Naturally acquired immunity to Plasmodium pitheci in Bornean orangutans (Pongo pygmaeus).

Naturally acquired immunity to the different types of malaria in humans occurs in areas of endemic transmission and results in asymptomatic infection of peripheral blood. The current study examined the possibility of naturally acquired immunity in Bornean orangutans, Pongo pygmaeus, exposed to endemic Plasmodium pitheci malaria. A total of 2140 peripheral blood samples were collected between January 2017 and December 2022 from a cohort of 135 orangutans housed at a natural forested Rescue and Rehabilitation Centre in West Kalimantan, Indonesia. Each individual was observed for an average of 4.3 years during the study period. Blood samples were examined by microscopy and polymerase chain reaction for the presence of plasmodial parasites. Infection rates and parasitaemia levels were measured among age groups and all 20 documented clinical malaria cases were reviewed to estimate the incidence of illness and risk ratios among age groups. A case group of all 17 individuals that had experienced clinical malaria and a control group of 34 individuals having an event of >2000 parasites µL−1 blood but with no outward or clinical sign of illness were studied. Immature orangutans had higher-grade and more frequent parasitaemia events, but mature individuals were more likely to suffer from clinical malaria than juveniles. The case orangutans having patent clinical malaria were 256 times more likely to have had no parasitaemia event in the prior year relative to asymptomatic control orangutans. The findings are consistent with rapidly acquired immunity to P. pitheci illness among orangutans that wanes without re-exposure to the pathogen.

The effect of a 4-week, remotely administered, post-exercise passive leg heating intervention on determinants of endurance performance.

PURPOSE: Post-exercise passive heating has been reported to augment adaptations associated with endurance training. The current study evaluated the effect of a 4-week remotely administered, post-exercise passive leg heating protocol, using an electrically heated layering ensemble, on determinants of endurance performance. METHODS: Thirty recreationally trained participants were randomly allocated to either a post-exercise passive leg heating (PAH, n = 16) or unsupervised training only control group (CON, n = 14). The PAH group wore the passive heating ensemble for 90-120 min/day, completing a total of 20 (16 post-exercise and 4 stand-alone leg heating) sessions across 4 weeks. Whole-body (peak oxygen uptake, gas exchange threshold, gross efficiency and pulmonary oxygen uptake kinetics), single-leg exercise (critical torque and NIRS-derived muscle oxygenation), resting vascular characteristics (flow-mediated dilation) and angiogenic blood measures (nitrate, vascular endothelial growth factor and hypoxia inducible factor 1-α) were recorded to characterize the endurance phenotype. All measures were assessed before (PRE), at 2 weeks (MID) and after (POST) the intervention. RESULTS: There was no effect of the intervention on test of whole-body endurance capacity, vascular function or blood markers (p > 0.05). However, oxygen kinetics were adversely affected by PAH, denoted by a slowing of the phase II time constant; τ (p = 0.02). Furthermore, critical torque-deoxygenation ratio was improved in CON relative to PAH (p = 0.03). CONCLUSION: We have demonstrated that PAH had no ergogenic benefit but instead elicited some unfavourable effects on sub-maximal exercise characteristics in recreationally trained individuals.

Caffeine ingestion compromises thermoregulation and does not improve cycling time to exhaustion in the heat amongst males.

PURPOSE: Caffeine is a commonly used ergogenic aid for endurance events; however, its efficacy and safety have been questioned in hot environmental conditions. The aim of this study was to investigate the effects of acute caffeine supplementation on cycling time to exhaustion and thermoregulation in the heat. METHODS: In a double-blind, randomised, cross-over trial, 12 healthy caffeine-habituated and unacclimatised males cycled to exhaustion in the heat (35 °C, 40% RH) at an intensity associated with the thermoneutral gas exchange threshold, on two separate occasions, 60 min after ingesting caffeine (5 mg/kg) or placebo (5 mg/kg). RESULTS: There was no effect of caffeine supplementation on cycling time to exhaustion (TTE) (caffeine; 28.5 ± 8.3 min vs. placebo; 29.9 ± 8.8 min, P = 0.251). Caffeine increased pulmonary oxygen uptake by 7.4% (P = 0.003), heat production by 7.9% (P = 0.004), whole-body sweat rate (WBSR) by 21% (P = 0.008), evaporative heat transfer by 16.5% (P = 0.006) and decreased estimated skin blood flow by 14.1% (P < 0.001) compared to placebo. Core temperature was higher by 0.6% (P = 0.013) but thermal comfort decreased by - 18.3% (P = 0.040), in the caffeine condition, with no changes in rate of perceived exertion (P > 0.05). CONCLUSION: The greater heat production and storage, as indicated by a sustained increase in core temperature, corroborate previous research showing a thermogenic effect of caffeine ingestion. When exercising at the pre-determined gas exchange threshold in the heat, 5 mg/kg of caffeine did not provide a performance benefit and increased the thermal strain of participants.

Costs & outcomes of hospitalized scrub typhus infection in a tertiary hospital in south India.

Background & objectives: Scrub typhus is a rickettsial infection seen along the Asian-Pacific rim and imposes a considerable burden on affected people in low- and middle-income countries. The present study was aimed to determine the direct cost of hospitalization of scrub typhus and its trend over six years. Methods: This was a retrospective, observational, hospital based study of individuals admitted to the hospital, diagnosed with scrub typhus over six years, from January 2013 to December 2018. The potential out of pocket expenditure was evaluated. Results: A total of 198 patients were included in the study. The median cost of admission (adjusted to INR 2020) for the six years (2013 to 2018) was found to be ₹ 37,026 (US $ 490) [interquartile range (IQR) 22,996-64,992]. The median cost for patients admitted to the intensive care unit (ICU) was ₹ 128,046 (US $ 1695) (IQR 71,575-201,171), while the cost for patients admitted to the ward-alone was ₹ 33,232 (US $ 440) (IQR 19,609-45,373). The multivariable analysis showed that ARDS and SOFA score were the independent predictors of ICU admission. Interpretation & conclusions: Hospitalisation for scrub typhus is associated with a substantial healthcare expense. The predictors of increased cost were the presence of acute respiratory distress syndrome (ARDS), shock, increasing sequential organ failure assessment (SOFA) score and duration of hospital stay.

Developing skin cancer education materials for darker skin populations: crowdsourced design, message targeting, and acral lentiginous melanoma.

Despite decreased susceptibility, darker skin individuals who develop melanoma have worse survival. This disparity in melanoma mortality is the largest for any cancer, and partly driven by a lack of patient education materials targeted to darker skin populations in whom acral lentiginous melanoma (ALM) is the most common subtype. To address this communication disparity, the current study reports a multi-phase design process that leverages crowdsourcing and message testing to develop ALM-focused patient education materials for darker skin populations. Crowdsourced design was utilized to develop a pool of designs (phase 1), the pool was narrowed and thematically analyzed (phase 2), and select designs were evaluated via a message experiment (N = 1877). For darker skin populations, designs that depicted people enhanced knowledge of ALM through message memorability. The current study engages melanoma disparities by providing ALM patient education materials for darker skin populations vetted via a multi-phase process.

Spit, Disgust, and Parasite Stress Theory: A Message Experiment.

Public health interventions targeting coughing and spitting during the Tuberculosis and 1918 flu epidemics were largely successful. Specifically, public health officials' messaging framed the behavior of spitting as repulsive and endangering to others, prompting an elicitation of disgust. Anti-spitting campaigns - messaging that focuses on the threat of spit or sputum - have long been common during pandemics and manifested once again to combat the spread of COVID-19. Yet, few scholars have theorized if and how anti-spitting campaigns function to change behavior. One possibility is parasite stress theory, which posits that human behavior is driven by a desire to avoid pathogenic threats like spit. The application of these types of disgust appeals in public health messaging remains understudied and warrants exploration. To test the applicability of the parasite stress theory, our message experiment with US adults (N = 488) examined reactions to anti-spit messages that varied in visual disgust (low and high). For more highly educated respondents, the high disgust appeal directly decreased spitting intentions, and this relationship was stronger for individuals with higher levels of pathogen and moral disgust. Given the importance of public messaging during pandemics, future research should continue to examine the efficacy and theoretical underpinnings of specific disgust appeals.

Visual Tailoring and Skin Cancer Prevention: Comparing Personalized, Stock, and Non-Ultraviolet Images.

Past research has demonstrated that ultraviolet (UV) photos - which reveal skin damage as dark patches - can increase preventive behaviors. Emerging camera technology facilitates personalized UV photos for interventions, yet little is known about how personalized photos compare to other visuals and what cognitive or affective mechanism explains their persuasive impact. To engage this research line, the current study compared the impact of personalized UV (PUV), stock UV (SUV), and non-UV (NUV) photos and, to advance theorizing on fear appeals, explored underlying affective mechanisms including physiological fear. A sample of 169 undergraduate students participated in a 3 (Visual conditions: PUV, SUV, NUV) × 2 (Efficacy conditions: No efficacy and Efficacy) between-participants message experiment on a computer equipped with iMotions 6.4 that tracked real-time physiological responses (facial expression and skin conductance). Results demonstrated that PUV skin damage photos produced significantly greater self-reported fear and positive valence (detected by facial expression analysis) than NUV and SUV visuals. Mediation analysis demonstrated that fear had a significant indirect effect on the relationship between exposure to PUV skin damage visuals and behavior expectations.

Feasibility study of a novel digital health platform for patients undergoing transcatheter aortic valve replacement.

INTRODUCTION: Despite abundant evidence indicating that digital health solutions improve outcomes in chronic medical conditions, there are few validated solutions for acute surgical episodes. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to open surgery that is becoming more prevalent. We assessed the feasibility of ManageMySurgery (MMS), a smartphone application that combines patient education and outcomes tracking for patients undergoing TAVR procedures. METHODS: MMS was offered to patients receiving TAVR at an academic health center. Pre- and postoperatively, patients completed app-based tasks and reported clinical results using validated NYHA and KCCQ-12 surveys. Additionally, users reported levels of satisfaction with the digital platform. RESULTS: Sixty-nine patients were invited to use MMS, of which 43 (62%) downloaded and used the platform. The median age of patients was 77 years and 66.7% were male. The platform was accessed at an average of 2.6 times per user, with 79.1% of patients logging in one to three times. On average, 5.2 frequently asked questions were viewed. Of the 37 patients who completed the feedback survey (86%), 73.0% said it was helpful in preparation for surgery and 86.5% would recommend MMS to others. DISCUSSION: It is possible to utilize a digital health platform to guide patients undergoing TAVR through their interventional journey. Additional research is warranted to assess whether digital patient navigation tools provide an added benefit over traditional perioperative care alone, in terms of long-term patient engagement and outcomes.

Infections precipitating Takotsubo cardiomyopathy, an uncommon complication of a common infection.

Takotsubo cardiomyopathy (TTC) is a non-ischemic cardiomyopathy precipitated by stress. Various infections are reported to precipitate this form of cardiomyopathy. We report a patient presenting with TTC secondary to influenza.  In this article, we also discuss the various infections reported to precipitate this form of reversible cardiomyopathy in literature. We have also included the recent reports of TTC among patients with COVID-19.

Coronavirus disease 2019 and mechanical circulatory support devices: a comprehensive review.

Coronavirus disease (COVID-19) can cause circulatory shock refractory to medical therapy. Such patients can be managed with mechanical circulatory support (MCS) devices like IABP, Impella, VA ECMO, and Left Ventricular Assist Devices (LVADs). Moreover, patients on long-term durable LVADs are a special population having increased susceptibility and mortality to COVID-19 infection. In this narrative review, we searched PubMed and Medline for studies on COVID-19 patients on short-term MCS devices. We found 36 papers with 110 patients who met our review criteria, including 89 LVAD patients and 21 COVID-19 patients who needed MCS device therapy. These studies were used to extract patient demographics, clinical presentation, MCS device details, management, and outcomes. Mean age of patients with COVID-19 infection on LVADs was 60, 73% were male, and HeartMate 3 was the most common device (53%). Most patients (77.5%) needed hospitalization, and mortality was 23.6%. Among the 21 reported cases of critically ill COVID-19 patients who required MCS, the mean age was 49.8 years, 52% were women, and the most common MCS device used was VA ECMO (62%) in conjunction with an Impella for LV venting. Comorbidities were not present in 43%, but 71% had abnormal ventricular function on echocardiography. MCS is a viable option for managing severe COVID-19 infection with shock, with many reported cases of favorable outcomes.

The benzoate plant metabolite ethyl gallate prevents cellular- and vascular-lipid accumulation in experimental models of atherosclerosis.

Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE-/- mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.

Is there a dry season in the Southeast US?

Fill et al. (Global Change Biology, 25, 3562-3569, 2019) reported significant increases in dry season length over the past 120 years in the Southeast US, suggesting increased wildfire risk in a region associated with a frequent fire regime. We identified two flaws that call into question the findings and their relevance to regional wildfire risk. First, with the exception of Florida, there is little evidence for a climatologically meaningful 'dry season' in the Southeast because most areas experience relatively evenly distributed monthly precipitation. Second, the sampling method used to derive Cumulative Rainfall Anomalies does not appear to actually reflect a bootstrap sample as described.

Plasmodium in the bone marrow: case series from a hospital in Pakistan, 2007-2015.

BACKGROUND: Malaria is a life-threatening, multisystem disease caused by the plasmodial parasite with a global incidence of approximately 229 million annually. The parasites are known to have unique and crucial interactions with various body tissues during its life cycle, notably the liver, spleen, and recent work has shown the bone marrow to be a reservoir of infection. METHODS: This study is a case series of patients in whom examination of bone marrow revealed malarial parasites. A retrospective record review of 35 parasite-positive bone marrow specimens examined at Aga Khan University Hospital (AKUH), Karachi, Pakistan, over the years 2007 to 2015 was conducted. Bone marrow aspirates were collected as per International Council for Standardization in Haematology (ICSH) guidelines. RESULTS: The median age of patients was 22 years (range 1-75), and 60 % (n = 21) were male. 22 patients had evidence of Plasmodium falciparum, 12 had evidence of Plasmodium vivax and 1 patient had a mixed infection. Gametocytes and trophozoites were the most common stages identified on both peripheral blood and bone marrow examinations. Indications for bone marrow examination included fever of unknown origin and the workup of cytopenias and malignancies. CONCLUSIONS: The incidental finding of Plasmodium in samples of bone marrow suggests the reticuloendothelial system may be regularly harbour these parasites, be the infection acute or chronic in character.

Diversity of protease-producing bacteria in the soils of the South Shetland Islands, Antarctica.

Proteases secreted from bacteria into soil play a key role in the degradation of organic nitrogen, which is the first and, usually, the rate-limiting step of nitrogen cycling. However, the diversity of protease-producing bacteria and their excreted proteases in Antarctic soil have not yet been fully explored. Here we studied 20 soil samples from the South Shetland Islands, Antarctica and isolated 253 strains with protease activity. These protease-producing bacteria belonged to the phyla Bacteroidetes, Proteobacteria, Actinobacteria, Firmicutes, and Deinococcus-Thermus. Thhe predominant genera were Arthrobacter (14.9%), Chryseobacterium (14.5%), Flavobacterium (14.5%), and Pseudomonas (14.5%). Most of these bacteria secreted serine proteases and metalloproteases. There was quite a large distribution in activity as quantified by protease and inhibition assays. Only a few strains secreted aspartic and/or cysteine proteases. Together these data provided novel insight into the diversity and mechanism of organic nitrogen degradation in Antarctic soils by various proteases, which may have potential in new biotechnological applications.

A review of the presentation and outcome of takotsubo cardiomyopathy in COVID-19.

Although the most frequent presentation of the novel Coronavirus disease-2019 (COVID-19) is a respiratory syndrome, cardiac involvement is being increasingly recognized. One such entity is takotsubo cardiomyopathy. We sought to review the various cases of takotsubo cardiomyopathy reported during the COVID-19 pandemic and consolidate the information available on its clinical features, evaluation and treatment. We performed a PubMed search using the MeSH terms "Takotsubo Cardiomyopathy" or "Stress Cardiomyopathy" and "COVID-19", and identified 16 case reports, two case series, and one retrospective cohort study. There was a total of 24 reported patients with COVID-19 infection, who developed takotsubo cardiomyopathy, and two patients without COVID-19 who developed takotsubo cardiomyopathy due to the emotional stress associated with the global pandemic. The mean age of the patients was 67.19 years (SD 15.83) and 16(59.3%) were women. Chest pain was reported in only ten patients (38.46 %) and ST-elevation was seen in 11 patients (42.3%). While most patients had typical takotsubo cardiomyopathy, four patients had inverted(reverse) takotsubo cardiomyopathy, two had bi-ventricular involvement, one had median takotsubo and another had global takotsubo with apical sparing variant. Most patients had a positive outcome with complete or near-complete reversal of cardiac dysfunction at the time of discharge. Five deaths (19.23%) were reported. Takotsubo cardiomyopathy is a rare, but increasingly reported reversible cardiomyopathy that can be seen in patients with COVID-19 infection and the diagnosis must be actively sought for in these patients.

Endocrinological abnormalities and Takotsubo cardiomyopathy.

Dear Editor, We read with much excitement in the article "Takotsubo syndrome and pheochromocytoma: an insidious combination" published by Maffé et al. in your esteemed journal...

Deep Brain Stimulation Lead Implantation Using a Customized Rapidly Manufactured Stereotactic Fixture with Submillimetric Euclidean Accuracy.

BACKGROUND: The microTargetingTM MicrotableTM Platform is a novel stereotactic system that can be more rapidly fabricated than currently available 3D-printed alternatives. We present the first case series of patients who underwent deep brain stimulation (DBS) surgery guided by this platform and demonstrate its in vivo accuracy. METHODS: Ten patients underwent DBS at a single institution by the senior author and 15 leads were placed. The mean age was 69.1 years; four were female. The ventralis intermedius nucleus was targeted for patients with essential tremor and the subthalamic nucleus was targeted for patients with Parkinson's disease. RESULTS: Nine DBS leads in 6 patients were appropriately imaged to enable measurement of accuracy. The mean Euclidean electrode placement error (EPE) was 0.97 ± 0.37 mm, and the mean radial error was 0.80 ± 0.41 mm (n = 9). In the subset of CT scans performed greater than 1 month postoperatively (n = 3), the mean Euclidean EPE was 0.75 ± 0.17 mm and the mean radial error was 0.69 ± 0.17 mm. There were no surgical complications. CONCLUSION: The MicrotableTM platform is capable of submillimetric accuracy in patients undergoing stereotactic surgery. It has achieved clinical efficacy in our patients without surgical complications and has demonstrated the potential for superior accuracy compared to both traditional stereotactic frames and other common frameless systems.

Three-Dimensional Volumetric Changes in Posterior Vault Distraction With Distraction Osteogenesis.

OBJECT: Distraction osteogenesis (DO) may allow for maximal volumetric expansion in the posterior vault (PV) by overcoming viscoelastic forces of overlying soft tissues. Little evidence exists regarding surgical planning and anticipated 3D volumetric changes pre- and post-operatively. We aim to study the volumetric changes occurring in PV distraction in lambdoid craniosynostosis. METHODS: From 2007 to 2019, a single institution retrospective review revealed 232 craniosynostosis patients. Fourteen demonstrated lambdoid synostosis (6%), and of those, 11 patients were included in the study due to treatment with PVDO or representative sample. Six patients had unilateral synostosis and 5 had bilateral synostosis. Imaging protocol for PVDO patients included preoperative head CT within 1 month of surgery and 8 weeks following distraction cessation with weekly skull plain films. 3D volumetric analyses were performed on pre and postoperative head CT using 3D Slicer software. RESULTS: Posterior fossa volume (PFV) increased by 38.7% and foramen magnum area increased by 26.9% postoperatively. Unilateral lambdoid craniosynostosis patients had greater increases in PFV versus bilateral lambdoid craniosynostosis patients (63.5% versus 8.9%, P = 0.007). Osteotomy to the asterion was more effective in increasing PFV versus osteotomy to foramen magnum (P = 0.050). Placement of distractor in the inferior third of the lambdoid suture is more effective in increasing PFV versus placement in the middle or top third of the suture (P = 0.041). CONCLUSIONS: Highest volumetric increases are seen in unilateral lambdoid synostosis. Extending osteotomy beyond the asterion is not necessary for maximal PV volumetric gain. Placement of distractor in the inferior third of the suture leads to maximal PV volumetric gains.

Obstacles to skin self-examination: are frontier adults inclined abstainers?

Individuals residing in U.S. frontier counties have limited access to dermatology care and higher melanoma mortality rates. Given these limitations, frontier residents rely disproportionately on skin self-examinations (SSE) for early detection of melanoma, though little is known about their SSE behaviors and barriers to conducting SSEs. The goal of the present study was to identify obstacles to SSE performance via a survey of adults (N = 107) living in a U.S. frontier county. Approximately 43% of participants were classified as inclined abstainers - individuals who intended to perform SSE, but failed to follow through. Compared to those who did follow through, inclined abstainers were more likely to be hindered by twelve barriers, including forgetting, letting other tasks get in the way of SSE, and struggling to identify a good time or routine for SSE performance. The barriers to action for these inclined abstainers are modifiable - for example, not remembering to do it - and well positioned for a behavioral intervention.

Advancing Chelation Chemistry for Actinium and Other +3 f-Elements, Am, Cm, and La.

A major chemical challenge facing implementation of 225Ac in targeted alpha therapy-an emerging technology that has potential for treatment of disease-is identifying an 225Ac chelator that is compatible with in vivo applications. It is unclear how to tailor a chelator for Ac binding because Ac coordination chemistry is poorly defined. Most Ac chemistry is inferred from radiochemical experiments carried out on microscopic scales. Of the few Ac compounds that have been characterized spectroscopically, success has only been reported for simple inorganic ligands. Toward advancing understanding in Ac chelation chemistry, we have developed a method for characterizing Ac complexes that contain highly complex chelating agents using small quantities (µg) of 227Ac. We successfully characterized the chelation of Ac3+ by DOTP8- using EXAFS, NMR, and DFT techniques. To develop confidence and credibility in the Ac results, comparisons with +3 cations (Am, Cm, and La) that could be handled on the mg scale were carried out. We discovered that all M3+ cations (M = Ac, Am, Cm, La) were completely encapsulated within the binding pocket of the DOTP8- macrocycle. The computational results highlighted the stability of the M(DOTP)5- complexes.