Histology of non-melanoma skin cancers. An Update

Non-melanoma skin cancer (NMSC) is the most frequently diagnosed cancer in humans. Several different non-melanoma skin cancers have been reported in the literature, with several histologic variants that frequently cause important differential diagnoses with other cutaneous tumors basal cell carcinoma (BCC) is the most common malignant skin tumor, with different histologic variants that are associated with a greater or less aggressive behavior and that usually may be confused with other primitive skin tumors. Actinic keratosis, Bowen's disease, keratoacanthoma, and invasive squamous cell carcinoma (SCC) correspond to the other line of NMSC, that may have only local tumoral behavior, easy to treat and with local management (as in the case of actinic keratosis (AK), Bowen's disease, and keratoacanthoma) or a more aggressive behavior with a potential metastatic spread, as in case of invasive SCC. Therefore, histopathology serves as the gold standard during daily clinical practice, in order to improve the therapeutical approaches to patients with NMSC and to understand the distinct histopathological features of NMSC. Here, we reported the main pathological features of different non-melanoma skin cancers

Skeletal features in patient affected by maxillary canine impaction

Objective: To analyze the skeletal features of patients with maxillary canine impaction. Material and Methods: The complete pre-treatment records of 1674 orthodontic patients were examined. From the subjects with maxillary impacted canine 12 patients were excluded , remaining 108. The subjects with maxillary impacted canine were divided into two study groups: a palatally displaced canine group (PDCG) (77 patients) and a buccally displaced canine group (BDCG) (31 patients). The values of the skeletal features measured on the lateral cephalometric radiograph were compared with a control group (CG) of 121 subjects randomly selected from the initial sample without maxillary canine impaction. The statistical analysis of the difference between the study groups and the CG was tested using X2 test and Fisher's exact test. The level of significance was set at P <=0.05. Results: The CG was characterized by increased values of A point-Nasion-B point angle (ANB) and by a retropositioned or smaller lower jaw. PDCG patients showed normal skeletal features compared to the CG, presenting mainly I class and lower rank of II and III sagittal skeletal features. PDCG subjects presented also normal values of the Steiner vertical skeletal relationship angles with normal facial divergence compared to the CG. PDCG cases were also characterized by horizontal and prognathic growth. BDCG did not present significant differences in skeletal features compared to the CG, except for an increased ANB. Conclusions: Palatally displaced canine (PDC) was frequently the only orthodontic problem of patients and was not associated whit altered skeletal features. The frequent absence of malocclusion in PDC patients explains the delayed identification of this problem. BDCG patients did not present significant differences in skeletal features with respect to the orthodontic population. The presence of both buccally displaced canine (BDC) and malocclusion makes the patient with BDC both aware of the need for, and motivated to undergo, orthodontic treatment

Paraneoplastic pemphigus: insight into the autoimmune pathogenesis, clinical features and therapy

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed “paraneoplastic pemphigus”. We included also papers in French, German, and Spanish. We found 613 papers for “paraneoplastic pemphigus”. Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

The environmental and evolutionary history of Lake Ohrid (FYROM/Albania). Interim results from the SCOPSCO deep drilling project

This study reviews and synthesises existing information generated within the SCOPSCO (Scientific Collaboration on Past Speciation Conditions in Lake Ohrid) deep drilling project. The four main aims of the project are to infer (i) the age and origin of Lake Ohrid (Former Yugoslav Republic of Macedonia/Republic of Albania), (ii) its regional seismotectonic history, (iii) volcanic activity and climate change in the central northern Mediterranean region, and (iv) the influence of major geological events on the evolution of its endemic species. The Ohrid basin formed by transtension during the Miocene, opened during the Pliocene and Pleistocene, and the lake established de novo in the still relatively narrow valley between 1.9 and 1.3 Ma. The lake history is recorded in a 584 m long sediment sequence, which was recovered within the framework of the International Continental Scientific Drilling Program (ICDP) from the central part (DEEP site) of the lake in spring 2013. To date, 54 tephra and cryptotephra horizons have been found in the upper 460 m of this sequence. Tephrochronology and tuning biogeochemical proxy data to orbital parameters revealed that the upper 247.8 m represent the last 637 kyr. The multi-proxy data set covering these 637 kyr indicates long- term variability. Some proxies show a change from generally cooler and wetter to drier and warmer glacial and interglacial periods around 300 ka. Short-term environmental change caused, for example, by tephra deposition or the climatic impact of millennial-scale Dansgaard–Oeschger and Heinrich events are superimposed on the long-term trends. Evolutionary studies on the extant fauna indicate that Lake Ohrid was not a refugial area for regional freshwater animals. This differs from the surrounding catchment, where the mountainous setting with relatively high water availability provided a refuge for temperate and montane trees during the relatively cold and dry glacial periods. Although Lake Ohrid experienced significant environmental change over the last 637 kyr, preliminary molecular data from extant microgastropod species do not indicate significant changes in diversification rate during this period. The reasons for this constant rate remain largely unknown, but a possible lack of environ- mentally induced extinction events in Lake Ohrid and/or the high resilience of the ecosystems may have played a role

ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies

Dystroglycanopathies are a clinically and genetically diverse group of recessively inherited conditions ranging from the most severe of the congenital muscular dystrophies, Walker-Warburg syndrome, to mild forms of adult-onset limb-girdle muscular dystrophy. Their hallmark is a reduction in the functional glycosylation of α-dystroglycan, which can be detected in muscle biopsies. An important part of this glycosylation is a unique O-mannosylation, essential for the interaction of α-dystroglycan with extracellular matrix proteins such as laminin-α2. Mutations in eight genes coding for proteins in the glycosylation pathway are responsible for ∼50% of dystroglycanopathy cases. Despite multiple efforts using traditional positional cloning, the causative genes for unsolved dystroglycanopathy cases have escaped discovery for several years. In a recent collaborative study, we discovered that loss-of-function recessive mutations in a novel gene, called isoprenoid synthase domain containing (ISPD), are a relatively common cause of Walker-Warburg syndrome. In this article, we report the involvement of the ISPD gene in milder dystroglycanopathy phenotypes ranging from congenital muscular dystrophy to limb-girdle muscular dystrophy and identified allelic ISPD variants in nine cases belonging to seven families. In two ambulant cases, there was evidence of structural brain involvement, whereas in seven, the clinical manifestation was restricted to a dystrophic skeletal muscle phenotype. Although the function of ISPD in mammals is not yet known, mutations in this gene clearly lead to a reduction in the functional glycosylation of α-dystroglycan, which not only causes the severe Walker-Warburg syndrome but is also a common cause of the milder forms of dystroglycanopathy

Integrating Generative AI and Large Language Models in Financial Sector Risk Management: Regulatory Frameworks and Practical Applications

The rapid advancement of artificial intelligence (AI) technologies, particularly generative AI and large language models (LLMs), has ushered in a new era of possibilities for the financial sector. This paper explores the integration of these cutting-edge technologies into financial sector risk management, examining both the potential applications and the necessary regulatory frameworks. We provide a comprehensive analysis of how generative AI and LLMs can revolutionize risk assessment, fraud detection, market analysis, and regulatory compliance. The study delves into the technical aspects of these AI models, their implementation challenges, and the implications for existing risk management practices. Furthermore, we propose a novel framework for the responsible adoption of AI in financial risk management, addressing concerns related to model interpretability, data privacy, and algorithmic bias. Our findings suggest that while generative AI and LLMs offer unprecedented opportunities for enhancing risk management capabilities, they also necessitate a recalibration of regulatory approaches to ensure financial stability and consumer protection. This research contributes to the growing body of literature on AI in finance and provides actionable insights for practitioners, policymakers, and researchers in the field

The Lived Experience of Adults With Inflammatory Bowel Disease in Rural Areas: Phenomenological Study

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic gastrointestinal condition with a multifactorial etiology. It significantly impacts patients' quality of life, particularly, in rural areas where access to specialized care is limited. Challenges such as increased travel costs, social isolation, and restricted healthcare access are recognized, but their specific impact on rural Italian patients remains underexplored. This study aims to fill this gap. Using Cohen's hermeneutic phenomenological approach, in-depth interviews were conducted with 17 IBD patients from rural areas. Thematic analysis identified key patterns and themes. Two main themes emerged: “challenges of rural living,” including economic concerns and social isolation, and “communication that bridges distances.” Rural IBD patients face unique challenges extending beyond disease management, with economic hardship and social isolation being prominent. These findings highlight the need for tailored interventions to bridge healthcare gaps and improve the quality of life for rural patients, offering novel insights into their lived experiences in Italy