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The crystallographic structure of the hirulog 3-thrombin complex was approximated at a resolution of 2.3 angstrom based on thrombin coordinates of the hirugen-thrombin complex and refined using restrained least squares methods. Hirulog 3 structure residues were mostly well-defined in the electron density, including those of the pentaglycine bridge and the C-terminal helical turndisordered in the hirulog 1 complex. Except for slight positional shifts, D-Phe 1'-Pro2'-beta-homoArg3' interactions with the thrombin active site were very similar to those of D-Phe-Pro-Arg in the D-Phe-Pro-Arg chloromethyl ketone and hirulog 1- thrombin structures.

Skin pathologies are posing a growing concern among patients with diabetes. Putting the emphasis on the high pace at which are increasing cases of patients with diabetes globally, the main role in this increase seems to play sociodemographic factors and lifestyle. High level of glycated hemoglobin (HbA1C), triglycerides and cholesterol clearly reflects the low level of control and diabetes patients management affected by this medical condition. Also attention should be given even greater body mass index (BMI) of patients with diabetes because of the high obesity increases the risk for health complications fairly and early mortality among diabetics pacients. [ABSTRACT FROM AUTHOR]

This goal of study is to evaluate the role of stress, tobacco, drugs, infections, allergies, heredity, alcohol, hormones and skin aggressions as trigger factors and the impact on quality of life in a sample of psoriasis patients. Used methods: A transversal study performed in 90 patients affected by psoriasis interviewed between January and November 2012 at the "Mother Teresa" University Hospital, Tirana, Albania. It is based on two scored questionnaires, the first inquiring about potential trigger factors and the second assessing the quality of life. The collected data was statistically analyzed using the chi-squared statistical test (2 test). From analyzing data have some results: More than 70 % of patients reported that stressful events caused a flare-up of their psoriasis (p< 0.05). More than 60% of males and 20% of females were smokers (p< 0.05). About 20% of our patients were taking one or more of the medications listed in the questionnaire (p> 0.05). About 20% of patients reported having had recurrent infections (p<0,05). About 80% of males patients consumed alcohol (p<0,05). More than 40% reported a relative with psoriasis. Statistical comparison of the group that reported skin aggressions with the group that did not revealed a significant difference (p<0,05). Only a few of them reported to have allergies (p>0,05). About 36% of females reported that hormonal changes (puberty and menopause) exacerbated their psoriasis (p<0,05). More than 40% of patients reported that psoriasis seriously affects their quality of life. Stress, tobacco, infections, heredity, alcohol, hormonal changes and skin aggressions were confirmed as trigger factors for psoriasis in the present sample. We found that psoriasis had a serious impact in the quality of life in over of 40% of the patients interviewed. [ABSTRACT FROM AUTHOR]

Obesity has become a pandemic threat in the latest 30 years. The trend of the prevalence of overweight and obesity has got an overall increase in every part of the world, regardless of ethnicity, life-style and social ties. High food intake, genetic, and sedentary have been related to obesity; it has been also hypothesized that gut microbiota could have an impact on the complex mechanism underlying the weight gain. This review aims to illustrate the actual literature about gut microbiota and its relation with obesity and to analyze the possible implications of factors such as diet and life-style onto the composition of gut microbiota, that can lead to overweight/obesity condition.

This article presents the findings of a prospective epidemiologic study on hidradenitis suppurativa (HS) in Albania. The study included 43 patients with HS and found a prevalence rate of 0.0085% in the population of Tirana. The study also revealed a higher prevalence of HS in men compared to women, potentially due to higher rates of smoking and obesity among men in Albania. The most affected age group was 19-29 years. The study emphasizes the need for comprehensive national studies with unified diagnostic criteria to provide accurate demographic data on HS. [Extracted from the article]

The COVID-19 pandemic has caused a global health crisis, presenting novel challenges while worsening preexisting difficulties for individuals with rare diseases. Internationally, they have experienced disruptions in their medical care, with a lack of access to essential treatments and diagnostics. We focused on the specific challenges faced by individuals living with rare skin diseases in Albania, a country with limited healthcare infrastructure. The pandemic led to a significant decrease in our service, resulting in an 87.1% reduction in patients hospitalized in 2020 compared to 2019. Notable gender and age disparities were observed in hospitalizations, with a shift towards more male patients and a decline in younger age groups seeking medical attention. Innovative approaches such as telemedicine helped maintain care for this vulnerable patient population. Further research is required to understand the long-term impacts of the pandemic on individuals with rare skin diseases and develop strategies for their care in future emergencies., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (Copyright © 2023, the Author(s).)

α-, β-, and γ-Synuclein are intrinsically disordered proteins implicated in physiological processes in the nervous system of vertebrates. α-synuclein (αSyn) is the amyloidogenic protein associated with Parkinson's disease and certain other neurodegenerative disorders. Intensive research has focused on the mechanisms that cause αSyn to form amyloid structures, identifying its NAC region as being necessary and sufficient for amyloid assembly. Recent work has shown that a 7-residue sequence (P1) is necessary for αSyn amyloid formation. Although γ-synuclein (γSyn) is 55% identical in sequence to αSyn and its pathological deposits are also observed in association with neurodegenerative conditions, γSyn is resilient to amyloid formation in vitro. Here, we report a rare single nucleotide polymorphism (SNP) in the SNCG gene encoding γSyn, found in two patients with amyotrophic lateral sclerosis (ALS). The SNP results in the substitution of Met38 with Ile in the P1 region of the protein. These individuals also had a second, common and nonpathological, SNP in SNCG resulting in the substitution of Glu110 with Val. In vitro studies demonstrate that the Ile38 variant accelerates amyloid fibril assembly. Contrastingly, Val110 retards fibril assembly and mitigates the effect of Ile38. Substitution of residue 38 with Leu had little effect, while Val retards, and Ala increases the rate of amyloid formation. Ile38 γSyn also results in the formation of γSyn-containing inclusions in cells. The results show how a single point substitution can enhance amyloid formation of γSyn and highlight the P1 region in driving amyloid formation in another synuclein family member., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Onychomycosis is a common nail infection caused by dermatophytes, nondermatophytes molds (NDM), and yeasts. The prevalence of Aspergillus spp. is increasing worldwide. This study aims to describe the epidemiological and microbiological features of onychomycosis, especially for Aspergillus spp., Methods: This is a 5-year retrospective study of clinically suspected onychomycosis in one microbiological clinic in Albania. The mycological examination, which included direct microscopic examination of nail scrapings with 20% KOH and culture, was performed on 411 patients. After incubation, we studied the macroscopic characteristics of the colonies, size, shape, and color, and their microscopic examination. We evaluated positive cases for Aspergillus, all cases where Aspergillus was grown in the culture, the microscopy was positive, and the culture was negative for dermatophyte., Results: Onychomycosis resulted positive in 267 patients (52.9% females vs. 47.1% males). A total of 62.2% resulted infected by dermatophytes, 29.6% by yeasts, and 8.2% by NDM. Onychomycosis resulted more frequent in the age group 15-64 years old (63%). Aspergillus spp. were found in 19 patients from 22 patients with NDM onychomycosis. Males (11 patients) and the age group 15-64 years old (14 patients) were more vulnerable to Aspergillus spp. A. niger, A. flavus, and A. terreus isolated from the nail cultures in our study. The culture resulted more superior to KOH examinations., Conclusions: Our study indicates that NDM, including Aspergillus spp., are still rare findings from fungal examinations. However, dermatologist's clinical suspicion and microbiologist's skills are mandatory in diagnosing and properly managing patients with Aspergillus spp., (© 2023 the International Society of Dermatology.)

Background: Synucleinopathies are disorders characterized by the abnormal accumulation of α-synuclein (aSyn). Synaptic compromise is observed in synucleinopathies parallel to aSyn aggregation and is accompanied by transcript deregulation., Objective: We sought to identify microRNAs associated with synaptic processes that may contribute to synaptic dysfunction and degeneration in synucleinopathies., Methods: We performed small RNA-sequencing of midbrain from 6-month-old transgenic mice expressing A30P mutant aSyn, followed by comparative expression analysis. We then used real-time quantitative polymerase chain reaction (qPCR) for validation. Functional analysis was performed in primary neurons by biochemical assays and imaging., Results: We found several deregulated biological processes linked to the synapse. miR-101a-3p was validated as a synaptic miRNA upregulated in aSyn Tg mice and in the cortex of dementia with Lewy bodies patients. Mice and primary cultured neurons overexpressing miR-101a-3p showed downregulation of postsynaptic proteins GABA Ab2 and SAPAP3 and altered dendritic morphology resembling synaptic plasticity impairments and/or synaptic damage. Interestingly, primary cultured neuron exposure to recombinant wild-type aSyn species efficiently increased miR-101a-3p levels. Finally, a dynamic role of miR-101a-3p in synapse plasticity was shown by identifying downregulation of miR-101a-3p in a condition of enhanced synaptic plasticity modelled in Wt animals housed in enriched environment., Conclusion: To conclude, we correlated pathologic aSyn with high levels of miR-101a-3p and a novel dynamic role of the miRNA in synaptic plasticity.

Glycation is a nonenzymatic posttranslational modification (PTM) known to be increased in the brains of hyperglycemic patients. Alpha-synuclein (αSN), a central player in the etiology of Parkinson's disease, can be glycated at lysine residues, thereby reducing αSN fibril formation in vitro and modulating αSN aggregation in cells. However, the molecular basis for these effects is unclear. To elucidate this, we investigated the aggregation of αSN modified by eight glycating agents, namely the dicarbonyl compound methylglyoxal (MGO) and the sugars ribose, fructose, mannose, glucose, galactose, sucrose, and lactose. We found that MGO and ribose modify αSN to the greatest extent, and these glycation products are the most efficient inhibitors of fibril formation. We show glycation primarily inhibits elongation rather than nucleation of αSN and has only a modest effect on the level of oligomerization. Furthermore, glycated αSN is not significantly incorporated into fibrils. For both MGO and ribose, we discovered that a level of ∼5 modifications per αSN is optimal for inhibition of elongation. The remaining sugars showed a weak but optimal inhibition at ∼2 modifications per αSN. We propose that this optimal level balances the affinity for the growing ends of the fibril (which decreases with the extent of modification) with the ability to block incorporation of subsequent αSN subunits (which increases with modification). Our results are not only relevant for other αSN PTMs but also for understanding PTMs affecting other fibrillogenic proteins and may thus open novel avenues for therapeutic intervention in protein aggregation disorders., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, as well as the accumulation of intraneuronal proteinaceous inclusions known as Lewy bodies and Lewy neurites. The major protein component of Lewy inclusions is the intrinsically disordered protein α-synuclein (α-Syn), which can adopt diverse amyloid structures. Different conformational strains of α-Syn have been proposed to be related to the onset of distinct synucleinopathies; however, how specific amyloid fibrils cause distinctive pathological traits is not clear. Here, we generated three different α-Syn amyloid conformations at different pH and salt concentrations and analyzed the activity of SynuClean-D (SC-D), a small aromatic molecule, on these strains. We show that incubation of α-Syn with SC-D reduced the formation of aggregates and the seeded polymerization of α-Syn in all cases. Moreover, we found that SC-D exhibited a general fibril disaggregation activity. Finally, we demonstrate that treatment with SC-D also reduced strain-specific intracellular accumulation of phosphorylated α-Syn inclusions. Taken together, we conclude that SC-D may be a promising hit compound to inhibit polymorphic α-Syn aggregation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

α-Synuclein (α-syn) phosphorylation at serine 129 (pS129–α-syn) is substantially increased in Lewy body disease, such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the pathogenic relevance of pS129–α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation and its role in initiation, progression and cellular toxicity of disease. Using diverse aggregation assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from PD and DLB cases, we demonstrated that pS129–α-syn inhibits α-syn fibril formation and seeded aggregation. We also identified lower seeding propensity of pS129–α-syn in cultured cells and correspondingly attenuated cellular toxicity. To build upon these findings, we developed a monoclonal antibody (4B1) specifically recognizing nonphosphorylated S129–α-syn (WT–α-syn) and noted that S129 residue is more efficiently phosphorylated when the protein is aggregated. Using this antibody, we characterized the time-course of α-syn phosphorylation in organotypic mouse hippocampal cultures and mice injected with α-syn preformed fibrils, and we observed aggregation of nonphosphorylated α-syn followed by later pS129–α-syn. Furthermore, in postmortem brain tissue from PD and DLB patients, we observed an inverse relationship between relative abundance of nonphosphorylated α-syn and disease duration. These findings suggest that pS129–α-syn occurs subsequent to initial protein aggregation and apparently inhibits further aggregation. This could possibly imply a potential protective role for pS129–α-syn, which has major implications for understanding the pathobiology of Lewy body disease and the continued use of reduced pS129–α-syn as a measure of efficacy in clinical trials.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson's disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson's disease and other synucleinopathies., (© 2022. The Author(s).)

Background: Various cellular pathways have been implicated in the transfer of disease-related proteins between cells, contributing to disease progression and neurodegeneration. However, the overall effects of protein transfer are still unclear., Objective: Here, we performed a systematic comparison of basic molecular mechanisms involved in the release of alpha-synuclein, Tau, and huntingtin, and evaluated functional effects upon internalization by receiving cells., Methods: Evaluation of protein release to the extracellular space in a free form and in extracellular vesicles using an optimized ultracentrifugation protocol. The extracellular effects of the proteins and extracellular vesicles in primary neuronal cultures were assessed using multi-channel electrophysiological recordings combined with a customized spike sorting framework., Results: We demonstrate cells differentially release free-forms of each protein to the extracellular space. Importantly, neuronal activity is distinctly modulated upon protein internalization in primary cortical cultures. In addition, these disease-related proteins also occur in extracellular vesicles, and are enriched in ectosomes. Internalization of ectosomes and exosomes by primary microglial or astrocytic cells elicits the production of pro-inflammatory cytokines, and modifies spontaneous electrical activity in neurons., Objective: Overall, our study demonstrates that released proteins can have detrimental effects for surrounding cells, and suggests protein release pathways may be exploited as therapeutic targets in different neurodegenerative diseases.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Tauopathies are neurodegenerative disorders characterized by the deposition of aggregates composed of abnormal tau protein in the brain. Additionally, misfolded forms of tau can propagate from cell to cell and throughout the brain. This process is thought to lead to the templated misfolding of the native forms of tau, and thereby, to the formation of newer toxic aggregates, thereby propagating the disease. Therefore, modulation of the processes that lead to tau aggregation and spreading is of utmost importance in the fight against tauopathies. In recent years, several molecules have been developed for the modulation of tau aggregation and spreading. In this review, we discuss the processes of tau aggregation and spreading and highlight selected chemicals developed for the modulation of these processes, their usefulness, and putative mechanisms of action. Ultimately, a stronger understanding of the molecular mechanisms involved, and the properties of the substances developed to modulate them, will lead to the development of safer and better strategies for the treatment of tauopathies.

NMSC is the most common cancer in countries with a largely fair skin phenotype population and moderate sun exposure. Assessing risk factors in the military personnel. Comparing the risk factors in this occupational group to the general population. 200 active-duty military members and 1000 individuals (the control group) were randomly selected from the general population. We used transversal data collection through a questionnaire, filled in by all participants in the study based on self-report on general data, skin type, habits, lifestyle and inheritance risk for cutaneous cancer. Analyzing the connection between risk factors reported and incidence for NMSC and melanoma, the following factors resulted significant: The control group the age variable >50 yo and BMI ≥25 were significant. The study group (military personnel), among the variables statistically examined through Pearson's test resulted significant: age > 50 years old, fair skin phenotype, sunburn during childhood, familial history of cutaneous cancer, dark spots (>20) on the arm, and coffee consumption as a protective factor. Military personnel has more significant risk factors for developing cutaneous cancer compared to other population groups therefore, prevention and early detection strategies are needed., (© 2020 Wiley Periodicals LLC.)

Parkinson's disease (PD) and Alzheimer's disease (AD) are common neurodegenerative disorders of the elderly and, therefore, affect a growing number of patients worldwide. Both diseases share, as a common hallmark, the accumulation of characteristic protein aggregates, known as Lewy bodies (LB) in PD, and neurofibrillary tangles in AD. LBs are primarily composed of misfolded α-synuclein (aSyn), and neurofibrillary tangles are primarily composed of tau protein. Importantly, upon pathological evaluation, most AD and PD/Lewy body dementia cases exhibit mixed pathology, with the co-occurrence of both LB and neurofibrillary tangles, among other protein inclusions. Recent studies suggest that both aSyn and tau pathology can spread and propagate through neuronal connections. Therefore, it is important to investigate the mechanisms underlying aggregation and propagation of these proteins for the development of novel therapeutic strategies. Here, we assessed the effects of different pharmacological interventions on the aggregation and internalization of tau and aSyn. We found that anle138b and fulvic acid decrease aSyn and tau aggregation, that epigallocatechin gallate decreases aSyn aggregation, and that dynasore reduces tau internalization. Establishing the effects of small molecules with different chemical properties on the aggregation and spreading of aSyn and tau will be important for the development of future therapeutic interventions.

To compare results of different treatment regimens based on stratification of acne to prescribe the right treatment protocol according to clinical form and grade of acne. A transversal, cohort study conducted in 230 patients with acne vulgaris. Patients were divided into three groups according to acne severity and the results of each protocol determined in 0, 4, 6, 8, 12, 18 and 24 weeks. Statistical analysis was conducted using Wilcoxon and Mann-Whitney tests 230 patients (99 females and 131 males) took part in the study. In first grade acne (70 patients), the most effective drug for papulo-pustular lesions was azelaic acid, where the average value of the reduction was 1.03% per week. For comedone reduction, the most effective drug resulted retinol with 17.7% mean reduction per week. In second grade acne (66 patients), the most effective scheme was: doxycycline + topical retinoid + benzoyl peroxide. In the third grade (92 patients), the most effective drug was oral isotretinoin. Accurate stratification, based on clinical characteristics is required for better outcome. Treatment success is related to the respective individually tailored treatment schemes in patients with acne., (© 2020 Wiley Periodicals LLC.)

Acne vulgaris is a common adolescents' disorder. Nevertheless, there is lack of knowledge about acne among adolescents. To evaluate the adolescents' knowledge and beliefs about acne, to investigate help-seeking behavior and treatment preferences. A cross-sectional study conducted in 10 public high schools in Tirana. A total of 2036 students enrolled. All participants were asked about socio-demographic data, knowledge and beliefs about acne, treatment-seeking behaviors and clinical preferences. Of participants 45.3% thought acne is a medical problem, 23.1% thought it's a cosmetic problem, and less than 10% thought acne is a normal condition for their age. Of adolescents 30% did not know that acne is not contagious, 49.7% believed acne is curable with prescribed medication, 33.4% thought acne heals by itself, and only 0.9% believed acne is non-curable. Male adolescents were more likely to have lower level of knowledge and misconceptions about acne compared to females. Only 18.5% had consulted a dermatologist. The majority (54.7%) were using anti-acne products recommended by their friends or pharmacists. Only minority of Albanian adolescents with acne consults a dermatologist. Age, gender and acne severity play a significant role in determining help-seeking behavior. Patient and parent education can significantly improve the treatment outcome., (© 2020 Wiley Periodicals LLC.)

Synucleinopathies are a group of disorders characterized by the accumulation of inclusions rich in the a-synuclein (aSyn) protein. This group of disorders includes Parkinson's disease, dementia with Lewy bodies (DLB), multiple systems atrophy, and pure autonomic failure (PAF). In addition, genetic alterations (point mutations and multiplications) in the gene encoding for aSyn (SNCA) are associated with familial forms of Parkinson's disease, the most common synucleinopathy. The Synuclein Meetings are a series that has been taking place every 2 years for about 12 years. The Synuclein Meetings bring together leading experts in the field of Synuclein and related human conditions with the goal of discussing and advancing the research. In 2019, the Synuclein meeting took place in Ofir, a city in the outskirts of Porto, Portugal. The meeting, entitled "Synuclein Meeting 2019: Where we are and where we need to go", brought together >300 scientists studying both clinical and molecular aspects of synucleinopathies. The meeting covered a many of the open questions in the field, in a format that prompted open discussions between the participants, and underscored the need for additional research that, hopefully, will lead to future therapies for a group of as of yet incurable disorders. Here, we provide a summary of the topics discussed in each session and highlight what we know, what we do not know, and what progress needs to be made in order to enable the field to continue to advance. We are confident this systematic assessment of where we stand will be useful to steer the field and contribute to filling knowledge gaps that may form the foundations for future therapeutic strategies, which is where we need to go., (© 2020 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Acne vulgaris is a common adolescent disorder but the data related to acne vulgaris is insufficient in Albania. The aim of this study was to assess the epidemiologic features of acne vulgaris and to identify lifestyle and constitutional factors in formulating a proper management protocol. A cross-sectional study conducted on a representative sample of 2036 adolescents from 10 high schools located in Tirana. A self-administered questionnaire was administered to collect the data. The binary logistic regression was applied to assess the factors linked to the presence of acne vulgaris in adolescents. The mean age in the study population was 16.2 ± 0.9 years. The self-reported prevalence of acne was 50.3% (52.1% in females and 47.9% in males). Lifetime prevalence was 68.5%. The factors significantly associated with an increased likelihood over time were: frequent consumption of sweets, frequent endurance of stress, poor quality of sleep, positive family history of acne, oily and combination skin, menstrual disorders. Acne vulgaris is common among adolescents in our country. The identification of various modifiable factors related to acne generates opportunities to tailor and focus prevention efforts and better management and treatment planning in relevant high-risk groups., (© 2020 Wiley Periodicals LLC.)

Wegener's granulomatosis, is a rare form of systemic vasculitis characterized by necrotic granulomas around the blood vessels. We report a case of a healthy 43-year-old man presented with multiple ulcerated lesions in head and all over the body, that has appeared spontaneously. It was characterized by a giant deep ulceration covered by thick purulent, in size from 3 to 4 cm, deep; sub febrile temperature, and minimal pain associated. Skin biopsies results pyoderma gangrenosum (PG)-like features: anti-neutrophil cytoplasmic antibody (cANCA) positive. Six months later, the patient developed dispea episodes. CT scan (CT) result with multiple focal opacities. He was diagnosed with wegener granulomatosis (WG) and was treated with corticosteroids and ciclophosphamide. Skin involvement in WG is not common and lesions in the skin vary from purpura, paniculitis to ulceration. In our case, skin elements are the first manifestations. Whether these elements are Wegener manifestation or we have coexistence of PG with WG, it remains a still uncertain question to answer. There is no histopathologic pathognomic elements for both. Skin involvement in WG with PG-like lesions have been rarely reported. In front of this type of widespread ulcerations, resistant to treatment we should be aware that one of the reasons may be a disease of autoimmune etiology such as WG., (© 2020 Wiley Periodicals, Inc.)

Psoriasis is a chronic, immune-mediated skin disease that also has systemic manifestations. Biologic preparates: Adalimumab, Etanercept, and Infliximab are licensed for psoriasis vulgaris treatment in Albania. To compare the efficacy of biologic therapies used for psoriasis based in our experience. A cohort prospective study during the years 2016-2018 at UHC "Mother Teresa" Tirana. In the study took place 78 patient diagnosed with psoriasis and treated with biologic therapies. Psoriasis Area Severity Index (PASI) 50 and PASI 75 index were the parameters of response outcomes. PASI 50 was achieved for 6.8, 7.02, and 7.2 weeks in patients with Etanercept, Adalimumab, and Infliximab respectively and PASI 75 for 12.8, 11.4, and 11.42 weeks. X2 = 0.076, p > .05, nonsignificant difference. PASI 50 was achieved in 27.2% of subject treated with Etanercept, 67.4% Adalimumab, and 55.5% with Infliximab for the weeks mentioned above. Meanwhile PASI 75 was achieved in 45.4% of subject treated with Etanercept, 61.7% Adalimumab, and 25% with Infliximab. X2 = 15.28, p < .05, significant difference. Biologics have revolutionized the treatment of psoriasis. To select the most appropriate agent for patient, should be considered multiple factors including adverse effects, tolerance, patient preference, cost, and mode of administration., (© 2019 Wiley Periodicals, Inc.)

Alzheimer's disease (AD) and Parkinson's disease (PD) are age-associated neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn) and tau, respectively. The coexistence of aSyn and tau aggregates suggests a strong overlap between tauopathies and synucleinopathies. Interestingly, misfolded forms of aSyn and tau can propagate from cell to cell, and throughout the brain, thereby templating the misfolding of native forms of the proteins. The exact mechanisms involved in the propagation of the two proteins show similarities, and are reminiscent of the spreading characteristic of prion diseases. Recently, several models were developed to study the spreading of aSyn and tau. Here, we discuss the mechanisms involved, the similarities and differences between the spreading of the two proteins and that of the prion protein, and the different cell and animal models used for studying these processes. Ultimately, a deeper understanding of the molecular mechanisms involved may lead to the identification of novel targets for therapeutic intervention in a variety of devastating neurodegenerative diseases.

Nowadays tuberculosis has become a reemerging infectious disease due to the many forms of immunodeficiency. Patients with eating disorders like anorexia nervosa and bulimia are a susceptible group due to the immune impairment correlated with severe malnutrition and their prevalence and incidence is growing. We describe the case of a 31-year-old woman, with long-standing history of anorexia nervosa and bulimia, diagnosed with advanced pulmonary tuberculosis. This case underlines the importance on never neglecting even the slightest symptoms in patients with malnutrition and never excluding this pathology without a proper investigation.

We present the case of an adult male who arrived to our emergency room with progressive dyspnea that had been ongoing for 2 months. During the radiological investigation, we found a large intracardiac mass, which invaded the pericardium, pulmonary trunk, pulmonary arteries, and left ventricle. Studies done with the 18FDG-PET/CT scan helped us to determine the malignant nature of the mass and to suspect the diagnosis of rhabdomyosarcoma.

Acute superior mesenteric vein thrombosis was first described in 1935 by Warren and Eberhardt. It is a potentially life-threatening condition, as it can lead to bowel ischemia and, ultimately, infarction. Its etiology may be primary or secondary to acquired prothrombotic conditions. Early recognition of mesenteric venous thrombosis is important, but can be challenging due to its nonspecific clinical presentation. Contrast-enhanced computed tomography is currently the gold standard for diagnosis. Systemic anticoagulation and surgical resection of the necrotic segment are the two main treatments. Here, we describe a case of acute post-traumatic superior mesenteric vein thrombosis, which was treated with systemic anticoagulation and resection of the ischemic bowel segment, with subsequent extension of the thrombosis to the portal vein.

Soft-tissue hematomas are a common clinical entity often associated with trauma, surgery, and bleeding disorders. In the majority of cases, soft-tissue hematomas acutely appear and spontaneously resolve, but sometimes, they present as swellings that slowly expand and progressively increase with time. We present a case of a 70-year-old man with chronic expanding hematoma of the left flank without any history of recent trauma or other medical disease. The diagnosis could not be confirmed on imaging features alone, so the patient was taken to surgery for open biopsy and excision. In patients with slowly growing extremity masses without recent trauma or chronic medical disorders, the differential diagnosis becomes challenging, and chronic expanding hematoma should be considered in addition to soft-tissue sarcomas and other malignancies.

Bifid sternum is a rare fusion anomaly of the chest wall that accounts for 0.15% of all chest deformities and may be associated with cardiac or vascular anomalies. It is usually diagnosed and surgically corrected at birth or within the first month of life. Being a diagnosis made during the neonatal period, computed tomography scan and magnetic resonance imaging are not often performed; not so many cases in literature have been studied with II level diagnostic imaging, such as computed tomography or magnetic resonance. We describe a case of bifid sternum, rarely diagnosed in adults, discovered in a 21-year-old woman who came to our Diagnostic Imaging Department to perform a chest magnetic resonance after a chest X-ray.

Purpose: To report an unusual late type Ia endoleak after endovascular aneurysm repair with a low-profile sealing ring endograft and its treatment with transcaval sac embolization., Case Report: An 82-year-old man was treated for a 47-mm abdominal aortic aneurysm associated with a 35-mm left common iliac artery aneurysm using an Ovation Abdominal Stent Graft System. Correct endograft placement was documented at 3-month follow-up. Seven months after the repair, the patient was admitted to the emergency department with acute left inguinal pain. Computed tomography showed aneurysm sac enlargement (57 mm) and a contained rupture of the left common iliac artery due to a late type Ia endoleak. The endoleak was embolized with coils and thrombin via a transcaval approach. Sac shrinkage without signs of endoleak was observed at 12-month follow-up., Conclusion: In this case, late endograft failure with sealing ring collapse created an inflow channel into the aneurysm sac, with massive type Ia endoleak., (© The Author(s) 2015.)

Introduction: Onychomycosis is a fungal infection of the nail unit. Anatomical and physiological characteristics of the nail apparatus impose the need for long-term treatment to achieve complete cure., Goal: The main goal of this project is to study the effectiveness of several treatment protocols for onychomycosis based on Scoring Clinical Index for Onychomycosis (SCIO)., Material and Methods: The study included 133 patients with onychomycosis, diagnosed by KOH microscopy and culture. Based on disease severity, patients were grouped into groups with SCIO values: 6-9, and 12-16. These groups were randomly subdivided to 5 subgroups according to the given treatment protocols: fluconazole 150 mg 1x weekly, itraconazole continual therapy, itraconazole pulse therapy, terbinafine 250 mg/d, and terbinafine + ciclopirox 8% lacquer, respectively. The cure rate was evaluated at the end of 48 week., Results: The obtained cure rates according to the above mentioned protocols were: 92.30%, 81.81%, 83.33%, 90.90%, and 100%, respectively for groups of patients with SCIO values 6 - 9. Within patients with SCIO values 12-16, were achieved cure rates as follows: 78.57%, 78.57%, 75%, 80%, and 86.66%., Conclusions: There was no statistically significant difference in cure rate between five treatment protocols applied in this study. In patients with high SCIO values is expected a decrease in cure rate.

Purpose: To evaluate the potential role, safety, and efficacy of paclitaxel-eluting balloon angioplasty for treatment of recurrent carotid in-stent restenosis (ISR)., Methods: Among 856 consecutive patients who underwent carotid artery stenting from May 2002 to January 2008, 41 patients had a significant ISR (>80% stenosis). Of these, 9 patients (7 women; mean age 78.1±5.6 years) had recurrent ISR despite multiple endovascular treatments (3.4±0.9 interventions) within a short period of time (2-5 months). These patients were treated with drug-eluting balloon (DEB) angioplasty for neointimal hyperplasia. Imaging (ultrasound or computed tomographic angiography) was performed at 1, 3, and 6 months and yearly thereafter., Results: Technical success was obtained in 100% of cases, with angiographic stenosis decreasing from 87%±4% to 6%±4% post treatment. Peak systolic velocity decreased significantly from 4.7±1.5 m/s to 0.6.±0.3 m/s after the procedure. Over a mean follow-up of 36.6±2.7 months, ultrasound imaging indicated recurrent ISR in only 3 patients at 18, 25, and 32 months after DEB angioplasty, respectively. The target vessel revascularization rate was 33.3% at 36 months. No neurological or myocardial events were recorded during follow-up. One patient died at 3 months., Conclusion: DEB may have a potential role improving outcomes of those patients treated for early recurrent carotid ISR.

Objective: to evaluate the role of stress, tobacco, drugs, infections, allergies, heredity, alcohol, hormones and skin aggressions as trigger factors and the impact on quality of life in a sample of psoriasis patients., Methods: a transversal study performed in 90 patients affected by psoriasis between January and November 2012 at the "Nene Tereza" University Hospital, Tirane, Albania, based on two scored questionnaires., Results: more than 70 % of patients reported that stressful events caused a flare- up of their psoriasis (p< 0.05). More than 60% of males and 20% of females were smokers (p< 0.05). About 20% of our patients were taking one or more of the medications listed in the questionnaire (p> 0.05). About 20% of patients reported having had recurrent infections (p<0,05). About 80% of males patients consumed alcohol (p<0,05). More than 40% reported a relative with psoriasis. Statistical comparison of the group that reported skin aggressions with the group that did not revealed a significant difference (p<0,05). Only a few of them reported to have allergies (p>0,05). About 36% of females reported that hormonal changes (puberty and menopause) exacerbated their psoriasis (p<0,05). More than 40% of patients reported that psoriasis seriously affects their quality of life., Conclusion: stress, tobacco, infections, heredity, alcohol, hormonal changes and skin aggressions were confirmed as trigger factors for psoriasis in the present sample. Allergies and the investigated drugs seemed not to have any influence in flare-ups. We found that psoriasis had a serious impact in the quality of life in over of 40% of the patients interviewed.

Aim. To compare the diagnostic performance of diffusion weighted imaging (DWI) using b-values of 1000 s/mm(2) and 2000 s/mm(2) at 3 Tesla (T) for the evaluation of clinically significant prostate cancer. Matherials and Methods. Seventy-eight prostate cancer patients underwent a 3T MRI scan followed by radical prostatectomy. DWI was performed using b-values of 0, 1000, and 2000 s/mm(2) and qualitatively analysed by two radiologists. ADC maps were obtained at b-values of 1000 and 2000 s/mm(2) and quantitatively analyzed in consensus. Results. For diagnosis of 78 prostate cancers the accuracy of DWI for the young reader was significantly greater at b = 2000 s/mm(2) for the peripheral zone (PZ) but not for the transitional zone (TZ). For the experienced reader, DWI did not show significant differences in accuracy between b-values of 1000 and 2000 s/mm(2). The quantitative analysis in the PZ and TZ was substantially superimposable between the two b-values, albeit with a higher accuracy with a b-value of 2000 s/mm(2). Conclusions. With a b-value of 2000 s/mm(2) at 3T both readers differentiated clinical significant cancer from benign tissue; higher b-values can be helpful for the less experienced readers.

Idiopathic calcinosis cutis is an uncommon condition characterized by calcium deposits in the dermis, subcutis, and muscles that most commonly are localized in one area. We report the rare case of a 16-year-old adolescent girl who exhibited unusually widespread calcium deposits. The laboratory results showed a normal biochemistry profile. Ultrasonography revealed calcifications in the fat tissue under the skin but not in deeper tissues or muscles. The histopathologic evaluation showed deep cutaneous and subcutaneous calcium deposits. Laboratory investigation revealed normal calcium, phosphate, and parathyroid hormone levels. Calcium excretion in a 24-hour urine sample was normal, but phosphate excretion was slightly low. Scintigraphic research showed no pathology in the thyroid and parathyroid glands but revealed soft-tissue calcification. A chest roentgenogram, blood tests, and testing of stools for occult blood showed no indication of internal malignancy. On the basis of these findings,the diagnosis of idiopathic calcinosis cutis was made. We discuss the pathogenesis, clinical and histologic picture, and differential diagnosis of calcinosis cutis.