Patients' burden from lung cancer treatment is not well researched, but this understanding can facilitate a patient-centred treatment approach. Current models of treatment burden suggest it is ...influenced by a patient's perception of their disease and treatment and their capacity to do the work required to treat their disease.
Sixteen patients and 1 carer who were undergoing or had completed conventional or stereotactic ablative radiotherapy, chemotherapy or immunotherapy for lung cancer in the last 6 months participated in a semi-structured interview. A treatment burden framework was used with three main themes: a) treatment work, b) consequences of treatment and c) psychosocial factors affecting treatment burden.
The majority of patients did not feel unduly burdened by treatment tasks, despite having a large treatment-associated workload. Many saw treatment as a priority, causing them to restructure their life to accommodate for it. Patients wished that they would have been better informed about the lifestyle changes that they would have to make before treatment for lung cancer commenced and that the health service would provide services to assist them with this task.
While there was a large burden associated with lung cancer treatment, patients felt motivated and equipped to manage the workload because the disease was considered severe and life-threatening, and the treatment was seen as beneficial. Before initiating treatment for lung cancer, patients should be informed about lifestyle changes they likely have to make and should be offered assistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among ...patients with primary hyperparathyroidism.
Methods
In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function.
Results
During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05–1.81) before surgery and 2.47 years (1.37–6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (− 1.67 versus − 2.73 mL/min/1.73 m
2
/year,
p
< 0.001). More importantly, parathyroidectomy made more beneficial effects on kidney function in patients with age < 65 years and those without chronic kidney disease or hypertension.
Conclusions
Our study showed that parathyroidectomy slows renal function decline irrespective of age or comorbidities, which offers novel insight into the revision of guidelines for surgical indications in primary hyperparathyroidism. Given small sample size, further large-scale controlled studies are warranted to confirm our findings.
A speleothem δ ¹⁸O record from Xiaobailong cave in southwest China characterizes changes in summer monsoon precipitation in Northeastern India, the Himalayan foothills, Bangladesh, and northern ...Indochina over the last 252 kyr. This record is dominated by 23-kyr precessional cycles punctuated by prominent millennial-scale oscillations that are synchronous with Heinrich events in the North Atlantic. It also shows clear glacial–interglacial variations that are consistent with marine and other terrestrial proxies but are different from the cave records in East China. Corroborated by isotope-enabled global circulation modeling, we hypothesize that this disparity reflects differing changes in atmospheric circulation and moisture trajectories associated with climate forcing as well as with associated topographic changes during glacial periods, in particular redistribution of air mass above the growing ice sheets and the exposure of the “land bridge” in the Maritime continents in the western equatorial Pacific.
Significance This paper presents a new long speleothem δ ¹⁸O time series from Xiaobailong cave in southwest China that characterizes changes in a major branch of Indian summer monsoon precipitation over the last 252 kyrs. This record shows not only 23-kyr precessional cycles punctuated by prominent millennial-scale weak monsoon events synchronous with Heinrich events in the North Atlantic, but also clear glacial–interglacial variations that are consistent with marine records but different from the cave records in East China. The speleothem records of Xiaobailong and other caves in East China show that the relationship between the Indian and the East Asian summer monsoon precipitation is not invariant, but rather varies on different timescales depending on the nature and magnitude of the climate forcing.
We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
Background
In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys‐regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates ...microglia in the spinal dorsal horn (SDH). However, information on diabetes‐induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain.
Methods
Sixty‐six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration.
Results
All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up‐regulation of Nav1.3 and down‐regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ‐induced diabetes was mediated, in part, by phosphorylation of p‐38 mitogen‐activated protein kinase.
Conclusions
Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.
Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, ...neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction. Monocytes would transdifferentiate into macrophages after transmigrating into the infarct area. Both neutrophils and monocytes-derived macrophages are known to release proteases and cytokines that are detrimental to the surviving cardiomyocytes. Paradoxically, these inflammatory cells also play critical roles in repairing the injured myocardium. Depletion of either neutrophils or monocytes do not improve overall cardiac function after myocardial infarction. Instead, the left ventricular function is further impaired and cardiac fibrosis persists. Moreover, the inflammatory microenvironment created by the infiltrated neutrophils and monocytes-derived macrophages is essential for the recruitment of cardiac progenitor cells. Recent studies also suggest that treatment with anti-inflammatory drugs may cause cardiac dysfunction after injury. Indeed, clinical studies have shown that traditional ant-inflammatory strategies are ineffective to improve cardiac function after infarction. Thus, the focus should be on how to harness these inflammatory events to either improve the efficacy of the delivered drugs or to favor the recruitment of cardiac progenitor cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Purpose To determine whether a fish scale-derived collagen matrix (FSCM) meets the basic criteria to serve as an artificial cornea, as determined with in vitro and in vivo tests. Methods ...Primary corneal epithelial and stromal cells were obtained from human donor corneas and used to examine the (in)direct cytotoxicity effects of the scaffold. Cytotoxicity was assessed by an MTT assay, while cellular proliferation, corneal cell phenotype and adhesion markers were assessed using an EdU-assay and immunofluorescence. For in vivo- testing, FSCMs were implanted subcutaneously in rats. Ologen® Collagen Matrices were used as controls. A second implant was implanted as an immunological challenge. The FSCM was implanted in a corneal pocket of seven New Zealand White rabbits, and compared to sham surgery. Results The FSCM was used as a scaffold to grow corneal epithelial and stromal cells, and displayed no cytotoxicity to these cells. Corneal epithelial cells displayed their normal phenotypical markers (CK3/12 and E-cadherin), as well as cell-matrix adhesion molecules: integrin-α6 and β4, laminin 332, and hemi-desmosomes. Corneal stromal cells similarly expressed adhesion molecules (integrin-α6 and β1). A subcutaneous implant of the FSCM in rats did not induce inflammation or sensitization; the response was comparable to the response against the Ologen® Collagen Matrix. Implantation of the FSCM in a corneal stromal pocket in rabbits led to a transparent cornea, healthy epithelium, and, on histology, hardly any infiltrating immune cells. Conclusion The FSCM allows excellent cell growth, is not immunogenic and is well-tolerated in the cornea, and thus meets the basic criteria to serve as a scaffold to reconstitute the cornea.
The explosive eruption of the Hunga-Tonga volcano in the southwest Pacific at 0415UT on 15 January 2022 triggered gigantic atmospheric disturbances with surface air pressure waves propagating around ...the globe in Lamb mode. In space, concentric traveling ionosphere disturbances (CTIDs) are also observed as a manifestation of air pressure waves in New Zealand ∼0500UT and Australia ∼0630UT. As soon as the air pressure waves reached central Australia ∼0800UT, conjugate CTIDs appeared almost simultaneously in the northern hemispheres through interhemispheric coupling, much earlier than the arrival of the surface air pressure waves to Japan after 1100UT. Combining observations over Australia and Japan between 0800 and 1000UT, both direct and conjugate CTIDs show similar horizontal phase velocities of 320–390 m/s, matching with the dispersion relation of Lamb mode. The arrival of atmospheric Lamb wave to Japan later created in situ CTIDs showing the same Lamb mode characteristics as the earlier conjugate CTIDs.
To explore mechanisms underlying the association of TSG-6 with osteoarthritis (OA) progression.
TSG-6-mediated heavy chain (HC) transfer (TSG-6 activity) and its association with inflammatory ...mediators were quantified in knee OA (n=25) synovial fluids (SFs). Paired intact and damaged cartilages from the same individuals (20 tibial and 12 meniscal) were analyzed by qRT-PCR and immunohistochemistry (IHC) for gene and protein expression of TSG-6 and components of Inter-alpha-Inhibitor (IαI) and TSG-6 activity ± spiked in IαI. Primary chondrocyte cultures (n=5) ± IL1β or TNFα were evaluated for gene expression. The effects of TSG-6 activity on cartilage extracellular matrix (ECM) assembly were explored using quantitative hyaluronan (HA)-aggrecan binding assays.
TSG-6 activity was significantly associated (R > 0.683, P < 0.0002) with inflammatory mediators including TIMP-1, A2M, MMP3, VEGF, VCAM-1, ICAM-1 and IL-6. Although TSG-6 protein and mRNA were highly expressed in damaged articular and meniscal cartilage and cytokine-treated chondrocytes, there was little or no cartilage expression of components of the IαI complex (containing HC1). By IHC, TSG-6 was present throughout lesioned cartilage but HC1 only at lesioned surfaces. TSG-6 impaired HA-aggrecan assembly, but TSG-6 mediated HA-HC formation reduced this negative effect.
TSG-6 activity is a global inflammatory biomarker in knee OA SF. IαI, supplied from outside cartilage, only penetrates the cartilage surface, restricting TSG-6 activity (HC transfer) to this region. Therefore, unopposed TSG-6 in intermediate and deep regions of OA cartilage could possibly block matrix assembly, leading to futile synthesis and account for increased risk of OA progression.
Summary
Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)‐positive grafts used to be discarded in the past. The ...aim of this study was to examine viral activity and outcome of HBsAg‐positive deceased grafts transplanted to HBsAg‐positive recipients. Eleven HBsAg‐positive deceased grafts were transplanted to HBsAg‐positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end‐stage liver disease score for the recipients was 19 (16‐32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg‐positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg‐positive deceased grafts is feasible and increases the donor pool to rescue dying patients.
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