Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results after Two Years of Follow-Up with an Adult Team

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.     

Meta-Analysis and Systematic Review of Micro- and Macro-Nutrient Intakes and Trajectories of Macro-Nutrient Supply in the Eastern Mediterranean Region

The Eastern Mediterranean Region (EMR) is experiencing a nutrition transition, characterized by the emergence of overnutrition and micro-nutrient deficiencies. No previous study has comparatively examined nutrient intake in adults across countries in the EMR. This review examined the adequacy of nutrients in adults living in the EMR. Moreover, it analyzed the food balance sheets (FBS) for 1961–2018 to identify the trajectory of energy supply from macro-nutrients in the EMR. A systematic search was conducted from January 2012 to September 2020. Only observational studies were retained with a random sampling design. An assessment of the methodological quality was conducted. Levels of nutrient daily intake and their adequacy compared to the daily reference intake of the Institute of Medicine were reported across the region. No studies were identified for half of the region’s countries. Although nutrient energy intake was satisfactory overall, fat and carbohydrate intake were high. Intake of vitamin D, calcium, potassium, zinc, and magnesium were below that recommended. The analysis of the FBS data allowed for the identification of four linear patterns of trajectories, with countries in the EMR best fitting the ‘high-energy-supply from carbohydrate’ group. This systematic review warrants multi-sectorial commitment to optimize nutrient intake.     

The Design and Development of a Food Composition Database for an Electronic Tool to Assess Food Intake in New Caledonian Families

The food environment in New Caledonia is undergoing a transition, with movement away from traditional diets towards processed and discretionary foods and beverages. This study aimed to develop an up-to-date food composition database that could be used to analyze food and nutritional intake data of New Caledonian children and adults. Development of this database occurred in three phases: Phase 1, updating and expanding the number of food items to represent current food supply; Phase 2, refining the database items and naming and assigning portion size images for food items; Phase 3, ensuring comprehensive nutrient values for all foods, including saturated fat and total sugar. The final New Caledonian database comprised a total of 972 food items, with 40 associated food categories and 25 nutrient values and 615 items with portion size images. To improve the searchability of the database, the names of 593 food items were shortened and synonyms or alternate spelling were included for 462 foods. Once integrated into a mobile app-based multiple-pass 24-h recall tool, named iRecall.24, this country-specific food composition database would support the assessment of food and nutritional intakes of families in New Caledonia, in a cross-sectional and longitudinal manner, and with translational opportunities for use across the wider Pacific region.     

Assessing Residents’ Perceptions of Their Relocation to Long-Term Care: Psychometric Validation of the View of Relocation Scale

ObjectivesRelocation to long-term care is a major challenge for older people. The View of Relocation Scale (VRS) was developed to address the need for a brief instrument to assess residents’ perceptions of the relocation.DesignSecondary analysis of data collected in a cluster randomized trial. The psychometric properties of the VRS examined in this study included factorial structure (using exploratory factor analysis), unidimensionality (Rasch modeling), internal consistency reliability (Kuder-Richardson Formula 20, squared multiple correlations, and item-total correlations), and known groups validity (analysis of variance). The results were used to identify the psychometrically most robust items for inclusion into the final version of the instrument.Setting and ParticipantsParticipants were 202 long-term care residents in Melbourne, Australia (mean age = 85.52 years, standard deviation = 7.33), who had relocated to the facility a mean of 4.4 weeks previously. Residents with moderately severe and severe dementia were excluded.MeasuresThe VRS was developed following a review of the literature describing residents’ views of relocation and was designed for administration shortly after their relocation.ResultsThere was support for a 2-factor, 10-item solution, with separate subscales assessing Perceived Control (degree of control in the decision making and planning for the relocation) and Perceived Need (perceived need for the relocation to long-term care). Participants who were admitted directly from hospital reported higher perceived need but lower perceived control than those admitted to the facility from home.Conclusion and ImplicationsThe VRS can be used to understand the impact of older people's perceptions of relocation to long-term care on their subsequent adjustment and well-being, and to identify those who may benefit from tailored support.     

基于非编码RNA的中药有效成分抗肿瘤作用机制研究进展

非编码RNA(non-coding RNA,ncRNA)的失调与癌症的发生息息相关,并影响所有主要的癌症标志物。以ncRNA为切入点,根据中药药效物质基础及抗肿瘤机制,探究中药调控ncRNA诱导肿瘤细胞凋亡、抑制肿瘤细胞侵袭与迁移等作用机制,对于研发以ncRNA为基础的治疗药物具有重要意义。通过PubMed等数据库进行相关文献检索,对近5年有关中药调控ncRNA发挥抗肿瘤作用的研究进行综述,发现中药通过调节ncRNA,进而影响调节上皮间质转化、凋亡信号通路及耐药相关蛋白等多种途径,抑制肿瘤侵袭与迁移、促进肿瘤细胞凋亡和逆转肿瘤药物耐药的调控机制,为中药抗肿瘤药物相关研究提供参考。     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.     

The Relationship Between Protein Aggregation and Molecular Mobility Below the Glass Transition Temperature of Lyophilized Formulations Containing a Monoclonal Antibody

Purpose. To find out if the physical instability of a lyophilized dosage form is related to molecular mobility below the glass transition temperature. Further, to explore if the stability data generated at temperatures below the glass transition temperature can be used to predict the stability of a lyophilized solid under recommended storage conditions. Methods. The temperature dependence of relaxation time constant, , was obtained for sucrose and trehalose formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy relaxation studies using differential scanning calorimetry. The non-exponentiality parameter, , in the relaxation behavior was also obtained using dielectric relaxation spectroscopy. Results. For both sucrose and trehalose formulations, the variation in with temperature could be fitted Vogel-Tammann-Fulcher (VTF) equation. The two formulations exhibited difference sensitivities to temperature. Sucrose formulation was more fragile and exhibited a stronger non-Arrhenius behavior compared to trehalose formulation below glass transition. Both formulations exhibited <2% aggregation at t values <10, where t is the time of storage. Conclusions. Since the relaxation times for sucrose and trehalose formulations at 5°C are on the order of 10⁸ and 10⁶ hrs, it is likely that both formulations would undergo very little (<2%) aggregation in a practical time scale under refrigerated conditions.     

Effect of 2-Hydroxypropyl-β-cyclodextrin on Crystallization and Polymorphic Transition of Nifedipine in Solid State

The glassy state of nifedipine (NP) was prepared in the absence and presence of 2-hydroxypropyl--cyclodextrin (HP--CyD), and its crystallization and polymorphic transition behavior was investigated by differential scanning calorimetry (DSC) and powder X-ray diffractometry. In DSC thermograms, the glassy NP exhibited an en-dothermic peak at 48°C representing the glass transition of NP, an exothermic peak at 105°C for the crystallization to a metastable form of NP (Form B), an exothermic peak at 125°C for the polymorphic transition of Form B to a stable form of NP (Form A), and an endothermic peak at 171°C for the melting of Form A. The powder X-ray diffractogram of Form B was apparently different from that of Form A. In the presence of HP--CyD, the exothermic peak at 125°C for the Form B to A transition disappeared and a new en-dothermic peak appeared at 163°C. This new peak was ascribed to the melting of Form B, and the conversion of Form B to Form A was significantly suppressed in HP--CyD matrix. Upon storage at 60°C, the glassy NP was converted to Form A with an activation energy of 18 kcal/mol. The apparent dissolution rate of the NP/HP--CyD (molar ratio 1:1) increased in the order of glassy NP < Form A < Form B, because the glassy NP was readily converted to Form A upon contact with water, resulting in a lower dissolution rate. The present data suggest that HP--CyD is useful for the preparation of a fast dissolving form of metastable NP through glassy NP.