The human antimicrobial peptide hCAP18 in epithelial defense

Gene-encoded antimicrobial peptides serve a protective role in host defense. They are multifunctional effector molecules in innate immunity - the nonadaptive immune system -with the capacity to kill a broad spectrum of microorganisms. In contrast to adaptive immunity, which is highly specific, the innate immune system provides a rapid and nonspecific response, thereby contributing to the first line of defense. Cathelecidins constitute a family of antibacterial peptides. hCAP1 8, the precursor of the LL-37 antimicrobial peptide, is the only cathelecidin in humans while there are several in other species. We first analyzed fluid from wounds with different etiology for antibacterial and biochemical factors. We showed that wound fluid can be analyzed reproducibly and characterized biochemically. Separation and identification of such fluids yielded peptide components likely to reflect necrosis and to function as antibacterial and possible wound healing factors (Paper 1). We studied the role of hCAP1 8 in normal wound healing and in chronic non-healing ulcers. Using skin biopsies from healthy volunteers and from patients, we determined the level and expression pattern of hCAP1 8. Our results demonstrate the presence of hCAP1 8 in both types of wounds. Maximal levels of hCAP 18 were attained at 12h-2days post-wounding in surgical wounds. Total hCAP 18 protein levels in the chronic ulcers were below 20% of the maxima detected in the surgical wounds. Processed active LL-37 peptide was demonstrated in normal wound healing but was barely detectable in the chronic ulcers (Paper 2). In addition to providing a mechanical barrier between the body and the environment epithelia function as an immunological organ. Investigating the expression of hCAP 18 in inflammatory skin disorders we found up- regulation of the hCAP 18 gene in the keratinocytes of inflammatory dermatoses such as lesional psoriasis, nickel allergy and atopic dermatitis, but not in normal quiescent epidermis (Paper3). Further investigation of hCAP1 8 in squamous epithelia demonstrated that hCAP1 8 was constantly expressed at both RNA and protein levels in epithelia of tongue, esophagus, cervix and vagina. Expression of IL- 6 co-localized with hCAP 18 in these tissues. The hCAP 18 gene contains promotor elements that are potentially regulated by IL-6, and our findings suggest a potential local mechanism for the up-regulation of hCAP 18 on epithelial surfaces (Paper 4). To assess the potential role of hCAP 18 in tumor host defense, we investigated its expression in human breast cancer of varying types and malignancy. hCAP 18 was strongly up-regulated in the tumor cells compared to the low constitutive expression in normal benign mammary epithelia. Further, the highest levels of hCAP 18 protein were detected in the most malignant tumors, and immunoblotting revealed processed active LL-37 only in these tumors. Thus our results do not support a protective role for hCAP 18 in tumor host defense, but rather suggest that hCAP 18 may provide a survival advantage for the tumor (Paper 5). In summary our studies reveal a role for the innate immunity effector hCAP 18 in epithelial defense

Differences in cutaneous melanoma treatment and patient satisfaction.

Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers with potential dysfunctions ultimately mirrored in the overall patient satisfaction. The aim of the present study was to investigate the CM management as related to lead times, surgical quality and diagnosis communication with the hypothesis that the care may differ between providers and disparities may impact patient satisfaction. Medical records of 181 patients were retrospectively analyzed with parallel patient satisfaction evaluation by telephone interviews. Overall mean lead times from initial diagnosis until completion of all surgery and histopathology reports were 80-100 days and delays occurred at every step of the process. General practitioners performed excision biopsies faster however this was mitigated by slower histopathology processing. University level CM care showed less lag time between excision biopsy, wide local excision for thick melanomas and histopathology confirmation. University level care operated with twice the surgical margin as compared to general practitioners and non-university level specialists. Male patients had larger excision biopsy margins and significantly shorter lead times than female patients. Patient satisfaction rates were generally higher in the academic hospitals as compared to general practitioners and non-university dermatology clinics. Surprisingly, there was no correlation between lead times and patient satisfaction. Taken together, CM show substantial variation and caution should be practiced when using patient satisfaction as a quality indicator

Correction: Differences in cutaneous melanoma treatment and patient satisfaction.

[This corrects the article DOI: 10.1371/journal.pone.0205517.]

Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from sweden.

To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM)

Playing as an early-childhood promotion of communication skills

Darba autore: Agita Kaža Darba tēma: Rotaļa kā saskarsmes prasmju sekmētāja agrās bērnības vecumā Darba vadītājs: Prof. Dr. psych.Tija Zīriņa Pētījuma mērķis: Pētīt 2 – 3 gadīgu bērnu saskarsmes prasmes rotaļās Pētījuma saturs: darba teorētiskās daļas pirmajā nodaļā tiek aplūkotas un analizētas dažādu pedagogu, psihologu atziņas par saskarsmi, kā veidojas saskarsme pirmsskolā. Darba otrajā nodaļā tiek pētīta agrās bērnības saskarsmju prasmju sekmēšanā rotaļās. Nodaļas saturs lielākoties balstās uz praktisko pētījumu. Pētījumā piedalās agrās bērnības vecuma 16 bērni. Pētījumā tiek organizētas rotaļas ar kuru palīdzību bērni veicina sekmīgu saskarsmes prasmju veidošanos. Secinājumos apkopota nozīmīgākā informācija saskarsmes prasmju attīstību rotaļā. Atslēgas vārdi: saskarsme, saskarsmes prasmju attīstība, rotaļa, pirmsskola, bērni. Darba apjoms: darbs sastāv no 4 nodaļām un 5 apakšnodaļām, tam ir 55 lapas. Darbā aplūkojamas 2 tabulas, 2 attēli un pielikums, kurā ir redzams 21 attēls, izmantotās literatūras saraksts sastāv no 45 avotiem.Author of the work: Agita Kaza Theme of the work: Playing as an early-childhood promotion of communication skills Supervisor of the work: Prof. Dr. psych. Tija Zirina The aim of the research: To study 2-3-year-olds' skills in games Study content: the first chapter of the theoretical part of the work looks at and analyzes the knowledge of various educators, psychologists, about how they come into contact in preschool. The second section of work examines the promotion of early childhood communication skills in games. The content of the chapter is largely based on the practical study. 16 children of the age of early childhood are involved in the study. The study organizes games to help children develop successful communication skills. The conclusions summarise key information on the development of communication skills in play. Keywords: communication, development of communication skills, playing, preschool, children. Scope of the work: the work consists of 4 chapters and 5 subdivisions, with 55 pages. The work includes 2 tables, 2 pictures and an attachment showing 21 figures, a list of authorities used consisting of 45 sources

Interobserver Variability of Histopathological Prognostic Parameters in Cutaneous Malignant Melanoma : Impact on Patient Management

Clinical management of primary cutaneous melanomas is based on histopathological staging of the tumour. The aim of this study was to investigate, in a non-selected population in clinical practice, the agreement rate between general pathologists and pathologists experienced in melanoma in terms of the evaluation of histopathological prognostic parameters in cutaneous malignant melanomas, and to what extent the putative variability affected clinical management. A total of 234 cases of invasive cutaneous malignant melanoma were included in the study from the Stockholm-Gotland Healthcare Region in Sweden. Overall interobserver variability between a general pathologist and an expert review was 68.8-84.8%. Approximately 15.5% of melanomas <= 1 mm were re-classified either as melanoma in situ or melanomas >1 mm after review. In conclusion, review by a pathologist experienced in melanoma resulted in a change in recommendations about surgical excision margins and/or sentinel node biopsy in subgroups of Ti melanomas