Novel Heme Oxygenase-1 Inducers Palliate Inflammatory Pain and Emotional Disorders by Regulating NLRP3 Inflammasome and Activating the Antioxidant Pathway.

Chronic pain caused by persistent inflammation is current in multiple diseases and has a strong negative impact on society. It is commonly associated with several mental illnesses, which can exert a negative influence on pain perception, and needs to be eradicated. Nevertheless, actual therapies are not sufficiently safe and effective. Recent reports demonstrate that the induction of heme oxygenase-1 (HO-1) enzyme produces analgesic effects in animals with osteoarthritis pain and reverses the grip strength loss caused by sciatic nerve crush. In this research, we evaluated the potential use of three new HO-1 inducers, 1m, 1a, and 1b, as well as dimethyl fumarate (DMF), for treating persistent inflammatory pain induced by the subplantar injection of complete Freud's adjuvant and the functional deficits and emotional sickness associated. The modulator role of these treatments on the inflammatory and antioxidant pathways were also assessed. Our findings revealed that repeated treatment, for four days, with 1m, 1a, 1b, or DMF inhibited inflammatory pain, reversed grip strength deficits, and reversed the linked anxious- and depressive-like behaviors, with 1m being the most effective. These treatments also suppressed the up-regulation of the inflammasome NLRP3 and activated the expression of the Nrf2 transcription factor and the HO-1 and superoxide dismutase 1 enzymes in the paw and/or amygdala, thus revealing the anti-inflammatory and antioxidant capacity of these compounds during inflammatory pain. Results suggest the use of 1m, 1a, 1b, and DMF, particularly 1m, as promising therapies for inflammatory pain and the accompanying functional disabilities and emotional diseases.

The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated.

Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.

Parir en tiempos de pandemia: atención al parto en Cataluña en función del diagnóstico de COVID-19 / Giving birth in times of pandemic: childbirth care in Catalonia based on the diagnosis of COVID-19

Objective: To analyze the differences in birth labor care in the pandemic context according to women's diagnosis of COVID-19, specifically considering the information they received, the humanized nature of care and the degree of medicalization of their labor and delivery. People and method: It is a quantitative research where the data result from a survey conducted to women who were pregnant from January 1, 2018 to September 2021. While the larger research project includes care data during the pandemic -target group- and previous to the pandemic -control group- in this article we exclusively analyze data referring to the pandemic context. Using descriptive and inferential statistical analysis by cross-sectional study of cases and control, in this article we compare the experiences of women who gave birth during the pandemic being positive in COVID-19 with those of women who were negative. Results: We obtained 2,600 responses and 2,070 were considered valid (1,862 target group and 208 control group), with a confidence level of 95.5% and a margin of error of ±2.33%. Women with a positive result received less information (84.40% were informed of the procedures versus 91.30% of women with a negative result) and had less possibility to decide on procedures (51.90% versus 70.80% of women with a negative result). They also could be less accompanied (59.4% could be accompanied at all times compared to 81.3% of women with a negative result); they consider to a greater extent that the pandemic has been detrimental to a personalized care (66.7% vs. 34.7% of women with a negative result); and they grade worse both the professional care received and the atmosphere of the spaces in which they gave birth (on average, the treatment received is scored at 3.73 out of 5 for the different spaces compared to 4.11 for women with a negative result). (AU)

Objetivo: Analizar las diferencias en la atención al parto en pandemia según el diagnóstico de COVID-19 de las mujeres, considerando de forma específica la información que recibieron, el carácter humanizado de la atención y el nivel de medicalización de su parto. Personas y método: Se trata de un estudio cuantitativo a partir de una encuesta a mujeres que estuvieron embarazadas del 1 de enero de 2018 hasta finales de septiembre de 2021. Si bien el estudio incluyó datos de atención durante la pandemia -grupo diana- y datos prepandemia -grupo control (experiencia anterior a esa fecha)-, en el presente artículo se analizan exclusivamente datos referentes al contexto pandémico. En el artículo se comparan, mediante análisis estadístico descriptivo e inferencial por estudio transversal de casos y control, las experiencias de mujeres que parieron durante la pandemia siendo positivas en la COVID-19 con aquellas negativas. Resultados: Se obtuvieron 2600 respuestas: 2070 se consideraron válidas (1862 del grupo diana y 208 del grupo control), con un nivel de confianza del 95,5 % y un margen de error de ±2,33 %. Las mujeres con resultado positivo recibieron menos información (al 84,40 % se les informó de los procedimientos frente al 91,30 % de las mujeres con resultado negativo), menos posibilidad de decidir sobre procedimientos (el 51,90 frente al 70,80 % de las mujeres con resultado negativo) y pudieron estar menos acompañadas (el 59,4 % pudo estar acompañada en todo momento frente al 81,3 % de las mujeres con resultado negativo). Consideran en mayor medida que la pandemia ha ido en detrimento de una atención personalizada (el 66,7 frente al 34,7 % de las mujeres con resultado negativo), y valoran peor tanto el trato profesional recibido como el ambiente de los espacios donde dieron a luz (de media, el trato recibido se puntúa en 3,73 sobre 5 para los diferentes espacios, frente al 4,11 de las mujeres con resultado negativo). (AU)

Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach.

Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.

Morphometry of corpus callosum in Williams syndrome: shape as an index of neural development.

Brain abnormalities in Williams syndrome (WS) have been consistently reported, despite few studies have devoted attention to connectivity between different brain regions in WS. In this study, we evaluated corpus callosum (CC) morphometry: bending angle, length, thickness and curvature of CC using a new shape analysis method in a group of 17 individuals with WS matched with a typically developing group. We used this multimethod approach because we hypothesized that neurodevelopmental abnormalities might result in both volume changes and structure deformation. Overall, we found reduced absolute CC cross-sectional area and volume in WS (mean CC and subsections). In parallel, we observed group differences regarding CC shape and thickness. Specifically, CC of WS is morphologically different, characterized by a larger bending angle and being more curved in the posterior part. Moreover, although CC in WS is shorter, a larger relative thickness of CC was found in all callosal sections. Finally, groups differed regarding the association between CC measures, age, white matter volume and cognitive performance. In conclusions, abnormal patterns of CC morphology and shape may be implicated in WS cognitive and behavioural phenotype.

MRI amygdala volume in Williams Syndrome.

One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched controls. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices and were used to measure whole gray matter, white matter and cerebrospinal fluid volumes, as well as amygdala volume (right and left). Results revealed significantly reduced intracranial volume in individuals with WS, compared with controls. There were no differences between groups in absolute amygdalae volume, although there was a relative increase in amygdalae volumes, when adjusted for total intracranial content. There were no inter-hemispheric differences in amygdalae volumes in both groups. These results suggest a relative increase in amygdala volume in WS compared with healthy controls that likely reflects abnormal neurodevelopmental processes of midline brain structures.

Williams syndrome hypersociability: a neuropsychological study of the amygdala and prefrontal cortex hypotheses.

Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS hypersociability was explored using three behavioral tasks--facial emotional recognition task, a social approach task and a go no/go task. Thus, a group 15 individuals with Williams syndrome was compared to two groups of normal developing individuals--a group of 15 individuals matched for chronological age (CA) and 15 individuals matched for mental age (MA), and sex. Individuals with WS present a specific impairment in recognizing negative facial expressions and do not display impairments in response inhibition when compared with typically developing groups. Although these findings partially support the amygdala contribution to WS hypersociability, we found that general cognitive functioning predicted this performance. Additionally, individuals with WS did not differ from both CA and MA groups in the recognition of angry facial expressions, a finding suggesting that they are actually able to identify stimuli associated with social threat. Overall, the results seem to indicate that this social profile must be understood within a developmental framework.

Williams syndrome and memory: a neuroanatomic and cognitive approach.

Williams Syndrome (WS) is described as displaying a dissociation within memory systems. As the integrity of hippocampal formation (HF) is determinant for memory performance, we examined HF volumes and its association with memory measures in a group of WS and in a typically development group. A significantly reduced intracranial content was found in WS, despite no differences were observed for HF absolute volumes between groups. When volumes were normalized, left HF was increased in WS. Moreover, a lack of the normal right > left HF asymmetry was observed in WS. No positive correlations were found between volumetric and neurocognitive data in WS. In sum, a relative enlargement of HF and atypical patterns of asymmetry suggest abnormal brain development in WS.

Cognitive functioning in Williams syndrome: a study in Portuguese and Spanish patients.

Williams Syndrome (WS) is a genetic neurodevelopmental disorder caused by a submicroscopic deletion on chromosome 7 q11.23. This is a systemic disorder in which cardiac problems and mental retardation are the key phenotypic symptoms. Although displaying a general cognitive impairment, they are most often described as exhibiting a peak and valley profile, with relative sparing of language and face processing abilities and severe impairment of visual-spatial cognition. In this study, we conducted a detailed cognitive assessment using Wechsler Intelligence Scales on a WS and a normal development control group. To explore the hypothesis of a dissociative cognitive architecture in WS, performance on subtests, factorial indexes and composite measures of Verbal, Performance and Full Scale Intelligence Quotient were analysed. Individuals with WS were found to score in Full Scale Intelligence Quotient (FSIQ) within mild to moderate mental retardation interval, and had significantly lower scores in all measures when they were compared with the normal development group. However, a specific intragroup cognitive profile was found for Williams Syndrome (confirming Mervis' definition of the WS cognitive profile) along with a specific developmental pathway (absence of an age-associated cognitive decline).

MRI assessment of superior temporal gyrus in Williams syndrome.

OBJECTIVE: To evaluate volumes and asymmetry of superior temporal gyrus (STG) and correlate these measures with a neurocognitive evaluation of verbal performance in Williams syndrome (WS) and in a typically developing age-matched and sex-matched group. BACKGROUND: Despite initial claims of language strength in WS, recent studies suggest delayed language milestones. The STG is implicated in linguistic processing and is a highly lateralized brain region. METHOD: Here, we examined STG volumes and asymmetry of STG in WS patients and in age-matched controls. We also correlated volume of STG with a subset of verbal measures. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices, and were used to measure whole gray matter, white matter, and cerebrospinal fluid volumes, and also STG volume. RESULTS: Results revealed significantly reduced intracranial volume in WS patients, compared with controls. Right and left STG were also significantly smaller in WS patients. In addition, compared with normal controls, a lack of normal left >right STG asymmetry was evident in WS. Also of note was the finding that, in contrast to controls, WS patients did not reveal a positive correlation between verbal intelligence quotient and left STG volume, which further suggests a disruption in this region of the brain. CONCLUSIONS: In conclusion, atypical patterns of asymmetry and reduced STG volume in WS were observed, which may, in part, contribute to some of the linguistic impairments found in this cohort of WS patients.

Memory abilities in Williams syndrome: dissociation or developmental delay hypothesis?

Williams syndrome (WS) is a neurodevelopmental genetic disorder often described as being characterized by a dissociative cognitive architecture, in which profound impairments of visuo-spatial cognition contrast with relative preservation of linguistic, face recognition and auditory short-memory abilities. This asymmetric and dissociative cognition has been also proposed to characterize WS memory ability, with sparing of auditory short-term memory and impairment of spatial and long-term memory abilities. In this study, we explored the possibility of a double memory dissociation in WS (short- versus long-term memory; verbal versus visual memory). Thus, verbal memory abilities were assessed using California Verbal Learning Test and Digit Span and Rey-Osterrieth Complex Figure and Corsi Blocks was used to assess visual-spatial memory abilities. Overall, WS subjects were found to present a generalized significant impairment in verbal and visuo-spatial components either in short- or long-term memory. In sum, data from this study brings support for a developmental delay hypothesis, rather than a double dissociation within memory systems in WS.

Limpieza y desinfección de los endoscopios flexibles / Cleaning and disinfecting flexible endoscopes

El endoscopio flexible es una herramienta de trabajo para el diagnóstico y procedimientos quirúrgicos (por ejemplo polipectomías) en el tracto gastrointestinal. Su uso implica un riesgo potencial de transmisión de microorganismos patógenos entre pacientes, debido a la estructura propia del instrumento, constituido por lúmenes largos y estrechos y múltiples válvulas, que dificultan su limpieza y desinfección (AU)

[Cleaning and disinfecting flexible endoscopes]. / Limpieza y desinfección de los endoscopios flexibles.

A flexible endoscope is a tool employed for surgical and diagnostic procedures, for example the removal of polyps, in the gastrointestinal tract. Its use bears a potential risk to transmit pathogenic microorganisms among patients due to the structure of the instrument itself since it is comprised of long, narrow lumens and multiple valves which make its cleaning and disinfecting difficult.