Geological activity shapes the microbiome in deep-subsurface aquifers by advection.

Subsurface environments host diverse microorganisms in fluid-filled fractures; however, little is known about how geological and hydrological processes shape the subterranean biosphere. Here, we sampled three flowing boreholes weekly for 10 mo in a 1478-m-deep fractured rock aquifer to study the role of fracture activity (defined as seismically or aseismically induced fracture aperture change) and advection on fluid-associated microbial community composition. We found that despite a largely stable deep-subsurface fluid microbiome, drastic community-level shifts occurred after events signifying physical changes in the permeable fracture network. The community-level shifts include the emergence of microbial families from undetected to over 50% relative abundance, as well as the replacement of the community in one borehole by the earlier community from a different borehole. Null-model analysis indicates that the observed spatial and temporal community turnover was primarily driven by stochastic processes (as opposed to deterministic processes). We, therefore, conclude that the observed community-level shifts resulted from the physical transport of distinct microbial communities from other fracture(s) that outpaced environmental selection. Given that geological activity is a major cause of fracture activity and that geological activity is ubiquitous across space and time on Earth, our findings suggest that advection induced by geological activity is a general mechanism shaping the microbial biogeography and diversity in deep-subsurface habitats across the globe.

Stop codon readthrough as a treatment option for epidermolysis bullosa-Where we are and where we are going.

In the context of rare genetic diseases caused by nonsense mutations, the concept of induced stop codon readthrough (SCR) represents an attractive avenue in the ongoing search for improved treatment options. Epidermolysis bullosa (EB)-exemplary for this group of diseases-describes a diverse group of rare, blistering genodermatoses. Characterized by extreme skin fragility upon minor mechanical trauma, the most severe forms often result from nonsense mutations that lead to premature translation termination and loss of function of essential proteins at the dermo-epidermal junction. Since no curative interventions are currently available, medical care is mainly limited to alleviating symptoms and preventing complications. Complementary to attempts of gene, cell and protein therapy in EB, SCR represents a promising medical alternative. While gentamicin has already been examined in several clinical trials involving EB, other potent SCR inducers, such as ataluren, may also show promise in treating the hitherto non-curative disease. In addition to the extensively studied aminoglycosides and their derivatives, several other substance classes-non-aminoglycoside antibiotics and non-aminoglycoside compounds-are currently under investigation. The extensive data gathered in numerous in vitro experiments and the perspectives they reveal in the clinical setting will be discussed in this review.

Validation of Two Scoring Tools to Predict Risk of Augmented Renal Clearance in Trauma Patients.

INTRODUCTION: Augmented renal clearance (ARC) is prevalent in trauma populations. Identification is underrecognized by calculated creatinine clearance or estimated glomerular filtration rate equations. Predictive scores may assist with ARC identification. The goal of this study was to evaluate validity of the ARCTIC score and ARC Predictor to predict ARC in critically ill trauma patients. METHODS: This single center, retrospective study was performed at an academic level 1 trauma center. Critically ill adult trauma patients undergoing 24-h urine-collection were included. Patients with serum creatinine >1.5 mg/dL, kidney replacement therapy, suspected rhabdomyolysis, chronic kidney disease, or inaccurate urine collection were excluded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ARCTIC Score and ARC Predictor were calculated. Receiver operating characteristic curves were created for ARCTIC score and ARC Predictor models. RESULTS: One-hundred and twenty-two patients with ARC and 78 patients without ARC were included. The ARCTIC score sensitivity, specificity, PPV, and NPV were 89%, 54%, 75%, and 75%, respectively. The ARC Predictor demonstrated sensitivity, specificity, PPV, and NPV of 77%, 88%, 91%, and 71%, respectively. Regression analyses revealed both ARCTIC score ≥6 and ARC Predictor threshold >0.5 as significant risk factors for ARC in presence of traumatic brain injury, obesity, injury severity score, and negative nitrogen balance (ARCTIC ≥6: odds ratio 8.59 [95% confidence interval 3.90-18.92], P < 0.001; ARC Predictor >0.5: odds ratio 20.07 [95% confidence interval 8.53-47.19], P < 0.001). CONCLUSIONS: These findings corroborate validity of two pragmatic prediction tools to identify patients at high risk of ARC. Future studies evaluating correlations between ARCTIC score, ARC Predictor, and clinical outcomes are warranted.

Emerging Personalized Opportunities for Enhancing Translational Readthrough in Rare Genetic Diseases and Beyond.

Nonsense mutations trigger premature translation termination and often give rise to prevalent and rare genetic diseases. Consequently, the pharmacological suppression of an unscheduled stop codon represents an attractive treatment option and is of high clinical relevance. At the molecular level, the ability of the ribosome to continue translation past a stop codon is designated stop codon readthrough (SCR). SCR of disease-causing premature termination codons (PTCs) is minimal but small molecule interventions, such as treatment with aminoglycoside antibiotics, can enhance its frequency. In this review, we summarize the current understanding of translation termination (both at PTCs and at cognate stop codons) and highlight recently discovered pathways that influence its fidelity. We describe the mechanisms involved in the recognition and readthrough of PTCs and report on SCR-inducing compounds currently explored in preclinical research and clinical trials. We conclude by reviewing the ongoing attempts of personalized nonsense suppression therapy in different disease contexts, including the genetic skin condition epidermolysis bullosa.

Significant Published Articles in 2022 for Pharmacy Nutrition Support Practice.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2022 considered important to their clinical practice. The citation list was compiled into a spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the article to be important. Guideline and consensus papers, important to practice but not ranked, were also included. Results: A total of 162 articles were identified; 8 from the primary literature were voted by the group to be of high importance. An additional 10 guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Obesity and critical care nutrition: current practice gaps and directions for future research.

BACKGROUND: This review has been developed following a panel discussion with an international group of experts in the care of patients with obesity in the critical care setting and focuses on current best practices in malnutrition screening and assessment, estimation of energy needs for patients with obesity, the risks and management of sarcopenic obesity, the value of tailored nutrition recommendations, and the emerging role of immunonutrition. Patients admitted to the intensive care unit (ICU) increasingly present with overweight and obesity that require individualized nutrition considerations due to underlying comorbidities, immunological factors such as inflammation, and changes in energy expenditure and other aspects of metabolism. While research continues to accumulate, important knowledge gaps persist in recognizing and managing the complex nutritional needs in ICU patients with obesity. Available malnutrition screening and assessment tools are limited in patients with obesity due to a lack of validation and heterogeneous factors impacting nutrition status in this population. Estimations of energy and protein demands are also complex in patients with obesity and may include estimations based upon ideal, actual, or adjusted body weight. Evidence is still sparse on the role of immunonutrition in patients with obesity, but the presence of inflammation that impacts immune function may suggest a role for these nutrients in hemodynamically stable ICU patients. Educational efforts are needed for all clinicians who care for complex cases of critically ill patients with obesity, with a focus on strategies for optimal nutrition and the consideration of issues such as weight stigma and bias impacting the delivery of care. CONCLUSIONS: Current nutritional strategies for these patients should be undertaken with a focus on individualized care that considers the whole person, including the possibility of preexisting comorbidities, altered metabolism, and chronic stigma, which may impact the provision of nutritional care. Additional research should focus on the applicability of current guidelines and evidence for nutrition therapy in populations with obesity, especially in the setting of critical illness.

A wearable multi-modal acoustic system for breathing analysis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide with over 3 × 106 deaths in 2019. Such an alarming figure becomes frightening when combined with the number of lost lives resulting from COVID-caused respiratory failure. Because COPD exacerbations identified early can commonly be treated at home, early symptom detections may enable a major reduction of COPD patient readmission and associated healthcare costs; this is particularly important during pandemics such as COVID-19 in which healthcare facilities are overwhelmed. The standard adjuncts used to assess lung function (e.g., spirometry, plethysmography, and CT scan) are expensive, time consuming, and cannot be used in remote patient monitoring of an acute exacerbation. In this paper, a wearable multi-modal system for breathing analysis is presented, which can be used in quantifying various airflow obstructions. The wearable multi-modal electroacoustic system employs a body area sensor network with each sensor-node having a multi-modal sensing capability, such as a digital stethoscope, electrocardiogram monitor, thermometer, and goniometer. The signal-to-noise ratio (SNR) of the resulting acoustic spectrum is used as a measure of breathing intensity. The results are shown from data collected from over 35 healthy subjects and 3 COPD subjects, demonstrating a positive correlation of SNR values to the health-scale score.

Can your patient read this? The need to move to patient-centered medication product labels and patient information leaflets.

Medication product package labels (MPPLs) and patient information leaflets (PILs) are sometimes the last source of information for patients before they take their medications. They provide a setting in which patients can immediately inform themselves about the medication they are taking or reread any content provided by physicians or pharmacists, as needed. Despite the growing number of people who are at risk of vision impairement, some pharmaceutical companies print MPPLs and PILs in fonts that patients cannot read. Problems arising from MPPLs and PILs have been identified as remarkable sources of medication errors and fatalities. As a result, the purpose of this article is to emphasize the need for patient-centered MPPLs and PILs to protect public health.

Significant Published Articles in 2021 for Pharmacy Nutrition Support Practice.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2021 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not ranked, were also included. Results: A total of 211 articles were identified; 8 from the primary literature were voted by the group to be of high importance. An additional 18 guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Epigenetic and metabolic regulation of epidermal homeostasis.

Continuous exposure of the skin to environmental, mechanical and chemical stress necessitates constant self-renewal of the epidermis to maintain its barrier function. This self-renewal ability is attributed to epidermal stem cells (EPSCs), which are long-lived, multipotent cells located in the basal layer of the epidermis. Epidermal homeostasis - coordinated proliferation and differentiation of EPSCs - relies on fine-tuned adaptations in gene expression which in turn are tightly associated with specific epigenetic signatures and metabolic requirements. In this review, we will briefly summarize basic concepts of EPSC biology and epigenetic regulation with relevance to epidermal homeostasis. We will highlight the intricate interplay between mitochondrial energy metabolism and epigenetic events - including miRNA-mediated mechanisms - and discuss how the loss of epigenetic regulation and epidermal homeostasis manifests in skin disease. Discussion of inherited epidermolysis bullosa (EB) and disorders of cornification will focus on evidence for epigenetic deregulation and failure in epidermal homeostasis, including stem cell exhaustion and signs of premature ageing. We reason that the epigenetic and metabolic component of epidermal homeostasis is significant and warrants close attention. Charting epigenetic and metabolic complexities also represents an important step in the development of future systemic interventions aimed at restoring epidermal homeostasis and ameliorating disease burden in severe skin conditions.

Smart Multimodal Telehealth-IoT System for COVID-19 Patients.

The COVID-19 pandemic has highlighted how the healthcare system could be overwhelmed. Telehealth stands out to be an effective solution, where patients can be monitored remotely without packing hospitals and exposing healthcare givers to the deadly virus. This article presents our Intel award winning solution for diagnosing COVID-19 related symptoms and similar contagious diseases. Our solution realizes an Internet of Things system with multimodal physiological sensing capabilities. The sensor nodes are integrated in a wearable shirt (vest) to enable continuous monitoring in a noninvasive manner; the data are collected and analyzed using advanced machine learning techniques at a gateway for remote access by a healthcare provider. Our system can be used by both patients and quarantined individuals. The article presents an overview of the system and briefly describes some novel techniques for increased resource efficiency and assessment fidelity. Preliminary results are provided and the roadmap for full clinical trials is discussed.

Significant Published Articles in 2020 for Pharmacy Nutrition Support Practice.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2020 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not ranked, were also included. Results: A total of 169 articles were identified; 5 from the primary literature were voted by the group to be of high importance. An additional 17 guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data.

August Krogh twice won the prestigious international Steegen Prize, for nitrogen metabolism (1906) and overturning the concept of active transport of gases across the pulmonary epithelium (1910). Despite this, at the beginning of 1920, the consummate experimentalist was relatively unknown worldwide and even among his own University of Copenhagen faculty. But, in early 1919, he had submitted three papers to Dr Langley, then editor of The Journal of Physiology in England. These papers coalesced anatomical observations of skeletal muscle capillary numbers with O2 diffusion theory to propose a novel active role for capillaries that explained the prodigious increase in blood-muscle O2 flux from rest to exercise. Despite his own appraisal of the first two papers as "rather dull" to his friend, the eminent Cambridge respiratory physiologist, Joseph Barcroft, Krogh believed that the third one, dealing with O2 supply and capillary regulation, was"interesting". These papers, which won Krogh an unopposed Nobel Prize for Physiology or Medicine in 1920, form the foundation for this review. They single-handedly transformed the role of capillaries from passive conduit and exchange vessels, functioning at the mercy of their upstream arterioles, into independent contractile units that were predominantly closed at rest and opened actively during muscle contractions in a process he termed 'capillary recruitment'. Herein we examine Krogh's findings and some of the experimental difficulties he faced. In particular, the boundary conditions selected for his model (e.g. heavily anaesthetized animals, negligible intramyocyte O2 partial pressure, binary open-closed capillary function) have not withstood the test of time. Subsequently, we update the reader with intervening discoveries that underpin our current understanding of muscle microcirculatory control and place a retrospectroscope on Krogh's discoveries. The perspective is presented that the imprimatur of the Nobel Prize, in this instance, may have led scientists to discount compelling evidence. Much as he and Marie Krogh demonstrated that active transport of gases across the blood-gas barrier was unnecessary in the lung, capillaries in skeletal muscle do not open and close spontaneously or actively, nor is this necessary to account for the increase in blood-muscle O2 flux during exercise. Thus, a contemporary model of capillary function features most muscle capillaries supporting blood flow at rest, and, rather than capillaries actively vasodilating from rest to exercise, increased blood-myocyte O2 flux occurs predominantly via elevating red blood cell and plasma flux in already flowing capillaries. Krogh is lauded for his brilliance as an experimentalist and for raising scientific questions that led to fertile avenues of investigation, including the study of microvascular function.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2019.

The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2019 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not ranked, were also included. Results: A total of 111 articles were identified; 6 from the primary literature were voted by the group to be of high importance. An additional 9 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Parkinsonism in essential tremor cases: A clinicopathological study.

BACKGROUND: Essential tremor and Parkinson's syndrome are two common movement disorders that may co-occur in some individuals. There is no diagnostic neuropathology for essential tremor, but in PD and other Parkinson's syndrome variants, the neuropathology is well known. The spectrum of Parkinson's syndrome variants associated with essential tremor, their clinical features, and course have not been determined in autopsy-confirmed cases. OBJECTIVES: To identify: diagnostic features of essential tremor/Parkinson's syndrome, different Parkinson's syndrome variants, and long-term clinical profile in such cases. METHODS: Patients that had an essential tremor diagnosis and a subsequent clinical or pathological diagnosis of Parkinson's syndrome seen in our clinic during 50 years were included. The diagnosis of parkinsonism was made when bradykinesia, rigidity, and resting tremor were all clinically evident. RESULTS: Twenty-one cases were included. All the common variants of parkinsonism co-occurred with essential tremor. The most common was PD (67%) followed by PSP. The pathological findings were not predicted clinically in 2 cases that had essential tremor/PD and in all 5 essential tremor/PSP cases. CONCLUSION: In most essential tremor/Parkinson's syndrome patients, the main motor features of parkinsonism-bradykinesia, rigidity, and resting tremor-were identifiable. All known degenerative Parkinson's syndrome variants co-occurred in essential tremor patients. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

May Measurement Month 2017: an analysis of blood pressure screening results in Cote d'Ivoire-Sub-Saharan Africa.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. In Cote d'Ivoire, high BP is the first risk factor for stroke and myocardial infarction. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM17 protocol. A Coordinators Team was created. All doctors in cardiology training of Abidjan Institute of Cardiology (N = 72) were briefed to carry out the MMM study as investigators, and 55 sites were created. These were major urban transport stations, supermarkets and markets, and churches. BP was calculated from the mean of the 2nd and 3rd readings, and hypertension was defined as a systolic BP of at least 140 mmHg and/or a diastolic BP of at least 90 mmHg or being on BP-lowering treatment. We screened 24 563 individuals during MMM17, with mean age of 37 years. After multiple imputations, 5015 (20.4%) had hypertension. Of individuals not receiving anti-hypertensive medication, 3943 (16.8%) were hypertensive. Of individuals receiving anti-hypertensive medication, 583 (54.4%) had uncontrolled BP. MMM17 was the largest BP screening campaign undertaken in Cote d'Ivoire. MMM allowed us to identify many undiagnosed and inadequately treated hypertension cases and could usefully lower the burden attributed to increased BP. MMM should be continued.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2018.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2018 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 of 8) considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not scored, were also included. Results: A total of 117 articles were identified; 8 from the primary literature were voted by the group to be of high importance. An additional 13 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Avoiding Patient Harm With Parenteral Nutrition During Electrolyte Shortages.

Purpose: We report a case of a patient with gastrointestinal dysmotility and substantial drainage losses who required parenteral nutrition (PN) and developed a non-anion gap metabolic acidosis secondary to a shortage of concurrent potassium acetate and sodium acetate PN additives. We describe how severe PN-associated metabolic consequences were averted during this acetate shortage. Summary: The patient with inability to swallow and significant weight loss was admitted to the hospital and given PN after failure to tolerate either gastric or jejunal feeding due to dysmotility and severe abdominal distension and discomfort. PN was initiated and the nasogastric and jejunal tubes were left to low intermittent suction or gravity drainage (average losses of 800 mL and 1600 mL daily, respectively) to reduce abdominal distension. The patient had been stable on PN for approximately 2 months prior to when a shortage in potassium acetate and sodium acetate occurred. As a result, potassium and sodium requirements had to be met with chloride and phosphate salts. The patient developed a non-anion gap metabolic acidosis after 11 days of acetate-free PN. Progression to severe acidemia was avoided by administration of sodium bicarbonate daily for 3 days and replacement of 0.9% sodium chloride supplemental intravenous fluid with lactated ringers solution. Conclusion: This case report illustrates that PN component shortages require clinicians to closely monitor patients who require PN. In addition, clinicians may need to use creative therapeutic strategies to avoid potential serious patient harm during PN component shortages.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2017.

Purpose: The purpose of the article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2017 considered important to their clinical practice. The citation list was compiled into a spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority (at least 5 out of 8 authors) considered the article to be of significance. Guideline and consensus articles from professional organizations, important to practice but not scored, were also included. Results: A total of 95 articles were identified; six from the primary literature were voted by the group to be of high importance. An additional 13 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: It is recommended that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.