Progression in Myeloid Neoplasms: Beyond the Myeloblast.

Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths. These MN-transformation types exhibit a propensity for extramedullary sites (e.g., skin, lymph nodes, liver), highlighting the importance of lesional biopsies in diagnosis. Gain of distinct mutations/mutational patterns seems to be causative or at least accompanying several of the above-mentioned scenarios. MDS developing MPN features often acquire MPN driver mutations (usually JAK2), and MF. Conversely, MPN gaining MDS features develop, e.g., ASXL1, IDH1/2, SF3B1, and/or SRSF2 mutations. Mutations of RAS-genes are often detected in CMML-like MPN progression. MS ex MN is characterized by complex karyotypes, FLT3 and/or NPM1 mutations, and often monoblastic phenotype. MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1. Finally, the acquisition of MAPK-pathway gene mutations may shape MN toward histiocytic differentiation. Awareness of all these less well-known MN-progression types is important to guide optimal individual patient management.

Underwater Energy Harvesting to Extend Operation Time of Submersible Sensors.

A linear electromagnetic energy harvesting device for underwater applications, fabricated with a simple manufacturing process, was developed to operate with movement frequencies from 0.1 to 0.4 Hz. The generator has two coils, and the effect of the combination of the two coils was investigated. The experimental study has shown that the energy capture system was able to supply energy to several ocean sensors, producing 7.77 mJ per second with wave movements at 0.4 Hz. This study shows that this energy is enough to restore the energy used by the battery or the capacitor and continue supplying energy to the sensors used in the experimental work. For an ocean wave frequency of 0.4 Hz, the generator can supply power to 8 sensors or 48 sensors, depending on the energy consumed and its optimization.

Erratum: Martins, M.S., et al. Wideband and Wide Beam Polyvinylidene Difluoride (PVDF) Acoustic Transducer for Broadband Underwater. Sensors 2019, 19, 3991.

The authors wish to make the following erratum to this paper [...].

Wideband and Wide Beam Polyvinylidene Difluoride (PVDF) Acoustic Transducer for Broadband Underwater Communications.

The advances in wireless communications are still very limited when intended to be used on Underwater Communication Systems mainly due to the adverse proprieties of the submarine channel to the acoustic and radio frequency (RF) waves propagation. This work describes the development and characterization of a polyvinylidene difluoride ultrasound transducer to be used as an emitter in underwater wireless communications. The transducer has a beam up to 10° × 70° degrees and a usable frequency band up to 1 MHz. The transducer was designed using Finite Elements Methods and compared with real measurements. Pool trials show a transmitting voltage response (TVR) of approximately 150 dB re µPa/V@1 m from 750 kHz to 1 MHz. Sea trials were carried in Ria Formosa, Faro (Portugal) over a 15 m source-receiver communication link. All the signals were successfully detected by cross-correlation using 10 chirp signals between 10 to 900 kHz.

Conservative versus Invasive Approaches in Temporomandibular Disc Displacement: A Systematic Review of Randomized Controlled Clinical Trials.

BACKGROUND: Temporomandibular disorders (TMDs) frequently cause orofacial pain and dysfunction, with treatment options spanning from conservative therapies to invasive surgical procedures. The aim of this systematic review was to analyze and compare the efficacy and safety profiles of conservative, minimally invasive interventions and surgical procedures in patients diagnosed with TMDs and disc displacement. METHODS: Following PRISMA recommendations, PubMed, Scopus, and Web of Science databases were searched for randomized clinical trials (RCT). Data were synthesized in a table and evaluated through the Cochrane risk of bias 2 (RoB 2) tool. RESULTS: Thirty-eight RCTs, most with moderate RoB, were selected. Conservative approaches, including physical therapy and occlusal devices, led to an improvement in symptoms and function. Pharmacological treatments demonstrated effectiveness in reducing pain and improving function; however, they can have undesirable side effects. Minimally invasive and invasive treatments also demonstrated efficacy, although most trials did not show their superiority to conservative treatments. CONCLUSION: The primary approach to TMDs should be a conservative, multimodal treatment plan tailored to patient complaints and characteristics. Treatment goals should focus on symptom control and functional recovery. Surgical treatment should be reserved for cases with a precise diagnosis and a clear etiology.

Nonbacterial thrombotic endocarditis of mitral valve associated with a lymphoproliferative malignancy: case report and literature review.

BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is a rare condition marked by sterile vegetations on cardiac valves, often linked to rheumatologic diseases, autoimmune disorders, and advanced solid malignancies. An early diagnosis and treatment of the associated clinical condition are mandatory, although they do not usually eliminate valvular vegetations, making anticoagulation essential to prevent embolic events. Despite variability, the prognosis of NBTE is usually unfavorable due to recurrent embolic events and the severity of the primary condition, typically advanced cancer. CASE PRESENTATION: We present a case of a 57 years-old male who presented to the emergency department with a 5-day history of painful bilateral digital edema and color change episodes (from pallor to cyanosis). Physical examination revealed erythrocyanosis in the distal extremities, prompting consideration of secondary Raynaud syndrome. Despite medical therapy, progressive digital ischemia led to multiple finger amputations. During etiological investigation, anticoagulation tests and autoimmune analysis yielded negative results. A transesophageal echocardiogram was performed, revealing an irregular hyperechogenic mass on the anterior leaflet of the mitral valve without valve dysfunction, and a thoracic computed tomography scan with contrast showed an enlarged right paratracheal lymph node. Histopathological analysis from a transthoracic needle biopsy of the paratracheal lymph node revealed diffuse large B-cell lymphoma. The patient underwent aggressive R-CHOP chemotherapy, achieving a favorable complete response. CONCLUSION: This is a particular case involving the occurrence of NBTE and Raynaud phenomenon as the initial paraneoplastic manifestations in a previously healthy young man. Reports of NBTE associated with lymphoproliferative conditions are quite rare, with fewer than ten cases described in the literature. To our knowledge, this is the first case of NBTE specifically associated with diffuse large B-cell lymphoma.

Corrigendum: Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

[This corrects the article DOI: 10.3389/fmolb.2023.1082915.].

Childbearing in adolescence: intergenerational dejà-vu? Evidence from a Brazilian birth cohort.

BACKGROUND: Pregnancy in adolescence tends to repeat over generations. This event has been little studied in middle and low-income societies undergoing a rapid epidemiological transition. To assess this association it is important to adjust for socioeconomic conditions at different points in lifetime. Therefore, the aim of this study is to analyze the independent effect of adolescent childbearing in a generation on its recurrence in the subsequent generation, after adjusting for socioeconomic status at different points in life. METHODS: The study was conducted on a prospective cohort of singleton liveborn females from the city of Ribeirão Preto, Brazil, evaluated in 1978/79, and their daughters assessed in 2002/04. A total of 1059 mother-daughter pairs were evaluated. The women who had their first childbirth before 20 years of age were considered to be adolescent mothers. The risk of childbearing in adolescence for the daughter was modeled as a function of the occurrence of teenage childbearing in her mother, after adjustment for socio-demographic variables in a Poisson regression model. RESULTS: The rate of childbearing during adolescence was 31.4% in 1978/79 and 17.1% in 2002/04. Among the daughters of the 1st generation adolescent mothers, this rate was 26.7%, as opposed to 12.7% among the daughters of non adolescent mothers. After adjustments the risk of adolescent childbearing for the 2nd generation was 35% higher for women whose mothers had been pregnant during adolescence - RR = 1.35 (95% CI 1.04-1.74). CONCLUSION: Adolescent childbearing in the 1st generation was a predictor of adolescent childbearing in the 2nd, regardless of socioeconomic factors determined at different points in lifetime.

Knowledge about human papillomavirus transmission and prevention among physicians in Rio de Janeiro state, Brazil.

OBJECTIVE: This study aimed to assess physicians' knowledge about human papillomavirus infection and its prevention. METHODS: Descriptive web-based survey with 15 objective questions targeted to physicians affiliated with the Regional Council of Medicine from Rio de Janeiro state, Brazil. Participants were invited by e-mail and the Council social networks, between January and December 2019. RESULTS: The study sample had 623 participants, with a median age of 45 years, predominantly women (63%). The most frequent specialties were Obstetrics and Gynecology (21.1%), Pediatrics (11.2%), and Internists (10.5%). Concerning human papillomavirus knowledge, 27.9% of the participants were able to identify accurately all possible forms of transmission, and none of them could recognize all the risk factors of infection. Nevertheless, 95% recognized that asymptomatic infection could occur in both sexes. Regarding knowledge about clinical manifestations, diagnosis, and screening, only 46.5% were able to identify all human papillomavirus-related cancers, 42.6% were aware of the periodicity of Pap smears, and 39.4% indicated that serological test was not adequate for diagnosis. The recommended age group for human papillomavirus vaccination was recognized by 94% of the participants, as well as the need for a Pap smear and the use of condoms, even after vaccination. CONCLUSIONS: There is good knowledge about prevention and screening for human papillomavirus infections; many gaps were identified regarding transmission, risk factors, and associated diseases among physicians in Rio de Janeiro state.

Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

Background: Around 40% of ER+/HER2-breast carcinomas (BC) present mutations in the PIK3CA gene. Assessment of PIK3CA mutational status is required to identify patients eligible for treatment with PI3Kα inhibitors, with alpelisib currently the only approved tyrosine kinase inhibitor in this setting. U-PIK project aimed to conduct a ring trial to validate and implement the PIK3CA mutation testing in several Portuguese centers, decentralizing it and optimizing its quality at national level. Methods: Eight Tester centers selected two samples of patients with advanced ER+/HER2- BC and generated eight replicates of each (n = 16). PIK3CA mutational status was assessed in two rounds. Six centers used the cobas® PIK3CA mutation test, and two used PCR and Sanger sequencing. In parallel, two reference centers (IPATIMUP and the Portuguese Institute of Oncology [IPO]-Porto) performed PIK3CA mutation testing by NGS in the two rounds. The quality of molecular reports describing the results was also assessed. Testing results and molecular reports were received and analyzed by U-PIK coordinators: IPATIMUP, IPO-Porto, and IPO-Lisboa. Results: Overall, five centers achieved a concordance rate with NGS results (allele frequency [AF] ≥5%) of 100%, one of 94%, one of 93%, and one of 87.5%, considering the overall performance in the two testing rounds. NGS reassessment of discrepancies in the results of the methods used by the Tester centers and the reference centers identified one probable false positive and two mutations with low AF (1-3%, at the analytical sensitivity threshold), interpreted as subclonal variants with heterogeneous representation in the tissue sections processed by the respective centers. The analysis of molecular reports revealed the need to implement the use of appropriate sequence variant nomenclature with the identification of reference sequences (HGVS-nomenclature) and to state the tumor cell content in each sample. Conclusion: The concordance rates between the method used by each tester center and NGS validate the use of the PIK3CA mutational status test performed at these centers in clinical practice in patients with advanced ER+/HER2- BC.

Hodgkin's variant of Richter transformation during ibrutinib therapy: A case report and review of the literature.

Hodgkin's variant of Richter transformation is a rare complication of chronic lymphocytic leukemia and is associated with inferior outcomes compared to de novo Hodgkin lymphoma. Further data concerning prognosis and treatment of Hodgkin's variant of Richter transformation occurring in the setting of novel targeted therapies are needed.

Evaluation of sensitivity profiles to fosfomycin in bacterial urine samples from outpatients.

OBJECTIVE: To evaluate and compare the susceptibilities of bacteria found in outpatient cultures to fosfomycin and other main antibiotics commonly available in clinical practice. STUDY DESIGN: A retrospective cross-sectional study was conducted using 2,673 positive urine cultures collected between 2014 and 2017 at private laboratories located in the cities of Niterói and São Gonçalo. Susceptibilities to fosfomycin and other antibiotics were tested using the McNemar test with the level of significance set at 5 %. RESULTS: Out of the 2,673 samples tested, 94.1 % were susceptible to fosfomycin. Escherichia coli was responsible for 68.8 % of the positive samples, and susceptibility to fosfomycin was observed in 97.9 % of these cases. Susceptibility to fosfomycin in Klebsiella spp. represented 86.6 % of cases, Enterococcus spp., 94.9 % and Proteus mirabilis, 83.3 %. The highest rate of susceptibility for E. coli was observed with fosfomycin, with the only exception being imipenem (p < 0.001). Klebsiella spp. showed a similar profile, except that there was no difference between susceptibilities to fosfomycin and gentamicin (p = 0.91). Susceptibility of Enterococcus spp. to fosfomycin was like that of nitrofurantoin and ampicillin. Finally, the susceptibility of P. mirabilis to fosfomycin was greater than it was for trimethoprim-sulfamethoxazole and nitrofurantoin. CONCLUSIONS: The microbiological profile established here shows substantial sensitivity to fosfomycin in the urine samples analysed. In most cases, there was a sensitivity profile that was favourable to the use of fosfomycin or at least comparable to the other antibiotics studied.

Nocturia: Prevalence and associated factors in community-dwelling subjects - a population- based study

OBJECTIVES To assess the prevalence of nocturia and identify factors associated with it in a community-dwelling population. METHODS A cross-sectional study was conducted in subjects aged 45 years or more and registered with a Family Doctor Program. Information was collected about nocturia, other urinary symptoms, physical examination, co-morbidities, demographics, socio-economic, and lifestyle factors. Multiple logistics regression models were developed to analyze associated factors for nocturia according to gender and the number of nocturnal micturitions(≥1 and ≥2). RESULTS Out of the 661 individuals included in the study, 62.3% were women. Among the women, the prevalence rates for nocturia ≥1 time and ≥2 times were, respectively, 68.4% and 49%, whereas, among the men, they were 64.3% and 43.8%. Among the women, nocturia ≥1 time was associated with brown skin, a higher BMI, lower schooling, and calcium channel blockers(CCB) use, while nocturia ≥2 times showed association with higher BMI, lower schooling, obstructive sleep apnea (OSA), and the use of CCB. Among the men, nocturia ≥1 time was associated positively with age, alcohol intake, and OSA, and negatively with angiotensin receptor blockers and beta-blockers use. Besides, nocturia ≥2 times was associated with age, not having health insurance, and OSA. CONCLUSIONS Nocturia is a condition highly prevalent in the studied population. For the female subjects, a higher BMI, lower schooling, and the use of CCB were associated with nocturia regardless of the definition used, whereas, among the men, that same association was found with age, not having health insurance, and OSA.

Predictors for de novo stress urinary incontinence following pelvic reconstructive surgery with mesh.

OBJECTIVE: The aims of this study are to describe the postoperative incidence of de novo stress urinary incontinence (SUI) in women who underwent anterior vaginal compartment prolapse repair using synthetic polypropylene mesh and to identify risk factors for this outcome. STUDY DESIGN: A retrospective cohort study of 146 women who underwent anterior vaginal repair from 2007 to 2017 and followed by a minimum period of 12 months was performed. The incidence of de novo SUI was evaluated at 3 and 12 months of follow-up. Women with concomitant or prior anti-incontinence surgery were not included. Preoperatively, all patients had a negative stress test and no evidence of occult SUI on urodynamics. The outcome was considered positive if the patient had complaints of SUI at the follow-up. Variables associated with the outcome with a p-value ≤ 0.10 were included in a logistic regression model to calculate the relative risk (RR) for de novo SUI. For multivariate analysis, all analyzes were performed considering a significant p-value ≤ 0.05. RESULTS: The incidence of de novo SUI at 3 and 12 months of follow-up was 15.8 % and 20.5 %, respectively. Higher body mass index (BMI), diabetes, anterior vaginal wall prolapse stage ≥ 3, older age at first pregnancy and higher first desire to void during the urodynamic evaluation were positively associated with de novo SUI in the bivariate analysis (p ≤ 0.10). Previous perineoplasty had a negative association with the outcome analyzed, suggesting a protective effect. After the multivariate analysis, higher BMI (RR 1.19, 95 % confidence interval [CI] 1.05-1.36), diabetes (RR 4.18, 95 % CI 1.32-13.21) and anterior vaginal wall prolapse stage ≥ 3 (RR 14.74, 95 % CI 1.64-132.0) remained as risk factors for de novo SUI (p ≤ 0.01). CONCLUSION: The incidence of de novo SUI after the surgical correction of anterior vaginal wall prolapse with synthetic mesh in this population was 15.8 % and 20.5 % at 3 and 12 months of follow-up, respectively. Continent women who underwent this surgical procedure and who had a higher BMI, diabetes and anterior vaginal wall prolapse stage ≥ 3 had a higher risk of presenting de novo SUI.

Captive-born collared peccaries learning about their predators: Lessons learnt but not remembered.

Captive-born animals frequently lose their anti-predatory abilities due to the absence of encounters with their predators, but these abilities can be regained through specific training. Anti-predator training can, thus, enhance the success of reintroduction programs with predator naïve animals. In addition, a good memory is important to guarantee the effects of the anti-predator training and increase survival rate after release into the wild. In the present study, anti-predator training sessions were applied to 11 captive-born collared peccaries (Pecari tajacu), followed by memory tests at 30, 60 and 90 days after the end of the training sessions. The collared peccaries responded appropriately to training against predators, showing alert, escape and predator avoidance behaviors after anti-predator training; however, the animals maintained these acquired behaviors for only 30 days after the end of the anti-predator training. After 60 days, peccaries responded to the predator in a 'relaxed' manner, exhibiting no anti-predator behaviors. For the trained collared peccaries to be released into the wild, reinforcement in the anti-predator training would be required at least 30 days prior to release.

Autonomic modulation in patients with congenital generalized lipodystrophy (Berardinelli-Seip syndrome).

AIMS: This study was designed to assess cardiac autonomic regulation in congenital generalized lipodystrophy (CGL) patients using 24 h heart rate variability (HRV). METHODS AND RESULTS: A cross-sectional study was carried out to evaluate 18 patients with CGL and 19 healthy controls matched by sex and age. We measured blood pressure, plasma concentrations of glucose, triglycerides, cholesterol, high-density lipoprotein-cholesterol, insulin resistance by the homeostatic model assessment (HOMA-R), left ventricular mass (LVM) (by two-dimensional echocardiography), and 24 h HRV (by the time domain indices MeanRR, SDNN, and rMSSD). Compared with controls, CGL patients had higher blood pressure (systolic, 131.1 vs. 106.3 mmHg, P < 0.05; diastolic, 85.0 vs. 68.2 mmHg, P < 0.05) and 10 patients met criteria for arterial hypertension and concentric left ventricular hypertrophy (LVM index > or =115 g/m(2)and relative left ventricular wall thickness > or =0.42). Patients with CGL had higher levels of glucose, triglycerides, cholesterol, and HOMA-R and 12 met criteria for type 2 diabetes mellitus. Compared with controls, CGL patients had lower MeanRR (639.8 vs. 780.5 ms, P < 0.001), SDNN (79.2 vs. 168.5 ms, P < 0.001), and rMSSD (15.8 vs. 59.6 ms, P < 0.001). In CGL patients, the reduction in HRV was independent of the metabolic and haemodynamic disturbances. CONCLUSION: Congenital generalized lipodystrophy patients have abnormal autonomic modulation, reflected by increased heart rate and pronounced reduction in HRV, independent of the metabolic and haemodynamic disturbances observed in this disorder.

Prevalência de noctúria e fatores associados em mulheres atendidas em dois ambulatórios de uroginecologia no estado do Rio de Janeiro: um estudo transversal / Prevalence of nocturia and associated factors in women attending two urogynecology outpatient clinics in the state of Rio de Janeiro: a cross-sectional study

Resumo Objetivo Identificar a prevalência e fatores relacionados à noctúria em mulheres que apresentam sintomas do trato urinário inferior. Métodos Inquérito observacional transversal, individuado, de base hospitalar, envolvendo mulheres atendidas pelo Sistema Único de Saúde em ambulatórios de uroginecologia em Niterói e Petrópolis, RJ, Brasil. Foram coletados dados sociodemográficos, clínicos e hábitos de vida. Foram considerados dois desfechos de noctúria: uma ou mais micções e duas ou mais micções, o segundo devido ao maior impacto na qualidade de vida. As associações entre as variáveis investigadas e os desfechos foram avaliadas por modelo de regressão logística, e obtidas razões de chances brutas e ajustadas. Resultados Foram incluídas 132 participantes. A prevalência de noctúria foi 71,2% e, de duas ou mais micções, 56,8%. Houve associação de menor escolaridade (OR: 0,260 [0,106;0,637], p=0,003), incontinência urinária mista (OR: 2,533 [1,103;5,817], p=0,028) e três ou mais comorbidades (OR: 3,105 [1,340;7,196], p=0,008) com maior chance de noctúria. Menor escolaridade (OR: 0,324 [0,148;0,709], p=0,005), menor consumo de cafeína (OR: 0,995 [0,990;1,000], p=0,041) e síndrome da bexiga hiperativa (OR: 2,761 [1,189;6,409], p=0,018) mostraram-se associadas a uma maior chance de duas ou mais micções. Conclusões Na população atendida em serviços especializados, a prevalência de noctúria foi semelhante à da população em geral e à de serviços semelhantes, mas a prevalência de duas ou mais micções foi superior. Mostrou-se importante a busca ativa de noctúria em mulheres com comorbidades, em especial três ou mais, e a adequada compensação das mesmas no manejo do sintoma.

Abstract Objective To identify the prevalence and factors related to nocturia in women presenting lower urinary tract symptoms. Methods Observational cross-sectional survey, individualized, hospital-based, involving women attended by the Unified Health System in urogynecology outpatient clinics in Niterói and Petrópolis, RJ, Brazil. Sociodemographic, clinical, and lifestyle data were collected. Two outcomes of nocturia were considered: one or more nocturnal voids and two or more nocturnal voids, the latter due to its greater impact on quality of life. Associations between the investigated variables and the outcomes were assessed by logistic regression models, and crude and adjusted odds ratios were obtained. Results A total of 132 participants were included. The prevalence of nocturia was 71.2%, and of two or more voids, 56.8%. Lower education level OR 0,260 (0,106; 0,637), mixed urinary incontinence OR 2,533 (1,103; 5,817), and three or more comorbidities OR 3,105 (1,340; 7,196) were associated with a higher chance of nocturia. Lower education level OR 0,324 (0,148; 0,709), lower caffeine consumption OR 0,995 (0,990; 1,000), and overactive bladder syndrome OR 2,761 (1,189; 6,409) were associated with a higher chance of two or more voids. Conclusions In the population attending specialized services, the prevalence of nocturia was similar to that of the general population and to that of similar services, but the prevalence of two or more voids was higher. Active screening for nocturia in women with comorbidities, especially three or more, and their adequate management, proved to be important in addressing the symptom.

Pure tone audiometry with and without specific ear protectors.

UNLABELLED: The authors evaluated pure tone audiometry with and without specific ear protectors. AIM: The purpose of this case control study was to measure the level of sound attenuation by earplugs. MATERIAL AND METHODS: The evaluation included sixty ears of 30 subjects of both sexes, aged between 20 and 58 years, of various professional activities, with normal hearing thresholds, and following ten hours of auditory rest. The statistical results of pure tone audiometry at 500 to 4000 Hertz with and without specific ear protectors were analyzed. RESULTS: These results were compared with those provided by the ear protector manufacturer. CONCLUSION: The results show that the rate of sound reduction was similar to the manufacturer's specifications.