WFS1 and non-syndromic low-frequency sensorineural hearing loss: a novel mutation in a Portuguese case.

Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2,000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin. A Portuguese patient aged 49, reporting HL since her third decade of life, and also referring tinnitus, was shown to display bilateral moderate LFSNHL after audiological evaluation. Molecular analysis led to the identification of a novel mutation, c.511G>A (p.Asp171Asn), found in heterozygosity in the exon 5 of the WFS1 gene, and changing the aspartic acid at position 171 to an asparagine, in the extracellular N-terminus domain of the wolframin protein. This novel mutation wasn't present either in 200 control chromosomes analyzed or in the hearing proband's half-brother, and it had not been reported in 1000 Genomes, Exome Variant Server, HGMD or dbSNP databases. No mutations were found in GJB2 and GJB6 genes. Multi-alignment of 27 wolframin sequences from mammalian species, against the human wolframin sequence in ConSurf, indicated a conservation score corresponding to 7 in a 1-9 color scale where 9 is conserved and 1 is variable. In addition, the mutation p.Asp171Asn was predicted to be damaging and possibly damaging by SIFT and Polyphen-2, respectively. The auditory phenotype of this patient could thus be due to the novel mutation p.Asp171Asn. Further functional characterization might enable to elucidate in which way the change in the residue 171, as other changes introduced by LFSNHL-associated mutations previously described, leads to this type of HL.

The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico.

During the last decade, the veterinary anesthetics have gained popularity as recreational drugs. The aim of this study was to document the use of "anestecia de caballo" (xylazine) and its consequences among drug users in Puerto Rico. The study combined a cross-sectional survey with 89 drug users and two focus groups conducted in Mayagüez with frontline drug treatment providers. Drug users were recruited from communities of the San Juan metropolitan area using a variety of ethnographic and outreach strategies. A short questionnaire developed for the study collected information on sociodemographics, xylazine use, and its consequences. The two focus groups were conducted to discuss the details related to xylazine use, its consequences, and utilization awareness. The sample comprised 63 males (70.8%) and 26 females with a mean age of 37.2 years. The mean number of years of drug use was 14.3, with a mean frequency of drug use of 5.9 times daily. More than 65% reported speedball as the principal drug of use. The prevalence of xylazine use was 80.7%. More than 42% of the sample used xylazine in a mixture with speedball. The main route of administration of xylazine was injection but 14% reported the use of xylazine by inhalation. More than 35% of the sample reported skin lesions and 21.1% reported at least one overdose episode. Multiple logistic regression analysis revealed that males (OR = 3.47, CI = 1.10-12.00) and those who reported speedball as their main drug of use (OR = 9.34, CI = 2.51-34.70) were significantly more likely to be xylazine users. Focus groups revealed that drug users claimed to recognize the presence of xylaxine in a mixture of speedball based on its effects, taste, the color of the drug (dark brown), and its odor. In conclusion, the use of xylazine among drug users in Puerto Rico seems to be an emerging trend with potentially serious health consequences.

Assessing Noncoding Sequence Variants of GJB2 for Hearing Loss Association.

Involvement of GJB2 noncoding regions in hearing loss (HL) has not been extensively investigated. However, three noncoding mutations, c.-259C>T, c.-23G>T, and c.-23+1G>A, were reported. Also, c.-684_-675del, of uncertain pathogenicity, was found upstream of the basal promoter. We performed a detailed analysis of GJB2 noncoding regions in Portuguese HL patients (previously screened for GJB2 coding mutations and the common GJB6 deletions) and in control subjects, by sequencing the basal promoter and flanking upstream region, exon 1, and 3'UTR. All individuals were genotyped for c.-684_-675del and 14 SNPs. Novel variants (c.-731C>T, c.-26G>T, c.*45G>A, and c.*985A>T) were found in controls. A hearing individual homozygous for c.-684_-675del was for the first time identified, supporting the nonpathogenicity of this deletion. Our data indicate linkage disequilibrium (LD) between SNPs rs55704559 (c.*168A>G) and rs5030700 (c.*931C>T) and suggest the association of c.[*168G;*931T] allele with HL. The c.*168A>G change, predicted to alter mRNA folding, might be involved in HL.

A novel M163L mutation in connexin 26 causing cell death and associated with autosomal dominant hearing loss.

Mutations in GJB2 gene (encoding connexin 26) are the most common cause of hereditary non-syndromic sensorineural hearing loss (NSSHL) in different populations. The majority of GJB2 mutations are recessive, but a few dominant mutations have been associated with hearing loss either isolated or associated with skin disease. We describe a novel dominant pathogenic GJB2 mutation, identified in a Portuguese family affected with bilateral mild/moderate high-frequency NSSHL. In vitro functional studies demonstrate that the mutant protein (p.M163L) has defective trafficking to the plasma membrane and is associated with increased cell death.

A novel hearing-loss-related mutation occurring in the GJB2 basal promoter.

Mutations in the GJB2 gene are a major cause of non-syndromic recessive hearing loss in many countries. In a significant fraction of patients, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity are identified. This paper reports a novel GJB2 mutation, -3438C-->T, found in the basal promoter of the gene, in trans with V84M, in a patient with profound hearing impairment. This novel mutation can abolish the basal promoter activity of GJB2. These results highlight the importance of extending the mutational screening to regions outside the coding region of GJB2.

Correlates of early sexual activity among Hispanic children in middle adolescence

OBJECTIVE: We analyzed early sexual activity among Hispanic 14 to 15-year-old adolescents residing in a poor neighborhood in Puerto Rico. METHODS: Information from a sample of 325 adolescents was collected from a randomized sample of community households. Logistic regression analysis was used to identify the variables that help explained adolescents' sexual behavior. RESULTS: Adolescents whose parents reported poor communication and poor parent control were more likely to engage in early sexual activity that those peers that did not report this type of family relationship. Adolescents who reported poor parent bonding and lack of discipline were more likely to engage in early sexual relationships. CONCLUSIONS: Intervention and prevention programs need to be aware and address the role of the Hispanic culture in gender differences in early sexual activity in adolescence. If sexual norms related to gender role are changing in Puerto Rico, is a question that needs to be answered in future research.

Alcohol use among adolescents in Puerto Rico: the influence of physical and social neighborhood disorder.

INTRODUCTION: The characteristics of social settings are increasingly being recognized as important factors influencing the health of individuals. This study examines the association of neighborhood physical and social disorganization with alcohol consumption in a sample of adolescents 12- to 15-years-old residing in communities of the San Juan metropolitan area with high availability of illicit drugs. METHODS: The sampling frame was developed encompassing all census sectors in three municipalities of the San Juan metropolitan area with outdoor illegal drug-selling areas operating within them. Consent from parents and their adolescent offspring was obtained from 691 of these households for a response rate of 96%. Alcohol use was measured by asking adolescents if they had consumed alcohol during the last 12 months. Neighborhood social disorganization included hearing gunfire in the neighborhood, seeing neighbors selling stolen merchandise and drugs, vandalism, neighbors using alcohol and drugs, and seeing persons carrying weapons. Neighborhood physical disorganization included the presence of abandoned vehicles and buildings in the neighborhood, graffiti, and places where people go to inject drugs. RESULTS: Multiple logistic regression analysis revealed that older participants were more likely to use alcohol. Neighborhood social disorder was significantly associated with alcohol use. The strong positive gradient between neighborhood social disorder and alcohol use remained highly significant after controlling by sociodemographic characteristics. In contrast, neighborhood physical disorder was not significantly associated with alcohol use. CONCLUSION: These findings suggest that social signs of neighborhood disorganization have a more direct influence over adolescents' behaviors than the physical signs. Health professionals need to be cognizant of the strong effects that social environments have on adolescents and develop strategies to address these when intervening with adolescents.

Mortality among Hispanic drug users in Puerto Rico

This paper assesses mortality rate for a cohort of drug users in Puerto Rico compared with that of the Island's general population, examining causes of death and estimating relative risk of death. Date and cause of death were obtained from death certificates during 1998. Vital status was confirmed through contact with subjects, family, and friends. HIV/AIDS was the major cause of death (47.7%), followed by homicide (14.6%), and accidental poisoning (6.3%). Females had higher relative risk of death than males in all age categories. Not living with a sex partner and not receiving drug treatment were related to higher mortality due to HIV/AIDS. Drug injection was the only variable explaining relative risk of death due to overdose. Puerto Rico needs to continue developing programs to prevent HIV/AIDS among drug users. Special attention should be given to young women, who appear to be in greatest need of programs to prevent early mortality.

Prevalence and correlates of anergy among drug users in Puerto Rico.

OBJECTIVES: This study assessed prevalence and correlates of anergy among a cohort of drug users in communities in the San Juan metropolitan area. METHODS: In all, 719 drug injectors and crack users were recruited in neighbourhoods in the San Juan metropolitan area following a stratified cluster design of 30 copping areas (places where drugs are sold). RESULTS: Slightly more than one-third of the total proportion of participants, 34.2%, were HIV positive and 30.3% anergic. Subjects with a history of incarceration, the HIV positive, and those reporting chronic illness were more likely to be anergic than those subjects without these characteristics. CONCLUSIONS: Most studies addressing drug users' immune system dysfunction are related to HIV infection. Additional studies are needed to provide a more comprehensive understanding of drug users' immune systems.

Factors associated with changes in sex behaviour among drug users in Puerto Rico.

Despite available strategies to prevent sex risk behaviours in Puerto Rico, heterosexual transmission of HIV continues to increase. Since 1990, heterosexual contact has been the fastest growing infection risk category among the island's general population, and the primary transmission route for women and children. To understand change in sex risk behaviours and factors related to change, 911 drug injectors and 359 crack smokers were recruited from the San Juan metropolitan area following a stratified cluster design. This study comprised a total of 1,004 (79.1%) drug users who were assessed at follow-up. Abstinence from sex behaviour increased from 54.6% to 61.1% (p < 0.01), use of condoms during vaginal sex also increased from 26.4% to 36.9% (p < 0.01). In multivariate analysis, significant predictors of abstinence were gender, injection drug use, HIV seropositivity and not having a steady partner. Predictors of using condoms during vaginal sex were HIV seropositivity, STD diagnosis and participation in an HIV preventive programme. These findings indicate that additional HIV preventive efforts are needed to reduce sex risk behaviours among drug users who have a steady sex partner, as well as among drug users who are HIV-negative.

PIP: Factors associated with changes in HIV risk behaviors were investigated in a prospective study of 911 injecting drug users and 359 crack smokers recruited on the basis of a stratified cluster design in metropolitan San Juan, Puerto Rico, in 1992-93. The findings presented in this paper are based on the 1004 drug users (79.1%) who were available for a follow-up interview 6 months after the baseline interview. Respondents were randomly assigned to receive a standard HIV prevention intervention (pretest counseling, optional HIV testing, and provision of HIV results) or the standard intervention plus a site-specific enhanced intervention entailing access to condoms and needle hygiene equipment, development of a personal risk reduction plan and training in the skills required to implement it, and ongoing contact with outreach workers. Overall, abstinence from sexual behavior increased from 54.6% at baseline to 61.1% at follow-up (p 0.01) while condom use during vaginal sex rose from 26.4% to 36.9% (p 0.01). In multivariate analysis, significant predictors of abstinence were male gender, injecting drug use, a positive HIV test at baseline, and not having a steady partner. Significant predictors of condom use were HIV seropositivity and a sexually transmitted disease diagnosis. Participation in the enhanced compared to the standard HIV prevention program was associated with an odds ratio of 1.29 (95% confidence interval, 0.95-1.74) for abstinence and 1.97 (95% confidence interval, 1.18-3.29) for condom use in vaginal sex.

Risk behaviors, HIV seropositivity, and tuberculosis infection in injecting drug users who operate shooting galleries in Puerto Rico.

This study was designed to assess HIV risk behaviors, HIV seroprevalence, and tuberculosis (TB) infection in shooting gallery managers in Puerto Rico. The subjects were 464 injection drug users (IDUs), of whom 12.5% reported managing shooting galleries. The median frequency of drug injection was higher in shooting gallery managers than in nonmanagers. A trend was observed for purified protein derivative (PPD) reactivity to increase according to the length of time spent as a gallery manager, but this trend was not statistically significant. However, anergy rates increased significantly with increase in the number of months spent as shooting gallery manager (p = .021). Multivariate analyses showed that IDUs reporting shooting gallery management experience of > or = 25 months were more likely to be infected with HIV. Prevention programs need to emphasize strategies to protect the health of shooting gallery clients and, in particular, shooting gallery managers. Additional studies are required to determine effective strategies for reducing the risk of HIV and TB infection in shooting galleries.

PIP: Little information is currently available on the health status of individuals who manage the settings in which drug injection-related behaviors occur. The present study investigated HIV risk behaviors, HIV seroprevalence, and tuberculosis infection among 464 injecting drug users recruited from areas in San Juan, Puerto Rico, known to have high levels of drug activity. 58 respondents (12.5%) reported having been a shooting gallery manager, for a median duration of 18 months. Managers were more likely to be female, over 35 years of age, not married, homeless, to inject only cocaine, to inject more frequently, to have a history of incarceration, and to report disability than drug users who were not managers. No differences in rates of HIV, tuberculosis, or anergy existed between managers with 1-24 months of management experience and nonmanagers. However, gallery managers with 25 or more months of experience were nearly 3 times more likely to be infected with HIV, nearly 2 times more likely to be anergic, and 2.5 times more likely to have tuberculosis than nonmanagers. 41% of nonmanagers, 48% of managers with 1-24 months of experience, and 71% of those who had been managers for 25 months or more were HIV-seropositive. The compromised health status of long-term shooting gallery managers underscores the need for public health interventions to interrupt the spread of sexually transmitted diseases, HIV, and tuberculosis in this high-risk setting.

Syringe and needle exchange as HIV/AIDS prevention for injection drug users in Puerto Rico.

This study evaluated the effectiveness of the first needle exchange program (NEP) established in Puerto Rico. The data for this study were collected during the first months of the NEP from July 1995 to March 1996 in 13 communities of the San Juan metropolitan area. Subjects were the participants of two modalities of the NEP: a mobile team and a community-based drug treatment program. During the 3-week evaluation period, 2401 injection drug users (IDUs) were recruited, resulting in a total of 19,195 exchange contacts and 146,323 syringes exchanged. No significant change in drug injection was observed. However, the program was effective in reducing sharing of syringes and cookers. The study suggests that the NEP did help in reducing needle sharing in Puerto Rico. However, the HIV seropositivity in returned syringes suggests the need to continue aggressive prevention programs to arrest the epidemic among IDUs. However, factors related to the socio-cultural environment as well as cultural norms and traditions need to be considered when planning and expanding NEPs.

Crack use in Puerto Rico: evidence of a recent epidemic.

This study examines the prevalence of crack use among out-of-treatment drug users in the San Juan metropolitan area. Of the sample of 849 drug users, 310 (36.5%) were crack users only, 179 (21.1%) were drug injectors and crack users, and 360 (42.4%) were drug injectors only. To study the characteristics of crack users we selected the subjects who reported the use of crack only. Of the 310 subjects, 193 (62.3%) men and 117 (37.7%) women, the mean age was 29 years. Significant differences were observed by gender. Females reported higher education, living in a nuclear family, crack/cocaine as the first drug used, history of sexually transmitted diseases and higher rates of HIV seropositivity. Males were more likely to report income from illegal activities, incarceration, use of multiple drugs, and more years of drug use. Among those sexually active, females were more likely to practice unprotected vaginal sex, have multiple sex partners, engage in prostitution (exchange of sex for money and/or drugs) and use condoms.

Risk factors for shooting gallery use among drug injectors in Puerto Rico.

Needle sharing is one of the principal risk behaviors leading to HIV transmission among injection drug users (IDUs). Shooting galleries, a social context where IDUs rent, share, and borrow needles, are locations usually found near drug markets. This study, which interviewed 1,700 IDUs from May 1989 to June 1990, assesses sociodemographic characteristics and HIV risk behaviors among shooting gallery users in Puerto Rico. Multivariate analyses showed that shooting gallery use is associated with speedball (a concoction of heroin and cocaine) injection, income from illegal activities and previous drug treatment. Shooting gallery users were more likely to rent, share, and borrow needles, and less likely to always use bleach and water to clean needles. Strategies to reduce shooting gallery use among drug injectors are discussed.

Risk factors for shooting gallery use among drug injectors in Puerto Rico

Needle sharing is one of the principal risk behaviors leading to HIV transmission among injection drug users (IDUs). Shooting galleries, a social context where IDUs rent, share, and borrow needles, are locations usually found near drug markets. This study, which interviewed 1,700 IDUs from May 1989 to June 1990, assesses sociodemographic characteristics and HIV risk behaviors among shooting gallery users in Puerto Rico. Multivariate analyses showed that shooting gallery use is associated with speedball (a concoction of heroin and cocaine) injection, income from illegal activities and previous drug treatment. Shooting gallery users were more likely to rent, share, and borrow needles, and less likely to always use bleach and water to clean needles. Strategies to reduce shooting gallery use among drug injectors are discussed

Crack use in Puerto Rico: evidence of a recent epidemic

This study examines the prevalence of crack use among out-of-treatment drug users in the San Juan metropolitan area. Of the sample of 849 drug users, 310 (36.5 percent) were crack users only, 179 (21.1 percent) were drug injectors and crack users, and 360 (42.4 percent) were drug injectors only. To study the characteristics of crack users we selected the subjects who reported the use of crack only. Of the 310 subjects, 193 (62.3 percent) men and 117 (37.7 percent) women, the mean age was 29 years. Significant differences were observed by gender. Females reported higher education, living in a nuclear family, crack/cocaine as the first drug used, history of sexually transmitted diseases and higher rates of HIV seropositivity. Males were more likely to report income from illegal activities, incarceration, use of multiple drugs, and more years of drug use. Among those sexually active, females were more likely to practice unprotected vaginal sex, have multiple sex partners, engage in prostitution (exchange of sex for money and/or drugs) and use condoms

Effects of HIV testing and counseling on reducing HIV risk behavior among two ethnic groups.

PIP: The impact of an HIV testing and counseling program on the risk behaviors of drug users was assessed in 981 African American heroin and crack cocaine users living in the US and 144 Puerto Ricans living both in Puerto Rico and the US. Respondents were part of the US National Institute on Drug Abuse's multi-site Cooperative Agreement for Acquired Immunodeficiency Syndrome Community-Based Outreach/Intervention Research. At each site, active drug injectors and crack cocaine users were selected by targeted sampling methods. The intervention included pre-HIV test counseling, voluntary HIV testing, a post-testing counseling session focused on risk-reduction strategies, and an optional session for HIV-positive participants. The mean age of respondents was 38.5 years; 82.9% were unemployed. 62.5% had a history of sexually transmitted diseases and 12.5% (9.3% of African Americans and 31.9% of Puerto Ricans) were HIV-positive. At baseline, 63.5% of African Americans and 47.2% of Puerto Ricans were engaging in unprotected vaginal intercourse and 3.1% and 8.3%, respectively, were practicing unprotected anal intercourse. Injection risk factors after counseling were independent of HIV test result among African Americans; among Puerto Ricans, a positive HIV test increased the likelihood of shared use of cookers. In both ethnic groups, seropositives were significantly less likely to persist in practicing unprotected vaginal sex. Seropositive African Americans were also less likely to continue to practice unprotected oral sex. Since heterosexual relations with an HIV-positive drug user is a major risk factor for sex partners and children, this screening and counseling program can have a substantial impact on control of the AIDS epidemic in the US.^ieng

Prospective effects of perceived risk of developing HIV/AIDS on risk behaviors among injection drug users in Puerto Rico.

The relationship between perceived risk of developing AIDS and subsequent behavioral risk status is estimated for 1740 Puerto Rican injection drug users (IDUs). Prospective behavioral effects were examined comparing data collected at two intervals approximately 6 months apart. We estimated the association between perceived risk at baseline and risky behaviors at follow-up with unadjusted odds ratios. We confirmed the results with adjusted odds ratios using logistic regressions which included baseline risk status as well as socio-demographic and health status covariates. The analyses showed that having a high HIV/AIDS risk perception was related to subsequent sharing of needles, injection of drugs in shooting galleries and sharing of cookers. None of the tests between risk perception and sex risk behaviors showed a significance association. Increasing IDUs' perceived vulnerability to HIV/AIDS might not be effective in helping reduce HIV risk behaviors. IDUs perceiving themselves to be at high risk of AIDS might believe there is little they can do to reverse the consequences of risky behavior.

Effects of a community outreach program in HIV risk behaviors among injection drug users in San Juan, Puerto Rico: an analysis of trends.

This report assesses the effects of a community outreach program in reducing HIV risk behaviors among injection drug users (IDUs) in San Juan, Puerto Rico. Participants were 1,113 IDUs, 88.3% of whom were also assessed at post-intervention. The analytic strategy consisted in modeling pre- and post-intervention trends in risk behavior levels from successive cohorts of IDUs. The trend analyses showed that secular trends, unrelated to the direct effects of the outreach intervention, accounted for significant portions of the reported risk reductions. Nevertheless, the post-intervention trends in the shared use of cookers and in needle bleaching showed shifts that could not be accounted for by the modeled secular trends. The outreach intervention appears to have had significant but partial effects on the behavioral risks associated to drug injection and no effect on sexual behaviors. The strengths and weaknesses of time-trend analyses for evaluating community HIV-prevention programs lacking experimental designs are discussed.

HIV/AIDS risk perception, HIV risk behaviors, and HIV seropositivity among injection drug users in Puerto Rico.

This paper assesses the factors related to self perception of developing AIDS among a group of 1,568 Puerto Rican injection drug users (IDUs). Incarceration history, years of drug injection, sharing needles, renting and borrowing needles, sharing rinse water or cooker, and having an IDU sex partner yielded a moderate association with HIV/AIDS risk perception. Use of sterile needles, shooting drugs alone, having had previous treatment episodes, and all the variables related to health status were also moderately associated with HIV/AIDS risk perception. A logistic regression model based on backwards elimination procedure, which included statistically significant variables in the bivariate analyses, yielded the variables living with children, sex with an IDU partner, shooting drugs alone, perception of health, having had a sexually transmitted disease, and results of HIV testing as statistically significant (p < 0.05).