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Antibiotic resistance was once confined primarily to hospitals but is becoming increasingly prevalent in family practice settings, making daily therapeutic decisions more challenging. Recent reports of pediatric deaths and illnesses in communities in the United States have raised concerns about the implications and future of antibiotic resistance. Because 20 percent to 50 percent of antibiotic prescriptions in community settings are believed to be unnecessary, primary care physicians must adjust their prescribing behaviors to ensure that the crisis does not worsen. Clinicians should not accommodate patient demands for unnecessary antibiotics and should take steps to educate patients about the prudent use of these drugs. Prescriptions for targeted-spectrum antibiotics, when appropriate, can help preserve the normal susceptible flora. Antimicrobials intended for the treatment of bacterial infections should not be used to manage viral illnesses. Local resistance trends may be used to guide prescribing decisions. [ABSTRACT FROM AUTHOR]

Mutating, mingling, and ever-resourceful, pathogenic bacteria seem able to outwit antibiotics as quickly as researchers develop them. Are doctors permitting the miracle drugs to destroy their own miracle? [ABSTRACT FROM AUTHOR]

Fluoroquinolone resistance in Escherichia coli is principally caused by two kinds of mutations: those affecting the target proteins of the drugs, i.e. DNA gyrase and topoisomerase IV, and those affecting regulatory genes such as marA, soxS or robA. Recently, overexpression of the latter genes was linked to increased organic solvent tolerance in E. coli. Among 138 clinical fluoroquinolone-resistant and -susceptible clinical isolates of E. coli we found a high association between fluoroquinolone resistance and organic solvent tolerance. This finding suggests that E. coli may undergo an adaptive response to extrinsic substances other than quinolones while mutating to fluoroquinolone resistance. [ABSTRACT FROM PUBLISHER]

Objectives: This study investigates the energetic costs associated with Oldowan-style flake production and how skill differences influence these costs., Materials and Methods: Nine adult participants, including novice and expert toolmakers, underwent a 2-h experimental session where we measured energy expenditure and flaking outcomes. We measured body mass (kg), percent body fat, and fat-free mass (kg) and used open-circuit indirect calorimetry to quantify energy expenditure. The lithic analysis used standard linear and mass measurements on the resulting cores and flakes. Qualitative observations from the video recordings provide insight into the subject's body positions and hand grips., Results: Results reveal significant differences in energy expenditure between novice and expert toolmakers, with experts demonstrating lower overall energy expenditure. Additionally, experts produced more flakes, reduced greater core mass per unit of energy expenditure, and exhibited distinct body positions, hand grips, and core/flake morphologies compared with novices., Discussion: The study provides novel insights into the bio-cultural impacts of stone toolmaking skill acquisition, suggesting that skilled performance reduces the metabolic costs of stone tool production. These findings contribute to debates surrounding the origins of human cultural capacities and highlight the importance of including energy expenditure measures in knapping experiments. Moreover, the results suggest that the presence or absence of expertise in the Paleolithic would have fundamentally altered selective pressures and the reliability of skill reproduction. This study enhances our understanding of differences in stone toolmaking skill and their implications for human energy allocation strategies during early technological evolution., (© 2024 The Author(s). American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

Objective: To examine racial differences in lip hydration values- a retrospective analysis., Methods: Baseline lip hydration data collected as Corneometer® CM 825 measurements were culled from sixteen clinical studies conducted under a standard protocol. Data for the three largest subject groups were compared by ANOVA. Possible weather and age effects were also examined., Results: The groups ranked, in order of increasing lip hydration: Black < Caucasian < Hispanic. Two smaller groups not included in the ANOVA, Asian-American and Native-American, had baseline lip hydration values numerically comparable to the Hispanic group. The observed hydration trend was consistent with some literature reports of skin hydration differences due to race measured in other body areas., Limitations: This work had two primary limitations: (1) the studies were conducted by four different clinical research laboratories at different times of the year; (2) the studies relied on the self-classification of race., Conclusion: Given that there is lack of information in the literature on lip biophysical properties, the results of this analysis shed new light on and suggest that racial differences in lip hydration exist, as have been reported for other body areas., Competing Interests: DISCLOSURES: Dr. Gunt is an employee of Burts’ Bees. Dr. Levy serves as a scientific advisor to Burt’s Bees., (Copyright © 2024. Matrix Medical Communications. All rights reserved.)

The evolution of human life history characteristics required dramatic shifts in energy allocation mechanisms compared with our primate ancestors. Thyroid hormones, such as thyroxine (T4) and triiodothyronine (T3), are sensitive to energy balance, and are significant determinants for both tissue-specific and whole-body metabolic rate. Thus, thyroid hormones are in part responsible for setting the body's overall energy budget and likely played an important role in the evolution of human life history patterns. We propose that the dynamics of mammalian T3 production, uptake, and action have evolved so that energy allocation prioritizes the high demands of brain development and functioning, often at the expense of growth and reproduction. This paper explores the role of thyroid hormone dynamics in the evolution of human encephalization, prolonged childhood and adolescence, long lifespans, reproduction, and human aging., (© 2023 The Authors. Evolutionary Anthropology published by Wiley Periodicals LLC.)

Objectives: Recent research suggests that brown adipose tissue (BAT) plays a functional role in non-shivering thermogenesis; however, few studies have examined population variation in BAT or its relationship with other mechanisms of adaptation to cold stress. This study characterized BAT thermogenesis and other adaptive responses to low temperatures among Indigenous Siberian young adults and young adults living near Chicago, IL., Materials and Methods: We recruited 72 Yakut participants (42 females; 30 males) and 54 participants in Evanston, IL (40 females; 14 males). Anthropometric dimensions and resting metabolic rate (RMR) were measured, and we calculated percent divergence in RMR from expected values (divRMR). We also quantified change in supraclavicular temperature, sternum temperature, and energy expenditure after a mild cooling condition., Results: Participants in Yakutia were less likely to shiver during the cooling condition (p < .05) and exhibited significantly greater evidence of BAT thermogenesis, warmer sternum temperatures, and higher divRMR than participants in Evanston (p < .05). Additionally, the relationship between change in supraclavicular temperature and energy expenditure differed between the two samples., Conclusions: Yakut young adults displayed greater evidence of BAT thermogenesis in response to mild cooling compared with young adults living near Chicago, IL. Furthermore, the relationship between BAT thermogenesis and change in energy expenditure appears to be stronger among Yakut adults. Adults that exhibited greater metabolic response to cold stress, such as higher BAT thermogenesis and divRMR, maintained warmer sternum temperatures. These results highlight the degree to which adaptation to cold climates involves multiple integrated biological pathways., (© 2022 Wiley Periodicals LLC.)

While human adaptability is regarded as a classical topic in anthropology, recent work provides new insight into metabolic adaptations to cold climates and the role of phenotypic plasticity in human evolution. A growing body of literature demonstrates that adults retain brown adipose tissue (BAT) which may play a role in non-shivering thermogenesis. In this narrative review, we apply the timescales of adaptation framework in order to explore the adaptive significance of human BAT. Human variation in BAT is shaped by multiple adaptive modes (i.e., allostasis, acclimatization, developmental adaptation, epigenetic inheritance, and genetic adaptation), and together the adaptive modes act as an integrated system. We hypothesize that plasticity in BAT facilitated the successful expansion of human populations into circumpolar regions, allowing for selection of genetic adaptations to cold climates to take place. Future research rooted in human energetics and biocultural perspectives is essential for understanding BAT's adaptive and health significance., (© 2021 Wiley Periodicals LLC.)

Background: Recent studies in adults indicate that cold-induced temperature change of supraclavicular skin corresponds with brown adipose tissue (BAT) thermogenesis., Aim: This study examined the feasibility of using thermography to assess temperature changes in infants aged 18-25 months after mild cooling. Further, this study sought to evaluate whether cold exposure induces a thermal response suggestive of BAT activity underlying the supraclavicular region., Subjects and Methods: Changes in maximum skin temperature at the supraclavicular and interscapular regions were determined using thermal imaging following a mild 5-minute cooling condition (by removal of clothes in a climate-controlled room) in 67 Samoan infants. Temperature changes of the forehead and hand, known BAT-free regions, served as indicators of cooling efficacy., Results: Infants with increased hand and forehead temperatures after cold exposure were excluded from analysis, reducing the effective sample size to 19 infants. On average, forehead ( p  < 0.001), hand ( p  < 0.001) and back (0.029) temperatures dropped significantly while supraclavicular temperatures remained constant. Participants with greater decreases in forehead temperature tended to exhibit greater supraclavicular thermogenesis ( p  = 0.084), suggesting potential BAT activity in this region., Conclusions: While further work is necessary to develop a reliable cooling condition, this study provides proof-of-concept for non-invasive assessment of BAT activity in infants.

Objectives: Evolutionary theorists have debated the adaptive significance of developmental plasticity in organisms with long lifespans such as humans. This debate in part stems from uncertainty regarding the timing of sensitive periods. Does sensitivity to environmental signals fluctuate across development or does it steadily decline? We investigated developmental plasticity in brown adipose tissue (BAT) among indigenous Siberians in order to explore the timing of phenotypic sensitivity to cold stress., Methods: BAT thermogenesis was quantified using infrared thermal imaging in 78 adults (25 men; 33 women). Cold exposure during gestation, infancy, early childhood, middle childhood, and adolescence was quantified using: (1) the average ambient temperature across each period; (2) the number of times daily temperature dropped below -40°F during each period. We also assessed past cold exposure with a retrospective survey of participation in outdoor activities., Results: Adult BAT thermogenesis was significantly associated with the average temperature (p = 0.021), the number of times it was below -40°F (p = 0.026), and participation in winter outdoor activities (p = 0.037) during early childhood., Conclusions: Our results suggest that early childhood represents an important stage for developmental plasticity, and that culture may play a critical role in shaping the timing of environmental signals. The findings highlight a new pathway through which the local consequences of global climate change may influence human biology, and they suggest that ambient temperature may represent an understudied component of the developmental origins of health and disease., (© 2021 Wiley Periodicals LLC.)

Objectives: Increasing obesity rates and accelerating climate change represent two global health challenges shaped by lifestyle change and human environmental modifications. Yet, few studies have considered how these issues may interact to exacerbate disease risk., Methods: In this theory article, we explore evidence that obesity-related disease and climatic changes share socio-ecological drivers and may interact to increase human morbidity and mortality risks. Additionally, we consider how obesity-climate change interactions may disproportionately affect vulnerable populations and how anthropological research can be applied to address this concern., Results: Interactions between heat stress and cardiometabolic disease represent an important pathway through which climate change and obesity-related morbidities may jointly impair health. For example, individuals with higher body fatness and obesity-related metabolic conditions (eg, type 2 diabetes) exhibit a reduced ability to dissipate heat. The risk of poor health resulting from these interactions is expected to be heterogeneous, with low- and middle-income countries, individuals of lower socioeconomic status, and minority populations facing a greater disease burden due to relative lack of resource access (eg, air conditioning). Moreover, older adults are at higher risk due to aging-associated changes in body composition and loss of thermoregulation capabilities., Conclusions: Few policy makers appear to be considering how interventions can be designed to simultaneously address the medical burden posed by increasing obesity rates and climate change. Anthropological research is well situated to address this need in a nuanced and culturally-sensitive way; producing research that can be used to support community resilience, promote holistic well-being, and improve health outcomes., (© 2020 Wiley Periodicals LLC.)

Introduction: UV-induced oxidative skin stress leads to cutaneous photoaging. The objective of these 2 studies was to evaluate a nature-based botanical facial oil for the ability to decrease UV-induced oxidative skin stress., Methods: 22 females were enrolled in the UVA study, and 10 females were enrolled in the UVB study. Skin chemiluminescence induced by UVA exposure was measured at baseline and after 2 weeks of daily topical application of the nature-based facial oil was evaluated in study 1. In study 2, UVB-induced erythema was measured after 8 weeks of twice-daily topical application of the nature-based facial oil to a photoprotected site followed by skin biopsy to evaluate sunburn cell formation. In both studies, the treatment response was compared to the response on untreated skin., Results: The nature-based facial oil significantly reduced skin chemiluminescence following UVA exposure, demonstrating antioxidant activity. The nature-based facial oil also significantly reduced erythema formation following UVB exposure and resulted in reduced sunburn cell formation in 66.67% of subjects., Conclusion: Topical nature-based facial oil can reduce UV-induced oxidative cutaneous damage., (© 2020 Wiley Periodicals LLC.)

Non-shivering thermogenesis (NST) is a metabolic response to acute cold exposure that involves the liberation of chemical energy through physiological mechanisms that are separate from muscle shivering. Recent research suggests that the metabolic and endocrine action of brown adipose tissue (BAT) may play an important role in adult human NST. Thus, characterizing variation in BAT across human populations is of central importance to human biologists interested in human energetics and cardio-metabolic health. The gold standard for measuring BAT requires positron emission tomography (PET) and computed tomography (CT)-a technique that is expensive, exposes the participant to radiation, and is inaccessible to researchers working in many regions. Here, the author outline a noninvasive, portable alternative approach to quantifying BAT that modifies the protocols commonly used in PET/CT studies. The method consists of three components: (a) activating BAT thermogenesis using a mild cooling condition; (b) indirectly quantifying BAT thermogenesis by measuring the change in skin temperature where BAT is commonly stored using infrared thermal imaging; and (c) estimating NST by measuring the change in energy expenditure using open-circuit indirect calorimetry. The development of "field-friendly" methods will allow human biologists to better characterize population variation in BAT as well as its adaptive and health significance., (© 2019 Wiley Periodicals, Inc.)

Background and Objectives: The significance of intravenous over oral acetaminophen (APAP) as part of multimodal analgesic protocols is contested, particularly when considering its relatively high price and use in a surgical cohort such as total hip or knee arthroplasty (THA/TKA), which generally tolerates oral medications. This study aims to elucidate APAP's effectiveness in a large, population-based patient sample., Methods: 1 039 647 THA/TKA procedures were sampled from the Premier Healthcare claims database 2011-2016. APAP use was categorized by intravenous/oral and use on the day of surgery, postoperative day 1 and thereafter. Outcomes were opioid utilization (in oral morphine equivalents), length and cost of hospitalization, and opioid-related adverse effects (respiratory, gastrointestinal, and naloxone use as a proxy). Mixed-effects models measured the associations between intravenous/oral APAP use and outcomes. Percent (%) change and 95% CIs are reported., Results: Overall, 23.6% (n=245 454) of patients received intravenous APAP; of these, 56.3% (n=138 180) received just one dose on the day of surgery. After adjustment for relevant covariates, particularly use of >1 dose of intravenous APAP (compared with no use) on postoperative day 1 was associated with -6.0% (CI -7.2% to -4.7%) reduced opioid utilization; this was -10.7% (CI -11.4% to -9.9%) for use of > 1 dose oral APAP on postoperative day 1. Further comparisons regarding other outcomes also favored oral (over intravenous) APAP., Conclusions: These results do not support the routine use of intravenous APAP in patients undergoing lower joint arthroplasty, especially since oral APAP shows more beneficial outcome patterns., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

This article discusses sexually transmitted infections (STI) screening and focuses on reportable STIs. This includes gonorrhea, chlamydia, syphilis, and human immunodeficiency virus. Hepatitis B and C, trichomonas, and herpes are covered as well. Recommendations are summarized from the various organizations that produce screening recommendations. These screening recommendations only apply to asymptomatic individuals. Once an individual has symptoms, testing becomes diagnostic. It is important to know the prevalence of STIs within your population. If you work in a population with a high prevalence of a specific disease, you may want to screen regardless of the recommendations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Rosacea is characterized by irritation associated with erythema, telangiectasias and papules/pustules. Whole formula nature-based sensitive skin products are formulated to maintain skin barrier and appropriate hydration that can lead to soothing benefits. Objective: To evaluate the efficacy and tolerability of a regimen consisting of a cleanser containing natural oils, beeswax, and witch hazel and day and night creams containing natural oils, glycerin, and botanical anti-inflammatories (NR); and a synthetic dermatologist-recommended regimen of cetyl alcohol, sodium lauryl sulphate-containing cleanser, and glycerin, polyisobutene-containing lotion (CR) in subjects with rosacea. Methods: 80 female subjects with rosacea who received 6 weeks of 0.75% metronidazole gel, were randomized to receive NR or CR, twice daily, for 4 weeks in conjunction with the gel. Blinded investigator global assessment of rosacea, investigator-rated, and subject-rated overall skin appearance was assessed using a 5-point scale (0=none, 4=severe) at baseline, 2 weeks, and 4 weeks. Noninvasive skin assessments for skin hydration and skin barrier function were made by corneometry and TEWL, respectively. Results: NR resulted in improvement in investigator global assessment of rosacea measures at 4 weeks from baseline (erythema, 28%; telangiectasia, 26%; papules/pustules, 34%: P<0.001) and CR resulted in a 8 to 12% improvement. Differences between treatments were statistically significant. Overall skin appearance measured by the investigator was clinically and statistically improved from baseline by 32% and 12% with NR and CR, respectively. Overall skin appearance measured by subjects was improved by both NR and CR from baseline with no differences between treatments. Both regimens improved barrier function from baseline to week 4 (13%, NR; 14%, CR). NR decreased hydration by 21% from baseline at week 4 while CR increased hydration by 14% (P<0.001 from NR). No clinically significant tolerability issues were reported in either regimen at week 4. Conclusion: NR was effective, well tolerated, and superior to CR in the management of rosacea, concomitantly treated with metronidazole. National Clinical Trial Identifier: NCT03392558 J Drugs Dermatol. 2019;18(2):141-146.

Objectives: This study provides the first investigation of non-shivering thermogenesis (NST) and brown adipose tissue (BAT) activity among an indigenous circumpolar population, the Yakut of northeastern Siberia. The study also examines the health significance of BAT activity in this population by testing the relationships between BAT thermogenesis and biomarkers of cardio-metabolic disease risk, such as percent body fat and blood glucose and cholesterol levels., Methods: Data were collected in the Sakha Republic (Yakutia) for 31 men and 43 women. Change in energy expenditure and BAT thermogenesis were quantified after a 30-minute mild cooling condition. Anthropometric dimensions, blood glucose, and lipid levels were also collected., Results: On average, the skin temperature of the supraclavicular area was constant after cooling while the skin temperature of a point on the sternum dropped significantly (P < .001), thus suggesting the presence of active supraclavicular BAT among Yakut adults. Participants with evidence of greater BAT thermogenesis exhibited a larger percent change in energy expenditure (% ΔEE) and an increase in respiratory quotient (RQ) after cooling (P ≤ .05). While there was no relationship between BAT activity and blood lipid levels, BAT thermogenesis was positively associated with blood glucose levels (P < .01)., Conclusions: Yakut adults exhibit evidence of active BAT deposits. Given that there is a significant relationship between BAT activity and % ΔEE, it is possible that BAT plays a role in NST among Yakut adults. While the relationship between BAT and body composition is inconclusive, participants with greater BAT seemed to preferentially utilize glucose during cold stress exposure., (© 2018 Wiley Periodicals, Inc.)

Background: Unique whole formula nature-based sensitive skin products are formulated to minimize irritation while providing conditioning and soothing benefits to clinically diagnosed sensitive skin., Objective: To evaluate and compare the efficacy and tolerability of a regimen of cleanser containing natural oils, beeswax, and witch hazel, and day & night creams containing natural oils, glycerin, and botanical anti-inflammatories (NR); and a synthetic dermatologist-recommended regimen of cetyl alcohol, sodium lauryl sulphate-containing cleanser and glycerin, polyisobutene-containing lotion (CR) in clinically diagnosed sensitive skin resulting from eczema/atopic dermatitis, rosacea, or cosmetic intolerance., Methods: 120 subjects were randomized to receive either NR or CR, twice daily for 4 weeks in this double-blind study. Blinded investigator-rated and subject-rated overall skin appearance was assessed using a 5-point scale (0=none, 4=severe) at baseline, 2 weeks, and 4 weeks. Noninvasive skin assessments for skin hydration and skin barrier function were made by corneometry and TEWL, respectively., Results: NR resulted in a 34% improvement from baseline in investigator-rated overall skin appearance (P less than 0.001); and CR resulted in a 4% improvement. Similar NR and CR results were found in the other efficacy parameters: tactile and visual smoothness, clarity, and radiance. Both regimens improved barrier function from baseline to week 4 (17%, 15%; NR, CR, P equals NS). NR maintained hydration from baseline to week 4 while CR increased hydration by 21% (P less than 0.001). No clinically significant tolerability issues were reported in either regimen at week 4., Conclusions: The study demonstrated that NR was effective, well tolerated, and superior to CR in the management of sensitive skin. J Drugs Dermatol. 2018;17(8):908-913.

The objective of this 6-week clinical study was to demonstrate the effectiveness of a natural ingredient-based moisturizing cream versus a colloidal oatmeal moisturizing cream in improving the hydration, barrier function, appearance, and feel of dry leg skin. Thirty-two subjects completed the study. After a 5-day washout, subjects used the natural ingredient-based moisturizing cream and oatmeal-containing cream on randomly-assigned legs twice a day for a period of three weeks. For the following two weeks subjects did not use any moisturizer on their legs. Skin moisture measurements showed a statistically significant increase in hydration for both products at all time points during the treatment phase of the study. Both products reduced transepidermal water loss measurements during the treatment phase of the study, showing their abilities to improve stratum corneum barrier function. Clinical evaluations showed that both products significantly decreased visual dryness and tactile roughness during the treatment phase. Improvements in the assessed clinical parameters persisted even after treatment cessation. In conclusion, the natural ingredient-based moisturizing cream was highly effective in providing moisturization and improving the skin barrier of subjects with very dry leg skin. It also produced significant improvements in visual dryness and tactile roughness that persisted during regression. Overall, these results show that the natural ingredient-based moisturizing cream delivers comparable benefits to that of a colloidal oatmeal-containing benchmark product and is an option for health care providers and consumers who seek relief from dry skin and prefer a product with all-natural ingredients. J Drugs Dermatol. 2018;17(7):758-764.

Introduction: Diaper dermatitis is a common condition that develops in the diaper area due to factors such as elevated moisture, increased skin surface pH, and exposure to irritants from urine and feces. These factors suggest interventions to prevent or treat diaper dermatitis such as exposing the skin to air, frequent diaper changes, and thorough cleansing of the diaper area. Barrier creams and powders also have a role in preventing and treating diaper dermatitis. We developed a cream-to-powder product with a formula based on corn starch and other natural ingredients for use in the diaper area., Methods: Dye exclusion study: The barrier properties of the cream-to-powder product were assessed using a dye exclusion protocol. Skin color at treated and untreated forearm sites was measured at baseline and after exposure to crystal violet stain. The cream-to-powder product's ability to inhibit the water-soluble dye from reaching the skin was judged by comparing color changes at the treated and untreated sites. Tolerance-in-use study: The safety of the cream-to-powder product was assessed in a four-week tolerance-in-use study conducted in a group of 52 diaper-wearing infants and toddlers. Subjects' parents/guardians applied the cream-to-powder product at each diaper change. A pediatrician judged safety endpoints of erythema, dryness, and edema in the diaper area at baseline and at study end. Parents/guardians also completed a questionnaire at study end. These studies have complied with Good Clinical Practices (GCP/ICH)., Outcomes: The cream-to-powder product prevented about 70% of the test dye from reaching the skin surface, demonstrating its ability to supplement the skin barrier. The tolerance-in-use study showed no statistically significant changes in any of the safety endpoints; there were no adverse events. Parents/guardians responses to the cream-to-powder product were overwhelmingly positive. Taken together, these results support that the cream-to-powder formulation is safe and effective for helping to prevent diaper dermatitis. J Drugs Dermatol. 2018;17(5):566-570.

Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli , as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli , the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds., (Copyright © 2018 Molina-Quiroz et al.)

In Escherichia coli , OmpF is an important outer membrane protein, which serves as a passive diffusion pore for small compounds including nutrients, antibiotics, and toxic compounds. OmpF expression responds to environmental changes such as temperature, osmolarity, nutrients availability, and toxic compounds via complex regulatory pathways involving transcriptional and post-transcriptional regulation. Our study identified a new regulatory cascade that controls the expression of OmpF porin. This pathway involves BluR, a transcriptional regulator repressing the expression of the ycgZ-ymgABC operon. We showed that BluR was responsible for the temperature-dependent regulation of the ycgZ-ymgABC operon. Furthermore, our results showed that independent expression of YcgZ led to a decreased activity of the ompF promoter, while YmgA, YmgB, and YmgC expression had no effect. We also determined that YcgZ accumulates in the absence of the Lon protease. Thus, mutation in bluR leads to de-repression of ycgZ-ymgABC transcription. With a second mutation in lon , YcgZ protein accumulates to reach levels that do not allow increased expression of OmpF under growth conditions that usually would, i.e., low temperature. With BluR responding to blue-light and temperature, this study sheds a new light on novel signals able to regulate OmpF porin.

Atrial fibrillation (AF) is the most common cardiac rhythm disturbance encountered in clinical practice, and its prevalence is increasing as the population ages. The American College of Cardiology, the American Heart Association, and the European Society of Cardiology established guidelines for the management of patients with AF. Atrial flutter (Afl) is less common and is often associated with or preceded by AF or occurs in an isolated pattern. A major limitation of the currently published guidelines for the management of patients with AF and Afl is their complexity, the fact that official guidelines are published separately for each of these arrhythmias, and that they were published several years ago. To address these deficiencies, we have developed a novel pathway for the management of AF and Afl. The pathway has been designated with the acronym RACE, which reflects the 4 main components in patient management: rate control, anticoagulation therapy, cardioversion, and electrophysiology/antiarrhythmic medication. This pathway is an attempt to incorporate, in a user-friendly format, the key concepts of the initial diagnosis and management of these prevalent arrhythmias. This is followed by a comprehensive guideline for therapy using the RACE acronym.

The Food and Drug Administration (FDA) recently released a final rule to ban triclosan and 18 other antimicrobial chemicals from soaps. We applaud this rule specifically because of the associated risks that triclosan poses to the spread of antibiotic resistance throughout the environment. This persistent chemical constantly stresses bacteria to adapt, and behavior that promotes antibiotic resistance needs to be stopped immediately when the benefits are null., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Objectives: Among indigenous circumpolar populations, extreme seasonality influences food availability and energy metabolism. Furthermore, subsistence patterns and wage labor opportunities shift with season. Thus, health measures among circumpolar populations likely exhibit seasonal changes that are influenced by lifestyle factors. This study examines how markers of cardio-metabolic health vary between summer and winter as a function of an individual's lifestyle and sex among the Yakut of northeastern Siberia., Methods: Anthropometric dimensions, serum lipids and glucose levels, blood pressure, and lifestyle data were collected for a sample of 115 Yakut participants (71 women, 44 men) in Berdygestiakh, Sakha Republic, Russia in the summer of 2009 and winter of 2011., Results: Men and women experienced significant increases in total and HDL cholesterol and triglyceride levels from summer to winter. Women exhibited winter-time increases in adiposity and glucose levels. Men who reported greater market integration were more likely to have lower winter blood pressure levels. Additionally, time spent fishing was associated with lower winter-time LDL cholesterol, while foraging time was associated with higher HDL cholesterol., Conclusions: While seasonal changes in anthropometric dimensions were modest, Yakut men and women experienced significant increases in total cholesterol and HDL cholesterol from summer to winter. These results also suggest that while Yakut individuals with greater subsistence participation are more buffered from adverse seasonal changes in cholesterol levels, they may be at a greater risk for winter increases in blood pressure. Furthermore, the interactions between lifestyle and seasonal change in metabolic health appear to differ between Yakut women and men. Am. J. Hum. Biol. 28:868-878, 2016. © 2016Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Persister cells are highly tolerant to different antibiotics and are associated with relapsing infections. In order to understand this phenomenon further, we exposed a transposon library to a lethal concentration of ampicillin, and mutants that survived were identified by transposon sequencing (Tn-Seq). We determined that mutations related to carbon metabolism, cell envelope (cell wall generation and membrane proteins), and stress response have a role in persister cell generation., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The division of labour is a central feature of the most sophisticated biological systems, including genomes, multicellular organisms and societies, which took millions of years to evolve. Here we show that a well-organized and robust division of labour can evolve in a matter of days. Mutants emerge within bacterial colonies and work with the parent strain to gain new territory. The two strains self-organize in space: one provides a wetting polymer at the colony edge, whereas the other sits behind and pushes them both along. The emergence of the interaction is repeatable, bidirectional and only requires a single mutation to alter production of the intracellular messenger, cyclic-di-GMP. Our work demonstrates the power of the division of labour to rapidly solve biological problems without the need for long-term evolution or derived sociality. We predict that the division of labour will evolve frequently in microbial populations, where rapid genetic diversification is common.

Natamycin is a poorly soluble, polyene macrolide antifungal agent used in the food industry for the surface treatment of cheese and sausages. This use is not of safety concern. However, highly soluble natamycin-cyclodextrin inclusion complexes have been developed for the protection of beverages. This practice leads to high drug exposures exceeding the safety level. Apart from the definition of an acceptable daily dietary exposure to natamycin, its effect on the faecal flora as a reservoir for resistance has to be examined. Consumption of food to which natamycin has been added and mixed homogeneously, such as yoghurt, and in particular the addition of cyclodextrin inclusion complexes to beverages and wine generates high faecal natamycin concentrations resulting in high drug exposures of faecal Candida spp. Development of natamycin resistance has been observed in Candida spp. colonising the intestinal tract of patients following natamycin treatment of fungal infections. Horizontal gene transfer among different Candida spp. and within Aspergillus fumigatus spreads resistance. Therefore, it cannot be denied that use of natamycin for preservation of yoghurt and beverages may foster development of resistance to polyenes in Candida spp., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Previous research has shown that indigenous circumpolar populations have elevated basal metabolic rates (BMRs), yet few studies have explored whether metabolic rates increase during the winter. This study addresses this gap by examining seasonal variation in BMR and its associations with thyroid function and lifestyle factors among the Yakut (Sakha) of Siberia., Methods: Anthropometric dimensions, BMR, and thyroid hormone levels (free triiodothyronine [fT3], free thyroxine [fT4], thyroid-stimulating hormone [TSH]) were measured on two occasions (July/August, 2009 and January 2011) on a sample of 94 Yakut (Sakha) adults (35 men, 59 women) from the rural village of Berdygestiakh, Sakha Republic, Russia., Results: Seasonal changes in BMR varied by age. Younger Yakut adults (19-49 years) showed significant elevations in winter-time BMR of 6% (P < 0.05), whereas older individuals (≥50 years) showed modest declines (2%; n.s.). Both younger and older Yakut men and women showed increased respiratory quotients during the winter. FT3 and fT4 levels significantly declined during the winter in both younger and older Yakut men and women (P < 0.05). Lifestyle factors were significant predictors of BMR variation, particularly among older men and women., Conclusions: Among the Yakut, increased wintertime BMR was observed among younger but not older adults, whereas all adults showed sharp reductions in free thyroid hormone levels during the winter. Among men, greater participation in subsistence activities was associated with increased BMRs and greater fat oxidation. Among women, variation in food use had the strongest impact on metabolic function., (Copyright © 2014 Wiley Periodicals, Inc.)

Microbes commonly live in dense surface-attached communities where cells layer on top of one another such that only those at the edges have unimpeded access to limiting nutrients and space. Theory predicts that this simple spatial effect, akin to plants competing for light in a forest, generates strong natural selection on microbial phenotypes. However, we require direct empirical tests of the importance of this spatial structuring. Here we show that spontaneous mutants repeatedly arise, push their way to the surface, and dominate colonies of the bacterium Pseudomonas fluorescens Pf0-1. Microscopy and modeling suggests that these mutants use secretions to expand and push themselves up to the growth surface to gain the best access to oxygen. Physically mixing the cells in the colony, or introducing space limitations, largely removes the mutant's advantage, showing a key link between fitness and the ability of the cells to position themselves in the colony. We next follow over 500 independent adaptation events and show that all occur through mutation of a single repressor of secretions, RsmE, but that the mutants differ in competitiveness. This process allows us to map the genetic basis of their adaptation at high molecular resolution and we show how evolutionary competitiveness is explained by the specific effects of each mutation. By combining population level and molecular analyses, we demonstrate how living in dense microbial communities can generate strong natural selection to reach the growing edge.

Objectives: Multidrug efflux pumps mediate resistance to antibiotics and other toxic compounds. We studied the role of AcrAB-TolC, the main efflux pump in Escherichia coli, in regulating gene expression., Methods: Deletion mutants, an acrABp-lacZ fusion and reverse transcription-real-time quantitative PCR experiments were used to study the role of AcrAB-TolC and metabolism in regulating gene expression of the acrAB operon and its transcriptional regulators., Results: Deletion of the acrB gene increased the expression of the acrAB operon. A similar induction of acrAB was found when acrA or tolC was deleted, and when the pump function was inhibited using phenylalanine-arginine-β-naphthylamide. The induction of acrAB in the ΔacrB strain was totally (AcrR or SoxS) or partially (SoxR or MarA) prevented when the genes for these acrAB regulators were also deleted. The expression of soxS and marA, but not of acrR, was increased in the ΔacrB strain, which also showed altered expression of many other genes related to different cellular processes, including motility. Deletion of the metabolic genes entA and entE (enterobactin biosysnthesis), glpX (gluconeogenesis), cysH (cysteine biosynthesis) and purA (purine biosynthesis) also prevented activation of the acrAB promoter in the ΔacrB strain. Addition of the enterobactin biosynthesis intermediate metabolite 2,3-dihydroxybenzoate induced the expression of acrAB., Conclusions: These results together suggest a model in which the AcrAB-TolC pump effluxes cellular metabolites that are toxic and/or have a signalling role. If the pump is inactivated or inhibited, these metabolites would accumulate, inactivating AcrR and/or up-regulating soxS and marA expression, ultimately triggering the up-regulation of acrAB expression to restore homeostasis.

Omadacycline is a novel first-in-class aminomethylcycline with potent activity against important skin and pneumonia pathogens, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA), β-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae, Haemophilus influenzae, and Legionella. In this work, the mechanism of action for omadacycline was further elucidated using a variety of models. Functional assays demonstrated that omadacycline is active against strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection). Macromolecular synthesis experiments confirmed that the primary effect of omadacycline is on bacterial protein synthesis, inhibiting protein synthesis with a potency greater than that of tetracycline. Biophysical studies with isolated ribosomes confirmed that the binding site for omadacycline is similar to that for tetracycline. In addition, unlike tetracycline, omadacycline is active in vitro in the presence of the ribosomal protection protein Tet(O).

Omadacycline is the first intravenous and oral 9-aminomethylcycline in clinical development for use against multiple infectious diseases including acute bacterial skin and skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP), and urinary tract infections (UTI). The comparative in vitro activity of omadacycline was determined against a broad panel of Gram-positive clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Lancefield groups A and B beta-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae (PRSP), and Haemophilus influenzae (H. influenzae). The omadacycline MIC90s for MRSA, VRE, and beta-hemolytic streptococci were 1.0 μg/ml, 0.25 μg/ml, and 0.5 μg/ml, respectively, and the omadacycline MIC90s for PRSP and H. influenzae were 0.25 μg/ml and 2.0 μg/ml, respectively. Omadacycline was active against organisms demonstrating the two major mechanisms of resistance, ribosomal protection and active tetracycline efflux. In vivo efficacy of omadacycline was demonstrated using an intraperitoneal infection model in mice. A single intravenous dose of omadacycline exhibited efficacy against Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, including tet(M) and tet(K) efflux-containing strains and MRSA strains. The 50% effective doses (ED50s) for Streptococcus pneumoniae obtained ranged from 0.45 mg/kg to 3.39 mg/kg, the ED50s for Staphylococcus aureus obtained ranged from 0.30 mg/kg to 1.74 mg/kg, and the ED50 for Escherichia coli was 2.02 mg/kg. These results demonstrate potent in vivo efficacy including activity against strains containing common resistance determinants. Omadacycline demonstrated in vitro activity against a broad range of Gram-positive and select Gram-negative pathogens, including resistance determinant-containing strains, and this activity translated to potent efficacy in vivo.

Objectives: Previous research has shown that the extreme cold and short day lengths of polar winters promote increased production and uptake of thyroid hormones, resulting in marked declines in free triiodothyronine (fT3). However, this "polar T3 syndrome" has been documented almost exclusively on small samples of male sojourners and little is known about seasonal changes in thyroid function among indigenous circumpolar groups. The present study addresses this gap by examining seasonal changes in thyroid hormone levels among the indigenous Yakut (Sakha) of northeastern Siberia., Methods: Anthropometric dimensions and thyroid measures (fT3, free thyroxine [fT4], thyroid-stimulating hormone [TSH]) were obtained on two occasions (July/August, 2009 and January 2011) on a sample of 134 Yakut adults (51 men, 83 women) from the village of Berdygestiakh, Sakha Republic/Yakutia, Russia., Results: Yakut men and women both displayed significant declines in fT3 and fT4, and significant increases in TSH from summer to winter despite showing only modest seasonal changes in body mass and composition. Among men, gains in fat-free mass (FFM) were associated with larger reductions in fT3 and greater increases in TSH. Men living more traditional lifeways showed larger winter declines in fT4 and greater increases in TSH., Conclusions: The Yakut exhibited significant winter declines in fT3 levels similar to other circumpolar groups studied. However, the magnitude of seasonal change was greater in the Yakut, perhaps reflecting their distinctive metabolic physiology. Lifestyle factors play a mediating role in thyroid responses, such that men with more traditional lifeways had more exaggerated seasonal changes., (Copyright © 2013 Wiley Periodicals, Inc.)

Previous data from our laboratory suggest a relationship between increased pmrAB expression and virulence in an Escherichia coli mouse infection model of pyelonephritis. Competitive infections with wild type and pmrAB mutants showed that disruption of pmrAB caused decreased persistence of E. coli within the mouse kidney. These results were confirmed with plasmid-mediated complementation of the pmrAB mutant. Additionally, increased expression of pmrAB from this complementing plasmid in a previously attenuated marA-rob-soxS triple mutant displayed increased bacterial persistence in the infection when compared with the triple mutant alone. These findings suggest a role for this two-component regulatory system in the virulence of E. coli in a murine pyelonephritis model.