Emotional and behavioral outcomes among youths with mental disorders during the first Covid lockdown and school closures in England: a large clinical population study using health care record integrated surveys.

PURPOSE: Emotional and behavioral problems in children and young people (CYP) have increased over the pandemic. Those with pre-existing mental disorders are more vulnerable but have been understudied. We investigated emotional and behavioral outcomes in this population; differences across diagnostic groups; and social, educational, and clinical determinants. METHODS: We invited 5386 caregivers and CYP (aged 5-17) under child mental health services pre-pandemic to complete an online survey on CYP's emotional/behavioral symptoms and pandemic-related circumstances, and integrated responses with clinicodemographic information extracted from electronic health records. We compared four parent-rated outcomes (total emotional/behavioral scores and emotional/behavioral changes as compared to before the pandemic) across the three most common diagnostic groups in our population (Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and emotional disorders (EmD)). We then estimated the association of clinicodemographic and pandemic-related characteristics with emotional/behavioral outcomes. RESULTS: A total of 1741 parents (32.3%) completed the survey. Parents of CYP with ADHD or ASD reported more behavioral difficulties (t(591) = 5.618 (0.001); t(663) = 6.527 (0.001)); greater emotional deterioration (t(591) = 2.592 (0.009); t(664) = 4.670 (< 0.001); and greater behavioral deterioration (t(594) = 4.529 (< 0.001); t(664) = 5.082 (< 0.001)) as compared to the EmD group. Those with ASD and EmD showed more emotional difficulties than ADHD (t(891) = - 4.431 (< 0.001); t(590) = - 3.254 (0.001)). Across diagnoses, poor parental mental health and challenges with education were most strongly associated with worse outcomes. CONCLUSIONS: Within our clinical population, CYP with ADHD/ASD were the most adversely affected during lockdown. Enhancing clinical service provision that tackles parental stress and supports education may help mitigate the impact of future restrictions.

Linking data on women in public family law court proceedings concerning their children to mental health service records in South London.

INTRODUCTION: Maternal mental health problems and substance misuse are key risk factors for child neglect or abuse and court-mandated placement into care. Linkage between mental health records and family court data could raise awareness about parent mental health needs and inform approaches to address them. OBJECTIVES: To evaluate data linkage between administrative family court data and electronic mental health records for a population-based mental health service for 1.3 million people in South London. METHODS: We deterministically linked administrative family court data for women (n=5463) involved in care proceedings in South London with service user records from the South London and Maudsley NHS Mental Health Trust (SLaM). We restricted the cohort to women involved in proceedings between 2007 and 2019, in local authorities where SLaM solely provides secondary/tertiary mental health services and the Improving Access to Psychological Therapies (IAPT) (n=3226). We analysed the associations between match status and sociodemographic/case characteristics using multivariable logistic regression. RESULTS: Two-thirds (2317/3226; 66%) of women linked to a SLaM service user record at some point; most (91%) who linked accessed secondary/tertiary mental health services, indicating serious mental illness. Accounting for possible missed matches, we estimated that 70-83% of women accessed SLaM services at some point. Older women at index proceedings (>35yrs OR: 0.69, 95%CI: 0.54-0.88vs <25yrs) and Black women or women from other ethnic groups (Black ethnic groups 0.65, 0.50-0.83; other ethnicity 0.59, 0.43-0.81 vs White ethnic groups) had lower odds of linking. Odds of linking were higher for women with an infant in proceedings (1.42, 1.18-1.71), or with curtailed/terminated parental responsibility (1.44, 1.20-1.73). CONCLUSION: Our linkage supports growing evidence of a high burden of mental health problems and substance misuse among women whose children enter care in England, compared to the general population. Research using this linkage should inform strategies to address the considerable mental health needs of vulnerable women and their children.

Clozapine and all-cause mortality in treatment-resistant schizophrenia: a historical cohort study.

OBJECTIVE: Large-scale epidemiological studies have demonstrated a protective effect of clozapine on mortality in people with schizophrenia. Clozapine is reserved for use in patients with treatment-resistant schizophrenia (TRS), but evidence of clozapine's effect on mortality exclusively within TRS samples is inconclusive. Hence, we aimed to investigate the effect of clozapine use on all-cause mortality in TRS patients. METHODS: A historical patient cohort sample of 2837 patients, who met criteria for TRS between 1 Jan 2008 and 1 Jan 2016, were selected from the South London and Maudsley NHS Foundation Trust (SLAM) electronic health records (EHR). The national Zaponex Treatment Access System (ZTAS) mandatory monitoring system linked to the SLAM EHR was used to distinguish which patients were initiated on clozapine (n = 1025). Cox proportional hazard models were used, adjusting for sociodemographics, clinical monitoring, mental and physical illness severity and functional status. RESULTS: After controlling for potential confounders, the protective effect of clozapine on all-cause mortality was significant (adjusted hazard ratio 0.61; 95% confidence interval 0.38-0.97; P = 0.04). CONCLUSIONS: Clozapine reduces the risk of mortality in patients who meet criteria for TRS. We provide further evidence that improving access to clozapine in TRS is likely to reduce the mortality gap in schizophrenia.

Segregation of Fischer-Tropsch reactants on cobalt nanoparticle surfaces.

Using scanning tunnelling microscopy, we have visualized the segregation of carbon monoxide and hydrogen, the two reactants in Fischer-Tropsch synthesis, on cobalt nanoparticles at catalytically relevant coverages. Density functional theory was used to interrogate the relevant energetics.

Role of estrogen in diastolic dysfunction.

The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after menopause and may lead to heart failure. While evidence suggests that estrogens protect the premenopausal heart from hypertension and ventricular remodeling, the specific mechanisms involved remain elusive. Moreover, whether there is a protective role of estrogens against cardiovascular disease, and specifically LVDD, continues to be controversial. Clinical and basic science have implicated activation of the renin-angiotensin-aldosterone system (RAAS), linked to the loss of ovarian estrogens, in the pathogenesis of postmenopausal diastolic dysfunction. As a consequence of increased tissue ANG II and low estrogen, a maladaptive nitric oxide synthase (NOS) system produces ROS that contribute to female sex-specific hypertensive heart disease. Recent insights from rodent models that mimic the cardiac phenotype of an estrogen-insufficient or -deficient woman (e.g., premature ovarian failure or postmenopausal), including the ovariectomized congenic mRen2.Lewis female rat, provide evidence showing that estrogen modulates the tissue RAAS and NOS system and related intracellular signaling pathways, in part via the membrane G protein-coupled receptor 30 (GPR30; also called G protein-coupled estrogen receptor 1). Complementing the cardiovascular research in this field, the echocardiographic correlates of LVDD as well as inherent limitations to its use in preclinical rodent studies will be briefly presented. Understanding the roles of estrogen and GPR30, their interactions with the local RAAS and NOS system, and the relationship of each of these to LVDD is necessary to identify new therapeutic targets and alternative treatments for diastolic heart failure that achieve the cardiovascular benefits of estrogen replacement without its side effects and contraindications.

Hemodynamic and hormonal patterns of untreated essential hypertension in men and women.

BACKGROUND: Knowledge of hemodynamic factors accounting for the development of hypertension should help to tailor therapeutic approaches and improve blood pressure control. Few data exist regarding sex differences of hemodynamic factors contributing to hypertension progression among patients with untreated nondiabetic stage I and II prehypertension (PreHyp) as defined by the Joint National Committee-7 guidelines (JNC-7). METHODS: We utilized noninvasive impedance cardiography, applanation tonometry and plasma measures of angiotensin II, angiotensin (1-7), serum aldosterone, high-sensitivity C-reactive protein (hs-CRP) and cytokine biomarkers of inflammation to characterize the hemodynamic and hormonal profile of 100 patients with untreated hypertension (39 women). RESULTS: Despite there being no differences between women and men in terms of office blood pressure, heart rate and body mass index, men demonstrated lower values of pulse pressure, systemic vascular resistance, brachial artery pulse wave velocity and augmentation index. In each of the three hypertension categories, the increased blood pressure in men was associated with significant augmentations in stroke volume and cardiac output compared with women. Sex-related hemodynamic differences were associated in women with higher plasma levels of leptin, hs-CRP, plasma angiotensin II and serum aldosterone, and no differences in the serum concentrations of cytokinins. In women but not men, hs-CRP correlated with plasma concentrations of transforming growth factor ß1 (TGFß1) and body weight; in addition, plasma TGFß1 correlated with levels of serum vascular cell adhesion molecule 1. CONCLUSION: The impact of sex differences in the hemodynamic factors accounting for the elevation in arterial pressure in subjects with essential hypertension has been poorly characterized or this information is not available. We suggest that this gap in knowledge may adversely influence choices of drug treatment since our study shows for the first time significant differences in the hemodynamic and hormonal mechanisms accounting for the increased blood pressure in women compared to men.

Characterization of the cardiac renin angiotensin system in oophorectomized and estrogen-replete mRen2.Lewis rats.

The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17) or sham-operation (Sham; n = 13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 ß-estradiol (E2, 36 µg/pellet, 60-day release, n = 8) or vehicle (OVX-V, n = 9) for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang) II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1-7) content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R). E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1-7) mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.

Estrogen therapy, independent of timing, improves cardiac structure and function in oophorectomized mRen2.Lewis rats.

OBJECTIVE: mRen2.Lewis rats exhibit exacerbated increases in blood pressure, left ventricular (LV) remodeling, and diastolic impairment after the loss of estrogens. In this same model, depletion of estrogens has marked effects on the cardiac biopterin profile concomitant with suppressed nitric oxide release. With respect to the establishment of overt systolic hypertension after oophorectomy (OVX), we assessed the effects of timing long-term 17ß-estradiol (E2) therapy on myocardial function, myocardial structure, and the cardiac nitric oxide system. METHODS: OVX (n = 24) or sham operation (Sham; n = 13) was performed in 4-week-old female mRen2.Lewis rats. After randomization, OVX rats received E2 immediately (OVX + E2-early; n = 7), E2 at 11 weeks of age (OVX + E2-late; n = 8), or no E2 at all (OVX; n = 9). RESULTS: E2-early was associated with lower body weight, less hypertension-related cardiac remodeling, and decreased LV filling pressure compared with OVX rats without E2 supplementation. E2-late similarly attenuated the adverse effects of ovarian hormone loss on tissue Doppler-derived LV filling pressures and perivascular fibrosis, and significantly improved myocardial relaxation or mitral annular velocity (e'). Early and late exposures to E2 decreased dihydrobiopterin, but only E2-late yielded significant increases in cardiac nitrite concentrations. CONCLUSIONS: Although there are some similarities between E2-early and E2-late treatments in relation to preservation of diastolic function and cardiac structure after OVX, the lusitropic potential of E2 is most consistent with late supplementation. The cardioprotective effects of E2-late are independent of blood pressure and may have occurred through regulation of cardiac biopterins and nitric oxide production.

Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats.

AIMS: GPR30 is a novel oestrogen receptor expressed in various tissues, including the heart. We determined the role of GPR30 in the maintenance of left ventricular (LV) structure and diastolic function after the surgical loss of ovarian hormones in the female mRen2.Lewis rat, a model emulating the cardiac phenotype of the post-menopausal woman. METHODS AND RESULTS: Bilateral oophorectomy (OVX) or sham surgery was performed in study rats; the selective GPR30 agonist, G-1 (50 µg/kg/day), or vehicle was given subcutaneously to OVX rats from 13-15 weeks of age. Similar to the cardiac phenotype of sham rats, G-1 preserved diastolic function and structure relative to vehicle-treated OVX littermates independent of changes in blood pressure. G-1 limited the OVX-induced increase in LV filling pressure, LV mass, wall thickness, interstitial collagen deposition, atrial natriuretic factor and brain natriuretic peptide mRNA levels, and cardiac NAD(P)H oxidase 4 (NOX4) expression. In vitro studies showed that G-1 inhibited angiotensin II-induced hypertrophy in H9c2 cardiomyocytes, evidenced by reductions in cell size, protein content per cell, and atrial natriuretic factor mRNA levels. The GPR30 antagonist, G15, inhibited the protective effects of both oestradiol and G-1 on this hypertrophy. CONCLUSION: These data show that the GPR30 agonist G-1 mitigates the adverse effects of oestrogen loss on LV remodelling and the development of diastolic dysfunction in the study rats. This expands our knowledge of the sex-specific mechanisms underlying diastolic dysfunction and provides a potential therapeutic target for reducing the progression of this cardiovascular disease process in post-menopausal women.

Tetrahydrobiopterin restores diastolic function and attenuates superoxide production in ovariectomized mRen2.Lewis rats.

After oophorectomy, mRen2.Lewis rats exhibit diastolic dysfunction associated with elevated superoxide, increased cardiac neuronal nitric oxide synthase (nNOS) expression, and diminished myocardial tetrahydrobiopterin (BH4) content, effects that are attenuated with selective nNOS inhibition. BH4 is an essential cofactor of nNOS catalytic activity leading to nitric oxide production. Therefore, we assessed the effect of 4 wk BH4 supplementation on diastolic function and left ventricular (LV) remodeling in oophorectomized mRen2.Lewis rats compared with sham-operated controls. Female mRen2.Lewis rats underwent either bilateral ovariectomy (OVX) (n = 19) or sham operation (n = 13) at 4 wk of age. Beginning at 11 wk of age, OVX rats were randomized to receive either BH4 (10 mg/kg · d) or saline, whereas the sham rats received saline via sc mini-pumps. Loss of ovarian hormones reduced cardiac BH4 when compared with control hearts; this was associated with impaired myocardial relaxation, augmented filling pressures, increased collagen deposition, and thickened LV walls. Additionally, superoxide production increased and nitric oxide decreased in hearts from OVX compared with sham rats. Chronic BH4 supplementation after OVX improved diastolic function and attenuated LV remodeling while restoring myocardial nitric oxide release and preventing reactive oxygen species generation. These data indicate that BH4 supplementation protects against the adverse effects of ovarian hormonal loss on diastolic function and cardiac structure in mRen2.Lewis rats by restoring myocardial NO release and mitigating myocardial O2⁻ generation. Whether BH4 supplementation is a therapeutic option for the management of diastolic dysfunction in postmenopausal women will require direct testing in humans.

Dietary fish oil modestly attenuates the effect of age on diastolic function but has no effect on memory or brain inflammation in aged rats.

Fish oil (FO) mediates a number of cardioprotective benefits in patients with cardiovascular disease. In the absence of cardiovascular disease, however, the effects of FO on cardiac structure and function are not clear. In addition, it is not known if an effective dosing strategy for attenuating age-related cardiac dysfunction is also effective at limiting cognitive dysfunction. Therefore, we determined if 4 months of FO supplementation in aged rats would lessen age-related cardiac dysfunction while concomitantly preventing the cognitive decline that is normally observed in this population. The results indicate that FO initiated late in life modifies diastolic function in a small but positive way by attenuating the age-related increases in filling pressure, posterior wall thickness, and interstitial collagen without mitigating age-related deficits in memory or increases in brain inflammation. These data raise the possibility that FO supplementation for purposes of cardiac and brain protection may need to occur earlier in the life span.

Neuronal nitric oxide synthase inhibition improves diastolic function and reduces oxidative stress in ovariectomized mRen2.Lewis rats.

OBJECTIVE: The loss of estrogen in mRen2.Lewis rats leads to an exacerbation of diastolic dysfunction. Because specific neuronal nitric oxide synthase (nNOS) inhibition reverses renal damage in the same model, we assessed the effects of inhibiting neuronal nitric oxide on diastolic function, left ventricular remodeling, and the components of the cardiac nitric oxide system in ovariectomized (OVX) and sham-operated mRen2.Lewis rats treated with N5-(1-imino-3-butenyl)-L-ornithine (L-VNIO; 0.5 mg/kg per day for 28 d) or vehicle (saline). METHODS: Female mRen2.Lewis rats underwent either bilateral oophorectomy (OVX; n = 15) or sham operation (or surgical procedure) (sham; n = 19) at 4 weeks of age. Beginning at 11 weeks of age, the rats were randomized to receive either L-VNIO or vehicle. RESULTS: The surgical loss of ovarian hormones, particularly estrogen, led to exacerbated hypertension, impaired myocardial relaxation, diminished diastolic compliance, increased perivascular fibrosis, and increased relative wall thickness. The cardiac tetrahydrobiopterin-to-dihydrobiopterin levels were lower among OVX rats compared with sham-operated rats, and this altered cardiac biopterin profile was associated with enhanced myocardial superoxide production and decreased nitric oxide release. L-VNIO decreased myocardial reactive oxygen species production, increased nitrite concentrations, attenuated cardiac remodeling, and improved diastolic function. CONCLUSIONS: Impaired relaxation, diastolic stiffness, and cardiac remodeling were found among OVX mRen2.Lewis rats. A possible mechanism for this unfavorable cardiac phenotype may have resulted from a deficiency in available tetrahydrobiopterin and subsequent increase in nNOS-derived superoxide and reduction in nitric oxide synthase metabolites within the heart. Selective nNOS inhibition with L-VNIO attenuated cardiac superoxide production and limited remodeling, leading to improved diastolic function in OVX mRen2.Lewis rats.

Virologic and immunologic outcome of treatment of HIV infection with a herbal concoction, A-Zam, among clients seeking herbal remedy in Nigeria

Abstract: This study was to determine the effectiveness (CD4 count and viral load) of a safe herbal concoction, α-Zam used by clients seeking herbal remedy for treatment of HIV infection in Nigeria. 51 patients taking α-Zam as complementary and alternative therapy through the herbal therapist were studied for a period of 16 months. Preliminary medical and laboratory examinations using WHO and CDC criteria were done after confirmation of HIV infection by Western blotting in the nearest teaching hospitals to the residence of the patients. Regular visits were paid to the patients after commencement of the α-Zam to assess the side-effects, drug interactions, toxicity and effectiveness of the herbal remedy. There was a statistical significance (P<0.05) between pre-treatment and post-treatment CD4 count. 4 (7.8%) of the patients had average increase in CD4 count of 262±16 cell/µL, 23 (45.1%) patients with average increase 310±16 cell/µL, 16 (31.4%) patients with average increase 456±25 cell/µL and 8 (15.7%) patients with average increase 510±36 cell/µL( %) were at WHO staging I , II, III and IV respectively within 4 months on herbal therapy. There was very marked reduction in viral (HIV-RNA) load with 41 (80.4%) and 10 (19.6%) HIV infected patients had undetectable viral load and <1000 copies/ml respectively after the therapy. All symptoms and signs associated with HIV infection in all patients fully subsided within 4 weeks of commencement of α-zam therapy and there was no evidence of negative drug interaction in those HIV patients using both the herbal and highly active anti-retroviral therapy (HAART). The study is in progress to determine periodic immunological outcomes of post therapy in all patients

Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats.

INTRODUCTION: The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH) on cardiac function and structure. METHODS: Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS) diet or a high salt (4% sodium; HS) diet for 10 weeks beginning at 5 weeks of age. RESULTS: Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV) diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope), increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e')] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05) as determined by tissue Doppler. CONCLUSION: Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.

Hepatitis C virus prevalence and serotypes associated with HIV in The Gambia.

Hepatitis C virus (HCV) serotypes are important in the epidemiology and pathogenesis of HCV-related disease, but little is known of this connection in West Africa. Coinfection with human immunodeficiency virus (HIV) is associated with significant morbidity and mortality. This study aims to determine the prevalence of HCV and its serotypes associated with HIV in The Gambia. A total of 1500 individuals referred to the Royal Victoria Teaching Hospital for HIV serology between July and December, 2002 were screened for antibodies to HIV and subsequently for HCV, and seropositive samples were typed. This study shows HIV and HCV prevalence of 6.7% and 1.6%, respectively, with a co-infection rate of 0.6%. Serotype 2 showed the highest prevalence (58.1%), followed by serotype 1 (19.4%). Prevalence of HCV serotype 3 was 6.5% and five samples were untypeable. Co-infection of HIV-1 with HCV serotype 1 showed a prevalence of 44.4%, and with HCV serotype 2 of 33.3%. The findings support the evidence to suggest the West African subregion as the origin of HCV serotype 2. It also demonstrates the need for routine HCV screening of HIV-infected persons and blood donations, and calls for further studies to elucidate the sources of the HCV virus.

Influence of tart cherry juice on indices of recovery following marathon running.

This investigation determined the efficacy of a tart cherry juice in aiding recovery and reducing muscle damage, inflammation and oxidative stress. Twenty recreational Marathon runners assigned to either consumed cherry juice or placebo for 5 days before, the day of and for 48 h following a Marathon run. Markers of muscle damage (creatine kinase, lactate dehydrogenase, muscle soreness and isometric strength), inflammation [interleukin-6 (IL-6), C-reactive protein (CRP) and uric acid], total antioxidant status (TAS) and oxidative stress [thiobarbituric acid reactive species (TBARS) and protein carbonyls] were examined before and following the race. Isometric strength recovered significantly faster (P=0.024) in the cherry juice group. No other damage indices were significantly different. Inflammation was reduced in the cherry juice group (IL-6, P<0.001; CRP, P<0.01; uric acid, P<0.05). TAS was ~10% greater in the cherry juice than the placebo group for all post-supplementation measures (P<0.05). Protein carbonyls was not different; however, TBARS was lower in the cherry juice than the placebo at 48 h (P<0.05). The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function.

Prevalence of HIV-1, HIV-2, hepatitis C and co-infection in The Gambia.

BACKGROUND: In most West African countries, the distribution and risk factors for co-infection with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) is unknown despite the current HIV epidemic and evidence of increasing prevalence of HCV in the region. OBJECTIVE: This study aimed to evaluate the distribution and the risk factors for the transmission of co-infection between HIV and HCV in The Gambia. METHODS: A total of 1500 persons referred for HIV serology at the Royal Victoria teaching Hospital were interviewed following informed consent to obtain information on their demographic variables, knowledge of sexually transmitted diseases and their prevention, and patterns of risk behavior. Blood was collected and tested for anti-HIV and anti-HCV antibodies by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: In the general population, the prevalence of HIV was 6.7%, while that of HCV was 2.1%. Both infections occurred more frequently in males than in females. HIV and HCV coinfection rate was 0.6%. Co-infection was significantly more common in males than females. All types of infection--HIV, HCV and HIV/HCV co-infections occurred much more in polygamous settings than in monogamy. CONCLUSION: This study has demonstrated the extent of coinfection with HIV and HCV in The Gambia. The prevalence of female circumcision may be a contributory occurrence factor in the transmission of HIV but not in that of HCV.

Dual ACE-inhibition and AT1 receptor antagonism improves ventricular lusitropy without affecting cardiac fibrosis in the congenic mRen2.Lewis rat.

BACKGROUND: Hypertension and left ventricular (LV) hypertrophy often precede diastolic dysfunction and are risk factors for diastolic heart failure. Although pharmacologic inhibition of the renin-angiotensin system (RAS) improves diastolic function and functional capacity in hypertensive patients with LV hypertrophy, the effects of combination therapy with an angiotensin converting enzyme inhibitor (ACEi) and an angiotensin receptor blocker (ARB) are unclear. METHOD: We assessed the effects of the combined 10-week administration of lisinopril (10 mg/kg/ day, p.o.) and losartan (10 mg/kg/day, p.o.) (LIS/LOS) on diastolic function and LV structure in seven young (5 weeks), prehypertensive congenic mRen2.Lewis male rat, a model of tissue renin overexpression and angiotensin II (Ang II)-dependent hypertension compared to vehicle (VEH) treated (n = 7), age-matched rats. RESULTS: Systolic blood pressures were 64% lower with the combination therapy (p < 0.001), but there were no differences in heart rate or systolic function between groups. RAS inhibition increased myocardial relaxation, defined by tissue Doppler mitral annular descent (e') by 2.2 fold (p < 0.001). The preserved lusitropy in the LIS/LOS-treated rats was accompanied by a reduction in phospholamban-to-SERCA2 ratio (p < 0.001). Despite lower relative wall thicknesses (VEH: 1.56+/-0.17 versus LIS/LOS: 0.78+/-0.05) and filling pressures, defined by the transmitral Doppler-to-mitral annular descent ratio (E/e', VEH: 28.7+/-1.9 versus LIS/LOS: 17.96+/-1.5), no differences in cardiac collagen were observed. CONCLUSION: We conclude that the lusitropic benefit of early dual RAS blockade may be due to improved vascular hemodynamics and/or cardiac calcium handling rather than effects on extracellular matrix reduction.

Mild chronic hypoxemia modifies expression of brain stem angiotensin peptide receptors and reflex responses in fetal sheep.

The effects of chronic mild hypoxemia on the binding of angiotensin receptors in selected brain stem nuclei and reflex responses were studied in fetal sheep. Fetal and maternal catheters were placed at 120 days' gestation, and animals received intratracheal maternal administration of nitrogen (n = 16) or compressed air in controls (n = 19). Nitrogen infusion was adjusted to reduce fetal brachial artery PO(2) by 25% during 5 days. Spontaneous baroreflex sensitivity and spectral analysis of the pulse interval were analyzed during the 5 days hypoxemia period using 90 min of daily recording. Brains of control and hypoxemic animals were collected, and brain stem angiotensin receptor binding was studied by in vitro autoradiography at 130 days of gestation. After 5 days of hypoxemia, some animals in each group were submitted to one complete umbilical cord occlusion during 5 min. [(125)I]sarthran binding showed that chronic mild hypoxemia significantly increases angiotensin type 1 receptor, angiotensin type 2 receptor, and ANG-(1-7) angiotensin receptor binding sites in the nucleus tractus solitarius and dorsal motor nucleus of the vagus (P < 0.05). Hypoxemia induced lower baroreflex sensitivity and a higher low frequency-to-high frequency ratio in the fetus, consistent with a shift from vagal to sympathetic autonomic cardiac regulation. Cord occlusion to elicit a chemoreflex response induced a greater bradycardic response in hypoxemic fetuses (slope of the initial fall in heart rate; 11.3 +/- 1.9 vs. 6.4 +/- 1.2 beats x min(-1) x s(-1), P < 0.05). In summary, chronic mild hypoxemia increased binding of angiotensin receptors in brain stem nuclei, decreased spontaneous baroreflex gain, and increased chemoreflex responses to asphyxia in the fetus. These results suggest hypoxemia-induced alterations in brain stem mechanisms for cardiovascular control.