A 36‐year‐old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially ...suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.
The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were ...assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
Background/Objectives: The purpose of this study was to investigate whether vitamin B6 supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid ...arthritis (RA). Subjects/Methods: This was a single-blind co-intervention study performed at the Division of Allergy, Immunology and Rheumatology of Chung Shan Medical University Hospital, Taiwan. Patients were diagnosed with RA according to the 1991 American College of Rheumatology criteria for RA. Patients were randomly allocated into two groups: control (5 mg/day folic acid only; n=15) or vitamin B6 (5 mg/day folic acid plus 100 mg/day vitamin B6; n=20) for 12 weeks. Plasma pyridoxal 5′-phosphate (PLP), serum folate, inflammatory parameters (that is, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)) and immune parameters (that is, white blood cell, total lymphocyte, T-cell (CD3), B-cell (CD19), T-helper cell (CD4), T-suppressor (CD8)) were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention. Results: In the group receiving vitamin B6, plasma IL-6 and TNF-α levels significantly decreased at week 12. There were no significant changes with respect to immune responses in both groups except for the percentage of total lymphocytes in the vitamin B6 group when compared with week 0 and week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP after adjusting for confounders (β=−0.01, P=0.01). Conclusions: A large dose of vitamin B6 supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-α) in patients with RA.
Medication-related adverse events, or adverse drug reactions (ADRs) are harmful events caused by medication. ADRs could have profound effects on the patients' quality of life, as well as creating an ...increased burden on the healthcare system. ADRs are one of the rising causes of morbidity and mortality internationally, and will continue to be a significant public health issue with the increased complexity in medication, to treat various diseases in an aging society. This scoping review aims to provide a detailed map of the most common adverse drug reactions experienced in primary healthcare setting, the drug classes that are most commonly associated with different levels/types of adverse drug reactions, causes of ADRs, their prevalence and consequences of experiencing ADRs.
We systematically reviewed electronic databases Ovid MEDLINE, Embase, CINAHL Plus, Cochrane Central Register of Controlled Trials, PsycINFO and Scopus. In addition, the National Patient Safety Foundation Bibliography and the Agency for Health Care Research and Quality and Patient Safety Net Bibliography were searched. Studies published from 1990 onwards until December 7, 2018 were included as the incidence of reporting drug reactions were not prevalent before 1990. We only include studies published in English.
The final search yielded a total of 19 citations for inclusion published over a 15-year period that primarily focused on investigating the different types of adverse drug reactions in primary healthcare. The most causes of adverse events were related to drug related and allergies. Idiosyncratic adverse reactions were not very commonly reported. The most common adverse drug reactions reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with adverse events.
This scoping review identified that the most causes of ADRs were drug related and due to allergies. Idiosyncratic adverse reactions were not very commonly reported in the literature. This is mainly because it is hard to predict and these reactions are not associated with drug doses or routes of administration. The most common ADRs reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with ADRs.
UCSF ChimeraX is the next‐generation interactive visualization program from the Resource for Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. ChimeraX brings (a) ...significant performance and graphics enhancements; (b) new implementations of Chimera's most highly used tools, many with further improvements; (c) several entirely new analysis features; (d) support for new areas such as virtual reality, light‐sheet microscopy, and medical imaging data; (e) major ease‐of‐use advances, including toolbars with icons to perform actions with a single click, basic “undo” capabilities, and more logical and consistent commands; and (f) an app store for researchers to contribute new tools. ChimeraX includes full user documentation and is free for noncommercial use, with downloads available for Windows, Linux, and macOS from https://www.rbvi.ucsf.edu/chimerax.
A ZnFe2O4-TiO2 nanocomposite combining p-type ZnFe2O4 and n-type TiO2 was successfully fabricated. The ZnFe2O4-TiO2 nanocomposite greatly enhanced the bisphenol A (BPA) photodegradation under visible ...light irradiation at 465 ± 40 nm. Loading TiO2 with 1 wt% of ZnFe2O4 produced high photocurrent and low charge transfer resistance. The photodegradation rate of BPA by ZnFe2O4-TiO2, which was highly dependent on the water chemistry including pH, anions, and humic acid, was 20.8–21.4 times higher than that of commercial TiO2 photocatalysts. Chloride and sulfate ions enhanced BPA photodegradation mostly due to the production of more radical species; whereas nitrate, dihydrogen phosphate, and bicarbonate ions decreased the photodegradation rate of BPA due to the scavenge of hydroxyl radicals. The photoactivity and recyclability of ZnFe2O4-TiO2 in lake water was also assessed. A near complete BPA removal from lake water was observed under visible light irradiation. Furthermore, >90% of photocatalytic activity toward BPA degradation was achieved in 5 cycles of continuous addition of BPA to the lake water. The BPA degradation intermediates were identified by HPLC/MS/MS and possible reaction pathways were proposed. Results clearly demonstrate the excellent visible-light-sensitive photocatalytic degradation of BPA over ZnFe2O4-TiO2 composite which has a great application potential for the decomposition of emerging contaminants in impaired waters.
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•TiO2 doped with 1.0-wt% ZnFe2O4 exhibited the highest visible-light BPA photodegradation.•The kobs of BPA photodegradation followed the order: pH 9.0 > pH 7.0 > pH 5.0 > pH 3.0 > pH 11.0.•Cl− and SO42− enhance and humic acid inhibits BPA degradation over ZnFe2O4-TiO2.•Near complete BPA removal (>90%) in lake water was observed under visible light irradiation•BPA degradation over ZnFe2O4-TiO2 in lake water was high for at least five continuous cycles.
There are still no effective therapies for hyposalivation caused by irradiation. In our previous study, bone marrow stem cells can be transdifferentiated into acinar-like cells in vitro. Therefore, ...we hypothesized that transplantation with bone marrow stem cells or acinar-like cells may help functional regeneration of salivary glands. Bone marrow stem cells were labeled with nanoparticles and directly co-cultured with acinar cells to obtain labeled acinar-like cells. In total, 140 severely combined immune-deficiency mice were divided into 4 groups for cell therapy experiments: (1) normal mice, (2) mice receiving irradiation around their head-and-neck areas; (3) mice receiving irradiation and intra-gland transplantation with labeled stem cells; and (4) mice receiving irradiation and intra-gland transplantation with labeled acinar-like cells. Our results showed that salivary glands damaged due to irradiation can be rescued by cell therapy with either bone marrow stem cells or acinar-like cells for recovery of saliva production, body weight, and gland weight. Transdifferentiation of bone marrow stem cells into acinar-like cells in vivo was also noted. This study demonstrated that cell therapy with bone marrow stem cells or acinar-like cells can help functional regeneration of salivary glands, and that acinar-like cells showed better therapeutic potentials than those of bone marrow stem cells.
UCSF ChimeraX is next‐generation software for the visualization and analysis of molecular structures, density maps, 3D microscopy, and associated data. It addresses challenges in the size, scope, and ...disparate types of data attendant with cutting‐edge experimental methods, while providing advanced options for high‐quality rendering (interactive ambient occlusion, reliable molecular surface calculations, etc.) and professional approaches to software design and distribution. This article highlights some specific advances in the areas of visualization and usability, performance, and extensibility. ChimeraX is free for noncommercial use and is available from http://www.rbvi.ucsf.edu/chimerax/ for Windows, Mac, and Linux.
Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is ...an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.
We report on features of solar wind‐magnetosphere coupling elicited by shocks propagating through coronal mass ejections (CMEs) by analyzing the intense geomagnetic storm of 6 August 1998. During ...this event, the dynamic pressure enhancement at the shock combined with a simultaneous increase in the southward component of the magnetic field resulted in a large earthward retreat of Earth's magnetopause, which remained close to geosynchronous orbit for more than 4 h. This occurred despite the fact that both shock and CME were weak and relatively slow. Another similar example of a weak shock inside a slow CME resulting in an intense geomagnetic storm is the 30 September 2012 event, which strongly depleted the outer radiation belt. We discuss the potential of shocks inside CMEs to cause large geomagnetic effects at Earth, including magnetopause shadowing.
Key Points
Shocks inside CME have simultaneous dynamic pressure and Bz increases
Shocks inside CMEs can cause magnetopause shadowing
Extreme solar wind‐magnetosphere coupling for weak drivers
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