Enhanced catalytic reduction through in situ synthesized gold nanoparticles embedded in glucosamine/alginate nanocomposites.

This study introduces a highly efficient and straightforward method for synthesizing gold nanoparticles (AuNPs) within a glucosamine/alginate (GluN/Alg) nanocomposite via an ionotropic gelation mechanism in aqueous environment. The resulting nanocomposite, AuNPs@GluN/Alg, underwent thorough characterization using UV-vis, EDX, FTIR, SEM, TEM, SAED, and XRD analyses. The spherical AuNPs exhibited uniform size with an average diameter of 10.0 nm. The nanocomposites facilitated the recyclable reduction of organic dyes, including 2-nitrophenol, 4-nitrophenol, and methyl orange, employing NaBH4 as the reducing agent. Kinetic studies further underscored the potential of this nanocomposite as a versatile catalyst with promising applications across various industrial sectors.

A Method to Estimate the Dietary α-Linolenic Acid (ALA) Requirement Using Non-Esterified DHA and Arachidonic Acid (ARA) Oxylipins and Fatty Acids.

BACKGROUND: The dietary requirement for ALA remains unclear, as evidenced by the absence of an RDA for this essential fatty acid (FA). In previous studies we observed that the amount of dietary ALA required to maximize non-esterified (NE) DHA oxylipins appears to be higher than the amount required to maximize tissue esterified DHA levels, which have classically been used to estimate the ALA requirement. Further, we observed that dietary ALA reduces esterified arachidonic acid (ARA) and its NE oxylipins. OBJECTIVE: Since NE oxylipins and FA mediate biologic activities of FA, we examined whether these DHA and ARA pools could be used to determine the dietary ALA requirement. METHODS: Nine groups of 4-week-old male Sprague-Dawley rats (n=5) and 10 groups of male and female CD1 mice (n=6) were provided 0.1 to 2.5g ALA and 2g of linoleic acid per 100g of AIN93G-based diets. NE DHA and ARA and their oxylipins in serum, liver, kidney and brain homogenates underwent solid phase extraction and were quantified by HPLC-MS/MS. Breakpoint analysis of transitions from increase to plateau were conducted using piecewise regression. RESULTS: In response to increasing dietary ALA, NE DHA oxylipins and DHA in serum, liver and kidney (but not brain) initially increased rapidly and then plateaued whereas ARA oxylipins and ARA tended to decrease and plateau. Thus, breakpoints were calculated for the ratios of DHA/ARA and hydroxy-DHA/hydroxy-ARA (DHAOH/ARAOH), which consisted of oxylipins synthesized via pathways common to both FA. In serum, liver and kidney the highest estimated breakpoint indicated an ALA requirement of ∼0.7g/100g diet (1.7%energy), approximately twice that of previous estimations. CONCLUSION: This study supports the use of NE DHAOH/ARAOH or DHA/ARA as biochemical indicators of the ALA requirement. Applying this method in rats and mice indicates that the requirement is higher than previously estimated using esterified DHA alone.

Clinical Significance Unveiled: Understanding the Meaning of FACE-Q Skin Cancer Scores for Improved Patient Care.

OBJECTIVE: The FACE-Q Skin Cancer Module is a Patient-Reported Outcome Measure (PROM) utilized to assess outcomes following facial skin cancer resection. However, the lack of Minimal Important Difference (MID) estimates hinders the interpretability of the PROM scores. This study established MID estimates for the four outcome scales from the FACE-Q Skin Cancer Module using distribution-based methods. METHODS: A prospective cohort study at four hospitals in the United States, enrolled participants who underwent Mohs Micrographic Surgery (MMS) for facial skin cancer between April 2020 and April 2022. Participants completed the Satisfaction with Facial Appearance, Appearance-related Psychosocial Distress, Cancer Worry, and Appraisal of Scars scales at four time points: pre-operatively, 2-week, 6-month, and 1-year post-surgery. RESULTS: A total of 990 patients participated in the study, with completion rates of 98.4% for the pre-operative assessment, 70.8% at 2 weeks, 59.3% at 6 months, and 60.4% at 1 year. MID estimates, calculated using 0.2 standard deviation and 0.2 standardized response mean, were determined for the four scales. The mean MID estimates, based on a Rasch transformed score ranging from 0 to 100, were 5 for the Appraisal of Scars scale and 4 for the remaining three scales. CONCLUSION: This multicenter study provides valuable MID estimates for the FACE-Q Skin Cancer Module, specifically for the MMS patient population, enabling clinicians and researchers to better interpret scores, determine appropriate sample sizes, and apply the findings in clinical care.

Prevalence, antimicrobial resistance and genomic comparison of non-typhoidal salmonella isolated from pig farms with different levels of intensification in Yangon Region, Myanmar.

In Myanmar, where backyard, semi-intensive, and intensive pig (Sus scrofa domesticus) farming coexist, there is limited understanding of the zoonotic risks and antimicrobial resistance (AMR) associated with these farming practices. This study was conducted to investigate the prevalence, AMR and genomic features of Salmonella in pig farms in the Yangon region and the impact of farm intensification to provide evidence to support risk-based future management approaches. Twenty-three farms with different production scales were sampled for two periods with three sampling-visit each. Antimicrobial susceptibility tests and whole-genome sequencing were performed on the isolates. The prevalence of Salmonella was 44.5% in samples collected from backyard farms, followed by intensive (39.5%) and semi-intensive farms (19.5%). The prevalence of multi-drug resistant isolates from intensive farms (45/84, 53.6%) was higher than those from backyard (32/171, 18.7%) and semi-intensive farms (25/161, 15.5%). Among 28 different serovars identified, S. Weltevreden (40; 14.5%), S. Kentucky (38; 13.8%), S. Stanley (35, 12.7%), S. Typhimurium (22; 8.0%) and S. Brancaster (20; 7.3%) were the most prevalent serovars and accounted for 56.3% of the genome sequenced strains. The diversity of Salmonella serovars was highest in semi-intensive and backyard farms (21 and 19 different serovars, respectively). The high prevalence of globally emerging S. Kentucky ST198 was detected on backyard farms. The invasive-infection linked typhoid-toxin gene (cdtB) was found in the backyard farm isolated S. Typhimurium, relatively enriched in virulence and AMR genes, presented an important target for future surveillance. While intensification, in terms of semi-intensive versus backyard production, maybe a mitigator for zoonotic risk through a lower prevalence of Salmonella, intensive production appears to enhance AMR-associated risks. Therefore, it remains crucial to closely monitor the AMR and virulence potential of this pathogen at all scales of production. The results underscored the complex relationship between intensification of animal production and the prevalence, diversity and AMR of Salmonella from pig farms in Myanmar.

Emerging Monkeypox Virus Sublineage C.1 Causing Community Transmission, Vietnam, 2023.

We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.

A deep intronic splice-altering AIRE variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a life-threatening monogenic autoimmune disorder primarily caused by biallelic deleterious variants in the autoimmune regulator (AIRE) gene. We prospectively evaluated 104 patients with clinically diagnosed APECED syndrome and identified 17 patients (16%) from 14 kindreds lacking biallelic AIRE variants in exons or flanking intronic regions; 15 had Puerto Rican ancestry. Through whole-genome sequencing, we identified a deep intronic AIRE variant (c.1504-818 G>A) cosegregating with the disease in all 17 patients. We developed a culture system of AIRE-expressing primary patient monocyte-derived dendritic cells and demonstrated that c.1504-818 G>A creates a cryptic splice site and activates inclusion of a 109-base pair frame-shifting pseudoexon. We also found low-level AIRE expression in patient-derived lymphoblastoid cell lines (LCLs) and confirmed pseudoexon inclusion in independent extrathymic AIRE-expressing cell lines. Through protein modeling and transcriptomic analyses of AIRE-transfected human embryonic kidney 293 and thymic epithelial cell 4D6 cells, we showed that this variant alters the carboxyl terminus of the AIRE protein, abrogating its function. Last, we developed an antisense oligonucleotide (ASO) that reversed pseudoexon inclusion and restored the normal AIRE transcript sequence in LCLs. Thus, our findings revealed c.1504-818 G>A as a founder APECED-causing AIRE variant in the Puerto Rican population and uncovered pseudoexon inclusion as an ASO-reversible genetic mechanism underlying APECED.

Isolation and Characterization Identification of Edophytic Nitrogen-Fixing Bacteria from Peanut Nodules.

This work was carried out to isolate and perform molecular identification and selection of endophytic nitrogen-fixing bacteria (ENFB) to be utilized as biofertilizer. In this research, nodulous samples of peanuts were collected from inside dyke areas, namely, Phuoc Hung of An Phu, An Giang, Vietnam. Ten colonies were isolated from nutrient agar plates containing YMA's medium. All isolates were rod shaped, Gram negative, and no spore creation. Biochemical tests indicated that they were obligate aerobes, catalase, oxidase, urea hydrolysis, well motile ability, and no nitrate reduction. The salt tolerance observed that most survived at 0.5% and 2% salinity (except Enterobacter cloacae subsp. dissolvens strain LMG 2683), while at 4%, only 3 isolates (Bacillus aryabhattai strain CM44, Enterobacter asburiae strain IIWM-JS-07L, and Bacillus songklensis strain KCa6) and at 5% only, 2 isolates survived, namely, Enterobacter asburiae strain IIWM-JS-07L and Bacillus songklensis strain KCa6. The result showed that most of ten ENFB strains could adapt to the range of 25°C and 45°C (except Enterobacter cloacae subsp. dissolvens strain LMG 2683 and Enterobacter mori strain cjy13 at 25°C). Out of ten isolates, three were finally selected for the next studies, which potentially have N-fixing ability and are utilized as biofertilizer in agricultural cultivation.

Immunogenicity of Abdala COVID-19 vaccine in Vietnamese people after primary and booster vaccinations: A prospective observational study in Vietnam.

OBJECTIVES: We studied the immunogenicity after primary and booster vaccinations of the Abdala COVID-19 vaccine, a receptor-binding domain protein subunit vaccine, in Vietnamese people by determining the level of neutralization and cross-neutralization activities against the ancestral SARS-CoV-2 and its variants and SARS-CoV-1. METHODS: We performed a prospective observational study, enrolling adults aged 19-59 years in Dong Thap province, southern Vietnam, and collected blood samples from baseline until 4 weeks after the booster dose. We measured anti-nucleocapsid, anti-spike, and neutralizing antibodies against SARS-CoV-2 and assessed the cross-neutralization against 14 SARS-CoV-2 variants and SARS-CoV-1. Complementary antibody data came from Vietnamese health care workers fully vaccinated with ChAdOx1-S. RESULTS: After primary vaccination, anti-spike antibody and neutralizing antibodies were detectable in 98.4% and 87% of 251 study participants, respectively, with neutralizing antibody titers similar to that induced by ChAdOx1-S vaccine. Antibody responses after a homologous (Abdala COVID-19) or heterologous (messenger RNA BNT162b2) booster could neutralize 14 SARS-CoV-2 variants (including Omicron) and SARS-CoV-1. CONCLUSIONS: Abdala COVID-19 vaccine is immunogenic in Vietnamese people. Enhanced antibody response after a booster dose could cross-neutralize 14 SARS-CoV-2 variants and SARS-CoV-1. Our results have added to the growing body of knowledge about the contribution of protein subunit vaccine platforms to pandemic control.

IL-2-armored peptide-major histocompatibility class I bispecific antibodies redirect antiviral effector memory CD8+ T cells to induce potent anti-cancer cytotoxic activity with limited cytokine release.

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

Protein Adequacy, Plant Protein Proportion, and Main Plant Protein Sources Consumed Across Vegan, Vegetarian, Pescovegetarian, and Semivegetarian Diets: A Systematic Review.

BACKGROUND: There are several types of plant-based diets, with unknown differences across diets on total/plant protein intake and variety of plant protein sources consumed. OBJECTIVES: This systematic review aimed to compare total protein intake, proportion of plant proteins, and main plant protein sources consumed across 4 primarily plant-based diets: vegan, vegetarian, pescovegetarian, and semivegetarian. METHODS: We included observational studies reporting on protein intake and/or protein sources in generally healthy adults that were published between 2002 and 2023. We determined the following: 1) % energy from total and plant protein; 2) the proportion of plant protein relative to total protein intake; and 3) main plant protein sources (median percentage contribution of each source to total plant protein intake; interquartile range) consumed across the 4 diets. The plant protein sources were broadly classified into the following United States Department of Agriculture food groups: grains; nuts and seeds; soy products; and beans, peas, and lentils. RESULTS: We included 13 studies reporting on protein intake/sources that were conducted in the United States, Europe, and South Korea. Of these, 7 reported on vegan, 11 on vegetarian, 7 on pescovegetarian, and 7 on semivegetarian diets with total protein intake ranging from 10% to 17.4%. Vegan diets had the highest plant protein proportion (range: 77%-98%) and semivegetarian diets the lowest (range: 37%-83%). Plant protein source contribution was the highest from grains (range: 60%-78%). Nuts and seeds were the most consumed in vegetarian diets (7.9%; 2.9%-10.3%) and least in semivegetarian diets (3.7%; 2%-14.8%). Soy products and beans, peas, and lentils were most consumed in vegan diets (17.3%; 16.3%-19.9, and 19.6%; 14.6%-21.3, respectively) and least in semivegetarian (3.7%; 1.3%-13.9%, and 8.5%; 5.2%-10.2%) diets. CONCLUSIONS: Vegan diets has the highest plant protein proportion and a variety of plant protein sources, while semivegetarian diets has the lowest plant protein proportion and mainly relied on grains as a plant protein source.

Cytopathic Effect Detection and Clonal Selection using Deep Learning.

PURPOSE: In biotechnology, microscopic cell imaging is often used to identify and analyze cell morphology and cell state for a variety of applications. For example, microscopy can be used to detect the presence of cytopathic effects (CPE) in cell culture samples to determine virus contamination. Another application of microscopy is to verify clonality during cell line development. Conventionally, inspection of these microscopy images is performed manually by human analysts. This is both tedious and time consuming. In this paper, we propose using supervised deep learning algorithms to automate the cell detection processes mentioned above. METHODS: The proposed algorithms utilize image processing techniques and convolutional neural networks (CNN) to detect the presence of CPE and to verify the clonality in cell line development. RESULTS: We train and test the algorithms on image data which have been collected and labeled by domain experts. Our experiments have shown promising results in terms of both accuracy and speed. CONCLUSION: Deep learning algorithms achieve high accuracy (more than 95%) on both CPE detection and clonal selection applications, resulting in a highly efficient and cost-effective automation process.

Real-World Noninferiority Assessment of Two Filgrastim Biosimilars in Patients Receiving Myelosuppressive Chemotherapy.

PURPOSE: Although multiple filgrastim biosimilars are now available in the United States, no studies comparing clinical outcomes between products have been reported. This analysis evaluated real-world outcomes of filgrastim-aafi and filgrastim-sndz in patients with select solid tumors receiving myelosuppressive chemotherapy to compare the two filgrastim biosimilars. METHODS: This was an observational, noninferiority, cohort study of patients from three integrated health care systems who received myelosuppressive chemotherapy and were prophylactically initiated on filgrastim-sndz between January and November 2021 or filgrastim-aafi between June and November 2022. Patients were followed from filgrastim biosimilar initiation until the start of their next chemotherapy cycle. The primary outcome of severe neutropenia was analyzed using a binary noninferiority test with a 5% upper margin. Secondary outcomes included the incidence of emergency department or hospital encounters due to febrile neutropenia and systemic antibiotic/antifungal medication use. If noninferiority was met, adjusted logistic regression modeling was conducted. RESULTS: A total of 2,730 patients who initiated filgrastim-aafi (n = 880) or filgrastim-sndz (n = 1,850) during the study period were included. The overall mean age was 55 years, 87.4% were female, 42.3% were White, and 76.6% had breast cancer. Severe neutropenia occurred in 1.8% and 1.7% of patients initiated on filgrastim-aafi and filgrastim-sndz, respectively (P < .01 for noninferiority). The adjusted odds ratio for severe neutropenia with filgrastim-aafi compared with filgrastim-sndz was 0.91 (95% CI, 0.49 to 1.68; P = .76). Noninferiority was met for all secondary outcomes (P < .01), and there were no adjusted statistically significant differences between the groups (all P > .05). CONCLUSION: Among patients with select solid tumors receiving myelosuppressive chemotherapy, severe neutropenia outcomes were comparable between filgrastim-aafi and filgrastim-sndz biosimilars. Findings from this study may support utilization of different filgrastim biosimilars in clinical practice.

Impact of pharmacist managed oral epidermal growth factor receptor inhibitors.

BACKGROUND: Pharmacists are an integral part of medication management, with the positive impact of their clinical services in patient outcomes previously studied and reported in literature. The roles and responsibilities of pharmacists continue to expand, including optimizing patient medication and health outcomes related to complex oral anticancer drugs. OBJECTIVE: To evaluate the impact of a pharmacist-managed oral chemotherapy clinic in patients with non-small cell lung cancer (NSCLC) taking oral epidermal growth factor receptor inhibitor (EGFRi) regimens within an integrated healthcare delivery system. METHODS: This was an observational cohort study using data from Kaiser Permanente Northern and Southern California regions on adult patients who received oncology pharmacist-managed care compared to patients with usual care. Patients were newly initiated with EGFRi therapy to treat NSCLC between 2017 and 2019. The follow-up period was defined as the time from index date (first sold date of EGFRi) to December 2020 or end of membership or death, whichever occurred first. Primary outcome measures included adherence to EGFRi, frequency of imaging during drug exposure, and presence of imaging prior to treatment change. Outcomes were analyzed with Chi-square test for categorical variables, and Student's t-test or Wilcoxon rank-sum test for continuous variables. RESULTS: There were 613 patients in the pharmacist-managed group and 714 patients in the usual care group. Overall, the mean age was 68.2 ± 11.3 years, and 65.1% were female. In the pharmacist-managed group, there was a significantly higher mean proportion of days covered (PDC) during the first three months of therapy (0.86 ± 0.24 vs 0.82 ± 0.36, p = 0.01) and a higher percentage of patients who were adherent to EGFRi therapy (with PDC ≥0.80) during the drug exposure period (95.8% vs 92.4%, p = 0.01). The rate of computed tomography (CT) and magnetic resonance imaging (MRI) during drug exposure was higher in the pharmacist-managed group compared to the usual care group (31.8% vs 20.7%, p < 0.01) with a higher number of mean scans completed per patient (1.15 ± 2.42 vs 0.62 ± 1.63, p < 0.01) and per patient-year (2.60 ± 7.27 vs 1.58 ± 5.95, p < 0.01). Overall, 66.2% of patients had a treatment change, with a higher percentage of patients in the pharmacist-managed group who completed a CT or MRI scan prior to treatment change (36.3% vs 26.3%, p < 0.01). Additionally, the median time between the scan and treatment change was shorter for patients with pharmacist-managed care (1.8 vs 4 months, p = 0.04). CONCLUSION: Clinical pharmacy services contributed to improved adherence, higher rates of imaging, and shorter time between imaging and treatment changes in NSCLC patients who were taking EGFRi regimens.

The Importance and Challenges of Implementing and Maintaining Biorepositories for High-Consequence Veterinary and One Health Pathogens in South-East Asia.

Introduction: Emerging infectious diseases pose a threat to public health and the economy, especially in developing countries. Southeast Asian veterinary laboratories handle numerous high-risk pathogens, making pathogen accountability crucial for safe handling and storage. Methods: Thirteen veterinary laboratories in Cambodia (n = 1), Lao People's Democratic Republic (n = 1), and Thailand (n = 11) participated in a study conducted between 2019 and 2020. Data were collected using a questionnaire, group discussions, and interviews. Conclusion: Significant gaps in biosecurity and biorepository management were recognized and discussed in the context of regional biosafety and biosecurity. Laboratories could use the findings and recommendations of the study to develop or improve their pathogen inventory and biosecurity systems. Governments play a significant role in setting standards and regulations and providing necessary support for laboratories to maintain inventory controls sustainably and have a very important role to play in ensuring biosafety and biosecurity compliance.

Age-time-specific transmission of hand-foot-and-mouth disease enterovirus serotypes in Vietnam: A catalytic model with maternal immunity.

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013-2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

Emerging Enterovirus A71 Subgenogroup B5 Causing Severe Hand, Foot, and Mouth Disease, Vietnam, 2023.

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

NAD metabolism: Role in senescence regulation and aging.

The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field.

Characterization of Immune Cell Populations of Cutaneous Neurofibromas in Neurofibromatosis 1.

Cutaneous neurofibromas (cNFs) are characteristic of neurofibromatosis 1 (NF1), yet their immune microenvironment is incompletely known. A total of 61 cNFs from 10 patients with NF1 were immunolabeled for different types of T cells and macrophages, and the cell densities were correlated with clinical characteristics. Eight cNFs and their overlying skin were analyzed for T cell receptor CDR domain sequences, and mass spectrometry of 15 cNFs and the overlying skin was performed to study immune-related processes. Intratumoral T cells were detected in all cNFs. Tumors from individuals younger than the median age of the study participants (33 years), growing tumors, and tumors smaller than the data set median showed increased T cell density. Most samples displayed intratumoral or peritumoral aggregations of CD3-positive cells. T cell receptor sequencing demonstrated that the skin and cNFs host distinct T cell populations, whereas no dominant cNF-specific T cell clones were detected. Unique T cell clones were fewer in cNFs than in skin, and mass spectrometry suggested lower expression of proteins related to T cell-mediated immunity in cNFs than in skin. CD163-positive cells, suggestive of M2 macrophages, were abundant in cNFs. Human cNFs have substantial T cell and macrophage populations that may be tumor-specific.

Elevated Liver Enzymes With Positive Hepatitis B Serology After Intravenous Immunoglobulin Treatment of Guillain-Barré Syndrome.

Intravenous immunoglobulin (IVIG) is used to treat multiple conditions, one of which is Guillain-Barré syndrome. Despite its multiple benefits, IVIG can cause a wide variety of side effects, most of which resolve with supportive care. We present a case in which a patient with new-onset Guillain-Barré syndrome was treated with IVIG and subsequently developed an acute elevation in liver enzymes with positive hepatitis B serology.