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We showed that DNA in antibiotic-susceptible cells has increased accessibility upon exposure to β-lactams and that a judiciously chosen surfactant permeabilized the outer membrane and enhanced this effect. We tested penicillin, cefixime, and ceftriaxone and found good agreement between the results of the nuc-aAST after 15-30 min of antibiotic exposure and the results of the gold-standard culture-based AST measured over days. These results provide a new pathway toward developing a critically needed phenotypic AST for Ng and additional global-health threats.The ability to vocalize is ubiquitous in vertebrates, but neural networks underlying vocal control remain poorly understood. Here, we performed simultaneous neuronal recordings in the frontal cortex and dorsal striatum (caudate nucleus, CN) during the production of echolocation pulses and communication calls in bats. This approach allowed us to assess the general aspects underlying vocal production in mammals and the unique evolutionary adaptations of bat echolocation. Our data indicate that before vocalization, a distinctive change in high-gamma and beta oscillations (50-80 Hz and 12-30 Hz, respectively) takes place in the bat frontal cortex and dorsal striatum. Such precise fine-tuning of neural oscillations could allow animals to selectively activate motor programs required for the production of either echolocation or communication vocalizations. Moreover, the functional coupling between frontal and striatal areas, occurring in the theta oscillatory band (4-8 Hz), differs markedly at the millisecond level, depending on whether the animals are in a navigational mode (that is, emitting echolocation pulses) or in a social communication mode (emitting communication calls). Overall, this study indicates that fronto-striatal oscillations could provide a neural correlate for vocal control in bats.Compromising mitochondrial fusion or fission disrupts cellular homeostasis; however, the underlying mechanism(s) are not fully understood. The loss of C. elegans fzo-1MFN results in mitochondrial fragmentation, decreased mitochondrial membrane potential and the induction of the mitochondrial unfolded protein response (UPRmt). We performed a genome-wide RNAi screen for genes that when knocked-down suppress fzo-1MFN(lf)-induced UPRmt. Of the 299 genes identified, 143 encode negative regulators of autophagy, many of which have previously not been implicated in this cellular quality control mechanism. We present evidence that increased autophagic flux suppresses fzo-1MFN(lf)-induced UPRmt by increasing mitochondrial membrane potential rather than restoring mitochondrial morphology. Furthermore, we demonstrate that increased autophagic flux also suppresses UPRmt induction in response to a block in mitochondrial fission, but not in response to the loss of spg-7, which encodes a mitochondrial metalloprotease. Finally, we found that blocking mitochondrial fusion or fission leads to increased levels of certain types of triacylglycerols and that this is at least partially reverted by the induction of autophagy. We propose that the breakdown of these triacylglycerols through autophagy leads to elevated metabolic activity, thereby increasing mitochondrial membrane potential and restoring mitochondrial and cellular homeostasis.Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019, and has since spread globally, resulting in >95,000 confirmed COVID-19 cases worldwide by March 5, 2020 (1). Singapore adopted a multipronged surveillance strategy that included applying the case definition at medical consults, tracing contacts of patients with laboratory-confirmed COVID-19, enhancing surveillance among different patient groups (all patients with pneumonia, hospitalized patients in intensive care units [ICUs] with possible infectious diseases, primary care patients with influenza-like illness, and deaths from possible infectious etiologies), and allowing clinician discretion (i.e., option to order a test based on clinical suspicion, even if the case definition was not met) to identify COVID-19 patients. Containment measures, including patient isolation and quarantine, active monitoring of contacts, border controls, and community education and precautions, were performed to minimize disease spread. As of March 5, 2020, a total of 117 COVID-19 cases had been identified in Singapore. This report analyzes the first 100 COVID-19 patients in Singapore to determine the effectiveness of the surveillance and containment measures. COVID-19 patients were classified by the primary means by which they were detected. Application of the case definition and contact tracing identified 73 patients, 16 were detected by enhanced surveillance, and 11 were identified by laboratory testing based on providers' clinical discretion. Effectiveness of these measures was assessed by calculating the 7-day moving average of the interval from symptom onset to isolation in hospital or quarantine, which indicated significant decreasing trends for both local and imported COVID-19 cases. Rapid identification and isolation of cases, quarantine of close contacts, and active monitoring of other contacts have been effective in suppressing expansion of the outbreak and have implications for other countries experiencing outbreaks.Few studies have examined factors associated with the timing of identification of hearing loss within a cohort of infants identified as deaf or hard of hearing (DHH) and what factors are associated with delayed identification. Minnesota Early Hearing Detection and Intervention (EHDI) personnel studied deidentified data from 729 infants with confirmed congenital hearing loss (i.e., hearing loss identification after not passing newborn hearing screening) born in Minnesota during 2012-2016. Differences in likelihood of delayed identification of congenital hearing loss (defined as not passing newborn hearing screening and age >3 months at the time of identification as DHH) based on multiple variables were analyzed. Overall, 222 (30.4%) infants identified as DHH had delayed identification. Multivariate regression showed that infants identified as DHH were significantly more likely to have delayed identification if they had 1) low birthweight, 2) public insurance, 3) a residence outside the metropolitan area, 4) a mother with a lower level of education, 5) a mother aged less then 25 years, or 6) a mother who was Hmong. Despite achievements of EHDI programs, disparities exist in timely identification of hearing loss. Using this information to develop public health initiatives that target certain populations could improve timely identification, reduce the risk for language delay, and enhance outcomes in children who are DHH.An outbreak of coronavirus disease 2019 (COVID-19) among passengers and crew on a cruise ship led to quarantine of approximately 3,700 passengers and crew that began on February 3, 2020, and lasted for nearly 4 weeks at the Port of Yokohama, Japan (1). By February 9, 20 cases had occurred among the ship's crew members. By the end of quarantine, approximately 700 cases of COVID-19 had been laboratory-confirmed among passengers and crew. This report describes findings from the initial phase of the cruise ship investigation into COVID-19 cases among crew members during February 4-12, 2020.Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. selleck compound Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety.Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1), including among persons living with human immunodeficiency virus (HIV) infection (2). A World Health Organization (WHO) initiative, The End Tuberculosis Strategy, set ambitious targets for 2020-2035, including 20% reduction in TB incidence and 35% reduction in the absolute number of TB deaths by 2020 and 90% reduction in TB incidence and 95% reduction in TB deaths by 2035, compared with 2015 (3). This report evaluated global progress toward these targets based on data reported by WHO (1). Annual TB data routinely reported to WHO by 194 member states were used to estimate TB incidence and mortality overall and among persons with HIV infection, TB-preventive treatment (TPT) initiation, and drug-resistant TB for 2018 (1). In 2018, an estimated 10 million persons had incident TB, and 1.5 million TB-related deaths occurred, representing 2% and 5% declines from 2017, respectively. The number of persons with both igimens, and prevention and control of HIV will contribute to decreasing TB.In 2017, prescription opioids were involved in 36% of opioid-involved overdose deaths in the United States (1). Prescription opioids can be obtained by prescription or through diversion (the channeling of regulated drugs from legal to illegal sources) (2). Among new heroin users, 66%-83% reported that their opioid use began with the misuse of a prescription opioid (3). "Misuse" is generally defined as drugs taken for a purpose other than that directed by the prescribing physician, in greater amounts, more often, or for a longer duration than prescribed (2). Exposure to prescription opioids can be lessened by ensuring recommended prescribing, thereby potentially reducing the risk for misuse, opioid use disorder, and overdose (4). Sex and age groups with high exposure to prescription opioids are not well defined. Using a retail pharmaceutical database from IQVIA,* nationwide trends in opioid prescription fill rates for adult outpatients by age and sex were examined during 2008-2018. Opioid prescription fill rates were disproportionately higher among men and women aged ≥65 years and women of all ages.
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