Nobody's land? The oldest evidence of early Upper Paleolithic settlements in inland Iberia.

The Iberian Peninsula is a key region for unraveling human settlement histories of Eurasia during the period spanning the decline of Neandertals and the emergence of anatomically modern humans (AMH). There is no evidence of human occupation in central Iberia after the disappearance of Neandertals ~42,000 years ago until approximately 26,000 years ago, rendering the region "nobody's land" during the Aurignacian period. The Abrigo de la Malia provides irrefutable evidence of human settlements dating back to 36,200 to 31,760 calibrated years before the present (cal B.P.) This site also records additional levels of occupation around 32,420 to 26,260 cal B.P., suggesting repeated settlement of this territory. Our multiproxy examination identifies a change in climate trending toward colder and more arid conditions. However, this climatic deterioration does not appear to have affected AMH subsistence strategies or their capacity to inhabit this region. These findings reveal the ability of AMH groups to colonize regions hitherto considered uninhabitable, reopening the debate on early Upper Paleolithic population dynamics of southwestern Europe.

Exposome and basal cell carcinoma: a multicenter case-control study.

BACKGROUND: While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute. This study aimed to investigate the association of BCC and exposome-related factors in the Spanish population. METHODS: BCC cases (n = 119) and controls (n = 127) with no history of skin cancer were recruited between April 2020 and August 2022 by 13 dermatologists throughout Spain in this prospective multicenter case-control study. RESULTS: The BCC group had a higher proportion of outdoor workers, more years of UVR exposure, and a greater consumption of drugs (statins, ASA, hydrochlorothiazide, ACE inhibitors and omeprazole), P < 0.05. Avoidance of sun exposure was the most used photoprotection measure in both groups. The use of hats or caps was higher in the BCC group (P = 0.01). The solar protection factor (SPF) used 15 years previously was higher in the control group (P = 0.04). The control group had a higher daily screen time (P < 0.001), and practiced more relaxation activities (P = 0.03). Higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with BCC (P < 0.05). Statistical significance for all the aforementioned variables was maintained in the multivariate analysis (P < 0.05). CONCLUSIONS: The study found a significant association between BCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers, promoting sun-safe behaviors and stress-reducing activities, and also adequate skin photoprotection in patients on certain medications associated with increased BCC risk.

The Influence of the Exposome in the Cutaneous Squamous Cell Carcinoma, a Multicenter Case-Control Study.

INTRODUCTION: The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism's biological responses over time. Ultraviolet radiation (UVR) from sun exposure has been recognized as the main etiological agent of skin cancer, and squamous cell carcinoma (SCC) is one most commonly associated with chronic exposure. However, in recent years, evidence suggests that lifestyle, environmental pollution, and contaminants in water and food can have an influence. OBJECTIVES: To study the relationship between SCC and sun exposure, pollution, stress, and lifestyle in a Spanish cohort. MATERIALS AND METHOD: A multicenter case-control study was carried out in which 13 dermatologists from different regions of Spain recruited cases and controls between April 2020 and August 2022. The group of cases were patients diagnosed with SCC and, as a control group, people who attended Dermatology consultations as companions with no history of skin cancer. RESULTS: A total of 62 patients with SCC and 126 controls were included (62.9% males, median age 76.46 (10.1) and 33.3%, median age 55.7 (15), respectively). The SCC group had experienced more outside work than the controls (75% vs. 22.4%, p < 0.001), less recreational exposure (sunbathing, p = 0.05, and outdoor sports, p = 0.01), and a lower annual income (p = 0.01), with an increase in tobacco exposure (p < 0.001), without differences in other carcinogens, such as ionizing radiation or chemical exposure. The control group had a higher daily screentime use (p < 0.001) and practiced more relaxation activities (p = 0.03). A higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with SCC (p < 0.05). Some chronic medications (anxiolytics, antidepressants, beta-blockers, statins, hydrochlorothiazide, ACE inhibitors, metformin, and omeprazole) were also statistically associated with SCC. Statistical significance for all aforementioned variables was maintained in the multivariate analysis (p < 0.05). CONCLUSIONS: The study found a significant association between SCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers promoting sun-safe behaviors and stress-reducing activities, in addition to adequate skin photoprotection in patients under certain medications associated with SCC.

A multicenter case-control study comparing sun exposure habits and use of photoprotection measures in patients diagnosed with different types of skin cancer.

BACKGROUND: While skin cancer awareness programs have significantly furthered public understanding about the harmful effects of the sun, there is a disparity between photoprotection knowledge and protection practices. OBJECTIVE: To compare sun exposure habits and photoprotection measures in patients diagnosed with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma versus controls. METHODS: Multicentre case-control observational study carried out by 13 Spanish dermatologists between April 2020 and August 2022. Patients diagnosed with BCC, SCC, or melanoma were considered cases. The control group consisted of individuals with no history of skin cancer. RESULTS: Of the 254 cases (56.2% female; mean age, 62.67 ± 15.65), 119 (31.2%) had BCC, 62 (16.27%) SCC, and 73 (19.1%) melanoma. The control group consisted of 127 (33.33%) individuals. Avoiding sun exposure between 12:00 and 16:00 was the most commonly used photoprotection measure (habitually/always: 63.1%), followed by the use of sunscreen (habitually/always: 58.9%). Patients with melanoma were less likely to use clothing and shade to avoid sun exposure (p < .05), whereas those with BCC and SCC reported greater use of head coverings (p = .01). BCC and SCC groups reported greater sun exposure 15 years prior, whereas controls reported greater use of sunscreen. However, at the time of this study all groups reported using SPF ≥ 21, and the majority SPF > 50. No differences were observed in photoprotection measures between people with and without a previous history of skin cancer. CONCLUSIONS: We describe differences in photoprotection measures and sun exposure patterns among patients diagnosed with different skin tumor types. Whether these differences may influence the type of tumor each developed will require further investigation.

PUVA therapy in persistent cutaneous histiocytosis: Case report and literature review.

BACKGROUND: Cutaneous and mucocutaneous histiocytosis (group C) comprise a wide variety of entities affecting skin and/or mucosae. Although they are considered as reactive proliferations, their exact pathophysiology remains unknown and, therefore, they lack a specific treatment. AIMS: The aim of this study is to review the evidence on cases of histiocytosis treated with UVB and/or UVA and to report a new case of relapsing group C histiocytosis that has been successfully treated with PUVA therapy. MATERIALS & METHODS: We have conducted a review of the literature published over the last 40 years on the treatment of histiocytosis with phototherapy in the online PubMed database. We also describe a new case of successful treatment of histiocytosis with PUVA therapy. RESULTS: Our patient was a 27-year-old man with persistent outbreaks of cutaneous histiocytosis over the previous 8 years. He responded successfully to PUVA therapy, and no relapse has been detected after one year of follow-up. DISCUSSION: Self-involution is usual in group C histiocytosis, so conservative management is usually the first approach. Relapsing cases pose a therapeutic challenge. Reported treatment options for these patients include isotretinoin, cryotherapy, immunosuppressants, low-dose chemotherapy, CO2 laser, radiotherapy, and surgery. Phototherapy and photochemotherapy have been used in a small number of patients with considerable success. The main limitation to provide firm recommendations on histiocytosis therapy is the absence of solid evidence, as the articles published are mainly case reports with a short follow-up. In our patient, despite the short follow-up we have considered photochemotherapy to be effective since no spontaneous remission had been achieved in the previous 8 years. CONCLUSION: PUVA therapy could be a safe and effective option to treat persistent cutaneous manifestations in patients with histiocytosis, although more evidence is required to support this statement.

Whose Words Hurt? Contextual Determinants of Offensive Speech.

Tracing the boundaries of freedom of expression is a matter of wide societal and academic import-especially, as these boundaries encroach on the politics of inclusion. Yet, the elements that constitute offensive speech and determine its legal status remain poorly defined. In two studies, we examined how lay judges evaluate the offensiveness of apparently descriptive statements. Replicating prior work, we found that non-linguistic features (including speaker intent and outcomes on the audience) modulated the statements' meaning. The speaker's identity-and, in particular, their membership in the target group-independently influenced evaluations of offensive speech among conservatives and progressives alike. When asked to disclose their abstract principles, or jointly evaluate two contrastive cases, participants tended to deny the relevance of identity while primarily endorsing the intent principle. Taken together, our findings confirm that assessments of offensive speech are governed by contextual features, some of which are not introspectively deemed relevant.

Systemic amyloidosis with an exceptional cutaneous presentation.

Alopecia and nail distrophy are rare signs of systemic amyloidosis. We present a case with both manifestations and give a brief review of the cutaneous signs of this disease. A biopsy of affected or unaffected skin may provide the diagnosis.

TCR-γ expression in primary cutaneous T-cell lymphomas.

Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30(+) primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3(+)/CD8(+), and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30(+) and CD56(+), respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primary cutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.

Changes in activatory and inhibitory natural killer (NK) receptors may induce progression to multiple myeloma: implications for tumor evasion of T and NK cells.

The molecular basis of monoclonal gammopathy of undetermined significance (MGUS) progression to a malignant monoclonal gammopathy remains poorly understood. It was recently suggested that this process involves the suppression of innate and adaptive immunity. In this study, we examined immunogenic differences in bone marrow plasma cells among individuals without gammopathy (controls) and patients with MGUS, multiple myeloma (MM), and plasma cell leukemia. We detected differences in major histocompatibility complex (MHC) class I expression, MHC class I chain-related molecule A, and CD95 that were more evident between MGUS and MM samples; there appeared to be a critical imbalance between natural killer (NK)-cell activating and inhibitory signals during the transition from MGUS to MM. Our results indicate that the human leukocyte antigen (HLA) class I(bright), MICA(dim/-), and CD95(dim/-) immunophenotype reported in myeloma cells may result from an extensive interaction of malignant cells with cytotoxic T and NK cells and appears to be immunoedited for the evasion of immunosurveillance.

Mucinous carcinoma of the skin: evaluation of lymphatic invasion with D2-40.

Primary cutaneous mucinous carcinoma is a rare adnexal sweat gland neoplasm that mainly affects elderly people. Differential diagnosis includes mammary and gastrointestinal metastatic mucinous carcinoma (MC) and secondary cutaneous involvement by underlying neoplasms. An 83-year-old woman presented with an 8-year history of slow-growing infiltrate plaque in her right hemithorax, with ulceration on supraclavicular area, right upper limb edema and palpable axillary lymphadenopathies. She underwent partial excision of the tumor and local radiotherapy. Imaging studies showed widespread cutaneous dissemination with enlargement of ipsilateral axillary lymph nodes but without evidence of underlying breast cancer. Histopathological examination showed large amounts of mucin in the dermis including small islands of epithelial cells. They stained positive for cytokeratin 7, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15, and c-erbB-2. Lymphatic invasion was demonstrated by D2-40-immunostained sections. A diagnosis of primary cutaneous mucinous carcinoma was made. Our aim was to reevaluate the differential clinical, histopathological, and immunohistochemical criteria for distinguishing primary cutaneous mucinous carcinoma from skin metastases of visceral mucinous carcinoma, especially those arising in breast. We also propose D2-40 as a reliable marker to detect lymphatic invasion that indicates a strong aggressive trend with shorter recurrence-free and predicts nodal metastases.

Necrotizing vasculitis with a polyarteritis nodosa-like pattern and selective immunoglobulin A deficiency: case report and review of the literature.

Selective immunoglobulin A deficiency (IgAD) is a primary immunodeficiency disease characterized by low levels (< 7 mg/dl) of serum immunoglobulin (Ig) A and normal serum levels of IgG and IgM. Patients with IgAD have increased risk for recurrent respiratory and gastrointestinal infections, autoimmune disease, asthma and allergy. A 26-year-old woman was admitted with sudden onset of painful cutaneous lesions on her lower extremities, pyrexia and arthromyalgia. Her medical history was remarkable for recurrent respiratory tract infections, self-limited episodes of acute diarrhea, atopy, splenomegaly and a 4-year history of a lung granulomatous lesion. Laboratory and imaging tests ruled out severe life-threatening infection, connective tissue disease and neoplasm. Serum protein electrophoresis showed a low IgA serum level (6.67 mg/dl), with normal serum levels of IgG and IgM, conducting to a diagnosis of selective IgAD. A skin biopsy showed necrotizing vasculitis without any sign of internal organ disease. We report a patient with IgAD and granulomatous involvement of lungs, spleen and medium-sized arteries of the skin. Although IgAD results from a failure of B-cell differentiation, we propose that deregulated immune response with production of cross-reactive antibodies and hyperstimulation of T cells and macrophages could contribute to this widespread granulomatous reaction.

Anetodermic mastocytosis: response to PUVA therapy.

Mastocytosis is a group of disorders characterized by the accumulation of mast cells in different tissues and organs. The skin is the most frequently involved organ (90% of cases) where mastocytosis may show a heterogenic clinical expression. Anetodermic lesions are an unusual clinical presentation of mastocytosis. We report a case of anetodermic mastocytosis in a 26-year-old man, with sparse lesions and a benign course. PUVA therapy obtained excellent results in this case. Darier's sign should be investigated in patients with anetodermic lesions of unclear origin in order to exclude cutaneous mastocytosis.

Información, ansiedad y depresión en pacientes sometidos a trasplante de progenitores hematopoyéticos (TPH) en un estudio de intervención psicológica / Information, anxiety and depression in patients submitted to bone marrow transplantation (BMT) in a study of psychological intervention

En el Servicio de Hematología del hospital Universitario Virgen de las Nieves de Granada se ha puesto en marcha un programa psicológico para pacientes candidatos a trasplante de progenitores hematopoyéticos (TPH). Con dicho programa se pretende favorecer la adaptación, amortiguar el impacto psicológico y el sufrimiento asociado. Se potencian los recursos para disminuir, en los posibles, los efectos negativos como son la ansiedad y la depresión, en base a las diferencias individuales, el nivel de información a cerca del proceso y a sus propios recursos de afrontamiento. El programa psicológico consiste en cuatro sesiones que incluyen. 1. Análisis y manejo de la información, 2. Habilidades de afrontamiento, 3. Manejo del estrés y 4. Preparación para el aislamiento a nivel familiar. Se midieron las variables de ansiedad, depresión con la Escala de Ansiedad y Depresión (HAD) y el nivel de información con una escala categorial diseñada específicamente para este estudio. Los momentos de medida se realizaron al diagnóstico, al ingreso en cámara de aislamiento, a los cien días, a los seis meses, al año y a los dos años después del trasplante. Se contemplan dos grupos principales; un grupo intervención, que recibe el programa de intervención psicológica y un grupo control al cual no se aplica el programa debido a la mecánica de ingreso. En este trabajo se muestra como los pacientes que reciben la intervención psicológica antes del trasplante, obtienen niveles menores en ansiedad y depresión, mostrando un nivel de información más elevado que los que no reciben dicha intervención. Se concluye con la importancia de la intervención psicológica especializada y adaptada en un proceso agresivo como es el trasplante de progenitores hematopoyéticos (AU)

At the department of Haematology on the University Hospital Virgen de las Nieves, Granada, it is applied a psychological program for patient bone marrow transplantation (BMT) candidates. With this program it is tried to favors the adjustment, to muffle the psychological impact and to determine the associated suffering. The resources are promoted to diminish the negative effects such as anxiety and depression, on the basis of the individual differences, the level of information to near the process and to it own resources of confrontation. The psychological program consist of four meetings which include: 1. Analysis and information management, 2. Confrontation skills, 3. Stress management and 4. Preparation for the isolation to family level. It is measured anxiety and depression by the hospital anxiety and depression scale (HADS); and the level information about the disease process and transplantation by a categorical scale designed for this research. The assessments are realized at following phases: the moment of diagnosis, at the revenue in chamber of isolation, at hundred days, at six months, one year and two years after BMT. Two principal groups were studied: an intervention group, which received the psychological intervention program and a control group for which did not apply the program due to the mechanics of revenue. In this work it appears as the patients who receive the psychological intervention before the transplant, they obtain minor levels in anxiety and depression; showing a level of information higher than it the patient did not receive the above mentioned intervention. These results stress the importance of psychological intervention for BMT patients (AU)