Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity.

While the search for an efficacious HIV-1 vaccine remains elusive, emergence of a new generation of virus-neutralizing monoclonal antibodies (mAbs) has re-ignited the field of passive immunization for HIV-1 prevention. However, the plasticity of HIV-1 demands additional improvements to these mAbs to better ensure their clinical utility. Here, we report engineered bispecific antibodies that are the most potent and broad HIV-neutralizing antibodies to date. One bispecific antibody, 10E8V2.0/iMab, neutralized 118 HIV-1 pseudotyped viruses tested with a mean 50% inhibitory concentration (IC50) of 0.002 µg/mL. 10E8V2.0/iMab also potently neutralized 99% of viruses in a second panel of 200 HIV-1 isolates belonging to clade C, the dominant subtype accounting for ∼50% of new infections worldwide. Importantly, 10E8V2.0/iMab reduced virus load substantially in HIV-1-infected humanized mice and also provided complete protection when administered prior to virus challenge. These bispecific antibodies hold promise as novel prophylactic and/or therapeutic agents in the fight against HIV-1.

The experiences and perceptions of immigrant informal caregivers about engaging with professional services in the host country: A scoping review.

AIM: The inquiry explored immigrant informal caregivers' experiences and perceptions about engaging with professional services in the host country. BACKGROUND: The number of informal caregivers is rising, with more people providing home caring. Nurses and other health services are crucial in supporting informal caregivers. Research needs to focus more on immigrants, not just other caregivers. DESIGN: This was a scoping review. DATA SOURCES: Five databases (January 2017-December 2022) were searched, and 16 articles were included in this inquiry. REVIEW METHODS: This scoping review used the Joanna Briggs Institute Scoping Review methodology. This inquiry asked one question: What is the current knowledge about immigrant informal caregivers' experiences and perceptions when engaging mainstream professional services? Themes were identified using a thematic analysis approach. RESULTS: Three themes emerged from the review: 'finding cultural bridges: culturally connecting with services'; 'building cultural bridges: addressing "them and us" and "acculturation-sensitive services"'. CONCLUSION: Professional service providers are currently not meeting immigrant caregivers' needs. New knowledge is presented, that nurses and health professional services must provide acculturation-sensitive care, commencing with an assessment of the individual's acculturation status. By understanding acculturation status, nurses are more likely to customize person-centred care. Acculturation status refers to the degree that the individual has adapted to the new culture while retaining some traditional cultural beliefs and practices. Acculturation-sensitive care is more likely to provide authentic holistic care that optimizes well-being.

Health coaching provided by registered nurses described: a systematic review and narrative synthesis.

AIMS: The aim of this systematic review and narrative synthesis was to identify how and why health coaching is delivered by Registered Nurses. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Articles were identified through a search of CINAHL, Medline, Scopus, and PsychINFO databases. Articles published in English between 2010 and 2021 were included. REVIEW METHODS: Quality appraisal of relevant literature was independently undertaken by two authors to assess for risk of bias. The Critical Appraisal Skills Program (CASP) was used to appraise quality of potential papers. RESULTS: A main purpose of coaching by Registered Nurses is to optimise patient self-care. How coaching was conducted varied across studies, with the most common coaching approaches via telephone or online. Majority of studies highlight some effectiveness of coaching by nurses; however, some results were inconclusive. Health coaching generally reduced mental distress. Other benefits reported by patients included reduced pain and fatigue. Outcomes for changing lifestyle behaviours were mixed. However, for health coaching to be efficient greater evidence is needed to determine length of time to use coaching, number of habits to focus on to produce change, and to determine best training for coaches. CONCLUSIONS: Registered Nurses are most suitable for implementing health coaching for self-care, including preventing and managing chronic illness and recovering from situations like post-surgical needs. Nurses already promote health, and therefore, are skilled in educating people in self-care. Coaching is an additional strategy for motivating, targeting and assessing progress of self-care. Extending the scope of nursing practice to routinely coach in self-care would be ideal.

A qualitative exploration of a mindful resiliency program for community healthcare providers.

Despite the important contribution of nongovernmental organizations (NGOs) to the community healthcare sector, the building and maintenance of occupational resilience in community health workers has received little attention. However, it is recognized that employees in this sector are exposed to significant stressors from the high demand work environment which negatively impacts on their well-being. Therefore, this research examined the acceptability, feasibility, and sustainability of a mindful resiliency program by employing a qualitative analysis of participant subjective experience of the program in this cohort. This was the first study to be conducted with senior managers and frontline healthcare providers in the nongovernmental organizations community sector. A 1-month post-delivery qualitative review of the program identified four major themes: applicability, changes to participant's skills, social support, and coping with COVID-19. A major finding was the ability of the participants to immediately recognize their stress levels and then manage them. Additionally, lessons from the program were shown to be usefully applied with colleagues and clients within the work environment, and with family members.

Current practice for genetic counselling by nurses: An integrative review.

AIM: To examine current practice of genetic counselling by nurses. BACKGROUND: Recent debate argues that genetic counselling is a specialist advanced practice role, whilst others argue it is the role of all nurses. Current evidence is required to determine if genetic counselling could be included in all nurses' scope of practice. DESIGN: Integrative literature review. DATA SOURCES: A search of electronic databases (CINHAL, Medline, PubMed, Scopus), and reference lists published between January 2012 and March 2017, was undertaken. REVIEW METHODS: Studies were critically appraised for methodological quality using the Critical Appraisal Skills Programme. Data from each study were extracted and categorized according to their primary findings. RESULTS: The inclusion criteria were met in 10 studies. Main findings were identified: role of genetic counselling, current knowledge, need for further education, and client satisfaction with nurse genetic counsellors. CONCLUSION: This paper concludes that some nurses do engage in genetic counselling, but how they engage is not consistent, nor is there consensus about what should be the scope of practice. Further investigation into credentialing, role recognition support and education for nurse genetic counselling are strongly recommended. As nurses are widely available, nurses can make a significant contribution to supporting those affected by genetic problems.

Single mothering as experienced by Burundian refugees in Australia: a qualitative inquiry.

BACKGROUND: Refugee mothers have fled from their homeland to escape persecutions with their children only to find other threats to their well-being in the new country. Building on previous research, it is known that being a new immigrant is challenging and requires adaptation. The adaptation process, known as acculturation, may not be successful leading to psychological distress. It is also known that a generation gap can occur when children acculturate faster than their parents. What was lacking was understanding about the experiences of single refugee mothers. METHODS: Interpretative phenomenological study was undertaken to explore the lived experiences of eight Burundian refugee single mothers in Australia. Data were collected by in-depth interviews. Each interviews were transcribed and analyzed using thematic analysis. RESULTS: Findings revealed three themes. First theme 'Traditional mothering practices of Burundian culture' illustrated mothering strategies as practiced prior to their arrival in Australia including mothering with sufficient social support, strong position of parents, and regular use of physical disciplining. Second theme 'Challenges identified after arrival to new country' revealed that mothers felt their children acculturated faster than themselves which led to intergenerational gap. This has also led participants to live in a continuous dilemma, experiencing inner conflicts and struggles associated with their mothering practices, especially when mothers had arrived with a lack of knowledge relating to acceptable mothering practices in a new culture. Final theme, 'Reforming family life in Australia' highlighted the decisions made by single refugee mothers which is to embrace both new and original cultures, leading to successful acculturation. However, lack of appropriate knowledge of acceptable mothering practices led to involvement of legal authorities who threatening to remove children from the mother's care. This has led mothers feeling change of power from 'mother to child, 'to child to mother', raises concerns for family wellbeing. CONCLUSIONS: A need for parenting information when entering a new country including education about any legal obligations for parents such as a Child Protection Act will assist successful acculturation. As nurses are likely to encounter refugee single mothers, they are well placed to provide support and education to new refugee single mothers.

An integrative review of absenteeism in newly graduated nurses.

Managing sickness and absenteeism in the workplace is challenging, and nurse managers must consider their various causes so they can implement effective management strategies. It is also vital to consider the factors that influence absenteeism and turnover among newly graduated registered nurses (RNs), whose retention can help to address staff shortages. This article describes a literature review that aimed to identify the potential causes of sickness absence in newly graduated RNs. It also discusses strategies that nurse managers can use to retain and maintain their workforce.

Emergence of CD4 independence envelopes and astrocyte infection in R5 simian-human immunodeficiency virus model of encephalitis.

UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) infection in the central nervous system (CNS) is characterized by replication in macrophages or brain microglia that express low levels of the CD4 receptor and is the cause of HIV-associated dementia and related cognitive and motor disorders that affect 20 to 30% of treatment-naive patients with AIDS. Independent viral envelope evolution in the brain has been reported, with the need for robust replication in resident CD4(low) cells, as well as CD4-negative cells, such as astrocytes, proposed as a major selective pressure. We previously reported giant-cell encephalitis in subtype B and C R5 simian-human immunodeficiency virus (SHIV)-infected macaques (SHIV-induced encephalitis [SHIVE]) that experienced very high chronic viral loads and progressed rapidly to AIDS, with varying degrees of macrophage or microglia infection and activation of these immune cells, as well as astrocytes, in the CNS. In this study, we characterized envelopes (Env) amplified from the brains of subtype B and C R5 SHIVE macaques. We obtained data in support of an association between severe neuropathological changes, robust macrophage and microglia infection, and evolution to CD4 independence. Moreover, the degree of Env CD4 independence appeared to correlate with the extent of astrocyte infection in vivo. These findings further our knowledge of the CNS viral population phenotypes that are associated with the severity of HIV/SHIV-induced neurological injury and improve our understanding of the mechanism of HIV-1 cellular tropism and persistence in the brain. IMPORTANCE: Human immunodeficiency virus type 1 (HIV-1) infection of astrocytes in the brain has been suggested to be important in HIV persistence and neuropathogenesis but has not been definitively demonstrated in an animal model of HIV-induced encephalitis (HIVE). Here, we describe a new nonhuman primate (NHP) model of R5 simian-human immunodeficiency virus (SHIV)-induced encephalitis (SHIVE) with several classical HIVE features that include astrocyte infection. We further show an association between severe neuropathological changes, robust resident microglia infection, and evolution to CD4 independence of viruses in the central nervous system (CNS), with expansion to infection of truly CD4-negative cells in vivo. These findings support the use of the R5 SHIVE models to study the contribution of the HIV envelope and viral clades to neurovirulence and residual virus replication in the CNS, providing information that should guide efforts to eradicate HIV from the body.

The number and genetic relatedness of transmitted/founder virus impact clinical outcome in vaginal R5 SHIVSF162P3N infection.

BACKGROUND: Severe genetic bottleneck occurs during HIV-1 sexual transmission whereby most infections are initiated by a single transmitted/founder (T/F) virus. Similar observations had been made in nonhuman primates exposed mucosally to SIV/SHIV. We previously reported variable clinical outcome in rhesus macaques inoculated intravaginally (ivg) with a high dose of R5 SHIVSF162P3N. Given the potential contributions of viral diversity to HIV-1 persistence and AIDS pathogenesis and recombination between retroviral genomes increases the genetic diversity, we tested the hypothesis that transmission of multiple variants contributes to heightened levels of virus replication and faster disease progression in the SHIVSF162P3N ivg-infected monkeys. RESULTS: We found that the differences in viral replication and disease progression between the transiently viremic (TV; n = 2), chronically-infected (CP; n = 8) and rapid progressor (RP; n = 4) ivg-infected macaques cannot be explained by which variant in the inoculum was infecting the animal. Rather, transmission of a single variant was observed in both TV rhesus, with 1-2 T/F viruses found in the CPs and 2-4 in all four RP macaques. Moreover, the genetic relatedness of the T/F viruses in the CP monkeys with multivariant transmission was greater than that seen in the RPs. Biological characterization of a subset of T/F envelopes from chronic and rapid progressors revealed differences in their ability to mediate entry into monocyte-derived macrophages, with enhanced macrophage tropism observed in the former as compared to the latter. CONCLUSION: Our study supports the tenet that sequence diversity of the infecting virus contributes to higher steady-state levels of HIV-1 virus replication and faster disease progression and highlights the role of macrophage tropism in HIV-1 transmission and persistence.

Sex and COVID-19 vaccination uptake and intention in the Democratic Republic of Congo, Nigeria, Senegal, and Uganda.

The introduction of vaccines marked a game changer in the fight against COVID-19. In sub-Saharan Africa, studies have documented the intention to vaccinate and the uptake of COVID-19 vaccines. However, little is documented about how sex differences could have impacted COVID-19 vaccination. We conducted a multi-country cross-sectional study to assess the sex differences in COVID-19 vaccine uptake and intention to vaccinate in the Democratic Republic of Congo (DRC), Nigeria, Senegal, and Uganda. This study involved analysis of data from mobile surveys conducted between March and June 2022 among nationally constituted samples of adults in each country. Bivariate and multivariable logistic regression models were run. The self-reported uptake of COVID-19 vaccines was not significantly different between males and females (p = 0.47), while the intention to vaccinate was significantly higher among males (p = 0.008). Among males, obtaining COVID-19 information from health workers, testing for COVID-19, and having high trust in the Ministry of Health were associated with higher vaccination uptake. Among females, having high trust in the government was associated with higher vaccination uptake. For intention to vaccinate, males who resided in semi-urban areas and females who resided in rural areas had significantly higher vaccination intention compared to their counterparts in urban areas. Other factors positively associated with vaccination intention among males were trust in the World Health Organization and perceived truthfulness of institutions, while males from households with a higher socio-economic index and those who had declined a vaccine before had a lower vaccine intention. Overall, the factors differentiating vaccine uptake and intention to vaccinate among males and females were mostly related to trust in government institutions, perceived truthfulness of institutions, and respondent's residence. These factors are key in guiding the tailoring of interventions to increase COVID-19 vaccine uptake in sub-Saharan Africa and similar contexts.

Pathogenic consequences of vaginal infection with CCR5-tropic simian-human immunodeficiency virus SHIVSF162P3N.

We previously reported efficient transmission of the pathogenic R5 simian-human immunodeficiency virus SHIV(SF162P3N) isolate in Indian rhesus macaques by intravenous and intrarectal inoculations, with a switch to CXCR4 coreceptor usage in ∼50% of infected animals that progressed rapidly to disease. Since women continue to be disproportionately affected by HIV, we developed an animal model based on the intravaginal challenge of female rhesus monkeys with SHIV(SF162P3N) and sought to validate the utility of this model to study relevant aspects of HIV transmission and pathogenesis. The effect of viral dose on infection outcome was evaluated to determine the optimal conditions for the evaluation of HIV-1 preventive and therapeutic strategies. We found that the virus can successfully cross the vaginal mucosal surface to establish infection and induce disease with coreceptor switch, but with lower efficiencies compared to intravenous and rectal transmissions. In contrast to intrarectal infection, peak and cumulative viral load over a 1 year-infection period were significantly greater in macaques exposed intravaginally to lower rather than higher inoculum doses. Moreover, low and transient viremia was observed only in macaques that were challenged intravaginally twice within the same day with a high dose of virus, which can be seen as doubling the dose. Taken together, these results show that SHIV(SF162P3N) can successfully transmit across the genital mucosa, undergo coreceptor switch, and induce disease. However, the administered dose appears to impact SHIV(SF162P3N) vaginal infection outcome in an unexpected manner.

Using call detail records to determine mobility patterns of different socio-demographic groups in the western area of Sierra Leone during early COVID-19 crisis.

Human mobility patterns created from mobile phone call detail records (CDRs) can provide an essential resource in data-poor environments to monitor the effects of health outbreaks. Analysis of this data can be instrumental for understanding the movement pattern of populations allowing governments to set and refine policies to respond to community health risks. Building on CDR mobility analysis techniques, this research set out to test whether combining CDR mobility indicators with socio-economic information can illustrate differences between different socio-economic groups' exposure risks to COVID-19. The work focuses on the Western Area of Sierra Leone which houses the capital Freetown because it lacks existing mobility data and therefore can be a great example of how CDR can be transformed for this use. To determine mobility patterns, we applied the radius of gyration, regularity of movement, and motif types analytics commonly used in CDR research. We then applied a clustering algorithm to these results to understand user trends. Then we compared the results of the three methods with socio-economic status determined from census data in the same geography. The results show the daily movement of cell phone users of lower socio-economic status covered greater distances in the Western Area before and after lockdown, thereby showing a greater risk to COVID-19. The research also shows that groups of higher social status decreased mobility significantly after lockdown and did not return to pre-COVID-19 levels, unlike lower-social status groups.

Managing United States-China university relations and risks.

US universities must proactively address potential concerns.

Uptake of COVID-19 vaccines and associated factors among adults in Uganda: a cross-sectional survey.

OBJECTIVE: COVID-19 pandemic remains one of the most significant public health challenges ever faced globally. Vaccines are key to ending the pandemic as well as minimise its consequences. This study determined the uptake of COVID-19 vaccines and associated factors among adults in Uganda. DESIGN, SETTING AND PARTICIPANTS: We conducted a cross-sectional mobile phone survey among adults in Uganda. MAIN OUTCOME VARIABLE: Participants reported their uptake of COVID-19 vaccines. RESULTS: Of the participants contacted, 94% (1173) completed the survey. Overall, 49.7% had received COVID-19 vaccines with 19.2% having obtained a full dose and 30.5% an incomplete dose. Among the unvaccinated, 91.0% indicated intention to vaccinate. Major reasons for vaccine uptake were protection of self from COVID-19 (86.8%) and a high perceived risk of getting the virus (19.6%). On the other hand, non-uptake was related to vaccine unavailability (42.4%), lack of time (24.1%) and perceived safety (12.5%) and effectiveness concerns (6.9%). The factors associated with receiving COVID-19 vaccines were older age (≥65 years) (Adjusted Prevalence Ratio (APR)=1.32 (95% CI: 1.08 to 1.61)), secondary (APR=1.36 (95% CI: 1.12 to 1.65)) or tertiary education (APR=1.62 (95% CI: 1.31 to 2.00)) and health workers as a source of information on COVID-19 (APR=1.26 (95% CI: 1.10 to 1.45)). Also, reporting a medium-income (APR=1.24 (95% CI: 1.02 to 1.52)) and residence in Northern (APR=1.55, 95% CI: 1.18 to 2.02) and Central regions (APR=1.48, 95% CI: 1.16 to 1.89) were associated with vaccine uptake. CONCLUSIONS: Uptake of COVID-19 vaccines was moderate in this sample and was associated with older age, secondary and tertiary education, medium-income, region of residence and health workers as a source of COVID-19 information. Efforts are needed to increase access to vaccines and should use health workers as champions to enhance uptake.

Community policing does not build citizen trust in police or reduce crime in the Global South.

Is it possible to reduce crime without exacerbating adversarial relationships between police and citizens? Community policing is a celebrated reform with that aim, which is now adopted on six continents. However, the evidence base is limited, studying reform components in isolation in a limited set of countries, and remaining largely silent on citizen-police trust. We designed six field experiments with Global South police agencies to study locally designed models of community policing using coordinated measures of crime and the attitudes and behaviors of citizens and police. In a preregistered meta-analysis, we found that these interventions led to mixed implementation, largely failed to improve citizen-police relations, and did not reduce crime. Societies may need to implement structural changes first for incremental police reforms such as community policing to succeed.

Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning.

Signalling by intracellular second messengers such as cyclic nucleotides and Ca2+ is known to regulate attractive and repulsive guidance of axons by extracellular factors. However, the mechanism of interaction among these second messengers in determining the polarity of the guidance response is largely unknown. Here, we report that the ratio of cyclic AMP to cyclic GMP activities sets the polarity of netrin-1-induced axon guidance: high ratios favour attraction, whereas low ratios favour repulsion. Whole-cell recordings of Ca2+ currents at Xenopus spinal neuron growth cones indicate that cyclic nucleotide signalling directly modulates the activity of L-type Ca2+ channels (LCCs) in axonal growth cones. Furthermore, cGMP signalling activated by an arachidonate 12-lipoxygenase metabolite suppresses LCC activity triggered by netrin-1, and is required for growth-cone repulsion mediated by the DCC-UNC5 receptor complex. By linking cAMP and cGMP signalling and modulation of Ca2+ channel activity in growth cones, these findings delineate an early membrane-associated event responsible for signal transduction during bi-directional axon guidance.

Ultrasound screening for fetal aneuploidy using soft markers in the overweight and obese gravida.

OBJECTIVE: To determine the completion rate of ultrasound surveys for aneuploidy markers by maternal body mass index (BMI). METHODS: A retrospective review of ultrasounds on midtrimester singleton pregnancies was performed. Subjects were grouped as normal, overweight (BMI 25-29.9 kg/m(2)), and obese: class I (30-34.9 kg/m(2)), class II (35-39.9 kg/m(2)), and class III (>or= 40 kg/m(2)). Examinations with visualization of at least seven of eight markers were considered complete. RESULTS: Of 14 353 ultrasounds reviewed, 5690 patients were eligible: 43% normal, 29% overweight, 27% obese. Completion rates differed significantly between groups (64% normal, 64% overweight, 61% class I, 55% class II, 47% class III, p < 0.001). The screen positive rates (>or=1 marker) differed significantly overall (16% normal, 13% overweight, 15% class I, 12% class II, 10% class III, p < 0.02), but not for complete examinations (p = 0.42). CONCLUSIONS: Since completion rates for ultrasound aneuploidy screening are inversely related to maternal obesity, obese women are underscreened.

Facilitating an early career transition pathway to community nursing: A Delphi Policy Study.

Aim: To further develop and validate a new model of the early career transition pathway in the speciality of community nursing. Design: Delphi policy approach, guided by a previous systematic review and semi-structured interviews. Methods: Four rounds of an expert panel (N = 19). Rounds one, two and four were questionnaires consisting of a combination of closed (Likert response) and open-ended questions. Round three comprised of a focus group conducted using virtual meeting technology. Results: The final model demonstrated reliable and valid measures. There were deficiencies in "pre-entry"-where the marketing of community nursing was negligible and the support around orientation informal and minimal, mainly due to tight budgetary concerns. Community practice holds a whole new dimension for nurses transitioning from acute care as the concept of "knowing your community" took time and support-time to be accepted reciprocally and develop a sense of belonging to the community.

Preemptive Oral Compared With Intravenous Acetaminophen for Postoperative Pain After Robotic-Assisted Laparoscopic Hysterectomy: A Randomized Controlled Trial.

OBJECTIVE: To compare pain after robotic-assisted laparoscopic hysterectomy when giving preoperative oral compared with intravenous acetaminophen. METHODS: This double-blind randomized trial included women undergoing robotic-assisted laparoscopic hysterectomy for benign indications. Participants received either acetaminophen 1 g orally then normal saline 100 mL intravenously before surgery, or a placebo orally then acetaminophen 1 g intravenously. The primary outcome measured was difference in pain between the groups 2 hours postoperatively. A sample size of 74 participants (37/group) was needed to achieve 80% power to detect noninferiority using a one-sided, two-sample t-test with an alpha of 0.025 and a noninferiority margin of 10 mm. RESULTS: From April 2016 through August 2017, 77 patients were enrolled, with 75 participants included in the final analysis. Characteristics were similar between groups. No difference in average pain score was noted 2 hours after surgery, nor at any of the measured time points. Average scores for the oral and intravenous group, respectively, at 2 hours were 35 and 36 mm (P=.86), at 4 hours 36 and 37 mm (P=.96), and at 24 hours 35 and 36 mm (P=.79). Thirty-eight percent of participants in the oral group and 19% of participants in the intravenous group experienced nausea (P=.12). The oral group used 9.7 morphine equivalents in the recovery room, and the intravenous group used 9.5 morphine equivalents (P=.9). The oral group requested analgesia in 45 minutes on average, and the intravenous group requested analgesia in 43 minutes (P=.79). CONCLUSION: No difference in pain was observed 2 hours postoperatively when comparing preoperative administration of oral compared with intravenous acetaminophen. Given the ease of administration and lower cost of oral dosing, this study supports the oral route as part of the enhanced recovery after surgery protocol for minimally invasive gynecologic surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03391284.