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.

Scalable optical manufacture of dynamic structural colour in stretchable materials.

Structurally coloured materials that change their colour in response to mechanical stimuli are uniquely suited for optical sensing and visual communication1-4. The main barrier to their widespread adoption is a lack of manufacturing techniques that offer spatial control of the materials' nanoscale structures across macroscale areas. Here, by adapting Lippmann photography5, we report an approach for producing large-area, structurally coloured sheets with a rich and easily controlled design space of colour patterns, spectral properties, angular scattering characteristics and responses to mechanical stimuli. Relying on just a digital projector and commercially available photosensitive elastomers, our approach is fast, scalable, affordable and relevant for a wide range of manufacturing settings. We also demonstrate prototypes for mechanosensitive healthcare materials and colorimetric strain and stress sensing for human-computer interaction and robotics.

Racial Disparities in Documented Chief Complaints and Diagnoses in Sepsis Patients.

BACKGROUND: Using History and Physical Examination (H&P) notes, we investigated potential racial differences in documented chief complaints and problems among sepsis patients admitted to the intensive care unit. METHODS: Patient records from Medical Information Mart for Intensive Care (MIMIC-III) dataset indicating a diagnosis of sepsis were included. First recorded clinical notes for each hospital admission were assessed; free text information was specifically extracted on (1) chief complaints, and (2) problems recorded in the Assessment & Plan (A&P) section. The top 10 for each were compared between Black and White patients. RESULTS: In initial H&P notes of 17 434 sepsis patients (n = 1229 Black and n = 9806 White), the top 10 most common chief complaints were somewhat similar between Black and White patients. However, relative differences existed in terms of ranking, specifically for altered mental status which was more commonly reported in Black versus White patients (11.7% vs 7.8% P < .001). Among text in the A&P, sepsis was documented significantly less frequently among Black versus White patients: 11.8% versus 14.3%, P = .001. Racial differences were not detected in vital signs and laboratory values. CONCLUSIONS: This analysis supports the hypothesis that there may be racial differences in early sepsis presentation and possible provider interpretation of these complaints.

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..

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.

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.

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis.

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥ 50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91-0.95, I2 = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88-0.93, I2 = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91-0.94, I2 = 86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF > 40%, higher average SBP (> 130 mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence.

Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape.

OBJECTIVE: To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N2 O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape. METHODS: A comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLINE, Embase, APA PsycInfo) and the clinical trial registries (ClinicalTrials.gov, ICTRP). RESULTS: In total, five relevant published articles were identified, among which four investigated N2 O for depression. One single-dose randomized controlled trial (RCT) for treatment-resistant depression (TRD), one triple crossover RCT comparing 50% vs. 25% N2 O for TRD, and one repeated-dose RCT for major depressive disorder (MDD) suggest that N2 O has preliminary feasibility with rapid-acting effects on symptoms of depression. From the public registries, 10 relevant ongoing clinical trials were identified. They aim to explore the use of N2 O for MDD, post-traumatic stress disorder, bipolar disorder, obsessive-compulsive disorder, and suicidal ideation. To date, the typical treatment protocol parameters were a single session of 50% N2 O delivered for 60 min, although the concentration of 25% is also being explored. Projected enrolment numbers for ongoing trials (M = 55.0) were much higher than sample sizes for published studies (M = 13.0), suggesting that there potentially will be more large-scale RCTs published in the next few years. CONCLUSION: Preliminary studies support the feasibility of administering N2 O for depression; however, appropriate blinding is a critical challenge. Larger-scale RCTs with repeated doses of N2 O and follow-up times beyond 1 month are needed to confirm the feasibility, therapeutic efficacy, and sustainability of response.

Comparison of Transcarotid Artery Revascularization and Transfemoral Carotid Artery Stenting Based on High Risk Anatomic Characteristics.

BACKGROUND: Anatomic details affecting the adverse outcomes following carotid artery stenting have not been well characterized. We compared in-hospital outcomes following transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) among symptomatic and asymptomatic patients stratified by degree of lesion calcification and aortic arch type. METHODS: Data from patients in the Society for Vascular Surgery's Vascular Quality Initiative database undergoing TCAR (January 2017 to April 2020) or TFCAS (May 2005 to April 2020) and had non-missing grading on carotid artery calcification or aortic arch type was analyzed. Degree of calcification was stratified into 3 groups: none, ≤ 50% calcification, and >50% calcification. Arch type was stratified as Type I, Type II, and Type III. RESULTS: A total of 9,868 patients (TCAR: 4,224; TFCAS: 5,644) were included in the calcification analysis. TCAR patients were generally older, white, smokers, and had more comorbidities than TFCAS patients. Among the symptomatic patients, there was no difference in rates of stroke, stroke/transient ischemic attack (TIA), and myocardial infarction (MI) by calcification severity between TCAR and TFCAS. However, there was a trend towards increased risk in all 3 events with higher calcification only after TFCAS. Symptomatic patients with severe (>50%) calcification had lower rates of death (TCAR: 0.9% vs. TFCAS: 2.8%, P = 0.013), stroke/death (TCAR: 2.7% vs. TFCAS: 5.8%, P = 0.006), stroke/death/MI (TCAR: 3.3% vs. TFCAS: 6.5%, P = 0.007), and postop complications (TCAR: 6.0% vs. TFCAS: 12.4%, P < 0.001) after TCAR compared to TFCAS. Furthermore, TCAR had lower risk of mortality at all degrees of calcification compared to TFCAS. Similar findings were noted among asymptomatic TCAR patients with >50% calcification, in which the rates of death (TCAR: 0.4% vs. TFCAS: 1.1%, P = 0.080) and stroke/death (TCAR: 1.5% vs. TFCAS: 3.1%, P = 0.029) were reduced. A comparison of TCAR to TFCAS by arch type showed that rates of stroke/death after TCAR were similar regardless of arch complexity (Type I: 2.6% vs. Type II: 2.8%), but increased after TFCAS with complex, high risk anatomy (Type I: 4.2% vs. Type II: 5.2%). CONCLUSIONS: While increased calcification increased rates of adverse events after TFCAS, this trend was not observed after TCAR, which also had lower rates of death and stroke/death among patients with severe calcification. Furthermore, TCAR had lower risk of mortality than TFCAS across all degrees of calcification. TFCAS was associated with increased risk of stroke/death with complex aortic arch anatomy, however, rates of stroke/death after TCAR were similar regardless of arch complexity. Our results suggests that TCAR should be preferentially considered in revascularization of patients with anatomy considered high-risk for TFCAS.

Can Frailty Indices Predict Surgical Risk in Open Reduction and Fixation of Facial Fractures?

PURPOSE: The present study sought to evaluate whether the mFI-5 and modified Charlson Comorbidity Index (mCCI) are stronger predictors of 30-day postoperative complications after open reduction of facial fractures compared with historic risk proxies. METHODS: A retrospective review of the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was conducted to investigate patients who underwent open reduction facial fracture surgery between 2013 and 2018. Risk factors including age, smoking status, body mass index (BMI), comorbidities, and American Society of Anesthesiologists (ASA) class were extracted for each patient. The mFI-5 score and mCCI score were calculated based on this data. Univariate logistic regressions were performed (P<0.05). RESULTS: A total of 2667 cases were included. Of these, 2131 (80%) were male. The strongest predictors for overall 30-day complications and complication severity were ASA class ≥3 (Odds Ratio [OR]=3.34), comorbidities ≥2 (OR=2.78), mCCl score ≥2 (OR=2.19), and mFI-5 ≥1 (OR=1.96). Smoking status and BMI were not strong predictors of total complications or complication severity. Age was found to be a statically significant, but low-impact, predictor of complications, and severity (OR=1.02, P<0.001). The only significant predictors of surgical site infections (SSI) were smoking status (OR=1.56) and ASA class ≥3 (OR=2.40). mFI-5 ≥1 was a significant predictor of hospital readmission. BMI was not associated with any increased risk. CONCLUSIONS: The mCCI and mFI-5 are statistically significant predictors of total complications and complication severity in open reduction of facial fracture repair, and thus provide a tool to inform decision making and improve care. Smoking status may increase risk for SSIs following facial fracture repair.

Craniofacial Dysmorphology in Infants With Non-Syndromic Unilateral Coronal Craniosynostosis.

BACKGROUND: Unilateral coronal craniosynostosis (UCS) is a congenital disorder resulting from the premature suture fusion, leading to complex primary and compensatory morphologic changes in the shape of not only the calvarium and but also into the skull base. This deformity typically requires surgery to correct the shape of the skull and prevent neurologic sequelae, including increased intracranial pressure, sensory deficits, and cognitive impairment. METHODS: The present multicenter study sought to reverse-engineer the bone dysmorphogenesis seen in non-syndromic UCS using a geometric morphometric approach. Computed tomography scans for 26 non-syndromic UCS patients were converted to three-dimensional mesh models. Two hundred thirty-six unique anatomical landmarks and semi-landmarked curves were then plotted on each model, creating wireframe representations of the Patients' skulls. RESULTS: Generalized Procrustes superimposition, Principal Component Analysis, and heatmaps identified significant superior displacement of the ipsilateral orbit ("harlequin" eye deformity), anterior displacement of the ear ipsilateral to the fused coronal suture, acute deviation of midline skull base structures ipsilateral to the fused coronal suture and flattening of the parietal bone and associated failure to expand superiorly. CONCLUSIONS: The described technique illustrates the impact of premature coronal suture fusion on the development of the entire skull and proposes how bone dysmorphology contributes to the Patients' neurologic sequelae. By bridging novel basic science methodologies with clinical research, the present study quantitatively describes craniofacial development and bone dysmorphogenesis.

Using the Modified Frailty Index to Predict Complications in Breast Reduction: A National Surgical Quality Improvement Program Study of 14,160 Cases.

BACKGROUND: Breast reduction is a generally well-tolerated procedure with high patient satisfaction and low risk of surgical site infection and other complications. Although age, obesity, and comorbidities have historically been used as surgical risk proxies, recent literature suggests "frailty" measures, such as the modified 5-item Frailty Index (mFI-5), may be a superior predictor. OBJECTIVES: The aim of this study was to investigate if mFI-5 can predict the likelihood and magnitude of 30-day complications resulting from breast reductions. METHODS: A retrospective review was performed of the National Surgical Quality Improvement Program (NSQIP) database to assess patients who underwent breast reduction without other concurrent procedures, from 2013 to 2019. mFI-5 scores were calculated for each patient, and complication data were gathered. Age, BMI, number of major comorbidities, American Association of Anesthesiologists class, smoking status, diabetes, steroid use, and mFI-5 score were compared as predictors of all-cause 30-day complications, 30-day surgical site complications of any kind, length of stay, and aggregate Clavien-Dindo complication severity score. Univariate logistic, linear regressions, and multivariate logistic regression analyses were performed to evaluate predictive value. Statistical significance was set at P < 0.05. RESULTS: A total of 14,160 patients were analyzed. The overall complication rate was 5.6%. The mFI-5 score significantly predicted overall 30-day complications, surgical site complications, complication severity, overnight stay, and likelihood of readmission (all P < 0.0001). CONCLUSIONS: The mFI-5 is a statistically significant predictor for adverse outcomes in breast reduction surgery. The mFI-5 is a simple and reliable tool that can be efficiently used to conduct a preoperative evaluation of patients requesting breast reductions.

Development and psychometric properties of surveys to assess provider perspectives on the barriers and facilitators of effective care transitions.

BACKGROUND: The quality of the discharge process and effective care transitions between settings of care are critical to minimize gaps in patient care and reduce hospital readmissions. Few studies have explored which care transition components and strategies are most valuable to patients and providers. This study describes the development, pilot testing, and psychometric analysis of surveys designed to gain providers' perspectives on current practices in delivering transitional care services. METHODS: We underwent a comprehensive process to develop items measuring unique aspects of care transitions from the perspectives of the three types of providers (downstream, ambulatory, and hospital providers). The process involved 1) an environmental scan, 2) provider interviews, 3) survey cognitive testing, 4) pilot testing, 5) a Stakeholder Advisory Group, 6) a Scientific Advisory Council, and 7) a collaborative Project ACHIEVE (Achieving Patient-Centered Care and Optimized Health in Care Transitions by Evaluating the Value of Evidence) research team. Three surveys were developed and fielded to providers affiliated with 43 hospitals participating in Project ACHIEVE. Web-based survey administration resulted in 948 provider respondents. We assessed response variability and response missingness. To evaluate the composites' psychometric properties, we examined intercorrelations of survey items, item factor loadings, model fit indices, internal consistency reliability, and intercorrelations between the composite measures and overall rating items. RESULTS: Results from psychometric analyses of the three surveys provided support for five composite measures: 1) Effort in Coordinating Patient Care, 2) Quality of Patient Information Received, 3) Organizational Support for Transitional Care, 4) Access to Community Resources, and 5) Strength of Relationships Among Community Providers. All factor loadings and reliability estimates were acceptable (loadings ≥ 0.40, α ≥ 0.70), and the fit indices showed a good model fit. All composite measures positively and significantly correlated with the overall ratings (0.13 ≤ r ≤ 0.71). CONCLUSIONS: We determined that the items and composite measures assessing the barriers and facilitators to care transitions within this survey are reliable and demonstrate satisfactory psychometric properties. The instruments may be useful to healthcare organizations and researchers to assess the quality of care transitions and target areas of improvement across different provider settings.

Hyperbaric oxygen therapy for COVID-19 patients with respiratory distress: treated cases versus propensity-matched controls.

Objective: Given the high mortality and prolonged duration of mechanical ventilation of COVID-19 patients, we evaluated the safety and efficacy of hyperbaric oxygen for COVID-19 patients with respiratory distress. Methods: This is a single-center clinical trial of COVID-19 patients at NYU Winthrop Hospital from March 31 to April 28, 2020. Patients in this trial received hyperbaric oxygen therapy at 2.0 atmospheres of pressure in monoplace hyperbaric chambers for 90 minutes daily for a maximum of five total treatments. Controls were identified using propensity score matching among COVID-19 patients admitted during the same time period. Using competing-risks survival regression, we analyzed our primary outcome of inpatient mortality and secondary outcome of mechanical ventilation. Results: We treated 20 COVID-19 patients with hyperbaric oxygen. Ages ranged from 30 to 79 years with an oxygen requirement ranging from 2 to 15 liters on hospital days 0 to 14. Of these 20 patients, two (10%) were intubated and died, and none remain hospitalized. Among 60 propensity-matched controls based on age, sex, body mass index, coronary artery disease, troponin, D-dimer, hospital day, and oxygen requirement, 18 (30%) were intubated, 13 (22%) have died, and three (5%) remain hospitalized (with one still requiring mechanical ventilation). Assuming no further deaths among controls, we estimate that the adjusted subdistribution hazard ratios were 0.37 for inpatient mortality (p=0.14) and 0.26 for mechanical ventilation (p=0.046). Conclusion: Though limited by its study design, our results demonstrate the safety of hyperbaric oxygen among COVID-19 patients and strongly suggests the need for a well-designed, multicenter randomized control trial.

The histone demethylase UTX enables RB-dependent cell fate control.

Trimethylation of histone H3 on Lys 27 (H3K27me3) is key for cell fate regulation. The H3K27me3 demethylase UTX functions in development and tumor suppression with undefined mechanisms. Here, genome-wide chromatin occupancy analysis of UTX and associated histone modifications reveals distinct classes of UTX target genes, including genes encoding Retinoblastoma (RB)-binding proteins. UTX removes H3K27me3 and maintains expression of several RB-binding proteins, enabling cell cycle arrest. Genetic interactions in mammalian cells and Caenorhabditis elegans show that UTX regulates cell fates via RB-dependent pathways. Thus, UTX defines an evolutionarily conserved mechanism to enable coordinate transcription of a RB network in cell fate control.

Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer.

BACKGROUND: This exploratory analysis evaluated second-line (2L) therapy for metastatic pancreatic cancer in a large phase 3 trial (MPACT). METHODS: Patients who received first-line (1L) nab-paclitaxel+gemcitabine (nab-P+Gem) or Gem were assessed for survival based on 2L treatment received. Multivariate analyses tested influence of treatment effect and prognostic factors on survival. RESULTS: The majority of 2L treatments (267 out of 347, 77%) contained a fluoropyrimidine (5-fluorouracil or capecitabine). Median total survival (1L randomisation to death) for patients who received 2L treatment after 1L nab-P+Gem vs Gem alone was 12.8 vs 9.9 months (P=0.015). Median total survival for patients with a fluoropyrimidine-containing 2L therapy after nab-P+Gem vs Gem was 13.5 vs 9.5 months (P=0.012). Median 2L survival (duration from start of 2L therapy to death) was 5.3 vs 4.5 months for nab-P+Gem vs Gem, respectively (P=0.886). Factors significantly associated with longer post-1L survival by multivariate analyses included 1L nab-P+Gem, receiving 2L treatment, longer 1L progression-free survival, and Karnofsky performance status⩾70 and neutrophil-to-lymphocyte ratio⩽5 at the end of 1L treatment. CONCLUSIONS: These findings support the use of 2L therapy for patients with metastatic pancreatic cancer. Fluoropyrimidine-containing treatment after 1L nab-P+Gem is an active regimen with significant clinical effect.

Longitudinal analysis of the electroencephalogram and sleep phenotype in the R6/2 mouse model of Huntington's disease.

Deficits in sleep and circadian organization have been identified as common early features in patients with Huntington's disease that correlate with symptom severity and may be instrumental in disease progression. Studies in Huntington's disease gene carriers suggest that alterations in the electroencephalogram may reflect underlying neuronal dysfunction that is present in the premanifest stage. We conducted a longitudinal characterization of sleep/wake and electroencephalographic activity in the R6/2 mouse model of Huntington's disease to determine whether analogous electroencephalographic 'signatures' could be identified early in disease progression. R6/2 and wild-type mice were implanted for electroencephalographic recordings along with telemetry for the continuous recording of activity and body temperature. Diurnal patterns of activity and core body temperature were progressively disrupted in R6/2 mice, with a large reduction in the amplitude of these rhythms apparent by 13 weeks of age. The diurnal variation in sleep/wake states was gradually attenuated as sleep became more fragmented and total sleep time was reduced relative to wild-type mice. These genotypic differences were augmented at 17 weeks and evident across the entire 24-h period. Quantitative electroencephalogram analysis revealed anomalous increases in high beta and gamma activity (25-60 Hz) in all sleep/wake states in R6/2 mice, along with increases in theta activity during both non-rapid eye movement and rapid eye movement sleep and a reduction of delta power in non-rapid eye movement sleep. These dramatic alterations in quantitative electroencephalographic measures were apparent from our earliest recording (9 weeks), before any major differences in diurnal physiology or sleep/wake behaviour occurred. In addition, the homeostatic response to sleep deprivation was greatly attenuated with disease progression. These findings demonstrate the sensitivity of quantitative electroencephalographic analysis to identify early pathophysiological alterations in the R6/2 model of Huntington's disease and suggest longitudinal studies in other preclinical Huntington's disease models are needed to determine the generality of these observations as a potential adjunct in therapeutic development.

Eruptive purpuric papules on the arms; a case of chemotherapy-induced inflammation of actinic keratoses and review of the literature.

Chemotherapy-induced inflammation of actinic keratosis can present in patients with subclinical actinic keratoses that become erythematous and pruritic within weeks of initiating systemic chemotherapy. The reaction is limited to sun-exposed areas and, classically, histologic findings of parakeratosis and epidermal necrosis with keratinocyte nuclear pleomorphism are present. Exuberant reactions with extensive epidermal necrosis may lead to subepidermal vesiculation. We report a case of a 67-year-old man with a history of chronic hepatitis B virus infection and recently diagnosed squamous cell carcinoma of the lung who was noted to have progressive asymptomatic violaceous papules on the extensor forearms and distal upper arms while hospitalized for possible sepsis following initiation of chemotherapy. A dermatology consulatation was requested to rule out possible vasculitis. It is important to recognize chemotherapy-induced inflammation of actinic keratoses in predisposed patients; it may be managed successfully with topical corticosteroids and does not necessitate discontinuation of the offending chemotherapeutic agent.

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.