The Relationship between Anthropometric Indices and Breast Cancer in Central Iran.

Background: Anthropometric indices have a debatable relationship with breast cancer (BC) among different ethnicity. In the current study, we have evaluated the relationship between anthropometric indices and BC in Iranian participants. Methods: Between 2012 and 2014, a total of 7,805 women were enrolled from different mammography centers in Isfahan province, Iran. For each participant, a detailed questionnaire was filled out and anthropometric indices were measured by trained technicians. We used logistic regression models to estimate odds ratios (OR) and 95% confidence interval (CI) for BC risk associated with anthropometry measurements, stratified on menopausal status. Results: In the postmenopausal group, weight ≥68 kg compared to weight <61.75 kg was associated with decreased risk of BC (OR = 0.78; 95% CI: 0.63-0.97). Postmenopausal women with Waist-Hip Ratio (WHR) ≥ 0.85 compared to WHR < 0.77 were at increased risk of BC (OR = 1.36; 95% CI: 1.07-1.73). Both premenopausal and postmenopausal women had a decreased risk of BC with higher Obesity Index (OI) and Relative Weight. Conclusion: Ethnicity appears to play an important role in the discrepancies between results of different studies about the correlation of anthropometric features with BC.

Evaluating the Clinical Utility of Epstein-Barr Virus Antibodies as Biomarkers in Multiple Sclerosis: A Systematic Review.

BACKGROUND: EBV is a necessary but not sufficient factor in the pathophysiology of multiple sclerosis (MS). EBV antibodies to the nuclear antigen (EBNA1) and viral capsid antigen (VCA) rise rapidly prior to MS disease manifestations, and their absence has clinical utility with a high negative predictive value. It remains unclear whether EBV levels act as prognostic, monitoring, or pharmacodynamic/response biomarkers. Substantial literature on this topic exists but has not been systematically reviewed. We hypothesized that EBV levels against EBNA1 and VCA are potential prognostic and monitoring biomarkers in MS, and that patient population, MS clinical phenotype, and EBV assay method may play important roles in explaining variation among study outcomes. METHODS: We systematically searched PubMed and EMBASE from inception to April 1, 2022. After removal of duplicates, records were screened by abstract. Remaining full-text articles were reviewed. Clinical and MRI data were extracted from full-text articles for comparison and synthesis. RESULTS: Searches yielded 696 unique results; 285 were reviewed in full, and 36 met criteria for data extraction. Heterogeneity in sample population, clinical outcome measures, assay methods and statistical analyses precluded a meta-analysis. EBV levels were not consistently associated with clinical disease markers including conversion from CIS to RRMS, neurological disability, or disease phenotype. Studies using repeated-measures design suggest that EBNA1 levels may temporarily reflect inflammatory disease activity as assessed by gadolinium-enhancing Magnetic Resonance Imaging (MRI) lesions. Limited data also suggest a decrease in EBV levels following initiation of certain disease-modifying therapies. CONCLUSION: Heterogeneous methodology limited generalization and meta-analysis. EBV antibody levels are unlikely to represent prognostic biomarkers in MS. The areas of highest ongoing promise relate to diagnostic exclusion and pharmacodynamic/disease response. Use of EBV antibodies as biomarkers in clinical practice remains additionally limited by lack of methodological precision, reliability, and validation.

Multi-omics analysis of magnetically levitated plasma biomolecules.

We recently discovered that superparamagnetic iron oxide nanoparticles (SPIONs) can levitate plasma biomolecules in the magnetic levitation (MagLev) system and cause formation of ellipsoidal biomolecular bands. To better understand the composition of the levitated biomolecules in various bands, we comprehensively characterized them by multi-omics analyses. To probe whether the biomolecular composition of the levitated ellipsoidal bands correlates with the health of plasma donors, we used plasma from individuals who had various types of multiple sclerosis (MS), as a model disease with significant clinical importance. Our findings reveal that, while the composition of proteins does not show much variability, there are significant differences in the lipidome and metabolome profiles of each magnetically levitated ellipsoidal band. By comparing the lipidome and metabolome compositions of various plasma samples, we found that the levitated biomolecular ellipsoidal bands do contain information on the health status of the plasma donors. More specifically, we demonstrate that there are particular lipids and metabolites in various layers of each specific plasma pattern that significantly contribute to the discrimination of different MS subtypes, i.e., relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), and primary-progressive MS (PPMS). These findings will pave the way for utilization of MagLev of biomolecules in biomarker discovery for identification of diseases and discrimination of their subtypes.

A real-world cohort analysis of alemtuzumab outcomes in relapsing multiple sclerosis.

Multiple sclerosis (MS) is a chronic and progressive neurological disease characterized by recurrent episodes of inflammatory demyelination of the brain and spinal cord. Alemtuzumab has been previously shown in large phase III trials to be an effective therapy in reducing MS clinical flares as well as new radiological activity and atrophy rates. The purpose of this study was to examine real-world effectiveness and safety data from a large cohort of people treated with alemtuzumab at an academic medical center, including those who failed B-cell depletion therapy. Over an average of 2.6 years follow-up, there were small but significant improvements in neurological disability scores, and a 61% rate of the composite "No Evidence of Disease Activity" (NEDA-3) outcome at 2-year follow-up. There were no substantial safety issues encountered in our review; rates of adverse events were similar or below those reported in Phase III trials. We compare and contrast our results to other available real-world data using alemtuzumab in multiple sclerosis.

Non-ambulatory measures of lower extremity sensorimotor function are associated with walking function in Multiple Sclerosis.

BACKGROUND: Disease progression of multiple sclerosis (MS) is often monitored by ambulatory measures, but how non-ambulatory sensorimotor measures differentially associate to walking measures in MS subtypes is unknown. We determined whether there are characteristic differences between relapsing-remitting MS (RRMS), progressive MS (PMS), and non-MS controls in lower extremity sensorimotor function and clinical walking tasks and the sensorimotor associations with walking function in each group. METHODS: 18 RRMS, 13 PMS and 28 non-MS control participants were evaluated in their plantar cutaneous sensitivity (vibration perception threshold, Volts), proprioception during ankle joint position-matching (|∆°| in dorsiflexion), motor coordination (rapid foot-tap count/10 s), and walking function with three tests: Timed 25-foot walk (T25FW) at preferred and fast speeds (s), and timed-up-and-go (TUG, s). RESULTS: Foot-tapping (p = 0.039, Mean difference (MD)= 5.65 taps) and plantar cutaneous sensation (p = 0.026, MD= -10.30 V) differed between the MS subtypes. For the RRMS group faster walking was related to better proprioceptive function (preferred T25FW: p = 0.019, Root mean square error (RMSE)=1.94; fast T25FW: p = 0.004, RMSE=1.65; TUG: p = 0.001, RMSE=2.12) and foot-tap performance (preferred T25FW: p = 0.033, RMSE = 2.74; fast T25FW: p = 0.010, RMSE=2.02). These associations were not observed in the PMS group. CONCLUSIONS: Foot-tap performance and plantar cutaneous sensitivity but not ankle proprioception differed between MS subtypes. Lower walking performance was associated with lower foot-tapping and plantar cutaneous sensitivity in the RRMS but not the PMS group. This result suggests a change in the relationship of lower extremity sensorimotor function to walking performance in the PMS subtype.

Intravenous immunoglobulins in an adult case of post-EBV cerebellitis.

Post-Epstein-Barr virus (EBV) cerebellitis is very rare complication of infectious mononucleosis and only a few adult cases are reported in literature. We present a 23-year-old patient who was admitted to the neurology service with worsening ataxia, nystagmus and dysarthria, 1 week after infectious mononucleosis. Imaging and cerebrospinal fluid studies were normal, serum studies revealed acute transaminitis and positive EBV viral capsid IgM and IgG. The patient underwent a 5-day course of intravenous immunoglobulins with rapid resolution of all his symptoms and was safely discharged home. The pathophysiology of post-EBV cerebellitis involves autoreactive antibodies, rather than a direct viral insult. Antineuronal antibodies might be the result of a mimicry between EBV proteins and neuronal antigens or they can be secreted by the EBV-transformed lymphocytes themselves. Many reports stress the benign, self-limiting nature of this syndrome; however, immunotherapy might de facto decrease the severity and duration of illness.

Spinal Intradural Extramedullary Dermoid Cyst.

BACKGROUND: Dermoid cysts are benign congenital tumors that develop early in life. These tumors are classified by the presence of all 3 germ layers. Spinal intradural extramedullary teratoma is a rare disease, which is more common in children under 5 years of age than in adults. CASE DESCRIPTION: A 12-year-old girl with a dermoid cyst at the lower lumbar level presented with 2-month low back pain and intermittent lower extremity radicular symptoms on the right side. Magnetic resonance imaging scan of the spine revealed an intradural extramedullary mass lesion at L4-5. Surgical excision of the cyst was successfully performed. Surgical and histopathologic findings confirmed extramedullary ruptured matured teratoma. Postoperatively, the patient had remarkable clinical improvement. CONCLUSIONS: Although dermoid cysts are uncommon, they should be considered in the differential diagnosis of spinal lesions in patients with lower back pain. It can be successfully treated with surgical excision.

Sensorimotor function in progressive multiple sclerosis.

BACKGROUND: A sensitive test reflecting subtle sensorimotor changes throughout disease progression independent of mobility impairment is currently lacking in progressive multiple sclerosis. OBJECTIVES: We examined non-ambulatory measures of upper and lower extremity sensorimotor function that may reveal differences between relapsing-remitting and progressive forms of multiple sclerosis. METHODS: Cutaneous sensitivity, proprioception, central motor function and mobility were assessed in 32 relapsing-remitting and 31 progressive multiple sclerosis patients and 30 non-multiple sclerosis controls. RESULTS: Cutaneous sensation differed between relapsing-remitting and progressive multiple sclerosis at the foot and to a lesser extent the hand. Proprioception function in the upper but not the lower extremity differed between relapsing-remitting and progressive multiple sclerosis, but was different for both upper and lower extremities between multiple sclerosis patients and non-multiple sclerosis controls. Foot-tap but not hand-tap speed was slower in progressive compared to relapsing-remitting multiple sclerosis, suggestive of greater central motor function impairment in the lower extremity in progressive multiple sclerosis. In addition, the non-ambulatory sensorimotor measures were more sensitive in detecting differences between relapsing-remitting and progressive multiple sclerosis than mobility assessed with the 25-foot walk test. CONCLUSION: This study provides novel information about changes in sensorimotor function in progressive compared with relapsing-remitting forms of multiple sclerosis, and in particular the importance of assessing both upper and lower extremity function. Importantly, our findings showed loss of proprioceptive function in multiple sclerosis but also in progressive compared to relapsing-remitting multiple sclerosis.

Rapid foot-tapping but not hand-tapping ability is different between relapsing-remitting and progressive multiple sclerosis.

BACKGROUND: Rapid tapping tests have been shown to be reliable measures of upper motor neuron disease, and effectively examine motor function differences between multiple sclerosis (MS) and non-MS controls (CON), and between relapsing-remitting and progressive MS subtypes. To successfully perform rapid repetitive movements such as tapping, a person must be able to consistently turn on and off motor units to switch between the up and down movement phases. However, it is not clear which specific movement phase that occurs during tapping is different between MS subtypes. The objective of this study was to quantify and characterize performance differences during rapid hand- and foot-tapping tests between relapsing-remitting (RRMS) and progressive (PMS) forms of MS, as well as how both subtypes differ from non-MS controls. METHODS: Participants in this study included 30 non-MS controls, 32 RRMS, and 31 PMS. Participants wore inertial sensors on all hands and feet and were instructed to tap as fast as possible for 10 s. Angular velocity from the gyroscope was used to quantify inter-tap interval (ms), coefficient of variation of inter-tap interval (COV), and up- and down-movement characteristics (duration (ms), COV, peak angular velocity (rad/s)). Differences between groups were examined with ANOVA and independent t-tests. Inter-tap interval was examined for its ability to distinguish between RRMS and PMS by a binary logistic regression analysis. Up-down movement characteristics were further evaluated for within-group directional differences (up- vs. down-phase movement components) with paired-sample t-tests. RESULTS: Inter-tap interval for both hand- and foot-tapping differed between controls and MS, but only foot tapping was different between RRMS and PMS (RRMS = 286.7 ± 83.0 ms; PMS = 379.5 ± 170.9 ms; mean difference (d) = -92.8 ms). Logistic regression analysis showed foot-tap interval but not hand-tap interval has the potential to distinguish between RRMS and PMS (Area under the ROC = 0.71). Both up- and down-movement duration differences were consistent with the results for inter-tap interval, but up-movement duration showed larger mean group differences than down-movement differences. No significant group differences in overall inter-tap interval COV were detected for either hand- or foot-tapping; however, up-movement foot-tapping variation (CON = 18.7 ± 6.1; RRMS = 25.5 ± 11.2; PMS = 23.3 ± 8.6; CON vs RRMS d = -6.8; CON vs PMS d = -4.7), but not down-movement variation was different between controls and MS. Up- and down-peak angular velocity during foot-tapping were different between controls and PMS (CON Up = 1.4 ± 0.5 rad/s; PMS Up = 1.0 ± 0.4 rad/s; Up d = 0.4 rad/s; CON Down= 1.5 ± 0.6 rad/s; PMS Down = 1.2 ± 0.5 rad/s; Down d = 0.3 rad/s), and up-movement peak angular velocity differences showed larger mean group differences than the down-movement peak angular velocity between controls and PMS. CONCLUSION: Foot-tapping differs between MS disease subtypes and has greater potential than hand-tapping to distinguish between subtypes. Performance in the up-movement showed larger group differences than the down-movement, suggesting that the anti-gravity up-movement during tapping may be more important diagnostically. Future studies should be conducted on the nature of the physiological mechanisms underlying impairments in anti-gravity movements in people with MS.

Succination inactivates gasdermin D and blocks pyroptosis.

Activated macrophages undergo a metabolic switch to aerobic glycolysis, accumulating Krebs' cycle intermediates that alter transcription of immune response genes. We extended these observations by defining fumarate as an inhibitor of pyroptotic cell death. We found that dimethyl fumarate (DMF) delivered to cells or endogenous fumarate reacts with gasdermin D (GSDMD) at critical cysteine residues to form S-(2-succinyl)-cysteine. GSDMD succination prevents its interaction with caspases, limiting its processing, oligomerization, and capacity to induce cell death. In mice, the administration of DMF protects against lipopolysaccharide shock and alleviates familial Mediterranean fever and experimental autoimmune encephalitis by targeting GSDMD. Collectively, these findings identify GSDMD as a target of fumarate and reveal a mechanism of action for fumarate-based therapeutics that include DMF, for the treatment of multiple sclerosis.

A case of isolated cortical venous thrombosis presenting radiographically as a subacute multifocal leukoencephalopathy, and review of literature.

A 55-year-old man presented with brief seizure with associated acute aphasia, right head turn and subsequent generalised convulsion. On imaging, he was found to have patchy juxtacortical and cortical T2 hyperintensity with high radiographic suspicion for subacute multifocal leukoencephalopathy. Serum and cerebrospinal fluid testing were unremarkable. Clinically, the patient recovered completely and had no recurrence of symptoms. On follow-up MRI 1 month later, the T2 hyperintensity had resolved almost entirely while hypointensity on susceptibility-weighted angiography MRI remained, suggesting isolated cortical venous thrombosis.

Serum level measurement of progranulin in relapsing-remitting multiple sclerosis and neuromyelitis optica patients.

BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS) with unknown etiology and variable clinical evolution. Although the role of serum progranulin levels in the pathogenesis of MS remains unclear, it is well known that progranulin is involved in several physiological and pathophysiological process of CNS including modulation of neurite outgrowth, neuronal differentiation, and neuronal survival. Therefore, in this study, we aimed to measure serum levels of progranulin in patients with neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS) in comparison with healthy control subjects. METHODS: In a case-control study, plasma was collected from healthy controls (n = 37) and also patients with RRMS (n = 115) and NMO (n = 33). Serum level measurement of progranulin was performed using a sandwich ELISA method. RESULTS: The serum levels of progranulin were 65.07 ± 11.64, 56.81 ± 10.34, and 47.73 ± 10.37 in NMO and MS patients and healthy controls, respectively, showing a statistically significant difference between them (P = 0.00). Furthermore, we found a positive correlation between serum levels of progranulin and EDSS of patients (r = 0.79 and P = 0.00). CONCLUSION: The present study demonstrated that progranulin is up-regulated in MS patients and our findings strengthen the evidence for progranulin being involved in the pathogenesis of MS. However, further studies will be required to establish progranulin as an important marker for MS.

Geranisetron versus gabapentin in preventing postoperative nausea and vomiting after middle ear surgery in adults: A double-blinded randomized clinical trial study.

BACKGROUND: The incidence of postoperative nausea and vomiting (PONV) after middle ear surgery is high. In this study we want to compare the effects of intravenous granisetron and oral gabapentin as a premedication before surgery on the incidence and severity of PONV after middle ear surgery in adult patents. MATERIALS AND METHODS: We enrolled 90 patients that were randomly divided into the three groups of 30 in each. Group I received granisetron 3 mg iv 2 minutes before induction of anesthesia; Group II received oral gabapentin 300 mg 1 hour before anesthesia and Group III received placebo. The incidence and severity of PONV were recorded each 15 minutes in the post-anesthesia care unit (PACU) and each 8 hours until 24 hours after discharge from the PACU. RESULT: The incidence and severity of nausea and vomiting at different time intervals in Groups I and Group II was significantly lower compared with Group III (P < 0.05). There was no significant difference in the incidence of side effects of study drug administration including respiratory depression, apnea, extra pyramidal disorders, drowsiness, dizziness, vertigo and headache in three groups. CONCLUSION: The study was shown that using gabapentin and granisetron have equal anti-emetic effects, but significant differences were seen between these two groups compared to the control group. These submit the efficiency of these drugs in preventing PONV.

A comparison of the effect of pretreatment with intravenous dexamethasone, intravenous ketamine, and their combination, for suppression of remifentanil-induced cough: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The injection of remifentanil can cause cough during induction of anesthesia. This study was designed to examine the efficacy of ketamine, dexamethasone, and their combination on remifentanil-induced cough (RIC). MATERIALS AND METHODS: ONE HUNDRED AND TWENTY PATIENTS SCHEDULED FOR ELECTIVE SURGERY WERE RANDOMLY ASSIGNED INTO FOUR GROUPS: Group K received 10 mg ketamine; Group D received 10 mg dexamethasone; Group KD received 10 mg ketamine in combination with dexamethasone; and Group S received saline in a similar volume, five minutes prior to the injection of remifentanil. The incidence and severity of the cough was recorded in each person. RESULTS: The incidence of RIC was significantly lower in Group KD compared to Group K, Group D, and Group S (3.3 vs. 20%, 20%, and 46.7%, respectively, P < 0.05). The severity of RIC was significantly lower in Group KD compared to Group K, Group D, and Group S (P < 0.05). There was no significant difference between Group K and Group D in this regard (P > 0.05). There was no significant difference in the onset time of coughing among the four groups (19.8 ± 1.3, 20.8 ± 0.9, 19.0 ± 1.1, and 19.9 ± 2.2 in Group K, Group D, Group KD, and Group S, respectively, P > 0.05). CONCLUSION: We found that pretreatment with 10 mg ketamine in combination with 10 mg dexamethasone five minutes prior to the injection of remifentanil could significantly reduce the incidence of RIC, and it was better than using each drug singly.