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Neoplasias , Humanos , Neoplasias/epidemiologia , França/epidemiologia , Sistema de Registros , IncidênciaRESUMO
The objective of this paper is to present the technical and feasibility analysis of an innovative mechanical recycling system for exhausted coffee capsules. This recycling process involved the sorting of spent coffee grounds (SGC) and the subsequent drying and melt-mixing of a portion of these grounds with the remaining capsule components, mainly composed of polypropylene (PP), along with optional virgin PP. These newly developed composite materials exhibited mechanical and rheological properties comparable or even surpassing those of virgin PP. They were also successfully utilized for the injection of new capsule shells, thus alignin with the principles of the circular economy. In addition to the technical aspects, this paper present a comprehensive Techno-Economic Analysis (TEA) of the proposed recycling processes, considering the inclusion of virgin PP (0-20 %) and the initial moisture content (MSGC) of SGC(5-55 %) as varying factors. An industrial plant, designed to handle up to 190 million exhausted coffee capsules and produce up to 1500 tons of recycled compund was appropriately sized. The analysis revealed that processes are profitable across all examined scenarios and that the Net Present Value ranged between 800 k (for vPP = 20 % and MSGC = 55 %) and 2000 k (for vPP = 0 % and MSGC = 5 %).
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Café , Reciclagem , Polipropilenos , Instalações Industriais e de ManufaturaRESUMO
OBJECTIVE: Surgical reconstruction of soft tissue defects in the distal third of the lower limbs has always been challenging for surgeons. The adipofascial flaps are made up of vascularized adipose tissue, which plastically conforms to the site to be reconstructed with its rich presence of stem cells. In this study, we resumed our case history of reverse neuroadipofascial sural flap, and we evaluated the stability of the scar to verify if this type of reconstruction can ensure long-term results and its regenerative power. PATIENTS AND METHODS: In this retrospective cohort study, we analyzed 32 patients who had undergone lower limb reconstruction with the sural neuroadipovenous flap. RESULTS: A total of 32 patients were included in the study. The average age was 62.2 years. Chronic skin ulcer was the cause of the defects in 13 (40.6%) patients, chronic wound after trauma in 7 (21.9%) patients, wheel bedsores in 4 (12.5%) patients, osteomyelitis in 5 (15.6%) patients, exposed internal hardware in 2 (6.3%) patients, dog bite in 1 (3.1%). The site defect comprised 11 heels (34.4%), 4 external malleoli (12.5%), three medial malleoli (9.4%), 12 lower third of the leg (37.5%), and two dorsa of the foot (6.3%). In all cases, defects were covered with reverse sural island flap. The dimension of the flap ranged from 5 to 9 cm in length and from 3 to 7 in width. Six patients showed early or later postoperative complications. CONCLUSIONS: The neuroadipofascial sural flap is versatile, fast, and easy-to-perform to cover a chronic defect in the distal part of the lower limb, including both the malleoli and the heel, due to its long vascular pedicle. Consistent with the studies carried out in other districts, the present study confirms the remarkable regenerative power of the vascularized adipose tissue at the level of complex wounds of the lower third of the leg.
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Procedimentos de Cirurgia Plástica , Extremidade Inferior , Estudos Retrospectivos , Retalhos Cirúrgicos/irrigação sanguínea , Resultado do Tratamento , Úlcera , HumanosRESUMO
Background: Breast is a symbol of femininity, motherhood and sexuality. Breast cancer (BC) is the leading cause of cancer death in women worldwide and most frequent cancer in Italy: in 2019, 53.500 new cases were diagnosed. BC and its treatment, the disturbances of body image, and mental health problems such as anxiety and depression could influence sexuality. Very often the aspect of sexuality in BC is likely not to be fully investigated: cultural barriers may also contribute to lack of attention to these issues. In Italy, there are very few Breast Units that provide the figure of the sexologist and psycho-oncologist. Methods: We enlisted 141 BC patients (pts), mean age was 54 years afferent to Breast Unit S. Maria Goretti Hospital, Latina, from March 2019 to March 2020. All pts had undergone surgical intervention. Participants were invited to complete a structured questionnaire, which included four close-up questions regarding self-image, sexual activity, sexual satisfaction, analyzing these aspects before and after BC and its treatments. Finally the participants were asked if they needed the sexologist and psycho-oncologist. Results: Only 2/141 pts (1.41%) refused to participate in our study. Of 139 participants, 68 (48.92%) had disturbances of body image, 26 (18.7%) had sexuality greatly negatively affected, and 103 (74.1%) every kind of sexual dissatisfaction after BC. 38 pts (27.3%) would require the help of the sexologist. 135 ( 97%) would require the help of the psycho-oncologist. Despite the negative influence in their body-image and sexuality, few pts require the help of the sexologist, but nearly all pts require the help of the psycho-oncologist. Conclusion: In our study nearly all pts require the help of the psycho-oncologist, but few pts of the sexologist. Further studies will be needed to understand the reasons for this disparity: at the moment we are carrying out another project following this illustration, with the aim of understanding why this disparity.
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Neoplasias da Mama , Imagem Corporal/psicologia , Neoplasias da Mama/complicações , Cicatriz , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Comportamento Sexual/psicologia , Sexualidade/psicologiaRESUMO
OBJECTIVE: To analyze trends in cancer incidence and mortality (France, 1990-2018), with a focus on men-women disparities. METHODS: Incidence data stemmed from cancer registries (FRANCIM) and mortality data from national statistics (CépiDc). Incidence and mortality rates were modelled using bidimensional penalized splines of age and year (at diagnosis and at death, respectively). Trends in age-standardized rates were summarized by the average annual percent changes (AAPC) for all-cancers combined, 19 solid tumors, and 8 subsites. Sex gaps were indicated using male-to-female rate ratios (relative difference) and male-to-female rate differences (absolute difference) in 1990 and 2018, for incidence and mortality, respectively. RESULTS: For all-cancers, the sex gap narrowed over 1990-2018 in incidence (1.6 to 1.2) and mortality (2.3 to 1.7). The largest decreases of the male-to-female incidence rate ratio were for cancers of the lung (9.5 to 2.2), lip - oral cavity - pharynx (10.9 to 3.1), esophagus (12.6 to 4.5) and larynx (17.1 to 7.1). Mixed trends emerged in lung and oesophageal cancers, probably explained by differing risk factors for the two main histological subtypes. Sex incidence gaps narrowed due to increasing trends in men and women for skin melanoma (0.7 to 1, due to initially higher rates in women), cancers of the liver (7.4 to 4.4) and pancreas (2.0 to 1.4). Sex incidence gaps narrowed for colon-rectum (1.7 to 1.4), urinary bladder (6.9 to 6.1) and stomach (2.7 to 2.4) driven by decreasing trends among men. Other cancers showed similar increasing incidence trends in both sexes leading to stable sex gaps: thyroid gland (0.3 to 0.3), kidney (2.2 to 2.4) and central nervous system (1.4 to 1.5). CONCLUSION: In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends.
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Neoplasias/epidemiologia , Feminino , Identidade de Gênero , História do Século XX , História do Século XXI , Humanos , Incidência , Masculino , Neoplasias/mortalidadeRESUMO
Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions.
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Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/imunologia , Hipóxia/metabolismo , Imunidade Inata , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Animais , Infecções por Clostridium/etiologia , Infecções por Clostridium/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Estabilidade Proteica , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
The study aimed to evaluate the effects of linseed and oregano supplementation to the diet of goats on fatty acid profile and sensory properties of Padraccio, a typical cheese produced during spring through summer in the Basilicata region (southern Italy). Extruded linseed and dried oregano inflorescences were integrated in the pelleted concentrate supplementation (500 g/head per day) in 21 grazing goats that were randomly assigned, 7 per group, to the following experimental treatments: concentrate, concentrate with addition of linseed, and concentrate with addition of linseed and oregano. Pooled milk from each group was used in cheesemaking. From a nutritional perspective, integration of extruded linseed in the goat diet improved the fatty acid profile of Padraccio cheese. Moreover, the cheese from this group evidenced the highest scoring on color, flavor, texture, and overall liking.
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Queijo/análise , Ácidos Graxos/análise , Linho , Cabras , Leite/química , Origanum , Animais , Dieta/veterinária , Suplementos Nutricionais , Feminino , Itália , LactaçãoRESUMO
The aims of this study were to evaluate the impact of the COVID-19 pandemic on emergency and elective hand surgery in four Italian regions that had either a high (Lombardy and Piemonte) or a low (Sicilia and Puglia) COVID-19 case load to discuss problems and to elaborate strategies to improve treatment pathways. A panel of hand surgeons from these different regions compared and discussed data from the centers they work in. The COVID-19 pandemic had an enormous impact on both elective and emergency surgery in Italy, not only in highly affected regions but also - and paradoxically even at a higher extent - in regions with a low COVID-19 case load. A durable and flexible redesign of hand surgery activities should be promoted, while changing and hopefully increasing human resources and enhancing administrative support. Telematics must also be implemented, especially for delivering rehabilitation therapy.
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COVID-19/epidemiologia , Mãos/cirurgia , Procedimentos Ortopédicos/estatística & dados numéricos , Pandemias , Teste para COVID-19/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Itália/epidemiologia , Admissão e Escalonamento de Pessoal/organização & administração , Modalidades de Fisioterapia/organização & administração , Modalidades de Fisioterapia/estatística & dados numéricos , Cuidados Pós-Operatórios , Inquéritos e Questionários , Telemedicina/estatística & dados numéricosRESUMO
PURPOSE: A reliable model to simulate nuclear interactions is fundamental for Ion-therapy. We already showed how BLOB ("Boltzmann-Langevin One Body"), a model developed to simulate heavy ion interactions up to few hundreds of MeV/u, could simulate also 12C reactions in the same energy domain. However, its computation time is too long for any medical application. For this reason we present the possibility of emulating it with a Deep Learning algorithm. METHODS: The BLOB final state is a Probability Density Function (PDF) of finding a nucleon in a position of the phase space. We discretised this PDF and trained a Variational Auto-Encoder (VAE) to reproduce such a discrete PDF. As a proof of concept, we developed and trained a VAE to emulate BLOB in simulating the interactions of 12C with 12C at 62 MeV/u. To have more control on the generation, we forced the VAE latent space to be organised with respect to the impact parameter (b) training a classifier of b jointly with the VAE. RESULTS: The distributions obtained from the VAE are similar to the input ones and the computation time needed to use the VAE as a generator is negligible. CONCLUSIONS: We show that it is possible to use a Deep Learning approach to emulate a model developed to simulate nuclear reactions in the energy range of interest for Ion-therapy. We foresee the implementation of the generation part in C++ and to interface it with the most used Monte Carlo toolkit: Geant4.
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Aprendizado Profundo , Radiobiologia , Método de Monte CarloRESUMO
PURPOSE: Monte Carlo (MC) simulations are widely used for medical applications and nuclear reaction models are fundamental for the simulation of the particle interactions with patients in ion therapy. Therefore, it is of utmost importance to have reliable models in MC simulations for such interactions. Geant4 is one of the most used toolkits for MC simulation. However, its models showed severe limitations in reproducing the yields measured in the interaction of ion beams below 100â¯MeV/u with thin targets. For this reason, we interfaced two models, SMF ("Stochastic Mean Field") and BLOB ("Boltzmann-Langevin One Body"), dedicated to simulate such reactions, with Geant4. METHODS: Both SMF and BLOB are semi-classical, one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. Furthermore, we tested a correction to the excitation energy calculated for the light fragments emerging from the simulations and a simple coalescence model. RESULTS: While both SMF and BLOB have been developed to simulate heavy ion interactions, they show very good results in reproducing the experimental yields of light fragments, up to alpha particles, obtained in the interaction of 12C with a thin carbon target at 62â¯MeV/u. CONCLUSIONS: BLOB in particular gives promising results and this stresses the importance of integrating it into the Geant4 toolkit.
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Método de Monte Carlo , Radioterapia , Processos EstocásticosRESUMO
BACKGROUND: Survival rates of lung cancer remains poor and the impact of comorbidities on the prognosis is discussed. The objective of this study was to assess if the Charlson Comorbidity Index (CCI) was associated with 8-year survival rates by histological type. METHODS: A cohort study was conducted using randomly selected cases from 10 French cancer registries. Net survival rates were computed using the Pohar-Perme estimator of the net cumulative rate. Three Cox models were independently built for adenocarcinomas, squamous cell and small cell cancers to estimate prognostic factors including CCI grade. RESULTS: A total of 646 adenocarcinomas, 524 squamous cell and 233 small cell cancers were included in the analysis. The net 8-year survival rate ranged from 12.6% (95% CI: 9.8-15.4%) for adenocarcinomas and 13.4% (95% CI: 10.1-16.7%) for squamous cell carcinomas, to 3.7% (95% CI: 1.1-6.3%) for small cell cancers. Observed and net survival rates decreased for CCI grades ≥3 for all histological group considered. After adjustment for sex, age group, stage and diagnostic mode, CCI grades 1 (HR = 1.6 [95% CI: 1.1-2.3]), 2 (HR = 1.7 [95% CI: 1.1-2.7]) and ≥ 3 (HR = 2.7 [95% CI: 1.7-4.4]) were associated with lower survival rates only for small cell cancers. CONCLUSION: After adjustment for age, sex, stage and diagnostic mode, the presence of comorbidity based on CCI grades 1-2 and ≥ 3 was associated with lower survival rates for small cell cancers whereas no differences were observed for adenocarcinomas and squamous cell cancers.
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Neoplasias Pulmonares/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Comorbidade , Feminino , Seguimentos , França/epidemiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância da População , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Herein we describe a 43 year-old Caucasian female patient with acute myeloid leukemia that developed an unconventional form of invasive Aspergillosis. For therapeutic reasons, a Groshong-type central venous catheter was positioned. Monitoring the patient's clinical conditions, positive values for C-reactive protein and galactomannan were correlated with a probably Aspergillosis. Surprisingly no pulmonary evidences were observed. Due to worsening conditions, she was re-hospitalized and a blood culture was performed, whom positivity resulted as the first clinical evidence of Aspergillus fumigatus. Further evidence about species identification was obtained by sequencing the fungal ITS region. We support the clinical value of blood culture as a decisive factor to improve the diagnosis of catheter-related Aspergillosis.
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Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Infecções Relacionadas a Cateter/diagnóstico , Leucemia Mieloide Aguda/complicações , Adulto , Antifúngicos/uso terapêutico , Aspergilose/sangue , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/crescimento & desenvolvimento , Hemocultura , Proteína C-Reativa/análise , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/tratamento farmacológico , Meios de Cultura , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Feminino , Galactose/análogos & derivados , Humanos , Mananas/análise , Neutropenia/sangue , Análise de Sequência de DNA , Resultado do TratamentoRESUMO
BACKGROUND: This study analyzes time trends in cancer prevalence in France and provides short-term projections up to the year 2017. The 15-year prevalence for 24 cancers was estimated from the French cancer registries network (FRANCIM) incidence and survival data. METHOD: We estimated prevalence using the P = I × S relationship, with flexible modeling of incidence and survival. Based on observations of the incidence and survival up to 2010, different scenarios for evolution up to 2017 were studied, combining stable and dynamic incidence and survival. The determinants of variations in prevalence (incidence, survival and demography) were quantified. RESULTS: At the end of 2017, an estimated 1,396,000 men and 1,359,000 women having had cancer in the previous 15 years were alive, respectively 5.4% and 4.8% of the population. Twelve percent had been diagnosed in the preceding year and 23% between 10 and 15 years. Between 2010 and 2017, changes in incidence and survival depended on the cancer site. The effect of the demographic change was null for those under age 65, whereas above age 65, the contribution of this factor was 20% in men and 17% in women at 15 years. The different projection scenarios led to very different estimates for some cancers for which incidence strongly varied in the last decades. CONCLUSION: Prevalent cases are numerous in a country such as France, where incidence and survival are high. Due to the sensitivity of prevalence to changes in incidence and survival, we recommend that the results of projections are presented under different scenarios. We propose a robust and flexible prevalence estimate.
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Neoplasias/epidemiologia , Neoplasias/mortalidade , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
Abstract The attention to nuclear clustering has been renewed due to the study of weakly bound nuclei at the drip lines. In particular, clustering structural properties in medium-mass systems have been studied by looking at the competition between the evaporation and pre-equilibrium particle emission in central collisions. Although for light nuclei at an excitation energy close to the particle separation value there are experimental evidence of such structure effects, this is still not the case for heavier systems since the determination of pre-formed clusters within nuclear matter is less obvious. Two systems, leading to the same 81Rb* compound nucleus, have been studied at the same beam velocity 16 AMeV: 16O + 65Cu and 19F + 62Ni. The experiment has been performed using the GARFIELD + RCo detection system installed at the Legnaro National Laboratories.Light charged particles energy distributions and multiplicities have been compared with different statistical and dynamical model calculations. From the first comparison between the two systems a difference in the fast α-decay channel has been evidenced, which can be related to the difference in the projectile structure. Recent data analysis results and comparisons with model calculations are presented in this contribution.
Resumen La atención a la agrupación nuclear se ha renovado debido al estudio de núcleos débilmente unidos en las líneas de goteo. En particular, se han estudiado las propiedades estructurales del agrupamiento en sistemas de masa media al observar la competencia entre la evaporación y la emisión de partículas de preequilibrio en colisiones centrales. Aunque para núcleos ligeros a una energía de excitación cercana al valor de separación de la partícula hay evidencia experimental de tales efectos de estructura, este no es el caso para sistemas más pesados ya que la determinación de agrupamientos preformados dentro de la materia nuclear es menos obvia. Se han estudiado dos sistemas, que conducen al mismo núcleo compuesto 81Rb *, a la misma velocidad de haz 16 AMeV: 16O + 65Cu y 19F + 62Ni. El experimento se ha realizado utilizando el sistema de detección GARFIELD + RCo instalado en los Laboratorios Nacionales Legnaro. Las distribuciones de energía y las multiplicidades de partículas de carga ligera se han comparado con diferentes cálculos de modelos estadísticos y dinámicos. Desde la primera comparación entre los dos sistemas, se ha evidenciado una diferencia en el canal de desintegración α rápida, que se puede relacionar con la diferencia en la estructura del proyectil. En esta contribución se presentan los resultados del análisis de datos recientes y las comparaciones con los cálculos del modelo.
RESUMO
BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are scarce and have never been analysed in France to identify the main epidemiological trends. METHODS: Data from MCC patients diagnosed between 1998 and 2010 were obtained from 11 French cancer registries in the FRANCIM network. The main epidemiological characteristics of MCC were investigated between 2006 and 2010 because comprehensive data were only available for this period. The main focus was tumour incidence and mortality over time. RESULTS: Between 1998 and 2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290 cases), European- and world-standardized incidence rates were 0.26 and 0.43 per 100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women. MCC is more frequent in females in France (56.9%) with male/female ratio 1.1. Relative survival rates were 84%, 56% and 42% at one, three and 5 years, respectively. CONCLUSIONS: The incidence of MCC clearly increased over time in all areas under focus. The standardized incidence in France was comparable to the incidence observed in other countries for the same period, but French data are too recent to conclude on an increase in MCC incidence. Prognosis remains poor in all countries in which data are available.
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Carcinoma de Célula de Merkel/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/mortalidade , Criança , Pré-Escolar , Estudos Epidemiológicos , Feminino , França/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: Although communications between branches and cords of the brachial plexus have been extensively published, there is a scarcity of reports concerning radial and ulnar nerve (RN-UN) communication in the arm. The current study aims to demonstrate the incidence, topography, and length of communicating branches between RN and UN. Any additional coexisted variations were also recorded. MATERIALS AND METHODS: Two hundred and sixty-six upper limbs collected from one hundred and thirty-three (81 males and 52 females) Greek cadavers were dissected. RESULTS: Three out of one hundred and thirty-three cadavers, accounting for an incidence of up to 2.3%, were found to have an atypical communicating branch originating at a high humeral level from RN towards UN. In two cadavers, communicating branches were detected on the left side and in one cadaver bilaterally. CONCLUSIONS: The study of atypical communications between RN and UN attracts great attention for its clinical importance, mainly in cases of peripheral neuropathies with diagnostic dilemma or upper limb nerve injury producing an otherwise unexpected symptomatology due to the aberrant nerve supply. Familiarity with these variations is crucial in avoiding misdiagnosis and preserving valuable communicating branches, thus achieving an uneventful outcome in cases of upper limb nerve injury repair.
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Úmero/inervação , Nervo Radial/anatomia & histologia , Nervo Ulnar/anatomia & histologia , Variação Anatômica , Cadáver , Dissecação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6.Cg-Nr1d1tm1Ven/LazJ mouse line purchased from Jackson Laboratories harbors a spontaneous mutation in Jak3, generating a SCID phenotype and an inability to generate antigen-independent professional cytokine-producing innate lymphoid cells (ILCs). Mechanistically, Jak3 deficiency blocks ILC differentiation in the bone marrow at the ILC precursor and the pre-NK cell progenitor. We further demonstrate that the pan-JAK inhibitor tofacitinib and the specific JAK3 inhibitor PF-06651600 impair the ability of human intraepithelial ILC1 (iILC1) to produce IFN-γ, without affecting ILC3 production of IL-22. Both inhibitors impaired the proliferation of iILC1 and ILC3 and differentiation of human ILC in vitro. Tofacitinib is currently approved for the treatment of moderate-to-severely active rheumatoid arthritis. Both tofacitinib and PF-06651600 are currently in clinical trials for several other immune-mediated conditions. Our data suggest that therapeutic inhibition of JAK may also impact ILCs and, to some extent, underlie clinical efficacy.
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Artrite Reumatoide/tratamento farmacológico , Células da Medula Óssea/fisiologia , Janus Quinase 3/genética , Células Matadoras Naturais/fisiologia , Mutação/genética , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Imunodeficiência Combinada Severa/genética , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Humanos , Imunidade Inata , Interferon gama/metabolismo , Janus Quinase 3/antagonistas & inibidores , Camundongos , Camundongos Mutantes , Fenótipo , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologiaRESUMO
BACKGROUND: In retrospective case-control studies performed following nuclear tests or nuclear accidents, individual thyroid radiation dose reconstructions are based on fallout and meteorological data from the residential area, demographic characteristics, and lifestyle as well as dietary information. Collecting the latter is a controversial step, as dietary declarations may be affected by the subjects' beliefs about their risk behavior. This report analyses the potential for such bias in a case-control study performed in eastern France. METHODS: The study included 765 cases of differentiated thyroid carcinoma matched with 831 controls. Risk perceptions and beliefs of cases and controls were compared using Chi2 tests and differences in dietary reports were analyzed using a two-way ANOVA. RESULTS: In general, atmospheric pollution and living near a nuclear power plant were the two major risks that may influence thyroid cancer occurrence cited by cases and controls. When focusing in particular on the consequences of the Chernobyl accident, cases were more likely to think that the consequences were responsible for thyroid cancer occurrence than controls. Vegetable consumption during the two months after the Chernobyl accident was correlated with the status of subjects, but not to their beliefs. Conversely, consumption of fresh dairy products was not correlated with the status or beliefs of subjects. CONCLUSION: We found no evidence of systematic bias in dietary reports according to the status or beliefs held by subjects about the link between thyroid cancer occurrence and Chernobyl fallout. As such, these dietary reports may be used in further studies involving individual dosimetric reconstructions.