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1.
RSC Med Chem ; 15(6): 2165-2178, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38911162

RESUMO

3,3'-Diselenodipropionic acid (DSePA), a selenocystine derivative, has been previously reported as an oral supplement for anticancer/radio-modulation activities. The present study is focused on devising a strategy to synthesize and characterize the deuterated derivative of DSePA and on understanding the effect of deuteration on its therapeutic index by comparing its cytotoxicity in cancerous versus non-cancerous cell types. In this context, the synthesis of 3,3'-diselenodipropionic acid-D8 (D-DSePA) was accomplished in ∼42% yield. Further, the results clearly established that the deuteration of DSePA significantly reduced its cytotoxicity in non-cancerous cell types while retaining its cytotoxicity in cancerous cell lines. Together, D-DSePA displayed a ∼5-fold higher therapeutic index than the non-deuterated derivative for anticancer activity. The biochemical and NMR studies confirmed that the better biocompatibility of D-DSePA than its non-deuterated derivative in non-cancerous cells was due to its ability to undergo slower redox reactions and to cause lesser inhibition of intracellular redox enzymes.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38531090

RESUMO

BACKGROUND AND OBJECTIVES: Cranial reconstruction presents a significant challenge in cases involving pathologies with skull invasion, and various techniques have been used, including the intraoperative shaping of titanium mesh and the manual sculpting of bone cement serving as surrogates for the excised bone graft. In the context of prefabricated patient-specific implants (PSIs) for cranioplasty, precise surgical execution of craniotomies is paramount. This ensures optimal congruity between the implant and the defect created during the craniotomy, leading to a successful single-stage procedure encompassing both bone removal and reconstruction. This article presents a meticulous method for achieving such high-fidelity craniotomy and subsequent cranioplasty using PSIs in a single-stage surgery. METHODS: The procedure was implemented for 2 cases of meningiomas with osseous invasion. Through meticulous preoperative planning, the craniotomy template and implant were designed using computer-assisted design and manufactured on a 3-dimensional printer using the patient's computed tomography scans. Intraoperative fabrication of sterile polymethyl methacrylate replicas was achieved through the creation of silicone molds and subsequent injection molding techniques. Predesignated screw holes facilitated neuronavigation-assisted positioning of the template, aligning it accurately with the target site using registration points. Mini-screws firmly secured the template to the skull. Guided by the template, a craniotomy router performed the bone resection. On completion, the implant was affixed into place using plates and screws. RESULTS: This technique demonstrably facilitated a cost-effective, streamlined and precise application of prefabricated PSIs within a single-stage craniotomy-cranioplasty procedure. Subjective patient reports indicated high levels of satisfaction with the outcome. CONCLUSION: The template routed patient-specific implant 1-stage cranioplasty technique refines previous approaches through precise template localization on the skull, enabling an accurate craniotomy to match a prefabricated PSI. This single-stage procedure rivals hand-shaped methods in aesthetics and compares with the outcomes of 2-stage PSI cranioplasties. Additional studies are needed to validate our results.

4.
J Autism Dev Disord ; 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37751097

RESUMO

PURPOSE: Disorders on the autism spectrum have characteristics that can manifest as difficulties with communication, executive functioning, daily living, and more. These challenges can be mitigated with early identification. However, diagnostic criteria has changed from DSM-IV to DSM-5, which can make diagnosing a disorder on the autism spectrum complex. We evaluated machine learning to classify individuals as having one of three disorders of the autism spectrum under DSM-IV, or as non-spectrum. METHODS: We employed machine learning to analyze retrospective data from 38,560 individuals. Inputs encompassed clinical, demographic, and assessment data. RESULTS: The algorithm achieved AUROCs ranging from 0.863 to 0.980. The model correctly classified 80.5% individuals; 12.6% of individuals from this dataset were misclassified with another disorder on the autism spectrum. CONCLUSION: Machine learning can classify individuals as having a disorder on the autism spectrum or as non-spectrum using minimal data inputs.

5.
CVIR Endovasc ; 6(1): 31, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37284993

RESUMO

BACKGROUND: True visceral artery aneurysms are potentially complex to treat but with advances in technology and increasing interventional radiology expertise over the past decade are now increasingly the domain of the interventional radiologist. BODY: The interventional approach is based on localization of the aneurysm and identification of the anatomical determinants to treat these lesions to prevent aneurysm rupture. Several different endovascular techniques are available and should be selected carefully, dependent on the aneurysm morphology. Standard endovascular treatment options include stent-graft placement and trans-arterial embolisation. Different strategies are divided into parent artery preservation and parent artery sacrifice techniques. Endovascular device innovations now include multilayer flow-diverting stents, double-layer micromesh stents, double-lumen balloons and microvascular plugs and are also associated with high rates of technical success. CONCLUSION: Complex techniques such as stent-assisted coiling and balloon-remodeling techniques are useful techniques and require advanced embolisation skills and are further described.

6.
Soft comput ; : 1-11, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37362260

RESUMO

In the innovative concept of the "Social Internet of Things" (IoT), the IoT is combined with social platforms so that inanimate devices can form their interactions with one another. Still, customers have a wary attitude toward this new standard. They worry that their privacy will be invaded and their information will be made public. IoT won't become a frontrunner technology until we have tried true techniques to improve trustworthy connections between nodes. As a result, data privacy becomes extremely difficult, further increasing the difficulty of providing high-quality services and absolute safety. Several articles have attempted to analyze this issue. To categorize safe nodes in the IoT network, they suggested many models based on various attributes and aggregation techniques. In contrast, prior works failed to provide a means of identifying fraudulent nodes or distinguishing between different forms of assaults. To identify attacks carried out by hostile nodes and separate them from the network, we propose a novel Multi-hop Convolutional Neural Network with an attention mechanism (MH-CNN-AM). To achieve the best performance in the suggested research, performance measures including accuracy, precision, recall, F1-score, and MAE are studied and compared with the of existing methodologies.

7.
PNAS Nexus ; 2(4): pgad082, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37091545

RESUMO

This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI https://doi.org/10.1210/pnasnexus/pgad075.

8.
PNAS Nexus ; 2(3): pgad075, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37007715

RESUMO

Post-yield softening (PYS) plays an important role in guiding the design of high-performance energy-absorbing lattice materials. PYS is usually restricted to lattice materials that are stretching dominated according to the Gibson-Ashby model. Contrary to this long-held assumption, this work shows that PYS can also occur in various bending-dominated Ti-6Al-4V lattices with increasing relative density. The underlying mechanism for this unusual property is elucidated using the Timoshenko beam theory. It is attributed to the increase in stretching and shear deformation with increasing relative density, thereby increasing the tendency towards PYS. The finding of this work extends perspectives on PYS for the design of high-performance energy-absorbing lattice materials.

9.
Folia Morphol (Warsz) ; 82(1): 102-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35099044

RESUMO

BACKGROUND: Coronary artery disease is the most common cause of morbidity and mortality especially in the developing countries. The aim of the study was to find out cardiac dominance percentages and its association with coronary artery stenosis among each pattern of dominance. The objectives were to assess coronary vessel morphology of patients within each pattern of dominance, to find if gender differences exist among dominance patterns and also to find the distribution percentages of stenosis among dominance patterns. MATERIALS AND METHODS: Four thousand angiograms from patients of Indian origin were studied prospectively after procuring the sanction for the same from the ethical committee of the pre-selected hospitals from four states of South India. Informed consents were obtained. Post coronary artery bypass grafting, post percutaneous coronary intervention patients and patient being diabetic for ≥ 5 years were excluded from the study. RESULTS: Right cardiac dominance was seen in 85.5%, left in 9.7%, and co-dominant in 4.8% cases. The percentages of dominance were almost similar among both genders except for left dominance which were higher among male samples. The diameter of right coronary artery and left circumflex coronary artery coronary arteries were significantly associated with dominance patterns. The prevalence of stenosis was more for left dominance patterns, followed by right dominance patterns and least for co-dominant patterns. CONCLUSIONS: There is a necessity to see association between dominance patterns with the coronary artery disease which can help the interventional cardiologists. The disease patterns in the present study were predominantly in the left dominant or in the co-dominant hearts.


Assuntos
Doença da Artéria Coronariana , Humanos , Masculino , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Constrição Patológica , Relevância Clínica , Angiografia Coronária , Vasos Coronários/anatomia & histologia
10.
Ind Psychiatry J ; 32(Suppl 1): S166-S173, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38370959

RESUMO

Background: Mental health literacy (MHL) helps in acknowledging the symptoms at an early stage, thus promoting prompt management of negative stress behaviors. Despite the central thrust towards augmentation of MHL of troops, there is a paucity of available literature on the subject matter, especially in the Indian context. Current research explores the efficacy of a standardized Information Education and Communication (IEC) module for the promotion of MHL among troops. Materials and Methods: 1200 soldiers posted in a large military station underwent a psycho-educational module about stress and related mental health conditions in an open-label experimental study. Data was collected using a simple demographic tool and a specially constructed Armed Forces Medical College (AFMC) mental health awareness questionnaire. The same sample was studied before the IEC activity, immediately after the IEC activity, and again after six months. Results: Community-based psycho-educational module helped in improvement in MHL and the gains were stable at six months. Conclusions: Well-standardized and structured module was found to be an effective strategy for improving MHL. The authors consider this study as seminal for bringing objectivity to mental health promotional programs in the Armed Forces.

11.
Front Immunol ; 13: 956478, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119096

RESUMO

Ichthyophthirius multifiliis, a ciliated parasite causing ichthyophthiriasis (white spot disease) in freshwater fishes, results in significant economic loss to the aquaculture sector. One of the important predisposing factors for ichthyophthiriasis is low water temperature (i.e., below 20°C), which affects the health and makes freshwater fishes more susceptible to parasitic infections. During ichthyophthiriasis, fishes are stressed and acute immune reactions are compromised, which enables the aquatic bacterial pathogens to simultaneously infect the host and increase the severity of disease. In the present work, we aimed to understand the parasite-bacteria co-infection mechanism in fish. Later, Curcuma longa (turmeric) essential oil was used as a promising management strategy to improve immunity and control co-infections in fish. A natural outbreak of I. multifiliis was reported (validated by 16S rRNA PCR and sequencing method) in Pangasianodon hypophthalmus from a culture facility of ICAR-CIFRI, India. The fish showed clinical signs including hemorrhage, ulcer, discoloration, and redness in the body surface. Further microbiological analysis revealed that Aeromonas hydrophila was associated (validated by 16S rRNA PCR and sequencing method) with the infection and mortality of P. hypophthalmus, confirmed by hemolysin and survival assay. This created a scenario of co-infections, where both infectious agents are active together, causing ichthyophthiriasis and motile Aeromonas septicemia (MAS) in P. hypophthalmus. Interestingly, turmeric oil supplementation induced protective immunity in P. hypophthalmus against the co-infection condition. The study showed that P. hypophthalmus fingerlings supplemented with turmeric oil, at an optimum concentration (10 ppm), exhibited significantly increased survival against co-infection. The optimum concentration induced anti-stress and antioxidative response in fingerlings, marked by a significant decrease in cortisol and elevated levels of superoxide dismutase (SOD) and catalase (CAT) in treated animals as compared with the controls. Furthermore, the study indicated that supplementation of turmeric oil increases both non-specific and specific immune response, and significantly higher values of immune genes (interleukin-1ß, transferrin, and C3), HSP70, HSP90, and IgM were observed in P. hypophthalmus treatment groups. Our findings suggest that C. longa (turmeric) oil modulates stress, antioxidant, and immunological responses, probably contributing to enhanced protection in P. hypophthalmus. Hence, the application of turmeric oil treatment in aquaculture might become a management strategy to control co-infections in fishes. However, this hypothesis needs further validation.


Assuntos
Peixes-Gato , Infecções por Cilióforos , Coinfecção , Doenças dos Peixes , Hymenostomatida , Óleos Voláteis , Aeromonas hydrophila , Animais , Antioxidantes/uso terapêutico , Catalase , Infecções por Cilióforos/parasitologia , Infecções por Cilióforos/veterinária , Curcuma , Surtos de Doenças , Proteínas Hemolisinas , Hidrocortisona/uso terapêutico , Imunoglobulina M/uso terapêutico , Interleucina-1beta , Complexo Ferro-Dextran/uso terapêutico , Óleos Voláteis/farmacologia , RNA Ribossômico 16S , Superóxido Dismutase , Transferrinas/uso terapêutico , Água
12.
CVIR Endovasc ; 5(1): 43, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35986797

RESUMO

BACKGROUND: Proximal splenic artery embolisation (PSAE) can be performed in stable patients with Association for the Surgery of Trauma (AAST) grade III-V splenic injury. PSAE reduces splenic perfusion but maintains viability of the spleen and pancreas via the collateral circulation. The hypothesized ideal location is between the dorsal pancreatic artery (DPA) and great pancreatic artery (GPA). This study compares the outcomes resulting from PSAE embolisation in different locations along the splenic artery. MATERIALS AND METHODS: Retrospective review was performed of PSAE for blunt splenic trauma (2015-2020). Embolisation locations were divided into: Type I, proximal to DPA; Type II, DPA-GPA; Type III, distal to GPA. Fifty-eight patients underwent 59 PSAE: Type I (7); Type II (27); Type III (25). Data was collected on technical and clinical success, post-embolisation pancreatitis and splenic perfusion. Statistical significance was assessed using a chi-squared test. RESULTS: Technical success was achieved in 100% of cases. Clinical success was 100% for Type I/II embolisation and 88% for Type III: one patient underwent reintervention and two had splenectomies for ongoing instability. Clinical success was significantly higher in Type II embolisation compared to Type III (p = 0.02). No episodes of pancreatitis occurred post-embolisation. Where post-procedural imaging was obtained, splenic perfusion remained 100% in Type I and II embolisation and 94% in Type III. Splenic perfusion was significantly higher in the theorized ideal Type II group compared to Type I and III combined (p = 0.01). CONCLUSION: The results support the proposed optimal embolisation location as being between the DPA and GPA.

13.
Indian Pediatr ; 59(7): 524-530, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35596649

RESUMO

BACKGROUND: The current estimates of energy and protein to bridge nutrient gap in the beneficiaries of the Integrated Child Development Services (ICDS) supplementary nutrition program use sub-optimal methodology for deficit calculation. OBJECTIVE: To estimate the nutrient deficit and the risk of inadequate nutrient intake in beneficiaries of the ICDS, aged 6-36 months, using individual 24-hour diet recalls, from districts of Chitradurga and Davanagere in Karnataka. STUDY DESIGN: Cross-sectional design. PARTICIPANTS: Children (aged 6 to 36 months) registered as beneficiaries of the ICDS in these districts. METHODS: Data were collected on socio-demographic factors, child feeding patterns, perception and usage of take home ration (THR), between August to October, 2019. Three non-consecutive days' 24-hour diet recall data of children were obtained from mothers, and anthropometric measurements were taken. The proportion of children at risk of inadequate nutrient intakes was estimated using the probability approach. Assuming that 50% of a healthy population will be at risk of nutrient inadequacy such that intake and requirement distributions overlap, the proportion at actual risk of nutrient inadequacy (≥50%) was calculated. RESULTS: A combined district analysis showed a median energy deficit of 109 kcal and 161 kcal in children belonging to the age groups of 6-12 month and 13-36 month, respectively. The actual risk of inadequate intake for both age groups ranged between 12-47% for fat and other micronutrient (iron, calcium, zinc, folate, vitamin B12 and vitamin A), despite breastfeeding, complementary feeding and reported THR use. CONCLUSION: Children who receive supplementary nutrition as part of the national program fail to meet their nutrient requirements that are essential for growth and development. The study results may help in strengthening the IYCF counselling and in modification of the existing THR, with quality and cost implications.


Assuntos
Desenvolvimento Infantil , Ingestão de Energia , Criança , Estudos Transversais , Dieta , Ingestão de Alimentos , Feminino , Humanos , Índia/epidemiologia , Lactente
14.
Probiotics Antimicrob Proteins ; 14(2): 277-287, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35192183

RESUMO

Experiments were conducted to evaluate the probiotic effect of bio-augmented Bacillus tequilensis AP BFT3 on improving production, immune response, and proteomic changes of Penaeus vannamei reared in a biofloc system. Penaeus vannamei larvae (PL13) were stocked in 100-L tanks at a rate of 100 no per tank to study the effect of B. tequilensis AP BFT3 with and without biofloc (BFT-PRO and PRO). Control tanks devoid of probiotic strain were maintained in a clear water system. The growth and survival considerably increased in probiotic added biofloc reared shrimp than probiotic added clear water reared ones and control. Water quality significantly improved in probiotic added (PRO) and biofloc-probiotics (BFT-PRO) system than control. Microbiological investigations indicate increased heterotrophic bacterial load in BFT-PRO compared to the PRO and control. The quality of the isolated microbes was analyzed in terms of enzyme production, and an abundance of enzyme-producing bacterial population was observed in BFT-PRO shrimp. Immune-related genes were significantly upregulated in BFT-PRO shrimp, followed by the PRO and control. The proteomic data (2D gel electrophoresis and MALDI-TOF) of muscle tissue from the experimental animals identified 11 differentially expressed proteins. The Daxx OS and Lit v 1 tropomyosin was found upregulated in BFT-PRO shrimps. Downregulation of Na+/K+ATPase was observed in biofloc with probiotic-supplied groups. The findings revealed that the BFT system's efficacy could be improved through the addition of probiotics. The addition of B. tequilensis AP BFT3 as a probiotic in biofloc induced the expression of essential proteins, reducing contracting diseases during culture.


Assuntos
Penaeidae , Probióticos , Animais , Aquicultura/métodos , Bacillus , Bactérias/genética , Penaeidae/microbiologia , Probióticos/farmacologia , Proteômica
15.
Kathmandu Univ Med J (KUMJ) ; 20(78): 128-135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37017154

RESUMO

Background There is an age-old notion that family planning is women's responsibility disregarding the fact that men have equal responsibility in fertility regulation. Although male involvement is getting more recognition, studies on men's role in family planning are very few in the number in this part of the world. Objective To assess the knowledge, attitude and level of male involvement in family planning and to find out the factors associated with male involvement by contraceptive usage. Method A community based cross-sectional study was done from May to July 2021 among 165 currently married male, who had at least one child, living in Singur district of West Bengal. Cluster sampling method was done to select study participants and data were collected by pre-designed pretested questionnaire. Descriptive statistics, multivariable logistic regression was applied and data were analysed applying SPSS software. Result Only 36.4% participants were directly involved in family planning either by using condom or by withdrawal method but 65.5% participants were indirectly involved in family planning through spousal communication either by approving contraceptive use to their spouse or by decision making regarding family planning. Moreover, barrier of contraceptives usage were side effect (27%) and fear of impotence (25.5%). Male involvement was significantly associated with participant's education [AOR (95% CI= 3.63 (1.45-9.05)], caste [AOR (95% CI= 7.06 (2.55-19.51)], number of living children [AOR (95%CI= 5.01(1.95-12.87)], desire for more child [AOR (95% CI=0.34 (.13-.87)] and attitude on family planning [AOR (95% CI= 3.55 (1.41-8.94)]. Conclusion This study identified the prevailing gender norms in rural areas. Advocacy for male involvement in family planning by health personnel during counselling of eligible couples should help in increasing contraceptive coverage in the long run.


Assuntos
Serviços de Planejamento Familiar , Conhecimentos, Atitudes e Prática em Saúde , Criança , Humanos , Masculino , Feminino , Estudos Transversais , Casamento , Anticoncepcionais , Comportamento Contraceptivo
16.
Fish Shellfish Immunol ; 119: 31-41, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34487828

RESUMO

The present study focuses on the immunity and growth of Penaeus indicus fed with varying protein levels (25%, 30%, and 35%) in a biofloc based rearing system. A 120 days growth trial was carried out using juvenile Penaeus indicus (0.71 ± 0.01) with dietary protein level, 25% (LP), 30% (MP), and 35% (HP), and a control diet-fed with 35% acted as control group resulting in 4 treatments each with four replicates and were randomly assigned 16 tank units (7500 L each). A combination of different carbon sources (molasses, wheat flour, and rice bran in 2:1:1 ratio), yeast and a probiotic (Bacillus sp.) consortium were used for the development of biofloc. At the end of the trial, the growth parameters of shrimps viz., initial weight, feed conversion ratio (FCR), and daily growth coefficient (DGC) were computed. The results indicated that shrimp fed with medium (30%) protein (MP) diet recorded significantly (P < 0.05) improved growth performance compared to high protein fed group (35%) and low protein (25%) fed group (LP) in a biofloc system and control group (35%). The immunological parameters such as hemagglutination activity (HA) assay, serum protein, lysozyme, phenol oxidase (PO), and inhibition of superoxide dismutase (SOD) activity were observed in serum, plasma, and hemocyte lysate supernatant (HLS). The HA activity, PO activity in plasma was found to be higher in high protein fed animals, whereas medium protein resulted in enhanced PO activity in serum. Similarly, lysozyme and SOD were inhibited well in high protein fed animals compared to the low protein fed group. The vital immune genes's mRNA profiling showed a potential rise in the expressional pattern in MP and HP treatments compared to LP and control. BGBP (beta-1,3-glucan binding protein) and hemocyanin mRNA transcript levels were highly upregulated in the HP (5 fold) and moderately expressed in MP (2 fold) and LP (1-2 fold). The transcripts of peroxinectin, antimicrobial peptides like crustin showed significant upregulation in HP followed by in MP and LP and control. Likewise, other immune genes, such as SOD, prophenoloxidase (proPO), showed a similar trend in a marginal way, indicating immunomodulation in the biofloc groups. This study suggested that biofloc with high protein (35%) supplementation can substantially enhance the immune response of shrimps, although medium protein level (30%) is optimum for improving the survival, growth, and in turn economic return in Indian white shrimp.


Assuntos
Penaeidae , Ração Animal/análise , Animais , Peptídeos Antimicrobianos , Aquicultura , Dieta/veterinária , Suplementos Nutricionais , Farinha , Imunidade , Imunidade Inata , Muramidase , Penaeidae/genética , RNA Mensageiro , Superóxido Dismutase , Triticum
17.
Soft Matter ; 17(33): 7628-7644, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34318861

RESUMO

Liquid marbles refer to droplets that are covered with a layer of non-wetting particles. They are observed in nature and have practical significance. These squishy objects bounce, coalesce, break, inflate, and deflate while the liquid does not touch the substrate underneath. Despite the considerable cross-disciplinary interest and value of the research on liquid marbles, a unified framework for describing the mechanics of deflating liquid marbles-as the liquid evaporates-is unavailable. For instance, analytical approaches for modeling the evaporation of liquid marbles exploit empirical parameters that are not based on liquid-particle and particle-particle interactions. Here, we have combined complementary experiments and theory to fill this gap. To unentangle the contributions of particle size, roughness, friction, and chemical make-up, we investigated the evaporation of liquid marbles formed with particles of sizes varying over 7 nm-300 µm and chemical compositions ranging from hydrophilic to superhydrophobic. We demonstrate that the potential final states of evaporating liquid marbles are characterized by one of the following: (I) constant surface area, (II) particle ejection, or (III) multilayering. Based on these insights, we developed an evaporation model for liquid marbles that takes into account their time-dependent shape evolution. The model fits are in excellent agreement with our experimental results. Furthermore, this model and the general framework can provide mechanistic insights into extant literature on the evaporation of liquid marbles. Altogether, these findings advance our fundamental understanding of liquid marbles and should contribute to the rational development of technologies.

18.
Clin Exp Dermatol ; 46(4): 795-799, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33625737

RESUMO

A 5-year-old boy presented with generalized cutaneous erosions, severe scarring, depigmentation and contractures affecting major joints. The lesions had initially affected his ears, nose, feet, and the genital and ocular mucosa, leading to significant depigmentation, scarring, contractures and mutilation. The whole of the trunk and limbs were involved at the time of presentation, with the exception of some islands of spared skin on the proximal thighs, legs, nipples and external genitalia. Electron microscopy revealed a split in the sublamina densa with the absence of anchoring fibrils, suggestive of dystrophic epidermolysis bullosa (EB). Immunofluorescence antigen mapping demonstrated a broad reticulate pattern of staining with collagen IV, VII, and laminin 332 in the floor of the blister, suggestive of Kindler syndrome. Next-generation sequencing revealed a de novo heterozygous missense mutation (a variant of unknown significance) in exon 22 of the phospholipase-C gamma 2 gene (PLCG2), which resulted in a substitution of serine by asparagine at codon 798 (p.Asp798Ser), a result that was validated using Sanger sequencing. The child was diagnosed with PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. The cutaneous and corneal erosions, inflammation and scarring of this magnitude, and the eventual result of death have not been described previously for the PLAID/APLAID spectrum previously. In conclusion, this was an unusual acquired autoinflammatory severe EB-like disease that may be associated with de novo PLCG2 mutation.


Assuntos
Epidermólise Bolhosa/genética , Mutação de Sentido Incorreto , Fosfolipase C gama/genética , Vesícula/genética , Pré-Escolar , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Microscopia Eletrônica , Doenças Periodontais/genética , Fenótipo , Transtornos de Fotossensibilidade/genética , Pele/patologia
19.
J Appl Microbiol ; 130(3): 786-796, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32615006

RESUMO

AIMS: The emergence of multidrug resistant strains of Mycobacterium tuberculosis has made tuberculosis more difficult to manage clinically. With the aim of obtaining new and effective anti-mycobacterial agent(s), this study investigated the anti-mycobacterial activity of several imidazole and piperidine derivatives. METHODS AND RESULTS: Towards obtaining new anti-mycobacterial agents, Mycobacterium smegmatis cells were treated with different compounds for their growth inhibitory activity. Among these, benzyl 1H-imidazole-1-carbodithioate and allyl piperidine-1-carbodiothioate exhibited better inhibition than the others. Thereafter, anti-biofilm property of these two was examined by treating M. smegmatis with these agents before and after the formation of biofilm. The result showed that both the compounds at their sublethal dose inhibited the formation of biofilm as well as dispersed preformed biofilm. Consistently, they augmented the activity of isoniazid or rifampicin against biofilm-encapsulated cells. MTT assay was performed to examine the toxic effects of this combinatorial therapy on different cell lines. Results exhibited a low cytotoxicity for this combinatorial treatment. The activity of these two was also verified against dormant mycobacterial cells and was found to be effective. CONCLUSION: The present study identified two compounds that exhibited anti-mycobacterial activities against both planktonic and dormant cells. These two also exhibited anti-biofilm activity at their sublethal dose and augmented the activity of isoniazid and rifampicin against biofilm encapsulated cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The current study provides two new agents that have the potential to be used in anti-mycobacterial therapy and may help in public health management.


Assuntos
Antibacterianos/farmacologia , Imidazóis/farmacologia , Mycobacterium smegmatis/efeitos dos fármacos , Piperidinas/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Rifampina/farmacologia
20.
New Microbes New Infect ; 38: 100800, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33133611

RESUMO

Coronavirus disease 2019 (COVID-19) is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Genome sequencing of the virus revealed that it is a new zoonotic virus that might have evolved by jumping from bats to humans with one or more intermediate hosts. The immediate availability of the sequence information in the public domain has accelerated the development of quantitative RT-PCR-based diagnostics. Numerous clinical trials have been prioritized globally for testing new vaccines and treatments against this disease. This review provides a broad insight into different aspects of COVID-19, an introduction to SARS-CoV-2 mitigation strategies and the present status of diagnostics and therapeutics.

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