Revisiting the use of the EORTC QLQ-STO22 to assess health-related quality of life of patients with gastric cancer: incorporating updated treatment options and cross-cultural perspectives.

BACKGROUND: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia. METHODS: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability. RESULTS: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions. CONCLUSIONS: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required.

Delayed presentation of transdermal cyanide poisoning.

A 45-year-old man attended to a warehouse fire involving burning plastic, without wearing full protective equipment. He subsequently presented to hospital with shortness of breath and his trachea was intubated for airway protection due to initial concerns of inhalational injury. However, a post-intubation bronchoscopy was normal. The patient's serum lactate level was normal on admission but was increased when measured 14 h after the initial event and accompanied by a metabolic acidosis. Transdermal cyanide poisoning was suspected given this delayed biochemical presentation and the absence of another apparent cause. A handheld chemical detector detected a high level of toxins on the patient's skin. Clinical improvement was not observed after the first dose of intravenous hydroxocobalamin, which was administered before full body decontamination. After decontamination and the administration of a second dose of hydroxocobalamin, the patient's acid-base status rapidly improved and serum lactate level returned to normal. Clinicians should have a high index of suspicion for transdermal cyanide poisoning in patients presenting after exposure to a fire.

A Timely Burst: Tuberculous Retropharyngeal Abscess.

Tuberculous retropharyngeal abscess is a rare form of extrapulmonary tuberculosis. We describe an immunocompetent teenager who has her tuberculous retropharyngeal abscess ruptured and then diagnosis confirmed by the presence of acid-fast bacilli from the gastric lavage.

Non-gestational choriocarcinoma of the ovary: A case report.

Non-gestational choriocarcinoma of the ovary is an extremely rare clinical condition. Very few cases of this high-grade malignancy of the ovary are reported in the literature worldwide. Given the rarity of the tumour, this disease is generally overlooked, which leads to delayed diagnosis and management. For the attending clinicians, the non-gestational choriocarcinoma of the ovary poses a diagnostic challenge due to its non-specific clinical presentations. A 16-year-old girl presented with pain in the right iliac fossa and with a positive urine pregnancy test. Despite being sexually inactive, the patient was diagnosed with an ectopic pregnancy and underwent emergency laparoscopic surgery. Six weeks later, the histopathological analysis revealed a diagnosis of non-gestational choriocarcinoma of the ovary. Further evaluations showed that her cancer had already advanced to stage IV. In this case report, the non-specific presentations of the disease, radiological features, current treatments, and possible safety strategies are discussed.

Formulation of chelating agent with surfactant in cloud point extraction of methylphenol in water.

Cloud point extraction (CPE) is a separation and preconcentration of non-ionic surfactant from one liquid phase to another. In this study, Sylgard 309 and three different types of additives for CPE, namely CPE-Sylgard, CPE-Sylgard-BMIMBr and CPE-Sylgard-GLDA, are investigated to extract methylphenol from water samples. The methylphenols are well separated by reversed-phase high-performance liquid chromatography (HPLC) with isocratic elution of acetonitrile : water; 60 : 40 (v/v) and detection at 260 nm. The optimized parameters for the effect of salt, surfactant, temperature, time of extraction, pH, interference study and the performance of different additives on methylphenol extraction are investigated. CPE-Sylgard-GLDA is chosen because it gives us a high peak and good peak area compared with CPE-Sylgard and CPE-Sylgard-BMIMBr. The recovery extractions of CPE-Sylgard-GLDA are obtained in the range of 80-99% as the percentage of relative standard deviation (RSD) is less than 10. The LOD and LOQ are 0.05 ppm and 0.18 ppm, respectively. The method developed for CPE-Sylgard-GLDA coupled with HPLC is feasible for the determination of methylphenol because it is simple, effective, cheap, and produces a high percentage of recovery.

Role of T helper 17 cells and T regulatory cells in alopecia areata: comparison of lesion and serum cytokine between controls and patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease with T-cell-mediated attack of hair follicle autoantigens. As T helper 17 (Th17) cells and T regulatory (Treg) cells are crucially involved in the pathogenesis, the role of Th17 and Treg cytokines has not been studied yet. OBJECTIVE: To determine whether AA is associated with alterations in lesional and serum Th17 and Treg cytokines and studied whether they were associated with clinical type. METHODS: Scalp skin samples from 45 patients and eight normal controls were obtained for PCR specific for IFN-γ, TNF-α, TGF-ß, IL-1, IL-2, IL-4, IL-10, IL-12A, IL-13, IL-17, IL-22 and IL-23. Serum cytokines were measured from 55 patients and 15 normal controls using ELISA. RESULTS: Lesional IL-17 and IL-22 were significantly increased in patient group. Moreover, positive correlations were shown between lesional IL-17, IL-22 and disease severity. Serum IL-1, IL-17, TNF-α and TGF-ß were significantly increased, and positive correlation was shown between serum IL-17 and disease severity. CONCLUSION: These results showed significantly high Th17 cytokines in both lesion and serum in AA patients, which may highlight a functional role of these cytokines in the pathogenesis of AA.

Breast cancer survivors: return to work and wage loss in selected hospitals in Malaysia.

PURPOSE: This study aimed, firstly, to assess the determinants of return to work (RTW), secondly, to explore the amount of annual wage loss, and finally, to discover the determinants of wage loss among breast cancer (BC) survivors. METHODS: A cross-sectional study design was used in this research. The data was collected via interview using a validated questionnaire. Logistic regression models were developed to discover the significant determinants of RTW and of wage loss among BC survivors. RESULTS: A total of 256 BC survivors were included in this study. The analysis showed that there was a 21% loss of or reduction in mean income within 1 year after diagnosis. The significant predictors of RTW are being a government employee, having reduced wages or wage loss, and if the case had been diagnosed 1 year or more ago. Being a private sector employee and having a late stage of cancer was a barrier to RTW. The main risk factors for reduced wages or wage loss were belonging to the age group of 40-59 years, being of Chinese or Indian ethnicity, having low educational status, and not returning to work. However, belonging to the higher monthly income group (earning > RM 2000) is a protective factor against the risk of reduced wages or wage loss. CONCLUSIONS: Non-RTW and wage loss after diagnosis of BC may result in the survivors experiencing a significant financial burden. Assessment of these patients is becoming more crucial because more women participate in the workforce in Malaysia nowadays and because BC is managed using multiple treatment modalities with their consequences could lead to long absences from work.

Influence of testosterone on mean arterial pressure: A physiological study in male and female normotensive WKY and hypertensive SHR rats.

Introduction Testosterone plays an important role in the blood pressure regulation. However, information with regard to the effect of this hormone on blood pressure in normotensive and hypertensive conditions is limited. Therefore, in this study, the relationship between plasma testosterone level and mean arterial pressure (MAP) was investigated under these conditions. Methods Normotensive Wistar-Kyoto (WKY) and hypertensive Spontaneous Hypertensive (SHR) male and female rats were gonadectomized with female rats treated with testosterone. Estrous cycle stages of intact female rats of both strains were identified by vaginal smear. Pressure in the carotid artery of anesthetized rats was measured via direct cannulation technique. The blood was withdrawn for plasma testosterone level measurement by enzyme-linked immunosorbent assay. Results Treatment of ovariectomized female WKY and SHR rats with testosterone for 6-week duration has resulted in MAP to increase (P < 0.05). In male WKY and SHR rats, MAP and plasma testosterone levels decreased by orchidectomy (P < 0.05). No significant differences in MAP and plasma testosterone levels were observed in intact female WKY and SHR rats between stages of the estrous cycle. Conclusions The effects seen in testosterone-treated ovariectomized female rats and in orchidectomized male rats suggested that testosterone could play an important role in causing the blood pressure to increase.

Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease.

Mutations in PINK1 and PARKIN cause early-onset Parkinson's disease (PD), thought to be due to mitochondrial toxicity. Here, we show that in Drosophila pink1 and parkin mutants, defective mitochondria also give rise to endoplasmic reticulum (ER) stress signalling, specifically to the activation of the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the unfolded protein response (UPR). We show that enhanced ER stress signalling in pink1 and parkin mutants is mediated by mitofusin bridges, which occur between defective mitochondria and the ER. Reducing mitofusin contacts with the ER is neuroprotective, through suppression of PERK signalling, while mitochondrial dysfunction remains unchanged. Further, both genetic inhibition of dPerk-dependent ER stress signalling and pharmacological inhibition using the PERK inhibitor GSK2606414 were neuroprotective in both pink1 and parkin mutants. We conclude that activation of ER stress by defective mitochondria is neurotoxic in pink1 and parkin flies and that the reduction of this signalling is neuroprotective, independently of defective mitochondria. A video abstract for this article is available online in the supplementary information.

Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson's disease.

The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is an essential co-factor for cellular energy generation in mitochondria as well as for DNA repair mechanisms in the cell nucleus involving NAD(+)-consuming poly (ADP-ribose) polymerases (PARPs). Mitochondrial function is compromised in animal models of Parkinson's disease (PD) associated with PARKIN mutations. Here, we uncovered alterations in NAD(+) salvage metabolism in Drosophila parkin mutants. We show that a dietary supplementation with the NAD(+) precursor nicotinamide rescues mitochondrial function and is neuroprotective. Further, by mutating Parp in parkin mutants, we show that this increases levels of NAD(+) and its salvage metabolites. This also rescues mitochondrial function and suppresses dopaminergic neurodegeneration. We conclude that strategies to enhance NAD(+) levels by administration of dietary precursors or the inhibition of NAD(+)-dependent enzymes, such as PARP, that compete with mitochondria for NAD(+) could be used to delay neuronal death associated with mitochondrial dysfunction.

Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: analysis of the Singapore Multiple Myeloma Working Group.

The clinical outcome of multiple myeloma is heterogeneous. Both the depth of response to induction and transplant as well as early relapse within a year are correlated with survival, but it is unclear which factor is most relevant in Southeast Asian patients with multiple myeloma. We retrospectively analyzed outcomes of 215 patients who were treated with upfront autologous transplant in Singapore between 2000 and 2014. In patients who received novel agent (NA)-based induction, achieving only partial response (PR) post-induction was associated with poorer OS (HR 1.95, P=0.047) and PFS (HR 2.9, P<0.001), while achieving only PR post-transplant was strongly correlated with both OS (HR 3.3, P=0.001) and PFS (HR 7.6, P<0.001), compared with patients who achieved very good partial response (VGPR) or better. Early relapse was detected in 18% of all patients, although nearly half had initially achieved VGPR or better post-transplant. Early relapse after NA-based induction led to significantly shorter OS (median 22 months vs not reached, P<0.001), and was strongly associated with OS (HR 13.7, P<0.001). The impact of suboptimal post-transplant response and early relapse on survival may be more important than pretransplant factors, such as International Staging System or cytogenetics, and should be considered in risk stratification systems to rationalize therapy.

Epigenetic Control of the Vasopressin Promoter Explains Physiological Ability to Regulate Vasopressin Transcription in Dehydration and Salt Loading States in the Rat.

The synthesis of arginine vasopressin (AVP) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus is sensitive to increased plasma osmolality and a decreased blood volume, and thus is robustly increased by both dehydration (increased plasma osmolality and decreased blood volume) and salt loading (increased plasma osmolality). Both stimuli result in functional remodelling of the SON and PVN, a process referred to as functional-related plasticity. Such plastic changes in the brain have recently been associated with altered patterns of DNA methylation at CpG (cytosine-phosphate-guanine) residues, a process considered to be important for the regulation of gene transcription. In this regard, the proximal Avp promoter contains a number of CpG sites and is recognised as one of four CpG islands for the Avp gene, suggesting that methylation may be regulating Avp transcription. In the present study, we show that, in an immortalised hypothalamic cell line 4B, the proximal Avp promoter is highly methylated, and treatment of these cells with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine to demethylate DNA dramatically increases basal and stimulated Avp biosynthesis. We report no changes in the expression of DNA methyltransferases, Dnmt1 and Dnmt3a, whereas there is decreased expression of the demethylating enzyme ten-eleven-translocation 2, Tet2, in the SON by dehydration and salt loading. We found higher methylation of the SON Avp promoter in dehydrated but not salt-loaded rats. By analysis of individual CpG sites, we observed hypomethylation, hypermethylation and no change in methylation of specific CpGs in the SON Avp promoter of the dehydrated rat. Using reporter gene assays, we show that mutation of individual CpGs can result in altered Avp promoter activity. We propose that methylation of the SON Avp promoter is necessary to co-ordinate the duel inputs of increased plasma osmolality and decreased blood volume on Avp transcription in the chronically dehydrated rat.

Intestinal CD103(+)CD11b(-) dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells.

A crosstalk between commensals, gut immune cells, and colonic epithelia is required for a proper function of intestinal mucosal barrier. Here we investigated the importance of two distinct intestinal dendritic cell (DC) subsets in controlling intestinal inflammation. We show that Clec9A-diphtheria toxin receptor (DTR) mice after depletion of CD103(+)CD11b(-) DCs developed severe, low-dose dextran sodium sulfate (DSS)-induced colitis, whereas the lack of CD103(+)CD11b(+) DCs in Clec4a4-DTR mice did not exacerbate intestinal inflammation. The CD103(+)CD11b(-) DC subset has gained a functional specialization that able them to repress inflammation via several epithelial interferon-γ (IFN-γ)-induced proteins. Among others, we identified that epithelial IDO1 and interleukin-18-binding protein (IL-18bp) were strongly modulated by CD103(+)CD11b(-) DCs. Through its preferential property to express IL-12 and IL-15, this particular DC subset can induce lymphocytes in colonic lamina propria and in epithelia to secrete IFN-γ that then can trigger a reversible early anti-inflammatory response in intestinal epithelial cells.

Impact of phytic acid on nutrient bioaccessibility and antioxidant properties of dehusked rice.

Whole grains consumption promotes health benefits, but demonstrates controversial impacts from phytic acid in meeting requirements of good health. Therefore, this study was aimed to determine the nutrient bioaccessibility and antioxidant properties of rice cultivars named "Adan" or "Bario" and deduce the nutritional impact of phytic acid. Majority of the dehusked rice in the collection showed an acceptable level of in-vitro starch digestibility and in-vitro protein digestibility, but were poor in antioxidant properties and bioaccessibility of minerals (Ca, Fe and Zn). The drawbacks identified in the rice cultivars were due to relatively high phytic acid content (2420.6 ± 94.6 mg/100 g) and low phenolic content (152.39 ± 18.84 µg GAE/g). The relationship between phytic acid content and mineral bioaccessibility was strongest in calcium (r = 0.60), followed by iron (r = 0.40) and zinc (r = 0.27). Phytic acid content did not significantly correlate with in-vitro starch digestibility and in-vitro protein digestibility but showed a weak relationship with antioxidant properties. These suggest that phytic acid could significantly impair the mineral bioaccessibility of dehusked rice, and also act as an important antioxidant in non-pigmented rice. Bario rice cultivars offered dehusked rice with wide range of in-vitro digestibility of starch and protein, and also pigmented rice as a good source of antioxidants. However, there is a need to reduce phytic acid content in dehusked rice for improved mineral bioaccessibility among Bario rice cultivars.

Actinomyces Species Isolated from Breast Infections.

Actinomycosis is a chronic infection caused by Actinomyces species characterized by abscess formation, tissue fibrosis, and draining sinuses. The spectrum of infections caused by Actinomyces species ranges from classical invasive actinomycosis to a less invasive form of superficial skin and soft tissue infection. We present a review detailing all Actinomyces species isolated from breast infections in NHS Lothian between 2005 and 2013, Actinomyces species isolated from breast infections referred to the United Kingdom Anaerobe Reference Unit between 1988 and 2014, and cases describing Actinomyces breast infections published in the medical literature since 1994. Actinomyces species are fastidious organisms which can be difficult to identify and are likely to be underascertained as a cause of breast infections. Due to improved diagnostic methods, they are increasingly associated with chronic, recurrent breast infections and may play a more significant role in these infections than has previously been appreciated.

Long-term follow-up for percutaneous transluminal angioplasty in renal artery fibromuscular dysplasia.

AIM: Percutaneous transluminal angioplasty (PTA) is an effective treatment for renal artery stenosis secondary to fibromuscular dysplasia (FMD). This study aimed to evaluate the short-and long-term outcomes of percutaneous transluminal angioplasty in patients with hypertension and renal artery fibromuscular dysplasia (FMD). Additionally, we sought to identify specific patient factors that may affect outcomes. METHODS: This study prospectively enrolled 29 patients with uncontrolled hypertension and renal artery FMD diagnosed by duplex ultrasound and angiography. All patients underwent PTA with the goal of cure or improvement of hypertension. Follow-up was at one-month, 6 months, 12 months and then yearly with minimum follow-up of 2 years and maximum of 5 years. RESULTS: Technical success from the intervention was 100%. 21 patients were included in the final analysis. Short-term outcomes: One month after PTA mean systolic blood pressure (138.1 mmHg), diastolic blood pressure (78.6 mmHg), and number of anti-hypertensive medications (1.4) were significantly reduced. Blood pressure improvement was driven by 14/21 (67%) patients who had significant improvement in blood pressure, while 7/21 (33%) did not. These two groups (improved vs. not improved) differed significantly in mean age at intervention (40.6 vs. 58.3 years), duration of hypertension (3.1 vs. 15.4 years), systolic blood pressure (150.4 mmHg vs. 162.1 mmHg), diastolic blood pressure (86.4 mmHg vs. 95.7 mmHg), number of anti-hypertensive medications (2.2 vs. 3.0), serum creatinine (0.82 vs. 1.45), and renal resistive index (0.59 vs. 0.74) prior to intervention. Long-term outcomes: Mean follow-up was 3.86 years. Improvements in blood pressure and anti-hypertensive medications remained significant at five-year follow-up. CONCLUSION: PTA is effective at reducing blood pressure in patients with renal artery FMD. Age at intervention, duration of hypertension, and renal function may be used to predict outcomes prior to intervention.

Female ageing and reproductive outcome in assisted reproduction cycles.

INTRODUCTION: Fertility in women declines with increasing age. With the deferment of marriage and childbearing, couples are turning to assisted reproductive technology to counteract this decline. We aimed to evaluate the results of in vitrofertilisation (IVF)/intracytoplasmic sperm injection (ICSI) in women of different age groups, and highlight the cost-effectiveness of IVF treatment in these groups while assessing its implications on the national healthcare provision model. METHODS: Retrospective analysis of 3,412 stimulated IVF/ICSI cycles in a hospital-based IVF centre was performed from January 2008 to December 2010. Patients were stratified into seven age groups: < 30 years; 30-35 years; 36-37 years; 38 years; 39 years; 40-44 years; and ≥ 45 years. RESULTS: Age had a significant effect on the number of cycles leading to embryo transfer (p < 0.001). The number of oocytes retrieved decreased across the various age groups (p < 0.001) and was the highest among women aged < 30 (mean 18.5 ± 10.3) years. With increasing age, there was a trend toward a lower fertilisation rate. Age also had a significant effect on the rates of clinical pregnancy, live birth and multiple pregnancies (p < 0.001). CONCLUSION: Patients aged < 30 years had the best IVF outcomes, reflecting optimal reproductive capacity. Age-related decline in fertility starts after 30 years. Women opting for IVF should be counselled about age-specific success rates while taking into account individual risk factors.

First pregnancy and live birth resulting from cryopreserved embryos obtained from in vitro matured oocytes after oophorectomy in an ovarian cancer patient.

In vitro maturation (IVM) of immature oocytes retrieved from surgically resected ovaries has been proposed as a method of fertility preservation in ovarian cancer patients undergoing definitive surgery. While there had been several reports of successful derivation of mature oocytes and or embryos, there have been no reports as yet of successful pregnancies. In this case report, we present a pregnancy and live birth from a young patient, with stage IIIC ovarian cancer, who had undergone fertility sparing surgery. The immature oocytes recovered after oophorectomy were fertilized after IVM. The embryos obtained were cryopreserved and later transferred to achieve a singleton healthy pregnancy leading to a live birth.