IoT-based external attacks aware secure healthcare framework using blockchain and SB-RNN-NVS-FU techniques.

BACKGROUND: In recent times, there has been widespread deployment of Internet of Things (IoT) applications, particularly in the healthcare sector, where computations involving user-specific data are carried out on cloud servers. However, the network nodes in IoT healthcare are vulnerable to an increased level of security threats. OBJECTIVE: This paper introduces a secure Electronic Health Record (EHR) framework with a focus on IoT. METHODS: Initially, the IoT sensor nodes are designated as registered patients and undergo initialization. Subsequently, a trust evaluation is conducted, and the clustering of trusted nodes is achieved through the application of Tasmanian Devil Optimization (STD-TDO) utilizing the Student's T-Distribution. Utilizing the Transposition Cipher-Squared random number generator-based-Elliptic Curve Cryptography (TCS-ECC), the clustered nodes encrypt four types of sensed patient data. The resulting encrypted data undergoes hashing and is subsequently added to the blockchain. This configuration functions as a network, actively monitored to detect any external attacks. To accomplish this, a feature reputation score is calculated for the network's features. This score is then input into the Swish Beta activated-Recurrent Neural Network (SB-RNN) model to classify potential attacks. The latest transactions on the blockchain are scrutinized using the Neutrosophic Vague Set Fuzzy (NVS-Fu) algorithm to identify any double-spending attacks on non-compromised nodes. Finally, genuine nodes are granted permission to decrypt medical records. RESULTS: In the experimental analysis, the performance of the proposed methods was compared to existing models. The results demonstrated that the suggested approach significantly increased the security level to 98%, reduced attack detection time to 1300 ms, and maximized accuracy to 98%. Furthermore, a comprehensive comparative analysis affirmed the reliability of the proposed model across all metrics. CONCLUSION: The proposed healthcare framework's efficiency is proved by the experimental evaluation.

1D and 2D NMR for KRAS:Ligand Binding.

Fragment-based screening by ligand-observed 1D NMR and binding interface mapping by protein-observed 2D NMR are popular methods used in drug discovery. These methods allow researchers to detect compound binding over a wide range of affinities and offer a simultaneous assessment of solubility, purity, and chemical formula accuracy of the target compounds and the 15N-labeled protein when examined by 1D and 2D NMR, respectively. These methods can be applied for screening fragment binding to the active (GMPPNP-bound) and inactive (GDP-bound) states of oncogenic KRAS mutants.

Repurposing of US-FDA-approved drugs as negative modulators of ubiquitin specific protease-7 (USP7).

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of USP7 with dissociation constant (Kd) values in the range of 0.6-1.49 mM. These 11 compounds could thermally destabilize the USP7 enzyme by decreasing its melting temperature up to 9 °C. Molecular docking and simulation studies provided structural insights into the ligand-protein complexes, suggesting that these compounds bind to the putative substrate binding pocket of USP7, and interact with its catalytically important residues. Among the identified 11 hits, compound 6 (oxybutynin), 7 (ketotifen), 10 (pantoprazole sodium), and 11 (escitalopram) also showed anti-cancer activity with an effect on the expression of proto-oncogenes and tumor-suppressor gene at mRNA level in HCT116 cells. The compounds identified in this study can serve as potential leads for further studies.

Estimation of the Population Size of Street- and Venue-Based Female Sex Workers and Sexually Exploited Minors in Rwanda in 2022: 3-Source Capture-Recapture.

BACKGROUND: HIV surveillance among key populations is a priority in all epidemic settings. Female sex workers (FSWs) globally as well as in Rwanda are disproportionately affected by the HIV epidemic; hence, the Rwanda HIV and AIDS National Strategic Plan (2018-2024) has adopted regular surveillance of population size estimation (PSE) of FSWs every 2-3 years. OBJECTIVE: We aimed at estimating, for the fourth time, the population size of street- and venue-based FSWs and sexually exploited minors aged ≥15 years in Rwanda. METHODS: In August 2022, the 3-source capture-recapture method was used to estimate the population size of FSWs and sexually exploited minors in Rwanda. The field work took 3 weeks to complete, with each capture occasion lasting for a week. The sample size for each capture was calculated using shinyrecap with inputs drawn from previously conducted estimation exercises. In each capture round, a stratified multistage sampling process was used, with administrative provinces as strata and FSW hotspots as the primary sampling unit. Different unique objects were distributed to FSWs in each capture round; acceptance of the unique object was marked as successful capture. Sampled FSWs for the subsequent capture occasions were asked if they had received the previously distributed unique object in order to determine recaptures. Statistical analysis was performed in R (version 4.0.5), and Bayesian Model Averaging was performed to produce the final PSE with a 95% credibility set (CS). RESULTS: We sampled 1766, 1848, and 1865 FSWs and sexually exploited minors in each capture round. There were 169 recaptures strictly between captures 1 and 2, 210 recaptures exclusively between captures 2 and 3, and 65 recaptures between captures 1 and 3 only. In all 3 captures, 61 FSWs were captured. The median PSE of street- and venue-based FSWs and sexually exploited minors in Rwanda was 37,647 (95% CS 31,873-43,354), corresponding to 1.1% (95% CI 0.9%-1.3%) of the total adult females in the general population. Relative to the adult females in the general population, the western and northern provinces ranked first and second with a higher concentration of FSWs, respectively. The cities of Kigali and eastern province ranked third and fourth, respectively. The southern province was identified as having a low concentration of FSWs. CONCLUSIONS: We provide, for the first time, both the national and provincial level population size estimate of street- and venue-based FSWs in Rwanda. Compared with the previous 2 rounds of FSW PSEs at the national level, we observed differences in the street- and venue-based FSW population size in Rwanda. Our study might not have considered FSWs who do not want anyone to know they are FSWs due to several reasons, leading to a possible underestimation of the true PSE.

Using Social Listening for Digital Public Health Surveillance of Human Papillomavirus Vaccine Misinformation Online: Exploratory Study.

Despite challenges related to the data quality, representativeness, and accuracy of artificial intelligence-driven tools, commercially available social listening platforms have many of the attributes needed to be used for digital public health surveillance of human papillomavirus vaccination misinformation in the online ecosystem.

Characteristics of reproductive tract infections caused by common pathogens among the outpatients of reproductive medicine center in Putian: retrospective study.

BACKGROUND: This study aims to explore the infection and age distribution of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Herpes simplex virus type II (HSV II) among the outpatients of Reproductive Medicine Center in Putian, Fujian Province to provide a clinical basis for the early diagnosis and treatment of various reproductive tract diseases and infertility in this region. METHODS: A total of 1736 samples of secretions and exfoliated cervical cells were collected from the outpatients of the Reproductive Medicine Center of the Affiliated Hospital of Putian University from December 2021 to April 2023. The infections of UU, CT, NG and HSVII were detected by real-time fluorescence polymerase chain reaction (PCR), and the infection statuses of the patients with different genders, ages and diagnoses were analysed. RESULTS: Among the 1736 patients, 611 were male and 1125 were female. The male patients had higher UU infection rate but lower HSV II infection rate than the female patients. No significant difference in CT and NG infection rates was observed between the genders. The CT infection rate gradually decreased with the increase in the age. The difference in UU, NG and HSV II infection rates among the different age groups was not statistically significant. For UU infection, the male infertile patients had the highest rate of 37.72% (172/456). Meanwhile, the differences in CT, NG and HSV II infection rates among the different diagnosis groups were not statistically significant. Among the male and female infertile patients, the CT infection rate was the highest in the 21-25 years of age group at 11.11% (2/18) and 9.47% (9/95), respectively. No statistically significant difference in UU, CT, NG and HSV II infection rates was observed among the different age groups of patients diagnosed in relation to the family planning guidance and between the male and female patients with other diagnoses results. CONCLUSIONS: This study showed that UU was the most frequently identified pathogen in infertile men in Putian, Fujian Province. The CT infection rate was the highest in people under 20 years old, and the infection showed a tendency toward young individuals. Therefore, the publicity of sexual health knowledge must be strengthened, and the prevention and treatment of venereal diseases among young and middle-aged people must be improved. Moreover, the pathogen infection is related to infertility to a certain extent, which is conducive to clinical diagnosis and treatment.

The Complexity of Skeletal Transverse Dimension: From Diagnosis, Management, and Treatment Strategies to the Application of Collaborative Cross (CC) Mouse Model.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

A retrospective review of the rate of sexually transmitted infections in adolescents after universal screening protocol implementation in an urban United States clinic.

Objective: Despite expanded guidelines, adolescent gonorrhea and chlamydia (GC/CT) screening rates remain low due to multiple psychosocial barriers and biases. This intervention aimed to improve screening and diagnosis rates at adolescent well visits by establishing a streamlined universal screening protocol for all patients ages 13-18 years old. Methods: A universal sexually transmitted infection (STI) screening approach was introduced at an urban clinic affiliated with an academic medical center near Philadelphia, Pennsylvania (PA) in September 2018 for all adolescent well-visits. GC/CT screening and diagnosis rates were compared two years prior to and two years after implementation, deemed the baseline and intervention groups, respectively. Results: In total, 1,168 encounters were included for analysis. The patient cohort consisted of 47% females, with an average age of 15, and were predominantly publicly insured (79%). STI screening rates increased significantly from 16.7% (89/534) to 83.6% (530/634) of adolescents with implementation of the universal screening protocol. Furthermore, there was a 1.6-fold increase in total positive cases detected after implementation of ok universal screening. Conclusion: This study demonstrates improved adolescent GC/CT capture rates by establishing a universal screening protocol and highlights a streamlined means of implementation in virtually any pediatric clinic. Limitations include sample size, as this is a single academic practice, as well as any issues with lab collection and results reporting.

Optimization of reverse NOE pumping experiments in the analysis of complex systems with densely crowded NMR spectra.

We present an optimization of Reverse NOE-pumping (RNP) in order to observe the 1H signals of ligands bound to proteins. Although various ligand-based NMR screening methods have been proposed, the most frequently used method has been Saturation-Transfer Difference (STD), owing to the relatively easy setup of experiments. Yet the critical point of STD is the selective irradiation of protein without irradiating ligand, and thus the STD technique is unable to observe 1H ligand signals, which resonate across the entire 1H spectral width. In the present study, the RNP experiment has been improved to develop an effective NMR-based screening technique. The optimized RNP spectra reveal less subtraction artifacts and phase distortion than the original RNP spectra, indicating its applicability to any type of ligand molecules.

A systematic review and meta-analysis of sexually transmitted infections and blood-borne viruses in travellers.

BACKGROUND: Sexually transmitted infections (STIs) and blood-borne viruses (BBVs) impose a global health and economic burden. International travellers facilitate the spread of infectious diseases, including STIs. Hence, this review assessed the prevalence/proportionate morbidity of travellers with STIs and sexually transmitted BBVs, and factors associated with the infection in this population. METHODS: PubMed, Scopus, Web of Science, CINHAL, Embase, and Cochrane Library were searched from inception of the databases until November 2022. Published analytical observational studies reporting the prevalence/proportionate morbidity of travellers with STIs and factors associated with STIs by type of traveller (i.e. tourists, business travellers, students, visiting friends or relatives [VFRs], international truck drivers, backpackers, expatriates, and men who have sex with men [MSM]) were included. The selection of articles, data extraction, and risk of bias assessment were conducted by two independent reviewers. Meta-analyses were conducted for each STI by clinical presentation and type of traveller. RESULTS: Thirty-two studies (n = 387 731 travellers) were included, 19 evaluated the proportionate morbidity of STIs among symptomatic travellers, while 13 examined the prevalence of STIs in asymptomatic travellers. The highest proportionate morbidity was found among VFRs (syphilis, 1.67%; 95%CI:1.03-2.81%), backpackers (chlamydia trachomatis, 6.58%; 95%CI: 5.96-7.25%), and MSM (HIV [2.50%;95%CI:0.44-12.88%], gonorrhoea [4.17%;95%CI:1.1.5-13.98%], lymphogranuloma venereum [4.17%;95%CI:1.1.5-13.98%], and HAV [20.0%; 95% CI: 14.99-26.17%]). The highest prevalence of STIs among asymptomatic were found in MSM (HIV [25.94%;95%CI:22.21-30.05%] and HBV [24.90%; 95%CI:21.23-28.96%]) and backpackers (chlamydia trachomatis, 3.92%;95% CI:2.72-5.32%). Short duration of the trip (<1 month), not having pre-travel consultation, travelling to Southeast Asia, and being unvaccinated for HBV were identified as risk factors for STIs. CONCLUSION: Strategies to prevent STIs and sexually transmitted BBVs should be discussed at pretravel consultations and recommendations should be prioritized in high-risk groups of travellers, such as backpackers, VFRs, and MSMs. Additionally, healthcare providers should tailor recommendations for safe sex practices to individual travellers' unique needs.

Lack of evidence of acute HEV infections as a sexually transmitted disease: Data from a German cohort of PrEP users.

BACKGROUND: While the sexual transmissibility of HAV in MSM has been extensively described, the potential for sexual transmission of HEV has not been definitively established. Although HEV has been detected in the ejaculate of chronically infected men, studies among MSM PrEP users in France did not observe an elevated anti-HEV seroprevalence as an indicator of increased exposure risk by sexual intercourse. PATIENTS AND METHODS: A total of 111 unselected PrEP users and 111 age- and sex-matched blood donors were tested for anti-HEV IgG, IgM and HEV (PCR). Of the participants 79/111 (71 %) responded to a questionnaire covering topics as sexual preferences, previous sexually transmitted diseases, profession, food consumption, and pet ownership. RESULTS: The anti-HEV IgG seroprevalence in PrEP users (22 %) did not differ significantly from the rate in controls (17 %). While one PrEP user and three controls tested positive for anti-HEV IgM, all PrEP users and controls tested PCR negative. CONCLUSION: In immunocompetent individuals with frequent changes of sexual partners, the epidemiology of Hepatitis E Virus does not significantly involve the sexual transmission route.

Saturation Transfer Difference NMR and Molecular Docking Interaction Study of Aralkyl-Thiodigalactosides as Potential Inhibitors of the Human-Galectin-3 Protein.

Human Galectin-3 (hGal-3) is a protein that selectively binds to ß-galactosides and holds diverse roles in both normal and pathological circumstances. Therefore, targeting hGal-3 has become a vibrant area of research in the pharmaceutical chemistry. As a step towards the development of novel hGal-3 inhibitors, we synthesized and investigated derivatives of thiodigalactoside (TDG) modified with different aromatic substituents. Specifically, we describe a high-yielding synthetic route of thiodigalactoside (TDG); an optimized procedure for the synthesis of the novel 3,3'-di-O-(quinoline-2-yl)methyl)-TDG and three other known, symmetric 3,3'-di-O-TDG derivatives ((naphthalene-2yl)methyl, benzyl, (7-methoxy-2H-1-benzopyran-2-on-4-yl)methyl). In the present study, using competition Saturation Transfer Difference (STD) NMR spectroscopy, we determined the dissociation constant (Kd) of the former three TDG derivatives produced to characterize the strength of the interaction with the target protein (hGal-3). Based on the Kd values determined, the (naphthalen-2-yl)methyl, the (quinolin-2-yl)methyl and the benzyl derivatives bind to hGal-3 94, 30 and 24 times more strongly than TDG. Then, we studied the binding modes of the derivatives in silico by molecular docking calculations. Docking poses similar to the canonical binding modes of well-known hGal-3 inhibitors have been found. However, additional binding forces, cation-π interactions between the arginine residues in the binding pocket of the protein and the aromatic groups of the ligands, have been established as significant features. Our results offer a molecular-level understanding of the varying affinities observed among the synthesized thiodigalactoside derivatives, which can be a key aspect in the future development of more effective ligands of hGal-3.

Consumption of Health-Related Videos and Human Papillomavirus Awareness: Cross-Sectional Analyses of a US National Survey and YouTube From the Urban-Rural Context.

BACKGROUND: Nearly 70% of Americans use the internet as their first source of information for health-related questions. Contemporary data on the consumption of web-based videos containing health information among American adults by urbanity or rurality is currently unavailable, and its link with health topic awareness, particularly for human papillomavirus (HPV), is not known. OBJECTIVE: We aim to describe trends and patterns in the consumption of health-related videos on social media from an urban-rural context, examine the association between exposure to health-related videos on social media and awareness of health topics (ie, HPV and HPV vaccine), and understand public interest in HPV-related video content through search terms and engagement analytics. METHODS: We conducted a cross-sectional analysis of the US Health Information National Trends Survey 6, a nationally representative survey that collects data from civilian, noninstitutionalized adults aged 18 years or older residing in the United States. Bivariable analyses were used to estimate the prevalence of consumption of health-related videos on social media among US adults overall and by urbanity or rurality. Multivariable logistic regression models were used to examine the association between the consumption of health-related videos and HPV awareness among urban and rural adults. To provide additional context on the public's interest in HPV-specific video content, we examined search volumes (quantitative) and related query searches (qualitative) for the terms "HPV" and "HPV vaccine" on YouTube. RESULTS: In 2022, 59.6% of US adults (152.3 million) consumed health-related videos on social media, an increase of nearly 100% from 2017 to 2022. Prevalence increased among adults living in both urban (from 31.4% in 2017 to 59.8% in 2022; P<.001) and rural (from 22.4% in 2017 to 58% in 2022; P<.001) regions. Within the urban and rural groups, consumption of health-related videos on social media was most prevalent among adults aged between 18 and 40 years and college graduates or higher-educated adults. Among both urban and rural groups, adults who consumed health-related videos had a significantly higher probability of being aware of HPV and the HPV vaccine compared with those who did not watch health videos on the internet. The term "HPV" was more frequently searched on YouTube compared with "HPV vaccine." Individuals were most commonly searching for videos that covered content about the HPV vaccine, HPV in males, and side effects of the HPV vaccine. CONCLUSIONS: The consumption of health-related videos on social media in the United States increased dramatically between 2017 and 2022. The rise was prominent among both urban and rural adults. Watching a health-related video on social media was associated with a greater probability of being aware of HPV and the HPV vaccine. Additional research on designing and developing social media strategies is needed to increase public awareness of health topics.

Evaluation of an emergency department opt-out provider-driven HIV and syphilis screening and linkage-to-care program.

OBJECTIVE: While the effectiveness of emergency departments (ED) in screening for HIV and syphilis is understood, less is known about dual screening programs. We aim to evaluate the impact of an opt-out provider-initiated HIV and syphilis program on screening, diagnosis, and linkage to care outcomes. METHODS: We performed a retrospective review of patients screened pre (2014-2017) and post (2017-2021) program implementation. Primary outcomes include HIV and syphilis screening, incidence of positive tests, and proportion of patients linked to care. Secondary outcomes included pre-exposure prophylaxis (PrEP) referral and successful linkage rates for HIV-negative syphilis-positive patients. RESULTS: Pre-implementation, 882 HIV tests were performed, of which 22 (2.49%) were new cases and 18 (81.82%) were linked to care; 754 syphilis tests were performed, of which 33 (4.38%) were active infections and 30 (90.91%) were treated. No eligible patients received PrEP referral. Post-implementation, 12,999 HIV tests were performed, of which 73 (0.56%) were new cases and 55 (75.34%) were linked to care; 10,885 syphilis tests were performed, of which 216 (1.98%) were active infections and 188 (87.04%) were treated. 25 (9.09%) eligible patients were referred for PrEP, and four (16.0%) attended their appointment. CONCLUSIONS: Post-implementation, there was a 1373.81% and 1343.63% increase in screening, and a 231.82% and 554.55% increase in positive cases of HIV and syphilis, respectively. Dual screening programs can be successfully implemented within the existing ED framework to increase screening and early detection for HIV and syphilis.

Digital Triage Tools for Sexually Transmitted Infection Testing Compared With General Practitioners' Advice: Vignette-Based Qualitative Study With Interviews Among General Practitioners.

BACKGROUND: Digital triage tools for sexually transmitted infection (STI) testing can potentially be used as a substitute for the triage that general practitioners (GPs) perform to lower their work pressure. The studied tool is based on medical guidelines. The same guidelines support GPs' decision-making process. However, research has shown that GPs make decisions from a holistic perspective and, therefore, do not always adhere to those guidelines. To have a high-quality digital triage tool that results in an efficient care process, it is important to learn more about GPs' decision-making process. OBJECTIVE: The first objective was to identify whether the advice of the studied digital triage tool aligned with GPs' daily medical practice. The second objective was to learn which factors influence GPs' decisions regarding referral for diagnostic testing. In addition, this study provides insights into GPs' decision-making process. METHODS: A qualitative vignette-based study using semistructured interviews was conducted. In total, 6 vignettes representing patient cases were discussed with the participants (GPs). The participants needed to think aloud whether they would advise an STI test for the patient and why. A thematic analysis was conducted on the transcripts of the interviews. The vignette patient cases were also passed through the digital triage tool, resulting in advice to test or not for an STI. A comparison was made between the advice of the tool and that of the participants. RESULTS: In total, 10 interviews were conducted. Participants (GPs) had a mean age of 48.30 (SD 11.88) years. For 3 vignettes, the advice of the digital triage tool and of all participants was the same. In those vignettes, the patients' risk factors were sufficiently clear for the participants to advise the same as the digital tool. For 3 vignettes, the advice of the digital tool differed from that of the participants. Patient-related factors that influenced the participants' decision-making process were the patient's anxiety, young age, and willingness to be tested. Participants would test at a lower threshold than the triage tool because of those factors. Sometimes, participants wanted more information than was provided in the vignette or would like to conduct a physical examination. These elements were not part of the digital triage tool. CONCLUSIONS: The advice to conduct a diagnostic STI test differed between a digital triage tool and GPs. The digital triage tool considered only medical guidelines, whereas GPs were open to discussion reasoning from a holistic perspective. The GPs' decision-making process was influenced by patients' anxiety, willingness to be tested, and age. On the basis of these results, we believe that the digital triage tool for STI testing could support GPs and even replace consultations in the future. Further research must substantiate how this can be done safely.

Utilizing the drug repurposing strategy on current drugs: new leads for peptic ulcers via biochemical and biomolecular dynamics studies.

The hyperactivity of urease enzymes plays a crucial role in the development of hepatic coma, hepatic encephalopathy, urolithiasis, gastric and peptic ulcers. Additionally, these enzymes adversely impact the soil's nitrogen efficiency for crop production. In the current study 100 known drugs were tested against Jack Bean urease and Proteus mirabilis urease and identified three inhibitors i.e. terbutaline (compound 1), Ketoprofen (compound 2) and norepinephrine bitartrate (compound 3). As a result, these compounds showed excellent inhibition against Jack Bean urease i.e. (IC50 = 2.1-11.3 µM), and Proteus mirabilis urease (4.8-11.9 µM). Moreover, in silico studies demonstrate maximum interactions of compounds in the enzyme's active site. Furthermore, intermolecular interactions between compounds and enzyme atoms were examined using STD-NMR spectrophotometry. In parallel, molecular dynamics simulation was carried out to study compounds dynamic behavior within the urease binding region. Urease remained stable during most of the simulation time and ligands were bound in the protein active pocket as observed from the Root mean square deviation (RMSD) and ligand RMSD analyses. Furthermore, these compounds display interactions with the crucial residues, including His492 and Asp633, in 100 ns simulations. In the binding energy analysis, norepinephrine bitartrate exhibited the highest binding energy (-76.32 kcal/mol) followed by Ketoprofen (-65.56 kcal/mol) and terbutaline (-62.15 kcal/mol), as compared to acetohydroxamic acid (-52.86 kcal/mol). The current findings highlight the potential of drug repurposing as an effective approach for identifying novel anti-urease compounds.Communicated by Ramaswamy H. Sarma.

Lack of evidence of acute HEV infections as a sexually transmitted disease: Data from a German cohort of PrEP users

Abstract Background While the sexual transmissibility of HAV in MSM has been extensively described, the potential for sexual transmission of HEV has not been definitively established. Although HEV has been detected in the ejaculate of chronically infected men, studies among MSM PrEP users in France did not observe an elevated anti-HEV seroprevalence as an indicator of increased exposure risk by sexual intercourse. Patients and methods A total of 111 unselected PrEP users and 111 age- and sex-matched blood donors were tested for anti-HEV IgG, IgM and HEV (PCR). Of the participants 79/111 (71 %) responded to a questionnaire covering topics as sexual preferences, previous sexually transmitted diseases, profession, food consumption, and pet ownership. Results The anti-HEV IgG seroprevalence in PrEP users (22 %) did not differ significantly from the rate in controls (17 %). While one PrEP user and three controls tested positive for anti-HEV IgM, all PrEP users and controls tested PCR negative. Conclusion In immunocompetent individuals with frequent changes of sexual partners, the epidemiology of Hepatitis E Virus does not significantly involve the sexual transmission route.

Sexually transmitted diseases knowledge assessment and associated factors among university students in the United Arab Emirates: a cross-sectional study.

Background: Sexually transmitted diseases and infections (STDIs) remain a serious public health menace with over 350 million cases each year. Poor knowledge of STDIs has been identified as one of the bottlenecks in their control and prevention. Hence, assessment of knowledge, both general and domain-specific, is key to the prevention and control of these diseases. This study assessed the knowledge of STDIs and identified factors associated with STDI knowledge among university students in the United Arab Emirates (UAE). Methods: This is a cross-sectional study among 778 UAE University students across all colleges. An online data collection tool was used to collect data regarding the participants' demographics and their level of knowledge of STDIs across different domains including general STDI pathogens knowledge (8 items), signs and symptoms (9 items), mode of transmission (5 items), and prevention (5 items). Knowledge was presented both as absolute and percentage scores. Differences in STDI knowledge were statistically assessed using Mann-Whitney U and Chi-squared tests. Logistic regression models were further used to identify factors associated with STDI knowledge. Results: A total of 778 students participated in the study with a median age of 21 years (IQR = 19, 23). The overall median STDI knowledge score of the participants was 7 (out of 27), with some differences within STDI domains-signs & symptoms (1 out of 9), modes of transmission (2 out of 5), general STDI pathogens (2 out of 8), and prevention (1 out of 5). Higher STDI knowledge was significantly associated with being non-Emirati (OR = 1.85, 95% CI = 1.24-2.75), being married (OR = 2.89, 95% CI = 1.50-5.56), residing in emirates other than Abu Dhabi (OR = 1.61, 95% CI = 1.16-2.25), and being a student of health sciences (OR = 4.45, 95% CI = 3.07-6.45). Conclusion: In general, STDI knowledge was low among the students. Having good knowledge of STDIs is essential for their prevention and control. Therefore, there is a need for informed interventions to address the knowledge gap among students, youths, and the general population at large.

NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow's Drug Binding Sites in Human Serum Albumin.

Saturation transfer difference (STD), inter-ligand NOEs (INPHARMA NMR), and docking calculations are reported for investigating specific binding sites of the high-affinity synthetic 7-nitrobenz-2-oxa-1,3-diazoyl-4-C12 fatty acid (NBD-C12 FA) with non-labeled human serum albumin (HSA) and in competition with the drugs warfarin and ibuprofen. A limited number of negative interligand NOEs between NBD-C12 FA and warfarin were interpreted in terms of a short-range allosteric competitive binding in the wide Sudlow's binding site II (FA7) of NBD-C12 FA with Ser-202, Lys-199, and Trp-214 and warfarin with Arg-218 and Arg-222. In contrast, the significant number of interligand NOEs between NBD-C12 FA and ibuprofen were interpreted in terms of a competitive binding mode in Sudlow's binding site I (FA3 and FA4) with Ser-342, Arg-348, Arg-485, Arg-410, and Tyr-411. NBD-C12 FA has the unique structural properties, compared to short-, medium-, and long-chain saturated and unsaturated natural free fatty acids, of interacting with well-defined structures with amino acids of both the internal and external polar anchor sites in Sudlow's binding site I and with amino acids in both FA3 and FA4 in Sudlow's binding site II. The NBD-C12 FA, therefore, interacts with novel structural characteristics in the drug binding sites I and II and can be regarded as a prototype molecule for drug development.

Sitafloxacin- Versus Moxifloxacin-Based Sequential Treatment for Mycoplasma Genitalium Infections: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains. OBJECTIVE: This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections. METHODS: We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains. RESULTS: Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate. CONCLUSIONS: This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52565.