The role of connectivity on COVID-19 preventive approaches.

Preventive and modelling approaches to address the COVID-19 pandemic have been primarily based on the age or occupation, and often disregard the importance of heterogeneity in population contact structure and individual connectivity. To address this gap, we developed models based on Erdos-Rényi and a power law degree distribution that first incorporate the role of heterogeneity and connectivity and then can be expanded to make assumptions about demographic characteristics. Results demonstrate that variations in the number of connections of individuals within a population modify the impact of public health interventions such as lockdown or vaccination approaches. We conclude that the most effective strategy will vary depending on the underlying contact structure of individuals within a population and on timing of the interventions.

Study of the possible link of 25-hydroxyvitamin D with Epstein-Barr virus and human herpesvirus 6 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Although the causes of multiple sclerosis (MS) remain partially unknown, environmental and genetic factors are thought to play a role in its aetiopathogenesis. Hypovitaminosis D, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) infections have been described as possible MS triggers. Our aim was to analyse the possible link between 25-hydroxyvitamin D [25(OH)D] and viruses in patients with MS. METHODS: We included 482 patients with MS in a 2-year study. Serum samples were collected to analyse 25(OH)D levels and, according to sample availability, antibody titres against EBV and HHV-6 by enzyme-linked immunosorbent assay. DNA was extracted from blood in order to analyse EBV and HHV-6 viral load by quantitative real-time polymerase chain reaction and to genotype MS-related single nucleotide polymorphisms (rs3135388, rs2248359 and rs12368653) when possible. RESULTS: The 25(OH)D levels were significantly higher in the first semester of the year than in the second. Carriers of the risk allele rs2248359-C showed lower 25(OH)D levels than non-carriers. For EBV, viral load was significantly higher when 25(OH)D levels were low, demonstrating an inverse correlation between 25(OH)D levels and EBV load. CONCLUSIONS: The 25(OH)D levels could be involved in the regulation of EBV replication/reactivation in patients with MS.

Metal complexes of a novel heterocyclic benzimidazole ligand formed by rearrangement-cyclization of the corresponding Schiff base. Electrosynthesis, structural characterization and antimicrobial activity.

The electrochemical oxidation of anodic metals (M = cobalt, nickel, copper, zinc and cadmium) in a solution of the ligand 1H-anthra[1,2-d]imidazol-6,11-dione-2-[2-hydroxyphenyl] [H2L] afforded homoleptic [ML] compounds. The addition to the electrochemical cell of coligands (L') such as 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) allowed the synthesis, in one step, of heteroleptic [MLL'] compounds. The crystal structures of H2L (1), [CoL(MeOH)]2 (2), [CoL(phen)]2 (3), [NiL(bpy)]2 (4), [CuL(bpy)] (5), [CuL(phen)] (6) and [CdL(bpy)]2 (7) have been determined by X-ray diffraction techniques. The crystal structures of 2, 3, 4 and 7 consist of dimeric species in which both metallic atoms are connected through two phenolate bridges in a penta-coordinated (2) or hexa-coordinated (3, 4 and 7) environment. Copper compounds 5 and 6 are monomeric species with the metal in a pentacoordinated [N4O] environment. In all the compounds, the main interactions responsible for the crystal packing are classic (N-HO, O-HN and O-HO) and non-classic (C-HO and C-HN) hydrogen bond interactions, and π interactions (π-π-stacking and C-Hπ). All compounds were also characterized by microanalysis, IR spectroscopy, FAB mass spectrometry and 1H NMR spectroscopy. Magnetic susceptibility data were measured for 2-4 over the temperature range 2-300 K, and their analysis has revealed the occurrence of intramolecular antiferromagnetic coupling for 2 (J = -2 cm-1) and ferromagnetic coupling for 3 (J = 7.8 cm-1) and 4 (J = 2.8 cm-1) [J being the isotropic magnetic coupling parameter]. The nature of the magnetic coupling in 2-4 is correlated with the magnitude of the M-Ophenolate-M angle between the phenolate bridge and the metallic centers [M(ii) = Co, Ni]. The in vitro antimicrobial properties of the novel ligand and its metal complexes were detected against Gram positive and Gram negative bacteria and fungi. [NiL(bpy)]2 and all tested Cd(ii) complexes were the most active compounds, showing the highest inhibitory effect against bacilli (MIC 1.5-3 µg mL-1) and Sarcina, Streptococci and Haemophilus influenzae bacterial strains (MIC 12-50 µg mL-1), while almost no antifungal properties were observed.

Monitoring the John Cunningham virus throughout natalizumab treatment in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) cases have arisen amongst multiple sclerosis patients treated with natalizumab. Our objective was to gain a better understanding of the mechanisms that underlie the John Cunningham virus (JCV) infection which causes PML. METHODS: A study was made of (i) the quarterly JCV DNA levels in peripheral blood mononuclear cells (PBMCs), serum and urine samples in 100 multiple sclerosis patients during their natalizumab treatment (3-39 months), (ii) the association between human leukocyte antigen (HLA) class II and the previous viral detection and (iii) the identification of the JCV variants in those patients suspected of having PML. RESULTS: (i) JCV DNA in PBMCs and/or serum was detected in 23% of our cohort. Patients with an intermittent JCV excretion in urine had a significant increase of the viral load and prevalence in this compartment during natalizumab treatment. (ii) The frequency of the DRB1*07/DQA1*02:01/DQB1*02:02 haplotype tended to be higher in patients with detectable versus undetectable JCV DNA in PBMCs (P(corrected) = 0.108). (iii) The variants in PBMCs and serum of the non-PML patient matched the archetype. In the patient with non-fatal PML, the archetype and the same neurotropic variant in PBMCs, serum and cerebrospinal fluid was identified at the time PML was diagnosed, whereas in the patient with a worse PML prognosis, four neurotropic variants in the three previous compartments were found by the PML diagnosis. CONCLUSIONS: The detection of the neurotropic variant in blood during natalizumab treatment could be critical in the prevention of the development of severe PML, since this variant appears simultaneously with the clinical symptoms of PML and mutates quickly.

Síndrome de encefalopatía posterior reversible en el postoperatorio de neurocirugía. Revisión de la literatura / Posterior reversible encephalopathy syndrome after neurosurgery: a literature review

El síndrome de encefalopatía posterior reversible es una entidad clínico-radiológica que se manifiesta con disminución del nivel de consciencia, convulsiones y alteraciones visuales, y radiológicamente, como edema cerebral predominantemente en la sustancia blanca de regiones parietoccipitales. Son múltiples las situaciones que pueden desencadenar el cuadro, entre ellas, la administración de inmunosupresores, quimioterapia, estados hipertensivos y la sepsis. Se describe el caso de un paciente diagnosticado de adenocarcinoma de próstata en estadio iv que recibió quimioterapia, presentando un síndrome de encefalopatía posterior reversible en el postoperatorio inmediato de una resección de metástasis cerebral (AU)

Posterior reversible encephalopathy syndrome is a clinical-radiological characterized by decreased level of consciousness, seizures, and visual disturbances, as well as radiologically ras brain edema, predominantly in parieto-occipital white matter regions. There are many situations that can trigger the disorder, including the administration of immunosuppressants, chemotherapy agents, hypertensive disorders, and sepsis. The case is described of a patient diagnosed with stage IV prostate adenocarcinoma, receiving chemotherapy, andundergoing a posterior reversible encephalopathy syndrome after surgery for resection of brain metastasis (AU)

Hematoma retroperitoneal en una paciente anticoagulada y portadora de un catéter femoral / Retroperitoneal haematoma in an anticoagulated patient with a femoral catheter

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[Posterior reversible encephalopathy syndrome after neurosurgery: A literature review]. / Síndrome de encefalopatía posterior reversible en el postoperatorio de neurocirugía. Revisión de la literatura.

Posterior reversible encephalopathy syndrome is a clinical-radiological characterized by decreased level of consciousness, seizures, and visual disturbances, as well as radiologically ras brain edema, predominantly in parieto-occipital white matter regions. There are many situations that can trigger the disorder, including the administration of immunosuppressants, chemotherapy agents, hypertensive disorders, and sepsis. The case is described of a patient diagnosed with stage IV prostate adenocarcinoma, receiving chemotherapy, andundergoing a posterior reversible encephalopathy syndrome after surgery for resection of brain metastasis.

Multicausal etiology of anemia among women of reproductive age in Vietnam.

BACKGROUND/OBJECTIVES: Anemia is a significant public health concern, especially among women and young children. An improved understanding of the complex etiology of anemia is crucial for developing appropriate prevention strategies. This paper examines the determinants of anemia in a large sample of Vietnamese women of reproductive age (WRA). METHODS: We included baseline data from 4986 WRA participating in a randomized controlled trial (PRECONCEPT). Hemoglobin (Hb) concentrations were measured with Hemocue. Plasma ferritin (Fe), retinol binding protein (RBP) and markers of inflammation were assessed using the ELISA technique. We used multivariate logistic regression to describe associations with anemia and structural equation modeling (SEM) to characterize direct and indirect pathways influencing Hb concentrations. RESULTS: Prevalence of anemia, iron deficiency (Fe <12 µg/l), insufficient iron stores (Fe<30 µg/l) and iron deficiency anemia was 19.7, 3.5, 14.4 and 1.9%, respectively. Ferritin concentration (0.29 per log-mg/dl), being an ethnic minority (-0.24 compared with Kinh), number of children (-0.17) and socioeconomic status (0.09) were directly associated with Hb concentration (P<0.05). Similarly, RBP was directly (0.27 per mg/dl) associated with Hb and also indirectly (0.09 mg/dl) with ferritin. Hookworm infection was indirectly associated with Hb (-0.11) through RBP and ferritin. CONCLUSION: These findings illustrate the complex etiology of anemia and provide a useful framework for designing, targeting and evaluating appropriate strategies for the prevention and control of anemia. Contrary to expectations, iron deficiency accounted for a very small proportion of anemia in Northern Vietnam.

Motor excitability measurements: the influence of gender, body mass index, age and temperature in healthy controls.

STUDY AIMS: The technique of threshold tracking to test axonal excitability gives information about nodal and internodal ion channel function. We aimed to investigate variability of the motor excitability measurements in healthy controls, taking into account age, gender, body mass index (BMI) and small changes in skin temperature. MATERIALS AND METHODS: We examined the left median nerve of 47 healthy controls using the automated threshold-tacking program, QTRAC. Statistical multiple regression analysis was applied to test relationship between nerve excitability measurements and subject variables. RESULTS: Comparisons between genders did not find any significant difference (P>0.2 for all comparisons). Multiple regression analysis showed that motor amplitude decreases with age and temperature, stimulus-response slope decreases with age and BMI, and that accommodation half-time decrease with age and temperature. CONCLUSION: The changes related to demographic features on TRONDE protocol parameters are small and less important than in conventional nerve conduction studies. Nonetheless, our results underscore the relevance of careful temperature control, and indicate that interpretation of stimulus-response slope and accommodation half-time should take into account age and BMI. In contrast, gender is not of major relevance to axonal threshold findings in motor nerves.

Toll-like receptor-9 in Spanish multiple sclerosis patients: an association with the gender.

BACKGROUND AND PURPOSE: Toll-like receptor-9 (TLR9) is a potent inducer of innate immune system triggered by infection with viruses, some of them previously related to multiple sclerosis (MS). The aim of this study was to analyze the possible association of two TLR9 single nucleotide polymorphisms (SNPs; rs352162 and rs187084) with susceptibility to MS. METHODS: Two independent cohorts of MS patients and controls were included: 574 clinically definite relapsing-remitting MS patients (367 females) and 807 healthy controls (418 females) for the first cohort; and 366 relapsing-remitting MS patients (238 females) and 224 healthy controls (160 females) for the second cohort. Genotyping was performed by TaqMan assays. RESULTS: The AT haplotype was found to be significantly higher in women than in men (P = 0.013 and P = 0.044). CONCLUSIONS: Here two possible genetic markers are proposed that could be also associated with the differences observed in the clinical course of MS in both genders. Further studies with larger cohorts should be performed to confirm these results.

Bloqueo paravertebral continuo para analgesia en cirugía cardiaca mínimamente invasiva. Respuesta de los autores / Continuous paravertebral block for analgesia in minimally invasive cardiac surgery. Reply of the authors

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Analgesia paravertebral continua frente a analgesia intravenosa en cirugía cardiaca mínimamente invasiva por minitoracotomía / Continuous paravertebral analgesia versus intravenous analgesia in minimally invasive cardiac surgery by mini-thoracotomy

Objetivos. La cirugía cardiaca de acceso mínimo mediante minitoracotomía tiene como objetivo principal una reincorporación precoz a la actividad diaria. Para ello, el control del dolor postoperatorio es fundamental. Realizamos un estudio para valorar la calidad de la analgesia postoperatoria tras cirugía cardiaca por minitoracotomía, según la técnica analgésica. Material y métodos. Estudio descriptivo observacional retrospectivo. Se incluyeron los pacientes intervenidos de cirugía cardiaca de acceso mínimo en nuestro centro, desde el año 2009 hasta 2011. Los pacientes se dividieron en 2 grupos dependiendo del tipo de analgesia recibida: analgesia por catéter paravertebral, mediante la infusión de anestésicos locales (grupo BPV), y analgesia intravenosa con opiáceos (grupo AIO). Los objetivos del estudio fueron la comparación de la calidad analgésica y las complicaciones asociadas a la técnica analgésica, tiempo de extubación, complicaciones posquirúrgicas y tiempos de estancia hospitalaria, entre ambas técnicas. Resultados. Treinta y siete pacientes fueron intervenidos mediante cirugía cardiaca de acceso mínimo tipo «Heart-Port» modificado. Quince pacientes recibieron analgesia mediante bloqueo paravertebral y 22 mediante analgesia con opiáceos. Los datos se muestran como media y desviación estándar (DE). Se apreció un tiempo de extubación traqueal inferior a 4h en el 60% de los pacientes en el grupo BPV, frente al 22% del grupo AIO (p<0,05). La estancia en la UCI para el grupo BPV fue de 1,2 (0,7) días frente a 2,2 (0,7) días del grupo AIO (p<0,05). La estancia hospitalaria fue de 4,8 (1,2) días para el grupo PVB y de 5,6 (2,8) días para el grupo AIO (p>0,05). No se observaron complicaciones asociadas al bloqueo paravertebral continuo. Discusión. La analgesia mediante bloqueo paravertebral es una técnica aceptablemente segura en cirugía cardiaca por toracotomía, que permite una extubación precoz con un control óptimo del dolor cuando se compara con analgesia iv con opiáceos(AU)

Objectives. Minimal access cardiac surgery via minithoracotomy aims faster recovery and shorter hospital length of stay. Pain control is essential in order to achieve this goal. A study was conducted to assess the quality of post-operative analgesia and complications related to the analgesia techniques after cardiac surgery by minithoracotomy. Material and methods. A descriptive, observational and retrospective study was conducted on the patients subjected to minimal access cardiac surgery in our centre between the years 2009 to 2011. The patients were divided into two groups according to the type of analgesia received: analgesia through a paravertebral catheter, with an infusion of local anaesthetics (PVB group), and intravenous analgesia with opioids (IOA group). The aim of the study was to compare the analgesic quality and the complications associated to the analgesic technique, extubation time, post-surgical complications, and length of hospital stay between both techniques. Results. A total of 37 patients underwent to a modified minimally invasive Heart-Port access cardiac surgery. Fifteen patients received analgesia through a paravertebral block and the other 22 IV analgesia with opioids. Data are shown as means and standard deviation (SD). Mean tracheal extubation time less than 4hours was observed in 60% of the patients in the PVB group, compared to 22% in the IOA group (P<.05). Length of stay in ICU for the PVB group was 1.2 (0.7) days compared to 2.2 (0.7) days in the IOA group (P<.05). Mean hospital stay was 4.8 (1.2) days for the PVB group, and 5.6 (2.8) for the IOA group (P>.05. No complications associated to the continuous paravertebral block were observed. Discussion. PVB analgesia is an acceptable safe technique in cardiac surgery via thoracotomy which enables early extubation with optimal pain control when compared with IV analgesia with opioids(AU)

[Continuous paravertebral analgesia versus intravenous analgesia in minimally invasive cardiac surgery by mini-thoracotomy]. / Analgesia paravertebral continua frente a analgesia intravenosa en cirugía cardiaca mínimamente invasiva por minitoracotomía.

OBJECTIVES: Minimal access cardiac surgery via minithoracotomy aims faster recovery and shorter hospital length of stay. Pain control is essential in order to achieve this goal. A study was conducted to assess the quality of post-operative analgesia and complications related to the analgesia techniques after cardiac surgery by minithoracotomy. MATERIAL AND METHODS: A descriptive, observational and retrospective study was conducted on the patients subjected to minimal access cardiac surgery in our centre between the years 2009 to 2011. The patients were divided into two groups according to the type of analgesia received: analgesia through a paravertebral catheter, with an infusion of local anaesthetics (PVB group), and intravenous analgesia with opioids (IOA group). The aim of the study was to compare the analgesic quality and the complications associated to the analgesic technique, extubation time, post-surgical complications, and length of hospital stay between both techniques. RESULTS: A total of 37 patients underwent to a modified minimally invasive Heart-Port access cardiac surgery. Fifteen patients received analgesia through a paravertebral block and the other 22 IV analgesia with opioids. Data are shown as means and standard deviation (SD). Mean tracheal extubation time less than 4 hours was observed in 60% of the patients in the PVB group, compared to 22% in the IOA group (P<.05). Length of stay in ICU for the PVB group was 1.2 (0.7) days compared to 2.2 (0.7) days in the IOA group (P<.05). Mean hospital stay was 4.8 (1.2) days for the PVB group, and 5.6 (2.8) for the IOA group (P>.05. No complications associated to the continuous paravertebral block were observed. DISCUSSION: PVB analgesia is an acceptable safe technique in cardiac surgery via thoracotomy which enables early extubation with optimal pain control when compared with IV analgesia with opioids.

Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma.

The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P<0.001), progression free-survival (PFS) (P<0.009) and overall survival (OS) (P<0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-κB and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.

Sepsis puerperal tardía con shock séptico y disfunción cardiaca / Late-onset postpartum sepsis with septic shock and heart dysfunction

Presentamos el caso de una mujer de raza blanca de 37 años con diagnóstico de sepsis puerperal tardía por endometritis causada por estreptococo del grupo A (SGA) y shock séptico con insuficiencia mitral y disfunción cardiaca. La instauración precoz de antibioterapia de amplio espectro y soporte hemodinámico fue fundamental para la evolución favorable de la paciente. Debido al resurgir de cepas virulentas de SGA y las consecuencias fatales que pueden llegar a desencadenar, es importante incluir este microorganismo en el diagnóstico diferencial de las infecciones maternas relacionadas con el puerperio. La afectación cardiaca es poco frecuente en el contexto de infección por este microorganismo, sin embargo ante una sepsis con mala evolución el diagnóstico con ecocardiografía parece imprescindible para descartar disfunción cardiaca(AU)

We report a case of late-onset postpartum sepsis from endometritis due to group A streptococci (GAS) in a 37-year-old white woman. The patient developed septic shock, with mitral regurgitation and cardiac dysfunction. Early treatment with broad-spectrum antibiotics and hemodynamic support was essential for a favorable outcome. Because of the resurgence of virulent strains of GAS that can cause fatal infections, these pathogens should be included in the differential diagnosis of postpartum infections in the mother. Although cardiac dysfunction is rare in association with GAS infection, it should be ruled out by echocardiography when the condition of a patient with sepsis does not improve(AU)

[Late-onset postpartum sepsis with septic shock and heart dysfunction]. / Sepsis puerperal tardía con shock séptico y disfunción cardiaca.

We report a case of late-onset postpartum sepsis from endometritis due to group A streptococci (GAS) in a 37-year-old white woman. The patient developed septic shock, with mitral regurgitation and cardiac dysfunction. Early treatment with broad-spectrum antibiotics and hemodynamic support was essential for a favorable outcome. Because of the resurgence of virulent strains of GAS that can cause fatal infections, these pathogens should be included in the differential diagnosis of postpartum infections in the mother. Although cardiac dysfunction is rare in association with GAS infection, it should be ruled out by echocardiography when the condition of a patient with sepsis does not improve.

Sepsis puerperal tardía con shock séptico y disfunción cardiaca / Late-onset postpartum sepsis with septic shock and heart dysfunction

Presentamos el caso de una mujer de raza blanca de 37 años con diagnóstico de sepsis puerperal tardía por endometritis causada por estreptococo del grupo A (SGA) y shock séptico con insuficiencia mitral y disfunción cardiaca. La instauración precoz de antibioterapia de amplio espectro y soporte hemodinámico fue fundamental para la evolución favorable de la paciente. Debido al resurgir de cepas virulentas de SGA y las consecuencias fatales que pueden llegar a desencadenar, es importante incluir este microorganismo en el diagnóstico diferencial de las infecciones maternas relacionadas con el puerperio. La afectación cardiaca es poco frecuente en el contexto de infección por este microorganismo, sin embargo ante una sepsis con mala evolución el diagnóstico con ecocardiografía parece imprescindible para descartar disfunción cardiaca(AU)

We report a case of late-onset postpartum sepsis from endometritis due to group A streptococci (GAS) in a 37-year-old white woman. The patient developed septic shock, with mitral regurgitation and cardiac dysfunction. Early treatment with broad-spectrum antibiotics and hemodynamic support was essential for a favorable outcome. Because of the resurgence of virulent strains of GAS that can cause fatal infections, these pathogens should be included in the differential diagnosis of postpartum infections in the mother. Although cardiac dysfunction is rare in association with GAS infection, it should be ruled out by echocardiography when the condition of a patient with sepsis does not improve(AU)