Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors.

Accurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.

Laparoscopic percutaneous closure of patent processus vaginalis without hydrocelectomy for childhood primary hydrocele.

PURPOSE: To present our surgical technique and the outcome of single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of patent processus vaginalis (PPV) without hydrocelectomy for childhood primary hydrocele (CPH). METHODS: A prospective study was conducted on all cases of CPH treated with SILPEC at our center between June 2016 and December 2021. In our SILPEC procedure, PPV was closed extraperitoneally using a percutaneous needle with a wire lasso. No hydrocelectomy or fenestration of the hydrocele was performed. Percutaneous aspiration was performed when the hydrocele fluid could not be pushed back to the peritoneal cavity. RESULTS: 553 patients were enrolled, with a median age of 34 months (range from 22 months to 13 years). Ipsilateral PPV was present in all cases. There were no intraoperative complications and no conversion. At follow-up 6-72 months, recurrent hydrocele occurred in 0.36%, and subcutaneous stitch inflammatory reaction was noted in 0.7%. There was no case of testicular atrophy or iatrogenic cryptorchidism. Postoperative cosmesis was excellent as all patients were virtually scarless. CONCLUSIONS: Ipsilateral PPV was present in all cases of CPH in our series. Our technique of SILPEC of PPV without hydrocelectomy is feasible and safe, with excellent postoperative cosmesis in the management of CPH.

Reduction of recurrence by peritoneal thermal injury in laparoscopic percutaneous extraperitoneal closure of internal ring for inguinal hernia in children.

PURPOSE: To evaluate the impact of peritoneal thermal injury (PTI) in the reduction of recurrence incidence in laparoscopic percutaneous extra-peritoneal closure of internal ring (LPEC) for pediatric inguinal hernia (PIH) in children. METHODS: Medical records of patients undergoing LPEC for PIH at our center were reviewed and divided into 2 groups: Group A (period from June 2017 to December 2017)-without PTI and Group B (period from January 2018 to December 2018) with PTI. The surgical technique and the type of suture used for LPEC were the same for both groups. The outcomes of the two groups were analyzed and compared. RESULTS: 277 patients with 283 IHs in group A were compared to 376 patients with 389 IHs in group B. There were no significant differences between the two groups in terms of age, gender, uni- or bilateral hernia. At a median follow-up period of 48 months, there was no hydrocele, suture granuloma, testicular atrophy, or iatrogenic cryptorchidism in both groups. The recurrence rate in group A was 6.4%, significantly higher than 1.8% in group B (p = 0.002). CONCLUSIONS: Our study showed that PTI in LPEC for PIH is safe and associated with a significant reduction of recurrence incidence.

How Does Community-Based Housing Foster Social Participation in Older Adults: Importance of Well-Designed Common Space, Proximity to Resources, Flexible Rules and Policies, and Benevolent Communities.

As supporting active and healthy aging calls for different community-based housing alternatives, integrated knowledge of their impacts on older adults' social participation is required. This study aimed to explore how community-based housing fostered social participation in older adults. A scoping review was used to systematically identify relevant studies according to 32 keywords in 8 electronic databases. Published during 2000-2021, the 46 studies were carried out in North America, Europe, Oceania, and Asia, documenting older adults' social participation in six community-based housing models. Targeting different clienteles, these models mainly promote older adults' social participation by providing: 1) accessible common space in a design favorable to social interactions; 2) proximity to resources; 3) flexible rules and policies that facilitate residents' interactions with not only co-residents but community neighbors; and 4) benevolent communities. These results highlight the interactions between the physical and social environments; they suggest the importance of building benevolent communities as well as of sharing resources among residences and local communities to create a supportive living and neighborhood environment for active and healthy aging. Future studies should further explore the role of different stakeholders in developing benevolent communities by considering the dynamics between the person and the environment.

Janus kinase inhibitors for atopic dermatitis: a promising treatment modality.

Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For nonresponders to conventional therapies, AD can significantly reduce sleep quality and quality of life. AD pathogenesis is multifactorial and involves multiple immune pathways, with recent evidence of T helper (Th)2, Th17 and Th22 axis attenuation in various AD endotypes and racial subtypes. Inhibition of the conserved Janus kinase (JAK) signalling pathway represents a promising therapeutic avenue to reduce the activation of multiple proinflammatory mediators involved in AD pathogenesis. JAK inhibitors exist in both oral and topical forms with variable specificity for the receptor tyrosine kinases JAK1, JAK2, JAK3 and tyrosine kinase 2. Oral formulations include abrocitinib, upadacitinib, baricitinib and gusacitinib, and are most appropriate for patients with moderate to severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment to revolutionize the management of AD.

Characterisation of gastrointestinal helminths and their impact in commercial small-scale chicken flocks in the Mekong Delta of Vietnam.

Commercial small-scale chicken farms managed as all-in-all-out but operating with low standards of hygiene/biosecurity are increasingly common in Vietnam. These conditions facilitate the transmission of gastrointestinal helminths. However, there are no published data on helminths in these systems. We aimed (1) to determine the prevalence/burden of gastrointestinal helminths in small-scale commercial flocks in the Mekong Delta region and (2) to investigate the association between worm burdens and birds' weight and disease status. Randomly selected chickens (n = 120) from 'normal' flocks were investigated at the end of their production cycle (~ 18 weeks), as well as 90 chickens from 'diseased' flocks with signs of respiratory and/or severe disease. The gastrointestinal tract of chickens was dissected and all visible helminths were identified and counted. A total of 54.2% and 54.4% normal and diseased chickens contained helminths. Among colonised birds, the diseased ones harboured a higher mass of helminth worms than normal (healthy) birds (3.8 ± SD 8.6 g vs. 1.9 ± SD 6.3 g, respectively). Eight species were identified, including nematodes (Ascaridia galli, Cheilospirura hamulosa and Heterakis gallinarum), cestodes (Hymenolepis, Raillietina cesticillus, Raillietina echinobothrida, Raillietina tetragona,) and one trematode (Echinostomatidae). Heterakis gallinarum was the most prevalent helminth (43.3% and 42.2% in normal and sick chickens, respectively), followed by A. galli (26.7% and 41.1%). Colonised chickens weighed 101.5 g less than non-colonised birds. Colonisation was higher during the rainy months (May-November) for both H. gallinarum and A. galli. Anthelminthic usage was not associated with reduced helminth burdens. We recommend upgrading cleaning and disinfection and limiting access to ranging areas to control helminths in small-scale chicken flocks.

Pretreatment Cerebrospinal Fluid Bacterial Load Correlates With Inflammatory Response and Predicts Neurological Events During Tuberculous Meningitis Treatment.

BACKGROUND: The Mycobacterium tuberculosis load in the brain of individuals with tuberculous meningitis (TBM) may reflect the host's ability to control the pathogen, determine disease severity, and determine treatment outcomes. METHODS: We used the GeneXpert assay to measure the pretreatment M. tuberculosis load in cerebrospinal fluid (CSF) specimens from 692 adults with TBM. We sought to understand the relationship between CSF bacterial load and inflammation, and their respective impact on disease severity and treatment outcomes. RESULTS: A 10-fold higher M. tuberculosis load was associated with increased disease severity (odds ratio, 1.59; P = .001 for the comparison between grade 1 and grade 3 severity), CSF neutrophil count (r = 0.364 and P < .0001), and cytokine concentrations (r = 0.438 and P < .0001). A high M. tuberculosis load predicted new neurological events after starting treatment (P = .005, by multinomial logistic regression) but not death. Patients who died had an attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations as compared to survivors. In contrast, patients with high pretreatment CSF bacterial loads, cytokine concentrations, and neutrophil counts were more likely to subsequently experience neurological events. CONCLUSIONS: The pretreatment GeneXpert-determined M. tuberculosis load may be a useful predictor of neurological complications occurring during TBM treatment. Given the evidence for the divergent pathogenesis of TBM-associated neurological complications and deaths, therapeutic strategies to reduce them may need reassessment.

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis.

BACKGROUND: Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization. RESULTS: A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08). CONCLUSIONS: Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.).

Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration.

Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.

Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. Methods: We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. Results: LTA4H genotype predicted survival of human immunodeficiency virus (HIV)-uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM. HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. Conclusions: LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals.

Standardized Methods for Enhanced Quality and Comparability of Tuberculous Meningitis Studies.

Tuberculous meningitis (TBM) remains a major cause of death and disability in tuberculosis-endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the conduct of TBM clinical research that were drafted at an international tuberculous meningitis research meeting organized by the Oxford University Clinical Research Unit in Vietnam. We propose a core dataset including demographic and clinical information to be collected at study enrollment, important aspects related to patient management and monitoring, and standardized reporting of patient outcomes. The criteria proposed for the conduct of observational and intervention TBM studies should improve the quality of future research outputs, can facilitate multicenter studies and meta-analyses of pooled data, and could provide the foundation for a global TBM data repository.

Recent advances in the diagnosis and management of tuberculous meningitis.

PURPOSE OF REVIEW: Tuberculous meningitis is a devastating infection that is hard to diagnose and treat. We have reviewed tuberculous meningitis original research published within the past 18 months, selecting studies which we consider have most advanced knowledge. RECENT FINDINGS: We review advances in diagnostic methods, anti-tuberculosis chemotherapy, and the common complications of tuberculous meningitis. New commercial molecular diagnostic tests, such as GeneXpert MTB/RIF, have an important role in tuberculous meningitis diagnosis, but as with all other available tests, they lack sensitivity and cannot rule out the disease. Recent trials and pharmacokinetic studies have advanced understanding of the best anti-tuberculosis drug regimens for tuberculous meningitis, although optimal doses and duration remain uncertain, especially for young children. Good outcomes depend upon the careful management of the common complications (brain infarcts, tuberculomas, hydrocephalus and hyponatraemia) and controlling intracranial pressure. New tools, such as point-of-care ultrasound, may assist in the management, especially in the assessment of intravascular volume and raised intracranial pressure. SUMMARY: Disability-free survival from tuberculous meningitis depends upon rapid diagnosis, starting anti-tuberculosis drugs before the onset of coma and managing complications. Progress is slow and threatened by emerging drug-resistant bacteria, but new drugs and diagnostic technologies offer hope to future patients.

Liver regeneration following repeated reversible portal vein embolization in an experimental model.

BACKGROUND: Portal vein embolization (PVE) is used routinely to prevent postoperative liver failure as a result of anticipated insufficient future liver remnant volume following resection. The authors have recently developed a technique for temporary PVE. The aim of this study was to assess the effect of repeated reversible PVE on hepatocyte proliferation and subsequent liver hypertrophy in rodents. METHODS: Four treatments were compared (n = 21 rats per group): single reversible PVE, two PVEs separated by 14 days, partial portal vein ligation or sham procedure. The feasibility and tolerance of the procedure were assessed. Volumetric imaging by CT was used to estimate the evolution of liver volumes. After death, the weight of liver lobes was measured and hepatocyte proliferation evaluated by immunostaining. RESULTS: Embolization of portal branches corresponding to 70 per cent of total portal flow was performed successfully in all animals. Repeated PVE induced additional hepatocyte proliferation. Repeated embolization resulted in superior hepatocyte proliferation in the non-occluded segments compared with portal vein ligation (31·1 versus 22·2 per cent; P = 0·003). The non-occluded to total liver volume ratio was higher in the repeated PVE group than in the single PVE and sham groups (P = 0·050 and P = 0·001 respectively). CONCLUSION: Repeated reversible PVE successfully induced additional hepatocyte proliferation and subsequent liver hypertrophy. Surgical relevance Portal vein embolization (PVE) is used routinely to prevent postoperative liver failure as a result of anticipated insufficient future liver remnant volume following resection. In the present study, a technique of repeated temporary PVE was developed in a rat model; this induced additional hepatocyte proliferation and an increase in liver volume compared with single embolization. This novel approach might help induce major hypertrophy of the future remnant liver, which could increase the rate of patients amenable to major liver resections.

Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated by lentiviral transgenesis.

Lentiviral technology has been recently proposed to generate transgenic farm animals more efficiently and easier than traditional techniques. The objective was to evaluate several parameters of lambs obtained by lentiviral transgenesis in comparison with non-transgenic counterparts. In vitro produced embryos were microinjected (TG group) at two-cell stage with a lentiviral construct containing enhanced green fluorescent protein (eGFP) gene, while embryos produced by in vitro fertilization (IVF group) or intrauterine insemination (IUI group) were not microinjected. Microinjection technique efficiently generated eight-cell transgenic embryos (97.4%; 114/117). Development rate on day 5 after fertilization was similar for TG (39.3%, 46/117) and IVF embryos (39.6%, 44/111). Pregnancy rate was detected in 50.0% (6/12) of recipient ewes with TG embryos, in 46.7% (7/15) with IVF embryos, and in 65.0% (13/20) of IUI ewes (P = NS). Nine lambs were born in TG group, six lambs in IVF group, and 16 lambs in IUI group. All TG lambs (9/9) were GFP positive to real-time PCR and eight (88.9%) showed a strong and evident GFP expression in mucosae, eyes and keratin tissues. Fetal growth monitored every 15 day by ultrasonography did not show significant differences. Transgenic lambs neither differ in morphometric variables in comparison with non transgenic IVF lambs within 3 months after birth. Transmission of the transgene to the progeny was observed in green fluorescent embryos produced by IVF using semen from the TG founder lambs. In conclusion, this study demonstrates the high efficiency of lentiviral technology to produce transgenic sheep, with no clinic differences in comparison with non transgenic lambs.

Common isolation of New Delhi metallo-beta-lactamase 1-producing Enterobacteriaceae in a large surgical hospital in Vietnam.

This study sought to monitor the presence of carbapenem-resistant Enterobacteriaceae (CRE) and the proportion New Delhi metallo-beta-lactamase 1 (NDM-1)-producing bacteria between August 2010 and December 2012 in a surgical hospital in Vietnam. We identified 47 CRE strains from a total of 4,096 Enterobacteriaceae isolates (1.1 %) that were NDM-1-positive from 45 patients admitted to 11 different departments, with the majority being from the urology department. The NDM-1 gene was found in seven different species. Genotyping revealed limited clonality of NDM-1-positive isolates. Most of the isolates carried the NDM-1 gene on a plasmid and 17.8 % (8/45) of those were readily transferable. We found five patients at admission and one patient at discharge with NDM-1-positive bacteria in their stool. From 200 screening environmental hospital samples, five were confirmed to be NDM-1-positive and included Acinetobacter species (n = 3) and Enterobacter aerogenes (n = 2). The results reveal that NDM-1-producing Enterobacteriaceae are commonly isolated in patients admitted to a Vietnamese surgical hospital and are also detected in the hospital environment.

Temporal and spatial patterns of diarrhoea in the Mekong Delta area, Vietnam.

This study examined the temporal and spatial patterns of diarrhoea in relation to hydro-meteorological factors in the Mekong Delta area in Vietnam. A time-series design was applied to examine the temporal pattern of the climate-diarrhoea relationship using Poisson regression models. Spatial analysis was applied to examine the spatial clusters of diarrhoea using Global Moran's I and local indicators of spatial autocorrelation (LISA). The temporal pattern showed that the highest peak of diarrhoea was from weeks 30-42 corresponding to August-October annually. A 1 cm increase in river water level at a lag of 1 week was associated with a small [0·07%, 95% confidence interval (CI) 0·01-0·1] increase in the diarrhoeal rate. A 1 °C increase in temperature at lag of 2 and 4 weeks was associated with a 1·5% (95% CI 0·3-2·7) and 1·1% (95% CI 0·1-2·3) increase in diarrhoeal risk, respectively. Relative humidity and diarrhoeal risk were in nonlinear relationship. The spatial analysis showed significant clustering of diarrhoea, and the LISA map shows three multi-centred diarrhoeal clusters and three single-centred clusters in the research location. The findings suggest that climatic conditions projected to be associated with climate change have important implication for human health impact in the Mekong Delta region.

40 Gb/s optical subassembly module for a multi-channel bidirectional optical link.

A 40 Gb/s bidirectional optical link using four-channel optical subassembly (OSA) modules and two different wavelengths for the up- and down-link is demonstrated. Widely separated wavelengths of 850 nm and 1060 nm are used to reduce the optical crosstalk between the up- and down-link signals. Due to the integration capabilities of silicon, the OSA is implemented, all based on silicon: V-grooved silicon substrates to embed fibers and silicon optical benches (SiOBs) to mount optical components. The SiOBs are separately prepared for array chips of photodiodes (PDs), vertical-cavity surface-emitting lasers (VCSELs), and monitoring PDs, which are serially configured on an optical fiber array for direct coupling to the transmission fibers. The separation of the up- and down-link wavelengths is implemented using a wavelength-filtering 45° mirror which is formed in the fiber under the VCSEL. To guide the light signal to the PD another 45° mirror is formed at the end of the fiber. The fabricated bidirectional OSA module shows good performances with a clear eye-diagram and a BER of less than 10(-12) at a data rate of 10 Gb/s for each of the channels with input powers of -8 dBm and -6.5 dBm for the up-link and the down-link, respectively. The measured inter-channel crosstalk of the bidirectional 40 Gb/s optical link is about -22.6 dB, while the full-duplex operation mode demonstrates negligible crosstalk between the up- and down-link.

Quantitative phase imaging with partially coherent illumination.

In this Letter, we formulate a mathematical model for predicting experimental outcomes in quantitative phase imaging (QPI) when the illumination field is partially spatially coherent. We derive formulae that apply to QPI and discuss expected results for two classes of QPI experiments: common path and traditional interferometry, under varying degrees of spatial coherence. In particular, our results describe the physical relationship between the spatial coherence of the illuminating field and the halo effect, which is well known in phase-contrast microscopy. We performed experiments relevant to this common situation and found that our theory is in excellent agreement with the data. With this new understanding of the effects of spatial coherence, our formulae offer an avenue for removing halo artifacts from phase images.

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.

Quantitative assessment of molecular, microstructural, and macroscopic changes of red kidney beans (Phaseolus vulgaris L.) during cooking provides detailed insights in their cooking behavior.

Quantitative changes at different length scales (molecular, microscopic, and macroscopic levels) during cooking were evaluated to better understand the cooking behavior of common beans. The microstructural evolution of presoaked fresh and aged red kidney beans during cooking at 95 °C was quantified using light microscopy coupled with image analysis. These data were related to macroscopic properties, being hardness and volume changes representing texture and swelling of the beans during cooking. Microstructural properties included the cell area (Acell), the fraction of intercellular spaces (%Ais), and the fraction of starch area within the cells (%As/c), reflecting respectively cell expansion, cell separation, and starch swelling. A strong linear correlation between hardness and %Ais (r = -0.886, p = 0.07), along with a significant relative change in %Ais (∼5 times), suggests that softening is predominantly due to cell separation rather than cell expansion. Regarding volume changes, substantial cell expansion (Acell increased by ∼1.5 times) during the initial 30 min of cooking was greatly associated with the increase in the cotyledon volume, while the significance of cell separation became more prominent during the later stages of cooking. Furthermore, we found that the seed coat, rather than the cotyledon, played a major role in the swelling of whole beans, which became less pronounced after aging. The macroscopic properties did not correlate with %As/c. However, the evolution of %As/c conveyed information on the swelling of the starch granules during cooking. During the initial phase, the starch granule swelling mainly filled the cells, while during the later phase, the further swelling was confined by the cell wall. This study provides strong microscopic evidence supporting the direct involvement of the cell wall/ middle lamella network in microstructural changes during cooking as affected by aging, which is in line with the results of molecular changes.