Search

BACKGROUND: Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. METHODS: This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log(10) copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of > or =1.0 log(10) copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions. RESULTS: We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log(10) copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from > or =8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P<.001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL. CONCLUSION: The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used. Copyright © 2005 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Rickettsial diseases have affected the military throughout history. Efforts such as those of the Joint U.S. Typhus Commission near the beginning of World War II and of military researchers since have reduced the impact of these diseases on U.S. and Allied forces. Despite the postwar development of effective antibiotic therapies, the newly emerging antibiotic-resistant scrub typhus rickettsial strains of the Asian Pacific region mandate continued research and surveillance. Similarly, tick-infested training areas in the United States and similar exposure abroad render the spotted fevers and the ehrlichioses problematic to deployed troops. The military continues to work on countermeasures to control the arthropod vectors, as well as actively participating in the development of rapid accurate diagnostic tests, vaccines, and improved surveillance methods. Several rickettsial diseases, including epidemic typhus, scrub typhus, the ehrlichioses, and the spotted fevers, are reviewed, with emphasis on the military historical significance and contributions. [ABSTRACT FROM AUTHOR]

We describe a case series of group A Streptococcus (GAS) necrotizing fasciitis occurring over a 10-week period in military recruits undergoing intense physical training. These cases highlight that GAS may cause life-threatening infections in addition to mild diseases such as pharyngitis. This series suggests that the incidence of severe GAS infections may be increasing in certain populations and it emphasizes the importance of considering prophylactic measures against GAS in high-risk populations. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the pain-related behavioral and physiological responses and puncture-related characteristics between automated and laser lancets and examine the correlation between infants' pain-related responses and facial expressions during heel lancing in a neonatal intensive care unit. Methods: Pain-related responses were assessed using the Neonatal Infant Pain Scale, heart rate, and oxygen saturation through pulse oximetry. Facial expressions were also analyzed using a facial recognition application. Puncture-related characteristics were assessed through puncture marks, number of punctures, and hemostasis. Results: There was a significantly higher puncture mark frequency at 3 min in the automated lancet group than in the laser lancet group. There were no interaction effects of time and group on pain-related behavioral response, heart rate, or oxygen saturation. There were significant positive correlations between the pain-related behavioral response and anger, disgust, fear, and sadness. Conclusion: The laser lancet had relatively good outcomes regarding puncture-related characteristics, although there was no significant difference in pain-related responses. A laser lancet is a novel option for preterm babies at risk of scar-related inflammation and coagulopathies.

Plasma exchange (PE) outcomes in patients with trigger-associated thrombotic microangiopathy (TMA) have not been comprehensively reviewed. Embase and MEDLINE® were searched on 03/14/2022 for English language articles published after 2007, alongside a congress materials search (2019-2022; PROSPERO: CRD42022325170). Studies with patients with trigger-associated TMA (excluding thrombotic thrombocytopenic purpura, 'typical' hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli, post-partum TMA, and TMAs with known genetic cause) who received PE or plasma infusion (PI) and reported treatment response (including measures), safety, patient-/caregiver-reported outcomes, or economic burden data were examined. The NICE quality appraisal checklist assessed bias risk. After screening 695 articles, 49 PE or PI studies were identified, of which 42 reported PE exclusively; most were retrospective observational studies (n = 37). The most common TMA trigger was transplantation (n = 12). The median number of PE sessions was 3.5-25.0. Outcomes following PE varied by trigger type. Treatment response rates and definitions varied (0-100 %; 24 studies); in studies of > 25 patients, response rates were 5-63 %. TMA relapse rates were 0-67 % (7 studies). Mortality was 10-91 % (23 studies). Progression to chronic kidney disease (CKD; 5 studies) and end-stage renal disease (ESRD; 6 studies) occurred in 0-93 % and 17-100 % of patients, respectively. Two serious adverse events were identified (transfusion-related injury, acute lung injury; 10 studies; 231 patients). Patients with trigger-associated TMA may experience a substantial burden in terms of mortality, relapse, and progression to CKD and ESRD following PE, leading to increased healthcare resource utilization. Additional interventions may be required., Competing Interests: Declaration of Competing Interest Shinya Kaname has received advisory fees and speaker fees from Alexion Pharmaceutical Co., Ltd. Moh-Lim Ong is an employee and shareholder of Alexion, AstraZeneca Rare Disease, Boston, Massachusetts. Jonathan Mathias is an employee and shareholder of Alexion, AstraZeneca Rare Disease, Boston, Massachusetts. Francesca Gatta is an employee and shareholder of Alexion Pharma GmbH, AstraZeneca Rare Disease, Zurich, Switzerland. Lisa Law was an employee of Oxford PharmaGenesis Ltd, Oxford, UK at the time of the study, which was contracted by Alexion, AstraZeneca Rare Disease to support the design and conduct of the systematic literature review. Yan Wang is an employee and shareholder of Alexion, AstraZeneca Rare Disease, Boston, Massachusetts., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To determine if postanesthesia forced-air warming as a nonpharmacologic intervention for emergence delirium (ED)/emergence agitation (EA) decreased the incidence and severity of ED in children aged 18 months to 6 years old., Design: Prospective nonrandomized controlled trial., Methods: Participants included children aged 18 months to 6 years old receiving general anesthesia within a radiation oncology setting. Status of ED/EA was based on the participants' Pediatric Anesthesia Emergence Delirium (PAED) scale score (two consecutive scores greater than 10 out of 20) or inconsolable agitation behaviors post computed tomography simulation (day 0). Interrater reliability was conducted among the center's perianesthesia care nurses. Participants who scored positive for ED/EA received a forced-air warming blanket for the remainder of treatment with data collection 1 to 14 days postanesthesia. Non-ED/EA participants were followed for 14 days and provided forced-air warming if ED/EA occurred. Data consisted of daily PAED scores and self- or parent-report on the anxiety scale. If the participants received forced-air warming, nurses' clinical observations and parent satisfaction surveys were collected 3 times during the 14-day study period., Findings: A total of 59 participants completed the study (mean age 3.43 years; 60% male; 63% non-Hispanic White); 16 were identified with ED or EA (mean age 3.56 years; 50% male; 69% non-Hispanic White) with an incidence rate of 28%. For the 16 participants with ED/EA, the primary diagnosis consisted of solid tumors and an American Society of Anesthesia Classification III to IV. Prior to the forced-air warming intervention, all 16 participants exhibited inconsolable ED/EA behaviors, including 8 who had PAED scores greater than 10. ED/EA behaviors expressed included inconsolability, confusion, thrashing, and combativeness. Within the 14-day period, 3 participants received forced-air warming on day 1, while the other 13 received an average of 4.23 days of treatment (range 1 to 11 days; mode 1 day; median 4 days). Comparison of PAED scores pre (mean 4.4) and post (mean 1.8) indicated that the use of forced-air warming was statistically significant (P = .001). ED/EA behaviors and PAED scores after the forced-air warming period decreased in all but one participant. Some agitation behaviors were not captured within the PAED score., Conclusions: Forced-air warming impacted PAED scores and agitation behaviors for studied participants, offering a safe, nonpharmacological nursing intervention that may be an effective tool for helping to manage this baffling condition., Competing Interests: Declaration of Competing Interest None to report., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Subtropical coral reefs are comparatively understudied compared to tropical coral reef ecosystems, yet also host a diverse and abundant array of marine life and provide substantial socio-economic benefits to communities. Research into the impacts of ocean warming on subtropical coral reefs has increased over the past two decades due to increase frequency and intensity of bleaching and degradation of these ecosystems. Understanding the extent of research effort and type of evidence assessing the response of subtropical corals and reefs to ocean warming provides valuable insight into global patterns in research efforts allowing critical knowledge gaps to be identified. A comprehensive understanding the impact of ocean warming on these systems will underpin our ability to predict and respond to future changes on subtropical coral reefs. Here, a systematic-map approach is used to identify recent research effort, from 2010 to 2023, and highlight patterns in the type, scale, and location of research conducted and as well as identify the availability of data and evidence reported., Methods: Primary literature was identified by searching Scopus and Science Citation Index Expanded through Web of Science Core Collection databases. The methodologies provided in a previously published systematic map protocol were applied, and 90 primary research publications were subsequently identified. Data extraction from the identified literature included bibliometric data, discipline and type of research, type of data reported and how it was recorded, and data availability., Findings: The identified literature consisted primarily of experimental (49%) and observational (39%) studies. The majority of the primary literature investigated corals in the ecoregions of Southern China (13%), Western Mediterranean (10%) and across a total of seven ecoregions grouped within Oceania (29%). Stressors reported in the literature as drivers of ocean warming reflect the standardisation of methods applied in reporting of events within the literature. Standardised metrics related to degree heating weeks (DHW) and marine heatwaves (MHW) have been reported when assessing the occurrence and severity of drivers, and are increasing in recent years, particularly in Australia. Finally, the need for increased research effort across much of the subtropics is evident, particularly for understudied regions such as the Western Indian Ocean where there are far fewer studies than other similar subtropical coral reef ecosystems., Conclusions: Climatic change, increasing ocean temperatures, and the impacts to subtropical and temperate coral reefs are of increasing concern to policy makers and researchers alike. This systematic map provides a broad overview of research topics and effort around the globe since 2010 and identifies areas where more research effort is urgently needed. Our study has identified major research clusters in Asia, Australia, the Mediterranean, and North America and gaps of research in regions such as the East Indian Oceans. Of the research conducted to date approximately one third reports on evidence related to marine protected areas and the vast majority of evidence is from close/territorial sea locations, providing important knowledge base for management of these areas. Of the 17 studies reporting on specific extreme events (rather than experimental studies which is the majority of evidence identified here) 13 have been published since 2019, with the majority reporting on events occurring in 2019/20 indicating a trend of increasing evidence in recent years (a total of 7 studies from 2010 to 2013, compared to over 10 studies published annually since 2019 up to mid-2023)., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

The soil microbiome is crucial for nutrient cycling, health, and plant growth. This study presents a smartphone-based approach as a low-cost and portable alternative to traditional methods for classifying bacterial species and characterizing microbial communities in soil samples. By harnessing bacterial autofluorescence detection and machine learning algorithms, the platform achieved an average accuracy of 88% in distinguishing common soil-related bacterial species despite the lack of biomarkers, nucleic acid amplification, or gene sequencing. Furthermore, it successfully identified dominant species within various bacterial mixtures with an accuracy of 76% and three-level soil health identification at an accuracy of 80%-82%, providing insights into microbial community dynamics. The influence of other soil conditions (pH and moisture) was relatively minor, showcasing the platform's robustness. Various field soil samples were also tested with this platform at 80% accuracy compared with the laboratory analyses, demonstrating the practicality and usability of this approach for on-site soil analysis. This study highlights the potential of the smartphone-based system as a valuable tool for soil assessment, microbial monitoring, and environmental management., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Background: For years, nurse researchers have been called upon to engage with "big data" in the electronic health record (EHR) by leading studies focusing on nurse-centric patient outcomes and providing clinical analysis of potential outcome indicators. However, the current gap in nurses' data science education and training poses a significant barrier., Objectives: We aimed to evaluate the viability of conducting nurse-led, big-data research projects within a custom-designed computational laboratory and examine the support required by a team of researchers with little to no big-data experience., Methods: Four nurse-led research teams developed a research question reliant on existing EHR data. Each team was given its own virtual computational laboratory populated with raw data. A data science education team provided instruction in coding languages-primarily structured query language and R-and data science techniques to organize and analyze the data., Results: Three research teams have completed studies, resulting in one manuscript currently undergoing peer review and two manuscripts in progress. The final team is performing data analysis. Five barriers and five facilitators to big-data projects were identified., Discussion: As the data science learning curve is steep, organizations need to help bridge the gap between what is currently taught in doctoral nursing programs and what is required of clinical nurse researchers to successfully engage in big-data methods. In addition, clinical nurse researchers require protected research time and a data science infrastructure that supports novice efforts with education, mentorship, and computational laboratory resources., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Medical students in Singapore engage in short term medical missions, locally known as Overseas Community Involvement Projects (OCIPs). Little is known about the learning outcomes of an OCIP and how this complements their medical education back home. Understanding this can help the medical educators structure the OCIP to optimise its learning value., Objectives: This study aims to gain an in-depth understanding of the experiences and learning outcomes of the medical students who participated in the OCIP., Methods: This was a qualitative study involving Singaporean students from one medical school travelling to Nepal. Data was collected from reflective journals, overall group reflections and two focus group discussions. The data was thematically analysed using the Accreditation Council for Graduate Medical (ACGME) core competencies for medical professionals., Results: The data could be classified under various themes within the six domains of the ACGME framework. The study revealed themes of: humanism, socioeconomic and cultural determinants of health under the domain of patient care, application of medical knowledge, investigating and evaluating the needs of a population and feedback to drive improvement under the domain of practice-based learning and improvement, use of non-verbal cues and communicating across language barriers under the domain of interpersonal and communication skills, healthcare systems and delivery, resourcefulness and adaptability, health equity and accessibility under the domain of systems-based practice, ethics, role-modelling, teamwork and leadership skills, interprofessional skills and resilience under the domain of professionalism. Understanding the students' motivations, utilising reflections, and following the patients' journey facilitated attainment of these outcomes., Conclusions: This OCIP experience translated to learning outcomes aligned with the ACGME framework. There is great potential for the experiential learning from a well-structured OCIP to help with personal and professional development and global health education., (© 2024. The Author(s).)

While plaques comprised of fibrillar Aβ aggregates are hallmarks of Alzheimer's disease, soluble Aβ oligomers present higher neurotoxicity. Thus, one therapeutic approach is to prevent the formation of Aβ oligomers and reduce their associated harmful effects. We have proposed a peptoid mimic of the Aβ hydrophobic KLVFF core as an ideal candidate aggregation inhibitor due to its ability to evade proteolytic degradation via repositioning of the side chain from the α-carbon to the amide nitrogen. This peptoid, JPT1, utilizes chiral sidechains to achieve a helical structure, while C-terminal addition of two phenylalanine residues places aromatic groups on two sides of the helix with spacing designed to facilitate interaction with amyloid β-sheet structure. We have previously shown that JPT1 modulates Aβ fibril formation. Here, we demonstrate that JPT1 also modulates Aβ oligomerization, and we explore the role of the charge on the linker between the KLVFF mimic and the extended aromatic residues. Additionally, we demonstrate that peptoid-induced changes in Aβ oligomerization correlate with attenuation of oligomer-induced nuclear factor-κB activation in SH-SY5Y human neuroblastoma cells. These findings support the therapeutic potential of peptoids to target early stages of Aβ aggregation and impact the associated Aβ-induced cellular response., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Purpose: With an ageing population, the use of mobility scooters by community-dwelling older adults with mobility limitations has been increasingly prevalent in Singapore. Their experiences in using mobility scooters remain unclear. This study aimed to explore the impact of mobility scooters on occupational performance and engagement among elderly Singaporeans., Materials and Methods: Mobility scooter users were recruited via purposive and snowballing sampling. Semi-structured interviews were conducted in English or Mandarin via phone call or face-to-face and audio-recorded with permission. Interviews were transcribed verbatim in their original language and translated to English (when applicable) for thematic analysis., Results: Twelve eligible participants (mean age: 75 years) completed the interviews. They were predominantly female Chinese with 7 receiving training from occupational therapists (OT). Four main themes emerged from the interviews describing their experiences of using mobility scooters: factors of decision-making in getting a mobility scooter, enhanced occupational participation with the use of the mobility scooter, enablers for community participation and barriers to community participation. Despite having barriers, older adults with mobility limitations generally still had positive experiences to continue using mobility scooters to perform occupations in the community., Conclusions: This study highlights the benefits of mobility scooters in supporting users' occupational performance and engagement in the community. Continual efforts are required from all stakeholders to provide an accessible environment and improve societal attitudes to further support the mobility scooter users.IMPLICATIONS FOR REHABILITATIONMobility scooter users can be deterred from performing their preferred occupations if they had a prior negative encounter and they mainly rely on self-developed coping strategies to overcome possible barriers in the community.Occupational therapists should identify and address the potential barriers when prescribing mobility scooters to older adult users.Occupational therapists should work collaboratively with other key stakeholders, such as external vendors and government agencies, to co-create a universal guideline to support and safeguard mobility scooter users.

Background: Social isolation and low levels of physical activity are strong drivers for frailty, which is linked to poor health outcomes and transition to long-term care. Frailty is multifactorial, and thus an integrated approach is needed to maintain older adults' health and well-being. Intergenerational programs represent a novel multifactorial approach to target frailty, social isolation and physical decline but these have not yet been rigorously tested in Australia. Here, we present the results of our pilot study which aimed to test the feasibility of a 10-week intergenerational program between older adults and preschool children., Methods: A non-randomised wait-listed controlled trial was conducted. Participants were allocated to either the intervention or wait-list control group. The intervention group received 10 weekly 2-h intergenerational sessions led by trained child educators; the control group continued with their usual routine and received their intergenerational program after the 10-week control period. All participants were assessed at baseline and 10 weeks. The primary outcome was the feasibility and acceptability of the program including measures of recruitment eligibility, adherence and effective data collection across the multiple domains important for frailty, including functional mobility and balance, grip strength, cognitive function, mood, social engagement, quality of life and concerns about falling., Results: Nineteen adults were included, with nine in the intervention and ten in the control group. A total of 42% of older adults screened were eligible, 75% of participants were present at each intervention session and the overall attrition rate was 21% (n = 4). The reasons for participant absence were primarily health-related. Missing data was minimal for the majority of assessments but more apparent for the cognitive testing where completion rates ranged from 53 to 79% for baseline tests and 73 to 100% for those who received follow-up testing., Conclusions: The high program compliance and low attrition show that a 10-week intergenerational program embedded in the local community, designed for community-living older adults and preschool children, is feasible and acceptable to older adults. Our next trial will test the efficacy of intergenerational programs in this setting., (© 2024. The Author(s).)

Introduction: Concerns about falling (CaF) are common in older people and have been associated with avoidance of activities of daily life. Exercise designed to prevent falls can reduce CaF, but the effects are usually short-lived. Cognitive behavioural therapy (CBT) can reduce CaF for longer but is not readily available in the community and unlikely to prevent falls. A multidomain intervention that combines CBT, motivational interviewing and exercise could be the long-term solution to treat CaF and reduce falls in older people with CaF. This paper describes the design of a randomised controlled trial to test the effectiveness of two different 12 week self-managed eHealth programmes to reduce CaF compared with an active control., Methods: A total of 246 participants (82 per group) aged 65 and over, with substantial concerns about falls or balance will be recruited from the community. They will be randomised into: (1) myCompass-Own Your Balance (OYB) (online CBT programme) intervention or (2) myCompass-OYB plus StandingTall intervention (an eHealth balance exercise programme), both including motivational interviewing and online health education or (3) an active control group (online health education alone). The primary outcome is change in CaF over 12 months from baseline of both intervention groups compared with control. The secondary outcomes at 2, 6 and 12 months include balance confidence, physical activity, habitual daily activity, enjoyment of physical activity, social activity, exercise self-efficacy, rate of falls, falls health literacy, mood, psychological well-being, quality of life, exercise self-efficacy, programme adherence, healthcare use, user experience and attitudes towards the programme. An intention-to-treat analysis will be applied. The healthcare funder's perspective will be adopted for the economic evaluation if appropriate., Ethics and Dissemination: Ethical approval was obtained from the South Eastern Sydney Local Health District Human Research Ethics Committee (2019/ETH12840). Results will be disseminated via peer-reviewed journals, local and international conferences, community events and media releases., Trial Registration Number: ACTRN12621000440820., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

NSCLC, the most common type of lung cancer, is often diagnosed late due to minimal early symptoms. Its high risk of recurrence or metastasis post-chemotherapy makes DC-based immunotherapy a promising strategy, offering targeted cancer destruction, low side effects, memory formation, and overcoming the immune evasive ability of cancers. However, the limited response to DCs pulsed with single antigens remains a significant challenge. To overcome this, we enhanced DC antigen presentation by pulsing with TAAs. Our study focused on enhancing DC-mediated immune response specificity and intensity by combinatorial pulsing of TAAs, selected for their prevalence in NSCLC. We selected four types of TAAs expressed in NSCLC and pulsed DCs with the optimal combination. Next, we administered TAAs-pulsed DCs into the LLC1 mouse model to evaluate their anti-tumor efficacy. Our results showed that TAAs-pulsed DCs significantly reduced tumor size and promoted apoptosis in tumor tissue. Moreover, TAAs-pulsed DCs significantly increased total T cells in the spleen compared to the unpulsed DCs. Additionally, in vitro stimulation of splenocytes from the TAAs-pulsed DCs showed notable T-cell proliferation and increased IFN-γ secretion. Our findings demonstrate the potential of multiple TAA pulsing to enhance the antigen-presenting capacity of DCs, thereby strengthening the immune response against tumors.

We present a single-shot detection method of terahertz correlated second harmonic generation in plasma-based sources by directly mixing an optical probe into femtosecond laser-induced plasma filaments in air. The single-shot second harmonic trace is obtained by measuring a second harmonic generation on a conventional CCD with a spatiotemporally distorted probe beam. The system shows a spectrometer resolution of 22 fs/pixel on the CCD and a true resolution on the order of the probe pulse duration. With considerable THz peak electric field strength, this formalism can open the door to single-shot THz detection without bandwidth limitations.

Introduction: Deep brain stimulation (DBS) is a well-established surgical therapy for patients with Parkinsons' Disease (PD). Traditionally, DBS surgery for PD is performed under local anesthesia, whereby the patient is awake to facilitate intraoperative neurophysiological confirmation of the intended target using microelectrode recordings. General anesthesia allows for improved patient comfort without sacrificing anatomic precision and clinical outcomes., Methods: We performed a systemic review and meta-analysis on patients undergoing DBS for PD. Published randomized controlled trials, prospective and retrospective studies, and case series which compared asleep and awake techniques for patients undergoing DBS for PD were included. A total of 19 studies and 1,900 patients were included in the analysis., Results: We analyzed the (i) clinical effectiveness - postoperative UPDRS III score, levodopa equivalent daily doses and DBS stimulation requirements. (ii) Surgical and anesthesia related complications, number of lead insertions and operative time (iii) patient's quality of life, mood and cognitive measures using PDQ-39, MDRS, and MMSE scores. There was no significant difference in results between the awake and asleep groups, other than for operative time, for which there was significant heterogeneity., Conclusion: With the advent of newer technology, there is likely to have narrowing differences in outcomes between awake or asleep DBS. What would therefore be more important would be to consider the patient's comfort and clinical status as well as the operative team's familiarity with the procedure to ensure seamless transition and care., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

While the primary pathology of Alzheimer's disease (AD) is defined by brain deposition of amyloid-β (Aβ) plaques and tau neurofibrillary tangles, chronic inflammation has emerged as an important factor in AD etiology. Upregulated cell surface expression of the receptor for advanced glycation end-products (RAGE), a key receptor of innate immune response, is reported in AD. In parallel, RAGE ligands, including Aβ aggregates, HMGB1, and S100B, are elevated in AD brain. Activation of RAGE by these ligands triggers release of inflammatory cytokines and upregulates cell surface RAGE. Despite such observation, there are currently no therapeutics that target RAGE for treatment of AD-associated neuroinflammation. Peptoids, a novel class of potential AD therapeutics, display low toxicity, facile blood-brain barrier permeability, and resistance to proteolytic degradation. In the current study, peptoids were designed to mimic Aβ, a ligand that binds the V-domain of RAGE, and curtail RAGE inflammatory activation. We reveal the nanomolar binding capability of peptoids JPT1 and JPT1a to RAGE and demonstrate their ability to attenuate lipopolysaccharide-induced pro-inflammatory cytokine production as well as upregulation of RAGE cell surface expression. These results support RAGE antagonist peptoid-based mimics as a prospective therapeutic strategy to counter neuroinflammation in AD and other neurodegenerative diseases., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Adherence and participation can be improved in health programs for older people with concerns about falling. While health literacy empowers older people to have greater control over their health, little is known about the extent to which health literacy influences health behaviours associated with concerns about falling in older people. This study aimed to synthesise current findings on health literacy, concerns about falling and falls to propose a multicomponent theoretical model on health literacy and concerns about falling. The model was developed based on a review of the literature, existing frameworks and models on health literacy and concerns about falling. Existing evidence on the relationship between health literacy and concerns about falling in older people is limited. Evidence from other research areas, however, shows that health literacy is closely related to many of the determinants of concerns about falling. More research is needed to clarify the impact of health literacy on intervention adherence and decision-making processes of older people with concerns about falling. Our model offers a novel perspective on the role of health literacy in health behaviours associated with concerns about falling, suggesting new research directions and providing insights for clinicians to consider health literacy when managing older patients with concerns about falling., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We report a systematic investigation into the processes behind a near hundred-fold enhanced second harmonic wave generated from a laser-induced air plasma, by examining the temporal dynamics of the frequency conversion processes, and the polarization of the emitted second harmonic beam. Contrary to typical nonlinear optical processes, the enhanced second harmonic generation efficiency is only observed within a sub-picosecond time window and found to be nearly constant across fundamental pulse durations spanning from 0.1 ps to over 2 ps. We further demonstrate that with the adopted orthogonal pump-probe configuration, the polarization of the second harmonic field exhibits a complex dependence on the polarization of both input fundamental beams, contrasting with most of the previous experiments with a single-beam geometry.

Background: Traditional face-to-face cognitive behavioural therapy (CBT) has been successful at reducing fear of falling (FOF) in older people but can be labour-intensive and costly. Online CBT has been suggested as a cost-effective alternative but has not yet been tested in the context of FOF. This study evaluates the effectiveness of a readily available, self-guided and generalised online CBT program (myCompass) on reducing FOF in older people., Methods: Fifty community-dwelling older people with FOF received a paper-based health education program, and half were randomly assigned to receive three selected modules from myCompass for 6 weeks. The primary outcome was feared consequences of falling at 6 weeks. Secondary outcomes were concern about falling, balance confidence, activity avoidance, physical activity, exercise self-efficacy, health literacy and mental health at 6/26/52 weeks and falls incidence at 12 months., Results: All intervention participants completed at least 2-out-of-3 myCompass modules. There was a significant main effect of time on feared consequences of falling (Cohen's f = 0.55). The group by time interactions for concern about falling (f = 0.28), stress (f = 0.26) and social support for health (health literacy) (f = 0.26) was also significant, favouring the control group. The overall attrition rate at 12 months was 24% (n = 12)., Conclusion: The high program compliance and low attrition rate suggest that online CBT is feasible among older people. However, the myCompass program had no effect at reducing FOF in older people. A more targeted CBT program with a well-integrated psychoeducation module on FOF might be the solution to boost the therapeutic effects of a generalised CBT program at reducing FOF for older people., (© 2022. International Society of Behavioral Medicine.)

Background: Pelvic organ prolapse (POP) refers to symptomatic descent of the vaginal wall. To reduce surgical failure rates, surgical correction can be augmented with the insertion of polypropylene mesh. This benefit is offset by the risk of mesh complication, predominantly mesh exposure through the vaginal wall. If mesh placement is under consideration as part of prolapse repair, patient selection and counseling would benefit from the prediction of mesh exposure; yet, no such reliable preoperative method currently exists. Past studies indicate that inflammation and associated cytokine release is correlated with mesh complication. While some degree of mesh-induced cytokine response accompanies implantation, excessive or persistent cytokine responses may elicit inflammation and implant rejection., Objective: Here, we explore the levels of biomaterial-induced blood cytokines from patients who have undergone POP repair surgery to (1) identify correlations among cytokine expression and (2) predict postsurgical mesh exposure through the vaginal wall., Methods: Blood samples from 20 female patients who previously underwent surgical intervention with transvaginal placement of polypropylene mesh to correct POP were collected for the study. These included 10 who experienced postsurgical mesh exposure through the vaginal wall and 10 who did not. Blood samples incubated with inflammatory agent lipopolysaccharide, with sterile polypropylene mesh, or alone were analyzed for plasma levels of 13 proinflammatory and anti-inflammatory cytokines using multiplex assay. Data were analyzed by principal component analysis (PCA) to uncover associations among cytokines and identify cytokine patterns that correlate with postsurgical mesh exposure through the vaginal wall. Supervised machine learning models were created to predict the presence or absence of mesh exposure and probe the number of cytokine measurements required for effective predictions., Results: PCA revealed that proinflammatory cytokines interferon gamma, interleukin 12p70, and interleukin 2 are the largest contributors to the variance explained in PC 1, while anti-inflammatory cytokines interleukins 10, 4, and 6 are the largest contributors to the variance explained in PC 2. Additionally, PCA distinguished cytokine correlations that implicate prospective therapies to improve postsurgical outcomes. Among machine learning models trained with all 13 cytokines, the artificial neural network, the highest performing model, predicted POP surgical outcomes with 83% (15/18) accuracy; the same model predicted POP surgical outcomes with 78% (14/18) accuracy when trained with just 7 cytokines, demonstrating retention of predictive capability using a smaller cytokine group., Conclusions: This preliminary study, incorporating a sample size of just 20 participants, identified correlations among cytokines and demonstrated the potential of this novel approach to predict mesh exposure through the vaginal wall following transvaginal POP repair surgery. Further study with a larger sample size will be pursued to confirm these results. If corroborated, this method could provide a personalized medicine approach to assist surgeons in their recommendation of POP repair surgeries with minimal potential for adverse outcomes., (©Mihyun Lim Waugh, Nicholas Boltin, Lauren Wolf, Jane Goodwin, Patti Parker, Ronnie Horner, Matthew Hermes, Thomas Wheeler, Richard Goodwin, Melissa Moss. Originally published in JMIR Perioperative Medicine (http://periop.jmir.org), 31.05.2023.)

Rationale and Objective: Ravulizumab and eculizumab have shown efficacy for the treatment of atypical hemolytic uremic syndrome (aHUS), but real-world evidence for ravulizumab is limited owing to its more recent approval. This real-world database study examined outcomes for adult patients switching to ravulizumab from eculizumab and patients treated with individual treatments., Study Design: A retrospective, observational study using the Clarivate Real World Database., Setting and Population: US health-insurance billing data (January 2012 to March 2021) of patients aged 18 years or older with ≥1 diagnosis relevant to aHUS, ≥1 claim for treatment with eculizumab or ravulizumab, and no evidence of other indicated conditions., Exposures: Treatment-switch (to ravulizumab after eculizumab), ravulizumab-only, and eculizumab-only cohorts were examined., Outcomes: Clinical procedures, facility visits, health care costs, and clinical manifestations., Analytical Approach: Paired-sample statistical testing compared the mean numbers of claims for each group 0-3 months before (preindex period) and 0-3 months and 3-6 months after (postindex period) the index date (point of initiation with a single treatment or treatment switch)., Results: In total, 322 patients met the eligibility criteria at 3-6 months postindex in the treatment-switch (n=65), ravulizumab-only (n=9), and eculizumab-only (n=248) cohorts. The proportions of patients with claims for key clinical procedures continued to be small after treatment switch and were small (0%-11%) across all cohorts at 3-6 months postindex. Inpatient visits were reduced in the postindex period across all cohorts. At 3-6 months after treatment switch, patients reported fewer claims for outpatient, private practice, and home visits and lower median health care costs. The proportions of patients with claims for clinical manifestations of aHUS were generally reduced in the postindex period compared with those of the preindex period., Limitations: Low patient numbers receiving ravulizumab only., Conclusions: The health-insurance claims data showed a reduced health care burden for US adult patients after treatment with ravulizumab or eculizumab for treatment of aHUS., (© 2023 The Authors.)

Background: The aim of the study was to determine the rate of cytomegalovirus virolactia in the human milk (HM) of mothers of VLBW infants, compare the CMV infection rates and the changes in CMV DNA viral load and nutrient profile among different HM preparation methods., Methods: A prospective randomized controlled study was performed in infants with gestational age < 32 weeks or birth-weight < 1500 g admitted to neonatal intensive care unit of Asan Medical Center and Haeundae Paik Hospital who were given mother's own milk. Enrolled infants were randomized into three groups according to the HM preparation methods: freezing-thawing (FT), FT + low-temperature Holder pasteurization (FT + LP), and FT + high-temperature short-term pasteurization (FT + HP). Urine CMV culture and PCR were obtained at birth and at 4, 8, and 12 weeks. HM CMV culture and PCR were obtained at birth and at 3, 6, 9, and 12 weeks. Changes in macronutrients in HM was obtained at 4 ~ 6 weeks., Results: Of 564 infants, 217 mothers (38.5%) produced CMV PCR positive milk. After exclusion, a total of 125 infants were randomized into the FT (n = 41), FT + LP (n = 42), and FT + HP (n = 42) groups, whose rate of HM-acquired CMV infection was 4.9% (n = 2), 9.5% (n = 4), and 2.4% (n = 1), respectively. Out of seven CMV infected infants, two infants fed with FT + LP HM developed CMV infection- associated symptoms. Ages at diagnoses were earlier (28.5 days after birth) and at younger post conceptional age (< 32 weeks) in comparison to infants with asymptomatic CMV infection. CMV DNA viral load significantly decreased after pasturizations, especially in FT + HP group., Conclusions: HM-acquired symptomatic CMV infection rate is low and its impact on clinical course was not serious in our VLBW infants. However, evidences showing poor neurodevelopmental outcome in later life, we need to generate a guideline to protect VLBW infant form HM transmitted CMV infection. Based on our small sized study, we did not find any superiority in pasteurizing HM with frequently used LP in comparison to frozen or HP HM. More research is needed to determine the method and duration of pasteurization to reduce the HM-acquired CMV infection., (© 2023. The Author(s).)

Concerns (or 'fears') about falling (CaF) are common in older adults. As part of the 'World Falls Guidelines Working Group on Concerns about Falling', we recommended that clinicians working in falls prevention services should regularly assess CaF. Here, we expand upon these recommendations and argue that CaF can be both 'adaptive' and 'maladaptive' with respect to falls risk. On the one hand, high CaF can lead to overly cautious or hypervigilant behaviours that increase the risk of falling, and may also cause undue activity restriction ('maladaptive CaF'). But concerns can also encourage individuals to make appropriate modifications to their behaviour to maximise safety ('adaptive CaF'). We discuss this paradox and argue that high CaF-irrespective of whether 'adaptive' or 'maladaptive'-should be considered an indication that 'something is not right', and that is represents an opportunity for clinical engagement. We also highlight how CaF can be maladaptive in terms of inappropriately high confidence about one's balance. We present different routes for clinical intervention based on the types of concerns disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Subpial hemorrhage (SPH) is a subtype of intracranial hemorrhage characterized by damage to the adjacent brain parenchyma. The aim of this study was to describe the sonographic features of SPH in neonates., Methods: The cranial ultrasound (US) findings of neonates with SPH confirmed by brain magnetic resonance imaging (MRI) were analyzed retrospectively. Initial and follow-up US and MRI scans were reviewed by two pediatric radiologists who were blinded to both clinical history and outcomes. The US features were compared with the MRI findings., Results: Sixteen patients were included (median gestational age, 38 weeks; range, 26 to 40 weeks; 69% term). SPH was detected most often in the temporal lobe (63%), and multiple SPHs were found in seven of 16 neonates, based on MRI. Acute SPH with an underlying venous infarct (UVI) was detected on US in 15 of 16 patients: small or large fan-shaped hyperechoic lesions (n=7 and 4, respectively) and gyriform hyperechoic lesions (n=4). The sonographic yin-yang sign was observed in three of the four large fan-shaped SPH cases. The accompanying findings on US were intraventricular hemorrhage (four out of six MRI-confirmed cases), and concurrent periventricular venous infarcts (five out of nine MRI-confirmed cases). In five patients, subpial cysts were observed on follow-up US or MRI (n=4 and n=4, respectively)., Conclusion: Acute SPH with UVI can appear as a peripheral fan-shaped or gyriform hyperechoic lesion on cranial US. SPH can be detected and suspected based on the US features of SPH with the accompanying findings.

The energy consumed in buildings constitutes more than half of the total electricity consumption and is highly correlated with the number of occupants; therefore, it is necessary to use occupancy information in energy consumption analysis. However, the number of occupants may not be accurate owing to measurement errors caused by various factors, such as the locations of sensors or cameras and the communication environment. In this study, occupancy was measured using an object recognition camera, the number of people was additionally collected by manual aggregation, measurement error in occupancy count was analyzed, and the true count was estimated using a deep learning model. The energy consumption based on occupancy was predicted using the measured and estimated values. To this end, deep learning was used to predict energy consumption after analyzing the correlation between occupancy and energy consumption. Results showed that the performance of occupancy estimation was 1.9 based on RMSE, which is a 71.1% improvement compared to the original occupancy sensing. The RMSE of predicted energy consumption based on the estimated occupancy was 56.0, which is a 5.2% improvement compared to the original energy estimation.

We report the observation of terahertz field-induced second harmonic (TFISH) generation produced by directly mixing an optical probe beam onto femtosecond plasma filaments. The produced TFISH signal is spatially separated from the laser-induced supercontinuum by impinging on the plasma at a noncollinear angle. The conversion efficiency of the fundamental probe beam to its second harmonic (SH) beam is greater than 0.02%, which represents a record in optical probe to TFISH conversion efficiency that is nearly five orders of magnitude larger than previous experiments. We also present the terahertz (THz) spectral buildup of the source along the plasma filament and retrieve coherent terahertz signal measurements. This method of analysis has the potential to provide local electric field strength measurements inside of the filament.

Background: Nursing professional organizations and media sources indicated early in the pandemic that the physical and psychological effects of COVID-19 might be distinct and possibly greater in nurses than in other types of healthcare workers (HCWs)., Objectives: Based on survey data collected in Healthcare Worker Exposure Response and Outcomes (HERO), a national registry of U.S. HCWs, this study compared the self-reported experiences of nurses with other HCWs during the first 13 months of the pandemic., Methods: Nurse responses were compared to responses of nonnurse HCWs in terms of viral exposure, testing and infection, access to personal protective equipment (PPE), burnout, and well-being. Logistic regression models were used to examine associations between nurse and nonnurse roles for the binary end points of viral testing and test positivity for COVID-19. We also examined differences by race/ethnicity and high-risk versus low-risk practice settings., Results: Of 24,343 HCWs in the registry, one third self-identified as nurses. Nurses were more likely than other HCWs to report exposure to SARS-CoV-2, problems accessing PPE, and decreased personal well-being, including burnout, feeling tired, stress, trouble sleeping, and worry. In adjusted models, nurses were more likely than nonnurse HCWs to report viral testing and test positivity for COVID-19 infection. Nurses in high-risk settings were more likely to report viral exposure and symptoms related to well-being; nurses in low-risk settings were more likely to report viral testing and test positivity. Black or Hispanic nurses were most likely to report test positivity., Discussion: Differences were identified between nurses and nonnurse HCWs in access to PPE, physical and mental well-being measures, and likelihood of reporting exposure and infection. Among nurses, testing and infection differed based on race and ethnicity, and type of work setting. Our findings suggest further research and policy are needed to elucidate and address social and occupational disparities., Competing Interests: Drs. Thomas, O’Brien, and Forrest report grants from PCORI, during the conduct of the study. Dr. O’Brien also reports grant from Pfizer. The remaining authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Air pollution is a significant contributor to cardiovascular and cerebrovascular diseases. including intracranial hemorrhage (ICH). However, associations between air pollution, various pollutants, and ICH are complex and remain poorly understood. Limited data are available on the relationship between ICH and individual air pollutants. In this review, we present an overview of the current literature about ambient air pollutants that are believed to contribute towards ICH as well as possible underlying mechanisms., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Lance-Adams syndrome (chronic post-hypoxic myoclonus) is a rare syndrome occurring in patients after cardiopulmonary resuscitation. Awareness of this condition is important to distinguish it from myoclonic status epilepticus, which is a poor prognostic sign. We present the case of a 32-year-old woman who developed Lance-Adams syndrome after an episode of hypoxic cardiac arrest from severe pneumonia. Brain computed tomography, magnetic resonance imaging, and an electroencephalogram were used to rule out other causes of myoclonus. In this report, we discuss the diagnosis, treatment, and prognosis of patients with Lance-Adams syndrome., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Objectives: (i) To develop the Falls Health Literacy Scale (FHLS), a health literacy tool specific to falls, (ii) to evaluate the FHLS's construct validity towards differentiating individuals with different fall-related health literacy, and (iii) to determine its reliability, construct validity and structure in an older population., Methods: The initial FHLS, developed based on Sørensen et al.'s health literacy model, was first administered to 144 participants aged ≥18 years for feedback and scale improvement and preliminary analysis to determine the FHLS's construct validity in identifying individuals with different fall-related health literacy. After scale refinement, the FHLS was validated in 227 community-living people aged ≥65 years., Results: Adult participants with more fall prevention knowledge scored higher on the initial FHLS than those with less fall prevention knowledge (p≤0.001). The final FHLS includes a 25-item subjective and a 14-item objective scale. Older people with ≥1 fall in the past year reported lower FHLS-subjective scores than those who had no falls (Cohen's [d]=0.29, confidence interval [CI]:0.03-0.56, p=0.03). Older people with lower levels of education had lower FHLS-objective scores than their more educated counterparts (d=0.51, CI:0.38-1.43, p≤0.001). Factor analysis of the FHLS-subjective generated six subscales, with CFA showing adequate model fit (RMSEA=0.077, CFI=0.883 and χ2/df =2.35). FHLS-subjective (25-item) showed good reliability, with Cronbach's alpha=0.93, mean inter-item correlation=0.34 (range -0.03-0.81) and intra-class coefficient =0.86 (95% CI:0.69-0.93)., Conclusion: The novel, context-specific FHLS displayed good construct validity and reliability. The FHLS holds promise as a screening tool to differentiate individuals with different degrees of fall-related health literacy, which may help guide fall prevention interventions., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)