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This publisher's note contains corrections to Opt. Lett.47, 6201 (2022)10.1364/OL.471241.
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We report on a signal-to-noise ratio characterizing the generation of identical photon pairs of more than 4 orders of magnitude in a ring resonator system. Parasitic noise, associated with single-pump spontaneous four-wave mixing, is essentially eliminated by employing a novel system design involving two resonators that are linearly uncoupled but nonlinearly coupled. This opens the way to a new class of integrated devices exploiting the unique properties of identical photon pairs in the same optical mode.
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HIV-1 Nef, a protein important for the development of AIDS, has well-characterized effects on host membrane trafficking and receptor downregulation. By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1 virions in a host-cell-dependent manner. Here we identify the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma membrane, where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef redirects SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV-1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by diverse primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus. These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 as a potent anti-retroviral factor.
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HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Vírion/química , Vírion/metabolismo , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , Animais , Linhagem Celular , Membrana Celular/metabolismo , Membrana Celular/virologia , Endossomos/química , Endossomos/metabolismo , Evolução Molecular , Produtos do Gene gag/metabolismo , Produtos do Gene nef/química , Produtos do Gene nef/metabolismo , HIV-1/química , Especificidade de Hospedeiro , Humanos , Vírus da Leucemia Murina/química , Vírus da Leucemia Murina/fisiologia , Glicoproteínas de Membrana , Proteínas de Membrana/análise , Proteínas de Neoplasias/metabolismo , Primatas/virologia , Receptores de Superfície Celular/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7RESUMO
BACKGROUND: Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept. METHODS: This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%. RESULTS: In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, -1.2%; 95% confidence interval, -10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32. CONCLUSIONS: Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.
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Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Etanercepte/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Resultado do TratamentoRESUMO
Time-energy entangled photon pairs are fundamental resources for quantum communication protocols since they are robust against environmental fluctuations in optical fiber networks. Pair sources based on spontaneous four-wave mixing in silicon microring resonators usually employ expensive external tunable lasers to compensate for ambient fluctuations; adopting self-pumped configurations, instead, lifts the need for such external source. Here we demonstrate the emission of time-energy entangled photon pairs at telecom wavelengths from a silicon self-pumped ring, obtaining a Franson interference fringe with 93.9%±0.9% visibility.
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BACKGROUND: Consanguinity is an important risk factor for autosomal recessive (AR) disorders. Extended genomic regions identical by descent (IBD) in the offspring of consanguineous parents give rise to recessive disorders with identical (homozygous) pathogenic variants in both alleles. However, many clinical phenotypes presenting in the offspring of consanguineous couples are still of unknown etiology. Nowadays advances in High Throughput Sequencing provide an excellent opportunity to achieve a molecular diagnosis or to identify novel candidate genes. RESULTS: To exploit all available information from the family structure we developed CATCH, an algorithm that combines genotyped SNPs of all family members for the optimal detection of Runs Of Homozygosity (ROH) and exome sequencing data from one affected individual to identify putative causative variants in consanguineous families. CONCLUSIONS: CATCH proved to be effective in discovering known or putative new causative variants in 43 out of 50 consanguineous families. Among them, novel variants causative of familial thrombocytopenia, sclerosis bone dysplasia and the first homozygous loss-of-function mutation in FGFR3 in human causing severe skeletal deformities, tall stature and hearing impairment were identified.
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Interface Usuário-Computador , Algoritmos , Consanguinidade , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Internet , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/patologia , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Análise de Sequência de DNARESUMO
Existence of some extra-genetic (epigenetic) codes has been postulated since the discovery of the primary genetic code. Evident effects of histone post-translational modifications or DNA methylation over the efficiency and the regulation of DNA processes are supporting this postulation. EMdeCODE is an original algorithm that approximate the genomic distribution of given DNA features (e.g. promoter, enhancer, viral integration) by identifying relevant ChIPSeq profiles of post-translational histone marks or DNA binding proteins and combining them in a supermark. EMdeCODE kernel is essentially a two-step procedure: (i) an expectation-maximization process calculates the mixture of epigenetic factors that maximize the Sensitivity (recall) of the association with the feature under study; (ii) the approximated density is then recursively trimmed with respect to a control dataset to increase the precision by reducing the number of false positives. EMdeCODE densities improve significantly the prediction of enhancer loci and retroviral integration sites with respect to previous methods. Importantly, it can also be used to extract distinctive factors between two arbitrary conditions. Indeed EMdeCODE identifies unexpected epigenetic profiles specific for coding versus non-coding RNA, pointing towards a new role for H3R2me1 in coding regions.
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Algoritmos , Elementos Facilitadores Genéticos , Epigênese Genética , Histonas/análise , Retroviridae/genética , Integração Viral , Imunoprecipitação da Cromatina , Genes , Sequenciamento de Nucleotídeos em Larga Escala , RNA Longo não Codificante/genéticaRESUMO
Mechanical tests on bone plates are mandatory for regulatory purposes and, typically, the ASTM F382 standard is used, which involves a four-point bending test setup to evaluate the cyclic bending fatigue performance of the bone plate. These test campaigns require a considerable financial outlay and long execution times; therefore, an accurate prediction of experimental outcomes can reduce test runtime with beneficial cost cuts for manufacturers. Hence, an analytical framework is here proposed for the direct estimation of the maximum bending moment of a bone plate under fatigue loading, to guide the identification of the runout load for regulatory testing. Eleven bone plates awaiting certification were subjected to a comprehensive testing campaign following ASTM F382 protocols to evaluate their static and fatigue bending properties. An analytical prediction of the maximum bending moment was subsequently implemented based on ultimate strength and plate geometry. The experimental loads obtained from fatigue testing were then used to verify the prediction accuracy of the analytical approach. Results showed promising predictive ability, with R2 coefficients above 0.95 in the runout condition, with potential impact in reducing the experimental tests needed for the CE marking of bone plates.
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Placas Ósseas , Testes Mecânicos , Resistência à Tração , Teste de Materiais , Fenômenos BiomecânicosRESUMO
BACKGROUND: Although hysteroscopy with endometrial biopsy is the gold standard in the diagnosis of endometrial pathology, the gynecologist experience is crucial for a correct diagnosis. Deep learning (DL), as an artificial intelligence method, might help to overcome this limitation. Unfortunately, only preliminary findings are available, with the absence of studies evaluating the performance of DL models in identifying intrauterine lesions and the possible aid related to the inclusion of clinical factors in the model. AIM: To develop a DL model as an automated tool for detecting and classifying endometrial pathologies from hysteroscopic images. METHODS: A monocentric observational retrospective cohort study was performed by reviewing clinical records, electronic databases, and stored videos of hysteroscopies from consecutive patients with pathologically confirmed intrauterine lesions at our Center from January 2021 to May 2021. Retrieved hysteroscopic images were used to build a DL model for the classification and identification of intracavitary uterine lesions with or without the aid of clinical factors. Study outcomes were DL model diagnostic metrics in the classification and identification of intracavitary uterine lesions with and without the aid of clinical factors. RESULTS: We reviewed 1500 images from 266 patients: 186 patients had benign focal lesions, 25 benign diffuse lesions, and 55 preneoplastic/neoplastic lesions. For both the classification and identification tasks, the best performance was achieved with the aid of clinical factors, with an overall precision of 80.11%, recall of 80.11%, specificity of 90.06%, F1 score of 80.11%, and accuracy of 86.74 for the classification task, and overall detection of 85.82%, precision of 93.12%, recall of 91.63%, and an F1 score of 92.37% for the identification task. CONCLUSION: Our DL model achieved a low diagnostic performance in the detection and classification of intracavitary uterine lesions from hysteroscopic images. Although the best diagnostic performance was obtained with the aid of clinical data, such an improvement was slight.
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BACKGROUND: This study aims to evaluate the diagnostic performance of Deep Learning (DL) machine for the detection of adenomyosis on uterine ultrasonographic images and compare it to intermediate ultrasound skilled trainees. METHODS: Prospective observational study were conducted between 1 and 30 April 2022. Transvaginal ultrasound (TVUS) diagnosis of adenomyosis was investigated by an experienced sonographer on 100 fertile-age patients. Videoclips of the uterine corpus were recorded and sequential ultrasound images were extracted. Intermediate ultrasound-skilled trainees and DL machine were asked to make a diagnosis reviewing uterine images. We evaluated and compared the accuracy, sensitivity, positive predictive value, F1-score, specificity and negative predictive value of the DL model and the trainees for adenomyosis diagnosis. RESULTS: Accuracy of DL and intermediate ultrasound-skilled trainees for the diagnosis of adenomyosis were 0.51 (95% CI, 0.48-0.54) and 0.70 (95% CI, 0.60-0.79), respectively. Sensitivity, specificity and F1-score of DL were 0.43 (95% CI, 0.38-0.48), 0.82 (95% CI, 0.79-0.85) and 0.46 (0.42-0.50), respectively, whereas intermediate ultrasound-skilled trainees had sensitivity of 0.72 (95% CI, 0.52-0.86), specificity of 0.69 (95% CI, 0.58-0.79) and F1-score of 0.55 (95% CI, 0.43-0.66). CONCLUSIONS: In this preliminary study DL model showed a lower accuracy but a higher specificity in diagnosing adenomyosis on ultrasonographic images compared to intermediate-skilled trainees.
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Adenomiose , Aprendizado Profundo , Endometriose , Feminino , Humanos , Adenomiose/diagnóstico por imagem , Ultrassonografia/métodos , Útero/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
Photonic qubits should be controllable on-chip and noise-tolerant when transmitted over optical networks for practical applications. Furthermore, qubit sources should be programmable and have high brightness to be useful for quantum algorithms and grant resilience to losses. However, widespread encoding schemes only combine at most two of these properties. Here, we overcome this hurdle by demonstrating a programmable silicon nano-photonic chip generating frequency-bin entangled photons, an encoding scheme compatible with long-range transmission over optical links. The emitted quantum states can be manipulated using existing telecommunication components, including active devices that can be integrated in silicon photonics. As a demonstration, we show our chip can be programmed to generate the four computational basis states, and the four maximally-entangled Bell states, of a two-qubits system. Our device combines all the key properties of on-chip state reconfigurability and dense integration, while ensuring high brightness, fidelity, and purity.
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Introduction: In March 2020, the World Health Organization (WHO) declared a pandemic for coronavirus 19. Typical symptoms were fever, cough, asthenia, dyspnea, and muscle pain. Pulmonary and central nervous system compromise presented challenging characteristics for healthcare physicians. The objectives of this study were to identify epidemiological and clinical characteristics of SARS-COV-2 infection survivors in a region of Argentina and to determine differences between gender, age groups, year of infection, and evolution time since diagnosis. Methods: A descriptive and analytical cross-sectional observational study was carried out. A self-administered questionnaire was applied, which was available between August and December 2021. Results: Among 1868 individuals included, the mean age was 39.4 ± 13.9 years, and 72.8% were female. Arterial hypertension was the most frequent comorbidity (11.7%). The majority were outpatients (81.9%). The most frequent presentation symptoms at all ages were asthenia (83.7%), fever (54.9%), headache (60.8%), anosmia (64.8%), ageusia (53.2%), cough (54.4%) and myalgias (53.7%). For the 18 to 29 years old age group, the most prevalent presentation symptoms were: headache (69.4%), anosmia (69.1%), ageusia (60.2%), odynophagia (45%), and rhinitis/nasal congestion (46.9%). In the 30 to 64 years old age group, there was a higher prevalence of myalgias (55.8%), arthralgias (41%), and concentration/memory disorder (28.3%). Male showed higher prevalence of fever (64.9% versus 51.1%; p < 0.001) and pneumonia (23.5% versus 13.4%; p < 0.001). After 12 weeks from diagnosis, 38.1% of patients persisted with asthenia, 23.6% with anosmia/dysosmia, and 21.2% with concentration/memory disorders. Conclusions: Systemic symptoms were common to all age groups with coronavirus 19 disease; however, younger, and intermediate age groups presented a higher prevalence of central nervous system symptoms such as anosmia and cognitive disorders, respectively. Symptoms beyond 12 weeks of diagnosis reached slightly more than 10% of the participants.
Introducción: En marzo de 2020 la enfermedad por coronavirus 19 fue declarada pandemia por la Organización Mundial de la Salud. Los síntomas más comunes fueron fiebre, tos, astenia, disnea y dolor muscular. Los compromisos pulmonar y del sistema nervioso central presentaron características desafiantes para los médicos asistenciales. Los objetivos del estudio fueron conocer las características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2 en una región de Argentina, y determinar las diferencias entre género, grupos etarias, año de contagio, tiempo de evolución desde el diagnóstico. Métodos: Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó un cuestionario auto administrado, que estuvo disponible entre agosto y diciembre de 2021. Resultados: La media de edad fue de 39,4 ± 13,9 años, el 72,8% fueron mujeres. La comorbilidad más frecuente fue hipertensión arterial (11,7%). La mayoría de los pacientes fueron ambulatorios (81,9%). Los síntomas de presentación más frecuentes a cualquier edad, fueron astenia (83,7%), fiebre (54,9%), cefalea (60,8%), anosmia (64,8%), ageusia (53,2%), tos (54,4%) y mialgias (53,7%). Para el grupo de 18 a 29 años los síntomas de presentación más prevalentes fueron cefalea (69,4%), anosmia 69,1%), ageusia (60,2%), odinofagia (45%) y rinitis/congestión nasal (46,9%). En el grupo de 30 a 64 años se observó mayor prevalencia de mialgias (55,8%), artralgias (41%), falta de concentración/memoria (28,3%). Los hombres mostraron más prevalencia de fiebre (64,9% versus 51,1%; p < 0,001) y neumonía (23,5% versus 13,4%; p < 0,001). Luego de las 12 semanas del diagnóstico 38,1% de los pacientes persistían con astenia, 23,6% con anosmia/disosmia y 21,2% con trastornos de concentración/memoria. Conclusiones: La enfermedad por coronavirus 19 presenta un patrón de síntomas sistémicos común a todos los grupos etarios. No obstante, los grupos más jóvenes presentan más prevalencia de síntomas de afección del sistema nervioso central como la anosmia y los grupos intermedios, mayor prevalencia de trastornos cognitivos. Los síntomas más allá de las 12 semanas del diagnóstico alcanzaron a algo más del 10% de los participantes.
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Ageusia , COVID-19 , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , COVID-19/complicações , COVID-19/epidemiologia , Ageusia/diagnóstico , Ageusia/epidemiologia , Anosmia , SARS-CoV-2 , Tosse/epidemiologia , Tosse/etiologia , Estudos Transversais , Astenia , Febre/epidemiologia , Febre/etiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , SobreviventesRESUMO
PURPOSE: This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer. METHODS: This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs). RESULTS: A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR (P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, -0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, -0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia. CONCLUSION: Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.
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Antineoplásicos , Medicamentos Biossimilares , Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neutropenia , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/prevenção & controle , PolietilenoglicóisRESUMO
Upon cell invasion, retroviruses generate a DNA copy of their RNA genome and integrate retroviral cDNA within host chromosomal DNA. Integration occurs throughout the host cell genome, but target site selection is not random. Each subgroup of retrovirus is distinguished from the others by attraction to particular features on chromosomes. Despite extensive efforts to identify host factors that interact with retrovirion components or chromosome features predictive of integration, little is known about how integration sites are selected. We attempted to identify markers predictive of retroviral integration by exploiting Precision-Recall methods for extracting information from highly skewed datasets to derive robust and discriminating measures of association. ChIPSeq datasets for more than 60 factors were compared with 14 retroviral integration datasets. When compared with MLV, PERV or XMRV integration sites, strong association was observed with STAT1, acetylation of H3 and H4 at several positions, and methylation of H2AZ, H3K4, and K9. By combining peaks from ChIPSeq datasets, a supermarker was identified that localized within 2 kB of 75% of MLV proviruses and detected differences in integration preferences among different cell types. The supermarker predicted the likelihood of integration within specific chromosomal regions in a cell-type specific manner, yielding probabilities for integration into proto-oncogene LMO2 identical to experimentally determined values. The supermarker thus identifies chromosomal features highly favored for retroviral integration, provides clues to the mechanism by which retrovirus integration sites are selected, and offers a tool for predicting cell-type specific proto-oncogene activation by retroviruses.
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Biologia Computacional/métodos , Retroviridae/fisiologia , Integração Viral/fisiologia , Algoritmos , Animais , Linhagem Celular , Distribuição de Qui-Quadrado , Cromatina/química , Cromatina/genética , Imunoprecipitação da Cromatina , Análise por Conglomerados , Ilhas de CpG/genética , Bases de Dados Genéticas , Marcadores Genéticos , Genoma/genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Camundongos , Proto-Oncogene Mas , Retroviridae/genética , Retroviridae/patogenicidade , Fator de Transcrição STAT1/genética , Análise de Sequência de DNA , Integração Viral/genéticaRESUMO
OBJECTIVE: We compared the efï¬cacy, safety, and immunogenicity of a biosimilar recombinant human follicle-stimulating hormone (Folitime®) with Gonal-f® in women undergoing ovarian stimulation for in-vitro fertilization. METHODS: This randomized (1:1), multicenter, assessor-blinded, non-inferiority, parallel-group, controlled study conducted at four infertility clinics in Argentina included infertile normogonadotropic women with ages below 39 years, with menstrual cycles of 25/35 days and a body mass index of 18-32 kg/m2 undergoing assisted reproductive technology therapy. During a 5-day fixed-dose phase, the women received 225 IU/day of Folitime® (n=49) or Gonal-f® (n=44), followed by a dose-adaptation phase up to a maximum of 450 IU/day. The non-inferiority margin for oocyte retrieval was estimated at -4 oocytes (one-sided test). Immunogenicity was investigated on days 9 and 84, following the start of treatment. RESULTS: The mean number of oocytes retrieved was 12.6 (SD 7.4) in the Folitime® group and 13.4 (SD 6.9) in the Gonal-f® group (per protocol analysis, 95% confidence interval = -3.82; 2.33), within the non-inferiority margin. Pregnancy rate at week 10 was 24.4% among subjects treated with Folitime® and 19.5% for subjects treated with Gonal-f®. One serious adverse drug reaction-late mild ovarian hyper stimulation syndrome and deep venous thrombosis in the left deep jugular vein-occurred in a subject treated with Folitime®. None of the subjects developed antibodies against the study drugs. There were no unexpected safety findings. CONCLUSIONS: Folitime® is non-inferior to Gonal-f®, with no differences in the safety profile and has been approved as a biosimilar in Argentina.
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Medicamentos Biossimilares , Adulto , Medicamentos Biossimilares/efeitos adversos , Feminino , Fertilização in vitro , Hormônio Foliculoestimulante Humano/efeitos adversos , Humanos , Indução da Ovulação , Gravidez , Proteínas RecombinantesRESUMO
Elastofibroma is a rare, benign pseudotumor that arises from connective tissue, most commonly found at the right scapular tip. These tumors usually can be distinguished from malignant soft-tissue tumors by their anatomical location and also through imaging techniques. Although elastofibroma is rare, it is important for surgeons to be aware of this diagnosis to prevent unnecessary biopsies and unnecessary operations. We report a series of six patients, four of whom were female, with a median age of 62.5 years, diagnosed with and treated for elastofibroma. Five of the six patients had unilateral lesions, while one patient had bilateral elastofibromas. All unilateral lesions were found on the right side. The elastofibroma in five of six patients was located on the subscapular tip, the remaining patient's elastofibroma was found on the chest wall external to the pleural surface. The pathogenesis of this lesion is discussed, as recent evidence suggests a neoplastic origin to elastofibroma. Additionally, cellular changes occurring in elastofibroma may reflect the pathogenesis of other disorders of elastic fibers.
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Fibroma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias Torácicas/diagnóstico , Procedimentos Cirúrgicos Torácicos/métodos , Idoso , Diagnóstico Diferencial , Feminino , Fibroma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Escápula , Neoplasias de Tecidos Moles/cirurgia , Neoplasias Torácicas/cirurgiaRESUMO
Pseudoxanthoma elasticum (PXE) is a genetic disorder in which elastic fibers become calcified with prominent cutaneous, ocular, and cardiovascular features. Calcinosis cutis is an acquired disorder of calcium deposition in cutaneous tissues that occurs as one of the following forms: dystrophic, metastatic, idiopathic, and iatrogenic. We report a case of a woman with PXE who developed widespread dystrophic calcinosis cutis in areas affected by PXE. Although tumoral calcification and nephrolithiasis have been reported in patients with PXE, only one other case in the English-language literature of PXE and calcinosis cutis has been reported and this case was characterized by small, milia-like papules on the front of the neck, without significant discomfort, whereas our patient had widespread involvement that was very painful and pruritic. On 6-month follow-up, this patient had only mild improvement after treatment with an anti-itch lotion and aluminum hydroxide, with which she was noncompliant.
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Calcinose/etiologia , Pseudoxantoma Elástico/complicações , Dermatopatias/etiologia , Calcinose/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Dermatopatias/patologiaRESUMO
RESUMEN INTRODUCCIÓN En Argentina, la obesidad en adultos es una problemática con una prevalencia media de 25,4%. En la relación entre COVID-19 y obesidad, se observa mayor prevalencia de sobrepeso/obesidad y enfermedad severa entre los pacientes con COVID-19. Por ello, el objetivo del estudio fue conocer las características clínicas y epidemiológicas en pacientes con diagnóstico de obesidad sobrevivientes a la infección por SARS-CoV-2. MÉTODOS Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó una encuesta autoadministrada. RESULTADOS La mediana de edad fue 41 años, y hubo un 69,9% de mujeres. Los síntomas de presentación más prevalentes fueron astenia (86,7%), anosmia (64,5%) y tos (64%). Con respecto a los síntomas persistentes luego de las 12 semanas del diagnóstico, los más prevalentes fueron astenia (52,9%), trastornos de sueño (32,4%) y falta de concentración/memoria (31,7%). Hubo mayor riesgo en mujeres (OR: 2,86; IC95%: 2,23-3,67) con obesidad (OR: 1,58; IC95%: 1,16-2,16). La enfermedad grave en obesos fue casi el triple comparado con no obesos (15,7% vs. 5,4%; p<0,001). DISCUSIÓN Los pacientes obesos mostraron síntomas de presentación que orientan a un estado inflamatorio sistémico, con disnea y tos más frecuentes, y tienen mayor prevalencia de enfermedad grave y neumonía, así como mayor riesgo de desarrollar síntomas persistentes, sobre todo si las personas son mujeres y sedentarias.
ABSTRACT INTRODUCTION In Argentina, obesity in adults is a problem with an average prevalence of 25.4%. The relationship between COVID-19 and obesity shows a higher prevalence of overweight/obesity and severe disease among patients with COVID-19. Therefore, the objective of the study was to know the clinical and epidemiological characteristics of patients diagnosed with obesity who survived SARSCoV- 2 infection. METHODS A descriptive and analytical cross-sectional observational study was carried out. A self-administered survey was applied. RESULTS The median age was 41 years and 69.9% were women. The most prevalent presenting symptoms were asthenia (86.7%), anosmia (64.5%) and cough (64%). Regarding persistent symptoms 12 weeks after diagnosis, the most prevalent ones were asthenia (52.9%), sleep disorders (32.4%) and lack of concentration/memory (31.7%). The risk was higher for women (OR: 2.865; CI95%: 2.23-3.67) with obesity (OR: 1.58; CI95%: 1.16-2.16). Severe disease in obese was almost threefold that in non-obese patients (15.7% vs. 5.4%; p<0.001). DISCUSSION Obese patients showed presenting symptoms that point to a systemic inflammatory state, with dyspnea and cough being more common, and have a higher prevalence of severe disease and pneumonia, as well as a higher risk of developing persistent symptoms, especially if they are women and sedentary.
RESUMO
The role of integrin-mediated adhesion during T cell progenitor homing to and differentiation within the thymus is ill-defined, mainly due to functional overlap. To circumvent compensation, we disrupted the hematopoietic integrin regulator kindlin-3 in mice and found a progressive thymus atrophy that is primarily caused by an impaired homing capacity of T cell progenitors to the vascularized thymus. Notably, the low shear flow conditions in the vascular system at midgestation allow kindlin-3-deficient fetal liver-derived T cell progenitors to extravasate via pharyngeal vessels and colonize the avascular thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceed without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell progenitor adhesion and signalling at low and indispensable at high shear forces.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Linfócitos T/citologia , Timo/irrigação sanguínea , Animais , Animais Recém-Nascidos , Atrofia , Velocidade do Fluxo Sanguíneo , Adesão Celular , Proliferação de Células , Fígado/citologia , Fígado/embriologia , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica , Células-Tronco/metabolismo , Timócitos/patologia , Timo/patologiaRESUMO
INTRODUCCIÓN: En marzo de 2020 la enfermedad por coronavirus 19 fue declarada pandemia por la Organización Mundial de la Salud. Los síntomas más comunes fueron fiebre, tos, astenia, disnea y dolor muscular. Los compromisos pulmonar y del sistema nervioso central presentaron características desafiantes para los médicos asistenciales. Los objetivos del estudio fueron conocer las características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2 en una región de Argentina, y determinar las diferencias entre género, grupos etarias, año de contagio, tiempo de evolución desde el diagnóstico. MÉTODOS: Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó un cuestionario auto administrado, que estuvo disponible entre agosto y diciembre de 2021. RESULTADOS: La media de edad fue de 39,4 ± 13,9 años, el 72,8% fueron mujeres. La comorbilidad más frecuente fue hipertensión arterial (11,7%). La mayoría de los pacientes fueron ambulatorios (81,9%). Los síntomas de presentación más frecuentes a cualquier edad, fueron astenia (83,7%), fiebre (54,9%), cefalea (60,8%), anosmia (64,8%), ageusia (53,2%), tos (54,4%) y mialgias (53,7%). Para el grupo de 18 a 29 años los síntomas de presentación más prevalentes fueron cefalea (69,4%), anosmia 69,1%), ageusia (60,2%), odinofagia (45%) y rinitis/congestión nasal (46,9%). En el grupo de 30 a 64 años se observó mayor prevalencia de mialgias (55,8%), artralgias (41%), falta de concentración/memoria (28,3%). Los hombres mostraron más prevalencia de fiebre (64,9% versus 51,1%; p < 0,001) y neumonía (23,5% versus 13,4%; p < 0,001). Luego de las 12 semanas del diagnóstico 38,1% de los pacientes persistían con astenia, 23,6% con anosmia/disosmia y 21,2% con trastornos de concentración/memoria. CONCLUSIONES: La enfermedad por coronavirus 19 presenta un patrón de síntomas sistémicos común a todos los grupos etarios. No obstante, los grupos más jóvenes presentan más prevalencia de síntomas de afección del sistema nervioso central como la anosmia y los grupos intermedios, mayor prevalencia de trastornos cognitivos. Los síntomas más allá de las 12 semanas del diagnóstico alcanzaron a algo más del 10% de los participantes.
INTRIDUCTION: In March 2020, the World Health Organization (WHO) declared a pandemic for coronavirus 19. Typical symptoms were fever, cough, asthenia, dyspnea, and muscle pain. Pulmonary and central nervous system compromise presented challenging characteristics for healthcare physicians. The objectives of this study were to identify epidemiological and clinical characteristics of SARS-COV-2 infection survivors in a region of Argentina and to determine differences between gender, age groups, year of infection, and evolution time since diagnosis. METHODS: A descriptive and analytical cross-sectional observational study was carried out. A self-administered questionnaire was applied, which was available between August and December 2021. RESULTS: Among 1868 individuals included, the mean age was 39.4 ± 13.9 years, and 72.8% were female. Arterial hypertension was the most frequent comorbidity (11.7%). The majority were outpatients (81.9%). The most frequent presentation symptoms at all ages were asthenia (83.7%), fever (54.9%), headache (60.8%), anosmia (64.8%), ageusia (53.2%), cough (54.4%) and myalgias (53.7%). For the 18 to 29 years old age group, the most prevalent presentation symptoms were: headache (69.4%), anosmia (69.1%), ageusia (60.2%), odynophagia (45%), and rhinitis/nasal congestion (46.9%). In the 30 to 64 years old age group, there was a higher prevalence of myalgias (55.8%), arthralgias (41%), and concentration/memory disorder (28.3%). Male showed higher prevalence of fever (64.9% versus 51.1%; p < 0.001) and pneumonia (23.5% versus 13.4%; p < 0.001). After 12 weeks from diagnosis, 38.1% of patients persisted with asthenia, 23.6% with anosmia/dysosmia, and 21.2% with concentration/memory disorders. CONCLUSIONS: Systemic symptoms were common to all age groups with coronavirus 19 disease; however, younger, and intermediate age groups presented a higher prevalence of central nervous system symptoms such as anosmia and cognitive disorders, respectively. Symptoms beyond 12 weeks of diagnosis reached slightly more than 10% of the participants.