Effects of Compression Processing Parameters and Antioxidants on Molecular Degradation of Biodegradable Poly-L-Lactide (PLLA)

The purpose of this research was to find a combination of poly (L-lactic acid), also known as poly-L-lactide or (PLLA) and antioxidants that would, together, produce a product whose degradation rate would be advantageous for use in biodegradable medical implants. Intrinsic viscosity tests were conducted on compression molded samples of PLLA that were molded at various processing parameters in order to find optimal parameters. The optimal processing parameters were found to be time 10 minutes, temperature 220°C, and pressure 1000 psi. The molecular weight of PLLA sample was taken while pressure, time, and temperature were varied. As pressure increased, no significant change in molecular weight was noticed. When the time was increased, the molecular weight decreased. Then when temperature increased, the molecular weight of PLLA also decreased. Compression molded samples were also made with a mixture of PLLA and antioxidants. At 0.6% of concentration, antioxidants in this study did not prove any benefits for PLLA to reduce the molecular degradation. All samples with 0.6% antioxidants showed lower molecular weight than pure PLLA. Outcomes of this research provide a better understanding of biodegradable polymers and the factors that contribute to a successful mold. This research develops the best possible poly-L-lactic acid compression sample for further studies in the industry, including medical applications

Effects of Compression Processing Parameters and Antioxidants on Molecular Degradation of Biodegradable Poly-L-Lactide (PLLA)

The purpose of this research was to find a combination of poly (L-lactic acid), also known as poly-L-lactide or (PLLA) and antioxidants that would, together, produce a product whose degradation rate would be advantageous for use in biodegradable medical implants. Intrinsic viscosity tests were conducted on compression molded samples of PLLA that were molded at various processing parameters in order to find optimal parameters. The optimal processing parameters were found to be time 10 minutes, temperature 220°C, and pressure 1000 psi. The molecular weight of PLLA sample was taken while pressure, time, and temperature were varied. As pressure increased, no significant change in molecular weight was noticed. When the time was increased, the molecular weight decreased. Then when temperature increased, the molecular weight of PLLA also decreased. Compression molded samples were also made with a mixture of PLLA and antioxidants. At 0.6% of concentration, antioxidants in this study did not prove any benefits for PLLA to reduce the molecular degradation. All samples with 0.6% antioxidants showed lower molecular weight than pure PLLA. Outcomes of this research provide a better understanding of biodegradable polymers and the factors that contribute to a successful mold. This research develops the best possible poly-L-lactic acid compression sample for further studies in the industry, including medical applications

Associations of region-specific foot pain and foot biomechanics: the framingham foot study

BACKGROUND. Specific regions of the foot are responsible for the gait tasks of weight acceptance, single-limb support, and forward propulsion. With region foot pain, gait abnormalities may arise and affect the plantar pressure and force pattern utilized. Therefore, this study’s purpose was to evaluate plantar pressure and force pattern differences between adults with and without region-specific foot pain. METHODS. Plantar pressure and force data were collected on Framingham Foot Study members while walking barefoot at a self-selected pace. Foot pain was evaluated by self-report and grouped by foot region (toe, forefoot, midfoot, or rearfoot) or regions (two or three or more regions) of pain. Unadjusted and adjusted linear regression with generalized estimating equations was used to determine associations between feet with and without foot pain. RESULTS. Individuals with distal foot (forefoot or toes) pain had similar maximum vertical forces under the pain region, while those with proximal foot (rearfoot or midfoot) pain had different maximum vertical forces compared to those without regional foot pain (referent). During walking, there were significant differences in plantar loading and propulsion ranging from 2% to 4% between those with and without regional foot pain. Significant differences in normalized maximum vertical force and plantar pressure ranged from 5.3% to 12.4% and 3.4% to 24.1%, respectively, between those with and without regional foot pain. CONCLUSIONS. Associations of regional foot pain with plantar pressure and force were different by regions of pain. Region-specific foot pain was not uniformly associated with an increase or decrease in loading and pressure patterns regions of pain

Uropathogenic Escherichia coli superinfection enhances the severity of mouse bladder infection

Urinary tract infections (UTIs) afflict over 9 million women in America every year, often necessitating long-term prophylactic antibiotics. One risk factor for UTI is frequent sexual intercourse, which dramatically increases the risk of UTI. The mechanism behind this increased risk is unknown; however, bacteriuria increases immediately after sexual intercourse episodes, suggesting that physical manipulation introduces periurethral flora into the urinary tract. In this paper, we investigated whether superinfection (repeat introduction of bacteria) resulted in increased risk of severe UTI, manifesting as persistent bacteriuria, high titer bladder bacterial burdens and chronic inflammation, an outcome referred to as chronic cystitis. Chronic cystitis represents unchecked luminal bacterial replication and is defined histologically by urothelial hyperplasia and submucosal lymphoid aggregates, a histological pattern similar to that seen in humans suffering chronic UTI. C57BL/6J mice are resistant to chronic cystitis after a single infection; however, they developed persistent bacteriuria and chronic cystitis when superinfected 24 hours apart. Elevated levels of interleukin-6 (IL-6), keratinocyte cytokine (KC/CXCL1), and granulocyte colony-stimulating factor (G-CSF) in the serum of C57BL/6J mice prior to the second infection predicted the development of chronic cystitis. These same cytokines have been found to precede chronic cystitis in singly infected C3H/HeN mice. Furthermore, inoculating C3H/HeN mice twice within a six-hour period doubled the proportion of mice that developed chronic cystitis. Intracellular bacterial replication, regulated hemolysin (HlyA) expression, and caspase 1/11 activation were essential for this increase. Microarrays conducted at four weeks post inoculation in both mouse strains revealed upregulation of IL-1 and antimicrobial peptides during chronic cystitis. These data suggest a mechanism by which caspase-1/11 activation and IL-1 secretion could predispose certain women to recurrent UTI after frequent intercourse, a predisposition predictable by several serum biomarkers in two murine models

Enterococcus faecalis overcomes foreign body-mediated inflammation to establish urinary tract infections

Urinary catheterization elicits major histological and immunological changes that render the bladder susceptible to microbial invasion, colonization, and dissemination. However, it is not understood how catheters induce these changes, how these changes act to promote infection, or whether they may have any protective benefit. In the present study, we examined how catheter-associated inflammation impacts infection by Enterococcus faecalis, a leading cause of catheter-associated urinary tract infection (CAUTI), a source of significant societal and clinical challenges. Using a recently optimized murine model of foreign body-associated UTI, we found that the implanted catheter itself was the primary inducer of inflammation. In the absence of the silicone tubing implant, E. faecalis induced only minimal inflammation and was rapidly cleared from the bladder. The catheter-induced inflammation was only minimally altered by subsequent enterococcal infection and was not suppressed by inhibitors of the neurogenic pathway and only partially by dexamethasone. Despite the robust inflammatory response induced by urinary implantation, E. faecalis produced biofilm and high bladder titers in these animals. Induction of inflammation in the absence of an implanted catheter failed to promote infection, suggesting that the presence of the catheter itself is essential for E. faecalis persistence in the bladder. Immunosuppression prior to urinary catheterization enhanced E. faecalis colonization, suggesting that implant-mediated inflammation contributes to the control of enterococcal infection. Thus, this study underscores the need for novel strategies against CAUTIs that seek to reduce the deleterious effects of implant-mediated inflammation on bladder homeostasis while maintaining an active immune response that effectively limits bacterial invaders

Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection

Urinary tract infections (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), are one of the leading bacterial infections due to their high frequency and rate of recurrence. Both type 1 pilus adhesive organelles (fim) and the QseC sensor kinase have been implicated in UPEC virulence during UTI and have been individually reported to be promising drug targets. Deletion of qseC leads to pleiotropic effects due to unregulated activation of the cognate response regulator QseB, influencing conserved metabolic processes and diminishing expression of virulence genes, including type 1 pili. Here, we discern the type 1 pilus-dependent and -independent effects that contribute to the virulence attenuation of a UPEC qseC deletion mutant in a murine model of experimental UTI. We show that although a ΔqseC mutant restored for type 1 pilus expression regains the ability to colonize the host and initiate acute infection up to 16 h postinfection, it is rapidly outcompeted during acute infection when coinoculated with a wild-type strain. As a result, this strain has a diminished capacity to establish chronic infection. A prophylactic oral dose of a FimH small-molecular-weight antagonist (ZFH-02056) further reduced the ability of the qseC mutant to establish chronic infection. Thus, loss of QseC significantly enhances the efficacy of ZFH-02056. Collectively, our work indicates that type 1 pili and QseC become critical in different infection stages, and that dual targeting of these factors has an additive effect on ablating UPEC virulence

Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions

Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state–mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved “moderate” affinity to optimize persistence in the bladder during UTI

Hallux valgus and plantar pressure loading: the Framingham foot study

Background: Hallux valgus (HV), a common structural foot deformity, can cause foot pain and lead to limited mobility. The purpose of this study was to evaluate differences in plantar pressure and force during gait by HV status in a large population-based cohort of men and women. Methods: A trained examiner performed a validated physical examination on participants’ feet and recorded the presence of hallux valgus and other specific foot disorders. Each foot was classified into one of four mutually exclusive groups based on the foot examination. Foot groups were: (i) HV only, (ii) HV and at least one additional foot disorder (FD), (iii) no HV but at least one other FD, and (iv) neither HV nor FD (referent). Biomechanical data for both feet were collected using Tekscan Matscan. Foot posture during quiet standing, using modified arch index (MAI), and foot function during gait, using center of pressure excursion index (CPEI), were calculated per foot. Further, walking scans were masked into eight sub-regions using Novel Automask, and peak pressure and maximum force exerted in each region were calculated. Results: There were 3205 participants, contributing 6393 feet with complete foot exam data and valid biomechanical measurements. Participants with HV had lower hallucal loading and higher forces at lesser toes as well as higher MAI and lower CPEI values compared to the referent. Participants with HV and other FDs were also noted to have aberrant rearfoot forces and pressures. Conclusions: These results suggest that HV alters foot loading patterns and pressure profiles. Future work should investigate how these changes affect the risk of other foot and lower extremity ailments

Factors affecting center of pressure in older adults: the Framingham Foot Study

Background: Although aberrant foot movement during gait has been associated with adverse outcomes in the lower extremities in clinical patients, few studies have analyzed population differences in foot function. The purpose of this study was to assess demographic differences in foot function in a large population-based study of community-dwelling adults. Methods: Participants in this study were from the Framingham Foot Study. Walking data were collected from both feet using a Tekscan Matscan pressure mat. Foot function was characterized using the center of pressure excursion index (CPEI). T-tests were used to assess differences between population subsets based on sex, and in men and women separately, age, body mass index (BMI), physical activity and in women, past high heel use. Results: There were 2111 participants included in this analysis. Significant differences in CPEI were noted by sex (p< 0.0001), by age in women (p = 0.04), and by past high heel use in women (p = 0.04). Conclusions: Foot function during gait was affected by sex, as well as by age and shoe-wear in women, but not by BMI or physical activity. Future work will evaluate possible relations between CPEI and outcomes such as falls, sarcopenia, and lower extremity function

Foot Disorders, Foot Posture, and Foot Function: The Framingham Foot Study

Introduction: Foot disorders are common among older adults and may lead to outcomes such as falls and functional limitation. However, the associations of foot posture and foot function to specific foot disorders at the population level remain poorly understood. The purpose of this study was to assess the relation between specific foot disorders, foot posture, and foot function. Methods: Participants were from the population-based Framingham Foot Study. Quintiles of the modified arch index and center of pressure excursion index from plantar pressure scans were used to create foot posture and function subgroups. Adjusted odds ratios of having each specific disorder were calculated for foot posture and function subgroups relative to a referent 3 quintiles. Results: Pes planus foot posture was associated with increased odds of hammer toes and overlapping toes. Cavus foot posture was not associated with the foot disorders evaluated. Odds of having hallux valgus and overlapping toes were significantly increased in those with pronated foot function, while odds of hallux valgus and hallux rigidus were significantly decreased in those with supinated function. Conclusions: Foot posture and foot function were associated with the presence of specific foot disorders