The hindbrain and cortico-reticular pathway in adolescent idiopathic scoliosis.

AIM: To characterise the corticoreticular pathway (CRP) in a case-control cohort of adolescent idiopathic scoliosis (AIS) patients using high-resolution slice-accelerated readout-segmented echo-planar diffusion tensor imaging (DTI) to enhance the discrimination of small brainstem nuclei in comparison to automated whole-brain volumetry and tractography and their clinical correlates. MATERIALS AND METHODS: Thirty-four participants (16 AIS patients, 18 healthy controls) underwent clinical and orthopaedic assessments and brain magnetic resonance imaging (MRI) on a 3 T MRI machine. Automated whole-brain volume-based morphometry, tract-based spatial statistics analysis, and manual CRP tractography by two independent raters were performed. Intra-rater and inter-rater agreement of DTI metrics from CRP tractography were assessed by intraclass correlation coefficient. Normalised structural brain volumes and DTI metrics were compared between groups using Student's t-tests. Linear correlation analysis between imaging parameters and clinical scores was also performed. RESULTS: AIS patients demonstrated a significantly larger pons volume compared to controls (p=0.006). Significant inter-side CRP differences in mean (p=0.02) and axial diffusivity (p=0.01) were found in patients only. Asymmetry in CRP fractional anisotropy significantly correlated with the Cobb angle (p=0.03). CONCLUSION: Relative pontine hypertrophy and asymmetry in CRP DTI metrics suggest central supranuclear inter-hemispheric imbalance in AIS, and support the role of the CRP in axial muscle tone. Longitudinal evaluation of CRP DTI metrics in the prediction of AIS progression may be clinically relevant.

Society for Cardiovascular Magnetic Resonance 2020 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). Case of the week is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. Each case consists of the clinical presentation and a discussion of the condition and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2020 Case of the Week series of 11 cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

A multicentre, randomized, double-masked, parallel group, vehicle-controlled phase IIb study to evaluate the safety and efficacy of 1% and 3% topical minocycline gel in patients with papulopustular rosacea.

BACKGROUND: Papulopustular rosacea is characterized by chronic facial erythema and inflammatory facial lesions. Minocycline has anti-inflammatory properties which may be effective in the treatment of rosacea inflammatory lesions. OBJECTIVES: To assess the safety and efficacy of once-daily topical minocycline gel 1% and 3% in patients with papulopustular rosacea. METHODS: This was a prospective, 12-week, double-blinded study conducted at 26 sites in the United States; 270 patients with papulopustular rosacea and 12-40 inflammatory lesions were randomized to minocycline 1%, minocycline 3% or vehicle. The primary endpoint was the mean change in inflammatory lesions at week 12. Key secondary endpoints included success on an Investigator's Global Assessment (IGA). RESULTS: Baseline mean lesion counts were 24·6, 25·1 and 24·3 in the minocycline 1%, minocycline 3% and vehicle groups, respectively; at week 12, the counts had decreased by 12·6, 13·1 and 7·9, respectively. Minocycline significantly decreased lesions, compared with the vehicle [P = 0·01, 95% confidence interval (CI) 7·9 to 0·9, for minocycline 1%; P = 0·007, 95% CI 8·3 to 1·3, for minocycline 3%]. The proportion of patients achieving IGA success was 39% in the minocycline 1% arm [P = 0·34, odds ratio (OR) 1·396 and OR 95% CI 0·71 to 2·75 vs. vehicle], 46% in the minocycline 3% arm (P = 0·04, OR 2·03 and OR 95% CI 1·04 to 3·95 vs. vehicle) and 31% in the vehicle arm. CONCLUSIONS: Minocycline topical gel appears to be safe and tolerable at concentrations of 1% and 3%, and both concentrations significantly decreased inflammatory lesion counts, with a significantly larger proportion of patients achieving IGA success at week 12 in the minocycline 3% arm. These findings support further evaluation of minocycline gel for treating inflammatory lesions associated with papulopustular rosacea. Linked Comment: Hampton. Br J Dermatol 2020; 183:412-413.

Switching to tenofovir vs continuing entecavir for hepatitis B virus with partial virologic response to entecavir: a randomized controlled trial.

Entecavir 0.5 mg (ETV) is widely used among treatment-naïve chronic hepatitis B (CHB) patients. However, 10%-30% of patients show partial virologic response (PVR) to the drug. If the hepatitis B virus (HBV) continues to replicate, the underlying liver disease may progress. Herein, we compared the efficacy of switching to tenofovir disoproxil fumarate (TDF) with that of continuing ETV in CHB patients with PVR to ETV. This was an open-label randomized controlled trial including CHB patients who had been receiving 0.5 mg of ETV for >12 months, but who still had detectable HBV DNA levels of >60 IU/mL without known resistance to ETV. Sixty patients were enrolled and 45 qualified for the study: Twenty-two patients were randomly assigned into the TDF group and 23 into the ETV group. After 12 months of treatment, the virologic response rate (HBV DNA <20 IU/mL) was significantly higher in the TDF group than in the ETV group, as measured using per-protocol analysis (55% vs 20%; P = .022) and intention-to-treat analysis (50% vs 17.4%; P = .020). The reduction in HBV DNA was greater (-1.13 vs -0.67 log10 IU/mL; P = .024), and the mean HBV DNA level was lower (1.54 vs 2.01 log10 IU/mL; P = .011) in the TDF group than in the ETV group. In conclusion, to achieve optimal response in CHB patients with PVR to ETV, switching to TDF would be a better strategy than continuing ETV. Appropriate modification of therapy would further improve the outcome of chronic HBV infection.

Impaired finger dexterity and nigrostriatal dopamine loss in Parkinson's disease.

Impaired finger dexterity occurs in Parkinson's disease (PD) and has been considered a limb-kinetic apraxia associated with primary sensory cortical dysfunction. To study the role of nigrostriatal dopamine loss and elementary parkinsonian motor deficits in impaired finger dexterity of PD. Thirty-two right-handed untreated PD patients and 30 right-handed healthy controls were included. All patients underwent [18F] FP-CIT positron emission tomography studies. We examined the associations among unilateral coin rotation (CR) score, Unified Parkinson's Disease Rating Scale (UPDRS) subscores for bradykinesia and rigidity of the corresponding arm, and contralateral regional striatal dopamine transporter (DAT) uptake. We also measured the effect of oral levodopa dose on CR scores and UPDRS subscores. PD patients performed worse than controls on the CR task. Unilateral arm UPDRS bradykinesia scores were associated with DAT uptake in the contralateral putamen. The left CR score was associated with left arm bradykinesia and rigidity scores and DAT uptake in the right posterior putamen, whereas no such associations were found for the right CR score. There was a significant effect of handedness on the association of putamen DAT uptake with CR scores, but not with UPDRS subscores. An oral levodopa challenge improved CR scores and UPDRS subscores on both sides. Impaired finger dexterity in PD is related to elementary parkinsonian motor deficits and nigrostriatal dopamine loss. Impaired dominant hand dexterity associated with nigrostriatal dopamine loss seems to be compensated to some extent by the dominant cerebral cortex specialized for controlling precise finger movements.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

Early administration of neuraminidase inhibitors in adult patients hospitalized for influenza does not benefit survival: a retrospective cohort study.

The administration of neuraminidase inhibitors (NAIs) within 2 days after the onset of symptoms (early NAI therapy) has been shown to reduce mortality in adult patients with severe influenza. However, there is no sufficiently solid evidence supporting the effectiveness of early NAI therapy on mortality. We reviewed the clinical data from 506 adult patients who were hospitalized for influenza between March 2010 and March 2014, to investigate the impact of early NAI therapy on mortality. Nearly one-third of the study patients were infected with influenza B (influenza A, influenza B, and co-infection of both in 68.8%, 28.1%, and 3.2%, respectively), and were diagnosed using the polymerase chain reaction (PCR) method (33.6%). Less than half (233, 46.0%) had received early NAI therapy. Patients with early NAI therapy were admitted to the hospital earlier, more frequently infected with influenza A, and more frequently diagnosed using rapid influenza detection tests compared to those without early NAI therapy. Although patients without early NAI therapy presented with more serious clinical manifestations, such as an initial symptom of dyspnea, pneumonia, and intensive care unit admission, than those with early NAI therapy, the in-hospital mortality of the former (2.9%, 8/273) did not differ from that of the latter (3.4%, 8/233) (p = 0.75). We did not find a reduction in mortality associated with early NAI therapy in adult patients hospitalized for influenza. Further clinical studies including a large number of influenza B-infected patients with virus identification using PCR methodology rather than viral culture may be required to confirm the beneficial impact of early NAI therapy on mortality.

Learning curve for endoscopic submucosal dissection of esophageal neoplasms.

There is a significant learning curve for endoscopic submucosal dissection of esophageal neoplasms that has not been fully characterized. This retrospective study included 33 consecutive superficial esophageal neoplasms for analysis of the learning curve for esophageal endoscopic submucosal dissection based on a single, novice endoscopist's experience. The study was divided into three periods (T1, T2, and T3) of 10 endoscopic submucosal dissection procedures in chronological order, with 13 procedures in the last period. Patient factors (age, sex, coexistent esophageal varices, or submucosal fibrosis) and tumor factors (location at upper esophagus, involving >3/4 esophageal circumference) for endoscopic submucosal dissection were not statistically different between the periods. The mean procedure time was 74.6 min/cm(2) , 23.4 min/cm(2) , and 10.5 min/cm(2) for T1, T2, and T3, respectively. The procedure time decreased over time (P = 0.02) and post hoc test revealed significant difference was only between T3 and T1 (P = 0.019). The en bloc resection rate was 50%, 100%, and 92.3% for T1, T2, and T3, respectively (P for trend = 0.015). R0 resection rate was 40%, 100%, and 84.6% for T1, T2, and T3, respectively (P for trend = 0.023). Two patients had complications: each one patient in T1 and T3 period experienced major bleeding during the procedure (P for trend = 0.875). None of the patients had esophageal perforation. The results of the study concluded that at least 30 cases of endoscopic submucosal dissection of esophageal neoplasms are needed for a novice endoscopist to gain early proficiency in this technique.

BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability.

BACKGROUND: We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR. METHODS: Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively. RESULTS: BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome. CONCLUSIONS: In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa.

Improved revascularization of islet grafts using an angiogenic monocyte subpopulation derived from spheroid culture of bone marrow mononuclear cells.

The spheroid culture method is an effective strategy for ex vivo expansion of an autologous therapeutic cell population. We investigated if cotransplantation of bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived mononuclear cells (BM-MNCs) could improve the posttransplant outcome of islet grafts using a mouse syngeneic marginal mass renal subcapsular islet transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice, the role of the BM-spheroids and the contribution of vessels derived from donors and recipients in grafted areas were assessed by immunohistochemistry. Compared to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM-spheroids, mainly composed of CXCR4(+) CD14(+) myeloid cells, showed higher angiogenic capacity, such as in vitro self-formed vessel structures; increased expression of angiogenic and chemoattractive factors; and incorporation into new vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation with islets improved the posttransplant outcomes in terms of glucose tolerance, serum insulin level, and diabetes reversal rate when compared with cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that cotransplantation of the BM-spheroids increased vessel density, area of grafted endocrine and non-endocrine tissue, and ß cell proliferation. In conclusion, cotransplantation of islets and BM-spheroids improved islet function through facilitation of revascularization and an increase in cell proliferation and islet cell mass.

Characterizing the patterns of clonal selection in circulating tumor DNA from patients with colorectal cancer refractory to anti-EGFR treatment.

INTRODUCTION: KRAS and EGFR ectodomain-acquired mutations in patients with metastatic colorectal cancer (mCRC) have been correlated with acquired resistance to anti-EGFR monoclonal antibodies (mAbs). We investigated the frequency, co-occurrence, and distribution of acquired KRAS and EGFR mutations in patients with mCRC refractory to anti-EGFR mAbs using circulating tumor DNA (ctDNA). PATIENTS AND METHODS: Sixty-two post-treatment plasma and 20 matching pretreatment archival tissue samples from KRAS (wt) mCRC patients refractory to anti-EGFR mAbs were evaluated by high-sensitivity emulsion polymerase chain reaction for KRAS codon 12, 13, 61, and 146 and EGFR 492 mutations. RESULTS: Plasma analyses showed newly detectable EGFR and KRAS mutations in 5/62 [8%; 95% confidence interval (CI) 0.02-0.18] and 27/62 (44%; 95% CI 0.3-0.56) samples, respectively. KRAS codon 61 and 146 mutations were predominant (33% and 11%, respectively), and multiple EGFR and/or KRAS mutations were detected in 11/27 (41%) cases. The percentage of mutant allele reads was inversely correlated with time since last treatment with EGFR mAbs (P = 0.038). In the matching archival tissue, these mutations were detectable as low-allele-frequency clones in 35% of patients with plasma mutations after treatment with anti-EGFR mAbs and correlated with shorter progression-free survival (PFS) compared with the cases with no new mutations (3.0 versus 8.0 months, P = 0.0004). CONCLUSION: Newly detected KRAS and/or EGFR mutations in plasma ctDNA from patients refractory to anti-EGFR treatment appear to derive from rare, pre-existing clones in the primary tumors. These rare clones were associated with shorter PFS in patients receiving anti-EGFR treatment. Multiple simultaneous mutations in KRAS and EGFR in the ctDNA and the decline in allele frequency after discontinuation of anti-EGFR therapy in a subset of patients suggest that several resistance mechanisms can co-exist and that relative clonal burdens may change over time. Monitoring treatment-induced genetic alterations by sequencing ctDNA could identify biomarkers for treatment screening in anti-EGFR-refractory patients.

Rheumatoid arthritis patients with hip fracture: a nationwide study.

SUMMARY: The study was to investigate the outcomes of rheumatoid arthritis (RA) patients with hip fractures with a large-scale, population-based, nationwide, case-cohort study using the Taiwan National Health Insurance database. The group has hip fractures at a younger age, higher complication, and mortality rate, which indicate that early intervention is necessary. INTRODUCTION: This study seeks to evaluate the incidence, mortality, and complication rates in RA patients with hip fractures, using a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 117,129 patients with hip fractures diagnosed from January 2004 to December 2010. Matching based on the propensity of RA patients was used. In total, 1,088 hip fractures were reported among patients with RA. Patients with hip fractures were divided into two groups: those without RA (controls) and those with RA (RA group). The incidence of hip fracture and mortality and complication rates after the hip fracture were then compared between the two groups. RESULTS: RA patients had a significantly higher incidence of hip fracture (3,260/100,000 person-years) compared with the general population (72/100,000 person-years). Hip fractures occurred significantly earlier among RA patients (70.6±5.3 years) compared with the control group (76.1±6.2 years). Cumulative mortality rates at 6-month and 1-year follow-up were significantly higher among patients in the RA group (9.47 and 18.47%) compared to the controls (8.47 and 13.62%) and among RA patients without hip fractures (3.24 and 6.16%). There was a significantly higher incidence of osteomyelitis after hip fracture among the RA group than among the body mass index-, comorbidity-, age-, and sex-matched patients in the control group. CONCLUSIONS: Compared to patients without RA, those with RA have a higher incidence of hip fractures at a relatively younger age and with higher complication and mortality rates. Steroid and disease-modifying anti-rheumatic drugs, the most common medicine in Taiwanese RA patients, might contribute to the high incidence of fracture and post-op infection. Appropriate early intervention to prevent hip fractures in RA patients is a critical issue in rheumatology care.

Association between the extent of urinary albumin excretion and glycaemic variability indices measured by continuous glucose monitoring.

AIMS: The contribution of glycaemic variability to the microvascular complication of diabetes has not been established. We examined whether there is an independent association between indices of glycaemic variability in continuous glucose monitoring and extent of albuminuria. METHODS: A total of 173 patients with Type 2 diabetes (without insulin therapy, n = 96; with insulin therapy, n = 77) who had unexplained large fluctuations in blood glucose values underwent three-day continuous glucose monitoring. We used a multinomial logistic regression model to determine whether the indices of glycaemic variability independently affected the odds of having a spot urine albumin/creatinine ratio of 30-299 mg/g and ≥ 300 mg/g. RESULTS: Higher standard deviation (P = 0.002), mean of daily differences (P = 0.023) and mean amplitude of glycaemic excursion (P = 0.043) significantly increased the odds of having a urine albumin/creatinine ratio of ≥ 300 mg/g. In multivariable analysis, only higher standard deviation, but not mean amplitude of glycaemic excursion and mean of daily differences, independently increased the odds of having a urine albumin/creatinine ratio of ≥ 300 mg/g (P = 0.025). Coefficient of variation (sd/mean) was not associated with the odds of having a urine albumin/creatinine ratio of 30-299 or ≥ 300 mg/g. CONCLUSIONS: The independent association between standard deviation and the extent of albuminuria was lost when the measures were normalized by mean glucose level. At least in terms of relative measures of glycaemic variability, we failed to demonstrate an independent association between glycaemic variability and albuminuria extent in patients with inadequately controlled Type 2 diabetes.

Risk factors for methicillin-resistant Staphylococcus aureus skin and soft-tissue infections in outpatients in Taiwan.

Information on the risk factors for community-associated skin and soft-tissue infections (SSTIs) due to methicillin-resistant Staphylococcus aureus in Asian populations is scarce. To this end we performed a case-control study of patients treated at two hospital-affiliated outpatient clinics in Taiwan to determine potential risk factors for MRSA SSTIs. S. aureus was isolated from 39 of 100 eligible patients, and 74% were MRSA. Apart from resistance to clindamycin and erythromycin, most MRSA isolates were susceptible to appropriate antimicrobials. The significant risk factors identified by multivariate analysis for MRSA SSTIs were male gender (P = 0·09), nasal carriage of MRSA (P = 0·02), exposure to an individual who had surgery within a year before infection (P = 0·02), and antibiotic treatment for SSTI in the year before infection (P = 0·04). The identification of such factors may assist provision of appropriate treatment to patients with suspected S. aureus SSTIs particularly in Taiwan.

Skeletal muscle mass and risk of death in an elderly population.

BACKGROUND AND AIM: Body mass index (BMI) has a U-shaped relationship with mortality among the elderly, in contrast to the general adult population. Skeletal muscle mass may be more appropriate than BMI for classifying mortality risk among the elderly. We investigated the relationship between skeletal muscle mass and mortality among elderly Chinese persons. METHOD AND RESULTS: A total of 1512 elderly from the Nutrition and Health Survey in Taiwanese Elderly (1999-2000) was enrolled, and the survival status was followed using data from the National Death Registry. The skeletal muscle mass index (SMMI) was calculated by dividing skeletal muscle mass by height in meters squared. The Cox proportional hazard model was used to estimate the association between SMMI and mortality. During the follow-up (average time: 7.9 years), one-third elderly died (n = 506) by any cause and 25% of them was cardiovascular mortality (ICD-9-CM: between 390 and 459). The total mortality and cardiovascular mortality were 4.23 and 1.07 per 100 person-years. Elderly participants with the lowest SMMI had the highest total mortality and cardiovascular mortality among the four quartiles (6.72, 3.76, 3.25 and 3.50 per 100 PY for total mortality; 1.81, 0.76, 0.87, 0.93 for cardiovascular mortality). Those with a low (1st quartile) SMMI had a 2-fold increase in total mortality (1.96; 1.63-2.35) and cardiovascular mortality (2.16; 1.51-3.08) risk compared to those with a normal [2nd, 3rd, or 4th quartile] SMMI. CONCLUSIONS: The threshold relationship between SMMI and mortality is contrast to the reverse J-shaped relationship between BMI and total mortality. Therefore, skeletal muscle mass measurement may be considered with a high priority to identify elderly individuals with a high mortality risk.

Acupuncture for surgical conditions: an overview of systematic reviews.

AIM: Several systematic reviews (SRs) of acupuncture for surgical conditions have recently been published with sometimes contradicting results. The aim of this overview was to summarise recent SRs of acupuncture for surgical conditions. METHOD: Thirteen electronic databases were searched for relevant reviews published since 2000. Data were extracted by two independent reviewers according to predefined criteria. RESULTS: Twelve SRs met our inclusion criteria. They related to the prevention or treatment of postoperative nausea and vomiting as well as to surgical or postoperative pain. Their results were far from uniform, and several caveats need to be considered. CONCLUSION: The evidence is insufficient to suggest that acupuncture is an effective intervention in surgical settings. More rigorous research seems warranted. This protocol was registered with PROSPERO database (registration number: CRD42013004817).

Severe dietary lysine restriction affects growth and body composition and hepatic gene expression for nitrogen metabolism in growing rats.

Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p < 0.05) food intake, but retarded (p < 0.05) growth, increased (p < 0.05) liver and muscle lipid contents and abdominal fat accumulation, increased (p < 0.05) blood urea nitrogen levels and mRNA levels of the serine-synthesizing 3-phosphoglycerate dehydrogenase gene, but decreased (p < 0.05) urea cycle arginase gene mRNA levels. In contrast, the 50% lysine restriction did not significantly (p > 0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism.

An intrauterine catch-up growth regimen increases food intake and post-natal growth in rats.

Nutritional conditions during the intrauterine stage are an important developmental programming factor that can affect the growth and metabolic status during foetal development and permanently alter the phenotypes of newborn offspring and adults. This study was performed to examine the effects of intrauterine catch-up growth (IUCG) on food intake, post-natal body growth and the metabolic status of offspring and growing rats. Control pregnant rats were fed ad libitum during the entire gestation period. For the IUCG regimen, pregnant rats were fed 50% of the food of the controls from pregnancy days 4 through 11 (8 days), followed by ad libitum feeding from pregnancy days 12 through parturition. The birth weight of offspring was not affected by the IUCG regimen. At weaning, offspring from each treatment group were assigned to two groups and given either a normal diet or high-fat diet (HFD) for 12 weeks until 103 days of age. In the normal diet group, the IUCG offspring showed a 9.0% increase (P < 0.05) in total food intake, were 11.2% heavier (p < 0.05) at 103 days of age and had an 11.0% greater (p < 0.05) daily weight gain compared with control offspring. The IUCG regimen did not affect body glucose and lipid metabolism. After exposure to the HFD, the IUCG regimen has not exacerbated metabolic disorders. In conclusion, our findings suggest that the IUCG nutritional regimen during pregnancy can increase the food intake and post-natal body growth of offspring without inducing metabolic disorders such as obesity and insulin resistance. The IUCG nutritional regimen might be used to improve the food intake and post-natal body growth of domestic animals.

Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts.

Bone marrow-derived early endothelial progenitor cells (BM-EPCs) are a clinical tool for enhancing revascularization. However, the therapeutic efficacy of co-transplantation of BM-EPC with islets has not been investigated. In this study, marginal mass islets were co-transplanted with or without BM-EPCs under the kidney capsules of syngeneic streptozotocin-induced diabetic mice. Using green fluorescent protein transgenic (GFP-Tg) mice as BM-EPC and islet donors or recipients, the role of EPCs in revascularization was assessed for graft morphology, vascular density and fate of EPCs by immunohistochemistry. Islet-EPC co-transplantation improved the outcome of islet transplantation as measured by glucose tolerance, serum insulin level and diabetes reversal rate, compared with transplantation of islets alone. Between groups, the morphology of islet grafts showed significant differences in size and composition of grafted endocrine tissues. Significantly more vessel density derived from donors and recipients was detected with islet-EPC co-transplantation. Abundant GFP-Tg mice-derived BM-EPCs (GFP-EPCs) were observed in or around islet grafts and incorporated into CD31-positive capillaries. Remaining GFP-EPCs expressed VEGF. In conclusion, co-transplantation of islets with BM-EPCs could improve the outcome of marginal mass islet transplantation by promoting revascularization and preserving islet morphology.