Food and Drug Administration perspective: Advancing product development for non-healing chronic wounds.

The US Food and Drug Administration (FDA) understands that innovative product development is essential to addressing the unmet medical need of non-healing chronic wounds. Barriers to product development for non-healing chronic wounds may involve but are not limited to a dearth of biological models, challenges in drug delivery, challenges in clinical trial execution, and limited commercial viability. This perspective article discusses FDA's renewed focus on non-healing chronic wounds and outlines efforts to address identified barriers to product development for non-healing chronic wounds. In collaboration with key wound healing stakeholders including academia, professional associations, patient groups, reimbursement organizations and industry, FDA intends to help advance product development for non-healing chronic wounds for the ultimate betterment of patients.

Genetic portrait of 23 Y-STR loci in the Naga tribes of Nagaland, India.

To explore the genomic diversity and forensic characterization of Naga tribes, Nagaland, haplotypes for 23 Y-STR markers have been analyzed. In this study, 203 unrelated male individuals residing in the Northeast Indian state of Nagaland were selected. A total of 203 unique haplotypes were observed. The value of gene diversity (GD) and discrimination capacity (DC) was observed as 0.999999998927955 and 1 respectively. Forensic interest parameters viz., power of discrimination (PD), polymorphic information content (PIC), and matching probability (PM) were found to be 0.999999998695503, 0.999999976671191, and 1.3 × 10-9 respectively, for the studied population. Inter-population comparison study showed that the Naga tribes were found to have a distinct gene pool which is reflected in the neighbor-joining tree, principle coordinate analysis, and heat map. This is the first genetic study on Naga tribes based on 23 Y-STR markers. The Y chromosomal STR data will be useful for forensic DNA application and will enrich the existing Indian Y-STR database.

The implication of morphometrics and growth rate of dipteran flies in forensic entomotoxicology research: a review.

Forensic entomotoxicology integrates toxicology into forensic entomology to estimate minimum postmortem interval (PMImin) and circumstances of death where toxicants and poisonous substances are the suspected cause of death. Forensic entomotoxicology not only confirms the presence of toxicants in insects feeding off a cadaver but also studies its effect on the bio-morphometry and growth rate of insects. This review article highlights the effects of various toxicants on forensically important species of dipteran flies. It also discusses the parameters that may affect accuracy in estimation of time since death. The bio-physical effects of toxicants (excluding the analytical approach for qualitative detection) would help understand the trends in forensic entomotoxicological research worldwide.

Medical tourism in plastic surgery: ethical guidelines and practice standards for perioperative care.

BACKGROUND: The goal of this review was to identify the safety and medical care issues that surround the management of patients who had previously undergone medical care through tourism medicine. Medical tourism in plastic surgery occurs via three main referral patterns: macrotourism, in which a patient receives treatments abroad; microtourism, in which a patient undergoes a procedure by a distant plastic surgeon but requires postoperative and/or long-term management by a local plastic surgeon; and specialty tourism, in which a patient receives plastic surgery from a non-plastic surgeon. METHODS: The ethical practice guidelines of the American Medical Association, International Society of Aesthetic Plastic Surgery, American Society of Plastic Surgeons, and American Board of Plastic Surgeons were reviewed with respect to patient care and the practice of medical tourism. CONCLUSIONS: Safe and responsible care should start prior to surgery, with communication and postoperative planning between the treating physician and the accepting physician. Complications can arise at any time; however, it is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Phage Therapy in Bacterial Pneumonia Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Phage therapy could play an important role in the bacterial pneumonia. However, the exact role of phage therapy in bacterial pneumonia is unclear to date. AIM: The current study aims to find out the role of phage therapy in preclinical models of bacterial pneumonia. METHODS: The studies were searched in databases with proper MeSH terms along with Boolean operators and selected based on eligibility criteria as per the PRISMA guidelines. The Odd Ratio (OR) was calculated with a 95% confidence interval and the heterogeneity was also calculated. The funnel plot was used to conduct a qualitative examination of publication bias. RESULTS: The OR was observed to be 0.11 (0.04, 0.27)] after 24 hrs, 0.11 [0.03, 0.34] after 7 days and 0.04 [0.01, 0.15] after 10 days that showed a significant role of phage therapy in reduction of deaths in the bacterial pneumonia models as compared to the placebo group. However, after 48hrs, a non-significant reduction was observed. CONCLUSION: There was a significant role of phage therapy in the reduction of deaths in the bacterial pneumonia models.

Minimizing complications with the use of acellular dermal matrix for immediate implant-based breast reconstruction.

BACKGROUND: Acellular dermal matrix (ADM) use in implant-based breast reconstruction has been associated with higher rates of postoperative seroma and infection. This follow-up study was performed to determine whether specific modifications in technique are associated with a reduction in the rate of complications. METHODS: The authors performed a retrospective analysis of immediate ADM-assisted implant-based breast reconstructions performed by the lead author (Y.C.) during an 18-month period after instituting specific modifications to prevent seroma. These included draining both the submastectomy and sub-ADM planes, lowering the threshold for drain removal, and addition of postoperative soft compression dressings and surgical bras. A total of 179 implant-based reconstructions were evaluated for rates of complications, including infection, hematoma, seroma, and skin flap necrosis. These were compared to results of a series of 150 similar procedures performed by the lead author before institution of the procedural modifications described. RESULTS: Seroma rate decreased from 18.6% to 4.7% (P = 0.0022), and major infection rate decreased from 7% to 1.9% (0.0250). CONCLUSIONS: Although implant-based breast reconstruction using ADM has been associated with increased seroma and possible infection rates, the use of specific clinical practices designed to prevent seroma has minimized our rate of these postoperative complications.

Impact of prior ipsilateral chest wall radiation on pedicled TRAM flap breast reconstruction.

BACKGROUND: This study compares complication rates between transverse rectus abdominis myocutaneous (TRAM) flaps based on previously irradiated versus nonirradiated superior pedicles to assess the impact of prior ipsilateral chest wall radiation on pedicled TRAM flap breast reconstruction. METHODS: A retrospective study of 302 consecutive TRAM flap reconstructions was performed; 76 TRAM flaps based on a previously irradiated superior epigastric pedicle were compared to 226 TRAM flaps based on a nonirradiated pedicle in medical comorbidities, oncologic data, and complications. RESULTS: Patients having undergone previous chest wall irradiation had a higher cancer stage, but demographic data were otherwise similar within the groups. Previous chest wall irradiation did not result in increased rate of flap loss, infection, and fat necrosis. However, there was a trend toward higher revision rate in the previously irradiated TRAM group. CONCLUSIONS: Previous radiation to the superior epigastric pedicle is not associated with a significant increase in flap complications and should be considered a viable modality for pedicled TRAM flap breast reconstruction.

Seasonal study of the decomposition pattern and insects on a submerged pig cadaver.

Research on studying the decomposition pattern in aquatic habitat is very sparse worldwide. Due to this void, assessment of the postmortem submersion interval (PMSI) of drowned and submerged cadavers is still inaccurate and imprecise. The current work focused on studying the decomposition pattern and insects associated with submerged pig (Sus scrofa) carcasses during various seasons (winter, spring, summer, and rainy) for two years. The total postmortem submersion interval (PMSI) from the fresh stage till the sunken remains stage varied from 25 days for rainy season (624.5 ADD) to 78 days (1890.5 ADD) for winter season. The spring season at 44 days (1067.5 ADD) and summer season at 31 days (763.5 ADD) had moderate PMSI. During this time interval, five stages of decomposition were studied: submerged fresh, early floating, floating decay, advanced floating decay, and sunken remains. A total of 2385 insect specimens were found to be associated with different decomposition stages. The terrestrial activity during the first stage (submerged fresh) was almost nil as the carcasses were submerged. During the early floating stage (2nd stage), various terrestrial insect species visited the carcass and laid their eggs along with the presence of Chironomidae, Coenagrionidae, Lestidae, Aeshnidae families (order Odonata) were also found associated with this stage. In the floating decay (3rd stage), the insects visiting and colonizing the carcass were from Coenagrionidae, Gomphidae, Aeshnidae, Gomphidae, Libellulidae Chironomidae (Order-Odonata) families along with Calliphoridae (order- Diptera). Species from the group of scavenging aquatic beetles (Hydrophilidae), Enochrus esuriens (Walker), Regimbartia attenuata (Fab), Helochares sp. and burrowing water beetles, Canthydrus laetabilis (Family: Noteridae) and some terrestrial species of beetles, i.e. Saprinus sp., Saprinus pensylvenicus and Necrobia rufipus (Family: Cleridae) were also present during the 3rd, 4th and 5th stages. During advanced floating decay (4th stage) and sunken remains (5th stage), many hemipteran species such as Ranatra digitata and Ranatra filiformis (Fab) along with many coleopterans were found visiting the corpse.

Visualizing dynamic E2F-mediated repression in vivo.

Although many E2F target genes have been identified recently, very little is known about how any single E2F site controls the expression of an E2F target gene in vivo. To test the requirement for a single E2F site in vivo and to learn how E2F-mediated repression is regulated during development and tumorigenesis, we have constructed a novel series of wild-type and mutant Rb promoter-LacZ transgenic reporter lines that allow us to visualize the activity of a crucial E2F target in vivo, the retinoblastoma tumor suppressor gene (Rb). Two mutant Rb promoter-LacZ constructs were used to evaluate the importance of a single E2F site or a nearby activator (Sp1/Ets) site that is found mutated in low-penetrance retinoblastomas. The activity of the wild-type Rb promoter is dynamic, varying spatially and temporally within the developing nervous system. While loss of the activator site silences the Rb promoter, loss of the E2F site stimulates its activity in the neocortex, retina, and trigeminal ganglion. Surprisingly, E2F-mediated repression of Rb does not act globally or in a static manner but, instead, is a highly dynamic process in vivo. Using neocortical extracts, we detected GA-binding protein alpha (GABPalpha, an Ets family member) bound to the activator site and both E2F1 and E2F4 bound to the repressor site of the Rb promoter in vitro. Additionally, we detected binding of both E2F1 and E2F4 to the Rb promoter in vivo using chromatin immunoprecipitation analysis on embryonic day 13.5 brain. Unexpectedly, we detect no evidence for Rb promoter autoregulation in neuroendocrine tumors from Rb+/-; RbP-LacZ mice that undergo loss of heterozygosity at the Rb locus, in contrast to the situation in human retinoblastomas where high RB mRNA levels are found. In summary, this study provides the first demonstration that loss of an E2F site is critical for target gene repression in vivo and underscores the complexity of the Rb and E2F family network in vivo.

Modulation of scarring in a liquid environment in the Yorkshire pig.

ABSTRACT Decreased inflammatory response seen in wet wound healing may be correlated with diminished scarring. This study seeks to test this hypothesis and to validate a model of scarring in the Yorkshire pig. Four Yorkshire pigs were used to create 36 dorsal wounds per pig (144 wounds total) in the following groups: full-thickness excisional, partial thickness, meshed split-thickness skin grafts, sheet split-thickness skin grafts, minced skin, and incisional wounds. Wounds were randomized into wet and dry groups. Wet wounds were enclosed in polyurethane chambers with 2 mL of normal saline. Dry wounds were covered with regular gauze. Terminal biopsies were performed at 72 hours and day 28. Histology demonstrated significantly less inflammatory infiltrate, thicker neoepidermis, more pronounced rete ridge formation, and decreased scar tissue thickness in wet wounds. The mean macroscopic scar surface area was significantly decreased in full-thickness excisional wet wounds compared with dry wounds (61.2 mm(2) vs. 150.8 mm(2), p<0.01). Hydroxyproline content was decreased in full-thickness wet compared with dry groups (44.81 vs. 62.21 mg/g, p<0.01). Tensile strength was 90% greater in full-thickness wet compared with dry groups (p<0.01). Healing in the liquid environment significantly reduced scar formation. This model will allow for future investigation of high-concentration topical scar-modulating agents in the liquid environment.

Data on haplotype diversity in the hypervariable region I, II and III of mtDNA amongst the Brahmin population of Haryana.

Human mitochondrial DNA (mtDNA) is routinely analysed for pathogenic mutations, evolutionary studies, estimation of time of divergence within or between species, phylogenetic studies and identification of degraded remains. The data on various regions of human mtDNA has added enormously to the knowledge pool of population genetics as well as forensic genetics. The displacement-loop (D-loop) in the control region of mtDNA is rated as the most rapidly evolving part, due to the presence of variations in this region. The control region consists of three hypervariable regions. These hypervariable regions (HVI, HVII and HVIII) tend to mutate 5-10 times faster than nuclear DNA. The high mutation rate of these hypervariable regions is used in population genetic studies and human identity testing. In the present data, potentially informative hypervariable regions of mitochondrial DNA (mtDNA) i.e. HVI (np 16024-16365), HVII (np 73-340) and HVIII (np 438-576) were estimated to understand the genetic diversity amongst Brahmin population of Haryana. Blood samples had been collected from maternally unrelated individuals from the different districts of Haryana. An array of parameters comprising of polymorphic sites, transitions, transversions, deletions, gene diversity, nucleotide diversity, pairwise differences, Tajima's D test, Fu's Fs test, mismatch observed variance and expected heterozygosity were estimated. The observed polymorphisms with their respective haplogroups in comparison to rCRS were assigned.

A data-based study in support of Blackbuck related cases from Haryana.

Haryana State (located in the northern part of India), is lacking in natural forest, but it has rich biodiversity of some wild animals, especially the Blackbuck antelopes. The maximum population of Blackbucks in the state is living in open cultivated fields. Blackbucks were once found abundantly throughout Haryana, but now they are limited to the south-west part of the state, driven almost to extinction in the rest of Haryana, mainly because of habitat destruction and wildlife crime. This data report is an outcome of six years (January 2012-September 2017), based on assessment of records in terms of location, year and month wise frequency of death and rescued cases related to Blackbuck reported, as registered by the State Wildlife Department. It is envisioned that this data report will provide appropriate information for the conservationist to plan future conservation strategy for Blackbucks in Haryana.

Sequence polymorphism data of the hypervariable regions of mitochondrial DNA in the Yadav population of Haryana.

Genetic variations among humans occur both within and among populations and range from single nucleotide changes to multiple-nucleotide variants. These multiple-nucleotide variants are useful for studying the relationships among individuals or various population groups. The study of human genetic variations can help scientists understand how different population groups are biologically related to one another. Sequence analysis of hypervariable regions of human mitochondrial DNA (mtDNA) has been successfully used for the genetic characterization of different population groups for forensic purposes. It is well established that different ethnic or population groups differ significantly in their mtDNA distributions. In the last decade, very little research has been conducted on mtDNA variations in the Indian population, although such data would be useful for elucidating the history of human population expansion across the world. Moreover, forensic studies on mtDNA variations in the Indian subcontinent are also scarce, particularly in the northern part of India. In this report, variations in the hypervariable regions of mtDNA were analyzed in the Yadav population of Haryana. Different molecular diversity indices were computed. Further, the obtained haplotypes were classified into different haplogroups and the phylogenetic relationship between different haplogroups was inferred.

Data of drowning related deaths with reference to entomological evidence from Haryana.

Most often the newspapers and bulletin come out with voluminous cases of deaths due to drowning. At the same time an ample section of such cases encompass entomological evidences, that can be scrutinized as a very useful parameter in estimating post mortem interval (PMI). This research database is an outcome of a 2 years reflective study, based on an assessment of records related to human deaths due to drowning. The drowned bodies from various districts of Haryana are sent to PGIMS (Post Graduate Institute of Medical Sciences), Rohtak. The study took the data of year 2015-2016 into consideration. All the cases were reviewed and summarized in terms of monthly occurrence of total cases, age differentiation, gender differentiation and month wise occurrence of entomological evidences on the dead bodies through detailed study of post mortem findings. This data will lead to an insight into the magnitude of drowning deaths in Haryana along with the usage of entomological data for determining Post Mortem Submersion Intervals (PMSI).

Management of hidradenitis suppurativa wounds with an internal vacuum-assisted closure device.

BACKGROUND: Hidradenitis suppurativa is a chronic, debilitating disease that is difficult to treat. Once medical management fails, wide local excision offers the best chance for cure. However, the resultant wound often proves too large or contaminated for immediate closure. METHODS: The authors performed a retrospective chart review of hidradenitis cases managed surgically between 2005 and 2010. Data collected included patient characteristics, management method, and outcomes. Approximately half of the patients received internal vacuum-assisted closure therapy using the vacuum-assisted closure system and delayed closure and half of the patients received immediate primary closure at the time of their excision. Delayed closure consisted of closing the majority of the wound in a linear fashion following internal vacuum-assisted closure while accepting healing by means of secondary intention for small wound areas. RESULTS: Patients managed with internal vacuum-assisted closure had wounds on average four times larger in area than patients managed without internal vacuum-assisted closure. In both groups, all wounds were eventually closed primarily. Healing times averaged 2.2 months with internal vacuum-assisted closure and 2.7 months without. At an average follow-up time of 2.3 months, all patients with internal vacuum-assisted closure had no recurrence of their local disease. CONCLUSIONS: Severe hidradenitis presents a treatment challenge, as surgical excisions are often complicated by difficult closures and unsatisfactory recurrence rates. This study demonstrates that wide local excision with reasonable outcomes can be achieved using accelerated delayed primary closure. This method uses internal vacuum-assisted closure as a bridge between excision and delayed primary closure, facilitating closure without recurrence in large, heavily contaminated wounds. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Breast reconstruction following nipple-sparing mastectomy: a systematic review of the literature with pooled analysis.

BACKGROUND: Nipple-sparing mastectomy is a controversial option for breast cancer treatment due to locoregional recurrence and distant metastasis. In addition to these oncologic factors, technical factors such as ideal incision type or reconstructive options are also debatable. This systematic review examines current trends with nipple-sparing mastectomy, including selection criteria, locoregional and distant metastasis rates, incision choice, and reconstructive options. METHODS: Systematic electronic searches were performed in the PubMed and Ovid databases using search terms for studies reporting outcomes following nipple-sparing mastectomy and all forms of reconstruction. Studies between 1970 and 2013 were reviewed. Pooled descriptive statistics with separate analyses for incision type and reconstructive method were performed. RESULTS: Forty-eight studies met inclusion criteria, yielding 6615 nipple-sparing mastectomies for analysis. The overall pooled complication rate was 22 percent, the nipple necrosis rate was 7 percent, the locoregional recurrence rate was 1.8 percent, and the distant metastasis rate was 2.2 percent. Comparing combined patient cohorts for two-stage expander to implant, one-stage direct to implant, and autologous reconstruction demonstrated overall complication rates of 52.8, 16.7, and 23.7 percent and nipple necrosis rates of 4.5, 4.1, and 17.3 percent, respectively. Incision types were divided into five categories: radial, periareolar/circumareolar, inframammary, mastopexy, and transareolar, with nipple necrosis rates of 8.83, 17.81, 9.09, 4.76, and 81.82 percent, respectively CONCLUSIONS: Nipple-sparing mastectomy appears to be an oncologically safe option for properly selected patients, with low rates of locoregional and distant metastasis. Overall complication and nipple necrosis rates are affected by incision location and reconstruction method. Randomized controlled trials are warranted to determine best incision and reconstructive methods. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Single-stage full-thickness scalp reconstruction using acellular dermal matrix and skin graft.

Full-thickness scalp defects with exposed calvarium pose a reconstructive challenge, particularly in patients with extensive comorbidities. A single-stage acellular dermal matrix and split-thickness skin graft reconstruction represents a simple and valuable surgical approach to achieving durable scalp coverage without requiring a donor-site or prolonged treatment. Reconstruction of full-thickness scalp defects with exposed calvarium is a difficult problem that generally requires local or free flap reconstruction. However, patients with significant medical comorbidities present a further challenge given the risks of a major surgical procedure. Simple skin graft directly onto bone frequently fails and does not provide durable coverage, while combined artificial skin substitute and split-thickness skin graft approach involves a prolonged treatment period with multiple-staged procedures. Herein, we present a case of an 82-year-old female patient with complex medical comorbidities with a large scalp defect and calvarial exposure following Moh's surgery. She was successfully treated with a single-stage acellular dermal matrix and a STSG reconstruction. Her treatment period was effectively shortened, and she had an excellent clinical outcome.