PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, q=subject:"Biotechnology"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&unformattedQuery=subject:%22Biotechnology%22&sort=Date,+newest+firstAll PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-19T10:18:18ZRecovery following discharge from intensive care: What do patients think is helpful and what services are missing?Brenda O’NeillNatasha GreenBronagh BlackwoodDanny McAuleyFidelma MoranNiamh MacCormacPaul JohnstonJames J. McNameeClaire ShevlinJudy Bradley10.1371/journal.pone.02970122024-03-18T14:00:00Z2024-03-18T14:00:00Z<p>by Brenda O’Neill, Natasha Green, Bronagh Blackwood, Danny McAuley, Fidelma Moran, Niamh MacCormac, Paul Johnston, James J. McNamee, Claire Shevlin, Judy Bradley</p>
Background <p>Recovery following critical illness is complex due to the many challenges patients face which influence their long-term outcomes. We explored patients’ views about facilitators of recovery after critical illness which could be used to inform the components and timing of specific rehabilitation interventions.</p> Aims <p>To explore the views of patients after discharge from an intensive care unit (ICU) about their recovery and factors that facilitated recovery, and to determine additional services that patients felt were missing during their recovery.</p> Methods <p>Qualitative study involving individual face-to-face semi-structured interviews at six months (n = 11) and twelve months (n = 10). Written, informed consent was obtained. [Ethics approval 17/NI/0115]. Interviews were audiotaped, transcribed and analysed using template analysis.</p> Findings <p>Template analysis revealed four core themes: (1) Physical activity and function; (2) Recovery of cognitive and emotional function; (3) Facilitators to recovery; and (4) Gaps in healthcare services.</p> Conclusion <p>Patient reported facilitators to recovery include support and guidance from others and self-motivation and goal setting, equipment for mobility and use of technology. Barriers include a lack of follow up services, exercise rehabilitation, peer support and personal feedback. Patients perceived that access to specific healthcare services was fragmented and where services were unavailable this contributed to slower or poorer quality of recovery. ICU patient recover could be facilitated by a comprehensive rehabilitation intervention that includes patient-directed strategies and health care services.</p>A meta-analysis into the mediatory effects of family planning utilization on complications of pregnancy in women of reproductive ageShayesteh JahanfarOlivia MaurerAmy LapidowAnjali Rajkumari OberoiMeredith SteinfeldtMoazzam Ali10.1371/journal.pone.02944752024-03-18T14:00:00Z2024-03-18T14:00:00Z<p>by Shayesteh Jahanfar, Olivia Maurer, Amy Lapidow, Anjali Rajkumari Oberoi, Meredith Steinfeldt, Moazzam Ali</p>
Background <p>Despite conflicting findings in the current literature regarding the correlation between contraceptives and maternal health consequences, statistical analyses indicate that family planning may decrease the occurrence of such outcomes. Consequently, it is crucial to assess the capability of family planning to mitigate adverse maternal health outcomes.</p> Objectives <p>This review investigates the effects of modern contraceptive use on maternal health.</p> Search methods <p>This systematic review is registered on Prospero (CRD42022332783). We searched numerous databases with an upper date limit of February 2022 and no geographical boundaries.</p> Selection criteria <p>We included observational studies, including cross-sectional, cohort, case-control studies, and non-RCT with a comparison group. We excluded systematic reviews, scoping reviews, narrative reviews, and meta-analyses from the body of this review.</p> Main results <p>The review included nineteen studies, with five studies reporting a reduction in maternal mortality linked to increased access to family planning resources and contraceptive use. Another three studies examined the impact of contraception on the risk of preeclampsia and our analysis found that preeclampsia risk was lower by approximately 6% among contraceptive users (95% CI 0.82–1.13) compared to non-users. Two studies assessed the effect of hormonal contraceptives on postpartum glucose tolerance and found that low-androgen contraception was associated with a reduced risk of gestational diabetes (OR 0.84, 95% CI 0.58–1.22), while DMPA injection was possibly linked to a higher risk of falling glucose status postpartum (OR 1.42, 95% CI 0.85–2.36). Two studies evaluated high-risk pregnancies and births in contraceptive users versus non-users, with the risk ratio being 30% lower among contraceptive users of any form (95% CI 0.61, 0.80). None of these results were statistically significant except the latter. In terms of adverse maternal health outcomes, certain contraceptives were found to be associated with ectopic pregnancy and pregnancy-related venous thromboembolism through additional analysis.</p>Anaesthesia delivery systems in low and lower-middle-income Asian countries: A scoping review of capacity and effectivenessSumbal ShahbazNatasha Howard10.1371/journal.pgph.00019532024-03-18T14:00:00Z2024-03-18T14:00:00Z<p>by Sumbal Shahbaz, Natasha Howard</p>
Literature on anaesthesia systems in low and lower middle-income countries is limited, focused on the Africa region, and provides minimal data on anaesthesia or associated disciplines within intensive care, pain management and emergency medicine. We thus conducted a scoping review of primary and secondary research literature on capacity and effectiveness of anaesthesia delivery in low and lower middle-income countries in the Asia region from 2000–2021, to clarify existing knowledge, important gaps, and possible subsequent steps. We applied Arksey and O’Malley’s scoping literature review method to search five databases (i.e. EMBASE, CINAHL, Medline, Scopus, Web of Science), screen, extract, and synthesise data under three themes: (i) availability and type of anaesthesia workforce; (ii) anaesthesia system infrastructure, equipment, and supplies; and (iii) effectiveness of anaesthesia provision. We included 25 eligible sources of 603 identified. Only ten (40%) were published in the last 5 years and Asian lower-income countries were primarily represented in 15 multi-country sources. Fifteen (60%) sources used quantitative methods and provided limited information on data collection, e.g. sampling criteria or geographic areas included. No sources included countrywide data, despite anaesthesia delivery and resources differing significantly sub-nationally (e.g. central versus rural/remote, or insecure areas). Data on anaesthesiology delivery were limited, with findings including insufficiencies in workforce, supplies, training, and skills-building of anaesthesia personnel, along with the lack of consistent strategies for overcoming maldistribution of resources and improving anaesthesia delivery systems in the region. This review, a first attempt to synthesise existing data on anaesthesia delivery systems in low and lower-middle-income Asian countries, shows the anaesthesia literature is still limited. Findings highlight the urgent need for additional research and collaboration nationally and regionally to strengthen anaesthesia delivery and surgical facilities in resource-constrained settings.Altered Fhod3 expression involved in progressive high-frequency hearing loss via dysregulation of actin polymerization stoichiometry in the cuticular plateEly Cheikh BoussatyYuzuru NinoyuLeonardo R. AndradeQingzhong LiRyu TakeyaHideki SumimotoTakahiro OhyamaKarl J. WahlinUri ManorRick A. Friedman10.1371/journal.pgen.10112112024-03-18T14:00:00Z2024-03-18T14:00:00Z<p>by Ely Cheikh Boussaty, Yuzuru Ninoyu, Leonardo R. Andrade, Qingzhong Li, Ryu Takeya, Hideki Sumimoto, Takahiro Ohyama, Karl J. Wahlin, Uri Manor, Rick A. Friedman</p>
Age-related hearing loss (ARHL) is a common sensory impairment with complex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the GWAS results. We observed Fhod3 expression in auditory hair cells (HCs) primarily localized at the cuticular plate (CP). To understand the functional implications of Fhod3 in the cochlea, we generated Fhod3 overexpression mice (<i>Pax2-Cre</i><sup>+/-</sup><i>; Fhod3</i><sup>Tg/+</sup>) (TG) and HC-specific conditional knockout mice (<i>Atoh1-Cre</i><sup>+/-</sup><i>; Fhod3</i><sup>fl/fl</sup>) (KO). Audiological assessments in TG mice demonstrated progressive high-frequency hearing loss, characterized by predominant loss of outer hair cells, and a decreased phalloidin intensities of CP. Ultrastructural analysis revealed loss of the shortest row of stereocilia in the basal turn of the cochlea, and alterations in the cuticular plate surrounding stereocilia rootlets. Importantly, the hearing and HC phenotype in TG mice phenocopied that of the KO mice. These findings suggest that balanced expression of Fhod3 is critical for proper CP and stereocilia structure and function. Further investigation of Fhod3 related hearing impairment mechanisms may lend new insight towards the myriad mechanisms underlying ARHL, which in turn could facilitate the development of therapeutic strategies for ARHL.Statistical determination of service quality gaps in primary health care in Guayas, EcuadorMiguel A. Bustamante U.Michelle TelloMauricio Carvache-FrancoOrly Carvache-FrancoWilmer Carvache-Franco10.1371/journal.pone.02999942024-03-15T14:00:00Z2024-03-15T14:00:00Z<p>by Miguel A. Bustamante U., Michelle Tello, Mauricio Carvache-Franco, Orly Carvache-Franco, Wilmer Carvache-Franco</p>
The present work determines the gaps between expectations and perceptions about the quality of the service that patients and families receive in primary health care (PHC) in Guayas, Ecuador. A descriptive, cross-sectional and non-experimental study was carried out, primarily prospective with respect to expectations and retrospective with respect to perceptions of service quality. For its development, a random sample of 533 users from the northern and southern urban sectors of the city of Guayaquil was determined, who were asked to answer a questionnaire. Their responses were collected using a seven-point scale intended to determine magnitudes of gaps, which were confirmed using the Wilcoxon test. The results reveal a significant gap between women, specifically those over 21 years of age who have studied at the technological and university level, and those who work. In general, the five dimensions of quality present significant gaps, highlighting that the lowest gap occurs when the medical professional listens attentively and treats the patient with kindness. Instead, the largest gap occurs because there are no available or easily accessible times for medical appointments. Finally, the dimension that indicates the gaps that service providers best resolve are the empathy items, recording the smallest deviations; On the contrary, the reliability dimension presents the greatest deviation, thus showing higher degrees of dissatisfaction, in both cases significant.Engineering of Cas12a nuclease variants with enhanced genome-editing specificityPeng ChenJin ZhouHuan LiuErchi ZhouBoxiao HeYankang WuHongjian WangZaiqiao SunChonil PaekJun LeiYongshun ChenXinghua ZhangLei Yin10.1371/journal.pbio.30025142024-03-14T14:00:00Z2024-03-14T14:00:00Z<p>by Peng Chen, Jin Zhou, Huan Liu, Erchi Zhou, Boxiao He, Yankang Wu, Hongjian Wang, Zaiqiao Sun, Chonil Paek, Jun Lei, Yongshun Chen, Xinghua Zhang, Lei Yin</p>
The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a system is a powerful tool in gene editing; however, crRNA-DNA mismatches might induce unwanted cleavage events, especially at the distal end of the PAM. To minimize this limitation, we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand. HyperFi-As retains on-target activities comparable to wild-type AsCas12a (AsCas12aWT) in human cells. We demonstrated that HyperFi-As has dramatically reduced off-target effects in human cells, and HyperFi-As possessed notably a lower tolerance to mismatch at the position of the PAM-distal region compared with the wild type. Further, a modified single-molecule DNA unzipping assay at proper constant force was applied to evaluate the stability and transient stages of the CRISPR/Cas ribonucleoprotein (RNP) complex. Multiple states were sensitively detected during the disassembly of the DNA-Cas12a-crRNA complexes. On off-target DNA substrates, the HyperFi-As-crRNA was harder to maintain the R-loop complex state compared to the AsCas12aWT, which could explain exactly why the HyperFi-As has low off-targeting effects in human cells. Our findings provide a novel version of AsCas12a variant with low off-target effects, especially capable of dealing with the high off-targeting in the distal region from the PAM. An insight into how the AsCas12a variant behaves at off-target sites was also revealed at the single-molecule level and the unzipping assay to evaluate multiple states of CRISPR/Cas RNP complexes might be greatly helpful for a deep understanding of how CRISPR/Cas behaves and how to engineer it in future.Cytokinin oxidase gene <i>CKX5</i> is modulated in the immunity of <i>Arabidopsis</i> to <i>Botrytis cinerea</i>Ruolin WangBeibei LiJiang ZhangLing Chang10.1371/journal.pone.02982602024-03-13T14:00:00Z2024-03-13T14:00:00Z<p>by Ruolin Wang, Beibei Li, Jiang Zhang, Ling Chang</p>
In our previous work, cytokinin (CK) signaling and biosynthesis were found to be modulated during <i>Arabidopsis</i> defense against infection by the necrotrophic pathogen <i>Botrytis cinerea</i>. Notably, the expression level of <i>CYTOKININ OXIDASE/DEHYDROGENASE 5</i> (<i>CKX5</i>) was significantly induced in <i>B</i>. <i>cinerea</i>-infected leaves and later in distant <i>B</i>. <i>cinerea</i>-untreated leaves of the same plant. To confirm and determine how <i>CKX5</i> is involved in the response to <i>B</i>. <i>cinerea</i> infection, transcript levels of <i>CKX</i> family genes were analyzed in <i>B</i>. <i>cinerea</i>-inoculated leaves, and only <i>CKX5</i> was remarkably induced by <i>B</i>. <i>cinerea</i> infection. Furthermore, <i>CKX5</i>-overexpressing <i>Arabidopsis</i> plants were more resistant to <i>B</i>. <i>cinerea</i> than wild-type plants. Transcription factors (TFs) binding to the <i>CKX5</i> promoter were then screened by yeast one-hybrid assays. Quantitative Real-Time Reverse Transcription PCR (qRT-PCR) analysis further showed that genes encoding TFs, including <i>WRKY40</i>, <i>WRKY33</i>, <i>ERF6</i>, <i>AHL15</i>, <i>AHL17</i>, <i>ANAC003</i>, <i>TCP13</i> and <i>ANAC019</i>, were also strongly induced in infected leaves, similar to <i>CKX5</i>. Analysis of <i>ERF6</i>-overexpressing plants and <i>ERF6</i>-and <i>AHL15</i>-knockout mutants indicated that <i>ERF6</i> and <i>AHL15</i> are involved in plant immunity to <i>B</i>. <i>cinerea</i>. Furthermore, <i>CKX5</i> upregulation by <i>B</i>. <i>cinerea</i> infection was affected when <i>ERF6</i> or <i>AHL1</i>5 levels were altered. Our work suggests that <i>CKX5</i> levels are controlled by the plant defense system to defend against attack by the pathogen <i>B</i>. <i>cinerea</i>.Constructed wetland as a green remediation technology for the treatment of wastewater from underground coal gasification processŁukasz JałowieckiAleksandra Strugała-WilczekKatarzyna PonikiewskaJacek BorgulatGrażyna PłazaKrzysztof Stańczyk10.1371/journal.pone.03004852024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Łukasz Jałowiecki, Aleksandra Strugała-Wilczek, Katarzyna Ponikiewska, Jacek Borgulat, Grażyna Płaza, Krzysztof Stańczyk</p>
The wastewater from underground coal gasification (UCG) process has extremely complex composition and high concentrations of toxic and refractory compounds including phenolics, aliphatic and aromatic hydrocarbons, ammonia, cyanides, hazardous metals and metalloids. So, the development of biological processes for treating UCG wastewater poses a serious challenge in the sustainable coal industry. The aim of the study was to develop an innovative and efficient wetland construction technology suitable for a treatment of UCG wastewater using available and low-cost media. During the bioremediation process the toxicity of the raw wastewater decreased significantly between 74%—99%. The toxicity units (TU) ranged from values corresponding to very high acute toxic for raw wastewater to non-toxic for effluents from wetland columns after 60 days of the experiment. The toxicity results correlated with the decrease of some organic and inorganic compounds such as phenols, aromatic hydrocarbons, cyanides, metals and ammonia observed during the bioremediation process. The removal percentage of organic compounds like BTEX, PAHs and phenol was around 99% just after 14 days of treatment. A similar removal rate was indicated for cyanide and metals (Zn, Cr, Cd and Pb). Concluded, in order to effectively assess remediation technologies, it is desirable to consider combination of physicochemical parameters with ecotoxicity measurements. The present findings show that wetland remediation technology can be used to clean-up the heavily contaminated waters from the UCG process. Wetland technology as a nature-based solution has the potential to turn coal gasification wastewater into usable recycled water. It is economically and environmentally alternative treatment method.Validation of ToucHb, a non-invasive haemoglobin estimation: Effective for normal ranges, needs improvement for anaemia detectionYogish Channa BasappaSumanth Mallikarjuna MajgiShashidhar Byrappa ShashidharPrashanth Nuggehalli Srinivas10.1371/journal.pgph.00015412024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Yogish Channa Basappa, Sumanth Mallikarjuna Majgi, Shashidhar Byrappa Shashidhar, Prashanth Nuggehalli Srinivas</p>
Non-invasive methods for haemoglobin estimation hold enormous potential for early detection and treatment of anaemia, especially in limited resource settings. We sought to validate the diagnostic accuracy of ToucHb, a non-invasive haemoglobin estimation device available in the Indian market. We prospectively evaluated the diagnostic performance of the ToucHb device using the Automated complete blood count (CBC) method as the gold standard. Persons referred for haemoglobin estimation to the central laboratory of the government medical college hospital in Mysore, southern India were included in the study. Out Of 140 people approached, 127 gave consent; 65% (n = 82) were female with median age of 37 (IQR 28–45). ToucHB reported median haemoglobin value of 14 g/dL compared to 13.3 g/dL for CBC. Within 1 g/dL and 2 g/dL of CBC, 55.2% (70/127) and 74% (94/127) of ToucHb haemoglobin observations fell, respectively. The Bland-Altman plot showed a mean difference of 3 g/dL in haemoglobin between ToucHb and CBC among those with anaemia. The ToucHb device showed 22.2% sensitivity and 94.5% specificity for anaemia detection. In rural resource-limited settings, point of care non-invasive devices such as ToucHb can improve access and acceptance for anaemia screening. However, ToucHb has showed low sensitivity for anaemia detection and low accuracy at lower haemoglobin values. The utility of the instrument is especially limited in detecting anaemia, while it can estimate haemoglobin accurately among those with haemoglobin is in the normal range. Based on these findings, ToucHb and devices that work on the core technology deployed in ToucHb may be better suited to monitor known haemoglobin level rather than in anaemia screening or detection in primary/ secondary care and community settings.It is theoretically possible to avoid misfolding into non-covalent lasso entanglements using small molecule drugsYang JiangCharlotte M. DeaneGarrett M. MorrisEdward P. O’Brien10.1371/journal.pcbi.10119012024-03-12T14:00:00Z2024-03-12T14:00:00Z<p>by Yang Jiang, Charlotte M. Deane, Garrett M. Morris, Edward P. O’Brien</p>
A novel class of protein misfolding characterized by either the formation of non-native noncovalent lasso entanglements in the misfolded structure or loss of native entanglements has been predicted to exist and found circumstantial support through biochemical assays and limited-proteolysis mass spectrometry data. Here, we examine whether it is possible to design small molecule compounds that can bind to specific folding intermediates and thereby avoid these misfolded states in computer simulations under idealized conditions (perfect drug-binding specificity, zero promiscuity, and a smooth energy landscape). Studying two proteins, type III chloramphenicol acetyltransferase (CAT-III) and D-alanyl-D-alanine ligase B (DDLB), that were previously suggested to form soluble misfolded states through a mechanism involving a failure-to-form of native entanglements, we explore two different drug design strategies using coarse-grained structure-based models. The first strategy, in which the native entanglement is stabilized by drug binding, failed to decrease misfolding because it formed an alternative entanglement at a nearby region. The second strategy, in which a small molecule was designed to bind to a non-native tertiary structure and thereby destabilize the native entanglement, succeeded in decreasing misfolding and increasing the native state population. This strategy worked because destabilizing the entanglement loop provided more time for the threading segment to position itself correctly to be wrapped by the loop to form the native entanglement. Further, we computationally identified several FDA-approved drugs with the potential to bind these intermediate states and rescue misfolding in these proteins. This study suggests it is possible for small molecule drugs to prevent protein misfolding of this type.Design and development of patient health tracking, monitoring and big data storage using Internet of Things and real time cloud computingImran ShafiSadia DinSiddique FarooqIsabel de la Torre DíezJose BreñosaJulio César Martínez EspinosaImran Ashraf10.1371/journal.pone.02985822024-03-11T14:00:00Z2024-03-11T14:00:00Z<p>by Imran Shafi, Sadia Din, Siddique Farooq, Isabel de la Torre Díez, Jose Breñosa, Julio César Martínez Espinosa, Imran Ashraf</p>
With the outbreak of the COVID-19 pandemic, social isolation and quarantine have become commonplace across the world. IoT health monitoring solutions eliminate the need for regular doctor visits and interactions among patients and medical personnel. Many patients in wards or intensive care units require continuous monitoring of their health. Continuous patient monitoring is a hectic practice in hospitals with limited staff; in a pandemic situation like COVID-19, it becomes much more difficult practice when hospitals are working at full capacity and there is still a risk of medical workers being infected. In this study, we propose an Internet of Things (IoT)-based patient health monitoring system that collects real-time data on important health indicators such as pulse rate, blood oxygen saturation, and body temperature but can be expanded to include more parameters. Our system is comprised of a hardware component that collects and transmits data from sensors to a cloud-based storage system, where it can be accessed and analyzed by healthcare specialists. The ESP-32 microcontroller interfaces with the multiple sensors and wirelessly transmits the collected data to the cloud storage system. A pulse oximeter is utilized in our system to measure blood oxygen saturation and body temperature, as well as a heart rate monitor to measure pulse rate. A web-based interface is also implemented, allowing healthcare practitioners to access and visualize the collected data in real-time, making remote patient monitoring easier. Overall, our IoT-based patient health monitoring system represents a significant advancement in remote patient monitoring, allowing healthcare practitioners to access real-time data on important health metrics and detect potential health issues before they escalate.Learning curves for itinerant nurses to master the operation skill of Ti-robot-assisted spinal surgery equipment by CUSUM analysis: A pilot studyYichao YaoHuiyue WangQi ZhangHaimao TengHui QiQian Zhang10.1371/journal.pone.02911472024-03-11T14:00:00Z2024-03-11T14:00:00Z<p>by Yichao Yao, Huiyue Wang, Qi Zhang, Haimao Teng, Hui Qi, Qian Zhang</p>
This study aimed to investigate the minimum number of operations required for itinerant nurses in the operating room to master the skills needed to operate the Ti-robot-assisted spinal surgery equipment. Additionally, we aimed to provide a corresponding basis for the development of qualification admission criteria and skill training for nurses who cooperate with this type of surgery. Nine operating room itinerant nurses independently performed Ti-robot equipment simulations using a spine model as a tool, with 16 operations per trainee. Four evaluation indices were recorded: time spent on equipment preparation and line connections, time spent on image acquisition and transmission, time spent on surgical spine screw placement planning, and time spent on robot arm operation. Individual and general learning curves were plotted using cumulative sum analysis. The number of cases in which the slope of the individual learning curves began to decrease was 3–11 cases, and the number of cases in which the slope of the general learning curve began to decrease was 8 cases. The numbers of cases in which the learning curves began to decrease in the four phases were the 5th, 8th, 11th, and 3rd cases. Itinerant nurses required at least eight cases to master the equipment operation skills of Ti-robot-assisted spinal surgery. Among the four phases, the image acquisition and transmission phases and the surgical spine screw placement planning phase were the most difficult and must be emphasized in future training.Unintended pregnancy and contraception use among African women living with HIV: Baseline analysis of the multi-country US PEPFAR PROMOTE cohortJim AizireNonhlanhla Yende-ZumaSherika HanleyTeacler NematadziraMandisa M. NyatiSufia DadabhaiLameck ChinulaCatherine NakayeMary Glenn FowlerTaha Tahafor the US-PEPFAR PROMOTE Cohort Study team10.1371/journal.pone.02902852024-03-11T14:00:00Z2024-03-11T14:00:00Z<p>by Jim Aizire, Nonhlanhla Yende-Zuma, Sherika Hanley, Teacler Nematadzira, Mandisa M. Nyati, Sufia Dadabhai, Lameck Chinula, Catherine Nakaye, Mary Glenn Fowler, Taha Taha, for the US-PEPFAR PROMOTE Cohort Study team </p>
Background <p>About 90% of unintended pregnancies are attributed to non-use of effective contraception–tubal ligation, or reversible effective contraception (REC) including injectables, oral pills, intra-uterine contraceptive device (IUCD), and implant. We assessed the prevalence of unintended pregnancy and factors associated with using RECs, and Long-Acting-Reversible-Contraceptives (LARCs)–implants and IUCDs, among women living with HIV (WLHIV) receiving antiretroviral therapy (ART).</p> Methods <p>We conducted cross-sectional analyses of the US-PEPFAR PROMOTE study WLHIV on ART at enrollment. Separate outcome (REC and LARC) modified-Poisson regression models were used to estimate prevalence risk ratio (PRR) and corresponding 95% confidence interval (CI).</p> Results <p>Of 1,987 enrolled WLHIV, 990 (49.8%) reported their last/current pregnancy was unintended; 1,027/1,254 (81.9%) non-pregnant women with a potential to become pregnant reported current use of effective contraception including 215/1,254 (17.1%) LARC users. Compared to Zimbabwe, REC rates were similar in South Africa, aPRR = 0.97 (95% CI: 0.90–1.04), p = 0.355, lower in Malawi, aPRR = 0.84 (95% CI: 0.78–0.91), p<0.001, and Uganda, 0.82 (95% CI: 0.73–0.91), p<0.001. Additionally, REC use was independently associated with education attained, primary versus higher education, aPRR = 1.10 (95% CI: 1.02–1.18), p = 0.013; marriage/stable union, aPRR = 1.10 (95% CI: 1.01–1.21), p = 0.039; no desire for another child, PRR = 1.10 (95% CI: 1.02–1.16), p = 0.016; infrequent sex (none in the last 3 months), aPRR = 1.24 (95% CI: 1.15–1.33), p<0001; and controlled HIV load (≤ 1000 copies/ml), PRR = 1.10 (95% CI: 1.02–1.19), p = 0.014. LARC use was independently associated with country (Zimbabwe ref: South Africa, PRR = 0.39 (95% CI: 0.26–0.57), p<0.001; Uganda, PRR = 0.65 (95% CI: 0.42–1.01), p = 0.054; and Malawi, aPRR = 0.87 (95% CI: 0.64–1.19), p = 0.386; HIV load (≤ 1000 copies/ml copies/ml), aPRR=1.73 (95% CI: 1.26–2.37), p<0.001; and formal/self-employment, aPRR = 1.37 (95% CI: 1.02-1.91), p = 0.027.</p> Conclusions <p>Unintended pregnancy was common while use of effective contraception methods particularly LARCs was low among these African WLHIV. HIV viral load, education, sexual-activity, fertility desires, and economic independence are pertinent individual-level factors integral to the multi-level barriers to utilization of effective contraception among African WLHIV. National programs should prioritize strategies for effective integration of HIV and reproductive health care in the respective African countries.</p>Novel insights into RAGE signaling pathways during the progression of amyotrophic lateral sclerosis in RAGE-deficient SOD1 G93A miceNatalia NowickaKamila Zglejc-WaszakJudyta JuranekAgnieszka KorytkoKrzysztof WąsowiczMałgorzata Chmielewska-KrzesińskaJoanna Wojtkiewicz10.1371/journal.pone.02995672024-03-08T14:00:00Z2024-03-08T14:00:00Z<p>by Natalia Nowicka, Kamila Zglejc-Waszak, Judyta Juranek, Agnieszka Korytko, Krzysztof Wąsowicz, Małgorzata Chmielewska-Krzesińska, Joanna Wojtkiewicz</p>
Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a progressive loss of motor neurons resulting in paralysis and muscle atrophy. One of the most prospective hypothesis on the ALS pathogenesis suggests that excessive inflammation and advanced glycation end-products (AGEs) accumulation play a crucial role in the development of ALS in patients and SOD1 G93A mice. Hence, we may speculate that RAGE, receptor for advanced glycation end-products and its proinflammatory ligands such as: HMGB1, S100B and CML contribute to ALS pathogenesis. The aim of our studies was to decipher the role of RAGE as well as provide insight into RAGE signaling pathways during the progression of ALS in SOD1 G93A and RAGE-deficient SOD1 G93A mice. In our study, we observed alternations in molecular pattern of proinflammatory RAGE ligands during progression of disease in RAGE KO SOD1 G93A mice compared to SOD1 G93A mice. Moreover, we observed that the amount of beta actin (ACTB) as well as Glial fibrillary acidic protein (GFAP) was elevated in SOD1 G93A mice when compared to mice with deletion of RAGE. These data contributes to our understanding of implications of RAGE and its ligands in pathogenesis of ALS and highlight potential targeted therapeutic interventions at the early stage of this devastating disease. Moreover, inhibition of the molecular cross-talk between RAGE and its proinflammatory ligands may abolish neuroinflammation, gliosis and motor neuron damage in SOD1 G93A mice. Hence, we hypothesize that attenuated interaction of RAGE with its proinflammatory ligands may improve well-being and health status during ALS in SOD1 G93A mice. Therefore, we emphasize that the inhibition of RAGE signaling pathway may be a therapeutic target for neurodegenerative diseases.Effect of foot orthoses on balance among individuals with flatfoot: A systematic review and meta-analysisChatanun ChinpeerasathianPhyu Sin OoAkkradate SiriphornPraneet Pensri10.1371/journal.pone.02994462024-03-08T14:00:00Z2024-03-08T14:00:00Z<p>by Chatanun Chinpeerasathian, Phyu Sin Oo, Akkradate Siriphorn, Praneet Pensri</p>
Individuals with flatfoot have impaired proprioception owing to ligament laxity and impaired tendons, which can result in poor balance. Foot orthoses (FOs) have been reported to stimulate plantar mechanical receptors and are used to manage foot overpronation in individuals with flatfoot. However, the results of the use of FOs to improve balance are inconsistent. In this systematic review and meta-analysis, we aimed to identify and investigate the effects of FOs on balance in individuals with flatfoot. Electronic databases were searched for articles published before March 2023. Peer-reviewed journal studies that included adult participants with flexible flatfoot and reported the effects of FOs on balance were included and classified based on the study design: randomized control trials (RCT) and non-RCTs. Four RCT studies were retained, and their methodological quality was assessed (mean, 63.2%; range 47.3%–73.1%: high), as were three non-RCT studies (mean, 54.1%; range, 42.1%–68.4%: high). Meta-analysis was performed by calculating the effect size using the standardized mean differences between the control and FO conditions. Transverse-arch insoles immediately improved static balance after use. However, no immediate significant effect was found for medial archsupport FOs, cuboid-posting FOs, or University of California Berkeley Laboratory FOs during the study period (2–5 weeks) when compared with the controls. The transverse-arch insole is the most effective FO feature for improving static balance. However, the high heterogeneity between study protocols contributes to the lack of evidence for the effects of FO on balance in people with flatfoot.