A synthetic coolant (WS-23) in disposable electronic cigarettes impairs cytoskeletal function in EpiAirway microtissues exposed at the air liquid interface.

The design of popular disposable electronic cigarettes (ECs) was analyzed, and the concentrations of WS-23, a synthetic coolant, in EC fluids were determined for 22 devices from 4 different brands. All products contained WS-23 in concentrations that ranged from 1.0 to 40.1 mg/mL (mean = 21.4 ± 9.2 mg/mL). To determine the effects of WS-23 on human bronchial epithelium in isolation of other chemicals, we exposed EpiAirway 3-D microtissues to WS-23 at the air liquid interface (ALI) using a cloud chamber that generated aerosols without heating. Proteomics analysis of exposed tissues revealed that the cytoskeleton was a major target of WS-23. BEAS-2B cells were exposed to WS-23 in submerged culture to validate the main results from proteomics. F-actin, which was visualized with phalloidin, decreased concentration dependently in WS-23 treated BEAS-2B cells, and cells became immotile in concentrations above 1.5 mg/mL. Gap closure, which depends on both cell proliferation and migration, was inhibited by 0.45 mg/mL of WS-23. These data show that WS-23 is being added to popular EC fluids at concentrations that can impair processes dependent on the actin cytoskeleton and disturb homeostasis of the bronchial epithelium. The unregulated use of WS-23 in EC products may harm human health.

Isolated oculomotor nerve palsy secondary to non-aneurysmal subarachnoid hemorrhage.

We present a case series of two patients who developed unilateral cranial nerve III (CNIII) palsy following non-aneurysmal SAH (NASAH). Subarachnoid hemorrhage (SAH) can present with various signs and symptoms. Early diagnosis is paramount to determine treatment course. Thus, clinicians must be aware of the variable clinical presentations of this condition. Two patients were admitted to a single institution for SAH. Patient 1, 52-year-old male, presented with headache, left eye ptosis, and painless diplopia. A non-contrast head computed tomography (CT) demonstrated a SAH within the left sylvian fissure and blood surrounding the mesencephalon and falx. Patient 2, 70-year-old male, presented with mild headache, acute onset of blurry vision, and right eye ptosis. A non-contrast head CT demonstrated a diffuse SAH predominantly in the Sylvian and suprasellar cisterns. Patients were admitted to the neuro intensive care unit and underwent diagnostic angiograms to identify possible aneurysms. Magnetic resonance imaging and angiograms for both patients were negative. Patients were managed with best medical therapy and followed up in the outpatient setting. Unilateral CNIII palsy in the setting of NASAH was identified in both patients. Diagnostic angiograms were negative for aneurysms; therefore, SAH were determined to be spontaneous. We propose that unilateral CNIII palsy is a possible sign of NASAH.

[ETHNIC DIVERSITY AND CLINICAL CHARACTERISTICS OF HOSPITALIZED PATIENTS WITH ACUTE PANCREATITIS].

BACKGROUND: Previous studies have shown a correlation between acute pancreatitis and several different risk factors that vary in different countries and ethnic groups. The aims of this study are to examine the clinical characteristics and outcomes of acute pancreatitis in patients of Jewish and Bedouin origin. METHODS: We performed a retrospective cohort study of patients hospitalized with acute pancreatitis in the Soroka University Medical Center between the years 2012 and 2016 and compared two groups of patients: patients of Jewish and Bedouin origin. The primary outcome was a composite outcome consisting of 30-days mortality, ICU admission, complications (defined as necrotizing pancreatitis or pseudocyst formation), surgery due to these complications and 30-days re-admission due to pancreatitis. RESULTS: A total of 560 patients were included, 483 patients (86.3%) of Jewish origin and 77 patients (13.7%) of Bedouin origin. The most common cause in both groups was biliary pancreatitis: 49.7% among Jewish, 61% among Bedouin. In our study alcohol consumption, the most common worldwide risk factor of pancreatitis, accounts for only a small percentage of the disease in the Jewish population (5.6%) and does not exist in the Bedouin population. We found no significant differences in outcomes between the two groups. CONCLUSIONS: Biliary pancreatitis was the most common cause in both groups of patients. The important finding of our study is that alcohol use is a minor cause of acute pancreatitis in the Negev. Moreover, it is uncommon in the Jewish population and is completely non-existent among Bedouins. No differences were found in the primary outcomes between the two groups.

Acute Liver Failure From Sickle Cell Hepatopathy Treated With Exchange Transfusion.

Sickle cell disease (SCD) is a qualitative hemoglobinopathy that can cause widespread sickling and vaso-occlusive events in all organ systems. Sickle cell hepatopathy is an umbrella term for various acute and chronic pathologies of the liver as a result of sickling in SCD patients. We present below the case of a 49-year-old woman who had an acute liver failure in the setting of a hepatic crisis with recovery after exchange transfusion. Hepatic involvement in SCD may be life-threatening. Understanding the etiology and severity of hepatic involvement by sickling is necessary for appropriate treatment.

Risk of Non-Hodgkin's Lymphoma in HCV Patients in the United States Between 2013 and 2020: A Population-Based Study.

Hepatitis C virus (HCV) is a significant healthcare problem affecting ~1% of the United States population. Meta-analyses of epidemiological studies reported a strong association between non-Hodgkin's lymphoma (NHL) and HCV. Direct oncogenic properties of HCV proteins and chronic antigenic stimulation are possible etiologies. We explored if NHL's prevalence has changed since older HCV therapy based on interferon that shared antiviral and anti-lymphoma properties was replaced with interferon-free direct-acting antivirals (DAA). We reviewed data from a nationwide database (Explorys, IBM) that aggregates records from 26 health-care-systems. We identified patients with chronic hepatitis C infection between June 2013 and June 2020. The control group was gender, race, and age-matched HCV-negative population. Statistical analysis used the odds ratio (OR) with P value <.001 for significance. There were 940 cases of NHL of 129,970 patients in the HCV group versus 107,480 cases of NHL of 37,961,970 in the control cohort [OR 2.6, 95% confidence interval (CI) 2.4-2.7]. A positive association was present for chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, non-Hodgkin T-cell lymphoma, and primary cutaneous T-cell lymphoma. There were no differences in Mantle cell lymphoma. The increased risk of HCV-associated lymphoma was persistent across genders, Caucasians and African-Americans, and age groups. While the risk of NHL in the HCV-negative population was higher in Caucasians than African-Americans (OR 1.8, 95% CI 1.7-1.8), the risk of HCV-associated NHL was not different. Further prospective studies examining the risk of HCV-associated lymphoma following DAA are warranted.

Hyperhomocysteinemia and Pulmonary Embolism in a Young Male.

The association of hyperhomocysteinemia with thrombosis has provoked debate in the medical literature. Although studies have found associations between moderate homocysteine elevations and thrombotic events, others dispute this relationship. We present herein the case of a 24-year-old male who presented with unprovoked bilateral submassive pulmonary emboli. Extensive hypercoagulability workup was notable for an elevated homocysteine level, in addition to low vitamin B12 and folate levels. Of note, the patient had a history of small bowel resection after trauma, which may have contributed to the aforementioned metabolic derangements, potentially increasing his risk for thrombosis and interfering with the efficacy of his anticoagulation.

Traffic congestion and blood pressure elevation: A comparative cross-sectional study in Lebanon.

This comparative cross-sectional study examines the association between traffic congestion and elevation of systolic and/or diastolic blood pressure levels among a convenience sample of 310 drivers. Data collection took place during a gas station pause at a fixed time of day. Higher average systolic (142 vs 123 mm Hg) and diastolic (87 vs 78 mm Hg) blood pressures were detected among drivers exposed to traffic congestion compared with those who were not exposed (P<.001), while controlling for body mass index, age, sex, pack-year smoking, driving hours per week, and occupational driving. Moreover, among persons exposed to traffic congestion, longer exposure time was associated with higher systolic and diastolic blood pressures. Further studies are needed to better understand the mechanisms of the significant association between elevated blood pressure and traffic congestion.

Elevated IFN-alpha/beta levels in a streptozotocin-induced type I diabetic mouse model promote oxidative stress and mediate depletion of spleen-homing CD8+ T cells by apoptosis through impaired CCL21/CCR7 axis and IL-7/CD127 signaling.

Type 1 diabetes mellitus (T1D) is associated with increased type 1 interferon (IFN) levels and subsequent severe defects in lymphocyte function, which increase susceptibility to infections. The blockade of type 1 IFN receptor 1 (IFNAR1) in non-obese diabetic mice has been shown to delay T1D onset and decrease T1D incidence by enhancing spleen CD4+ T cells and restoring B cell function. However, the effect of type 1 IFN blockade during T1D on splenic CD8+ T cells has not previously been studied. Therefore, we investigated, for the first time, the effect of IFNAR1 blockade on the survival and architecture of spleen-homing CD8+ T cells in a streptozotocin-induced T1D mouse model. Three groups of mice were examined: a non-diabetic control group; a diabetic group; and a diabetic group treated with an anti-IFNAR1 blocking antibody. We observed that T1D induction was accompanied by a marked destruction of ß cells followed by a marked reduction in insulin levels and increased IFN-α and IFN-ß levels in the diabetic group. The diabetic mice also exhibited many abnormal changes including an elevation in blood and spleen free radical (reactive oxygen species and nitric oxide) and pro-inflammatory cytokine (IL-6 and TNF-α) levels, a significant decrease in IL-7 levels, and subsequently, a significant decrease in the numbers of spleen-homing CD8+ T cells. This decrease in spleen-homing CD8+ T cells resulted from a marked reduction in the CCL21-mediated entry of CD8+ T cells into the spleen and from increased apoptosis due to a marked reduction in IL-7-mediated STAT5 and AKT phosphorylation. Interestingly, type 1 IFN signaling blockade in diabetic mice significantly restored the numbers of splenic CD8+ T cells by restoring free radical, pro-inflammatory cytokine and IL-7 levels. These effects subsequently rescued splenic CD8+ T cells from apoptosis through a mechanism that was dependent upon CCL21- and IL-7-mediated signaling. Our data suggest that type 1 IFN is an essential mediator of pathogenesis in T1D and that this role results from the negative effect of IFN signaling on the survival of splenic CD8+ T cells.

Development of an Arabic version of the National Eye Institute Visual Function Questionnaire as a tool to study eye diseases patients in Egypt.

AIM: To develop and test an Arabic version of the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). METHODS: NEI-VFQ-25 was translated into Arabic according to WHO translation guidelines. We enrolled adult consenting patients with bilateral chronic eye diseases who presented to 14 hospitals across Egypt from October to December 2012, and documented their clinical findings. Psychometric properties were then tested using STATA. RESULTS: We recruited 379 patients, whose mean age was (54.5±15)y. Of 46.2% were males, 227 had cataract, 31 had glaucoma, 23 had retinal detachment, 37 had diabetic retinopathy, and 61 had miscellaneous visual defects. Non-response rate and the floor and ceiling numbers of the Arabic version (ARB-VFQ-25) were calculated. Internal consistency was high in all subscales (except general health), with Cronbach-α ranging from 0.702-0.911. Test-retest reliability was high (intraclass correlation coefficient 0.79). CONCLUSION: ARB-VFQ-25 is a reliable and valid tool for assessing visual functions of Arabic speaking patients. However, some questions had high non-response rates and should be substituted by available alternatives. Our results support the importance of including self-reported visual functions as part of routine ophthalmologic examination.

Detection of a novel truncating Merkel cell polyomavirus large T antigen deletion in chronic lymphocytic leukemia cells.

Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of Merkel cell carcinomas (MCC). Yet, clonal integration and truncating mutations of the large T antigen (LTAg) of MCPyV are restricted to MCC. We tested the presence and mutations of MCPyV in highly purified leukemic cells of 70 chronic lymphocytic leukemia (CLL) patients. MCPyV was detected in 27.1% (n = 19) of these CLL cases. In contrast, MCPyV was detected only in 13.4% of normal controls (P < .036) in which no LTAg mutations were found. Mutational analyses revealed a novel 246bp LTAg deletion in the helicase gene in 6 of 19 MCPyV-positive CLL cases. 2 CLL cases showed concomitant mutated and wild-type MCPyV. Immunohistochemistry revealed protein expression of the LTAg in MCPyV-positive CLL cases. The detection of MCPyV, including LTAg deletions and LTAg expression in CLL cells argues for a potential role of MCPyV in a significant subset of CLL cases.

Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1.

AIMS: As one of the five lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate. LDH5 overexpression in cancer cells induces an upregulated glycolytic metabolism and reduced dependence on the presence of oxygen. Here we analyzed LDH5 protein expression in a well characterized large cohort of primary lung cancers in correlation to clinico-pathological data and its possible impact on patient survival. METHODS: Primary lung cancers (n = 269) and non neoplastic lung tissue (n = 35) were tested for LDH5 expression by immunohistochemistry using a polyclonal LDH5 antibody (ab53010). The results of LDH5 expression were correlated to clinico-pathological data as well as to patient's survival. In addition, the results of the previously tested transketolase like 1 protein (TKTL1) expression were correlated to LDH5 expression. RESULTS: 89.5% (n = 238) of NSCLC revealed LDH5 expression whereas LDH5 expression was not detected in non neoplastic lung tissues (n = 34) (p < 0.0001). LDH5 overexpression was associated with histological type (adenocarcinoma = 57%, squamous cell carcinoma = 45%, large cell carcinoma = 46%, p = 0.006). No significant correlation could be detected with regard to TNM-stage, grading or survival. A two sided correlation between the expression of TKTL1 and LDH5 could be shown (p = 0.002) within the overall cohort as well as for each grading and pN group. A significant correlation between LDH5 and TKTL1 within each histologic tumortype could not be revealed. CONCLUSIONS: LDH5 is overexpressed in NSCLC and could hence serve as an additional marker for malignancy. Furthermore, LDH5 correlates positively with the prognostic marker TKTL1. Our results confirm a close link between the two metabolic enzymes and indicate an alteration in the glucose metabolism in the process of malignant transformation.

Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin cancer of immunosuppressed patients.

Recently, a new human polyoma virus has been identified in Merkel cell carcinomas (MCC). MCC is a highly aggressive neuroendocrine nonmelanoma skin cancer (NMSC) associated with immunosuppression. Clonal integration of this virus which was termed Merkel cell polyoma virus (MCPyV) was reported in a number of MCC. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are also NMSC and are the most frequent cancers in the setting of immunosuppression. A unique group of 56 NMSC from 11 immunosuppressed patients and 147 NMSC of 125 immunocompetent patients was tested for MCPyV by DNA PCR, targeting the Large T Antigen and the structural Viral Protein 1. NMSC included SCC, BCC and Bowen's disease (BD). In addition, normal skin and 89 colorectal cancers were tested. MCPyV specific sequences were significantly more frequently found in NMSC of immunosuppressed patients compared to immunocompetent patients (p < 0.001). In particular BD and BCC revealed a significant increased association of MCPyV of immunosuppressed patients (p = 0.002 and p = 0.006). Forty-seven of 147 (32%) sporadic NMSC were MCPyV positive. Interestingly, 37.5% (36/96) of sporadic BCC of immunocompetent patients were MCPyV positive. No MCPyV was detected within normal skin and only 3 out of 89 of additionally tested colorectal cancers were MCPyV positive. Our data show that MCPyV is a frequently reactivated virus in immunocompromized patients. How MCPyV contributes to the pathogenesis of NMSC, i.e., BD, SCC and BCC, in immunosuppressed patients and in addition, potentially to the pathogenesis of a subset of sporadic BCC needs further investigations.

Report of rare bilateral nasolabial cysts.

PURPOSE: Nasolabial cysts are usually unilateral and are quite rare, while bilateral cysts are even rarer. PATIENT AND METHOD: Our report concerns a 48-year-old female with bilateral nasolabial cysts. After many years of misdiagnosis she was finally referred to our clinic with a subnasal swelling of unknown origin. RESULT: Evaluation of the patient's medical history, clinical examination and of a previous CT scan led to the diagnosis of a nasolabial cyst, which was later confirmed by histological examination. Treatment involved the surgical excision. CONCLUSION: A complete surgical excision is recommended using a sublabial approach as the treatment of choice, although transnasal endoscopic marsupialization seems to be a simple and effective alternative. It has been shown that after successful marsupialization, the nasolabial cyst is converted to an air-containing paranasal sinus.

Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene.

Merkel cell carcinoma (MCC) is a rare but very aggressive human malignancy of the elderly or immunosuppressed patients. Recently, the clonal integration of a new human polyoma virus, which was termed Merkel cell polyomavirus (MCPyV), has been reported in 8 of 10 MCC patients. In the present study, we studied the formalin-fixed and paraffin-embedded tissue specimens of 39 MCC for the presence of MCPyV by PCR. We applied four different primer sets directed against the large T antigen and the VP1 gene of MCPyV. We were able to detect MCPyV in 77% (n = 30) of MCC as confirmed by sequence analyses of the PCR products. Sequence analyses showed only minor nucleotide changes compared with the previously published MCC sequences. In addition, one patient revealed the amplification of two PCR products using PCR primers directed against the VP1 gene. Sequence analyses confirmed the presence of the expected 351-bp PCR product and in addition a second PCR product of 261 bp containing a unique 90-bp deletion in the VP1 gene, which will lead to a predicted loss of 28 amino acids. The unique 90-bp deletion within the VP1 gene possibly is a result of incomplete viral integration of MCPyV in the MCC. The presence of MCPyV in the majority of MCC tissue specimens in our study strongly underlines a possible role for MCPyV as an etiologic agent in the carcinogenesis of MCC.