Reduced risk for Omicron SARS-CoV-2 infection observed in older adults with hybrid immunity.

BACKGROUND: Hybrid SARS-CoV-2 immunity may provide longer duration protection against severe SARS-CoV-2 infection and hospitalisation than purely vaccine-derived immunity. Older adults represent a high-risk group for severe disease, yet available data is skewed towards younger adults. METHODS: A prospective longitudinal study at a large London long-term care facility (LTCF) was conducted from March 2020 to April 2022 to assess the effect of hybrid versus vaccine-only immunity on SARS-CoV-2 infection in older adults during Omicron variant dominance. Hybrid immunity was assessed by a combination of SARS-CoV-2 polymerase chain reaction testing weekly (asymptomatic screening) and as required (symptomatic testing), as well as serial SARS-CoV-2 serology. RESULTS: 280 participants (median age 82 yrs, IQR 76-88 yrs; 95.4% male) were followed up. 168/280 (60%) had evidence of hybrid immunity prior to the Omicron variant wave. Participants with hybrid immunity had substantially lower odds of acquiring COVID-19 infection during the Omicron wave compared to those with vaccine-only immunity (unadjusted odds ratio 0.26, 95% CI 0.14-0.47, chi-squared P < .0001). Participants with hybrid immunity had an odds ratio of 0.40 (0.19-0.79) for asymptomatic infection and 0.15 (0.06-0.34) for symptomatic infection (Likelihood ratio test, P < .0001). DISCUSSION: Our data highlight potential opportunities to target ongoing booster vaccination campaigns for those most at risk of severe infection. Reporting of data in older adults will be of particular value to examine the effect of hybrid immunity as new variants continue to emerge and vaccination strategies evolve.

Synthetic Strategies toward Lysergic Acid Diethylamide: Ergoline Synthesis via α-Arylation, Borrowing Hydrogen Alkylation, and C-H Insertion.

Lysergic acid diethylamide (LSD), a semisynthetic ergoline alkaloid analogue and hallucinogen, is a potent psychoplastogen with promising therapeutic potential. While a variety of synthetic strategies for accessing ergoline alkaloids have emerged, the complexity of the tetracyclic ring system results in distinct challenges in preparing analogues with novel substitution patterns. Methods of modulating the hallucinogenic activity of LSD by functionalization at previously inaccessible positions are of continued interest, and efficient syntheses of the ergoline scaffold are integral toward this purpose. Here, we report novel C-C bond forming strategies for preparing the ergoline tetracyclic core, focusing on the relatively unexplored strategy of bridging the B- and D-ring systems last. Following cross-coupling to first join the A- and D-rings, we explored a variety of methods for establishing the C-ring, including intramolecular α-arylation, borrowing hydrogen alkylation, and rhodium-catalyzed C-H insertion. Our results led to a seven-step formal synthesis of LSD and the first methods for readily introducing substitution on the C-ring. These strategies are efficient for forming ergoline-like tetracyclic compounds and analogues, though they each face unique challenges associated with elaboration to ergoline natural products. Taken together, these studies provide important insights that will guide future synthetic strategies toward ergolines.

Calculated oxidation potentials predict reactivity in Baeyer-Mills reactions.

Azobenzenes are widely used as dyes and photochromic compounds, with the Baeyer-Mills reaction serving as the most common method for their preparation. This transformation is often plagued by low yields due to the formation of undesired azoxybenzene. Here, we explore electronic effects dictating the formation of the azoxybenzene side-product. Using calculated oxidation potentials, we were able to predict reaction outcomes and improve reaction efficiency simply by modulating the oxidation potential of the arylamine component.

A Modular Approach to Arylazo-1,2,3-triazole Photoswitches.

Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore, methods for synthesizing azoheteroarenes are highly desirable. Here, we utilize azide-alkyne click chemistry to access arylazo-1,2,3-triazoles, a previously unexplored class of azoheteroarenes that exhibit high thermal stabilities and near-quantitative bidirectional photoconversion. Controlling the catalyst or 1,3-dipole grants access to both regioisomeric arylazotriazoles and arylazoisoxazoles, highlighting the versatility of our approach.

A Redox Isomerization Strategy for Accessing Modular Azobenzene Photoswitches with Near Quantitative Bidirectional Photoconversion.

Photoswitches capable of accessing two geometric states are highly desirable, especially if their design is modular and incorporates a pharmacophore tethering site. We describe a redox isomerization strategy for synthesizing p-formylazobenzenes from p-nitrobenzyl alcohol. The resulting azo-aldehydes can be readily converted to photoswitchable compounds with excellent photophysical properties using simple hydrazide click chemistry. As a proof of principle, we synthesized a photoswitchable surfactant enabling the photocontrol of an emulsion with exceptionally high spatiotemporal precision.

Metabolic and hormonal changes during the refeeding period of prolonged fasting.

OBJECTIVE: The discovery of leptin, a hormone primarily involved in adaptation to fasting, led to an increased interest in appetite regulation and appetite-modulating hormones. Here, we present unique data from a case of extreme starvation and refeeding, showing changes in plasma concentrations of appetite-modulating and metabolic hormones as well as biochemical changes, and draw attention to the dangers of the refeeding syndrome. PATIENTS AND METHODS: We studied the refeeding period of a 44-day voluntary fast uncomplicated by underlying disease. Biochemical and hormonal variables were compared with 16 matched subjects such that the BMI range of the controls covered the entire spectrum for the index subject's recovering BMI. RESULTS: Lack of calorie intake with free access to water resulted in 25% loss of body weight. Haemoconcentration was observed and feeding was started with a low sodium, hypocaloric liquid formulation. During early refeeding, marked hypophosphataemia, haemodilution and slight oedema developed. Vitamins B1, B12 and B6 were depleted while serum free fatty acids, ketone bodies and zinc levels were abnormally high; abnormal liver function developed over the first week. The hormonal profile showed low IGF-I and insulin levels, and elevated IGF-binding protein-1 concentrations. Appetite-regulating hormones were either very low (leptin and ghrelin) or showed no marked difference from the control group (peptide YY, agouti-related peptide, alpha-melanocyte-stimulating hormone, neuropeptide Y and pro-opiomelanocortin). Appetite was low at the beginning of refeeding and a transient increase in orexin and resistin was observed coincidently with an increase in subjective hunger. CONCLUSIONS: Our study illustrates the potential dangers of refeeding and provides a comprehensive insight into the endocrinology of prolonged fasting and the refeeding process.

Novel substrates.

Enteral and parenteral feeds need at least to contain adequate amounts of water, energy, protein, electrolytes, vitamins and trace elements. Ready-manufactured parenteral feeds for example are incomplete because of shelf-life constraints and require the addition of vitamins (especially) and trace elements. Acute vitamin deficiencies, notably thiamine deficiency, can be precipitated if this is not adhered to. An increasing interest, however, exists in the use of feeds containing substrates, which are intended to improve patient outcome in particular clinical circumstances. The purpose of this article is to examine as to what is available and make recommendations on their use. It deals with artificial feeds only - disease-specific diets are outside our remit.

Improving the dental fitness of the British Army by changing the strategy for dental care provision for recruits from a vertically equitable model to a horizontally equitable model.

BACKGROUNDd: The dental health of the British Army has been reported as being in decline for the past 10 years, and this is having a significant impact on operations. One of the major factors in the decline is the increasing number of recruits who enlist with outstanding dental treatment needs. The current policy for provision of routine dental care to recruits targets resources toward those with the worst dental health and provides only emergency dental care for the remainder.AIMSs: The goal was to review recruit dental care provision, to determine whether improvements in the overall dental health of the trained Army could be made during recruit training.RESULTSs: It was found that >85% of recruit dental treatment need could be met with the routine provision of 2 hours of dental treatment during training.CONCLUSIONn: A horizontally equitable model of recruit dental care, whereby all recruits access routine dental care during training, has been recommended to and accepted by the chain of command.

Malaria risk assessment and preventive recommendations: a new approach for the Canadian military.

Western militaries deploying to international locations are often confronted with the threat of malaria. For the Canadian military, the consequent response has been prescriptive-any risk of malaria warrants use of personal protective measures and chemoprophylaxis. In reality, however, malaria risk is highly variable and a one-size-fits-all strategy to mitigation may not be appropriate. In line with this, the Canadian military has revised its approach to malaria risk assessment and preventive response. More effort is now spent on predictive modeling and, where risk is deemed to be low, chemoprophylaxis may not be recommended. We describe here an application of the revised methodology to the recent Canadian military deployment to Kandahar province, Afghanistan.

Longitudinal trends in quality of life after starting home parenteral nutrition: a randomised controlled study of telemedicine.

BACKGROUND AND AIMS: This study defines and quantifies longitudinal changes in quality of life (QoL) at the time of first discharge home on home parenteral nutrition (HPN) and over the first year. METHODS: Results were compared in patients in standard contact with a nutrition nurse specialist by telephone, with results of those in contact via telemedicine in a randomised controlled trial. Participants were recruited from nine UK HPN centres. Patients were randomised to receive telemedicine upon initial discharge or after 1 year. The SF36 was the principal instrument chosen to determine QoL throughout the year on three predetermined occasions. EQ5D and hospital anxiety and depression scores were also recorded. RESULTS: Thirty participants were recruited to the study from March 2001 to June 2003. In all domains, QoL scores were significantly lower than normative data at discharge. QoL scores significantly improved over the first 6 months in physical functioning, physical role (RP), vitality (VT), social functioning (SF), emotional-role (RE) domains, and mental component summary (MCS). At 6 months RE, mental health (MH) and MCS were no longer significantly lower than normative data. There was no significant change in bodily pain (BP), general health (GH), MH, and physical component summary (PCS). Opiate use significantly reduced SF36 domains RP, BP, VT, SF, MH, and MCS at 6 months and was associated with more subsequent inpatient episodes and central line reinsertions. Patients with an acute onset of intestinal failure had less pain and better GH scores at 6 months, and had less inpatient episodes after discharge than patients with a more chronic onset. Telemedicine had no impact on QoL or subsequent clinical outcome. CONCLUSIONS: Aspects of QoL improve over the first 6 months of HPN. Opiate use and chronic diagnosis have a negative impact on some elements of QoL and clinical outcome variables.

Measurements of gastric emptying during continuous nasogastric infusion of liquid feed: electric impedance tomography versus gamma scintigraphy.

BACKGROUND & AIMS: Continuous nasogastric infusion is commonly used to deliver enteral feed but current methods used to assess tolerance based on aspiration and measurement of gastric residual volume have been criticised. Electric impedance tomography (EIT) measures gastric emptying by monitoring changes in epigastric impedance when a meal progressively empties from the stomach. AIMS: (1) to establish whether EIT was a valid method for measuring gastric emptying during continuous nasogastric infusion by comparing it with gamma scintigraphy (GS) and (2) to provide data on gastric emptying patterns during continuous nasogastric infusion. METHODS: Gastric emptying of 400 ml of enteral feed given over 200 min was measured simultaneously using EIT and GS in 10 healthy volunteers (five male and five female). RESULTS: Gastric emptying curves were obtained in 10 subjects by EIT but only eight by GS. Visual examination of the curves showed reasonable agreement. Patterns of emptying and filling during continuous nasogastric infusion were variable between individuals; the prevailing pattern was a trend towards a steady-state volume of approximately 50-125 ml. CONCLUSIONS: While EIT does not provide an accurate estimate of gastric volume during continuous infusion, it does show patterns of gastric emptying over time. With further development this could make it a useful tool for monitoring gastric emptying in patients at risk of gastroparesis.

Macro- and micronutrient losses and nutritional status resulting from 44 days of total fasting in a non-obese man.

OBJECTIVE: We wanted to establish and understand how the fractional losses of fat, fat-free tissues, and selected nutrients compare with that of body mass during a 44-d voluntary starvation (water only) and measurements of nutrient status. METHODS: We used anthropometry, sequential measurements of urinary substances during the fast, and blood analytes at the end of the fast. RESULTS: At the start of the fast, body weight was 96.0 kg (20% fat) and body mass index was 28.36 kg/m(2). The changes in body mass and arm anthropometry and in the pattern of urinary excretion of creatinine, ammonia, sodium, and ketone bodies during the study were consistent with starvation. At the end of the fast, body mass had decreased by 25.5%, of which a quarter to a third was due to loss of fat and the remainder to fat-free mass, predominantly muscle. There was an estimated loss of 20% of total body protein, 20-25% of fat-free mass, and a greater fractional loss of fat. Total energy expenditure was estimated to be 1638-2155 kcal/d of which 13.0-17.1% was from protein oxidation. Differential losses of minerals in urine ranged from 1.2% of estimated initial body content for manganese to 17.3% for selenium and 40.5% for zinc. At the end of the study, plasma concentrations of zinc and vitamin B12 were increased, those of copper, selenium, and manganese were normal, and there was biochemical evidence of deficiency in thiamine, riboflavin, and vitamin K (prothrombin time). CONCLUSION: The data confirm and extend the available information on prolonged fasting in lean individuals and have relevance to the understanding of the physiologic responses to starvation and the associated homeostatic mechanisms.

What do British service personnel know about malaria?

BACKGROUND: Approximately 2000 cases of malaria are imported into the United Kingdom each year, and 10 to 14 patients die. Evidence has been published suggesting that levels of knowledge about the disease are chronically poor among travelers. OBJECTIVE: The aim of this study was to describe the levels of knowledge of malaria in a deployable population from all three services of the U.K. armed forces. METHOD: A questionnaire-based survey was undertaken, asking questions regarding core knowledge about malaria and regarding other health issues, beliefs, and experiences that might influence knowledge about malaria. RESULTS: Core knowledge concerning malaria was variable, and questions concerning experiences and beliefs generated from other health issues were generally answered poorly. The Royal Air Force showed the best knowledge and the Army the worst. Those with longer service and higher rank had better knowledge than did junior soldiers with shorter service. Core knowledge about malaria among male subjects was generally good, but overall knowledge appeared to be better among female subjects. CONCLUSIONS: Levels of malaria awareness are variable in the U.K. armed forces and, in general, worse in the Army and among those with less time in the services.

Malaria protection in Sierra Leone during the Ebola outbreak 2014/15; The UK military experience with malaria chemoprophylaxis Sep 14-Feb 15.

BACKGROUND: The UK deployed a task force to Sierra Leone to assist in ending the 2014/15 Ebola outbreak. Malaria protection was based on existing Defence Policy which saw a wide range of bite prevention measures deployed. Atovaquone/Proguanil ("A/P"), Doxycycline ("D") and Mefloquine ("M") were the chemoprophylactic medications that were prescribed. A survey was undertaken to audit the Adverse Effect (AE) burden experienced by the population. METHOD: A questionnaire based survey was administered that sought information on individuals' experiences with malaria chemoprophylaxis. RESULTS: 337 personnel were eligible to take part and 151 (46.3%) individuals returned questionnaires. The reported AE rates for the three drugs were "A/P" 28% of the respondents, "D" 25% and "M" 23.1%. 24 individuals (15.9%) reported 1 AE while 34 (22.5%) reported multiple AEs. Eight (5.3%) individuals changed medication (Five "A/P", two "M" and one "D") because of unacceptable AE but no significant neuro/psychological conditions were reported. The malaria attack rate for the deployed population was 0.4 cases per thousand person weeks which is very low when compared to other military deployments to the West African Area. CONCLUSION: UK Defence policy is effective in the way it balances the risk of malaria with that of AE due to chemoprophylaxis. "M" remains an acceptable chemoprophylactic agent for a section of the population.

Medical management of Iraqi enemy prisoners of war during Operation Telic.

OBJECTIVE: To describe the background to the provision of medical support to enemy prisoners of war (EPW) and the clinical activity undertaken at the EPW medical treatment facility. METHODS: Data were recovered from operational diaries and individual patient records to show EPW attendance rates at routine sick call, diagnoses made, and medications prescribed. RESULTS: EPW presented at an average rate of 1.2 cases per 100 EPW per day. Trauma, musculoskeletal, and dental problems accounted for 52% of presentations. Medications for mild/moderate pain and broad-spectrum antibiotics accounted for nearly 65% of prescriptions. Cultural and security issues presented additional challenges to medical staff members. CONCLUSIONS: Provision of medical support for EPW is an enduring task covered by the Geneva Conventions. EPW present a wide range of ailments at routine sick call that require suitable medications, all provided in a culturally appropriate and secure environment.

Malaria on a military peacekeeping operation: a case study with no cases.

BACKGROUND: Malaria continues to be a disease of importance to travelers and the military is no exception. Individual protection measures based on advice, bite avoidance, chemoprophylaxis, and diagnosis are advocated for protection against the disease. However, the military has an additional strand to malaria protection--the chain of command. AIM: To describe the experience of a British military deployment where the Force Commander took a proactive approach to malaria protection. RESULTS: In 512 person-weeks of exposure in a theater with high rates of transmission of malaria, with an enduring threat of asymmetric military action and with a proactive approach by the chain of command to the implementation of malaria protection policy, no malaria cases developed. CONCLUSION: The chain of command can have a significant impact on compliance with malaria protection measures, which might reduce incidence of the disease in the deployed population.

A comparison of mid upper arm circumference, body mass index and weight loss as indices of undernutrition in acutely hospitalized patients.

A nutritional supplementation trial (Vlaming et al., Clin Nutr 2001; 20: 517) enabled us to assess the nutrition of 1561 patients on emergency admission to hospital. Patients acutely admitted to the 15 relevant medical, surgical and orthopaedic wards were identified. Mid upper arm circumference (MUAC) measurements were obtained in 95% (848 m, 635f) patients. For clinical reasons, Body mass index (BMI) was assessable in only 44% patients (408 m, 285f). Data on three month weight loss were obtainable in 509 patients. These measurements combined to demonstrate that 18.3% of patients were undernourished (At least one of : BMI<20 kg/m(2) or MUAC<25 cm or loss of weight > or =10%). There was a close relationship between BMI and MUAC. Regression equations (excluding age)were for men : BMI=1.01 x MUAC-4.7, (R(2)=0.76), and for women BMI=1.10 x MUAC-6.7, (R(2)=0.76). After adjustment for age, weight loss > or =10% was the most significant of the three as a predictor of mortality. Among patients in whom weight loss was not recorded MUAC was a significant predictor of mortality either alone (P=0.002) or after adjustment for BMI (P=0.007), but BMI was not significant. All three measures, even when adjusted for age and sex, were poor predictors of hospital stay although MUAC was significant in the larger group with a MUAC measure (R(2)=0.7% P<0.001). MUAC correlates closely with BMI, is easier to measure and predicts poor outcome better.

Falciparum malaria: an outbreak in a military population on an operational deployment.

BACKGROUND: In May 2000, the United Kingdom deployed a joint force to Sierra Leone on an operation covering four phases. Each phase was characterized by high exposure risk of falciparum malaria but with varying risks due to the combat environment that affected implementation of malarial protection policy. AIM: This study will describe the risks managed concerning malarial protection for the force and match these to the attack rates (AR) suffered by the force. METHODS: The evidence concerning current malarial protection will be revisited. The risks attributable to disease and combat environment will be described and AR calculated using disease notifications as the numerator and operational personnel returns as the denominator. RESULTS: ARs appeared to be higher where the risk of hostile activity was higher. The evidence base concerning the use of malarial protection measures remains valid. The AR associated with deployment of a force to a high malaria risk area with a high associated risk of hostile action appears to be 0.78 cases per person-years exposure. The AR for personnel deployed to a high malaria risk area with a low risk of hostile action appears to be 0.078 cases per person-years exposure.