Minimal processed infant formula vs. conventional shows comparable protein quality and increased postprandial plasma amino acid kinetics in rats.

During industrial processing, heat treatments applied to infant formulas may affect protein digestion. Recently, innovative processing routes have been developed to produce minimally heat-processed infant formula. Our objective was to compare the in vivo protein digestion kinetics and protein quality of a minimally processed (T−) and a heat-treated (T+++) infant formula. Sixty-eight male Wistar rats (21 d) were fed with either a diet containing 40 % T− (n 30) or T+++ (n 30), or a milk protein control diet (n 8) during 2 weeks. T− and T+++ rats were then sequentially euthanised 0, 1, 2, 3 or 6 h (n 6/time point) after ingestion of a meal containing their experimental diet. Control rats were euthanised 6 h after ingestion of a protein-free meal to determine nitrogen and amino acid endogenous losses. Nitrogen and amino acid true caecal digestibility was high for both T− and T+++ diets (> 90 %), but a tendency towards higher nitrogen digestibility was observed for the T− diet (96·6 ± 3·1 %) compared with the T+++ diet (91·9 ± 5·4 %, P = 0·0891). This slightly increased digestibility led to a greater increase in total amino acid concentration in plasma after ingestion of the T− diet (P = 0·0010). Comparable protein quality between the two infant formulas was found with a digestible indispensable amino acid score of 0·8. In conclusion, this study showed that minimal processing routes to produce native infant formula do not modify protein quality but tend to enhance its true nitrogen digestibility and increase postprandial plasma amino acid kinetics in rats.

Efficiency of Orexin-A for Inflammatory Flare and Mucosal Healing in Experimental Colitis: Comparison with the Anti-TNF Alpha Infliximab.

Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing-remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn's disease and ulcerative colitis (UC). High variability between treated patients and loss of IFX efficiency over time support the further development of drug therapy. An innovative approach has been suggested based on the presence of orexin receptor (OX1R) in the inflamed human epithelium of UC patients. In that context, the aim of this study was to compare, in a mouse model of chemically induced colitis, the efficacy of IFX compared to the hypothalamic peptide orexin-A (OxA). C57BL/6 mice received 3.5% dextran sodium sulfate (DSS) in drinking water for 5 days. Since the inflammatory flare was maximal at day 7, IFX or OxA was administered based on a curative perspective at that time for 4 days using intraperitoneal injection. Treatment with OxA promoted mucosal healing and decreased colonic myeloperoxidase activity, circulating concentrations of lipopolysaccharide-binding protein, IL-6 and tumor necrosis factor alpha (TNFα) and decreased expression of genes encoding cytokines in colonic tissues with better efficacy than IFX allowing for more rapid re-epithelization. This study demonstrates the comparable anti-inflammatory properties of OxA and IFX and shows that OxA is efficient in promoting mucosal healing, suggesting that OxA treatment is a promising new biotherapy.

Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies.

Amino acid supplementation may be indicated to correct for insufficient amino acid intake in healthy individuals, and in specific physiological or pathophysiological situations. However, there is a concern to not supplement beyond the tolerable upper intake level (UL) by determining parameters of no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) for each amino acid. Since the NOAEL and LOAEL values are at least one order of magnitude different when comparing the values obtained in rats and humans, the aim of this review is to evaluate to what extent the amino acid UL measured in the rat model, when referenced to the dietary usual consumption (UC) and dietary requirement (RQ) for indispensable amino acids, may be used as an approximation of the UL in humans. This review then compares the ratios of the NOAEL or LOAEL over UC and RQ in the rat model with the same ratios calculated in humans for the nine amino acids (arginine, serine, glycine, histidine, leucine, lysine, methionine, phenylalanine, and tryptophan) for which this comparison can be done. From the calculations made, it appears that for these 9 amino acids, the calculated ratios for rats and humans, although rather different for several amino acids, remains for all of them in the same order of magnitude. For tryptophan, tyrosine, and valine, the ratios calculated in rats are markedly different according to the sex of animals, raising the view that it may be also the case in humans.

Challenges in pediatric urologic practice: a lifelong view.

The role of the pediatric urologic surgeon does not end with initial reconstructive surgery. Many of the congenital anomalies encountered require multiple staged operations while others may not involve further surgery but require a life-long follow-up and often revisions. Management of most of these disorders must extend into and through adolescence before transitioning these patients to adult colleagues. The primary goal of management of all congenital uropathies is protection and/or reversal of renal insult. For posterior urethral valves, in particular, avoidance of end-stage renal failure may not be possible in severe cases due to the congenital nephropathy but usually can be prolonged. Likewise, prevention or minimization of urinary tract infections is important for overall health and eventual renal function. Attainment of urinary continence is an important goal for most with a proven positive impact on quality of life; however, measures to achieve that goal can require significant efforts for those with neuropathic bladder dysfunction, obstructive uropathies, and bladder exstrophy. A particular challenge is maximizing future self-esteem, sexual function, and reproductive potential for those with genital anomalies such as hypospadias, the bladder exstrophy epispadias complex, prune belly syndrome, and Mullerian anomalies. Few endeavors are rewarding as working with children and their families throughout childhood and adolescence to help them attain these goals, and modern advances have enhanced our ability to get them to adulthood in better physical and mental health than ever before.

Competency in Tubularized Incised Plate Repair for Distal Hypospadias: Cumulative Sum Learning Curve Analysis of a Single Surgeon Experience.

PURPOSE: We sought to determine the number of cases to achieve competency and proficiency in tubularized incised plate technique for distal hypospadias repair using cumulative sum analysis. MATERIALS AND METHODS: From 2001 to 2015 we reviewed all distal tubularized incised plate repairs performed by a single surgeon since independent practice. Data for 450 consecutive cases included age, meatal location, presence of curvature, operative time, occurrence of complications and followup duration. A cumulative sum analysis cohort chart was used to determine trends in complication rate and operative time during the evaluation period. In order to account for surgical experience with time, the highest peak, plateau, and down trends in operative time and complication rate were identified on the plot and set as the transition points between learning (phase 1), competence (phase 2) and proficiency (phase 3). RESULTS: Based on the cumulative sum analysis learning curve, the competence phase with plateau of operative time and complication rate commences beyond the 127th case, and the proficiency phase with notable decline in operative time and complication rate was noted beyond the 234th case. When comparing case characteristics and surgical outcomes between phases and learning curve, the proficiency phase involved younger patients and more severe degree of distal hypospadias being repaired using the tubularized incised plate approach with fewer complications related to meatal stenosis and fewer cosmetic complications. CONCLUSIONS: In our study competency in distal hypospadias tubularized incised plate repair was reached beyond the 127th case, while proficiency was attained beyond the 234th case.

Sulfur-Containing Amino Acids and Lipid Metabolism.

The metabolism of methionine and cysteine in the body tissues determines the concentrations of several metabolites with various biologic activities, including homocysteine, hydrogen sulfide (H2S), taurine, and glutathione. Hyperhomocysteinemia, which is correlated with lower HDL cholesterol in blood in volunteers and animal models, has been associated with an increased risk for cardiovascular diseases. In humans, the relation between methionine intake and hyperhomocysteinemia is dependent on vitamin status (vitamins B-6 and B-12 and folic acid) and on the supply of other amino acids. However, lowering homocysteinemia by itself is not sufficient for decreasing the risk of cardiovascular disease progression. Other compounds related to methionine metabolism have recently been identified as being involved in the risk of atherosclerosis and steatohepatitis. Indeed, the metabolism of sulfur amino acids has an impact on phosphatidylcholine (PC) metabolism, and anomalies in PC synthesis due to global hypomethylation have been associated with disturbances of lipid metabolism. In addition, impairment of H2S synthesis from cysteine favors atherosclerosis and steatosis in animal models. The effects of taurine on lipid metabolism appear heterogeneous depending on the populations of volunteers studied. A decrease in the concentration of intracellular glutathione, a tripeptide involved in redox homeostasis, is implicated in the etiology of cardiovascular diseases and steatosis. Last, supplementation with betaine, a compound that allows remethylation of homocysteine to methionine, decreases basal and methionine-stimulated homocysteinemia; however, it adversely increases plasma total and LDL cholesterol. The study of these metabolites may help determine the range of optimal and safe intakes of methionine and cysteine in dietary proteins and supplements. The amino acid requirement for protein synthesis in different situations and for optimal production of intracellular compounds involved in the regulation of lipid metabolism also needs to be considered for dietary attenuation of atherosclerosis and steatosis risk.

Volumetric assessment of unaffected parenchyma and Wilms' tumours: analysis of response to chemotherapy and surgery using a semi-automated segmentation algorithm in children with renal neoplasms.

OBJECTIVE: To present our proof of concept with semi-automatic image recognition/segmentation technology for calculation of tumour/parenchyma volume. METHODS: We reviewed Wilms' tumours (WTs) between 2000 and 2018, capturing computed tomography images at baseline, after neoadjuvant chemotherapy (NaC) and postoperatively. Images were uploaded into MATLAB-3-D volumetric image processing software. The program was trained by two clinicians who supervised the demarcation of tumour and parenchyma, followed by automatic recognition and delineation of tumour margins on serial imaging, and differentiation from uninvolved renal parenchyma. Volume was automatically calculated for both. RESULTS: During the study period, 98 patients were identified. Of these, based on image quality and availability, 32 (38 affected moieties) were selected. Most patients (65%) were girls, diagnosed at age 50 ± 37 months of age. NaC was employed in 64% of patients. Surgical management included 27 radical and 11 partial nephrectomies. Automated volume assessment demonstrated objective response to NaC for unilateral and bilateral tumours (68 ± 20% and 53 ± 39%, respectively), as well as preservation on uninvolved parenchyma with partial nephrectomy (70 ± 46 cm3 at presentation to 57 ± 41 cm3 post-surgery). CONCLUSION: Volumetric analysis is feasible and allows objective assessment of tumour and parenchyma volume in response to chemotherapy and surgery. Our data show changes after therapy that may be otherwise difficult to quantify. Use of such technology may improve surgical planning and quantification of response to treatment, as well as serving as a tool to predict renal reserve and long-term changes in renal function.

Low-protein and methionine, high-starch diets increase energy intake and expenditure, increase FGF21, decrease IGF-1, and have little effect on adiposity in mice.

Low-protein diets most often induce increased energy intake in an attempt to increase protein intake to meet protein needs with a risk of accumulation as fat of the excess energy intake. In female adult BALB/c mice, a decrease in dietary casein from 20% to 6% and 3% increased energy intake and slightly increased adiposity, and this response was exacerbated with soy proteins with low methionine content. The effect on fat mass was however limited because total energy expenditure increased to the same extent as energy intake. Lean body mass was preserved in all 6% fed mice and reduced only in 3% casein-fed animals. Insulin response to an oral glucose tolerance test was reduced in soy-fed mice and in low-protein-fed mice. Low-protein diets did not affect uncoupling protein 1 and increased fibroblast growth factor 21 (FGF21) in brown adipose tissue and increased FGF21, fatty acid synthase, and cluster of differentiation 36 in the liver. In the hypothalamus, neuropeptide Y was increased and proopiomelanocortin was decreased only in 3% casein-fed mice. In plasma, when protein was decreased, insulin-like growth factor-1 decreased and FGF21 increased and plasma FGF21 was best described by using a combination of dietary protein level, protein-to-carbohydrate ratio, and protein-to-methionine ratio in the diet. In conclusion, reducing dietary protein and protein quality increases energy intake but also energy expenditure resulting in an only slight increase in adiposity. In this process, FGF21 is probably an important signal that responds to a complex combination of protein restriction, protein quality, and carbohydrate content of the diet.

Low-protein diet-induced hyperphagia and adiposity are modulated through interactions involving thermoregulation, motor activity, and protein quality in mice.

Low protein (LP)-containing diets can induce overeating in rodents and possibly in humans in an effort to meet protein requirement, but the effects on energy expenditure (EE) are unclear. The present study evaluated the changes induced by reducing dietary protein from 20% to 6%-using either soy protein or casein-on energy intake, body composition, and EE in mice housed at 22°C or at 30°C (thermal neutrality). LP feeding increased energy intake and adiposity, more in soy-fed than in casein-fed mice, but also increased EE, thus limiting fat accumulation. The increase in EE was due mainly to an increase in spontaneous motor activity related to EE and not to thermoregulation. However, the high cost of thermoregulation at 22°C and the subsequent heat exchanges between nonshivering thermogenesis, motor activity, and feeding induced large differences in adaptation between mice housed at 22°C and at 30°C.

Dual Therapy for Refractory Overactive Bladder in Children: A Prospective Open-Label Study.

PURPOSE: Mirabegron (ß3 adrenoreceptor agonist) is a new molecule with a mechanism of action distinct from antimuscarinics. Combination therapy with solifenacin was recently studied in an adult population. We evaluated the efficacy and safety of mirabegron as add-on therapy to treat urinary incontinence in children with idiopathic overactive bladder refractory/intolerant to antimuscarinics. MATERIALS AND METHODS: A prospective off-label study using add-on regimens of mirabegron was conducted in pediatric patients presenting with no symptom improvement while undergoing intensive behavioral and medical therapies and/or significant side effects while undergoing antimuscarinic dose escalation. Our primary outcome was better reported efficacy than with the use of prior antimuscarinic monotherapy. Secondary end points were tolerability, safety and satisfaction. Efficacy and tolerability were assessed based on voiding diaries, post-void residuals, urine cultures, electrocardiograms and vital signs. Families were questioned regarding continence, side effects and compliance. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: A total of 35 patients were recruited at a median age of 10.3 years and were administered add-on mirabegron for a median of 16.4 months. Median bladder capacity improved from 50% to 74% expected bladder capacity (p <0.001). Continence improved in all patients, with 12 being completely dry. Post-void residual was increased in 2 patients and 1 urinary tract infection was reported. Seven patients reported mild or moderate side effects, with 2 withdrawals because of side effects (1 patient) and post-void residual (1). CONCLUSIONS: Add-on mirabegron appears to be a safe alternative for children with refractory overactive bladder. Dual therapy is well tolerated and adjusted dose regimen appears safe in this first pediatric study.

Polyacrylamide Hydrogel as a Bulking Agent for the Endoscopic Treatment of Vesicoureteral Reflux: Long-Term Results and Safety.

PURPOSE: Polyacrylamide hydrogel has been shown to offer good short-term success for the endoscopic treatment of vesicoureteral reflux. Our objective was to provide long-term results of its efficacy and safety. MATERIALS AND METHODS: We performed a prospective study using polyacrylamide hydrogel to treat all grades of vesicoureteral reflux. Every patient underwent endoscopic injection of polyacrylamide hydrogel followed by 3-month postoperative renal ultrasound and voiding cystourethrogram. Renal ultrasound was repeated at 12 and 36 months. Treatment success was defined as the absence of de novo or worsening hydronephrosis and the absence of reflux. Safety elements included new or worsening hydronephrosis, calcifications of the injected material and urinary tract infections. RESULTS: A total of 76 patients (123 refluxing renal units) were assessed. Median age at surgery was 45 months and median followup was 36 months. Median injected volume of hydrogel per refluxing renal unit was 1.0 ml. The overall success rate 3 months after a single injection was 71%. During long-term followup 68 of 70 eligible patients underwent 12-month ultrasound and 40 of 46 underwent 36-month ultrasound. No upper tract deterioration or bulking agent calcifications were reported. Nine (12%) and 2 patients (3%) presented with nonfebrile and febrile urinary tract infections, respectively. CONCLUSIONS: The success rate of polyacrylamide hydrogel for endoscopic treatment of vesicoureteral reflux is comparable to published results of dextranomer hyaluronic acid. The long-term safety data and potential lower cost of polyacrylamide hydrogel provide further support for the use of this nonparticulate bulking agent to treat reflux.

Dual effects of a high-protein diet on DSS-treated mice during colitis resolution phase.

The impact of the dietary protein level on the process of colonic mucosal inflammation and subsequent recovery remains largely unknown. In this study, we fed DSS-treated mice with either a normoproteic (NP) or a high-protein (HP) isocaloric diet from the beginning of the 5-day dextran sulfate sodium (DSS) treatment to 14 days later. Measurements of colitis indicators (colon weight:length ratio, myeloperoxidase activity, cytokine expressions) showed a similar level of colonic inflammation in both DSS groups during the colitis induction phase. However, during the colitis resolution phase, inflammation intensity was higher in the DSS-HP group than in the DSS-NP group as evidenced by higher inflammatory score and body weight loss. This coincided with a higher mortality rate. In surviving animals, an increase in colonic crypt height associated with a higher number of colon epithelial cells per crypt, and TGF-ß3 content was observed in the DSS-HP vs. DSS-NP group. Moreover, colonic expression patterns of tight junction proteins and E-cadherin were also different according to the diet. Altogether, our results indicate that the HP diet, when given during both the induction and resolution periods of DSS-induced colitis, showed deleterious effects during the post-induction phase. However, HP diet ingestion was also associated with morphological and biochemical differences compatible with higher colonic epithelium restoration in surviving animals, indicating an effect of the dietary protein level on colonic crypt repair after acute inflammation. These data highlight the potential impact of the dietary protein amount during the colitis course.

Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study.

This study was designed to analyse the effects of human (h) and bovine lactoferrin (bLF) on the growth and differentiation of intestinal cells using the mice model supplemented with Lactoferrin (LF) and the enterocyte-like model of Caco-2 cells which spontaneously differentiate after confluency. In mice, bLF supplementation increased jejunal villus height and the expression of several intestinal brush border membrane enzymes activities. Addition of bLF or hLF to undifferentiated Caco-2 cells was able to increase cell proliferation with confluency being reached more rapidly. Moreover, when Caco-2 cells were grown in the presence of LF for 3 weeks, brush-border membrane-associated enzyme activities i.e. sucrase, alkaline phosphatase and neutral aminopeptidase, as well as the L-glutamate transporter expression were all increased indicating an increased Caco-2 cell differentiation. Accordingly, cDNA Atlas array and Western blot analysis of cell cycle proteins shown a decreased expression of Cdck2 and an increased TAF1 expression; these proteins being implicated in the regulation of numerous genes related to cellular proliferation and differentiation. These modifications were associated with an inhibition of Caco-2 cell spontaneous apoptosis. Altogether, our results indicate that LF increase in vivo and in vitro enterocyte differentiation. In addition, LF was found to increase in vitro enterocyte proliferation resulting in higher cell density in cell flasks, an effect that was likely partly due to a reduction of the cellular apoptosis. The different stimulation patterns observed for the different parameters associated with cell differentiation in relationship with specific gene regulation is discussed.

Prospective study using a new bulking agent for the treatment of vesicoureteral reflux: polyacrylamide hydrogel.

PURPOSE: Vesicoureteral reflux is frequently diagnosed in the pediatric population. Endoscopic treatment has become a popular form of first-line therapy. Available products offer good short-term success rates. However, the cost of these injected implants is an issue. We evaluated the success of endoscopic treatment for vesicoureteral reflux using polyacrylamide hydrogel. MATERIALS AND METHODS: We performed a single center, single surgeon, prospective, off-label study using polyacrylamide hydrogel to treat vesicoureteral reflux. All patients underwent endoscopic subureteral double hydrodistention implantation technique injection followed by renal ultrasound and voiding cystourethrogram at 3 months postoperatively to confirm the absence of de novo hydronephrosis and correction of vesicoureteral reflux (grade 0). RESULTS: A total of 40 patients (69 refluxing ureters) underwent polyacrylamide hydrogel injection. Median age at surgery was 50 months. Bilateral reflux was identified in 29 patients (73%). Nine patients had duplex systems, 2 with reflux into both moieties. Reflux was graded using the International Reflux Study in Children grading system, with grade I seen in 9 ureters, II in 17, III in 20, IV in 18 and V in 5. Mean volume injected was 1.1 ml. Success rate for grade I to III vesicoureteral reflux at 3 months after a single treatment was 87%, and the overall success for all grades was 81.2%. CONCLUSIONS: Off-label use of polyacrylamide hydrogel injection therapy for primarily low grade vesicoureteral reflux demonstrates that the technique and short-term success rates are comparable to the most popular bulking agent, dextranomer/hyaluronic acid. These results suggest that further trials comparing polyacrylamide hydrogel and dextranomer/hyaluronic acid would be worthwhile.

Lactoferrin Supplementation during Gestation and Lactation Is Efficient for Boosting Rat Pup Development.

Lactoferrin (LF) is an iron-binding protein found at relatively high concentrations in human milk. LF, which is little degraded in the infant intestinal lumen, is known to stimulate the proliferation and differentiation of the small intestine epithelial cells. The present study was designed to evaluate in the rat model the effects of bovine LF (bLF) given to the mothers during gestation and lactation on the growth of the offspring. Female Wistar rats were randomly separated into two groups of animals that received from mating and during gestation and lactation a standard diet including or not including bLF (10 g/kg of diet). The pups' growth was determined up to postnatal day 17 (PND17), and parameters related to lean and fat mass, intestinal differentiation, intestinal barrier function, bone mineral density, osteoblast activity, and brain development were measured. In addition, metabolites in pup plasma were determined at PND17. bLF was detected in the plasma and milk of the supplemented mothers as well as in the pup plasma. Although the body weight of the pups in the two groups did not differ at birth, the pups recovered from the supplemented mothers displayed an increase body weight from PND12 up to PND17. At PND17 in the bLF group, increased small intestine epithelial cell differentiation was detected, and colon barrier function was reinforced in association with increased expression of genes coding for the tight-junction proteins. Regarding bone physiology, improved bone mineral density was measured in the pups. Lastly, the plasma metabolite analysis revealed mainly higher amino acid concentrations in the LF pups as compared to the control group. Our results support that bLF ingestion by the mother during gestation and lactation can promote pup early life development. The potential interest of supplementing the mothers with bLF in the case of risk of compromised early life development of the offspring in the context of animal and human nutrition is discussed.

Lysine or Threonine Deficiency Decreases Body Weight Gain in Growing Rats despite an Increase in Food Intake without Increasing Energy Expenditure in Response to FGF21.

The objective of this study is to evaluate the effects of a strictly essential amino acid (lysine or threonine; EAA) deficiency on energy metabolism in growing rats. Rats were fed for three weeks severely (15% and 25% of recommendation), moderately (40% and 60%), and adequate (75% and 100%) lysine or threonine-deficient diets. Food intake and body weight were measured daily and indirect calorimetry was performed the week three. At the end of the experimentation, body composition, gene expression, and biochemical analysis were performed. Lysine and threonine deficiency induced a lower body weight gain and an increase in relative food intake. Lysine or threonine deficiency induced liver FGF21 synthesis and plasma release. However, no changes in energy expenditure were observed for lysine deficiency, unlike threonine deficiency, which leads to a decrease in total and resting energy expenditure. Interestingly, threonine severe deficiency, but not lysine deficiency, increase orexigenic and decreases anorexigenic hypothalamic neuropeptides expression, which could explain the higher food intake. Our results show that the deficiency in one EAA, induces a decrease in body weight gain, despite an increased relative food intake, without any increase in energy expenditure despite an induction of FGF21.

Perception and satisfaction of patients after telemedicine urology consultations: A matched analysis with physicians' perspective.

INTRODUCTION: During the first regional COVID-19 lockdown in March 2020, we conducted a study aimed at evaluating completeness of telemedicine consultation in urology. Of 1679 consultations, 67% were considered completely managed by phone. The aim of the present study was to assess patients' experience and satisfaction with telemedicine and to compare them with urologists' perceptions about quality and completeness of the telemedicine consultation. METHODS: We contacted a randomly selected sample of patients (n=356) from our previous study to enquire about their experience. We used a home patient experience questionnaire, inspired by the Patient Experiences Questionnaire for Out-of-Hours Care (PEQOHC) and the Consumer Assessment Health Profile Survey (CAHPS). RESULTS: Of 356 patients contacted, 315 agreed to complete the questionnaire. Urological consultations were for non-oncological (104), oncological (121), cancer suspicion (41), and pediatric (49) indications. Mean patient satisfaction score after telemedicine consultation was 8.8/10 (median 9/10) and 86.3% of patients rated the quality of the consultation as either excellent (54.6%) or very good (31.7%). Consultations regarding cancer suspicion had the lowest score (8.3/10). Overall, 46.7% of all patients would have preferred an in-person visit outside of the pandemic situation. Among patients whose consultations were rated suboptimal by urologists, almost a third more (31.2%) would have preferred an in-person visit (p=0.03). CONCLUSIONS: Despite high reported patient satisfaction rates with telemedicine, it is noteworthy that nearly half of the patients would have preferred an in-person visit. Post-pandemic, it will be important to incorporate telemedicine as an alternative, while retaining and offering in-person visits.

Orexins: A promising target to digestive cancers, inflammation, obesity and metabolism dysfunctions.

Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system. These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation, intestinal motility, hormone secretion, lipolyze and reproduction functions. Associated to these peripheral functions, it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation, metabolic syndrome and cancers. The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease, multiple sclerosis and septic shock, obesity and digestive cancers.

Spermatogenesis in pre-pubertal boys with Leydig cell neoplasms suggests paracrine stimulation by testosterone.

INTRODUCTION: Pediatric Leydig cell tumors (LCTs) represent approximately 4% of pre-pubertal testicular tumors and are known to cause precocious puberty secondary to testosterone production. While gonadotropins and testosterone are known to initiate spermatogenesis beginning in puberty, it is yet to be determined if a similar phenomenon is triggered by isolated testosterone production in prepubescent boys. OBJECTIVE: To determine if testicular pathology in pre-pubertal pediatric patients with LCTs exhibit spermatogenesis secondary to paracrine testosterone stimulation. STUDY DESIGN: We reviewed patients who underwent orchiectomy for a testicular tumor from 2003-17. We included patients with LCTs and compared them to children with non-LCT pathology (teratomas and epidermoid cysts). We excluded other pathologies and tumors in pubertal patients. Data were collected on the presence of spermatogenesis on pathology, tumor markers and serum hormone results. RESULTS: Orchiectomy for testicular tumors were completed in 66 patients, of which 20 were included in the non-LCT group and 9 in the LCT group. Two of the 9 LCT patients had bilateral pathology. Age at presentation was 6.3 ± 5.8 years for the non-LCT group vs. 8.4 ± 1.6 years for LCTs (p = 0.261). Spermatogenesis was detected in 7 (64%) LCT specimens vs 2 (10%) non-LCT specimens (p = 0.002). Age of the spermatogenesis patients in the non-LCT group (11.08 ± 2.5 years) was older than LCT ones (8.3 ± 2.0 years), suggesting that spermatogenesis in the non-LCT group may be due to early pubertal development. The summary figure demonstrates spermatogenesis identified in a pre-pubertal LCT patient. DISCUSSION: In this study, pre-pubertal males with LCTs were identified to have pathology evidence of spermatogenesis compared to controls with non-LCT pathology. This represents the first study assessing paracrine testosterone effects on spermatogenesis in pre-pubertal patients with LCTs. In contrast, adult literature on LCTs primarily report on resulting concerns for fertility, gynecomastia and testicular atrophy. CONCLUSION: LCTs can induce spermatogenesis in prepubertal patients. This reinforces the hypothesis that paracrine testosterone signaling plays a role in spermatogenesis. Our findings could help explore novel fertility preservation opportunities in children.

Severe protein deficiency induces hepatic expression and systemic level of FGF21 but inhibits its hypothalamic expression in growing rats.

To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.