Effects of individualized anemia therapy on hemoglobin stability: a randomized controlled pilot trial in hemodialysis patients.

BACKGROUND: Anemia is common among hemodialysis patients. Maintaining stable hemoglobin levels within predefined target levels can be challenging, particularly in patients with frequent hemoglobin fluctuations both above and below the desired targets. We conducted a multi-center, randomized, controlled trial comparing our anemia therapy assistance software against a standard population-based anemia treatment protocol. We hypothesized that personalized dosing of erythropoiesis stimulating agents (ESA) improves hemoglobin target attainment. METHODS: Ninety-six patients undergoing hemodialysis and receiving methoxy polyethylene glycol-epoetin beta were randomized 1:1 to the intervention group (personalized ESA dose recommendations computed by the software) or the standard of care group for twenty-six weeks. The therapy assistance software combined a physiology-based mathematical model and a model predictive controller designed to stabilize hemoglobin levels within a tight target range (10 to 11 g/dl). The primary outcome measure was the percentage of hemoglobin measurements within the target. Secondary outcome measures included measures of hemoglobin variability and ESA utilization. RESULTS: The intervention group showed an improved median percentage of hemoglobin measurements within target at 47% (IQR 39 to 58), with a 10 percentage points median difference between the two groups (95% CI: 3 to 16; P=0.008). The odds ratio of being within the hemoglobin target in the standard of care group compared to the group receiving the personalized ESA recommendations was 0.68 (95% CI: 0.51 to 0.92). The variability of hemoglobin levels decreased in the intervention group, with the percentage of patients experiencing fluctuating hemoglobin levels being 45% vs 82% in the standard of care group. ESA usage was reduced by about 25% in the intervention group. CONCLUSIONS: Our results demonstrated an improved hemoglobin target attainment and variability by employing personalized ESA recommendations using the physiology-based anemia therapy assistance software.

Helicobacter Pylori and Gastric Cancer: An Update in the Literature.

Of the chronic bacterial infections that affect humans, Helicobacter pylori (H. pylori) infection is one of the most common. It inhabits the stomachs of half of the adult human population. In Puerto Rico, a US territory, it has an overall prevalence of 33%, similar to the prevalence reported in the population of the US as a whole. Helicobacter pylori infection is responsible for mucosal inflammation that may lead to chronic gastritis, most peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The International Agency for Research on Cancer identified H. pylori as a definite carcinogen in 1994, the only bacterium to be given such a classification. Its oncogenic effect has been postulated to be caused by different mechanisms, including bacterial characteristics and host factors. Epidemiologic studies have shown that gastric cancer risk differs among regions. One of the top 10 causes of cancer death in Puerto Rico is gastric cancer. Although the eradication of H. pylori has well-known benefits, there are some concerns when considering mass screening and treatment of infected patients. These include the fact that such eradication could provoke an increase in antibiotic resistance rates, the disturbance of the gut microbiota, an increase in body weight, and the aggravation of existing gastroesophageal reflux symptoms. Gastric cancer is a major health concern, and we should understand the role of H. pylori eradication in its prevention. This article is geared to summarize current knowledge and controversies.

Inactivation of Tulane virus and feline calicivirus by aqueous ozone.

Ongoing challenges with reproducible human norovirus cultivable assays necessitate the use of surrogates, such as feline calicivirus (FCV-F9) and Tulane virus (TV), during inactivation studies. Chlorine alternates used as control strategies include aqueous and gaseous ozone. This study aimed at determining the inactivation of FCV-F9 and TV by a portable ozone-generating device. FCV-F9 (∼8 log PFU/mL) or TV (∼6 log PFU/mL) in sterile-low-organic matter-containing-water was treated for 0-5 min, or in sterile-water containing newborn calf serum (high-organic matter/protein) for 0-38 min with ∼1 ppm ozone (pH 7-6). Infectivity was determined from triplicate treatments using plaque assays. FCV-F9 titers significantly decreased by 6.07 log PFU/mL after 5 min in ozonated low-organic-matter-containing-water and was non-detectable (≤2 log PFU/mL) after 36 min treatments in high-organic-matter-containing water (p < 0.05). TV titers decreased by 4.18 log PFU/mL after 4 min in ozonated low-organic-matter water (non-detectable after 4.5 min) and were non-detectable after 22.5 min treatments of high-organic-matter-containing water (p < 0.05). Overall, ∼1 ppm aqueous ozone significantly decreased FCV-F9 by >6 log PFU/mL after 5 min, TV to non-detectable levels (≤2 log PFU/mL) after 4.5 min and required longer treatments (>32 and >20 min, respectively) for ≥4 log reduction in high-organic-matter-containing water (p < 0.05). For ozone treatment of both viruses, the linear and Weibull models were similar for low-organic-load water, though the Weibull model was better for the high-organic load water. Prior filtration or organic load removal is recommended before ozonation for increased viral inactivation with decreased treatment-time.

Assessment of antimicrobial activity of melittin encapsulated in bicontinuous microemulsions prepared using renewable oils.

The objective of this study is to demonstrate that melittin, a well-studied antimicrobial peptide (AMP), can be solubilized in an active form in bicontinuous microemulsions (BMEs) that employ biocompatible oils. The systems investigated consisted of Winsor-III and -IV BME phases composed of Water/Aerosol-OT (AOT)/Polysorbate 85/isopropyl myristate and a Winsor-IV BME employing Polysorbate 80 and limonene. We found that melittin resided in an α-helix-rich configuration and was in an apolar environment for the AOT/Polysorbate 85 Winsor-III system, suggesting that melittin interacted with the surfactant monolayer and was in an active conformation. An apolar environment was also detected for melittin in the two Winsor-IV systems, but to a lesser extent than the Winsor-III system. Small-angle X-ray scattering analysis indicated that melittin at a concentration of 1.0 g/Laq in the aqueous subphase of the Winsor-IV systems led to the greatest impact on the BME structure (e.g., decrease of quasi-periodic repeat distance and correlation length and induction of interfacial fluidity). The antimicrobial activity of the Polysorbate 80 Winsor-IV system was evaluated against several bacteria prominent in chronic wounds and surgical site infections (SSIs). Melittin-free BMEs inhibited the growth of all tested bacteria due to its oil, limonene, while the inclusion of 1.0 g/Laq of melittin in the BMEs enhanced the activity against several bacteria. A further increase of melittin concentration in the BMEs had no further enhancement. These results demonstrate the potential utility of BMEs as a delivery platform for AMPs and other hydrophilic and lipophilic drugs to inhibit antibiotic-resistant microorganisms in chronic wounds and SSIs.

Increased Prevalence of Advanced Histologic Features in Small and Diminutive Polyps in Patients Undergoing Surveillance and Diagnostic Colonoscopy.

OBJECTIVE: Studies addressing small and diminutive polyps and their potential of harboring advanced histologic features (AH) are scarce in Hispanics. We aimed to determine the prevalence of AH in a cohort of Hispanics. METHODS: A retrospective review of medical records of patients who had a colonoscopy from 2005 through 2010. The data collected included demographics, indications, history (personal/family) of colon cancer and/or polyps, and polyp histology. Polyps with high-grade dysplasia, prominent villous component, adenocarcinoma or serrated were classified as having AH. RESULTS: The population comprised 1884 patients, and 3835 polyps were evaluated; 63.3% were diminutive (1-5 mm), 22.7% small (6-9 mm), and 13.9% large (≥10 mm). The prevalence of AH for small and diminutive polyps were 4.9% and 1.1%, respectively. Of the polyps with AH, 11.9% were diminutive and 19.6% small. Small polyps were 5.04 times more likely to harbor AH than were diminutive polyps. Distal rather than proximal polyps were more likely to harbor AH. Furthermore, AH was >7 times more common in small (6-9 mm) polyps identified during diagnostic or surveillance colonoscopies compared to screening colonoscopies. CONCLUSION: The prevalence of AH was significantly associated with size, location (distal), and procedure indication. Although diminutive polyps (<6 mm) were less likely to harbor AH, the risk for non-Hispanics was higher than previously reported. The "resect and discard" strategy for polyps ≤ 1 cm should be used with caution in ethnically diverse cohorts, as the risk for AH may be higher in Hispanics than in non-Hispanic Whites.

Normoglycemia partially recovers the disrupted osteoblast differentiation of mesenchymal stem cells induced by type 1 but not type 2 diabetes mellitus.

Type 1 (T1DM) and type 2 (T2DM) diabetes mellitus are characterized by changes in glucose metabolism and cause bone damage via a variety of mechanisms, including effects on osteoblasts. We aimed to evaluate the osteoblast differentiation of mesenchymal stem cells (MSCs) from rats with T1DM or T2DM and the effects of removing the hyperglycemic stimulus on the osteogenic potential of these cells. MSCs from healthy rats were cultured in normoglycemic medium, whereas MSCs from rats with T1DM or T2DM were cultured in hyperglycemic or normoglycemic medium. T1DM and T2DM reduced osteoblast differentiation of MSCs grown in hyperglycemic media, with T1DM having a more pronounced effect, as evidenced by alkaline phosphatase activity, RUNX2 protein expression, and extracellular matrix mineralization, and modulated the gene expression of several components of the bone morphogenetic protein signaling pathway. The restoration of the normoglycemic environment partially recovers the osteogenic potential of MSCs from rats with T1DM but not with T2DM. Our findings highlight the need for specific therapies to treat T1DM- or T2DM-induced bone loss, as both disrupt osteoblast differentiation at distinct levels and likely through different mechanisms.

Lunasin reduces the susceptibility of IL-10 deficient mice to inflammatory bowel disease and modulates the activation of the NLRP3 inflammasome.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that can cause severe damage to the gastrointestinal tract leading to lower quality of life and productivity. Our goal was to investigate the protective effect of the soy peptide lunasin in an in vivo model of susceptibility to IBD and to identify the potential mechanism of action in vitro. In IL-10 deficient mice, oral administration of lunasin reduced the number and frequency of mice exhibiting macroscopic signs of susceptibility to inflammation and significantly decreased levels of the proinflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-18 by up to 95%, 90%, 90%, and 47%, respectively, in different sections of the small and large intestines. Dose-dependent decrease of caspase-1, IL-1ß, and IL-18 in LPS-primed and ATP-activated THP-1 human macrophages demonstrated the ability of lunasin to modulate the NLRP3 inflammasome. We demonstrated that lunasin can decrease susceptibility to IBD in genetically susceptible mice by exerting anti-inflammatory properties.

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico.

BACKGROUND: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.

Acute Liver Infarct with a Superimposed Liver Abscess as a Consequence of Hypercoagulable State in a Patient with COVID-19 without Respiratory Manifestations.

COVID-19 infection has been associated, particularly in severely ill patients requiring hospitalization, with a hypercoagulable state. The case presented herein was a 66-year-old man with SARS-CoV-2 infection who did not have any respiratory symptoms. He presented with the following clinical manifestations: portal vein and hepatic artery thrombosis, liver infarction, and a superimposed abscess of the liver. In this case, early detection and the administration of anticoagulants and antibiotics led to a significant improvement within weeks of the diagnosis. We encourage physicians to be aware of COVID-19-associated hypercoagulable state and its potential complications, regardless of the acuity of the presentation or the absence of respiratory symptoms.

Antiviral Effects of Quillaja saponaria Extracts Against Human Noroviral Surrogates.

Aqueous extracts of Quillaja saponaria Molina are US FDA approved as food additives in beverages with known antiviral activity. Due to lack of commercially available vaccines against human noroviruses (HNoVs), alternate methods to prevent their spread and the subsequent emergence of variant strains are being researched. Furthermore, HNoVs are not yet culturable at high enough titers to determine inactivation, therefore surrogates continue to be used. This research analyzed the effect of aqueous Quillaja saponaria extracts (QE) against HNoV surrogates, Tulane virus (TV), murine norovirus (MNV-1), and feline calicivirus (FCV-F9) at room temperature (RT) and 37 °C. Viruses (~ 5 log PFU/mL) were individually treated with 1:1 or 1:5 (v/v) diluted QE (pH ~ 3.75), malic acid control (pH 3.0) or phosphate-buffered saline (pH 7.2, as control) at 37 °C or RT for up to 6 h. Individual treatments were replicated three times using duplicate plaque assays for each treatment. FCV-F9 at ~ 5 log PFU/mL was not detectable after 15 min by 1:1 QE at 37 °C and RT. At RT, 1:5 QE lowered FCV-F9 titers by 2.05, 2.14 and 2.74 log PFU/mL after 0.5 h, 1 h and 2 h, respectively. MNV-1 showed marginal reduction of < 1 log PFU/mL after 15 min with 1:1 or 1:5 QE at 37 °C without any significant reduction at RT, while TV titers decreased by 2.2 log PFU/mL after 30 min and were undetectable after 3 h at 37 °C. Longer incubation with higher QE concentrations may be required for improved antiviral activity against MNV-1 and TV.

Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents.

Patients with renal anemia are frequently treated with erythropoiesis-stimulating agents (ESAs), which are dynamically dosed in order to stabilize blood hemoglobin levels within a specified target range. During typical ESA treatments, a fraction of patients experience hemoglobin 'cycling' periods during which hemoglobin levels periodically over- and undershoot the target range. Here we report a specific mechanism of hemoglobin cycling, whereby cycles emerge from the patient's delayed physiological response to ESAs and concurrent ESA dose adjustments. We introduce a minimal theoretical model that can explain dynamic hallmarks of observed hemoglobin cycling events in clinical time series and elucidates how physiological factors (such as red blood cell lifespan and ESA responsiveness) and treatment-related factors (such as dosing schemes) affect cycling. These results show that in general, hemoglobin cycling cannot be attributed to patient physiology or ESA treatment alone but emerges through an interplay of both, with consequences for the design of ESA treatment strategies.

The Impact of a Sustained Virologic Response to Hepatitis C Virus Treatment on Liver Stiffness in the Puerto Rico Veterans Attending Liver Clinics in the Veterans Affairs Caribbean Healthcare System.

OBJECTIVE: To evaluate the impact of sustained virologic response (SVR) on liver stiffness, as measured by transient elastography (TE), in Hispanic patients treated with direct-acting antivirals (DAAs) in the outpatient clinics in the Veterans Affairs Caribbean Healthcare System. METHODS: We included hepatitis C virus (HCV) patients treated with DAA regimens from 11/2017 through 06/2019. Patient demographics and variables such as body mass index, HCV genotype, and treatment regimen were collected. The patients had a TE measurement before treatment initiation, and a repeat study 6 to 9 months after the achievement of SVR. A comparison between pre and post-treatment TE scores was performed via a paired t test. RESULTS: Forty-three subjects met all the inclusion criteria and completed a posttreatment TE. Most of the subjects were infected with genotypes 1a or 1b. Six to 9 months post SVR, we measured liver stiffness and found a statistically significant reduction in TE score (P value = .0003). The pretreatment median TE score was 10.2 kPa. On a repeat TE study at 6 to 9 months post-treatment, our subjects had a median score of 7.2 kPa. CONCLUSION: The eradication of HCV infection with DAAs is associated with improved TE scores. Fibrosis-stage reduction was more frequent in those who had stage 4 fibrosis prior to treatment. These results suggest that achieving SVR may spare patients from future clinical decompensation and complications. Adequate screening of this potentially deadly chronic infection can lead to early therapy with DAAs and the significant regression of fibrosis in this kind of patient.

Effectiveness of Multiple Consecutive Fecal Immunohistochemical Testing for Colorectal Cancer Screening.

OBJECTIVE: The fecal immunohistochemical test (FIT) is a simple colorectal-cancer screening test. There are no recent studies evaluating the benefits of doing more than one a year. Our study aimed to evaluate the effectiveness of performing the test for 3 consecutive days in terms of detecting cancer and advanced adenomas. METHODS: This was a single-center retrospective review of records of patients who had daily tests for 3 consecutive days and had at least one positive during the period from 2009-2011. RESULTS: A total of 456 records were reviewed, 410 met the inclusion criteria. Most of the participants were men (95.9%), with the mean age of all the participants being 64.3 (±7.8) years. Regarding the FIT results, 18.8% had positive results on all 3 tests, 20.2% had 2 positive tests, and 61.0% had 1 positive FIT. There were 16 (3.9%) patients in the studied sample that had colon cancer. Their lesions were located predominantly in the distal colon (ratio of distal to proximal: 2:1). The patients with 3 positive FITs had a higher prevalence of advanced adenomas (33.3% vs. 13.4%, respectively; P < .05). DISCUSSION: Our study showed a low concordance between daily consecutive tests results. those patients with more than 1 positive FIT had a higher prevalence of advanced adenoma or adenocarcinoma than patients who had only one. Fewer than 4% of the patients in our study had colon cancer. Prospective studies would be needed to determine the effectiveness of more than 1 annual FIT in colon cancer prevention.

Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.

For the treatment of postmenopausal osteoporosis, several drug classes with different mechanisms of action are available. Since only a limited set of dosing regimens and drug combinations can be tested in clinical trials, it is currently unclear whether common medication strategies achieve optimal bone mineral density gains or are outperformed by alternative dosing schemes and combination therapies that have not been explored so far. Here, we develop a mathematical framework of drug interventions for postmenopausal osteoporosis that unifies fundamental mechanisms of bone remodeling and the mechanisms of action of four drug classes: bisphosphonates, parathyroid hormone analogs, sclerostin inhibitors, and receptor activator of NF-κB ligand inhibitors. Using data from several clinical trials, we calibrate and validate the model, demonstrating its predictive capacity for complex medication scenarios, including sequential and parallel drug combinations. Via simulations, we reveal that there is a large potential to improve gains in bone mineral density by exploiting synergistic interactions between different drug classes, without increasing the total amount of drug administered.

Our bones are constantly being renewed in a fine-tuned cycle of destruction and formation that helps keep them healthy and strong. However, this process can become imbalanced and lead to osteoporosis, where the bones are weakened and have a high risk of fracturing. This is particularly common post-menopause, with one in three women over the age of 50 experiencing a broken bone due to osteoporosis. There are several drug types available for treating osteoporosis, which work in different ways to strengthen bones. These drugs can be taken individually or combined, meaning that a huge number of drug combinations and treatment strategies are theoretically possible. However, it is not practical to test the effectiveness of all of these options in human trials. This could mean that patients are not getting the maximum potential benefit from the drugs available. Jörg et al. developed a mathematical model to predict how different osteoporosis drugs affect the process of bone renewal in the human body. The model could then simulate the effect of changing the order in which the therapies were taken, which showed that the sequence had a considerable impact on the efficacy of the treatment. This occurs because different drugs can interact with each other, leading to an improved outcome when they work in the right order. These results suggest that people with osteoporosis may benefit from altered treatment schemes without changing the type or amount of medication taken. The model could suggest new treatment combinations that reduce the risk of bone fracture, potentially even developing personalised plans for individual patients based on routine clinical measurements in response to different drugs.

Prevalence of Antimicrobial Resistant and Extended-Spectrum Beta-Lactamase-producing Escherichia coli in Dairy Cattle Farms in East Tennessee.

Antimicrobials have been widely used in dairy farms to prevent and control dairy cattle diseases since 1960s. This led to the emergence of antimicrobial resistant bacteria (ARB) that, along with their antimicrobial resistance genes (ARGs), can spread from dairy farms to humans. Therefore, regular antimicrobial resistance (AMR) monitoring is important to implement proper mitigation measures. The objective of this study was to determine the prevalence of AMR and extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli in dairy cattle. A cross-sectional study was conducted in four dairy cattle farms (A-D) in East Tennessee. A total of 80 samples consisting of 20 samples each of bulk tank milk, feces, dairy cattle manure-amended soil, and prairie soil adjacent to the farms were collected and cultured for the isolation of E. coli. Tetracycline (TETr)-, third-generation cephalosporin (TGCr)- and nalidixic acid (NALr)-resistant E. coli (n = 88) were isolated and identified on agar media supplemented with TET, cefotaxime, and NAL, respectively. TGCr E. coli were tested for ESBLs and other coselected ARGs. TETr (74%, n = 88) was the most common, followed by TGCr (20%) and NALr (8%). Farms had significant (p < 0.001) differences: the highest prevalence of TGCr (55%) and TETr (100%) were observed in farm D, while all NALr isolates were from farm C. Over 83% of TGCr isolates (n = 18) harbored ESBL gene blaCTX-M. Majority (78%) of the E. coli isolates were multidrug-resistant (MDR), being positive for beta-lactams (blaCTX-M), TETs tet(A), tet(B), tet(M)), sulfonamides (sul2), aminoglycosides (strA), and phenicols (floR). This study indicated the widespread occurrence of MDR ESBLs-E. coli in dairy cattle farms. AMR surveillance of more dairy farms and identification of farm-level risk factors are important to mitigate the occurrence and spread of ARB of significant public health importance, such as ESBLs-E. coli.

Proportional integral feedback control of ultrafiltration rate in hemodialysis.

BACKGROUND: Most hemodialysis patients without residual kidney function accumulate fluid between dialysis session that needs to be removed by ultrafiltration. Ultrafiltration usually results in a decline in relative blood volume (RBV). Recent epidemiological research has identified RBV ranges that were associated with significantly better survival. The objective of this work was to develop an ultrafiltration controller to steer a patient's RBV trajectory into these favorable RBV ranges. METHODS: We designed a proportional-integral feedback ultrafiltration controller that utilizes signals from a device that reports RBV. The control goal is to attain the RBV trajectory associated with improved patient survival. Additional constraints such as upper and lower bounds of ultrafiltration volume and rate were realized. The controller was evaluated in in silico and ex vivo bench experiments, and in a clinical proof-of-concept study in two maintenance dialysis patients. RESULTS: In all tests, the ultrafiltration controller performed as expected. In the in silico and ex vivo bench experiments, the controller showed robust reaction toward deliberate disruptive interventions (e.g. signal noise; extreme plasma refill rates). No adverse events were observed in the clinical study. CONCLUSIONS: The ultrafiltration controller can steer RBV trajectories toward desired RBV ranges while obeying to a set of constraints. Prospective studies in hemodialysis patients with diverse clinical characteristics are warranted to further explore the controllers impact on intradialytic hemodynamic stability, quality of life, and long-term outcomes.

Fibrin with Laminin-Nidogen Reduces Fibrosis and Improves Soft Palate Regeneration Following Palatal Injury.

This study aimed to analyze the effects of fibrin constructs enhanced with laminin-nidogen, implanted in the wounded rat soft palate. Fibrin constructs with and without laminin-nidogen were implanted in 1 mm excisional wounds in the soft palate of 9-week-old rats and compared with the wounded soft palate without implantation. Collagen deposition and myofiber formation were analyzed at days 3, 7, 28 and 56 after wounding by histochemistry. In addition, immune staining was performed for a-smooth muscle actin (a-SMA), myosin heavy chain (MyHC) and paired homeobox protein 7 (Pax7). At day 56, collagen areas were smaller in both implant groups (31.25 ± 7.73% fibrin only and 21.11 ± 6.06% fibrin with laminin-nidogen)) compared to the empty wounds (38.25 ± 8.89%, p < 0.05). Moreover, the collagen area in the fibrin with laminin-nidogen group was smaller than in the fibrin only group (p ˂ 0.05). The areas of myofiber formation in the fibrin only group (31.77 ± 10.81%) and fibrin with laminin-nidogen group (43.13 ± 10.39%) were larger than in the empty wounds (28.10 ± 11.68%, p ˂ 0.05). Fibrin-based constructs with laminin-nidogen reduce fibrosis and improve muscle regeneration in the wounded soft palate. This is a promising strategy to enhance cleft soft palate repair and other severe muscle injuries.

Prevalence of Mastitis and Antibiotic Resistance of Bacterial Isolates from CMT Positive Milk Samples Obtained from Dairy Cows, Camels, and Goats in Two Pastoral Districts in Southern Ethiopia.

A study was carried out from August 2017 to February 2018 on lactating dairy cows, one-humped dromedary camels, and goats to determine mastitis in the Bule Hora and Dugda Dawa districts of in Southern Ethiopia. Milk samples from 564 udder quarters and udder halves from 171 animals consisting of 60 dairy cows, 51 camels, and 60 goats were tested for mastitis. Sixty-four positive udder milk samples were cultured, and bacterial mastitis pathogens were isolated and identified. The antibiotic resistance of bacterial isolates from milk with mastitis was tested against nine antimicrobials commonly used in the study area. Cow- and quarter-level prevalence of mastitis in dairy cows, camels, and goats was 33.3%, 26.3%, and 25% and 17.6%, 14.5%, and 20%, respectively. In cattle, the prevalence was significantly higher in Dugda Dawa than in Bule Hora. Major bacterial isolates were coagulase-negative Staphylococcus species (39.1%), S. aureus (17.2%), S. hyicus (14.1%), and S. intermedius and Escherichia coli (9.4% each). In camels, udder abnormality and mastitis were significantly higher in late lactation than in early lactation. Mastitis tends to increase with parity in camels. E. coli isolates were highly resistant to spectinomycin, vancomycin, and doxycycline, whereas most S. aureus isolates were multidrug-resistant. Most of the rural and periurban communities in this area consume raw milk, which indicates a high risk of infection with multidrug-resistant bacteria. We recommend a community-focused training program to improve community awareness of the need to boil milk and the risk of raw milk consumption.

Production and Characterization of High Value Prebiotics From Biorefinery-Relevant Feedstocks.

Hemicellulose, a structural polysaccharide and often underutilized co-product stream of biorefineries, could be used to produce prebiotic ingredients with novel functionalities. Since hot water pre-extraction is a cost-effective strategy for integrated biorefineries to partially fractionate hemicellulose and improve feedstock quality and performance for downstream operations, the approach was applied to process switchgrass (SG), hybrid poplar (HP), and southern pine (SP) biomass at 160°C for 60 min. As a result, different hemicellulose-rich fractions were generated and the chemical characterization studies showed that they were composed of 76-91% of glucan, xylan, galactan, arabinan, and mannan oligosaccharides. The hot water extracts also contained minor concentrations of monomeric sugars (≤18%), phenolic components (≤1%), and other degradation products (≤3%), but were tested for probiotic activity without any purification. When subjected to batch fermentations by individual cultures of Lactobacillus casei, Bifidobacterium bifidum, and Bacteroides fragilis, the hemicellulosic hydrolysates elicited varied responses. SG hydrolysates induced the highest cell count in L. casei at 8.6 log10 cells/ml, whereas the highest cell counts for B. fragilis and B. bifidum were obtained with southern pine (5.8 log10 cells/ml) and HP hydrolysates (6.4 log10 cells/ml), respectively. The observed differences were attributed to the preferential consumption of mannooligosaccharides in SP hydrolysates by B. fragilis. Lactobacillus casei preferentially consumed xylooligosaccharides in the switchgrass and southern pine hydrolysates, whereas B. bifidum consumed galactose in the hybrid poplar hydrolysates. Thus, this study (1) reveals the potential to produce prebiotic ingredients from biorefinery-relevant lignocellulosic biomass, and (2) demonstrates how the chemical composition of hemicellulose-derived sources could regulate the viability and selective proliferation of probiotic microorganisms.