Health care access, psychosocial outcomes and mental health in adults living with epilepsy during the COVID-19 pandemic.

PURPOSE: People living with epilepsy (PLWE) have a higher prevalence of mental health comorbidities and poorer psychosocial outcomes compared to the general population. The aim of this study was to examine psychosocial outcomes, mental health, healthcare accessibility, and seizure burden in PLWE during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study of adults with epilepsy treated in an urban multicenter health system from 2021 to 2022. A standardized questionnaire assessed for COVID-19 history, comorbidities, access to antiseizure medications (ASMs) and neurological care, seizure burden, and psychosocial outcomes (e.g., employment, social and financial support). The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were administered to evaluate for depression and anxiety. Frequency and proportions for categorical variables and median and interquartile ranges for continuous variables were calculated. RESULTS: Fifty-five PLWE participated (95 % response rate). Median age was 40 years (IQR 31.5-66.5), 61.8 % were women, 47.3 % had a bachelor's degree or higher and 29.1 % each had Medicaid and Medicare insurance. Race (from highest to lowest %) was: 32.7 % White, 20 % Black, 20 % Latinx, 14.5 % Asian, and 12.7 % selected "other" or "prefer not to say." COVID-19 had been diagnosed in 21.8 % of participants. Symptoms of anxiety and depression were self-reported by 43.6 % and 34.5 % of patients, respectively, with many describing this symptom as new post-pandemic (37.5 % and 31.6 %, respectively). Using validated scales, 52.7 % had depression (PHQ-9 score ≥ 5) with 30.9 % having moderate/severe depression (PHQ-9 score ≥ 10), while 29.1 % had probable generalized anxiety disorder (GAD-7 score ≥ 8). Seizure burden increased in 21.8 % of participants, while 20 % reported fewer seizures and 29.1 % were seizure free since the COVID-19 pandemic. Economic impacts of the pandemic included job loss (25 % amongst those employed at onset of pandemic), new or worsened financial difficulties (40 %), and new or worsened social support issues (30.9 %). Of all participants, 18.2 % reported difficulties accessing ASMs and 25.5 % cancelled visits, but of those with cancelled visits, 78.6 % had their appointments rescheduled as a telehealth visit. CONCLUSION: Our cohort of PLWE experienced some challenges during the COVID-19 pandemic including poorer mental health and financial and employment-related stressors. Encouragingly, healthcare access was relatively spared during the COVID-19 crisis, with some patients even reporting a reduction in seizure burden. However, PLWE require ongoing psychosocial support with particular attention to decompensation of mental health and social stressors that may be exacerbated by the COVID-19 pandemic.

Antimicrobial and cytotoxic activity of 18 prenylated flavonoids isolated from medicinal plants: Morus alba L., Morus mongolica Schneider, Broussnetia papyrifera (L.) Vent, Sophora flavescens Ait and Echinosophora koreensis Nakai.

Antimicrobial activity of the 18 prenylated flavonoids, which were purified from five different medicinal plants, was evaluated by determination of MIC using the broth microdilution methods against four bacterial and two fungal microorganisms (Candida albicans, Saccaromyces cerevisiae, Escherichia coli, Salmonella typhimurium, Staphylococcus epidermis and S. aureus). Papyriflavonol A, kuraridin, sophoraflavanone D and sophoraisoflavanone A exhibited a good antifungal activity with strong antibacterial activity. Kuwanon C, mulberrofuran G, albanol B, kenusanone A and sophoraflavanone G showed strong antibacterial activity with 5-30 microg/ml of MICs. Morusin, sanggenon B and D, kazinol B, kurarinone, kenusanone C and isosophoranone were effective to only gram positive bacteria, and broussochalcone A was effective to C. albicans. IC50 values of papyriflavonol A, kuraridin, sophoraflavanone D, sophoraisoflavanone A and broussochalcone A in HepG2 cells were 20.9, 37.8, 39.1, 22.1, and 22.0 microg/ml, respectively. These results support the use of prenylated flavonoids in Asian traditional medicine to treat microbial infection and indicate a high potential for prenylated flavonoids as antimicrobial agents as well as anti-inflammatory agents.

Estimated dietary isoflavone intake of Korean population based on National Nutrition Survey.

The dietary isoflavone intake of the Korean population was estimated based on data from the Korean National Nutrition Survey conducted in 1995, which included 3224 male and 3475 female subjects with a wide age range. Data on the isoflavone content of soybeans and their products were collected from a literature survey of Korean journals. This information was then screened based on the methodological validity, compared with values reported in international journals, and an average value adopted for each food. Thereafter, the total isoflavone intake per capita was estimated as 14.88 mg/d, which was attributed to genistein (7.32 mg), daidzein (5.81 mg), and glycitein (1.75 mg). Soybeans and three traditional soy foods (tofu, soybean paste, soybean sprouts) contributed to more than 94% of the total isoflavone intake of the Korean population. Slight differences in the isoflavone intake level and pattern were observed between the various residential areas. The rural and urban isoflavone intakes were estimated at 15.18 and 14.85 mg per capita, respectively. Rural residents were more dependent on soybeans than processed soy products for their isoflavone intake, while urban residents extracted more isoflavones from tofu, compared to their rural counterparts. The total isoflavone intake reported in this study may be underestimated, as other products containing soyflour and soy protein were not accounted for.

Dietary molar ratios of phytate:zinc and millimolar ratios of phytate x calcium:zinc in South Koreans.

The zinc nutritional status in south Koreans was established by evaluation of zinc, calcium and phytate intakes, the molar ratio of phytate:zinc, and the millimolar ratio of phytate x calcium:zinc. The intakes of iron and magnesium were also estimated. Sampling was designed so that it was representative of the national population. Two-day food records were used for the calculation of nutrient intakes, using food consumption data from the 1995 National Nutrition Survey ('95NNS) for South Korea. Daily intakes of zinc and calcium were estimated to be 10.1 mg/d and 426.5 mg/d, respectively, and those of iron and magnesium were 15.2 mg/d and 268.0 mg/d, respectively. The estimated daily phytate intake was 1676.6 mg/d. The ratio of phytate:zinc was 15.9 mol/d and that of phytate x calcium:zinc was 168.9 mmol/d. The ratio in millimoles per 4.2 MJ (1000 kcal) of phytate x calcium:zinc was 91.8. The major food groups for zinc intake were meat, poultry and their products (43%), and cereals and grain products (18%). Sixty-two percent of zinc was from animal food sources. Cereal and grain products supplied most of the phytate intake (46%) followed by seasonings, fruits, and legumes and their products. The major food source of phytate was rice (39%). The results of the study raise concern about the suboptimal zinc status in relation to the Western diet.

Differential roles of the 5' untranslated regions of cucumber mosaic virus RNAs 1, 2, 3 and 4 in translational competition.

RNA species of plant tripartite RNA viruses show distinct translational activities in vitro when the viral RNA concentration is high. However, it is not known what causes the differential translation of virion RNAs. Using an in vitro wheat germ translation system, we investigated the translation efficiencies and competitive activities of chimeric cucumber mosaic virus (CMV) RNAs that contained viral untranslated regions (UTRs) and a luciferase-coding sequence. The chimeric RNAs exhibited distinct translation efficiencies and competitive activities. For example, the translation of chimeric CMV RNA 4 was about 40-fold higher than that of chimeric CMV RNA 3 in a competitive environment. The distinct translation resulted mainly from differences in competitive activities rather than translation efficiencies of the chimeric RNAs. The differential competitive activities were specified by viral 5 UTRs, but not by 3 UTRs or viral proteins. The competitive translational activities of the 5 UTRs were as follows: RNA 4 (coat protein)>RNAs 2 and 1 (2a and 1a protein, or replicase )> RNA 3 (3a protein).

Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid.

Twenty-one naturally occurring flavonoids were tested for inhibitory activities against alpha-glucosidase (EC 3.2.1.20) and alpha-amylase (EC 3.2.1.1). Luteolin, amentoflavone, luteolin 7-O-glucoside, and daidzein were the strongest inhibitors among the compounds tested. Luteolin inhibited alpha-glucosidase by 36% at the concentration of 0.5 mg/ml and was stronger than acarbose, the most widely prescribed drug, in inhibitory potency, suggesting that it has the possibility to effectively suppress postprandial hyperglycemia in patients with non-insulin dependent diabetes mellitus. Luteolin also inhibited alpha-amylase effectively although it was less potent than acarbose. The clinical value of luteolin needs to be further evaluated.

A single-stranded loop in the 5' untranslated region of cucumber mosaic virus RNA 4 contributes to competitive translational activity.

The 5' untranslated region (UTR) of cucumber mosaic virus (CMV) RNA 4 confers a highly competitive translational advantage on a heterologous luciferase open reading frame. Here we investigated whether secondary structure in the 5' UTR contributes to this translational advantage. Stabilization of the 5' UTR RNA secondary structure inhibited competitive translational activity. Alteration of a potential single-stranded loop to a stem by substitution mutations greatly inhibited the competitive translational activity. Tobacco plants infected with wild type virus showed a 2.5-fold higher accumulation of maximal coat protein than did plants infected with a loop-mutant virus. Amplification of viral RNA in these plants could not explain the difference in accumulation of coat protein. Phylogenetic comparison showed that potential single-stranded loops of 12-23 nucleotides in length exist widely in subgroups of CMV.

The 5' untranslated region of cucumber mosaic virus RNA4 confers highly competitive activity on heterologous luciferase mRNA in cell-free translation.

The cell-free translation of virion RNAs of several tripartite RNA viruses has shown that RNA4, a subgenomic RNA, is more competitive than other virion RNAs. Recently, the 3' untranslated region (UTR) of alfalfa mosaic virus (AMV) RNA4 was identified to be a competitive determinant. In this study, we observed that the RNA4 of cucumber mosaic virus (CMV), another tripartite RNA virus, was also found to be a strong competitor in translational competition among CMV virion RNAs. To identify the competitive determinant of CMV RNA4, we constructed various chimeric luciferase mRNAs containing RNA4 and/or vector-derived UTRs. The relative translations of luciferase-containing mRNA in the presence of a competitor mRNA showed that the 5' UTR, not the 3' UTR, substantially contributed to the highly competitive activity of CMV RNA4.

Ribozyme mediated targeting of cucumber mosaic virus RNA 1 and 2 in transgenic tobacco plants.

Hammerhead ribozymes have been extensively used to inhibit the expression of cellular genes or viral genes mainly in the animal study. In this study, we designed a ribozyme targeting the conserved leader sequences of cucumber mosaic virus (CMV) RNA 1 and 2. The ribozyme, with asymmetric lengths of flanking complementary regions, cleaved a model substrate RNA efficiently at 26 degrees C as well as at 37 degrees C or 50 degrees C in vitro. And the ribozyme encoding sequence was introduced into tobacco plants and expressed with the CaMV 35S promoter and 3' NOS terminator in a monomeric type (pBIR1), tandemly repeated type (pBIR3), and cotranscriptionally combined type (pRokR) with 2.2 copies of I17N satellite RNA. Virus challenging experiments in F1 plants of respective transformants with CMV-Y showed specific reductions of viral RNA 1 and 2 in comparison with RNA 3 or 4. Although young plants of a three-leaf-stage showed rather similar mild symptom attenuations in all constructions compared to CMV-Y inoculated wild type, fully grown plants showed a differential degree of resistance upon systemic infections of CMV-Y in pRokR, pBIR3 and pBIR1 transformed plants in a decreasing order.

Alcohol consumption and breast cancer: estrogen receptor status and histology.

Data from a case-control study conducted in New York State during 1982-1984 were used to evaluate the relation between alcohol consumption and estrogen receptor-positive and estrogen receptor-negative breast cancers and alcohol and various histologic subtypes. The cases were women between 20 and 79 years of age with a diagnosis of primary breast cancer. A total of 794 estrogen receptor-positive and 358 estrogen receptor-negative breast cancer cases were available for study. Controls (n = 1,617) were selected from driver's license files of the New York State Department of Motor Vehicles. Information on estrogen receptor status and histology was obtained from hospital records. The risk of estrogen receptor-positive breast cancer was shown to increase with increasing amounts of alcohol consumption in grams per day (odds ratio (OR) = 1.18 (95% confidence interval (CI) 0.88-1.57) for < 1.5 g/day, 1.28 (95% CI 0.91-1.80) for 1.5-4.9 g/day, 1.28 (95% CI 0.96-1.70) for 5.0-14.9 g/day, and 1.35 (95% CI 0.99-1.85) for > or = 15.0 g/day). There was no relation between alcohol consumption and estrogen receptor-negative tumors (OR = 0.92 (95% CI 0.62-1.36) for < 1.5 g/day, 1.19 (95% CI 0.77-1.83) for 1.5-4.9 g/day, 0.94 (95% CI 0.64-1.35) for 5.0-14.9 g/day, and 1.05 (95% CI 0.70-1.59) for > or = 15.0 g/day). The risk for each of the histologic subtypes studied increased with increasing daily alcohol consumption. These findings suggest that alcohol may only increase a woman's risk of estrogen receptor-positive breast cancers.

An epidemiological case-control study of breast cancer and alcohol consumption.

A case-control study of breast cancer and alcohol consumption was conducted with 1617 patients diagnosed with a primary cancer of the breast between 1982 and 1984 in 18 New York State counties. For each case, one control, matched for year of birth and county of residence, was selected from the driver's license files of the New York State Department of Motor Vehicles. Breast cancer risk was shown to increase as daily consumption of alcohol increased, with a risk of 1.37 (95% Cl = 1.07, 1.75) observed among women who consumed 15 or more grams of alcohol per day. Breast cancer risk did not appear to be related to the total number of years a woman drank or to be restricted to specific types of alcoholic beverages. The data suggest that this may be higher in women who began drinking at a later age. The increased risk associated with alcohol consumption, observed in the current study, persisted within strata of various breast cancer risk factors.

A nationwide study of breast disease.

Records of histopathology from the 3734 Jewish women having breast biopsy and/or operations in all Israeli hospitals during the year from July 1979 to June 1980 were reviewed. Approximately 28.5% of these women were diagnosed as having breast cancer and 71.5% as having benign breast disease: 48.5% had benign proliferative mastopathy (BPM), 16.6% had fibroadenoma (FA) without coexistent BPM, and 6.4% had other benign breast conditions. The age-specific incidence rate was 66 in 100,000 for breast cancer and 165.2 in 100,000 for benign breast disease. Native European or American women and native Israeli women had significantly higher age standardized incidence rates of both breast cancer and BPM, but not of FA, as compared to African/Asian-born women (P less than 0.01). Age-related ratios between invasive to precursor breast lesions were similar in all ethnic groups. The data suggest that breast cancer and benign proliferative mastopathy may have a common etiologic component.

Family history, oral contraceptive usage, and breast cancer.

When breast cancer patients were grouped according to their family history of breast cancer striking differences were found in age distribution. Thus, the proportion of cases less than 45 years of age was grandmother greater than aunt greater than mother greater than FH-negative greater than sister. A similar FH-related sequence was observed in regard to current OC usage among breast cancer patients less than 45 years of age. It also appeared that current oral contraceptive (OC) usage increased the risk of invasive breast cancer among grandmother- or aunt-positive women while decreasing the risk among FH-negative women. There are important practical and conceptual reasons for further studies of the influence of interactions between age, OC usage and family history on the stepwise development of breast cancer.

Family history and oral contraceptives: unique relationships in breast cancer patients.

The relative frequency of a history of breast cancer among specific blood relatives was determined for breast cancer patients according to their prior use of oral contraceptives (OC). These data were compared with those derived from patients having various types of noninvasive breast lesions and from control women. It was found that a history of breast cancer among grandmothers or aunts was significantly more frequent among breast cancer patients who had used OC for one or more years continuously than among OC-negative breast cancer patients, and among patients with noninvasive breast lesions and control women, regardless of OC usage. Breast cancer patients whose grandmothers or aunts had breast cancer used OC significantly more frequently than did family history (FH)-negative breast cancer patients and breast cancer patients having a history of breast cancer limited to relatives other than grandmothers and aunts (mothers, sisters, cousins). It appears that the family history is a significant covariable in the relationship between OC usage and breast cancer. There is a need for specific studies to test the possibilities that OC usage increases the risk of breast cancer among women whose grandmothers or aunts had breast cancer, and reduces the risk of breast cancer in FH-negative women.

Fibrocystic disease of the breast.

Fibrocystic disease is the most common type of lesion in the female breast. It is a common dumping ground for a variety of distinct clinical and histologic entities which require different modalities of therapy and which have different malignant transformation potentials. In general, fibrocystic disease is managed medically unless a dominant lump or other adverse symptom develops, in which case a biopsy is performed. The exception to this rule is a cyst which can be safely aspirated under controlled conditions. If, on biopsy, one of the histologic types of fibrocystic disease called "precancerous mastopathy" is found, which has a high potential for malignant transformation, then serious consideration must be given to definitive surgical procedures, especially if the patient has other risk factors that would increase her risk of developing breast cancer even further.

Ultrastructural characteristics of sinus histiocytic reaction in lymph nodes draining various stages of breast cancer.

An ultrastructural study of sinus histiocytosis (SH) in axillary lymph nodes was undertaken in 20 patients with primary cancer of the breast. The lymph node responses were first classified by means of light microscopy, according to previously established criteria. The ultrastructural findings established three major patterns of SH response in cancer-draining lymph nodes: developing SH, positive SH, and degenerative SH. These patterns followed closely the classification obtained by light microscopy. An important finding of electron microscopy was the presence of early activation of histiocytes (developing SH) in microscopy (negative SH). The striking ultrastructural resemblance of histiocytes in positive SH to epithelioid cells seen in delayed hypersensitivity reactions (TB) again points to the fact that the positive SH pattern represents a tumor-host reaction of the delayed hypersensitivity type. Finally, although the presence of virus has been shown to play a role in spontaneous BALB/c murine breast tumor, no virions could be found in human cancer-draining lymph nodes.