The Covid-19 pandemic and associated restrictions have the potential to alter sexual risk behaviours for HIV acquisition with important implications for HIV prevention programmes in sub-Saharan ...Africa. To date, no large-scale data have been published to substantiate hypothesised changes in sexual risk behaviours. We used longitudinal survey data to assess the impact of Covid-19 on sexual risk behaviours in east Zimbabwe. Data on sexual behaviours in HIV-negative adults aged 15–54 years were collected in two rounds of a general population open-cohort survey conducted in Manicaland, Zimbabwe shortly before (July 2018 to December 2019; N = 7316) and several months into the Covid-19 epidemic (February to July 2021; N = 6356). Descriptive statistics and logistic regression models of serial cross-sectional and prospective cohort data were used to assess changes in sexual risk behaviours. The proportion of females aged 15–19 years reporting sexual debut declined from 29.7% before Covid-19 to 20.3% during Covid-19 (adjusted odds ratio (AOR) = 0.49, 95% confidence interval (95% CI), 0.38–0.63). Fewer sexually-active females reported multiple sexual partners during Covid-19 (3.35% versus 6.07%; AOR = 0.55, 95% CI, 0.43–0.72). No population-level changes in male behaviour between survey rounds were recorded but the cohort analysis revealed a complex pattern of behaviour change with HIV risk behaviours increasing for some individuals and decreasing for others. Overall HIV risk behaviours remained high in a sub-Saharan African population with a generalised HIV epidemic over a period of Covid-19 lockdowns when movements and social contacts were restricted.
Objectives
The 2018 British HIV Association (BHIVA) Standards of Care state that people living with HIV should be questioned annually for symptoms of cognitive or memory decline. If symptoms are ...identified, screening should be considered and services offered if impairment is detected. We examined the availability of services, along with current practices related to the screening and management of cognitive impairment in people living with HIV, in UK HIV services.
Methods
A survey was distributed via email to all UK HIV services leads on the BHIVA audit mailing list. Questions related to screening practices, referral pathways, and the management of patients with suspected cognitive impairment. Descriptive analyses were conducted on all data returned.
Results
In total, 190 surveys were distributed. Of the respondents, 39 (60.6%) stated that they undertook screening for cognitive impairment in their HIV service, and 30 (47.6%) reported not offering a specific service or referral pathway. Awareness of BHIVA screening guidelines was high (49 84.48%), yet 15 (30.6%) respondents stated that they were not followed in their service and 41 (71.9%) felt there was a need for training on screening, assessment, and management of cognitive impairment in patients with HIV within their department.
Conclusions
Despite no directive, a substantial number of HIV services surveyed are routinely screening patients for cognitive impairment without guidance on when to screen and which screening tools should be used. A UK consensus on screening, along with guidance and training for services, may help to resolve this gap in service provision.
The aim of this study was to analyze the experience of the National Institute for Health and Care Excellence (NICE) in identifying new procedures entering the United Kingdom (UK) healthcare system, ...for assessment and publication of recommendations on their use. This system is designed to provide guidance in an area where regulation is lacking worldwide.
Retrospective analysis of all procedures notified to the Interventional Procedures Programme (NICE) between 2002 and 2012. Notifications were analyzed year by year for their source (who notified them), clinical specialties involved, and whether guidance was subsequently published.
A total of 1,094 procedures were notified by clinicians (51 percent), and by others, including hospitals (6 percent), horizon scanners (5 percent), patients (4 percent), private health insurers (4 percent), and medical device manufacturers (3 percent). Guidance was published on 44 percent of procedures notified to the program. There was a decrease in the numbers of procedures notified during 2003-2012 (p = .049). There were notifications across all specialties, with the largest numbers in general surgery (125), urology (104), orthopedics (99), interventional radiology (93), cardiology (82), and obstetrics and gynecology (82).
The "open" NICE Web portal allows anyone to notify new procedures, aiming to maximize the opportunity of identifying all those procedures entering clinical practice. This has resulted in identification of large numbers of procedures from across the whole range of medical specialties. The fact that similar proportions of procedures notified from diverse sources have been selected for assessment and publication of practice recommendations suggests that this inclusive approach is worthwhile.
Young adults are at the greatest risk for initiation of smoking or becoming daily smokers. Smoking has a unique history in the United States and is associated with health risks beyond heart disease ...and lung cancer, many specifically affecting women. Although the majority of people are aware of the risks for heart disease and lung cancer, many other risks are not recognized. By evaluating the known knowledge of smoking-related health risks beyond and including heart disease and lung cancer in the high risk population of female college students, education programs and cessation teaching can be altered, potentially resulting in lower start rates and higher cessation rates. In order to accomplish these changes, known health risks and unknown or unrecognized health risks need to be identified. Data were analyzed using comparative descriptive statistics gathered by a survey tool that was dispersed to college students' email as a Survey Monkey questionnaire. All female students attending Minnesota State University, Mankato during the previous spring 2011, current summer 2011 and upcoming fall 2011 semesters received the email request. Data were included from 473 students aged 18 to 24. Questions addressed personal and family experience with smoking, current smoking status, perceived risk of smoking-related health conditions, participation in high-risk behaviors, and identification of the three most common health consequences of smoking. As indicated by previous research, the majority of current and former smokers began smoking between the ages of 16 and 19. The data corroborated with previous studies indicating low perceived risk for smoking-related health conditions. Correlations between participation in high-risk behaviors and tobacco use were supported by the research. Positive family history with smoking-related health consequence appears to be a factor in tobacco use. Results from this study duplicate previous research indicating the health care system's failure in making advances in educating young women about smoking-related health risks. Additionally, the media's attempts at educating the public of the link between smoking and heart disease in women has failed with over 75% of respondents incorrectly identifying lung cancer as the most common health consequence of smoking. A need for assessment of the smoking status of and education regarding the health risks of tobacco use is indicated by the results.
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•An unnatural base pair has been developed and used as the foundation of semi-synthetic organisms.•The semi-synthetic organisms can use the unnatural base pair to efficiently make ...unnatural proteins.•Hydrophobic and packing interactions can replace hydrogen bonds to control base pairing.
Current methods to expand the genetic code enable site-specific incorporation of non-canonical amino acids (ncAAs) into proteins in eukaryotic and prokaryotic cells. However, current methods are limited by the number of codons possible, their orthogonality, and possibly their effects on protein synthesis and folding. An alternative approach relies on unnatural base pairs to create a virtually unlimited number of genuinely new codons that are efficiently translated and highly orthogonal because they direct ncAA incorporation using forces other than the complementary hydrogen bonds employed by their natural counterparts. This review outlines progress and achievements made towards developing a functional unnatural base pair and its use to generate semi-synthetic organisms with an expanded genetic alphabet that serves as the basis of an expanded genetic code.
Lymphatic filariasis (LF), a morbid disease caused by the tissue-invasive nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori, affects millions of people worldwide. Global eradication ...efforts have significantly reduced worldwide prevalence, but complete elimination has been hampered by limitations of current anti-filarial drugs and the lack of a vaccine. The goal of this study was to evaluate B. malayi intestinal UDP-glucuronosyltransferase (Bm-UGT) as a potential therapeutic target. To evaluate whether Bm-UGT is essential for adult filarial worms, we inhibited its expression using siRNA. This resulted in a 75% knockdown of Bm-ugt mRNA for 6 days and almost complete suppression of detectable Bm-UGT by immunoblot. Reduction in Bm-UGT expression resulted in decreased worm motility for 6 days, 70% reduction in microfilaria release from adult worms, and significant reduction in adult worm metabolism as detected by MTT assays. Because prior allergic-sensitization to a filarial antigen would be a contraindication for its use as a vaccine candidate, we tested plasma from infected and endemic normal populations for Bm-UGT-specific IgE using a luciferase immunoprecipitation assay. All samples (n = 35) tested negative. We then tested two commercially available medicines known to be broad inhibitors of UGTs, sulfinpyrazone and probenecid, for in vitro activity against B. malayi. There were marked macrofilaricidal effects at concentrations achievable in humans and very little effect on microfilariae. In addition, we observed that probenecid and sulfinpyrazone exhibit a synergistic macrofilaricidal effect when used in combination with albendazole. The results of this study demonstrate that Bm-UGT is an essential protein for adult worm survival. Lack of prior IgE sensitization in infected and endemic populations suggest it may be a feasible vaccine candidate. The finding that sulfinpyrazone and probenecid have in vitro effects against adult B. malayi worms suggests that these medications have promise as potential macrofilaricides in humans.
The series of unnatural base pairs (UBPs) developed by the Romesberg lab, which pair via hydrophobic and packing interactions have been replicated, transcribed, and translated inside of a living ...organism. However, as to why these UBPs exhibit variable fidelity and efficiency when used in different contexts is not clear. In an effort to gain some insights, we investigated the thermal stability and pairing selectivity of the (d)NaM‐(d)TPT3 UBP in 11nt duplexes via UV spectroscopy and the effects on helical structure via CD spectroscopy. We observed that while the duplexes containing a UBP are less stable than fully natural duplexes, they are generally more stable than duplexes containing natural mispairs. This work provides the first insights connecting the thermal stability of the (d)NaM‐(d)TPT3 UBP to the molecular mechanisms for varying replication fidelity in different sequence contexts in DNA, asymmetrical transcription fidelity, and codon:anticodon interactions and can assist in future UBP development.
An interdisciplinary study: The (d)NaM:(d)TPT3 unnatural base pair (UBP) can be replicated, transcribed, and translated in an organism, but its sequence context and orientation affects the fidelity and efficiency of these processes. We determined how this UBP affects nucleic acid duplexes, which provides mechanisms for variable behavior and can inform future UBP development.
Envenomation by snakes in
and
families have been associated with respiratory failure in dogs and cats. Mechanical ventilation may be required for hypoventilation due to neuromuscular paralysis or ...hypoxemia due to pulmonary hemorrhage or aspiration pneumonia. Median incidence of dogs and cats with snake envenomation that require mechanical ventilation is 13% (0.06-40%). Standard treatment of snake envenomation in dogs and cats includes prompt administration of appropriate antivenom and management of envenomation complications such as coagulopathy, rhabdomyolysis and acute kidney injury. When mechanical ventilation is required, overall prognosis is good with appropriate treatment. Standard anesthetic protocols and mechanical ventilator settings are generally appropriate, with lung protective ventilation strategies typically reserved for patients with pulmonary disease. Median survival to discharge for cats and dogs with elapid envenomation is 72% (76-84%) with 33 h (19.5-58 h) median duration of mechanical ventilation and 140 h (84-196 h) median hospitalization. This article reviews indications for mechanical ventilation in cats and dogs with snake envenomation, and discusses ventilator settings, anesthetic and nursing considerations, complications and outcomes specific to this disease.
Filarial worms are parasitic nematodes that cause devastating diseases such as lymphatic filariasis (LF) and onchocerciasis. Filariae are nematodes with complex anatomy including fully developed ...digestive tracts and reproductive organs. To better understand the basic biology of filarial parasites and to provide insights into drug targets and vaccine design, we conducted a proteomic analysis of different anatomic fractions of Brugia malayi, a causative agent of LF. Approximately 500 adult female B. malayi worms were dissected, and three anatomical fractions (body wall, digestive tract, and reproductive tract) were obtained. Proteins from each anatomical fraction were extracted, desalted, trypsinized, and analyzed by microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry. In total, we identified 4,785 B. malayi proteins. While 1,894 were identified in all three anatomic fractions, 396 were positively identified only within the digestive tract, 114 only within the body wall, and 1,011 only within the reproductive tract. Gene set enrichment analysis revealed a bias for transporters to be present within the digestive tract, suggesting that the intestine of adult filariae is functional and important for nutrient uptake or waste removal. As expected, the body wall exhibited increased frequencies of cytoskeletal proteins, and the reproductive tract had increased frequencies of proteins involved in nuclear regulation and transcription. In assessing for possible vaccine candidates, we focused on proteins sequestered within the digestive tract, as these could possibly represent "hidden antigens" with low risk of prior allergic sensitization. We identified 106 proteins that are enriched in the digestive tract and are predicted to localize to the surface of cells in the the digestive tract. It is possible that some of these proteins are on the luminal surface and may be accessible by antibodies ingested by the worm. A subset of 27 of these proteins appear especially promising vaccine candidates as they contain significant non-cytoplasmic domains, only 1-2 transmembrane domains, and a high degree of homology to W. bancrofti and/or O. volvulus.
Abstract This study is the first to investigate the presence and movement of the novel Liberibacter species ‘ Candidatus Liberibacter brunswickensis’ (CLbr) in eggplant, Solanum melongena . The ...psyllid, Acizzia solanicola can transmit CLbr to eggplant and CLbr can be acquired by CLbr-negative A. solanicola individuals from CLbr-positive eggplants. In planta , CLbr can replicate, move and persist. Investigation into the early development of eggplants showed that CLbr titres had increased at the inoculation site at 14 days post inoculation access period (DPIAP). CLbr had become systemic in the majority of plants tested by 28 DPIAP. The highest bacterial titres were recorded at 35 DPIAP in all samples of the inoculated leaf, the roots, stems and the midrib and petiole samples of the newest leaf (the top leaf). This finding strongly suggests that CLbr movement in planta follows the source to sink relationship as previously described for ‘ Ca. Liberibacter asiaticus’ (CLas) and ‘ Ca. Liberibacter solanacearum’ (CLso). No symptoms consistent with Liberibacter-associated diseases were noted for plants colonised by CLbr during this study, consistent with the hypothesis that CLbr does not cause disease of eggplant during the early stages of host colonisation. In addition, no significant differences in biomass were found between eggplant colonised with CLbr, compared to those that were exposed to CLbr-negative A. solanicola, and to control plants.
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