Search

Background: Patients with type 2 diabetes (T2D) are at an increased risk of genital urinary (GU) infections, with the risk increasing with higher A1Cs. Given the broad adoption of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in patients with T2D, both providers and patients need to be aware of common adverse effects associated with these medications, specifically GU infections. However trials involving SGLT2is looked at patients with an average A1C of less than 9%, and thus, the incidence of GU infections may not truly reflect the general diabetic population. Objective: The purpose of this study is to assess the association between GU infections in patients started on SGLT2is and A1C levels. Methods: A retrospective study was conducted on patients seen in an adult, primary care clinic, at New York City Health and Hospitals, South Brooklyn Health. Men and nonpregnant, nonlactating women >18 years old with a diagnosis of T2D who were initiated on an SGLT2i between January 2018 and January 2023 were included in the analysis. The primary endpoint is to compare the risk of GU infections in patients with T2D who were started on SGLT2is, regardless of dose, with hemoglobin A1C of >9% to those with hemoglobin A1C <9% at baseline. Results: Three hundred and twenty-eight patients were eligible based on specified inclusion and exclusion criteria. Overall, there was a statistically significant difference in the number of GU infections that occurred in patients with a baseline A1C >9% compared with those with an A1C <9% (95% confidence interval [CI] = 1.05-2.88; P = 0.041). Conclusions and Relevance: Type 2 diabetes patients initiated on SGLT2is may experience an increased risk of GU infection, especially in those patients with an A1C of 9% or greater. Further research is necessary to validate and expand upon these findings. [ABSTRACT FROM AUTHOR]

Background: Gastroschisis is a congenital anomaly of the umbilical ring with increasing prevalence, especially amongst younger mothers. There is increasing evidence that exposure to genitourinary infections (GUTI) may play an important role in the etiology of gastroschisis. This systematic review and meta‐analysis aimed to identify, appraise, and summarize the literature on exposure to GUTI and gastroschisis. Methods: Six electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, Cochrane Library electronic databases, and Prospero) were searched using a comprehensive search strategy. Citations and cited articles for all included studies were searched. Peer‐reviewed, quantitative studies reporting an association of urinary tract infections (UTI) and/or sexually transmitted infections (STI) with gastroschisis were included. Prospero registration CRD42022377420. Results: A total of 2392 papers were identified via the searches of which 15 met our inclusion criteria and were included after title and abstract and full text screening. The study period for included studies ranged from 1995 to 2016, most were from the USA. Four studies considering exposure to STIs and five to UTIs were eligible to progress to meta‐analysis. Meta‐analysis identified a significantly increased risk of gastroschisis in association with periconceptional exposure to UTI [OR 1.54 (95% CI 1.29, 1.8)], STI [OR 1.4 (95% CI 1.01, 1.79)]. Conclusions: Periconceptional exposure to GUTI is associated with an increased risk of gastroschisis. The prevention and timely treatment of GUTI amongst women of childbearing age may help to reduce the occurrence of gastroschisis. [ABSTRACT FROM AUTHOR]

Objective: Study of the prevalence of genitourinary infections in diabetic patients on SGLT2 inhibitors Study design: A cross-sectional study Place and Duration: This study was conducted at Services Institute of Medical Sciences Lahore hospital from January 2018 to January 2019 Methodology: The SGLT-2 inhibitors drugs given to the patients were empagliflozin and dapagliflozin as a combination or monotherapy over three months. The patients were asked for a detailed medical history and their medical records were observed to assess the genitourinary infections. The questionnaire included queries related to pain during micturition, frequency of micturition, the urgency of micturition, itching, vaginal or penile discharge, redness, soreness, abdominal pain, back pain, suprapubic pain, vomiting, diarrhea, fever, chills, discomfort around the perianal area, tenderness in the costovertebral angle and sepsis Results: A total of 1050 patients were considered, out of which 504 (48%) were commenced on dapagliflozin while 546 (52%) were commenced on empagliflozin. Out of 504 patients taking dapagliflozin, 327 (64.88%) were male and 177 (35.11%) were female. On the other hand, 393 (71.97%) male patients and 153 (28.02%) female patients were among those 546 that were using empagliflozin. The risk of urinary tract infection in the patients using dapagliflozin was 22 (4.3%) and it was 34 (6.74%) in those using empagliflozin. Similarly, the risk of genital tract infections in the patients using dapagliflozin was 19 (3.76%) and those using empagliflozin were 23 (4.56%). The predominance of genital infections and urinary infections was more in females than males in both empagliflozin and dapagliflozin users. The correlation between uncontrolled diabetes and female gender with the frequency of genitourinary infection was significant with a p-value of 0.003 and 0.001, respectively. Conclusion: Diabetic patients are more prone to have genitourinary infections than healthy individuals. Patients taking SGLT-2 inhibitors have been shown to have a higher prevalence of catching genitourinary infections. SGLT-2 inhibitors intake is related to genitourinary infections in patients of diabetes mellitus type 2. [ABSTRACT FROM AUTHOR]

Female patients are at a greater risk for infections such as urinary tract infections and mastitis, as well as complications from abortions/miscarriages, and sexually transmitted infections. This review highlights risk factors, pathogenesis, complications, diagnostic, and treatment modalities associated with the following infections: mastitis, sexually transmitted diseases, postpartum/abortion-related infections, and urinary tract infections. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial (NTM) genitourinary (GU) infections are relatively rare, and there is frequently a delay in diagnosis. Mycobacterium avium-intracellulare complex (MAC) cases seem to be less frequent than other NTM as a cause of these infections. In addition, there are no set treatment guidelines for these organisms in the GU tract. Given the limitations of data this review summarizes a case presentation of this infection and the literature available on the topic. Many different antimicrobial regimens and durations have been used in the published literature. While the infrequency of these infections suggests that there will not be randomized controlled trials to determine optimal therapy, our case suggests that a brief course of amikacin may play a useful role in those who cannot tolerate other antibiotics.

Mycobacterium abscessus is one of the nontuberculous mycobacteria (NTM), which can cause many clinical spectra, predominantly pulmonary infections followed by skin and soft tissue infections. The prevalence of Mycobacterium abscessus infections has been growing worldwide over the last two decades. Urinary tract infection (UTI) secondary to M. abscessus is a rare condition, and only five cases have been described in the literature so far. Therefore, managing such a condition is challenging and based on limited evidence. Here, we report a case of an adult male with a history of previous urological procedures who presented with lower urinary tract symptoms (LUTS) and was found to have a UTI secondary to Mycobacterium abscessus. In this case, we described our successful management approach of this rare entity of Mycobacterium abscessus infection, and we reviewed similar cases in the literature.

Nontuberculous mycobacterial (NTM) genitourinary (GU) infections are relatively rare, and there is frequently a delay in diagnosis. Mycobacterium avium-intracellulare complex (MAC) cases seem to be less frequent than other NTM as a cause of these infections. In addition, there are no set treatment guidelines for these organisms in the GU tract. Given the limitations of data this review summarizes a case presentation of this infection and the literature available on the topic. Many different antimicrobial regimens and durations have been used in the published literature. While the infrequency of these infections suggests that there will not be randomized controlled trials to determine optimal therapy, our case suggests that a brief course of amikacin may play a useful role in those who cannot tolerate other antibiotics. [ABSTRACT FROM AUTHOR]

Background: Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are associated with an increased risk of genitourinary infections in patients with type 2 diabetes mellitus (T2DM). It is unknown which factors may predispose patients to an increased risk of developing a genitourinary infection. Objective: To evaluate whether hemoglobin A1c levels and other patient‐specific factors at initiation of SGLT2 inhibitor therapy were a predictor for increased risk for genitourinary infections. Methods: A retrospective, multicenter cohort analysis was conducted using data from ambulatory care clinics within a large medical group. Patients 18 years of age or older with a diagnosis of T2DM who were prescribed a SGLT2 inhibitor between January 1, 2013 and October 31, 2018 and completed therapy for at least seven days were included in the analysis. Firth logistic regression was used to detect differences in baseline characteristics and paired t‐tests were used to compare baseline to post‐initiation values for prespecified variables for those patients with a confirmed genitourinary infection. Results: Of the 739 patients prescribed a SGLT2 inhibitor, 584 were included. Thirty (5.14%) patients experienced a genitourinary infection on SGLT2 inhibitor therapy. Baseline hemoglobin A1c did not confer a significant difference in risk for genitourinary infection (p=0.4239). Estimated glomerular filtration rate (eGFR) was the only variable that significantly differed between those who did and did not develop an infection (p=0.0228). A post hoc analysis reviewing 30 patients initially excluded for a history of genitourinary infection showed 13 (43%) of those patients experienced a genitourinary infection after initiating SGLT2 inhibitor therapy with no difference in risk stratified by baseline hemoglobin A1c level (p=0.9648). Conclusions: The incidence of genitourinary infection with SGLT2 inhibitor use was lower than suggested in clinical trials, with lower eGFR and history of genitourinary infection the only identified predictors for increased risk in this population. Genitourinary infection risk should not deter clinicians from recommending or prescribing SGLT2 inhibitor therapy. [ABSTRACT FROM AUTHOR]

Background: Many countries have initiated school-based human papillomavirus (HPV) vaccination programs. The real-life effectiveness of HPV vaccines has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. In 2009, Norway initiated a school-based HPV vaccination program for 12-year-old girls using the quadrivalent HPV vaccine (Gardasil®), which targets HPV6, 11, 16, and 18. Here, we aim to assess type-specific vaginal and oral HPV prevalence in vaccinated compared with unvaccinated girls in the first birth cohort eligible for school-based vaccination (born in 1997). Methods: This observational, cross-sectional study measured the HPV prevalence ratio (PR) between vaccinated and unvaccinated girls in Norway. Facebook advertisement was used to recruit participants and disseminate information about the study. Participants self-sampled vaginal and oral specimens using an Evalyn® Brush and a FLOQSwab™, respectively. Sexual behavior was ascertained through a short questionnaire. Results: Among the 312 participants, 239 (76.6%) had received at least one dose of HPV vaccine prior to sexual debut. 39.1% of vaginal samples were positive for any HPV type, with similar prevalence among vaccinated and unvaccinated girls (38.5% vs 41.1%, PR: 0.93, 95% confidence interval [CI]: 0.62–1.41). For vaccine-targeted types there was some evidence of lower prevalence in the vaccinated (0.4%) compared to the unvaccinated (6.8%) group (PR: 0.06, 95%CI: 0.01–0.52). This difference remained after adjusting for sexual behavior (PR: 0.04, 95%CI: 0.00–0.42). Only four oral samples were positive for any HPV type, and all of these participants had received at least one dose of HPV vaccine at least 1 year before oral sexual debut. Conclusion: There is evidence of a lower prevalence of vaccine-targeted HPV types in the vagina of vaccinated girls from the first birth cohort eligible for school-based HPV vaccination in Norway; this was not the case when considering all HPV types or types not included in the quadrivalent HPV vaccine. [ABSTRACT FROM AUTHOR]

Prior research has found that places and people that are more economically disadvantaged have higher rates and risks, respectively, of sexually transmitted infections (STIs). Economic disadvantages at the level of places and people, however, are themselves influenced by economic policies. To enhance the policy relevance of STI research, we explore, for the first time, the relationship between state-level minimum wage policies and STI rates among women in a cohort of 66 large metropolitan statistical areas (MSAs) in the US spanning 2003–2015. Our annual state-level minimum wage measure was adjusted for inflation and cost of living. STI outcomes (rates of primary and secondary syphilis, gonorrhea and chlamydia per 100,000 women) were obtained from the CDC. We used multivariable hierarchical linear models to test the hypothesis that higher minimum wages would be associated with lower STI rates. We preliminarily explored possible socioeconomic mediators of the minimum wage/STI relationship (e.g., MSA-level rates of poverty, employment, and incarceration). We found that a $1 increase in the price-adjusted minimum wage over time was associated with a 19.7% decrease in syphilis rates among women and with an 8.5% drop in gonorrhea rates among women. The association between minimum wage and chlamydia rates did not meet our cutpoint for substantive significance. Preliminary mediation analyses suggest that MSA-level employment among women may mediate the relationship between minimum wage and gonorrhea. Consistent with an emerging body of research on minimum wage and health, our findings suggest that increasing the minimum wage may have a protective effect on STI rates among women. If other studies support this finding, public health strategies to reduce STIs among women should include advocating for a higher minimum wage. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer imposes a substantial health burden worldwide including in Australia and is caused by persistent infection with one of 13 sexually transmitted high-risk human papillomavirus (HPV) types. The objective of this study was to assess the cost-effectiveness of adding a nonavalent new Gardasil-9® (9vHPV) vaccine to the national immunisation schedule in Australia across three different delivery strategies. Materials and methods: The Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to examine the cost-effectiveness of 9vHPV vaccine introduction to prevent HPV infection. Academic literature and anecdotal evidence were included on the demographic variables, cervical cancer incidence and mortality, treatment costs, and vaccine delivery costs. The incremental cost-effectiveness ratios (ICERs) were measured per disability-adjusted life years (DALYs) averted, using the heuristic cost-effectiveness threshold defined by the World Health Organisation (WHO). Analyses and data from international agencies were used in scenario analysis from the health system and societal perspectives. Results: The 9vHPV vaccination was estimated to prevent 113 new cases of cervical cancer (discounted) during a 20-year period. From the health system and societal perspectives, the 9vHPV vaccination was very cost-effective in comparison with the status quo, with an ICER of A$47,008 and A$44,678 per DALY averted, respectively, using the heuristic cost-effectiveness threshold level. Considering delivery strategies, the ICERs per DALY averted were A$47,605, A$46,682, and A$46,738 for school, health facilities, and outreach-based vaccination programs from the health system perspective, wherein, from the societal perspective, the ICERs per DALY averted were A$46,378, A$43,729, A$43,930, respectively. All estimates of ICERs fell below the threshold level (A$73,267). Conclusions: This cost-effectiveness evaluation suggests that the routine two-dose 9vHPV vaccination strategy of preadolescent girls against HPV is very cost-effective in Australia from both the health system and societal perspectives. If equally priced, the 9vHPV option is the most economically viable vaccine. Overall, this analysis seeks to contribute to an evidence-based recommendation about the new 9vHPV vaccination in the national immunisation program in Australia. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the HIV/syphilis epidemic among men who have sex with men (MSM) aged <50 years and ≥50 years in Shenzhen, and explore the associated factors of HIV/syphilis co-infections among MSM in Shenzhen, in order to help prevention and intervention programs determine their target sub-group. A serial cross-sectional study was conducted on MSM in Shenzhen city, China from 2009 to 2017. A questionnaire was used to collect demographic characteristics, history of HIV testing, history of blood donation and sexual behaviors. 5 ml of venous blood were collected for syphilis and HIV tests. The overall prevalence of HIV, syphilis, HIV/syphilis co-infection was 9.40%, 18.97%, and 4.91%, respectively. The prevalence of HIV (15.26%), syphilis (27.71%), HIV/syphilis co-infection (9.24%) in aged ≥50 years MSM was significantly higher than aged <50 years MSM (9.15%, 18.59% and 4.72%, respectively). The following factors were found to be significantly associated with HIV/syphilis co-infections (P<0.05): age≥50 years (OR = 1.78, 95% CI = 1.10–2.87), high school or lower (OR = 1.49, 95% CI = 1.10–2.01), monthly income ≤436.2 USD (OR = 1.74, 95% CI = 1.25–2.42), monthly income 436.4–727.2 USD (OR = 1.46, 95% CI = 1.05–2.03), ≥2 anal sex partners in the past 6 months (OR = 1.59, 95% CI = 1.02–2.49), ≥2 oral sex partners in the past 6 months (OR = 1.60, 95% CI = 1.08–2.36), inconsistent condom use during anal sex in the past 6 months (OR = 1.50, 95% CI = 1.11–2.03). We found that aged <50 years and ≥50 years MSM in Shenzhen had a high prevalence of HIV/syphilis infection in a period from 2009 to 2017. Age-specific sexually transmitted diseases education, prevention, and intervention programs for aged ≥50 years MSM should be implemented urgently and integrated interventions of both HIV and syphilis infections on MSM are needed in the future. [ABSTRACT FROM AUTHOR]

Japanese Encephalitis virus (JEV) is a zoonotic flavivirus that represents the most significant etiology of childhood viral neurological infections throughout the Asia. During the last 20 years, JEV genotype dominance has shifted from genotype III (GIII) to genotype I (GI). To date, the exact mechanism of this displacement is still not known. Culex (Cx.) mosquitoes are the most common species in China and play an essential role in maintaining JEV enzootic transmission cycle. In this study, we used Cx. pipiens mosquitoes from China as an in vivo mosquito model to explore if mosquitoes played a potential role in JEV genotype shift. We exposed female Cx. pipiens mosquitoes orally to either GI or GIII JEV strains. Midgut, whole mosquitoes, secondary organs, and salivary glands of JEV-infected mosquitoes were collected at 7 and 14 days of post infection (dpi) and subjected to measure the infection rate, replication kinetics, dissemination rate and transmission potential of the infected JEV strains in Cx. pipiens mosquitoes by 50% tissue culture infective dose assay. We found that Cx. pipiens mosquito was competent vector for both GI and GIII JEV infection, with similar infection rates and growth kinetics. After the establishment of infection, Cx. pipiens mosquitoes disseminated both JEV genotypes to secondary organs at similar rates of dissemination. A few GI-infected mosquito salivary glands (16.2%) were positive for GI virus, whereas GIII virus was undetectable in GIII-infected mosquito salivary glands at 7 dpi. However, 29.4% (5/17) and 36.3% (8/22) were positive for GI- and GIII-infected mosquito salivary glands at 14 dpi, respectively, showing an increase in JEV positive rate. No statistical difference in the transmission rate between GI- and GIII-infected mosquitoes was detected. Our experiment data demonstrated that GI and GIII viruses have similar infectivity in Cx. pipiens mosquitoes, suggesting that Cx. pipiens mosquitoes from China may not play a critical role in JEV genotype shift. Although the current data were obtained solely from Cx. pipiens mosquitoes, it is likely that the conclusion drawn could be extrapolated to the role of mosquitoes in JEV genotype shift. [ABSTRACT FROM AUTHOR]

Aim: To investigate the correlation between the dorsal tongue porphyrin autofluorescence, revealed using VELscope, and Candida saprophytism. Material and methods: Consecutive patients underwent an autofluorescence examination by the VELscope device to establish the presence or absence of porphyrin fluorescence. A tongue swab was collected for the Candida cultural test. Sensitivity, specificity, accuracy, negative predictive value and positive predictive value were calculated considering the oral swab as the gold standard. The degree of agreement between the two tests was calculated using Cohen's K coefficient. Results: One hundred twenty-six patients were enrolled. Porphyrin fluorescence method showed a sensitivity of 78%, specificity of 76% and an accuracy of 78%. Negative predictive value and positive predictive value were respectively 90% and 59%. The strength of agreement between the two methods resulted to be moderate (k = 0.551). Conclusions: Off-label use of tongue autofluorescence examination to detect the presence of Candida species is characterized by a loss of porphyrin fluorescence. The high negative predictive value of porphyrin fluorescence loss suggests its use in preliminary selection of Candida carriers, in order to plan preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]

A microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi living in different niches of the human body, which plays an essential role in many metabolic functions. Modifications in the microbiota composition can lead to several diseases, including metabolic disorders. The aim of this study was to analyze the prevalence of four viruses which can cause persistent infections–Epstein-Barr virus (EBV), human papillomavirus (HPV), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) in patients with diabetes mellitus type 2 (DM2). Blood, saliva and oral swabs were collected from all the study participants. The nested-PCR technique was used to detect the viral DNA. DNA of at least one virus was detected in 71.1% of diabetic patients and in 30% of individuals without diabetes. In patients with diabetes EBV DNA was detected the most frequently (25.4%), followed by HPV– 19.1%, HSV– 10.4% and CMV– 5.2%. A higher percentage of EBV+HPV co-infection was found among men (30.8%). EBV DNA was statistically more often detected in patients living in rural areas (53.7%), while HPV (91.5%) and EBV+HPV co-infection (22.2%) prevailed among patients from urban areas. In patients with a DM2 history longer than 10 years viral infection was detected more frequently. The prevalence of EBV, HPV and the EBV+HPV co-infection was significantly higher in diabetic patients than in individuals without diabetes. The frequency of these infections depended on the duration of the disease (DM2). [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) related tumours account for a significant proportion of head and neck squamous cell carcinomas (HNSCCs) in developed countries. They respond better to chemo- and radio-therapy, and have a better stage specific prognosis. To establish their prevalence in China, we assessed a series of histology confirmed HNSCCs collected in Zhejiang and Guangdong provinces by PCR for HPV DNA and by immunohistochemistry for p16 protein status. Among 303 HNSCCs, HPV DNA was detected in 26.4%, with HPV16 DNA in 71% of these. Of HNSCC located in the oropharynx, 38.55% (32/83) were HPV+ve. In this series, p16 status was a relatively poor predictor of HPV status as detected by PCR. The stage specific survival time of HPV+ HNSCCs was significantly longer than for HPV- HNSCC. HPV status should be assessed for oropharyngeal cancers in China to assist with appropriate management, and prophylaxis against HPV infection should be considered to reduce the incidence of this disease. [ABSTRACT FROM AUTHOR]

Objective: Blood transfusion is the most frequently used and life-saving therapeutic procedure today. Transmission of virus, bacteria and parasitic microorganisms may occur due to transfusion (Transfusion transmitted infections-TTIs). Hepatitis B and C, human immunodeficiency virus (HIV) and syphilis (Treponema pallidum) bear the risk of transmission by transfusion. Hepatitis B surface antigen (HBsAg), anti-HCV, anti-HIV½ and syphilis antibody (VDRL: Venereal Disease Research Laboratory) are routinely controlled in all donated blood samples. The aim of the present study was to analyze the seroprevalence rates of blood donors through screening test results according to duration, age range and gender. Material and methods: Data of all blood donors obtained from blood Centre of Marmara University Pendik Training and Research Hospital between January 2013 and October 2018 were analyzed retrospectively. Serum samples of the donors were analyzed for HBsAg, anti-HCV, anti-HIV½ and VDRL. Test results of 114.240 donors were scanned. Gender, age range and distribution by years of these donors were analyzed. According to age distribution of donors were divided into 4 groups. Results: There were 114.240 participants including 106.153 (92.9%) males and 8.087 (7.1%) females. The positivity rate of HBsAg was detected 0.4% (36/8087) in females and 0.5% (500/106.153) in males. The positivity rate of anti-HCV was detected 0.4% (32/8.087) in females and 0.3% (344/106.153) in males. The positivity rate of anti HIV½ was 0.1% (9/8.087) in females and 0.1% (92/106.153) in males whereas the positivity rate of VDRL was 0.5% (41/8.087) in females and 0.3% (362/ 106.153) in males. Positivity rate for HBsAg and HCV were lower in the cases between 18 and 30 years of age. The positivity rates for anti-HIV½ was not significantly different according to the age range. Positivity rate for VDRL was higher in the cases at 51 years of age and older. Conclusion: No difference was found between men and women in terms of HBsAg, anti-HCV and anti-HIV½positivity. However, VDRL test positivity was significantly higher in female participants. Furthermore, HBsAg, anti-HCV and VDRL positivity rates increased by age. [ABSTRACT FROM AUTHOR]

Introduction: Mozambique continues to have a significant burden of HIV. Developing strategies to control the HIV epidemic remains a key priority for the Mozambican public health community. The primary aim of this study was to determine HIV prevalence and risk behavior among males and females screened for a HIV vaccine preparedness study in Maputo, Mozambique. Methods: Male and female participants between 18–35 years old were recruited from the general community and from female sex worker (FSW) and lesbian, gay, bisexual, and transgender (LGBT) associations in Maputo. All participants were screened for HIV and a questionnaire was administered to each participant to assess HIV risk behavior. Results: A total of 1125 adults were screened for HIV infection, among whom 506 (45%) were male. Among men, 5.7% reported having had sex with men (MSM) and 12% of female participants reported having exchanged sex for money, goods or favors in the past 3 months. The overall HIV prevalence was 10.4%; 10.7% of women, and 10.1% of men were HIV infected; 41.4% of MSM were seropositive. HIV infection was associated with older age (25–35 years old) (OR: 6.13, 95% CI: 3.01, 12.5), MSM (OR: 9.07, 95% CI: 3.85, 21.4), self-perception of being at high-risk for HIV (OR: 3.99, 95% CI: 1.27, 12.5) and self-report of a history of a diagnosis of sexually transmitted infection (OR: 3.75, 95% CI: 1.57, 8.98). Conclusion: In our cohort, HIV prevalence was much higher among MSM compared to the overall prevalence. Behavioral factors were found to be more associated with HIV prevalence than demographic factors. The study findings demonstrate the critical importance of directing services to minority communities, such as MSM, when prevention strategies are being devised for the general population. [ABSTRACT FROM AUTHOR]

Cytology remains the mainstay of cervical cancer screening in South Africa (SA), however false negative rates are 25–50%. In contrast, human papillomavirus (HPV) screening techniques have higher sensitivity for cervical cancer precursors. The cobas® 4800 HPV test detects pooled high-risk HPV types and individual genotypes HPV 16 and 18. Using a mathematical budget impact model, the study objective was to evaluate the clinical and budget impact of replacing primary liquid-based cytology (LBC) with primary HPV-based screening strategies. In SA, current LBC screening practice recommends one test every ten years, followed by large loop excision of the transformation zone (LLETZ) if indicated. HPV testing can be performed from an LBC sample, where no additional consultations nor samples are required. In the budget impact model, LBC screening for 2 cycles (one test every ten years) was compared to cobas® 4800 HPV test for 2 cycles (one test every 5 years). The model inputs were gathered from literature and primary data sources. Indicative prices for LBC and cobas® 4800 HPV test were R189 and R457, respectively. Model results indicate that best outcomes for detection of disease were seen using cobas® 4800 HPV test. Forty-eight percent of cervical cancer cases were detected compared to 28% using LBC, and 50% of cervical intraepithelial neoplasia (CIN) 2 and CIN3 cases, compared to 25% with LBC. The budget impact analysis predicted that the cost per detected case of CIN2 or higher would be R 56,835 and R46,980 for the cobas® 4800 HPV and LBC scenarios, respectively. This equates to an incremental cost per detected case of CIN2 or higher of R9 855. From this model we conclude that a primary HPV screening strategy will have a significant clinical impact on disease burden in South Africa. [ABSTRACT FROM AUTHOR]

Our earlier studies indicated an important role of inducible transcription factor STAT3 in the establishment of persistent infection of human papillomavirus (HPV) type 16 and promotion of cervical carcinogenesis. Since HPV load and its physical state are two potential determinants of this virally-induced carcinogensis, though with some exceptions, we extended our study to examine the role of active STAT3 level in cervical precancer and cancer lesions and it’s association with HPV viral load and physical state. An elevated level of active STAT3 was measured by assessing phospho-STAT3-Y705 (pSTAT3), in tumor tissues harboring higher viral load irrespective of the disease grade. Physical state analysis of HPV16 by assessing the degree of amplification of full length E2 and comparing it with E6 (E2:E6 ratio), which predominantly represent episomal form of HPV16, revealed low or undetectable pSTAT3. A strong pSTAT3 immunoreactivity was found in tissues those harbored either mixed or predominantly integrated form of viral genome. Cumulative analysis of pSTAT3 expression, viral load and physical state demonstrated a direct correlation between pSTAT3 expression, viral load and physical state of HPV. The study suggests that there exists a strong clinical correlation between level of active STAT3 expression and HPV genome copy number, and integrated state of the virus that may play a pivotal role in promotion/maintanence of tumorigenic phenotype. [ABSTRACT FROM AUTHOR]

An association between HIV infection and cervical cancer, a major public health issue worldwide, has been reported. The aim of this study was to estimate the prevalence of human papillomavirus (HPV) infection and the distribution of HPV genotypes in HIV-infected women living in French Antilles and Guiana and to determine HIV-related characteristics associated with HPV infection. This cross-sectional study included 439 HIV-infected women who were followed between January 2011 and May 2014. Variables related to HIV infections were collected, and cervical samples were analysed to determine HPV genotypes. The median age of the population was 46 years. Estimated prevalence of HPV and high-risk (HR)-HPV infection were 50.1% IC95 [45.4–54.7] and 42% IC95 [37.3–46.6], respectively. HR-HPV 16, 52, 53 or intermediate risk-HPV-68 were found in 25% to 30% of the HPV-infected patients. Gynaecological screening revealed abnormal cervical smear in 24% and 42% of HR-HPV-negative and HPV-positive women, respectively (p = 0.003). Approximately 90% of women were on antiretroviral therapy (ART). Demographic characteristics associated with a higher prevalence of HPV infection included alcohol consumption. Regarding HIV-related characteristics, current therapy on ART, its duration, and undetectable plasma concentrations of RNA-HIV1 were associated with a lower risk of HPV infection. Infection rate with HR-HPV was higher than what is commonly reported in HIV-negative women worldwide and was more likely in women with incomplete HIV suppression. These results highlight the need for supporting adherence to ART, cervical cytology, HPV testing and HPV vaccination. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni is one of the most common helminth infections affecting a large population of people in sub-Saharan Africa. This helminth infection is known to cause immunomodulation which has affected the efficacy of a number of vaccines. This study examined whether a chronic schistosoma infection has an effect on the immunogenicity of HPV vaccine which is currently administered to girls and women aged 9 to 24. Little is known about the immune responses of the HPV vaccine in individuals with chronic schistosomiasis. Methods: This study was carried out at the Institute of Primate Research (IPR) and involved an Olive baboon model. The experimental animals were randomly placed into three groups (n = 3–4); Two groups were infected with S. mansoni cercaria, and allowed to reach chronic stage (week 12 onwards), at week 13 and 14 post-infection, one group was treated with 80mg/kg of praziquantel (PZQ). Sixty four weeks post schistosoma infection, all groups received 2 doses of the Cervarix HPV vaccine a month apart. Specific immune responses to the HPV and parasite specific antigens were evaluated. Results: Animals with chronic S. mansoni infection elicited significantly reduced levels of HPV specific IgG antibodies 8 weeks after vaccination compared the PZQ treated and uninfected groups. There was no significant difference in cellular proliferation nor IL-4 and IFN-γ production in all groups. Conclusion: Chronic S. mansoni infection results in reduction of protective HPV specific IgG antibodies in a Nonhuman Primate model, suggesting a compromised effect of the vaccine. Treatment of schistosomiasis infection with PZQ prior to HPV vaccination, however, reversed this effect supporting anti-helminthic treatment before vaccination. [ABSTRACT FROM AUTHOR]

Viral hepatitis, syphilis, HIV, and tuberculosis infections in prisons have been identified globally as a public health problem. Tuberculosis (TB) and viral hepatitis co-infection may increase the risk of anti-tuberculosis treatment-induced hepatotoxicity, leading to the frequent cause of discontinuation of the first-line anti-tuberculosis drugs. Therefore, the aim of this cross-sectional study was to investigate the epidemiological features of HCV, HBV, syphilis and HIV infections among bacteriologically confirmed tuberculosis prisoners in Campo Grande (MS), Central Brazil. The participants who agreed to participate (n = 279) were interviewed and tested for the presence of active or current HCV, HBV, syphilis and HIV infections. The prevalence of HCV exposure was 4.7% (13/279; 95% CI 2.2–7.1). HCV RNA was detected in 84.6% (11/13) of anti-HCV positive samples. Out of 279 participants, 19 (6.8%; 95% CI 4.4–10.4) were HIV co-infected, 1.4% (4/279, 95% CI 0.5–3.8) had chronic hepatitis B virus (HBsAg positive) and 9.3% (26/279, 95% CI 6.4–13.4) had serological marker of exposure to hepatitis B virus (total anti-HBc positive). The prevalence of lifetime syphilis infection (anti-T. pallidum positive) was 10% (28/279, 95% CI 7.0–14.2) and active syphilis (VDRL ≥ 1/8 titre) was 5% (14/279, 95% CI 2.9–8.3). The prevalence of TB/HCV co-infection among prisoners with HIV (15.8%) was higher than among HIV-non-infected prisoners (3.8%; P<0.05). These results highlight the importance of hepatitis testing among prisoners with bacteriologically confirmed case of TB who can be more effectively and safely treated in order to reduce the side effects of hepatotoxic anti-TB drugs. [ABSTRACT FROM AUTHOR]

Objective: To assess triage compliance and the effect of the time from screening to triage on follow-up among HPV-positive women. Methods: We recruited 1232 women in a screening campaign in Madagascar from February to October 2015. In the first period (February–May), HPV tests were performed remotely using the cobas test. In the second period (May–October), testing was performed on-site using the Xpert HPV assay. HPV-positive women were invited for triage with visual inspection with acetic acid (VIA) and Lugol’s iodine (VILI). Systematic biopsy and endocervical brushing were performed on all HPV-positive women for quality control. Three groups were defined according to time from HPV testing to triage invitation for HPV-positive women—Group I: delayed (> 3 months), Group II: prompt (24–48 hours), and Group III: immediate (< 24 hours). Results: A total 1232 self-sampled HPV tests were performed in the study period (496 in Group I, 512 in Group II, and 224 in Group III). Participants’ mean age was 43.2 ± 9.3 years. Mean time from screening to VIA/VILI testing was 103.5 ± 43.6 days. Overall HPV prevalence was 28.0%. HPV prevalence was 27.2% in Group I (cobas test), 29.2% in Group 2 (Xpert test), and 26,7% in Group III (Xpert test). The VIA/VILI compliance rate was 77.8% for Group I, 82.7% for Group II, and 95.0% for Group III. Of women undergoing VIA/VILI, 56.3% in Group I and 43.5% in Groups II/III had positive results. Prevalence of cervical intraepithelial neoplasia grade 2 or worse among HPV-positive women was 9.8% for Group I and 6.8% for Groups II/III. Non-adherence was higher among rural women, uneducated women, and women in Group I. Conclusion: HPV-positive women with immediate VIA/VILI triage invitation had the best triage compliance. A single-day test and triage strategy is preferred for low-resource settings. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus 68 (HPV68) is a probable carcinogenic HPV genotype which is included in almost all HPV screening assays and exists as two genetically variable subtypes (HPV68a and HPV68b). Routine HPV sample testing has shown that the cobas 4800 HPV Test (Roche) provides higher false-negative rates for HPV68 status than PapilloCheck HPV-Screening (Greiner Bio-One). The aim of our study was to evaluate the efficacy of cobas 4800 in HPV68 detection. Methods: A total of 2,145 cervical/cervicovaginal samples from women aged 17–88 were tested for HPV68 status using the cobas 4800 and PapilloCheck HPV tests. Viral load was assessed by quantitative PCR in all of the HPV68-positive cases. HPV68a/b subtyping was performed with real-time PCR followed by high resolution melting curve analysis, and was subsequently confirmed by Sanger sequencing. Results: Cobas 4800 detected HPV positivity in only 13/33 HPV68 single-genotype infection cases. Viral load was comparable across both tested subgroups. HRM analysis and Sanger sequencing identified the HPV68a subtype in all of the 20 instances of cobas 4800 false negatives. HPV68a and HPV68b were detected in 3/13 and 10/13 cases identified as other HPV-positive by cobas 4800. Conclusion: The HPV68a subtype was missed by cobas 4800 in more than 85% of all HPV68a-positive cases. Therefore, commercially available assays may underestimate HPV68 prevalence. [ABSTRACT FROM AUTHOR]

Genotype I (GI) virus has replaced genotype III (GIII) virus as the dominant Japanese encephalitis virus (JEV) in the epidemic area of Asia. The mechanism underlying the genotype replacement remains unclear. Therefore, we focused our current study on investigating the roles of mosquito vector and amplifying host(s) in JEV genotype replacement by comparing the replication ability of GI and GIII viruses. GI and GIII viruses had similar infection rates and replicated to similar viral titers after blood meal feedings in Culex tritaeniorhynchus. However, GI virus yielded a higher viral titer in amplifying host-derived cells, especially at an elevated temperature, and produced an earlier and higher viremia in experimentally inoculated pigs, ducklings, and young chickens. Subsequently we identified the amplification advantage of viral genetic determinants from GI viruses by utilizing chimeric and recombinant JEVs (rJEVs). Compared to the recombinant GIII virus (rGIII virus), we observed that both the recombinant GI virus and the chimeric rJEVs encoding GI virus-derived NS1-3 genes supported higher replication ability in amplifying hosts. The replication advantage of the chimeric rJEVs was lost after introduction of a single substitution from a GIII viral mutation (NS2B-L99V, NS3-S78A, or NS3-D177E). In addition, the gain-of-function assay further elucidated that rGIII virus encoding GI virus NS2B-V99L/NS3-A78S/E177E substitutions re-gained the enhanced replication ability. Thus, we conclude that the replication advantage of GI virus in pigs and poultry is the result of three critical NS2B/NS3 substitutions. This may lead to more efficient transmission of GI virus than GIII virus in the amplifying host-mosquito cycle. [ABSTRACT FROM AUTHOR]

Genotype III (GIII) Japanese encephalitis virus (JEV) predominance has gradually been replaced by genotype I (GI) over the last 20 years in many Asian countries. This genotype shift raises concerns about the protective efficacy of Japanese encephalitis (JE) vaccines, as all of the currently licensed JE vaccines are derived from GIII strains. In this study, we conducted vaccination-challenge protection assays to evaluate the cross-protective efficacy of GI- or GIII-derived vaccines against the challenge of a heterologous genotype using a mouse challenge model. Titration of the neutralizing antibodies elicited by SA14-14-2 live-attenuated JE vaccine (SA14-14-2 vaccine), a GIII-derived vaccine, indicated that the titer of neutralizing antibodies specific to heterologous genotype GI stain was significantly lower than that specific to homologous genotype GIII strain in both pigs and mice immunized with the SA14-14-2 vaccine. Vaccination of mice with SA14-14-2 vaccine or a GIII-inactivated vaccine at high and medium doses completely protected vaccinated mice against challenge with the homologous genotype GIII strains, but failed to provide the vaccinated mice complete protection against the challenge of heterologous genotype GI strains. The protection rates against GI strain challenge were 60%–80%, showing that these vaccines were partially protective against GI strain challenge. Additionally, vaccination of mice with a GI-inactivated vaccine conferred 100% protection against the challenge of homologous genotype GI strains, but 50%–90% protection against the challenge of heterologous genotype GIII strains, showing a reduced protective efficacy of a GI-derived vaccine against GIII strain challenge. Overall, these observations demonstrated a partial cross-protection between GI and GIII strains and suggested a potential need for new JE vaccine strategies, including options like a bivalent vaccine, to control both genotype infection. [ABSTRACT FROM AUTHOR]

Background: Correlation with HPV viral load and worsening cervical lesions had been reported, but its potential for triage after primary HPV screening has not been adequately explored, especially when combined with HPV-16/18 genotyping. Objective: To evaluate combinations of human papillomavirus (HPV) viral load and genotyping for HPV-16/18 as secondary screening strategies. Methods: The Shenzhen Cervical Cancer Screening Trial Ⅱ (SHENCCAST Ⅱ) database was re-analyzed to explore new screening algorithms using the results of Hybrid Capture 2 (HC2), Mass Array Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass spectrometry System (MALDI-TOF-MS) and the ThinPrep cytologic test (TCT) obtained by endocervical sampling. Results: Compared with the recommended screening strategy of genotyping HPV-16/18 plus reflex to cytology, using viral load (10 RLU/CO as threshold) plus reflex to cytology resulted in less cytology but had a significantly higher sensitivity for cervical intraepithelial neoplasia 2+ (CIN2+)/CIN3+ without considerable changes in specificity and referral rates. Both of the strategy of using viral load ≥10 RLU/CO as cut-point for immediate colposcopy followed by triage genotyping HPV-16/18 for the other positive (≥1<10 RLU/CO) and the strategy of referring HPV-16/18 positives for immediate colposcopy followed by triage viral load (10 RLU/CO as threshold) for non-HPV-16/18 positives had comparable screening efficacy with algorithims that contain cytology. Conclusions: Primary HPV screening with triage of HPV-positive women by a combination of viral load and genotyping for HPV-16/18 provides good balance between sensitivity and specificity, the number of tests required, and referral rates. [ABSTRACT FROM AUTHOR]

Background: Although the tprK gene of Treponema pallidum are thought to play a critical role in the pathogenesis of syphilis, the profile of variations in tprK during the development of human syphilis infection have remained unclear. Methods/Principal findings: Through next-generation sequencing, we compared the tprK gene of 14 secondary syphilis patients with that of 14 primary syphilis patients, and the results showed an increased number of variants within the seven V regions of the tprK gene in the secondary syphilis samples. The length of the sequences within each V region also presented a 3-bp changing pattern. Interestingly, the frequencies of predominant sequences within the V regions in the secondary syphilis samples were generally decreased compared with those found in the primary syphilis samples, particularly in the V7 region, where a frequency below 60% was found in up to 57% (8/14) of all secondary samples compared with 7% (1/14) of all primary samples. Moreover, the number of minor variants distributed between frequencies of 10 and 49.9% was increased. The alignment of all amino acid sequences within each V region of the primary and secondary syphilis samples revealed that some amino acid sequences, particularly the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1, were highly stable. Additionally, the amino acid sequences in V6 also exhibited notable intrastrain heterogeneity and were likely to form a strain-specific pattern at the interstrain level. Conclusions: The identification of different profiles of the tprK gene in primary and secondary syphilis patients indicated that the tprK gene of T. pallidum undergoes constant variation to result in the best adaptation to the host. The highly stable peptides found in V1 are likely promising potential vaccine components. The highly heterogenetic regions (e.g., V6) could help to understand the role of tprK in immune evasion. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppressive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independent pathway through its C-terminal domain, which has yet been largely undetermined, with a lack of structural information in a complex form with a host protein. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the high-risk HPV genotypes bound to the catalytic domain of human nonreceptor-type protein tyrosine phosphatase 14 (PTPN14). They interact directly and potently with each other, with a dissociation constant of 18.2 nM. Ensuing structural analysis revealed the molecular basis of the PTPN14-binding specificity of E7 over other protein tyrosine phosphatases and also led to the identification of PTPN21 as a direct interacting partner of E7. Disruption of HPV18 E7 binding to PTPN14 by structure-based mutagenesis impaired E7’s ability to promote keratinocyte proliferation and migration. Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective than wild-type PTPN14 in attenuating the activity of downstream effectors of Hippo signaling and negatively regulating cell proliferation, migration, and invasion when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell transformation and tumorigenesis. [ABSTRACT FROM AUTHOR]

Objectives: Sexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine. Methods: Between November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy. Results: In 242 women (median age 29 years [IQR = 24–34], median gestation 19 weeks [IQR = 14–24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02–3.67), being unmarried or not cohabiting with the fetus’ father (aOR = 2.19; 95% CI = 1.16–4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08–20.95) were associated with STI diagnosis. Conclusion: We found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Despite being preventable, cervical cancer remains a major health concern among women. Persistent Human Papillomavirus (HPV) and other viral co-infections may influence cervical dysplasia. We determined and compared the prevalence and risk factors of cervical viral infections among the tribal and general population of southern coastal Karnataka, India. Methods: A population-based cross-sectional survey was conducted among 1140 and 1100 women from tribal and general population, respectively. Cervical infections with HPV, Epstein-Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes-Simplex Virus (HSV) were examined using polymerase chain reactions (PCR) and DNA sequencing. Results: HPV prevalence was higher among tribal women (40.6%) than general population (14.3%) while the prevalence of EBV (55.1%) and CMV (49.4%) were lower among tribal women than general population (74.3% and 77.5%, respectively). HSV infection was observed in tribal women only (1.8%). Among HR-HPV strains, HPV-18 was predominant among tribal population (28.3%) while, HPV-16 was predominant among the general population (9.1%). Infections were associated with age, educational status, unemployment and personal hygiene of tribal women. Phylogenetic analysis revealed that HPV-16 variants of tribal participants were closely related to non-European sublineages indicating greater risk of HPV persistence and carcinogenesis. Conclusion: The study provides a comparative estimate for DNA virus infections of the cervix among women from general as well as tribal population in this region and also reveals a different type-specific pattern of viral infection. Further research is required to delineate the role of specific interactions between multiple virus infections and their role in carcinogenesis. [ABSTRACT FROM AUTHOR]

Introduction: This population-based study aimed to fill the knowledge gap on Human Papillomavirus (HPV) prevalence and associated sociodemographic risk factors of the general population in the North Tongu District, Ghana. These results are needed to guide cervical cancer prevention efforts, as the leading type of female cancers. Methods: A cross-sectional study including 2002 women in the North Tongu District, Ghana investigated HPV prevalence and associated sociodemographic risk factors. Women were recruited by geographical distribution through the local community-based health system and samples collected using a self-sampling device. For HPV genotyping BSGP5+/6+-PCR with Luminex-MPG readout was used. Multivariate logistic regression analyzed sociodemographic risk factors for HPV positivity. Results: Of 2002 self-collected samples, 1943 were eligible, contained sufficient DNA and provided valid HPV genotyping results. Prevalence of single high risk HPV types was 32.3% and of multiple high risk types 9.7%. The five most common detected HPV types were HPV16 (7.4%; 95%CI: 6.3–8.7), HPV52 (7.2%; 95%CI: 6.1–8.5), HPV35 (4.8%; 95%CI: 3.9–5.8), HPV59 (4.7%; 95%CI: 3.8–5.8), HPV56 (3.9%; 95%CI: 3.1–4.8). Highest prevalence was observed among women aged 18–24 years, while age 25–54 years was inversely associated with high risk HPV positivity in multivariate analysis. Sociodemographic risk factors identified were i) having any sexual partner, ii) more partners increased the odds for high risk HPV positivity, iii) independently from this marital status, in particular not being married. Discussion & conclusion: Most importantly, the high risk HPV prevalence detected from this study is higher than estimates reported for Western Africa. This needs be considered, when deciding on the cervical cancer screening algorithms introduced on a wider scale. Follow-up and triage, depending on the methods chosen, can easily overburden the health system. Self-sampling worked well and provided adequate samples for HPV-based screening. Women with increasing number of sexual partners and not being married were found to have higher odds of being high risk HPV positive, therefore could be a higher prioritized screening target group. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is one of the leading causes of cancer mortality among women from Paraguay, with high incidence and mortality rates (31.2 and 16 per 100 000 women, respectively). Although the risk factors associated with high-risk human papillomavirus (hrHPV) infection and preneoplastic cervical lesions are widely studied, population-based characteristics of particular settings may influence the feasibility of HPV-based CC screening implementation. This study aimed to explore factors associated with hrHPV infection and high-grade cervical neoplasia in hrHPV-positive (hrHPV+) women from Paraguay. Methods: A total of 5677 women aged 30–64 years from the Central Department of Paraguay were screened with HPV test (Hybrid Capture 2) and Pap smear. Sociodemographic and risk factor interviews were conducted. hrHPV+ women were referred to colposcopy and women with an abnormal colposcopy had a biopsy taken. The outcomes recorded were the hrHPV status and the presence of high-grade cervical intraepithelial neoplasia or worse (CIN2+) among hrHPV+ women. Associations were investigated using multivariate logistic regressions. Results: hrHPV prevalence was 13.8% (95%CI 13.0–14.8). This value decreased with the age of women (p-trend<0.001) and increased with the lifetime number of sexual partners (p-trend<0.001) and number of previous female partners of their current male partner if women had had one lifetime sexual partner (p-trend<0.001), increasing from 3.06 (95%CI 0.073–20.9) if partners had had one previous female partner to 9.19 (95%CI 2.36–61.1) if they had had eight or more. In hrHPV+ women, CIN2+ prevalence was 10.7% (95%CI 8.58–13.2) and increased with time since the last Pap smear (p-trend<0.001) and with the increasing number of pregnancies (p-trend = 0.05). Conclusion: In these settings, the sexual behavior of women and their male partners is associated with hrHPV infection. In hrHPV+ women, underscreening practices and multiple pregnancies are associated with CIN2+. This knowledge can contribute to public health policies for CC prevention and control in Paraguay. [ABSTRACT FROM AUTHOR]

Background: Human papillomaviruses are the most important causative agents for invasive cervical cancer development. HPV type-specific vaccination and HPV cervical cancer screening methods are being widely recommended to control the disease but the epidemiology of the circulating HPV types may vary locally. The circulating HPV-strains have never been assessed in Burundi. This study determined the prevalence and genotype-specific distribution of HPV in four different strata in Burundi: HIV-infected or non-infected and women living in rural or urban areas. Implications for HPV diagnosis and vaccine implementation was discussed. Methods: Four cross-sectional surveys were conducted in Burundi (2013 in a rural area and 2016 in urban area) among HIV-infected and uninfected women living in rural and urban areas. Liquid-Based Cytology (LBC) and HPV genotyping were performed and risk factors for HPV infection and cervical pre-cancer lesions were determined using logistic regression model. Results: HPV prevalence was very high in urban area with significant differences between HIV-positive and negative women (p<0.0001). In fact, 45.7% of HIV-positive participants were infected with any HPV type and all were infected with at least one HR/pHR-HPV type. Among the HIV-negative participants, 13.4% were HPV-infected, of whom, only four women (2.7%) were infected with HR/pHR-HPV types. In rural area, HPV infection did not significantly differ between HIV-positive and negative women (30.0% and 31.3% respectively; p = 0.80). In urban area, multiple infections with HR/pHR-HPV types were detected in 13.9% and 2.7% among HIV-positive and negative women respectively (p<0.0001), whereas in rural area, multiple infections with HR/pHR-HPV types were detected in 4.7% and 3.3% of HIV-positive and negative women respectively (p = 0.56). The most prevalent HR/pHR-HPV types in HIV-positive women living in urban area were HPV 52, 51, 56, 18 and 16 types. In HIV-negative women living in urban area, the most prevalent HR/pHR-HPV types were HPV 66, 67, 18, 45 and 39 types. In HIV-positive women living in rural area, the most prevalent HR/pHR-HPV types were HPV 66, 16, 18 and 33 types. In HIV-negative women living in rural area, the most prevalent HR/pHR-HPV types were HPV 16, 66, 18, 35 and 45 types. Independent risk factors associated with cervical lesions were HPV and HIV infections. Conclusions: There is a high burden of HR and pHR-HPV infections, in particular among HIV-infected women living in urban area. The study points out the need to introduce a comprehensive cervical cancer control programme adapted to the context. This study shows that the nonavalent vaccine covers most of the HR/pHR-HPV infections in rural and urban areas among HIV-infected and uninfected women. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is a risk factor for oral diseases, which may be associated with premature death. We evaluated the risk of all-cause and cardiovascular mortality associated with oral mucosal lesions in adults with kidney failure treated with long-term haemodialysis. Methods: Oral mucosal lesions (herpes, ulceration, neoformation, white lesion, red lesion, oral candidiasis, geographical tongue, petechial lesions, and fissured tongue) were evaluated within the Oral Diseases in Haemodialysis (ORAL-D) study, a multinational cohort study of 4726 haemodialysis adults. We conducted cox regression analyses adjusted for demographic and clinical variables to evaluate the association with all-cause and cardiovascular mortality. Results: Overall, 4205 adults (mean age 61.6 ± 15.6 years) underwent oral mucosal examination with 40% affected by at least one lesion. The prevalence of oral lesions was (in order of frequency): oral herpes 0.5%, mucosal ulceration 1.7%, neoformation 2.0%, white lesion 3.5%, red lesion 4.0%, oral candidiasis 4.6%, geographical tongue 4.9%, petechial lesions 7.9%, and fissured tongue 10.7%. During median follow-up of 3.5 years, 2114 patients died (1013 due to cardiovascular disease). No association was observed between any individual oral lesion and all-cause or cardiovascular mortality when adjusted for comorbidities, except for oral candidiasis, which was associated with all-cause mortality (adjusted hazard ratio 1.37, 95% CI 1.00 to 1.86) and cardiovascular mortality (adjusted hazard ratio 1.64, 95% CI 1.09 to 2.46). Conclusion: Oral mucosal lesions are prevalent in haemodialysis patients. Oral candidiasis appears to be a risk factor for death due to cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Pathogenic treponemes related to Treponema pallidum are both human (causing syphilis, yaws, bejel) and animal pathogens (infections of primates, venereal spirochetosis in rabbits). A set of 11 treponemal genome sequences including those of five Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14, Chicago), four T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), one T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPeC) were tested for the presence of positively selected genes. Methodology/Principal findings: A total of 1068 orthologous genes annotated in all 11 genomes were tested for the presence of positively selected genes using both site and branch-site models with CODEML (PAML package). Subsequent analyses with sequences obtained from 62 treponemal draft genomes were used for the identification of positively selected amino acid positions. Synthetic biotinylated peptides were designed to cover positively selected protein regions and these peptides were tested for reactivity with the patient's syphilis sera. Altogether, 22 positively selected genes were identified in the TP genomes and TPA sets of positively selected genes differed from TPE genes. While genetic variability among TPA strains was predominantly present in a number of genetic loci, genetic variability within TPE and TEN strains was distributed more equally along the chromosome. Several syphilitic sera were shown to react with some peptides derived from the protein sequences evolving under positive selection. Conclusions/Significance: The syphilis-, yaws-, and bejel-causing strains differed relative to sets of positively selected genes. Most of the positively selected chromosomal loci were identified among the TPA treponemes. The local accumulation of genetic variability suggests that the diversification of TPA strains took place predominantly in a limited number of genomic regions compared to the more dispersed genetic diversity differentiating TPE and TEN strains. The identification of positively selected sites in tpr genes and genes encoding outer membrane proteins suggests their role during infection of human and animal hosts. The driving force for adaptive evolution at these loci thus appears to be the host immune response as supported by observed reactivity of syphilitic sera with some peptides derived from protein sequences showing adaptive evolution. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the short-term efficacy and safety of Poly-gamma-glutamic acid (γ-PGA) and the immunologic changes in patients with CIN 1. Methods: Participants were randomly assigned to one of two groups and orally treated with placebo or 1,500 mg of γ-PGA for 4 weeks. The primary endpoint of the study was histologic regression rate of CIN 1 at 12 weeks between γ-PGA and control groups. The secondary endpoints were HPV clearance and change in immune responses. Result: From April 2013 to December 2015, 195 patients participated in the study. In the intention-to-treat analysis, 42 (42.4%) of the women who received γ-PGA experienced histologic remission versus 26 (27.1%) in the control group, with a statistically significant difference (p = 0.018). In the γ-PGA group, HPV clearance was found in 37 (43.5%) of 85 patients infected with high-risk HPV, showing a significant difference compared to the control group, in which 20 (26.7%) of 75 patients exhibited HPV clearance (p = 0.026). However, there was no significant difference between the two groups in the change of NK cell activity, major histocompatibility complex (MHC) class II CD8 count, and CD56 count. Conclusion: γ-PGA showed a short-term therapeutic effect on CIN 1 and high-risk HPV infection. It is a non-invasive, promising oral medication for women with these conditions. Trial registration: Clinical Trials . [ABSTRACT FROM AUTHOR]

Objective: To examine the test performance of careHPV, Hybrid Capture2 (HC2) and visual inspection with acetic acid (VIA) for detection of cytologically diagnosed high-grade cervical lesions or cancer (HSIL+). Design: Cross-sectional study. Setting: Ocean Road Cancer Institute (ORCI) and Kilimanjaro Christian Medical Center (KCMC), Tanzania. Population: Women attending routine cervical cancer screening. Method: We enrolled 4080 women (25–60 years) in the study. The women were interviewed on lifestyle habits, and tested for HIV. A cervical specimen for careHPV testing (performed at ORCI and KCMC), and a liquid-based cytology sample for HPV DNA detection using HC2 (performed at Tuebingen University Hospital, Germany) and for cytology assessment (performed at Vejle Hospital, Denmark) were obtained at a gynecological examination. Subsequently, VIA was performed. With cytology as gold standard, the sensitivity and specificity of careHPV, HC2, and VIA for detection of HSIL+ were calculated. Results: Altogether, 23.6% had a positive careHPV test, 19.1% had positive HC2 test, and 6.3% had a positive VIA test. The sensitivity/specificity was 88.9%/78.9% for careHPV and 91.1%/83.7%, for HC2. VIA showed a low sensitivity of 31.1% but a high specificity (94.6%) for detection of HSIL+. The sensitivity of careHPV, HC2 and VIA was higher among younger women, and among HIV positive women. VIA triage of careHPV positive women improved specificity, but sensitivity dropped to 27%. Conclusion: Our results confirm the low sensitivity of VIA for detection of HSIL+ and further document that careHPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. A suitable triage test has to be identified. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Neisseria gonorrhoeae is a global health problem. Monoclonal antibody (mAb) 2C7 recognizes a gonococcal lipooligosaccharide epitope that is expressed by >95% of clinical isolates and hastens gonococcal vaginal clearance in mice. Chimeric mAb 2C7 (human immunoglobulin G1 [IgG1]) with an E430G Fc modification that enhances Fc:Fc interactions and hexamerization following surface-target binding and increases complement activation (HexaBody technology) showed significantly greater C1q engagement and C4 and C3 deposition compared to mAb 2C7 with wild-type Fc. Greater complement activation by 2C7-E430G Fc translated to increased bactericidal activity in vitro and, consequently, enhanced efficacy in mice, compared with “Fc-unmodified” chimeric 2C7. Gonococci bind the complement inhibitors factor H (FH) and C4b-binding protein (C4BP) in a human-specific manner, which dampens antibody (Ab)-mediated complement-dependent killing. The variant 2C7-E430G Fc overcame the barrier posed by these inhibitors in human FH/C4BP transgenic mice, for which a single 1 μg intravenous dose cleared established infection. Chlamydia frequently coexists with and exacerbates gonorrhea; 2C7-E430G Fc also proved effective against gonorrhea in gonorrhea/chlamydia-coinfected mice. Complement activation alone was necessary and sufficient for 2C7 function, evidenced by the fact that (1) “complement-inactive” Fc modifications that engaged Fc gamma receptor (FcγR) rendered 2C7 ineffective, nonetheless; (2) 2C7 was nonfunctional in C1q−/− mice, when C5 function was blocked, or in C9−/− mice; and (3) 2C7 remained effective in neutrophil-depleted mice and in mice treated with PMX205, a C5a receptor (C5aR1) inhibitor. We highlight the importance of complement activation for antigonococcal Ab function in the genital tract. Elucidating the correlates of protection against gonorrhea will inform the development of Ab-based gonococcal vaccines and immunotherapeutics. [ABSTRACT FROM AUTHOR]

HTLV-1/2 are transmitted sexually, by whole cell blood products and from mother-to-child (MTC), mainly through breastfeeding. HTLV-1/2 prevalence in pregnant women is high in Rio de Janeiro, however there were no local studies addressing the rate of adverse pregnancy outcomes (APO) and MTC transmission. The aim was to study sociodemographic characteristics which may be associated to HTLV-1/2 infection and describe pregnancy outcomes and MTC transmission in HTLV-1/2-positive women. The cross-sectional study screened 1,628 pregnant women in of Rio de Janeiro (2012–2014) and found 12 asymptomatic carrier mothers (prevalence = 0.74%). Pregnancy outcome information was retrieved from medical records. Sociodemographic characteristics were similar between the positive and negative groups except for maternal age, which was higher in carrier mothers. The incidence of adverse pregnancy outcomes was similar in infected and non-infected patients (p = 0.33), however there was a high rate of premature rupture of membranes (PROM) amid infected mothers (3/12). Multilevel logistic regression found that for each additional year of age, the chance of being HTLV-1/2-positive increased 11% and that having another sexually transmitted infection (STI) increased 9 times the chance of being infected. Carrier mothers had more antenatal visits (OR = 5.26). Among the children of HTLV-1/2-positive mothers there was one fetal death, one infant death and one loss of follow-up. After two years of follow-up there was one case of MTC transmission (1/9). The mother reported breastfeeding for one month only. Knowledge about factors associated to HTLV-1/2 infection, its impact on pregnancy outcomes and the MTC transmission rate is important to guide public health policies on antenatal screening and management. [ABSTRACT FROM AUTHOR]

Background: We conducted in 2018 a descriptive, quantitative, population-based, cross-sectional survey estimating the prevalence of cervical high-risk human papillomavirus (HR-HPV) infection and associated risk factors among adult women living in N’Djamena, Chad. Methods: Five of the 10 districts of N’Djamena were randomly selected for inclusion. Peer educators contacted adult women in community-churches or women association networks to participate in the survey and come to the clinic for women’s sexual health “La Renaissance Plus”, N’Djamena. Medical, socio-demographical and behavioral informations were collected. HPV DNA was detected and genotyped in endocervical swab using Anyplex II HPV28 genotyping test (Seegene, Seoul, South Korea). Results: 253 women (mean age, 35.0 years; range, 25–65) including 3.5% of HIV-positive women were prospectively enrolled. The prevalence of HPV infection was 22.9%, including 68.9% of HR-HPV infection and 27.6% being infected with multiple genotypes, providing a total HR-HPV prevalence of 15.8% (95% CI%: 11.3–20.3). The most prevalent HR-HPV genotypes were HPV-58, HPV-35, HPV-56, HPV-31, HPV-16, HPV-45, HPV-52 and HPV-18. HPV types targeted by the prophylactic Gardasil-9 vaccine were detected in nearly 70% (67.5%) and HPV-58 was the most frequently detected. HIV infection was a risk factor strongly associated with cervical infection with any HPV [adjusted Odds ratio (aOR): 17.4], multiple types of HPV (aOR: 8.9), HR-HPV (aOR: 13.2) and cervical infection with multiple HR-HPV (aOR: 8.4). Conclusion: These observations highlight the unsuspected high burden of cervical HR-HPV infection in Chadian women, and point the potential risk of further development of HPV-associated cervical precancerous and neoplastic lesions in a large proportion of women in Chad. The high rate of preventable Gardasil-9 vaccine genotypes constitutes the rationale for introducing primary vaccine prevention against cervical cancer in young female adolescents living in Chad. [ABSTRACT FROM AUTHOR]

Dapagliflozine is a highly selective sodium-glucose cotransporter 2 inhibitor (SGLT2i) , approved for the treatment of type 2 DM patients, as a monotherapy or in combination with other medications. Compared to the placebo groups whom administered dapagliflozin have a significant reduce in HbA1c: -0.58% (dapagliflozine 2.5mg), -0.77% (dapagliflozin 5mg) and -0.89% (dapagliflozin 10mg) in comparison to the placebo group (0.23%). Weight loss associated with the use of SGLT2 inhibitor is maintained during clinical studies up to 104 weeks.The use of these drugs in the population of patients with type 2 diabetes and high risk for cardiovascular disease is associated with reduction of mortality and morbidity from cardiovascular diseases. Indirectly renoprotective effect SGLT2i is achieved by decreasing renal glucose resorption and decreasing the blood glucose concentration, with the reduction in body weight and the body mass index. Genital infections are the most common side effects of dapagliflozine and should not be used in patients with bladder carcinoma and should be prescribed cautiously in people with a history of bladder cancer and unexplained hematuria.Due to good drug tolerance, easy dosing and minimal risk of the side effects, except for genitourinary infections, dapagliflozine, as well as other drugs in this group are an adequate choice in all patients with DM type 2, especially those with high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Objective: To investigate the long-term prophylactic effect of a vaccine on lower urinary tract infections (UTI) of bacterial and the impact of the intensity of the symptoms on the quality of life (QoL). Methods: Adult female could be enrolled in this study if they had acute UTI at the enrolment visit and bacterial microbiological count of ≥103 CFU/mL of Escherichia coli. Results: A total of 21 patients were included. Fifteen days after the administration of a vaccine for 3 months, the number of infections dropped almost to zero. Significant differences were observed in the QoL score (p < 0.05). The safety profile was good. Conclusions: In patients diagnosed with recurrent UTI and treated for 3 months with the vaccine the number of UTI episodes fell very quickly (15 days), and patients remained free of episodes and improved their QoL significantly for 1 year. These results suggest that bacterial vaccines are a possible effective alternative in the prevention of recurrent UTI. [ABSTRACT FROM AUTHOR]

Background: Although more than 95% of viral sequences found in skin tumors typically belong to human papillomaviruses (HPVs), HPV transcription has so far not been detected. As current technology allows very deep transcriptome sequencing, we examined skin tumors and precursor lesions for HPV transcription. Method: Fresh frozen biopsies from 12 skin specimens (11/12 were positive for HPV DNA) were subjected to total RNA sequencing. The cervical cancer cell line CaSki was included as a positive control for HPV transcription. Results: HPV RNA was detected and confirmed in 1/12 skin lesions at a median depth of 66 million reads per sample. One specimen was positive for HPV 110 transcripts mapping to E6, E7, E2/E4 and L2 open reading frames, as well as to a spliced E1^E4 transcript. Conclusion: In conclusion, the study revealed that a minority of skin lesions contains HPV transcripts and that HPV DNA detection does not predict HPV transcriptional activity. [ABSTRACT FROM AUTHOR]

A recently introduced Multilocus Sequence Typing scheme for Treponema pallidum subsp. pallidum was applied to clinical samples collected from 2004 to 2017 from the two largest cities (Prague and Brno) in the Czech Republic. Altogether, a total of 675 samples were tested in this study and 281 of them were found PCR-positive for treponemal DNA and typeable. Most of the typed samples (n = 281) were swabs from primary or secondary syphilis lesions (n = 231), and only a minority were whole blood or tissue samples (n = 50). Swab samples from patients with rapid plasma regain (RPR) values of 1–1024 were more frequently PCR-positive (84.6%) compared to samples from patients with non-reactive RPR test (46.5%; p-value = 0.0001). Out of 281 typeable samples, 136 were fully-typed at all TP0136, TP0548, and TP0705 loci. Among the fully and partially typed samples, 25 different allelic profiles were identified. Altogether, eight novel allelic variants were found among fully (n = 5) and partially (n = 3) typed samples. The distribution of TPA allelic profiles identified in the Czech Republic from 2004 to 2017 revealed a dynamic character with allelic profiles disappearing and emerging over time. While the number of samples with the A2058G mutation was seen to increase (86.7% in 2016/2017), the number of samples harboring the A2059G mutation was found to have decreased over time (3.3% in 2016/2017). In addition, we found several allelic profile associations with macrolide resistance or susceptibility, the gender of patients, as well as patient residence. [ABSTRACT FROM AUTHOR]

Background: The exponential decrease in molecular sequencing cost generates unprecedented amounts of data. Hence, scalable methods to analyze these data are required. Phylogenetic (or Evolutionary) Placement methods identify the evolutionary provenance of anonymous sequences with respect to a given reference phylogeny. This increasingly popular method is deployed for scrutinizing metagenomic samples from environments such as water, soil, or the human gut. Novel methods: Here, we present novel and, more importantly, highly scalable methods for analyzing phylogenetic placements of metagenomic samples. More specifically, we introduce methods for (a) visualizing differences between samples and their correlation with associated meta-data on the reference phylogeny, (b) clustering similar samples using a variant of the k-means method, and (c) finding phylogenetic factors using an adaptation of the Phylofactorization method. These methods enable to interpret metagenomic data in a phylogenetic context, to find patterns in the data, and to identify branches of the phylogeny that are driving these patterns. Results: To demonstrate the scalability and utility of our methods, as well as to provide exemplary interpretations of our methods, we applied them to 3 publicly available datasets comprising 9782 samples with a total of approximately 168 million sequences. The results indicate that new biological insights can be attained via our methods. [ABSTRACT FROM AUTHOR]

Background: The incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes. Methods: This retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC. Results: In total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141–0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients. Conclusion: Even when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia. [ABSTRACT FROM AUTHOR]

Inhibition of human papillomavirus (HPV) replication is a promising therapeutic approach for intervening with HPV-related pathologies. Primary targets for interference are two viral proteins, E1 and E2, which are required for HPV replication. Both E1 and E2 are phosphoproteins; thus, the protein kinases that phosphorylate them might represent secondary targets to achieve inhibition of HPV replication. In the present study, we show that CX4945, an ATP-competitive small molecule inhibitor of casein kinase 2 (CK2) catalytic activity, suppresses replication of different HPV types, including novel HPV5NLuc, HPV11NLuc and HPV18NLuc marker genomes, but enhances the replication of HPV16 and HPV31. We further corroborate our findings using short interfering RNA (siRNA)-mediated knockdown of CK2 α and α’ subunits in U2OS and CIN612 cells; we show that while both subunits are expressed in these cell lines, CK2α is required for HPV replication, but CK2α’ is not. Furthermore, we demonstrate that CK2α acts in a kinase activity-dependent manner and regulates the stability and nuclear retention of endogenous E1 proteins of HPV11 and HPV18. This unique feature of CK2α makes it an attractive target for developing antiviral agents. [ABSTRACT FROM AUTHOR]