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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.

Purpose: Hydrocephalus is a multifactorial neurological disorder and one of the most common neurosurgical conditions characterized by excessive cerebrospinal fluid (CSF) accumulation within the brain's ventricles. It can result in dilatation of the ventricular system caused by the inadequate passage of CSF from its point of production within the ventricles to its point of absorption into the systemic circulation. Recent findings on the genetics and molecular studies of hydrocephalus have the potential to improve treatment and quality of life. Methods: Review of literature on the novel studies of the pathogenesis of hydrocephalus. Conclusion: Molecular studies on the pathogenesis of hydrocephalus have provided a means to improve the treatment and follow-up of patients with hydrocephalus. [ABSTRACT FROM AUTHOR]

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.

The rise of digital technologies and open innovation has revolutionized innovation practices, creating new opportunities for moving born-physical open innovation settings to metaverse-like virtual environments. This study explores a virtual corporate-startup collaboration program in the energy industry to understand how digital feature usage facilitates trusted relationships and enables successful pilots. This article presents a framework that emphasizes the strategic use of digital information and interaction features for targeting and bonding with partners. Program managers can tackle the unrealized metaverse through ubiquitous program management and overcome social barriers through adaptive social engineering of digital interactions. This article also provides an outlook on evolving technologies and hybrid designs. [ABSTRACT FROM AUTHOR]

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".

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]

In this paper, we generalize a classical comparison result for solutions to Hamilton-- Jacobi equations with Dirichlet boundary conditions, to solutions to Hamilton--Jacobi equations with non-zero boundary trace. As a consequence, we prove the isoperimetric inequality for the torsional rigidity (with Robin boundary conditions) and for other functionals involving such boundary conditions. [ABSTRACT FROM AUTHOR]

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]

Let Ω ⊂ R n , n ≥ 2 , be a non-empty, bounded, open and convex set and let f be a positive and non-increasing function depending only on the distance from the boundary of Ω . We consider the p-torsional rigidity associated to Ω for the Poisson problem with Dirichlet boundary conditions, denoted by T f , p (Ω) . Firstly, we prove a Pólya type lower bound for T f , p (Ω) in any dimension; then, we consider the planar case and we provide two quantitative estimates in the case f ≡ 1 . [ABSTRACT FROM AUTHOR]

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium. [ABSTRACT FROM AUTHOR]

Nowadays, plastic contamination worldwide is a concerning reality that can be addressed with appropriate society education as well as looking for innovative polymeric alternatives based on the reuse of waste and recycling with a circular economy point of view, thus taking into consideration that a future world without plastic is quite impossible to conceive. In this regard, in this review, we focus on sustainable polymeric materials, biodegradable and bio-based polymers, additives, and micro/nanoparticles to be used to obtain new environmentally friendly polymeric-based materials. Although biodegradable polymers possess poorer overall properties than traditional ones, they have gained a huge interest in many industrial sectors due to their inherent biodegradability in natural environments. Therefore, several strategies have been proposed to improve their properties and extend their industrial applications. Blending strategies, as well as the development of composites and nanocomposites, have shown promising perspectives for improving their performances, emphasizing biopolymeric blend formulations and bio-based micro and nanoparticles to produce fully sustainable polymeric-based materials. The Review also summarizes recent developments in polymeric blends, composites, and nanocomposite plasticization, with a particular focus on naturally derived plasticizers and their chemical modifications to increase their compatibility with the polymeric matrices. The current state of the art of the most important bio-based and biodegradable polymers is also reviewed, mainly focusing on their synthesis and processing methods scalable to the industrial sector, such as melt and solution blending approaches like melt-extrusion, injection molding, film forming as well as solution electrospinning, among others, without neglecting their degradation processes. [ABSTRACT FROM AUTHOR]

Carbapenem-Resistant Acinetobacter baumannii (CRAB) outbreak in intensive care units (ICUs) is a significant problem for healthcare facilities. In this study, we aimed to investigate the occurrence of CRAB isolates among ICU-admitted patients during the three waves of the COVID-19 pandemic in Iran using Multiple-Locus Variable Number Tandem-Repeat Analysis (MLVA). We obtained 50 (A) baumannii isolates from tracheal aspirate and blood culture samples. In the disc diffusion method, all isolates were cefotaxime, ceftriaxone, and cefepime-resistant, while 98% (49/50) of isolates were resistant to piperacillin, piperacillin-tazobactam, ceftazidime, and ciprofloxacin. Levofloxacin and tobramycin resistance was found in 76% (38/50) of isolates. In the microbroth dilution test all isolates were resistant to imipenem, 98% (49/50) to meropenem, 68% (34/50) to colistin, and 20% (10/50) to polymyxin (B) Based on the PCR findings, all isolates harbored blaOXA−40, ISAba-1, and int-2 genes. There were no isolates found that have the blaOXA−58, blaOXA−143, blaVEB−1, blaVIM, and int-3 genes. Among Extended-spectrum beta-lactamases (ESBL) genes, blaCTX−M, blaTEM, blaSHV, blaGES, and blaPER−1 have a prevalence of 42% (21/50), 84% (42/50), 58% (29/50), 78% (39/50), and 54% (27/50), respectively. 74% (37/50) of the isolates had the blaOXA−23 gene, while all of the isolates carried the blaOXA−40 gene. Among MBL genes, blaIPM, blaGIM, blaSIM, and blaNDM−1 have a prevalence of 20% (10/50), 8% (4/50), 22% (11/50), and 60% (30/50), respectively. The prevalence of int-1 was documented as 74% (37/50). Accordingly, all isolates were identified as CRAB. The co-existence of blaOXA−23/int-2 and blaOXA−23/isaba-1 was 74% (37/50). The co-existence of blaNDM−1/ISAba-1 was observed in 30 (60%) isolates. Using an 80% similarity threshold on the dendrogram constructed through MLVA typing, all isolates were grouped into two clusters: cluster A with 9 isolates from wave 3, and cluster B with 41 isolates from waves 3, 4, and 5. Our study confirms a clonal transmission of CRAB during the study period and suggests using molecular typing methods like MLVA in healthcare settings to identify dominant clones, antibiotic resistance patterns, and transmission routes. This will help to better manage the emergence and spread of antibiotic-resistant strains in future outbreaks. [ABSTRACT FROM AUTHOR]

SUMOylation regulates numerous cellular stress responses, yet targets in the apoptotic machinery remain elusive. We show that a single, DNA damage-induced monoSUMOylation event controls PIDDosome (PIDD1/RAIDD/caspase-2) formation and apoptotic death in response to unresolved DNA interstrand crosslinks (ICLs). SUMO-1 conjugation occurs on conserved K879 in the PIDD1 death domain (DD); is catalyzed by PIAS1 and countered by SENP3; and is triggered by ATR phosphorylation of neighboring T788 in the PIDD1 DD, which enables PIAS1 docking. Phospho/SUMO-PIDD1 proteins are captured by nucleolar RAIDD monomers via a SUMO-interacting motif (SIM) in the RAIDD DD, thus compartmentalizing nascent PIDDosomes for caspase-2 recruitment. Denying SUMOylation or the SUMO-SIM interaction spares the onset of PIDDosome assembly but blocks its completion, thus eliminating the apoptotic response to ICL repair failure. Conversely, removal of SENP3 forces apoptosis, even in cells with tolerable ICL levels. SUMO-mediated PIDDosome control is also seen in response to DNA breaks but not supernumerary centrosomes. These results illuminate PIDDosome formation in space and time and identify a direct role for SUMOylation in the assembly of a major pro-apoptotic device. After DNA damage a caspase-2 activating PIDDosome can be formed. Here the authors identify sequential post-translational modifications of PIDD1 which orchestrate PIDDosome formation in space and time. [ABSTRACT FROM AUTHOR]

This study investigates the impact of adding varying concentrations (1%, 3%, 5%, 7%, and 9%) of chia seeds on the physicochemical and antioxidant properties of oat-based yogurt fortified with 2% honey. The research analyzed changes in pH, titratable acidity, water-holding capacity (WHC), dry matter content, total phenolic content (TPC), and antioxidant activity over a 7-day storage period. The pH values ranged from 4.33 ± 0.01 to 4.57 ± 0.01, with no significant impact observed due to chia seed addition. Titratable acidity increased most rapidly in the 9% chia seed sample, particularly between days 5 and 7. WHC significantly improved with higher chia seed concentrations, with the 9% chia sample reaching 99.9 ± 0.07% compared with 69.9 ± 0.12% in the control. Dry matter content showed a similar trend, with the highest increase observed in the 9% chia sample. TPC and antioxidant activity were positively correlated with chia seed concentration and storage time, with the 9% chia sample exhibiting the highest values on day 7. Sensory evaluation revealed that the 3% chia seed concentration was most preferred by panelists for its balanced texture and flavor. Principal Component Analysis (PCA) highlighted the clustering of higher chia concentrations with improved functional properties. This study presents novel insights into the impact of varying concentrations of chia seeds on the physicochemical properties and antioxidant potential of oat-based yogurt, specifically fortified with honey, contributing to the development of functional plant-based dairy alternatives. [ABSTRACT FROM AUTHOR]

Introduction: Contradictory claims about the efficacy of several medicinal plants to promote glycemic control in patients with type 2 diabetes mellitus (T2DM) have been explained by divergences in the administration form and by extrapolation of data obtained from healthy individuals. It is not known whether the antidiabetic effects of traditional herbal medicines are influenced by gelatin capsules. This randomized crossover trial aimed to evaluate the acute effect of a single dose of raw cinnamon consumed orally either dissolved in water as a beverage or as ordinary hard gelatin capsules on postprandial hyperglycemia (>140 mg/dL; >7.8 mmol/L) in T2DM patients elicited by a nutritionally-balanced meal providing 50 g of complex carbohydrates. Methods: Fasting T2DM patients (n = 19) randomly ingested a standardized meal in five experimental sessions, one alone (Control) and the other after prior intake of 3 or 6 g of crude cinnamon in the form of hard gelatin capsules or powder dissolved in water. Blood glucose was measured at fasting and at 0.25, 0.5, 0.75, 1, 1.5 and 2 hours postprandially. After each breakfast, its palatability scores for visual appeal, smell and pleasantness of taste were assessed, as well as the taste intensity sweetness, saltiness, bitterness, sourness and creaminess. Results: The intake of raw cinnamon dissolved in water, independently of the dose, decreased the meal-induced large glucose spike (peak-rise of +87 mg/dL and Δ1-hour glycemia of +79 mg/dL) and the hyperglycemic blood glucose peak. When cinnamon was taken as capsules, these anti-hyperglycemic effects were lost or significantly diminished. Raw cinnamon intake did not change time-to-peak or the 2-h post-meal glycaemia, but flattened the glycemic curve (lower iAUC) without changing the shape that is typical of T2DM patients. Conclusions: This cinnamon's antihyperglycemic action confirms its acarbose-like property to inhibit the activities of the carbohydrate-digesting enzymes α-amylases/α-glucosidases, which is in accordance with its exceptionally high content of raw insoluble fiber. The efficacy of using raw cinnamon as a diabetes treatment strategy seems to require its intake at a specific time before/concomitantly the main hyperglycemic daily meals. Trial registration: Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-98tx28b. [ABSTRACT FROM AUTHOR]

Objective: To clarify the incidence of excessive distension absorption in hysteroscopic surgery using 5% mannitol solution, evaluate the associated risks, and help to establish a safe fluid deficit threshold for such complication. Design: Retrospective descriptive study. Setting: Academic medical center. Patients: Ten thousand six hundred ninety-three patients underwent inpatient hysteroscopic surgery with 5% mannitol perfusion using a monopolar electrosurgical instrument from Jan. 2015 to Sep. 2020. Intervention(s): None. This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital. Measurements and main results: A fluid deficit of more than 1000 mL was defined as the diagnostic criteria for excessive distension absorption. The overall incidence of excessive distension absorption in this study was 0.46% (49/10693). The incidence was 2.57% (16/623) for transcervical resection of fibroid (TCRF), 2.36% (9/381) for retained products of conception (RPOC) removal, 1.20% (6/501) for hysteroscopic uterine septum resection (HSR), 0.48% (4/828) for transcervical resection of the endometrium (TCRE), and 0.53% (14/2621) for transcervical resections of adhesion (TCRA). Excessive distension absorption could occur within seven minutes in HSR. Among the patients diagnosed with excessive distension absorption, 30.77% (12/39) exhibited signs or symptoms related to circulation overload with a fluid deficit under 2500 mL, and 10.26% (4/39) developed pulmonary edema. Conclusion: Excessive distension absorption could happen in all kinds hysteroscopic surgical treatment including RPOC removal and TCRA which were rarely reported. The overall incidence of excessive distension absorption could be low. But it would be five times higher in certain procedures such as TCRF, RPOC removal and TCRA. Resection using a needle electrode in HSR and TCRA may contribute to the short time development of excessive distension absorption. 30.77% of the patients could not tolerate the fluid deficit of less than 2500 mL which was set as a threshold for isotonic distending media and presented with circulation overload related signs or symptoms. [ABSTRACT FROM AUTHOR]

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as autism spectrum disorder (ASD) necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. If possible, the severity of the symptoms should also be assessed. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, communication deficits, and restricted, repetitive behavioral patterns, with association to several additional impairments such as somatosensory, motor, and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD-like-behavior from the etiologic, pathogenetic, and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), lipopolysaccharide (LPS), and propionic acid, or other well-documented immunogens or pathogens, like Mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, polychlorinated biphenyls (PCBs), organophosphate pesticides like chlorpyrifos (CPF), and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic-like behavior (i.e., fragile X, Rett syndrome, SHANK gene mutation, neuroligin genes, and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior, but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans. We therefore propose a scoring system for improved assessment of ASD-like behavior in animal models. [ABSTRACT FROM AUTHOR]

Advances in testing of composite materials in recent years have mostly resulted in the ability to actively characterize the uniaxial response of composites while investigations of multiaxial load cases are rare due to various challenges. One of these challenges is the lack of a suitable specimen geometry for multiaxial testing without unwanted failure modes. Ideally, such geometry should be developed and assessed virtually by means of simulation before costly and time-consuming manufacturing and testing. Therefore, reliable, and efficient simulation methods are required that incorporate the evolution of damage in FRP composites. This study investigates various geometric features virtually of cruciform specimens to test fiber-reinforced composites subjected to in-plane biaxial tensile loadings. The goal is to achieve uniform failure in the gauge region of the specimen due to biaxial stress states and to reduce any premature failure outside the gauge region. Efficient finite element simulation in the commercial software LS-DYNA is used to identify the optimal geometric features. [ABSTRACT FROM AUTHOR]

Introduction: Fragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females. Methods: We used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females. Results: Our behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased "approach" behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression. Discussion: In summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward. [ABSTRACT FROM AUTHOR]

Background: Predictions based on patient-derived materials of CFTR modulators efficacy have been performed lately in patient-derived cells, extending FDA-approved drugs for CF patients harboring rare variants. Here we developed intestinal organoids from subjects carrying S737F- and T465N-CFTR in trans with null alleles to evaluate their functional impact on CFTR protein function and their restoration upon CFTR modulator treatment. The characterization of S737F-CFTR was performed in two subjects recently assessed in nasal epithelial cells but not in colonoids. Results: Our functional analysis (Ussing chamber) confirmed that S737F-CFTR is a mild variant with residual function as investigated in colonoids of patients with S737F/Dele22-24 and S737F/W1282X genotypes. An increase of current upon Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment was recorded for the former genotype. T465N is a poorly characterized missense variant that strongly impacts CFTR function, as almost no CFTR-mediated anion secretion was registered for T465N/Q39X colonoids. ETI treatment substantially improved CFTR-mediated anion secretion and increased the rescue of mature CFTR expression compared to either untreated colonoids or to dual CFTR modulator therapies. Conclusions: Our study confirms the presence of a residual function of the S737F variant and its limited response to CFTR modulators while predicting for the first time the potential clinical benefit of Trikafta® for patients carrying the rare T465N variant. [ABSTRACT FROM AUTHOR]

Anticipating a wide range of morphological variations of arterial anatomy of foregut derivatives beyond the classical pattern, a precise understanding is pertinent to preoperative diagnosis, operative procedure and to avoid potentially devastating post-operative outcome during various traumatic and non-traumatic vascular insult of foregut. The study aimed to revisit the morphological details and update unusual configurations of arteries of foregut to establish clinico-anatomical correlations. This study described the detailed branching pattern of coeliac trunk (CT) as principal artery of foregut with source & course of hepatic, gastric, duodenal and pancreatic branches in 58 cadaveric dissections. Based on morphology, different types and subtypes were made. The descriptions were explained using figures and pertinent tables. Among classical branches of CT, splenic artery was found as most stable whereas other two branches were found to be most variable with missing common hepatic artery in 11 cases. In addition to classical trifurcation (65.52%), different types of bifurcation (12.07%) and tetrafurcations (22.41%) of CT were observed. Regarding variations of hepatic arteries (27.59%), both non-classical origin and accessory hepatic branches were found. In case of gastric branches, more variant origins were seen with right gastric (50%) as compared to left gastric artery (34.48%). Other morphological variations included non-classical origin of gastro-duodenal artery (18.96%) along with presence of accessory pancreatic (17.13%) and duodenal arteries (6.38%). Awareness of anatomical variations regarding circulatory dynamics of foregut is worth knowing in order to facilitate successful planning of surgery involving upper abdominal organs with least complications. [ABSTRACT FROM AUTHOR]

Limited research has been conducted on porcine miR-155 promoters, and previous study from our group have identified two haplotypes (TT and CC) in different pig breeds, each associated with five fully linked mutation sites within or near the miR-155 gene (Li et al. Dev Comp Immunol 39(1):110–116, 2013). In this study, the promoter region of porcine miR-155 was screened, and two important transcription factors, Foxp3 and RelA, were identified. The binding ability of Foxp3 protein was found to be affected by the first mutation site (A/C) using EMSA analysis. In vitro experiments revealed that the expression level of miR-155 was significantly higher in the C haplotype compared to the T haplotype. Additionally, northern blotting assays indicated that both the first mutation site (A/C) and the fourth mutation site (G/T) had a significant impact on miR-155 expression levels. These findings provide further insights into the transcriptional regulation of porcine miR-155 and identify crucial mutation sites that influence miR-155 expression. This knowledge can serve as a basis for identifying potential molecular markers associated with disease resistance in swine. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant therapy with targeted therapy or immunotherapy has become the standard of care for fully resected stage III–IV melanoma. In this scenario, real-world data are needed to relate the actual effectiveness and safety of these regimens with the evidence provided in the clinical trials. This study provides clinicians and researchers with the results of an Italian single-center real-world experience on the use of adjuvant therapy in resected stage III–IV melanoma patients. Our findings confirm the real-world effectiveness and safety of adjuvant regimens, yet underscores the need for further research to explore biomarker-based predictors for relapse and to assess the translation of improved relapse-free survival into long-term overall survival benefit. This study was carried out at the Dermatologic Clinic of the University of Turin, Italy, to assess the effectiveness and safety of adjuvant therapy in patients who received either targeted therapy (TT: dabrafenib + trametinib) or immunotherapy (IT: nivolumab or pembrolizumab) for up to 12 months. A total of 163 patients participated, including 147 with stage III and 19 with stage IV with no evidence of disease. The primary outcomes were relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). At 48 months, both TT and IT approaches yielded comparable outcomes in terms of RFS (55.6–55.4%, p = 0.532), DMFS (58.2–59.8%, p = 0.761), and OS (62.4–69.5%, p = 0.889). Whilst temporary therapy suspension was more common among TT-treated patients compared to IT-treated individuals, therapy discontinuation due to adverse events occurred at comparable rates in both groups. Predictors of relapse included mitoses, lymphovascular invasion, ulceration, and positive sentinel lymph nodes. Overall, the proportion of BRAF-mutated patients receiving IT stood at 7.4%, lower than what was observed in clinical trials. [ABSTRACT FROM AUTHOR]