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Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations. Temporal artery biopsy is considered the gold standard; however, its sensitivity is low at 47%. We report a unique case of Bing-Neel Syndrome (BNS) presenting as biopsy-proven GCA. BNS is a rare complication (1%) of Waldenstrom Macroglobulinemia (WM), which results from infiltration of lymph plasmacytoid cells and plasma cells into the central nervous system. A 77-year-old female with a past medical history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome in her right eye presented with progressive left eye vision loss for 5 days. Fundoscopic examination was notable for pseudophakic pseudopallor but no optic disc edema. Intraocular pressure was >40 and normalized after acetazolamide. The patient was started on pulse dose steroids by her neuro-ophthalmologist. She was discharged home on 60 mg of prednisone. At follow up with her neuro-ophthalmologist, new dot blot hemorrhages in the left eye were noted and she was readmitted for pulse dose of intravenous methylprednisolone. Temporal artery biopsy was consistent with GCA spectrum. Work up revealed paraproteinemia and subsequent bone marrow biopsy demonstrated WM. The patient was treated for her WM and her ophthalmic complications stabilized.
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Class A biosolids from water resource recovery facilities (WRRFs) are increasingly used as sustainable alternatives to synthetic fertilizers. However, the high phosphorus to nitrogen ratio in biosolids leads to a potential accumulation of phosphorus after repeated land applications. Extracting vivianite, an FeP mineral, prior to the final dewatering step in the biosolids treatment can reduce the P content in the resulting class A biosolids and achieve a P:N ratio closer to the 1:2 of synthetic fertilizers. Using ICP-MS, IC, UV-Vis colorimetric methods, Mössbauer spectroscopy, and SEM-EDX, a full-scale characterization of vivianite at the Blue Plains Advanced Wastewater Treatment Plant (AWTTP) was surveyed throughout the biosolids treatment train. Results showed that the vivianite-bound phosphorus in primary sludge thickening, before pre-dewatering, after thermal hydrolysis, and after anaerobic digestion corresponded to 8 %, 52 %, 40 %, and 49 % of the total phosphorus in the treatment influent. Similarly, the vivianite-bound iron concentration also corresponded to 8 %, 52 %, 40 %, and 49 % of the total iron present (from FeCl3 dosing), because the molar ratio between total iron and total incoming phosphorus was 1.5:1, which is the same stoichiometry of vivianite. Based on current P:N levels in the Class A biosolids at Blue Plains, a vivianite recovery target of 40 % to ideally 70 % is required in locations with high vivianite content to reach a P:N ratio in the resulting class A biosolid that matches synthetic fertilizers of 1:1.3 to 1:2, respectively. A financial analysis on recycling iron from the recovered vivianite had estimated that 14-25 % of Blue Plain's annual FeCl3 demand can potentially be met. Additionally, model simulations with Visual Minteq were used to evaluate the pre-treatment options that maximize vivianite recovery at different solids treatment train locations.
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Fósforo , Eliminación de Residuos Líquidos , Aguas Residuales , Fósforo/análisis , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Fertilizantes , Nitrógeno/análisis , Contaminantes Químicos del Agua/análisis , Nutrientes/análisis , Aguas del Alcantarillado/química , HierroRESUMEN
Sjögren's disease is an autoimmune disorder affecting exocrine glands, causing dry eyes and mouth and other morbidities. Polypharmacy or a history of radiation to the head and neck can also lead to dry mouth. Sjogren's disease is often underdiagnosed due to its non-specific symptoms, limited awareness among healthcare professionals, and the complexity of diagnostic criteria, limiting the ability to provide therapy early. Current diagnostic methods suffer from limitations including the variation in individuals, the absence of a single diagnostic marker, and the low sensitivity and specificity, high cost, complexity, and invasiveness of current procedures. Here we utilized Raman hyperspectroscopy combined with machine learning to develop a novel screening test for Sjögren's disease. The method effectively distinguished Sjögren's disease patients from healthy controls and radiation patients. This technique shows potential for development of a single non-invasive, efficient, rapid, and inexpensive medical screening test for Sjögren's disease using a Raman hyper-spectral signature.
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Aprendizaje Automático , Saliva , Síndrome de Sjögren , Espectrometría Raman , Humanos , Espectrometría Raman/métodos , Saliva/química , Saliva/metabolismo , Síndrome de Sjögren/diagnóstico , Femenino , Persona de Mediana Edad , Masculino , Adulto , AncianoRESUMEN
To design safe, selective, and effective new therapies, there must be a deep understanding of the structure and function of the drug target. One of the most difficult problems to solve has been resolution of discrete conformational states of transmembrane ion channel proteins. An example is KV11.1 (hERG), comprising the primary cardiac repolarizing current, IKr. hERG is a notorious drug anti-target against which all promising drugs are screened to determine potential for arrhythmia. Drug interactions with the hERG inactivated state are linked to elevated arrhythmia risk, and drugs may become trapped during channel closure. However, the structural details of multiple conformational states have remained elusive. Here, we guided AlphaFold2 to predict plausible hERG inactivated and closed conformations, obtaining results consistent with myriad available experimental data. Drug docking simulations demonstrated hERG state-specific drug interactions aligning well with experimental results, revealing that most drugs bind more effectively in the inactivated state and are trapped in the closed state. Molecular dynamics simulations demonstrated ion conduction that aligned with earlier studies. Finally, we identified key molecular determinants of state transitions by analyzing interaction networks across closed, open, and inactivated states in agreement with earlier mutagenesis studies. Here, we demonstrate a readily generalizable application of AlphaFold2 as a novel method to predict discrete protein conformations and novel linkages from structure to function.
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Our case report involved a 36-year-old man who sustained injury during manual labor caused by a machine press. The patient had extensive fourth-degree burns in the right dorsal hand with total loss of extensor tendons in zones V and VI of the index, middle, and ring finger. We performed a reverse radial forearm tendinocutaneous flap (the radial artery flap permits the inclusion of three "strips" of vascularized tendons: brachioradialis, flexor carpi radialis, and palmaris longus) to cover his hand defects. Six months after the operation, the active extension of the index, middle, and ring metacarpophalangeal joints had recovered well. The patient is satisfied with the outcome.
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Human voltage-gated sodium (hNaV) channels are responsible for initiating and propagating action potentials in excitable cells, and mutations have been associated with numerous cardiac and neurological disorders. hNaV1.7 channels are expressed in peripheral neurons and are promising targets for pain therapy. The tarantula venom peptide protoxin-II (PTx2) has high selectivity for hNaV1.7 and is a valuable scaffold for designing novel therapeutics to treat pain. Here, we used computational modeling to study the molecular mechanisms of the state-dependent binding of PTx2 to hNaV1.7 voltage-sensing domains (VSDs). Using Rosetta structural modeling methods, we constructed atomistic models of the hNaV1.7 VSD II and IV in the activated and deactivated states with docked PTx2. We then performed microsecond-long all-atom molecular dynamics (MD) simulations of the systems in hydrated lipid bilayers. Our simulations revealed that PTx2 binds most favorably to the deactivated VSD II and activated VSD IV. These state-specific interactions are mediated primarily by PTx2's residues R22, K26, K27, K28, and W30 with VSD and the surrounding membrane lipids. Our work revealed important protein-protein and protein-lipid contacts that contribute to high-affinity state-dependent toxin interaction with the channel. The workflow presented will prove useful for designing novel peptides with improved selectivity and potency for more effective and safe treatment of pain.
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Canal de Sodio Activado por Voltaje NAV1.7 , Péptidos , Venenos de Araña , Humanos , Potenciales de Acción , Interneuronas , Simulación de Dinámica Molecular , Dolor , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Venenos de Araña/metabolismo , Péptidos/metabolismoRESUMEN
Tobacco smoking is carcinogenic to humans. Besides cigarettes, the most common form of tobacco smoking, there was sparse evidence of waterpipe's carcinogenicity-induced nasopharyngeal cancer (NPC). This study investigated the association between waterpipe smoking and NPC mortality. Our study followed up with 20,144 eligible man participants from nine northern Vietnam communes between 2007 and 2019. Face-to-face interviews were conducted to gather data on exclusive waterpipe and cigarette smoking and dietary intake using structured semi-quantitative food frequency and lifestyle questionnaires. Nasopharyngeal cancer was determined by accessing the medical records at the state health facilities. We estimated the Cox proportional hazard ratio and 95% confidence intervals, HR (95% CI). The proportion of never smokers, exclusive waterpipe, exclusive cigarette, and dual waterpipe and cigarette smokers was 55.8%, 14.5%, 16.6%, and 13.1%, respectively. Exclusively waterpipe smokers increased the risk of NPC death compared to exclusively cigarette smokers, HR (95% CI): 4.51 (1.25, 16.31), p = 0.022. A dose-dependent positive relationship between NPC and exclusive waterpipe smoking was significantly seen for higher intensity HR (95% CI): 1.35 (1.07, 1.71), earlier age of smoking initiation HR (95% CI): 1.26 (1.06, 1.50), longer duration HR (95% CI): 1.31 (1.04, 1.66), and the cumulative number of a smoke lifetime HR (95% CI): 1.37 (1.08, 1.74). We observed a significant positive association between exclusive waterpipe smoking and NPC in men. The findings suggested that waterpipe smoking is likely more harmful than cigarettes in developing this cancer. A firm tobacco control against waterpipe smoking is highly recommended.
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Neoplasias Nasofaríngeas , Fumar en Pipa de Agua , Humanos , Masculino , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/etiología , Estudios Prospectivos , Pueblos del Sudeste Asiático , Vietnam/epidemiología , Fumar en Pipa de Agua/efectos adversos , Fumar en Pipa de Agua/epidemiología , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/epidemiologíaRESUMEN
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a class of small vessel vasculitis that includes granulomatosis with polyangiitis (GPA), eosinophilic GPA (EGPA), and microscopic polyangiitis (MPA). Despite extensive research, the mechanisms behind AAV etiology remain obscure. The genetics of AAV is a complex area of investigation because of the rarity of familial cases. However, recent multi-center genome-wide association studies (GWAS) have greatly contributed to our understanding of the genetic basis of AAV. In this study, we report a rare occurrence of GPA in two Caucasian family members who presented with similar clinical symptoms and performed a comprehensive review to study the present literature available regarding the heritability of this disease.
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We adapted an existing, spaceflight-proven, robust "electronic nose" (E-Nose) that uses an array of electrical resistivity-based nanosensors mimicking aspects of mammalian olfaction to conduct on-site, rapid screening for COVID-19 infection by measuring the pattern of sensor responses to volatile organic compounds (VOCs) in exhaled human breath. We built and tested multiple copies of a hand-held prototype E-Nose sensor system, composed of 64 chemically sensitive nanomaterial sensing elements tailored to COVID-19 VOC detection; data acquisition electronics; a smart tablet with software (App) for sensor control, data acquisition and display; and a sampling fixture to capture exhaled breath samples and deliver them to the sensor array inside the E-Nose. The sensing elements detect the combination of VOCs typical in breath at parts-per-billion (ppb) levels, with repeatability of 0.02% and reproducibility of 1.2%; the measurement electronics in the E-Nose provide measurement accuracy and signal-to-noise ratios comparable to benchtop instrumentation. Preliminary clinical testing at Stanford Medicine with 63 participants, their COVID-19-positive or COVID-19-negative status determined by concomitant RT-PCR, discriminated between these two categories of human breath with a 79% correct identification rate using "leave-one-out" training-and-analysis methods. Analyzing the E-Nose response in conjunction with body temperature and other non-invasive symptom screening using advanced machine learning methods, with a much larger database of responses from a wider swath of the population, is expected to provide more accurate on-the-spot answers. Additional clinical testing, design refinement, and a mass manufacturing approach are the main steps toward deploying this technology to rapidly screen for active infection in clinics and hospitals, public and commercial venues, or at home.
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COVID-19 , Nanoestructuras , Compuestos Orgánicos Volátiles , Animales , Humanos , Nariz Electrónica , Reproducibilidad de los Resultados , COVID-19/diagnóstico , Pruebas Respiratorias/métodos , Compuestos Orgánicos Volátiles/análisis , MamíferosRESUMEN
Human voltage-gated sodium (hNaV) channels are responsible for initiating and propagating action potentials in excitable cells and mutations have been associated with numerous cardiac and neurological disorders. hNaV1.7 channels are expressed in peripheral neurons and are promising targets for pain therapy. The tarantula venom peptide protoxin-2 (PTx2) has high selectivity for hNaV1.7 and serves as a valuable scaffold to design novel therapeutics to treat pain. Here, we used computational modeling to study the molecular mechanisms of the state-dependent binding of PTx2 to hNaV1.7 voltage-sensing domains (VSDs). Using Rosetta structural modeling methods, we constructed atomistic models of the hNaV1.7 VSD II and IV in the activated and deactivated states with docked PTx2. We then performed microsecond-long all-atom molecular dynamics (MD) simulations of the systems in hydrated lipid bilayers. Our simulations revealed that PTx2 binds most favorably to the deactivated VSD II and activated VSD IV. These state-specific interactions are mediated primarily by PTx2's residues R22, K26, K27, K28, and W30 with VSD as well as the surrounding membrane lipids. Our work revealed important protein-protein and protein-lipid contacts that contribute to high-affinity state-dependent toxin interaction with the channel. The workflow presented will prove useful for designing novel peptides with improved selectivity and potency for more effective and safe treatment of pain.
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Achiral and chiral isomers of dipyrenoheteroles were synthesized via alkyne benzannulation. The electronic properties of these compounds were examined using cyclic voltammetry and differential pulse voltammetry. The enantiomers of the chiral isomers were separated, and their optical properties were examined in circular dichroism and circularly polarized luminescence studies. The chiral isomers exhibited a large bathochromic shift, relative to the achiral isomer, in both absorbance and fluorescence, resulting from decreased symmetry, rather than a change in the size of the backbone.
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High-rate activated sludge (HRAS) systems suffer from high variability of effluent quality, clarifier performance, and carbon capture. This study proposed a novel control approach using bioflocculation boundaries for wasting control strategy to enhance effluent quality and stability while still meeting carbon capture goals. The bioflocculation boundaries were developed based on the oxygen uptake rate (OUR) ratio between contactor and stabilizer (feast/famine) in a high-rate contact stabilization (CS) system and this OUR ratio was used to manipulate the wasting setpoint. Increased oxidation of carbon or decreased wasting was applied when OUR ratio was <0.52 or >0.95 to overcome bioflocculation limitation and maintain effluent quality. When no bioflocculation limitations (OUR ratio within 0.52-0.95) were detected, carbon capture was maximized. The proposed control concept was shown for a fully automated OUR-based control system as well as for a simplified version based on direct waste flow control. For both cases, significant improvements in effluent suspended solids level and stability (<50-mg TSS/L), solids capture over the clarifier (>90%), and COD capture (median of 32%) were achieved. This study shows how one can overcome the process instability of current HRAS systems and provide a path to achieve more reliable outcomes. PRACTITIONER POINTS: Online bioflocculation boundaries (upper and lower limit) were defined by the OUR ratio between contactor and stabilizer (feast/famine). To maintain effluent quality, carbon oxidation was minimized when bioflocculation was not limited (0.52-0.95 OUR ratio) and increased otherwise. A fully automated control concept was piloted, also a more simplified semiautomated option was proposed. Wasting control strategies with bioflocculation boundaries improved effluent quality while meeting carbon capture goals. Bioflocculation boundaries are easily applied to current wasting control schemes applied to HRAS systems (i.e., MLSS, SRT, and OUR controls).
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Reactores Biológicos , Eliminación de Residuos Líquidos , Carbono , Aguas del AlcantarilladoRESUMEN
Background: Both free medial sural artery perforator flaps and pedicled medial sural artery perforator flaps have been being effectively used in treatment of body defects especially in head and neck region by plastic surgeons worldwide. However, there is a lack of comprehensive studies on the anatomy of perforating artery branches in Vietnam. This study aims to describe anatomical vascular pedicles of medial sural artery perforator flap in Vietnamese adults . Methods: A descriptive cross-sectional study, dissected 62 lower limbs of 41 Vietnamese adult cadavers preserved by formalin in Department of Anatomy, Hanoi Medical University and Ho Chi Minh Medicine and Pharmacy University. Results: Origin of medial sural artery was branched constantly from popliteal artery. Common stem of artery was 8.39 ± 3.5 cm in mean length. The diameter of common stem, which was measured from origin, was 2.88 ± 0.98 mm averagely. The common stem of artery, which did not have any branch (15%), divided in to 2 branches (15%), 3 branches (30%), 4 branches (40%) before entering muscle. Medial sural artery had 1 to 5 branches perforating to the skin. The distance from perforating branch to the knee joint (popliteal crease) was 10.12 ± 3.7 cm, the distance from perforator branch to middle posterior leg was 1.6 ± 0.96 cm. Conclusions: The medial sural artery constantly originates from popliteal artery, supplies blood for medial gastrocnemius muscle. The skin area covering this muscle is nourished by one of five perforators of the medial sural artery. The perforating flaps can be created using medial sural artery perforating branches.
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Introducción: La longitud axial ocular, la profundidad de la cámara anterior y el grosor corneal central, son tres índices biométricos oculares importantes. Estas medidas son útiles para mostrar los cambios en la población vietnamita con presbicia. Objetivos: Determinar los índices biométricos oculares, longitud axial ocular, profundidad de la cámara anterior y espesor corneal central, en población vietnamita y evaluar la correlación entre ellos y con la edad y el sexo. Métodos: Se realizó un estudio transversal en población vietnamita, con edad de 46 a 65 años. Se recogieron los datos de longitud axial ocular, profundidad de la cámara anterior y grosor corneal central. Se utilizaron la prueba t de Student y ANOVA para comparar las medias de los índices, agrupados por edad y sexo. La relación entre los índices biométricos oculares fue probada mediante la correlación de Pearson, con un nivel de significación de p < 0,05. Resultados: Se analizaron 390 ojos de 195 personas. La longitud media del eje ocular fue 23,13 ± 0,66 mm, la profundidad de la cámara anterior, 3,15 ± 0,36 mm, el grosor corneal central, 529,15 ± 30,57 µm. Los tres índices biométricos disminuyeron con la edad y fueron mayores en los hombres (p < 0,05). La longitud del eje ocular tuvo relación positiva con la profundidad de la cámara anterior (r = 0,411 y p < 0,001) y el espesor corneal central (r = 0,141 y p < 0,001). No hubo relación entre la profundidad de la cámara anterior y el grosor corneal central (r = 0,039 y p = 0,44). Conclusión: Los tres índices biométricos oculares disminuyeron con la edad y fueron mayores en los hombres. La longitud del eje ocular se relacionó con la profundidad de la cámara anterior y el grosor de la córnea central(AU)
Introduction: Ocular axial length, anterior chamber depth and central corneal thickness are three important ocular biometric indices. These measurements are useful to show changes in the Vietnamese population with presbyopia. Objectives: To determine the ocular biometric indices, ocular axial length, anterior chamber depth and central corneal thickness, in Vietnamese population and evaluate the correlation between these indices. Methods: A cross-sectional study was carried out in a Vietnamese population, aged 46 to 65 years. Data on ocular axial length, anterior chamber depth and central corneal thickness were collected. The Student's t test and ANOVA were used to compare the means of the indices, grouped by age and sex. The relationship between the ocular biometric indices was tested using Pearson's correlation, with a significance level of p <0.05. Results: 390 eyes of 195 people were analyzed. The mean length of the ocular axis was 23.13 ± 0.66 mm, the depth of the anterior chamber, 3.15 ± 0.36 mm, and the central corneal thickness, 529.15 ± 30.57 µm. The three biometric indices decreased with age and were higher in men (p <0.05). The length of the ocular axis had a positive relationship with the depth of the anterior chamber (r = 0.411 and p <0.001) and the central corneal thickness (r = 0.141 and p <0.001). There was no relationship between anterior chamber depth and central corneal thickness (r = 0.039 and p = 0.44). Conclusion: Three ocular biometric indices decreased with age and were higher in men. The length of the ocular axis was related to the depth of the anterior chamber and the thickness of the central cornea(AU)
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Humanos , Persona de Mediana Edad , Longitud Axial del Ojo/fisiología , Cámara Anterior/fisiología , Estudios Transversales , Biometría/métodosRESUMEN
The rational improvement of the enzyme catalytic activity is one of the most significant challenges in biotechnology. Most conventional strategies used to engineer enzymes involve selecting mutations to increase their thermostability. Determining good criteria for choosing these substitutions continues to be a challenge. In this work, we combine bioinformatics, electrostatic analysis, and molecular dynamics to predict beneficial mutations that may improve the thermostability of XynA from Bacillus subtilis. First, the Tanford-Kirkwood surface accessibility method is used to characterize each ionizable residue contribution to the protein native state stability. Residues identified to be destabilizing were mutated with the corresponding residues determined by the consensus or ancestral sequences at the same locations. Five mutants (K99T/N151D, K99T, S31R, N151D, and K154A) were investigated and compared with 12 control mutants derived from experimental approaches from the literature. Molecular dynamics results show that the mutants exhibited folding temperatures in the order K99T > K99T/N151D > S31R > N151D > WT > K154A. The combined approaches employed provide an effective strategy for low-cost enzyme optimization needed for large-scale biotechnological and medical applications.
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Bacillus subtilis , Endo-1,4-beta Xilanasas , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas Bacterianas/genética , Biología Computacional , Endo-1,4-beta Xilanasas/genética , Endo-1,4-beta Xilanasas/metabolismo , Estabilidad de Enzimas , Mutación , Electricidad EstáticaRESUMEN
Systemic sclerosis is a complex, often progressive, multisystem autoimmune disease. It is commonly categorized into limited cutaneous or diffuse cutaneous systemic sclerosis. There is near universal involvement of skin fibrosis and gastrointestinal dysfunction, but lung disease is not only common but also a most serious complication. Severe lung disease is the top cause of mortality, displacing scleroderma renal crisis as the leading cause of death. Whether there is limited cutaneous or diffuse cutaneous manifestations can be predictive of what type of lung disease that can present in the patient. Limited cutaneous systemic sclerosis patients tend to have pulmonary hypertension whereas diffuse cutaneous systemic sclerosis patients tend to have interstitial lung disease. There are more rare phenotypes associated with antibodies Th/To and U3RNP that can have both pulmonary hypertension and interstitial lung disease concomitantly. There are inherent challenges in the management for both pulmonary hypertension and interstitial lung disease but with the focus on early diagnosis for each of these lung complications, treatment may have a higher chance of efficacy.
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Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Enfermedades de la Piel , Humanos , Hipertensión Pulmonar/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , PielRESUMEN
Improved settleability has become an essential feature of new wastewater treatment innovations. To accelerate adoption of such new technologies, improved clarifier models are needed to help with designing and predicting improvement in settleability. In general, the level of mathematics of settling clarifier models has gone far beyond the level of existing experimental methods available to support these models. To date, even for simple one-dimensional (1D) clarifier models, no experimental method has been described for flocculent settling coefficient (rp). As a consequence, rp cannot be considered as a sludge characteristic and is used as a calibration parameter to achieve observed effluent quality. In this study, we focused on the development of an empirical function based on a simple and practical experimental approach for the calculation of the rp value from sludge characteristics. This approach provided a similar approach as currently taken for hindered settling coefficient calculations (Veslind equation) and allowed for the model to predict effluent quality, thus increasing the power of the 1D model. The threshold of flocculation (TOF), which describes the collision efficiency of particles, directly correlated with the effluent quality of the five tested activated sludge systems and was selected as experimental method. The proposed empirical function between TOF and rp was validated for four years of validating data with five different sludge types operated under different operational conditions and configurations. The good effluent quality prediction with this approach brings us one step closer in making the clarification models more predictive towards effluent quality and clarifier performance.