Circulating Biomarkers, Fraction of Exhaled Nitric Oxide, and Lung Function in Patients With Human Immunodeficiency Virus and Tuberculosis.

BACKGROUND: Identification of proinflammatory factors responding to Mycobacterium tuberculosis is important to reduce long-term sequelae of pulmonary tuberculosis (TB). METHODS: We examined the association between plasma biomarkers, the fraction of exhaled nitric oxide (FeNO), and lung function among a prospective cohort of 105 adults newly diagnosed with TB/human immunodeficiency virus (HIV) in South Africa. Participants were followed for 48 weeks from antiretroviral therapy (ART) initiation with serial assessments of plasma biomarkers, FeNO, lung function, and respiratory symptoms. Linear regression and generalized estimating equations were used to examine the associations at baseline and over the course of TB treatment, respectively. RESULTS: At baseline, higher FeNO levels were associated with preserved lung function, whereas greater respiratory symptoms and higher interleukin (IL)-6 plasma levels were associated with worse lung function. After ART and TB treatment initiation, improvements in lung function were associated with increases in FeNO (rate ratio [RR] = 86 mL, 95% confidence interval [CI] = 34-139) and decreases in IL-6 (RR = -118 mL, 95% CI = -193 to -43) and vascular endothelial growth factor ([VEGF] RR = -178 mL, 95% CI = -314 to -43). CONCLUSIONS: Circulating IL-6, VEGF, and FeNO are associated with lung function in adults being treated for TB/HIV. These biomarkers may help identify individuals at higher risk for post-TB lung disease and elucidate targetable pathways to modify the risk of chronic lung impairment among TB survivors.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Corymbiform cutaneous disorders in pediatric dermatology: Exploring this pattern of presentation beyond secondary syphilis.

"Corymbiform" is a term found in medical literature as early as 1876 to describe a central larger lesion with smaller surrounding lesions, leading to the appearance of an irregular border. While the term in current medical literature most often describes a possible morphology of secondary syphilis, the authors have noted this pattern presenting in other cutaneous conditions. We present a commentary on the corymbiform pattern in dermatology including a series of photographs of cutaneous disorders presenting in a corymbiform morphology in pediatric patients. While the term corymbiform is not commonly used in the present-day dermatologic literature, increased recognition and use of this term may aid in the recognition of various dermatologic diagnoses presenting in a less common morphology and may also lend to increased fluidity of dermatologic descriptions in the literature.

Stop and Think: A Case Study Illustrating the Implementation of Bright IDEAS-YA Being Delivered via Telehealth to a Young Adult Cancer Patient.

Bright IDEAS-Young Adults (Bright IDEAS-YA) is a problem-solving skills training intervention that has been adapted for young adults with cancer. Presently, a multisite randomized control trial is being conducted to determine Bright IDEAS-YA's efficacy in supporting a young adult population. This case study demonstrates the young adult adaptation of Bright IDEAS - Bright IDEAS-YA - being delivered to a young adult cancer patient via telehealth. Telehealth is a novel delivery method for Bright IDEAS and Bright IDEAS-YA that was established due to COVID-19 safety precautions. The patient, who reported challenges in several life domains, was taught how to apply the Bright IDEAS-YA framework over six telehealth sessions. After completing the Bright IDEAS-YA framework, the patient reported increased feelings of confidence in managing new stressors, which was corroborated through outcome measures delivered during and following intervention. This case illustrates how early psychosocial intervention following a cancer diagnosis, delivered via telehealth, can help patients develop and implement personal strategies to reduce stress levels.

Loss-of-function mutations in WRKY22 and WRKY25 impair stomatal-mediated immunity and PTI and ETI responses against Pseudomonas syringae pv. tomato.

Plants defend themselves against pathogens using a two-layered immune system. The first response, pattern-triggered immunity (PTI), is activated upon recognition of microbe-associated molecular patterns (MAMPs). Virulent bacteria such as Pseudomonas syringae pv. tomato (Pst), deliver effector proteins into the plant cell to promote susceptibility. However, some plants possess resistance (R) proteins that recognize specific effectors leading to the activation of the second response, effector-triggered immunity (ETI). Resistant tomatoes such as Río Grande-PtoR recognize two Pst effectors (AvrPto and AvrPtoB) through the host Pto/Prf complex and activate ETI. We previously showed that the transcription factors (TF) WRKY22 and WRKY25 are positive regulators of plant immunity against bacterial and potentially non-bacterial pathogens in Nicotiana benthamiana. Here, the CRISPR-Cas9 technique was used to develop three knockout tomato lines for either one or both TFs. The single and double mutants were all compromised in Pto/Prf-mediated ETI and had a weaker PTI response. The stomata apertures in all of the mutant lines did not respond to darkness or challenge with Pst DC3000. The WRKY22 and WRKY25 proteins both localize in the nucleus, but we found no evidence of a physical interaction between them. The WRKY22 TF was found to be involved in the transcriptional regulation of WRKY25, supporting the idea that they are not functionally redundant. Together, our results indicate that both WRKY TFs play a role in modulating stomata and are positive regulators of plant immunity in tomato.

Solvent-Dependent Structural Dynamics in the Ultrafast Photodissociation Reaction of Triiodide Observed with Time-Resolved X-ray Solution Scattering.

Resolving the structural dynamics of bond breaking, bond formation, and solvation is required for a deeper understanding of solution-phase chemical reactions. In this work, we investigate the photodissociation of triiodide in four solvents using femtosecond time-resolved X-ray solution scattering following 400 nm photoexcitation. Structural analysis of the scattering data resolves the solvent-dependent structural evolution during the bond cleavage, internal rearrangements, solvent-cage escape, and bond reformation in real time. The nature and structure of the reaction intermediates during the recombination are determined, elucidating the full mechanism of photodissociation and recombination on ultrafast time scales. We resolve the structure of the precursor state for recombination as a geminate pair. Further, we determine the size of the solvent cages from the refined structures of the radical pair. The observed structural dynamics present a comprehensive picture of the solvent influence on structure and dynamics of dissociation reactions.

Exploring fingerprints of ultrafast structural dynamics in molecular solutions with an X-ray laser.

We apply ultrashort X-ray laser pulses to track optically excited structural dynamics of [Ir2(dimen)4]2+ molecules in solution. In our exploratory study we determine angular correlations in the scattered X-rays, which comprise a complex fingerprint of the ultrafast dynamics. Model-assisted analysis of the experimental correlation data allows us to elucidate various aspects of the photoinduced changes in the excited molecular ensembles. We unambiguously identify that in our experiment the photoinduced transition dipole moments in [Ir2(dimen)4]2+ molecules are oriented perpendicular to the Ir-Ir bond. The analysis also shows that the ground state conformer of [Ir2(dimen)4]2+ with a larger Ir-Ir distance is mostly responsible for the formation of the excited state. We also reveal that the ensemble of solute molecules can be characterized with a substantial structural heterogeneity due to solvent influence. The proposed X-ray correlation approach offers an alternative path for studies of ultrafast structural dynamics of molecular ensembles in the liquid and gas phases.

Two-dimensional phase unwrapping based on Fourier transforms and the Yukawa potential spectrum.

The two-dimensional phase unwrapping problem (PHUP) has been solved with discrete Fourier transforms (FTs) and many other techniques traditionally. Nevertheless, a formal way of solving the continuous Poisson equation for the PHUP, with the use of continuous FT and based on distribution theory, has not been reported yet, to our knowledge. The well-known specific solution of this equation is given in general by a convolution of a continuous Laplacian estimate with a particular Green function, whose FT does not exist mathematically. However, an alternative Green function called the Yukawa potential, with a guaranteed Fourier spectrum, can be considered for solving an approximated Poisson equation, inducing a standard procedure of a FT-based unwrapping algorithm. Thus, the general steps for this approach are described in this work by considering some reconstructions with synthetic and real data.

Botulinum toxin for refractory Raynaud's phenomenon: A "how to" guide for pediatric patients.

Raynaud's phenomenon describes symptoms caused by digital vascular spasm and is classically induced by cold exposure. Severe cases can result in ulceration, necrosis, and digital autoamputation. When standard and adjunctive medical therapies fail or are contraindicated, botulinum toxin A (BTX-A) is an effective treatment option that can be added to existing regimens and should be considered before utilizing rescue therapies associated with higher risk and often higher cost. This report describes our technique, highlights considerations relevant to pediatric patients, and provides photos and videos of the procedure performed on a 16-year-old girl.

Medium-term Outcome of Prenatally Diagnosed Hypoplastic Left-Heart Syndrome and Impact of a Restrictive Atrial Septum Diagnosed in-utero.

OBJECTIVE: Surgical outcome data differs from overall outcomes of prenatally diagnosed fetuses with hypoplastic left heart syndrome (HLHS). Our aim was to describe outcome of prenatally diagnosed fetuses with this anomaly. METHODS: Retrospective review of prenatally diagnosed classical HLHS at a tertiary hospital over a 13-year period, estimated due dates 01/08/2006 to 31/12/2019. HLHS-variants and ventricular disproportion were excluded. RESULTS: 203 fetuses were identified with outcome information available for 201. There were extra-cardiac abnormalities in 8% (16/203), with genetic variants in 14% of those tested (17/122). There were 55 (27%) terminations of pregnancy, 5 (2%) intrauterine deaths and 10 (5%) babies had prenatally planned compassionate care. There was intention to treat (ITT) in the remaining 131/201(65%). Of these, there were 8 neonatal deaths before intervention, two patients had surgery in other centers. Of the other 121 patients, Norwood procedure performed in 113 (93%), initial hybrid in 7 (6%), and 1 had palliative coarctation stenting. Survival for the ITT group from birth at 6-months, 1-year and 5-years was 70%, 65%, 62% respectively. Altogether of the initial 201 prenatally diagnosed fetuses, 80 patients (40%) are currently alive. A restrictive atrial septum (RAS) is an important sub-category associated with death, HR 2.61, 95%CI 1.34-5.05, p = 0.005, with only 5/29 patients still alive. CONCLUSION: Medium-term outcomes of prenatally diagnosed HLHS have improved however it should be noted that almost 40% do not get to surgical palliation, which is vital to those doing fetal counselling. There remains significant mortality particularly in fetuses with in-utero diagnosed RAS.

A Collaborative Pilot to Support Patients With Diabetes Through Tailored Food Box Home Delivery.

We conducted a randomized, controlled prospective pilot study to determine feasibility and impact of food bank and health system collaboration to home-delivered food to adults with type 2 diabetes mellitus experiencing food insecurity. Treatment group received biweekly, ethnically tailored, home-delivered food for 24 weeks. Analysis included intervention feasibility and impact on healthcare utilization, HbA1c, and other health-related measures. Intervention was feasible and successful with high levels of participant satisfaction. At baseline, participants with highest HbA1c reported poorer health, lower medication adherence and self-care, and higher diabetes distress and medicine for food tradeoffs. At 24 weeks, treatment group reported improved food security and health status. There were no differences in HbA1c or healthcare utilization measures between the two groups. It is feasible for a community food bank and nearby hospital to successfully collaborate and provide supplemental food staples to food insecure adults with type 2 diabetes and improve food insecurity and health status. Public policy efforts should utilize and expand this strategy with the goal of improving health and reducing health disparities. Future work could include more comprehensive food support focused on those with poorest glycemic control, and expanded, coordinated interventions directed at other social determinants of health. Future programming and policies should be cocreated with community input to ensure greatest success.

Scaffolds for Dentin-Pulp Complex Regeneration.

Background and Objectives: Regenerative dentistry aims to regenerate the pulp-dentin complex and restore those of its functions that have become compromised by pulp injury and/or inflammation. Scaffold-based techniques are a regeneration strategy that replicate a biological environment by utilizing a suitable scaffold, which is considered crucial for the successful regeneration of dental pulp. The aim of the present review is to address the main characteristics of the different scaffolds, as well as their application in dentin-pulp complex regeneration. Materials and Methods: A narrative review was conducted by two independent reviewers to answer the research question: What type of scaffolds can be used in dentin-pulp complex regeneration? An electronic search of PubMed, EMBASE and Cochrane library databases was undertaken. Keywords including "pulp-dentin regeneration scaffold" and "pulp-dentin complex regeneration" were used. To locate additional reports, reference mining of the identified papers was undertaken. Results: A wide variety of biomaterials is already available for tissue engineering and can be broadly categorized into two groups: (i) natural, and (ii) synthetic, scaffolds. Natural scaffolds often contain bioactive molecules, growth factors, and signaling cues that can positively influence cell behavior. These signaling molecules can promote specific cellular responses, such as cell proliferation and differentiation, crucial for effective tissue regeneration. Synthetic scaffolds offer flexibility in design and can be tailored to meet specific requirements, such as size, shape, and mechanical properties. Moreover, they can be functionalized with bioactive molecules, growth factors, or signaling cues to enhance their biological properties and the manufacturing process can be standardized, ensuring consistent quality for widespread clinical use. Conclusions: There is still a lack of evidence to determine the optimal scaffold composition that meets the specific requirements and complexities needed for effectively promoting dental pulp tissue engineering and achieving successful clinical outcomes.

Detecting single ORAI1 proteins within the plasma membrane reveals higher-order channel complexes.

ORAI1 proteins form highly selective Ca2+ channels in the plasma membrane. Crystallographic data point towards a hexameric stoichiometry of ORAI1 channels, whereas optical methods postulated ORAI1 channels to reside as dimers at rest, and other data suggests that they have a tetrameric configuration. Here, liquid-phase scanning transmission electron microscopy (STEM) and quantum dot (QD) labeling was utilized to study the conformation of ORAI1 proteins at rest. To address the question of whether ORAI1 was present as a dimer, experiments were designed using single ORAI1 monomers and covalently linked ORAI1 dimers with either one or two label-binding positions. The microscopic data was statistically analyzed via the pair correlation function. Label pairs were found in all cases, even for concatenated dimers with one label-binding position, which is only possible if a significant fraction of ORAI1 was assembled in larger order oligomers than dimers, binding at least two QDs. This interpretation of the data was consistent with Blue Native PAGE analysis showing that ORAI1 is mainly present as a complex of an apparent molecular mass larger than that calculated for a dimer.

Extending the benefit of nutrition intervention beyond the operative setting.

PURPOSE OF REVIEW: To provide an update of the recent evidence on the potential of perioperative nutritional interventions to benefit adult patients undergoing head and neck and digestive procedures. RECENT FINDINGS: Perioperative nutrition within multimodal prehabilitation programs improve postoperative outcomes. Perioperative fasting time can be reduced with beverages containing carbohydrate alone or blended with a nitrogenous source such as whey protein; this approach seems to be safe and improve outcome. The choice of protein-containing formula, as well as diet composition to be recommended early during the postoperative refeeding, can be optimized to reduce complications. Sarcopenia is an important risk factor for surgical patients, as such, prehabilitation along with preoperative nutrition is strongly advised. Perioperative supplementation with ß-hydroxy ß-methylbutyrate to mitigate sarcopenia requires further investigation. Although perioperative nutritional interventions reduce healthcare costs, recent data suggest it has been scarcely prescribed. SUMMARY: Nutritional intervention is key in multimodal programs of enhanced recovery after surgery to ensure better outcomes. Perioperative fasting should be shortened, and include clear fluids containing carbohydrates and protein, especially in the early postoperative period. Multimodal prehabilitation is key to mitigate sarcopenia. Action to improve knowledge on the cost-effectiveness of nutritional interventions in the perioperative setting are needed.

Systematic assessment of process analytical technologies for biologics.

The application of process analytical technology (PAT) for biotherapeutic development and manufacturing has been employed owing to technological, economic, and regulatory advantages across the industry. Typically, chromatographic, spectroscopic, and/or mass spectrometric sensors are integrated into upstream and downstream unit operations in in-line, on-line, or at-line fashion to enable real-time monitoring and control of the process. Despite the widespread utility of PAT technologies at various unit operations of the bioprocess, a holistic business value assessment of PAT has not been well addressed in biologics. Thus, in this study, we evaluated PAT technologies based on predefined criteria for their technological attributes such as enablement of better process understanding, control, and high-throughput capabilities; as well as for business attributes such as simplicity of implementation, lead time, and cost reduction. The study involved an industry-wide survey, where input from subject matter industry experts on various PAT tools were collected, assessed, and ranked. The survey results demonstrated on-line liquid Chromatography (LC), in-line Raman, and gas analysis techniques are of high business value especially at the production bioreactor unit operation of upstream processing. In-line variable path-length UV/VIS measurements (VPE), on-line LC, multiangle light scattering (MALS), and automated sampling are of high business value in Protein A purification and polishing steps of the downstream process. We also provide insights, based on our experience in clinical and commercial manufacturing of biologics, into the development and implementation of some of the PAT tools. The results presented in this study are intended to be helpful for the current practitioners of PAT as well as those new to the field to gauge, prioritize and steer their projects for success.

Design and Development of a Community-Based, Interdisciplinary, Collaborative Dementia Care Program.

OBJECTIVE: To describe the design, development, and baseline characteristics of enrollees of a home-based, interdisciplinary, dyadic, pilot dementia care program. DESIGN: Single-arm, dementia care intervention in partnership with primary care providers delivered by Health Coaches to persons with dementia and caregiver "dyads" and supervised by an interdisciplinary team. SETTING: Home- and virtual-based dyad support. PARTICIPANTS: Persons with mild cognitive impairment or dementia diagnosis and/or who were prescribed antidementia medications; had an identified caregiver willing to participate; were under the care of a partner primary care provider; and had health insurance through the affiliated accountable care organization (Banner Health Network). INTERVENTION: Provision of personalized dementia education and support in the home or virtually by Health Coaches supported by an interdisciplinary team. MEASUREMENTS: Cognition, function, mood, and behavior of persons with dementia; caregiver stress and program satisfaction; primary care provider satisfaction. RESULTS: Served dyads from three primary care clinics with a total of 87 dyads enrolled between December 2018 and June 2020. CONCLUSION: A pilot Dementia Care Partners demonstrated feasibility and suggested acceptability, and high satisfaction among primary care providers and caregivers.

Tracking structural solvent reorganization and recombination dynamics following e- photoabstraction from aqueous I- with femtosecond x-ray spectroscopy and scattering.

We present a sub-picosecond resolved investigation of the structural solvent reorganization and geminate recombination dynamics following 400 nm two-photon excitation and photodetachment of a valence p electron from the aqueous atomic solute, I-(aq). The measurements utilized time-resolved X-ray Absorption Near Edge Structure (TR-XANES) spectroscopy and X-ray Solution Scattering (TR-XSS) at the Linac Coherent Light Source x-ray free electron laser in a laser pump/x-ray probe experiment. The XANES measurements around the L1-edge of the generated nascent iodine atoms (I0) yield an average electron ejection distance from the iodine parent of 7.4 ± 1.5 Å with an excitation yield of about 1/3 of the 0.1M NaI aqueous solution. The kinetic traces of the XANES measurement are in agreement with a purely diffusion-driven geminate iodine-electron recombination model without the need for a long-lived (I0:e-) contact pair. Nonequilibrium classical molecular dynamics simulations indicate a delayed response of the caging H2O solvent shell and this is supported by the structural analysis of the XSS data: We identify a two-step process exhibiting a 0.1 ps delayed solvent shell reorganization time within the tight H-bond network and a 0.3 ps time constant for the mean iodine-oxygen distance changes. The results indicate that most of the reorganization can be explained classically by a transition from a hydrophilic cavity with a well-ordered first solvation shell (hydrogens pointing toward I-) to an expanded cavity around I0 with a more random orientation of the H2O molecules in a broadened first solvation shell.

Valorization of Seaweed Wracks: Inclusion as Additive in Diets for Grass Carp (Ctenopharyngodon idella).

Macroalgae have been recently described as a potential ingredient for aquafeeds, exerting several physiological benefits. Grass carp (Ctenopharyngodon idella) is a freshwater species, which has been the major fish species produced in the world in the last years. In order to determine the potential use of macroalgal wracks in fish feeding, C. idella juveniles were fed with an extruded commercial diet (CD) or the CD supplemented with 7% of a wind dried-powder (1 mm) from either a multispecific macroalgal wrack (CD + MU7) or a monospecific macroalgal wrack (CD + MO7) obtained from Gran Canaria island (Spain) coasts. After 100 days of feeding, survival, fish weight, and body indexes were determined, and muscle, liver, and digestive tract samples were collected. The total antioxidant capacity of macroalgal wracks was analyzed by assesing the antioxidant defense response and digestive enzymes activity in fish. Finally, muscle proximate composition, lipid classes (LC), and fatty acid (FA) profiles were also studied. Our results suggest that dietary inclusion of macroalgal wracks does not have negative effects on growth, proximate, and lipid composition, antioxidative status, or digestive capacity of C. idella. In fact, both macroalgal wracks caused a general lower fat deposition, and the multispecific wrack enhanced catalase activity in the liver.

School-based obesity interventions in the metropolitan area of Rio De Janeiro, Brazil: pooled analysis from five randomised studies.

School-based studies, despite the large number of studies conducted, have reported inconclusive results on obesity prevention. The sample size is a major constraint in such studies by requiring large samples. This pooled analysis overcomes this problem by analysing 5926 students (mean age 11·5 years) from five randomised school-based interventions. These studies focused on encouraging students to change their drinking and eating habits, and physical activities over the one school year, with monthly 1-h sessions in the classroom; culinary class aimed at developing cooking skills to increase healthy eating and attempts to family engagement. Pooled intention-to-treat analysis using linear mixed models accounted for school clusters. Control and intervention groups were balanced at baseline. The overall result was a non-significant change in BMI after one school year of positive changes in behaviours associated with obesity. Estimated mean BMI changed from 19·02 to 19·22 kg/m2 in the control group and from 19·08 to 19·32 kg/m2 in the intervention group (P value of change over time = 0·09). Subgroup analyses among those overweight or with obesity at baseline also did not show differences between intervention and control groups. The percentage of fat measured by bioimpedance indicated a small reduction in the control compared with intervention (P = 0·05). This large pooled analysis showed no effect on obesity measures, although promising results were observed about modifying behaviours associated with obesity.

Effectiveness of a school-based randomized controlled trial aimed at increasing physical activity time in adolescents.

BACKGROUND: This study aimed to evaluate the effectiveness of obesity prevention educational activities, isolated or combined with the modification of the school environment on total physical activity time. METHODS: This is a school-based randomized controlled trial, conducted with 2511 students from fifth and sixth-grade in Brazil, that employed a parallel, three-group experimental arms: control group (CG), PAAPPAS group (PG) and PAAPPAS-environment group (PEG). During the 2016 school year, the PG received educational activities in the classroom, providing a general basis for a healthy lifestyle. The PEG received the same educational activities and also modifications in the school environment to stimulate physical activity practice during one month. Physical activity was evaluated through a validated physical activity questionnaire. Intention-to-treat analysis was performed to evaluate the rate of change of physical activity time between groups using PROC GENMOD procedure. All analyses were performed using SAS. RESULTS: Total physical activity time increased by 22% in PEG compared with CG (P = 0.003). No difference was observed between PEG and PG (Δ = 60.20 vs. 36.37, respectively; P = 0.27) and between PG and CG (Δ = 36.37 vs. 9.70, respectively; P = 0.23). The proportion of individuals who attended at least 150 min week-1 of physical activity increased in PEG compared with PG (P = 0.04); however, no difference was observed between PEG and CG (P = 0.19) and between PG and CG (P = 0.26). For 300 min week-1, no difference was observed between groups. CONCLUSION: A school-based multi-component intervention including modification of the school environment was effective for increasing physical activity time among adolescents.