Critical Evaluation of Lateral Calcaneal Artery Fascio-Cutaneous Flap in Re-Surfacing Posterior Heel Defects: A Review of 24 Cases.

Purpose and background: To assess feasibility and functional acceptability of lateral calcaneal artery fascio-cutaneous flap (LCAFCF) in providing cover to posterior heel defects in single stage. Aims and objectives: To provide stable and sensate cover to small and moderate posterior heel defects. Materials and methods: This review was conducted in department of Burns & Plastic Surgery of Postgraduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana between October 2021 and September 2022 to analyse the clinical outcome of LCAFCF in 24 patients (18 males, 6 females) aged between 20 and 35 years who had chronic dry wounds n = 9, failed primary reconstruction by reverse sural flap n = 1, granulated wounds n = 8, exposed achilles tendons n = 4 and scarred tissue restricting ankle joint movements n = 2 in region of posterior heel following trauma, while riding motor-cycle. Course of lateral calcaneal artery was marked with hand-held doppler. Flap size ranged from 3 to 3.5 cm in width and 5.5-7.5 cm length. The donor sites were split skin grafted. Sutures were removed on 22nd day of surgery. Mean follow up was 13 months. Results: All flaps survived. Two had partial loss of skin graft and two developed hyperkeratosis on grafted site. Sensations in flap, regain of movements of ankle joint, comfort of walking and driving were acceptable. Conclusions: LCAFCF is handy, safe and reliable flap for re-surfacing difficult wounds of posterior heel, therefore should be included in surgical armamentarium.

Comparing the Effectiveness of Hands-on vs. Observational Training of Residents in Interlaminar Epidural Steroid Injections (ILESI) Using a High-Fidelity Spine Simulator.

Introduction The Accreditation Council for Graduate Medical Education (ACGME) requires that residents in the Physical Medicine and Rehabilitation (PM&R) residency observe or perform certain interventional procedures, one of which is an interlaminar epidural steroid injection (ILESI). While the traditional learning model relying heavily on observation is commonplace, it leaves the practice phase of learning to happen on real patients. High-fidelity simulation may be a worthwhile alternative as a training approach to increase physician comfort with the procedure and improve patient safety. Methods Current PM&R residents from two programs between their second and fourth year, inclusively, who lacked prior training experience in ILESI attended one hour of either: (1) an experimental arm of supervised hands-on training on a simulation device or (2) a control arm observing the procedures performed by an attending on the same device. Assignments were made based on resident schedule availability. Pre-training knowledge, training, and post-training knowledge were assessed at the Multidisciplinary Pain Clinic at Montefiore Medical Center. Participants were assessed on their procedural competence using an adapted version of a previously published grading checklist before the session. Participants also evaluated their confidence in performing the procedure prior to and after training. Data was analyzed using the Wilcoxon signed-rank test and the Wilcoxon rank-sum test. SAS Version 9.4 was used for analysis. Results Fifteen residents initially participated, but three residents dropped out at the 15-week follow-up. There was a significant increase in test scores in both arms immediately after the intervention (p=0.008 in control, p=0.016 in the experiment), with greater improvement shown in the hands-on training group (p=0.063). At the 15-week follow-up, there was no significant change in test scores in the control arm (p=0.969) while there was a decrease in the experiment arm (p<0.001). Conclusion Hands-on learning with high-fidelity simulation demonstrated more improvement for short-term motor-skill acquisition, while observational learning with repetition showed more benefits for long-term retention. Optimal procedural training should employ both educational modalities for best short- and long-term results.

Bacterial infections in cancer: A bilateral relationship.

Bacteria share a long commensal relationship with the human body. New findings, however, continue to unravel many complexities associated with this old alliance. In the past decades, the dysbiosis of human microbiome has been linked to tumorigenesis, and more recently to spontaneous colonization of existing tumors. The topic, however, remains open for debate as the claims for causative-prevailing dual characteristics of bacteria are mostly based on epidemiological evidence rather than robust mechanistic models. There are also no reviews linking the collective impact of bacteria in tumor microenvironments to the efficacy of cancer drugs, mechanisms of pathogen-initiated cancer and bacterial colonization, personalized nanomedicine, nanotechnology, and antimicrobial resistance. In this review, we provide a holistic overview of the bilateral relationship between cancer and bacteria covering all these aspects. Our collated evidence from the literature does not merely categorize bacteria as cancer causative or prevailing agents, but also critically highlights the gaps in the literature where more detailed studies may be required to reach such a conclusion. Arguments are made in favor of dual drug therapies that can simultaneously co-target bacteria and cancer cells to overcome drug resistance. Also discussed are the opportunities for leveraging the natural colonization and remission power of bacteria for cancer treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Wolbachia-infected ant colonies have increased reproductive investment and an accelerated life cycle.

Wolbachia is a widespread genus of maternally transmitted endosymbiotic bacteria that often manipulates the reproductive strategy and life history of its hosts to favor its own transmission. Wolbachia-mediated phenotypic effects are well characterized in solitary hosts, but effects in social hosts are unclear. The invasive pharaoh ant, Monomorium pharaonis, shows natural variation in Wolbachia infection between colonies and can be readily bred under laboratory conditions. We previously showed that Wolbachia-infected pharaoh ant colonies had more queen-biased sex ratios than uninfected colonies, which is expected to favor the spread of maternally transmitted Wolbachia Here, we further characterize the effects of Wolbachia on the short- and longer-term reproductive and life history traits of pharaoh ant colonies. First, we characterized the reproductive differences between naturally infected and uninfected colonies at three discrete time points and found that infected colonies had higher reproductive investment (i.e. infected colonies produced more new queens), particularly when existing colony queens were 3 months old. Next, we compared the long-term growth and reproduction dynamics of infected and uninfected colonies across their whole life cycle. Infected colonies had increased colony-level growth and early colony reproduction, resulting in a shorter colony life cycle, when compared with uninfected colonies.

ε-Polylysine Nanoconjugates: Value-Added Antimicrobials for Drug-Resistant Bacteria.

Antimicrobial resistance poses a serious threat to human health and is evidently not restricted to any one part of the globe. Over the last few decades, no new antibiotics have been discovered, and many antibiotics currently available are failing against several critical pathogenic strains due to emerging drug resistance. We have designed a strategy to combat deadly drug-resistant bacteria by using nanocargos that consist of gold nanoparticles (AuNPs) conjugated to ε-polylysine (PLL) and octadecanethiol (C18) either alone or in combination. These nanocargos when tested against reference strains of carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA) showed 15-20-fold higher antibacterial activity compared to free PLL. The minimum inhibitory concentration (MIC) of the nanoconjugates was found to lie between 8 and 15 µg/mL for both these bacteria, and they were also found to be nonhemolytic and nontoxic to mammalian cells. The mechanistic evaluation of antibacterial action showed alternate pathways of uptake for free PLL and the nanoconjugates. Further, the nanocargos were successfully used and found to be superior to free PLL in preventing biofilm formation in MRSA and CRAB. The PLL nanoconjugates may find applications in prevention of bacterial biofilm formation on surfaces such as surgical instruments and indwelling devices like stents, catheters, cannulas, orthopedic implants, and pacemakers.

A Dual Drug Delivery Platform for Cancer-Bacteria Cotargeting.

Bacteria can associate with mammalian cells in different ways. While some are essential for the body, others can manipulate their local environment to cause tumor-like conditions or find refuge in already existing cancerous tissues or cells, impacting not only chemotherapy through drug transformation but also antibiotic resistance through immune evasion. Despite these facts, cancer and bacterial therapies continue to be administered independently. We have developed a dual drug delivery platform, called "dualosome", that not only targets cancer cells but also clears bacteria from the cancer niche. Dualosomes comprise liposomes loaded with an anticancer drug (doxorubicin) in their core and a cationic antibacterial peptide (sushi S3) on their surface. Folic acid is also attached to the liposomal surface to impart cancer cell specificity. The efficacy of dualosomes is demonstrated on model S. typhi-infected hepatoma (Huh-7) cells, and it shows that the copackaged system is at least 75% more effective in eliminating both cell types than either drug alone, in the nanoformulated or free form. This improved performance is attributed to the bacteria-linked doxorubicin activity, as well as the enhanced internalization of the liposomes due to their cationic surface charge. Overall, our system holds great promise for curbing cancer-related bacterial infections and drug resistance in both cell types.

A Flowthrough Assay for Rapid Bedside Stratification of Bloodstream Bacterial Infection in Critically Ill Patients: a Pilot Study.

Bacterial infections affect more than 2 million people annually. Of these, systemic infections caused by bacteria in critically ill patients may lead to life-threatening conditions such as sepsis. We have developed a point-of-care (POC) device called Septiflo that can detect and stratify the Gram status of bloodstream bacterial infections in less than 10 min from a drop of human plasma. It works on the principle of identifying pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides (LPS) and lipoteichoic acid (LTA) that are released into the bloodstream at the onset of Gram-negative and Gram-positive bacterial infections, respectively. The biomarkers are captured on a membrane without a receptor, and the Gram status specificity is conferred by the ligands attached to gold nanoparticles (AuNPs) used as signal amplification probes. The ultrasensitive colorimetric results are read by eye down to a 100-fg/ml detection limit without an instrument. No cross-interference between the PAMPs is seen during Gram stratification. Septiflo results also display better performance than commercial enzyme-linked immunosorbent assays (ELISAs). Tests performed on 60 clinical samples from patients showed a correlation accuracy of 70% against procalcitonin (PCT), an accepted surrogate biomarker for sepsis. A direct comparison with eubacterial PCR yielded up to 94% accuracy in 31 patients at a chosen cutoff level for LPS and LTA and area under the curve (AUC) values of 0.927 and 0.885, respectively, though blood culture was negative for most samples. The high sensitivity, low cost, and simple bedside utility of the assay may aid in better sepsis management apparently at the presymptomatic stage, lowering empirical therapy, medical costs, antimicrobial resistance, and mortality.

Dual functionality nanobioconjugates targeting intracellular bacteria in cancer cells with enhanced antimicrobial activity.

Bacterial drug resistance has emerged as a serious global threat mandating the development of novel methodologies that allow facile modulation of antimicrobial action in a controlled fashion. Conjugating antibiotics to nanoparticles helps to meet this goal by increasing the drug's overall avidity, bioavailability and easier internalisation into mammalian cells, targeting bacteria that otherwise escape antibacterial action by host cell-localisation. We used polymyxin B sulfate (PMB) and sushi peptide as model drugs against Gram-negative bacteria and established their enhanced antimicrobial activity on Escherichia coli (E. coli) cells after conjugation to gold nanoparticles (AuNPs). The efficacy of the bioconjugates was also tested on Salmonella typhi (S. typhi) bacteria infected into cervical cancer cells (HeLa) and further improved through specific targeting via folate receptors. Our results demonstrate significantly lower inhibitory concentration values for sushi-NP assemblies as compared to free drug, especially at optimal drug loading levels. No major cytotoxicity was observed in mammalian cells alone.

Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate.

Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0 x 10(-8)). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism.

Tiled ChrI RHS collection: a pilot high-throughput screening tool for identification of allelic variants.

Reciprocal hemizygosity analysis is a genetic technique that allows phenotypic determination of the allelic effects of a gene in a genetically uniform background. Expanding this single gene technique to generate a genome-wide collection is termed as reciprocal hemizygosity scanning (RHS). The RHS collection should circumvent the need for linkage mapping and provide the power to identify all possible allelic variants for a given phenotype. However, the published RHS collections based on the existing genome-wide haploid deletion library reported a high rate of false positives. In this study, we report de novo construction of a RHS collection that is not based on the yeast deletion library. This collection has been constructed for the shortest yeast chromosome, ChrI. Using this ChrI RHS collection, we identified 13 allelic variants for the previously mapped loci and novel allelic variants for the growth differences in different environments. A few of these novel variants, which were fine mapped to a gene level, identified novel genetic variation for the previously studied environmental conditions. The availability of a genome-wide RHS collection would thus help us uncover a comprehensive list of allelic variants and better our understanding of the molecular pathways modulating a quantitative trait.

Preventing post-traumatic stress disorder after mass exposure to violence.

Bioterrorism preparedness plans must take into account the psychosocial consequences of exposure to mass violence. If possible, post-traumatic stress disorder (PTSD), which is associated with significant morbidity and cost, should be prevented. There are, however, no effective interventions that have been scaled up to prevent PTSD following mass exposure to violence. In fact, randomized controlled trials of the most commonly used preventive intervention, psychological debriefing, suggest no efficacy, or even potential harm. Fortunately, randomized controlled trials of cognitive behavioral therapy--that is, targeting individuals who are symptomatic in the weeks after trauma--reveal significant efficacy. Given the potential for repeated mass violence exposure, public health professionals need to refine methods for screening and tracking large numbers of casualties. At the same time, the use of telephone and internet-based cognitive behavioral therapy protocols should be further tested as strategies for bringing the only effective early intervention for PTSD to scale. Research on preventive pharmacotherapy for PTSD and on the effects of media exposure on PTSD severity is also a priority.

Identification of immunodominant regions of Brassica juncea glyoxalase I as potential antitumor immunomodulation targets.

Glyoxalase I activity has been shown to be directly related to cancer and its inhibitors have been used as anti-cancer drugs. Immunochemical studies have shown immunochemical relatedness among animal and plant glyoxalase I, but its potential application for biomedical research has not been investigated. In order to understand the conserved immunochemical regions of the protein and to determine probable immunomodulation targets, a cellulose-bound scanning peptide library for Brassica juncea glyoxalase I was made using the spot synthesis method. Immuno-probing of the library, using B. juncea anti-glyoxalase I monospecific polyclonal antibodies, revealed three immunodominant regions, epitope I, II, and III. In the homology model of B. juncea glyoxalase I generated by threading its sequence onto the human glyoxalase I, the high accessible surface area and the hydrophilic nature of the epitopes confirmed their surface localization and hence their accessibility for antigen-antibody interaction. Epitopes I and II were specific to B. juncea glyoxalase I. Localizing the epitopes on available glyoxalase I sequences showed that epitope III containing the active site region was conserved across phyla. Therefore, this could be used as a potential immunomodulation target for cancer therapy. Moreover, as the most immunogenic epitopes were mapped on the surface of the protein, this method could be used to discover potential therapeutic targets. It is a simple and fast approach for such investigations. This study, to our knowledge, is the first in epitope mapping of glyoxalase I and has great biomedical potential.