Plant-based zinc nanoflowers assisted molecularly imprinted polymer for the design of an electrochemical sensor for selective determination of abrocitinib.

The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1 inhibitor abrocitinib (ABR). ABR is approved by the U.S. Food and Drug Administration (FDA) for the treatment of atopic dermatitis. The molecularly imprinted polymer (MIP)-based sensor was designed to incorporate zinc nanoflower (ZnNFs)-graphene oxide (GO) conjugate (ZnNFs@GO), synthesized from the root methanolic extract (RME) of the species Alkanna cappadocica Boiss. et Bal. to improve the porosity and effective surface area of the glassy carbon electrode (GCE). Furthermore, the MIP structure was prepared using ABR as a template molecule, 4-aminobenzoic acid (4-ABA) as a functional monomer, and other additional components. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the surface and structure of the synthesized nanomaterial and MIP-based surface. Among the electrochemical methods, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were preferred for detailed electrochemical characterization, and differential pulse voltammetry (DPV) was preferred for all other electrochemical measurements using 5.0 mM [Fe(CN)6]3-/4- solution as the redox probe. The MIP-based sensor, which was the result of a detailed optimization phase, gave a linear response in the 1.0 × 10-13 - 1.0 × 10-12 M range in standard solution and serum sample. The obtained limit of detection (LOD) and limit of quantification (LOQ) values and recovery studies demonstrated the sensitivity, accuracy, and applicability of the sensor. Selectivity, the most important feature of the MIP-based sensor, was verified by imprinting factor calculations using ibrutinib, ruxolitinib, tofacitinib, zonisamide, and acetazolamide.

Long-Term Experience with Anaphylaxis and Desensitization to Alglucosidase Alfa in Pompe Disease.

BACKGROUND AND OBJECTIVE: Pompe disease (PD) is an inherited lysosomal storage disease that progresses with glycogen accumulation in many tissues, due to the deficiency of the acid-alpha glucosidase enzyme. Recombinant alglucosidase alfa (rhGAA) is the only disease-specific treatment option, in the form of enzyme replacement therapy (ERT). Anaphylaxis can develop with rhGAA. There is no study evaluating anaphylaxis and its management in PD in the long term. We aimed to evaluate the development of anaphylaxis and rapid drug desensitization (RDD) with rhGAA in children with PD. MATERIALS AND METHODS: All children diagnosed and followed up in our institution with PD over 12 years between January 2009 and September 2021 were evaluated for development of anaphylaxis and RDD with rhGAA from medical records. RESULTS: Fourteen patients, 64% of whom were female and diagnosed with PD (1 juvenile, 13 infantile types) during the study period included in the study. The median age at diagnosis was 3.2 months (1-40 months). The median follow-up time of the patients was 20 months (1-129 months). Thirteen patients were given rhGAA, one died before ERT. Four (30.8%) patients developed moderate to severe anaphylaxis, and RDD was applied with rhGAA. A total of 390 RDDs have been performed so far without any serious breakthrough reactions during all RDDs. CONCLUSIONS: Anaphylaxis with rhGAA is not rare and RDD with rhGAA is safe and effective in the long term.

Human NK Cell Cytoskeletal Dynamics and Cytotoxicity Are Regulated by LIM Kinase.

NK cells provide immune surveillance and host protection against viruses and tumors through their cytotoxic effector function. Cytoskeletal rearrangement is necessary for NK cell lytic granule trafficking and immune synapse formation to trigger apoptosis of targeted cells. LIM kinase (LIMK) regulates F-actin remodeling by phosphorylating cofilin to inhibit actin severing and depolymerization. In this study, in human NK cells, the glucocorticoid dexamethasone downregulated LIMK expression, F-actin accumulation at the immune synapse, lytic granule trafficking, and cytotoxicity. In contrast, the specialized proresolving mediator lipoxin A4 promoted NK cell LIMK expression, lytic granule polarization to the immune synapse and cytotoxicity. Using a LIMK inhibitor, we show that LIMK activity is necessary for NK cell cytotoxicity, including lipoxin A4's proresolving actions. Together, our findings identify LIMK as an important control mechanism for NK cell cytoskeletal rearrangement that is differentially regulated by glucocorticoids and specialized proresolving mediators to influence NK cell cytotoxicity.

Spotlight on microRNAs in allergy and asthma.

In past 10 years, microRNAs (miRNAs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases and their potential as biomarkers in liquid biopsies. They act as master post-transcriptional regulators that control most cellular processes. As one miRNA can target several mRNAs, often within the same pathway, dysregulated expression of miRNAs may alter particular cellular responses and contribute, or lead, to the development of various diseases. In this review, we give an overview of the current research on miRNAs in allergic diseases, including atopic dermatitis, allergic rhinitis, and asthma. Specifically, we discuss how individual miRNAs function in the regulation of immune responses in epithelial cells and specialized immune cells in response to different environmental factors and respiratory viruses. In addition, we review insights obtained from experiments with murine models of allergic airway and skin inflammation and offer an overview of studies focusing on miRNA discovery using profiling techniques and bioinformatic modeling of the network effect of multiple miRNAs. In conclusion, we highlight the importance of research into miRNA function in allergy and asthma to improve our knowledge of the molecular mechanisms involved in the pathogenesis of this heterogeneous group of diseases.

Foreign Body Reaction Due to a Forgotten Rubber Band on the Neck of a Toddler Girl.

ABSTRACT: In the presence of an unhealed granulation tissue-like wound, a possibility of abuse and neglect along with a foreign body should come to mind. However, it may be difficult to recognize a foreign body in patients with atypical clinical presentations. We demonstrated delayed diagnosis of a rubber band embedded into subcutaneous tissue in a 2½-year-old girl who presented with a circumferential scar with 2 granulation tissue-like wounds on her neck due to a foreign body reaction developed over years. With this rare case presentation, we remind the possibility of abuse/neglect along with foreign bodies in neck lesions of children.

Sedative Effects of Latexes Obtained from Some Lactuca L. Species Growing in Turkey.

Lactuca L. species belong to the Asteraceae family and these plants are traditionally used for therapeutic purposes around the world. The dried milky latex of L. serriola is known as "lettuce oil" and is used as a sedative in Turkey. This study aimed to evaluate the sedative effects and analyze the chemical compositions of latexes obtained from some Lactuca species growing in Turkey. The sedative effects were evaluated through various behavioral tests on mice. For this purpose, latexes were obtained from L. glareosa Boiss., L. viminea (L.) J. Presl and C. P, L. mulgedioides (Vis and Pancic) Boiss. and Kotschy ex. Boiss., L. saligna L., and L. serriola L. The latex from L. saligna showed the highest sedative effects, whilst L. serriola and L. viminea latexes also displayed significant sedative effects compared to the control group at a dose of 100 mg/kg. However, the latexes from L. glareosa and L. mulqedioides did not exhibit any sedative effects on mice. Characteristic sesquiterpene lactones (lactucin, lactucopicrin, 11,13ß-dihydrolactucin, and 11,13ß-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.

Breast and cervical cancer screening for women with physical disabilities: A qualitative study of experiences and barriers.

AIM: To determine the experiences of women with physical disabilities regarding the barriers to their participation in breast and cervical cancer screening. DESIGN: Qualitative descriptive study. METHOD: Sixteen women who use wheelchairs were recruited. Data were collected via semi-structured face-to-face interviews between January - March 2017. Interviews were transcribed and data were analysed thematically. RESULTS: Three main themes were uncovered: (a) Personal factors; such as lack of knowledge, fear and embarrassment, feeling anxious about the examination process and dependency on others; (b) Environmental and structural factors; and (c) expectations and suggestions of women with disabilities to enable their participation in screening. CONCLUSION: The participation rate of women with physical disabilities in screening is low. The participation of women with disabilities in breast and cervical cancer screening may increase if physical barriers to accessing healthcare services are removed, appropriate and less time-consuming examination conditions are met, and healthcare personnel are informed about the needs of persons with disabilities. IMPACT: Knowing the barriers for women with physical disabilities to participate in cancer screening can help health professionals develop new procedures to increase their participation to cancer screening. Women with physical disabilities encountered various barriers such as; lack of knowledge, fear and embarrassment, feeling anxious about the examination process and dependency on others, access to the healthcare services, environmental, physical limitations, and inadequate knowledge of healthcare professional about their disability. This study will guide healthcare professionals in developing strategies to increase the participation of women with physical disabilities in screening.

Reliability and validity of a Turkish version of the Sexual Quality of Life - Male questionnaire: a methodological study.

Background The aim of this methodological study was to assess the reliability and validity of the Sexual Quality of Life - Male (SQoL-M) questionnaire translated and adapted to measure the sexual quality of life of men in Turkey and Northern Cyprus. METHODS: To assess the reliability and validity of the Turkish version of the SQoL-M questionnaire, in January and February 2017 we formed a sample of 128 men from Ankara, Turkey, and Girne, Northern Cyprus, to complete the questionnaire. Two weeks later, 65 of these men completed the questionnaire during a retest. Factor analysis was conducted to evaluate the questionnaire's factor structure, internal consistency and test-retest reliability analyses were used to assess reliability and Pearson's correlation coefficient was used to measure criterion-related validity. RESULTS: Cronbach's α for the Turkish version of the SQoL-M questionnaire was 0.91, with corrected item-total score correlations ranging from 0.432 to 0.819. The test-retest correlation, calculated to compare scale scores of both groups of participants, was 0.83 (P<0.001). We also observed a statistically significant relationship between the Turkish version of the SQoL-M questionnaire and the Arizona Sexual Experience scale. CONCLUSIONS: The Turkish version of the SQoL-M questionnaire is a valid, reliable instrument for evaluating the sexual quality of life of men in Turkey and Northern Cyprus.

Axillary and Tympanic Temperature Measurement in Children and Normal Values for Ages.

AIM: The aim of the study was define the normal values of tympanic and axillary body temperature in healthy children. METHODS: This observational cross-sectional study was performed in healthy children aged 0 to 17 years who visited the ambulatory general pediatric of Istanbul Medical Faculty. RESULTS: Of 1364 children, 651 (47.7%) were girls and 713 were boys, the mean (SD, range) age was 72.5 (53.6, 1-204) months. The mean (SD) axillary body temperature was 36.04°C (0.46°C; minimum, 35.0°C; maximum, 37.6°C). The 95th and 99th percentiles were 36.8°C and 37.0°C, respectively. The mean (SD) tympanic body temperature was 36.91°C (0.46°C; minimum, 35.15°C; maximum, 37.9°C). The 95th and 99th percentiles were 37.6°C and 37.8°C, respectively. There were statistically significant differences between sexes for only tympanic body temperatures. Both axillary and tympanic body temperatures were statistically higher in 0 to 2 months compared with other age groups. For this age group, the 99th percentile was 37.5°C for axillary and 37.85°C for tympanic temperature. CONCLUSIONS: Axillary and tympanic body temperatures should be considered as fever when they are more than 37.0°C and 37.8°C, respectively. For 0 to 2 months, fever is 37.5°C and 37.85°C in axillary and tympanic temperatures, respectively.

Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to epigenetic modifications in mice lacking the post-synaptic scaffolding protein SHANK1: Implications for autism spectrum disorder.

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by persistent deficits in social communication/interaction, together with restricted/repetitive patterns of behavior. ASD is among the most heritable neuropsychiatric conditions, and while available evidence points to a complex set of genetic factors, the SHANK gene family has emerged as one of the most promising candidates. Here, we assessed ASD-related phenotypes with particular emphasis on social behavior and cognition in Shank1 mouse mutants in comparison to heterozygous and wildtype littermate controls across development in both sexes. While social approach behavior was evident in all experimental conditions and social recognition was only mildly affected by genotype, Shank1-/- null mutant mice were severely impaired in object recognition memory. This effect was particularly prominent in juveniles, not due to impairments in object discrimination, and replicated in independent mouse cohorts. At the neurobiological level, object recognition deficits were paralleled by increased brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of Shank1-/- mice; yet BDNF levels did not differ under baseline conditions. We therefore investigated changes in the epigenetic regulation of hippocampal BDNF expression and detected an enrichment of histone H3 acetylation at the Bdnf promoter1 in Shank1-/- mice, consistent with increased learning-associated BDNF. Together, our findings indicate that Shank1 deletions lead to an aberrant cognitive phenotype characterized by severe impairments in object recognition memory and increased hippocampal BDNF levels, possibly due to epigenetic modifications. This result supports the link between ASD and intellectual disability, and suggests epigenetic regulation as a potential therapeutic target.

A tertiary care center's experience with febrile seizures: evaluation of 632 cases.

BACKGROUND: The aim of this paper was to evaluate demographic and prognostic features of febrile seizures (FSs) in a tertiary center in Turkey. METHODS: A retrospective study of 632 children with FS was conducted from January 1995 to January 2002 in the pediatric neurology and general pediatrics departments of Istanbul University, Istanbul Medical School. Patients data was collected and eligible patients were included in the study. RESULTS: There were 386 male (61.1%) and 246 female (38.9%) patients, with a male-to-female ratio of 1.57. Twenty six (4.1%) patients had prenatal, 104 (16.5%) patients had perinatal-neonatal problems. Age at first seizure was 3-72 months with an average of 20.1 months. While 193 patients (30%) were admitted with two seizures, 246 (39%) were admitted with three or more. Out of 632 patients, 501 (79.2%) had recurrences. In an average of 5.8 years (4-8.8), 30 out of 632 patients (4.7%) were diagnosed with epilepsy. First degree relative with FS, age at first FS less than 18 months, height of peak temperature (<38.5 °C), less than 1 or 3 hours between onset of fever and seizure, complex first seizure, complex FS were all related to febrile seizure recurrence in a statistically significant way. Some risk factors for subsequent epilepsy development included complex FS and less than one hour of fever before FS. No patient with FS had died. CONCLUSIONS: Complex FS and less than 1 hour of fever before FS are common risk factors for both epilepsy and FS recurrence.

Amphiphilic biodegradable PEG-PCL-PEI triblock copolymers for FRET-capable in vitro and in vivo delivery of siRNA and quantum dots.

Amphiphilic triblock copolymers represent a versatile delivery platform capable of co-delivery of nucleic acids, drugs, and/or dyes. Multifunctional cationic triblock copolymers based on poly(ethylene glycol), poly-ε-caprolactone, and polyethylene imine, designed for the delivery of siRNA, were evaluated in vitro and in vivo. Moreover, a nucleic acid-unpacking-sensitive imaging technique based on quantum dot-mediated fluorescence resonance energy transfer (QD-FRET) was established. Cell uptake in vitro was measured by flow cytometry, whereas transfection efficiencies of nanocarriers with different hydrophilic block lengths were determined in vitro and in vivo by quantitative real-time PCR. Furthermore, after the proof of concept was demonstrated by fluorescence spectroscopy/microscopy, a prototype FRET pair was established by co-loading QDs and fluorescently labeled siRNA. The hydrophobic copolymer mediated a 5-fold higher cellular uptake and good knockdown efficiency (61 ± 5% in vitro, 55 ± 18% in vivo) compared to its hydrophilic counterpart (13 ± 6% in vitro, 30 ± 17% in vivo), which exhibited poor performance. FRET was demonstrated by UV-induced emission of the acceptor dye. Upon complex dissociation, which was simulated by the addition of heparin, a dose-dependent decrease in FRET efficiency was observed. We believe that in vitro/in vivo correlation of the structure and function of polymeric nanocarriers as well as sensitive imaging functionality for mechanistic investigations are prerequisites for a more rational design of amphiphilic gene carriers.

Role of vitamin D in children with hepatosteatosis.

BACKGROUND: The increasing incidence of obesity in children is a significant risk factor for nonalcoholic fatty liver disease and obesity-associated morbidity. Vitamin D has a major role in bone mineral metabolism and has antimicrobial, antioxidant properties. In this study we aimed to investigate the role of vitamin D in children with obesity with hepatosteatosis. METHODS: A total of 101 children with obesity were included in this study. Hepatosteatosis was diagnosed and graded using ultrasonography. Serum levels of 25-hydroxyvitamin D (25-(OH) vitamin D), calcium, phosphate, alkaline phosphatase, and parathormone were tested. Two-sided t test and Pearson χ tests were used for the relation between vitamin D and hepatosteatosis. RESULTS: In our study group, 45.5% were girls (n=46) and the mean age was 11.5 ± 2.8 years (range 3-17 years). Hepatosteatosis was identified in 58 children (57.4%). The diagnosis of grade 1 and grade 2 hepatosteatosis was made in 41 (40.6%) and 17 (16.8%) children, respectively. Median serum 25-(OH) vitamin D levels in children without hepatosteatosis was 16.4 ng/mL (interquartile range 12.4-24.8 ng/mL), whereas children with grade 1 and grade 2 hepatosteatosis had 25-(OH) vitamin D levels of 14.2 ng/mL (interquartile range 9.5-21.2 ng/mL) and 11.5 ng/mL (interquartile range 7.5-16.7 ng/mL), respectively (P=0.005). There was a positive correlation between insulin resistance and the grade of hepatosteatosis (P=0.03). CONCLUSIONS: Serum vitamin D levels in children with obesity with hepatosteatosis are significantly lower than vitamin D levels in children with obesity without hepatosteatosis. In this observational study we only refer to the association of vitamin D deficiency/insufficiency with hepatosteatosis.

Design of a molecularly imprinted polymer sensor modified with saffron-based copper nanoflowers for highly selective and sensitive determination of bortezomib.

This work represents the first successful application of a molecularly imprinted polymer (MIP)-based electrochemical sensor for the sensitive and selective determination of the first developed proteasome inhibitor, bortezomib (BOR). BOR is used for the treatment of multiple myeloma, gastrointestinal stromal tumors, and mantle cell lymphoma. It shows its desired effect through the boronate group and can be administered intravenously or subcutaneously. The MIP-based electrochemical sensor design includes the integration of green-synthesized saffron-based copper nanoflowers (CuNFs) from Crocus sativus L. to increase the active surface area and porosity of the glassy carbon electrode (GCE) surface. 2-Acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was selected as the functional monomer along with other MIP components. Detailed characterizations of the developed CuNFs/AMPS/MIP-GCE sensor and CuNFs were performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDX), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The indirect measurement approach using 5.0 mM [Fe(CN)6]3-/4- solution was used to determine BOR in the linear range of 2.5 × 10-13 M - 2.5 × 10-12 M (0.25-2.5 pM). The LOD and LOQ values of the sensor obtained at the fM level (29 fM and 96.7 fM), which has a linear response in the commercial human serum sample in the same concentration range, emphasize its sensitivity (1.89 × 1013 and 2.14 × 1013 µA/M for standard solution and serum). The repeatability and reproducibility of the sensor were between 0.87 % and 2.17 %, showing its reliability. The successful performance of the sensor in the presence of metabolites belonging to BOR demonstrates its unique selectivity. The selectivity was demonstrated via relative imprinting factor (IF') values (higher than 3.5) against BOR's metabolites. The stability of the CuNFs/AMPS/MIP-GCE sensor was found to be 5 days.

New perspectives for the treatment and follow-up of glycogen storage disease type V: DL-3-hydroxybutyric acid with modified Atkins diet and quadriceps femoris shear wave elastography.

OBJECTIVES: Glycogen storage disease type V is caused by the mutations in muscle glycogen phosphorylase gene. This is the first report which DL-3-hydroxybutyric acid was used in combination with modified Atkins diet for the treatment of a patient with glycogen storage disease type V and quadriceps femoris shear wave elastography was performed to evaluate the treatment efficacy. CASE PRESENTATION: A 13-year-old girl was referred with fatigue and muscle cramps with exercise and there were no pathological findings in physical examination. Creatine kinase levels with 442 U/L. No phosphorylase enzyme activity was detected in muscle biopsy, a homozygous c.1A>G (p.M1V) pathogenic mutation was found in PYGM gene. She was started on DL-3-hydroxybutyric acid and modified Atkins diet at age 16. Her walking and stair climbing capacity increased, the need for rest during exercise decreased. The stiffness of the quadriceps femoris exhibited a reduction. CONCLUSIONS: DL-3-hydroxybutyric acid and modified Atkins diet may provide an alternative fuel and shear wave elastography may be useful in demonstrating treatment efficacy. More clinical and pre-clinical studies are obviously needed to reach more definite conclusions.

A 37-kb Deletion in Region 16p13.3 in an Infant with Osteopetrosis and Congenital Diarrhea Including the CLCN7 and PERCC1 Genes.

Introduction: Congenital diarrhea presents a diagnostic challenge in cases where standard assessments are inconclusive. Case Presentation: We report a female infant with thrombocytopenia, increased bone density, and pale optic disc symptoms, suggestive of osteopetrosis. However, she also exhibited noninfectious, blood- and mucus-free diarrhea, not accounted for by osteopetrosis. Genetic testing, including clinical exome sequencing and chromosomal microarray analysis, revealed a homozygous 39-kb deletion on chromosome 16p13.3. This deletion spanned the CLCN7 gene associated with osteopetrosis and the PERCC1 gene implicated in congenital diarrhea. Conclusion: This case illustrates the importance of considering 16p13.3 deletions when confronted with the dual presentation of congenital diarrhea and osteopetrosis, expanding the diagnostic considerations for similar clinical presentations.

Endocrinological and metabolic profile of Gaucher disease patients treated with enzyme replacement therapy.

OBJECTIVES: Gaucher disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy. It has been hypothesized that this proinflammatory state of GD leads cytokines and chemokines release. As a result of inflammatory process, the cellular dysfunction caused by disruption of cellular signaling, organelle dysfunction, or autoimmune antibodies may affect endocrine profile of GD patients such as hormone levels, lipid profile, and bone mineral density status. METHODS: A total of 13 patients confirmed to have GD, 12 non-neuronopathic type and one subacute neuronopathic type, were enrolled in our study. RESULTS: The median treatment duration in the enzyme therapy was 13.33 years (9-26 years). At least one endocrinological abnormality was detected in blood tests of nine patients. Hyperinsulinism was the most common finding although fasting blood glucose levels HgbA1c levels were normal in all patients. Two patients had osteopenia, and osteoporosis was detected in two patients. Low HDL levels were detected in six patients, but HDL levels below 23 mg/dL associated with disease severity have been detected in two patients who have not receiving enzyme replacement therapy. None of patients had thyroidal dysfunction. CONCLUSIONS: This study had revealed endocrinological abnormalities in GD patients that have not led any severe morbidity in our patients. However, thyroid hormone abnormalities, insulin resistance, or lipid profile abnormalities may cause unpredictable comorbidities. Endocrinological assessment in GD patients in routine follow-up may prevent possible clinical manifestation in long term as well as can define efficacy of ERT on endocrine abnormalities.

A very rare presentation of mitochondrial elongation factor Tu deficiency-TUFM mutation and literature review.

OBJECTIVES: The mitochondrial elongation factor Tu (EF-Tu), encoded by the TUFM gene, is a GTPase, which is part of the mitochondrial protein translation mechanism. If it is activated, it delivers the aminoacyl-tRNAs to the mitochondrial ribosome. Here, a patient was described with a homozygous missense variant in the TUFM [c.1016G>A (p.Arg339Gln)] gene. To date, only six patients have been reported with bi-allelic pathogenic variants in TUFM, leading to combined oxidative phosphorylation deficiency 4 (COXPD4) characterized by severe early-onset lactic acidosis, encephalopathy, and cardiomyopathy. CASE PRESENTATION: The patient presented here had the phenotypic features of TUFM-related disease, lactic acidosis, hypotonia, liver dysfunction, optic atrophy, and mild encephalopathy. CONCLUSIONS: We aimed to expand the clinical spectrum of pathogenic variants of TUFM.

Science, Medicine, and Cytology: an educational program of the Diversity, Equity, and Inclusion Committee of the American Society of Cytopathology.

INTRODUCTION: As our field of pathology continues to grow, our trainee numbers are on the decline. To combat this trend, the ASC Diversity, Equity, and Inclusion Committee established the Science, Medicine, and Cytology SumMer Certificate program to improve exposure to pathology/cytopathology with a focus on diversity, equity, and inclusion. Herein, we report our findings of the first 2 years of the program. MATERIALS AND METHODS: An online course was developed targeting students who are underrepresented in medicine at the high school and college level. It consisted of several didactic sessions, presenting the common procedures involving cytopathologists and cytologists. Interviews with cytopathologists were also included. Participants were surveyed for demographic information and provided course evaluations. RESULTS: In the first year of the program (2021), 34 participants completed the program, which increased to 103 in 2022. In both years there was a diversity in participant demographic backgrounds; however, only a minority of participants self-identified as being underrepresented in medicine. A vast majority (>85%) of participants in both years were high school or college students. In 2021, 100% of participants stated that the program format was effective and 94% thought the content was appropriate for their level of education; in 2022 the results were similar. In 2021, 66% considered health care as a potential career; this value increased in 2022 to 83%. In 2021 and 2022, 31% and 38%, respectively, considered cytology as a career. CONCLUSIONS: Evaluations were excellent, generating interest in cytopathology. Barriers in reaching underrepresented minorities exist and additional work is needed. Expansion to a wider audience may increase outreach.

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.