Moderate Response Research Articles

Measurement properties of the Brazilian-Portuguese version of the PROMIS-29 questionnaire and the Impact Score in patients with chronic low back pain

BackgroundA task force from the US National Institute of Health aimed to establish parameters for surveys with patients with chronic low back pain (LBP) by recommending the use of the Patient-Reported Outcome Measurement Information System 29-item (PROMIS-29) questionnaire and the stratification according to the Impact Score. We aimed to assess the internal consistency, reliability, measurement error, construct validity and responsiveness of the Brazilian-Portuguese version of the PROMIS-29 questionnaire (version 2.1) and the Impact Score in patients with chronic LBP.MethodsA prospective cohort study was carried out with patients with chronic LBP who were receiving physiotherapy treatment in clinics in São Paulo and Vitória cities, Brazil. The sample included 102 patients with chronic LBP, aged between 18 and 80 years, and with the ability to read and write in the Brazilian-Portuguese language. Exclusion criteria were patients with serious spinal conditions, cognitive impairment, pregnant women, and patients who had undergone lumbar surgery within the past six months. The PROMIS-29 questionnaire, the 12-item Short-Form Health Survey and the Roland-Morris Disability Questionnaire were applied. The PROMIS-29 questionnaire was reapplied after 24 hours and 4 weeks.ResultsThe PROMIS-29 questionnaire showed Cronbach’s Alpha values between 0.81 (anxiety) and 0.91 (depression). The ICC2.1 ranged from 0.85 (95% CI: 0.77 to 0.89) to 0,97 (CI 95%: 0.95 to 0.98). The SEM values ranged between 0.85 (physical function) and 2.62 (ability to participate in social roles and activities). The Impact Score showed Cronbach’s Alpha, ICC2.1 and SEM values of 0.91, 0.97 (95% CI: 0.95 to 0.98) and 0.56, respectively. The PROMIS-29 questionnaire and the Impact Score showed sufficient construct validity. The PROMIS-29 questionnaire showed moderate responsiveness, while the Impact Score showed sufficient responsiveness.ConclusionsBoth the Brazilian-Portuguese version of the PROMIS-29 questionnaire and the Impact Score showed sufficient internal consistency, reliability, construct validity and responsiveness in Brazilian patients with chronic LBP. The results support the US National Institutes of Health’s recommendation to use the PROMIS-29 questionnaire and the Impact Score in patients with chronic LBP. We suggest that future studies evaluate the structural validity of the Brazilian-Portuguese version of the PROMIS-29 questionnaire.Clinical trial numberNot applicable.

Long-term outcomes of intravenous corticosteroid pulse therapy for rapidly progressive alopecia areata: A single-center retrospective analysis of 106 cases and usefulness evaluation of a scoring system originally designed for half-year efficacy prediction for extended periods.

Intravenous corticosteroid pulse therapy (IVPT) has been preferentially conducted for rapidly progressive alopecia areata (RP-AA); however, the evaluation of long-term outcomes has been insufficient. In this study, 106 IVPT-treated RP-AA patients (36 males and 70 females) who were followed up for more than 1 year and up to 6.8 years were retrospectively analyzed. The mean observation period was 1137.8 ± 587.9 days (range 380-2490). The mean severity of alopecia tool (SALT) score before IVPT was 21.3 ± 23.4 but whole-scalp hair loss was observed in all cases after the intervention, suggesting that IVPT was performed soon after the onset. With additional interventions represented by intralesional triamcinolone acetonide injection with or without topical potent corticosteroid for those who insufficiently responded at 6 months after IVPT, 64.2%, 14.2%, and 21.7% of the patients respectively achieved good response (GR; SALT score ≤25), moderate response (MR; 25 < SALT score <75), and poor response (PR; 75 ≤ SALT score) 1 year after IVPT. On the final evaluation, the proportions of patients with GR, MR, and PR were 79 (74.5%), 7 (6.6%), and 20 (18.9%). Sixteen patients achieved and maintained full hair regrowth with IVPT alone until the end of observation. A previously reported scoring system for the short-term outcome prediction was shown to be useful for distinguishing the final-point GR responders from PR responders (P = 0.003). Of note, 21 patients were found to have some symptoms suggestive of the existence of preceding infectious diseases and tended to relapse. The revised scoring system adding the absence of preceding infectious diseases as one factor successfully predicted the occurrence of the relapse in our cohort (P = 0.002). Taken together, previously unreported real-world efficacy of IVPT to RP-AA was elucidated with the invention of a tool putatively enabling optimal long-term management.

A-270 Evaluation of a multiplex panel to determine antibody profile to monkeypox virus in vaccinated, exposed, and naïve individuals

Abstract Background Monkeypox Virus (MPXV) is a double-stranded DNA virus of the Orthopoxvirus genus that causes Mpox disease with symptoms such as swollen lymph nodes, chills, exhaustion, and blisters that appear on the face, inside the mouth, hands, feet etc. The genus orthopoxvirus (OPXV) has four species, namely, MPXV, smallpox-causing variola major virus (VARV), variola minor virus, and cowpox virus (CPXV), that cause disease in humans. In 1980, the World Health Assembly declared that smallpox had been eradicated due to a successful global vaccination program. This vaccine also provided cross-protection against other OPXV. Historically, the pox disease was rarely seen outside West and Central Africa. The first case of Mpox was identified in 1970 in a 9-year-old boy from the Democratic Republic of Congo (DRC), two years after the smallpox vaccination was discontinued. Since then, it has been reported in 11 African countries. In 2003, the first Mpox outbreak outside of Africa was in the USA and was linked to contact with infected pet prairie dogs. The recent 2022-2023 Mpox outbreak has generated renewed interest in the scientific community to understand the level of OPXV-specific immunity in the various geographic regions, among different age groups, and especially in the risk groups and its impact on future outbreaks by using integrated serosurveillance. To meet the need of the hour, we developed a novel multiplex assay for the detection of human IgG antibodies using Luminex® xMAP® technology for the detection of the human IgG profiles. Methods We have evaluated 11 different recombinant antigens from VARV, Vaccinia virus (VACV), and MPXV in a multiplex assay for detecting human IgG antibodies to OPXV using Luminex® xMAP® technology. We have covalently coupled magnetic fluorescent microspheres to three recombinant proteins from VARV, three from VACV, and five from MPXV to interrogate IgG responses. This 15-plex assay also includes four internal controls that assure the assay and reagent performance. In this preliminary evaluation, we have tested 84 de-identified serum and plasma from healthy subjects. We evaluated 24 serum samples of MPXV-exposed individuals procured commercially. We performed principal component analysis to determine which of these 11 antigens contributed the maximum differential and a result analysis algorithm was developed to predict these individuals' positive and negative antibody outcomes. Results The healthy subjects that were assumed to have been vaccinated showed positive response to A35R of MPXV; A36R of VARV, A33R of VACV, the homologous proteins in the three species and were distinct from unvaccinated younger individuals. There was some reactivity with B6R of MPXV protein. In MPXV-exposed subjects, we observed strong positive antibody responses to A35R of MPXV, A36R of VARV, A33R of VACV, and B6R of MPXV proteins in 19 out of 24 individuals. Fifteen individuals showed a moderate positive response to the A27L protein of VACV, and 8 out of 24 showed a weak positive response to the A29 protein of MPXV. Conclusions This panel is a useful tool to understand the level of OPXV-specific immunity by measuring IgG profiles for successful serosurveillance programs for public health.

Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo.

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further.

Neurophysiological response to social feedback in stressful situations.

The relationship between external feedback and cognitive and neurophysiological performance has been extensively investigated in social neuroscience. However, few studies have considered the role of positive and negative external social feedback on electroencephalographic (EEG) and moderate stress response. Twenty-six healthy adults underwent a moderately stressful job interview consisting of a modified version of the Trier Social Stress Test. After each preparation, feedback was provided by an external committee, ranging from positive to negative with increasing impact on subjects. Stress response was measured by analysing response times (RTs) during the speech phase, while cognitive performance was assessed using a Stroop-like task before and after the test. Results indicate that RTs used to deliver the final speeches with negative feedback were significantly lower compared with those used for the initial speech with positive feedback. Moreover, a generalized improvement in Stroop-like task performance was observed in the post-SST compared with the pre-SST. Consistent with behavioural results, EEG data indicated greater delta, theta, and alpha band responses in right prefrontal and left central areas, and for delta and theta bands, also in parietal areas in response to positive feedback compared with aversive-neutral feedback, highlighting greater cognitive effort required by the former. Conversely, an increase in these bands in right and left temporal and left occipital areas was observed following negative and aversive feedback, indicative of an adaptive response to stress and emotion-regulatory processes. These findings suggest that negative social feedback in moderately stressful and noncritical conditions could contribute to improving individual cognitive performance.

Consequences of the perivascular niche remodeling for tumoricidal T-cell trafficking into metastasis of ovarian cancer.

The treatment-induced activation level within the perivascular tumor microenvironment (TME) that supports T-cell trafficking and optimal T-cell differentiation is unknown. We investigated the mechanisms by which inflammatory responses generated by tumor-specific T cells delivered to ovarian tumor-bearing mice alone or after oncolytic vaccinia virus-driven immunogenic cancer cell death affect antitumor efficacy. Analyses of the perivascular TME by spatially resolved omics technologies revealed reduced immunosuppression and increased tumoricidal T-cell trafficking and function after moderate inflammatory responses driven by a CXCR4 antagonist-armed oncolytic virus. Neither weak nor high inflammation created a permissive TME for T-cell trafficking. Notably, treatment-mediated differences in T-cell effector programs acquired within the perivascular TME contrasted with comparable antigenic priming in the tumor-draining lymph nodes regardless of the activation mode of antigen-presenting cells. These findings provide new insights into combinatorial treatment strategies that enable tumor-specific T cells to overcome multiple barriers for enhanced trafficking and control of tumor growth. .

Intralesional immunotherapy of cutaneous warts using tuberculin purified protein derivative and vitamin D3 – A randomized comparative study

Objectives: Numerous studies have been conducted on the clinical efficacy of immunotherapeutic agents in the treatment of cutaneous warts showing variable results. The present study aimed to compare the clinical efficacy and safety of intralesional tuberculin purified protein derivative (PPD) and Vitamin D3 therapy in recurrent and recalcitrant extra-genital cutaneous warts. Material and Methods: This study was conducted as a prospective, randomized, comparative, and single-blind study. A total of 104 patients were randomly distributed into two treatment groups: Group A (Tuberculin PPD, n = 53) and Group B (Vitamin D3, n = 51). Each patient in Group A received an intralesional injection of 0.1 mL tuberculin PPD (5 Tuberculin Units), while each patient in Group B received an intralesional injection of 0.2 mL Vitamin D3 (Cholecalciferol containing 120,000 IU). The injections were given at the initial visit (week 0) and after every 2 weeks for a maximum of four sessions (weeks 2, 4, and 6). The largest wart was selected for intralesional therapy. The categorization of clinical response was done based on the percent reduction in the size of warts into complete (appearance of normal skin), marked (&gt;50% reduction), moderate (&lt;50% reduction), and inadequate (no change in warts) responses. Adverse effects (if any) were recorded during each patient visit. The final response was evaluated at 6 months follow-up from the last treatment session. Results: Regarding the response of patients to tuberculin PPD therapy, out of a total of 53 patients, 40 (75.5%) showed a complete response. Regarding the response of patients to Vitamin D3 therapy, out of a total of 51 patients, 36 (70.6%) showed a complete response. However, the difference in the response to the treatment between the two groups was statistically insignificant (P = 0.402). Conclusion: Both intralesional tuberculin PPD and Vitamin D3 are effective and safe in the treatment of all recurrent and recalcitrant extra-genital cutaneous warts.

K3Y3(BO3)4: A Potential UV Nonlinear-Optical Crystal Designed by a Chemical Substitution Strategy.

Nonlinear-optical (NLO) crystals capable of controlling and manipulating light to generate coherent radiation at challenging wavelengths are of significant interest. However, designing a new UV NLO crystal remains difficult due to the rigid requirements for structure and properties. Herein, we have successfully designed and synthesized a novel noncentrosymmetric (NCS) rare-earth borate UV NLO crystal, K3Y3(BO3)4, through the heterovalence substitution of YAl3(BO3)4. K3Y3(BO3)4 (KYBO) crystallizes in the NCS and polar space group of P63mc, with the structure formed by the interconnectioned BO3 triangles and YO8 polyhedra through corner-sharing and edge-sharing. The property measurements indicate that KYBO is second-harmonic-generation-active with a moderate response, ∼2 × KDP. Meanwhile, KYBO can exhibit a short UV cutoff edge (λcutoff < 190 nm), indicating its potential as a new UV or deep-UV NLO crystal.

Design, synthesis, and biological evaluation of adenosine derivatives targeting DOT1L and HAT as anti-leukemia agents

Disruptor of telomeric silencing 1-like (DOT1L) is a key hub in histone lysine methyltransferase and an attractive therapeutic target for treating hematological malignancies including acute myeloid leukemia (AML). In this study, we report the design and synthesis of a new series of adenosine derivatives as DOT1L inhibitors by accommodating a basic linker piperidine-4-ylmethyl motif to respective aryl-urea/benzimidazole scaffolds. The anti-DOT1L enzyme activity analysis demonstrated that compounds 8, 12, and 13 strongly suppressed DOT1L activity with IC50 values ranging from 0.125 to 0.408 µM among all the synthetics, and the structure–activity relationships were summarized. Moreover, compound 12 possessed relatively potent DOT1L inhibitory activity by significantly reduced histone H3 di-methylation at lysine 79 (H3K79me2) level in cells. Subsequently, all the synthetics were screened against various leukemia cell lines, indicating the DOT1L active adenosine derivatives exhibited low to moderate while compound 15 showed strong cellular inhibition despite its unsuccessful DOT1L inhibition. Therefore, acknowledging the distinctive potency of compound 15 against five different leukemia cell lines, including MLL-r (MV4-11) and non-MLL-r cell lines (HL-60, HH, K562, and KG-1), with IC50 values in the 0.45 ∼ 1.66 μM range and its mode of action was explored. Furthermore, compound 15 hindered histone acetylation, induced remarkable DNA damage, and triggered apoptosis. Importantly, normal T lymphocytes only showed moderate response to compound 15. These findings provide a basis for future studies on its potential application against AML.

A Latent Profile Analysis of Religious Parents' Responses to Their Sexual and Gender Diverse Child.

Prior research indicates that religious parents can have negative, positive, or ambivalent responses to their child's sexual orientation and gender identity (SOGI). Yet, to our knowledge no research has quantitatively examined patterns of sexual and gender diverse (SGD) youth's perceptions of their religious parents' responses to their SOGI. Without examining variations in these patterns, we are unable to better understand the experiences of SGD youth with religious parents. In the current paper, we examined patterns of SGD youth's perceptions of their religious parents' SOGI-specific rejection, acceptance, and SOGI change efforts. We also examined if these patterns differed by SGD youth's individual and contextual factors. The analytic sample consisted of online responses from 5,686 SGD youth (Mage = 15.95). We found four distinct profiles: Positive Parental Response, Moderate Negative Parental Response, Low Parental Response, and High Negative Parental Response. The largest profile was the Positive Parental Response, suggesting that many SGD youth perceived positive responses from their religious parents. SGD youth with diverse gender identities and intersecting identities, such as race/ethnicity, were more vulnerable to religious parents' negative responses. Findings have implications for existing resources and programs aimed at strengthening SGD youth's relationship with their religious parents.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Study on characterization of moderate energy impact response of elastic-plastic plate structure

This paper presents a study on the characterization of the moderate energy impact response between the elastic-plastic plate and the elastic-plastic sphere. An equivalent contact stiffness is proposed to substitute the linear contact stiffness, and a universal analytical expression is presented according to the intensive FE simulations for different material combinations under moderate impact energy. Then, a modified characterization diagram is suggested using the analytical expression. The modified diagram is validated by the FE simulations and experimental results. The results show the modified diagram can predict the maximum impact force and the response type in a fast and simple way.

Postural Orthostatic Tachycardia Syndrome (POTS) as a Cause of Dizziness - Expanding the Etiological Spectrum.

Dizziness is a frequent complaint encountered in neurology clinics. Dizziness can be spontaneous or triggered, which includes orthostatic dizziness. Orthostatic dizziness can be acute (reflex/vasovagal syncope), chronic (orthostatic hypotension (OH), or postural orthostatic tachycardia syndrome (POTS). Since dizziness has numerous causes, these patients undergo extensive investigations before a diagnosis is made. Here, we describe five patients who presented with dizziness and were diagnosed to have POTS on evaluation. We conducted a retrospective study of patients who presented to the Department of Neurology from August 2020 to November 2021 with the complaint of dizziness and were diagnosed with POTS. The clinical history, neurological examination, treatment response, routine blood investigations, magnetic resonance imaging (MRI) brain, and autonomic function tests (AFTs) of the patients were reviewed from patients' clinical records. Patients with dizziness and with diagnosis other than POTS were excluded from the study. Among the five patients, males were predominant with a male to female ratio of 3:2. All the patients were in their early fourth decade with a mean age of 35.4 years. The presenting symptom was dizziness, and the key associated symptoms were anxiety and headache. Due to the orthostatic nature of symptoms and absence of orthostatic fall in blood pressure (BP), a detailed AFT was carried out, leading to the diagnosis of POTS. Patients were assessed at 3-6 months after treatment and there was a moderate response in one and no response in the remaining four patients. POTS should be considered a possible etiology when patients present with orthostatic dizziness in the absence of orthostatic fall in BP. Anxiety and headache may be associated with this type of dizziness.

Renin-angiotensin system-mediated nitric oxide signaling in podocytes.

Nitric oxide (NO) is widely recognized for its role in regulating renal function and blood pressure. However, the precise mechanisms by which NO affects renal epithelial cells remain understudied. Our previous research has shown that NO signaling in glomerular podocytes can be initiated by Angiotensin II (ANG II) but not by ATP. This study aims to elucidate the crucial interplay between the renin-angiotensin system (RAS) and NO production in podocytes. To conduct our research, we used cultured human podocytes and freshly isolated rat glomeruli. A variety of RAS peptides were used, alongside confocal microscopy, to detect NO production and NO/Ca2+ cross talk. Dynamic changes in the podocyte cytoskeleton, mediated by RAS-NO intracellular signaling, were observed using fluorescent labeling for F-actin and scanning probe microscopy. The experiments demonstrated that ANG II and ANG III generated high levels of NO by activating the angiotensin II type 2 receptor (AT2R). We did not detect functional MAS receptor presence in podocytes, and the moderate NO response to ANG 1-7 was also mediated through AT2R. Furthermore, NO production impacted intracellular Ca2+ signaling and correlated with an increase in podocyte volume and growth. Scanning probe experiments revealed that AT2R activation and the corresponding NO generation are responsible for the protrusion of podocyte lamellipodia. Taken together, our data indicate that AT2R activation enhances NO production in podocytes and subsequently mediates changes in Ca2+ signaling and podocyte volume dynamics. These mechanisms may play a significant role in both physiological and pathophysiological interactions between the RAS and podocytes.NEW & NOTEWORTHY The renin-angiotensin system plays a crucial role in the production of intracellular nitric oxide within podocytes. This mechanism operates through the activation of the angiotensin II type 2 receptor, leading to dynamic modifications in intracellular calcium levels and the actin filament network. This intricate process is vital for linking the activity of angiotensin receptors to podocyte function.

Sleeve-Gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of metabolic dysfunction-associated steatohepatitis

BackgroundBariatric surgery has been shown to improve the histopathological findings in patients with obesity and metabolic dysfunction-associated steatohepatitis, but there are also reports about non-responder or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery. Materials and MethodsIn the present study, 4 weeks old male C57/Bl6 mice were fed a Western Diet to induce metabolic dysfunction-associated steatohepatitis and sleeve-gastrectomy (SG), or sham operation in the pair-fed and ad libitum control group were performed. Mice were observed for two or eight weeks after surgery and metabolic assessment was performed throughout the experiment. Histopathology, flow cytometry and proteomic analysis were conducted to evaluate hepatic inflammation, liver metabolism and affected signaling pathways. ResultsWeight loss was higher, and metabolism significantly improved after SG. Two weeks after SG major inflammatory and regulatory disturbances in the liver were observed. The proportion of hepatic CD3+NK1.1+ cells were decreased, and proteins involved in apoptosis like Fas, Casp1 and Casp9 or in the acute phase response were upregulated in SG mice. These disturbances decreased in the long-term and we observed an increase of many proteins involved in lipid metabolism eight weeks following SG. ConclusionsThe rapid weight loss and decrease of hepatic fat after SG lead to a proinflammatory response in the liver in the early phase after surgery, which changes to a more moderate immune response in the long-term. We suggest a preoperative risk stratification and postoperative surveillance depending on the histopathological findings.

Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides

Background: Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum. Methods: This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method. Results: As alternatives to the rabbit Draize test, several protocols using ex vivo, in chemico, and in vitro skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (e.g., a moderate response reported in one study followed by a non-irritant response reported in another study). Conclusions: Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant in vitro test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.

Investigations of structure, thermal stability and optical properties of a new NLO crystal (C3H5N2)+(CF3COO)-

New NLO imidazolium trifluoro acetate (C3H5N2)+(CF3COO)- single crystals were synthesized by solution evaporation method, with its structure, thermal stability, absorption spectrum, photoluminescence and second order nonlinear optical (NLO) properties were systematically investigated. This crystal features 0-dimensional noncentrosymmetric structure with orthorhombic space group I212121 which consist of isolated organic imidazolium cation (C3H5N2)+ and trifluoro acetate anion (CF3CO2)-. A high thermal stability up to 125 °C, and the absorption edge at 260 nm with a wide band gap of 4.55 eV were respectively determined. In addition, the photoluminescence performance with an emission peak at 363 nm can be ascribed to the π-π* transition absorption of imidazole ring. Notably, moderate phase-matching SHG response of 0.64 times KH2PO4 was evaluated for (C3H5N2)+(CF3COO)-. All the results indicate the potential applications of (C3H5N2)+(CF3COO)- in optical field.

Removal of black tattoos by Picosecond Q-switched Nd-YAG laser in the middle eastern skin type IV: prospective study

Tattoo removal is considered a challenging field in cosmetic dermatology. Picosecond Q-switched Nd-YAG lasers targeting unique chromophores effectively manage this condition without serious complications. To evaluate the efficacy and safety of Picosecond Q-switched Nd-YAG laser in the treatment of black tattoos in the skin of middle eastern mostly skin type IV. The study was carried out on 20 patients with skin type IV the most common in middle eastern area with professional black tattoos. They were treated by Picosecond Nd-YAG laser (2 sessions 8 weeks apart). The percentage of improvement ranged from 20.0 to 95.0 (with a mean of 61 ± 24.6). 8 patients (40%) showed excellent improvement, 4 patients (20%) showed marked improvement, 4 patients (20%) showed moderate improvement, and 4 patients (20%) showed mild improvement. No severe side effects were detected. Picosecond Nd-YAG laser was an effective and safe technique in the treatment of professional black tattoos; with only 2 sessions most patients reached excellent to moderate response with minimal side effects.

DEVELOPMENT OF A STUDENT WORKSHEET ON MEGIBUNG TRADITION MATERIAL BASED ON PROJECT-BASED LEARNING IN THE CULINARY ARTS VOCATIONAL EDUCATION STUDY PROGRAM

This research aims to describe the student responses to the developed Student Worksheets on Megibung Tradition material in the Balinese Culinary course. It employs a type of development research intended to develop Student Worksheets for Balinese Culinary courses. The subjects of this study were third-semester students of Culinary Arts Vocational Education FTK Undiksha. The selection of these subjects is based on the urgency of providing Balinese Culinary teaching materials, researchers’ role as lecturers, and research respondents. This research instrument is an assessment format consisting of aspects related to (1) material/concept, (2) construction, and (3) technical elements. The results showed that: (1) there are two stages in developing Student Worksheets, namely the preparation stage and the development stage. (2) A feasibility analysis indicated that the use of Student Worksheets with a project-based learning approach is suitable for learning and can enhance student creativity, specifically in the Balinese Culinary course for the ability to serve food with Megibung. (3) After making improvements based on expert validation, student response measurements were taken as users of this Student Worksheet. In general, the results of the student response questionnaire were summarized as follows: 75% of students rated this Student Worksheet as good, 10% gave a moderate response, and 10% gave a very good response.

A Case of Anti-IgLON5 Disease with Aplastic Anemia and review of the literature

Anti-IgLON5 is a neurological condition with neurodegenerative and autoimmune etiology. A 64-year-old man with a 2-year history of aplastic anemia presented with symmetrical parkinsonism, fluctuating consciousness, supranuclear gaze palsy, mild fasciculation, and muscular atrophy. He had disturbances in his sleep cycle and brain MRI. CSF analysis was positive for the IgLON5 antibody. We initiated immunotherapy with high-dose methylprednisolone, intravenous immunoglobulin, and rituximab. The patient showed a mild to moderate response to treatment. We reviewed 29 published case reports regarding anti-Iglon-5 and examined the clinical manifestation. None of the cases showed aplastic anemia, which was the main presentation in our case. All of the patients experienced sleep disturbances, while other symptoms were heterogeneous. Anti-Iglon-5 is usually diagnosed late, leading to a weak prognosis. This study helped us establish a better understanding of the correlation between antiIglon5 disease and other autoimmune disorders like anemia.