Investigating dysregulation of TGF-ß1/SMAD3 signaling in Atopic Dermatitis: A Molecular and Immunohistochemical Analysis".

Atopic Dermatitis (AD) is a persistent and recurring inflammatory condition affecting the skin. An expanding corpus of evidence indicates the potential participation of TGF-ß1 in the modulation of inflammation and tissue remodeling in AD. The primary objective of this study was to examine the aberrant modulation of TGF-ß1/SMAD3 signaling through a comprehensive analysis of their molecular and protein expression profiles. The study encompassed an aggregate of 37 participants, which included 25 AD patients and 12 controls. The assessment of mRNA and protein levels of TGF-ß1 and SMAD3 was conducted utilizing quantitative real-time PCR and immunohistochemistry, whereas serum IgE and vitamin D levels were estimated by ELISA and chemiluminescence, respectively. Quantitative analysis demonstrated a 2.5-fold upregulation of TGF-ß1 mRNA expression in the lesional AD skin (p<0.0001). Immunohistochemistry also exhibited a comparable augmented pattern, characterized by moderate to strong staining intensities. In addition, TGF-ß1 mRNA showed an association with vitamin D deficiency in serum (p<0.02), and its protein expression was linked with the disease severity (p<0.01) Furthermore, a significant decrease in the expression of the SMAD3 gene was observed in the affected skin (p = 0.0004). This finding was further confirmed by evaluating the protein expression and phosphorylation of SMAD3, both of which exhibited a decrease. These findings suggest that there is a dysregulation in the TGF-ß1/SMAD3 signaling pathway in AD. Furthermore, the observed augmentation in mRNA and protein expression of TGF-ß1, along with its correlation with the disease severity, holds considerable clinical significance and emphasizes its potential role in AD pathogenesis.

Unveiling the TGF- ß1 paradox: Significant implication of TGF- ß1 promoter variants and its mRNA and protein expression in atopic dermatitis.

BACKGROUND: Atopic Dermatitis (AD) is a chronic inflammatory skin disorder with evidence of lichenification in later stages. There is mounting evidence supporting the role of TGF- ß1 in mediating inflammation as well as subsequent tissue remodeling, often resulting in fibrosis. Given the role of genetic variants in the differential expression of TGF-ß1 in various diseases, this study seeks to ascertain the role of TGF-ß1 promoter variants (rs1800469 and rs1800468) in AD susceptibility, as well as their association with TGF- ß1 mRNA expression, TGF- ß1 serum levels and skin prick test positivity in Atopic Dermatitis patients. METHODS: An aggregate of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for TGF-ß1 promoter polymorphisms by PCR-RFLP. TGF- ß1 mRNA was quantified by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and serum TGF- ß1, and total IgE levels were determined by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites and food allergens. RESULTS: A higher frequency of TT genotypes of rs1800469 (OR = 7.7, p = 0.0001) and GA+AA genotypes of rs1800468 (OR-4.4, p < 0.0001) were observed in AD cases than those in controls. Haplotype analysis demonstrated that TG haplotype carriers had an increased risk of AD (p = 0.013). Quantitative analysis revealed a significant upregulation of both mRNA (p = 0.0002) and serum levels (p < 0.0001) of TGF- ß1 with a substantial positive correlation between them (Correlation coefficient=0.504; p = 0.01). Moreover, serum TGF-ß1 levels were associated with quality of life (p = 0.03), the severity of the disease (p = 0.03), and House dust mite allergy (p = 0.01) whereas TGF-ß1 mRNA levels positively correlated with disease severity(p = 0.02). Stratification analysis revealed that the TT genotype of rs1800469 was associated with higher IgE levels (p = 0.01) and eosinophil percentage(p = 0.007) whereas the AA genotype of rs1800468 correlated with elevated serum IgE levels (p = 0.01). Besides, no significant association of genotypes with mRNA and serum expression of TGF-ß1 was observed. CONCLUSION: Our study indicates that TGF-ß1 promoter SNPs bear a significant risk of AD development. Moreover, upregulation of TGF-ß1 mRNA and serum levels and their association with disease severity, quality of life, and HDM allergy suggests its role as a diagnostic/prognostic biomarker that could help in the development of new therapeutic and prevention strategies.

Management of Wounds with Exposed Bones or Tendons in Children by Vacuum-Assisted Closure Therapy: A Prospective Study.

Background The management of complex soft tissue defects with exposed bones/tendons is always a challenging task for the surgeon and the problem becomes more pronounced when it comes to the management of these wounds in children. Though flap procedures are considered the standard for managing the complex soft tissue defects with exposed bones/tendons yet small blood vessels for anastomosis, long operative period, increased chances of perioperative thrombosis, and difficult perioperative management in children add to the difficulty in performing flap procedures in children. The vacuum-assisted closure (VAC) therapy has emerged as a novel modality for the management of the difficult wounds with added advantages, especially in children. Objective To evaluate the efficacy of VAC in the management of wounds with exposed bones/tendons in children. Patients and Method Forty-six children of complex wounds with exposed bones/tendons were included in the study from July 2016 to June 2018. Results Out of 46 patients, 31 were male; the patients had a mean age of 8.4 years. Road traffic accident was the most common mode of injury (54%), with most of the wounds located over extremities. The mean duration of VAC therapy was 12 days. More than 90% coverage of the exposed structure was seen in 89% of patients. The wounds were definitively managed by split-thickness skin graft in 89% of patients and flap cover in 6.5% of patients. The mean cost of the VAC therapy at our government run hospital was 187 Indian rupees per day. No significant major complications were seen during the treatment. Conclusion VAC therapy is an efficient, safe, and cost-effective modality of treatment for the management of complex wounds in the pediatric population.

Role of customised negative-pressure wound therapy in the integration of split-thickness skin grafts: A randomised control study.

BACKGROUND: Split-thickness skin grafting (STSG) is a time-tested technique in wound cover, but many factors lead to suboptimal graft take. Role of custom-made negative-pressure wound therapy (NPWT) is compared with conventional dress in the integration of STSG and its cost is compared with widely used commercially available NPWT. MATERIALS AND METHODS: This is a parallel group randomised control study. Block randomisation of 100 patients into one of the two groups (NPWT vs. non-NPWT; 50 patients each) was done. Graft take/loss, length of hospital stay post-grafting, need for regrafting and cost of custom-made negative pressure wound therapy (NPWT) dressings as compared to widely used commercially available NPWT were assessed. RESULTS: Mean graft take in the NPWT group was 99.74% ± 0.73% compared to 88.52% ± 9.47% in the non-NPWT group (P = 0.004). None of the patients in the NPWT group required second coverage procedure as opposed to six cases in the non-NPWT group (P = 0.035). All the patients in the NPWT group were discharged within 4-9 days from the day of grafting. No major complication was encountered with the use of custom-made NPWT. Custom-made NPWT dressings were found to be 22 times cheaper than the widely used commercially available NPWT. CONCLUSIONS: Custom-made NPWT is a safe, simple and effective technique in the integration of STSG as compared to the conventional dressings. We have been able to reduce the financial burden on the patients as well as the hospital significantly while achieving results at par with other studies which have used commercially available NPWT.

Contralateral lumbo-umbilical flap: A versatile technique for volar finger coverage.

BACKGROUND: While contemplating any difficult soft tissue reconstruction, patient comfort and compliance is of paramount importance. Reconstruction of the volar aspect of fingers and hand by the ipsilateral pedicled flaps (groin flap, abdominal flaps) is demanding as the flap inset is difficult for the surgeon and very uncomfortable for the patient. This often leads to flap complications. For the comfort of the patient, better compliance and ease of complete inset, we planned to manage soft tissue defects of the volar aspect of fingers and hand by a new contralateral pedicled lumbo-umbilical flap. This flap is based on the paraumbilical perforators of deep inferior epigastric artery. MATERIALS AND METHODS: The contralateral pedicled lumbo-umbilical flap was used in eight patients with high-tension electrical burn injuries involving the volar aspect of fingers and hand. The patients were closely observed for first 6 weeks for any flap or donor site complications and then followed monthly to assess donor and recipient site characteristics for 6 months to 2 years. RESULTS AND CONCLUSION: Large flaps up to 8 cm × 16 cm were raised. All but one flaps survived completely. All patients were mobilised within 48 h and five were discharged in less than a week after initial inset. The flap is reliable, easy to harvest and easy to inset on the volar aspect of fingers. The arm is positioned in a very comfortable position. The main disadvantage, however, is a conspicuous abdominal scar.

Silicone Foley's catheter as an effective alternative to Hunter's rod in staged flexor tendon reconstruction of the hand.

CONTEXT: Staged flexor tendon reconstruction is most suitable treatment method for extensive zone II tendon injuries. The Hunter's rod used in this procedure is costly and not easily available, which adds to the miseries of both patients as well as treating surgeon. AIMS: The aim of this study is to evaluate the results of staged zone II flexor tendon repair using silicone Foley's catheter as a cheaper and readily available alternative to Hunter's rod. SETTINGS AND DESIGN: This was a prospective study. MATERIALS AND METHODS: Seventy digits in 35 patients were treated by the staged flexor tendon reconstruction using silicone Foley's catheter in place of Hunter's rod, and the patients were followed for an average period of 18 months. Early controlled motion exercise protocol was instituted in all cases. RESULTS: As per the Strickland scale, total active motion obtained was excellent in 70%, good in 20%, fair in 7.1% and poor in 2.9% of patients. CONCLUSIONS: Silicone Foley's catheter is cheaper, easily available and an effective alternative to Hunter's rod in staged flexor tendon reconstruction procedure, yielding high rates of excellent and good results with fewer complications.

'Pheran' Induced Fourth Degree Friction Burn of the Brain.

Friction burns result from the rubbing between the skin and any other rough surface. We present a case of fourth degree friction burn of the brain, which was predisposed due to the wearing of traditional long loose clothing known as 'Pheran'. The patient was pillion riding a motor bike on a highway and was wearing a Pheran. The loose arm sleeves of the pheran were hanging by the side. The bike met with a side-on collision with a load-carrier lorry. The patient fell down and the left loose arm sleeve of the pheran was trapped in the axle of the lorry. He was dragged on the road for about half a km before the fast moving lorry stopped, the driver being oblivious of the accident. The patient developed friction injury to various parts of the body in addition to a severe fourth degree friction burn to brain and a fracture shaft of left femur.

Bear maul craniocerebral trauma in Kashmir Valley.

Craniocerebral injuries constitute the bulk of the trauma patients in all the tertiary-care hospitals. Bear attacks as a cause of trauma to the brain and its protective covering are rare. This was a hospital-based retrospective (January 1990 to July 2005) and prospective study (August 2005 to December 2010). Craniocerebral trauma was seen in 49 patients of bear maul injuries. Loss of scalp tissue was seen in 17 patients, 13 of whom had exposed pericranium and needed split-thickness skin grafting, while 4 patients with exposed skull bones required scalp transposition flaps as an initial procedure. Skull bone fractures without associated brain injury were observed in 24 cases. Frontal bone was the site of fracture in the majority of cases (95%). Surgical intervention was needed in 18 patients for significantly depressed fractures. Three of these patients had depressed frontal bone fractures with underlying contusions and needed brain debridement and duraplasty. Injury to the brain was observed in 8 patients. Trauma to the brain and its protective coverings as a result of bear attacks is rarely known. Brain injury occurs less commonly as compared to soft tissue and bony injury. Craniocerebral trauma as a result of bear assaults has been a hitherto neglected area of trauma as the past reported incidence has been very low. Of late, the incidence and severity of such attacks has assumed grave proportions in areas adjacent to known bear habitats. An innocuous-looking surface wound might be the only presentation of an underlying severe brain trauma. Public awareness has to be generated to protect the people living in hilly areas.

Giant lipoma: a case report.

A lipoma is a fatty tissue tumor presenting as a painless slowly growing mass that can affect any part of the body rich in adipose tissue. Lipomas can be present in the thigh, shoulder, trunk, etc, although they are usually small. We are reporting a 65-year-old man with a giant lipoma involving his left buttock and lumbar region.

Cleft palate associated with hamartomatous bifid tongue. Report of two cases.

Congenital tumours of the tongue may have a detrimental effect on the simultaneously developing adjacent structures. Palate formation may be affected as it develops in the same period of organogenesis as the tongue. We present two such rare cases of cleft palate with tumour of the dorsal tongue as the probable causative factor. To analyse such an entity, it is necessary to understand the embryogenesis of the palate and tongue. The management and possible elucidation of the occurrence with respect to the developmental phases of tongue and palate are detailed in brief.

An unusual case of frost bite autoamputation of toes.

BACKGROUND: We report a case of a 15 year old young female who suffered autoamputation of left mid foot and four digits of right foot following repeated application of snow to relieve the pain in her frost bitten feet. CASE PRESENTATION: The sociodemographic background, cause, resulting injury and subsequent management are discussed. CONCLUSION: Such injuries are relatively rare but awareness of the risk of this type of injury is important.

Distally based tenosynovial sheath flap of peroneal tendons for exposed tendo Achilles: preliminary report of five cases.

A distally based tenosynovial sheath of peroneal tendons was used as a flap with skin graft to cover the exposed tendo Achilles. The flap has a reliable blood supply being perfused by a constant sizeable musculofascial perforator. Cadaveric dissection with methylene blue dye study has been conducted to prove the rationality and reliability of blood supply. The position of the perforator had been confirmed prior to surgery by a hand-held Doppler. The flap used to cover the exposed Achilles tendon in five cases yielded positive results. To our knowledge, a retrograde flap of this nature is unprecedented though an antegrade flap of similar composition has been described.