Parallel neurodegenerative phenotypes in sporadic Parkinson's disease fibroblasts and midbrain dopamine neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they differed in their nature and scale. Furthermore, statistical analysis revealed potential novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments.

Impact of the COVID-19 pandemic on tuberculosis management in Spain.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. METHODS: Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. RESULTS: A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). CONCLUSIONS: The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.

Horizontal transmission of antimicrobial resistance genes from E. coli to Serratia spp. in minced meat using a gfp tagged plasmid.

The transmission of antimicrobial resistance genes from enteric bacteria from the animal reservoir to indigenous bacteria in meat is a serious concern, as it can contribute to human exposure to antimicrobial resistance genes. The aim of this study was to investigate plasmid-mediated horizontal transfer of antimicrobial resistance genes from Escherichia coli to indigenous environmental bacteria in minced pork stored at 10 and 37 °C. E. coli MG1555 containing a gfp-tagged plasmid carrying tetracycline, kanamycin and streptomycin resistance genes was used as the donor with the indigenous bacteria in minced pork acting as potential recipients. The results demonstrated that enteric members of the pork meat microbiota were able to receive gfp-plasmids from the E. coli donor strain at both 10 and 37 °C. The majority of transconjugants were identified as Serratia spp. through sequencing of their 16S rRNA genes. This indicates that environmental Serratia spp. and other Enterobacteriaceae may play a role as carrier of antimicrobial resistance genes through the meat production chain to the consumer.

Suspended LRSPP for the development of highly integrated active plasmonic devices.

We present a novel long-range surface plasmon polariton (LRSPP) device consisting of a suspended dielectric matrix in which an electrically active, millimeter-long metallic waveguide is embedded. We show that, by opening an air gap under the lower cladding, the influence of the substrate is suppressed and the symmetry of the thermo-optical distribution around the LRSPP waveguide is preserved over extended ranges of applied electrical current with minimal optical losses. Experimental results show that, compared to a standard nonsuspended structure, our device allows either the induction of a phase change that is three times larger, for a fixed electrical power, or, equivalently, a scaling down of the device to one-tenth of its original length, for a fixed phase change.

Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment.

OBJECTIVE: To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. METHODS: TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8-283.4); being retired (HR = 2.4;CI:1.1-5.1); having visited the emergency department (HR = 3.1;CI:1.2-7.7); HIV infection (HR = 3.4;CI:1.6-7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2-3.3) or non-standard treatments (HR = 2.68;CI:1.36-5.25); comprehension difficulties (HR = 2.8;CI:1.3-6.1); and smear-positive sputum (HR = 2.3-CI:1.0-4.8). CONCLUSION: There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs.

Screening for active tuberculosis in high-risk groups.

OBJECTIVE: To evaluate an active case-finding strategy among drug users (DUs), economically disadvantaged individuals and recent immigrants from hyperendemic countries, a population at high risk of developing tuberculosis (TB). METHODS: Retrospective, observational study carried out by the Tuberculosis Unit of the City of Barcelona from September 2009 to December 2012. All participants underwent chest X-ray and were screened for symptoms. RESULTS: Of 5982 participants screened, 30 TB cases were detected (total prevalence 0.5%): 26 were pulmonary, 8 were smear-positive and 2 were resistant to multiple drugs. Directly observed treatment was advised for 19 patients (63%). TB prevalence in the recent immigrants group was significantly greater (1.77%) than in all other groups studied: economically disadvantaged individuals 0.30% (RR 5.9, 95%CI 2.30-15.14); DUs 0.62% (RR 2.05, 95%CI 0.91-4.64), non-recent immigrants 0.41% (RR 4.31, 95%CI 1.68-11.4); and all native-born individuals 0.41% (RR 4.33, 95%CI 1.71-10.92). The rate was much greater than the estimated prevalence for the general population of the city (∼20 cases/100,000 population). CONCLUSIONS: In high-risk groups, active case finding can be used as a public health intervention to detect a large number of TB cases.

Monitoring changes in anti-tuberculosis treatment: associated factors determined at the time of diagnosis.

OBJECTIVES: To determine predictive factors for changes in standard anti-tuberculosis chemotherapy at the time of diagnosis. METHODS: A prospective study was performed among tuberculosis (TB) patients treated at specialised centres during 2008-2009. Treatment outcome was monitored per standard guidelines. Treatment was considered successful if the patient was cured or completed treatment. Factors associated with treatment modification were analysed at the bivariate and multivariate levels using logistic regression. RESULTS: A total of 427 patients were included in the study. The initial standard treatment regimen was retained for 249 patients (58.3%), extended to 9 months for 36 (8.4%) and changed for 142 (33.3%). Factors associated with a change of regimen at the multivariate level were female sex, age ≥ 50 years, human immunodeficiency virus infection, comorbidities, alcoholism, hospitalisation and culture-positive sputum. Drug resistance and toxicity were analysed independently. Treatment outcome was successful in 97.2% of cases without a regimen change and in 87.3% of those with a changed regimen (P < 0.001). CONCLUSION: Factors associated with changes in the initial anti-tuberculosis regimen should be considered for rigorous follow-up. Results obtained through individualised treatment provided by specialists were good despite the complexity of the cases treated.

Could 18F-FDG-PET/CT avoid unnecessary thyroidectomies in patients with cytological diagnosis of follicular neoplasm?

PURPOSE: Preoperative diagnosis of thyroid nodules with "follicular neoplasm" (FN) based on fine-needle aspiration cytology (FNAC) forces thyroidectomy to exclude malignancy. This study explores if (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) provides information enough to prevent unnecessary thyroidectomies in this clinical setting. METHODS: This is a prospective study involving 46 consecutive patients scheduled for thyroidectomy due to follicular neoplasm diagnosis in FNAC (36 follicular, 10 Hürthle cell neoplasms, Bethesda classification) since January 2009 until April 2012. All patients underwent preoperative (18)F-FDG-PET/CT. Abnormal (18)F-FDG thyroid uptake was assessed visually and by measuring the maximum standard uptake value (SUV max). Results were compared with definitive pathology reports. RESULTS: Thirteen out of 46 patients (28.3 %) were finally diagnosed with thyroid cancer. Focal uptake correlated with a greater risk of malignancy (p = 0.009). (18)F-FDG-PET/CT focal uptake showed sensitivity, specificity, positive and negative predictive values and overall accuracy of 92.3, 48.5, 41.4, 94.1 and 60.9 %, respectively. The optimal threshold SUV max to discriminate malignancy was 4.2 with an area under receiver-operating characteristic curve of 0.76 (95 % confidence interval, 0.60-0.90). Use of (18)F-FDG-PET/CT could reduce by 13-25 % the number of thyroidectomies performed for definitive benign nodules. However, it has demonstrated worse predictive ability in the subgroup of patients with diffuse uptake, oncocytic pattern in FNAC and lesions smaller than 2. CONCLUSIONS: (18)F-FDG-PET/CT can play a role in the management of thyroid nodules larger than 2 cm cytologically reported as follicular neoplasm without oncocytic differentiation, allowing the avoidance of a significant number of thyroidectomies for definitive benign lesions.

Rifampicin plus isoniazid for the prevention of tuberculosis in an immigrant population.

OBJECTIVES: To compare the tolerance, adherence and effectiveness of two approaches for the treatment of latent tuberculosis infection (LTBI): 6 months of isoniazid (6H) vs. 3 months of isoniazid plus rifampicin (3RH). POPULATION: Immigrants with LTBI. METHODS: Participants were enrolled in a controlled, randomised clinical trial in Barcelona, Spain, from April 2001 to April 2005. Monthly follow-up was done to assess tolerance, side effects and adherence. Effectiveness was evaluated at 5 years. RESULTS: In the 590 subjects enrolled, the rate of adherence was greater in the 3RH than in the 6H arm (72% vs. 52.4%, P = 0.001). No differences between study arms were observed with respect to hepatotoxicity or side effects. Variables associated with non-adherence were diagnosis by screening (OR 1.88, 95%CI 1.26-2.82, P = 0.001), illegal immigration status (OR 1.48, 95%CI 1.01-2.15, P = 0.03), unemployment (OR 1.91, 95%CI 1.28-2.85, P = 0.0008), illiteracy (OR 1.73, 95%CI 1.04-2.88, P = 0.02), lack of family support (OR 3.7, 95%CI 2.54-5.4, P = 0.001) and the 6-month treatment regimen (OR 2.45, 95%CI 1.68-3.57, P = 0.0001). None of the patients who completed either treatment developed tuberculosis. CONCLUSIONS: The 3RH regimen facilitates adherence to LTBI treatment and offers a safe, well-tolerated and effective alternative.

Falso negativo de la gammagrafía con 99mTc-sestamibi en un carcinoma paratiroideo con tumores pardos asociados. Aportaciones de la PET/TAC-18F-FDG / False negative of the scintigraphy with 99mTc-sestamibi in parathyroid carcinoma with associated brown tumors. Contributions of the 18F-FDG-PET/CT

El carcinoma paratiroideo (CPT) es un tumor poco frecuente que suele ser hiperfuncionante, produciendo un exceso de hormona paratiroidea. El hiperparatiroidismo produce trastornos del metabolismo óseo, como osteopenia y en ocasiones tumores pardos. Los tumores pardos son lesiones óseas benignas, pero localmente destructivas, cuyo diagnóstico diferencial con metástasis u otros tipos de tumores primarios puede ser complicado. La técnica habitual para la detección de patología paratiroidea es la gammagrafía con 99mTc-sestamibi, con una sensibilidad del 85–100% y una especificidad cercana al 100% en adenomas paratiroideos, presentando cifras muy similares en la detección del CPT. Presentamos el caso de un paciente diagnosticado de hiperparatiroidismo de origen tumoral con lesiones óseas asociadas en el que la gammagrafía con 99mTc-sestamibi presentó un falso negativo en la detección de patología paratiroidea. Sin embargo, la PET/TAC-18F-FDG detectó el CPT y ayudó en el diagnóstico diferencial de las lesiones óseas asociadas, que fueron finalmente tumores pardos(AU)

Parathyroid carcinoma (PTC) is a rare malignant disease that is usually hyperfunctioning, which produces an excess of parathyroid hormone. Hyperparathyroidism causes bone metabolism disorders, as osteopenia and sometimes brown tumors. Brown tumors are benign but locally aggressive bone lesions, whose differential diagnosis with metastases or other primary malignancies may be complicated. 99mTc-Sestamibi scan is the usual procedure for the detection of parathyroid pathology, with a sensitivity of 85–100% and specificity close to 100% in parathyroid adenomas, it having similar percentages in the detection of PTC. We present the case of a patient diagnosed of a malignant hyperparathyroidism associated with bone lesions in which the 99mTc-Sestamibi scan showed a false negative result in the detection of parathyroid condition. However, 18F-FDG-PET/CT detected the PTC and helped in the differential diagnosis of associated bone lesions, which were finally confirmed as brown tumors(AU)

Evolutionary modularity of the mouse mandible: dissecting the effect of chromosomal reorganizations and isolation by distance in a Robertsonian system of Mus musculus domesticus.

The mouse mandible consists of several morphogenetic units that are usually grouped into two main modules: the alveolar region and the ascending ramus. The genetic/ontogenetic modularity of the two regions implies that they might evolve independently to some extent. In particular, evolutionary modularity in quantitative traits could arise during chromosomal speciation due to lower gene flow in rearranged chromosomes. With the aim of uncovering the autonomous evolution of the mandible modules, the form variation of each of them was assessed in the house mouse Robertsonian system from Barcelona, in which chromosomal variation and geographical distance may act as isolation factors. The association between these factors and morphological changes was analysed to determine their contribution to the differentiation of each module. Although size changes in the two modules were highly correlated, shape changes were not, and their association with karyotype differences, but not geographical distance, was dependent on the module. The results support the existence of two evolutionary modules and highlight the importance of size in morphological integration of the mandible. They also suggest that geographical distance and chromosomal reorganizations reduce gene flow between karyotypically divergent populations, but although geographical distance represents a global barrier to gene flow, the isolation produced by a set of chromosomal reorganizations only affects particular modules, probably depending on the number and location of loci with effects on a particular morphological region.

[False negative of the scintigraphy with 99mTc-sestamibi in parathyroid carcinoma with associated brown tumors. Contributions of the 18F-FDG-PET/CT]. / Falso negativo de la gammagrafía con 99mTc-sestamibi en un carcinoma paratiroideo con tumores pardos asociados. Aportaciones de la PET/TAC-18F-FDG.

Parathyroid carcinoma (PTC) is a rare malignant disease that is usually hyperfunctioning, which produces an excess of parathyroid hormone. Hyperparathyroidism causes bone metabolism disorders, as osteopenia and sometimes brown tumors. Brown tumors are benign but locally aggressive bone lesions, whose differential diagnosis with metastases or other primary malignancies may be complicated. (99m)Tc-Sestamibi scan is the usual procedure for the detection of parathyroid pathology, with a sensitivity of 85-100% and specificity close to 100% in parathyroid adenomas, it having similar percentages in the detection of PTC. We present the case of a patient diagnosed of a malignant hyperparathyroidism associated with bone lesions in which the (99m)Tc-Sestamibi scan showed a false negative result in the detection of parathyroid condition. However, (18)F-FDG-PET/CT detected the PTC and helped in the differential diagnosis of associated bone lesions, which were finally confirmed as brown tumors.

[Air embolism during laparoscopic surgery in an infant girl with Cornelia de Lange syndrome]. / Embolia gaseosa durante cirugía laparoscópica en lactante con síndrome de Cornelia de Lange.

Cornelia de Lange syndrome involves multiple malformations with particular phenotypic features (craniofacial abnormalities such as microcephaly or hypertrichosis with synophrys; cutaneous abnormalities such as hirsutism, and limb anomalies) and it is associated with a high percentage of mental retardation and complications such as digestive tract abnormalities, cardiac defects, and endocrine disorders. We report the case of a 2-month-old infant girl who underwent a laparoscopic antireflux procedure, with closure of a diaphragmatic hernia and a gastric stoma. The medical history included repeated episodes of aspiration pneumonia and hypertension. Early in the procedure, 2 episodes of sudden desaturation, hypotension, and bradycardia with a probable diagnosis of air embolism. The complications resolved with specific treatment. Anesthetic management for laparoscopic surgery in these patients is truly complex and must be informed by a thorough understanding of the disease and complications that may develop.

Distinguishing noise from chaos.

Chaotic systems share with stochastic processes several properties that make them almost undistinguishable. In this communication we introduce a representation space, to be called the complexity-entropy causality plane. Its horizontal and vertical axis are suitable functionals of the pertinent probability distribution, namely, the entropy of the system and an appropriate statistical complexity measure, respectively. These two functionals are evaluated using the Bandt-Pompe recipe to assign a probability distribution function to the time series generated by the system. Several well-known model-generated time series, usually regarded as being of either stochastic or chaotic nature, are analyzed so as to illustrate the approach. The main achievement of this communication is the possibility of clearly distinguishing between them in our representation space, something that is rather difficult otherwise.

[Salivary cortisol determination in the diagnosis of pediatric Cushing's disease]. / Determinación de cortisol salival en el diagnóstico de la enfermedad de Cushing pediátrico.

Endogenous Cushing's syndrome in children is a very rare entity. Diagnosis is complex due to the wide variety of tests available. Recently, the utility of salivary cortisol has been proposed for the diagnosis of this entity, although greater evidence is required, especially in pediatric patients. We report a 14-year-old girl with Cushing's disease due to a pituitary microadenoma in whom salivary cortisol determination was very useful for the diagnosis.