A neurotherapeutic approach with Lacticaseibacillus rhamnosus E9 on gut microbiota and intestinal barrier in MPTP-induced mouse model of Parkinson's disease.

The gut microbiota plays a crucial role in neural development and progression of neural disorders like Parkinson's disease (PD). Probiotics have been suggested to impact neurodegenerative diseases via gut-brain axis. This study aims to investigate the therapeutic potential of Lacticaseibacillus rhamnosus E9, a high exopolysaccharide producer, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of PD. C57BL/6 mice subjected to MPTP were fed L. rhamnosus E9 for fifteen days and sacrificed after the last administration. Motor functions were determined by open-field, catalepsy, and wire-hanging tests. The ileum and the brain tissues were collected for ELISA, qPCR, and immunohistochemistry analyses. The cecum content was obtained for microbiota analysis. E9 supplementation alleviated MPTP-induced motor dysfunctions accompanied by decreased levels of striatal TH and dopamine. E9 also reduced the level of ROS in the striatum and decreased the DAT expression while increasing the DR1. Furthermore, E9 improved intestinal integrity by enhancing ZO-1 and Occludin levels and reversed the dysbiosis of the gut microbiota induced by MPTP. In conclusion, E9 supplementation improved the MPTP-induced motor deficits and neural damage as well as intestinal barrier by modulating the gut microbiota in PD mice. These findings suggest that E9 supplementation holds therapeutic potential in managing PD through the gut-brain axis.

Topical menthol for chemotherapy-induced peripheral neuropathy: a randomised controlled trial in breast cancer.

OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) symptom is one of the side effects of paclitaxel in breast cancer patients. This randomised controlled study was conducted to investigate the effect of topical menthol applied on the hands and feet of breast cancer patients receiving chemotherapy on CIPN symptoms. METHODS: 60 breast cancer patients receiving chemotherapy were randomly assigned to an intervention group (n=30), which received topical menthol treatment, or a control group (n=30), which received standard care. Both groups continued their routine pharmacological treatments throughout the study. The intervention group applied 1% menthol topically to their hands and feet two times a day. The effect of the intervention on CIPN symptoms was evaluated 3 weeks and 6 weeks after the intervention. RESULTS: The intervention group showed a significantly greater improvement in CIPN symptoms over time compared with the control group, with an effect size of η2=0.214 for the group×time interaction. Additionally, the intervention group exhibited a notable positive change in the exposure subscale of the CIPN rating scale, with an effect size of η2=0.114. CONCLUSIONS: Topical application of menthol significantly mitigates the symptoms of CIPN in breast cancer patients. This study supports the use of menthol as an effective adjunctive treatment for CIPN. TRIAL REGISTRATION NUMBER: NCT05429814.

The Effect of Thymoquinone on the TNF-α/OTULIN/NF-κB Axis Against Cisplatin-Induced Testicular Tissue Damage.

One of the adverse effects of the antineoplastic drug cisplatin (CS) is damage to testicular tissue. This study aimed to examine the potential therapeutic effect of thymoquinone (TQ), a strong antioxidant, against testicular damage caused by CS. In the experiment, 28 rats were used, and the rats were randomly divided into four groups: control (n = 7), CS (n = 7), CS + TQ (n = 7), and TQ (n = 7). The experiment was called off after all treatments were finished on day 15. Blood serum and testicular tissues were utilized for biochemical, histological, immunohistochemical, mRNA expression, and gene protein investigations. The testosterone level decreased and oxidative stress, histopathological damage, dysregulation in mitochondrial dynamics, inflammation and apoptotic cells increased in testicular tissue due to CS administration. TQ supplementation showed anti-inflammatory, antioxidant, and anti-apoptotic effects in response to CS-induced testicular damage. In addition, TQ contributed to the reduction of CS-induced toxic effects by regulating the TNF-α/OTULIN/NF-κB pathway. TQ supplementation may be a potential therapeutic strategy against CS-induced testicular damage by regulating the TNF-α/OTULIN/NF-κB axis, inhibiting inflammation, oxidative stress, and apoptosis.

Effect of hypoxia-inducible factor-1 alpha expression on survival in patients with metastatic cervical squamous cell carcinoma treated with first-line chemotherapy and bevacizumab.

This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

A Case of Nasal Glial Heterotopia That Can Be Misdiagnosed as Storiform Patterned Sclerotic Fibroma/Collagenoma.

OBJECTIVE: Nasal glioma, also known as nasal glial heterotopia, is a rare tumor-like lesion that often affects newborns or infants with no hereditary predisposition. CASE REPORT: A 4-year-old child with a growth on the nasal dorsum since birth was diagnosed with nasal glial heterotopia/nasal glioma. The lesion showed a sclerotic fibroma/collagenoma-like storiform pattern with entrapped glial tissue that was S100 and GFAP positive. CONCLUSION: When a biopsy of the nasal dorsum demonstrates sclerotic microscopic findings with a storiform pattern, nasal glioma should be considered before making a diagnosis in the collagen-rich tissue spectrum (collagenoma or Gardner's fibroma), and an immunohistochemical panel should be requested to demonstrate the presence of an unrecognized light microscopically visible glial component.

Is it Possible to Obtain Immunofluorescence Data in Formalin-Fixed Paraffin-Embedded Skin Samples for the Diagnosis of Pemphigus Vulgaris and Bullous Pemphigoid.

OBJECTIVE: The gold-standard method for assessment of autoimmune bullous disease is direct/indirect immunofluorescence (IF) examination applied to fresh frozen tissue. Since the sensitivity of IF is greatly reduced in formalin-fixed paraffin-embedded (FFPE) tissues, IF cannot be relied upon in these samples. However, immunohistochemistry with the C4d antibody is a promising marker used as a surrogate for immune complex deposition, in nephropathology practice, and the paraffin IF method is also used as a `salvage` technique when fresh frozen tissue is not available or lacks glomeruli. We aimed to investigate whether it is possible to obtain immunofluorescence data from FFPE tissues diagnosed with bullous pemphigoid (BP) and pemphigus vulgaris (PV) and its relationship with inflammatory parameters in the skin. MATERIAL AND METHODS: Eighty-nine in-house cases with both IgG and C3 positivity by routine immunofluorescence examination were included in the study. Inflammation parameters were evaluated in hematoxylin-eosin sections. Immunofluorescence study with IgG protease digestion and C4d immunohistochemistry were performed. RESULTS: Results of 83 biopsies were obtained by paraffin immunofluorescence with IgG. There were positive reactions in 28 (34%) of these 83 biopsies. Five of the 28 positive results belonged to BP (18%), and 23 were PV (82%). Ten positive results were on lesional skin (36%), and 18 (64%) were on non-lesional skin. In the immunohistochemical study with C4d, 84 biopsy results were obtained. There were positive reactions in 34 (40.4%) of 84 biopsies. Of the 34 positive results, 12 belonged to BP (35.3%) and 22 to PV (64.7%). Again, 22 (64.7%) of 34 positive results belonged to lesional skin, and 12 (35.3%) belonged to non-lesional skin. When both techniques were used together, 44 (54%) of 81 biopsies yielded positive results for at least one of the two studies, while in 37 (46%), both tests showed negative results. CONCLUSION: The sensitivity of both IgG and C4d was less than in the literature, especially in BP-diagnosed biopsies. Positive samples were mostly PV. In conclusion, obtaining immunofluorescence data in FFPE samples is possible and is independent of the related skin being lesional or not, however, negative results should not be relied upon.

Teriflunomide-Induced Palmoplantar Pustular Psoriasis: Case Report and Review of the Literature.

Teriflunomide is a once-daily oral immunomodulatory disease-modifying treatment for multiple sclerosis (MS). Skin reactions are an infrequent side effect of teriflunomide. Here, we present the case of a 52-year-old female patient with ankylosing spondylitis who was consulted for demyelinating lesions and limb weakness. She was diagnosed with multiple sclerosis and started treatment with teriflunomide. Palmoplantar pustular psoriasis developed after three weeks of treatment initiation. It is a rare side effect related to teriflunomide.

The impact of COVID-19 pandemic on anxiety levels among patients who have to go to the hospital due to chronic illnesses: A prospective study.

INTRODUCTION: Cancer and hemodialysis (HD) patients are at high risk for COVID-19. In our study, we aimed to evaluate the effect of pandemic on anxiety in these patients. METHODS: One hundred and six oncology and 97 HD patients participated in the study. Anxiety levels were assessed by using the Beck Anxiety Inventory (BAI) and State-Trait Anxiety Inventory (STAI). At the end of 8-month follow-up, these questionnaires were re-administered. RESULTS: During this period, 38 patients (38/203; 18.7%) had COVID-19 infection. Twenty-three patients (23/203; 11.3%) died due to COVID-19 and/or other causes. One hundred and thirteen of the remaining patients were participated in the second questionnaire. Having COVID-19 was not the independent factor for changes in STAI, and BAI scores in any regression models. CONCLUSION: Having COVID-19 does not affect the increased anxiety levels in HD and oncology patients. The effect of the pandemic may have remained in the background, as these patients have more concerns about their own diseases.

Stromal or intraepithelial tumor-infiltrating lymphocytes: which one has more prognostic significance in cervical cancer?

PURPOSE: To investigate the effect of tumor-infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) on treatment results in patients with cervical squamous cell carcinoma who underwent definitive or adjuvant radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: Pathological specimens were evaluated from 96 cervical cancer patients who were treated with definitive or adjuvant RT/CRT between April 2001 and January 2020. The percentage of intraepithelial TILs (iTILs) and stromal TILs (sTILs) were calculated, and immunohistochemistry was used for identifying lymphocyte lineage with CD4, CD8, and CD20 antibodies and macrophages with CD68 antibody. Prognostic values of TILs/TAMs on oncological outcomes were evaluated. RESULTS: Thirty patients had early-stage disease and 66 patients had advanced-stage disease. Sixty-three and 33 patients received adjuvant RT and definitive CRT, respectively. Low number of sCD20 positive cells was associated with large tumor size and parametrial invasion. In multivariate analysis, low percentage of sTILs and advanced-stage disease were independent poor prognostic factors for overall survival, disease-free survival (DFS), and distant metastasis-free survival; low number of sCD4 positive cells was also an independent poor prognostic factor for DFS. Low percentage of sTILs and low number of sCD8 positive cells was correlated with high rates of distant metastasis (p = 0.038 and p = 0.025, respectively). CONCLUSION: sTILs have superior predictive value than iTILs in terms of prognosis. Stromal compartment should be investigated as a routine practice in TIL studies in cervical cancer. Intensifying the treatment in cervical cancer patients with low number of sTILs should be studied in further investigations.

A Rare Case of Post-pubertal Pure Yolk-sac Tumour Incidentally Diagnosed after Surgical Intervention for Fournier's Gangrene.

The testicular tumour is the most common solid malignancy in males between the ages of 15 and 35 years. Testicular tumours most commonly present with a painless testicular mass. Fournier's gangrene is necrotising fasciitis of the genital, perineal, and perianal region characterized by the microvascular thrombosis and skin necrosis, and is most commonly seen in elderly males with the comorbid conditions. To the best of our knowledge, there is no published case of testicular tumour presenting as Fournier's gangrene. Herein, we report a case of a young adult male, otherwise healthy, who presented to the emergency room with Fournier's gangrene and was found to have a metastatic post-pubertal pure yolk-sac tumour of the testis which is extremely rare in the adults. Key Words: Fournier's gangrene, Yolk sac tumour, Testicular neoplasm.

Clonal B-cell proliferations developing in the background of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder: A case series.

Clonal B-cell proliferations and B-cell lymphomas may co-occur in the background of follicular helper T-cell (TFH)-derived lymphomas, most associated with EBV, which has been a well-known fact for many years in the prototypical entity "TFH lymphoma, angioimmunoblastic-type." Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is also a TFH-derived clonal proliferation. We searched the archives and identified four cases of CD4+ PCSM-LPD with accompanying clonal B-cell proliferation (one of which showed EBER positivity), and one longstanding case of CD4+ PCSM-LPD, in the background of which a B-cell lymphoma had developed. These five cases broaden experience on CD4+ PCSM-LPD with accompanying B-cell proliferations and also support routine evaluation of these cases with EBV in situ hybridization, to better determine whether or not there is an association with EBV.

Evaluation of the Preoperative Haematological Parameters Predicting the High T-Stage and Fuhrman Grade in Renal Cell Carcinoma.

OBJECTIVE: To investigate the role of cost-effective and widely used hemogram parameters in predicting stage and histological grade. STUDY DESIGN: An analytical study. PLACE AND DURATION OF STUDY: Konya Research and Training Hospital, Turkey from January to June 2020. METHODOLOGY: Pre-nephrectomy hemogram parameters and post-nephrectomy pathology reports of 180 renal cell carcinoma patients, among 553 patients, who had undergone nephrectomy between 2009-2019 were evaluated. The patients were grouped as low risk and high risk in terms of TNM stage and Fuhrman grade; and clinicopathological variables were compared between the groups. Multivariate logistic regression analysis was used to determine the parameters predicting independently the high T stage (T3-T4) and the high Fuhrman grade (G3-G4). RESULTS: While 31 (17.2%) of 180 patients were in the high T stage; 69 (38.3%) were in the high Fuhrman grade. In the logistic regression analysis, NLR, LMR, and hematocrit predicted independently high T stage, while hematocrit and LMR predicted independently the high Fuhrman grade. CONCLUSION: LMR, NLR, and hematocrit were found to be more significant than other parameters, which are among the hemogram parameters that can guide clinicians during staging, which is important for prognosis and treatment decisions. KEY WORDS: Renal cell carcinoma, Tumor staging, Tumor grading.

Growth Pattern of the Tympanic Ring in Human Fetuses.

OBJECTIVES: The study aimed to display the growth pattern of the tympanic ring in fetal cadavers of 20-30 weeks of gestation. METHODS: In the study, 32 temporal bones of 16 fetuses (8 males, 8 females) of 24.62 ± 3.44 weeks of gestation were dissected to measure the height (TRH), width (TRW), and perimeter (TRP) of the annulus, and the width (TNW) of the opening part of the annulus at the level of the tympanic notch. RESULTS: The TRH, TRW, TRP, and TNW were measured as 8.25 ± 1.04 mm, 7.64 ± 1.08 mm, 24.93 ± 3.40 mm, and 4.01 ± 0.91 mm, respectively. The parameters were similar at the seventh and eighth months of gestation; therefore, there was no variation from the seventh month. Linear function was calculated as y = 1.328 + 0.281 x weeks (P < .001) for the TRH, y = 1.284 + 0.258 x weeks (P < .001) for the TRW, y = 3.367 + 0.876 x weeks (P < .001) for the TRP, and y = -0.603 + 0.188 x weeks (P < .001) for the TNW. CONCLUSION: The parameters (TRH, TRW, TRP, and TNW) did not alter from the seventh month in utero. The linear functions (which represent the growth pattern of the parameters) of the tympanic ring may be useful for ear professionals to guess the annulus diameters, and to diagnose growth retardation and probable congenital anomalies in utero during sonographic imaging.

Perspectives on Open Science and The Future of Scholarly Communication: Internet Trackers and Algorithmic Persuasion.

The current digital content industry is heavily oriented towards building platforms that track users' behaviour and seek to convince them to stay longer and come back sooner onto the platform. Similarly, authors are incentivised to publish more and to become champions of dissemination. Arguably, these incentive systems are built around public reputation supported by a system of metrics, hard to be assessed. Generally, the digital content industry is permeable to non-human contributors (algorithms that are able to generate content and reactions), anonymity and identity fraud. It is pertinent to present a perspective paper about early signs of track and persuasion in scholarly communication. Building our views, we have run a pilot study to determine the opportunity for conducting research about the use of "track and persuade" technologies in scholarly communication. We collected observations on a sample of 148 relevant websites and we interviewed 15 that are experts related to the field. Through this work, we tried to identify 1) the essential questions that could inspire proper research, 2) good practices to be recommended for future research, and 3) whether citizen science is a suitable approach to further research in this field. The findings could contribute to determining a broader solution for building trust and infrastructure in scholarly communication. The principles of Open Science will be used as a framework to see if they offer insights into this work going forward.