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Nasogastric tube placement is frequently performed in various medical settings. While generally deemed safe in patients without risk factors, complications may occur due to malposition, justifying the need of systematic confirmation of position with chest radiographs. We present the case of a critically ill male adult patient for whom the tube position was initially deemed very unusual on postinsertion radiographs, prompting further workup which ultimately confirmed an oropharyngeal perforation with a left parapharyngeal, left visceral, retrotracheal, and right retrodiaphragmatic course, and resulting in a recurrent pneumothorax and empyema treated by surgical decortication., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The native hagfish slime threads, which are made up of two intermediate filament (IF)-like proteins, exhibit mechanical properties comparable to dragline spider silk fiber, the toughest fiber in nature. However, unlike silk, the design of artificial IF-protein-based fibers has been rarely studied, possibly because the unique hierarchical organization of the keratin-like proteins within these threads is challenging to mimic, and consequently, extraordinary fiber mechanics has not been shown in slime threads from recombinant IF-protein-based system. Here, we have reported the synthesis and properties of recombinant type V IF-protein, based on the Caenorhabditis elegans (Ce) lamin gene. The protein was solubilized and wet-spun into aqueous solutions to prepare Ce-lamin fibers by varying injection flow rates and Ca +2 ion concentrations in the coagulation buffer. At specific set of conditions, Ce-lamin fibers demonstrated remarkable toughness and stiffness, comparable to hagfish slime threads and natural dragline spider silk. Transmission electron microscopy analysis showed that paracrystals were the main nanometric structure within the fibers. This study demonstrates that outstanding mechanical properties can be achieved with recombinant IF-proteins through self-organization. Thus, these results have broadened the pool of fibrous proteins that can be used in functional materials for a diverse range of applications., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An effective epidermal barrier requires structural and functional integration of adherens junctions, tight junctions, gap junctions (GJ), and desmosomes. Desmosomes govern epidermal integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent of erythrokeratodermia variabilis, caused by mutations in connexin (Cx) genes. We, therefore, examined whether SAM syndrome-causing DSG1 mutations interfere with Cx expression and GJ function. Lesional skin biopsies from SAM syndrome patients (n = 7) revealed decreased Dsg1 and Cx43 plasma membrane localization compared with control and nonlesional skin. Cultured keratinocytes and organotypic skin equivalents depleted of Dsg1 exhibited reduced Cx43 expression, rescued upon re-introduction of wild-type Dsg1, but not Dsg1 constructs modeling SAM syndrome-causing mutations. Ectopic Dsg1 expression increased cell-cell dye transfer, which Cx43 silencing inhibited, suggesting that Dsg1 promotes GJ function through Cx43. As GJA1 gene expression was not decreased upon Dsg1 loss, we hypothesized that Cx43 reduction was due to enhanced protein degradation. Supporting this, PKC-dependent Cx43 S368 phosphorylation, which signals Cx43 turnover, increased after Dsg1 depletion, while lysosomal inhibition restored Cx43 levels. These data reveal a role for Dsg1 in regulating epidermal Cx43 turnover., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Gastric varices are a common manifestation of portal hypertension and are associated with a high rate of mortality and rebleeding. Balloon-occluded retrograde transvenous obliteration (BRTO) is a commonly used method to sclerose gastric varices and has a high clinical success. Common complications following BRTO include portal or splenic vein thrombosis, systemic sclerosant extravasation, pulmonary emboli, and inferior vena cava thrombosis. This report describes a patient with vascular plug migration into the left pulmonary artery with subsequent endovascular retrieval., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To characterize the vascular surgery Twitter network., Methods: A total of 20,841 consecutive tweets by 8,282 unique Twitter accounts regarding vascular surgery from October 23, 2014 to January 15, 2018 were analyzed. Twitter analytics, including activity metrics, content analysis, user characteristics, engagement, and network analysis were performed using Symplur Signals, a health care social media analytics platform., Results: Vascular surgery tweets, the number of users tweeting about vascular surgery, and vascular surgery tweet impressions have increased by an annual average of 77.8%, 55.3%, and 209.1% from 2015 to 2017, respectively. Twitter activity trend analysis showed consistent growth over the study period with an average of 25.7 ± 2.6 additional tweets per month (P < 0.001). As for tweet content, 2,220 tweets (10.7%) were pertaining to patients, and 2,198 tweets (10.5%) were regarding new or innovative topics. 15,422 tweets (74.0%) included links to journals or websites and 6,826 tweets (32.8%) contained at least 1 image. Deep venous thrombosis, pulmonary embolism, diabetes, endovascular interventions, trauma, and practice guidelines were among the most commonly discussed health topics. Physicians composed 5,618 tweets (27%), while patients submitted 2,447 tweets (11.7%). As for engagement, 8,886 tweets (42.6%) were retweets, 11,816 tweets (56.7%) mentioned at least 1 other user, and 786 tweets (3.8%) were replies. Network analysis revealed central hubs to be vascular surgery societies, academic institutions, academic journals, and physicians., Conclusions: The use of Twitter to discuss vascular surgery is growing rapidly with increasing use by vascular surgeons and vascular medicine physicians. An effort to involve more patients in the vascular surgery Twitter social network may allow for more opportunities to educate, and garner interest and support for vascular surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hematochezia may be a result of anatomic, vascular, inflammatory, infectious, or neoplastic diseases. Colonoscopic evaluation and therapy may be limited because of intermittent bleeding in the setting of numerous diverticula. This report describes a patient with diverticulosis who presented with hematochezia and hemodynamic instability with failed colonoscopic and arteriographic evaluations, and was treated with percutaneous transcolonic diverticular cyanoacrylate and epinephrine injection.

Intermediate filament (IF) proteins are known mainly by their propensity to form viscoelastic filamentous networks within cells. In addition, IF-proteins are essential parts of various biological materials, such as horn and hagfish slime threads, which exhibit a range of mechanical properties from hard to elastic. These properties and their self-assembly nature made IF-proteins attractive building blocks for biomimetic and biological materials in diverse applications. Here we show that a type V IF-protein, the Caenorhabditis elegans nuclear lamin (Ce-lamin), is a promising building block for protein-based fibers. Electron cryo-tomography of vitrified sections enabled us to depict the higher ordered assembly of the Ce-lamin into macroscopic fibers through the creation of paracrystalline fibers, which are prominent in vitro structures of lamins. The lamin fibers respond to tensile force as other IF-protein-based fibers, i.e., hagfish slime threads, and possess unique mechanical properties that may potentially be used in certain applications. The self-assembly nature of lamin proteins into a filamentous structure, which is further assembled into a complex network, can be easily modulated. This knowledge may lead to a better understanding of the relationship in IF-proteins-based fibers and materials, between their hierarchical structures and their mechanical properties., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We studied three siblings, born to consanguineous parents who presented with severe intellectual disability, cachexia, strabismus, seizures and episodes of abnormal respiratory rhythm. Whole exome sequencing led to identification of a novel homozygous splice site mutation, IVS29-1G > A in the NALCN gene, that resulted in aberrant transcript in the patients. NALCN encodes a voltage-independent cation channel, involved in regulation of neuronal excitability. Three homozygous mutations in the NALCN gene were previously identified in only eight patients with severe hypotonia, speech impairment, cognitive delay, constipation and Infantile-Neuroaxonal-dystrophy- like symptoms. Our patients broaden the clinical spectrum associated with recessive mutations in NALCN, featuring also disrupted respiratory rhythm mimicking homozygous Nalcn knockout mice., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased rebleeding from tail wounds., Patients and Methods: We studied a previously reported family of five children from two consanguineous sibships of Arab Christian descent affected with a novel autosomal recessive bleeding disorder with small-platelet thrombocytopenia. Homozygosity mapping and exome sequencing were used to identify the genetic lesion causing the disease phenotype on chromosome 5. Bone-marrow morphology and platelet function were analyzed. Platelets were characterized by scanning electron microscopy., Results: We identified a homozygous deleterious nonsense mutation, c.393G>A, in FYB. A reduced percentage of mature megakaryocytes was found in the bone marrow. Patients' platelets showed increased basal expression of P-selectin and PAC-1, and reduced increments of activation markers after stimulation with ADP, as detected by flow cytometry; they also showed reduced pseudopodium formation and the presence of trapped platelets between the fibrin fibers after thrombin addition, as observed on scanning electron microscopy., Conclusions: This is the first report of a disease caused by an FYB defect in humans, manifested by remarkable small-platelet thrombocytopenia and a significant bleeding tendency. The described phenotype shows ADAP to be important for normal platelet production, morphologic changes, and function. It is suggested that mutation analysis of this gene be included in the diagnosis of inherited thrombocytopenia., (© 2015 International Society on Thrombosis and Haemostasis.)

Neuronal ceroid lipofuscinosis (NCL) refers to a growing heterogeneous group of neurodegenerative disorders characterized by lysosomal accumulation of abnormal autofluorescent material. NCLs are traditionally classified clinically according to their age of onset. Variable late infantile NCL (vLINCL) is the most genetically heterogeneous subtype as it has been shown to be caused by mutations in at least six genes. We report on 5 patients of a consanguineous family who presented in early childhood with intractable seizures, severe cognitive and motor decline, behavioral impairment and progressive retinal degeneration. Disease course was severe; all patients were in a vegetative state by the second decade of life, and eventually die prematurely (except in one case). Ultrastructural studies of brain and rectal mucosa disclosed accumulation of storage material in various patterns including fingerprint, curvilinear, and granular osmiophilic deposits consistent with the diagnosis of NCL. Brain pathologic features from a living patient are first reported here and shed light on disease progression and pathogenesis. Using a combination of whole genome autozygosity mapping and candidate gene direct sequencing, we identified a mutation in MFSD8, c.472G>A (p.Gly158Ser), which was found to segregate with the disease phenotype in the family. This study underscores the importance of a combined clinic-molecular workup in NCLs and other neurodegenerative conditions., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

In the present study, we investigate the impact of a tightly bound water molecule on ligand binding in the S1 pocket of thrombin. The S1 pocket contains a deeply buried deprotonated aspartate residue (Asp189) that is, due to its charged state, well hydrated in the uncomplexed state. We systematically studied the importance of this water molecule by evaluating a series of ligands that contains pyridine-type P1 side chains that could potentially alter the binding properties of this water molecule. All of the pyridine derivatives retain the original hydration state albeit sometimes with a slight perturbance. In order to prevent a direct H-bond formation with Asp189, and to create a permanent positive charge on the P1 side chain that is positioned adjacent to the Asp189 carboxylate anion, we methylated the pyridine nitrogen. This methylation resulted in displacement of water but was accompanied by a loss in binding affinity. Quantum chemical calculations of the ligand solvation free energy showed that the positively charged methylpyridinium derivatives suffer a large penalty of desolvation upon binding. Consequently, they have a substantially less favorable enthalpy of binding. In addition to the ligand desolvation penalty, the hydration shell around Asp189 has to be overcome, which is achieved in nearly all pyridinium derivatives. Only for the ortho derivative is a partial population of a water next to Asp189 found. Possibly, the gain of electrostatic interactions between the charged P1 side chain and Asp189 helps to compensate for the desolvation penalty. In all uncharged pyridine derivatives, the solvation shell remains next to Asp189, partly mediating interactions between ligand and protein. In the case of the para-pyridine derivative, a strongly disordered cluster of water sites is observed between ligand and Asp189., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A congeneric series of benzamidine-type ligands with a central proline moiety and a terminal cycloalkyl group--linked by a secondary amine, ether, or methylene bridge--was synthesized as trypsin inhibitors. This series of inhibitors was investigated by isothermal titration calorimetry, crystal structure analysis in two crystal forms, and molecular dynamics simulations. Even though all of these congeneric ligands exhibited essentially the same affinity for trypsin, their binding profiles at the structural, dynamic, and thermodynamic levels are very distinct. The ligands display a pronounced enthalpy/entropy compensation that results in a nearly unchanged free energy of binding, even though individual enthalpy and entropy terms change significantly across the series. Crystal structures revealed that the secondary amine-linked analogs scatter over two distinct conformational families of binding modes that occupy either the inside or of the outside the protein's S3/S4 specificity pocket. In contrast, the ether-linked and methylene-linked ligands preferentially occupy the hydrophobic specificity pocket. This also explains why the latter ligands could only be crystallized in the conformationally restricting closed crystal form whereas the derivative with the highest residual mobility in the series escaped our attempts to crystallize it in the closed form; instead, a well-resolved structure could only be achieved in the open form with the ligand in disordered orientation. These distinct binding modes are supported by molecular dynamics simulations and correlate with the shifting enthalpic/entropic signatures of ligand binding. The examples demonstrate that, at the molecular level, binding modes and thermodynamic binding signatures can be very different even for closely related ligands. However, deviating binding profiles provide the opportunity to optimally address a given target., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of platelet α-granules resulting in typical gray platelets on peripheral smears. GPS is associated with a bleeding tendency, myelofibrosis, and splenomegaly. Reports on GPS are limited to case presentations. The causative gene and underlying pathophysiology are largely unknown. We present the results of molecular genetic analysis of 116 individuals including 25 GPS patients from 14 independent families as well as novel clinical data on the natural history of the disease. The mode of inheritance was autosomal recessive (AR) in 11 and indeterminate in 3 families. Using genome-wide linkage analysis, we mapped the AR-GPS gene to a 9.4-Mb interval on 3p21.1-3p22.1, containing 197 protein-coding genes. Sequencing of 1423 (69%) of the 2075 exons in the interval did not identify the GPS gene. Long-term follow-up data demonstrated the progressive nature of the thrombocytopenia and myelofibrosis of GPS resulting in fatal hemorrhages in some patients. We identified high serum vitamin B(12) as a consistent, novel finding in GPS. Chromosome 3p21.1-3p22.1 has not been previously linked to a platelet disorder; identification of the GPS gene will likely lead to the discovery of novel components of platelet organelle biogenesis. This study is registered at www.clinicaltrials.gov as NCT00069680 and NCT00369421.

The construction and performance characteristics of polymeric membrane electrodes based on two neutral ionophores, 2,2'-(1Z,1'Z)-(1E,1'E)-(1,2-phenylenebis(methan-1-yl-1-ylidene))bis(azaan-1-yl-1-ylidene)bis(methylene)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-ylidene)diphenol (L(1)) and 4,4'-(1E,1'E)-(butane-1,4-diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)dinaphthalen-1-ol (L(2)) for quantification of cadmium ions, are described. The influences of membrane compositions on the potentiometric response of the electrodes have been found to substantially improve the performance characteristics. The best performance was obtained with the electrode having a membrane composition (w/w) of (L(1)) (2.6%):PVC (31.6%):DOP (63.2%):NaTPB (2.6%). The proposed electrode exhibits Nernstian response in the concentration range 5.0 x 10(-9) to 1.0 x 10(-1)M Cd(2+) with limit of detection 3.1 x 10(-9), performs satisfactorily over wide pH range (2.0-8.5) with a fast response time (11s). The electrode has been found to work satisfactorily in partially non-aqueous media up to 40% (v/v) content of methanol, ethanol and acetonitrile and could be used for a period of 2.5 months. The analytical usefulness of the proposed electrode has been evaluated by its application in the determination of cadmium in cigarette samples. The practical utility of the membrane electrode has also been observed in the presence of surfactants.

Purpose: The Druze community is characterized by consanguinity and endogamy, and by reluctance to genetic testing and technological interventions for the prevention of birth defects. Multiple patients with four rare and severe inborn errors of metabolism cerebrotendinous xanthomatosis, prolidase deficiency, argininosuccinate lyase deficiency, and carbamyl phosphate synthetase I deficiency were identified in an isolated Druze village in northern Israel. The aims of this study were to identify couples at risk for four inherited diseases, and to prevent birth defects in a community presenting religious and cultural obstacles to genetic testing., Methods: A genetic screening and counseling program in a high-risk community., Results: The 1425 residents who attended group genetic counseling sessions between 2003 and 2007 consented to genetic testing. We identified 217 carriers for either one or two disease causing mutations. High carrier frequencies for cerebrotendinous xanthomatosis, prolidase deficiency, argininosuccinate lyase deficiency, and carbamyl phosphate synthetase I deficiency were identified as 1:11, 1:21, 1:41, and 1:95, respectively. Fifty-eight percent (125) of the carriers' spouses agreed to genetic counseling and testing. Ten couples at risk for affected offspring were identified and offered prenatal genetic counseling and diagnosis., Conclusions: The genetic screening program, the first of its kind reported in a Druze community, was well received. We expect this program to increase awareness of genetic counseling, to contribute to disease prevention, and to serve as a model for other isolated communities.

The potentiometric response characteristics of mercury ion-selective membrane electrodes based on 2-amino-6-purinethiol (I(1)) and 5-amino-1, 3, 4-thiadiazole-2-thiol (I(2)) were described. Ion selectivities were tested for various plasticizers, which were used as solvent mediators to incorporate the ionophores into the membrane. Effects of experimental parameters such as membrane composition, nature and amount of plasticizers and additives, pH and concentration of internal solution on the potential response of Hg(2+) electrodes were investigated. The best performance was obtained with the electrode having a membrane composition (w/w) of (I(1)) (3.17%): PVC (31.7%): DOP (dioctylpthalate) (63.4%): NaTPB (sodium tetraphenylborate) (1.58%). The proposed electrode reveals a Nernstian response over Hg(2+) ion in the concentration range of 7.0 x 10(-8)-1.0 x 10(-1) M with limit of detection 4.4 x 10(-8) M. The electrode shows good discrimination toward Hg(2+) ion with respect to most common cations. It shows a short response time (10s) for whole concentration range and can be used for 2 months without any considerable divergence in potentials. For evaluation of the analytical applicability, the electrode was used in the determination of Hg(2+) ion in different environmental and biological samples. The practical utility of the membrane electrode has also been observed in the presence of surfactants.

Poly(vinyl chloride) (PVC) based membranes containing 4-tert-butylcalix[4]arene (I) as an electroactive material along with anion excluder sodiumtetraphenylborate (NaTPB) and plasticizer tri-butylphosphate (TBP) have been developed to fabricate a new zinc-selective sensor. Out of various compositions, the best performance was exhibited by the membrane having I, NaTPB, TBP and PVC in the ratio 8:5:100:200 (w/w). The sensor works well in the concentration range 9.8 x 10(-6) to 1.0 x 10(-1) mol dm(-3) with a near-Nernstian slope of 28.0+/-1.0 mV/decade of activity. The detection limit is down to 5.0 x 10(-7) mol dm(-3). The working pH range of this sensor is 2.5-4.3 and it works well in partially non-aqueous medium up to 15% (v/v) (methanol, ethanol and acetone). It exhibits a fast response time of 30s and could be used for more than four months without any considerable change in response characteristics. It has excellent selectivity for Zn(II) over other mono-, bi- and trivalent cations which have been reported to cause interference in the working of other sensors. It has been successfully used as an indicator electrode in the potentiometric titration of Zn(II) against EDTA and also to estimate zinc ions in industrial waste waters.

Epidermolysis bullosa (EB) encompasses a large group of inherited blistering skin disorders caused by mutations in at least 10 genes. Numerous studies, mainly performed in European and US families with EB, have revealed a number of characteristic epidemiological and genetic features, which form the basis for current diagnostic and counseling strategies. However, little is currently known about the molecular epidemiology of EB in Middle East populations. In the present study, we assessed 55 EB families for pathogenic sequence alterations in the 10 genes known to be associated with EB. Our results show unique EB subtype distribution and patterns of inheritance in our cohort. We also failed to detect recurrent mutations frequently encountered in Europe and the US, and did not consistently observe genotype-phenotype correlations formerly established in Western populations. Thus, the molecular epidemiology of EB in the Middle East is significantly different from that previously delineated in Europe and the US. Our data raise the possibility that similar differences may also be found in other genetically heterogeneous groups of disorders, and indicate the need for population-specific diagnostic and management approaches.

Between March 1987 and March 1993 we used pulsed transthrombotic fibrinolysis to treat 58 symptomatic thrombotic occlusions of lower limb bypass grafts in 45 patients. There were 17 suprainguinal grafts and 28 infrainguinal grafts. Treatment consisted of pulsed infusion of fibrinolytic agents into the thrombus followed by continuous infusion using an electric pump. Minor percutaneous or surgical procedures were often associated. The mean delay to treatment was 7 days. The mean duration of treatment was 150 +/- 66 minutes. Immediate patency was achieved in 88% of cases with no significant difference between suprainguinal and infrainguinal grafts. The clinical success rate was 55%. Actuarial patency at 1 year was 54% +/- 11% for suprainguinal grafts and 26% +/- 7% for infrainguinal grafts. The probability of patency was much lower in patients whose grafts had been implanted within 3 months before occlusion and in patients in whom an adjuvant procedure had not been performed. This study demonstrates that, in cases not requiring immediate surgery, pulsed transthrombotic fibrinolysis can achieve durable patency by treating both the bypass and distal arterial network. This technique allows identification of lesions causing thrombosis and adaptation of treatment specifically to these lesions.

The methods used to titrate plasmatic haemoglobin, an analysis which is of great interest to cardiac surgery, must be very accurate because the levels are much lower than those found in whole blood. This work introduces a comparison between two methods: the ammoniacal water method and Cripps's differential method. After studying various criteria (repeatability, limit of detection, accuracy, reference values, stability of the reaction), and after studying the correlation between each method and the benzidin method, used as reference method, as well as the correlation between all of them, Cripp's method turns out to be the closest to the benzidin method, as well as being simpler, more accurate, more specific, and also easier to use than the ammoniacal water method, the only problem occurring at the stage of the preparation of the standard solution.

The antioxidant activity of ten spices commonly used in the formulation of a fermented meat sausage (Pastourma) were evaluated using a hemoglobin peroxidation procedure involving safflower oil in a water emulsion (10%). Clove followed by rose petals and allspice exhibited the highest antioxidant index when used in a dry form. In an aqueous-based microbiological broth, cloves again showed the highest antioxidant index followed by black pepper, ginger and rose petals. Generally anti-oxidant indices were higher in emulsions containing dry spice than in an aqueous based microbiological broth.