Notes

Abomasal infusion involving floor callus and also ammonium chloride within early-lactating Holstein-Friesian dairy cows in order to induce hindgut along with metabolic acidosis.
The future of intraocular lens (IOL) technology has already begun with a number of recent innovations. The postoperative change of refractive power will lead to a customized fine-tuning that provides patients with the individual vision they expect and with as much spectacle independence as possible. The latest-generation (2.0) Light-Adjustable Lens (RxSight) was recently introduced into clinical practice, with the first results being very encouraging. Other methods of altering the power of an already implanted IOL are under development. The same can be said about the correction of presbyopia, the so-called last frontier in refractive surgery. Extended depth-of-focus IOLs have been introduced, as has the technology of the pinhole IOL. The latter has therapeutic potential beyond the refractive aspect and has already proven helpful in cases of iris defects and irregular corneas. Several technologies are currently being tested to achieve-finally-an accommodative IOL. One such concept uses the (remaining) strength of the ciliary muscle, whereas another is triggered by the pupil reaction when shifting focus from far to near. Not an IOL itself, but rather a high-tech innovation that so far has mostly been implanted during cataract surgery, is a microelectronic sensor that measures habitual intraocular pressure (IOP) at any given time and promises to revolutionize the management of glaucoma patients. The last generation of this device (Eyemate; Implandata Opthalmics Products GmbH) is implanted during small-incision cataract surgery; the latest development is an even smaller sensor that will be inserted suprachoroidally before, in the near future, such a device will be part of a capsular ring. These IOP sensors are a prime example that IOL technology will continue to be a driving force in ophthalmology, with a positive impact far beyond cataract surgery.There is an increasing demand for astaxanthin in food, feed, cosmetics and pharmaceutical applications because of its superior anti-oxidative and coloring properties. However, naturally produced astaxanthin is expensive, mainly due to low productivity and limited sources. Reprogramming of microorganisms for astaxanthin production via metabolic engineering is a promising strategy. We primarily focus on the application of synthetic biology, enzyme engineering and metabolic engineering in enhancing the synthesis and accumulation of astaxanthin in microorganisms in this review. We also discuss the biosynthetic pathways of astaxanthin within natural producers, and summarize the achievements and challenges in reprogramming microorganisms for enhancing astaxanthin production. This review illuminates recent biotechnological advances in microbial production of astaxanthin. Future perspectives on utilization of new technologies for boosting microbial astaxanthin production are also discussed.The design, fabrication, and application of edible nanoemulsions for the encapsulation and delivery of bioactive agents has been a highly active research field over the past decade or so. In particular, they have been widely used for the encapsulation and delivery of hydrophobic bioactive substances, such as hydrophobic drugs, lipids, vitamins, and phytochemicals. A great deal of progress has been made in creating stable edible nanoemulsions that can increase the stability and efficacy of these bioactive agents. This article highlights some of the most important recent advances within this area, including increasing the water-dispersibility of bioactives, protecting bioactives from chemical degradation during storage, increasing the bioavailability of bioactives after ingestion, and targeting the release of bioactives within the gastrointestinal tract. Moreover, it highlights progress that is being made in creating plant-based edible nanoemulsions. Finally, the potential toxicity of edible nanoemulsions is considered.
To investigate if abortion clinics follow Swedish national guidelines regarding early insertion of long-acting reversible contraception (LARC) after medical abortions up to 9 weeks of gestation and, if not, the reasons for not doing so.

We attempted to survey representatives of all 60 known Swedish abortion clinics by telephone in November 2019, including public hospitals and private clinics. We asked questions about clinic characteristics, clinic routines concerning early insertion of IUDs and implants, adherence to guidelines and, when applicable, perceived reasons for nonadherence. Current guidelines include offering implant placement at the time of mifepristone administration and intrauterine device (IUD) insertion within 7 days of misoprostol treatment.

We obtained responses from 57 (95%) clinics of which 22 (40%) followed guidelines for both implants and IUDs. Slightly more than half (n=33, 58%) follow implant guidelines and fewer (n=25, 44%) follow IUD guidelines. Respondents most commonly cited lack of updated local guidelines at the clinic (7/24, 29%) and a perceived lack of time (6/25, 24%) as the most common reasons for nonadherence to guidelines for insertion of implants and insufficient number of nurse midwives for insertion of IUDs 8/32, 25%).

Less than half of Swedish abortion clinics fully adhere to national evidence-based guidelines regarding early LARC insertion at the time of abortion.

National guidelines alone are not always sufficient to effect change in practice; awareness of existing guidelines is needed in Swedish abortion clinics and work is needed to address barriers that limit LARC access after abortion.
National guidelines alone are not always sufficient to effect change in practice; awareness of existing guidelines is needed in Swedish abortion clinics and work is needed to address barriers that limit LARC access after abortion.
Despite evidence that mandatory pelvic examinations deter contraceptive use and are not clinically necessary, survey research suggests that clinicians regularly perform pelvic examinations prior to prescribing contraceptives. This study estimates prevalence of nonindicated pelvic exams during contraceptive encounters, and variation in prevalence by provider specialty.

Using a national sample of commercial claims data, we identified contraceptive encounters without concurrent indication for pelvic examination among females aged 15 to 49 from 2007 to 2017. We first calculated the nonindicated exam rate by provider specialty and patient age. Using data from 2017 and linear probability models with metropolitan statistical area fixed effects, we estimated the differences in adjusted rates of nonindicated pelvic examination by provider specialty. To assess trends by provider specialty, we used all years of data and interacted specialty with year.

Of 7.9 million identified contraceptive encounters, 81.8% had ndicated pelvic exams will be necessary to change clinical practice.
This research provides real-world evidence that suggests pelvic exams are increasingly performed during contraceptive encounters and that patients regularly undergo a low-value, invasive examination while obtaining contraceptive care. Continuing education, reimbursement reform, and more evidence on the harms of non-indicated pelvic exams will be necessary to change clinical practice.
To explore abortion method preference, interpersonal and cultural factors associated with preference, and whether, among people with a preference for medication abortion, those presenting past 10 weeks gestation had experienced more obstacles to care.

In 2019, we invited people aged 15 to 45 years presenting to 4 U.S. abortion clinics to complete a self-administered, anonymous iPad survey prior to seeing the health care provider. Questions focused on their pregnancy, including self-reported gestational age and experiences accessing abortion care, including abortion method preference. We used multivariate logistic regressionto assess associations between worry about perceived pregnancy-related stigma or abortion-related health myths and abortion method preference.

The majority (784 [77%]) of those approached (1092) initiated the survey and 712 responded to the preference question. Most (597 [84%]) preferred a method 246 (41%) preferred medication abortion and 351 (59%) an in-clinic procedure. About one-tity to obtain their preferred method. Removing barriers to clinic access may enhance people's ability to obtain their preferred abortion method.
Pregnancy-related stigma and misinformation, such as health and safety myths promulgated by state-mandated abortion counseling, may motivate preference for medication abortion. Abortion access obstacles may impede individuals' ability to obtain their preferred method. Removing barriers to clinic access may enhance people's ability to obtain their preferred abortion method.Marine algae have long been explored as food, feed, additives, drugs, and pesticides, yet now the framework is moving towards the algae mediated green synthesis of nanoparticles (NPs). This work is expanding step by step, like algae, are a rich origin of natural compounds. Recently, algae capped and stabilized NPs have picked up far and wide consideration as a less toxic, easy handling, cost effective, eco-friendly, usage in several science fields in nano size, safer to use, and greener method. The natural substance from algae acts as capping or reducing and stabilizing agent in the metal salts to metal, metal oxide, or bimetallic NPs conversion. The NPs using algae could either be intracellular or extracellular relying upon the area of NPs. Among the different scope of algae, reviews are explored in the previous report, still, different NPs using algae and their characterization, mechanism of activity is yet to be summarized. Because of the biocompatibility, good and remarkable physicochemical properties of NPs, the algal biosynthesized NPs have additionally been read for their biomedical applications, which include antibacterial, antioxidant, free radical scavenging, antifungal, anticancer, and biocompatibility properties. In this survey, the reasoning behind the algae mediated biosynthesis of various NPs from different algae origin have been explored. Besides, a piece of knowledge into the component of biosynthesis of NPs from marine algae and their biomedical applications has been summarized.The objective of this short paper is to call upon the scientific community to channel its attention to the duty and heedfulness of social justice issues. While recognized for decades the impact of social injustice on public health and its disproportionate effects on poorer communities, little has been done to systematically address it. Here, we provide several examples pertinent to the health outcomes associated with social injustice and call upon the scientific community to attend to the issue and antagonize those who attempt to subvert science and its role in ensuring social justice in health.By mid-September 2020, over 1.33 million confirmed COVID-19 cases and 32 thousand deaths had been reported in Africa. Global research on COVID-19 went 'viral' with a record 3487 research contributions comprising of 2062 journal papers and 1425 preprints published within the first three months following the outbreak of COVID-19. Surprisingly, the silence of the African research community has been unprecedented - contributing a paltry 0.6% (22 contributions), a figure nearly matched by Colombia (18 publications). Until now, a comprehensive perspective on the reasons for this subdued research response, and COVID-19 themes critical to Africa has been missing. We posit that while a milieu of factors accounts for this silence, unprecedented research opportunities exist to support COVID-19 decision and policy formulation in Africa. The subdued response reflects weak research systems, characterized by deep-rooted challenges, including severe lack of research expertise, funding, and infrastructure, coupled with poor ws a need to (1) strengthen local research capacity and evaluation systems, (2) consider biosafety and ethical issues, (3) initiate cross-disciplinary research and global collaboration on COVID-19, and (4) integrate science communication in COVID-19 programs.Cutaneous melanoma is the deadliest form of skin cancer, and gambogic acid (GA) exhibits potent anti-melanoma activity. However, clinical application of GA via intravenous injection and oral administration is limited by systemic toxicity and rapid metabolism in the blood. Here, we developed a new, topical route of GA delivery for anti-melanoma activity and reduction of systemic toxicity. The results indicated that the barrier of the stratum corneum (SC) and low diffusion of GA in the hydrophilic viable skin (epidermis and dermis) limited the GA penetration through intact skin. The combination of azone (AZ) and propylene glycol (PG) showed obvious synergistic effects on skin penetration by GA via improving the permeability of the SC and greatly increasing the skin accumulation of GA, thereby forming a high drug concentration in the skin and achieving a topical targeted treatment of melanoma. In addition, GA (AZ-PG) achieved the same anti-melanoma effect via topical delivery as via intravenous injection. Intravenous injection and oral administration of GA induced remarkable pathological changes in various organs in mice, whereas GA was not toxic to various organs or to the skin via topical delivery. These findings indicated that topical administration of GA is an alternative route for melanoma treatment.Collagen membranes have been used as bioresorbable barrier membranes in guided tissue/bone regeneration. However, the collagen membranes currently used in clinics lack an active antibacterial function, although infection at surgical sites presents a realistic challenge for guided tissue/bone regeneration. In this study, we successfully prepared novel and advanced collagen composite membranes from collagen and complexes of heparin and chelates of minocycline and Ca2+ ions. These membranes were characterized for chemical structures, morphology, elemental compositions and tensile strength. In vitro release studies were conducted to evaluate the release kinetics of minocycline from these membranes. Agar disk diffusion assays were used to assess their sustained antibacterial capability against model pathogenic bacteria Staphylococcus aureus. The chemical and physical characterization confirmed the successful synthesis of minocycline-loaded collagen composite membranes, namely NCCM-1 and NCCM-2. Both membranes had weaker tensile strength as compared with commercial collagen membranes. They achieved sustained release of minocycline for at least 4 weeks in simulated body fluid (pH 7.4) at 37°C. Moreover, both membranes demonstrated potent sustained antibacterial effects against Staphylococcus aureus. These results suggested that the advanced collagen composite membranes containing minocycline can be exploited as novel guided tissue regeneration membranes or wound dressing by providing additional antibacterial functions.Novel dual redox/pH-sensitive star-like amphiphilic sucrose-oligo(butyl fumarate) (thioglycolic acid conjugate)-SS-poly(ethylene glycol) (Suc-OBF(TGA)-SS-PEG) copolymers and their self-assembled micelles were prepared and utilized for intracellular doxorubicin delivery. Importance of changing the hydrophobic chain length on micelles properties was investigated. Results showed that the micelles with longer hydrophobic chain exhibited smaller size and were more stable in aqueous solution. The redox and pH sensitivity of the micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic light scattering and the change of micellar morphology observed by scanning electron microscope. The micelles display a decent doxorubicin loading capacity. In vitro release studies showed that only 14.3% doxorubicin was released from doxorubicin-loaded micelles under physiological conditions in 30 h. The release of doxorubicin was accelerated at pH 5.5 or in the presence of 10 mM glutathione at pH 7.4 (46.9% and 76.9% of doxorubicin was released, respectively, in 30 h). The doxorubicin release was further expedited under pH 5.5 and 10 mM GSH conditions (91.4%). Suc-OBF(TGA)-SS-PEG micelles displayed no cytotoxicity toward HDF cells. MTT assays indicated that doxorubicin-loaded micelles had good cytotoxicity against MCF-7 cells. This work suggested that star-like amphiphilic Suc-OBF(TGA)-SS-PEG copolymer micelles may provide a promising platform for delivering doxorubicin and other hydrophobic anticancer drugs.Several restriction policies implemented in many states in the United States have demonstrated their effectiveness in mitigating the spread of the coronavirus disease (COVID-19), but less is known about the differences in views on the restriction policies among different population segments. This study aimed to understand which different population groups of adults in the United States consider several key restriction policies as necessary to combat COVID-19. Survey data from Wave 64 (March 19-24, 2020) of the Pew Research Center's American Trends Panel (n=10,609) and logistic regression were used to evaluate the association between socioeconomic and demographic characteristics, employment status, political party affiliation, news exposure, census region, and opinions about COVID-19 restriction policies. The policies included restricting international travel, imposing business closures, banning large group gatherings, cancelling entertainment events, closing schools, limiting restaurants to carry-out only, and postponing state primary elections. Most survey respondents viewed COVID-19 restriction policies as necessary. Views on each restriction policy varied substantially across some population segments such as age, race, and ethnicity. Regardless of population segments, those who followed news closely or considered themselves Democrat/lean Democrat were more likely to consider all the policies as necessary than those not following the news closely or those who considered themselves Republican/lean Republican. The effectiveness of key COVID-19 restriction policies is likely to vary substantially across population groups given that views on the need to implement these policies vary widely. Tailored health messages may be needed for some population segments given divergent views on COVID-19 restriction policies.First-line treatment of prolactinoma is usually medical, based on dopamine agonists receptors, mainly cabergoline. The classical side-effects of cabergoline (low blood pressure and nausea) have been well known since it was first introduced. Other side-effects, however, are more controversial or simply less frequent, but need to be considered during monitoring. This review will focus on these side-effects cardiac valvular fibrosis, pleural, pericardial and retroperitoneal fibrosis, addictive/compulsive behaviors, and risks secondary to significantly decreased tumor volume. We will also describe how such side-effects should be monitored and managed. In our opinion, the low prevalence of these side-effects should not cast doubt on the role of cabergoline in the therapeutic algorithm of prolactinoma.
The role of cardiac testing in the 3 zones (rule-out, observation, and rule-in) of the 0/1-hour algorithm to evaluate for acute myocardial infarction (AMI) has not been well studied. This study evaluated the 0/1-hour algorithm with a high-sensitivity cardiac troponin (hs-cTnI) assay and investigated cardiac testing in the 3 zones.

Patients (n = 552) at a single urban center were enrolled if they were evaluated for AMI. Blood samples were obtained at presentation, 1 hour, and 3 hours for hs-cTnI. Follow-up at 30 to 45 days for death/AMI was done. The results of echocardiograms, stress testing, and coronary angiography were recorded.

In total, 45 (8.2%) had AMI (27 Type 1 and 18 Type 2) during the index hospitalization while at follow-up death/AMI occurred in 11 (2.0%) of patients. The rule-out algorithm had a negative predictive value for AMI of 99.6% while the rule-in zone had a positive predictive value of 56.6%. The MACE rate at follow-up was 0.4% for those in the rule-out group. There were 6/95 (6.3%) abnormal stress tests in the rule-out zone and 4 of these were false positives.

The 0/1-hour algorithm had high diagnostic sensitivity and negative predictive value for AMI, and adverse events were very low in patients in the rule-out zone. Noninvasive testing in rule-out zone patients had low diagnostic yield.
The 0/1-hour algorithm had high diagnostic sensitivity and negative predictive value for AMI, and adverse events were very low in patients in the rule-out zone. Noninvasive testing in rule-out zone patients had low diagnostic yield.
To evaluate how self-reported problems change over time among people with spinal cord injury (SCI).

Cross-sequential analysis.

Medical university in the Southeastern United States.

Participants included 1997 individuals with traumatic SCI of at least 1-year duration who were identified from participation in the SCI Longitudinal Aging Study from 1993-2018.

None.

The outcomes analyzed were 6 problem factors defined as health, social isolation, emotional distress, environmental barriers, money, and lack of opportunities. A series of cross-sequential models, using PROC MIXED procedure, were developed to evaluate the initial and change of the 6 problem factors over the 6 times of measurements in 25 years.

Years post injury was negatively associated with initial status of problems of social isolation, emotional distress, environmental barriers, and lack of opportunities because participants with more years post injury at baseline reported lower scores on each factor. Longitudinally, with increased years post injury, higher scores were observed on the health problem factor. However, problems of social isolation, emotional distress, environmental barriers, money, and lack of opportunities decreased over time with increasing years post injury.

Participants had more health problems with increasing years after SCI, but fewer problems of social isolation, emotional distress, environmental barriers, money, and lack of opportunities.
Participants had more health problems with increasing years after SCI, but fewer problems of social isolation, emotional distress, environmental barriers, money, and lack of opportunities.Hospitalized patients often experience unnecessary immobility and inactivity leading to direct harms and poor outcomes. Despite growing evidence that early and regular mobility and activity are safe and helpful for patients in the hospital, there remains substantial room for improvement in clinical practice. Key to improvement is establishing an interdisciplinary approach to measurement and communication using a common language of function. Here we provide a framework for systematic functional measurement in the hospital. We also provide 3 specific examples of how this framework has been used to improve care (1) targeting specialized rehabilitation providers to the patients most likely to need their services, (2) generating a daily mobility goal for all patients, and (3) identifying patients early who are likely to require postacute care.
To investigate whether indicators of patient need (comorbidity burden, fall risk) predict acute care rehabilitation utilization, and whether this relation varies across patient characteristics (ie, demographic characteristics, insurance type).

Secondary analysis of electronic health records data.

Five acute care hospitals.

Adults (N=110,209) admitted to 5 regional hospitals between 2014 and2018.

Not applicable.

Occupational therapy (OT) and physical therapy (PT) utilization. Logistic regression models determined whether indicators of patient need predicted OT and PT utilization. Interactions between indicators of need and both demographic factors (eg, minority status, presence of significant other) and insurance type were included to investigate whether the relation between patient need and therapy access varied across patient characteristics.

Greater comorbidity burden was associated with a higher likelihood of receiving OT and PT. Relative to those with low fall risk, those with moderate and hbidity burden and fall risk were more likely to receive acute care rehabilitation. However, the relation between fall risk and utilization was moderated by insurance type, having a significant other, and race/ethnicity. Understanding the implications of these utilization patterns requires further research.This essay is an invited commentary on the report "Systematic Review of Clinical Guidelines Related to Care of Individuals With Cerebral Palsy as Part of the World Health Organization Efforts to Develop a Global Package of Interventions for Rehabilitation" published in this journal. As a blinded reviewer of the original and revised versions of this interesting article, I was stimulated to reflect on several ideas about "clinical guidelines" and to take the opportunity to share concerns I have long held and that this article identified. Having said that, the thoughts expressed are mine alone and should not be ascribed to the authors of the article that provoked them. The case I offer is that guidelines may in some ways risk being outdated, insofar as they are crafted based on what we already know from research done in "earlier" times and with different conceptual frameworks than we now apply. I use the example of 20th century concerns about spasticity to illustrate my argument. I also suggest that they may be too prescriptive and restrictive. Instead, I raise for consideration the idea that we should turn the guidelines process on its head and use best available valid data to build toward contextualized problem-focused approaches to issues that are relevant to the individuals for whom they are meant to be useful- in this case, individuals with cerebral palsy, their families, and the service providers who work with them. It is my hope that these ideas stimulate discussion and reflection.Parkinson's disease is an increasingly prevalent and currently incurable neurodegenerative disorder. At the molecular level, this disease is characterized by the formation of aberrant intracellular protein deposits known as Lewy bodies. Oligomeric forms of the protein α-synuclein (αS), which are believed to be both intermediates and by-products of Lewy body formation, are considered to be the main pathogenic species. Interactions of such oligomers with lipid membranes are increasingly emerging as a major molecular pathway underpinning their toxicity. Here we review recent progress in our understanding of the interactions of αS oligomers with lipid membranes. We highlight key structural and biophysical features of αS oligomers, the effects of these features on αS oligomer membrane binding properties, and resultant implications for understanding the etiology of Parkinson's disease. We discuss mechanistic modes of αS oligomer-lipid membrane interactions and the effects of environmental factors to such modes. Finally, we provide an overview of the current understanding of the main molecular determinants of αS oligomer toxicity in vivo.Congenital heart disease can lead to significant lymphatic complications such as chylothorax, plastic bronchitis, protein losing enteropathy and ascites. Recent improvements in lymphatic imaging and the development of new lymphatic procedures can help alleviate symptoms and improve outcomes.Although concurrent chemoradiotherapy followed by consolidation immunotherapy significantly improves the duration of survival in patients with unresectable stage III non-small cell lung cancer, little data are available on the management of local relapse after therapy. We present here, a patient with initially unresectable non-small cell lung cancer, who underwent right upper lobectomy with reconstruction of the bronchus and pulmonary artery after definitive chemoradiotherapy, followed by consolidation durvalumab. No postoperative complications occurred, and he was recurrence-free at the 10-month follow-up. Salvage surgery might be a viable option for local relapse of non-small cell lung cancer treated with definitive chemoradiotherapy and durvalumab.
Some studies suggest the observed higher mortality in women than men after coronary artery bypass grafting (CABG) is due to confounding. Our meta-analysis aimed to 1) summarize the effect of sex on mortality following CABG and 2) identify whether unmeasured confounding likely explains the apparent higher mortality in women.

MEDLINE, Embase, and CENTRAL databases were searched for studies examining sex and 30-day mortality following CABG. We used random-effects meta-analysis to estimate the summary odds ratio (OR) of mortality in women versus men using 1) unadjusted study results and 2) adjusted study results. Available confounders data from included studies was identified. Using the OR of measured confounders and the risk of death to inform unmeasured confounding effects, we performed bias analysis simulation to correct potential unmeasured confounding in our summary OR.

From 7138 retrieved studies, 112 were included (N=5,008,262 patients), 25 studies reported adjusted OR (N=770,450 patients). The overall 30-day mortality was 4.9% in women vs. 3.3% in men. The unadjusted summary OR (1.81, 95% CI 1.72 to 1.91) and adjusted summary OR (1.40, 95% CI 1.35 to 1.45) demonstrated that women had an increased risk of 30-day mortality compared to men. Simulations correcting for unmeasured confounding that mostly ranged from 1.05 to 1.80, supporting a higher risk of death in women after CABG.

The findings of this review suggest confounding is unlikely to account for the increased risk of mortality in women after CABG and that biological factors have a casual effect.
The findings of this review suggest confounding is unlikely to account for the increased risk of mortality in women after CABG and that biological factors have a casual effect.Development of γ-secretase inhibitors (GSIs) and modulators (GSMs) represents an attractive therapeutic opportunity for Alzheimer's disease (AD) and cancers. However, how these GSIs and GSMs target γ-secretase has remained largely unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human γ-secretase bound individually to two GSI clinical candidates, Semagacestat and Avagacestat, a transition state analog GSI L685,458, and a classic GSM E2012, at overall resolutions of 2.6-3.1 Å. Remarkably, each of the GSIs occupies the same general location on presenilin 1 (PS1) that accommodates the β strand from amyloid precursor protein or Notch, interfering with substrate recruitment. L685,458 directly coordinates the two catalytic aspartate residues of PS1. E2012 binds to an allosteric site of γ-secretase on the extracellular side, potentially explaining its modulating activity. Structural analysis reveals a set of shared themes and variations for inhibitor and modulator recognition that will guide development of the next-generation substrate-selective inhibitors.Determination of what is the specificity of subunits composing a protein complex is essential when studying gene variants on human pathophysiology. The pore-forming α-subunit KCNQ1, which belongs to the voltage-gated ion channel superfamily, associates to its β-auxiliary subunit KCNE1 to generate the slow cardiac potassium IKs current, whose dysfunction leads to cardiac arrhythmia. Using pharmacology, gene invalidation, and single-molecule fluorescence assays, we found that KCNE1 fulfils all criteria of a bona fide auxiliary subunit of the TMEM16A chloride channel, which belongs to the anoctamin superfamily. Strikingly, assembly with KCNE1 switches TMEM16A from a calcium-dependent to a voltage-dependent ion channel. Importantly, clinically relevant inherited mutations within the TMEM16A-regulating domain of KCNE1 abolish the TMEM16A modulation, suggesting that the TMEM16A-KCNE1 current may contribute to inherited pathologies. Altogether, these findings challenge the dogma of the specificity of auxiliary subunits regarding protein complexes and questions ion channel classification.Chagas disease is a neglected tropical disease strongly associated with low socioeconomic status, affecting nearly 8 million people - mainly Latin Americans. The current infection risk is based on acute case reports, most of which are typically associated with oral transmissions. In the semi-arid region of Northeastern Brazil, serious outbreaks of this transmission type have surged in the last years. One of those occurred in 2016 in the state of Rio Grande do Norte. Rural residents of four municipalities surrounding Marcelino Vieira ingested sugar cane juice - which was probably ground with Trypanosoma cruzi-infected insects. Eighteen cases of Chagas disease were confirmed serologically, with two deaths reported. Socioeconomic information, schooling of residents and the structure of peridomestic and domestic environments in the rural area of Marcelino Vieira, along with entomological indicators, were investigated to understand better the factors related to the outbreaks in this region. We found triatomines (m Chagas disease transmission (specifically oral transmission), a combination of factors that may have favored the Chagas disease outbreak. We here provide recommendations to avoid further outbreaks.RNA helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryoelectron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement may apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses suggest not only conserved substrates for TRIM proteins but also, unexpectedly, deep evolutionary connections between TRIM proteins and RNA helicases, linking ubiquitin and RNA biology throughout animal evolution.Systematic perturbation of cells followed by comprehensive measurements of molecular and phenotypic responses provides informative data resources for constructing computational models of cell biology. Models that generalize well beyond training data can be used to identify combinatorial perturbations of potential therapeutic interest. Major challenges for machine learning on large biological datasets are to find global optima in a complex multidimensional space and mechanistically interpret the solutions. To address these challenges, we introduce a hybrid approach that combines explicit mathematical models of cell dynamics with a machine-learning framework, implemented in TensorFlow. We tested the modeling framework on a perturbation-response dataset of a melanoma cell line after drug treatments. The models can be efficiently trained to describe cellular behavior accurately. Even though completely data driven and independent of prior knowledge, the resulting de novo network models recapitulate some known interactions. The approach is readily applicable to various kinetic models of cell biology. A record of this paper's Transparent Peer Review process is included in the Supplemental Information.Human brain research is moving into a dilemma. The best way to understand how the human brain works is to study living human brains in living human beings, but ethical and legal standards make it difficult to do powerful research with actual human beings. So neuroscientists have developed four types of surrogates for living human brains in human bodies genetically edited non-human animals, human/non-human brain chimeras, human neural organoids, and living ex vivo human brain tissues. These new and rapidly improving models offer the hope of understanding human brain function better. If we make our models "too good," they may themselves deserve some of the kinds of ethical and legal respect that have limited brain research in human beings. This article is an initial effort to outline that dilemma.Statements of the core ethical and professional responsibilities of medical professionals are incomplete in ways that threaten fundamental goals of medicine. First, in the absence of explicit guidance for responding to cases in which there is significant uncertainty or disagreement about the relative therapeutic, prophylactic or diagnostic merits of available interventions they perpetuate self-defeating practices. Second, without addressing the role of advertising in shaping patient and community preferences they risk creating moral loopholes that bypass and undermine professional duties of fidelity, honesty and transparency. In both cases, these flaws are exacerbated by an individualism that ignores the critical role of health systems in managing and reducing uncertainty and conflict over best practices, and in communicating with and shaping the expectations of the public. These points are illustrated with examples from the response to COVID-19 and suggestions for reform are proposed.Background and Objective The COVID-19 pandemic increased the use of telehealth around the world. The aim is to minimize health care service disruption as well as reducing COVID-19 exposure. However, one of the major operational concerns is cancellations and rescheduling (C/Rs). C/Rs may create additional burden and cost to the patient, provider, and the health system. Our aim is to understand the reasons for C/Rs of the telehealth session after the scheduled start time. Materials and Methods We reviewed electronic health records (EHRs) to identify the C/R reasons for behavioral health and speech language pathology departments. Documented C/Rs in the medical charts were identified from EHR by using a keyword-based and Natural Language Processing (NLP)-supported EHR search engine. From the search results, we randomly selected 200 notes and conducted a thematic analysis. Results We identified four themes explaining C/R reasons. Most frequent theme was "technicality" (47, 36%), followed by "engagement" (34, 25%), "scheduling" (31, 24%), and "unspecified" (20, 15%). The findings showed that technical reasons are the leading cause of C/Rs, constituting 36% of the cases (95% confidence interval [CI] 29-43%). Notably, "engagement" constituted a sizeable 25% (95% CI 19-31%) of C/Rs, as a result of the inability to engage a patient to complete the telehealth session. Conclusions The study shows that engagement is one of the new challenges to the pediatric telehealth visits. Future studies of new engagement models are needed for the success of telehealth. Our findings will help fill the literature gaps and may help with enhancing the digital experience for both caregivers and providers, reducing wasted time and resources due to preventable C/Rs, improving clinical operation efficiency, and treatment adherence.ABSTRACT Xenomelia is a rare condition characterized by a persistent and intense desire for amputation of one or more healthy limbs. Some frequent clinical manifestations suggest the involvement of distinct neural substrates. Specifically, recent aetiopathological hypotheses about xenomelia propose a neurodevelopmental origin, highlighting the putative contribution of the right parietal lobe and right insula, known to subserve the construction of a coherent representation of the body as a whole. This literature review is aimed at analysing relevant findings about structural and functional brain correlates of xenomelia, focusing on the identification of key regions and their hemispheric distribution. Finally, implications about the potential link between xenomelia and phylogenetic development of the right parietal lobe are discussed. Despite a certain degree of heterogeneity and the spatial extension of networks involved, signs of partial right-sided lateralization of cortical nodes and left-sided lateralization of subcortical nodes emerged. Indeed, some areas-rsPL, riPL, PMC and rInsula-have been consistently found altered in xenomelia. In conclusion, the presence of both structural and functional multi-layered brain abnormalities in xenomelia suggests a multifactorial aetiology; however, as the prevalence of correlational studies, causal relationships remain to be investigated.In response to COVID-19 international restriction of movement laws, the closure of health care facilities, and an ongoing need to support a medically ready force, the U.S. Department of Defense's Virtual Health Europe (VHE) program spearheaded a campaign for synchronous video virtual health (VH) across 42 specialties. Overcoming the challenges of a VH platform designed for nonclinical video teleconferencing, VHE augmented an existing pool of >300 VH-trained providers with an additional 276 providers who collectively performed >4,000 synchronous VH visits between 71 countries from April 2020 through May 2020. Providers proved eager to utilize VH to bring health care to the point of need, however, new challenges emerged highlighted by unreliable and poor connectivity, military-specific network security challenges, and an unfamiliarity with VH etiquette by patients. Addressing the hypothesized third wave of health care demand due to COVID-19 through VH is critical not only for ongoing military readiness requirements, but holds lessons both good and bad for civilian health care delivery as well.Background Access to patients' medical histories can be of vital importance to ensure proper treatment in an emergency. Germany is planning to introduce a medical emergency dataset (MED), accessible through an electronic health card, and comprising important patient information, such as diagnoses, medications, and allergies. Introduction This article evaluates the effect of MEDs on the comprehensiveness of a physician's documentation and handover process to the emergency department of a hospital. Materials and Methods In 2 randomized, crossover simulation studies, 72 emergency physicians participated in 2 emergency scenarios, either with or without access to an MED. Subsequently, they had to document the key information (pre-existing conditions, medications, and allergies) and hand it over to a fictional hospital. The influence of the MED on the documentation of key information was analyzed using the two-sided Prescott's exact test. Sensitivity analyses adjusting for scenario were conducted. Results The results show that in scenarios with an MED, documentation of key information in the handover process was more complete. In the first trial, 2 of 3 key items (pre-existing conditions/information and allergies) presented a statistically noticeable difference in scenarios with the MED. The second trial confirmed these results for all key items. Discussion The findings indicate that the use of MEDs in emergency care could be beneficial since documentation and handover in scenarios with an MED were superior to current real-world practices. Conclusions Access to more complete patient information through an MED could help to improve the patient's treatment.Open data initiatives such as the UK Biobank and Human Connectome Project provide researchers with access to neuroimaging, genetic, and other data for large samples of left-and right-handed participants, allowing for more robust investigations of handedness than ever before. Handedness inventories are universal tools for assessing participant handedness in these large-scale neuroimaging contexts. These self-report measures are typically used to screen and recruit subjects, but they are also widely used as variables in statistical analyses of fMRI and other data. Recent investigations into the validity of handedness inventories, however, suggest that self-report data from these inventories might not reflect hand preference/performance as faithfully as previously thought. Using data from the Human Connectome Project, we assessed correspondence between three handedness measures - the Edinburgh Handedness Inventory (EHI), the Rolyan 9-hole pegboard, and grip strength - in 1179 healthy subjects. We show poor association between the different handedness measures, with roughly 10% of the sample having at least one behavioural measure which indicates hand-performance bias opposite to the EHI score, and over 65% of left-handers having one or more mismatched handedness scores. We discuss implications for future work, urging researchers to critically consider direction, degree, and consistency of handedness in their data.It is widely accepted that metabolic changes associated with training are influenced by a person's genetic background. In this review, we explore the polymorphisms underlying interindividual variability in response to training of weight loss and muscle mass increase in obese individuals, with or without lymphedema, and in normal-weight subjects. We searched PubMed for articles in English published up to May 2019 using the following keywords (((physical training[Title/Abstract] OR sport activity[Title/Abstract]) AND predisposition[Title/Abstract]) AND polymorphism [Title/Abstract]). We identified 38 single-nucleotide polymorphisms that may modulate the genetic adaptive response to training. The identification of genetic marker(s) that improve the beneficial effects of training may in perspective make it possible to assess training programs, which in combination with dietary intervention can optimize body weight reduction in obese subjects, with or without lymphedema. This is particularly important for patients with lymphedema because obesity can worsen the clinical status, and therefore, a personalized approach that could reduce obesity would be fundamental in the clinical management of lymphedema.Introduction Nissen Sleeve (NS) was introduced in the bariatric armamentarium with the purpose to decrease the risk of reflux symptoms following sleeve gastrectomy. The aim of this study was to evaluate our personal experience with this new technique, in particular concerning early postoperative complications ( less then 30 days). Methods We retrospectively reviewed our prospectively collected data on consecutive morbid patients with obesity receiving NS from December 2019 to August 2020. All data pertaining to each patient, including demographic data and preoperative and postoperative clinical data, were collected. Results A total of 28 N-sleeve procedures were performed in the considered period. All the patients had a hiatal hernia that was evaluated between 2 and 6 cm of extent in the preoperative work. Esophagitis of stage A, according to the Los Angeles classification, was detected in 71% of the patients, while 8 out of 28 patients presented a stage B esophagitis. One of the patients had a preoperative diagnosis of Barrett esophagus. A complete disappearance of gastroesophageal reflux disease (GERD) symptoms was achieved in 25 patients out of 28, while the remaining patients reported an improvement in symptoms and continued to be treated with low doses of proton pomp inhibitors. Two reinterventions (7.1%) were performed (Clavien-Dindo IIIb). Three other patients (10.7%) experienced a transient postoperative dysphagia that in one case persisted for 4 months (Clavien-Dindo II). All the patients were managed with conservative treatment, and in each case an endoscopic dilatation was necessary. Conclusions NS appears to be a safe surgical technique with an acceptable early postoperative complication rate. NS appears to be effective in treating patients suffering from obesity and preoperative reflux, but the data are insufficient to establish whether it can reduce the long-term risk of de novo GERD in laparoscopic sleeve gastrectomy patients.Background Parents of children with higher weight are blamed and shamed for their children's weight. However, parents' experiences of this form of stigma, termed weight stigma by association, are poorly understood. The objective of this study was to investigate the sources, forms, and impacts of weight stigma by association among mothers of children with overweight or obesity. Methods In this qualitative study, mothers who reported concern about their children's weight participated in semistructured interviews administered by the research team. A coding scheme was developed and reliably applied to interview transcripts. Mothers' self-reported sociodemographic information, and height and weight were measured. Results Thirty-four mothers (Mage 43.4 years; 26.5% non-Hispanic Black or African American, 70.6% with obesity) participated in the study. Mothers reported that family members were a common source of negative comments about their children's weight; these comments were often critical of mothers' parenting and in some cases contributed to negative affect among mothers. Many mothers also reported negative experiences during children's physicians' visits as a result of their children's weight. Almost all mothers expressed guilt and sadness for their perceived role in their children's weight status, expressing regret that they did not parent differently. Conclusions Mothers of children with overweight and obesity are frequently the target of weight stigma by association and experience negative cognitions and emotions regarding their perceived role in their children's weight. Continued research is needed to elucidate the impacts of stigma by association due to child weight on parents' health, the parent/child relationship, and children's health.Objective This study was intended to investigate the caries prevention potential of carbon dioxide (CO2) laser (λ = 10,600 nm) irradiation followed by application of silver diamine fluoride (SDF) to enamel. Materials and methods Human enamel specimens were randomly allocated to four groups (n = 10 per group). Group 1 specimens were treated with SDF; Group 2 specimens were treated with a CO2 laser; Group 3 specimens were irradiated with a CO2 laser then treated with SDF, and Group 4 specimens received no treatment. All specimens were subjected to pH cycling for cariogenic challenge. Lesion depth, microhardness, surface morphology, and elemental analysis were assessed. Results The lesion depths for Groups 1-4 were 33 ± 16, 80 ± 9, 18 ± 15, and 102 ± 9 μm, respectively (p  less then  0.001; Group 3 less then Group 1 less then Group 2 less then Group 4). Knoop hardness values for Groups 1-4 were 61 ± 19, 68 ± 20, 78 ± 27, and 36 ± 8, respectively (p = 0.002; Group 4 less then Groups 1, 2, and 3). The enamel in Group 4 but not in the other groups showed a roughened surface resembling an acid-etched pattern.
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