A Novel Potential Treatment for Diabetic Foot Ulcers and Non-Healing Ulcers - Case Series.

INTRODUCTION: Appropriate care and treatment of a wound is the need of the hour whether it is an infected or a non-infected wound. If wound healing is delayed for some reason, it leads to serious complications and further increases the hospital stay and cost of treatment. Herein, we describe a novel antimicrobial wound dressing formulation (VG111), with an objective to generate the preliminary data showing the distinct advantages in various types of wounds. METHOD: This case series involved the treatment of acute cases of wounds or chronic wounds that did not respond well to conventional wound healing treatments with VG111 in patients with different etiologies. Thirteen cases of patients that included patients with diabetes, pressure ulcers, burns, trauma, and others treated with VG111 showed rapid wound healing in all the cases, even obviating the need for a graft when complete skin regeneration occurred RESULT: This was illustrated by clearing of the wound infections, reduction/disappearance of the exudate, appearance of intense granulation, epithelialization, and anti-biofilm activity followed by complete wound closure. This VG111 precludes the need for systemic antimicrobial agents in localized infections and therefore, this single agent is an attempt to address the limitations and the drawbacks of the available products. CONCLUSION: Despite patients belonging to the old age group and having comorbidities like diabetes, still VG111 showed effective rapid wound healing, and that too without any scar formation in hardto-heal, infected, and non-infected wounds

Telegraphic code for fingerprints: How justice was denied to the innovator who helped ameliorate the criminal justice system.

In the last decade of the nineteenth century, an Indian officer of the Bengal Police, sub-inspector Hem Chandra Bose (1867-1949) invented the telegraphic code system for fingerprints and published it in 1916. Sir Charles Stockley Collins of Scotland Yard, who is worldwide recognized as the originator of fingerprint telegraphic technique, published his findings in 1921-five years after Bose's publication. Likewise Bose devised the single digit fingerprint classification system three years prior to Harry Battley, also of the Scotland Yard. The then British government honored Bose by awarding him an honorarium of Rs. 5000/- and by conferring the title of Rai Bahadur on him. However, this is not enough; Bose ought to be more widely recognized as a pioneer of the science of fingerprinting.

The Influence of Coffee on Reducing Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients With Type 2 Diabetes: A Review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver disease characterized by hepatic fat accumulation associated with various severities of inflammation and scarring. As studies explore specialized treatments, emerging evidence suggests a potential protective effect of coffee consumption. Consumption of coffee or its components, such as caffeine and/or chlorogenic acid (CA), can reduce markers of liver injury and induce a myriad of other health benefits. However, there is limited research on patients with both MASLD and type 2 diabetes (T2D). Current research suggests that patients with MASLD are at greater risk of developing T2D and future liver-related complications and vice versa. Given that both MASLD and T2D are global burdens, the present literature review analyzes current research to identify trends and determine if coffee can be a viable treatment for MASLD patients with T2D. Results indicate that coffee consumption may protect against MASLD in T2D patients who are overweight/obese through a declined rate of weight gain, inhibition of the mammalian target of rapamycin (mTOR) gene, and insignificant changes to the gut microbiome. More longitudinal research on human subjects is needed to establish a causal relationship between coffee consumption and MASLD alleviation.

Exploring Endolysin-Loaded Alginate-Chitosan Nanoparticles as Future Remedy for Staphylococcal Infections.

Endolysins are a novel class of antibacterials with proven efficacy in combating various bacterial infections, in vitro and in vivo. LysMR-5, an endolysin derived from phage MR-5, demonstrated high lytic activity in our laboratory against multidrug-resistant S. aureus (MRSA) and S. epidermidis strains. However, endolysin and proteins in general are associated with instability and short in vivo half-life, consequently limiting their usage as pharmaceutical preparation to treat bacterial infections. Nanoencapsulation of endolysins could help to achieve better therapeutic outcome, by protecting the proteins from degradation, providing sustained release, thus could increase their stability, shelf life, and therapeutic efficacy. Hence, in this study, the feasibility of alginate-chitosan nanoparticles (Alg-Chi NPs) to serve as drug delivery platform for LysMR-5 was evaluated. LysMR-5-loaded nanoparticles were prepared by calcium ion-induced pre-gelation of alginate core and its complexation with chitosan. The formation of nanoparticles was confirmed on the basis of DLS, zeta potential, and electron microscopy imaging. The LysMR-5-loaded nanoparticles presented a hydrodynamic diameter of 276.5 ± 42, a PDI of 0.342 ± 0.02, a zeta potential - 25 mV, and an entrapment efficiency of 62 ± 3.1%. The potential ionic interaction between alginate, chitosan, and LysMR-5 was investigated by FT-IR and SEM-EDX analysis. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), nano-sized particles with characteristic morphology were seen. Different antibacterial assays and SDS-PAGE analysis showed no change in endolysin's structural integrity and bioactivity after entrapment. A direct antibacterial effect of blank Alg-Chi Nps, showing enhanced bactericidal activity upon LysMR-5 loading, was observed against S. aureus. At physiological pH (7.2), the release profile of LysMR-5 from Alg-Chi NPs showed a biphasic release and followed a non-Fickian release mechanism. The biocompatible nature as revealed by cytocompatibility and hemocompatibility studies endorsed their use as drug delivery system for in vivo studies. Collectively, these results demonstrate the potential of Alg-Chi NPs as nano-delivery vehicle for endolysin LysMR-5 and other therapeutic proteins for their use in various biomedical applications.

A potent enzybiotic against methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most dreadful infectious agents, responsible for high mortality and morbidity in both humans and animals. The increased prevalence of multidrug-resistant (MDR) Staphylococcus aureus strains has limited the number of available treatment options, which calls for the development of alternative and effective modalities against MDR S. aureus. Endolysins are bacteriophage-derived antibacterials, which attack essential conserved elements of peptidoglycan that are vital for bacterial survival, making them promising alternatives or complements to existing antibiotics for tackling such infections. For developing endolysin lysin-methicillin-resistant-5 (LysMR-5) as an effective antimicrobial agent, we evaluated its physical and chemical characteristics, and its intrinsic antibacterial activity against staphylococcal strains, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we cloned, expressed, and purified LysMR-5 from S. aureus phage MR-5. In silico analysis revealed that LysMR-5 harbors two catalytic and one cell wall-binding domain. Biochemical characterization and LC-MS analysis showed that both catalytic domains were active and had no dependence on divalent ions for their action, Zn2+ exerted a negative effect. The optimal lytic activity of the endolysin was at 37 °C/pH 7.0 and in the presence of ≥ 300 mM concentration of NaCl. Circular dichroism (CD) demonstrated a loss in secondary structure with an increase in temperature confirming the thermosensitive nature of endolysin. Antibacterial assays revealed that LysMR-5 was active against diverse clinical isolates of staphylococci. It showed high lytic efficacy against S. aureus ATCC 43300, as an endolysin concentration as low as 15 µg/ml was sufficient to achieve maximum lytic activity within 30 min and it was further confirmed by scanning electron microscopy. Our results indicate that rapid and strong bactericidal activity of LysMR-5 makes it a valuable candidate for eradicating multidrug-resistant S. aureus.

Liposome Entrapment of Bacteriophages Improves Wound Healing in a Diabetic Mouse MRSA Infection.

Diabetic populations are more prone to developing wound infections which results in poor and delayed wound healing. Infection with drug resistant organisms further worsen the situation, driving searches for alternative treatment approaches such as phage therapy. Major drawback of phage therapy, however, is low phage persistence in situ, suggesting further refinement of the approach. In the present work we address this issue by employing liposomes as delivery vehicles. A liposome entrapped phage cocktail was evaluated for its ability to resolve a Staphylococcus aureus-induced diabetic excission wound infection. Two characterized S. aureus specific lytic phages, MR-5 and MR-10 alone, in combination (cocktail), or entrapped in liposomes (versus as free phages) were assesed for their therapeutic efficacy in resolving diabetic wound infection. Mice treated with free phage cocktail showed significant reduction in wound bioburden, greater wound contraction and faster tissue healing than with free monophage therapy. However, to further enhance the availability of viable phages the encapsulation of phage cocktail in the liposomes was done. Results of in vitro stability studies and in vivo phage titer determination, suggests that liposomal entrapment of phage cocktail can lead to better phage persistence at the wound site. A 2 log increase in phage titre, however, was observed at the wound site with liposome entrapped as compared to the free phage cocktail, and this was associaed with increased rates of infection resolution and wound healing. Entrapment of phage cocktails within liposomes thus could represent an attractive approach for treatment of bacterial infections, not responding to antibiotis as increased phage persistence in vitro and in vivo at the wound site was observed.

A comparative study to check fracture strength of provisional fixed partial dentures made of autopolymerizing polymethylmethacrylate resin reinforced with different materials: An in vitro study.

AIM: The purpose of the study was to evaluate the fracture strength of provisional fixed partial dentures made of autopolymerizing polymethylmethacrylate (PMMA) resin using different types of reinforcement materials to determine the best among them. MATERIALS AND METHODS: Fifty samples were made (10 samples for each group) with autopolymerizing PMMA resin using reinforcement materials (stainless steel wire: looped and unlooped and glass fiber: loose and unidirectional) as 3-unit posterior bridge. The test specimens were divided into five groups depending on the reinforcing material as Group I, II, III, IV, and V; Group I: PMMA unreinforced (control group), Group II: PMMA reinforced with stainless steel wire (straight ends), Group III: PMMA reinforced with stainless steel wire (looped ends), Group IV: PMMA reinforced with unidirectional glass fibers, and Group V: PMMA reinforced with randomly distributed glass fibers. Universal testing machine was used to evaluate and compare the fracture strength of samples. Comparison of mean ultimate force and ultimate stress was done employing one-way analysis of variance and Tukey's post hoc tests. RESULTS: The highest and lowest mean ultimate force and mean ultimate stress were of Group IV and I, respectively. Tukey's post hoc honestly significant difference multiple comparison for mean ultimate force and stress shows the increase in strength to be statistically significant (P < 0.05) except for the samples reinforced with randomly distributed glass fibers (P > 0.05). CONCLUSION: Unidirectional glass fibers showed the maximum strength, which was comparable to mean values of both stainless steel wire groups. Low cost and easy technique of using stainless steel wire make it the material of choice over the unidirectional glass fiber for reinforcement in nonesthetic areas where high strength is required.

Photoreactivation and dark repair of environmental E. coli strains following 24 kHz continuous ultrasound and UV-C irradiation.

In this study, effects of 24 kHz continuous ultrasound and UV-C on inactivation and potential repair of environmental E. coli strains were studied through a culture based method and a metabolic activity assay. Three environmental E. coli strains isolated from fecal samples of feral hog and deer and treated wastewater effluent were studied and compared with a laboratory E. coli strain (ATCC® 10798). Metabolic activity of E. coli cells during the inactivation and repair period was assessed using the AlamarBlue® assay. Transmission electron microscopy assays were also performed to evaluate morphological damage of bacterial cell wall. After 24 h of photoreactivation period, laboratory E. coli strain (ATCC® 10798) reactivated by 30% and 42% in contrast to E. coli isolate from treated wastewater effluent, which reactivated by 53% and 82% after ultrasound and UV-C treatment, respectively. Possible shearing and reduction in cell size of E. coli strains exposed to ultrasound was revealed by transmission electron micrographs. Metabolic activity of E. coli strains was greatly reduced due to morphological damage to cell membrane caused by 24 kHz continuous ultrasound. Based upon experimental data and TEM micrographs, it could be concluded that ultrasound irradiation has potential in advanced water treatment and water reuse applications.

Functional Application of Noble Metal Nanoparticles In Situ Synthesized on Ramie Fibers.

Different functions were imparted to ramie fibers through treatment with noble metal nanoparticles including silver and gold nanoparticles. The in situ synthesis of silver and gold nanoparticles was achieved by heating in the presence of ramie fibers in the corresponding solutions of precursors. The unique optical property of synthesized noble metal nanoparticles, i.e., localized surface plasmon resonance, endowed ramie fibers with bright colors. Color strength (K/S) of fibers increased with heating temperature. Silver nanoparticles were obtained in alkaline solution, while acidic condition was conducive to gold nanoparticles. The optical properties of treated ramie fibers were investigated using UV-vis absorption spectroscopy. Scanning electron microscopy (SEM) was employed to observe the morphologies of silver and gold nanoparticles in situ synthesized on fibers. The ramie fibers treated with noble metal nanoparticles showed remarkable catalytic activity for reduction of 4-nitrophenol (4-NP) by sodium borohydride. Moreover, the silver nanoparticle treatment showed significant antibacterial property on ramie fibers.

Effectiveness of ultrasound, UV-C, and photocatalysis on inactivation kinetics of Aeromonas hydrophila.

In this study, bactericidal effects of 24 kHz ultrasound, ultraviolet (UV-C) irradiation, and titanium dioxide (TiO2) photocatalyst were studied on inactivation of Aeromonas hydrophila, an emerging pathogen listed on the US Environmental Protection Agency's (US EPA) candidate contaminant list. Metabolic activity (using the AlamarBlue dye) assays were performed to assess the residual activity of the microbial cells after the disinfection treatments along with culture-based methods. A faster inactivation rate of 1.52 log min(-1) and inactivation of 7.62 log10 was observed within 5 min of ultrasound exposure. Ultrasound treated cells repaired by 1.4 log10 in contrast to 5.3 log10 repair for UV-C treated cells. Ultrasound treatment significantly lowered the reactivation of Aeromonas hydrophila in comparison to UV-C- and UV-C-induced photocatalysis. Ultrasound appeared to be an effective means of inactivating Aeromonas hydrophila and could be used as a potential disinfection method for water and wastewater reuse.

Intrinsic tensile properties of cocoon silk fibres can be estimated by removing flaws through repeated tensile tests.

Silk fibres from silkworm cocoons have lower strength than spider silk and have received less attention as a source of high-performance fibres. In this work, we have used an innovative procedure to eliminate the flaws gradually of a single fibre specimen by retesting the unbroken portion of the fibre, after each fracture test. This was done multiple times so that the final test may provide the intrinsic fibre strength. During each retest, the fibre specimen began to yield once the failure load of the preceding test was exceeded. For each fibre specimen, a composite curve was constructed from multiple tests. The composite curves and analysis show that strengths of mass-produced Muga and Eri cocoon silk fibres increased from 446 to 618 MPa and from 337 to 452 MPa, respectively. Similarly, their toughness increased from 84 to 136 MJ m(-3) and from 61 to 104 MJ m(-3), respectively. Composite plots produced significantly less inter-specimen variations compared to values from single tests. The fibres with reduced flaws as a result of retests in the tested section have a tensile strength and toughness comparable to naturally spun dragline spider silk with a reported strength of 574 MPa and toughness of 91-158 MJ m(-3), which is used as a benchmark for developing high-performance fibres. This retesting approach is likely to provide useful insights into discrete flaw distributions and intrinsic mechanical properties of other fatigue-resistant materials.

Facts and myths of antibacterial properties of silk.

Silk cocoons provide protection to silkworm from biotic and abiotic hazards during the immobile pupal phase of the lifecycle of silkworms. Protection is particularly important for the wild silk cocoons reared in an open and harsh environment. To understand whether some of the cocoon components resist growth of microorganisms, in vitro studies were performed using gram negative bacteria Escherichia coli (E. coli) to investigate antibacterial properties of silk fiber, silk gum, and calcium oxalate crystals embedded inside some cocoons. The results show that the previously reported antibacterial properties of silk cocoons are actually due to residues of chemicals used to isolate/purify cocoon elements, and properly isolated silk fiber, gum, and embedded crystals free from such residues do not have inherent resistance to E. coli. This study removes the uncertainty created by previous studies over the presence of antibacterial properties of silk cocoons, particularly the silk gum and sericin.

Photoprotection by silk cocoons.

A silk cocoon protects a silkworm during its pupal stage from various threats. We systematically investigated the role of fiber, sericin, and embedded crystals in the UV protection of a silk cocoon. Diffuse reflectance and UV absorbance were measured and free radicals generated during exposure to UV radiation were quantified using photoinduced chemiluminescence (PICL). We identified the response to both UV-A and UV-B radiations by silk materials and found that sericin was primarily responsible for UV-A absorption. When sericin was removed, the photoinduced chemiluminescence intensity increased significantly, indicating higher UV-A-induced reactions of cocoons in the absence of sericin. There is progressively higher sericin content toward the outer part of the cocoon shell that allows an effective shield to pupae from UV radiation and resists photodegradation of silk fibers. The study will inspire development of advanced organic photoprotective materials and designing silk-based, free-radical-scavenging antioxidants.

Directed evolution: an approach to engineer enzymes.

Directed evolution is being used increasingly in industrial and academic laboratories to modify and improve commercially important enzymes. Laboratory evolution is thought to make its biggest contribution in explorations of non-natural functions, by allowing us to distinguish the properties nurtured by evolution. In this review we report the significant advances achieved with respect to the methods of biocatalyst improvement and some critical properties and applications of the modified enzymes. The application of directed evolution has been elaborately demonstrated for protein solubility, stability and catalytic efficiency. Modification of certain enzymes for their application in enantioselective catalysis has also been elucidated. By providing a simple and reliable route to enzyme improvement, directed evolution has emerged as a key technology for enzyme engineering and biocatalysis.

Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug delivery.

Pharmaceutical technologists have been working extensively on various mucoadhesive polymeric systems to create an intimate and prolonged contact at the site of administration. Chitosan is one of the most promising polymers because of its non-toxic, polycationic biocompatible, biodegradable nature, and particularly due to its mucoadhesive and permeation enhancing properties. Due to its potential importance in controlled drug delivery applications, pharmaceutical scientists have exploited this mucoadhesive polymer. However, chitosan suffers from limited solubility at physiological pH and causes presystemic metabolism of drugs in intestinal and gastric fluids in the presence of proteolytic enzymes. These inherent drawbacks of chitosan have been overcome by forming derivatives such as carboxylated, various conjugates, thiolated, and acylated chitosan, thus providing a platform for sustained release formulations at a controlled rate, prolonged residence time, improved patient compliance by reducing dosing frequency, enhanced bioavailability and a significant improvement in therapeutic efficacy. We have explored the potential benefits of these improved chitosan derivatives in modern drug delivery.

Control of blood pressure and other cardiovascular risk factors at different practice settings: outcomes of care provided to diabetic women compared to men.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes. To determine the proportion of patients who met the American Diabetes Association guidelines for control of CVD risk factors and to assess the achievement of these guidelines in women compared with men, we conducted a cross-sectional study of 3678 diabetic cohorts followed at seven medical centers, two Veteran Administration hospitals, three urban clinics, and two suburban clinics. Overall, 28% met the target blood pressure of <130/80 mm Hg, 48.8% achieved a goal low-density lipoprotein cholesterol of <100 mg/dL, and 35.8% had hemoglobin A1c of <7%. Gender comparisons of 2788 diabetic patients at urban and suburban centers showed that women had a lower percentage of low-density lipoprotein cholesterol <100 mg/dL (45.8 vs. 51.3, p<0.01) and a lower percentage of screening for retinopathy (54 vs. 60, p<0.01) and nephropathy (37 vs. 49, p<0.01). However, overall there were no gender differences in the percentage of patients who achieved a goal blood pressure <130/80 mm Hg or hemoglobin A1c <7%. Control of blood pressure and other CVD risk factors in diabetic patients was largely suboptimal, especially for diabetic women. These observations underscore the need for better strategies for control of CVD risk in the diabetic population in general, and women in particular.

Cytomegalovirus-induced gingival hyperplasia.

We report a rare presentation of gingival hyperplasia associated with cytomegalovirus infection in a 33-year-old human immunodeficiency virus-infected man.

Diabetes and cardiovascular diseases.

Diabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetic people have cardiovascular disease (CVD) risk factors comparable to those of nondiabetics who have had a myocardial infarction or stroke. Physiologic changes in diabetic hypertensive people include endothelial dysfunction, altered platelet activity, and microalbuminuria, all of which may increase coronary heart disease risk. Hyperglycemia and dyslipidemia have been shown to effect physiologic changes in the vasculature; therefore, establishing normoglycemia, reducing cholesterol levels, and controlling blood pressure are the primary and initial goals in the management of diabetic hypertensive patients. The atherosclerotic risk is greatest in poorly controlled patients, possibly because of associated hypercholesterolemia and hypertriglyceridemia. Aggressive management of risk factors such as hypertension, dyslipidemia, and platelet dysfunction in diabetics has been shown to reduce morbidity and mortality in prospective randomized controlled clinical trials. In this article we review the impact of diabetes mellitus on cardiovascular morbidity and mortality.

Control of cardiovascular risk factors in patients with diabetes and hypertension at urban academic medical centers.

OBJECTIVE: There are national mandates to reduce blood pressure (BP) to <130/85 mmHg, LDL cholesterol to <100 mg/dl, and HbA(1c) to <7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals. RESEARCH DESIGN AND METHODS: Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics. RESULTS: Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of <100 mg/dl, 26.7% had an HbA(1c) <7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA(1c). CONCLUSIONS: Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems.