Use of computer-assisted self-interview in detection of and referral for depression among adolescents living with HIV at an urban HIV treatment clinic in Uganda: a quasi-experimental study.

BACKGROUND: Depression is common among adolescents living with HIV (ALHIV) and impacts their quality of life. However, it is not routinely detected and treated due to a lack of screening tools, coupled with large numbers of clients in the HIV clinics and limited staff. Enabling adolescents to do a self-assessment for depression on a tablet computer could possibly improve the detection of depression in this population. We set out to assess the detection and referral of depression among ALHIV in care in Uganda. METHODS: This was a quasi-experimental study design with a historical control at Baylor College of Medicine of Children's Foundation. We conducted a retrospective chart review of 425 adolescents covering a 3-month period and documented the proportion screened for depression and referred to the clinic counsellors. From July to September 2022, eligible adolescents aged 10-19 years who had assented and consented self-assessed for depression using a Patient Health Questionnaire-Adolescent on a tablet computer-assisted self-interview (CASI). Adolescents who screened positive had a prompt on the tablet computers referring them to the counsellor for mental healthcare. We compared the proportions of participants screened for depression and referred to counsellors from clinic chart review and on the CASI using paired t-tests. RESULTS: Out of 425 medical records reviewed, 54% (231/425) were females and the median age was 15 years. Of the participants who self-assessed on the CASI, 52% (222/425) were males and the median age of all participants was 16 years. Self-assessment on the CASI increased the rate of detection of depression from 0% to 23.3%. Of those referred on the CASI, 15% accessed care at the referral point. CONCLUSION: The use of CASI improves the rate of detection of depression among ALHIV; however, there is a need to address the barriers to effective referral for mental health services.

Recent advances in emerging integrated anticorrosion and antifouling nanomaterial-based coating solutions.

The rapid progress in the marine industry has resulted in notable challenges related to biofouling and surface corrosion on underwater infrastructure. Conventional coating techniques prioritise individual protective properties, such as offering either antifouling or anticorrosion protection. Current progress and innovations in nanomaterials and technologies have presented novel prospects and possibilities in the domain of integrated multifunctional coatings. These coatings can provide simultaneous protection against fouling and corrosion. This review study focuses on the potential applications of various nanomaterials, such as carbon-based nanostructures, nano-metal oxides, polymers, metal-organic frameworks, and nanoclays, in developing integrated multifunctional nano-based coatings. These emerging integrated multifunctional coating technologies recently developed and are currently in the first phases of development. The potential opportunities and challenges of incorporating nanomaterial-based composites into multifunctional coatings and their future prospects are discussed. This review aims to improve the reader's understanding of the integrated multifunctional nano-material composite coating design and encourage valuable contributions to its development.

Patient characteristics and predictors of mortality among children hospitalised with tuberculosis: A six-year case series study in Uganda.

BACKGROUND: The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda. METHODS: We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes. RESULTS: Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis. CONCLUSIONS: In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among children.

The Safety of Volar to Dorsal Percutaneous Screw Fixation of Bennett Fracture-Dislocation - A Cadaveric Study.

Background: Bennett fractures are traditionally fixed with percutaneous K-wires from dorsal to volar, or with a volar to dorsal screw via a volar open approach. While volar to dorsal screw fixation is biomechanically advantageous, an open approach requires extensive soft tissue dissection, thus increasing morbidity. This study aims to investigate the practicality and safety of Bennett fracture fixation using a percutaneous, volar to dorsal screw, particularly with regard to the median nerve and its motor branch during wire and screw insertion. Methods: Fifteen fresh frozen forearm and hand specimens were obtained from the University of Auckland human cadaver laboratory. A guidewire is placed under image intensifier from volar to dorsal with the thumb held in traction, abduction and pronation. The wire is passed through the skin volarly under image intensifier, then the median nerve is dissected from the carpal tunnel and the motor branch of the median nerve (MBMN) is dissected from its origin to where it supplies the thenar musculature. The distance between the K-wire to the MBMN is measured. Results: In 14 of 15 specimens, the wire was superficial and radial to the carpal tunnel. The mean distance to the origin of the MBMN is 6.2 mm (95% CI 4.1-8.3) with the closest specimen 1 mm away. The mean closest distance the wire gets to any part of the MBMN is 3.7 mm (95% CI 1.6-5.8); in two specimens, the wire was through the MBMN. Conclusions: Wire placement, although done under image intensifier, is subject to significant variation in exiting location. While research has shown the thenar portal in arthroscopic thumb surgery is safe, our guidewire needs to exit further ulnar to capture the Bennett fracture fragment, placing the MBMN at risk. This cadaveric study has demonstrated the proposed technique is unsafe for use.

Viscoelastic high-molecular-weight hyaluronic acid hydrogels support rapid glioblastoma cell invasion with leader-follower dynamics.

Hyaluronic acid (HA), the primary component of brain extracellular matrix, is increasingly used to model neuropathological processes, including glioblastoma (GBM) tumor invasion. While elastic hydrogels based on crosslinked low-molecular-weight (LMW) HA are widely exploited for this purpose and have proven valuable for discovery and screening, brain tissue is both viscoelastic and rich in high-MW (HMW) HA, and it remains unclear how these differences influence invasion. To address this question, hydrogels comprised of either HMW (1.5 MDa) or LMW (60 kDa) HA are introduced, characterized, and applied in GBM invasion studies. Unlike LMW HA hydrogels, HMW HA hydrogels relax stresses quickly, to a similar extent as brain tissue, and to a greater extent than many conventional HA-based scaffolds. GBM cells implanted within HMW HA hydrogels invade much more rapidly than in their LMW HA counterparts and exhibit distinct leader-follower dynamics. Leader cells adopt dendritic morphologies, similar to invasive GBM cells observed in vivo. Transcriptomic, pharmacologic, and imaging studies suggest that leader cells exploit hyaluronidase, an enzyme strongly enriched in human GBMs, to prime a path for followers. This study offers new insight into how HA viscoelastic properties drive invasion and argues for the use of highly stress-relaxing materials to model GBM.

FATP5 Is Indispensable for the Growth of Intrahepatic Cholangiocarcinoma.

Altered lipid metabolism is a common hallmark of various cancers, including intrahepatic cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the expression of the firefly luciferase gene (FFL) to AKT1 (AKT-FFL) via an IRES linker, and then hydrodynamically injected mice with AKT-FFL and Notch1 intracellular cytoplasmic domain (NICD) to establish a luciferase-positive ICC model. This model not only enabled us to monitor and quantify tumor growth by injecting the mice with luciferin, but also allowed us to assess the fatty acid uptake rate by injecting the mice with free fatty acid luciferin (FFA-Luc). The ICC model exhibited robust uptake of exogenous fatty acids compared with the HCC model induced by AKT-FFL/ neuroblastoma Ras (Ras). Lipidomics analysis showed a dramatically higher level of fatty acid in ICC, further supporting the increased fatty acids uptake. Mechanistic studies identified FATP5 as the predominant mediator of fatty acid uptake required for ICC growth using Fatp5 knockout mice and AAV-based shRNA silencing of Fatp5. Our study discovered a novel therapeutic target for the treatment of ICC and shed light on the contributions of lipid metabolism to ICC development. IMPLICATIONS: This study provides the first in vivo evidence that FATP5 is a potential therapeutic target for treating ICC.

Hypoxia inducible factor 1-alpha in the pathogenesis of abdominal aortic aneurysms in vivo: A narrative review.

Abdominal aortic aneurysms (AAAs) are relatively common, primarily among older men, and, in the case of rupture, are associated with high mortality. Although procedure-related morbidity and mortality have improved with the advent of endovascular repair, noninvasive treatment and improved assessment of AAA rupture risk should still be sought. Several cellular pathways seem contributory to the histopathologic changes that drive AAA growth and rupture. Hypoxia inducible factor 1-alpha (HIF-1α) is an oxygen-sensitive protein that accumulates in the cytoplasm under hypoxic conditions and regulates a wide array of downstream effectors to hypoxia. Examining the potential role of HIF-1α in the pathogenesis of AAAs is alluring, because local hypoxia is known to be present in the AAA vessel wall. A systematic scoping review was performed to review the current evidence regarding the role of HIF-1α in AAA disease in vivo. After screening, 17 studies were included in the analysis. Experimental animal studies and human studies show increased HIF-1α activity in AAA tissue compared with healthy aorta and a correlation of HIF-1α activity with key histopathologic features of AAA disease. In vivo HIF-1α inhibition in animals protects against AAA development and growth. One study reveals a positive correlation between HIF-1α-activating genetic polymorphisms and the risk of AAA disease in humans. The main findings suggest a causal role of HIF-1α in the pathogenesis of AAAs in vivo. Further research into the HIF-1α pathway in AAA disease might reveal clinically applicable pharmacologic targets or biomarkers relevant in the treatment and monitoring of AAA disease.

Accuracy of C-Reactive Protein for Tuberculosis Detection in General-Population Screening and Ambulatory-Care Triage in Uganda.

Rationale: C-reactive protein (CRP) has demonstrated utility as a point-of-care triage test for tuberculosis (TB) in clinical settings, particularly among people with human immunodeficiency virus (HIV), but its performance for general-population TB screening is not well characterized. Objective: To assess the accuracy of CRP for detecting pulmonary TB disease among individuals undergoing community-based screening or presenting for evaluation of TB symptoms in Kampala, Uganda. Methods: We pooled data from two case-control studies conducted between May 2018 and December 2022 among adolescents and adults (⩾15 yr) in Kampala, Uganda. We conducted community-based screening for TB, regardless of symptoms. We enrolled people with Xpert MTB/RIF Ultra-positive (including trace) sputum results and a sample of people with Ultra-negative results. We also enrolled symptomatic patients diagnosed with TB and controls with negative TB evaluations from ambulatory care settings. Participants underwent further evaluation, including sputum culture, CRP, and HIV testing. We assessed the accuracy of CRP alone or with symptom screening against a bacteriologic reference standard. Our primary analysis evaluated the sensitivity and specificity of CRP at a cutoff of 5 mg/L. Diagnostic performance was summarized by calculating the area under the receiver operating curve (AUC). Results: In the community setting (n = 544), CRP ⩾ 5 mg/L had a sensitivity of 55.3% (95% confidence interval, 47.0-63.4%) and specificity of 84.7% (79.7-88.8%) for confirmed TB; AUC was 0.75 (0.70-0.79). Screening for CRP ⩾ 5 mg/L or positive symptoms increased sensitivity to 92.0% (86.4-95.8%) at the expense of specificity (57.1% [50.8-63.2%]). In the ambulatory care setting (n = 944), sensitivity of CRP ⩾ 5 mg/L was 86.7% (81.8-90.7%), specificity was 68.6% (64.8-72.2%), and AUC (0.84 [0.81-0.87]) did not differ significantly by HIV status. CRP ⩾ 5 mg/L was >90% sensitive among individuals with a medium or high semiquantitative Xpert result in both settings. Conclusions: Although CRP did not meet World Health Organization (WHO) TB screening benchmarks in the community, it demonstrated high specificity, and sensitivity was high among individuals with high sputum bacillary burden who are likely to be most infectious. In ambulatory care, estimated sensitivity and specificity were each within 4 percentage points of WHO benchmarks, with no meaningful difference in performance by HIV status.

Wearable Accelerometer and Gyroscope Sensors for Estimating the Severity of Essential Tremor.

BACKGROUND: Several validated clinical scales measure the severity of essential tremor (ET). Their assessments are subjective and can depend on familiarity and training with scoring systems. METHOD: We propose a multi-modal sensing using a wearable inertial measurement unit for estimating scores on the Fahn-Tolosa-Marin tremor rating scale (FTM) and determine the classification accuracy within the tremor type. 17 ET participants and 18 healthy controls were recruited for the study. Two movement disorder neurologists who were blinded to prior clinical information viewed video recordings and scored the FTM. Participants drew a guided Archimedes spiral while wearing an inertial measurement unit placed at the mid-point between the lateral epicondyle of the humerus and the anatomical snuff box. Acceleration and gyroscope recordings were analyzed. The ratio of the power spectral density between frequency bands 0.5-4 Hz and 4-12 Hz, and the sum of power spectrum density over the entire spectrum of 2-74 Hz, for both accelerometer and gyroscope data, were computed. FTM was estimated using regression model and classification using SVM was validated using the leave-one-out method. RESULTS: Regression analysis showed a moderate to good correlation when individual features were used, while correlation was high ([Formula: see text] = 0.818) when suitable features of the gyro and accelerometer were combined. The accuracy for two-class classification of the combined features using SVM was 91.42% while for four-class it was 68.57%. CONCLUSION: Potential applications of this novel wearable sensing method using a wearable Inertial Measurement Unit (IMU) include monitoring of ET and clinical trials of new treatments for the disorder.

Brown adipose tissue CoQ deficiency activates the integrated stress response and FGF21-dependent mitohormesis.

Coenzyme Q (CoQ) is essential for mitochondrial respiration and required for thermogenic activity in brown adipose tissues (BAT). CoQ deficiency leads to a wide range of pathological manifestations, but mechanistic consequences of CoQ deficiency in specific tissues, such as BAT, remain poorly understood. Here, we show that pharmacological or genetic CoQ deficiency in BAT leads to stress signals causing accumulation of cytosolic mitochondrial RNAs and activation of the eIF2α kinase PKR, resulting in activation of the integrated stress response (ISR) with suppression of UCP1 but induction of FGF21 expression. Strikingly, despite diminished UCP1 levels, BAT CoQ deficiency displays increased whole-body metabolic rates at room temperature and thermoneutrality resulting in decreased weight gain on high-fat diets (HFD). In line with enhanced metabolic rates, BAT and inguinal white adipose tissue (iWAT) interorgan crosstalk caused increased browning of iWAT in BAT-specific CoQ deficient animals. This mitohormesis-like effect depends on the ATF4-FGF21 axis and BAT-secreted FGF21, revealing an unexpected role for CoQ in the modulation of whole-body energy expenditure with wide-ranging implications for primary and secondary CoQ deficiencies.

Space-time data-driven modeling of precipitation-induced shallow landslides in South Tyrol, Italy.

Shallow landslides represent potentially damaging processes in mountain areas worldwide. These geomorphic processes are usually caused by an interplay of predisposing, preparatory, and triggering environmental factors. At regional scales, data-driven methods have been used to model shallow landslides by addressing the spatial and temporal components separately. So far, few studies have explored the integration of space and time for landslide prediction. This research leverages generalized additive mixed models to develop an integrated approach to model shallow landslides in space and time. We built upon data on precipitation-induced landslide records from 2000 to 2020 in South Tyrol, Italy (7400 km2). The slope unit-based model predicts landslide occurrence as a function of static and dynamic factors while seasonal effects are incorporated. The model also accounts for spatial and temporal biases inherent in the underlying landslide data. We validated the resulting predictions through a suite of cross-validation techniques, obtaining consistent performance scores above 0.85. The analyses revealed that the best-performing model combines static ground conditions and two precipitation time windows: a short-term cumulative precipitation of 2 days before the landslide event and a medium-term cumulative precipitation of 14 days. We demonstrated the model's predictive capabilities by predicting the dynamic landslide probabilities over historical data associated with a heavy precipitation event on August 4th and August 5th, 2016, and hypothetical non-spatially explicit precipitation (what-if) scenarios. The novel approach shows the potential to integrate static and dynamic landslide factors for large areas, accounting for the underlying data structure and data limitations.

Landscape of genetic counseling in the Philippines.

In this paper, we report on the professional development of genetic counselors in the Philippines as we discuss the status of genetic counseling training and research, along with the roles and scope of practice of genetic counselors. The development of a master's level training program for non-physician genetic counselors in the Philippines initiated in 2011 was in response to the increasing demand for genetic counseling services. There are currently 18 locally trained genetic counselors who are practicing in various fields including newborn screening, pediatrics, cancer, prenatal and preconception, neurology, and research. Despite the success of the genetic counseling training program, various professional challenges hinder maximizing the impact of genetic counselors in the health system. The challenges discussed in this paper include the limited number of genetic counselors, the lack of government positions officially recognizing the 'genetic counselor' title, and the absence of a regulatory framework. These issues require thorough discussion with appropriate government agencies and collaboration with other healthcare professional organizations with the ultimate goal of ensuring quality genetic counseling services nationwide.

Care Needs of Parents of Children With Cancer in a Low-Middle-Income Country.

Background: Mapping out actual supportive care needs assists nurses in providing holistic individualized care. This study aimed to explore the care needs of parents of children with cancer in the Philippines. Method: Guided by the Supportive Care Needs Framework (SCNF), this study used an embedded mixed-method design with the quantitative revised Cancer Patient Needs Questionnaire and qualitative semistructured interviews to describe parents' care needs and priorities. Results: Filipino parents (N = 156) of children with cancer have various care needs which could be classified along the SCNF categories-practical, informational, spiritual, physical, emotional, and physical needs as ranked from highest to lowest. A number of variables were significantly associated with care needs. Solid tumor diagnosis was associated with greater practical, emotional, and psychosocial care needs; having a child who had undergone surgery was associated with more practical and spiritual care needs; and being within one year of the child's diagnosis was associated with practical, psychosocial, and spiritual care needs. Parent priority needs included (a) addressing financial needs; (b) access to temporary housing to minimize treatment-related costs; (c) support groups among parents of children with cancer as a source of information; (d) financial and social support between members of family and partners of parents of children with cancer; and (e) using prayer to facilitate acceptance. Conclusions: Supportive care needs of parents of children with cancer are important components of care that should be given recognition to enhance holistic individualized care throughout the childhood cancer experience.

Fracture-related infection: Analysis of healthcare utilisation and associated costs.

AIMS: A consensus definition of fracture related infection (FRI) has been created with the aim of standardising diagnosis and eliminating heterogeneity that prevents accurate comparison between existing studies. FRI remains one of the most challenging complications in musculoskeletal trauma surgery and carries with it a significant cost burden. A review of UK finances has not been completed utilising consensus diagnostic criteria. The goal of this study was to investigate the hospital-associated healthcare cost related to the treatment of FRI within an NHS major trauma centre. METHOD: Through retrospective case-control analysis, 1240 patients with close fractures were identified. Of those, 21 patients with FRI were compared to 63 uninfected patients. Patients were matched based on fracture location, type of procedure and proximity in age. The costs assessed included hospitalisation, imaging, outpatient consultation, pharmaceuticals and procedure charges. Cost data was retrieved from healthcare resource group (HRG) guidelines, NHS Business Service Authority's (NBSA) prescription rates and internal costing. RESULTS: The FRI group were found to incur a 2.51 increase in total medial healthcare cost compared to the control group (£22,058 vs £8798 [p < 0.001]), which was primarily due to increased procedural costs (£13,020 vs £6291 [p < 0.001]) and length of hospital stay (£7552 vs £2124 [p < 0.001]). CONCLUSION: Whilst diagnosis of FRI has a more rigorous definition following the new consensus, prevalence and cost outcomes are similar to previous studies. Given the deficiency in funding and ongoing challenges of resource allocation to the NHS, it is prudent to incorporate studies such as this into stratifying departmental budgets and quality improvement. LEVEL OF EVIDENCE: III.

Community dialogue meetings among district leaders improved their willingness to receive COVID-19 vaccines in Western Uganda, May 2021.

BACKGROUND: Widespread COVID-19 vaccine uptake can facilitate epidemic control. A February 2021 study in Uganda suggested that public vaccine uptake would follow uptake among leaders. In May 2021, Baylor Uganda led community dialogue meetings with district leaders from Western Uganda to promote vaccine uptake. We assessed the effect of these meetings on the leaders' COVID-19 risk perception, vaccine concerns, perception of vaccine benefits and access, and willingness to receive COVID-19 vaccine. METHODS: All departmental district leaders in the 17 districts in Western Uganda, were invited to the meetings, which lasted approximately four hours. Printed reference materials about COVID-19 and COVID-19 vaccines were provided to attendees at the start of the meetings. The same topics were discussed in all meetings. Before and after the meetings, leaders completed self-administered questionnaires with questions on a five-point Likert Scale about risk perception, vaccine concerns, perceived vaccine benefits, vaccine access, and willingness to receive the vaccine. We analyzed the findings using Wilcoxon's signed-rank test. RESULTS: Among 268 attendees, 164 (61%) completed the pre- and post-meeting questionnaires, 56 (21%) declined to complete the questionnaires due to time constraints and 48 (18%) were already vaccinated. Among the 164, the median COVID-19 risk perception scores changed from 3 (neutral) pre-meeting to 5 (strong agreement with being at high risk) post-meeting (p < 0.001). Vaccine concern scores reduced, with medians changing from 4 (worried about vaccine side effects) pre-meeting to 2 (not worried) post-meeting (p < 0.001). Median scores regarding perceived COVID-19 vaccine benefits changed from 3 (neutral) pre-meeting to 5 (very beneficial) post-meeting (p < 0.001). The median scores for perceived vaccine access increased from 3 (neutral) pre-meeting to 5 (very accessible) post-meeting (p < 0.001). The median scores for willingness to receive the vaccine changed from 3 (neutral) pre-meeting to 5 (strong willingness) post-meeting (p < 0.001). CONCLUSION: COVID-19 dialogue meetings led to district leaders' increased risk perception, reduced concerns, and improvement in perceived vaccine benefits, vaccine access, and willingness to receive the COVID-19 vaccine. These could potentially influence public vaccine uptake if leaders are vaccinated publicly as a result. Broader use of such meetings with leaders could increase vaccine uptake among themselves and the community.

"See us as humans. Speak to us with respect. Listen to us." A qualitative study on UK ambulance staff requirements of leadership while working during the COVID-19 pandemic.

BACKGROUND: The COVID-19 Ambulance Response Assessment (CARA) study aimed to enable the experiences of UK frontline ambulance staff working during the first wave of the pandemic to be heard. Specifically, CARA aimed to assess feelings of preparedness and well-being and to collect suggestions for beneficial leadership support. METHODS: Three online surveys were sequentially presented between April and October 2020. Overall, 18 questions elicited free-text responses that were analysed qualitatively using an inductive thematic approach. FINDINGS: Analysis of 14 237 responses revealed participants' goals and their requirements of leadership to enable those goals to be achieved. A large number of participants expressed low confidence and anxiety resulting from disagreement, inconsistency and an absence of transparency related to policy implementation. Some staff struggled with large quantities of written correspondence and many desired more face-to-face training and an opportunity to communicate with policymakers. Suggestions were made on how best to allocate resources to reduce operational demands and maintain service delivery, and a need to learn from current events in order to plan for the future was stressed. To further support well-being, staff wanted leadership to understand and empathise with their working conditions, to work to reduce the risks and if required, to facilitate access to appropriate therapeutic interventions. CONCLUSIONS: This study demonstrates that ambulance staff desire both inclusive and compassionate leadership. Leadership should aim to engage in honest dialogue and attentive listening. Resultant learning can then inform policy development and resource allocation to effectively support both service delivery and staff well-being.

Targeted mutagenesis of the vacuolar H+ translocating pyrophosphatase gene reduces grain chalkiness in rice.

Grain chalkiness is a major concern in rice production because it impacts milling yield and cooking quality, eventually reducing market value of the rice. A gene encoding vacuolar H+ translocating pyrophosphatase (V-PPase) is a major quantitative trait locus in indica rice, controlling grain chalkiness. Higher transcriptional activity of this gene is associated with increased chalk content. However, whether the suppression of V-PPase could reduce chalkiness is not clear. Furthermore, natural variation in the chalkiness of japonica rice has not been linked with V-PPase. Here, we describe promoter targeting of the japonica V-PPase allele that led to reduced grain chalkiness and the development of more translucent grains. Disruption of a putative GATA element by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 suppressed V-PPase activity, reduced grain chalkiness and impacted post-germination growth that could be rescued by the exogenous supply of sucrose. The mature grains of the targeted lines showed a much lower percentage of large or medium chalk. Interestingly, the targeted lines developed a significantly lower chalk under heat stress, a major inducer of grain chalk. Metabolomic analysis showed that pathways related to starch and sugar metabolism were affected in the developing grains of the targeted lines that correlated with higher inorganic pyrophosphate and starch contents and upregulation of starch biosynthesis genes. In summary, we show a biotechnology approach of reducing grain chalkiness in rice by downregulating the transcriptional activity of V-PPase that presumably leads to altered metabolic rates, including starch biosynthesis, resulting in more compact packing of starch granules and formation of translucent rice grains.

Influence of time between surgery and adjuvant radiotherapy on prognosis for patients with head and neck squamous cell carcinoma: A systematic review.

The timing of postoperative radiotherapy following surgical intervention in patients with head and neck cancer remains a controversial issue. This review aims to summarize findings from available studies to investigate the influence of time delays between surgery and postoperative radiotherapy on clinical outcomes. Articles between 1 January 1995 and 1 February 2022 were sourced from PubMed, Web of Science, and ScienceDirect. Twenty-three articles met the study criteria and were included; ten studies showed that delaying postoperative radiotherapy might negatively impact patients and lead to a poorer prognosis. Delaying the start time of radiotherapy, 4 weeks after surgery did not result in poorer prognoses for patients with head and neck cancer, although delays beyond 6 weeks might worsen patients' overall survival, recurrence-free survival, and locoregional control. Prioritization of treatment plans to optimize the timing of postoperative radiotherapy regimes is recommended.

Human iPSC-Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System.

Chronic white adipose tissue (WAT) inflammation has been recognized as a critical early event in the pathogenesis of obesity-related disorders. This process is characterized by the increased residency of proinflammatory M1 macrophages in WAT. However, the lack of an isogenic human macrophage-adipocyte model has limited biological studies and drug discovery efforts, highlighting the need for human stem cell-based approaches. Here, human induced pluripotent stem cell (iPSC) derived macrophages (iMACs) and adipocytes (iADIPOs) are cocultured in a microphysiological system (MPS). iMACs migrate toward and infiltrate into the 3D iADIPOs cluster to form crown-like structures (CLSs)-like morphology around damaged iADIPOs, recreating classic histological features of WAT inflammation seen in obesity. Significantly more CLS-like morphologies formed in aged and palmitic acid-treated iMAC-iADIPO-MPS, showing the ability to mimic inflammatory severity. Importantly, M1 (proinflammatory) but not M2 (tissue repair) iMACs induced insulin resistance and dysregulated lipolysis in iADIPOs. Both RNAseq and cytokines analyses revealed a reciprocal proinflammatory loop in the interactions of M1 iMACs and iADIPOs. This iMAC-iADIPO-MPS thus successfully recreates pathological conditions of chronically inflamed human WAT, opening a door to study the dynamic inflammatory progression and identify clinically relevant therapies.