MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

The principles and art of plastic surgery

Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges.

Acinetobacter baumannii has emerged as a medically important pathogen because of the increasing number of infections produced by this organism over the preceding three decades and the global spread of strains with resistance to multiple antibiotic classes. In spite of its clinical relevance, until recently, there have been few studies addressing the factors that contribute to the pathogenesis of this organism. The availability of complete genome sequences, molecular tools for manipulating the bacterial genome, and animal models of infection have begun to facilitate the identification of factors that play a role in A. baumannii persistence and infection. This review summarizes the characteristics of A. baumannii that contribute to its pathogenesis, with a focus on motility, adherence, biofilm formation, and iron acquisition. In addition, the virulence factors that have been identified to date, which include the outer membrane protein OmpA, phospholipases, membrane polysaccharide components, penicillin-binding proteins, and outer membrane vesicles, are discussed. Animal models systems that have been developed during the last 15 years for the study of A. baumannii infection are overviewed, and the recent use of these models to identify factors involved in virulence and pathogenesis is highlighted.

https://www.bio.fiocruz.br/images/stories/pdfs/mpti/2013/selecao/acinetobacter-baumannii-human-infections-factors-contributing-to-pathogenesis-and-animal-models.pdf

Acinetobacter baumannii: Human infections, factors contributing to pathogenesis and animal models

Mohs micrographic surgery (MMS) is a specialized type of minimal marginal surgery that offers cure rates superior to other options in the treatment of contiguous skin cancers in selected settings. Developed by Dr. Frederic E. Mohs, the technique originally required in situ tissue fixation before excision. Most Mohs micrographic surgeons now use the fresh tissue technique exclusively. Horizontal frozen histologic sections of the excised tumor permit more complete microscopic examination of the surgical margin than traditional methods. Residual tumor is graphically mapped and malignant extensions are pursued with staged excisions until the tumor is removed. Maximum sparing of tumor-free adjacent tissue is achieved with histologic mapping of the tumor boundaries, thus optimizing subsequent wound reconstruction. The history, techniques, indications, cure rates, and current controversies of MMS are reviewed.

https://www.jaad.org/article/S0190-9622(98)70405-0/pdf

Mohs Micrographic Surgery

T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1+ and Vδ2+ cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.

/pdf/characterization-of-human-gd-t-lymphocytes-infiltrating-2ygbgrb9os.pdf

Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas.

Background:Despite the widespread use of free perforator flaps, pedicled perforator flaps seem not to be as widely accepted, probably because of the fear of vascular complications caused by transfer of a flap attached only by its vascular pedicle, prone to shearing, kinking, and trauma. In this arti

/pdf/freestyle-pedicled-perforator-flaps-safety-prevention-of-4tjbme9nr9.pdf

Freestyle pedicled perforator flaps: safety, prevention of complications, and management based on 85 consecutive cases.

Summary Background Gynaecomastia can be classified on the basis of the main characterising factors, i.e. pathogenesis, histopathology and morphology. The morphological classifications of gynaecomastia currently made often use subjective parameters and qualifying adjectives. In this paper the authors propose a scheme for morphological classification of gynaecomastia which can serve as a guide for choosing the surgical technique, once the diagnosis of gynaecomastia as a benign pathology has been confirmed by preoperative examinations. Methods A retrospective analysis was made of 121 cases of gynaecomastia operated on in the last 5 years. The extent of the clinical picture, the technique employed, the complications and the need to re-operate were observed and related. Results On the basis of this review the authors observed that when the nipple-areola complex is above the inframammary fold (grade I and grade II gynaecomastia), complete flattening of the thorax can be achieved by means of suction or ultrasound-assisted lipectomy and skin-sparing adenectomy. When the nipple-areola complex is at the same height as, or at most 1cm below the fold (grade III gynaecomastia), skin-sparing techniques are no longer sufficient to flatten the thorax, and it becomes necessary to remove the redundant skin by means of periareolar removal of epidermis. In cases of marked ptosis, when the nipple-areola complex is more than 1cm below the fold (grade IV gynaecomastia), reduction mastoplasty becomes necessary, with upper repositioning of the nipple-areola complex; in these cases central pedicle techniques make it possible to limit scarring in the periareolar areas. Conclusions In the preoperative phase this simple classification may help in choosing the most suitable treatment, thus avoiding insufficient or invasive treatments and undesirable scars.

https://www.jprasurg.com/article/S1748-6815(07)00493-7/pdf

Algorithm for clinical evaluation and surgical treatment of gynaecomastia.

Summary Background Scalp reconstruction after wide tumor excision is particularly challenging. Free tissue transfers, local flaps, or skin grafts can be used but present some disadvantages especially with old patients with local advanced cancers, systemic diseases and in patients with a prior history of recurring scalp skin cancers in which the risk of burying a recurring tumor with a flap is likely. The Authors expose their early experience with Integra ® dermal regeneration template for scalp reconstruction after scalp tumor excision. Methods Eight patients with primary or secondary scalp tumor underwent a first surgical procedure under local anaesthesia for tumor removal and Integra ® positioning followed by a second operation performed three weeks later to reconstruct the defect by removing the superficial silicon layer of Integra ® and by covering the defect with a split thickness skin graft. The average surface area of the defect was 143.27 cm 2 . The average operating time was 30.4 minutes for the first operation and 45.6 minutes for the second operation. In six cases Integra ® was grafted as a classic full-thickness skin graft. In the remaining two cases the Integra ® template was meshed. The artificial derma was attached to the edge of the wound by either sutures or staples. Results There was a full graft take on all cases. The mean follow-up was 24 months. In two cases we were able to detect early tumor recurrence two months after the operation. Satisfactory cosmetic and functional results were obtained in all patients. Conclusions In the scalp defect reconstructions after tumor excision, Integra ® allows to obtain a thicker and more durable coverage than skin graft on the skull, allowing to detect a tumor recurrence earlier than a flap reconstruction with no risk of burying an eventual underlying residual tumor. These operations are performed under local anaesthesia and are therefore suitable for elderly patients.

Reconstruction of full thickness scalp defects after tumour excision in elderly patients: our experience with Integra dermal regeneration template.

Summary The nasolabial skin is the ideal donor site for nasal ala reconstruction. The classic techniques involve a two-stage procedure to reconstruct an aesthetically pleasing nasal ala. A one-stage technique for reconstruction of the nasal ala with a free style nasolabial perforator flap is presented in this article. Patients and methods The technique has been used in eight patients between November 2004 and June 2007. In most of the cases (seven out of eight) the whole alar subunit was reconstructed. Results Besides a small distal 2mm necrosis in one flap – which healed without further treatment – all the flaps healed uneventfully with aesthetically pleasing results using the one-stage technique. Conclusions The free style perforator nasolabial island flap has become the method of choice in the authors' institution for nasal ala reconstruction, especially when the defect involves the whole subunit. It allows one-stage reconstruction with very similar tissue and a concealed scar in the natural groove.

Francesco Moschella

Papers

Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas.

Freestyle pedicled perforator flaps: safety, prevention of complications, and management based on 85 consecutive cases.

Algorithm for clinical evaluation and surgical treatment of gynaecomastia.

Reconstruction of full thickness scalp defects after tumour excision in elderly patients: our experience with Integra dermal regeneration template.

Free style facial artery perforator flap for one stage reconstruction of the nasal ala