to increase progenitor homing despite evidence that the effect on rapid neutrophil production is paralleled in time and amount by a loss of the homing of their committed clonogenic precursors to the bone marrow. These results highlight the inability of in vitro or phenotype assessments to reliably predict clinical engraftment kinetics of cultured CB cells.


Oocyte Selection for In Vitro Embryo Production in Bovine Species: Noninvasive Approaches for New Challenges of Oocyte Competence.
The efficiency of producing embryos using in vitro technologies in livestock species rarely exceeds the 30-40% threshold, indicating that the proportion of oocytes that fail to develop after in vitro fertilization and culture is considerably large. Considering that the intrinsic quality of the oocyte is one of the main factors affecting blastocyst yield, the precise identification of noninvasive cellular or molecular markers that predict oocyte competence is of major interest to research and practical applications. The aim of this review was to explore the current literature on different noninvasive markers associated with oocyte quality in the bovine model. Apart from some controversial findings, the presence of cycle-related structures in ovaries, a follicle size between 6 and 10 mm, large number of surrounding cumulus cells, slightly expanded investment without dark areas, large oocyte diameter (>120 microns), dark cytoplasm, and the presence of a round and smooth first polar body have been associated with better competence. In addition, the combination of oocyte and zygote selection via brilliant cresyl blue (BCB) test, spindle imaging, and the anti-Stokes Raman scattering microscopy together with studies decoding molecular cues in oocyte maturation have the potential to further optimize the identification of oocytes with better developmental competence for in-vitro-derived technologies in livestock species.