Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis.

Highly effective drugs modulating the defective protein encoded by the CFTR gene have revolutionized cystic fibrosis (CF) therapy. Preclinical drug-testing on human nasal epithelial (HNE) cell cultures and 3-dimensional human intestinal organoids (3D HIO) are used to address patient-specific variation in drug response and to optimize individual treatment for people with CF. This study is the first to report comparable CFTR functional responses to CFTR modulator treatment among patients with different classes of CFTR gene variants using the three methods of 2D HIO, 3D HIO, and HNE. Furthermore, 2D HIO showed good correlation to clinical outcome markers. A larger measurable CFTR functional range and access to the apical membrane were identified as advantages of 2D HIO over HNE and 3D HIO, respectively. Our study thus expands the utility of 2D intestinal monolayers as a preclinical drug testing tool for CF.

CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high-throughput screening variant of the Mammalian Membrane Two-Hybrid (MaMTH-HTS) to map the protein-protein interactions of wild-type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient-specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient-derived intestinal organoids has a significant effect on CFTR functional expression.

Intestinal epithelial tight junctions and permeability can be rescued through the regulation of endoplasmic reticulum stress by amniotic fluid stem cells during necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases affecting premature infants. It has been shown that NEC is associated with disrupted intestinal barrier and dysregulated endoplasmic reticulum (ER)-stress response. It has also been shown that stem cells derived from amniotic fluid (AFSC) rescued intestinal injury in experimental NEC. Herein, we hypothesized that the beneficial effects of AFSC in the injured intestine are due to the restoration of intestinal barrier function. We evaluated intestinal barrier function using an ex vivo intestinal organoid model of NEC. We found that AFSC restored the expression and localization of tight junction proteins in intestinal organoids, and subsequently decreased epithelial permeability. AFSC rescued tight junction expression by inducing a protective ER stress response that prevents epithelial cell apoptosis in injured intestinal organoids. Finally, we validated these results in our experimental mouse model of NEC and confirmed that AFSC induced sustained ER stress and prevented intestinal apoptosis. This response led to the restoration of tight junction expression and localization, which subsequently reduced intestinal permeability in NEC pups. These findings confirm that intestinal barrier function is disrupted during NEC intestinal injury, and further demonstrate the disruption can be reversed by the administration of AFSC through the activation of the ER stress pathway. This study provides insight into the pathogenesis of NEC and highlights potential therapeutic targets for the treatment of NEC.

Preclinical Studies of a Rare CF-Causing Mutation in the Second Nucleotide Binding Domain (c.3700A>G) Show Robust Functional Rescue in Primary Nasal Cultures by Novel CFTR Modulators.

The combination therapies ORKAMBITM and TRIKAFTATM are approved for people who have the F508del mutation on at least one allele. In this study we examine the effects of potentiator and corrector combinations on the rare mutation c.3700A>G. This mutation produces a cryptic splice site that deletes six amino acids in NBD2 (I1234-R1239del). Like F508del it causes protein misprocessing and reduced chloride channel function. We show that a novel cystic fibrosis transmembrane conductance regulator CFTR modulator triple combination (AC1, corrector, AC2-2, co-potentiator and AP2, potentiator), rescued I1234-R1239del-CFTR activity to WT-CFTR level in HEK293 cells. Moreover, we show that although the response to ORKAMBI was modest in nasal epithelial cells from two individuals homozygous for I1234-R1239del-CFTR, a substantial functional rescue was achieved with the novel triple combination. Interestingly, while both the novel CFTR triple combination and TRIKAFTATM treatment showed functional rescue in gene-edited I1234-R1239del-CFTR-expressing HBE cells and in nasal cells from two CF patients heterozygous for I1234-R1239del/W1282X, nasal cells homozygous for I1234-R1239del-CFTR showed no significant response to the TRIKAFTATM combination. These data suggest a potential benefit of CFTR modulators on the functional rescue of I1234-R1239del -CFTR, which arises from the rare CF-causing mutation c.3700A>G, and highlight that patient tissues are crucial to our full understanding of functional rescue in rare CFTR mutations.

ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Channel.

ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modest and variable, prompting the search for complementary interventions. As our previous work identified a positive effect of arginine-dependent nitric oxide signaling on residual F508del-Cftr function in murine intestinal epithelium, we were prompted to determine whether strategies aimed at increasing arginine would enhance F508del-cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in patient-derived airway epithelia. Now, we show that the addition of arginine together with inhibition of intracellular arginase activity increased cytosolic nitric oxide and enhanced the rescue effect of ORKAMBI on F508del-CFTR-mediated chloride conductance at the cell surface of patient-derived bronchial and nasal epithelial cultures. Interestingly, arginine addition plus arginase inhibition also enhanced ORKAMBI-mediated increases in ciliary beat frequency and mucociliary movement, two in vitro CF phenotypes that are downstream of the channel defect. This work suggests that strategies to manipulate the arginine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes. SIGNIFICANCE STATEMENT: These proof-of-concept studies highlight the potential to boost the response to cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, lumacaftor and ivacaftor, in patient-derived airway tissues expressing the major CF-causing mutant, F508del-CFTR, by enhancing other regulatory pathways. In this case, we observed enhancement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling through inhibition of endogenous arginase activity.

Augmentation of Cystic Fibrosis Transmembrane Conductance Regulator Function in Human Bronchial Epithelial Cells via SLC6A14-Dependent Amino Acid Uptake. Implications for Treatment of Cystic Fibrosis.

SLC6A14-mediated l-arginine transport has been shown to augment the residual anion channel activity of the major mutant, F508del-CFTR, in the murine gastrointestinal tract. It is not yet known if this transporter augments residual and pharmacological corrected F508del-CFTR in primary airway epithelia. We sought to determine the role of l-arginine uptake via SLC6A14 in modifying F508del-CFTR channel activity in airway cells from patients with cystic fibrosis (CF). Human bronchial epithelial (HBE) cells from lung explants of patients without CF (HBE) and those with CF (CF-HBE) were used for H3-flux, airway surface liquid, and Ussing chamber studies. We used α-methyltryptophan as a specific inhibitor for SLC6A14. CFBE41o-, a commonly used CF airway cell line, was employed for studying the mechanism of the functional interaction between SLC6A14 and F508del-CFTR. SLC6A14 is functionally expressed in CF-HBE cells. l-arginine uptake via SLC6A14 augmented F508del-CFTR function at baseline and after treatment with lumacaftor. SLC6A14-mediated l-arginine uptake also increased the airway surface liquid in CF-HBE cells. Using CFBE41o cells, we showed that the positive SLC6A14 effect was mainly dependent on the nitric oxide (NO) synthase activity, nitrogen oxides, including NO, and phosphorylation by protein kinase G. These finding were confirmed in CF-HBE, as inducible NO synthase inhibition abrogated the functional interaction between SLC6A14 and pharmacological corrected F508del-CFTR. In summary, SLC6A14-mediated l-arginine transport augments residual F508del-CFTR channel function via a noncanonical, NO pathway. This effect is enhanced with increasing pharmacological rescue of F508del-CFTR to the membrane. The current study demonstrates how endogenous pathways can be used for the development of companion therapy in CF.

Birth ball for pregnant women in labour research protocol: a multi-centre randomised controlled trial.

BACKGROUND: Birth ball is one of the non-pharmacologic pain relief methods to help mothers cope with the labouring process. A randomised controlled trial (RCT) is conducted to evaluate the effectiveness, safety and harm of birth ball use by pregnant women in labour compared to treatment as usual group. METHODS: A prospective multi-centre randomised controlled trial (RCT) will be conducted in Obstetrics and Gynaecological units of five public hospitals in Hong Kong, China. Data will be collected from March 2016 onward for 2 years. The target population is Chinese women with an uncomplicated singleton pregnancy at gestational age of 37 to 42 weeks. Participants are randomised based on parity (nulliparous and multiparous) and type of labour onset (spontaneous and induced). Women in the intervention group are actively offered and taught how to use a birth ball; those in the control group receive the usual midwifery care. The target sample size is 512. The primary outcome measures are maternal pain intensity, satisfaction with pain relief, sense of control in labour, assisted delivery and satisfaction with childbirth experience. Labour pain relief is measured by visual analogue scale (VAS). Other outcomes will be measured through four different validated questionnaires. To control for potential cluster effects, a linear mixed model will be used. An intention-to-treat analysis is adopted and performed by researchers unknown to subjects' group allocation. DISCUSSION: Results will provide rigorous scientific evidence for policy development and practice. We are using stratified randomisation according to potential confounders of parity and type of labour onset to give four possible combinations. If the results are favourable, it will facilitate systematic implementation to promote birth ball use for women in labour. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR), Registration number: ChiCTR-IIC-16008275 , Date of registration 12 April 2016 (retrospectively registered), Date of enrolment of the first participant to the trial 1 March 2016.

Effects of therapeutic play on children undergoing cast-removal procedures: a randomised controlled trial.

OBJECTIVES: To examine (1) the effectiveness of therapeutic play in reducing anxiety and negative emotional manifestations among children undergoing cast-removal procedures and (2) the satisfaction of parents and cast technicians with cast-removal procedures. DESIGN: A randomised controlled trial. SETTING: An orthopaedic outpatient department of a regional teaching hospital in Hong Kong. PARTICIPANTS: Children (n=208) aged 3-12 undergoing cast-removal procedure were invited to participate. INTERVENTIONS: Eligible children were randomly allocated to either the intervention (n=103) or control group (n=105) and stratified by the two age groups (3-7 and 8-12 years). The intervention group received therapeutic play intervention, whereas the control group received standard care only. Participants were assessed on three occasions: before, during and after completion of the cast-removal procedure. OUTCOME MEASURES: Children's anxiety level, emotional manifestation and heart rate. The satisfaction ratings of parents and cast technicians with respect to therapeutic play intervention were also examined. RESULTS: Findings suggested that therapeutic play assists children aged 3-7 to reduce anxiety levels with mean differences between the intervention and control group was -20.1 (95% CI -35.3 to -4.9; p=0.01). Overall, children (aged 3-7 and 8-12) in the intervention groups exhibited fewer negative emotional manifestations than the control group with a mean score difference -2.2 (95% CI -3.1 to -1.4; p<0.001). Parents and technicians in the intervention group also reported a higher level of satisfaction with the procedures than the control group with a mean score difference of 4.0 (95% CI -5.6 to 2.3; p<0.001) and 2.6 (95% CI 3.7 to 1.6; p<0.001), respectively. CONCLUSION: Therapeutic play effectively reduces anxiety and negative emotional manifestations among children undergoing cast-removal procedures. The findings highlight the importance of integrating therapeutic play into standard care, in particular for children in younger age. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006822; Pre-results.

Maternal intention to exclusively breast feed among mainland Chinese mothers: A cross-sectional study.

OBJECTIVE: to examine postpartum maternal recall of their intentions to exclusively breast feed among breastfeeding women and identify its predictors. DESIGN AND SETTING: a cross-sectional descriptive study was conducted in a regional teaching hospital at Guangzhou, China between April 1 and July 14, 2014. PARTICIPANTS: 571 mothers who were within four days after delivery were recruited to the study. MEASUREMENTS: data were collected by four research assistants with maternal intention to breast feed data sheet, the Network Support for Breastfeeding Scale (NSBS), and a socio-demographic data sheet. FINDINGS: greater than half of the mothers (69.5%) intended to exclusively breast feed. The logistic regression analysis revealed six variables which predicted postpartum maternal recall of their intentions to exclusively breast feed. They were support from husband, being breast-fed as an infant, previous breast feeding experience, attending antenatal breast feeding class, time of decision to breast feed, and the rating of the importance of my baby's health. CONCLUSION AND IMPLICATIONS FOR PRACTICE: health care professionals could develop strategies to enhance mothers' intention to exclusively breast feed, such as providing antenatal breast feeding class on internet, a strong focus on the benefits of exclusive breast feeding on the baby's health in the education programme, and more efforts directed toward educating school-aged children and adolescents to modify societal perceptions of what are considered normal infant feeding. Mothers' husband could be encouraged in supporting exclusive breast feeding.

Measuring Oral Mucositis of Pediatric Patients with Cancer: A Psychometric Evaluation of Chinese Version of the Oral Mucositis Daily Questionnaire.

OBJECTIVE: Oral mucositis is a frequent clinical condition that has been shown to affect pediatric cancer patients. Oral Mucositis Daily Questionnaire (OMDQ) is one of the few available patient-reported outcome measures to assess the extent and impact of oral mucositis. The objectives of the study were to translate the Mouth and Throat Soreness-Related Questions of the OMDQ into Chinese (OMDQ MTS-Ch) for children and adolescents aged 6-18 years receiving chemotherapy and to evaluate its psychometric properties. METHODS: This was part of a multicenter, prospective cohort study involving two phases. Phase I involved forward-backward translation to fit the cognitive and linguistic age level of the children and adolescents, followed by face and content validation, together with pretesting. In Phase II, which evaluated the internal consistency, test-retest reliability, and discriminant validity, a total of 140 patients completed the OMDQ MTS-Ch for 14 days. RESULTS: The OMDQ MTS-Ch had satisfactory face and content validities. The Cronbach's alpha coefficient of the OMDQ MTS-Ch was 0.984. All of the corrected item-total correlations were higher than 0.90. The test-retest intraclass correlation coefficient between consecutive days for the OMDQ MTS-Ch items ranged from 0.576 to 0.983; the only value that was not over 0.70 was that for the paired study days 7 and 8 for the item of talking. The mean area-under-the-curve OMDQ MTS-Ch item scores were significantly different among patients with different degrees of mucositis severity (P < 0.001), supporting the discriminant validity. CONCLUSIONS: It has been shown that the OMDQ MTS-Ch has a good level of reliability and discriminant validity and can be completed by children aged ≥6 years and adolescents on a daily basis to measure mucositis and its related functional limitations.

Orkambi® and amplifier co-therapy improves function from a rare CFTR mutation in gene-edited cells and patient tissue.

The combination therapy of lumacaftor and ivacaftor (Orkambi®) is approved for patients bearing the major cystic fibrosis (CF) mutation: ΔF508 It has been predicted that Orkambi® could treat patients with rarer mutations of similar "theratype"; however, a standardized approach confirming efficacy in these cohorts has not been reported. Here, we demonstrate that patients bearing the rare mutation: c.3700 A>G, causing protein misprocessing and altered channel function-similar to ΔF508-CFTR, are unlikely to yield a robust Orkambi® response. While in silico and biochemical studies confirmed that this mutation could be corrected and potentiated by lumacaftor and ivacaftor, respectively, this combination led to a minor in vitro response in patient-derived tissue. A CRISPR/Cas9-edited bronchial epithelial cell line bearing this mutation enabled studies showing that an "amplifier" compound, effective in increasing the levels of immature CFTR protein, augmented the Orkambi® response. Importantly, this "amplifier" effect was recapitulated in patient-derived nasal cultures-providing the first evidence for its efficacy in augmenting Orkambi® in tissues harboring a rare CF-causing mutation. We propose that this multi-disciplinary approach, including creation of CRISPR/Cas9-edited cells to profile modulators together with validation using primary tissue, will facilitate therapy development for patients with rare CF mutations.

Phenotypic profiling of CFTR modulators in patient-derived respiratory epithelia.

Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations. This platform faithfully recapitulated patient-specific responses previously observed in the "gold-standard" but relatively low-throughput Ussing chamber. Moreover, using this approach, we identified a novel strategy with which to augment the response to an approved drug in specific patients. In proof of concept studies, we also validated the use of this platform in measuring drug responses in lung cultures differentiated from cystic fibrosis iPS cells. Taken together, we show that this medium throughput assay of CFTR activity has the potential to stratify cystic fibrosis patient-specific responses to approved drugs and investigational compounds in vitro in primary and iPS cell-derived airway cultures.

Inhibition of corticotropin-releasing hormone receptor 1 and activation of receptor 2 protect against colonic injury and promote epithelium repair.

Maternal separation (MS) in neonates can lead to intestinal injury. MS in neonatal mice disrupts mucosal morphology, induces colonic inflammation and increases trans-cellular permeability. Several studies indicate that intestinal epithelial stem cells are capable of initiating gut repair in a variety of injury models but have not been reported in MS. The pathophysiology of MS-induced gut injury and subsequent repair remains unclear, but communication between the brain and gut contribute to MS-induced colonic injury. Corticotropin-releasing hormone (CRH) is one of the mediators involved in the brain-gut axis response to MS-induced damage. We investigated the roles of the CRH receptors, CRHR1 and CRHR2, in MS-induced intestinal injury and subsequent repair. To distinguish their specific roles in mucosal injury, we selectively blocked CRHR1 and CRHR2 with pharmacological antagonists. Our results show that in response to MS, CRHR1 mediates gut injury by promoting intestinal inflammation, increasing gut permeability, altering intestinal morphology, and modulating the intestinal microbiota. In contrast, CRHR2 activates intestinal stem cells and is important for gut repair. Thus, selectively blocking CRHR1 and promoting CRHR2 activity could prevent the development of intestinal injuries and enhance repair in the neonatal period when there is increased risk of intestinal injury such as necrotizing enterocolitis.

The Effect of Upper Limb Massage on Infants' Venipuncture Pain.

The purpose of the study was to investigate the effect of upper limb massage on relieving pain among infants undergoing venipuncture in Hong Kong. This study was a crossover, double-blind, randomized controlled trial. Eighty infants at the neonatal intensive care unit were randomly assigned to 2 groups in different order to receive interventions. The massage first group (N = 40) received 2-minute massage before venipuncture on the first occasion then received usual care (control) on the second occasion, and vice versa in the massage second group (N = 40). The infants' behavior and physiological responses were recorded on two occasions: (1) right after the intervention and (2) during the first 30 seconds of venipuncture procedure. The mean pain scores (Premature Infant Pain Profile) were significantly lower in infants who received massage (massage first: 6.0 [standard deviation = 3.3]; massage second: 7.30 [standard deviation = 4.4]) versus control (massage first: 12.0 [standard deviation = 4.3]; massage second: 12.7 [standard deviation = 3.1]). The crude and adjusted generalized estimating equations model showed that the infants had significantly lower pain score when receiving massage as compared to receiving the control treatment, and there were no significant time and carryover effects: -6.03 (95% confidence interval: -7.67 to -4.38), p < .001 and -5.96 (95% confidence interval: -7.56 to -4.36), p < .001, respectively. Upper limb massage may be effective in decreasing infants' venipuncture pain perception.

Predictors of breast feeding self-efficacy in the immediate postpartum period: A cross-sectional study.

OBJECTIVE: to examine breast feeding self-efficacy and identify its predictors among mainland Chinese mothers in the early postpartum period. DESIGN AND SETTING: a cross-sectional descriptive questionnaire survey was conducted in a regional teaching hospital with childbirth rate over 3000 per year at Guangzhou, China from April 1 to July 14, 2014. PARTICIPANTS: a total of 571 Chinese mothers who were within 72-96hours post partum were recruited consecutively to the study. MEASUREMENTS: data were collected by the Chinese version of the Breastfeeding Self-efficacy Scale-Short Form (BSES-SF), the Network Support for Breastfeeding Scale (NSBS) and a socio-demographic data sheet. FINDINGS: a total of 640 eligible women was approached and 571 mothers completed the study with the response rate of 89%. Mothers reported moderate level of breast feeding self-efficacy in the immediate postpartum period. The best-fit regression analysis revealed six variables that explained 43.9% of the variance in breast feeding self-efficacy in the immediate postpartum period. They were intention of breast feeding, support from husband, support from nurses/midwives, attending antenatal breast feeding classes, time from childbirth to initiate breast feeding and previous breast feeding experience. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this study found six predictors of breast feeding self-efficacy in the immediate postpartum period. In order to increase maternal breast feeding self-efficacy level, a more women-centred approach is recommended. Mothers and fathers should be facilitated to attend antenatal classes on breast feeding. New mother' husband could be encouraged in supporting breast feeding. Nurses and midwives could encourage new mothers to initiate breast feeding as soon as possible. Further work to promote early mother-infant contact post birth, such as via skin to skin contact should also be facilitated where possible.

The Short Form of the Breastfeeding Self-Efficacy Scale as a Prognostic Factor of Exclusive Breastfeeding among Mandarin-Speaking Chinese Mothers.

BACKGROUND: Little is known about the effect of maternal perceived breastfeeding self-efficacy on the exclusive breastfeeding rate at 6 months postpartum in mainland China. OBJECTIVE: The aim of this study was to examine the relative effect of maternal breastfeeding self-efficacy and selected relevant factors on the exclusive breastfeeding rate at 6 months postpartum. The internal consistency and construct validity of the Chinese (Mandarin) version of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) were also examined. METHODS: This was a prospective cohort study conducted at a regional teaching hospital in Guangzhou, China. A total of 562 in-hospital mothers who were within 72 hours postpartum were recruited to the study and followed up by telephone for 6 months. RESULTS: Although all of the mothers breastfed their babies within 72 hours postpartum, only 25% of the mothers breastfed exclusively. The mean survival time of continuation of exclusive breastfeeding was 16.7 days. The proportion of mothers who breastfed exclusively after discharge was 14.8%, 2.0%, and 0.2% at 1, 4, and 6 months, respectively. Cox regression analysis revealed that the mothers who had a higher BSES-SF score at baseline, underwent cesarean section, and practiced exclusive breastfeeding within 72 hours after delivery were significantly associated with a lower hazard of discontinuation of exclusive breastfeeding before 6 months postpartum. CONCLUSION: The exclusive breastfeeding rate among Chinese women is far from satisfactory. The Chinese (Mandarin) version of the BSES-SF can help in identifying mothers who need more support for exclusive breastfeeding before 6 months postpartum.

Self-Care Strategies among Chinese Adolescent Girls with Dysmenorrhea: A Qualitative Study.

Little is known about how Chinese adolescent girls manage dysmenorrhea. This study aims to explore self-care strategies among Chinese adolescent girls with dysmenorrhea. The study uses a mixed methods design with two phases: a cross-sectional survey in phase I and semistructured interviews in phase II. This paper reports phase II. In line with the phase I findings, 28 adolescent girls with different characteristics (high or low levels of self-care behavior and pain intensity, who did or did not self-medicate, and who had or had not received menstrual education) were recruited for interviews. Content analysis was used for data analysis. Four categories emerged from the data: lifestyle changes, symptom management, communicating dysmenorrhea with others, and seeking medical advice. Girls selected their diets carefully and reduced physical activity during menstruation to avoid aggravating symptoms. Heat therapy commonly was employed for symptom management. A few girls self-medicated to obtain immediate relief from pain, but the majority expressed reservations about using medication because they worried about dependence and side effects. Some girls communicated dysmenorrhea with their family and friends, but the majority did not seek medical advice. The present study showed that girls employed various self-care strategies for dysmenorrhea, including some strategies stemming from traditional Chinese medicine. The findings revealed menstrual etiquette among Chinese adolescent girls with dysmenorrhea, and demonstrated that self-medication was not part of most girls' self-care. Understanding the self-care strategies of these girls is important, as it can help nurses develop a culturally-specific intervention to promote self-care among adolescent girls with dysmenorrhea.

Endoplasmic reticulum stress is involved in the colonic epithelium damage induced by maternal separation.

BACKGROUND: Maternal separation (MS) leads to intestinal barrier dysfunction in neonatal mice. Endoplasmic reticulum (ER) stress is associated with apoptosis and pro-inflammatory response induction. We hypothesized that MS induced gut damage is associated with ER stress and that administration of an ER stress inhibitor protects gut damage. METHODS: C57BL/6 mice received intraperitoneal PBS (n=10) or Salubrinal (1mg/kg/day, n=10). MS was performed soon after treatment for 3h daily between P5 and P9. Ten untreated neonatal mice served as control. The colon was harvested on P9 and analyzed for ER stress markers (BiP, CHOP), apoptosis (CC3), goblet cell number per crypt and crypt length (Alcian blue, hematoxylin/eosin), and transcellular permeability (Ussing chamber). Groups were compared using one-way ANOVA with Bonferroni post-test. RESULTS: Compared to controls, MS mice had higher relative protein expression of ER stress and apoptosis markers (p<0.05) and reduced goblet cell number per crypt and crypt length (p<0.001). In comparison to PBS mice, Salubrinal treated mice had higher goblet cell number (p<0.05), crypt length (p<0.001), and lower transcellular permeability (p<0.05). CONCLUSIONS: Maternal separation induces ER stress and causes colon damage, but ER stress inhibitor protects morphology and permeability. This provides insights on bowel pathogenesis and potential novel treatments for diseases such as necrotizing enterocolitis.

The effect of a self-efficacy-based educational programme on maternal breast feeding self-efficacy, breast feeding duration and exclusive breast feeding rates: A longitudinal study.

BACKGROUND: breast feeding has a number of well-documented benefits. Numerous studies have been conducted to investigate an effective approach to increase the breast feeding rate, duration and exclusive breast feeding rate, in which maternal breast feeding self-efficacy was determined as one of the major contributors. Although numerous breast feeding educational programmes have been developed to enhance maternal breastfeeding self-efficacy, results on the effectiveness of these programmes remain inconclusive. OBJECTIVE: this study aims to investigate the effectiveness of a self-efficacy-based breast feeding educational programme (SEBEP) in enhancing breast feeding self-efficacy, breast feeding duration and exclusive breast feeding rates among mothers in Hong Kong. METHODS: eligible pregnant women were randomized to attend a 2.5-hour breast feeding workshop at 28-38 weeks of gestation and receive 30-60minutes of telephone counselling at two weeks post partum, whereas both intervention and control groups received usual care. At two weeks postpartum, the Breast feeding Self-Efficacy Scale-Short Form (BSES-SF) and a self-developed post partum questionnaire were completed via telephone interviews. The breast feeding duration, pattern of breast feeding and exclusive breast feeding rates were recorded at two weeks, four weeks, eight weeks and six months post partum. RESULTS: results of analyses based on an intention-to-treat (ITT) assumption showed a significant difference (p<0.01) in the change in BSES-SF mean scores between the mothers who received SEBEP and those who did not receive SEBEP at two weeks post partum. The exclusive breast feeding rate was 11.4% for the intervention group and 5.6% for the control group at six months post partum. CONCLUSION: the findings of this study highlight the feasibility of a major trial to implement breast feeding education targeted at increasing breast feeding self-efficacy and exclusive breast feeding rates in Hong Kong.

Cystic fibrosis gene modifier SLC26A9 modulates airway response to CFTR-directed therapeutics.

Cystic fibrosis is realizing the promise of personalized medicine. Recent advances in drug development that target the causal CFTR directly result in lung function improvement, but variability in response is demanding better prediction of outcomes to improve management decisions. The genetic modifier SLC26A9 contributes to disease severity in the CF pancreas and intestine at birth and here we assess its relationship with disease severity and therapeutic response in the airways. SLC26A9 association with lung disease was assessed in individuals from the Canadian and French CF Gene Modifier consortia with CFTR-gating mutations and in those homozygous for the common Phe508del mutation. Variability in response to a CFTR-directed therapy attributed to SLC26A9 genotype was assessed in Canadian patients with gating mutations. A primary airway model system determined if SLC26A9 shows modification of Phe508del CFTR function upon treatment with a CFTR corrector. In those with gating mutations that retain cell surface-localized CFTR we show that SLC26A9 modifies lung function while this is not the case in individuals homozygous for Phe508del where cell surface expression is lacking. Treatment response to ivacaftor, which aims to improve CFTR-channel opening probability in patients with gating mutations, shows substantial variability in response, 28% of which can be explained by rs7512462 in SLC26A9 (P = 0.0006). When homozygous Phe508del primary bronchial cells are treated to restore surface CFTR, SLC26A9 likewise modifies treatment response (P = 0.02). Our findings indicate that SLC26A9 airway modification requires CFTR at the cell surface, and that a common variant in SLC26A9 may predict response to CFTR-directed therapeutics.