Search

Comparative studies of carpal tunnel release with ultrasound guidance (CTR-US) vs. mini-open CTR (mOCTR) are limited, prompting development of this randomized trial to compare efficacy and safety of these techniques. Patients were randomized (2:1) to CTR-US or mOCTR, treated by experienced hand surgeons (median previous cases: 12 CTR-US; 1000 mOCTR), and followed for 3 months. Among 149 randomized patients, 122 received CTR-US (n = 94) or mOCTR (n = 28). Mean incision length was 6 ± 2 mm in the wrist (CTR-US) vs. 22 ± 7 mm in the palm (mOCTR) (p < 0.001). Median time to return to daily activities (2 vs. 2 days; p = 0.81) and work (3 vs. 4 days; p = 0.61) were similar. Both groups reported statistically significant and clinically important improvements in Boston Carpal Tunnel Questionnaire Symptom Severity and Functional Status Scales, Numeric Pain Scale, and EuroQoL-5 Dimension 5-Level, with no statistical differences between groups. Freedom from wound sensitivity and pain favored CTR-US (61.1% vs. 17.9%; p < 0.001). Adverse event rates were low in each group (2.1% vs. 3.6%; p = 0.55). The efficacy and safety of CTR-US were comparable to mOCTR despite less previous surgical experience with CTR-US. The choice of CTR technique should be determined by shared decision-making between patient and physician. www.clinicaltrials.gov identifier is NCT05405218.

Background: Both sleep deficiencies and Alzheimer’s disease (AD) disproportionately affect older African Americans. Genetic susceptibility to AD further compounds risk for cognitive decline in this population. Aside from APOE ɛ4, ABCA7 rs115550680 is the strongest genetic locus associated with late-onset AD in African Americans. While sleep and ABCA7 rs115550680 independently influence late-life cognitive outcomes, we know too little about the interplay between these two factors on cognitive function. Objective: We investigated the interaction between sleep and ABCA7 rs115550680 on hippocampal-dependent cognitive function in older African Americans. Methods: One-hundred fourteen cognitively healthy older African Americans were genotyped for ABCA7 risk (n = 57 carriers of risk “G” allele; n = 57 non-carriers), responded to lifestyle questionnaires, and completed a cognitive battery. Sleep was assessed via a self-reported rating of sleep quality (poor, average, good). Covariates included age and years of education. Results: Using ANCOVA, we found that carriers of the risk genotype who reported poor or average sleep quality demonstrated significantly poorer generalization of prior learning¾a cognitive marker of AD¾compared to their non-risk counterparts. Conversely, there was no genotype-related difference in generalization performance in individuals who reported good sleep quality. Conclusion: These results indicate that sleep quality may be neuroprotective against genetic risk for AD. Future studies employing more rigorous methodology should investigate the mechanistic role of sleep neurophysiology in the pathogenesis and progression of AD associated with ABCA7. There is also need for the continued development of non-invasive sleep interventions tailored to racial groups with specific AD genetic risk profiles.

PURPOSE Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit. METHODS Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate. RESULTS Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10). CONCLUSION We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings. [Media: see text]

Robustness with respect to climate models is often considered by philosophers of climate science to be a crucial issue in determining whether and to what extent the projections of the Earth’s future climate that models yield should be trusted. Parker (2011) and Lloyd (2009, 2015) have introduced influential accounts of robustness for climate models with seemingly conflicting conclusions. I argue that Parker and Lloyd are characterizing distinct notions of robustness and providing complementary insights. Confidence, if warranted, need be by virtue of causally consistent climate models rather than by agreement upon projections by a diverse range of models.

To investigate the effect of preemptive infiltration on postoperative pain and the use of analgesics after vaginal hysterectomy (VH).A retrospective study.An urogynecology unit in a tertiary medical center.A total of 120 patients who had undergone VH.The study group contained 60 patients who participated in a former randomized control study, in which preemptive local infiltration of bupivacaine (n = 30) or sodium chloride 0.9% (n = 30) was performed. The control group included 60 consecutive patients who underwent a VH, for whom no local infiltration was performed.Postoperative pain at rest was assessed using the 10 cm visual analog scale at 3, 8, and 24 hours after surgery. The levels of pain, as well as the use of analgesics, postoperatively, were compared between the groups. The mean surgery length in the infiltration group was shorter (86.4±29 vs 118.6±30, p.001) and the rate of posterior colporrhaphy was lower (73.1% vs 91.3%, p = .010) than the control group. There were no differences in levels of pain at all points of time. However, the infiltration group required a lower morphine dose in the recovery unit (3.7 ± 2.3 mg vs 5.3 ± 2.4 mg, p.001) and less use of analgesia (all kinds) 24 hours after surgery (54.2% vs 79.6%, p.001) compared with the control group. On multivariant analysis, preemptive infiltration was found to be independently inversely associated with the dose of morphine used in recovery, as well as analgesics used 24 hours after surgery.Preemptive local infiltration of either bupivacaine or sodium chloride 0.9% reduced the use of morphine in the recovery unit, as well as the use of analgesics 24 hours after VH, compared with no infiltration at all.

Background: Galectins are sugar binding proteins that play a role in adhesion, apoptosis, immune regulation, and many other cellular processes. There are three different classes of galectins, and they are all found intracellularly and secreted in serum. Galectins have an established relationship with breast cancer, and galectin-3 has been repeatedly associated with cancer cell survival and tumor progression. Most research regarding breast cancer and galectins has used immunohistochemistry (IHC) as a method for identifying galectin expression in breast cancer tissue samples. However, little research has identified a relationship between serum galectin concentrations and breast cancer subtypes. Breast cancer is characterized both by histological and molecular subtype, and this identification often directs treatment decisions. The current method for identifying breast cancer subtypes is through invasive biopsy and the subsequent use of IHC. This project characterized serum galectin concentrations in breast cancer patients to determine if they changed based on different histological and molecular subtypes, cancer stage, and other patient characteristics. Our goal was to evaluate a potential noninvasive means of breast cancer subtype identification and to identify potential therapeutic targets. Methods: One-hundred breast cancer patient serum samples were studied using Enzyme-linked Immunosorbent Assays (ELISAs) to determine concentrations of galectins -1, -3, -7, and -9. Results were compared using many patient characteristics, including breast cancer subtype, stage, and patient history (smoking status and treatment). Statistical Analysis was performed using ANOVA, Student’s t-test, and the Wilcoxon Method. Results: The concentrations of galectins -1, -3, and -9 in breast cancer patients were all significantly higher than those of healthy controls (Table 1), which is consistent with previous studies. The concentration of galectin-3 was significantly higher in invasive lobular carcinoma samples (N, 6; mean, 13.04 ng/mL) compared to invasive ductal carcinoma samples (N, 80; mean, 9.93 ng/mL; p-value, 0.0428). Galectin-3 concentrations were significantly lower in samples from breast cancer patients who received chemotherapy (N, 9; mean, 9.22 ng/mL) versus those who did not (N, 7; mean, 14.60 ng/mL; p-value, 0.0228). Concentrations of galectin-1 were found to increase by stage (p-value, 0.0031), with significant differences between samples from patients with stage I breast cancer (N, 45; mean, 19.02 ng/mL) and both stage II (N, 40; mean, 24.15 ng/mL; p-value, 0.0127) and stage III (N, 12; mean, 28.37 ng/mL; p-value, 0.0026) disease. Conclusions: Our findings suggest a potential use for serum galectin-3 concentrations as a non-invasive means for breast cancer histological subtype differentiation and more refined diagnosis. In addition, our results suggest a possible use of galectin-1 concentrations for more accurate cancer staging. Further research could explore the relationship of serum galectin concentrations and other breast cancer subtypes. Future studies could also analyze how galectin concentrations change with patient treatment status and determine the potential of galectins as specific targets for breast cancer treatment. Table 1: Galectin Concentrations in Breast Cancer vs Healthy Controls Citation Format: Jonah Shealy, Alex Kesic, Avery Funkhouser, Julie Martin, W. Larry Gluck, w. Jeffery Edenfield, Anna Blenda. Analysis of Serum Galectin Profiles by Breast Cancer Subtypes and Patient Characteristics [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-18.

Glycobiology has proved to be a new frontier in oncology research in recent years. One sector of glycobiology involves examining glycan expression of cancerous cells. Glycans are complex carbohydrates found on cell surfaces, and patterns of aberrant glycan expression, such as increased sialylation and fucosylation, have been proposed as potential novel biomarkers of cancer tumorigenesis and metastasis. However, to our knowledge, there is little literature examining the differences in expression of high mannose glycans, a subtype of N-linked glycans, which is the focus of this study. Thirty-nine samples of malignant and surrounding benign tissue from breast cancer patients were collected from the Prisma Health Cancer Institute Biorepository. Additionally, forty malignant serum samples were collected—ten of these samples were from the same patients included in the tissue samples. Serum samples from ten healthy volunteers were also obtained as controls. The malignant samples included specimens from breast cancer staged I through IV at the time of the patients’ diagnosis. Samples were analyzed using MALDI-TOF mass spectroscopy for the presence of glycans by Emory Glycomics and Molecular Interactions Core. The known masses of sixty-one unique glycans were then compared to the spectra of the samples analyzed to determine the type of glycans present, and the relative amount of each glycan present was determined using the area under the curve in the spectral data. Data analysis revealed the means of the area under the curve for high mannose glycans in the malignant and normal tissue samples to be 247.18 and 163.6 respectively; the t-test established the difference in these means to be statistically significant (p-value, 0.0138). This finding was consistent in serum samples; the mean area under the curve for malignant and normal serum was 1650.34 and 376.26 respectively (p-value, >.0001). Furthermore, there were differences in expression of high mannose glycans between stages of breast cancer, with expression in stage III being significantly greater than expression in stage II in both serum (p-value, .0097) and tissue (p-value, .0003) samples. The results of this analysis suggest a higher expression of high mannose glycans to be a promising biomarker for breast cancer. This could lead to important clinical applications such as being a helpful distinction in obtaining negative margins during tumor resection, as well as providing a non-invasive diagnostic method. Future research could include expanding the sample size and comparing the glycan composition of the samples to a library specific for high-mannose type glycans, with the goal of establishing a signature high-mannose expression pattern in each stage of cancer. Citation Format: Alex Kesic, Avery Funkhouser, Jonah Shealy, Julie Martin, W. Larry Gluck, William J. Edenfield, Anna Blenda. Elevated Expression of High Mannose Glycans in Tissue and Serum Samples of Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-22.

We engineered a textile-reinforced hydrogel vascular graft. The textile provides robustness while the hydrogel promotes endothelial cell attachment and growth. The composite enhanced macrophage activation, which increased endothelial cell migration.

Significant scarcity of a donor pool exists for heart transplantation (HT) as the prevalence of patients with end-stage refractory heart failure is increasing exceptionally. With the discovery of effective direct-acting antiviral and favorable short-term outcomes following HT, the hearts from hepatitis C virus (HCV) patient are being utilized to increase the donor pool. Short-term outcomes with regards to graft function, coronary artery vasculopathy, and kidney and liver disease is comparable in HCV-negative recipients undergoing HT from HCV-positive donors compared to HCV-negative donors. A significant high incidence of donor-derived HCV transmission was observed with great success of achieving sustained viral response with the use of direct-acting antivirals. By accepting HCV-positive organs, the donor pool has expanded with younger donors, a shorter waitlist time, and a reduction in waitlist mortality. However, the long-term outcomes and impact of specific HCV genotypes remains to be seen. We reviewed the current literature on HT from HCV-positive donors.

Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking.This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours.We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5).Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Annually, ≈30,000 Hasidic and Orthodox Jews travel to Uman, Ukraine, during the Jewish New Year to pray at the burial place of the founder of the Breslov Hasidic movement. Many pilgrims come from the northeastern United States. The global health implications of this event were seen in 2019 when measles outbreaks in the United States and Israel were linked to the pilgrimage. The 2020 pilgrimage was cancelled as part of the COVID-19 travel restrictions imposed by the government of Ukraine. To prepare for the 2021 event, the National Public Health Institute, the Public Health Center of Ukraine, organized mitigation measures for pilgrims arriving in Uman, and the CDC COVID-19 International Task Force assisted with mitigation measures for pilgrims coming from the United States. We describe efforts to support COVID-19 mitigation measures before, during, and after this mass gathering and lessons learned for future mass gatherings during pandemics.

The SARS-CoV-2 pandemic has increased the demand for antiviral technologies to mitigate or prevent the risk of viral transmission. Antiviral treated textiles have the potential to save lives, especially in healthcare settings that rely on reusable patient-care textiles and personal protective equipment. Currently, little is known about the role of textiles in cross-contamination and pathogen transmission, despite the wealth of information on hard surfaces and fomites harboring viruses that remain viable in certain circumstances. In addition, there is no international standard method for evaluating residual viral activity on textiles, which would allow a thorough investigation of the efficacy of antiviral textile products. Therefore, this pilot study aims to develop and refine a standardized protocol to quantitatively evaluate residual viral activity on antiviral textiles. Specifically, we focused on general textiles, such as bed linens, commonly used in healthcare settings for patient care. The Tissue Culture Infectious Dose 50 (TCID50) method is frequently used to quantitatively evaluate viral infectivity on textiles, but has not been established as a standard. This procedure involves observing the cytopathic effect of a given virus on cells grown in a 96-well plate after several days of incubation to determine the infectivity titer. We used HCoV-229E and Huh-7 human liver cancer cells for this investigation. We worked to improve the TCID50 method through variations of different steps within the protocol to attain reproducible results. Our proposed optimized hybrid protocol has shown evidence that the protocol is technically simpler and more efficient, and provides successful, consistent results. The analysis showed a significant difference between the treated fabric compared with controls.

Rodent models of early life adversity disrupt typical interactions between dams and offspring, impacting pup development over the lifespan. Predictability of caregiver interactions is a critical feature of the environment, and unpredictability is associated with behavioral and cognitive deficits in offspring. In the maternal separation (MS) paradigm, dams are not able to engage with pups while they are separated, and maternal care is impacted even after pups and dams are reunited. Using a 3.5-h daily MS protocol in rats, the present study sought to compare diurnal patterns of maternal behavior, specifically predictability and fragmentation of care, between MS- and control-reared dams. Three observation periods were assessed (1430, 2330, and 0830) between postnatal days 8-9. Frequencies and durations of maternal behaviors were measured, including pup-directed licking/grooming, arched-back and passive nursing, and carrying pups, as well as non-pup-directed self-grooming, rearing, burrowing, nest-building, and eating. The frequency of nest entries was interpreted as a measure of fragmentation, and entropy rate was calculated from transitional probability matrices to measure predictability of maternal behavioral sequences. After dam-pup reunion, MS dams engaged in more bouts of nursing and licking/grooming and more nest entries, and behavioral sequences were less predictable than control dams. MS-induced enhancement of care is a replication of previous research, but unpredictability and fragmented care during MS is a novel finding, as these measures have not been previously reported for MS.

Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m-2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h-1 vs. 0.034 ± 0.016% h-1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h-1 vs. 0.043 ± 0.018% h-1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.

Reduced dorsolateral prefrontal cortex (dlPFC) activity and inhibitory control may contribute to obesity. The study objective was to assess effects of repeated transcranial direct current stimulation (tDCS) on food Go/No-Go (GNG), food Stroop performance, and snack food intake.Twenty-nine individuals with obesity (12 male; mean [SD], age 42 [11] years; BMI 39 [8]) participated in a combined inpatient/outpatient randomized parallel-design trial and received 15 sessions of anodal or sham tDCS to the left dlPFC. Food-related inhibitory control (GNG), attentional bias (Stroop), and snack food intake were assessed at baseline, completion of inpatient sessions (day 7), and follow-up (day 31).GNG performance improved in the anodal group by day 31, compared with sham (p = 0.01), but Stroop scores did not differ by intervention. Greater snack food intake was associated with lower GNG scores (p = 0.01), driven by the sham group (p 0.001) and higher food and palatable bias scores on the Stroop (all p = 0.02) across both groups. Changes on tasks were not associated with changes in intake.Anodal tDCS to the left dlPFC improved performance on a food-related inhibitory control task, providing evidence of potential for therapeutic benefit of neuromodulation in areas controlling executive function. Results showed that tDCS to the dlPFC reduced snack food intake and hunger; however, underlying neurocognitive mechanisms remain uncertain.

This abstract is a companion piece to the ninth iteration of the “Me and My VE” interactive session. The purpose of this alternative format session is to allow human factors researchers to demonstrate how they use virtual reality, mixed reality, and virtual environments to support end-user research. The session begins with each presenter providing a brief introduction of their virtual reality, mixed reality, or virtual environment application. After this introduction, attendees engage with the presenters and their virtual environments in an interactive demonstration period. This year’s demonstrations include applications ranging from designing virtual environments for accessibility to using virtual and extended reality to support medical and aviation training, content validation, and human-computer interaction studies. The goal of the session is to allow attendees to experience how human factors professionals use virtual environments to support human factors-oriented research and to learn about the exciting work being conducted in this field.

Physiological systems responsible for water homeostasis and energy metabolism are interconnected. This study hypothesized altered responses to dehydration including thirst, ad libitum water intake, and copeptin in men with obesity.Forty-two men (22 lean and 20 with obesity) were stimulated by a 2-hour hypertonic saline infusion and a 24-hour water deprivation. In each dehydrating condition, thirst, ad libitum water intake after dehydration, and urinary and hormonal responses including copeptin were assessed.After each dehydration condition, ad libitum water intake was similar between both groups (p 0.05); however, those with obesity reported feeling less thirsty (p 0.05) and had decreased copeptin response and higher urinary sodium concentrations when stressed (p 0.05). Angiotensin II, aldosterone, atrial and brain natriuretic peptides, and apelin concentrations did not differ by adiposity group and did not explain the different thirst or copeptin responses in men with obesity. However, leptin was associated with copeptin response in lean individuals during the hypertonic saline infusion (p 0.05), but the relationship was diminished in those with obesity.Diminished thirst and copeptin responses are part of the obesity phenotype and may be influenced by leptin. Adiposity may impact pathways regulating thirst and vasopressin release, warranting further investigation.

Deficiency and dysfunction of corneal cells leads to the blindness observed in corneal diseases such as limbal stem cell deficiency (LSCD) and bullous keratopathy. Regenerative cell therapies and engineered corneal tissue are promising treatments for these diseases [1]. However, these treatments are not yet clinically feasible due to inadequate cell sources. The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has provided a multitude of opportunities in research because iPSCs can be generated from somatic cells, thus providing an autologous and unlimited source for corneal cells. Compared to other stem cell sources such as mesenchymal and embryonic, iPSCs have advantages in differentiation potential and ethical concerns, respectively. Efforts have been made to use iPSCs to model corneal disorders and diseases, drug testing [2], and regenerative medicine [1]. Autologous treatments based on iPSCs can be exorbitantly expensive and time-consuming, but development of stem cell banks with human leukocyte antigen (HLA)- homozygous cell lines can provide cost- and time-efficient allogeneic alternatives. In this review, we discuss the early development of the cornea because protocols differentiating iPSCs toward corneal lineages rely heavily upon recapitulating this development. Differentiation of iPSCs toward corneal cell phenotypes have been analyzed with an emphasis on feeder-free, xeno-free, and well-defined protocols, which have clinical relevance. The application, challenges, and potential of iPSCs in corneal research are also discussed with a focus on hurdles that prevent clinical translation.

Video capsule endoscopy (VCE) is an effective, noninvasive modality for small bowel (SB) investigation. Its usage in the older adults is rising. However, data in octa-nonagenarians regarding diagnostic yield and motility are lacking. Our aim was to evaluate and compare safety and efficacy of VCE between age subgroups of older adult patients.This was a retrospective study of prospectively documented data. All consecutive VCEs of patients ≥65 years (01/2010-12/2017) were included. Patients unable to swallow the capsule or videos with significant recording technical malfunction were excluded. The cohort was divided into the younger group aged 65-79 years old and octa-nonagenarians aged ≥80 years old. Indications for referral, diagnostic yield and transit times were compared between groups.A total of 535 VCEs were performed in 499 older adult patients (51.2% males); 82.8% were 65-79 years old and 17.2% were ≥80 years old. The ≥80-year-old group had higher rates of clinically significant findings (52.7% vs. 40.0%, p = 0.025), active bleeding (12.5% vs. 6.5%, p = 0.053) and angioectasia (36.0% vs. 23.4%, p = 0.014). Crohn's disease was newly diagnosed in approximately 8% of the entire cohort and 12% of the ≥80 years old. Anemia was the most common indication in both groups, followed by overt bleeding in the ≥80-year-old group (25% vs. 9.9% in 65-79-year-old group, p 0.001) and Crohn's disease in the 65-79 years old (17.2% vs. 5.4% in ≥80 years old, p = 0.004). Groups were comparable in transit time and cecal documentation rates.In octa-nonagenarians, VCE is as safe as in younger older-adults with a higher diagnostic yield of significant and treatable conditions.

With the implementation of the new heart transplant (HT) allocation system, patients requiring biventricular support systems have the highest priority, a shorter waitlist time, and a higher frequency of HT. However, the short-term and long-term outcomes of such patients are often disputed. Hence, we examined the outcomes of these patients who underwent HT before change in allocation scheme. Additionally, we compared post-HT outcomes of extracorporeal membrane oxygenation (ECMO) with other nondischargeable biventricular (BiVAD) supported patients. We identified adult ECMO or BiVAD supported HT recipients between 2000 and 2018 in the Scientific Registry of Transplant Recipients database. We compared survival with the Kaplan-Meier method. Using overlap propensity score weighting, we constructed Cox proportional hazards regression models to determine the risk-adjusted influence of BiVAD versus ECMO on survival. Of the 730 patients HT recipients; 528 (72.3%) and 202 (27.7%) were bridged with BiVAD and ECMO, respectively. For BiVAD versus ECMO patients, the 30-day, 1-year, 3-year, and 5-year mortality rates were 8.0% versus 14.4%, 16.3% versus 21.3%, 22.4% versus 25.3%, and 26.3% versus 25.7%, respectively. Risk-adjusted post-HT survival of BiVAD and ECMO patients at 30-day (HR 1.24 [95% CI, 0.68-2.27]; P = 0.4863), 1-year (HR 1.29 [95% CI, 0.80-2.09]; P = 0.3009), 3-year (HR 1.27 [95% CI, 0.83-1.94]; P = 0.2801), and 5-year (HR 1.35, 95% CI, 0.90-2.05; P = 0.1501) were similar. Around three-fourth of the ECMO or BiVAD supported patients were alive at 5-years post-HT. The short-term and long-term post-HT survivals of groups were comparable.

Carbon nanotubes (CNTs) are known for their excellent conductive properties. Here, we present two novel methods, "sandwich" (sCNT) and dual deposition (DD CNT), for incorporating CNTs into electrospun polycaprolactone (PCL) and gelatin scaffolds to increase their conductance. Based on CNT percentage, the DD CNT scaffolds contain significantly higher quantities of CNTs than the sCNT scaffolds. The inclusion of CNTs increased the electrical conductance of scaffolds from 0.0 ± 0.00 kS (non-CNT) to 0.54 ± 0.10 kS (sCNT) and 5.22 ± 0.49 kS (DD CNT) when measured parallel to CNT arrays and to 0.25 ± 0.003 kS (sCNT) and 2.85 ± 1.12 (DD CNT) when measured orthogonally to CNT arrays. The inclusion of CNTs increased fiber diameter and pore size, promoting cellular migration into the scaffolds. CNT inclusion also decreased the degradation rate and increased hydrophobicity of scaffolds. Additionally, CNT inclusion increased Young's modulus and failure load of scaffolds, increasing their mechanical robustness. Murine fibroblasts were maintained on the scaffolds for 30 days, demonstrating high cytocompatibility. The increased conductivity and high cytocompatibility of the CNT-incorporated scaffolds make them appropriate candidates for future use in cardiac and neural tissue engineering.

Workload plays important roles in sports-related injury and athletic performance by influencing exposure to external injury risk factors and potential events, promoting changes in fitness level, which involves positive adaptations to training that may lead to improved performance, and/or stimulating fatigue which leads to negative effects in the body that may increase the risk of injury and negatively affect performance. In addition to the physical stress and significant time required for practice and training, student athletes also face subjective stressors. The total workload affects injury risk, but acute changes or spikes in external and/or internal loads seem to affect injury risk the most. These also may lead to poor recovery practices that may affect physical and academic performance. It is important for the medical team, coaches, parents, and the student athlete to understand the vulnerability of this population to increased amounts of workload and its positive and negative effects.

OBJECTIVE: Food insecurity is known to be associated with obesity but its association with physiological measures is unclear. Therefore, we hypothesized that compared to food secure, individuals with food insecurity would have higher 24-h energy expenditure (EE[kcal/d]) and a 24-h respiratory quotient (RQ[ratio]). Subsequently, we explored hormones involved in appetite regulation, substrate oxidation, and EE. METHODS: One hundred-thirteen non-diabetic healthy participants (75M; Age 40±12 [years]; BMI 30±8 [kg/m(2)]) were included in this analysis. Participants completed the Food Security Short Form, a DXA scan, and spent 24 hours in a human respiratory chamber following a weight maintaining diet. RESULTS: Compared to individuals with food security, participants with food insecurity had no difference in 24-h EE. However, they had higher carbohydrate oxidation rates (p = 0.03), and lower lipid oxidation rates (p = 0.02), resulting in higher 24-h RQ (p

Despite record-breaking devices, interfaces in perovskite solar cells are still poorly understood, inhibiting further progress. The mixed ionic-electronic nature of lead-halide perovskites results in compositional variations at the interfaces, depending on the history of externally applied biases. This makes it difficult to measure critical parameters accurately, for example, the band energy alignment of charge extraction layers. As a result, the field often resorts to a lengthy trial-and-error process to optimise these interfaces. While techniques to measure interfacial energy level alignment exist, they are typically carried out in a vacuum and on incomplete cells, hence values may not reflect those found in complete device stacks. To address this, w e have developed a pulsed measurement technique that can characterise the electrostatic potential energy drop across the perovskite layer in a functioning device. O ur method reconstructs the JV curve for a range of stabilisation biases which hold the ion distribution "static" during subsequent rapid voltage pulses. W e observe two different regimes: at low applied biases, the reconstructed JV curve is "s-shaped", whereas, at high applied biases, typical diode-shaped curves are returned. Using drift-diffusion simulations, w e demonstrate that the intersection of the two regimes changes based on the band offsets at the transport layer interfaces. This approach effectively allows measurements of interfacial energy level alignment in a complete device under illumination and without the need for expensive vacuum equipment.

Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.

Familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2) are due to loss- and gain-of-function mutations, respectively, of the GNA11 gene that encodes the G protein subunit Gα11, a signaling partner of the calcium-sensing receptor (CaSR). To date, four probands with FHH2-associated Gα11 mutations and eight probands with ADH2-associated Gα11 mutations have been reported. In a 10-year period, we identified 37 different germline GNA11 variants in >1200 probands referred for investigation of genetic causes for hypercalcemia or hypocalcemia, comprising 14 synonymous, 12 noncoding, and 11 nonsynonymous variants. The synonymous and noncoding variants were predicted to be benign or likely benign by in silico analysis, with 5 and 3, respectively, occurring in both hypercalcemic and hypocalcemic individuals. Nine of the nonsynonymous variants (Thr54Met, Arg60His, Arg60Leu, Gly66Ser, Arg149His, Arg181Gln, Phe220Ser, Val340Met, Phe341Leu) identified in 13 probands have been reported to be FHH2- or ADH2-causing. Of the remaining nonsynonymous variants, Ala65Thr was predicted to be benign, and Met87Val, identified in a hypercalcemic individual, was predicted to be of uncertain significance. Three-dimensional homology modeling of the Val87 variant suggested it was likely benign, and expression of Val87 variant and wild-type Met87 Gα11 in CaSR-expressing HEK293 cells revealed no differences in intracellular calcium responses to alterations in extracellular calcium concentrations, consistent with Val87 being a benign polymorphism. Two noncoding region variants, a 40bp-5'UTR deletion and a 15bp-intronic deletion, identified only in hypercalcemic individuals, were associated with decreased luciferase expression in vitro but no alterations in GNA11 mRNA or Gα11 protein levels in cells from the patient and no abnormality in splicing of the GNA11 mRNA, respectively, confirming them to be benign polymorphisms. Thus, this study identified likely disease-causing GNA11 variants in

SummaryDefective centrosome function can disrupt embryonic kidney development, by causing changes to the renal interstitium that leads to fibrocystic disease pathologies. Yet, it remains unknown how mutations in centrosome genes impact kidney interstitial cells. Here, we examined the consequences of defective centrosome biogenesis on stromal progenitor cell growth, differentiation and fate. Conditional deletion ofCep120, a ciliopathy gene essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of pericytes, interstitial fibroblasts and mesangial cells. This was due to delayed mitosis, increased apoptosis, and changes in Wnt and Hedgehog signaling essential for differentiation of stromal lineages.Cep120ablation resulted in hypoplastic kidneys with medullary atrophy and delayed nephron maturation. Finally, centrosome loss in the interstitium sensitized kidneys of adult mice, causing rapid fibrosis via enhanced TGF-β/Smad3-Gli2 signaling after renal injury. Our study defines the cellular and developmental defects caused by centrosome dysfunction in embryonic kidney stroma.Graphical AbstractHighlightsDefective centrosome biogenesis in kidney stroma causes:Reduced abundance of stromal progenitors, interstitial and mesangial cell populationsDefects in cell-autonomous and paracrine signalingAbnormal/delayed nephrogenesis and tubular dilationsAccelerates injury-induced fibrosis via defective TGF-β/Smad3-Gli2 signaling axis

Background Once a mainstay of malaria elimination operations, larval source management (LSM)—namely, the treatment of mosquito breeding habitats–has been marginalized in Africa in favour of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). However, the development of new technologies, and mosquitoes' growing resistance to insecticides used in LLINs and IRS raise renewed interest in LSM. Methods A digitally managed larviciding (DML) operation in three of the seven districts of São Tomé and Príncipe (STP) was launched by the Ministry of Health (MOH) and ZzappMalaria LTD. The operation was guided by the Zzapp system, consisting of a designated GPS-based mobile application and an online dashboard, which facilitates the detection, sampling and treatment of mosquito breeding sites. During the operation, quality assurance (QA) procedures and field management methods were developed and implemented. Results 12,788 water bodies were located and treated a total of 128,864 times. The reduction impact on mosquito population and on malaria incidence was 74.90% and 52.5%, respectively. The overall cost per person protected (PPP) was US$ 0.86. The cost varied between areas: US$ 0.44 PPP in the urban area, and US$ 1.41 PPP in the rural area. The main cost drivers were labour, transportation and larvicide material. Conclusion DML can yield highly cost-effective results, especially in urban areas. Digital tools facilitate standardization of operations, implementation of QA procedures and monitoring of fieldworkers’ performance. Digitally generated spatial data also have the potential to assist integrated vector management (IVM) operations. A randomized controlled trial (RCT) with a larger sample is needed to further substantiate findings.

Supplementary table 2 (AEs of PA patients)

Immune-checkpoint inhibitor (ICI)–related diarrhea is attributed to inflammatory colitis, with no other drug-related differential diagnosis. Here, we investigated the occurrence of pancreatic atrophy (PA) in ICI-treated cancer patients and its correlation to exocrine pancreatic insufficiency (EPI). Metastatic melanoma, non–small cell lung carcinoma, and head and neck squamous cell carcinoma patients (n = 403) treated with anti–PD-1 (n = 356) or anti–CTLA-4 (n = 47) were divided into a case group (radiologic evidence of PA); control group matched by age, gender, and previous lines of treatment; and colitis group (ICI-induced colitis). Quantitative pancreatic volumetry was used for calculation of the decrease in pancreatic volume over time (atrophy rate). Thirty-one patients (7.7%) developed PA compared with 41 matched controls (P = 0.006). Four patients developed EPI, all from the anti–PD-1–treated group, which resolved with oral enzyme supplementation. The atrophy rate did not correlate with EPI (P = 0.87). EPI-related diarrhea presented at a median of 9 months, whereas the diarrhea of anti–PD-1–induced colitis patients (n = 22) was presented at a median of 2 months (P = 0.029). ICI-induced PA is irreversible and can result in EPI. EPI should be suspected in cases of late-onset steroid-resistant diarrhea with features of steatorrhea and treated with oral enzyme supplements.

Characteristics of pancreatic atrophy patients and their matched control patients

The Supplementary Material includes the full inclusion and exclusion criteria and additional methods for the skin punch biopsy. Supplementary Table 1 lists AMG 820 pharmacokinetic parameters, Figure S1 shows AMG 820 trough concentrations, Figure S2 shows AMG 820 and CSF1 concentration profiles, Figure S3 shows time-profile plots for IL-34 and TRAP5b, and Figure S4 shows skin punch biopsy images with staining for CD68 and CD115.

Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and IL34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0.5 mg/kg once weekly or 1.5 to 20 mg/kg every 2 weeks until disease progression, adverse event (AE), or consent withdrawal.Results: Twenty-five patients received ≥1 dose of AMG 820. AMG 820 was tolerated up to 20 mg/kg; the MTD was not reached. One dose-limiting toxicity was observed (20 mg/kg; nonreversible grade 3 deafness). Most patients (76%) had treatment-related AEs; the most common were periorbital edema (44%), increased aspartate aminotransferase (AST; 28%), fatigue (24%), nausea (16%), increased blood alkaline phosphatase (12%), and blurred vision (12%). No patients had serious or fatal treatment-related AEs; 28% had grade ≥3 treatment-related AEs. Grade 3 AST elevations resolved when treatment was withheld. AMG 820 showed linear pharmacokinetics, with minimal accumulation (Conclusions: AMG 820 was tolerated with manageable toxicities up to 20 mg/kg every 2 weeks. Pharmacodynamic response was demonstrated, and limited antitumor activity was observed. Clin Cancer Res; 23(19); 5703–10. ©2017 AACR.

Trichodermais a cosmopolitan genus with diverse lifestyles and nutritional modes, including mycotrophy, saprophytism, and endophytism. Previous research has reported greater metabolic gene repertoires in endophytic fungal species compared to closely-related non-endophytes. However, the extent of this ecological trend and its underlying mechanisms are unclear. Some endophytic fungi may also be mycotrophs and have one or more mycoparasitism mechanisms. Mycotrophic endophytes are prominent in certain genera likeTrichoderma, therefore, the mechanisms that enable these fungi to colonize both living plants and fungi may be the result of expanded metabolic gene repertoires. Our objective was to determine what, if any, genomic features are overrepresented in endophytic fungi genomes in order to undercover the genomic underpinning of the fungal endophytic lifestyle. Here we compared metabolic gene cluster and mycoparasitism gene diversity across a dataset of thirty-eightTrichodermagenomes representing the full breadth of environmentalTrichoderma’s diverse lifestyles and nutritional modes. We generated four newTrichoderma endophyticumgenomes to improve the sampling of endophytic isolates from this genus. As predicted, endophyticTrichodermagenomes contained, on average, more total biosynthetic and degradative gene clusters than non-endophytic isolates, suggesting that the ability to create/modify a diversity of metabolites potential is beneficial or necessary to the endophytic fungi. Still, once the phylogenetic signal was taken in consideration, no particular class of metabolic gene cluster was independently associated with theTrichodermaendophytic lifestyle. Several mycoparasitism genes, but no chitinase genes, were associated with endophyticTrichodermagenomes. Most genomic differences betweenTrichodermalifestyles and nutritional modes are difficult to disentangle from phylogenetic divergences among species, suggesting that Trichoderma genomes maybe particularly well-equipped for lifestyle plasticity. We also consider the role of endophytism in diversifying secondary metabolism after identifying the horizontal transfer of the ergot alkaloid gene cluster toTrichoderma.

Background/Objectives: Lower birthweight has been previously identified as a risk factor for multiple chronic diseases which are also associated with poor diet. We sought to determine whether birthweight is related to objectively measured energy intake in adulthood. We hypothesized a negative association between birthweight and overall energy intake in adulthood. Subjects/Methods: Healthy Indigenous American adults (n=65; age 33.2±8.0 years; female n=29; BMI 33.2±8.1 kg/m2) with measures of birthweight (mean 3465±376g; mean gestational age 40.1±1.2 weeks), ad libitum energy intake, and body composition were included. Three-day energy intake was measured using vending machines and categorized as high (≥45% kcal) or low in fat (Results: A birthweight-by-sex interaction was found such that birthweight was associated with energy intake negatively in males and positively in females (interaction p=0.04; simple slopes: male β=−64, female β= 93 kcal/day per 100 g birthweight). This pattern was evident in fat (interaction p=0.01; simple slopes: male β=−48, female β=42 kcal/day per 100g birthweight), protein (interaction p=0.02; simple slopes: male β=−5, female β=20 kcal/day per 100g birthweight), and high-fat/high-protein (interaction p=0.01; simple slopes: male β=−46, female β=45 kcal/day per 100g birthweight) consumption. Conclusion: Birthweight was negatively associated with energy intake in adult males but was positively associated with energy intake in adult females.

Background Disability is common following critical illness, impacting the quality of life of survivors, and is difficult to measure. ‘Participation’ can be quantified as involvement in life outside of their home requiring movement from their home to other locations. Participation restriction is a key element of disability, and following critical illness, participation may be diminished. It may be possible to quantify this change using pre-existing smartphone data. Objectives The feasibility of extracting location data from smartphones of survivors of intensive care unit (ICU) admission and assessing participation, using location-based outcomes, during recovery from critical illness was evaluated. Methods Fifty consecutively admitted, consenting adult survivors of non-elective admission to ICU of greater than 48-h duration were recruited to a prospective observational cohort study where they were followed up at 3 and 6 months following discharge. The feasibility of extracting location data from survivors' smartphones and creating location-derived outcomes assessing participation was investigated over three 28-d study periods: pre-ICU admission and at 3 and 6 months following discharge. The following were calculated: time spent at home; the number of destinations visited; linear distance travelled; and two ‘activity spaces’, a minimum convex polygon and standard deviation ellipse. Results Results are median [interquartile range] or n (%). The number of successful extractions was 9/50 (18%), 12/39 (31%), and 13/33 (39%); the percentage of time spent at home was 61 [56–68]%, 77 [66–87]%, and 67 [58–77]% (P = 0.16); the number of destinations visited was 34 [18–64], 38 [22–63], and 65 [46–88] (P = 0.02); linear distance travelled was 367 [56–788], 251 [114–323], and 747 [326–933] km over 28 d (P = 0.02), pre-ICU admission and at 3 and 6 months following ICU discharge, respectively. Activity spaces were successfully created. Conclusion Limited smartphone ownership, missing data, and time-consuming data extraction limit current implementation of mass extraction of location data from patients’ smartphones to aid prognostication or measure outcomes. The number of journeys taken and the linear distance travelled increased between 3 and 6 months, suggesting participation may improve over time.

This article examines the enduring entanglements of counterterror governance and refugee encampment in Kenya. The spectre of “terrorism” and its supposed remedy—“counterterrorism”—have loomed large in Kenyan politics since the 1990s and gained further traction since the country’s military invasion and occupation of southern Somalia in 2011. Few other spaces have been associated as persistently with threats to Kenya’s national security and sovereignty as the Dadaab and Kakuma refugee camps in the country’s Northern belt, which are popularly depicted as “wombs” of terror. In this article, we analyze the transformation of refugee governance in Kenya under the auspices of the War on Terror and consider how counterterrorism has become a way of governing both refugees and precarious ethnoracialized citizens. We provide a multi-scalar analysis that moves between the scales of global militarization, Kenyan state governance, as well as securitized spaces of camps, checkpoints, and policing. The article concludes that refugee camps are not only gateways for imported global counterterror initiatives, but key sites of locally defined state-making processes in which Kenya’s counterterror state is (re)assembled as part of a planetary architecture of humanitarian containment and militarized apartheid.

Long-term durability and functional outcome of laparoscopic sacrohysteropexy (LSH) remains to be confirmed. We set out to assess the development of surgical outcome in women with increasing minimal follow-up.All women after LSH with anterior and posterior mesh extension operated for advanced apical uterine prolapse at Geoffroy Saint-Hilaire clinic from July 2005 to June 2020 were enrolled in this retrospective study. Last known follow-up information was used for the analysis and allocation into groups. The surgical success was defined as no prolapse beyond hymen, no symptomatic recurrence or no retreatment. Functional outcome was evaluated from validated questionnaires and presence of pelvic floor disorders. The outcomes were compared with preoperative state using chi-square and Fisher's test; p 0.05 was considered significant.In total, 270 patients after LSH with a follow-up of up to 14.5 years were enrolled and divided into groups according to their last follow-up length: ≥ 1 year 242, ≥ 3 years 112, ≥ 5 years 76, ≥ 7 years 45 and ≥ 10 years 18 women. Increase of minimal follow-up was associated with gradual decrease in surgical success. Rates of stress urinary incontinence were unchanged by the surgery, while anal incontinence and constipation rates decreased significantly; 14.5% of women were operated on for SUI in the follow-up. The PFDI-20, PFIQ-7 and VAS bother scores decreased significantly regardless of minimal follow-up length.LSH with anterior and posterior mesh extension is a safe, effective and durable surgery with a positive long-term effect on quality of life. Although the surgical success gradually decreases, LSH remains a surgical success in most women.