Effects of Preoperative Chronic Steroid Use on Postoperative Outcomes in Orthopedic Surgery: A Systematic Review and Meta-Analysis.

Higher rates of postoperative complications have been found in preoperative chronic steroid users. However, the effects of preoperative chronic steroid use on outcomes in orthopedic surgery were unclear. We performed a systematic review of cohort studies examining the effects of chronic steroid use on postoperative outcomes following orthopedic surgery and searched PubMed, Embase, and CENTRAL through 29 April 2023. We included 17 studies with 1,546,562 patients. No increase in 30-day mortality (adjusted odds ratio (aOR) 1.40, 95% confidence interval (CI) 0.64-3.09) and composite thromboembolic events (aOR 1.61, 95% CI 0.99-2.63) but increases in 30-day overall complications (aOR 1.42, 95% CI 1.16-1.75), wound dehiscence (aOR 2.91, 95% CI 1.49-5.66), infectious complications (any infection (aOR 1.61, 95% CI 1.44-1.80), sepsis (aOR 2.07, 95% CI 1.34-3.21), superficial surgical site infection (SSI) (aOR 1.73, 95% CI 1.03-2.89) and deep SSI (aOR 1.96, 95% CI 1.26-3.05)), re-admission (aOR 1.62, 95% CI 1.48-1.77), both 30-day (aOR 1.28, 95% CI 1.03-1.59) and 1-year re-operation (aOR 1.78, 95% CI 1.09-2.92), pulmonary embolism (aOR 5.94, 95% CI 1.52-23.29), and deep vein thrombosis (aOR 2.07, 95% CI 1.24-3.46) were detected in preoperative steroid users. An increased risk of adverse outcomes following orthopedic surgery in chronic steroid users was found.

Using random forest to predict antimicrobial minimum inhibitory concentrations of nontyphoidal Salmonella in Taiwan.

Antimicrobial resistance (AMR) is a global health issue and surveillance of AMR can be useful for understanding AMR trends and planning intervention strategies. Salmonella, widely distributed in food-producing animals, has been considered the first priority for inclusion in the AMR surveillance program by the World Health Organization (WHO). Recent advances in rapid and affordable whole-genome sequencing (WGS) techniques lead to the emergence of WGS as a one-stop test to predict the antimicrobial susceptibility. Since the variation of sequencing and minimum inhibitory concentration (MIC) measurement methods could result in different results, this study aimed to develop WGS-based random forest models for predicting MIC values of 24 drugs using data generated from the same laboratories in Taiwan. The WGS data have been transformed as a feature vector of 10-mers for machine learning. Based on rigorous validation and independent tests, a good performance was obtained with an average mean absolute error (MAE) less than 1 for both validation and independent test. Feature selection was then applied to identify top-ranked 10-mers that can further improve the prediction performance. For surveillance purposes, the genome sequence-based machine learning methods could be utilized to monitor the difference between predicted and experimental MIC, where a large difference might be worthy of investigation on the emerging genomic determinants.

AAV8-Mediated Gene Therapy Rescues Retinal Degeneration Phenotype in a Tlcd3b Knockout Mouse Model.

Purpose: The purpose of this study was to assess the therapeutic efficacy of rAAV8-hGRK1-Tlcd3b in a Tlcd3b-/- mouse model of retinal generation and validate TLCD3B's role as a ceramide synthase in vivo. Methods: Using Tlcd3b-/- mice as an inherited retinal disease animal model, we performed subretinal injection of rAAV8-hGRK1-Tlcd3b and evaluated the efficacy of gene replacement therapy. Tlcd3b-/- mice were treated at two time points: postnatal day 21 (P21) and postnatal day 120 (P120) with various dosages. Results: Tlcd3b overexpression rescued retinal degeneration in the mutant mice, as indicated by significantly improved photoreceptor function and preservation of photoreceptor cells over the course of 1 year. Although Tlcd3b is expressed in all cell types in the retina, photoreceptor cell-specific expression of Tlcd3b is sufficient to rescue the phenotype, indicating the primary function of TLCD3B is in photoreceptors. Consistent with the idea that TLCD3B is a ceramide synthase, mass spectrometry analyses of the mutant retina indicate the reduction of C16-, C18-, and C20-ceramides in the retina, which are restored with Tlcd3b overexpression. Conclusions: Our findings demonstrated the therapeutic efficacy of gene therapy in treating Tlcd3b mutant retina, laying the foundation for developing future therapy for TLCD3B retinopathy.

Evaluation of a new-formula shampoo containing 6% glycyrrhetinic acid complex for scalp seborrheic dermatitis: A pilot study.

BACKGROUND: Scalp seborrheic dermatitis (SD) is a chronic inflammatory dermatosis associated with sebum imbalance and proliferation of Malassezia species. Various antifungal shampoos are commonly used for scalp SD. AIMS: Glycyrrhetinic acid is known to have antioxidative, anti-inflammatory, and anti-allergic effects. This study was designed to evaluate the effectiveness of a new-formula shampoo that contains glycyrrhetinic acid for the treatment of scalp SD. PATIENTS/METHODS: Thirty-four patients were enrolled and treated with the 6% glycyrrhetinic acid complex shampoo. Efficacy was assessed clinically with Dermatology Life Quality Index (DLQI) and Adherent Scalp Flaking Score (ASFS) by the same dermatologist at baseline, week 2, and week 5. Among the 24 subjects with the most significant clinical improvement, four common microorganisms from scalp samples were analyzed by quantitative polymerase chain reaction (qPCR) at baseline, and week 5. RESULTS: The DLQI and ASFS at week 2 and week 5 improved significantly relative to baseline. The bacteria profiles showed a significant increase of Cutibacterium acnes and a decrease of Staphylococcus epidermidis at week 5. The fungi profiles showed significant decreases of both Malassezia restricta and Malassezia globosa. The ratio of C. acne to S. epidermidis increased significantly from 0.93 at baseline to 1.55 at week 5. The ratio of M. restricta to M. globosa decreased from 5.02 at baseline to 1.00 at week 5. CONCLUSIONS: The effectiveness of this new regimen was objectively demonstrated at the clinical and microbiological levels. This new formula may alleviate the bacterial and fungal dysbiosis in scalp SD.

Antioxidant vitamins promote anticancer effects on low-concentration methotrexate-treated glioblastoma cells via enhancing the caspase-3 death pathway.

Vitamin C and vitamin E are well-known antioxidant vitamins, both of which are also applied as adjunct treatments for cancer therapy. Methotrexate (MTX) is a clinical drug that is used widely for rheumatoid arthritis and cancer treatment. Human glioblastoma multiforme (GBM) is an aggressive malignant brain tumor; the mean survival time for GBM patients is <2 years with traditional therapies. Developing and investigating novel treatments are important for clinical GBM therapy. Therefore, the aim of this study was to investigate whether combined treatment with vitamin C/E and MTX can display anticancer activities on GBM. Our studies showed that MTX displays anticancer effects on GBM in a dose-dependent manner, while vitamins C and E are not cytotoxic to glioblastoma. Importantly, this study showed that vitamins C and E can promote anticancer effects on low-concentration methotrexate-treated glioblastoma. Additionally, this study suggested that MTX alone or combined with vitamins C/E inhibits GBM cell growth via the caspase-3 death pathway.

Analysis and formation of polycyclic aromatic hydrocarbons and cholesterol oxidation products in thin slices of dried pork during processing.

This study aims to determine toxic compounds polycyclic aromatic hydrocarbons (PAHs) and cholesterol oxidation products (COPs) in thin slices of dried pork as affected by different flavorings and roasting temperature treatments through employing a QuEChERS method coupled with gas chromatograph-tandem mass spectrometer (GC-MS/MS) and gas chromatograph-mass spectrometer (GC-MS), respectively. By employing this method, high accuracy and precision was attained for freeze-dried pork hind leg sample. Following addition of 8 different flavorings with roasting temperature at 120, 160, and 200 °C, the levels of total COPs and PAHs in thin slices of dried pork followed a temperature-dependent increase during roasting, which was further confirmed by principle component analysis. High level of soy sauce or sugar inhibited COP formation, while the low-level minimized PAH formation in thin slices of dried pork during roasting. Sugar was more effective in inhibiting COP formation while soy sauce was more efficient in reducing PAH formation.

1-Aminocyclopropane-1-carboxylate (ACC) Deaminase Gene in Pseudomonas azotoformans Is Associated with the Amelioration of Salinity Stress in Tomato.

Although bacteria with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity have been used to mitigate biotic and abiotic stresses in crops, it is not well known whether the ACC deaminase gene (acdS) in Pseudomonas azotoformans is related to the alleviation of salt stress by the bacterium. This study aimed to evaluate the effects of acdS in P. azotoformans strain CHB 1107 on the nutrient uptake and growth of tomato plants under salt stress. The acdS mutant (CHB 1107 M) of P. azotoformans CHB 1107 was obtained through bacterial conjugation. Wild-type (CHB 1107 WT) and CHB 1107 M were used to inoculate tomato plants grown in a soil or solution with an electrical conductivity of 6 dS/m adjusted by NaCl. CHB 1107 M completely lost the ability to produce ACC deaminase, whereas the complementation of acdS in CHB 1107 M preserved its ACC deaminase activity. CHB 1107 WT significantly reduced the production of ethylene and proline by tomato plants under salt stress, increasing the shoot and root dry weights of tomato plants compared with the noninoculated control and CHB 1107 M. In addition, tomato plants inoculated with CHB 1107 M showed a significant reduction in K (27.5%), Ca (23.0%), and Mn uptake (17.5%) compared with those inoculated with CHB 1107 WT. In contrast, CHB 1107 WT significantly reduced Na uptake by tomato plants in comparison to CHB 1107 M in saline soil conditions. In addition, the inoculation of tomato plants with CHB 1107 WT resulted in a higher K/Na ratio than in those inoculated with CHB 1107 M and the noninoculated control. These findings suggest that acdS in P. azotoformans is associated with the amelioration of salinity stress in tomato. Plant transformation with acdS and the field application of P. azotoformans may be used as potential management tools for crops under salt stress.

Isolation of individual isoflavone species from soybean by solvent extraction followed by the combination of macroporous resin and aluminium oxide separation.

Growing interest in the health benefits of soy isoflavones has led to research in the isolation of individual isoflavone species for further application. Herein, we develop a new strategy to isolate daidzein, genistein, daidzin and genistin in soybean. We investigated the impact of solvents used and the extraction time on the extracted isoflavone contents from soybean. A 30-min extraction with 65% aqueous methanol gave a total isoflavone yield of 345 mg/100 g soybean, the highest value among tested conditions. Further, we proposed a two-stage adsorption/desorption chromatography comprising macroporous resin and aluminium oxide to isolate isoflavone. First, HP-20 resin was used to separate the glucosidic and aglyconic forms of isoflavone, then individual species of isoflavone could be isolated using aluminium oxide by specific retention of 5-hydroxy isoflavone. This process achieved overall high recovery (82-97%) and purity (92-95%) of the four isoflavones, which confirms a high separating efficiency for isoflavones from soybean.

The Effects of Task Prioritization on Dual-Tasking Postural Control in Patients With Parkinson Disease Who Have Different Postural Impairments.

OBJECTIVE: To investigate the effect of task prioritization on dual-task control in Parkinson disease (PD) associated with different postural impairments. DESIGN: Cross-sectional study. Participants were instructed to keep 2 interlocking rings apart and maintain balance in a tandem stance. Attention was focused on either stance stability (posture-focus strategy) or the interlocking rings (supraposture-focus strategy). SETTING: University research laboratory. PARTICIPANTS: Fifteen patients with PD and less postural impairment and 15 patients with PD and more postural impairment (N=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Postural sway, postural determinism (%DET), ankle co-contraction, and ring-touching time. RESULTS: In the less-impairment group, the supraposture-focus strategy provided smaller postural sway and postural %DET compared with the posture-focus strategy. In the more-impairment group, task prioritization showed lower effect on both postural sway and postural %DET. The supraposture-focus strategy led to less ankle co-contraction than the posture-focus strategy in the more-impairment group, but task prioritization did not affect ankle co-contraction in the less-impairment group. In both groups, the supraposture-focus strategy led to less ring-touching time than the posture-focus strategy. CONCLUSIONS: The supraposture-focus strategy provided better dual-task control than the posture-focus strategy in both PD groups. In the less-impairment group, the supraposture-focus strategy enhanced postural automaticity and postural stability. In the more-impairment group, the supraposture-focus strategy reduced ankle stiffness, owing to reduced muscle co-contraction.

Anti-Cancer Effects of Sulfasalazine and Vitamin E Succinate in MDA-MB 231 Triple-Negative Breast Cancer Cells.

Aim: Sulfasalazine (SSZ) displayed anti-cancer activities. Vitamin E succinate (VES) could inhibit cell growth in various cancer cells. However, chemical therapies were often not useful for triple-negative breast cancer cells (TNBCs) treatment. Here, this study investigated the anti-cancer effects and the mechanisms on TNBCs under combination treatment with SSZ and VES. Methods: Cell viability was analyzed by using the MTT assay. The H2O2 levels were determined by using lucigenin-amplified chemiluminescence method. In addition, caspase and MAPs signals were studied by using western blotting. Results: Low-dose VES antagonized the SSZ-induced cytotoxicity effects while high-dose VES promoted the SSZ-induced cytotoxicity effects on TNBCs. In addition, SSZ alone treatment activated both caspase-3 and ERK signals, however, VES alone treatment only activated JNK signals. On the other hand, activation of caspase-3, JNK, and ERK were found in SSZ plus VES-treated cells. Conclusion: Combined SSZ and VES has synergistic or antagonistic cytotoxic effects depending on VES concentration. In addition, different cytotoxic signals are induced on SSZ-treated, VES-treated and SSZ plus VES-treated cells.

Effects of irradiance on UVA-induced skin aging.

BACKGROUND: Ultraviolet A (UVA) radiation is the most relevant component of solar radiation-induced skin aging. Sunscreens were used to minimize the harmful effects of UV radiation on our skin by reducing UV irradiance. We previously found that at equivalent fluence, UVB radiation at low irradiance (LI) has higher photocarcinogenic potential as compared to its high irradiance (HI) counterpart. OBJECTIVES: To examine the effects of equivalent fluence of UVA radiation administered at different irradiance on photoaging. METHODS: Both the hairless mice (SKH-1) and human dermal fibroblasts were irradiated with high irradiance UVA (HIUVA) or low irradiance UVA (LIUVA; 50% irradiance of HIUVA) at equivalent fluence. Parameters related to skin photoaging were evaluated. RESULTS: For hairless mice receiving equivalent fluence of UVA radiation, LIUVA treated mice showed prominent skin aging as compared to its HIUVA treated counterpart. In addition, LIUVA radiation induced higher reactive oxygen species (ROS) production and c-Jun N-terminal kinases (JNK) phosphorylation as compared to their HIUVA treated counterparts. Pretreatment with N-acetylcysteine (NAC) abrogate the difference between HI and LIUVA radiation on fibroblasts in terms of intracellular ROS, JNK phosphorylation, MMP-1 expression and type I collagen expression. CONCLUSION: UVA radiation administered at LI (a scenario similar to sunscreen use) led to more severe aging process as compared to its HI counterpart. Unexpected negative effect may be imposed on the skin if sunscreen use is accompanied by longer duration spent under the sun.

Developing a Decision-Aid Website for Breast Cancer Surgery: An Action Research Approach.

BACKGROUND: Patients with early-stage breast cancer have numerous options when choosing the type of breast surgery method to be applied. Each of these options lead to a similar long-term survival rate, but result in significant differences in appearance, function, cost, recurrence rate, and various other relevant considerations. However, the time available for detailed communication with each patient is often limited in clinics, which puts these women under great psychological stress and can hinder their surgery-related decision making. OBJECTIVE: The objective of this study was to develop a multipurpose surgery decision-making website providing medical information, psychological support, and decision-related simulation for women during breast cancer surgery-related decision making. METHODS: Using the 4 steps of action research, which involve multigroup teamwork via regular team meetings, the following were performed: (1) Planning: searching, analyzing, and evaluating health websites to consensually decide the major infrastructure; (2) Action: work was performed simultaneously in 4 groups, which consisted of medical information collection and editing, patient interviews and data extraction, webpage content design, and programming to create or host the website; (3) Evaluation: the website was tested by clinical experts and focus groups of former breast cancer patients to assess its effectiveness and pinpoint appropriate improvements; and (4) Reflection: constant dialogue was conducted between the various participants at each step, which was used as the foundation and motivation of next plan-action-evaluation-reflection circle. RESULTS: Using the action research approach, we completed the development of our website, which includes the following: (1) "Woman's Voice"-an animated comic depicting the story of a female breast cancer patient with interspersed questions for the users that will help them better empathize with the experience; (2) "Cancer Information Treasure House"-providing breast cancer surgery-related information through text, tables, pictures and a presentation video; (3) "Decision-making Simulator"-helping patients think through and check the pros and cons of the different surgical options via visual-based interactions including "Stairs Climbing" and "Fruit of Hope"; and (4) "Recommended Links"-providing reliable websites for further reference. Additionally, we have further improved the website based on the feedback received from postsurgery breast cancer patients and clinicians. We hope to continue improving to better meet both the patients' and health providers' needs and become a practical decision-making aid for patients undergoing breast cancer surgery. CONCLUSIONS: We have created the first breast cancer surgery decision-making assistance tool in Taiwan using a "Web-based" and multifunctional website design. This site aims to provide health care knowledge, psychological healing, and emotional support functions, as well as decision-making capability enhancement simulations. We look forward to assisting breast cancer patients in their decision-making process and expect our website to increase patient's autonomy and improve their communication with clinicians.

Developing a Web-Based Comic for Newly Diagnosed Women With Breast Cancer: An Action Research Approach.

BACKGROUND: Personal narratives have been seen as a useful way of communicating about cancer treatment options and providing recovery information. Many printed versions of such material are available, including comics that explore the individual memories of patients who have gone through cancer treatment. These studies have been used to orientate patients, patients' relatives, and physicians. However, only a few Web-based comics have been specifically designed for patients with breast cancer and used as aids to decision making. OBJECTIVE: We aimed to describe the developmental process of creating an animated comic as a Web-based surgery decision-making tool; the comic was aimed at illustrating the feelings, thoughts, and meanings when a patient suffers from breast cancer. This was done by recounting the symptoms, diagnostic process, treatments, and treatment effects of such women from the diagnosis stage onward. METHODS: Using cycles of planning, action, evaluation, and reflection, which involved collaborative work, action research was conducted to develop a Web-based animated comic. The stages of action research consisted of (1) semistructured and in-depth interviews to collect experiences of women with breast cancer; (2) construction of an animated comic by editors, graphics designers, dubbers, and information technology engineers; (3) redrawing of pictures of the comic after gathering feedback from a breast surgeon; and (4) evaluation of the Web-based animated comic using 6 patient focus groups. RESULTS: The comic was produced and showcased on the website "The Network of Making-decision Aids for Breast Cancer Surgery"; the comic was accompanied by soft music and audio explanations. The comic functions as a personal statement that describes experiencing breast cancer. The animated comic consists of 8 chapters, based on the 8 themes deducted from the findings obtained during the analysis of relevant interviews. The 8 chapters include (1) the appearance of a lump; (2) confirmation by medical diagnosis; (3) the uncertainty of waiting (4) fear of life-threatening disease; (5) choosing life over despair; (6) being brave and deciding to undergo treatment; (7) choosing the type of surgery; and (8) being reborn. CONCLUSIONS: Using action research, this study illustrated that the comic that sheds light on issues of feelings, emotions, and thoughts that are present when a woman is diagnosed with breast cancer and provides a communication medium to explain the steps in the process. Meanwhile, it implies that hope will be able to overcome the challenges that will be faced. Within the Web-based decision aid for patients with breast cancer, the animated comic acts as an information resource and is aimed at patients' understanding of impacts of emotions arising when suffering from breast cancer. It is potentially applicable as a therapeutic tool that facilitates self-reflection and self-healing among newly diagnosed patients with breast cancer.

Anticancer effects of methotrexate in combination with α­tocopherol and α­tocopherol succinate on triple­negative breast cancer.

Triple­negative breast cancers (TNBCs) lack the estrogen receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Therefore, hormone or targeted therapies are not effective in the treatment of TNBC and thus the development of novel therapeutic strategies is crucial. Methotrexate (MTX), a folate antagonist, has been used in the treatment of various types of cancer; however, the anticancer effects of MTX treatment on breast cancer have thus far been ineffective. Vitamin E variants and derivatives have been applied for cancer therapy. Previous studies have indicated that vitamin E variants and derivatives exert distinct anticancer effects on different types of cancer. However, whether MTX plus vitamin E variants or its derivatives can inhibit TNBC remains unclear. The aim of the present study was to examine the anticancer effects and mechanisms of action of MTX in combination with vitamin E variants (α­tocopherol) and derivatives (α­tocopherol succinate) on TNBC. In the present study, MTT assay and western blot analysis were used to determine the cell survival rates and protein levels. The results demonstrated that combination treatment with MTX and α­tocopherol suppressed TNBC cell proliferation. In addition, various concentrations of MTX exerted distinct cytotoxic effects on α­tocopherol succinate­treated cells. Furthermore, high­dose MTX enhanced α­tocopherol succinate­induced anticancer activity; however, low­dose MTX inhibited α­tocopherol succinate­induced anticancer activity. The present study also demonstrated that caspase­3 activation and poly(adenosine diphosphate­ribose) polymerase cleavage were observed in the α­tocopherol succinate/MTX­treated cells. In conclusion, the findings of the present study demonstrated that high­dose MTX enhanced anticancer activity in α­TOS­treated TNBC, while low­dose MTX reduced anticancer activity in α­TOS­treated TNBC.

Cost-effectiveness analysis of lumacaftor and ivacaftor combination for the treatment of patients with cystic fibrosis in the United States.

BACKGROUND: Lumacaftor/ivacaftor was approved by the Food and Drug Administration (FDA) as a combination treatment for Cystic Fibrosis (CF) patients who are homozygous for the F508del mutation. The objective of this study was to assess the cost-effectiveness of lumacaftor/ivacaftor combination for the treatment of CF homozygous for F508del CF Transmembrane Conductance Regulator (CFTR) mutation. METHODS: A Markov-state transition model following a cohort of 12 year-old CF patients homozygous for F508del CFTR mutation in the United States (US) over two, four, six, eight and ten years from a payer's perspective was developed using TreeAge Pro 2016. Markov states included: mild (percentage of predicted forced expiratory volume in 1 s or FEV1 > 70%), moderate (FEV1 40-70%), severe (FEV1 < 40%) disease, post-transplant, and death. Pulmonary exacerbation and lung transplant were included as transition states. All the input parameters were estimated from the literature. A 1-year cycle length and 3% discount rate were applied. To assess uncertainty in long-term treatment effects, several scenarios were modelled: 100% long-term effectiveness (base-case), defined as improvement in FEV1 in the first year followed by no annual FEV1 decline and a constant reduction in pulmonary exacerbations throughout, 75%, 50%, 25% and 0% (worst case) long-term effectiveness, where treatment effects were intermediate from the second year of treatment until the end of the time horizon. Other scenarios included changing the starting age of the cohort to 6 and 25 years. Primary outcome included incremental cost-effectiveness ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to determine uncertainty. RESULTS: Under the base-case, Lumacaftor/ivacaftor resulted in higher QALYs (7.29 vs 6.84) but at a very high cost ($1,778,920.88) compared to usual care ($116,155.76) over a 10-year period. The ICER for base-case and worst-case scenarios were $3,655,352 / QALY, and $8,480,265/QALY gained, respectively. In the base-case, lumacaftor/ivacaftor was cost-effective at a threshold of $150,000/QALY-gained when annual drug costs were lower than $4153. The results were not substantially affected by the sensitivity analyses. CONCLUSIONS: The intervention produces large QALY gains but at an extremely high cost, resulting in an ICER that would not typically be covered by any insurer. Lumacaftor/ivacaftor's status as an orphan drug complicates coverage decisions.

Patient Experience-based Value Sets: Are They Stable?

BACKGROUND: Although societal preference weights are desirable to inform resource-allocation decision-making, patient experienced health state-based value sets can be useful for clinical decision-making, but context may matter. OBJECTIVE: To estimate EQ-5D value sets using visual analog scale (VAS) ratings for patients undergoing knee replacement surgery and compare the estimates before and after surgery. METHODS: We used the Patient Reported Outcome Measures data collected by the UK National Health Service on patients undergoing knee replacement from 2009 to 2012. Generalized least squares regression models were used to derive value sets based on the EQ-5D-3 level using a development sample before and after surgery, and model performance was examined using a validation sample. RESULTS: A total of 90,450 preoperative and postoperative valuations were included. For preoperative valuations, the largest decrement in VAS values was associated with the dimension of anxiety/depression, followed by self-care, mobility, usual activities, and pain/discomfort. However, pain/discomfort had a greater impact on VAS value decrement in postoperative valuations. Compared with preoperative health problems, postsurgical health problems were associated with larger value decrements, with significant differences in several levels and dimensions, including level 2 of mobility, level 2/3 of usual activities, level 3 of pain/discomfort, and level 3 of anxiety/depression. Similar results were observed across subgroups stratified by age and sex. CONCLUSIONS: Findings suggest patient experience-based value sets are not stable (ie, context such as timing matters). However, the knowledge that lower values are assigned to health states postsurgery compared with presurgery may be useful for the patient-doctor decision-making process.

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways.

Methotrexate (MTX) is widely used as both an anticancer and anti-rheumatoid arthritis drug. Although MTX has been used to inhibit the growth of many cancer cells, it cannot effectively inhibit growth of triple-negative breast cancer cells (TNBC cells). Vitamin C is an antioxidant that can prevent oxidative stress. In addition, vitamin C has been applied as adjunct treatment for growth inhibition of cancer cells. Recent studies indicated that combined treatment with vitamin C and MTX may inhibit MCF-7 and MDA-MB-231 breast cancer cell growth through G2/M elongation. However, the mechanisms remain unknown. The aim of the present study was to determine whether combined treatment with low-dose vitamin C and MTX inhibits TNBC cell growth and to investigate the mechanisms of vitamin C/MTX-induced cytotoxicity. Neither low-dose vitamin C alone nor MTX alone inhibited TNBC cell growth. However, combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection.

Streptococcus pyogenes (group A Streptococcus; GAS) causes clinical diseases, including pharyngitis, scarlet fever, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. A number of group A streptococcus vaccine candidates have been developed, but only one 26-valent recombinant M protein vaccine has entered clinical trials. Differing from the design of a 26-valent recombinant M protein vaccine, we provide here a vaccination using the polyvalence epitope recombinant FSBM protein (rFSBM), which contains four different epitopes, including the fibronectin-binding repeats domain of streptococcal fibronectin binding protein Sfb1, the C-terminal immunogenic segment of streptolysin S, the C3-binding motif of streptococcal pyrogenic exotoxin B, and the C-terminal conserved segment of M protein. Vaccination with the rFSBM protein successfully prevented mortality and skin lesions caused by several emm strains of GAS infection. Anti-FSBM antibodies collected from the rFSBM-immunized mice were able to opsonize at least six emm strains and can neutralize the hemolytic activity of streptolysin S. Furthermore, the internalization of GAS into nonphagocytic cells is also reduced by anti-FSBM serum. These findings suggest that rFSBM can be applied as a vaccine candidate to prevent different emm strains of GAS infection.

Association Between Proton Pump Inhibitors and Microscopic Colitis.

OBJECTIVE: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. DATA SOURCES: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. STUDY SELECTION: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. DATA EXTRACTION/SYNTHESIS: A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. CONCLUSIONS: There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.