Pomalidomide in patients with multiple myeloma: potential impact on the reconstitution of a functional T-cell immunity.

BACKGROUND: Pomalidomide, a third-generation oral immunomodulatory drug, exhibits efficacy in patients with relapsed multiple myeloma or those refractory to bortezomib and lenalidomide (RRMM). METHODS: In this clinical context, we employed flow cytometry and CDR3 spectratyping to monitor the dynamics of the T-cell repertoire during Pomalidomide treatment, aiming to investigate its potential to reverse the immunological abnormalities characteristic of RRMM. RESULTS: By flow cytometry at baseline we found a significant decrease in CD4 + frequency in MM patients, while CD8 + frequency were significantly higher in patients when compared to controls. Most T cell populations remained stable across all time points, except for CD4 + frequency, which notably decreased from t1 to subsequent assessments. Our investigation revealed as most relevant finding the notable increase in CD4 + expansions and the growing prevalence of patients manifesting these expansions. This pattern is even more evident in patients receiving their treatment until t3 and therefore still responding to treatment with Pomalidomide. We also conducted a comparison of spectratyping data before and after treatment, substantially demonstrating a relatively stable pattern throughout the course of Pomalidomide treatment. CONCLUSIONS: These observations imply that Pomalidomide treatment influences the T-cell repertoire, particularly in the CD4 + subpopulation during the later stages of treatment, raising speculation about the potential involvement of these lymphocyte expansions in mechanisms related to antitumor immunity.

Strain-specific effects of probiotics on depression and anxiety: a meta-analysis.

INTRODUCTION: Depression and anxiety are pervasive mental health disorders with substantial global burdens. Probiotics, live microorganisms known for their health benefits, have emerged as a potential therapeutic intervention for these conditions. This systematic review and meta-analysis aim to evaluate the strain-specific effects of probiotics on relieving depressive and anxiety symptoms while elucidating underlying mechanisms. METHODS: EMBASE, Cochrane CENTRAL and PubMed/Medline were systematically queried to identify studies released until May 15, 2024. Randomized Controlled Trials (RCTs) that employed standardized assessment tools for depression and anxiety namely Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Depression Anxiety Stress Scales (DASS), or Montgomery-Asberg Depression Rating Scale (MADRS) were included. RESULTS: 12 RCTs involving 707 participants were included. Seven RCTs utilizing the BDI questionnaire demonstrated a significant decrease in depressive symptoms favoring probiotics containing strains such as Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium breve, and Bifidobacterium longum (MD: -2.69, CI95%: -4.22/-1.16, p value: 0.00). Conversely, RCTs using HAMD showed a non-significant reduction in depressive symptoms (MD: -1.40, CI95%: -3.29/0.48, p value: 0.14). RCTs employing DASS and MADRS scales also showed no significant differences. CONCLUSION: This meta-analysis offers valuable insights into the strain-specific effects of probiotics containing Lactobacillus and Bifidobacterium species on depressive and anxiety symptoms. While our findings suggest a significant reduction in depressive symptoms based on the BDI scale favoring probiotics, the lack of significant effects observed on the HAMD, DASS, and MADRS scales underscores the complexity inherent in these conditions. It is imperative to acknowledge the mixed results across different measurement scales, indicating the need for cautious interpretation. Therefore, we advocate for a nuanced understanding of probiotics' impacts on various dimensions of mood, emphasizing the necessity for further research.

Muscle texture features on preoperative MRI for diagnosis and assessment of severity of congenital muscular torticollis.

OBJECTIVES: To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT). MATERIAL AND METHODS: The T1- and T2-weighted imaging, Q-dixon, and T1-mapping MRI data of 38 children with CMT were retrospectively analyzed. The region of interest (ROI) was manually drawn at the level of the largest cross-sectional area of the SCM on the affected side. MaZda software was used to obtain the texture features of the T2WI sequences of the ROI in healthy and affected SCM. A radiomics diagnostic model based on muscle texture features was constructed using logistic regression analysis. Fatty infiltration grade was calculated by hematoxylin and eosin staining, and fibrosis ratio by Masson staining. Correlation between the MRI parameters and pathological indicators was analyzed. RESULTS: There was positive correlation between fatty infiltration grade and mean value, standard deviation, and maximum value of the Q-dixon sequence of the affected SCM (correlation coefficients, 0.65, 0.59, and 0.58, respectively, P < 0.05).Three muscle texture features-S(2,2)SumAverg, S(3,3)SumVarnc, and T2WI extreme difference-were selected to construct the diagnostic model. The model showed significant diagnostic value for CMT (P < 0.05). The area under the curve of the multivariate conditional logistic regression model was 0.828 (95% confidence interval 0.735-0.922); the sensitivity was 0.684 and the specificity 0.868. CONCLUSION: The radiomics diagnostic model constructed using T2WI muscle texture features and MRI signal values appears to have good diagnostic efficiency. Q-dixon sequence can reflect the fatty infiltration grade of CMT.

TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.

TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 protein (ASRGL1) cleaves isoaspartates, which alter protein folding and susceptibility to proteolysis. ASRGL1 gene harbors a copy of the human endogenous retrovirus HML-2, whose overexpression contributes to ALS pathogenesis. Here we show that ASRGL1 expression was diminished in ALS brain samples by RNA sequencing, immunohistochemistry, and western blotting. TDP-43 and ASRGL1 colocalized in neurons but, in the absence of ASRGL1, TDP-43 aggregated in the cytoplasm. TDP-43 was found to be prone to isoaspartate formation and a substrate for ASRGL1. ASRGL1 silencing triggered accumulation of misfolded, fragmented, phosphorylated and mislocalized TDP-43 in cultured neurons and motor cortex of female mice. Overexpression of ASRGL1 restored neuronal viability. Overexpression of HML-2 led to ASRGL1 silencing. Loss of ASRGL1 leading to TDP-43 aggregation may be a critical mechanism in ALS pathophysiology.

Clinical analysis of 1301 children with hand and foot fractures and growth plate injuries.

BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.

The Genetic Landscape of Systemic Rheumatic Diseases: A Comprehensive Multigene-Panel Study Identifying Key Gene Polymorphisms.

Systemic rheumatic diseases, including conditions such as rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus, represent a complex array of autoimmune disorders characterized by chronic inflammation and diverse clinical manifestations. This study focuses on unraveling the genetic underpinnings of these diseases by examining polymorphisms in key genes related to their pathology. Utilizing a comprehensive genetic analysis, we have documented the involvement of these genetic variations in the pathogenesis of rheumatic diseases. Our study has identified several key polymorphisms with notable implications in rheumatic diseases. Polymorphism at chr11_112020916 within the IL-18 gene was prevalent across various conditions with a potential protective effect. Concurrently, the same IL18R1 gene polymorphism located at chr2_103010912, coding for the IL-18 receptor, was observed in most rheumatic conditions, reinforcing its potential protective role. Additionally, a further polymorphism in IL18R1 at chr2_103013408 seems to have a protective influence against the rheumatic diseases under investigation. In the context of emerging genes involved in rheumatic diseases, like PARK2, a significant polymorphism at chr6_161990516 was consistently identified across different conditions, exhibiting protective characteristics in these pathological contexts. The findings underscore the complexity of the genetic landscape in rheumatic autoimmune disorders and pave the way for a deeper understanding of their etiology and the possible development of more targeted and effective therapeutic strategies.

16S rRNA sequencing analysis of the oral and fecal microbiota in colorectal cancer positives versus colorectal cancer negatives in Iranian population.

BACKGROUND: Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers. MATERIAL AND METHODS: A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform. RESULTS: Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs. CONCLUSION: Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Evaluation of mycobacteria infection prevalence and optimization of the identification process in North Sardinia, Italy.

IMPORTANCE: Mycobacterial infection is a major threat to public health worldwide. Accurate identification of infected species and drug resistance detection are critical factors in treatment. We focused on shortening the turn-around time of identifying mycobacteria species and antibiotic resistance tests.

Epstein-Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders.

Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocytes glycoprotein-antibody disease (MOGAD) are distinct autoimmune demyelinating disorders characterized by varying clinical and pathological characteristics. While the precise origins of these diseases remain elusive, a combination of genetic and environmental factors, including viral elements, have been suggested as potential contributors to their development. Our goal was to assess the occurrence of antibodies against pathogenic peptides associated with Epstein-Barr virus (EBV) and the human endogenous retrovirus-W (HERV-W) in serum samples obtained from Japanese individuals diagnosed with MS, NMOSD, and MOGAD and to make comparisons with a group of healthy controls (HCs). We conducted a retrospective analysis involving 114 Japanese participants, comprising individuals with MS (34), NMOSD (20), MOGAD (20), and HCs (40). These individuals were tested using a peptide-based enzyme-linked immunosorbent assay. A marked increase in antibody response against EBV nuclear antigen 1 (EBNA1)386-405 was observed in the serum of MS and MOGAD patients, as compared to HCs. Notably, we observed a correlation between antibodies against EBNA1386-405 and HERV-W486-504 peptides in a subset of the antibody-positive MS patients. These findings emphasize the involvement of EBV in the pathogenesis of MS and potentially MOGAD, suggesting its role in the reactivation of HERV-W.

Unraveling the prognostic significance and molecular characteristics of tumor-infiltrating B lymphocytes in clear cell renal cell carcinoma through a comprehensive bioinformatics analysis.

Introduction: Clear cell renal cell carcinoma (ccRCC) is a prevalent subtype of kidney cancer that exhibits a complex tumor microenvironment, which significantly influences tumor progression and immunotherapy response. In recent years, emerging evidence has underscored the involvement of tumor-infiltrating B lymphocytes (TIL-Bs), a crucial component of adaptive immunity, and their roles in ccRCC as compared to other tumors. Therefore, the present study endeavors to systematically explore the prognostic and molecular features of TIL-Bs in ccRCC. Methods: Initially, xCell algorithm was used to predict TIL-Bs in TCGA-KIRC and other ccRCC transcriptomic datasets. The Log-Rank test and Cox regression were applied to explore the relationship of B-cells with ccRCC survival. Then, we used WGCNA method to identify important modules related to TIL-Bs combining Consensus subcluster and scRNA-seq data analysis. To narrow down the prospective biomarkers, a prognostic signature was proposed. Next, we explored the feature of the signature individual genes and the risk-score. Finally, the potential associations of signature with clinical phenotypes and drugs were investigated. Results: Preliminary, we found ccRCC survival was negatively associated with TIL-Bs, which was confirmed by other datasets. Afterwards, ten co-expression modules were identified and a distinct ccRCC cluster was subsequently detected. Moreover, we assessed the transcriptomic alteration of B-cell in ccRCC and a relevant B-cell subtype was also pinpointed. Based on two core modules (brown, red), a 10-gene signature (TNFSF13B, SHARPIN, B3GAT3, IL2RG, TBC1D10C, STAC3, MICB, LAG3, SMIM29, CTLA4) was developed in train set and validated in test sets. These biomarkers were further investigated with regards to their differential expression and correlation with immune characteristics, along with risk-score related mutations and pathways. Lastly, we established a nomogram combined tumor grade and discovered underlying drugs according to their sensitivity response. Discussion: In our research, we elucidated the remarkable association between ccRCC and B-cells. Then, we detected several key gene modules, together with close patient subcluster and B-cell subtype,which could be responsible for the TIL-Bs in ccRCC. Moreover, we proposed a 10-gene signature and investigated its molecular features from multiple perspectives. Overall, understanding the roles of TIL-Bs could aid in the immunotherapeutic approaches for ccRCC, which deserve further research to clarify the implications for patient prognosis and treatment.

Cross-reactivity between Mycobacterium avium subspecies paratuberculosis 4027 peptide and Human IRF5 may contribute to Multiple Sclerosis in Iranian patients.

Background: The etiology of Multiple sclerosis (MS) is complicated and can be affected by several environmental factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) infection in genetically predisposed individuals. The link between MAP and MS depends on host genetic and epigenetic aspects and population-based features that require further investigation. We aimed to study the possible role of MAP in triggering MS using molecular and serological methods. Materials and methods: This case-control study examined 200 blood samples (100 MS patients and 100 HCs) to search for the MAP-specific IS900 gene. In addition, ELISA was conducted to determine the humoral response against MAP_402718-32 and its human IRF5424-434 peptide homolog. Results: The frequency of MAP detection based on the molecular method in MS patients and HCs was 48 % and 13 %, respectively (p < 0.0001). The presence of antibodies against MAP_402718-32 and IRF5424-434 was 55 % and 65 % in MS patients versus 9 % and 7 % in HCs, respectively (p < 0.0001). A good correlation was observed between MAP_4027 and IRF5 antibodies (r = 0.5782, p < 0.0001), indicating that the same antibodies recognized common peptide epitopes. Conclusion: Our research revealed a significant association between MAP and MS, highlighting the possible role of MAP as an important infection trigger factor of MS. It is hypothesized that cross-reactivity between MAP4027 and IRF5 may dysregulate immune homeostasis.

Association of HLA-A*11:01, -A*24:02, and -B*18:01 with Prostate Cancer Risk: A Case-Control Study.

The major histocompatibility complex (MHC) loci, the most polymorphic regions within the human genome, encode protein complexes responsible for antigen presentation and CD4+ and CD8+ cell activation. In prostate cancer (PCa), the second most diagnosed cancer in the male population, MHC loci undergo significant changes in their expression patterns, which affect the ability of the immune system to attack and eliminate malignant cells. The purpose of this study was to explore the genetic diversity of human leukocyte antigen (HLA)-A and HLA-B in patients with PCa and healthy controls (HCs) by performing HLA genotyping using NGS technology. The analysis highlighted statistically significant differences (p < 0.05) in the prevalence of three alleles (A*11:01, A*24:02, and B*18:01). Among the HCs analyzed, 14.89% had A*11:01, 20.21% had A*24:02, and 30.61% had B*18:01; while 5.21% of patients with PCa presented A*11:01, 9.38% presented A*24:02, 18.08% presented B*18:01. Odds ratio (OR) calculations underlined a negative association between the three alleles and the risk of PCa (OR < 1). The results presented in this study suggest a protective role of A*11:01, A*24:02, and B*18:01 in PCa.

Detection of Mycobacterium avium Subspecies paratuberculosis in the Blood of Patients with Rheumatoid Arthritis by Using Serological and Molecular Techniques.

The role of Mycobacterium avium subspecies paratuberculosis (MAP) in triggering rheumatoid arthritis (RA) could be a population-specific phenomenon. This study explored the relationship between MAP and RA using serological and molecular techniques; In this case-control study, 239 Iranian participants, including 120 RA patients and 119 controls, were enrolled. The indirect ELISA was designed to diagnose antibodies against MAP3865c125-133 and Zinc transporter 8 (ZnT8)178-186. The Nested-Polymerase Chain Reaction (PCR) detected MAP in blood; The frequency of MAP in RA patients and controls was 31.9% and 12.5%, respectively (P = 0.002). The antibodies against MAP3865c125-133 and ZnT8178-186 were 42.9% and 37% in RA patients and 14.2% and 11.7% in the controls, respectively (P < 0.0001). Interestingly, positive ELISA results in previously diagnosed (PD) RA were more common than newly diagnosed (ND) RA patients (P < 0.05).; The findings showed a higher frequency of MAP and its antibodies in the RA patients than in the controls. This data indicated MAP as one of RA's predisposing factors. Also, this first report implies the high positivity of MAP in Iranian RA patients.

Clinical characteristics of 1124 children with epiphyseal fractures.

BACKGROUND: In this study, to provide a theoretical basis for understanding the clinical characteristics of epiphyseal fractures in children and improving their management, we explored and analyzed the proportions of different types of epiphyseal fractures in children and evaluated the causes of injury and epidemiological characteristics. METHODS: We retrospectively analyzed children younger than 18 years with fresh epiphyseal fractures who were admitted to our hospital from July 2015 to February 2020. Demographic information, injury mechanisms, fracture characteristics, fracture classification and surgical information were collected. RESULTS: A total of 1124 pediatric patients (1147 epiphyseal fractures), including 789 boys and 335 girls, were included in this study. Epiphyseal fractures were classified as Salter-Harris type II (1002 cases), type IV (105 cases), type III (25 cases), Salter-Harris type I (14 cases), and Salter-Harris type V (1 case). The number of fracture sites peaked in the adolescent group (440 cases). The most three common sites of epiphyseal fractures were the distal radius (460 cases) in which Salter-Harris type II fractures were the most common (454 cases) and Salter-Harris type I (3 cases), Salter-Harris type IV (2 cases), Salter-Harris type III was the least common (1 case). Followed by phalanges of fingers (233 cases) in which Salter-Harris type II fractures were the most common (224 cases) and Salter-Harris type IV (4 cases), Salter-Harris type I (3 cases), Salter-Harris type III fractures were the least common (2 cases). Distal humerus (146 cases) in which Salter-Harris type II fractures were the most common (95 cases), followed by Salter-Harris type IV (49 cases), Salter-Harris type I fractures were the least common (2 cases). The most three important causes of fractures were falls (720 patients), car accident injuries (68 patients), and basketball falls (43 patients). Among the 1124 children with epiphyseal fractures, 1058 were treated mainly by surgery and the ratio of open and closed reduction was 1:5.3. Eighty-eight patients showed an interval > 72 h between the injury and the hospital visit. Among these 88 patients, the most common fracture type was distal radial epiphyseal fracture (32 cases), and all fractures were of Salter-Harris type II. CONCLUSIONS: The epidemiological characteristics of epiphyseal fractures in children indicate the need to strengthen health and safety education and protective measures to prevent the occurrence of these fractures in children. In addition, emergency surgeons and orthopedic surgeons in general hospitals should strengthen their basic knowledge of diagnosing and treating epiphyseal injuries in children to reduce missed diagnoses, misdiagnoses or malpractice.

Olfactory Impairment Is the Main Predictor of Higher Scores at REM Sleep Behavior Disorder (RBD) Screening Questionnaire in Parkinson's Disease Patients.

INTRODUCTION: Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined. OBJECTIVE: The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients. METHODS: In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered. RESULTS: Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients (p ≤ 0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p ≤ 0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p ≤ 0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age. CONCLUSIONS: The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Anti-HERV-K Drugs and Vaccines, Possible Therapies against Tumors.

The footprint of human endogenous retroviruses (HERV), specifically HERV-K, has been found in malignancies, such as melanoma, teratocarcinoma, osteosarcoma, breast cancer, lymphoma, and ovary and prostate cancers. HERV-K is characterized as the most biologically active HERV due to possession of open reading frames (ORF) for all Gag, Pol, and Env genes, which enables it to be more infective and obstructive towards specific cell lines and other exogenous viruses, respectively. Some factors might contribute to carcinogenicity and at least one of them has been recognized in various tumors, including overexpression/methylation of long interspersed nuclear element 1 (LINE-1), HERV-K Gag, and Env genes themselves plus their transcripts and protein products, and HERV-K reverse transcriptase (RT). Therapies effective for HERV-K-associated tumors mostly target invasive autoimmune responses or growth of tumors through suppression of HERV-K Gag or Env protein and RT. To design new therapeutic options, more studies are needed to better understand whether HERV-K and its products (Gag/Env transcripts and HERV-K proteins/RT) are the initiators of tumor formation or just the disorder's developers. Accordingly, this review aims to present evidence that highlights the association between HERV-K and tumorigenicity and introduces some of the available or potential therapies against HERV-K-induced tumors.

Low concentrations of Ambrosia maritima L. phenolic extract protect endothelial cells from oxidative cell death induced by H2O2 and sera from Crohn's disease patients.

ETHNOPHARMACOLOGICAL RELEVANCE: A rising resort to herbal therapies in Crohn's disease (CD) alternative treatments has been recently observed due to their remarkable natural efficiency. In this context, the weed plant Ambrosia maritima L., traditionally known as Hachich el Aouinet in Algeria and as Damsissa in Egypt and Sudan, is widely used in North African folk medicine to treat infections, inflammatory diseases, gastrointestinal and urinary tract disturbances, rheumatic pain, respiratory problems, diabetes, hypertension and cancer. AIM OF THE STUDY: To assess an Ambrosia maritima L. phenolic extract for its phenolic profile composition, its potential antioxidant activity in vitro, and its cytoprotective effect on cultured primary human endothelial cells (ECs) stressed with H2O2 and sera from CD patients. MATERIALS AND METHODS: Phenolic compound extraction was performed with a low-temperature method. Extract chemical profile was attained by HPLC-DAD/ESI-MS. The extract in vitro antioxidant activity was assessed using several methods including cupric ion reducing power, DPPH radical scavenging assay, O-Phenanthroline free radical reducing activity, ABTS cation radical decolourisation assay, Galvinoxyl free radicals scavenging assay. Intracellular reactive oxygen species levels were evaluated in human endothelial cells by H2DCFDA, while cell viability was assessed by MTT. RESULTS: The phenolic compounds extraction showed a yield of 17.66% with three di-caffeoylquinic acid isomers detected for the first time in Ambrosia maritima L. Using different analytical methods, a significant in vitro antioxidant activity was reported for the Ambrosia maritima L. extract, with an IC50 value of 14.33 ± 3.86 µg/mL for the Galvinoxyl antioxidant activity method. Challenged with ECs the Ambrosia maritima L. extract showed a biphasic dose-dependent effect on H2O2-treated cells, cytoprotective and antioxidant at low doses, and cytotoxic and prooxidant at high doses, respectively. Viability and ROS levels data also demonstrated a prooxidant and cytotoxic effect of CD sera on cultured ECs. Interestingly, 10 µg/mL of Ambrosia maritima L. extract was able to counteract both CD sera-induced oxidative stress and ECs death. CONCLUSION: Our data indicated Ambrosia maritima L. as a source of bioactive phenolics potentially employable as a natural alternative for CD treatment.

Phantosmia in Parkinson's Disease: A Systematic Review of the Phenomenology of Olfactory Hallucinations.

Olfactory dysfunction is a prevalent non-motor symptom in Parkinson's disease (PD), affecting approximately 65-90% of subjects. PD patients may also report odor perception in the absence of any external source, often referred to as olfactory hallucinations (OHs) or phantosmia. This study aims to explore the current understanding of OHs in PD and offer a comprehensive overview of their prevalence and characteristics. We conducted a systematic search of the literature published on PubMed from inception to July 2023 regarding OHs in PD, following PRISMA guidelines. From the 2875 studies identified through database searching, 29 studies fulfilled the necessary criteria and underwent data extraction. The frequency of OHs in PD patients varies widely, ranging from 0.5% to 18.2%, with female prevalence ranging from 36% to 75% of the patients. Olfactory experiences may vary widely, ranging from pleasant scents to unpleasant odors. Several studies have indicated the concurrent presence of other types of hallucinations alongside phantosmia, especially visual and auditory hallucinations. OHs in PD are a type of hallucination that has been largely overlooked. To gain a deeper understanding of OHs in PD patients, the next crucial step should involve the development and validation of a dedicated questionnaire.

Segmentation of Substantia Nigra in Brain Parenchyma Sonographic Images Using Deep Learning.

Currently, Parkinson's Disease (PD) is diagnosed primarily based on symptoms by experts clinicians. Neuroimaging exams represent an important tool to confirm the clinical diagnosis. Among them, Brain Parenchyma Sonography (BPS) is used to evaluate the hyperechogenicity of Substantia Nigra (SN), found in more than 90% of PD patients. In this article, we exploit a new dataset of BPS images to investigate an automatic segmentation approach for SN that can increase the accuracy of the exam and its practicability in clinical routine. This study achieves state-of-the-art performance in SN segmentation of BPS images. Indeed, it is found that the modified U-Net network scores a Dice coefficient of 0.859 ± 0.037. The results presented in this study demonstrate the feasibility and usefulness of SN automatic segmentation in BPS medical images, to the point that this study can be considered as the first stage of the development of an end-to-end CAD (Computer Aided Detection) system. Furthermore, the used dataset, which will be further enriched in the future, has proven to be very effective in supporting the training of CNNs and may pave the way for future studies in the field of CAD applied to PD.