Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection.

The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by the lack of appropriate experimental platforms recapitulating human immune responses in a controlled human lung environment. Here, we report a mouse model (i.e., HNFL mice) co-engrafted with human fetal lung xenografts (fLX) and a myeloid-enhanced human immune system to identify cellular and molecular correlates of lung protection during SARS-CoV-2 infection. Unlike mice solely engrafted with human fLX, HNFL mice are protected against infection, severe inflammation, and histopathological phenotypes. Lung tissue protection from infection and severe histopathology associates with macrophage infiltration and differentiation and the upregulation of a macrophage-enriched signature composed of 11 specific genes mainly associated with the type I interferon signaling pathway. Our work highlights the HNFL model as a transformative platform to investigate, in controlled experimental settings, human myeloid immune mechanisms governing lung tissue protection during SARS-CoV-2 infection.

Instituting a Green Zone for Elective Surgery During the Second Wave of COVID-19.

Objective Elective surgery came to a standstill during the first wave of COVID-19. The safe resumption of elective surgery with COVID-19 prevalent in the community remains a significant challenge. The aim of this study was to look into the outcomes of elective general surgery in a dedicated 'Green Zone (GZ)' during the second wave of COVID-19 in the United Kingdom. Method A 'Green Zone' pathway, meant to provide a COVID-free environment, was created. A retrospective review of prospectively collected data was done on consecutive patients who underwent an elective general surgical procedure at a single NHS trust over a six-month period (September 1, 2020, to February 28, 2021). The primary outcome was 30-day COVID-19 mortality. Secondary outcomes included 30-day non-COVID-19 mortality, readmissions, and complications. Results The study included 331 patients with a median age of 55 years (interquartile range, IQR, 41-67); 169 (51%) were females. The majority of the patients were American Society of Anaesthesiologists grade 2 (ASA 2; n=177, 53%) followed by ASA 3 (n=76, 23%). Forty-seven patients (14%) had been shielding earlier in the year. Most of the cases were day cases (n=224, 67%). There was no 30-day COVID-19 or non-COVID-19 mortality. One patient developed COVID-19 three weeks after the index operation. Thirty-day readmission and complication rate were 4% (n=14) and 6% (n=21). Most of the complications were Clavien-Dindo grade 2 (n=10, 3%) followed by an equal number of grades 1 and 3b (n=5, 1.5%). Conclusion This study has shown that a dedicated 'Green Zone' elective operating pathway is safe and feasible provided a balanced risk assessment approach is adopted.

Designing Video Games for Nutrition Education: A Participatory Approach.

OBJECTIVE: To describe the participatory approach used to inform the development of a video game designed to increase children's nutrition knowledge. The objectives were to (1) assess children's nutrition areas of focus, (2) explore parents' and children's perceptions of video games for nutrition education, and (3) collect information on children's video game preferences. DESIGN: Qualitative research design using 10 focus group interviews and 5 workshops. Children's nutrition knowledge and game player type were assessed by questionnaires. SETTING: South Island, New Zealand. PARTICIPANTS: Sixty-two primary school children, aged 7-11 years. Ten parents completed an online questionnaire. PHENOMENON OF INTEREST: Participatory approach in designing digital nutrition education resources. ANALYSIS: A general inductive approach was used to develop the themes. RESULTS: The following 3 themes were identified through thematic analysis: (1) positive impacts associated with video games for nutrition education, (2) factors for engagement, and (3) barriers for sustained use. CONCLUSIONS AND IMPLICATIONS: Both children and parents perceived that video games offered an avenue to increase nutrition knowledge. However, negative views such as screen time usage need to be addressed before widespread adoption. The participatory design approach provided information about game mechanics that will inspire the game design and enhance engagement of video games for nutrition education.

External stoma diversion: a palliative measure for peristomal wound healing in resource-limited settings.

The provision of intestinal stoma care is challenging in austere settings due to limitations in surgical and wound care access as well as the high cost and sparsity of ostomy supplies. As a result, many surgical patients suffer from ostomy-related complications such as peristomal wounds and are unable to find relief for these complications from standard treatments and measures. This article describes the external stoma diversion, a cost-effective palliative surgical procedure that assists in the healing of peristomal wounds in resource-limited settings.

Intraoperative hypotensive resuscitation for patients undergoing laparotomy or thoracotomy for trauma: Early termination of a randomized prospective clinical trial.

BACKGROUND: Hemorrhagic shock is responsible for one third of trauma related deaths. We hypothesized that intraoperative hypotensive resuscitation would improve survival for patients undergoing operative control of hemorrhage following penetrating trauma. METHODS: Between July 1, 2007, and March 28, 2013, penetrating trauma patients aged 14 years to 45 years with a systolic blood pressure of 90 mm Hg or lower requiring laparotomy or thoracotomy for control of hemorrhage were randomized 1:1 based on a target minimum mean arterial pressure (MAP) of 50 mm Hg (experimental arm, LMAP) or 65 mm Hg (control arm, HMAP). Patients were followed up 30 days postoperatively. The primary outcome of mortality; secondary outcomes including stroke, myocardial infarction, renal failure, coagulopathy, and infection; and other clinical data were analyzed between study arms using univariate and Kaplan-Meier analyses. RESULTS: The trial enrolled 168 patients (86 LMAP, 82 HMAP patients) before early termination, in part because of clinical equipoise and futility. Injuries resulted from gunshot wounds (76%) and stab wounds (24%); 90% of the patients were male, and the median age was 31 years. Baseline vitals, laboratory results, and injury severity were similar between groups. Intraoperative MAP was 65.5 ± 11.6 mm Hg in the LMAP group and 69.1 ± 13.8 mm Hg in the HMAP group (p = 0.07). No significant survival advantage existed for the LMAP group at 30 days (p = 0.48) or 24 hours (p = 0.27). Secondary outcomes were similar for the LMAP and HMAP groups: acute myocardial infarction (1% vs. 2%), stroke (0% vs. 3%), any renal failure (15% vs. 12%), coagulopathy (28% vs. 29%), and infection (59% vs. 58%) (p > 0.05 for all). Acute renal injury occurred less often in the LMAP than in HMAP group (13% vs. 30%, p = 0.01). CONCLUSION: This study was unable to demonstrate that hypotensive resuscitation at a target MAP of 50 mm Hg could significantly improve 30-day mortality. Further study is necessary to fully realize the benefits of hypotensive resuscitation. LEVEL OF EVIDENCE: Therapeutic study, level II.

A mechanical analog of the two-bounce resonance of solitary waves: Modeling and experiment.

We describe a simple mechanical system, a ball rolling along a specially-designed landscape, which mimics the well-known two-bounce resonance in solitary wave collisions, a phenomenon that has been seen in countless numerical simulations but never in the laboratory. We provide a brief history of the solitary wave problem, stressing the fundamental role collective-coordinate models played in understanding this phenomenon. We derive the equations governing the motion of a point particle confined to such a surface and then design a surface on which to roll the ball, such that its motion will evolve under the same equations that approximately govern solitary wave collisions. We report on physical experiments, carried out in an undergraduate applied mathematics course, that seem to exhibit the two-bounce resonance.

Challenges to the provision of emergency services and critical care in resource-constrained settings.

The practice of intensive care unit (ICU) care in Sub-Saharan Africa is challenging and can have a significant impact on the lives of people in the region. Sub-Saharan Africa bears a disproportionate global burden of disease compared with the rest of the world. Inadequate emergency care services and transportation infrastructure; long lead times to hospital admission, evaluation, treatment and transfer to ICU; inadequate ICU and hospital infrastructure and, unreliable consumable and medical equipment supply chains all present significant challenges to the provision of ICU care in Sub-Saharan Africa. These challenges, coupled with an inadequate supply of trained healthcare workers and biomedical technicians and a lack of formal ICU-related research in Sub-Saharan Africa, would seem to be insurmountable. However, ICU care is being provided in district and regional hospitals throughout the region. We describe some of the challenges to the provision of emergency services and critical care in Tanzania.

Junior doctors' learning and development in foundation year 1 posts in palliative medicine.

BACKGROUND: The ability to provide good palliative care to patients is increasingly recognised as a core clinical skill that all doctors should possess. Few junior doctors, however, feel competent in breaking bad news, pain relief and the care of dying patients by the time they are fully registered to practice. AIM: The aim of this study was to explore doctors' experiences in foundation year 1 (F1) palliative medicine posts. DESIGN: Participants underwent semi-structured interviews and interview transcripts were analysed using Interpretative Phenomenological Analysis. SETTING/PARTICIPANTS: The study involved a purposive sample of six F1 doctors matched in 2005-2006 to rotations incorporating palliative medicine posts at two acute hospital National Health Service (NHS) Trusts and one NHS hospice in the UK. RESULTS: F1 doctors were satisfied with the learning opportunities provided by the posts, which achieved the right balance between supported and autonomous working. They described learning through their day-to-day interactions with staff, including specialist nurses, and by practising their skills on the job. Some struggled, however, to make the transition to a more independent learning style in the clinical environment. Trainees felt the post helped them to develop generic skills, such as symptom control, diagnosing dying and breaking bad news. Whilst they found split posts and on-call rotas disrupted their palliative care learning, these offered important opportunities to learn additional F1 skills. CONCLUSIONS: F1 posts in palliative medicine in the UK have positive influences on perceived generic skills development and practice. These findings might encourage the development of more rotations incorporating palliative medicine in the future.

Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six-month, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable. METHODS: In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids. RESULTS: A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine. CONCLUSION: Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive.

One step purification of alpha(1)-acid glycoprotein from human plasma. Fractionation of its polymorphic allele products.

Alpha(1)-acid glycoprotein is a plasma protein that exhibits both microheterogeneity and polymorphism. Its purification from human plasma is usually performed using a sequence of different fractionation steps. Here we report a one-step isolation technique of this protein based upon pseudo-ligand affinity chromatography on immobilized Cibacron Blue F3GA at acidic pH. In addition, the use of two narrow pH elution buffers allows us to separate the two genetic products of this protein, which differ from each other by 21 amino acid substitutions. This technique will facilitate the study of the structural, biological and pharmacokinetic properties of each individual allele product.