Because We Love You (BeWeL): A protocol for a randomized controlled trial of two brief interventions focused on social and cultural connectedness to reduce risk for suicide and substance misuse in young Alaska Native people.

Background: Suicide among young people in Alaska Native (AN) communities was nearly unheard of through the establishment of statehood in 1959, but in the 1970s, AN suicide rates began to double every five years, with most of the increase due to suicide among 15 to 25-year-olds. From 1960-1995, the suicide rate increased by approximately 500% during this period of rapid, imposed social transition. For example, families were forced to live in settlements and children were sent to boarding schools. These disruptions increased conditions associated with suicide risk (e.g., substance use disorders, cultural disconnection), and challenged the community-level social safety net of youth protective factors that might have moderated effects of these traumas. The present study addresses the significant gap in culturally appropriate evidence-based programming to address suicide prevention among AN young people as part of aftercare. Our key research questions and methodology have been informed by AN stakeholders, and the intervention approach is Indigenous-led. Methods: Our interventions are targeted toward Alaska Native young people ages 14-24 who present with suicide attempt, ideation, or associated risk behaviors, including alcohol-related injury in the Yukon-Kuskokwim region or the Interior. In a randomized controlled trial, 14-24-year-old AN individuals will receive either BeWeL (n = 185), which comprises a 45-minute virtual cultural talk addressing family and ancestral strengths and increasing protective factors, or BeWeL plus motivational interviewing with social networks, which includes an additional 15 minutes focused on discussion of the individual's social networks (n = 185). We will evaluate intervention effects on primary outcomes of suicide-intent risk, depression, anxiety, frequency of alcohol use, and alcohol consequences. Some of our secondary outcomes include individual and community protective factors, social networks, and awareness of connectedness. Discussion: This project has the potential to expand the range and effectiveness of suicide prevention services for AN young people and will help meet the need in Alaska to link clinical behavioral health services to AN community-based networks, and to engage local cultural resources in aftercare for individuals at risk for suicide. Findings have potential to provide practical information to advance the field of suicide prevention and enhance protective factors and resiliency among this population. Trial registration: ClinicalTrials.gov Identifier: NCT05360888.

Anti-Inflammatory, Antioxidant, Metabolic and Gut Microbiota Modulation Activities of Probiotic in Cardiac Remodeling Condition: Evidence from Systematic Study and Meta-Analysis of Randomized Controlled Trials.

Heart failure (HF) is a global pandemic with increasing prevalence and mortality rates annually. Its main cause is myocardial infarction (MI), followed by rapid cardiac remodeling. Several clinical studies have shown that probiotics can improve the quality of life and reduce cardiovascular risk factors. This systematic review and meta-analysis aimed to investigate the effectiveness of probiotics in preventing HF caused by a MI according to a prospectively registered protocol (PROSPERO: CRD42023388870). Four independent evaluators independently extracted the data using predefined extraction forms and evaluated the eligibility and accuracy of the studies. A total of six studies consisting of 366 participants were included in the systematic review. Probiotics are not significant in intervening left ventricular ejection fraction (LVEF) and high-sensitivity C-reactive protein (hs-CRP) when compared between the intervention group and the control group due to inadequate studies supporting its efficacy. Among sarcopenia indexes, hand grip strength (HGS) showed robust correlations with the Wnt biomarkers (p < 0.05), improved short physical performance battery (SPPB) scores were also strongly correlated with Dickkopf-related protein (Dkk)-3, followed by Dkk-1, and sterol regulatory element-binding protein 1 (SREBP-1) (p < 0.05). The probiotic group showed improvement in total cholesterol (p = 0.01) and uric acid (p = 0.014) compared to the baseline. Finally, probiotic supplements may be an anti-inflammatory, antioxidant, metabolic, and intestinal microbiota modulator in cardiac remodeling conditions. Probiotics have great potential to attenuate cardiac remodeling in HF or post-MI patients while also enhancing the Wnt signaling pathway which can improve sarcopenia under such conditions.

The impact of public health interventions in a developing nation: an overview

Introduction: Around 80% of factors that determine population health sit outside the control of health services. It is essential we influence these factors in addition to those within the remit of health services in order to improve and protect the health of population in a developing country. Public health functions encompass working across the domains that constitute population health systems with various partners. The objective of this article is to give an overview of public health interventions that can improve the health of the population of a developing nation. Method: A descriptive study, based on a review of the literature of key public health frameworks and interventions that are likely to have significant impacts on population health. Some selected public health interventions and case studies are highlighted to illustrate the importance of priority areas in developing countries. Results: Various public health frameworks recognise the importance of wider determinants of health (socio-economic factors), effective healthcare, healthy behaviours, working with communities as critical to securing population health. Another framework adopts a life-course model of intervention starting from public health interventions during preconception period and childhood, adolescence, working life and older age. For many developing countries, the author identified some examples of priority areas for interventions such as stopping and preventing wars; improving child health, including free school meals; achieving universal healthcare through integrated primary health care; addressing commercial determinants of health; embracing new technologies; and measuring and monitoring population health. Conclusion: In order to improve the health of a population in a developing country, attention needs to go beyond health services to influence the wider determinants of health, health behaviours and adopting the World Health Organisation's roadmap on essential public health functions.

Single-Molecule Fluorescence Imaging in Living Saccharomyces cerevisiae Cells.

This protocol describes how to image fluorescently tagged proteins, RNA, or DNA inside living Saccharomyces cerevisiae cells at the single-molecule level. Imaging inside living cells, as opposed to fixed materials, gives access to real-time kinetic information. Although various single-molecule imaging applications are discussed, we focus on imaging of gene transcription at the single-RNA level. To obtain the best possible results, it is important that both imaging parameters and yeast culture conditions are optimized. Here, both aspects are described. For complete details on the use and execution of this protocol, please refer to Lenstra et al. (2015) and Donovan et al. (2019).

Outcomes in patients with gunshot wounds to the brain.

INTRODUCTION: Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. METHODS: We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. RESULTS: 825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. CONCLUSION: We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. LEVEL OF EVIDENCE: Level II.

Firearm violence in the USA: a frank discussion on an American public health crisis-The Kansas City Firearm Violence Symposium.

Kansas City is a microcosm for USA. Although Kansas City shows a relatively diverse population, it is one that is segregated along the lines of race and income. This is an inequity that is common to all cities across the country. With this inequity comes unequal opportunity to survive and to thrive. Firearm violence is a core component of this societal inequity. In this article, we present the proceedings of the 2019 Kansas City Firearm Violence Symposium, where distinguished experts in trauma convened to share their experience, evidence and voices of gun violence-directly and indirectly. There were discussions on topics such as the human toll of gun violence, the role of structural violence in its perpetuation, the intersectional nature of race with both violence and medical care, and guidance on measures that could be taken to advocate for the reduction and elimination of gun violence. This was a symposium that started a country-wide conversation between academia, healthcare, survivors and the community on the most pressing public health crisis facing USA today.

Integrated Primary Health Care (iPHC) for developing countries: a practical approach in South Sudan

Introduction: The founding vision of Primary Health Care (PHC) adopted in Alma Atta in 1978 has not worked as a result a number of countries have sought to re-engineer their own healthcare systems. Healthcare model in most developing countries needs to change from that inherited from the colonial era, which is predominantly hospital-based. Objective: To describe an integrated primary health care (iPHC) model which encompasses public health services with enhanced basic diagnostic and curative services as a cost-effective delivery of healthcare in the rural areas where 95% of the population resides.Method: A descriptive study of a proposed iPHC model following situational analyses and literature review of primary healthcare experiences from around the world with a view to inform a practical approach in South Sudan.Results: The iPHC model consists of five pillars: (1) public health services (2) clinical services (3) universal registration of population in the catchment areas; (4) a standard building infrastructure; and (5) training of multi-disciplinary healthcare workforce. Once operational, within five years it is envisaged that one fully functioning iPHC centre can provide universal access to healthcare service to 10,000 population resident in a geographical catchment area.Conclusion: South Sudan has a unique opportunity to improve the health of its population by embracing a new model of delivering health care: the iPHC. This model is simple, and can be the basis of delivering a health service for the rural population

Key challenges in the development and implementation of telehealth projects.

A literature review was carried out to identify the key challenges in the implementation of telehealth. This was followed by a survey of organisations in England involved in telehealth projects in order to understand the challenges they faced. Ten of the 13 health or local authority organisations surveyed had telehealth projects and three were at the planning stage. The analysis revealed seven key challenges facing implementers of telehealth in England. Based on the findings from the literature review and the survey, a model was constructed and a checklist drawn up. The model contained the following elements: identifying issues, needs and partners; producing a strategy; securing funding; implementing changes; and monitoring and evaluating a telehealth project. The checklist was validated by using key informants from the organisations originally surveyed. The checklist may be useful to guide telehealth development and implementation in the future.

Effervescent morphine results in faster relief of breakthrough pain in patients compared to immediate release morphine sulfate tablet.

Morphine tablets have been formulated to produce an easily ingested effervescent solution when placed in water. It was hypothesized that an aqueous solution would result in fast gastrointestinal transit with a more rapid onset of action compared to immediate release morphine sulfate (IRMS), which would be especially beneficial in treating breakthrough pain (BTP). In an open-label safety and efficacy study, effervescent morphine was given to 76 chronic cancer pain patients for treatment of BTP evaluating time until pain relief, global satisfaction and side effects. Results were compared to those obtained using an IRMS formulation in a preceding run-in period. For BTP, a mean dose of 28 mg of effervescent morphine (range 10-80 mg) resulted in a highly significant reduction of pain score (mean 7.8 to mean 3.2; P < 0.001). Efficacy was not different from that observed with IRMS. However, mean time until sufficient pain relief was significantly shorter than with IRMS (13 +/- 5.6 vs. 27 +/- 4.4 minutes; P < 0.01). The incidence of side effects was similar with the new morphine formulation and with IRMS. There was no relationship between the previous dose of the daily opioid and the effective dose of effervescent morphine. The dose for treatment of BTP was determined by individual titration and not predicted by the dose taken with the basic pain medication. Compared to IRMS, overall satisfaction for effervescent morphine was rated "superior" by 16.7%, and "better" by 63.2% of patients. Effervescent morphine offers an alternative for management of breakthrough cancer pain compared with the commonly used IRMS.

Opioid rotation from high-dose morphine to transdermal buprenorphine (Transtec) in chronic pain patients.

Opioid rotation is increasingly becoming an option to improve pain management especially in long-term treatment. Because of insufficient analgesia and intolerable side effects, a total of 42 patients (23 male, 19 female; mean age 64.1 years) suffering from severe musculoskeletal (64%), cancer (21%) or neuropathic (19%) pain were converted from high-dose morphine (120 to >240 mg/day) to transdermal buprenorphine. The dose of buprenorphine necessary for conversion (at least 52.5 microg/h) was titrated individually by the treating physician. No conversion recommendations were given and the treating physician used his or her own judgment for dose adjustment. Pain relief, overall satisfaction and quality of sleep (very good, good, satisfactory, poor, or very poor), and the incidence and severity of adverse drug reactions over a period of at least 10 weeks and up to 1 year was assessed. Following rotation, patients experiencing good/very good pain relief increased from 5% to 76% (P < 0.001). Only 5% reported insufficient relief. Relief was achieved with buprenorphine alone in 77.4%, while 17% needed an additional opioid for breakthrough pain. Sleep quality (good/very good) increased from 14% to 74% (P < 0.005). Adverse effects were reported in 11.9%, mostly because of local irritation, did not result in termination of therapy. Neither tolerance nor refractory effect following rotation from morphine to buprenorphine was noted. Conversion tables with a fixed conversion ratio are of limited value in patients treated with high-dose morphine.

S(+)-ketamine attenuates increase in electroencephalograph activity and amplitude height of sensory-evoked potentials during rapid opioid detoxification.

Anesthesia-assisted opioid detoxification offers an opportunity for patients who have undergone unsuccessful conventional detoxifications. Little is known of excitatory effects taking place in the central nervous system during this procedure. Because acute withdrawal is accompanied by N-methyl-d-aspartic acid (NMDA)-receptor activation we tested whether the administration of the nonspecific N-methyl-d-aspartic acid antagonist S(+)-ketamine results in a reduction of hyperactivity in the central nervous system. Thirty-one patients with a long history of opioid abuse were acutely withdrawn with naltrexone during propofol/clonidine anesthesia and mechanical ventilation. Electroencephalogram (EEG) power spectra as well as median nerve-evoked somatosensory potentials (SSEP) were determined at the following times: evening before detoxification (control), steady-state propofol/clonidine-anesthesia, 30 min after naltrexone administration, and 5 min and 60 min after additional S(+)-ketamine (1.5 mg/kg). Compared to steady-state anesthesia, naltrexone induced a decrease by 270% in the low delta (0.5-3 Hz) and an increase by 110% in the fast beta (13-30 Hz) domain of the EEG with only minor changes in the theta-(3-7 Hz) and alpha-(7-13 Hz) band. Simultaneously, mean amplitude of the late N(100) peak of the SSEP increased from 3.3 muV to 10.5 muV. The changes could be attenuated by the additional administration of S(+)-ketamine, 5 min and 60 min after injection. Cardiovascular changes were not a reliable index for monitoring acute withdrawal symptoms and determining termination of rapid opioid detoxification. In this regard, EEG power spectra and SSEP were more consistent and clinically useful variables. S(+)-ketamine is a valuable adjunct in the anesthetic regimen, since it attenuates hyperactivity of the central nervous system during rapid opioid detoxification.

No potentiation of fentanyl by use of transdermal buprenorphine in patients undergoing fast-track anesthesia for open-heart surgery.

Simultaneous use of opioids with a different pharmacological profile during anesthesia may lead to unexpected prolongation of effects. In addition, long-term use of transdermal buprenorphine may result in a reduced sensitivity to opioid anesthesia. In a prospective study, possible overlap of opioid effects and vigilance was determined in a group of patients (n = 22) using a buprenorphine patch for at least two months for treatment of chronic pain, and undergoing fentanyl-based fast-track enflurane anesthesia for open-heart surgery. The patients using buprenorphine were compared with a control group (n = 21) undergoing similar open-heart procedures with no opioid other than fentanyl on board. Aside from time to extubation, total dose of fentanyl, postoperative blood gases, and vigilance assessment score were used to determine possible overlap of opioid effects and/or development of opioid tolerance in the buprenorphine group compared to the control group. Both groups had similar operation and anesthesia times and comparable doses of fentanyl (0.69 mg +/- 0.23 vs. 0.67 mg +/- 0.16 SD). There was no significant difference in postoperative arterial blood gases (PaO2 136 +/- 48 torr vs. 128 +/- 35 torr SD; PCO2 43.3 +/- 3.3 torr vs. 41.9 +/- 1.2 torr SD), time until extubation (27 +/- 22 min vs. 33 +/- 24 min), and postanesthetic vigilance and recovery score (6.8 +/- 1.0 vs. 7.5 +/- 0.8, arbitrary units) between the two groups. Because of adaptive mechanisms and the development of tolerance in patients using buprenorphine, respiratory depression or sedation does not project into the postoperative period. The significant (p < 0.05) lower incidence of nausea and emesis in patients with transdermal buprenorphine owes to the development of tolerance to these opioid-related side effects.