Subtype‐specific differences in transmission cluster dynamics of HIV‐1 B and CRF01_AE in New South Wales,Australia

IntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.     

Melatonin receptor mRNA expression in Xenopus oocytes: inhibition of G-protein-activated response.

Melatonin is the major endocrine product of the pineal gland in the mammalian brain and plays a variety of roles in photoperiodic functions. In order to investigate melatonin receptors, poly(A)+ RNA was extracted from pars tuberalis of the ovine pituitary and injected into oocytes of Xenopus laevis. After 3-5 days of incubation, functional melatonin receptors were expressed. Receptors were revealed by their inhibitory effect upon oscillatory currents resulting from AlF4-induced activation of G-proteins in the oocyte membrane under voltage clamp conditions. The effect of melatonin was dose-dependent, non-desensitizing and was not observed in uninjected oocytes.     

Premenstrual anxiety and depression: comparison of objective psychological tests with a retrospective questionnaire

Increased anxiety and depression are among the most frequently reported psychological problems in women seeking help for severe symptomatic premenstrual change, but there has been little objective evaluation of these symptoms. We therefore examined the results of objective psychological testing in 40 women with no apparent psychiatric or psychological disorder who had reported moderate to extreme increased anxiety and depression on a retrospective assessment form. Scores on the State-Trait Anxiety Inventory and Institute of Personality and Ability Testing (IPAT) Depression Scale increased from the low symptom intermenstrual phase of the cycle (days 5-10) to the premenstrual phase (within the last 6 days of the cycle), suggesting that retrospective complaints of increased premenstrual anxiety and depression can be confirmed on objective psychological assessment. However, it was observed that the distribution of intermenstrual IPAT depression scores was bimodal. Cyclic changes varied among the tests depending upon the IPAT depression score. The study suggests that 2 populations may exist in this screened sample; one population appears to have "pure PMS" and the second groups manifests a premenstrual exacerbation of subclinical depression.     

In vivo imaging of rat lymphocytes with an indium 111-labelled anti-T cell monoclonal antibody: a comparison with indium 111-labelled lymphocytes

An indium 111-labelled mouse anti-rat T cell monoclonal antibody, MRC OX-19, was injected intravenously into rats to establish the usefulness of radiolabelled anti-lymphocyte antibodies in imaging lymphoid tissues. Antibody binding in vivo, measured by immunofluorescence analysis of cell suspensions made from lymphoid tissues, was detectable on lymphocytes in blood, spleen and lymph nodes. The extent of binding was time and antibody-dose dependent. Doses of antibody above 80 g/kg body weight resulted in modulation, i.e. loss of CD 5 (T 1) molecules from the cell surface, although the cells remained in the circulation. Modulation was demonstrable within 2 h and for at least 24 h after a single injection of antibody. Intravenous injection of¹¹¹In-MRC OX-19 resulted in levels of in vivo binding comparable with those seen with unlabelled antibody. Scintillation imaging showed early splenic localisation persisting over 48h, a more gradual localisation in the lymph nodes seen clearly at 24 h and a steady background. Comparison of the in vivo distribution of labelled antibody and¹¹¹In-tropolone-labelled lymphocytes showed that both could be used for external imaging of lymphocytes by scintillation camera.     

Factors influencing birth weight in newborns of diabetic and non-diabetic women a population based study

Maternal diabetes is known to be related to an increase in birth weight of the offspring. However, the mechanism of the association is not entirely clear. In addition, the contribution of the demographic, obstetric and metabolic factors to birth weight in diabetic mothers is not well defined. All the diabetic women (68 requiring insulin-treatment and 403 on diet alone) and a random sample of 1 in 12 of all non-diabetic women (893 women) who delivered in one regional hospital between March 1987 and June 1988 inclusive, were included in the study. Tests for gestational diabetes are routinely performed in our pregnant women population, thus, the study is a population based one. The mean birth weight of infants of diabetic mothers adjusted for gestational age was higher than in those of non-diabetic mothers. However, no relationship was found between maternal glycosylated hemoglobin measured at delivery and the infants birth weight. Furthermore, at each week of gestation, infants born to diabetic mothers were heavier than the infants of non-diabetic mothers (for weeks 37 to 40, p < 0.05), while no differences were found in glycosylated hemoglobin levels between the two groups at any time. In a multivariate model we showed that after controlling for gestational age, the only factors which independently and significantly affected birth weight in our population were diabetes, ethnic origin, and the parity of the mother. Our findings support the possibility that substances which induce hyperinsulinemia, other than glucose, may be related to the higher birth weight of infants of diabetic mothers.     

A longitudinal study of changes in endometrial microvascular density in Norplant implant users.

This study aimed to investigate the effects of the subdermal levonorgestrel contraceptive implant Norplant on endometrial vascular density at different durations of exposure, and the relationship between endometrial histology, vascular density, and bleeding patterns. A prospective controlled trial of Norplant implant users compared endometrial vascular density in biopsies taken before and after Norplant implant insertion. A total of 34 women with regular menstrual cycles requesting long-term contraception were recruited at the Sydney Centre for Reproductive Health Research, Australia. A significant increase in mean endometrial microvascular density was observed from as early as 3 weeks after insertion of Norplant implants. Vascular density was increased from a control secretory phase value of 189.6 (7.0 vessels/mm2 (+/- SEM) to 253.80 +/- 7 vessels/mm2 at 2-13 weeks of Norplant implant exposure (t ratio = 2.08, p = 0.01) and 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks of exposure (t ratio = 2.03, p = 0.02). In those with atrophic endometrium, or in whom myometrium and basalis only were found in biopsies (20 of 66, 30%), mean endometrial vascular density was increased at 273.1 +/- 16.1 vessels/mm2 compared with 210.9 +/- 11.7 vessels/mm2 in other histological groups (F ratio = 9.74, p = 0.0028). Bleeding and spotting in the previous 30 days were less common in those with this histological appearance at a mean of 4.95 days compared with 8.22 days. This is the first study to assess endometrial vascular density in the early months of Norplant implant use. The findings suggest that the endometrial vasculature is profoundly altered in the early months of Norplant implant exposure when bleeding problems are most common.     

Effect of foot and ankle position on tarsal tunnel compartment pressure

Tarsal tunnel intracompartment pressures were determined in 10 fresh-frozen normal human adult cadaver specimens. With the foot and ankle held in mild plantarflexion and neutral eversion-inversion, mean tarsal tunnel pressure was minimal (2 +/- 1 mmHg). However, when the foot and ankle were positioned in full eversion, mean tarsal tunnel pressure increased to 32 +/- 5 mmHg (P < or = 0.005); in full inversion, mean pressure increased to 17 +/- 5 mmHg (P < or = 0.05). There was no significant difference in mean tarsal tunnel pressure between the everted and inverted positions. These results support the hypothesis that increased pressure within the tarsal tunnel when the foot is moved into the everted or inverted position may aggravate posterior tibial nerve entrapment. These findings may also provide an explanation for clinically observed aggravation of symptoms in these positions, night pain, and improvement of symptoms with neutral immobilization in some patients with tarsal tunnel syndrome.     

Prevalence and predictors of parasuicide in chronic psychosis. UK700 group

OBJECTIVE: This study estimates the prevalence of and risk factors for parasuicide in a large community-based sample of patients with chronic psychosis. METHOD: A total of 704 subjects with chronic psychosis were interviewed using a battery of instruments. The 2-year prevalence of parasuicide was estimated and a comparison was made between attempters and nonattempters on a wide range of sociodemographic and clinical variables. RESULTS: The 2-year prevalence of parasuicide was 18.8%. Attempters were significantly more likely to be younger, of white ethnic origin, to have a diagnosis of affective disorder, to be currently depressed, to have experienced more auditory hallucinations and to have received treatment with antipsychotic drugs for a longer period. CONCLUSION: Parasuicide was found to present a considerable clinical problem in this group. Continual risk assessment is essential to reduce this unacceptably high rate.     

Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis

PURPOSE: This study was conducted to examine effects of nitric oxide (NO) donors on bladder hyperactivity induced by cyclophosphamide (CYP)-induced cystitis. MATERIALS AND METHODS: Female Sprague-Dawley rats received a single intraperitoneal injection of CYP (100 mg./kg.), and then their micturition pattern including mean micturition volume and the number of micturitions during 24 hours was recorded in a metabolic cage before and after CYP treatment. Forty-eight hours after CYP injection, bladder function under urethane anesthesia was evaluated by cystometry with continuous saline infusion (0.04 ml. per minute) or under isovolumetric conditions (0.8 ml. bladder volume). NO donors, S-nitroso-N-acetyl-penicillamine (SNAP, 2 mM) or sodium nitroprusside (SNP, 1 mM), and an NO synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 20 mM) were administered intravesically. Direct action of SNAP on bladder afferent neurons was also tested in a patch-clamp recording study. RESULTS: The number of micturitions significantly increased during the first 24 hours after CYP injection (19.0 +/- 0.88 versus 92.1 +/- 16.3 micturitions/24 hours, mean +/- SE, n = 25) (p <0.001). There was no significant difference in total micturition volume before (12.3 +/- 1.0 ml./24 hours) and after CYP treatment (15.6 +/- 1.5 ml./24 hours). During continuous infusion cystometry, intercontraction interval (ICI) was smaller in CYP-injected rats than in control rats. In CYP-injected animals, NO donors increased the ICI, but did not change the amplitude of bladder contractions. Continuous intravesical infusion of the NOS inhibitor did not alter the cystometric parameters. During cystometry under isovolumetric conditions, contraction frequency was decreased after NO donor administration. NO donors did not influence bladder activity in control rats. In patch clamp recordings, when SNAP (500 microM) was directly applied to dissociated afferent neurons innervating the urinary bladder, high-voltage-activated Ca2+ channel currents were suppressed by approximately 30%. CONCLUSIONS: Intravesical NO donors can suppress CYP-induced bladder hyperactivity. We hypothesize that the effect of NO donors is not due to smooth muscle relaxation, but rather due to an inhibitory effect on bladder afferent pathways that was manifested by an increase in intercontraction interval without changes in contraction amplitude. NO donors may be considered as a possible treatment of CYP-induced and other types of bladder inflammation.