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Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34 + hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34 + grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

BackgroundThe prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease.MethodsIn an open-label, phase 1/phase 2 study, patients (N = 36) with long-standing T2D were divided into three groups (Group A, oral medications, n = 18; Group B, oral medications + insulin injections, n = 11; Group C having impaired β-cell function with oral medications + insulin injections, n = 7). All patients received one treatment with the Stem Cell Educator therapy in which a patient’s blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient’s circulation.ResultsClinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61% ± 1.12 at baseline to 7.25% ± 0.58 at 12 weeks (P = 2.62E-06), and 7.33% ± 1.02 at one year post-treatment (P = 0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production.ConclusionsClinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in metabolic control for individuals with moderate or severe T2D who receive a single treatment. In addition, this approach does not appear to have the safety and ethical concerns associated with conventional stem cell-based approaches.Trial registrationClinicalTrials.gov number, NCT01415726

Aim: The study was carried out with aim to isolate Staphylococcus aureus from milk and milk products (pedha and curd) and determine antibiogram pattern of S. aureus isolates. Materials and Methods: During 9 months duration of study a total of 160 milk and milk product samples (pedha and curd) were collected from different places in and around Anand city such as milk collection centre of Co-operative milk dairies, cattle farms, individual household, milk vendors and sweet shops. The samples were collected under aseptic precautions and were enriched in Peptone Water (PW) followed by direct plating on selective media viz. Baird-Parker Agar. The presumptive S. aureus isolates were identified by biochemical tests. Antibiogram pattern of S. aureus to antimicrobial agents were evaluated by disk diffusion method. Results: Analysis of result revealed that out of total 160 samples of milk (100) and milk products i.e. curd (30) and pedha (30) resulted in the isolation of 10 isolates (6.25 %) of S. aureus. In the present study S. aureus isolates were found variably resistant to the antibiotics tested. The S. aureus isolates showed highest sensitivity towards cephalothin (100.00 %), co-trimoxazole (100.00 %), cephalexin (100.00 %) and methicillin (100.00 %) followed by gentamicin (90.00 %), ciprofloxacin (80.00 %), oxacillin (70.00 %), streptomycin (60.00 %) and ampicillin (60.00 %). The pattern clearly indicated that the overall high percent of S. aureus isolates were resistant to Penicillin-G (100.00 %) followed by ampicillin (40.00 %), oxytetracycline and oxacillin (20.00 %) and streptomycin and gentamicin (10.00 %) Conclusions: Results clearly suggested a possibility of potential public health threat of S. aureus resulting from contamination of milk and milk products with pathogenic bacteria is mainly due to unhygienic processing, handling and unhygienic environment. [Vet World 2013; 6(1.000): 10-13

C. difficile is a major cause of antibiotic-associated gastrointestinal infections. Two C. difficile exotoxins (TcdA and TcdB) are major virulence factors associated with these infections, and chondroitin sulfate proteoglycan 4 (CSPG4) is a potential receptor for TcdB, but its pathophysiological relevance and the molecular details that govern recognition remain unknown. Here, we determine the cryo-EM structure of a TcdB–CSPG4 complex, revealing a unique binding site spatially composed of multiple discontinuous regions across TcdB. Mutations that selectively disrupt CSPG4 binding reduce TcdB toxicity in mice, while CSPG4-knockout mice show reduced damage to colonic tissues during C. difficile infections. We further show that bezlotoxumab, the only FDA approved anti-TcdB antibody, blocks CSPG4 binding via an allosteric mechanism, but it displays low neutralizing potency on many TcdB variants from epidemic hypervirulent strains due to sequence variations in its epitopes. In contrast, a CSPG4-mimicking decoy neutralizes major TcdB variants, suggesting a strategy to develop broad-spectrum therapeutics against TcdB.

Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings.

Aim : The study was carried out with aim to isolate Escherichia coli from raw milk samples and determine antibiogram pattern of E. coli isolates. Materials and Methods: During 6 months duration of study a total of 100 raw milk samples were collected from different places in and around Anand city such as individual household, cattle farms, milk collection centres of Co-operative milk dairies and milk vendors. All raw milk samples were enriched in peptone water and inoculated on selective media and various biochemical tests were performed for confirmation of isolates. Antibiogram pattern of E.coli to antimicrobial agents was evaluated by disk diffusion method. E. coli isolates were sent to National Salmonella and Escherichia Centre, Central Research Institute, Kasauli, Himachal Pradesh for serotyping. Results: The result of present study revealed that out of 100 samples, 38 samples were found contaminated with E.coli. Antibiogram pattern revealed high resistance against ampicillin (100 %), whereas moderate resistance was observed for streptomycin (57.89 %), oxytetracycline (47.37 %) and amoxy-clav (42.11 %). Also lesser percentage of resistance was observed for co-trimoxazole (13.16 %) and chloramphenicol (5.26 %). Serotypes detected were O24 (7 isolates), followed by O36 (1 isolate), O89 (1 isolate), O91 (1 isolate) and O153(1 isolate). Conclusions: Results suggested a possibility of potential public health threat of E.coli originating from raw milk sources.

The need for a consistent therapeutic approach to tendon injury repair is long overdue. Patients with tendon microtears or full ruptures are eligible for a wide range of invasive and non invasive interventions, often subjectively decided by the physician. Surgery produces the best outcomes, and while studies have been conducted to optimize graft constructs and to track outcomes, the data from these studies have been inconclusive on the whole. What has been established is a clear understanding of healthy tendon architecture and the inherent process of healing. With this knowledge, tissue regeneration efforts have achieved immense progress in scaffold design, cell line selection, and, more recently, the appropriate use of cytokines and growth factors. This paper evaluates the plasticity of bone-marrow-derived stem cells and the elasticity of recently developed biomaterials towards tendon regeneration efforts. Mesenchymal stem cells (MSCs), hematopoietic progenitor cells, and poly(1,8-octanediol co-citrate) scaffolds (POC) are discussed in the context of established grafting strategies. With POC scaffolds to cradle the growth of MSCs and hematopoietic progenitor cells, developing a fibroelastic network guided by cytokines and growth factors may contribute towards consistent graft constructs, enhanced functionality, and better patient outcomes.