Cefepime-induced encephalopathy in an older patient with polypharmacy and renal insufficiency: a case report.

The world population is rapidly aging. Societal aging poses many challenges for individuals, families, nations, and the global healthcare system. Therefore, geriatric care is a crucial issue that demands our attention. In this case report, we describe a woman in her early 70s with multiple comorbidities, polypharmacy, and renal insufficiency who developed cefepime-induced encephalopathy with moderate to severe cerebral dysfunction during treatment of a urinary tract infection. The patient's consciousness level gradually improved, and no further seizures were observed following the discontinuation of cefepime for several days. This case report underscores the fact that polypharmacy and medication safety are significant concerns that are often overlooked when caring for older patients. The report also highlights the increased susceptibility of older individuals to antibiotic-associated adverse reactions during the management of infectious diseases. Therefore, optimization of antibiotic therapy for older patients is a critical issue that requires thorough investigation and consideration in geriatric care.

Nepenthes Extract Induces Selective Killing, Necrosis, and Apoptosis in Oral Cancer Cells.

Ethyl acetate Nepenthes extract (EANT) from Nepenthes thorellii × (ventricosa × maxima) shows antiproliferation and apoptosis but not necrosis in breast cancer cells, but this has not been investigated in oral cancer cells. In the present study, EANT shows no cytotoxicity to normal oral cells but exhibits selective killing to six oral cancer cell lines. They were suppressed by pretreatment of the antioxidant inhibitor N-acetylcysteine (NAC), demonstrating that EANT-induced cell death was mediated by oxidative stress. Concerning high sensitivity to EANT, Ca9-22 and CAL 27 oral cancer cells were chosen for exploring detailed selective killing mechanisms. EANT triggers a mixture of necrosis and apoptosis as determined by annexin V/7-aminoactinmycin D analysis. Still, they show differential switches from necrosis at a low (10 µg/mL) concentration to apoptosis at high (25 µg/mL) concentration of EANT in oral cancer cells. NAC induces necrosis but suppresses annexin V-detected apoptosis in oral cancer cells. Necrostatin 1 (NEC1), a necroptosis inhibitor, moderately suppresses necrosis but induces apoptosis at 10 µg/mL EANT. In contrast, Z-VAD-FMK, a pancaspase inhibitor, slightly causes necrosis but suppresses apoptosis at 10 µg/mL EANT. Furthermore, the flow cytometry-detected pancaspase activity is dose-responsively increased but is suppressed by NAC and ZVAD, although not for NEC1 in oral cancer cells. EANT causes several oxidative stress events such as reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization. In response to oxidative stresses, the mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), heme oxygenase 1 (HMOX1), and thioredoxin (TXN), are overexpressed in oral cancer cells. Moreover, EANT also triggers DNA damage, as detected by γH2AX and 8-oxo-2'-deoxyguanosine adducts. The dependence of oxidative stress is validated by the evidence that NAC pretreatment reverts the changes of cellular and mitochondrial stress and DNA damage. Therefore, EANT exhibits antiproliferation involving an oxidative stress-dependent necrosis/apoptosis switch and DNA damage in oral cancer cells.

Nepenthes Ethyl Acetate Extract Provides Oxidative Stress-Dependent Anti-Leukemia Effects.

Several kinds of solvents have been applied to Nepenthes extractions exhibiting antioxidant and anticancer effects. However, they were rarely investigated for Nepenthes ethyl acetate extract (EANT), especially leukemia cells. The purpose of the present study was to evaluate the antioxidant properties and explore the antiproliferation impact and mechanism of EANT in leukemia cells. Five standard assays demonstrated that EANT exhibits antioxidant capability. In the cell line model, EANT dose-responsively inhibited cell viabilities of three leukemia cell lines (HL-60, K-562, and MOLT-4) based on 24 h MTS assays, which were reverted by pretreating oxidative stress and apoptosis inhibitors (N-acetylcysteine and Z-VAD-FMK). Due to similar sensitivities among the three cell lines, leukemia HL-60 cells were chosen for exploring antiproliferation mechanisms. EANT caused subG1 and G1 cumulations, triggered annexin V-detected apoptosis, activated apoptotic caspase 3/7 activity, and induced poly ADP-ribose polymerase expression. Moreover, reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization were generated by EANT, which was reverted by N-acetylcysteine. The antioxidant response to oxidative stress showed that EANT upregulated mRNA expressions for nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), thioredoxin (TXN), heme oxygenase 1 (HMOX1), and NAD(P)H quinone dehydrogenase 1 (NQO1) genes. Moreover, these oxidative stresses led to DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) and were alleviated by N-acetylcysteine. Taken together, EANT demonstrated oxidative stress-dependent anti-leukemia ability to HL-60 cells associated with apoptosis and DNA damage.

Correction: Ou-Yang, F. et al. Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima). Int. J. Mol. Sci. 2019, 20, 3238.

The authors would like to make corrections to their published paper [...].

Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima).

Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2'deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.

Environmental barriers and social participation in individuals with spinal cord injury.

OBJECTIVE: The study aimed to examine the relationship between environmental barriers and social participation among individuals with spinal cord injury (SCI). METHOD: Individuals admitted to regional centers of the Model Spinal Cord Injury System in the United States due to traumatic SCI were interviewed and included in the National Spinal Cord Injury Database. This cross-sectional study applied a secondary analysis with a mixed effect model on the data from 3,162 individuals who received interviews from 2000 through 2005. Five dimensions of environmental barriers were estimated using the short form of the Craig Hospital Inventory of Environmental Factors-Short Form (CHIEF-SF). Social participation was measured with the short form of the Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF) and their employment status. RESULTS: Subscales of environmental barriers were negatively associated with the social participation measures. Each 1 point increase in CHIEF-SF total score (indicated greater environmental barriers) was associated with a 0.82 point reduction in CHART-SF total score (95% CI: -1.07, -0.57) (decreased social participation) and 4% reduction in the odds of being employed. Among the 5 CHIEF-SF dimensions, assistance barriers exhibited the strongest negative association with CHART-SF social participation score when compared to other dimensions, while work/school dimension demonstrated the weakest association with CHART-SF. CONCLUSIONS: Environmental barriers are negatively associated with social participation in the SCI population. Working toward eliminating environmental barriers, especially assistance/service barriers, may help enhance social participation for people with SCI. (PsycINFO Database Record

Association of internet use and depression among the spinal cord injury population.

OBJECTIVE: To examine the relation between the frequency of Internet use and depression among people with spinal cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: SCI Model Systems. PARTICIPANTS: People with SCI (N=4618) who were interviewed between 2004 and 2010. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The frequency of Internet use and the severity of depressive symptoms were measured simultaneously by interview. Internet use was reported as daily, weekly, monthly, or none. The depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), with 2 published criteria being used to screen for depressive disorder. The diagnostic method places more weight on nonsomatic items (ie, items 1, 2, and 9), and the cut-off method that determines depression by a (PHQ-9) score ≥10 places more weight on somatic factors. The average scores of somatic and nonsomatic items represented the severity of somatic and nonsomatic symptoms, respectively. RESULTS: Our multivariate logistic regression model indicated that daily Internet users were less likely to have depressive symptoms (odds ratio=.77; 95% confidence interval, .64-.93), if the diagnostic method was used. The linear multivariate regression analysis indicated that daily and weekly Internet usage were associated with fewer nonsomatic symptoms; no significant association was observed between daily or weekly Internet usage and somatic symptoms. CONCLUSIONS: People with SCI who used the Internet daily were less likely to have depressive symptoms.