Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

Management of brain metastasis from rectal cancer using whole­brain radiation therapy followed by bevacizumab and chemotherapy: A case report.

Brain metastases in colorectal cancer are uncommon, which has resulted in a shortage of data concerning their screening and management. Multiple therapeutic modalities with chemotherapy, chemoradiation and targeted therapy, including bevacizumab and cetuximab regimens, have shown promising results. The present study describes the case of a 47-year-old male, diagnosed with T4N2M1 rectal cancer who underwent systemic therapy with modified FOLFOXIRI and cetuximab. The patient achieved a complete clinical response after 12 cycles. Following the discontinuation of cetuximab, the patient was given capecitabine as a maintenance therapy and subsequently developed brain metastasis. The patient received whole-brain radiation therapy (WBRT) followed by a bevacizumab plus FOLFIRI regimen. The patient showed a good response as revealed by cranial magnetic resonance imaging, with a reduction in lesion size and no sign of cerebral edema. In addition, the patient maintained a stable neurological condition for >10 months. These findings suggest that the early detection of brain metastases requires the close monitoring of neurological symptoms. In addition, WBRT followed by bevacizumab and chemotherapy is a potential management plan for brain metastasis from rectal cancer.

Prevalence of exclusive breastfeeding for the first six months of an infant's life and associated factors in a low-middle income country.

BACKGROUND: Although breastfeeding is practiced by 98% of mothers in Vietnam, infant breastfeeding behaviors remain far from World Health Organization recommendations and continues to decline. This study aims to explore the prevalence and factors associated with exclusive breastfeeding in the first six months of an infant's life. METHODS: A cross-sectional study utilized a self-administered maternal questionnaire to collect data on 1072 Vietnamese mothers who brought infants aged between 6 and 30 months to a community health centre (CHC) for routine vaccination. Data collection was conducted from March to May 2021 in two cities in Central and North Vietnam. In order to measure exclusive breastfeeding, we asked mothers to recall (yes / no), if the child had received breast milk, formula, colostrum milk powder, water, vitamin / medicine, fruit juice / honey, and complementary foods aged under six months. RESULTS: In the first six months, 14.2% of mothers exclusively breastfed their infants. Multivariable logistic regression analysis demonstrated a significant association between exclusive infant breastfeeding and the highest maternal education level (university or postgraduate) (adjusted odds ratio (aOR) 2.55; 95% confidence interval (CI) 1.10, 5.91); male infants (aOR 1.72; 95% CI 1.11, 2.68); duration of skin-to-skin contact greater than 90 min (aOR 7.69; 95% CI 1.95, 30.38); receiving first breastfeeding during skin-to-skin contact (aOR 2.31; 95% CI 1.30, 4.10); completely feeding infant directly at the breast (aOR 1.65; 95% CI 1.00, 2.71) and exclusive breastfeeding intention during pregnancy (aOR 2.48; 95% CI 1.53, 4.00). When compared with mothers who were prenatally exposed to infant formula advertising classified as "often", the prevalence of exclusive infant breastfeeding was higher in mothers who classified their prenatal exposure to infant formula advertising as "sometimes" (aOR 2.15; 95% CI 1.13, 4.10), and "seldom" (aOR 2.58; 95% CI 1.25, 5.36). CONCLUSION: The prevalence of mothers who practiced exclusive infant breastfeeding during the first six months in Vietnam was low. Infants should receive early maternal-infant skin-to-skin contact greater than 90 min and complete first breastfeeding during skin-to-skin contact. Further, mothers should be protected against infant formula advertisements to maximise the likelihood of exclusive breastfeeding during the child's infancy.

The Medical Outcome Study Social Support Survey (MOS-SSS): A psychometric systematic review.

AIMS: To evaluate and synthesize psychometric properties of the MOS-SSS and to identify quality versions of MOS-SSS for use in future research and practice. DESIGN: A psychometric systematic review. DATA SOURCES: Articles about the translation, adaptation, or validation of the MOS-SSS in Medline, PubMed, CINAHL, and Web of Science and their reference lists published before 11 November 2022. REVIEW METHODS: The review followed the Consensus Standards for the Selection of Health Measurement Instruments guidelines. RESULTS: The review included 35 articles. Eleven versions of MOS-SSS (3, 4, 5, 6, 8, 12, 13, 16, 18, 19, and 22 items) have been validated in various populations and 13 languages. Of 14 studies developing a translated version of MOS-SSS, four studies performed both an experts' evaluation of content validity and a face validity test; two studies reported translation evaluation in the form of a content validity index. Of 35 studies, six performed both exploratory factor analysis and confirmatory factor analysis for structural validity; hypotheses and measurements for construct validity testings were often not clearly stated; two examined criterion validity; and four assessed cross-cultural validity. Internal consistency reliabilities were commonly examined by calculating Cronbach's alpha and reported satisfactory. Five studies analysed test-retest reliabilities using intra correlation coefficient. Methodological concerns exist. CONCLUSION: The English 19-item, Farsi Persian 19-item, and Vietnamese 19-item versions are recommended for future use in research and practice. Italian 19-item and Malaysian 13-item versions are not recommended to be used in future research and practice. All other versions considered in this review have potential use in future research and practice. Proper procedures for developing a translated version of MOS-SSS and validating the scale are recommended. IMPACT: The review identified quality versions of MOS-SSS to measure social support in future research and practice. The study also indicated methodological issues in current validation studies. Application of the study findings and recommendations can be useful to improve outcome measurement quality and maximize the efficiency of resource use in future research and practice. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review synthesized the evidence from previous research and did not involve any human participation.

A simple and effective scaffold for mouse hepatic stellate cell primary culture.

Scaffold-based culture is necessary for hepatic stellate cells (HSCs) because HSCs are promptly autoactivated under plastic conditions. Our research aims to investigate the potential and role of fibrin scaffold in reducing autoactivation, maintaining cell function, and extending the in vitro culture time of primary HSCs. HSCs were isolated from BALB/c mice and cultured on the surface of plastic, Matrigel, and fibrin gel. HSC's characteristics, including recovery, morphology, proliferation, lipid droplet (LD) storage, and activation were evaluated. Cell recovery was 86%, 80%, and 60% in fibrin, Matrigel, and plastic, respectively (P < 0.05). HSCs cultured on a plastic dish were autoactivated until day 7 with high proliferation, loss of cytoplasmic LD lipid droplets, and increased expression of activation markers, including alpha-smooth muscle actin (α-sma) and collagen type I. In contrast, these phenomena were reduced in Matrigel and fibrin-based cultures (P < 0.05). HSC culture in fibrin scaffold was associated with altered expression of cell adhesion molecules, including increased E-cadherin and inhibited N-cadherin. HSCs were more stellate-like in morphology in fibrin than in the Matrigel scaffold. Interestingly, fibrin-scaffold-embedded culture was able to maintain HSC quiescent state for up to 14 days in vitro. Fibrin gel could provide a potential scaffold for primary HSC culture while preserving cell function and extending primary HSC in vitro culture time.NEW & NOTEWORTHY Fibrin gel is appropriate for maintaining quiescence characteristics in primary culture of mouse hepatic stellate cells. Embedded culture of hepatic stellate cells in fibrin gel simulates in vivo cell morphology. Stiffness and adhesion molecules of fibrin gel play a crucial role in the hepatic stellate cell's primary culture.

Autophagy Inhibitor Chloroquine Downmodulates Hepatic Stellate Cell Activation and Liver Damage in Bile-Duct-Ligated Mice.

Hepatic stellate cell (HSC) activation via the autophagy pathway is a critical factor in liver fibrogenesis. This study tests the hypothesis that chloroquine (CQ) treatment can prevent autophagy and HSC activation in vitro and in vivo in bile-duct-ligated (BDL) mice. Sham-operated and BDL mice were treated with either PBS or CQ in two 60 mg/kg doses the day (D) before and after surgery. On day 2 (2D), HSCs were isolated, and their biological activities were evaluated by measuring intracellular lipid content, α-sma/collagen, and expression of autophagy lc3, sqstm1/p62 markers. The treatment efficacy on liver function was evaluated with serum albumin, transaminases (AST/ALT), and hepatic histology. Primary HSCs were treated in vitro for 24 h with CQ at 0, 2.5, 5, 10, 30, and 50 µM. Autophagy and HSC activation were assessed after 2D of treatment. CQ treatment improved serum AST/ALT, albumin, and bile duct proliferation in 2D BDL mice. This is associated with a suppression of HSC activation, shown by higher HSC lipid content and collagen I staining, along with the blockage of HSC autophagy indicated by an increase in p62 level and reduction in lc3 staining. CQ 5 µM inhibited autophagy in primary HSCs in vitro by increasing p62 and lc3 accumulation, thereby suppressing their in vitro activation. The autophagy inhibitor CQ reduced HSC activation in vitro and in vivo. CQ improved liver function and reduced liver injury in BDL mice.

Tumor genomic profiling and personalized tracking of circulating tumor DNA in Vietnamese colorectal cancer patients.

Background: Colorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease. Method: In this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples. Results: The top mutated genes in our cohort were APC, TP53 and KRAS. 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases. Conclusion: Our assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries.

Self-report instruments for measuring patient dignity: A psychometric systematic review.

AIMS: To synthesize and evaluate the psychometric properties of self-report instruments that measure patient dignity. DESIGN: A psychometric systematic review. DATA SOURCES: A comprehensive search of studies published from inception until February 17, 2022, was performed using PubMed, Embase, CINAHL, Web of Science, and Scopus. REVIEW METHODS: The methodological quality of the psychometric studies was evaluated following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. RESULTS: Eleven self-report instruments that evaluate dignity were identified. For most instruments, psychometric properties, including reliability, cross-cultural validity, responsiveness, and measurement error, had not been adequately examined. The Patient Dignity Inventory (PDI), the Jacelon's Attributed Dignity Scale (JADS), and the Inpatient Dignity Scale (IPDS) had acceptable content validity, structure validity, and internal consistency to measure dignity among adult patients under palliative care, community-dwelling older adults, and inpatients receiving daily care. CONCLUSION: The PDI, the JADS, and the IPDS are recommended for future clinical practice and research to measure dignity among adult patients under palliative care, community-dwelling older adults, and inpatients receiving daily care. Early identification of patients' dignity-related problems in nursing care can prevent negative health outcomes and help develop a timely intervention to promote patients' health and recovery. IMPACT: Given that the psychometric properties of the existing self-report dignity instruments have not been systematically assessed, the present review utilized comprehensive methods according to COSMIN to evaluate and determine the most appropriate measure for research and practice. The PDI, the JADS, and the IPDS demonstrated satisfactory psychometric properties and are, thus, recommended for clinical and research applications. Nursing professionals can employ these instruments to assess and promptly identify dignity issues among both young and older adults in hospitals and communities.

Effects of autophagy inhibition by chloroquine on hepatic stellate cell activation in CCl4-induced acute liver injury mouse model.

BACKGROUND AND AIM: Hepatic stellate cells (HSCs) activation, a critical event in liver fibrosis, has been recently shown to be related to autophagy. Determine whether chloroquine (CQ) could affect (i) the activation of HSC in vivo and (ii) the hepatic damage in a mice acute liver injury model. METHODS: The acute liver injury was induced in BALB/c mice by carbon tetrachloride (CCl4 group); 24 h before and after CCl4 administration animals were treated by CQ (CCl4  + CQ group). As control, mice treated by olive oil were considered. After 48 h from CCl4 /olive oil administration, blood samples, liver tissues, and HSCs were harvested for analysis. RESULTS: In vivo, CQ attenuates CCl4 -induced acute liver damage as evidenced by (i) the reduction of liver enlargement, (ii) the reduction of liver swelling and necrosis also supported by a certain decrease of circulating transaminases level, and (iii) the reduction of liver fibrosis evaluated by collagen deposition and α-sma protein expression. In HSCs isolated from CQ treated group, we observed the inhibition of autophagy proved by the increase in p62 protein and the decrease of lc3 protein. In addition, CQ reduced the expression of the HSCs activation markers α-sma/collagen-I and down-regulated the expression of the proliferative marker ki67. CONCLUSION: The autophagy attenuation exerted by CQ together with the reduction of the expression of the proliferation marker in HSCs can lessen the acute liver damage potentially opening the way to novel therapeutic approaches for hepatic fibrosis.

Effects of Trehalose Content and Water Activity on the Fracture Properties of Deep-fried Wheat Flour Particles and Freeze-dried Porous Waxy Corn Starch Solids.

Wheat flour-based batter containing 0 to 20 % trehalose was deep-fried, dried and held in various water activity (a w) conditions. The effects of trehalose content and a w on oil content, water sorption, isothermal mechanical relaxation, and fracture properties were investigated. For comparison, the fracture properties of freeze-dried porous waxy corn starch solids were also investigated. The 10 % trehalose sample had the lowest oil content, water content, and a w. A force-reduction value (∆F) of the samples was evaluated as a typical mechanical relaxation parameter. ∆F gradually increased with increasing a w and sharply increased above a specific a w presumed to be associated with the glass to rubber transition. Compared to ∆F values among the glassy samples, 10 and 20 % trehalose samples had higher ∆F values (were more rigid) than 0 and 5 % trehalose samples. From the fracture measurements of the glassy samples, the first fracture force increased linearly and the number of fracture peaks decreased linearly with increasing a w. At each a w, 10 % trehalose had the lowest first fracture force and the highest the number of fracture peaks. Freeze-dried porous waxy corn starch solids showed similar fracture properties to deep-fried samples. These findings suggest that around 10 % trehalose content is optimal for producing deep-fried foods with a brittle texture.

Caffey disease is associated with distinct arginine to cysteine substitutions in the proα1(I) chain of type I procollagen.

PURPOSE: Infantile Caffey disease is a rare disorder characterized by acute inflammation with subperiosteal new bone formation, associated with fever, pain, and swelling of the overlying soft tissue. Symptoms arise within the first weeks after birth and spontaneously resolve before the age of two years. Many, but not all, affected individuals carry the heterozygous pathogenic COL1A1 variant (c.3040C>T, p.(Arg1014Cys)). METHODS: We sequenced COL1A1 in 28 families with a suspicion of Caffey disease and performed ultrastructural, immunocytochemical, and biochemical collagen studies on patient skin biopsies. RESULTS: We identified the p.(Arg1014Cys) variant in 23 families and discovered a novel heterozygous pathogenic COL1A1 variant (c.2752C>T, p.(Arg918Cys)) in five. Both arginine to cysteine substitutions are located in the triple helical domain of the proα1(I) procollagen chain. Dermal fibroblasts (one patient with p.(Arg1014Cys) and one with p.(Arg918Cys)) produced molecules with disulfide-linked proα1(I) chains, which were secreted only with p.(Arg1014Cys). No intracellular accumulation of type I procollagen was detected. The dermis revealed mild ultrastructural abnormalities in collagen fibril diameter and packing. CONCLUSION: The discovery of this novel pathogenic variant expands the limited spectrum of arginine to cysteine substitutions in type I procollagen. Furthermore, it confirms allelic heterogeneity in Caffey disease and impacts its molecular confirmation.

Surgical Treatment of Advanced Thyroid Cancer with Tracheal Invasion.

INTRODUCTION: Tracheal invasion in thyroid cancer occurs in one-third of locally advanced cases and is the third most common site of infiltration following strap muscles and recurrent laryngeal nerves. Surgical resection plays an important role in the management strategy followed by either radioactive iodine or external beam radiotherapy. Nonetheless, there has been still controversy about the optimal extension of the surgery. Case Presentation. Total thyroidectomy, airway resection and bilateral neck dissection were performed in two cases diagnosed as advanced thyroid cancer with tracheal invasion (stage IV according to McCaffrey). The first case underwent partial tracheal resection and direct anastomosis by the V-shape technique, while the latter one required tracheal resection and permanent tracheotomy. After one-year follow-up, no evidence of tumor recurrence or any postoperative complications were found. CONCLUSION: Surgical resection still remains the mainstay of management for advanced thyroid cancer in general and for tracheal invasion cases in particular. The decision of surgical resection and tracheal reconstruction methods mostly depends on the extent of tracheal invasion.

Optimization of the isolation procedure and culturing conditions for hepatic stellate cells obtained from mouse.

Liver fibrosis (LF) mortality rate is approximately 2 million per year. Irrespective of the etiology of LF, a key element in its development is the transition of hepatic stellate cells (HSCs) from a quiescent phenotype to a myofibroblast-like cell with the production of fibrotic proteins. It is necessary to define optimal isolation and culturing conditions for good HSCs yield and proper phenotype preservation for studying the activation of HSCs in vitro. In the present study, the optimal conditions of HSC isolation and culture were examined to maintain the HSC's undifferentiated phenotype. HSCs were isolated from Balb/c mice liver using Nycodenz, 8, 9.6, and 11%. The efficiency of the isolation procedure was evaluated by cell counting and purity determination by flow cytometry. Quiescent HSCs were cultured in test media supplemented with different combinations of fetal bovine serum (FBS), glutamine (GLN), vitamin A (vitA), insulin, and glucose. The cells were assessed at days 3 and 7 of culture by evaluating the morphology, proliferation using cell counting kit-8, lipid storage using Oil Red O (ORO) staining, expression of a-smooth muscle actin, collagen I, and lecithin-retinol acyltransferase by qRT-PCR and immunocytochemistry (ICC). The results showed that Nycodenz, at 9.6%, yielded the best purity and quantity of HSCs. Maintenance of HSC undifferentiated phenotype was achieved optimizing culturing conditions (serum-free Dulbecco's Modified Eagle's Medium (DMEM) supplemented with glucose (100 mg/dl), GLN (0.5 mM), vitA (100 µM), and insulin (50 ng/ml)) with a certain degree of proliferation allowing their perpetuation in culture. In conclusion, we have defined optimal conditions for HSCs isolation and culture.

Successful chemotherapy management of disseminated intravascular coagulation presenting with metastatic clear cell renal carcinoma: a case report and review of the literature.

BACKGROUND: Disseminated intravascular coagulation is a critical complication of advanced clear cell renal cell carcinoma, despite the rarity of the occurrence of disseminated intravascular coagulation in such tumors. The diagnosis of cancer-related disseminated intravascular coagulation is mostly based on clinical bleeding and laboratory test; available data suggest that treating the primary cancer also treats the disseminated intravascular coagulation. Among three reported cases of renal cell carcinoma-related disseminated intravascular coagulation in the literature, this is the first patient whose disseminated intravascular coagulation was successfully treated, in particular, with chemotherapy without any anti-disseminated intravascular coagulation therapies. CASE PRESENTATION: This case is a 66-year-old Vietnamese man who presented disseminated intravascular coagulation 2 weeks after his admission for severe back pain. At admission, his initial laboratory work-up revealed only a mild thrombocytopenia with a platelet count of 93 × 109/L (normal range, 150-450 × 109/L) without clinical bleeding. His past medical history and family history were unremarkable. An open-biopsy was performed and the definitive diagnosis was bone metastatic clear cell renal cell carcinoma based on immunohistochemistry. Two weeks after admission, the diagnosis of disseminated intravascular coagulation was confirmed according to the International Society on Thrombosis and Haemostasis. Immediately, he was treated with a paclitaxel plus carboplatin regimen and disseminated intravascular coagulation completely disappeared after one cycle of systemic chemotherapy. Until recently, 11 months subsequent to the diagnosis of disseminated intravascular coagulation, he had been being undergoing maintenance therapy for metastatic clear cell renal cell carcinoma. CONCLUSIONS: First, an early detection of overt disseminated intravascular coagulation is essential, although disseminated intravascular coagulation in cancer presents as a chronic or even subclinical process with unique thrombocytopenia. Second, making a decision of systemic chemotherapy without delay at the time of disseminated intravascular coagulation diagnosis is the key to successful cancer-related disseminated intravascular coagulation treatment.

S100A9-induced overexpression of PD-1/PD-L1 contributes to ineffective hematopoiesis in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death of hematopoietic stem and progenitor cells (HSPCs). The PD-1/PD-L1 immune checkpoint impairs immune responses by inducing T-cell exhaustion and apoptosis, but its role in MDS is uncharacterized. Here we report an increased expression of PD-1 on HSPCs and PD-L1 on MDSCs in MDS versus healthy donors, and that this checkpoint is also activated in S100A9 transgenic (S100A9Tg) mice, and by treatment of BM mononuclear cells (BM-MNC) with S100A9. Further, MDS BM-MNC treated with recombinant PD-L1 underwent cell death, suggesting that the PD-1/PD-L1 interaction contributes to HSPC death in MDS. In accordance with this notion, PD-1/PD-L1 blockade restores effective hematopoiesis and improves colony-forming capacity in BM-MNC from MDS patients. Similar findings were observed in aged S100A9Tg mice. Finally, we demonstrate that c-Myc is required for S100A9-induced upregulation of PD-1/PD-L1, and that treatment of MDS HSPCs with anti-PD-1 antibody suppresses the expression of Myc target genes and increases the expression of hematopoietic pathway genes. We conclude anti-PD-1/anti-PD-L1 blocking strategies offer therapeutic promise in MDS in restoring effective hematopoiesis.

The interactive effect of the season and estuary position on the concentration of persistent organic pollutants in water and sediment from the Cua Dai estuary in Vietnam.

The current study was conducted in the Cua Dai estuary, Vietnam, (1) to assess the status of persistent organic pollutants (POPs) and (2) to examine the interactive effect of season and estuary position on the concentration of the pollutants in surface water and sediment. Fifty-two water and sediment samples were taken in the dry and rainy seasons from inner- and outer-estuary positions to analyze for six POPs, including hexachlorocyclohexane isomers (HCHs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), heptachlor, aldrin, dieldrin, and polychlorinated biphenyl (PCBs). The averaged concentrations of the respective POPs in water samples were 0.07, 0.1, 0.01, 0.03, 0.001, and 0.2 µg L-1 and in sediment samples were 2.6, 3.1, 0.9, 0.2, 0.2, and 121 µg kg-1. Of the six POPs examined, the concentration of DDTs in sediment samples and PCBs in water samples was significantly affected by the interactive effect of the two examined factors. The concentrations of HCHs, DDTs, heptachlor, and aldrin in water samples and of HCHs in sediment samples were significantly higher in the rainy season than in the dry season. Sediment samples collected from the inner position had a significantly higher concentration of HCHs and PCBs than in the outer position. Some mechanisms possibly influenced the varying POP concentration could include (1) greater riverine discharge in the rainy season and (2) the sea dilution effect in the outer position. Therefore, the concentration of the individual examined POPs in water and sediment in the Cua Dai estuary significantly depended on either the season, estuary position, or their combination.

Inspiratory muscle strength training improves lung function in patients with the hypermobile Ehlers-Danlos syndrome: A randomized controlled trial.

As exertional inspiratory dyspnea is a common disabling complaint in hypermobile Ehlers-Danlos syndrome (hEDS) often also known as joint hypermobility syndrome (JHS), we investigated inspiratory muscle (IM) strength in patients with hEDS, and we assessed the effects of IM training (IMT) on IM strength, lung function, and exercise capacity. A prospective evaluation of IM strength followed by a randomized controlled trial of IMT was performed in women with hEDS. Sniff nasal inspiratory pressure (SNIP) was used to routinely measure IM strength and IMT was carried out using a pressure threshold device. IM strength (main outcome), cardiopulmonary function, exercise capacity, and emotional distress of both the treated and control groups were evaluated at the start and at the end of the 6-week training period. IM strength was reduced (<80% of predicted) in 77% of patients (80/104). Lung function was normal, although 24% of patients had a higher forced expiratory vital capacity (FVC) than normal and 12% of patients had a higher total lung capacity (TLC) than normal. Both the IMT and control groups (n = 20) had similar baseline characteristics. Significant changes were noted only in the IMT group after IMT. At the end of the program, IMT improved SNIP (20%) (before: 41 ± 17 cm H2 O [28, 53] vs. after: 49 ± 18 cm H2 O [34;65]), six-minute walking distance (6MWD) (60 m) (455 ± 107 m [379,532] vs. 515 ± 127 m [408, 621]), and forced expiratory volume in one second (FEV1) (285 mL) (94 ± 14% pred [84,104] vs. 103 ± 11% pred [94, 112]). IM strength is significantly reduced in patients with hEDS. IMT improved IM strength, lung function, and exercise capacity. Our findings suggest that IMT should be added to usual care.

Pharmacy informatics in multihospital health systems: Opportunities and challenges.

PURPOSE: Challenges and opportunities in managing pharmacy-related technology in a multihospital health system are reviewed. SUMMARY: With electronic medical record (EMR) implementations, pharmacy technology deployments, and increased numbers of hospitals merging into single health systems, opportunities and challenges for pharmacy informatics (PI) teams have grown. Pharmacy leaders must consider the implications of using technology in a multihospital health-system environment, as well as the impact of the health system's organizational structures on technology implementations and dedicated support teams. Common challenges in achieving EMR and other technology implementation and standardization initiatives in multihospital health systems include harmonization of practices across hospitals of various sizes and types and issues of platform compatibility and interoperability. PI teams must collaborate with information technology teams at the system level to identify practical strategies for making the best use of available resources to implement pharmacy automation and software to help pharmacists continue to provide safe and effective patient care. The organizational structures that affect informatics teams, pharmacy integration and standardization initiatives, formulary management practices, data management and analytics, and clinical decision support systems all must be areas of focus. CONCLUSION: An integrated pharmacy enterprise can be well positioned to leverage operational efficiencies gained from appropriate use of technology to enhance patient care. Careful attention must be paid to the manner in which these systems are designed, implemented, and managed in order to make the best use of the technological resources used by the health system.