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Osteosarcoma is the commonest primary bone malignancy occurring in patients aged <20, and humerus is the third most common site affected by it. In the past, ablative surgery with poor functional outcomes was the only option, but due to advances in chemotherapy, medical imaging and surgical techniques, patient survivorship and the rate of limb salvage surgery has increased significantly. Over the decades many treatment options have been proposed for the reconstruction of the defect following extirpation of the tumour in the proximal humerus, with every procedure having its merits and demerits. However, there is no agreement on the preferred treatment even in similar age groups, and the best way to reconstruct the proximal humerus remains debatable because the restoration of the function of the shoulder girdle remains primarily dependant on the extent of muscle-loss during tumour resection, available surgical expertise and financial constraints in different health systems. The current narrative review was planned to discuss the various reconstruction techniques with their advantages and disadvantages, and a present general review of the relevant literature.
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Neoplasias Ósseas , Osteossarcoma , Procedimentos de Cirurgia Plástica , Humanos , Ombro , Osteossarcoma/cirurgia , Osteossarcoma/patologia , Úmero/cirurgia , Salvamento de Membro/métodos , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Resultado do TratamentoRESUMO
Specific and rapid detection of proteins in biological fluids poses a challenging problem. In biological fluids, many proteins are present at low concentrations, requiring high affinity and specificity of the beacon-protein interaction. We report the design of a peptide-PNA hybrid beacon that exploits the dimeric nature of a target protein, S100B, a biomarker for brain trauma, to enhance binding affinity and specificity. The complementary base-pairing of the PNA bases brings the two arms of the beacon, one carrying an Alexa tag and the other carrying a Dabcyl moiety, into proximity, thus quenching Alexa fluorescence. Each of the arms carries a sequence that binds to one of the subunits. Binding to the target separates the quencher from the probe lifting the quenching of fluorescence. Enhanced affinity and specificity resulting from simultaneously binding to two sites allowed specific detection of S100B at low-nanomolar concentrations in the presence of serum. The design can be easily adapted for the detection of proteins containing multiple binding sites and could prove useful for rapid and sensitive biomarker detection.
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Limite de Detecção , Ácidos Nucleicos Peptídicos/química , Peptídeos/química , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/química , Sequência de Aminoácidos , Biomarcadores/sangue , Humanos , Modelos Moleculares , Conformação ProteicaRESUMO
Manifestation of male sterility in plants is an important requirement for hybrid seed production. Tapetum cell layer of anther is a primary target for genetic manipulation for male sterility. In our previous report, the targeted expression of Arachis cysteine protease in tapetum led to premature degeneration of tapetal layer that resulted in complete male sterility in transgenic tobacco plants. To correlate cysteine protease mediated cell death of tapetum, transmission electron microscopy (TEM) and proteomic pattern of anthers of cysteine protease induced male sterile plant were compared with the untransformed control plant. TEM study revealed the abnormal growth of tapetal cells exhibiting excessive vacuolization that synchronized with irregular exine wall formation of the microspores. In anther proteome, a total 250 protein spots were detected that were reproducible and exhibited similar distribution pattern. Further, anther proteome of male sterile plant showed the significant upregulation (≥ 1.5) of 56 protein spots. Using Mass spectroscopy (MALDI TOF/TOF), we have identified 14 protein spots that were involved in several processes such as energy metabolism, protein synthesis, plastid protein, lipid metabolism, and cell wall assembly. Upregulation of patatin-like protein-2 homolog, carboxylesterase 17 and dicer like protein-4 in male sterile anthers that have been demonstrated to induce cell death, suggesting that cysteine protease mediated premature tapetal cell death might involve the lipid peroxidation pathway in coordination with gene silencing mechanism.
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Annexins are multifunctional proteins with roles in plant development and alleviation of stress tolerance. In the present communication, we report on the effect of heterologous expression of Brassica juncea annexin, AnnBj2 in tobacco. Transgenic tobacco plants expressing AnnBj2 exhibited salt-tolerant and abscisic acid (ABA)-insensitive phenotype at the seedling stage. Biochemical analysis showed that AnnBj2 transgenic plants retained higher chlorophyll and proline content, and lower malondialdehyde (MDA) levels compared to the null line under salt stress. They exhibited better water retention capacity compared to the null segregant (NS) line. AnnBj2 overexpression altered the transcript levels of several stress-related marker genes involved in reactive oxygen species (ROS) scavenging and abiotic stress signaling. Taken together, these results suggest a positive role for AnnBj2 in salt stress response upon heterologous expression in tobacco.
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Ácido Abscísico/farmacologia , Anexinas/genética , Brassica/genética , Nicotiana/genética , Proteínas de Plantas/genética , Tolerância ao Sal , Anexinas/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plântula/efeitos dos fármacos , Plântula/genética , Nicotiana/efeitos dos fármacosRESUMO
Entamoeba histolytica (E. histolytica) produces an invasive disease called amoebiasis, which commonly produces diarrhea with or without blood in both children and adults, leading to high morbidity and mortality. Entamoeba dispar (E. Dispar) is a non invasive, non pathogenic organism. Both Entamoeba histolytica and Entamoeba Dispar look alike on microscopy and therefore cannot be differentiated unless checked on ELISA, PCR or other specific method. To calculate the actual prevalence of pathogenic amoebiasis in children by comparing the stool microscopy with ELISA stool antigen i.e. gold standard. Across sectional, comparative study. Children under five years in a community village Budhni, District Peshawar. A sample of 288 children aged <5 years were randomly selected. Information's were collected on the age and gender of the children. Fresh stool specimens were examined microscopically and with stool antigen kit of ELISA for detection of Entamoeba histolytica. The specificity and sensitivity of microscopic method was calculated against ELISA. Data was analyzed using statistical computer software package SPSS version 10.0. A total of 288 stool specimens were collected and examined for Entamoeba histolytica. Out of these 36(12.5%) stools were positive for E. histolyticaon microscopy while 14(4.9%) were positive on ELISA. Out of 14 ELISA positive samples, 10 samples were also positive on microscopy while 4 were ELISA positive but microscopy negative. About 22 samples, which were positive on microscopy were negative on ELISA indicating that these samples might have been of E. Dispar which is non pathogenic protozoa. The sensitivity and specificity of microscopic method was 71.4% and 90.5% respectively, as against stool antigen test. Actual prevalence of Entamoeba histolytica is low in the area. Stool ELISA was able to differentiate between pathogenic Entamoeba histolytica and the non-pathogenic Entamoeba dispar and thus can minimize unnecessary antiamoebic treatment in these children.
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Antígenos de Bactérias/imunologia , Entamoeba histolytica/imunologia , Entamebíase/diagnóstico , Entamebíase/epidemiologia , Ensaio de Imunoadsorção Enzimática , Pré-Escolar , Estudos Transversais , Diagnóstico Diferencial , Entamebíase/parasitologia , Reações Falso-Positivas , Fezes/parasitologia , Feminino , Humanos , Lactente , Masculino , Microscopia , Paquistão/epidemiologia , Valor Preditivo dos Testes , Prevalência , Reprodutibilidade dos TestesRESUMO
Usable male sterility systems have immense potential in developing hybrid varieties in crop plants, which can also be used as a biological safety containment to prevent horizontal transgene flow. Barnase-Barstar system developed earlier was the first approach to engineer male sterility in plants. In an analogous situation, we have evolved a system of inducing pollen abortion and male sterility in transgenic tobacco by expressing a plant gene coding for a protein with known developmental function in contrast to the Barnase-Barstar system, which deploys genes of prokaryotic origin, i.e., from Bacillus amyloliquefaciens. We have used a plant pathogen-induced gene, cysteine protease for inducing male sterility. This gene was identified in the wild peanut, Arachis diogoi differentially expressed when it was challenged with the late leaf spot pathogen, Phaeoisariopsis personata. Arachis diogoi cysteine protease (AdCP) was expressed under the strong tapetum-specific promoter (TA29) and tobacco transformants were generated. Morphological and histological analysis of AdCP transgenic plants showed ablated tapetum and complete pollen abortion in three transgenic lines. Furthermore, transcript analysis displayed the expression of cysteine protease in these male sterile lines and the expression of the protein was identified in western blot analysis using its polyclonal antibody raised in the rabbit system.
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Cisteína Proteases/genética , Regulação da Expressão Gênica de Plantas , Nicotiana/genética , Infertilidade das Plantas/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Sequência de Aminoácidos , Arachis/genética , Arachis/microbiologia , Ascomicetos/patogenicidade , Ascomicetos/fisiologia , Cisteína Proteases/metabolismo , Dados de Sequência Molecular , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/enzimologia , Pólen , Regiões Promotoras Genéticas , Alinhamento de Sequência , Nicotiana/enzimologia , TransgenesRESUMO
Protein-protein interactions are part of a large number of signaling networks and potential targets for drug development. However, discovering molecules that can specifically inhibit such interactions is a major challenge. S100B, a calcium-regulated protein, plays a crucial role in the proliferation of melanoma cells through protein-protein interactions. In this article, we report the design and development of a bidentate conformationally constrained peptide against dimeric S100B based on a natural tight-binding peptide, TRTK-12. The helical conformation of the peptide was constrained by the substitution of α-amino isobutyric acid--an amino acid having high helical propensity--in positions which do not interact with S100B. A branched bidentate version of the peptide was bound to S100B tightly with a dissociation constant of 8 nM. When conjugated to a cell-penetrating peptide, it caused growth inhibition and rapid apoptosis in melanoma cells. The molecule exerts antiproliferative action through simultaneous inhibition of key growth pathways, including reactivation of wild-type p53 and inhibition of Akt and STAT3 phosphorylation. The apoptosis induced by the bidentate constrained helix is caused by direct migration of p53 to mitochondria. At moderate intravenous dose, the peptide completely inhibits melanoma growth in a mouse model without any significant observable toxicity. The specificity was shown by lack of ability of a double mutant peptide to cause tumor regression at the same dose level. The methodology described here for direct protein-protein interaction inhibition may be effective for rapid development of inhibitors against relatively weak protein-protein interactions for de novo drug development.
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Proteína de Capeamento de Actina CapZ/química , Proteína de Capeamento de Actina CapZ/farmacologia , Melanoma/patologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Modelos Animais de Doenças , Humanos , Camundongos , Microscopia de Contraste de Fase , Dados de Sequência Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Indução de Remissão , Transdução de Sinais/efeitos dos fármacos , Temperatura , Proteína Supressora de Tumor p53/metabolismoRESUMO
UV sensing 3D printed optical fiber hydrogels provide a flexible and precise method of remotely of detecting exposure to UV radiations. The optical fibers were created using digital light processing 3D printing technique with hydrogel composites, including micro-sized photochromic dyes (pink, blue and their combination). When exposed to ultraviolet (UV) radiation, these dyes exhibited specific absorption characteristics, resulting in significant decreases in both reflection and transmittance mode spectra at 560 nm, 620 nm, and 590 nm. Optical fibers of lengths 1, 2, and 3 cm were manufactured in two orientations: vertical and horizontal. Scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction were utilized to characterize the printed fiber probes. The optical performance of the fibers was tested using customized measurement setups. The reflection and transmission of the printed fibers reduced as the length increased due to optical losses. Reflection and transmisson loss of 20-40% can be observed when the length is increased from 1 to 3 cm. The maximum loss in reflection is observed for pink fiber in the presence of UV irradiation. Also, the type of powder used impacted the response and retraction time, whereas the mixed fiber showed the highest response time of 12-20 s under various conditions. The pink dye added fiber probes shows quick response to UV radiation. An increase in the response time is observed with increasing fiber length. The impact of printing orientation on the transmission and reflectance mode operations of optical fibers was assessed. In addition, the stability of the fiber probes are assesed using a green laser having wavelength 532 nm. This work comprehensively examines the optical properties, manufacturing procedures, and sensing capacities of UV-sensitive photochromic optical fiber sensors.
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The skin has emerge as a compelling subject for investigation owing to its accessibility and the relatively straightforward application of optical procedures to it. Diffusive reflection spectroscopy (DRS) was employed to study the influence of probe pressure on human skin. A comprehensive non-invasive study was conducted, which covers almost all the important body parts for in vivo measurements. Reflection spectra were measured for the fingertip, forearm, forehead, neck, and foot under a set of probe pressures (0-265 kPa). Importantly, each tissue type's unique composition and morphology influenced the shape, size, intensity, and position of the recorded peak, highlighting the tissue-specific responses to pressure. In addition, time-based reflection spectroscopy was also performed on the forearm under blood occlusion for 5 min to study the effect. DRS measurements were performed on volunteers of different skin tones, including dark, medium, and fair. Later, a change in the intensity of the oxyhemoglobin peak was confirmed using a green laser light of a wavelength of 532 nm. Besides the dermal studies, diffusive reflection spectroscopy was also employed to investigate the probe pressure effect on human nails. A probe pressure ranging from 0 to 385 kPa was applied for nail spectroscopy. The same trend of intensity change was observed following the previous measurements. The suggested sensing system may be crucial in applications requiring pressure sensing when the human body is subjected to varying pressures, such as exercise, weightlifting, and other sports.
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Optical fiber (OF) sensors are critical optical devices with excellent sensing capabilities and the capacity to operate in remote and hostile environments. However, integrating functional materials and micro/nanostructures into the optical fiber systems for specific sensing applications has limitations of compatibility, readiness, poor control, robustness, and cost-effectiveness. Herein, we have demonstrated the fabrication and integration of stimuli-responsive optical fiber probe sensors using a novel, low-cost, and facile 3D printing process. Thermal stimulus-response of thermochromic pigment micro-powders was integrated with optical fibers by incorporating them into ultraviolet-sensitive transparent polymer resins and then printed via a single droplet 3D printing process. Hence, the thermally active polymer composite fibers were grown (additively manufactured) on top of the commercial optical fiber tips. Then, the thermal response was studied within the temperature range of (25-35 °C) and (25-31 °C) for unicolor and dual color pigment powders-based fiber-tip sensors, respectively. The unicolor (with color to colorless transition) and dual color (with color to color transition) powders-based sensors exhibited substantial variations in transmission and reflection spectra by reversibly increasing and decreasing temperatures. The sensitivities were calculated from the transmission spectra where average change in transmission spectra was recorded as 3.5% with every 1 °C for blue, 3% for red and 1% for orange-yellow thermochromic powders based optical fiber tip sensors. Our fabricated sensors are cost-effective, reusable, and flexible in terms of materials and process parameters. Thus, the fabrication process can potentially develop transparent and tunable thermochromic sensors for remote sensing with a much simpler manufacturing process compared to conventional and other 3D printing processes for optical fiber sensors. Moreover, this process can integrate micro/nanostructures as patterns on the optical fiber tips to increase sensitivity. The developed sensors may be employed as remote temperature sensors in biomedical and healthcare applications.
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Glutamate receptors like channels (GLRs) are ligand gated non-selective cation channels and are multigenic in nature. They are homologs of mammalian ionic glutamate receptors (iGLRs) that play an important role in neurotransmission. It has been more than 25 years of discovery of plant GLRs, since then, significant progress has been made to unravel their structure and function in plants. Recently, the first crystal structure of plant GLR has been resolved that suggests that, though, plant GLRs contain the conserved signature domains of iGLRs, their unique features enable agonist/antagonist-dependent change in their activity. GLRs exhibit diverse subcellular localization and undergo dynamic expression variation in response to developmental and environmental stress conditions in plants. The combined use of genetic, electrophysiology and calcium imaging using different genetically encoded calcium indicators has revealed that GLRs are involved in generating calcium (Ca2+) influx across the plasma membrane and are involved in shaping the Ca2+ signature in response to different developmental and environmental stimuli. These findings indicate that GLRs influence cytosolic Ca2+ dynamics, thus, highlighting "GLR-Ca2+-crosstalk (GCC)" in developmental and stress-responsive signaling pathways. With this background, the present review summarises the recent developments pertaining to GLR function, in the broader context of regulation of stress tolerance in plants.
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Cálcio , Animais , Cálcio/metabolismo , Sinalização do Cálcio , Mamíferos/metabolismo , Plantas/genética , Plantas/metabolismo , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismoRESUMO
Achieving carbon neutrality targets is crucial while considering the adverse impacts of carbon dioxide emissions (CE) on human life and the ecosystem. Therefore, its socioeconomic drivers have frequently been probed in the existing body of literature. Therefore, we investigate the impact of energy efficiency, FDI, financial development, urbanization, and economic growth on CE in Pakistan from 1975 to 2020. For this purpose, we apply the novel dynamic ARDL simulation approach to retrieve the short- and long-run estimates. The empirical results confirm that cointegration exists among the considered variables. Further, both the short- and long-run results reveal that energy efficiency impedes emissions, whereas urbanization, financial development, and FDI increase emissions. Considering the outcomes, there is a need to enhance energy efficiency in Pakistan. For this purpose, investment in technological advancements and innovations is required. Moreover, R&D in the energy sector should be promoted.
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The production of cement releases an enormous amount of CO2 into the environment. Besides, industrial wastes like silica fume and fly ash need effective utilization to reduce their impacts on the environment. This research aims to explore the influence of silica fume (SF) and fly ash (FA) individually and combine them as binary cementitious material (BCM) on the hardened properties and embodied carbon of roller compacted concrete (RCC). A total of ten mixes were prepared with 1:2:4 mix ratio at the different water-cement ratios to keep the zero slump of roller compacted concrete. However, the replacement proportions for SF were 5%-15%, and FA were 5%-15% by the weight of cement individually and combine in roller compacted concrete for determining the hardened properties and embodied carbon. In this regard, several numbers of concrete specimens (cubes and cylinders) were cast and cured for 7 and 28 days correspondingly. It was observed that the compressive strength of RCC is boosted by 33.6 MPa and 30.6 MPa while using 10% of cement replaced with SF and FA individually at 28 days, respectively. Similarly, the splitting tensile strength of RCC is enhanced by 3.5 MPa at 10% cement replaced with SF and FA on 28 days, respectively. The compressive and splitting tensile strength of RCC is increased by 34.2 MPa and 3.8 MPa at SF7.5FA7.5 as BCM after 28 days consistently. In addition, the water absorption of RCC decreased while using SF and FA as cementitious material individually and together at 28 days. Besides, the embodied carbon of RCC decreased with increasing the replacement level of SF and FA by the mass of cement individually and combined.
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Cinza de Carvão , Materiais de Construção , Carbono , Força Compressiva , Dióxido de SilícioRESUMO
Diabetes mellitus is a chronic disease requiring a careful management to prevent its collateral complications, such as cardiovascular and Alzheimer's diseases, retinopathy, nephropathy, foot and hearing impairment, and neuropathy. Self-monitoring of blood glucose at point-of-care settings is an established practice for diabetic patients. However, current technologies for glucose monitoring are invasive, costly, and only provide single snapshots for a widely varying parameter. On the other hand, tears are a source of physiological information that mirror the health state of an individual by expressing different concentrations of metabolites, enzymes, vitamins, salts, and proteins. Therefore, the eyes may be exploited as a sensing site with substantial diagnostic potential. Contact lens sensors represent a viable route for targeting minimally-invasive monitoring of disease onset and progression. Particularly, glucose concentration in tears may be used as a surrogate to estimate blood glucose levels. Extensive research efforts recently have been devoted to develop smart contact lenses for continual glucose detection. The latest advances in the field are reviewed herein. Sensing technologies are described, compared, and the associated challenges are critically discussed.
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Background Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well-known that untreated or under-treated pain can have a significant negative impact on an individual's quality of life (QoL). Objectives The current study aimed to assess the clinical response of Nuberol Forte® (paracetamol 650 mg + orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient's QoL. Methods A prospective, observational multicenter study (NFORT-EFFECT: Safety & Efficacy of Nuberol Forte in Pain Management). Three hundred ninety-nine patients with known prescreened musculoskeletal pain were recruited from 10 major healthcare facilities across six (6) major cities of Pakistan, as per the inclusion/exclusion criteria. After the baseline visit (Visit 1), the patients were followed up one to two weeks (Visit 2) after the treatment as per the physician's discretion. Data were collected using the Case Report Form (CRF) designed for the study, and adverse events (AEs) were also monitored to assess drug safety. Pain intensity was assessed through a visual analog scale (VAS), and QoL was assessed using the Muscle and Joint Measure (MJM) scale. Results Out of 399 enrolled patients, 49.4% were males and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with knee osteoarthritis (OA), i.e., 148 (38%), followed by backache 70 (18.2%). A significant reduction in the mean pain score was observed after treatment with the combination of paracetamol and orphenadrine (p<0.05). Furthermore, an overall improvement in the patient's QoL was also observed. During the study, only 10 patients reported mild adverse events (AEs), namely, dryness of the mouth, dizziness, gastric irritation, tachycardia, restlessness, etc. Conclusion The combination of paracetamol and orphenadrine (Nuberol Forte) exhibited effective pain management among patients with musculoskeletal conditions and improved their QoL.
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Self-care enables patients in improving quality of life and reducing hospital admissions. Research explored the experiences of patients about breathlessness, sleep problems and complication management in chronic obstructive pulmonary disease (COPD). However, the self-care experiences and the role of the family in self-care are underexplored. This study aimed to understand the self-care experiences of patients with COPD and explore the role of the family in self-care. An interpretive phenomenological inquiry was used, and 13 patients were interviewed in 2019 from two hospitals in Pakistan. The inclusion criteria were patients above 30 years of age at any stage of COPD, who received a confirmed diagnosis of COPD and were receiving the treatment, and engaged in self-care at their homes or communities. The interviews lasted for 35-60 min. Ricoeur's interpretation theory was used for data analysis comprising steps explanation, naive understanding and in-depth understanding. Self-care emerged as a complex individual and familial endeavour affected by personal, social and economic factors. Poverty was one of the core determinants of self-care. Patients emphasised the spiritual, cultural and traditional approaches to self-care. Future research is warranted to develop better understanding of spiritual and cultural self-care and how these dimensions of self-care affect patients' self-care behaviours.
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Doença Pulmonar Obstrutiva Crônica , Autocuidado , Humanos , Paquistão , Doença Pulmonar Obstrutiva Crônica/terapia , Pesquisa Qualitativa , Qualidade de VidaRESUMO
Direct texturing of nanostructures on consumable substrates and products is a challenge because of incompatible ingredients and materials' properties. Here, we developed a direct laser-based method to print nanostructured holograms on dried films of consumable corn syrup solutions. A holographic laser (λ = 1050 nm) interference system was used to construct the nanostructures of the holograms on food for rainbow effects. The relationship between wavelength and periodicity contributed to the changing diffraction angle through the change of the refractive index (1.642). Increasing the sugar concentration (25-175 mg) in the syrup increased the diffraction efficiency of these holograms. The added amount of sugar in the composition increased the refractive index (7%) and decreased the light absorption (12.9%), which influenced the change of diffraction angle by 4.4°. The surface holograms displayed wideband visual diffraction of light extending from violet to red wavelengths. These holograms on edible materials can be imprinted onto commercial food products for adding aesthetic value and controlling perception.
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BACKGROUND: Surgical site infections are a major cause of morbidity and mortality following orthopedic surgery. Recent efforts to identify sources of contamination in the operating rooms have implicated mobile phones. AIM: To investigate microbial colonization on the mobile phones of health care professionals in the orthopedic operating room. METHODS: We conducted a cross-sectional study involving culture and sensitivity analysis of swabs taken from the mobile phones of orthopedic and anesthesia attendings, residents, technicians and nurses working in the orthopedic operating rooms over a period of two months. Demographic and cell phone related factors were recorded using a questionnaire and the factors associated with contamination were analyzed. RESULTS: Ninety-three of 100 mobile phones were contaminated. Species isolated were Coagulase-negative Staphylococcus (62%), Micrococcus (41%) and Bacillus (26%). The risk of contamination was increased with mobile covers and cracked screens and decreased by cell phone cleaning. CONCLUSION: Mobile phones belonging to health care workers are frequently contaminated with pathogenic bacteria with the potential of transferring drug resistance to nosocomial pathogens. Studies investigating the relationship to surgical site infections need to be conducted. The concept of "mobile hygiene" involving the change of mobile covers, replacement of cracked screens or even wiping the phone with an alcohol swab could yield the cost-effective balance that contaminated cell phones deserve until they are established as a direct cause of surgical site infections.
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Aldehyde dehydrogenase (ALDH) carries out oxidation of toxic aldehydes using NAD+/NADP+ as cofactors. In the present study, we performed a genome-wide identification and expression analysis of genes in the ALDH gene family in Brassica rapa. A total of 23 ALDH genes in the superfamily have been identified according to the classification of ALDH Gene Nomenclature Committee (AGNC). They were distributed unevenly across all 10 chromosomes. All the 23 Brassica rapa ALDH (BrALDH) genes exhibited varied expression patterns during treatments with abiotic stress inducers and hormonal treatments. The relative expression profiles of ALDH genes in B. rapa showed that they are predominantly expressed in leaves and stem suggesting their function in the vegetative tissues. BrALDH7B2 showed a strong response to abiotic stress and hormonal treatments as compared to other ALDH genes; therefore, it was overexpressed in heterologous hosts, E. coli and yeast to study its possible function under abiotic stress conditions. Over-expression of BrALDH7B2 in heterologous systems, E. coli and yeast cells conferred significant tolerance to abiotic stress treatments. Results from this work demonstrate that BrALDH genes are a promising and untapped genetic resource for crop improvement and could be deployed further in the development of drought and salinity tolerance in B. rapa and other economically important crops.
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Aldeído Desidrogenase/genética , Brassica rapa/enzimologia , Escherichia coli/crescimento & desenvolvimento , Sequenciamento Completo do Genoma/métodos , Leveduras/crescimento & desenvolvimento , Aldeído Desidrogenase/metabolismo , Brassica rapa/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Escherichia coli/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Folhas de Planta/enzimologia , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Caules de Planta/enzimologia , Caules de Planta/genética , Estresse Fisiológico , Leveduras/genéticaRESUMO
Intracellular regulatory pathways are replete with protein-protein and protein-DNA interactions, offering attractive targets for therapeutic interventions. So far, most drugs are targeted toward enzymes and extracellular receptors. Protein-protein and protein-DNA interactions have long been considered as "undruggable". Protein-DNA interactions, in particular, present a difficult challenge due to the repetitive nature of the B-DNA. Recent studies have provided several breakthroughs; however, a design methodology for these classes of inhibitors is still at its infancy. A dominant motif of these macromolecular interactions is an α-helix, raising possibilities that an appropriate conformationally-constrained α-helical peptide may specifically disrupt these interactions. Several methods for conformationally constraining peptides to the α-helical conformation have been developed, including stapling, covalent surrogates of hydrogen bonds and incorporation of unnatural amino acids that restrict the conformational space of the peptide. We will discuss these methods and several case studies where constrained α-helices have been used as building blocks for appropriate molecules. Unlike small molecules, the delivery of these short peptides to their targets is not straightforward as they may possess unfavorable cell penetration and ADME properties. Several methods have been developed in recent times to overcome some of these problems. We will discuss these issues and the prospects of this class of molecules as drugs.