Nurse Corps' impact on increasing registered nurse staffing in critical shortage areas and facilities, 2017 to 2022.

BACKGROUND: The registered nurse (RN) workforce experienced critical pre-pandemic and pandemic shortages of labor in some areas in the United States. People living in these health professional shortage areas (HPSAs) may have less access to health services. The Bureau of Health Workforce within the Health Resources and Services Administration administers Nurse Corps scholarship and loan repayment programs to increase healthcare access by increasing the supply and distribution of RNs, nurse practitioners, and nurse faculty to HPSAs. The American Rescue Plan Act of 2021 (ARPA) made available considerable new resources for the program. PURPOSE: This paper reports on Nurse Corps applications, awards, and distribution in 2 cohorts in the period 2017 to 2022 to assess the impact of receiving an additional $200 million appropriated in 2021. DISCUSSION: Additional funds through ARPA were associated with nearly threefold increases in the number of Nurse Corps awards. Program participants worked in a total of 1,316 counties (42% of all U.S. counties) in 2020 to 2022, a 76% increase from 749 counties in 2017 to 2019. CONCLUSION: Increased funding for scholarship and loan repayment can help to improve the distribution of nurse labor to a greater number of critical shortage areas in the United States.

Chlamydomonas cells transition through distinct Fe nutrition stages within 48 h of transfer to Fe-free medium.

Low iron (Fe) bioavailability can limit the biosynthesis of Fe-containing proteins, which are especially abundant in photosynthetic organisms, thus negatively affecting global primary productivity. Understanding cellular coping mechanisms under Fe limitation is therefore of great interest. We surveyed the temporal responses of Chlamydomonas (Chlamydomonas reinhardtii) cells transitioning from an Fe-rich to an Fe-free medium to document their short and long-term adjustments. While slower growth, chlorosis and lower photosynthetic parameters are evident only after one or more days in Fe-free medium, the abundance of some transcripts, such as those for genes encoding transporters and enzymes involved in Fe assimilation, change within minutes, before changes in intracellular Fe content are noticeable, suggestive of a sensitive mechanism for sensing Fe. Promoter reporter constructs indicate a transcriptional component to this immediate primary response. With acetate provided as a source of reduced carbon, transcripts encoding respiratory components are maintained relative to transcripts encoding components of photosynthesis and tetrapyrrole biosynthesis, indicating metabolic prioritization of respiration over photosynthesis. In contrast to the loss of chlorophyll, carotenoid content is maintained under Fe limitation despite a decrease in the transcripts for carotenoid biosynthesis genes, indicating carotenoid stability. These changes occur more slowly, only after the intracellular Fe quota responds, indicating a phased response in Chlamydomonas, involving both primary and secondary responses during acclimation to poor Fe nutrition.

Bariatric and general surgical procedures in obese patients with a history of venous thromboembolism and concurrent anticoagulation therapy.

OBJECTIVE: The objective of this study was to examine the use and outcomes of perioperative anticoagulation (AC) in obese patients with a known history of venous thromboembolism event (VTE). METHOD: A retrospective review of a prospective database for patients with a VTE history undergoing bariatric and general surgery at a single center (1/2008-12/2017) was performed. Factors assessed included demographics, surgical details, and outcomes. RESULTS: Sixty-five patients underwent 76 procedures: 46 females (71%); mean age 51 years (range 26-73), mean weight 284 pounds (range 110-558), mean body mass index 45 (range 19-87). Comorbidities include hypertension (60%), gastroesophageal reflux disease (54%), osteoarthritis (49%), obstructive sleep apnea (45%), and diabetes (37%). Operations: 22 general surgeries (29%), 20 sleeve gastrectomies (26%), 12 revisions/conversions (16%), 12 Roux-en-Y gastric bypasses (16%), and 10 gastric bands (13%). Modalities: 67% laparoscopic, 28% robotic, and 5% open. Twenty-two patients (34%) had a pre-operative inferior vena cava filter placed with no complications. The mean length of stay was 4.4 days (range 1-31). Complications: seven 30-day readmissions (9%), one 30-day reoperation (1%), and two 90-day VTEs (3%). Thirty-day readmissions: four for inability to tolerate PO, two for small bowel obstruction, and one for symptomatic anastomotic ulcer. CONCLUSIONS: In our patients, post-operative AC could be started without an increased risk of bleeding in patients with a history of VTE undergoing bariatric surgery.

OBJETIVO: Examinar el uso y los resultados de la anticoagulación perioperatoria en pacientes bariátricos con antecedentes de tromboembolia venosa (TEV). MÉTODO: Revisión retrospectiva (base de datos prospectiva) de pacientes sometidos a cirugía general y bariátrica (1/2008-12/2017). Se evaluaron datos demográficos, detalles quirúrgicos y resultados. RESULTADOS: Sesenta y cinco pacientes se sometieron a 76 procedimientos: 46 mujeres (71%), edad media 51 años (rango: 26-73), peso medio 284 libras (rango: 110-558), índice de masa corporal medio 45 (rango: 19-87). Comorbilidad: hipertensión (60%), enfermedad por reflujo gastroesofágico (54%), osteoartritis (49%), apnea obstructiva del sueño (45%), diabetes (37%). Operaciones: 22 cirugía general (29%), 20 gastrectomías en manga (26%), 12 revisiones/conversiones (16%), 12 Y-de-Roux (16%), 10 bandas gástricas (13%). Modalidades: 67% laparoscópica, 28% robótica, 5% abierta. A 22 pacientes (34%) se les colocó un filtro de vena cava inferior preoperatorio sin complicaciones. La estancia media fue de 4.4 días (rango: 1-31). Complicaciones: 7 reingresos a los 30 días (9%), 1 reoperación a los 30 días (1%), 2 TEV a los 90 días (3%). Reingresos a los 30 días: 4 por incapacidad para tolerar la vía oral, 2 obstrucciones de intestino delgado y 1 úlcera anastomótica sintomática. CONCLUSIONES: En nuestros casos, la anticoagulación posoperatoria pudo iniciarse sin aumento del riesgo de sangrado en pacientes con antecedentes de TVE sometidos a cirugía bariátrica.

Optimized Properties and Synthesis of Photoactivatable Diazoketorhodamines Facilitate and Enhance High-Throughput Single-Molecule Tracking.

Photoactivatable (PA) rhodamine dyes are widely used in single-molecule tracking (SMT) and a variety of other fluorescence-based imaging modalities. One of the most commonly employed scaffolds uses a diazoketone to lock the rhodamine in the nonfluorescent closed form, which can be activated with 405 nm light. However, poor properties of previously reported dyes require significant washing, which can be resource- and cost-intensive, especially when performing microscopy in a large scale and high-throughput fashion. Here, we report improved diazoketorhodamines that perform exceptionally well in single-molecule tracking microscopy. We also report on the optimization of an improved synthetic method for further iteration and tailoring of diazoketorhodamines to the requirements of a specific user.

Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape.

Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.

Adolescent alcohol use is associated with differences in the diversity and composition of the oral microbiome.

BACKGROUND: Adolescence is a sensitive stage of oral microbial development that often coincides with the initiation and escalation of alcohol use. Thus, adolescents may be particularly susceptible to alcohol-induced alterations in the oral microbiome, though minimal research has been done in this area. Understanding the connection between the oral microbiome and alcohol use during adolescence is important to understand fully the biological consequences of alcohol use to mitigate potential adverse outcomes. METHODS: Saliva samples were collected from adolescents aged 17-19 who used alcohol heavily (n = 21, 52.4% female) and those who did not use alcohol or any other substances (n = 18, 44.4% female). We utilized 16S rRNA sequencing to examine differences in microbial diversity and composition between the groups. RESULTS: For alpha diversity, evenness was significantly lower in the drinking group than the control group as indicated by Pielou's evenness, Shannon, and Simpson indices. There were no statistically significant findings for beta diversity. Differential abundance analyses revealed higher abundances of Rothia and Corynebacterium in the alcohol-using group using both centered-log-ratio and relative abundance normalization. These genera are known for their high capacity to convert alcohol into acetaldehyde, a toxic metabolite reported to play a role in the neurobiological effects of alcohol. An unclassified Clostridia UCG-014, Streptobacillus, Comamonas, unclassified Lachnospiraceae, and Parvimonas were also identified as significantly different between groups when using only one of the normalization techniques. CONCLUSIONS: This is the first study designed specifically to compare the oral microbiome of adolescents who use alcohol with that of control participants. Our findings reveal distinct alcohol-related differences in microbial composition and taxon abundance, emphasizing the importance of understanding the impact on the oral microbiome of alcohol use during adolescence. Because the oral microbiome is malleable, this study provides foundational work for future prevention and intervention studies.

Predicting Postsurgical Complications of Peripheral Nerve Decompression: NSQIP Analysis of Frailty Measures Versus Historic Proxies.

Background: Peripheral nerve decompression (PND) is generally safe, and newer techniques allow frail patients to undergo PND at less common sites. Current literature suggests patient frailty measures may more accurately predict postsurgical complications versus other proxies, but no current literature examines frailty in PND. Methods: The authors reviewed data from the National Surgical Quality Improvement Program for patients who underwent PND outside the most common sites from 2013 to 2019. The modified 5-Item Frailty Index (mFI-5) and modified Charlson Comorbidity Index (mCCI) scores were calculated, and complications data were gathered. Age, body mass index (BMI), major comorbidities, American Society of Anesthesiologists class, and frailty were compared as predictors of all-cause 30-day complications, 30-day surgical site complications, length of stay, and complication severity, using univariate and multivariate logistic regression. Results: Of 1120 patients, the mean age was 51.3 (15.4) years and mean BMI was 30.6 (7.0) kg/m2. Patients were predominantly white and healthy. The complication rate was 3.4%. All-cause complications were predicted by ≥3 major comorbidities (odds ratio [OR], 95% confidence interval [CI]: 6.26, 1.36-21.32; P = .007), followed by mFI-5 score and mCCI score. Complication severity was associated with major comorbidities and mFI-5 score, while length of stay was most strongly predicted by age ≥ 65 years (OR, 95% CI: 2.17, 1.37-3.42; P = .0008) and mCCI score of 3 (OR, 95% CI: 1.77, 1.01-3.05; P = 0.041). The only risk factor for readmission was mFI-5 score of 1 (OR, 95% CI: 7.00, 1.68-47.16; P = .016). Conclusions: Frailty and risk proxies may predict postoperative complications in PND at uncommon sites. Use of frailty indices may expand the age range of patients offered PND. Further research is necessary to delineate contributing risk factors and to clarify 24-hour observation and admissions.

Multimodal pain management and postoperative outcomes in inpatient and outpatient shoulder arthroplasties: a population-based study.

INTRODUCTION: Multimodal analgesia has been associated with reduced opioid utilization, opioid-related complications, and improved recovery in various orthopedic surgeries; however, large sample size data is lacking for shoulder surgery. METHODS: A retrospective review using the Premier Healthcare Database of patients who underwent inpatient or outpatient (reverse, total, partial) shoulder arthroplasty from 2010 to 2019. Opioid-only analgesia was compared with multimodal analgesia, categorized into 1, 2, or >2 additional analgesic modes, with/without a nerve block. Multivariable regression models measured associations between multimodal analgesia and opioid charges (in oral morphine equivalents (OME)), cost and length of stay, and opioid-related adverse effects (approximated by naloxone use). We report % change and 95% CIs. RESULTS: Among 176 225 procedures, 169 679 (75.7% multimodal analgesia use) and 6546 (37.8% multimodal analgesia use) were inpatient and outpatient shoulder arthroplasties, respectively. Among inpatients, multimodal analgesia (>2 modes) without a nerve block (vs opioid-only analgesia) was associated with adjusted reductions in OMEs on postoperative day 1: -19.4% (95% CI -21.2% to -17.6%/representing unadjusted median OME reductions from 45 to 30 mg). For total hospitalization, this was -6.0% (95% CI -7.2% to -4.9%/representing unadjusted median OME reductions from 173 to 135 mg). Conversely, for outpatients, this was +13.7% change in OMEs (95% CI +4.4% to +23.0%/representing unadjusted median OME increases from 110 to 131 mg). In both settings, addition of a nerve block to multimodal analgesia attenuated effects in terms of opioid charges. CONCLUSIONS: Multimodal analgesia is associated with reductions in opioid charges-specifically inpatient setting-but not various other outcomes.

Association Between Age-stratified Cohorts and Perioperative Complications and 30-day and 90-day Readmission in Patients Undergoing Single-level Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To assess perioperative complication rates and readmission rates after ACDF in a patient population of advanced age. SUMMARY OF BACKGROUND DATA: Readmission rates after ACDF are important markers of surgical quality and, with recent shifts in reimbursement schedules, they are rapidly gaining weight in the determination of surgeon and hospital reimbursement. METHODS: Patients 18 years of age and older who underwent elective single-level ACDF were identified in the National Readmissions Database (NRD) and stratified into 4 cohorts: 18-39 ("young"), 40-64 ("middle"), 65-74 ("senior"), and 75+ ("elderly") years of age. For each cohort, the perioperative complications, frequency of those complications, and number of patients with at least 1 readmission within 30 and 90 days of discharge were analyzed. χ 2 tests were used to calculate likelihood of complications and readmissions. RESULTS: There were 1174 "elderly" patients in 2016, 1072 in 2017, and 1010 in 2018 who underwent ACDF. Their rate of any complication was 8.95%, 11.00%, and 13.47%, respectively ( P <0.0001), with dysphagia and acute posthemorrhagic anemia being the most common across all 3 years. They experienced complications at a greater frequency than their younger counterparts (15.80%, P <0.0001; 16.98%, P <0.0001; 21.68%, P <0.0001). They also required 30-day and 90-day readmission more frequently ( P <0.0001). CONCLUSION: It has been well-established that advanced patient age brings greater risk of perioperative complications in ACDF surgery. What remains unsettled is the characterization of this age-complication relationship within specific age cohorts and how these complications inform patient hospital course. Our study provides an updated analysis of age-specific complications and readmission rates in ACDF patients. Orthopedic surgeons may account for the rise in complication and readmission rates in this population with the corresponding reduction in length and stay and consider this relationship before discharging elderly ACDF patients.

Frailty Indices Outperform Historic Risk Proxies as Predictors of Postabdominoplasty Complications: An Analysis of a National Database.

BACKGROUND: Although age, body mass index (BMI), and major comorbidities were historically used as predictors of surgical risk, recent literature supports patient frailty as a more accurate predictor. Database studies and chart reviews support the modified Charlson Comorbidity Index (mCCI) and the Modified Five-Item Frailty Index (mFI-5) as predictors of postsurgical complications in plastic surgery. The authors hypothesized that the mFI-5 and mCCI are more predictive of abdominoplasty complications than historic risk proxies. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database was performed for abdominoplasty patients from 2013 to 2019. Demographics, comorbidities, and complications were gathered. The mFI-5 and mCCI scores were calculated per patient. Age, BMI, major comorbidities, American Society of Anesthesiologists class, mFI-5 score, and mCCI score were compared as predictors of all-cause 30-day complications, 30-day surgical-site complications, length of stay, and aggregate Clavien-Dindo complication severity score. RESULTS: Of 421 patients, the strongest predictors for all-cause complications and complication severity were mCCI score greater than or equal to 3 and mFI-5 score greater than or equal to 2. The mFI-5 score was the strongest predictor of unplanned reoperation. Length of stay was best predicted by age greater than or equal to 65. The only predictor of surgical-site complications was BMI greater than or equal to 30.0 kg/m 2 . Smoking was predictive of complication severity, but not any other outcome. CONCLUSIONS: The mFI-5 and mCCI are stronger outcome predictors than historically used factors, which showed little predictive value in this cohort. Although the mCCI is a stronger predictor than the mFI-5, the mFI-5 is easily calculated during an initial consultation. Surgeons can apply these tools to aid in risk stratification for abdominoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Is There an Association between Platelet Count and Blood Loss in the Parturient? A Retrospective Study.

OBJECTIVE: The influence of thrombocytopenia on blood loss and postpartum hemorrhage (PPH) has been conflicting. Our aim was to determine if there is an association between predelivery platelet count and quantitative blood loss (QBL) and PPH in both vaginal (VD) and cesarean deliveries (CD). STUDY DESIGN: We conducted a retrospective database study at a single institution from April 1, 2017 to September 9, 2020. The platelet count closest to time of delivery and the QBL was assessed separately for VD and CD. RESULTS: A total of 22,479 records were reviewed, of which 16,822 (75%) were VD and 5,657 (25%) were CD. A total of 2,600 (12%) patients had thrombocytopenia, defined as a platelet count <150,000/mm3. Of these, 1,980 (76%) had a VD and 620 (24%) had CD. We found a statistically significant difference in QBL between parturients with thrombocytopenia compared with those without, with a median estimated difference in QBL of 25 (95% confidence interval [CI]: 16-32) and 57 mL (95% CI: 31-87) in VD and CD patients, respectively. We also found a statistically significant difference in QBL when comparing patients among all the platelet count ranges except in the lowest platelet count range of 50,000 to 69,999/mm3 with a mean difference of 52 (95% CI: 25-81) and 107 mL (95% CI: 39-180) in the VD and CD patients, respectively in the platelet count range of 70,000 to 99,999/mm3 . We also found the incidence of PPH was greater in those with thrombocytopenia, p < 0.001, but the median difference in QBL in all platelet groups was small. CONCLUSION: We found a statistically significant association between lower predelivery platelet counts and QBL and PPH. The clinical significance of these results is debatable, because at all platelet count ranges, differences in blood loss were small. KEY POINTS: · Hemorrhage is etiology of morbidity and mortality in obstetric parturients.. · We found a small increase in blood loss in those with thrombocytopenia.. · The clinical relevance of these findings is debatable since the increased blood loss was small..

Pairwise comparisons of three medication adherence outcomes in adolescents who use alcohol.

BACKGROUND: Accurate assessment of medication adherence is important for understanding pharmacotherapy outcomes across all phases of adolescent substance use disorder (SUD) clinical trials. The objective of this study was to describe and assess the pairwise concordance between three commonly used non-biological medication adherence assessment methods in adolescents who use alcohol to inform the selection of medication adherence measures for use in future youth SUD trials. METHODS: Participants (N = 32, 17-19-years-old) took N-acetylcysteine and placebo, in a randomized cross-over design, for 10 days each. Medication adherence was assessed (20 days total) via pill count, medication videos submitted twice daily, and the Medication Event Monitoring System (MEMS®). Lin's Concordance Correlation Coefficient (CCC) assessed concordance and Bland-Altman plots are reported. Linear mixed-effects models with main effects of medication, treatment block (first medication, second medication), and sequence were also run. RESULTS: Medication videos yielded the lowest (64%) and pill count yielded the highest (89%) adherence estimates. CCC values indicated poor correspondence, except between pill count and MEMS. The Bland-Altman plots showed good pairwise agreement between all methods. Linear mixed-effects models indicated a difference between the first and second cross-over medication, with adherence estimates being lower for the second medication, regardless of whether it was N-acetylcysteine or placebo. CONCLUSIONS: The study yielded important and practical information. First, incorporating more than one method of adherence assessment may capture estimated floor and ceiling adherence in the absence of a biological marker. This is particularly relevant for remote or hybrid studies where bio-marker collection is challenging. Selection of the assessment methods will depend on study goals. Second, the continuation of medication adherence research can benefit each phase of clinical trials and inform rigorous pharmacotherapy evaluation.

The Role of Telemedicine in Glaucoma Care Triggered by the SARS-CoV-2 Pandemic: A Qualitative Study.

Purpose: To explore and report on how glaucoma care was impacted by the SARS-CoV-2 pandemic (COVID-19) in New York City (NYC) with a specific emphasis on the role of telemedicine. Patients and Methods: This was a qualitative, cross-sectional study that engaged glaucoma clinicians in semi-structured interviews to elicit perspectives on telemedicine and patient care experiences during the pandemic. Interview responses were coded and analyzed thematically. Results: Twenty clinicians participated. Mean participant age was 48.8 ± 12.3 years, and the mean number of years in practice post-glaucoma fellowship was 17.5 ± 12.4 years. Four main themes pertinent to the role of telemedicine triggered by the COVID-19 pandemic were identified: (1) The Need to Ensure Patient and Staff Safety Drove Telemedicine Uptake; (2) Telemedicine Allowed Providers to Address Subjective Complaints; (3) Telemedicine was Discontinued Due To Concerns of Compromised Patient Safety and Measurement Inaccuracy; (4) Technological Advances are Needed for Continued Telemedicine Usage and Uptake in Glaucoma Care. The interviews suggested that telemedicine usage dropped markedly within just a few months during the pandemic, and for most physicians interviewed, telemedicine is no longer part of their clinical practice. Several clinicians reported optimism towards future implementation of telemedicine as the technology develops. Conclusion: This study identified 4 themes outlining the uptake, application, discontinuation and overall perspectives on telemedicine by glaucoma clinicians. The role of telemedicine, as triggered by the COVID-19 pandemic, may have lasting implications for patient safety, continuity of care, and glaucoma care delivery beyond this public health crisis.

Efficacy of the Modified 5-Item Frailty Index in Predicting Surgical-Site Infections in Patients Undergoing Breast Implant Augmentation: A National Surgical Quality Improvement Project-Based 5-Year Study.

Background: The ability to predict breast implant augmentation complications can significantly inform patient management. A frailty measure, such as the modified 5-item frailty index (mFI-5), is becoming an increasingly established risk factor for adverse postoperative outcomes. The authors hypothesized that the mFI-5 is predictive of 30-day postoperative complications in breast augmentation. Objectives: To investigate if mFI-5 can predict the likelihood and magnitude of 30-day complications resulting from breast augmentations. Methods: A retrospective review study of the National Surgical Quality Improvement Program database for patients who underwent breast implant augmentation without other concurrent procedures, from 2015 to 2019. Age, BMI, number of major comorbidities, American Society of Anesthesiologists (ASA) classifications, smoking status, mFI-5 score, and modified Charlson comorbidity index score were compared as predictors of all-cause 30-day complications and 30-day surgical-site complications using regression analyses. Results: Overall, 2478 patients were analyzed, and among them, 53 patients developed complications (2.14%). mFI-5 score significantly predicted surgical-site infection (SSI) complications (odds ratio [OR] = 4.24, P = .026). Frail patients had a higher occurrence of SSIs than nonfrail patients (P = .049). Multivariable analyses showed ASA class predicted 30-day SSI complications (OR = 5.77, P = .027) and mFI-5 approached, but did not reach full significance in predicting overall 30-day complications (OR = 3.14, P = .085). Conclusions: To date, the impact of frailty on breast implant procedure outcomes has not been studied. Our analysis demonstrates that the mFI-5 is a significant predictor for SSIs in breast implant augmentation surgery and is associated with overall complications. By preoperatively identifying frail patients, the surgical team can better account for postoperative support to minimize the risk of complications.

Zn deficiency disrupts Cu and S homeostasis in Chlamydomonas resulting in over accumulation of Cu and Cysteine.

Growth of Chlamydomonas reinhardtii in zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding "first responder" proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine, and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ∼80-fold, corresponding to ∼2.8 × 109 molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is an in vivo Cu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.

What sticks after statistical learning: The persistence of implicit versus explicit memory traces.

Statistical learning is a powerful mechanism that extracts even subtle regularities from our information-dense worlds. Recent theories argue that statistical learning can occur through multiple mechanisms-both the conventionally assumed automatic process that precipitates unconscious learning, and an attention-dependent process that brings regularities into conscious awareness. While this view has gained popularity, there are few empirical dissociations of the hypothesized implicit and explicit forms of statistical learning. Here we provide strong evidence for this dissociation in two ways. First, we show in healthy adults (N = 60) that implicit and explicit traces have divergent consolidation trajectories, with implicit knowledge of structure strengthened over a 24-h period, while precise explicit representations tend to decay. Second, we demonstrate that repeated testing strengthens the retention of explicit representations but that implicit statistical learning is uninfluenced by testing. Together these dissociations provide much needed support for the reconceptualization of statistical learning as a multi-component construct.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

Orbital Foraminal Morphometrics in Nonsyndromic Unilateral Coronal Craniosynostosis.

ABSTRACT: Nonsyndromic unilateral coronal craniosynostosis (UCS) is a rare congenital disorder that results from premature fusion of either coronal suture. The result is growth restriction across the suture, between the ipsilateral frontal and parietal bones, leading to bony dysmorphogenesis affecting the calvarium, orbit, and skull base. Prior studies have reported associations between UCS and visual abnormalities. The present study utilizes a novel geometric morphometric analysis to compare dimensions of orbital foramina on synostotic versus nonsynostotic sides in patients with UCS. Computed tomography head scans of pediatric UCS patients were converted into 3-dimensional mesh models. Anatomical borders of left and right orbital structures were plotted by a single trained team member. Dimensions between synostotic and nonsynostotic sides were measured and compared. Medical records were examined to determine prevalence of visual abnormalities in this patient cohort. Visual abnormalities were reported in 22 of the 27 UCS patients (77.8%). Astigmatism (66.7%), anisometropic amblyopia (44.4%), and motor nerve palsies (33.3%) represented the 3 most prevalent ophthalmologic abnormalities. Orbits on synostotic sides were 11.3% narrower ( P < 0.001) with 21.2% less volume ( P = 0.028) than orbits on nonsynostotic sides. However, average widths, circumferences, and areas were similar between synostotic and nonsynostotic sides upon comparison of supraorbital foramina, infraorbital foramina, optic foramina, and foramina ovalia. Therefore, previously proposed compression or distortion of vital neurovascular structures within bony orbital foramina does not seem to be a likely etiology of visual abnormalities in UCS patients. Future studies will examine the role of ocular and/or neuro-ophthalmologic pathology in this disease process.

Cysteine: an ancestral Cu binding ligand in green algae?

Growth of Chlamydomonas reinhardtii in zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding "first responder" proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ~80-fold, corresponding to ~ 2.8 × 10 9 molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is an in vivo Cu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.

Examining Violaceous Skin Discoloration during the COVID-19 Pandemic: Conducting Research in Resource Scarcity.

OBJECTIVE: To describe the observed patterns and presentations of violaceous discoloration that appeared to be related to the COVID-19 disease process. METHODS: This retrospective observational cohort study included adults who were COVID-19 positive with purpuric/violaceous lesions in pressure-adjacent areas of the gluteus without preexisting pressure injury. Patients were admitted to an ICU at a single quaternary academic medical center between April 1 and May 15, 2020. Data were compiled by review of the electronic health record. The wounds were described by location, tissue type (violaceous, granulation, slough, eschar), wound margin (irregular, diffuse, nonlocalized), and periwound condition (intact). RESULTS: A total of 26 patients were included in the study. Purpuric/violaceous wounds were found predominantly on White (92.3%) men (88.0%) aged 60 to 89 years (76.9%) with a body mass index 30 kg/m2 or higher (46.1%). The majority of wounds were located on the sacrococcygeal (42.3%) and fleshy gluteal regions (46.1%). CONCLUSIONS: Wounds were heterogeneous in appearance (poorly defined violaceous skin discoloration of acute onset), and the patient population had clinical characteristics similar to acute skin failure (eg, concomitant organ failures and hemodynamic instability). Additional larger population-based studies with biopsies may assist in finding patterns related to these dermatologic changes.