Meta-analysis of 46,000 germline de novo mutations linked to human inherited disease.

BACKGROUND: De novo mutations (DNMs) are variants that occur anew in the offspring of noncarrier parents. They are not inherited from either parent but rather result from endogenous mutational processes involving errors of DNA repair/replication. These spontaneous errors play a significant role in the causation of genetic disorders, and their importance in the context of molecular diagnostic medicine has become steadily more apparent as more DNMs have been reported in the literature. In this study, we examined 46,489 disease-associated DNMs annotated by the Human Gene Mutation Database (HGMD) to ascertain their distribution across gene and disease categories. RESULTS: Most disease-associated DNMs reported to date are found to be associated with developmental and psychiatric disorders, a reflection of the focus of sequencing efforts over the last decade. Of the 13,277 human genes in which DNMs have so far been found, the top-10 genes with the highest proportions of DNM relative to gene size were H3-3 A, DDX3X, CSNK2B, PURA, ZC4H2, STXBP1, SCN1A, SATB2, H3-3B and TUBA1A. The distribution of CADD and REVEL scores for both disease-associated DNMs and those mutations not reported to be de novo revealed a trend towards higher deleteriousness for DNMs, consistent with the likely lower selection pressure impacting them. This contrasts with the non-DNMs, which are presumed to have been subject to continuous negative selection over multiple generations. CONCLUSION: This meta-analysis provides important information on the occurrence and distribution of disease-associated DNMs in association with heritable disease and should make a significant contribution to our understanding of this major type of mutation.

Atrazine adsorption and desorption on functionalized montmorillonite: aluminum-pillared and lithium saturated.

Atrazine is an herbicide used worldwide, and it is considered a severe environmental contaminant. The present study aims to evaluate the atrazine adsorption in aqueous media in montmorillonite samples which were either in natural state or functionalized through saturation with lithium and pillarization with aluminum by different methods. Montmorillonite saturated with lithium adsorbed significantly more atrazine than the natural montmorillonite sample. Among the samples obtained through the three aluminum-pillarization methods, the mass percentage of adsorbed atrazine was very similar. However, the best combination was the aluminum-pillarization (due to the maintenance of the open interlayer region) and saturation with lithium (due to the significant reduction of the cation exchange capacity of the mineral), because both processes facilitate the interaction of atrazine with the montmorillonite. Another advantage was that the adsorption of atrazine in the pillared and lithium saturated samples had small desorption, which is desirable in the environmental perspective. It is recommended to build filters with aluminum-hydroxy pillared, lithium saturated montmorillonite as an alternative method to rapidly remove atrazine from aqueous media. In addition to the shorter production time, this process resulted in montmorillonite with high occupancy rate and stability of the aluminum-hydroxy pillars.

Cabo Verde Telemedicine Program: An Update Report and Analysis of 2,442 Teleconsultations.

Introduction: The Cabo Verde Telemedicine program (CVTP) was established by the International Virtual e-Hospital Foundation using the Initiate-Build-Operate-Transfer strategy to improve access to specialty care for the population in the archipelago of Cabo Verde in 2012. Since its inception, the CVTP has proven a great success story of telemedicine in Africa. Our first report on the initial results of a nationwide CVTP was published in 2014. The aim of this article is to analyze the follow-up data and analyze the activity of CVTP. Methods: All telemedicine consultations of the CVTP from 2014 to 2018 were analyzed. Patient demographics, clinical discipline, and transfer status were analyzed. Categorical variables were compared with a chi-squared test. Results: There were 2,442 telemedicine consultations in 24 clinical programs performed during the study period. The most common clinical disciplines with >100 consultations were neurology, cardiology, orthopedic surgery, general surgery, endocrinology, otolaryngology, urology, and dermatology. Overall, the transfer rate was 34.3%. Conclusion: The nationwide CVTP continues to increase access to specialized care, prevent unnecessary and costly transfers, and has become a great success story of telemedicine in Africa. Moreover, this program should serve as a model for establishing island-nations telemedicine programs worldwide.

Study of colloidal properties of natural and Al-pillared smectite and removal of copper ions from an aqueous solution.

In this study, an Al-pillared smectite was synthesized and changes in its colloidal properties were investigated. The pillaring solution was prepared by mixing 0.4 mol L(-1) NaOH and 0.2 mol L(-1) AlCl3.6H2O solutions. Intercalated clays were heated to obtain the pillared clay, and X-ray diffractometry (XRD), X-ray fluorescence (XRF), Fourier transform infrared (FTIR) spectroscopy and N2 sorption/desorption isotherms analysis were done to characterize the changes in clay properties. Moreover, adsorption experiments were carried out in order to evaluate the capacity of the pillared clays to remove Cu2+ from an aqueous solution and to characterize the interaction between adsorbent and adsorbate. The results indicate that the natural clay has a basal spacing of 1.26 nm, whereas the pillared clays reached 1.78 nm (500°C) and 1.80 nm (350°C) after calcination. XRF analysis revealed an increase in the Al3+ in the pillared clay as compared to the natural clay. The surface area and pore volume (micro and mesoporous) were higher for the pillared clays. Experimental data from the adsorption experiment were fit to Langmuir and Freundlich and Temkin adsorption models, and the former one was the best fit (highest r2 value) for all the clays and lower standard deviation (Δg%) for the natural clay. On the other hand, the Temkin model exhibited Δg% value lower for the pillared clays. Thermodynamics parameters demonstrate that the Cu2+ adsorption process is spontaneous for all the clays, but with higher values for the pillared materials. In addition, application of the Dubinin-Radushkevich model revealed that the bond between the metal and the clay are weak, characterizing a physisorption.

Probing the Spin-Momentum Locking on Rashba Surfaces via Spin Current.

In this study, we investigate the spin-momentum locking phenomenon on Rashba states of antimony (Sb) films. Utilizing spin pumping in conjunction with an external charge current, we uncover the topological properties of Sb surface states. Our key finding is the precise manipulation of the direction and magnitude of the charge current generated by the inverse Rashba-Edelstein effect. This control is achieved through the dynamic interaction between out-of-equilibrium pumped spins and spin-momentum-locked flowing spins, which are perpendicular to the charge current. Our results highlight Sb as a promising material for both fundamental and applied spintronics research. The studied Sb nanostructures demonstrate potential for the development of low-power logic gates operating with currents in the microampere range, paving the way for advanced spintronic applications.

Identification of genetic modifiers of Huntington's disease somatic CAG repeat instability by in vivo CRISPR-Cas9 genome editing.

Huntington's disease (HD), one of >50 inherited repeat expansion disorders (Depienne and Mandel, 2021), is a dominantly-inherited neurodegenerative disease caused by a CAG expansion in HTT (The Huntington's Disease Collaborative Research Group, 1993). Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the property driving disease is the CAG length-dependent propensity of the repeat to further expand in brain (Swami et al ., 2009; GeM-HD, 2015; Hensman Moss et al ., 2017; Ciosi et al ., 2019; GeM-HD, 2019; Hong et al ., 2021). Routes to slowing somatic CAG expansion therefore hold great promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair (MMR) pathway, modify somatic expansion in HD mouse models (Wheeler and Dion, 2021). To identify novel modifiers of somatic expansion, we have used CRISPR-Cas9 editing in HD knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This has included testing of HD onset modifier genes emerging from human genome-wide association studies (GWAS), as well as interactions between modifier genes, thereby providing new insight into pathways underlying CAG expansion and potential therapeutic targets.

Microbial spoilage of portuguese chouriço along shelf life period.

Microbial flora of portuguese chouriço (Alentejano (A) and Ribatejano (R)) with abnormal sensorial characteristics along shelf life was studied. Mesophilic anaerobic bacteria, enterococci, mesophilic sporeformers, coliforms, coagulase-positive staphylococci, sulphite reducing clostridia, Clostridium perfringens, moulds and yeasts were the most representative in both types of chouriço.

Implications of Socio-Cultural Pressure for a Thin Body Image on Avoidance of Social Interaction and on Corrective, Compensatory or Compulsive Shopping Behaviour.

This paper aims to discuss the implications of body talk and socio-cultural pressure for the internalisation of a thin body image in purchase decisions, shopping habits and other outcomes of body dissatisfaction, in particular the proneness to avoid human/social interaction in retail contexts and proneness to engage in corrective, compensatory or compulsive shopping behaviour. This paper conducted an online questionnaire that measured the following constructs: body mass index; Socio-cultural Attitudes Towards Appearance Scale-4 (SATAQ-4), Body Appreciation Scale (BAS-2), Acceptance of Cosmetic Surgery Scale (ACSS), Compulsive Buying Follow-up Scale (CBFS), proneness to avoid social interaction in retail contexts, and the intention to purchase a list of products and services as a compensation for body dissatisfaction. A structural equations model supported the hypotheses proposing the influence of BAS-2 and SATAQ-4 (the internalisation of thin/athletic body and the social comparison induced by family, peers and media) upon the outcomes of social-interaction avoidance, ACSS and CBFS. Nevertheless, BAS-2 only influences social-interaction avoidance. This paper provides several recommendations to brand managers highlighting the social responsibility role of brand advertising in enhancing positive body appreciation, mitigating the psychological damage caused by socio-cultural pressure and preventing the stigmatisation bias against obese people.

Incorporation of strontium-containing bioactive particles into PEOT/PBT electrospun scaffolds for bone tissue regeneration.

The combination of biomaterials and bioactive particles has shown to be a successful strategy to fabricate electrospun scaffolds for bone tissue engineering. Among the range of bioactive particles, hydroxyapatite and mesoporous bioactive glasses (MBGs) have been widely used for their osteoconductive and osteoinductive properties. Yet, the comparison between the chemical and mechanical characteristics as well as the biological performances of these particle-containing scaffolds have been characterized to a limited extent. In this work, we fabricated PEOT/PBT-based composite scaffolds incorporating either nanohydroxyapatite (nHA), strontium-containing nanohydroxyapatite (nHA_Sr) or MBGs doped with strontium ions up to 15 wt./vol% and 12,5 wt./vol% for nHA and MBG, respectively. The composite scaffolds presented a homogeneous particle distribution. Morphological, chemical and mechanical analysis revealed that the introduction of particles into the electrospun meshes caused a decrease in the fiber diameter and mechanical properties, yet maintaining the hydrophilic nature of the scaffolds. The Sr2+ release profile differed according to the considered system, observing a 35-day slowly decreasing release from strontium-containing nHA scaffolds, whereas MBG-based scaffolds showed a strong burst release in the first week. In vitro, culture of human bone marrow-derived mesenchymal stromal cells (hMSCs) on composite scaffolds demonstrated excellent cell adhesion and proliferation. In maintenance and osteogenic media, all composite scaffolds showed high mineralization as well as expression of Col I and OCN compared to PEOT/PBT scaffolds, suggesting their ability to boost bone formation even without osteogenic factors. The presence of strontium led to an increase in collagen secretion and matrix mineralization in osteogenic medium, while gene expression analysis showed that hMSCs cultured on nHA-based scaffolds had a higher expression of OCN, ALP and RUNX2 compared to cells cultured on nHA_Sr scaffolds in osteogenic medium. Yet, cells cultured on MBGs-based scaffolds showed a higher gene expression of COL1, ALP, RUNX2 and BMP2 in osteogenic medium compared to nHA-based scaffolds, which is hypothesized to lead to high osteoinductivity in long term cultures.

Production and Shelf-Life Study of Probiotic Caja (Spondias mombin L.) Pulp Using Bifidobacterium animalis ssp. Lactis B94.

The highly nutritional caja fruit (Spondias mombin L.) is an accessible source of vitamins and antioxidants that are indispensable for the human diet. The objective of the present work was to study the production of a probiotic caja pulp using Bifidobacterium animalis ssp. lactis B94. Firstly, a kinetic study was performed on the fermentation of the caja pulp with Bifidobacterium animalis ssp. lactis B94 to determine the optimum conditions of the process. Growth kinetics revealed that the ideal time for ending the fermentation would be at 22 h because it corresponds to the end of the exponential phase. Both the whole pulp and the probiotic pulp were characterized for pH, acidity, total soluble solids, water content, phenolic content, reducing carbohydrates, ascorbic acid, and total carotenoids. Physicochemical characterization revealed similar results between the whole and the probiotic pulp. The stability test demonstrated that the probiotic pulp is stable and preserved the probiotic attributes of the final product. In conclusion, our results reveal that caja pulp can be considered a favorable medium for the Bifidobacterium animalis ssp. lactis B94 growth and consequently can be explored biotechnologically for new food products.

Mortar Bond Strength: A Brief Literature Review, Tests for Analysis, New Research Needs and Initial Experiments.

Despite technological advances in the production processes of the materials for ceramic façade coatings, the problems of detachments are still frequent. Therefore, this work aims to investigate, through a literature review, the existing gaps related to the adhesion ability of adhesive mortars, identifying new research needs that can better explain the behavior of the material. In addition, an experimental procedure was developed to evaluate the mechanical capacity of adhesive mortars when subjected to cyclic stresses. Dynamic stress measurements are presented for several blocks of mortar and on similar blocks but with a slot drilled prior to measurements (intended to represent failure). From these data we calculated values of stress energy, elastic energy, and dissipated energy. The experimental results showed that the energy involved in the test process accompanied the load values and current stress values. The mortar samples with the previous failure absorbed and dissipated less energy than mortars without failure, showing that materials that have less energy to dissipate, are materials that have developed less capacity to adhere, that is, to keep their parts together.

The Influence of Lime Solution in Kneading Water Substitution on Cement Roughcast and Mortar Coating.

The understanding of the mechanical fixation behavior of coatings is crucial for a better comprehension of the bonding systems, especially at the interface between the mortar and the substrate. Physical adherence is related, among other things, to the contents of the materials used in the roughcast and mortar coatings, due to the colloidal water penetration into the pores of the substrate. This work evaluated the influence of different lime solution additions replacing the kneading water in the preparation of roughcast and mortar coatings. Two types of substrates were investigated:ceramic bricks and concrete blocks. Three wall masonry panels were constructed, with dimensions of 220 × 180 cm2, one of concrete block and two of ceramic bricks, followed by the application of roughcast and mortar coating with an average thickness of 5 mm and 20 mm, respectively. Direct tensile bond strength tests were performed and the results, with a 95% confidence level, showed that substrate ceramic and treatment in the roughcast exhibited a better behavior regarding the distribution of the tensile bond strength of the tested specimens. However, no significant differences of the amount of addition used (0%, 5%, 10% and 15%) on the tensile bond strength were observed.

Artroplastia em Gap com Interposição de Fáscia de Temporal para o Tratamento de Anquilose de Articulação Temporomandibular: Relato de Caso / Gap Arthroplasty with Temporalis Fascia Interposition for the Treatment of Temporomandibular

A anquilose da articulação temporomandibular (ATM) é caracterizada pela união intracapsular do complexo disco-côndilo à superfície do osso temporal, podendo gerar restrição dos movimentos mandibulares e limitação de abertura bucal. São descritas ainda alterações como restrição da capacidade mastigatória, dificuldade de fonação e de uma adequada higiene bucal, além de dificuldade de interação social. O presente caso retrata um paciente feminino, 27 anos, com histórico de fratura de parassínfise e côndilo mandibular bilateral após trauma em 2014, evoluindo com anquilose da ATM direita, com abertura máxima de 13,27 mm. Para o tratamento do caso descrito, foi utilizado o acesso de Al-Kayat, coronoidectomia ipsilateral e ressecção de massa anquilótica em gap com interposição de retalho da fáscia do músculo temporal no lado direito. Após seis meses do procedimento cirúrgico, foi realizada uma nova tomografia da face na qual se observa ausência de lesões e de sinais de recidiva da anquilose e também foi observada a manutenção do espaço de lacuna feita pela ressecção óssea. O resultado satisfatório da técnica foi atribuído pela obtenção e estabilização de uma abertura bucal adequada, melhora da capacidade mastigatória e da fonação. Além do sucesso clínico, uma vantagem da técnica utilizada foi o baixo custo do procedimento por utilizar apenas interposição do músculo temporal sem uso de materiais aloplásticos. Além disso, a coronoidectomia ipsilateral associada foi suficiente para auxiliar na manutenção da abertura alcançada, não sendo necessária a coronoidectomia contralateral, o que minimizou o tempo operatório e a morbidade de mais um sítio cirúrgico acessado.

Ankylosis of the temporomandibular joint (TMJ) is characterized by the intracapsular union of the condyle- disc complex to the surface of the temporal bone, which can cause restriction of the mandibular movements and a limitation of a mouth opening. Alterations are also described as a restriction of masticatory capacity, difficulty in phonation and suitable oral hygiene, as well as difficulty in social interaction. A 27-year-old female patient with a bilateral history of parasymphysis and mandibular condyle fracture after a trauma in 2014, which evolved to an ankylosis of the right TMJ, with a maximum mouth opening of 13.27 mm. For the treatment of the described case, it was used the Al- Kayat approach, ipsilateral coronoidectomy and resection of the ankylotic mass in gap with interposition of temporalis muscle fascia flap on the right side. After six months of the surgical procedure, it was made a new computed tomography of the face in which it was possible to notice the absence of lesions and signs of recurrence of the ankylosis. It was also observed the maintenance of the gap space made by the bone resection. The satisfactory result of the technique was attributed to the achievement and stabilization of an adequate mouth opening, improved chewing ability and phonation. Besides the clinical success, an advantage of the technique used was the low cost of the procedure by using only temporal muscle interposition without the use of alloplastic materials. In addition, the associated ipsilateral coronoidectomy was sufficient to help maintaining the achieved mouth opening, and the contralateral coronoidectomy was not necessary, as a result it was minimized the surgical time and morbidity of one more accessed surgical site.

Oral health status of pregnant and puerperal women in the municipality of Feira de Santana, at three different times between 2005 and 2015. / Condição bucal de gestantes e puérperas no município de Feira de Santana, em três diferentes períodos entre os anos de 2005 e 2015.

OBJECTIVE: to evaluate the oral health condition of pregnant/postpartum women attending public services in the city of Feira de Santana, BA, Brazil, at three different times between 2005 and 2015. METHODS: this is a study socioeconomic and demographic characteristics, health condition and health care, lifestyle and oral health status of 1,245 participants obtained from a database of three previous investigations: I Intervention Study (2005-2007); II Case-Control Study (2010-2011); III Case-Control Study (2012-2015). RESULTS: comparing the three periods, the frequency of gingivitis (24.41% versus 8.90% versus 5.77%; p<0.01) and periodontitis (44.64% vs 9.16% vs 11.55%; p<0.01) was found to decrease; the worst dental conditions regarding the number of teeth present, healthy and extracted and the DMFT index were found in period III compared to period II. CONCLUSION: an improvement was seen in the participants' periodontal condition over time, which coincides with the implementation of policies pertaining to women's health, oral health and income redistribution in this city.

Geochemical markers of sedimentary organic matter in Todos os Santos Bay, Bahia - Brazil. Indicators of sources and preservation.

Natural stable isotopes, such as carbon (C) and nitrogen (N), are modern tools to assess geochemical processes. C and N in organic matter can carry fingerprints of their hydrologic flows and sedimentary processes, including any anthropogenic modification on the natural system. This study focuses on the determination of aliphatic and polycyclic aromatic hydrocarbons and isotopic ratio in the sediment of Todos os Santos Bay (TSB). The isotopic results of the total organic matter indicate varied contribution marine and terrigenous. Typical rates of PAHs mainly indicate a pyrogenic source and mixture between pyrogenic and petrogenic sources. Typical ratios for the n-alkanes indicate the presence of petroleum hydrocarbons. The isotopic composition of n-alkanes suggests a mixture of sources, with the possible contribution of petrogenic.

Characterization of organic matter in a sediment Core near the Mataripe refinery, Bahia-Brazil.

A sediment core was taken from the Todos os Santos Bay, near the Mataripe Bahia-Brazil refinery. The results of dating, (210)Pb and (137)Cs methods, combined with organic indicators, Polycyclic aromatic hydrocarbons (PAHs), n-alkanes and total organic carbon (TOC), showed significant change with the start of production of the oil fields of Aratu, Itaparica and Dom João (1939-1947) and the construction of the Mataripe refinery (1949-1950). This event was marked by a series of significant changes, including an abrupt increase in TOC and the growth of PAH concentrations and the presence Unresolved/Resolved ratio (UR/R)>4 in n-alkanes fraction, which indicated that the contamination was of petrogenic origin. The δ(13)C of specific n-alkanes compounds showed gradual deplete with the depth.

[Nephrocalcinosis and subcutaneous fat necrosis]. / Nefrocalcinose e Necrose Gorda do Tecido Celular Subcutâneo.

Subcutaneous fat necrosis of the newborn is an uncommon, transient and self-healing panniculits. This entity generally follows an uncomplicated course, however there are rare and important complications. The authors present a case of a newborn with subcutaneous fat necrosis complicated by hypercalcemia and nephrocalcinosis. The pathogenesis of hypercalcemia is not fully understood and the nephrocalcinosis can evolve to chronic kidney disease. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor for hypercalcemia and patients should have serial serum and urinary calcium determinations for up to 6 months after the appearance of the skin lesions. The early diagnosis and prompt treatment of hypercalcemia are essential to prevent severe complications.

A necrose gorda do tecido celular subcutâneo do recém-nascido é uma paniculite rara, transitória e auto-limitada. Tipicamente apresenta evolução favorável, contudo podem surgir complicações potencialmente graves. Apresenta-se um caso que evoluiu com hipercalcémia e nefrocalcinose. A etiopatogenia da hipercalcémia é ainda pouco compreendida e a nefrocalcinose pode constituir uma causa de doença renal crónica. A monitorização regular dos valores de cálcio sérico e urinário neste contexto é essencial, no mínimo até 6 meses após a resolução das lesões cutâneas, porque o diagnóstico precoce e a terapêutica adequada constituem a única possibilidade de prevenir complicações mais graves.

Fast dye removal from water by starch-based nanocomposites.

Robust and efficient methylene blue (MB) adsorbent was prepared based on starch/cellulose nanowhiskers hydrogel composite. Maximum MB adsorption capacity of ∼2050mgperg of dried hydrogel was obtained with the composite at 5wt.% of cellulose nanowhiskers and at pH 5. Adsorption capacity varied from 1450mg/g to 2050mg/g with increasing the initial MB concentration from 1500mg/L to 2500mg/L, respectively. For all the concentrations studied ca. 90% of MB was removed by the adsorbent. Optimal conditions were obtained at pH⩾5 due to the generation of negatively charged groups (COO(-)) in the adsorbent, which can strongly interact with the positive charges from MB. The main advantage of this system over other reported adsorbents, besides the fact of being synthesized from biodegradable polymers (starch and cellulose), is its fast adsorption kinetics that follows the pseudo-second order model, which is based on chimisorption phenomenon. Saturation condition was reached as fast as 1h of experiments owing to the formation of an adsorbed MB monolayer as suggested by the Langmuir isotherm model. Desorption experiments showed 60wt.% of MB loaded can be removed from the adsorbent by immersing it in a pH 1 solution, showing its feasibility to be reused. Therefore, starch/cellulose nanowhiskers hydrogel composite presents outstanding capacity to be employed in the remediation of MB contaminated wastewaters.

Odontologic use of copper/aluminum alloys: mitochondrial respiration as sensitive parameter of biocompatibility.

Copper/aluminum alloys are largely utilized in odontological restorations because they are less expensive than gold or platinum. However, tarnishing and important corrosion in intrabuccal prostheses made with copper/aluminum alloys after 28 days of use have been reported. Several kinds of food and beverage may attack and corrode these alloys. Copper is an essential component of several important enzymes directly involved in mitochondrial respiratory metabolism. Aluminum, in contrast, is very toxic and, when absorbed, plasma values as small as 1.65 to 21.55 microg/dl can cause severe lesions to the nervous system, kidneys, and bone marrow. Because mitochondria are extremely sensitive to minimal variation of cellular physiology, the direct relationship between the mitocondrial respiratory chain and cell lesions has been used as a sensitive parameter to evaluate cellular aggression by external agents. This work consisted in the polarographic study of mitochondrial respiratory metabolism of livers and kidneys of rabbits with femoral implants of titanium or copper/aluminum alloy screws. The experimental results obtained did not show physiological modifications of hepatic or renal mitochondria isolated from animals of the three experimental groups, which indicate good biocompatibility of copper/ aluminum alloys and suggest their odontological use.