Clinical Investigation Research Articles

Physiologically based pharmacokinetic modeling of long-acting extended-release naltrexone in pregnant women with opioid use disorder.

Opioid use disorders (OUD) are a major issue in the U.S. Current treatments for pregnant women, like methadone and buprenorphine require daily dosing and have adverse effects. Monthly injectable naltrexone (XR-NTX) mitigates these adverse effects but is not recommended during pregnancy due to limited pharmacokinetic and safety data. This study developed a physiologically based pharmacokinetic (PBPK) model to describe XR-NTX pharmacokinetics during pregnancy, and to predict dosing recommendations. Model predictions were successfully validated with observed data. Maternal plasma XR-NTX profiles were simulated for 400 non-pregnant virtual females at the approved dose of 380 mg, then randomized to continue with either 380, 285, 190, or 95 mg during pregnancy. The non-pregnant virtual females had a mean predicted Cmax, AUC0-7days, and AUC0-28days of 23.3 ng/mL, 142 ng·d/mL, and 148 ng·d/mL, respectively. Maternal XR-NTX exposure (AUC0-28days) were predicted to increase by 1.37, 1.43, and 1.72 times during the first, second, and third trimester of pregnancy. However, the fetal-to-maternal exposure (AUC0-28days) was lower in the first (15%), second (7%), and third (9%) trimesters. A dose of 285 mg of XR-NTX in pregnancy during the first/second trimester and dose of 190 mg in the third trimester were predicted to provide maternal exposures that were comparable to non-pregnant levels at the standard dose. This study provides crucial insights into XR-NTX pharmacokinetics and proposes a dosing strategy during pregnancy, potentially aiding further clinical investigations and decision making regarding XR-NTX use during pregnancy.

Investigation of research quality and transparency in neurosurgery through the utilization of open science practices.

Neurosurgical research is a rapidly evolving field, with numerous studies continuously published. As the body of research grows, upholding high-quality standards becomes increasingly essential. Open science practices offer tools to ensure quality and transparency. However, the prevalence of these practices remains unclear. This study investigated the extent to which neurosurgical publications have implemented open science practices. Five open science practices (preprint, equator guidelines, published peer review comments, preregistration, and open accessibility to data and methods) were measured from five top-ranked neurosurgical journals (Neurosurgery, Journal of Neurosurgery, World Neurosurgery, Neurosurgical Review, and Acta Neurochirurgica), according to Google Scholar. One hundred fifty articles were randomly sampled from January 1, 2022, to December 31, 2023. Two reviewers analyzed these articles for their utilization of open science practices. A third reviewer settled disagreements. One journal required (20%) and three journals (60%) recommended utilizing EQUATOR guidelines. Three journals (60%) allowed preprints, and all five journals (100%) recommended or required preregistration of clinical trials, but only two (40%) recommended preregistration for systematic reviews (Fig.1). All five journals (100%) recommended or required methods to be publicly available, but none (0%) published peer-review comments. Neurosurgical Review utilized the most open science practices, with a mean utilization of 1.4 open science practices per publication versus 0.9 across the other four journals (p < 0.001). Moreover, Neurosurgical Review significantly utilized more open science practices versus Journal of Neurosurgery (p < 0.05) and World Neurosurgery (p < 0.05). Both randomized controlled trials (p < 0.001) and systematic reviews (p < 0.001) significantly utilized more open science practices compared to observational studies. Despite advocacy from neurosurgical journals, the adoption of open science practices still needs improvement. Implementing incentives and clearer requirements may prove beneficial. Promoting these practices is crucial to enhancing research quality in neurosurgery.

Identifying prothrombin and bone sialoprotein as potential drug targets for idiopathic pulmonary fibrosis

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a fatal disease with scarce therapeutic alternatives, which imposes a significant economic burden on society. The identification of novel drug targets is thus critically essential. Plasma proteins with discernible causal evidence hold promise as viable drug targets for this condition.MethodsWe performed a proteome-wide Mendelian randomization (MR) analysis to assess the causal effects of 4,907 circulating proteins from the deCODE study on the risk of IPF from the Finngen Database (2,018 cases vs. 373,064 controls). We further replicated the MR analysis in 1426 proteins from the ARIC study and IPF from the UK Biobank (1,369 cases vs. 435,866 controls). Then a series of analyses including Bayesian colocalization, Steiger filtering, and phenotype scanning were conducted to validate the credibility of the MR results. Subsequently, protein-protein interaction (PPI) analysis, pathway enrichment analysis, and druggability assessment were executed to elucidate the underlying mechanisms. Finally, the findings were corroborated using a bleomycin-induced pulmonary fibrosis mouse model.ResultsThe MR analysis bolstered by robust evidence of colocalization, indicated a significant positive association between Prothrombin and increased IPF risk (OR = 3.26,95%CI 1.75–6.07). Conversely, Bone Sialoprotein (IBSP) demonstrated an inverse association with IPF susceptibility (OR = 0.27,95%CI 0.14–0.55).ConclusionsThe integrative analysis suggests that Prothrombin and IBSP are promising candidates as potential drug targets for IPF. Additional clinical investigations are warranted to substantiate these findings.

The rise of internet derived information obstruction treatment (IDIOT) syn-drome in Pakistan.

Abstract: Few decades ago, when there was no internet the management of the patient was entirely based upon the clinical ex-amination, clinical investigation and diagnosis by the doctor. However, with the availability of internet and easy ap-proach to smart phone has led to the introduction of a new element into the management of patient. This new element is information derived from internet by the patient or his/her family members. Keywords: : IDIOT Syndrome, Internet derived information, Pakistan, Health care

Incidence of erysipelas in waterfowl in Poland – clinical and pathological investigations

ABSTRACT 1. Erysipelas in geese and ducks is an infectious disease causing considerable economic losses in the poultry sector in Poland. The aim of this study was to determine the distribution of erysipelas cases in age groups of geese and in periods of the calendar year and to assess macroscopic lesions in birds infected with Erysipelothrix rhusiopathiae. 2. The study used 286 geese and 16 ducks delivered to the laboratory for diagnosis in the years 2019–2021. The birds came from 99 different farms. E. rhusiopathiae from clinical samples were cultured on Columbia blood agar and identified by real-time PCR. Pathological lesions were characterised during anatomopathological examination. 3. Distribution of erysipelas cases in age groups of geese and periods of the calendar year differed significantly from the assumed even distribution. Most cases were noted in August and September in birds aged between 11 and 13 weeks. Necropsy of birds infected with E. rhusiopathiae showed anatomopathological lesions characteristic of generalised infection, affecting multiple organs. 4. The uneven distribution of erysipelas cases in geese in different age groups and periods of the calendar year suggested that both the age of the birds and climatic conditions are predisposing factors for infection.

12382 A Prospective Analysis of De Novo Thyroglobulin Antibodies in Patients with Differentiated Thyroid Cancer Using the Italian Thyroid Cancer Observatory Repository

Abstract Disclosure: B.S. Neutel: None. G. Grani: None. S. D'elia: None. C. Durante: None. A.G. Gianoukakis: None. The prevalence and significance of newly developed (de novo) thyroglobulin antibodies (dnTgAb) in patients with differentiated thyroid cancer (DTC) who were initially thyroglobulin antibody (TgAb) negative, is not well established. We sought to examine the phenomenon of dnTgAb using the Italian Thyroid Cancer Observatory (ITCO) database. Beginning in 2013, the ITCO repository prospectively collected clinical data on DTC management in a consecutive series of newly diagnosed patients treated in large academic centers distributed across Italy. Patients were managed by treating physicians based on perceived best practice. Pre-specified parameters were collected. Clinical status, investigations, and treatments were updated periodically. We formulated inclusion and exclusion criteria to mirror previously published literature studying dnTgAb. Patients included in the analysis were initially TgAb negative at their first postoperative check and had no evidence of persistent disease at their 1 year follow up visit. The dnTgAb group included patients who were initially TgAb negative and then developed TgAb on at least one measurement from the second postoperative check or later. All patients included in the study had at least 3 years of follow up and 3 TgAb measurements. At the time of analysis, 5360 patients were without persistent disease at 1 year. 2107 of these patients had a least 3 years of follow up and 3 TgAb measurements. 334 patients with positive TgAb at their first lab check and an additional 124 patient with incomplete data were excluded. 1649 patients met criteria for inclusion. Median follow up time was 1.85 years. DnTgAb occurred in 4.3% of patients (n=71). We found no statically significant difference in gender, tumor size, tumor focality, extrathyroidal extension, AJCC stage and ATA risk level between the persistently negative TgAb group and the dnTgAb group. Only primary tumor vascular invasion occurred at a higher rate in patients within the dnTgAb group when compared to the persistently negative group (p=0.012). Structural DTC recurrences occurred in 1.4% (n=22) of persistently TgAb negative patients and 5.6% (n=4) of patients with dnTgAb (p=0.02).This is the largest and first prospective cohort used to evaluate the prevalence and clinical significance of dnTgAb. DnTgAb occurred at a clinically relevant rate and there was a statistically significant relationship between detection of dnTgAb and structural DTC recurrence. The study is limited by the small overall recurrence rates and the exclusion of patients with less than 3 years of follow up. Presentation: 6/3/2024

Endovascular intervention for carotid blowout syndrome and predictors of recurrence: A retrospective and multicenter cohort study

IntroductionCarotid blowout syndrome (CBS) is a potentially life-threatening complication of head and neck cancer and associated treatment. In this study, we assess the safety and efficacy of deconstructive and reconstructive procedures with a focus on CBS recurrence. MethodsWe conducted a multicenter retrospective analysis of a prospectively maintained database and identified 80 consecutive neurointerventions for CBS from 2016 to 2020. Patients were divided into 2 groups: deconstructive embolization (68 patients) and reconstructive stenting (12 patients). A comparative analysis was performed between the two groups. ResultsThe CBS recurrence rate was 23.8 % with 84.2 % of recurrences occurring within 90 days of the primary event. The median time to rebleeding was 8.0 days (IQR: 2.0 – 28.5) with a mortality rate of 26.3 %. There was no significant difference in rates of peri-operative ischemic stroke (1.5 % vs. 0 %, p=0.672) or peri-operative mortality (1.5 % vs. 0 %, p=0.670). CBS recurrence was significantly higher in the reconstructive group (58.3 % vs. 17.6 %, p=0.002). On multivariate analysis, reconstructive stenting independently predicted rebleeding (adjusted hazard ratio 8.31, 95 % CI: 2.34–29.59, p=0.001). There was no significant association between CBS recurrence and pre-operative (p=0.600) or post-operative (p=0.275) anticoagulant/antiplatelet use. ConclusionCBS remains a challenging and potentially catastrophic complication of head and neck cancers. Reconstructive procedures, including stenting, predicted CBS recurrence independent of bleeding site or tumor invasion. Postoperative surveillance based on time intervals to CBS recurrence and engineering advancements including improved vessel reconstruction devices have the potential to reduce rehemorrhage rates and improve patient outcomes. Further clinical investigations amongst larger cohorts are needed.

MAD—microbial (origin of) Alzheimer’s disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems

Microbes have been suspected to cause Alzheimer’s disease since at least 1908, but this has generally remained unpopular in comparison to the amyloid hypothesis and the dominance of Aβ and Tau. However, evidence has been accumulating to suggest that these earlier theories are but a manifestation of a common cause that can trigger and interact with all the major molecular players recognized in AD. Aβ, Tau and ApoE, in particular appear to be molecules with normal homeostatic functions but also with alternative antimicrobial functions. Their alternative functions confer the non-immune specialized neuron with some innate intracellular defenses that appear to be re-appropriated from their normal functions in times of need. Indeed, signs of infection of the neurons by biofilm-forming microbial colonies, in synergy with herpes viruses, are evident from the clinical and preclinical studies we discuss. Furthermore, we attempt to provide a mechanistic understanding of the AD landscape by discussing the antimicrobial effect of Aβ, Tau and ApoE and Lactoferrin in AD, and a possible mechanistic link with deficiency of vital copper-based systems. In particular, we focus on mitochondrial oxidative respiration via complex 4 and ceruloplasmin for iron homeostasis, and how this is similar and possibly central to neurodegenerative diseases in general. In the case of AD, we provide evidence for the microbial Alzheimer’s disease (MAD) theory, namely that AD could in fact be caused by a long-term microbial exposure or even long-term infection of the neurons themselves that results in a costly prolonged antimicrobial response that disrupts copper-based systems that govern neurotransmission, iron homeostasis and respiration. Finally, we discuss potential treatment modalities based on this holistic understanding of AD that incorporates the many separate and seemingly conflicting theories. If the MAD theory is correct, then the reduction of microbial exposure through use of broad antimicrobial and anti-inflammatory treatments could potentially alleviate AD although this requires further clinical investigation.

Unveiling Immunological and Hematological Markers in COVID-19: Insights from a Clinical Study.

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)-confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes.

The causal relationship between gut microbiota and lower extremity deep vein thrombosis combined with pulmonary embolism

BackgroundOver the years, numerous studies have explored the relationship between gut microbiota and lower extremity deep vein thrombosis (LEDVT) and pulmonary embolism (PE). The present study utilized Mendelian randomization (MR) to assess the causal link between gut microbiota and LEDVT combined with PE.MethodsHuman gut microbiota genome-wide association study (GWAS) summary data from the MiBioGen consortium (n = 18,340) were utilized. Summary-level data on LEDVT (2,116 cases and 359,078 controls) and LEDVT combined with PE (4,319 cases and 356,875 controls) were obtained from the IEU Open GWAS project. MR analysis was conducted using the inverse variance weighted (IVW) method as the primary analysis. Additionally, MR-Egger, weighted median, weighted mode, and simple mode were employed as supplementary methods. Sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed. Lastly, reverse MR analysis was performed.ResultsThe IVW analyses revealed seven causal relationships between genetic liability in the gut microbiota and LEDVT and five causal relationships between genetic liability in the gut microbiota and LEDVT combined with PE. The intersection of these outcomes identified that the genus Butyricicoccus reduced the risk of both LEDVT and LEDVT combined with PE, while the genus Clostridium innocuum increased the risk for both conditions.ConclusionThis study demonstrates that the gut microbiota is causally associated with LEDVT and LEDVT combined with PE. Our findings provide valuable insights into the underlying mechanisms and suggest potential avenues for further clinical investigations of these conditions.

B-150 Chromatographic Separation and Quantitation of Human Insulin and Lispro Analog in Serum Using Liquid Chromatography High-Resolution Mass Spectrometry

Abstract Background Factitious hypoglycemia, a deliberate attempt to induce low blood glucose levels occurring secondary to the surreptitious administration of exogenous insulin, can be difficult to diagnose due to a variety of factors including the increased use of synthetic insulin analogs in clinical practice. Traditional insulin immunoassays demonstrate variable cross-reactivity with commonly prescribed insulin analogues and their metabolites, making it difficult to measure specific analogs. The development of liquid chromatography high resolution accurate mass (LC-HRAM)-mass spectrometry (MS) assays has largely circumvented the limitations of traditional immunoassays for detection and quantitation of insulin analogs. Analytical challenges remain, however, specifically in differentiating lispro, an isomeric human insulin analog formed by the transposition of proline and lysine near the C-terminal end of the B chain, from human insulin in patient samples due to the equivalent mass-to-charge ratios of their precursor ions. Methods Immunoaffinity purification of insulin from calibrators and quality control material prepared by spiking insulin-depleted serum with pharmaceutical insulin preparations, as well as patient samples, was performed using tips coupled with anti-insulin monoclonal antibody. An automated liquid handler was programmed to perform aspiration and dispense cycles. Eluate from the purification protocol was submitted for analysis using a TLX-2 multiplex LC system paired with a Thermo Scientific Q Exactive Plus mass spectrometer. Various HPLC column chemistries were evaluated, a column passivation procedure was established, and column heater temperature was optimized to identify a combination of parameters yielding the best chromatographic separation of human insulin and lispro. Additionally, parallel reaction monitoring (PRM) targeted tandem mass spectrometry (MS/MS) analysis was utilized in combination with the full scan data to increase specificity through the monitoring of fragment ions produced from human insulin and each insulin analog. Results We found that a 1000 Å Diphenyl, 2.7 µm, 2.1 x 100 mm analytical column in a column heater maintained at a temperature of 80°C allowed for human insulin and lispro to be differentiated as two chromatographically separated extracted ion chromatographic peaks (XICs) and quantified down to 2.5 mcIU/mL with near-baseline separation. Before use, the column required passivation with a high protein buffer (0.05% bovine serum albumin in 20% acetonitrile [ACN] + 0.2% acetic acid) followed by increasingly organic buffers (20% ACN + 0.2% acetic acid and 50% ACN + 0.2% acetic acid). MS/MS was used to confirm the presence of analogs detected. Conclusions The LC-HRAM-MS method described here, coupled with optimized column chemistry, column passivation, and proper column temperature control allows for chromatographic separation of human insulin and lispro. Incorporating a PRM scan into the mass spectrometry full scan method provides confirmation of the insulin detected in the XICs. The results obtained from preliminary studies suggest this method is appropriate for use to facilitate the clinical investigation of suspected factitious hypoglycemia with the ability to differentiate isomeric compounds, such as human insulin and lispro.

Effect of tDCS combined with virtual reality for post-stroke cognitive impairment: a randomized controlled trial study protocol

BackgroundPost-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation.MethodsThis 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects’ speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex.DiscussionOur hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach.Trial registrationChictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

B-082 Clinical Investigation of Rods and Rings Pattern in Anti-Nuclear Antibody Test in Korean Patients

Abstract Background In the mid-2000s, a novel pattern in antinuclear antibody (ANA) testing was reported. Indirect immunofluorescence assays on HEp-2 cells, conducted with sera from patients with Hepatitis C virus (HCV) infection, revealed cytoplasmic structures in the form of rods and rings (RR). These structures typically displayed rod lengths of 3-10μm and ring diameters of 2-5μm. Inosine monophosphate dehydrogenase (IMPDH) was identified as the primary component of the RR structures. Research on the administration of interferon/ribavirin (IFN/RBV) showed that ribavirin, an IMPDH inhibitor, induced RR formation in over 95% of cells. Additionally, RR patterns were reported in patients receiving other IMPDH inhibitors such as mycophenolic acid and azathioprine. While cytidine triphosphate synthase 1 (CTPS1) was suggested to be associated with RR structures, there were no reported cases in patients. Interestingly, patients receiving methotrexate, which does not directly inhibit IMPDH but hinders GTP biosynthesis, also exhibited RR structures. To explore the clinical implications of specimens showing RR patterns, a study was conducted to investigate the actual clinical scenarios associated with these findings. Methods This is a retrospective study conducted at a single center, covering the period from January 2022 to December 2023, focusing on the results of ANA testing. The ANA tests were performed using HEp-2 cells (FLUORO HEPANA TEST, MBL, Nagoya, Japan) on slides manufactured with AP 16 IF Plus (das, Palombara Sabina, RM, Italy). ANA results were obtained through qualitative testing, ranging from 1+ to 4+, or quantitative testing based on dilutions ranging from 1:40 to 1:640, depending on clinical requirements. Results Out of the 7,648 ANA test results, the RR pattern was observed in 40 cases (0.5%). Among these, 2.5% had a history of HCV infection with IFN/RBV treatment, and an additional 2.5% had concurrent use of IMPDH inhibitors. There were no reported cases of medication history related to the synthetic pathway of nucleic acids, including CTPS1. Cases where RR patterns coexisted with autoimmune diseases accounted for 35%, infections for 25%, and other inflammatory conditions for 22.5%. RR patterns reported with an intensity of 3+ or at dilutions of 1:160 or higher constituted 27.5%. Among cases displaying strong fluorescence, 45% were associated with infections, 18% with autoimmune conditions, and another 18% with unexplained inflammatory causes. In the overall sample, elevated CRP or ESR was noted in 54.5% of cases with infections, autoimmune diseases, or other inflammatory conditions. Among samples with intense intensity, 55.5% showed elevated CRP or ESR when inflammatory conditions were present. Conclusions The majority of cases exhibiting the RR pattern showed no history of exposure to IMPDH inhibitors or drugs affecting the nucleic acid synthetic pathway. A high proportion of cases clinically diagnosed with inflammation showed a concurrent RR pattern, with only approximately half of them demonstrating elevated CRP or ESR levels. This study suggests the possibility of identifying inflammatory responses not captured by conventional acute inflammation markers through the RR pattern observed in ANA testing.

Rapid Analysis of Sterols in Blood-Derived Samples.

Dysregulations of cholesterol biosynthesis are known to be associated with several pathologies. Due to the rapid growth of clinical investigations in this research area, a specific, fast, and valid method for analyzing cholesterol, its precursors, and metabolites is required. Here, we describe a rapid method for sample preparation, separation, and quantification of sterols in blood-derived samples using polymeric solid phase extraction followed by gas chromatography-mass spectrometry. The validated method demonstrates a reliable quantification of cholesterol, its precursors, and metabolites.

High correlated color temperature white light-emitting diodes disrupt refractive development in guinea pigs

Ubiquitous white light-emitting diodes (LEDs) possess optical properties that differ from those of natural light. This difference can impact visual perception and biological functions, thus potentially affecting eye health. Myopia, which leads to visual impairments and potentially irreversible vision loss or blindness, is the most prevalent refractive error worldwide. Ambient light has been found to be a significant factor in refractive development. The overlap between the commonly utilized of white LEDs and the rapid increase in the prevalence of myopia raises suspicions that white LEDs may represent hidden visual cues. To clarify the potential effects of white LEDs on refractive development, we exposed guinea pigs to different forms of artificial lighting over a period of eight weeks. We found that exposure to white LEDs with a high correlated color temperature (CCT) of approximately 5000 K can induce significant myopic shifts in guinea pigs, along with a decrease in collagen accumulation in the sclera. Additionally, this exposure was found to significantly reduce choroidal tissue thickness in guinea pigs. Our study findings indicate that high CCT white LEDs disrupt refractive development in guinea pigs. These results suggest that high CCT white LEDs might similarly affect refractive development in humans, highlighting the need for further clinical investigation.

CAR T-cell therapy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive leukemic malignancy that affects myeloid lineage progenitors. Relapsed or refractory AML patients continue to have poor prognoses, necessitating the development of novel therapy alternatives. Adoptive T-cell therapy with chimeric antigen receptors (CARs) is an intriguing possibility in the field of leukemia treatment. Chimeric antigen receptor T-cell therapy is now being tested in clinical trials (mostly in phase I and phase II) using AML targets including CD33, CD123, and CLL-1. Preliminary data showed promising results. However, due to the cellular and molecular heterogeneity of AML and the co-expression of some AML targets on hematopoietic stem cells, these clinical investigations have shown substantial "on-target off-tumor" toxicities, indicating that more research is required. In this review, the latest significant breakthroughs in AML CAR T cell therapy are presented. Furthermore, the limitations of CAR T-cell technology and future directions to overcome these challenges are discussed.

LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.

Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

Clinical Profile and Mycological Profile of Dermatophytosis: A Cross-sectional Study at a Tertiary Care Hospital in Southern India

Abstract Background: This cross-sectional observational study aimed to analyze the clinical and mycological characteristics of dermatophytosis in patients visiting the outpatient clinic of the department of dermatology at a tertiary care hospital in Telangana. Methodology: The study was conducted from November 2017 to July 2019, involving patients clinically diagnosed with dermatophytosis. Data collection included detailed demographic and clinical information and laboratory investigations such as direct microscopy, fungal culture, and hematological examinations. Specimens were collected from skin lesions, nails, and hair, processed using appropriate methods, and subjected to culture and microscopic examination. Descriptive statistics was performed to present the findings. Results: A total of 100 participants were recruited, with a median age of 24 years. The majority were male (n = 75, 75%) and students (n = 47, 47%). Most participants (n = 71, 71%) presented with extensive tinea followed by tinea corporis and tinea capitis. Trichophyton mentagrophytes was the most isolated variant (n = 42, 97.7%) among positive cultures. Conclusion: Young male populations are the most common victims in this region. The significant number of tinea cases and the high prevalence of T. mentagrophytes underscore the necessity for precise diagnosis and effective management strategies in treating dermatophytosis.

Idiopathic unilateral complete oculomotor nerve palsy: a case report of diagnostic quandary

Introduction and importance: When compared to other cranial nerve palsies idiopathic unilateral oculomotor nerve palsy with pupillary sparing is one of the least noted neurological conditions. Moreover, there lies a series of diagnostic dilemmas to come into a final diagnosis resulting in several array of clinical investigations. Hence, there is a delay in prompt management. Case summary: An elderly female without any known comorbidities presented with the complaint of headache, dizziness and dropping of left eyelid. Several arrays of diagnostic workups was done to come to a diagnosis, but even with rigorous laboratory investigations and radiological examinations, a common working diagnosis could not be made. Hence with a diagnosis of exclusion after proper neurological and neuro-ophthalmological examination, idiopathic unilateral common oculomotor nerve palsy was identified for which improvement with steroids was noted in the patient. Discussion: Idiopathic unilateral complete oculomotor nerve palsy is considered as a diagnosis of exclusion when all the diagnostic parameters fail to signify and positive results. The vague symptomatic presentation of the disease condition further compels the treating physician to carry out several panels of laboratory to radiological investigations. But if identified in time the treatment modality is straightforward. Conclusion: The diagnostic quandary in timely identification of such disease conditions needs a pertinent diagnostic guideline so as to avoid the unwanted panel of investigations.

What every paediatrician needs to know about mechanical ventilation.

Invasive mechanical ventilation (MV) is one of the most practiced interventions in the intensive care unit (ICU) and is unmistakably lifesaving for children with acute respiratory failure (ARF). However, if delivered inappropriately (i.e. ignoring the respiratory system mechanics and not targeted to the need of the individual patient at a specific time point in the disease trajectory), the side effects will outweigh the benefits. Decades of experimental and clinical investigations have resulted in a better understanding of three important detrimental effects of MV. These are ventilation-induced lung injury (VILI), patient self-inflicted lung injury (P-SILI), and ventilation-induced diaphragmatic injury (VIDD). VILI, P-SILI, and VIDD have in common that they occur when there is either too much or too little ventilatory assistance.Conclusion:The purpose of this review is to give the paediatrician an overview of the challenges to prevent these detrimental effects and titrate MV to the individual patient needs.