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Determining the spatial thickness (z) of in situ and reworked fallout pyroclastic deposits plays a key role in volcanological studies and in shedding light on geomorphological and hydrogeological processes in peri-volcanic areas. However, this is a challenging line of research because (1) field-based measurements are expensive and time-consuming, (2) the ash might have been dispersed in the atmosphere by several volcanic eruptions, and (3) wind characteristics during an eruptive event and soil-forming and/or denudation processes after ash deposition on the ground surface affect the expected spatial distribution of these deposits. This article tries to bridge this knowledge gap by applying statistical techniques for making representative spatial thickness predictions to be used for the analysis of geomorphic processes at the catchment and sub-catchment scales. First, we compiled a field-based thickness measurement dataset (https://doi.org/10.5281/zenodo.8399487; Matano et al., 2023) of fallout pyroclastic deposits in the territories of several municipalities in Campania, southern Italy. Second, 18 predictor variables were derived mainly from digital elevation models and satellite images and were assigned to each measurement point. Third, the stepwise regression (STPW) model and random forest (RF) machine learning technique are used for thickness modeling. Fourth, the estimations are compared with those of three models that already exist in the literature. Finally, the statistical combination of different predictions is implemented to develop a less biased model for estimating pyroclastic thickness. The results show that the prediction accuracy of RF (RMSE <82.46 and MAE <48.36) is better than that of existing models in the literature. Moreover, statistical combination of the predictions obtained from the above-mentioned models through a least absolute deviation (LAD) combination approach leads to the most representative thickness estimation (MAE <45.12) in the study area. The maps for the values estimated by RF and LAD (as the best single model and combination approach, respectively) illustrate that the spatial patterns did not change significantly, but the estimations by LAD are smaller. This combined approach can help in estimating the thickness of fallout pyroclastic deposits in other volcanic regions and in managing geohazards in areas covered with loose pyroclastic materials.

We studied the Gioia Sannitica active normal fault (GF) along the southern Matese fault (SMF) system in the southern Apennines of Italy in detail. The current activity of the fault system and its potential to produce strong earthquakes have been underestimated so far and are now defined here. Precise mapping of the GF fault trace on a 1:20 000 geological map and point and line data on the geometry, kinematics, and slip rate of the faults forming the SMF system are made available in electronic format. The GF, and the entire fault system along the southern Matese mountain front in general, is made of slowly slipping faults with a long active history revealed by the large geologic offsets, mature geomorphology, and complex fault patterns and kinematics. Present activity has resulted in late Quaternary fault scarps resurrecting the foot of the mountain front and Holocene surface faulting. The resurrected mountain front indicates variation in slip rate through time. The slip rate varies along-strike, with a maximum Upper Pleistocene–Holocene slip rate of ∼ 0.5 mm yr−1. Activation of the 11.5 km long GF can produce up to M 6.2 earthquakes. If activated together with the 18.5 km long Ailano–Piedimonte Matese fault (APMF), the seismogenic potential would be M 6.8. The slip history of the two faults is compatible with a contemporaneous rupture. The observed Holocene displacements on the GF and APMF are compatible with activations during some poorly constrained historical earthquakes, such as the 1293 (M 5.8), 1349 (M 6.8; possibly a southern prolongation of the rupture on the Aquae Iuliae fault), and 346 CE earthquakes. A fault rupture during the poorly constrained 847 CE earthquake is also chronologically compatible with the dated displacements.

Flow cytometry is the gold-standard laser-based technique to measure and analyze fluorescence levels of immunostaining and DNA content in individual cells. It provides a valuable tool to assess cells in the G0/G1, S, and G2/M phases, and those with polyploidy, which holds prognostic significance. Frozen section analysis is the standard intraoperative assessment for tumor margin evaluation and tumor resection. Here, we present flow cytometry as a promising technique for intraoperative tumor analysis in different pathologies, including brain tumors, leptomeningeal dissemination, breast cancer, head and neck cancer, pancreatic tumor, and hepatic cancer. Flow cytometry is a valuable tool that can provide substantial information on tumor analysis and, consequently, maximize cancer treatment and expedite patients’ survival.

Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice. To determine how ASCs from obese mice impacted tumor growth, we mixed ASCs isolated from CD- or HFD-fed mice with mammary tumor cells and injected them into the mammary glands of lean mice. Tumor cells mixed with ASCs from obese mice grew significantly larger tumors and had increased invasion into surrounding adipose tissue than tumor cells mixed with control ASCs. ASCs from obese mice demonstrated enhanced tumor cell invasion in culture, a phenotype associated with increased expression of insulin-like growth factor-1 (IGF-1) and abrogated by IGF-1 neutralizing antibodies. Weight loss induced in obese mice significantly decreased expression of IGF-1 from ASCs and reduced the ability of the ASCs to induce an invasive phenotype. Together, these results suggest that obesity enhances local invasion of breast cancer cells through increased expression of IGF-1 by mammary ASCs, and weight loss may reverse this tumor-promoting phenotype.

Abstract Background Obesity is correlated with an increased risk for developing postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it is important to understand how the obese microenvironment influences normal mammary tissue to increase breast cancer risk. We hypothesized that obesity increases the proportion of luminal progenitor cells, which are thought to be the cells of origin for the most common types of breast cancer, potentially leading to an increased risk for breast cancer. Methods To study the obese microenvironment within the mammary gland, we used a high-fat diet mouse model of obesity and human breast tissue from reduction mammoplasty surgery. We identified changes in breast epithelial cell populations using flow cytometry for cell surface markers, in vitro functional assays and expression of markers on breast tissue sections. Results In both obese female mice and women, mammary epithelial cell populations demonstrated significant decreases in basal/myoepithelial cells, using either flow cytometry or cell-type-specific markers (SMA and p63). Estrogen receptor alpha (ERα) expression was significantly increased in luminal cells in obese mammary tissue, compared with control mice or breast tissue from lean women. Functional assays demonstrated significantly enhanced mammary epithelial progenitor activity in obese mammary epithelial cells and elevated numbers of ERα-positive epithelial cells that were co-labeled with markers of proliferation. Weight loss in a group of obese mice reversed increases in progenitor activity and ERα expression observed in obese mammary tissue. Conclusions Obesity enhances ERα-positive epithelial cells, reduces the number of basal/myoepithelial cells, and increases stem/progenitor activity within normal mammary tissue in both women and female mice. These changes in epithelial cell populations induced by obesity are reversible with weight loss. Our findings support further studies to examine how obesity-induced changes in stem/progenitor cells impact breast tumor incidence and histologic tumor types.

Obesity is correlated with breast tumor desmoplasia, leading to diminished chemotherapy response and disease-free survival. Obesity causes chronic, macrophage-driven inflammation within breast tissue, initiated by chemokine ligand 2 (CCL2) signaling from adipose stromal cells. To understand how CCL2-induced inflammation alters breast tumor pathology, we transplanted oncogenically transformed human breast epithelial cells with breast stromal cells expressing CCL2 or empty vector into murine mammary glands and examined tumor formation and progression with time. As tumors developed, macrophages were rapidly recruited, followed by the emergence of cancer-associated fibroblasts (CAFs) and collagen deposition. Depletion of CD11b + myeloid lineage cells early in tumor formation reduced tumor growth, CAF numbers, and collagen deposition. CCL2 expression within developing tumors also enhanced recruitment of myeloid progenitor cells from the bone marrow into the tumor site. The myeloid progenitor cell population contained elevated numbers of fibrocytes, which exhibited platelet-derived growth factor receptor-alpha (PDGFRα)-dependent colony formation and growth in vitro. Together, these results suggest that chronic inflammation induced by CCL2 significantly enhances tumor growth and promotes the formation of a desmoplastic stroma through early recruitment of macrophages and fibrocytes into the tumor microenvironment. Fibrocytes may be a novel target in the tumor microenvironment to reduce tumor fibrosis and enhance treatment responses for obese breast cancer patients.

Objective. To report a case of unusually widespread sporadic venous malformations of the head and neck associated with normal D-dimer levels and, due to the protean clinical manifestations and increased risk of coagulopathy of these lesions, to review their diagnosis and clinical management. Case Report. A 25-year-old man presented with a one-year history of intermittent right-sided neck swelling and tongue swelling. Physical exam revealed additional lesions present throughout the head and neck. There was no family history suggestive of heritable vascular malformations. Radiographic imaging demonstrated 15 lesions located in various tissue layers consistent with venous malformations. A coagulation screen showed a normal prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer level, and fibrinogen level. It was determined that the patient was not at increased risk for intraoperative coagulopathy and preoperative heparin administration would not be necessary. The patient’s buccal and tongue lesions were subsequently excised with no complications. The patient also underwent sclerotherapy evaluation for his neck mass. Conclusion. This case describes a unique presentation of sporadic multifocal venous malformations. It also emphasizes the importance of prompt diagnosis and workup when multiple venous malformations are present to prevent morbidity during surgical excision secondary to intravascular coagulopathy.

São descritos 3 casos de paracoccidioidomicose com a forma aguda da doença, nos quais formas leveduriformes de Paracoccidioides brasiliensis foram visualizadas ao exame direto de medula óssea, sendo a cultura também positiva em um caso. Salienta-se o acometimento do sistema fagocítico-mononuclear e a ausência de resposta às provas cutâneas de hipersensibilidade tardia a antígenos microbianos e de P. brasiliensis em todos, bem como a gravidade do quadro clínico e lesões ósseas generalizadas em um caso, com 20.260 eosinófilos/mm³ no sangue periférico. Os autores discutem o possível papel do eosinófilo na interação hospedeiro-parasita na paracoccidioidomicose, sugerindo que a ativação de subpopulação TH 2 e o aumento de secreção de IL 5 e de GM-CSF possam estar relacionados à grande eosinofilia presente no caso mais graveThe authors described three acute paracoccidioidomycosis patients with bone marrow involvement. P. brasiliensis yeast forms were observed in bone marrow smears of all them, and in one case, culture also revealed fungus growth. The mononuclear phagocytic sistem involvement, the blood eosinophilia and the negative skin hipersensibility responses were emphasized in all of them, as well as the severity of the disease in one case, with disseminated bone lesions and 20.260 eosinophils/mm³ in peripheral blood. The authors discuss the possible role of eosinophil in the host-parasite interaction in paracoccidioidomycosis, suggesting that TH 2 subpopulation activation and increased IL 5 and GM-CSF secretions may be responsible by eosinophilia in the most severe case

In October, 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. A 11-year-old boy exhibited atrial premature complexes and a 74-year-old patient developed acute heart failure. In two patients hospitalized in São Paulo city, acute Chagas' disease was diagnosed by the demonstration of circulating Trypanosoma cruzi. At autopsy in a fatal case, acute Chagas' cardiomyopathy was demonstrated. Xenodiagnosis were positive in 9 out of 14 tested patients. A specific IgG immune response was found in all patients and specific IgM antibodies were identified in 20 out of 22 tested patients. A epidemiological survey showed the existence of Triatoma brasiliensis in the outbuildings of this farm, but none in the house where most of the guests stayed. A high rate of infection with Trypanosoma cruzi was found in opossums. These observations together with those related to the food consumed by the patients, lead the authors to suggest that the human infections resulted from oral contamination probably originating from naturally infected marsupials in the area or crushed infected bugs.Em outubro de 1986, 7 a 22 dias após uma reunião em uma fazenda no estado da Paraíba, 26 pessoas apresentaram doença febril, associada a edema bipalpebral bilateral, e de membros inferiores, hepatoesplenomegalia leve, linfadenopatia e, mais raramente, a um exantema. Um menino de 11 anos apresentou arritmia atrial ao eletroeardiograma e um paciente de 74 anos desenvolveu insuficiência cardíaca aguda. Em 2 pacientes hospitalizados em São Paulo, foi estabelecido o diagnóstico de Doença de Chagas aguda por observação de T. cruzi em creme leucocitário. Em autópsia de um caso fatal foi demonstrada cardiomiopatia chagásica aguda. O xenodiagnóstico foi positivo em 9 de 14 pacientes testados. Anticorpos específicos de classe IgG foram encontrados em todos os pacientes e da classe IgM em 20 de 22 doentes examinados. Estudo epidemiológico revelou Triatoma brasiliensis nas vizinhanças desta fazenda, porem tal vetor não foi encontrado na casa onde a maioria dos hóspedes pernoitou. Observou-se alta taxa de gambás infectados por Trypanosoma cruzi. Essas observações, associadas as informações relativas aos alimentos consumidos, sugerem que a contaminação de alimentos tenha se originado de secreções de marsupiais naturalmente infectados ou de triatomíneos infectados, que poderiam ter sido esmagados durante o preparo do caldo de cana.

The fungicidal action of sodium hypochlorite (0.3, 1, 2.5, 5 and 10%); formaldehyde (2, 5, and 10%); and ethyl alcohol (70%) on yeast forms of Paracoccidioides brasiliensis Pb 18 and a newly-isolated Goiana strain was described. Contact between the fungus and the disinfectants was maintained for 1, 2, 24, 48 and 72 hours at room temperature. Viability was evaluated by the fluorescein diacetate-ethidium bromide treatment, culture in solid and liquid media (36ºC and 26ºC); yeast to mycelial germination at room temperature; and radiometric study of metabolic activity. All concentrations of disinfectants were found to be effective in inactivating Pb 18 and Goiana strains, except for the 1-hour contact with 2% formaldehyde, in which fluorescein diacetate-ethidium bromide treatment was found to reveal 40 and 27% of viable cells, respectively. The yeast to mycelial germination method was considered to reveal faster and similar results as compared to culture in solid and liquid media.Descreveu-se a ação fungicida do hipoclorito de sódio (0,3; 1; 2,5; 5 e 10%); do formaldeído (em solução aquosa a 2,5 e 10%); e álcool etílico a 70,0% sobre formas leveduriformes de 2 cepas de Paraccoccidioides brasiliensis: Pb 18 e cepa Goiana, recentemente isolada. A incubação do fungo e desinfetantes foi realizada à temperatura ambiente por períodos de 1, 2, 24, 48 e 72 horas. A viabilidade foi avaliada pelo tratamento com diacetato de fluoresceína-brometo de etídeo; pela cultura em meios sólidos e líquidos a 36ºC e 26ºC; transformação de levedura em micélio à temperatura ambiente; e estudo radiométrico da atividade metabólica. Todas as concentrações de todos os desinfetantes estudados foram capazes de inativar ambas as cepas, exceto na incubação com formaldeído a 2% por 1 hora, em que o tratamento por diacetato de fluoresceína-brometo de etídeo revelou 40% e 27% de células viáveis, respectivamente, para a cepa Pb 18 e Goiana. A transformação de levedura em micélio foi considerada um método rápido, com resultados semelhantes ao cultivo em meios sólidos e líquidos.

Relata-se o quadro clínico de 27 pacientes com doença de Chagas aguda, acompanhados no ambulatório da Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da FM-USP no período de 1974 a 1987. As vias de transmissão envolvidas foram: vetorial em 7 casos, transfusional em 9, transplante de rim e/ou transfusional em 4, acidental em 1, via oral em 3, provável aleitamento materno em 1, congênita ou aleitamento materno em 1, congênita ou transfusional em 1. Pacientes com infecção por via vetorial eram procedentes da Bahia e Minas Gerais, tendo 6 apresentado a doença de 1974 a 1980 e um em 1987. Já os pacientes infectados por via transfusional adquiriram a doença na Grande São Paulo, 7 deles após 1983. O quadro clínico foi oligossintomático ou assintomático em 4 pacientes, sendo 3 deles imunodeprimidos por doença de base ou por medicamentos. Em outros 2 pacientes imunodeprimidos ocorreu miocardite grave com insuficiência cardíaca congestiva. O quadro clínico foi também mais grave em 5 de 6 crianças menores de dois anos de idade, qualquer que fosse a via de transmissão. A avaliação de 16 pacientes tratados na fase aguda com benzonidazol (4-10mg/kg/dia) por 30 a 60 dias mostrou falha terapêutica em 4/16 (25,0%), possível sucesso terapêutico em 9/16 (56,2%), sendo inconclusivos os resultados em 3/16 (18,8%). A reação de LMC foi concordante com o xenodiagóstico em 18 e 22 casos (agudos e na fase crônica inicial), e se negativou mais precocemente que as RSC. No seguimento pós-terapêutico, observou-se aparecimento de doença linfoproliferativa em um paciente com anemia aplástica e que recebia corticosteróide 6 anos após o emprego de benzonidazol.The authors report clinical features and therapeutic response of 24 outpatients with acute Chagas' disease, and 3 in the initial chronic phase, referred to the Clinic for Infectious and Parasitic Diseases of the FMUSP "Clínicas" Hospital between 1974 and 1987. The following transmission routes were involved: triatominae in 7 cases, blood transfusion in 9, kidney transplantation and/or blood transfusion in 4, accidental in 1, oral route in 3, probably breast feeding in 1, congenital or breast feeding in 1, and congenital or blood transfusion in 1. Six patients infected by triatominae acquired the disease between 1974 and 1980 and one in 1987. The blood transfusion infected patients acquired the disease in Greater São Paulo, seven of whom after 1983. The acute phase Chagas' disease was oligosymptomatic in 4 patients: three of such patients being immunocompromised by drugs or other diseases. Another two adult immunocompromised patients developed myocarditis and congestive heart failure. Clinical features were severe in 5 from 6 children under two years, irrespective of the transmission route. Evaluation of the acute phase patients treated with benznidazol (4-10 mg/kg/day) showed: therapeutic failure in 4/16 (25.0%); possible cure in 9/16 (53.2%) and inconclusive results in 3/16 (18.8%). The antibody and complement-mediated lysis reaction was in keeping with the xenodiagnosis in 18/22 cases, having shown negative results after treatment earlier than classical serological reactions. One aplastic anaemia patient receiving corticosteroid presented lymphoproliferative disease 6 years after being treated with benznidazol for acute Chagas' disease.

Cinco pacientes portadores de esquistossomose mansônica hépato-esplênica, associada à salmonelose, foram tratados com dose única de praziquantel (60 mg/kg peso), havendo desaparecimento da hipertermia do 1.° ao 3.° dia após a terapêutica e cura clínica subseqüente da salmonelose e da esquistossomose. O estudo da sensibilidade "in vitro" das bactérias isoladas: Salmonella minnesota, Salmonella dublin, Salmonella panama e Salmonella typhi (2 pacientes) não mostrou ação direta do praziquantel sobre tais enterobactérias. Os soros coletados antes e 24 horas após o tratamento não foram capazes de inibir o crescimento das bactérias isoladas dos respectivos pacientes.

Estudaram-se quinze pacientes com infecção assintomática por Clonorchis sinensis, revelada através de exame parasitológico de fezes. Todos eram de origem asiática e procuraram o Laboratório Central do Instituto Adolfo Lutz para se submeterem a exames laboratoriais necessários à regularização de sua situação, face à nova legislação sobre imigrantes. Eram todos indivíduos adultos, seis pertencendo ao sexo feminino e nove ao masculino. Os quinze pacientes com clonorquíase foram internados no Hospital das Clínicas da FMUSP e tratados com Praziquantel, na dosagem de 60 mg/kg de peso corporal, dividida em duas tomadas. Foram realizados exames coprológicos quantitativos (método de Kato-Katz), antes do tratamento específico e no 15º, 30º e 60º dias após a terapêutica. Na última avaliação (60? dia após terapêutica), em nove pacientes (60,0%) não se encontraram ovos do trematódeo nas fezes e nos seis (40,0%), que continuavam eliminando ovos, notou-se redução na quantidade eliminada (superior a 90% em cinco e a 30% no paciente restante). Os pacientes foram também submetidos a exames subsidiários, para avaliação do estado geral e função hepática, antes da administração de Praziquantel e, posteriormente, no seguimento ambulatorial. A medicação foi relativamente bem tolerada pelos pacientes, verificando-se a ocorrência de efeitos colaterais representados por náuseas e vômitos (dois casos), vertigens e tonturas (dois casos), epigastralgia (dois casos) e diarréia no 3? dia após tratamento (um caso).Fifteen adult patients with assymptomatic infection due to Clonorchis sinensis, diagnosed by coprological examination, were studied. They all came from Asia (twelve from Taiwan, two from South Korea and one from Hong Kong) and were examined at the Adolfo Lutz Institute and the Department of Infectious Diseases, School of Medicine, University of São Paulo, in São Paulo, Brazil. Six patients were women and nine men. All studied patients were admitted to hospital and treated with praziquantel (60 mg/ kg). Previous to treatment and on the 15th, 30th and 60th days after praziquantel administration, patients were submitted to quantitative stool examinations, according to Kato-Katz's technique and to hematological and biochemical serum analysis. After a 60 day follow-up nine patients (609c) were negative for C. sinensis eggs in stools. Those not cured after praziquantel administration (six patients, 40%) revealed a sharp decline in faecal elimination of C. sinensis eggs.

Foram estudadas as alterações hematológicas de 30 pacientes com diagnóstico de leptospirose internados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de Sáo Paulo. Verificou-se que mais da metade dos pacientes 16 (53,3%) apresentavam contagem normal de leucócitos no momento da internação; 12 (40%) apresentavam leucócitos e 2 (6,6%) leucopenia. Vinte e cinco doentes (83,3%) apresentavam desvio à esquerda e 29 (96,6%) neutrofilia relativa. Vinte e quatro pacientes tiveram o diagnóstico de anemia. A plaquetopenia ocorreu em 26 (86,6%) dos doentes. Como alterações mais características no mielograma, ressaltamos a alteração da relação G/E (série Granulocítica/série Eritroblástica), às custas de hipercelula-ridade relativa e/ou absoluta da série granulocítica, e/ou hipocelularidade relativa e/ou absoluta da série vermelha; a eritropoese predominantemente microeritroblástica em vários doentes; o encontro de plasmocitose discreta ou moderada e, na série intersticial, o aumento da atividade macrofágica. A análise estatística da série megacariocitária do mielograma dos 30 pacientes revelou não existir relação de dependência significativa entre a celularidade da série megacariocitária e o número de plaquetas no sangue periférico; porém, verificou-se existência da relação de dependência entre a plaquetogênese medular e a contagem de plaquetas no sangue periférico. A possibilidade de haver inibição da plaquetogênese medular por algum produto bacteriano náo pode ser totalmente afastada, porém acreditamos que o exame estático da medula óssea não pode dar-nos uma idéia precisa do mecanismo dinâmico da formação de plaquetas na presença de "consumo periférico".

Abstract  A forensic case of suspected Leptospirosis with fatal course was resolved by the molecular detection of Leptospira interrogans in postmortem human tissues and in environmental samples. Polymerase chain reaction analysis and DNA sequencing confirmed the clinical diagnosis of Weil syndrome, and the death was considered to be an occupational accident with all the legal implications. [ABSTRACT FROM AUTHOR]

In vitro delayed hypersensitivity was studied in patients with either the chronic or the indeterminate phase of Chagas' disease. Normal healthy individuals were used as controls. The leucocyte migration inhibition test was applied using as antigen an extract of culture forms of T. cruzi or an extract of normal rat heart. The results showed that patients with the chronic phase of the disease reacted significantly with both antigens, whereas most patients with the indeterminate phase did not react with heart antigen and only five out of fourteen (35%) reacted with T. cruzi antigen. It is suggested that these individuals may represent patients about to develop the chronic phase of the disease. The relevance of these findings to the immune mechanism influencing the onset of the chronic phase of Chagas' disease is discussed. [ABSTRACT FROM AUTHOR]

Pannuti C S (Instituto de Medicine Tropical de Sao Paulo e Departamento de Microbiologia e Imunologiado Instituto de Ciencias Biomedicas da Unrversidade de Sao Paulo, Sao Paulo, Brazil), Carvalho R P S, Evans A S, Cenabre L C, Amato Neto V, Camargo M, Angelo M J O and Takimoto S. A prospective clinical study of the mononucleosis syndrome in a developing country. 1980, 9: 349–353. A prospective aetiologic analysis made of 70 children and adults with the clinical and haematologic features of infectious mononucleosis (IM) in Sao Paulo, Brazil, revealed 65.7% due to EBV (31 heterophile antibody positive (HA+), 15 HA negative (HA - ) cases), 8.6% due to and 4.3% due to CMV. One case was related to viral hepatitis and one to drug hypersensitivity. The other 18.6% were of unknown cause. In the 46 IM cases positive tests were found for EBV/IgM in 93.5%, for heterophile by the absorbed horse Rbc test in 64.2% and by sheep Rbc in 37%. The immune-adherence haemagglutination test was slightly more sensitive than the horse Rbc test in 39 IM sera tested. In 41 EBV/IgM positive sera, EBV/lgA was present in 17/25 containing heterophile antibody and in 2/16 lacking heterophile antibody; anti-EA was present in 85%. The average age of HA + IM cases was 13.2 years and of HA- cases 4.7 years. Three HA + and 5 HA—IM cases occurred in the 0–2 year old age group. Few clinical features differentiated between aetiological agents. Exudative tonsillitis was the most helpful one a.nd occurred in 67.7% of HA + IM cases, 26.7% of HA - cases, in 1 of 3 CMV cases,and not at all in 6 infections. [ABSTRACT FROM PUBLISHER]

Myocarditis is not an uncommon finding in autopsy series of patients with AIDS, although clinically important myocarditis is rarely noted. We describe a 50-year-old woman with AIDS and chronic chagasic megaesophagus, without previous cardiac abnormalities, who experienced reactivation of Chagas' disease, characterized by the finding of Trypanosoma cruzi via direct microscopic examination of the buffy coat, xenodiagnosis, and blood culture; she developed fatal acute myocarditis. Reactivation of Chagas' disease in patients with AIDS has been reported, but in the great majority of cases it has been associated with central nervous system involvement. In areas where Chagas' disease is endemic, reactivation may occur in patients with AIDS. [ABSTRACT FROM PUBLISHER]

The article presents a study about the detection of Trypanosoma cruzi in Triatoma infestans. The primary aim of the study is to explore and compare the potential usefulness of polymerase chain reaction (PCR) and direct microscopical examination for detecting Trypanosoma cruzi infection in bugs used for xenodiagnosis.

Background: The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients., Methods: We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001-2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used., Results: All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS., Conclusion: Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches., (© 2024. The Author(s).)

Mesenchymal tumors originate from mesenchymal cells and can be either benign or malignant, such as bone, soft tissue, and visceral sarcomas. Surgery is a cornerstone treatment in the management of mesenchymal tumors, often requiring complex procedures performed in high-volume referral centers. However, the COVID-19 pandemic has highlighted this need for alternative non-surgical approaches due to limited access to surgical resources. This review explores the role of non-surgical treatments in different clinical scenarios: for improving surgical outcomes, as a bridge to surgery, as better alternatives to surgery, and for non-curative treatment when surgery is not feasible. We discuss the effectiveness of active surveillance, cryoablation, high-intensity focused ultrasound, and other ablative techniques in managing these tumors. Additionally, we examine the use of tyrosine kinase inhibitors in gastrointestinal stromal tumors and hypofractionated radiotherapy in soft tissue sarcomas. The Sarculator tool is highlighted for its role in stratifying high-risk sarcoma patients and personalizing treatment plans. While surgery remains the mainstay of treatment, integrating advanced non-surgical strategies can enhance therapeutic possibilities and patient care, especially in specific clinical settings with limitations. A multidisciplinary approach in referral centers is vital to determine the optimal treatment course for each patient.

Introduction: Retroperitoneal sarcoma (RPS) surgery poses unique challenges. This retrospective study aimed to analyze the learning curve (LC) in RPS surgery, assessing the relationship between surgical experience and outcomes., Materials and Methods: Cumulative sum (CUSUM) analysis was used to analyze 62 RPS surgeries performed by a single surgeon between 2016 and 2022 at our center., Results: The number of cases where the surgeon acted as first operator increased from 3 in 2016 to 13 in 2022. The surgeon operated with his mentor in 66.7 % of cases in 2016, whereas in 7.7 % of cases in 2022. LC consisted of 3 phases. Phase 1 (16 cases), with a negative slope, represented shorter operative time (OT) and fewer number of resected organs (RO). Phase 2 (30 cases) was the plateau phase. Phase 3 (16 cases), with a positive slope, indicated longer OT and more RO. Statistically significant differences were observed in terms of size (p = 0.003), presentation (p = 0.048), number of resected organs (p = 0.046), pattern of resection (p = 0.033), OT (p = 0.006), and length of stay (p = 0.026) between the three phases., Conclusion: This study focused on the critical role of LC in RPS surgery, emphasizing its influence on outcomes. We identified three phases, highlighting the surgeon's evolution. This offers a framework for educating sarcoma surgeons and ensuring exposure to increasing surgical complexity. In discussions on sarcoma referral centers and the correlation between case volume and outcomes, this study underlines the importance of evaluating LC to distinguish surgeons qualified to manage sarcoma cases within a referral center., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Ltd.)

Background: Myeloid neoplasms, including acute myeloid leukemia, have been traditionally among the less investigated cancer types concerning germline predisposition. Indeed, myeloid neoplasms with germline predisposition are challenging to identify because often display similar clinical and morphological characteristics of sporadic cases and have similar age at diagnosis. However, a misidentifications of familiarity in myeloid neoplasms have a critical impact on clinical management both for the carriers and their relatives., Aims: We conducted a family segregation study, in order to identify novel cancer predisposing genes in myeloid neoplasms and classify novel identified variants., Methods and Results: We performed a thorough genomic analysis using a large custom gene panel (256 genes), the Myelo-Panel, targeted on cancer predisposing genes. In particular, we assessed both germline and somatic variants in four families, each with two siblings, who developed hematological neoplasms: seven acute myeloid leukemia and one Philadelphia-positive chronic myeloid leukemia. In each family, we identified at least one novel potentially predisposing variant, affecting also genes not included in the current European LeukemiaNet guidelines for AML management. Moreover, we suggest reclassification of two germline variants as pathogenic: likely pathogenic p.S21Tfs*139 in CEPBA and VUS p.K392Afs*66 in DDX41., Conclusion: We believe that predisposition to hematological neoplasms is still underestimated and particularly difficult to diagnosed. Considering that misidentification of familiarity in myeloid neoplasms have a critical impact on the clinical management both for the carriers and their relatives, our study highlights the importance of revision, in this clinical context, of clinical practices that should include thorough reconstruction of family history and in-depth genetic testing., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background: Young adults, aged between 17 and 25 years, experienced a strong impact on both their mental health and well-being due to COVID-19. Indeed, they were simultaneously faced with the normative tasks of their age and stressors associated with the long-lasting COVID-19 pandemic. This study offers further insights into the perceptions of the well-being (stress, anxiety, and depression) and social bonds in young Italian adults during and after the COVID-19 pandemic., Methods: The first survey was conducted between December and February 2021 (i.e., during the second wave in Italy) and included a total sample of 347 participants. The second survey took place between April and May 2022 (i.e., at the end of the health emergency in Italy) and consisted of a total sample of 313 participants., Results: T-tests, correlations, and linear regressions were performed. Overall, our findings showed an increased mood disturbance was positively correlated with having contracted COVID-19 and negatively associated with social connectedness. Furthermore, social assurance was found to negatively predict mood disorders during COVID-19., Conclusion: While numerous studies have focused on mental health, there has been limited exploration of protective factors, which could represent a different perspective that emphasizes individuals' resources rather than their vulnerabilities.

Background: Officinal plants, minerals, animal derivatives, and miscellaneous have always been used to treat and improve appearance despite the different aesthetic canons of a specific historical and cultural context., Objective: The aim of this work was to make a critical comparison between medieval and modern dermocosmetics analyzing the works of Trotula de Ruggiero, a female doctor of the 11th century teaching and working inside the illustrious "Medical School of Salerno," who devoted particular attention to the promotion of female care, beauty, and well-being., Methods: We applied the historical-critical method analyzing the Latin text and the nglish translation of the standardized corpus of the main Trotula medieval manuscript De Ornatu Mulierum with a multidisciplinary scientific approach ranging from botany to pharmaceutical chemistry and technology, pharmacology and pathology., Results: We identified the medicinal plants, derivatives of animal origin and minerals used in the recipes of Trotula, highlighting their biological properties in the light of current scientific knowledge. A critical comparison between medieval and modern dermocosmetics is reported also taking into consideration the chemical, pharmaceutical, and technological literature., Conclusion: Beyond the obvious changes in the paradigms of cosmetology and the different beauty canons of Middle Age with respect to modern times, our results emphasize the attention of Trotula to female care, beauty and well-being as well as the extraordinary combination of tradition and modernity in her work., (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: In the last decade, many steps forward have been made in acute myeloid leukemia prognostic stratification, adding next-generation sequencing techniques to the conventional molecular assays. This resulted in the revision of the current risk classification and the introduction of new target therapies., Aims and Methods: We wanted to evaluate the prognostic impact of acute myeloid leukemia (AML) mutational pattern on relapse occurrence and survival after allogeneic stem cell transplantation. A specific next-generation sequencing (NGS) panel containing 26 genes was designed for the study. Ninety-six patients studied with NGS at diagnosis were included and retrospectively studied for post-transplant outcomes., Results: Only eight patients did not show any mutations. Multivariate Cox regression revealed FLT3 (HR, 3.36; p=0.02), NRAS (HR, 4.78; p=0.01), TP53 (HR, 4.34; p=0.03), and WT1 (HR 5.97; p=0.005) mutations as predictive variables for relapse occurrence after transplantation. Other independent variables for relapse recurrence were donor age (HR, 0.97; p=0.04), the presence of an adverse cytogenetic risk at diagnosis (HR, 3.03; p=0.04), and the obtainment of complete remission of the disease before transplantation (HR, 0.23; p=0.001). Overall survival appeared to be affected only by grade 2-4 acute GvHD occurrence (HR, 2.29; p=0.05) and relapse occurrence (HR, 4.33; p=0.0001) in multivariate analysis., Conclusions: The small number of patients and the retrospective design of the study might affect the resonance of our data. Although results on TP53, FLT3, and WT1 were comparable to previous reports, the interesting data on NRAS deserve attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Metafuni, Amato, Giammarco, Bellesi, Rossi, Minnella, Frioni, Limongiello, Pagano, Bacigalupo, Sica and Chiusolo.)

Inhibitors of poly(ADP-ribose) polymerase (PARPi) are increasingly employed as salvage therapy in epithelial ovarian cancer (EOC), but cytotoxic drug exposure along with PARP inhibition may favor development of hematological disorders. In our study, of 182 women with EOC treated with PARPi, 16 (8.7%) developed therapy-related myeloid neoplasms (t-MNs), with 12 cases of myelodysplasia and 4 of acute myeloid leukemia. All experienced persistent cytopenia after PARPi discontinuation. Seven patients had del(5q)/-5 and/or del(7q)/-7, nine had a complex karyotype and TP53 mutations, recently reported as risk factor for t-MNs in EOC post-PARPi, were found in 12 out of 13 tested patients. Four patients had a rapid and fatal outcome, one had stable disease, eleven underwent induction therapy, followed by allogeneic hematopoietic cell transplantation in seven. Three of these 11 patients experienced refractory disease, and 8 had complete remission. During a 6.8 months (range 2.3-49) median observation time, 3 out of 16 patients were alive, with one surviving patient free of both solid and hematological tumors. Ten patients died because of leukemia, two because of transplant-related events, one from heart failure. Five more patients experienced persistent cell blood count abnormalities following PARPi discontinuation, without reaching MDS diagnostic criteria. A customized Myelo-panel showed clonal hematopoiesis in all five patients. These findings confirm the actual risk of t-MNs in EOC patients after chemotherapy and prolonged PARPi therapy. The management of these patients is complex and outcomes are extremely poor. Careful diagnostic procedures are strongly recommended whenever unusual cytopenias develop in patients receiving PARPi therapy., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The empirical evidence from different countries point out many of those who die from coronavirus would have died anyway in the relatively near future due to their existing frailties or co-morbidities. The acceleration of the mortality conceives the underlying insight according to deaths are "accelerated" ahead of schedule due to COVID-19. Starting from this idea, we forecast the future mortality acceleration, based on the deterioration due to the presence of the comorbidities at COVID-19 diagnosis. Accordingly, we explicitly determine the contribution of each comorbidity on the acceleration forecasting, showing the future trend of the excess of deaths due to the COVID-19. To this aim, our proposal consists in developing a revised Charlson Comorbidity Index in a stochastic environment. Based on a post-stratification scheme, we obtain an unbiased comorbidity index that varies by age, centered on the reference population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carannante, D'Amato and Iaccarino.)

Phaeodactylum tricornutum (Bacillariophyta) is a worldwide-distributed diatom with the ability to adapt and survive in different environmental habitats and nutrient-limited conditions. In this research, we investigated the growth performance, the total lipids productivity, the major categories of fatty acids, and the antioxidant content in P. tricornutum subjected for 15 days to nitrogen deprivation (N-) compared to standard culture conditions (N+). Furthermore, genes and pathways related to lipid biosynthesis (i.e., glucose-6-phosphate dehydrogenase, acetyl-coenzyme A carboxylase, citrate synthase, and isocitrate dehydrogenase) and photosynthetic activity (i.e., ribulose-1,5-bisphospate carboxylase/oxygenase and fucoxanthin-chlorophyll a/c binding protein B) were investigated through molecular approaches. P. tricornutum grown under starvation condition (N-) increased lipids production (42.5 ± 0.19 g/100 g) and decreased secondary metabolites productivity (phenolic content: 3.071 ± 0.17 mg GAE g -1 ; carotenoids: 0.35 ± 0.01 mg g -1 ) when compared to standard culture conditions (N+). Moreover, N deprivation led to an increase in the expression of genes involved in fatty acid biosynthesis and a decrease in genes related to photosynthesis. These results could be used as indicators of nitrogen limitation for environmental or industrial monitoring of P. tricornutum .

Comprehensive characterization of the urinary and urothelium-bound microbiomes in bladder cancer (BCa) and healthy state is essential to understand how these local microbiomes may play a role in BCa tumorigenesis and response to therapy, as well as to explain sex-based differences in BCa pathobiology. Performing 16 s rDNA microbiome analysis on 166 samples (urine and paired bladder tissues) from therapy-naïve BCa patients undergoing radical cystectomy and healthy controls, we defined (1) sex-specific microbiome differences in the urine and bladder tissue, and (2) representativeness of the tissue microenvironment by the voided urinary microbiome. The genus Klebsiella was more common in the urine of female BCa patients versus healthy controls, while no clinically relevant bacteria were found differently enriched in men. In tissues, the genus Burkholderia was more abundant in the neoplastic versus the non-neoplastic tissue in both sexes, suggesting a potential role in BCa pathobiology. Lastly, we found that the urinary microbiome shares >80% of the bacterial families present in the paired bladder tissue, making the urinary microbiome a fair proxy of the tissue bacterial environment. PATIENT SUMMARY: We identified specific bacteria present in the urine and tissues of male and female bladder cancer patients. These novel data represent a first step toward understanding the influence of the bladder microbiome on the development of bladder cancer and on the response to intravesical and systemic therapies., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Infections remain a significant problem, in patients undergoing an allogeneic hematopoietic stem-cell transplant (HSCT) and efforts have been made over the years, to reduce the incidence, morbidity and mortality of infectious complications., Areas Covered: This manuscript is focused on the epidemiology, risk factors and prevention of infections after allogeneic HSCT. A systematic literature review was performed using the PubMed database, between November 2019 and January 2020, with the following MeSH terms: stem-cell transplantation, infection, fungal, bacterial, viral, prophylaxis, vaccines, prevention. The authors reviewed all the publications, and following a common revision, a summary report was made and results were divided in three sections: bacterial, fungal and viral infections., Expert Opinion: Different infections occur in the early, intermediate and late post-transplant period, due to distinct risk factors. Improved diagnostic techniques, pre-emtive therapy and better prophylaxis of immunologic complications, have reduced the morbidity and mortality of infections. The role of the gut microbiota is under careful scrutiny and may further help us to identify high-risk patients.

Background: The role of microbiota in Lynch syndrome (LS) is still under debate. We compared oral and fecal microbiota of LS saliva and stool samples with normal healthy controls (NHC)., Methods: Total DNA was purified from feces and saliva to amplify the V3-V4 region of the 16s rRNA gene. Sequences with a high-quality score and length >250 bp were used for taxonomic analysis with QIIME software., Results: Compared to NHC, LS fecal samples demonstrated a statistically significant increase of Bacteroidetes and Proteobacteria and a significant decrease of Firmicutes at the phylum level and of Ruminococcaceae at the family level. Moreover, LS oral samples exhibited a statistically significant increase of Veillonellaceae and Leptotrichiaceae and a statistically significant decrease of Pasteurellaceae. A beta-diversity index allowed differentiation of the two groups., Conclusions: A peculiar microbial signature is associated with LS, similar to that of sporadic colorectal cancer and Crohn's disease. These data suggest a possible role of proinflammatory bacteria in tumor development in a condition of genetic predisposition, such as LS.

Objectives: A milder clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been anecdotally reported over the latest phase of COVID-19 pandemic in Italy. Several factors may contribute to this observation, including the effect of lockdown, social distancing, lower humidity, lower air pollution, and potential changes in the intrinsic pathogenicity of the virus. In this regard, the clinical severity of COVID-19 could be attenuated by mutations in SARS-CoV-2 genome that decrease its virulence, as well as by lower virus inocula., Methods: In this pilot study, we compared the reverse transcription polymerase chain reaction (RT-PCR) amplification profile of 100 nasopharyngeal swabs consecutively collected in April, during the peak of SARS-CoV-2 epidemic, to that of 100 swabs collected using the same procedure in May., Results: The mean Ct value of positive samples collected in May was significantly higher than that of samples collected in the previous period (ORF 1a/b gene: 31.85 ± 0.32 vs. 28.37 ± 0.5, p<0.001; E gene: 33.76 ± 0.38 vs. 29.79 ± 0.63, p<0.001), suggesting a lower viral load at the time of sampling. No significant differences were observed between male and females in the two periods, whilst higher viral loads were found in (i) patients over 60-years old, and (ii) patients that experienced severe COVID-19 during the early stages of the pandemic., Conclusions: This pilot study prompts further investigation on the correlation between SARS-CoV-2 load and different clinical manifestation of COVID-19 during different phases of the pandemic. Laboratories should consider reporting quantitative viral load data in the molecular diagnosis of SARS-CoV-2 infection.

In several tumors the PI3K/AKT/mTOR pathway is frequently disrupted, an event that results in uncontrolled cell proliferation and tumor growth. Through the years, several compounds have been developed to inhibit the pathway at different steps: the mammalian target of rapamycin (mTOR) seemed to be the most qualified target. However, this kinase has such a key role in cell survival that mechanisms of resistance are rapidly developed. Nevertheless, clinical results obtained with mTOR inhibitors in breast cancer, renal cell carcinoma, neuroendocrine tumors and mantle cell lymphoma push oncologists to actively further develop these drugs, maybe by better selecting the population to which they are offered, through the research of predictive factors of responsiveness. In this review, we aim to describe mechanisms of resistance to mTOR inhibitors, from preclinical and clinical perspectives., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)