Intra­ and Interobserver Reliability of Yamaguchi's Method for the Assessment of First Metatarsal Pronation in Hallux Valgus Deformity.

Pronation of the first metatarsal is a risk factor for the formation and progression of the hallux valgus deformity. Recently, Yamaguchi et al published a study that showed how the round sign increases on digitally reconstructed radiography taken from a CT scan when pronation is applied. In this study, the shape of the lateral edge of the first metatarsal head was evaluated on weightbearing dorsoplantar radiographs. Yamaguchi's signs were presented to observers after the visual presentation of each foot as an image. The best-fit circle was drawn using the PACS drawing function. Ninety radiographs of adults presenting hallux valgus deformities were classified as mild-to-moderate, based on hallux valgus angle and intermetatarsal angle. The global average observations were 3.72 ± 3.92 (range 2.3°-4.6°). The interclass correlation (Fleiss Kappa index κ = 0.225) and the Spearman correlation (0.16 of Kappa) coefficients were poor for interobserver measurements and statistically significant. Using the linear model, there was no significant variability between the repetitions corresponding to each observer (t-value -1.527, p value .127). Our findings show that the Yamaguchi method can be very subjective and should not be the exclusive technique to assess the rotation of the first metatarsal or head roundness.

Metabolic syndrome and male fertility disorders: Is there a causal link?

Infertility is a global health problem affecting 10-15% of couples in reproductive age. Recent studies have provided growing evidence supporting that lifestyle factors can affect male fertility through alterations in endocrine profiles, spermatogenesis and/or sperm function. One of these critical factors could be the change in the food intake behavior in modern societies that produces metabolic alterations. Regarding this, metabolic syndrome (MetS) prevalence has increased in epidemic in the last 40-50 years. Although MetS is associated with advanced age, changes in lifestyles have accelerated the appearance of symptoms in the reproductive age. We review herein the current understanding of the relationship between MetS and the male reproductive status. For this purpose, in this narrative review a comprehensive literature search was made in both animal models and men, allowing us to evaluate such relationship. This analysis showed a high variability in the reproductive phenotypes observed in patients and mice suffering MetS, including sperm parameters, fertility and offspring health. In view of this, we proposed that the reproductive effects, which are diverse and not robust, observed among MetS-affected males, might depend on additional factors not associated with the metabolic condition and contributed not only by the affected male but also by his partner. With this perspective, this review provides a more accurate insight of this syndrome critical for the identification of specific diagnostic indicators and treatment of MetS-induced fertility disorders.

Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans.

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11-24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1-13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident-intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors' sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

Percutaneous, intra-articular, chevron osteotomy (PeICO) for the treatment of mild-to-moderate hallux valgus: a case series.

PURPOSE: Treatment for hallux valgus (HV) remains challenging. Third-generation percutaneous procedures try to reproduce chevron-type osteotomies to replicate their benefits, such as intrinsic stability and reproducibility. We report the first results using a percutaneous, intra-articular, chevron osteotomy (PeICO) technique that mimics the classic intra-articular open chevron procedure, associated with a percutaneous adductor tendon release (PATR) for the treatment of mild-to-moderate HV. METHODS: From May 2015 to October 2018, a total of consecutive 114 feet (74 patients) were included. Primary outcome measures included radiographic (hallux valgus and intermetatarsal angles) and clinical parameters such as visual analog scale (VAS), FAAM Activities of Daily Living (ADL), and FAAM Sport, AOFAS Score, and MOXFQ, preoperatively and at final follow-up (Minimum 18 months). A patient satisfaction survey was also performed. Pronation and length of the first metatarsal were also assessed. Secondary outcomes included fluoroscopic time, length of surgery, complications, recurrence, and re-operation rates. RESULTS: At 24.09 months on average, the AOFAS score improved from 52.1 points preoperatively to 91.1 (p < 0.001) at the latest follow-up. VAS decreased from 6.3 to 1. Also, FAAM ALD, FAAM Sport, and MOXFQ showed statistically significant differences (p < 0.001) when comparing pre-operative and post-operative periods. Patients found the procedure to be excellent in 82% and very good in 13.5% of cases. Our global complication and re-operation rates were 5.26% and 3.5% (screw removal), respectively. CONCLUSION: PeICO combined with PATR proved to be a safe, reliable, and effective technique for the correction of mild-to-moderate HV deformity.

Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice-a new potential probiotic for appetite and body weight management.

BACKGROUND/OBJECTIVES: Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. METHODS: The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the "MetaHIT" database. RESULTS: Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia. CONCLUSIONS: H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.

A Radiologic Triangle Sign for Percutaneous Adductor Tendon Release (PATR): Cadaveric Study and Case Series.

Background: Combining osteotomies and soft tissue procedures is believed to reduce sesamoids in their anatomical position and maintain long-term correction when treating hallux valgus deformity. This study determines if a radiologic association exists between a radiolucent sign and a full percutaneous adductor tendon release (PATR), including a cadaveric study and a consecutive case series. Another aim was to determine the intra- and interobserver reliability of these observations. Methods: A prospective observational study was made between 2018 and 2019. First, a PATR was done on cadaveric specimens and, after the procedures, dissected to correlate what was seen fluoroscopically. The clinical group included 39 feet that presented mild-to-moderate HV deformity and were treated with percutaneous osteotomies associated with PATR. Results: Observers 1 and 2 saw a radioscopic radiolucent sign in 100% of cadavers and the patient population. They also observed a triangle-shaped image with an incidence of 75%, which we have named the "triangle sign." Conclusion: The triangle sign may be helpful in the intraoperative confirmation of PATR and latero-plantar capsule release using this percutaneous technique. Level of Evidence: Level II, development of diagnostic criteria.

Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and microfluidic-based gene expression profiling.

BACKGROUND: Diminished ovarian reserve (DOR) is one of the causes of infertility in young women. In this prospective study, gene expression profiling (GEP) of corona radiata cells (CRC) was performed to identify genes deregulated in DOR patients. METHODS: Microarray-based GEP of CRC isolated from eight women undergoing IVF was performed to identify genes differentially expressed between patients with normal ovarian reserve and DOR patients. Microfluidic-based quantitative RT-PCR assays were used to validate selected transcripts on 40 independent patients. A principal component analysis was used to identify more homogeneous subgroups of DOR patients. In silico analyses focusing on cis-regulation were performed to refine the interactions between patient's biological characteristics and their GEP. RESULTS: Forty-eight transcripts were differentially expressed, including CXXC finger protein 5 (CXXC5), forkhead box C1 (FOXC1) (down-regulated in DOR) as well as connective tissue growth factor (CTGF), follistatin-like 3 (FSTL3), prostaglandin-endoperoxide synthase 2 (PTGS2) and suppressor of cytokine signaling 2 (SOCS2) (up-regulated in DOR). According to these transcripts, two DOR patients' subgroups (DOR Gr1 and Gr2) were identified. In DOR Gr2 patients, C-terminal domain 2 (CITED2), CTGF, growth arrest-specific 1 (GAS1), insulin receptor substrate 2 (IRS2), PTGS2, SOCS2 and Versican (VCAN) were expressed at significantly higher levels and CXXC5, FOXC1, guanylate-binding protein 2 (GBP2) and zinc finger MIZ-domain containing 1 (ZMIZ1) at significantly lower levels. Higher baseline estradiol (E(2)) levels were observed in DOR Gr2 patients (P < 0.006). The in silico analyses suggested that all 11 genes differentially expressed between DOR Gr1 and DOR Gr2 subgroups could be transcriptional targets of estrogen. CONCLUSIONS: Despite small sample size limitations, 12 genes deregulated in the CRC of DOR patients were identified, which could be involved in DOR pathogenesis. A DOR patient's subgroup with high baseline E(2) levels and deregulated estrogen-responsive genes was also identified.

Bioindicators and biomarkers of environmental pollution in the middle-lower basin of the Suquía River (Córdoba, Argentina).

The Suquía River middle-lower basin (Córdoba, Argentina) is subject to a strong anthropogenic impact because it receives pollutants from different sources. Recent studies have shown the importance and the need of approaching the monitoring process of water quality from integral perspectives through the use of chemical as well as biological methods. The main goal of this study was to evaluate the fish species Jenynsia multidentata as a bioindicator of environmental pollution in the middle-lower basin of the Suquía River using biotransformation and antioxidant enzymes as well as gill and liver histopathology as biomarkers. We also studied the fish-assemblage characteristics through the fish species pattern variation and the application of a biotic index based on fish data. Our study also included the analysis of a water-quality index, heavy-metal concentrations in sediment and water, and pesticide concentrations in sediment. The chemical analyses of the middle-lower Suquía River basin showed a water-quality degradation gradient. Fish-assemblage structure changed with increasing water pollution, showing a simpler structure at the most polluted area. According to the biotic index, the variation pattern of fish assemblages reflected the aquatic environmental deterioration. Both molecular and histopathological biomarkers reflected the same trend in relation to water quality. However, enzymes varied with more acute precision between seasons. In addition, each enzyme presented with different sensibility. At tissue level, the histopathological analysis detected chronic contamination at both stations and seasons. The present work, which comprises different levels of biological organization together with chemical analyses, generated particular although complementary information, thus evidencing the same trend of aquatic contamination. Thus, the development of integral investigations gives a comprehensive approach and becomes the most effective tool to construct policies both preventive and palliative. Our study constitutes a good model to be applied in other endorheic basins of South America.

Modified Bösch Osteotomy Combined With a Percutaneous Adductor Tendon Release for the Treatment of Hallux Valgus Deformity: Learning Curve.

PURPOSE: The expression "learning curve" indicates the relation between the time needed to learn a new technique and the technique-related outcome. Percutaneous surgery (also called "minimally invasive surgery") has experienced sustained and respectable growth, especially in forefoot deformities. The main purpose was to assess the number of feet necessary to become skilled in a specific minimally invasive surgery (MIS) procedure. METHODS: From January 2015 to June 2018, 46 consecutive patients were evaluated and included in the study. Patients were divided into 2 groups according to the surgery period: first 30 feet (Group 1), and subsequent 30 feet (Group 2) from the whole population evaluated. Age, body mass index, and operative time were evaluated. Hallux valgus angle and the 1 to 2 intermetatarsal angle were also measured. Patients were assessed according to the American Orthopedic Foot and Ankle Society (AOFAS) forefoot scale, the Foot and Ankle Ability Measure activities of daily living (FAAM ADL) subscale and the visual analog scale (VAS). RESULTS: The comparison of the 2 groups showed statistically significant differences in hallux valgus angle (HVA) but not in intermetatarsal angle (IMA). The mean improvement between pre- and postoperative FAAM ADL, VAS, and AOFAS score in Group 1 were 12.83, 3.93, and 24.77 points, respectively. In Group 2, the mean improvement between pre- and postoperative FAAM ADL, VAS, and AOFAS scores were 15.19, 4.3, and 24.5 points, respectively. The differences between groups in FAAM ADL score was statistically significant (P = 0.0364). Group 1 showed a global complication rate of 16.67% (n = 5) while group 2 showed 3,3% (n = 1). CONCLUSION: After the first 30 cases, radiographic, clinical, and functional outcomes substantially improved, and the level of the perioperative complications decreased. The results suggest that the learning curve plateau for performing a percutaneous subcapital osteotomy can be reached after 30 surgeries. LEVELS OF EVIDENCE: Level III.

Midterm Outcomes of Sliding Distal Metatarsal Minimally Invasive Osteotomy to Treat Bunionette Deformity.

BACKGROUND: Bunionette deformity is described as a painful bony prominence on the lateral aspect of the fifth metatarsal head. The present study prospectively assessed the clinical, functional, and radiographic outcomes of sliding distal metatarsal minimally invasive osteotomy (S-DMMO) used in a large series of patients with a midterm follow-up period. METHODS: From December 2015 to December 2018, we evaluated 74 feet (57 patients). Radiologic (4-to-5 intermetatarsal angle, fifth metatarsophalangeal angle, the fifth metatarsal head width, lateral deviation angle, fifth metatarsal length, medial displacement, and elevation), clinician-reported scores (AOFAS score, visual analog scale [VAS]) and patient-reported outcomes measure (Foot and Ankle Ability Measure [FAAM] activities of daily living [ADL], FAAM sports, Manchester-Oxford Foot Questionnaire [MOXFQ], and patient satisfaction survey) were included in the analysis. The time to bone union was also assessed. RESULTS: The average 4-to-5 intermetatarsal angle improved from 11.1 degrees preoperatively to 4.5 degrees postoperatively (P < .001), whereas the average fifth metatarsophalangeal angle improved from 15.7 degrees preoperatively to 4.8 degrees postoperatively (P < .001). The lateral deviation angle was found to be 2.2 degrees. The fifth metatarsal length decreased from 66.6 to 64.3 mm postoperatively. The average initial medial displacement was 4.67 mm preoperatively and 4.54 mm at final follow-up. The elevation of the fifth metatarsal head was 1.08 mm. The American Orthopaedic Foot & Ankle Society score improved from 54.3 ± 20.86 points preoperatively to 93.4 ± 17.3 (P < .001). VAS score decreased from 7.9 to 0.7 (P < .001). Also, FAAM ALD, FAAM Sport, and MOXFQ showed statistically significant differences (P < .001) between preoperative and postoperative periods. Patients found the procedure excellent in 89.1% of cases, very good in 5.4%, and good in 5.4%. Bone union was obtained at 8.1 weeks. CONCLUSION: The most important finding of the present study is that S-DMMO showed improvement in function and pain associated with a high satisfaction rate. Also, we found substantial capacity to correct deformities and a low incidence of complications. LEVEL OF EVIDENCE: Level IV, case series.

Integrated survey of water pollution in the Suquía River basin (Córdoba, Argentina).

We report a combined two-year seasonal monitoring of Suquía River basin using both chemical parameters and biomarkers measured in Jenynsia multidentata, aiming to correlate external levels of contaminants with the response of oxidative stress biomarkers in this fish. Identified pollution sources correspond to city sewage as well as agricultural and small industry activities downstream from Córdoba city. Physicochemical parameters integrated into a water quality index (WQI) were measured in Suquía River during dry and wet seasons. Ag, Mn, Cu, Cr, Ni, Fe, Pb and Zn were also monitored in water and sediment samples. Biomarkers include detoxication and antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST) and glutathione reductase (GR). Enzymes showed a pollution dependent response, with increased activities in fish collected close to the sewage exit and progressive drop further downstream, matching changes in the Water Quality index. The combined use of biomarkers with water quality parameters allowed both the identification of pollution sources and the evaluation of effects of contaminants on the aquatic biota.

Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion.

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague-Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

Cryptococcus neoformans osteomyelitis of the calcaneus: Case report and literature review.

Cryptococcus neoformans is an encapsulated, yeast-like fungus that can cause a systemic mycosis, particularly in immunocompromised patients. Disseminated infections typically affect the central nervous system, and osseous lesions are infrequent. Only 5%-10% of disseminated cryptococcosis involves bones. A 69-year-old female presented pain, swelling, and a soft tissue mass in her right lateral hindfoot. Her medical history included a kidney transplant (10 years earlier) secondary to chronic disease due to IgA nephropathy. The patient underwent an excisional biopsy, surgical debridement, and secondarily negative pressure wound therapy to achieve skin closure. Biopsy revealed a rare Cryptococcus neoformans osteomyelitis of the calcaneus. The patient then received IV treatment with liposomal amphotericin B at 3 mg/kg/d for 25 days. In conclusion, we present a case of cryptococcal osteomyelitis which, although not a frequent disease, must be considered as one of the differential diagnoses of osteolytic osseous lesions in patients with chronic osteomyelitis. Cryptococcus neoformans may be a potential cause of below-knee infection, mainly in immunocompromised patients.

Intestinal lymphatic alteration in mouse models of energy imbalance.

In obesity or anorexia, changes in body composition and mostly alterations in fat mass distribution are observed. The lymphatic system, which is implicated in fat absorption, might play a major role in the phenotype and development of these pathologies. In this study, two mice animal models were used: the high-fat diet model used for obesity and the activity-based anorexia model for anorexia. Lymphatic system marker levels were measured by reverse transcriptase quantitative polymerase chain reaction on the different parts of the intestine. Moreover, the effects of these models were evaluated on lymphatic fat absorption using lipidic tracer. Using these two models, lymphatic system alterations were observed. Indeed, whether in the obesity or the anorectic model, lymphatic fat absorption modifications were noticed with an increase of this parameter in the anorectic mice and a decrease in obesity. Expression levels of lymphatic markers also were impaired in these models. Both obesity and anorectic models induced lymphatic system alterations mainly in the jejunum and ileum parts of the intestine. These alterations are associated with lipid absorption modifications.

Patient-specific three-dimensional printed hemi talar prostheses for the treatment of talar osteonecrosis, case report and literature review.

We present the case of a 43-year-old boy who presented with progressive pain as a result of history of lateral avascular necrosis of the talus secondary to traumatic open ankle luxation 20 years ago. Conservative treatment (12-month period) prior to surgery failed. It consisted of physiokinetic treatment, insoles and analgesic medication. A diagnostic injection was used in the ankle (positive) and subtalar joint (negative) in order to recognize origin of pain. Hemilateral avascular necrosis of the talus is rare. There are no prior reported cases of the use of hemi-implants. This case highlights the potential use of a patient-specific three-dimensional printed Ti6Al4V prosthesis presented in a complex scenario.

Comparison of two forced-air warming devices during foot and ankle surgery: a randomised controlled trial.

Inadvertent perioperative hypothermia is a frequent problem associated with surgical patients which can have significant consequences during surgery and in the immediate postoperative period. We compared 35 randomised patients using over vs. under body forced air heating. There were no statistically significant differences between some demographic and surgical parameters such as: age, weight, height, body mass index, length of anaesthesia and operation. Statistically significant differences were found between the patient's admission to the operating room and 30 minutes and the end of the procedure on the under body patients group. This study analyses a uniform population of patients (Foot and Ankle Surgery) previously not studied and supports the use of under body blankets.

Plasma Peptide Concentrations and Peptide-Reactive Immunoglobulins in Patients with Eating Disorders at Inclusion in the French EDILS Cohort (Eating Disorders Inventory and Longitudinal Survey).

Eating disorders (EDs) are increasingly frequent. Their pathophysiology involves disturbance of peptide signaling and the microbiota-gut-brain axis. This study analyzed peptides and corresponding immunoglobulin (Ig) concentrations in groups of ED. In 120 patients with restrictive (R), bulimic (B), and compulsive (C) ED, the plasma concentrations of leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin were analyzed by Milliplex and those of acyl ghrelin (AG), des-acyl ghrelin (DAG), and α-melanocyte-stimulating hormone (α-MSH) by ELISA kits. Immunoglobulin G (in response to an antigen) concentrations were analyzed by ELISA, and their affinity for the respective peptide was measured by surface plasmon resonance. The concentrations of leptin, insulin, GLP-1, and PYY were higher in C patients than in R patients. On the contrary, α-MSH, DAG, and AG concentrations were higher in R than in C patients. After adjustment for body mass index (BMI), differences among peptide concentrations were no longer different. No difference in the concentrations of the IgG was found, but the IgG concentrations were correlated with each other. Although differences of peptide concentrations exist among ED subtypes, they may be due to differences in BMI. Changes in the concentration and/or affinity of several anti-peptide IgG may contribute to the physiopathology of ED or may be related to fat mass.

Bacterial Protein Mimetic of Peptide Hormone as a New Class of Protein- based Drugs.

Specific peptide molecules classified as hormones, neuropeptides and cytokines are involved in intercellular signaling regulating various physiological processes in all organs and tissues. This justifies the peptidergic signaling as an attractive pharmacological target. Recently, a protein mimetic of a peptide hormone has been identified in Escherichia coli suggesting the potential use of specific bacterial proteins as a new type of peptide-like drugs. We review the scientific rational and technological approaches leading to the identification of the E. coli caseinolytic protease B (ClpB) homologue protein as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), a melanocortin peptide critically involved in the regulation of energy homeostasis in humans and animals. Theoretical and experimental backgrounds for the validation of bacterial ClpB as a potential drug are discussed based on the known E. coli ClpB amino acid sequence homology with α-MSH. Using in silico analysis, we show that other protein sources containing similar to E. coli ClpB α-MSH-like epitopes with potential biological activity may exist in Enterobacteriaceae and in some Brassicaceae. Thus, the original approach leading to the identification of E. coli ClpB as an α-MSH mimetic protein can be applied for the identification of mimetic proteins of other peptide hormones and development of a new type of peptide-like protein-based drugs.

Hafnia alvei HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity.

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria Hafnia alvei (H. alvei) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic ob/ob male mice received a daily treatment with 1.4 × 1010 CFU of H. alvei for 38 days. Effects of H. alvei were compared to those of a lipase inhibitor orlistat (80 mg/kg daily) and a vehicle (NaCl 0.9%) in HFD-fed ob/ob mice. A control untreated group of ob/ob mice received the standard diet throughout the experiment. The vehicle-treated HFD group displayed increased food intake, worsening of adiposity, and glycemia. Treatment with H. alvei was accompanied by decreased body weight and fat-mass gain along with reduced food intake to the level of the standard-diet-fed mice. At the end of the experiment, the group treated with H. alvei showed a decrease of glycemia, plasma total cholesterol, and alanine aminotransferase. The orlistat-treated mice showed a lower rate of body weight gain but were hyperphagic and hyperglycemic. These results demonstrate the beneficial anti-obesity and metabolic effects of H. alvei HA4597™ in mice with obesity resulting from hyperphagia and diet-induced adiposity.

Changes in Microbiota and Bacterial Protein Caseinolytic Peptidase B During Food Restriction in Mice: Relevance for the Onset and Perpetuation of Anorexia Nervosa.

Microbiota contributes to the regulation of eating behavior and might be implicated in the pathophysiology of anorexia nervosa. ClpB (Caseinolytic peptidase B) protein produced mainly by the Enterobacteriaceae family has been identified as a conformational mimetic of α-MSH, which could result in similar anorexigenic effects. The aim of this study was to highlight the role of the microbiome and the ClpB protein in deregulation and self-maintenance of anorexia pathology. Male C57Bl/6 mice were undergone to the ABA (Activity-Based Anorexia) protocol: after 5 days of acclimatization, both ABA and LFA (Limited Food Access) mice had progressively limited access to food until D17. At the end of protocol, the plasma ClpB concentration and Enterobacteriaceae DNA in colonic content were measured. As expected, dietary restriction induced lost weight in LFA and ABA mice. At D10, colonic permeability and plasma concentration of the ClpB protein were significantly increased in LFA and ABA mice vs. controls. At D17, plasma concentration of ClpB was increased in LFA and ABA mice and, it was correlated with proportion of Enterobacteriaceae in the faeces. These abnormally high ClpB concentrations and all associated factors, and therefore might contribute to the initiation and/or perpetuation of anorexia nervosa by interfering with satiety signaling.