Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study

OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.     

Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection

With human volunteers inoculated at two sites with Haemophilus ducreyi, outcomes for a subject were not independent. In a reinfection trial, 2 of 11 previous pustule formers and 6 of 10 previous resolvers resolved all sites of infection. There was no correlation between serum bactericidal or phagocytic activity and outcome in the trial. These data indicate that different hosts are differentially susceptible to disease progression versus resolution in the model.     

Neurophysiological responses to face, facial regions and objects in adults with Asperger's syndrome: an ERP investigation.

Face processing differences have been observed between AS and control subjects at the behavioural and neurological levels. The purpose of the present study was to investigate the neurophysiological basis of processing faces and facial features (eyes and mouths) in adults with AS relative to age- and gender-matched typically-developing controls. These results were compared with ERPs generated to objects in both groups to determine if any differences were specific to facial stimuli. Although both groups elicited earlier N170 latencies to faces than to face parts and to eyes relative to mouths, adults with AS exhibited delayed N170 latencies to faces and face parts relative to controls. This difference was not observed to objects. Together these findings suggest that adults with AS may be slower to process facial information.     

Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion

Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a "pore"-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell.     

Comparison of couples referred and not referred for genetic counseling in a genetic clinic after the birth of a child with a congenital anomaly: A study in a population in the northeastern Netherlands

After the birth of a child with a congenital anomaly, parents have many questions about cause, prognosis, and recurrence risk. An important means of transmitting such information is referral to a genetic clinic. We were interested in knowing what determines whether or not parents are referred for genetic counseling. Data from the local registration of congenital anomalies in the northeastern Netherlands (birth years 1981–1986; 1,217 children/fetuses) and data of the local genetic clinic were compared. The parents of 204 cases (16.8%) had been referred for genetic counseling. Of the couples referred, 76% were referred within one year after birth, usually by a pediatrician (48%). Parents of children with a single anomaly, recognized syndrome, or multiple anomalies not recognized as a syndrome were referred in 5%, 43%, and 26% of cases, respectively. Parents of liveborn children who died were referred in 38% of cases, parents of liveborn/still-alive and stillborn children in 13% and 22%, respectively. Previous affected sibs and absence of previous livebirths increased the likelihood of referral.     

Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

Background  

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1β is primarily neurotoxic in ischemic stroke, TNF-α may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1β and TNF-α are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice.     

Expression of the LspA1 and LspA2 proteins by Haemophilus ducreyi is required for virulence in human volunteers

Haemophilus ducreyi colocalizes with polymorphonuclear leukocytes and macrophages and evades phagocytosis during experimental infection of human volunteers. H. ducreyi contains two genes, lspA1 and lspA2, which encode predicted proteins of 456 and 543 kDa, respectively. Compared to its wild-type parent, an lspA1 lspA2 double mutant does not inhibit phagocytosis by macrophage and myelocytic cell lines in vitro and is attenuated in an experimental rabbit model of chancroid. To test whether expression of LspA1 and LspA2 was necessary for virulence in humans, six volunteers were experimentally infected. Each volunteer was inoculated with three doses (ranging from 85 to 112 CFU) of the parent (35000HP) in one arm and three doses (ranging from 60 to 822 CFU) of the mutant (35000HP Omega 12) in the other arm. The papule formation rates were 88% (95% confidence interval [95% CI], 76.8 to 99.9%) at 18 parent sites and 72% (95% CI, 44.4 to 99.9%) at 18 mutant sites (P = 0.19). However, papules were significantly smaller at mutant sites (mean size, 24.8 mm(2)) than at parent sites (mean size, 39.1 mm(2)) 24 h after inoculation (P = 0.0002). The pustule formation rates were 44% (95% CI, 5.8 to 77.6%) at parent sites and 0% (95% CI, 0 to 39.4%) at mutant sites (P = 0.009). With the caveat that biosafety regulations preclude testing of a complemented mutant in human subjects, these results indicate that expression of LspA1 and LspA2 facilitates the ability of H. ducreyi to initiate disease and to progress to pustule formation in humans.     

How are different types of continuity achieved? A mixed methods longitudinal study

BACKGROUND: In the context of developments in healthcare services that emphasise swift access to care, concern has been expressed about whether and how continuity of care, particularly interpersonal continuity, will continue to be achieved. AIM: To explore how patients regard and use primary care services in relation to continuity of provider and access to care, to identify factors that promote or hinder their success in achieving their preferences, and to describe what this means for how different types of continuity are achieved. DESIGN OF STUDY: Longitudinal, mixed methods. SETTING: Community in London and Leicester. METHOD: Purposive sample of 31 patients recruited from general practices, walk-in centres and direct advertising. Data collection involved in-depth interviews, consultation record booklets completed over 6 months and general practice records for the year including the study period. Data were analysed qualitatively. RESULTS: Four patterns were identified in the way patients used primary care. These were shaped by their own preferences, by the organisation and culture of their primary care practices, and by their own and their provider's efforts to achieve their preferences. Different configurations of these factors gave rise to different types of continuity. Patients were not always able to achieve the type they wanted. Patients with apparently similar consulting patterns could experience them differently. CONCLUSION: Within a programme of modernisation, policies that promote a commitment to meeting the preferences of different patients with flexibility and understanding are most likely to provide continued support for interpersonal and other types of continuity of care.     

Racial Identity Clusters and Their Relation to Postpartum Maternal Functioning in Black Women

Maternal and Child Health Journal - Racial identity, which is the degree that individuals define themselves regarding their racial group membership, may influence the mental well-being of Black...