Performance of a safe and dignified burial intervention during an Ebola epidemic in the eastern Democratic Republic of the Congo, 2018-2019.

BACKGROUND: A protracted Ebola Virus Disease (EVD) epidemic in the eastern Ituri, North and South Kivu provinces of the Democratic Republic of Congo (DRC) caused 3470 confirmed and probable cases between July 2018 and April 2020. During the epidemic, the International Federation of Red Cross and Red Crescent Societies (IFRC) supported the DRC Red Cross and other local actors to offer safe and dignified burials (SDB) for suspected and confirmed EVD cases, so as to reduce transmission associated with infectious dead bodies. We conducted a retrospective cohort study of the SDB service's performance in order to inform future applications of this intervention. METHODS: We analysed data on individual SDB responses to quantify performance based on key indicators and against pre-specified service standards. Specifically, we defined SDB timeliness as response within 24 h and success as all components of the service being implemented. Combining the database with other information sources, we also fit generalised linear mixed binomial models to explore factors associated with unsuccessful SDB. RESULTS: Out of 14,624 requests for SDB, 99% were responded to, 89% within 24 h. Overall, 61% of SDBs were successful, somewhat below target (80%), with failures clustered during a high-insecurity period. Factors associated with increased odds of unsuccessful SDB included reported community and/or family nonacceptance, insecurity and suspensions of the EVD response, low health facility coverage and high coverage of radio and telephony. Burials supported by mobile Civil Protection (local authorities) and/or static, community-based 'harm reduction' teams were associated with lower odds of failure. CONCLUSIONS: A large-scale, timely and moderately performant SDB service proved feasible during the challenging eastern DRC EVD response. Burial teams that are managed by community actors and operate locally, and supported rather than owned by the Red Cross or other humanitarian organisations, are a promising modality of delivering this pillar of EVD control.

Specialist oncological surgery for removal of the ovaries and fallopian tubes in BRCA1 and BRCA2 pathogenic variant carriers may reduce primary peritoneal cancer risk to very low levels.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is highly effective for the prevention of high-grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing. Expected annual rates of ovarian/peritoneal cancer were 1% for BRCA1 ≥ 35 years and 0.5% for BRCA2 ≥ 45 years. Follow-up before 35/45 years was "risk free" and lead time excluded RRBSO <35 years and <45 years for BRCA1 and BRCA2, respectively. Women were followed from personal mutation report (controls) or RRBSO (cases) to death, ovarian/peritoneal cancer or last follow-up, whichever was sooner. In total, 891 cases (BRCA1 = 468, BRCA2 = 423) and 1302 controls had follow-up ≥35 years (BRCA1 = 736) and ≥45 years (BRCA2 = 566), respectively, over a total of 7261.1 risk eligible years (mean = 8.15 years). Twenty-one occult ovarian cancers were found at RRBSO (2.4%), 16 at stage 1. Post RRBSO, 56.97 ovarian/peritoneal cancers were expected but only 3 were observed (HR = 0.053; 95% CI = 0.013-0.14), with combined Kaplan-Meier analysis HR = 0.029 (95% CI = 0.009-0.100, P < .001). Risk reduction was greater in specialist (HR = 0.03; 95% CI = 0.001-0.13) compared to non-specialist centres (HR = 0.11; 95% CI = 0.02-0.37) (P = .07). In controls, 23.35 ovarian/peritoneal cancers were expected with 32 observed (HR = 1.37; 95% CI = 0.95-1.91). RRBSO <35/<45 years reduces the risk of ovarian/peritoneal cancer by 95% in BRCA1/2 PVCs and may be greater in specialist centres.

Electronic data collection, management and analysis tools used for outbreak response in low- and middle-income countries: a systematic review and stakeholder survey.

BACKGROUND: Use of electronic data collection, management and analysis tools to support outbreak response is limited, especially in low income countries. This can hamper timely decision-making during outbreak response. Identifying available tools and assessing their functions in the context of outbreak response would support appropriate selection and use, and likely more timely data-driven decision-making during outbreaks. METHODS: We conducted a systematic review and a stakeholder survey of the Global Outbreak Alert and Response Network and other partners to identify and describe the use of, and technical characteristics of, electronic data tools used for outbreak response in low- and middle-income countries. Databases included were MEDLINE, EMBASE, Global Health, Web of Science and CINAHL with publications related to tools for outbreak response included from January 2010-May 2020. Software tool websites of identified tools were also reviewed. Inclusion and exclusion criteria were applied and counts, and proportions of data obtained from the review or stakeholder survey were calculated. RESULTS: We identified 75 electronic tools including for data collection (33/75), management (13/75) and analysis (49/75) based on data from the review and survey. Twenty-eight tools integrated all three functionalities upon collection of additional information from the tool developer websites. The majority were open source, capable of offline data collection and data visualisation. EpiInfo, KoBoCollect and Open Data Kit had the broadest use, including for health promotion, infection prevention and control, and surveillance data capture. Survey participants highlighted harmonisation of data tools as a key challenge in outbreaks and the need for preparedness through training front-line responders on data tools. In partnership with the Global Health Network, we created an online interactive decision-making tool using data derived from the survey and review. CONCLUSIONS: Many electronic tools are available for data -collection, -management and -analysis in outbreak response, but appropriate tool selection depends on knowledge of tools' functionalities and capabilities. The online decision-making tool created to assist selection of the most appropriate tool(s) for outbreak response helps by matching requirements with functionality. Applying the tool together with harmonisation of data formats, and training of front-line responders outside of epidemic periods can support more timely data-driven decision making in outbreaks.

Physeal-sparing posteromedial portal approach reduced distance between guide pin and neurovascular structures.

PURPOSE: To compare a femoral physeal sparing anterior cruciate ligament (ACL) reconstruction technique utilizing a posteromedial portal to traditional transphyseal techniques with regards to anatomic tunnel positioning and proximity to important neurovascular structures. METHODS: Eight cadaveric knees were obtained for the study. Femoral tunnel guide pins were placed utilizing four different techniques: accessory anterior medial portal, posteromedial portal, trans-tibial, and figure-4 methods. The knees were then dissected and the following measurements taken: distance of each pin to the saphenous and peroneal nerve, popliteus tendon, neurovascular bundle, femoral ACL footprint and articular cartilage, and the angle of the guide pin entering the lateral femoral condyle. Fluoroscopic imaging was taken to determine the disruption of the physeal scar. RESULTS: Posteromedial portal guide pin was significantly closer to the neurovascular bundle, popliteal tendon and saphenous nerve when compared to the other 3 techniques, but was further from the peroneal nerve. It also had the smallest distance from the anatomic footprint of the ACL, and the largest angle to the lateral femoral condyle. The posteromedial portal guide pin had similar distance from the articular cartilage as the accessory anterior medial portal and figure-4 guide pin, with the trans-tibial guide pin being the farthest. The posteromedial portal guide pin failed to disrupt the physeal scar in all specimens, while the other three techniques consistently violated the physeal scar. CONCLUSION: The posteromedial portal technique offers an appropriate method for anatomic ACL reconstruction while protecting the distal femoral physis from injury. Care needs to be taken with this technique as it comes in closer proximity to some of the important neurovascular structures. This study indicates that posteromedial portal technique is a less technically challenging approach for physeal-sparing ACL repair with special attention required for the protection of neurovascular bundle from potential injury.

Measles seroprevalence after reactive vaccination campaigns during the 2015 measles outbreak in four health zones of the former Katanga Province, Democratic Republic of Congo.

BACKGROUND: Measles continues to circulate in the Democratic Republic of Congo, and the country suffered from several important outbreaks over the last 5 years. Despite a large outbreak starting in the former province of Katanga in 2010 and the resulting immunization activities, another outbreak occurred in 2015 in this same region. We conducted measles seroprevalence surveys in four health zones (HZ) in the former Katanga Province in order to assess the immunity against measles in children 6 months to 14 years after the 2015 outbreak. METHODS: We conducted multi-stage cluster surveys stratified by age group in four HZs, Kayamba, Malemba-Nkulu, Fungurume, and Manono. The age groups were 6-11 months, 12-59 months, and 5-14 years in Kayamba and Malemba-Nkulu, 6-59 months and 5-14 years in Manono and Fungurume. The serological status was measured on dried capillary blood spots collected systematically along with vaccination status (including routine Extended Program of Immunization (EPI), and supplementary immunization activities (SIAs)) and previous self-reported history of suspected measles. RESULTS: Overall seroprevalence against measles was 82.7% in Kayamba, 97.6% in Malemba-Nkulu, 83.2% in Manono, and 74.4% in Fungurume, and it increased with age in all HZs. It was 70.7 and 93.8% in children 12-59 months in Kayamba and Malemba-Nkulu, and 49.8 and 64.7% in children 6-59 months in Fungurume and Manono. The EPI coverage was low but varied across HZ. The accumulation of any type of vaccination against measles resulted in an overall vaccine coverage (VC) of at least 85% in children 12-59 months in Kayamba and Malemba-Nkulu, 86.1 and 74.8% in children 6-59 months in Fungurume and Manono. Previous measles infection in 2015-early 2016 was more frequently reported in children aged 12-59 months or 6-59 months (depending on the HZ). CONCLUSION: The measured seroprevalence was consistent with the events that occurred in these HZs over the past few years. Measles seroprevalence might prove a valuable source of information to help adjust the timing of future SIAs and prioritizing support to the EPI in this region as long as the VC does not reach a level high enough to efficiently prevent epidemic flare-ups.

Assessment of HIV molecular surveillance capacity in the European Union, 2016.

IntroductionExpanding access to HIV antiretroviral treatment is expected to decrease HIV incidence and acquired immunodeficiency syndrome (AIDS) mortality. However, this may also result in increased HIV drug resistance (DR). Better monitoring and surveillance of HIV DR is required to inform treatment regimens and maintain the long term effectiveness of antiretroviral drugs. As there is currently no formal European Union (EU)-wide collection of HIV DR data, this study aimed to assess the current HIV molecular surveillance capacity in EU/European Economic Area (EEA) countries in order to inform the planning of HIV DR monitoring at EU level. Methods: Thirty EU/EEA countries were invited to participate in a survey on HIV molecular surveillance capacity, which also included laboratory aspects. Results: Among 21 responding countries, 13 reported using HIV sequence data (subtype and/or DR) for surveillance purposes at national level. Of those, nine stated that clinical, epidemiological and sequence data were routinely linked for analysis. Discussion/conclusion: We identified similarities between existing HIV molecular surveillance systems, but also found important challenges including human resources, data ownership and legal issues that would need to be addressed.Information on capacities should allow better planning of the phased introduction of HIV DR surveillance at EU/EEA level.

A systematic review of randomised control trials of sexual health interventions delivered by mobile technologies.

BACKGROUND: Sexually transmitted infections (STIs) pose a serious public health problem globally. The rapid spread of mobile technology creates an opportunity to use innovative methods to reduce the burden of STIs. This systematic review identified recent randomised controlled trials that employed mobile technology to improve sexual health outcomes. METHODS: The following databases were searched for randomised controlled trials of mobile technology based sexual health interventions with any outcome measures and all patient populations: MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, NHS Health Technology Assessment Database, and Web of Science (science and social science citation index) (Jan 1999-July 2014). Interventions designed to increase adherence to HIV medication were not included. Two authors independently extracted data on the following elements: interventions, allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. Trials were assessed for methodological quality using the Cochrane risk of bias tool. We calculated effect estimates using intention to treat analysis. RESULTS: A total of ten randomised trials were identified with nine separate study groups. No trials had a low risk of bias. The trials targeted: 1) promotion of uptake of sexual health services, 2) reduction of risky sexual behaviours and 3) reduction of recall bias in reporting sexual activity. Interventions employed up to five behaviour change techniques. Meta-analysis was not possible due to heterogeneity in trial assessment and reporting. Two trials reported statistically significant improvements in the uptake of sexual health services using SMS reminders compared to controls. One trial increased knowledge. One trial reported promising results in increasing condom use but no trial reported statistically significant increases in condom use. Finally, one trial showed that collection of sexual health information using mobile technology was acceptable. CONCLUSIONS: The findings suggest interventions delivered by SMS interventions can increase uptake of sexual health services and STI testing. High quality trials of interventions using standardised objective measures and employing a wider range of behavioural change techniques are needed to assess if interventions delivered by mobile phone can alter safer sex behaviours carried out between couples and reduce STIs.

Can obtaining informed consent alter self-reported drinking behaviour? A methodological experiment.

BACKGROUND: Informed consent is the foundation of the ethical conduct of health research. Obtaining informed consent may unwittingly interfere with the data collected in research studies, particularly if they concern sensitive behaviours that participants are requested to report on. To address gaps in evidence on such research participation effects, we conducted a methodological experiment evaluating the impact of the informed consent procedure on participants' reporting behaviour, specifically on their self-report of drinking behaviour as measured by Alcohol Use Disorder Identification Test (AUDIT). METHODS: A two arm double blinded randomised controlled trial was used. University students present in London student unions at the time of recruitment were contacted in two phases (an initial run-in phase followed by the main phase). Those providing positive responses to verbal questions: 1) "are you a student?"; 2) "do you drink alcohol?"; 3) "would you like to take part in a brief health survey, which will take around 5 minutes?" were recruited. Participants received one of the two envelopes by chance, with the sequence generated by an online random sequence generator. One contained the participant information sheet, informed consent form and the AUDIT questionnaire (the intervention group), while the other contained only the AUDIT questionnaire (the comparator group). The primary outcome was the mean AUDIT score, which ranges from 0 to 40. The secondary outcome was the proportion of participants in each group scoring 8 or more on the AUDIT, the threshold score for hazardous and harmful drinking warranting intervention. RESULTS: A total of 380 participants were successfully recruited, resulting in 190 participants in each group, of which 378 were included in the final analysis. There is no evidence of any statistically significant difference between groups in the primary outcome. A statistically significant difference in the secondary outcome was found in the run-in phase only, and not in the main phase, or overall. Moreover, between-group outcome differences between the two phases suggest an important influence of setting on reporting behaviour. CONCLUSIONS: There is no strong evidence that completion of informed consent itself alters self-reporting behaviour with regards to alcohol, though the effect of settings needs to be further studied.

Minding the gap: Prioritization of care issues among nurse practitioners, family physicians and geriatricians when caring for the elderly.

Accumulating health problems of the elderly requires recognition of geriatric syndromes, while shifting away from a conventional disease-specific approach. We surveyed 179 practitioners representing Family Physicians (FPs), Nurse Practitioners (NPs) and geriatricians in Ontario, in order to quantify how they prioritize syndromes, diseases and conditions in the elderly. Identifying differences may inform opportunities for interprofessional sharing of expertise among professionals pursuing a common goal, which is expected to improve interprofessional collaboration. Our survey (response rate 36%) identifies that NP, FP and geriatrician respondents all recognize co-occurrence of "multiple morbidities" as one of the most frequently encountered issues when serving the elderly, however FPs and NPs place higher priority on managing individual chronic diseases than explicitly prioritizing geriatric syndromes. Our findings identify a need for a more clearly defined role for the geriatrician as syndrome-educator and implies further need for collaborative approaches to caring for seniors that values different professional's expertise.

The impact of patient preference on dialysis modality and hemodialysis vascular access.

BACKGROUND: Home-based dialysis, including peritoneal dialysis (PD) and home hemodialysis (HHD), is associated with improved health related quality of life and reduced health resource costs. It is uncertain to what extent initial preferences for dialysis modality influence the first dialysis therapy actually utilized. We examined the relationship between initial dialysis modality choice and first dialysis therapy used. METHODS: Patients with chronic kidney disease (CKD) from a single centre who started dialysis after receiving modality education were included in this study. Multivariable logistic regression models were constructed to assess the independent association of patient characteristics and initial dialysis modality choice with actual dialysis therapy used and starting hemodialysis (HD) with a central venous catheter (CVC). RESULTS: Of 299 eligible patients, 175 (58.5%) initially chose a home-based therapy and 102 (58.3%) of these patients' first actual dialysis was a home-based therapy. Of the 89 patients that initially chose facility-based HD, 84 (94.4%) first actual dialysis was facility-based HD. The adjusted odds ratio (OR) for first actual dialysis as a home-based therapy was 29.0 for patients intending to perform PD (95% confidence interval [CI] 10.7-78.8; p < 0.001) and 12.4 for patients intending to perform HHD (95% CI 3.29-46.6; p < 0.001). Amongst patients whose first actual dialysis was HD, an initial choice of PD or not choosing a modality was associated with an increased risk of starting dialysis with a CVC (adjusted OR 3.73, 95% CI 1.51-9.21; p = 0.004 and 4.58, 95% CI 1.53-13.7; p = 0.007, respectively). CONCLUSIONS: Although initially choosing a home-based therapy substantially increases the probability of the first actual dialysis being home-based, many patients who initially prefer a home-based therapy start with facility-based HD. Programs that continually re-evaluate patient preferences and reinforce the values of home based therapies that led to the initial preference may improve home-based therapy uptake and improve preparedness for starting HD.

Assignment of the Lassa virus transmembrane domain in the prefusion and postfusion states in detergent micelles.

Lassa virus (LASV) is the most prevalent member of the arenavirus family and the causative agent of Lassa fever, a viral hemorrhagic fever. Although there are annual outbreaks in West Africa, and recently isolated cases worldwide, there are no current therapeutics or vaccines. As such, LASV poses a significant global public health threat. One of the key steps in LASV infection is delivering its genetic material by fusing its viral membrane with the host cell membrane. This process is facilitated by significant conformational changes within glycoprotein 2 (GP2), yielding distinct prefusion and postfusion structural states. However, structural information is missing to understand the changes that occur in the transmembrane domain (TM) during the fusion process. Previously, we showed that the TM undergoes pH-dependent structural changes that result in a helical extension. Here, we provide the 1H, 15N, and 13C assignment of the LASV TM backbone in the prefusion and postfusion states. We also provide the 1H, 15N, and 13C assignment of two mutants, G429P and D432P, which prevent this helical extension. These results will help understand the role the TM plays in membrane fusion and can lead to the design of therapeutics against LASV infection.

Lot quality assurance sampling survey for water, sanitation and hygiene monitoring and evidence-based advocacy in Bentiu IDP camp, South Sudan.

BACKGROUND: Every year, 60% of deaths from diarrhoeal disease occur in low and middle-income countries due to inadequate water, sanitation, and hygiene. In these countries, diarrhoeal diseases are the second leading cause of death in children under five, excluding neonatal deaths. The approximately 100,000 people residing in the Bentiu Internally Displaced Population (IDP) camp in South Sudan have previously experienced water, sanitation, and hygiene outbreaks, including an ongoing Hepatitis E outbreak in 2021. This study aimed to assess the gaps in Water, Sanitation, and Hygiene (WASH), prioritise areas for intervention, and advocate for the improvement of WASH services based on the findings. METHODS: A cross-sectional lot quality assurance sampling (LQAS) survey was conducted in ninety-five households to collect data on water, sanitation, and hygiene (WASH) coverage performance across five sectors. Nineteen households were allocated to each sector, referred to as supervision areas in LQAS surveys. Probability proportional to size sampling was used to determine the number of households to sample in each sector block selected using a geographic positioning system. One adult respondent, familiar with the household, was chosen to answer WASH-related questions, and one child under the age of five was selected through a lottery method to assess the prevalence of WASH-related disease morbidities in the previous two weeks. The data were collected using the KoBoCollect mobile application. Data analysis was conducted using R statistical software and a generic LQAS Excel analyser. Crude values, weighted averages, and 95% confidence intervals were calculated for each indicator. Target coverage benchmarks set by program managers and WASH guidelines were used to classify the performance of each indicator. RESULTS: The LQAS survey revealed that five out of 13 clean water supply indicators, eight out of 10 hygiene and sanitation indicators, and two out of four health indicators did not meet the target coverage. Regarding the clean water supply indicators, 68.9% (95% CI 60.8%-77.1%) of households reported having water available six days a week, while 37% (95% CI 27%-46%) had water containers in adequate condition. For the hygiene and sanitation indicators, 17.9% (95% CI 10.9%-24.8%) of households had handwashing points in their living area, 66.8% (95% CI 49%-84.6%) had their own jug for cleansing after defaecation, and 26.4% (95% CI 17.4%-35.3%) of households had one piece of soap. More than 40% of households wash dead bodies at funerals and wash their hands in a shared bowl. Households with sanitary facilities at an acceptable level were 22.8% (95% CI 15.6%-30.1%), while 13.2% (95% CI 6.6%-19.9%) of households had functioning handwashing points at the latrines. Over the previous two weeks, 57.9% (95% CI 49.6-69.7%) of households reported no diarrhoea, and 71.3% (95% CI 62.1%-80.6%) reported no eye infections among children under five. CONCLUSION: The camp's hygiene and sanitation situation necessitated immediate intervention to halt the hepatitis E outbreak and prevent further WASH-related outbreaks and health issues. The LQAS findings were employed to advocate for interventions addressing the WASH gaps, resulting in WASH and health actors stepping in.

Evaluation of a multi-component early warning system for pastoralist populations in Doolo zone, Ethiopia: mixed-methods study.

BACKGROUND: This study evaluated an early warning, alert and response system for a crisis-affected population in Doolo zone, Somali Region, Ethiopia, in 2019-2021, with a history of epidemics of outbreak-prone diseases. To adequately cover an area populated by a semi-nomadic pastoralist, or livestock herding, population with sparse access to healthcare facilities, the surveillance system included four components: health facility indicator-based surveillance, community indicator- and event-based surveillance, and alerts from other actors in the area. This evaluation described the usefulness, acceptability, completeness, timeliness, positive predictive value, and representativeness of these components. METHODS: We carried out a mixed-methods study retrospectively analysing data from the surveillance system February 2019-January 2021 along with key informant interviews with system implementers, and focus group discussions with local communities. Transcripts were analyzed using a mixed deductive and inductive approach. Surveillance quality indicators assessed included completeness, timeliness, and positive predictive value, among others. RESULTS: 1010 signals were analysed; these resulted in 168 verified events, 58 alerts, and 29 responses. Most of the alerts (46/58) and responses (22/29) were initiated through the community event-based branch of the surveillance system. In comparison, one alert and one response was initiated via the community indicator-based branch. Positive predictive value of signals received was about 6%. About 80% of signals were verified within 24 h of reports, and 40% were risk assessed within 48 h. System responses included new mobile clinic sites, measles vaccination catch-ups, and water and sanitation-related interventions. Focus group discussions emphasized that responses generated were an expected return by participant communities for their role in data collection and reporting. Participant communities found the system acceptable when it led to the responses they expected. Some event types, such as those around animal health, led to the community's response expectations not being met. CONCLUSIONS: Event-based surveillance can produce useful data for localized public health action for pastoralist populations. Improvements could include greater community involvement in the system design and potentially incorporating One Health approaches.

Involving older people in the preparedness, response, and recovery phases in humanitarian emergencies: a theoretical framework on ageism, epistemic injustice, and participation.

Humanitarian emergencies disproportionally affect older people. Although defining an older person by an age range can help alert us to emerging or changing needs and potential vulnerabilities during humanitarian emergencies, ageing is not necessarily synonymous with increasing vulnerability, and individual variations exist due to the heterogeneity of older people. In general, reduced access to safety, health services, clean water, and appropriate food puts older people at increased risk of poor health outcomes during humanitarian emergencies, including disability, injury, malnutrition, and mental health issues. The theoretical framework presented in this Personal View explains how ageism, further compounded by intersecting oppression, leads to the exclusion of older people from the preparedness, response, and recovery phases of humanitarian emergencies. The exclusion of older people is discriminatory, violates core humanitarian and bioethical principles, and leads to an epistemic injustice. We suggest that humanitarian actors implement participatory approaches with older people in humanitarian contexts. Through these approaches, solutions will be identified by and together with older people, leading to community-driven and context-appropriate ways to include the needs and strengths of older people in the preparedness, response, and recovery phases of humanitarian emergencies.

Correction: Evaluation of community based surveillance in the Rohingya refugee camps in Cox's Bazar, Bangladesh, 2019.

[This corrects the article DOI: 10.1371/journal.pone.0244214.].

Fourier-transform infrared spectroscopy coupled with a classification machine for the analysis of blood plasma or serum: a novel diagnostic approach for ovarian cancer.

Currently available screening tests do not deliver the required sensitivity and specificity for accurate diagnosis of ovarian or endometrial cancer. Infrared (IR) spectroscopy of blood plasma or serum is a rapid, versatile, and relatively non-invasive approach which could characterize biomolecular alterations due to cancer and has potential to be utilized as a screening or diagnostic tool. In the past, no such approach has been investigated for its applicability in screening and/or diagnosis of gynaecological cancers. We set out to determine whether attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy coupled with a proposed classification machine could be applied to IR spectra obtained from plasma and serum for accurate class prediction (cancer vs. normal). Plasma and serum samples were obtained from ovarian cancer cases (n = 30), endometrial cancer cases (n = 30) and non-cancer controls (n = 30), and subjected to ATR-FTIR spectroscopy. Four derived datasets were processed to estimate the real-world diagnosis of ovarian and endometrial cancer. Classification results for ovarian cancer were remarkable (up to 96.7%), whereas endometrial cancer was classified with a relatively high accuracy (up to 81.7%). The results from different combinations of feature extraction and classification methods, and also classifier ensembles, were compared. No single classification system performed best for all different datasets. This demonstrates the need for a framework that can accommodate a diverse set of analytical methods in order to be adaptable to different datasets. This pilot study suggests that ATR-FTIR spectroscopy of blood is a robust tool for accurate diagnosis, and carries the potential to be utilized as a screening test for ovarian cancer in primary care settings. The proposed classification machine is a powerful tool which could be applied to classify the vibrational spectroscopy data of different biological systems (e.g., tissue, urine, saliva), with their potential application in clinical practice.

Purification and characterization of the Lassa virus transmembrane domain.

Lassa virus (LASV) is the most prevalent arenavirus afflicting humans and has high potential to become a threat to global public health. The transmembrane domain (TM) of the LASV glycoprotein complex forms critical interactions with the LASV stable signal peptide that are important for the maturation and fusion activity of the virus. A further study of the structure-based molecular mechanisms is required to understand the role of the TM in the lifecycle of LASV in greater detail. However, it is challenging to obtain the TM in high quantity and purity due to its hydrophobic nature which results in solubility issues that makes it prone to aggregation in typical buffer systems. Here, we designed a purification and detergent screen protocol for the highly insoluble TM to enhance the yield and purity for structural studies. Based on the detergents tested, the TM had the highest incorporation in LMPG. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were utilized to confirm the best detergent system for structural studies. Through CD spectroscopy, we were able to characterize the secondary structure of the TM as largely alpha-helical, while NMR spectroscopy showed a well-structured and stable TM in LMPG. From these results, LMPG was determined to be the optimal detergent for further structural studies.

External jugular vein aneurysm presenting as submandibular neck mass.

External jugular vein aneurysms presenting as neck masses is very rare in the literature. This case report presents an 80-year-old female, who was referred to the office due to an incidental finding of a left submandibular neck mass. The patient presented to her primary care physician initially complaining of bilateral intermittent ear pain that was present for several years. After extensive workup, the patient was diagnosed with a left external jugular vein aneurysm. When asymptomatic, this rare condition can be followed safely on an outpatient basis. Vascular surgery consultation should also be considered.

Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores.

The conserved Aurora B protein kinase (Ipl1 in Saccharomyces cerevisiae) is essential for ensuring that sister kinetochores become attached to microtubules from opposite spindle poles (bi-orientation) before anaphase onset. When sister chromatids become attached to microtubules from a single pole, Aurora B/Ipl1 facilitates turnover of kinetochore-microtubule attachments. This process requires phosphorylation by Aurora B/Ipl1 of kinetochore components such as Dam1 in yeast. Once bi-orientation is established and tension is applied on kinetochores, Aurora B/Ipl1 must stop promoting this turnover, otherwise correct attachment would never be stabilised. How this is achieved remains elusive: it might be due to dephosphorylation of Aurora B/Ipl1 substrates at kinetochores, or might take place independently, for example because of conformational changes in kinetochores. Here, we show that Ipl1-dependent phosphorylation at crucial sites on Dam1 is maximal during S phase and minimal during metaphase, matching the cell cycle window when chromosome bi-orientation occurs. Intriguingly, when we reduced tension at kinetochores through failure to establish sister chromatid cohesion, Dam1 phosphorylation persisted in metaphase-arrested cells. We propose that Aurora B/Ipl1-facilitated bi-orientation is stabilised in response to tension at kinetochores by dephosphorylation of Dam1, resulting in termination of kinetochore-microtubule attachment turnover.

Evaluation of dopamine D2/3 specific binding in the cerebellum for the positron emission tomography radiotracer [¹¹C]FLB 457: implications for measuring cortical dopamine release.

In a recent positron emission tomography (PET) study, we demonstrated the ability to measure amphetamine-induced dopamine (DA) release in the human cortex with the DA D2/3 radioligand [¹¹C]FLB 457. As previous studies in animals have shown that a relatively high fraction of the [¹¹C]FLB 457 signal in the cerebellum represents specific binding to D2/3 receptors, there was concern that the use of the cerebellum as a measure of nonspecific binding (i.e., reference region) to derive [¹¹C]FLB 457 binding potential (BP) (BP(ND) ) would bias cortical DA release measurements. Thus, we evaluated the fractional contribution of specific binding to D2/3 receptors in the human cerebellum for [¹¹C]FLB 457. Six healthy human subjects (5M/1F) were studied twice with [¹¹C]FLB 457, once at baseline and again following a single oral dose of 15 mg of aripiprazole, a D2/3 partial agonist. [¹¹C]FLB 457 distribution volume (V(T) ) was estimated using kinetic analysis in the cortical regions of interest and potential reference regions. The change in [¹¹C]FLB 457 V(T) following aripiprazole ranged from -33 to -42% in the cortical regions of interest (ROIs). The aripiprazole-induced change in [¹¹C]FLB 457 V(T) in three potential reference regions suggests significant specific binding the cerebellum (CER, -17 ± 12%), but not pons (PON, -10 ± 10%) and centrum semiovale (CESVL, -3 ± 12%). Nevertheless, a reanalysis of the published [¹¹C]FLB 457 test-retest and amphetamine studies suggests that the use of the PON V(T) and CESVL V(T) as an estimate of nonspecific binding to derive [¹¹C]FLB 457 BP(ND) in DA release studies is unlikely to be successful because it leads to less reproducible outcome measures, which in turn diminishes the ability to measure DA release in the cortex. D2/3 blocking studies with aripiprazole and [¹¹C]FLB 457 suggest specific binding to D2/3 receptors in the cerebellum. These data also suggest that the contribution of specific binding to D2/3 receptors in the cerebellum is lower than that in the cortical ROIs and that CER V(T) is mostly representative of nonspecific binding. Nevertheless, caution is advised when using reference tissue methods that rely solely on the cerebellum signal as an input function to quantify [¹¹C]FLB 457 BP(ND).