Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

Cell-free assays reveal the HIV-1 capsid protects reverse transcripts from cGAS.

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect their genomes from cGAS even after completion of reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, capsid inhibitors also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling.

Influence of chitosan protonation degree in nanofibrillated cellulose/chitosan composite films and their morphological, mechanical, and surface properties.

Composite films of nanofibrillated cellulose (NFC) and chitosan (CS) were prepared by spray deposition method, and the influence of polymers ratio and protonation degree (α) of chitosan was evaluated. Films were characterized using morphological, mechanical, and surface techniques. Higher NFC content increased Young's modulus of film composites and reduced air permeability, while higher CS content increased water contact angle. Variations in the degree of protonation of chitosan from non-protonated (α = 0) to fully protonated (α = 1) in the NFC/CS composite film with a fixed composition allowed to modulate surface, mechanical, and structural properties, such as water contact angle (31.3-109.2°), Young's modulus (1.7-5.3 GPa), elongation at break (3.1-1.2 %), oxygen transmission rate (9.0-5.5 cm3/m2day) and air permeability (2074-426 s). Highly protonated chitosan composite films showed similar contact angles to pure chitosan films, while low protonated chitosan composite films presented contact angles similar to pure NFC films, suggesting a possible coating effect of NFC by CS through electrostatic interactions, evidenced by microscopy and spectroscopy analysis. By mixing both polymers and adjusting composition and protonation degree it was possible to enhance their properties, making pH adjustment a useful tool for NFC/CS composite films formation.

SQSTM1 Pro392Leu presenting as a corticobasal syndrome with progressive nonfluent aphasia.

Corticobasal syndrome is generally considered to be a sporadic condition. There are familial and isolated genetic cases, associated with GRN, MAPT, c9orf72 or PNRP variants. Some reports implicate other genes: LRRK2, CHMP2B, GBA, CYP27A1, PSEN1, APP, TARDBP and TBK1. Here, we report a case of a patient carrying a SQSTM1 Pro392Leu variant. We report a 57-year-old right-handed-woman with a history of progressive speech impairment, marked right side rigidity and bradykinesia, with rest tremor and stimulus sensitive myoclonus. She had predominantly right-sided apraxia. She had right side agraphestesia and astereognosis. MRI showed asymmetrical left frontotemporoparietal atrophy. DaTSCAN showed predominantly left involvement, PiB-PET was negative. CSF NfL was of 9356.5pg/mL. She carried a heterozygous variant P392L in SQSTM1. This case report expands the spectrum of phenotypes associated with SQSTM1 pathogenic variants. It also expands the list of genes associated with corticobasal syndrome, supporting the involvement of the ubiquitin-proteasome system in this condition.

Donna Jackson-Maldonado. A life dedicated to joining theory and practice in language development research / Donna Jackson-Maldonado. Una vida dedicada a unir teoría y práctica en la investigación del desarrollo del lenguaje

Precedents and objectives: Dr Donna Jackson-Maldonado, researcher and professor at the Centro de Estudios Lingüísticos y Literarios of the Universidad Autónoma de Querétaro in Mexico, left us on November 30, 2021. In this article, we review her main scientific contributions related to the three fundamental axes on which she worked: language acquisition, language disorders and language assessment. Methods and results: Dr Jackson-Maldonado's studies on language acquisition included groups of premature babies, late talkers, and typical development children in bilingual and diverse socioeconomic conditions. Moreover, she studied atypical language development in children with hearing loss, children with developmental language disorders and children with Down syndrome and other syndromes. Finally, regarding language assessment, it should be noted that she led the Mexican Spanish version of the Communicative Development Inventories (CDI) that was used as a model for later adaptations in other Romance languages. Discussion and conclusion: Dr Jackson-Maldonado's methodological approach combined rigour with a creative and innovative scientific spirit, yet she integrated theory and clinical practice from its very beginning. She left us an immense research and personal legacy that we want to honour in this paper.

Antecedentes y objetivos: La Dra. Donna Jackson-Maldonado, investigadora y profesora del Centro de Estudios Lingüísticos y Literarios de la Universidad Autónoma de Querétaro en México, nos dejó el 30 de noviembre de 2021. En este artículo repasamos sus principales aportaciones científicas relacionadas con los tres ejes fundamentales sobre los que trabajó: la adquisición del lenguaje, los trastornos del lenguaje y la evaluación del lenguaje. Método y resultados: Las investigaciones de la Dra. Jackson sobre la adquisición del lenguaje incluyeron grupos de bebés prematuros, hablantes tardíos y niños de desarrollo típico en condiciones socioeconómicas bilingües y diversas. Además, estudió el desarrollo atípico del lenguaje en niños con pérdida auditiva, con trastornos del desarrollo del lenguaje y con síndrome de Down, así como otros síndromes. Finalmente, en cuanto a la evaluación lingüística, cabe destacar que lideró la versión en español mexicano de los Inventarios de Desarrollo Comunicativo (CDI) que sirvió de modelo para posteriores adaptaciones en otras lenguas romances. Discusión y conclusiones: El enfoque metodológico de la Dra. Jackson combinó el rigor con un espíritu científico creativo e innovador, además, integró la teoría y la práctica clínica desde sus inicios. Nos dejó un inmenso legado personal e investigador que queremos honrar en este trabajo.(AU)

The Use of Tissue Grafts Associated with Immediate Implant Placement to Achieve Better Peri-Implant Stability and Efficacy: A Systematic Review and Meta-Analysis.

Background: The goal of this systematic study and meta-analysis was to evaluate the efficacy of hard and/or soft tissue grafts associated with type-1 implants on healing and treatment outcomes. The primary outcomes studied were implant survival rate, pocket depth, marginal peri-implant recession, bone loss, bone thickness (volumetric change), interproximal bone level, mesial and distal papilla migration, and radiographic evaluation; and the secondary parameters were Pink Esthetic Score (PES), vertical distance from implant shoulder and bone, Visual Analogue Score (VAS), Implant Stability Quotient (ISQ), and biological complications (fistulas, pain, mucositis, and peri-implantitis). Methods: The PICO strategy was used to formulate the hypothesis under study: "For patients who underwent extraction and immediate implant placement, what is the efficacy of using any type of graft (bone or soft tissue) compared to non-grafting regarding the peri-implant parameters?" The electronic search process was performed on the MedLine/PubMed and Cochrane databases. It included randomized controlled trials (RCTs) from the last 11 years (from 2012 to November 2023), which were identified and analyzed. Results: Nine RCTs (κ = 0.98) were selected (403 patients and 425 implants); they were divided into three groups: bone graft (75 patients and 75 implants inserted), bone graft and membrane (213 patients and 235 implants inserted), and without bone graft (115 patients and 115 implants inserted). Three studies calculated the mid-facial mucosa level and two reported better results when a connective tissue graft was combined with the xenograft, whereas another study found better results in the combination of a dual-zone technique with a xenograft. Three studies evaluated the total Pink Esthetic Score (PES) at 12 months, where the authors found no significant difference in using a xenogeneic graft with or without a membrane. In the same period, the facial bone thickness was assessed in two articles; the authors reported better results in graft-treated and flapless groups. The risk-of-bias assessment found four studies with low risk, four with moderate risk, and one with a high risk of bias. The meta-analysis showed a medium level of heterogeneity for the mid-facial mucosa level analysis (I2 = 46%) and an overall effect size of 0.79 (95% CI [0.18; 1.40]), a statistically significant results (p = 0.01), with a tendency to favor the experimental group. Also, there was a medium level of heterogeneity among studies regarding total PES (I2 = 45%), with no significant differences between studies (p = 0.91). Homogeneous results (I2 = 0%) were found among studies analyzing facial bone thickness, favoring the experimental group; the forest plot showed an effect of 0.37 (95% CI [0.25; 0.50]), which was statistically significant (p < 0.00001) for this parameter. Conclusions: Then, it was possible to conclude that using bone and soft tissue grafting techniques associated with immediate implant placement (IIP), even though they are not fundamental, was a valuable resource to prevent significant tissue reduction, reaching greater bone stability and higher levels in the Pink Esthetic Score (PES) and Visual Analogue Score (VAS).

Applying a novel kinomics approach to study decidualization and the effects of antigestagens using a canine model†.

Maternal decidual cells are crucial for the maintenance of canine pregnancy as they are the only cells expressing the nuclear progesterone (P4) receptor (PGR) in the placenta. Interfering with P4/PGR signaling adversely affects decidual cells and terminates pregnancy. Although immortalized dog uterine stromal (DUS) cells can be decidualized in vitro using cAMP, the involvement of cAMP-dependent kinases in canine decidualization had not been investigated. Therefore, the present project investigated changes in the kinome of DUS cells following in vitro decidualization, using the serine/threonine kinase (STK) PamChip assay (PamGene). Decidualization led to a predicted activation of 85 STKs in DUS cells, including protein kinase (PK) A, PKC, extracellular signal-regulated kinase (ERK)1/2 and other mitogen-activated protein kinases (MAPKs), calcium/calmodulin-dependent protein kinases (CAMKs), and Akt1/2. In addition, blocking PGR with type 2 antigestagens (aglepristone or mifepristone) decreased the activity of virtually all kinases modulated by decidualization. The underlying transcriptional effects were inferred from comparison with available transcriptomic data on antigestagen-mediated effects in DUS cells. In targeted studies, interfering with PKA or MAPK kinase (MEK)1/2 resulted in downregulation of important decidualization markers (e.g., insulin-like growth factor 1 (IGF1), prostaglandin E2 synthase (PTGES), prolactin receptor (PRLR), PGR, and prostaglandin-endoperoxide synthase 2 (PTGS2/COX2)). Conversely, blocking of PKC decreased the mRNA availability of IGF1, PGR, and PTGS2, but not of PTGES and PRLR. Moreover, suppressing PKA decreased the phosphorylation of the transcription factors cJUN and CREB, whereas blocking of PKC affected only cJUN. This first kinomics analysis to target decidualization showed an increased activity of a wide range of STKs, which could be hindered by disrupting P4/PGR signaling. Decidualization appears to be regulated in a kinase-dependent manner, with PKA and PKC evoking different effects.

Undiagnosed major risk factors in acute ischaemic stroke patients: frequency, profile, stroke mechanisms and outcome.

BACKGROUND AND PURPOSE: There is scarce clinical information about the clinical profile of patients with acute ischaemic stroke with previously undiagnosed major vascular risk factors (UMRFs). METHODS: This was a retrospective analysis of data from the Acute Stroke Registry and Analysis of Lausanne registry between 2003 and 2018 with univariate and multivariate logistic regression analyses comparing clinical profiles of patients with UMRFs to patients with at least one previously diagnosed MRF (DMRF). RESULTS: In all, 4354 patients (median age 70 years [interquartile range 15.2], 44.7% female) were included after excluding 763 (14.9%) for lack of consent and three for missing information. Amongst 1125 (25.8%) UMRF patients, 69.7% (n = 784) had at least one newly diagnosed MRF and the others none. The newly detected MRFs were dyslipidaemia (61.4%), hypertension (23.7%), atrial fibrillation (10.2%), diabetes mellitus (5.2%), ejection fraction <35% (2.0%) and coronary disease (1.0%). Comparing UMRF patients to DMRF patients, multivariate analysis showed a positive association with lower age, non-Caucasian ethnicity, contraceptive use (<55 years old), smoking (≥55 years old) and patent-foramen-ovale-related stroke mechanism. A negative association was found with pre-stroke antiplatelet use and higher body mass index. Functional outcome did not differ. Cerebrovascular recurrences were similar between groups. CONCLUSIONS: In this large single-centre cohort, 69.7% of patients with acute ischaemic stroke and UMRF were newly diagnosed with at least one new MRF, the most common being dyslipidaemia, hypertension or atrial fibrillation. Patients of the UMRF group were younger, more often smokers and on contraceptives, and had more patent-foramen-ovale-related strokes.

Montreal Cognitive Assessment in Mild Cognitive Impairment: Relationship with Cerebrospinal Fluid Biomarkers and Conversion to Dementia.

BACKGROUND: Mild cognitive impairment (MCI) is considered a prodromal state of dementia. Abnormal values of cerebrospinal fluid Alzheimer's disease biomarkers (CSF-AD-b) have been associated with a higher risk of conversion to dementia (due to Alzheimer's disease), but studies evaluating the ability of Montreal Cognitive Assessment (MoCA) in this task are lacking. OBJECTIVE: This study aims to investigate the relationship between MoCA and CSF-AD-b, as well as the ability of those tools to predict conversion to dementia. METHODS: Taking advantage of our MCI cohort with biological characterization on longitudinal follow-up (180 patients followed for 62.6 months during which 41.3% converted), we computed MoCA and MMSE z-scores, using Portuguese normative data. The performance in MoCA z-score was correlated with CSF-AD-b and the relative time to conversion and risk according to baseline characteristics were analyzed using Kaplan-Meier analysis and Cox regression models. RESULTS: MoCA z-scores were correlated with Aß42 (p = 0.026), t-tau (p = 0.033), and p-tau (p = 0.01). Impaired MMSE (p < 0.001) and MoCA z-scores (p = 0.019), decreased Aß42 (p < 0.001) and increased t-tau (p < 0.001) and p-tau (p < 0.001) were associated with shorter estimated time of conversion. Aß42 (p < 0.001) and MMSE z-scores (p = 0.029) were independent predictors of conversion. For those with at least 9 years of education, MoCA z-score (p = 0.004) (but not MMSE) was an independent predictor of conversion as well as Aß42. CONCLUSIONS: This study confirms the role of CSF-AD-b, namely Aß42, in predicting conversion from MCI to dementia and suggests the utility of MoCA in predicting conversion in highly educated subjects, supporting its use in the evaluation of MCI patients.

Serum Neurofilament Light Chain in the Diagnostic Evaluation of Patients with Cognitive Symptoms in the Neurological Consultation of a Tertiary Center.

Serum light-chain neurofilaments (sNfL) have been investigated as a potential minimally invasive biomarker that could help in the diagnosis of patients with cognitive symptoms. We assessed the correlation between sNfL and cerebrospinal fluid (CSF) biomarkers (sNfL versus CSF NfL, ρ= 0.70, p < 0.001), the performance of sNfL in distinguishing controls from patients (controls versus frontotemporal dementia, area under curve 0.86), and sNfL differences in mild cognitive impairment according to amyloid-ß (Aß) deposition (Aß versus non-Aß, p = 0.017). Our results support the role of this biomarker in the screening and risk stratification of patients followed in a neurological consultation of a tertiary center.

A Two-Year Retrospective Analysis of the Clinical Outcomes of Immediate Submuscular Breast Reconstructions With Native® Acellular Dermal Matrix.

BACKGROUND: Implant-based submuscular breast reconstruction (SBR) can be performed with the aid of acellular dermal matrices (ADM) for implant coverage on their inferolateral pole, aiming at providing a biological interface for hiding the implant and therefore reducing the risk of complications. The purpose of this study is to assess the long-term post-operative outcomes obtained using the SBR-specific Native® ADM (DECO med s.r.l., Marcon, Venice, Italy). METHODS: All cases of Native®-assisted immediate SBR performed at our institution between October 2016 and March 2020 were retrospectively analysed. Demographic and surgical data were collected, and post-operative outcomes, including minor and major complications, were evaluated. Particular attention was paid to complications emerging before and after patient discharge. Dependence analyses were performed to uncover statistically significant relationships between risk factors and reconstructive outcomes. RESULTS: Data on 100 patients were collected, for a total of 128 breasts. The mean age of the cohort was 49.5 years, the mean BMI was 23.4 kg/m2, and the mean follow-up was 24 months. Out of this, 14.1% of patients received pre-operative radiotherapy, while 16.4% underwent post-mastectomy radiotherapy. Breasts appeared to develop short-term minor complications more likely during hospitalisation (11.7% vs. 7.8%), while short-term major complications occurred more often after discharge (7.8% vs. 15.6%). The most frequent long-term complications were capsular contracture and contour defects (both 9.4%). Risk factors that showed a statistically significant relationship with complications were pre- and post-mastectomy radiotherapy and post-operative chemotherapy. CONCLUSIONS: The retrospective analysis showed results in line with clinical outcomes reported in the literature for the same reconstructive technique. The use of Native® ADM in SBR is safe and effective in the long term.

Communicative and linguistic factors influencing language development at 30 months of age in preterm and full-term children: a longitudinal study using the CDI.

Introduction: Previous studies showed that very preterm children have a delay in communicative (gestures) and linguistic development as compared to full-term children. Earlier use of gestures, as well as of word comprehension and production, have been found to be predictive of subsequent word production and/or language delay in both very preterm and full-term children. Not many studies on communicative antecedents of language, however, have been carried out with low-risk preterm children in comparison to full-term children. Methods: In the present study a sample (N = 142) of low-risk preterm children has been followed using the Galician version of the Communicative Development Inventories (CDI) at the ages of 10, 22, and 30 months of age and their results were compared to the results from a sample (N = 49) of full-term children at the same ages. The determinants of language measures (vocabulary and grammar) at 30 months of age have been studied through linear regression analyses. Results: ANOVA results indicate that there were no significant differences between the groups in any of the measures obtained with the CDI at any time, nor were there any differences in lexical or grammatical developmental trajectories between both groups (repeated measures ANOVA). Linear regression analyses showed that the predictors of language at 30 months of age are somewhat different for the full-term than for the preterm group. Discussion: While the use of first communicative gestures at 10 months is a predictor of word production at 30 months of age for the full-term group, participation in games and routines seems to play a significant predictive role for preterm children. Word production at 22 months is the factor with a major incidence on word production at the age of 30 months for both groups. Previous specific measures of grammatical development have a clear determinant role in grammar measures at 30 months of age for the full-term children, while in the case of preterm children previous lexical development seems to be more relevant.

Effect of biomedical complications on very and extremely preterm children's language.

Introduction: Very and extremely preterm children have been found to show delays in the development of language in early years. In some investigations, however, a rigorous control of biomedical complications, such as Periventricular Leukomalacia (PVL), Intraventricular Hemorrhage (IVH) or Bronchopulmonary Dysplasia (BPD), does not always exist. For that reason, a confounding effect of low gestational age and biomedical complications may lead to erroneous conclusions about the effect of gestational age. Methods: In this investigation we compare language development [use of words, sentence complexity and mean length of the three longest utterances (MLU3)] of three groups of Chilean children at 24 months of age (corrected age for preterm children). The first group was composed of 42 healthy full-term children (Full term group: FT), the second group of 60 preterm children born below 32 gestational weeks without medical complications (low risk preterm group: LRPT), and the third group was composed of 64 children below 32 gestational weeks who had medical complications (High risk preterm group: HRPT). The three groups were similar in terms of gender distribution, maternal education, and socio-economic environment. The instrument used to assess language was the Communicative Development Inventories (CDI). In addition, the Ages and Stages Questionnaire-3 (ASQ-3) was also used to assess other developmental dimensions. Results: The results indicate that HRPT and LRPT children obtained significantly lower results than the FT group in the three language measures obtained through the CDI. No significant differences were observed between the HRPT and the LRPT groups, although the HRPT obtained the lowest results in the three CDI measures. The results obtained through the administration of the ASQ-3 confirm the delay of both preterm groups in communicative development when compared to the FT group. No significant differences between the FT and the PT groups were observed in gross motor, fine motor and problem solving dimensions of the ASQ-3. The LRPT group obtained results that were significantly higher than those of the FT group and the HRPT group in gross motor development. Discussion: These results seem to indicate that the area of language development is particularly influenced by very or extremely low gestational age.

Membrane-bound progesterone receptors in the canine uterus and placenta; possible targets in the maintenance of pregnancy.

To date, the biological functions of P4 within the canine placenta have been attributed to maternal stroma-derived decidual cells as the only placental cells expressing the nuclear P4 receptor (PGR). However, P4 can also exert its effects via membrane-bound receptors. To test the hypothesis that membrane-bound P4 receptors are involved in regulating placental function in the dog, the expression of mPRα, -ß, -γ, PGRMC1 and -2 was investigated in the uterine and placental compartments derived from different stages of pregnancy and from prepartum luteolysis. Further, to assess the PGR signaling-mediated effects upon membrane P4 receptors in canine decidual cells, in vitro decidualized dog uterine stromal (DUS) cells were treated with type II antigestagens (aglepristone or mifepristone). The expression of all membrane P4 receptors was detectable in reproductive tissues and in DUS cells. The main findings indicate their distinguishable placental spatio-temporal distribution; PGRMC2 was predominantly found in decidual cells, PGRMC1 was strong in maternal endothelial compartments, and syncytiotrophoblast showed abundant levels of mPRα and mPRß. In vitro decidualization was associated with increased expression of PGRMC1 and -2, while their protein levels were diminished by antigestagen treatment. The involvement of membrane-bound P4 signaling in the regulation of canine placental function is implied, with P4 effects being directly exerted through maternal and fetal cellular compartments. The indirect effects of PGR might involve the modulation of membrane-bound receptors availability in decidual cells, implying a self-regulatory loop of P4 in regulating the availability of its own receptors in the canine placenta.

CAN THE PERCUTANEOUS CHEVRON AND AKIN (PECA) TECHNIQUE CORRECT THE PRONATION OF THE FIRST METATARSAL IN HALLUX VALGUS?

Objective: Pronation of the first metatarsal in hallux valgus has recently been discussed among foot and ankle surgeons. This study aimed to evaluate the potential radiographic correction of moderate and severe hallux valgus using the percutaneous Chevron and Akin (PECA) technique. Methods: We evaluated 45 feet in 38 patients (mean age 65.3 years old [36 - 83]; 4 men; 34 women; 7 bilateral) who underwent surgical correction using the PECA technique. The radiographic images evaluated were anteroposterior radiographs obtained pre- and postoperatively at least 6 months after surgery, including the metatarsophalangeal angle, the intermetatarsal angle, pronation of the first metatarsal, displacement of the distal fragment, medial sesamoid position and bone union. Results: All parameters evaluated showed significant postoperative improvement, including correction of pronation of the first metatarsal (p < .05) and position of the sesamoid (p < .05). There was a union of osteotomies in all feet. No complications were observed, such as screw loosening or necrosis of the first metatarsal head. Conclusion: The PECA technique can correct pronation of the first metatarsal in moderate and severe hallux valgus, and other deformity-associated parameters. Level of Evidence IV; Case Series.

Objetivo: A pronação do primeiro metatarso no hálux valgo tem sido um tema de discussão recente entre os cirurgiões de pé e tornozelo. O objetivo deste estudo foi avaliar o potencial de correção radiográfica do hálux valgo moderado e grave utilizando a técnica percutânea de Chevron e Akin (PECA). Métodos: Avaliamos 45 pés em 38 pacientes (média de idade 65,3 anos [36 - 83]; 4 homens; 34 mulheres; 7 bilaterais) submetidos à correção cirúrgica pela técnica PECA. As imagens radiográficas avaliadas foram radiografias anteroposteriores obtidas no pré e pós-operatório com no mínimo 6 meses após a cirurgia, incluindo ângulo metatarsofalângico, ângulo intermetatarsal, pronação do primeiro metatarso, deslocamento do fragmento distal, posição do sesamoide medial e união óssea. Resultados: Todos os parâmetros avaliados apresentaram melhora significativa no pós-operatório, incluindo correção da pronação do primeiro metatarso (p < 0,05) e posição do sesamoide (p < 0,05). Houve união de osteotomias em todos os pés. Não foram observadas complicações, como soltura do parafuso ou necrose da cabeça do primeiro metatarso. Conclusão: A técnica PECA pode corrigir a pronação do primeiro metatarso no hálux valgo moderado e grave, bem como outros parâmetros associados à deformidade. Nível de Evidência IV; Série De Casos.

Self-Assembled CNF/rGO/Tannin Composite: Study of the Physicochemical and Wound Healing Properties.

In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF), and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material, and a complete characterization including SEM, FTIR, XRD, XPS, and TGA was performed. Additionally, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. A successful physical interaction between CNF, TA, and GO was achieved. Increasing CNF amount in the composite reduced the thermal properties, surface charge, and conductivity, but its strength, cytotoxicity, and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the extract's chemical composition. However, the in-vitro-obtained results demonstrated that these composite materials can be suitable for wound healing.

Albumin-to-protein ratio in spot urine samples for analysis of proteinuria selectivity in chronic kidney disease / Razão albumina/proteína em amostras isoladas de urina para análise da seletividade de proteinúria na doença renal crônica

ABSTRACT Introduction: The albumin-to-creatinine ratio and total protein-to-creatinine ratio in spot urine samples have already been validated as surrogates for 24-hour albuminuria and proteinuria measurements. Thus, we hypothesized that the type of proteinuria, detected by the electrophoretic pattern of 24-hour urine, could be predicted by the simple proportion of albumin in the total urine protein content, using the albumin-to-protein ratio (APR). Our study sought to validate the use of APR as a cheaper substitute for urinary protein electrophoresis (UPE). Methods: Using different mathematical models, we compared, the albumin fraction in 24-hour urine samples by electrophoresis and the APR ratio in spot samples from 42 outpatients with chronic kidney disease (CKD). Results: A strong log-order correlation r = 0.84 (0.75-0.92; 95% CI, p = 0.001) was observed between APR and the albumin fraction in the UPE. Conclusion: The APR can substitute electrophoresis in CKD outpatients.

Resumo Introdução: A utilização da razão albumina/creatinina e da razão proteína total/creatinina em amostras isoladas de urina já foram validadas como substitutos para a albuminúria e proteinúria em 24 horas. Assim, nossa hipótese é que o tipo de proteinúria, dado pelo padrão eletroforético da urina de 24 horas, poderia ser previsto pela simples proporção de albumina no conteúdo total de proteínas na urina, utilizando a razão albumina/proteína (RAP). O presente estudo procurou validar o uso da RAP como um substituto mais prático e de menor custo da eletroforese de proteínas urinárias (EPU). Métodos: Foram utilizados diferentes modelos matemáticos a fim de comparar a fração de albumina pela eletroforese em amostras de urina de 24 horas e a RAP em amostras isoladas em 42 pacientes ambulatoriais com doença renal crônica. Resultados: Foi observada uma forte correlação logarítmica r = 0,84 (0,75-0,92; 95% CI, p = 0,001) entre a RAP e a fração de albumina pela EPU. Conclusão: A RAP pode substituir a eletroforese urinária em pacientes renais crônicos ambulatoriais.

Cross-cultural adaptability of parenting interventions designed for childhood behavior problems: A meta-analysis.

The dissemination of parenting interventions is one of the advised approaches to globally counteract childhood behavior problems, delinquency, and future criminal careers. Many of these interventions are developed in Anglosphere countries and transported to other contexts with distinct cultural backgrounds. However, there are no meta-analyses evaluating the overall effectiveness of these Anglosphere parenting programs in non-Anglosphere settings. This meta-analysis aimed to examine the effectiveness of parenting interventions developed in Anglosphere countries when transported to non-Anglosphere countries, as well as compare effectiveness levels between Anglosphere and non-Anglosphere trials; and analyze the impact of research and contextual factors in the dissemination of these interventions. Parenting interventions were included if they were: created in an Anglosphere setting; tested in non-Anglosphere countries; focused on reducing childhood behavioral problems; designed for children ranging from two to 12 years old; and tested in an experimental randomized trial. A random-effects model was selected for our meta-analysis. Standardized mean differences, confidence intervals and prediction intervals were also computed. Twenty studies were included, and results suggest that parenting interventions designed for childhood behavior problems can be transported to non-Anglosphere countries and potentially maintain effectiveness. This study is a relevant contribution to the evidence of cross-cultural transportability of parenting interventions.

Reconsidering the role of blood-brain barrier in Alzheimer's disease: From delivery to target.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-ß. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.

Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia.

BACKGROUND AND PURPOSE: Blood-based biomarkers are promising tools for the diagnosis of Alzheimer disease (AD) at prodromal stages (mild cognitive impairment [MCI]) and are hoped to be implemented as screening tools for patients with cognitive complaints. In this work, we evaluated the potential of peripheral neurological biomarkers to predict progression to AD dementia and the relation between blood and cerebrospinal fluid (CSF) AD markers in MCI patients referred from a general neurological department. METHODS: A group of 106 MCI patients followed at the Neurology Department of Coimbra University Hospital was included. Data regarding baseline neuropsychological evaluation, CSF levels of amyloid ß 42 (Aß42), Aß40, total tau (t-Tau), and phosphorylated tau 181 (p-Tau181) were available for all the patients. Aß42, Aß40, t-Tau, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were determined in baseline stored serum and plasma samples by commercial SiMoA (Single Molecule Array) assays. Progression from MCI to AD dementia was assessed at follow-up (mean = 5.8 ± 3.4 years). RESULTS: At baseline, blood markers NfL, GFAP, and p-Tau181 were significantly increased in patients who progressed to AD at follow-up (p < 0.001). In contrast, plasma Aß42/40 ratio and t-Tau showed no significant differences between groups. NfL, GFAP, and p-Tau181 demonstrated good diagnostic accuracy to identify progression to AD dementia (area under the curve [AUC] = 0.81, 0.80, and 0.76, respectively), which improved when combined (AUC = 0.89). GFAP and p-Tau181 were correlated with CSF Aß42. Association of p-Tau181 with NfL was mediated by GFAP, with a significant indirect association of 88% of the total effect. CONCLUSIONS: Our findings highlight the potential of combining blood-based GFAP, NfL, and p-Tau181 to be applied as a prognostic tool in MCI.