UNASSIGNED: Ménière\'s Disease, a long-term debilitating disorder has been increasingly found among patients with hypothyroidism. Our study aims to evaluate the prevalence of ménière\'s disease among hypothyroid patients and assess the interrelationship between patients\' symptomology and ménière\'s disease.
UNASSIGNED: A cross-sectional study was performed at the endocrinology clinics at Damascus Hospital and Syrian Red Crescent Hospital, Damascus, Syria between September 2021 and January 2022. Patients with hypothyroidism were interviewed using a questionnaire. The questionnaire contained questions about socio-demographic information, hypothyroid history, diagnostic criteria of ménière\'s disease, chief complaint, medical history, and lab test results. Patients, who reported ménière\'s disease symptoms, were referred to the otorhinolaryngology clinic for confirmation or exclusion of ménière\'s disease. At the clinic, patients underwent an otoscopy and a pure tone audiometry, probable and definite ménière\'s disease was diagnosed accordingly.
UNASSIGNED: Of 217 hypothyroid patients included in the sample, 17 (7.8%) were diagnosed with definite ménière\'s disease and 31 (14.3%) were diagnosed with probable ménière\'s disease. Hypothyroid symptoms reported among patients diagnosed with definite ménière\'s disease compared to no diagnosis differed by feeling low (χ2 (1, 217) = 4.014, p = 0.045), and depressive appearance (χ2 (1, 217) = 8.887, p = 0.003). Patients diagnosed with definite ménière\'s disease, probable ménière\'s disease, and both definite and probable ménière\'s disease were more likely to report that their symptoms affected their lifestyle compared to those that reported no effect (χ2 (3, 217) = 62.565, p < 0.001), (χ2 (3, 217) = 31.380, p < 0.001), and (χ2 (3, 217) = 35.542, p < 0.001), respectively.
UNASSIGNED: A high number of hypothyroid patients were diagnosed with MD. Clinicians should consider clinically screening for MD among hypothyroid patients presenting to clinics.

Cell therapy is a promising alternative treatment approach currently under study for osteoarthritis (OA), the most common chronic musculoskeletal disease. However, the mesenchymal stem cells (MSCs) used in cell therapy to treat OA are usually expanded in vitro to obtain sufficient numbers for transplantation, and their safety has not been fully assessed from multiple perspectives. Analysis of karyotypic abnormalities, in particular, is important to ensure the safety of cells; however, chromosomal mutations may also occur during the cell-expansion process. In addition, there have been many reports showing chromosome abnormalities, mainly trisomy 7, in the cartilage and synovium of patients with OA as well as in normal tissues. The suitability of cells with these karyotypic abnormalities as cells for cell therapy has not been evaluated. Recently, we assessed the safety of using cells with trisomy 7 from the osteoarthritic joint of a patient for transplantation, and we followed up with the patient for 5 years. This study showed analysis for copy number variant and whole-genome sequencing, compared with blood DNA from the same patient. We did not find any abnormalities in the genes regardless of trisomy 7. No side effects were observed for at least 5 years in the human clinical study. This suggests that the transplantation of cultured cells with trisomy 7 isolated from an osteoarthritic joint and transplanted into the osteoarthritic joints of the same person is not expected to cause serious adverse events. However, it is unclear what problems may arise in the case of allogeneic transplantation. Different types of risks will also exist depending on other transplantation routes, such as localization to the knee-joint only or circulation inflow and lung entrapment. In addition, since the cause of trisomy 7 occurrence remains unclear, it is necessary to clarify the mechanism of trisomy 7 in OA to perform cell therapy for OA patients in a safe manner.

Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an in silico prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis.

OBJECTIVE: The characteristics of COVID-19 in haematologic patients compared to non-haematologic patients have seldom been analyzed. Our aim was to analyze whether there are differences in clinical characteristics and outcome of haematologic patients with COVID-19 as compared to non-haematologic.
METHODS: Retrospective cohort study in 2 University hospitals of patients admitted with laboratory-confirmed COVID-19 included in the SEMICOVID19 database. The cohort with underlying haematologic disease was compared to a cohort of age and date-of-COVID-19-matched controls without haematologic disease (1:2).
RESULTS: 71 cases and 142 controls were included from March-May 2020.Twenty (28.1%) had received recent chemotherapy. Twelve (16.9%) were stem cell transplant recipients (SCT). Eleven (15.5%) were neutropenic concurrently with COVID-19 diagnosis.Haematologic patients presented ARDS (58.5 vs 20.7%, p = 0.0001), thrombotic complications (15.7 vs 2.1%, p = 0.002), DIC (5.7 vs 0.0%, p = 0.011), heart failure (14.3 vs 4.9%, p = 0.029) and required ICU admission (15.5 vs 2.8%, p = 0.001), MV (14.1% vs 2.1%, p 0.001), steroid (64.8 vs 33.1%, p = 0.0001), tocilizumab (33.8 vs 8.5%, p = 0.0001) or anakinra treatment (9.9% vs 0%, p = 0.0001) more often. In-hospital mortality was significantly higher (38.0% vs 18.3%, p = 0.002).
CONCLUSIONS: Our results suggest COVID-19 has worse outcomes in haematologic patients than in non-haematologic, independently of age, and that the development of ARDS and thrombotic complications drive the higher in-hospital mortality.

miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as \'oncomiR-1\', but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor. In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker.

Clinical studies have shown that renal injury in Corona Virus Disease 2019 (COVID-19) patients has been a real concern, which is associated with high mortality and an inflammation/apoptosis-related causality. Effective target therapy for renal injury has yet been developed. Besides, potential anti-COVID-19 medicines have also been reported to cause adverse side effects to kidney. Chinese Herbal Medicine (CHM), however, has rich experience in treating renal injury and has successfully applied in China in the battle of COVID-19. Nevertheless, the molecular mechanisms of CHM treatment are still unclear. In this study, we searched prescriptions in the treatment of renal injury extensively and the potential mechanisms to treat COVID-19 related renal injury were investigated. The association rules analysis showed that the core herbs includes Huang Qi, Fu Ling, Bai Zhu, Di Huang, Shan Yao. TCM herbs regulate core pathways, such as AGE-RAGE, PI3K-AKT, TNF and apoptosis pathway, etc. The ingredients (quercetin, formononetin, kaempferol, etc.,) from core herbs could modulate targets (PTGS2 (COX2), PTGS1 (COX1), IL6, CASP3, NOS2, and TNF, etc.), and thereby prevent the pharmacological and non-pharmacological renal injury comparable to that from COVID-19 infection. This study provides therapeutic potentials of CHM to combat COVID-19 related renal injury to reduce complications and mortality.

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV-2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID-19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers.

Breast cancer remains a substantial clinical problem worldwide, and cancer-associated cachexia is a condition associated with poor prognosis in this and other malignancies. Adipose tissue is involved in the development and progression of cancer-associated cachexia, but its various roles and mechanisms of action are not completely defined, especially as it relates to breast cancer. Interleukin 6 has been implicated in several mechanisms contributing to increased breast cancer tumorigenesis, as well as a net-negative energy balance and cancer-associated cachexia via adipose tissue remodeling in other models of cancer; however, its potential role in breast cancer-associated white adipose browning has not been explored. In this study, we demonstrate localized white adipose tissue browning in a spontaneous model of murine mammary cancer. We then used an in vitro murine adipocyte culture system with the E0771 and 4T1 cell lines as models of breast cancer. We demonstrate that while the E0771 and 4T1 secretomes and cross-talk with white adipocytes alter white adipocyte mRNA expression, they do not directly induce white adipocyte browning. Additionally, we show that neither exogenous administration of interleukin 6 alone or with its soluble receptor directly induce white adipocyte browning. Together, these results demonstrate that neither the E0771 or 4T1 murine breast cancer cell lines, nor interleukin 6, directly cause browning of cultured white adipocytes. This suggests that their roles in adipose tissue remodeling are more complex and indirect in nature.

γδ T cells, a small subset of T cell population (5-10%), forms a bridge between innate and adaptive immunity. Although the role of γδ T cells in infectious diseases and antitumor immunity is well investigated, their role in bone biology needs to be explored. Aminobisphosphonates are used as a standard treatment modality for bone related disorders and are potent activators of γδ T cells. In the present study, we have compared the effect of \"activated\" and \"freshly isolated\" γδ T cells on osteoclast generation and function. We have shown that \"activated\" (αCD3/CD28 + rhIL2 or BrHPP + rhIL2 stimulated) γδ T cells inhibit osteoclastogenesis, while \"freshly isolated\" γδ T cells enhance osteoclast generation and function. Upon stimulation with phosphoantigen (BrHPP), \"freshly isolated\" γδ T cells were also able to suppress osteoclast generation and function. Cytokine profiles of these cells revealed that, \"freshly isolated\" γδ T cells secrete higher amounts of IL6 (pro-osteoclastogenic), while \"activated\" γδ T cells secrete high IFNγ levels (anti-osteoclastogenic). Neutralization of IFNγ and IL6 reversed the \"inhibitory\" or \"stimulatory\" effect of γδ T cells on osteoclastogenesis. In conclusion, we have shown that, activation status and dynamics of IL6 and IFNγ secretion dictate pro and anti-osteoclastogenic role of γδ T cells.

OBJECTIVE: In this study, we analyzed the fatty acid profile of brains and plasma from male and female mice fed chow or a western-style high fat diet (WD) for 16 weeks to determine if males and females process fatty acids differently. Based on the differences in fatty acids observed in vivo, we performed in vitro experiments on N43 hypothalamic neuronal cells to begin to elucidate how the fatty acid milieu may impact brain inflammation.
METHODS: Using a comprehensive mass spectrometry fatty acid analysis, which includes a profile for 52 different fatty acid isomers, we assayed the plasma and brain fatty acid composition of age-matched male and female mice maintained on chow or a WD. Additionally, using the same techniques, we determined the fatty acid composition of N43 hypothalamic cells following exposure to palmitic and linoleic acid, alone or in combination.
RESULTS: Our data demonstrate there is a sexual dimorphism in brain fatty acid content both following the consumption of the chow diet, as well as the WD, with males having an increased percentage of saturated fatty acids and reductions in ω6-polyunsaturated fatty acids when compared to females. Interestingly, we did not observe a sexual dimorphism in fatty acid content in the plasma of the same mice. Furthermore, exposure of N43 cells to the ω6-PUFA linoleic acid, which is higher in female brains when compared to males, reduces palmitic acid-induced inflammation.
CONCLUSIONS: Our data suggest male and female brains, and not plasma, differ in their fatty acid profile. This is the first time, to our knowledge, lipidomic analyses has been used to directly test the hypothesis there is a sexual dimorphism in brain and plasma fatty acid composition following consumption of the chow diet, as well as following exposure to the WD.