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A dysregulated host response to infection resulting in life-threatening organ dysfunction defines the onset of sepsis. Unfortunately, sepsis is common, costly, and deadly. The Surviving Sepsis Campaign publishes regularly updated, evidence-informed, detection, and treatment guidelines culminating in time-sensitive care “bundles.” The goal of these bundles is to expedite sepsis recognition because it is widely held that early treatment is life-saving. Hospitals are mandated to publicly report their bundle compliance, and this will soon be tied to hospital reimbursement. For these reasons, hospitals are creating sepsis emergency response teams which are a form of a rapid response team consisting of dedicated medical professionals who evaluate patients with suspected sepsis and initiate therapy when appropriate. Evidence to date support sepsis emergency response teams as a mechanism to improve bundle compliance, and potentially, patient outcome. Nevertheless, some elements of bundled sepsis care are controversial (e.g., intravenous fluid administration) as some argue that mandated treatment precludes personalized care. Herein, we briefly describe general sepsis emergency response team structure, review evidence supporting sepsis emergency response teams to improve bundle compliance and patient outcome and report our unique experience incorporating point of care ultrasound—to guide intravenous fluid—into a nursing-led sepsis team. We propose that our sepsis emergency response team approach allays concern that sepsis care is either bundled or personalized. Instead, incorporating point of care ultrasound into a nursing-led sepsis emergency response team increases bundle compliance and individualizes care.

Background: Between 52–86% of people who menstruate in the United States use tampons—cotton and/or rayon/viscose ‘plugs’—to absorb menstrual blood in the vagina. Tampons may contain metals from agricultural or manufacturing processes, which could be absorbed by the vagina’s highly absorptive tissue, resulting in systemic exposure. To our knowledge, no previous studies have measured metals in tampons. Objectives: We evaluated the concentrations of 16 metal(loid)s in 30 tampons from 14 tampon brands and 18 product lines and compared the concentrations by tampon characteristics. Methods: About 0.2 – 0.3 g from each tampon (n = 60 samples) were microwave-acid digested and analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine concentrations of arsenic, barium, calcium, cadmium, cobalt, chromium, copper, iron, manganese, mercury, nickel, lead, selenium, strontium, vanadium, and zinc. We compared concentrations by several tampon characteristics (region of purchase, organic material, brand type) using median quantile mixed models. Results: We found measurable concentrations of all 16 metals assessed. We detected concentrations of several toxic metals, including elevated mean concentrations of lead (geometric mean [GM] = 120 ng/g), cadmium (GM = 6.74 ng/g), and arsenic (GM = 2.56 ng/g). Metal concentrations differed by region of tampon purchase (US versus European Union/United Kingdom), by organic versus non-organic material, and for store- versus name-brand tampons. Most metals differed by organic status; lead concentrations were higher in non-organic tampons while arsenic was higher in organic tampons. No categoriy had consistently lower concentrations of all or most metals. Discussion: Tampon use is a potential source of metal exposure. We detected all 16 metals in at least one sampled tampon, including some toxic metals like lead that has no “safe” exposure level. Future research is needed to replicate our findings and determine whether metals can leach out of tampons and cross the vaginal epithelium into systemic circulation.

BackgroundDigital phenotyping is a promising methodology for capturing moment-to-moment data that can inform individually adapted and timely interventions for youths with chronic pain. ObjectiveThis study aimed to investigate adolescent and parent endorsement, perceived utility, and concerns related to passive data stream collection through smartphones for digital phenotyping for clinical and research purposes in youths with chronic pain. MethodsThrough multiple-choice and open-response survey questions, we assessed the perspectives of patient-parent dyads (103 adolescents receiving treatment for chronic pain at a pediatric hospital with an average age of 15.6, SD 1.6 years, and 99 parents with an average age of 47.8, SD 6.3 years) on passive data collection from the following 9 smartphone-embedded passive data streams: accelerometer, apps, Bluetooth, SMS text message and call logs, keyboard, microphone, light, screen, and GPS. ResultsQuantitative and qualitative analyses indicated that adolescents and parent endorsement and perceived utility of digital phenotyping varied by stream, though participants generally endorsed the use of data collected by passive stream (35%-75.7% adolescent endorsement for clinical use and 37.9%-74.8% for research purposes; 53.5%-81.8% parent endorsement for clinical and 52.5%-82.8% for research purposes) if a certain level of utility could be provided. For adolescents and parents, adjusted logistic regression results indicated that the perceived utility of each stream significantly predicted the likelihood of endorsement of its use in both clinical practice and research (Ps

Pre-exposure prophylaxis (PrEP) offers a potential biomedical strategy to reduce HIV incidence among adolescent populations disproportionately affected by HIV. There is limited evidence on the social and clinical implications, including engagement in HIV prevention efforts, of PrEP for South African adolescents, who face high HIV risk. We conducted a mixed-methods study in Western Cape, South Africa from 2015 to 2016. Adolescents (N = 35) aged 16–17 and clinical service providers working with adolescents (N = 25) were recruited from community and clinic settings. Adolescents and service providers completed a survey about their overall perceptions of PrEP and completed interviews guided by semi-structured protocols. We performed descriptive analysis of quantitative data using SPSS and thematic analysis of qualitative data using NVivo. The majority of adolescents endorsed future PrEP use for themselves and partners, and all clinical service providers endorsed future PrEP use for sexually active adolescents. Both adolescents and service providers identified PrEP as an opportunity to engage youth as active participants in HIV prevention. Service providers also viewed PrEP as a potential mechanism for shifting life trajectories. Findings from this study enhance our understanding of the considerations needed to engage adolescents and clinical service providers in the roll-out of oral PrEP in South Africa.

Abstract Background In adults with diabetes, diabetic foot ulcer (DFU) and amputation are common and associated with significant morbidity and mortality. Purpose Identify tools predicting risk of DFU or amputation that are prognostically accurate and clinically feasible. Methods We searched for systematic reviews (SRs) of tools predicting DFU or amputation published in multiple databases from initiation to January, 2023. We assessed risk of bias (ROB) and provided a narrative review of reviews describing performance characteristics (calibration and discrimination) of prognostically accurate tools. For such tools, we additionally reviewed original studies to ascertain clinical applicability and usability (variables included, score calculation, and risk categorization). Results We identified 3 eligible SRs predicting DFU or amputation risk. Two recent SRs (2020 and 2021) were rated as moderate and low ROB respectively. Four risk prediction models – Boyko, Martins‐Mendes (simplified), Martins‐Mendes (original), and PODUS 2020 had good prognostic accuracy for predicting DFU or amputation over time horizons ranging from 1‐ to 5‐years. PODUS 2020 predicts absolute average risk (e.g., 6% risk of DFU at 2 years) and consists of 3‐binary variables with a simple, summative scoring (0–4) making it feasible for clinic use. The other 3 models categorize risk subjectively (e.g., high‐risk for DFU at 3 years), include 2–7 variables, and require a calculation device. No data exist to inform rescreening intervals. Furthermore, the effectiveness of targeted interventions in decreasing incidence of DFU or amputation in response to prediction scores is unknown. Conclusions In this review of reviews, we identified 4 prognostically accurate models that predict DFU or amputation in persons with diabetes. The PODUS 2020 model, predicting absolute average DFU risk at 2 years, has the most favorable prognostic accuracy and is clinically feasible. Rescreening intervals and effectiveness of intervention based on prediction score are uncertain.

Summary: Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28–3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13–2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63– 4.80) or troponin (OR 1.89; 95% 1.03–3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61–2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96–5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17–2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH.

Recently, we found that the anti-microtubule drugs colchicine and propham caused the absence of microtubules and thus loss of cytoplasmic zonation in in vitro growing pollen tubes of Nicotiana sylvestris, but did not seriously affect growth. In the present study we used the herbicide carbetamide as an anti-microtubule drug. It had the same effect as colchicine and propham: the cytoplasm, including the generative cell, was no longer concentrated in the tip but was distributed randomly. In addition, ultrastructural investigations have shown that even the vesicle zone, usually found at the very tip of pollen tubes, had disappeared in some tubes. Nonetheless, in vitro growth was not inhibited by more than 20% over a period of 22 h. In contrast, tube growth in plants ceased 1 cm down in the style when carbetamide was applied to the stigma before pollination. At the lowest concentration causing this effect, microtubules of the vegetative cell had disappeared and the cytoplasm was distributed randomly, as it was for in vitro grown tubes. It can be concluded that microtubules of the vegetative cell are essential for pollen tube growth in the style. [ABSTRACT FROM AUTHOR]

The polarity of a growing pollen tube is clearly reflected by a distinct zonation of the cytoplasmic content. The vegetative nucleus and the generative cell (GC) are located in the tip region of the tube, and the basal cytoplasmic portion is highly vacuolated. Using pollen tubes of Nicotiana sylvestris Spegazz. & Comes grown in vitro, we examined the effects of varying concentrations of the microtubule inhibitors colchicine and propham. The depolymerization of the cortical microtubules by 25 μM colchicine led to a disorganization of the cytoplasm, i.e., vacuolization of the tip region, and to a deranged position of both the vegetative nucleus and the generative cell. The same concentration of colchicine inhibited tube growth by 10-20% of the control. Mitosis of the GC was not affected. Only from concentrations of 200 μM the configuration of the GC's microtubules was altered and an inhibition of mitosis was observed. At this concentration the disorganization of the cytoplasm was always reversible, but neither inhibition of mitosis nor derangement of the nuclear positioning was. At 1,800 μM colchicine, pollen tube growth was inhibited by 50% of the control. Using propham, the same three steps of action were observed, although propham proved to be about a hundred times more effective than colchicine. We conclude that the cortical microtubules of the pollen tube are involved in maintaining cellular polarity, probably as a part of a heterogeneous cytoskeletal network including also microfilaments and membranous elements. Nuclear positioning seems to be dependent on both, the tube's cortical and the GC's microtubules. A possible involvement of the extracellular matrix in maintaining intracytoplasmic polarity is suggested. [ABSTRACT FROM AUTHOR]

Tobacco ( Nicotiana tabacum L.) pollen, germinated 4 hours in suspension culture, was labeled with radioactive leucine and fractionated into constituent membranes by the technique of preparative free-flow electrophoresis. Tubes were ruptured by sonication directly into the electrophoresis buffer. Unfortunately, the Golgi apparatus of the rapidly elongating pollen tubes did not survive the sonication step. However, it was possible to obtain useful fractions of endoplasmic reticulum and mitochondria. To obtain Golgi apparatus, glutaraldehyde was added to the homogenization buffer during sonication. Plasma membrane, which accounted for only about 3% of the total membrane of the homogenates as determined by staining with phosphotungstate at low pH, was obtained in insufficient quantity and fraction purity to permit analysis. Results show rapid incorporation of [H]leucine into endoplasmic reticulum followed by rapid chase out. The half-time for loss of radioactivity from the pollen tube endoplasmic reticulum was about 10 minutes. Concomitant with the loss of radioactivity from endoplasmic reticulum, the Golgi apparatus fraction was labeled reaching a maximum 20 minutes post chase. The findings suggest flow of membranes from endoplasmic reticulum to the Golgi apparatus during pollen tube growth. [ABSTRACT FROM AUTHOR]

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