Kidney stones impose a large and increasing public health burden. Previous studies showed that hyponatremia is associated with an increased risk of osteoporosis and bone fractures, which are also known to be associated with kidney stones. However, the relation between hyponatremia and kidney stones is not known. To assess the relation between hyponatremia and kidney stones, we designed a matched case-control study by using the electronic health records of the MedStar Health system with more than 3.4 million unique patient records as of March 2016. Data were extracted for clinical factors of patients with kidney stones (cases) and those without kidney stones (controls). Cases  and controls  were matched at a 1:1 ratio for age, sex, race, and the duration of encounter window. Case and control exposures for each of the hyponatremia variables were defined by serum sodium laboratory measurements reported within the encounter windows, and divided into 3 categories: prior hyponatremia, recent hyponatremia, and persistent hyponatremia. In the final conditional logistic models adjusted for potential confounders, the risk of kidney stones significantly increased in both recent and persistent hyponatremia categories: prior hyponatremia odds ratio (OR) 0.93 ; recent hyponatremia OR 2.02 ; persistent hyponatremia OR 6.25 . In conclusion, chronic persistent hyponatremia is a significant and clinically important risk factor for kidney stones in patients in the U.S. Approximately 11% of men and 7% of women in the United States (U.S.) will develop at least one kidney stone (KS) during their lifetime , thus th2+) excretion, which has been suggested in an animal model of hyponatremia-induced osteoporosis ) in the database, any concentration of serum [Na+] with a same-day glucose greater than 200 mg/dL, and cystic kidney disease by using ICD-9 codes, and intrinsic kidney diseases including chronic kidney disease (CKD) by using ICD-9 and/or -10 codes, were excluded from the analysis  hyperglycemia is known to affect serum [Na+] concentration  laboratory measurements reported within the encounter windows as follows: 1) prior hyponatremia group, 2) recent hyponatremia group, and 3) persistent hyponatremia group. Exposure to prior hyponatremia was defined as having at least one serum [Na+] measurement of less than 135 mEq/L within the encounter window. Based on our previous study [+] of less than 135 mEq/L within 30 days before the end of the encounter window. Patients categorized as having only recent hyponatremia had a hyponatremic value within 30 days before the close of the encounter window, may or may not have had a second [Na+] on record, and had no hyponatremic value at an interval 1 year or greater from the close of the encounter window. Exposure to persistent hyponatremia was defined by meeting criteria for having both at least one serum [Na+] of less than 135 mEq/L within 30 days before the end of the encounter window  and at least two serum [Na+] measurements of less than 135 mEq/L at least 1 year apart until 30 days before the end of the encounter window during the encounter window  and 95% confidence intervals (CIs) were presented to show the changes in the odds of experiencing KS in response to clinical and demographic variables of interest. Multiple covariables were included in the final conditional logistic models, for matched case-control design to estimate the change in the risk of KS in the form of the OR, which measures the change in the odds of experiencing the outcome (KS), given the categories of an exposure variable. Statistical significance was defined as P < 0.05. Analyses were performed using SAS version 9.3 (SAS Institute) and Stata version 14 (StataCorp).In total, 20,199 KS cases and 20,199 controls were matched using a 1:1 ratio for age, sex, race, and the duration of encounter window , as shown in Unadjusted analyses confirmed an increased risk of KS among patients with the known risk factors . UnadjusResults of the conditional multivariable logistic regression models for KS are presented in The exclusion of the thiazide use from the model did not change the results even though it may be a potential confounder for the relationship between hyponatremia  and KS , 20 S3 . We also2+ transport, both of which would potentiate the risk for CaKS via increased urinary Ca2+ excretion. Asplin et al. suggested an increased risk for bone loss in individuals with KS, primarily those with hypercalciuria, possibly associated with enhanced bone turnover [Thorleifsson et al. found that variants in CLDN14 (claudin 14) gene, a gene expressed in the kidney and involved in regulation of paracellular permeability at epithelial tight junctions, were associated with both KS and reduced BMD [2+ excretion.Following the first report of a correlation between BMD and KS by Alhava et al. , many stturnover . Thorleiuced BMD . The pri2+ excretion, which has been demonstrated in an animal model of hyponatremia [In addition to the above data on KS, many recent studies have indicated that hyponatremia is associated with osteoporosis and bone fractures , 29–35. natremia . Thus, i2+, but also for sodium (Na+) [+ with the extracellular fluid within a relatively short time period [+ signaling mechanisms in osteoclasts that may serve to mobilize Na+ from the bone as a Na+-rich reservoir during hyponatremia, thereby leading to resorptive osteoporosis in patients with SIADH [2+ is filtered at the glomerulus, and more than 95% of the filtered load is ultimately reabsorbed. In the proximal convoluted tubule and the loop of Henle, Ca2+ is absorbed in proportion to Na+ and water, and urinary Ca2+ excretion therefore increases in relation to urinary Na+ excretion [2+ excretion and urine volume, i.e., the urine Ca2+ concentration [In 1954, Bergstrom et al. first reported that the bone is a reservoir not only for Caum (Na+) . It is ae period , 42. A pth SIADH . Ca2+ isxcretion , 44. Addxcretion . Coe et ntration . Supersantration , 48.2+ (FECa) increased in patients with SIADH. During hyponatremia, FECa was significantly higher than in post-correction hyponatremia  [2+ and Na+ from the bone to blood thereby increasing urinary Ca2+ excretion.There are several highly suggestive clinical studies supporting the above studies. Decaux et al. demonstrated that the fractional excretion of Cactively) . AlthougIn our study, any “prior” hyponatremia was not significantly associated with KS by multivariable analysis. This is not surprising, since hyponatremia in hospitalized patients is often due to transient causes and does not persist chronically. Both “recent” hyponatremia and “persistent” hyponatremia were associated with a significantly increased risk of KS. However, the “persistent” hyponatremia group showed a much higher risk (OR 6.254 vs. 2.018). Although we could neither determine the causes of hyponatremia nor assess the severity of hyponatremia in this epidemiological study, nonetheless from our data it would appear that longer periods of hyponatremia might confer a higher risk of CaKS development regardless of the etiology of the hyponatremia. In the conditional logistic models used in our study, we utilized ORs for interpretation of significant effects, since these represented the estimated effect of hyponatremia on the group of KS cases compared to the controls. Interestingly, liver cirrhosis also significantly increased a risk for KS . Cirrhos2+, Na+, oxalate, citrate, and other modifying factors that influence the development of KS; 2) we could not assess patients’ volume status and the causes of hyponatremia in each patient; 3) we could not assess dietary factors , climate factors, family history, genetic factors, and bacterial contribution in each patient; 4) the result that persistent hyponatremia is associated with an OR of 6.2 of KS is based on a very small group size; 5) the encounter duration of the study subjects was highly variable; 6) we could not determine whether patients in each hyponatremia category showed continuous hyponatremia through the designated period; 7) it is possible that patients with hyponatremia might have undergone a higher number of imaging examinations such as ultrasound or computed tomography scans to detect the source of their condition or due to the higher burden of comorbidities, and this in turn could have increased the detection rate of KS; however we would not be able to obtain this information for each patient in the dataset because imaging data are not part of our searchable EMR databases, and additionally, some imaging studies may have been performed outside of our health system; 8) use of ICD codes for KS does not allow a determination of how the KS were discovered, and neither KS events nor comorbidities were validated through chart review, since this was not feasible in a matched case-control study using a very large EMR of almost 3.5 million charts; 9) it is possible that we did not exclude patients with CKD appropriately because ICD codes for CKD are less sensitive than serum creatinine or estimated glomerular filtration rate; and, 10) it is possible that we did not exclude all the patients with uric acid KS appropriately by ICD codes. Additionally, we did not exclude patients with struvite KS and cystine KS because there were no ICD codes for these diagnoses. As a result, we cannot be certain whether we selected only patients with CaKS. However, given the large number of patients included in the analysis based on the over 3.4 million patients from in the Maryland, Virginia, and greater Washington in the U.S., and the diversity of populations within clinics and hospitals, we are confident that our results are generalizable and robust for the occurrence of CaKS.The current analysis has several potential limitations that relate to the retrospective nature of the study: 1) we could not assess urine data, including CaIn conclusion, this is the first study to demonstrate an association between hyponatremia and KS in a large U.S. health system. In particular, our analysis suggests that longer periods of hyponatremia may increase the risk of CaKS.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S1 File(DTA)Click here for additional data file.S2 File(DO)Click here for additional data file.


Over the last decade, major technical developments such as larger axialcoverage (from 2 cm to 16 cm) and improved temporal resolution, have enabled CCTA tobecome by far the most accurate non-invasive imaging method for diagnosis of obstructiveCAD, with sensitivity and specificity of approximately 95% and 90%,respectively.2 Then the cost-effectiveness wave camewith societies rightfully demanding proof that CCTA offered more value at an acceptablecost compared to other imaging modalities, and CCTA once again proved to be morecost-effective than other modalities.3Although one hardly finds cost-effectiveness studies comparing nuclear scans with ECGtreadmill tests, providing better diagnosis performance is not enough anymore. Morerecently, this strategy has even been put into challenge in large randomized clinicaltrials comparing CCTA with the standard of care in the investigation of suspected CADboth in the acute and in the outpatient settings.4-9Then CCTA was burdened with the accusation of exposing patients to radiation doses sohigh, that warranted some society guidelines to specifically point this out and limitits use. At that time, CCTA exposed patients to doses ranging from 20 to 25 mSV, whiletriphasic abdomen CT exposed patients to 30 to 40 mSv and scintigraphic myocardialperfusion studies with Thallium used up to 40 mSv. In 2018, radiation exposure from CCTAdropped to well below 5 mSv , a fractionof the dose used in myocardial perfusion studies with MIBI tetrophosmin.But then CCTA adoption had to face another hurdle. People started demanding that CCTA, adiagnostic study, should demonstrate that it would alter clinical outcomes. Let’s stophere for a moment: a diagnostic study makes the diagnosis. It does not provide the cure,but it could lead to changes in therapy which could eventually lead to improvedoutcomes. As such, although a CCTA study is not therapeutic, it could guide and informtherapeutic decisions. Measuring blood pressure was never proven to alter clinicaloutcomes, treatment did. The same with cholesterol measurements, ischemia testing andresting ECG recordings. And yet, everybody has always rightly assumed that diagnosis isa fundamental part of sound medical practice and an angular stone of clinicalmanagement. Cardiovascular disease, predominantly in the form of atherosclerosis andhypertension, starts as early as 30 or 40 years, silently progressing across the yearsto finally kill around one-third of the adult population in the developed world. Theconventional strategy “to sit and wait” until patients present with symptoms certainlymisses the golden period of the early disease, when treatment is much more efficient andless expensive. Early detection and diagnosis of atherosclerosis using CCTA, might leadto significant downstream changes which could consequently improve outcomes.6 The potential impact of those findingshave recently been enhanced by the publication of the 5 years follow up data of theSCOT-HEART trial.5Despite those initial criticisms and the sceptical view of the use of CCTA in theinvestigation of suspected CAD, the evidence supporting its clinical use has beensteadily increasing over the years. From the initial studies defining the technicalfeasibility and accuracy of CCTA, followed by the development of techniques aimed atreducing radiation dose and improving imaging quality, CCTA has evolved to be part ofthe routine armamentarium for the investigation of suspected CAD. More recent evidencehas led a wide variety of interpretations, as CCTA lead to an increase in the diagnosisof CAD, accompanied by a 31% reduction in the rate of myocardial infarction, while alsobeing associated with a modest increase in the use of invasive coronary angiography(ICA) and revascularization, according to a recent meta-analysis.9 the authors demonstratedthat the use of CCTA led to change in the initial clinical diagnosis in more than one inevery four patients. It is particularly interesting to note that this was driven by anincrease in the prevalence and certainty for the diagnosis of CAD overall, but also byan increase in certainty with a decrease in the prevalence of angina due to CAD. Thosechanges in diagnosis also led to meaningful changes in the management of thispopulation.The SCOT-HEART study randomized more than 4,000 individuals with symptoms suggestive ofCAD to usual care (UC), which includes the use of stress treadmill testing or nuclearperfusion studies, versus UC combined with CCTA. In their initial report in2015,When compared to the UC arm, the addition of CCTA resulted in a changed in the use ofadditional testing in 15% of the population (vs. 1% in the UC), and the use ofmedications in 23%  for both. It is particularlyimportant to dissect those changes to appropriately understand the impact of CCTA on theinitial management of this population. The additional information provided by the CCTAimproved diagnostic certainty both due to the increase and decrease in the likelihood ofdisease after a positive and negative CCTA result, respectively. Thus, for thedownstream use of diagnostic testing in the UC group, upon the 6-week return visit,there were overall 6 additional stress imaging tests, 8 ICAs performed and only one ICAcancelled. On the other hand, in the UC + CCTA group there were 121 stress imagingtests, 29 ICA cancelled, 5 additional stress imaging tests and 94 ICA tests performed.Collectively, this suggests that these differences in downstream additional testing werethe result of additional information provided by the CCTA.A similar pattern of change was also noted on the use of medications in both groups. Inthe UC there was minimal cancellation of preventive and antianginal medication , but a significant increase in its use . On the other hand, a much larger shift in the use ofmedications was noted in the UC + CCTA arm, in both directions and both for preventiveand antianginal medications. Those medications were started in 14.1% and 4.0%individuals, respectively, and stopped in 3.7% and 5.4% individuals, respectively. It isalso worth noting that those results might underestimate the true changes in management,as the authors did not capture changes in medication dose/intensity, nor were anydocumentation of changes in non-pharmacological therapy available. Importantly, thechanges in revascularization did not reach statistical significance, though they werenumerically more frequent in the UC + coronary CTA arm .It is important to highlight that even this extent of detail in medication change duringthe course of the SCOT-HEART study still overly simplifies its potential impact in eventreduction. The actual change in therapy cannot be fully appreciated simple by countingthe number of individuals who underwent changes in prescription without qualitativeinformation on this population. Individuals in whom therapy was reduced were, ingeneral, individuals with no or mild coronary atherosclerosis, whereas individuals inwhom therapy was increased were individuals with more extensive and severe CAD. Thus,therapy was targeted and individuals more likely to derive benefit.10Despite those changes in management, the initial publication of SCOT-HEART left some gapsin the understanding of the impact of those findings, as both groups had similarimprovement in the angina frequency and stability after 6 weeks, and the changes in hardoutcomes did not reach formal statistical significance despite the almost 40% reductionin events noted in the study. Those results were questioned even further as theconcurrent U.S. based study PROMISE, published simultaneously, showed no difference inoutcomes in individuals with suspected CAD investigated with coronary CTA vs. UC, whichin the U.S. was mostly based on imaging stress testing. However, several differencesbetween the two studies justify differences in the findings, from differences in patientpopulation, age, sex, symptoms, as well as pre-test probability of disease.Additionally, differences in medication changes during the follow up were noted. Whilecare after testing was left at the discretion of the attending physician in both trials,SCOT-HEART had a structured protocol to recommend preventive medical therapy toindividuals with non-obstructive CAD on the coronary CTA, whereas PROMISE did not makeany recommendations.5,11In both studies an increase in revascularization was also noted, and the Danish studyalso demonstrated that a concurrent increase in the use of preventive therapy (aspirinand statin) was noted.The trend in outcomes reduction documented in SCOT-HEART was further replicated in ameta-analysis and in a large Danish registry.12 In the longer term follow up of the same cohort ofpatients, several important differences need to be highlighted. First, with the largernumber of events, there is a higher precision on the estimates of benefit, and a 40%reduction in the rate of coronary heart disease death or myocardial infarction (p <0.004) was now documented. A second important finding of the study is the fact that theinitial increase in the rate of ICA and revascularizations was no longer seen at 5years. While the rate of ICA was 23.6% in the UC + coronary CTA arm, it was 24.2% in theUC arm . This fact occurred asthe UC arm had higher rates of ICA and revascularizations after the initial evaluation.Using a landmark analysis with a starting point at 12 months, the UC + CCTA arm had a30% reduction in the rate of ICA through 5 years and a 40% reduction in laterevascularizations when compared to UC.Yet, none of those results led to nearly as much repercussion on the topic as the recentpublication of the 5-year follow up of the SCOT-HEART.Another relevant aspect of SCOT-HEART is that approximately half of the myocardialinfarctions occurred in individuals without the obstructive coronary disease. Althoughit is well known that nonobstructive plaques may be responsible for a significantproportion of those events, no study had provided data on its prevalence in lower riskstable individuals until these recent CCTA studies. This finding highlights the need toincorporate the investigation of nonobstructive CAD, regardless of the presence ofischemia (and perhaps symptoms), as those findings can have significant clinical impactand should prompt pharmacological and non-pharmacological interventions.13 The findings fromSCOT-HEART, along with the results of Danish registry,11 as well as cost-effectiveness analyses14 all support the NICE guidelines in itsrecommendation. Together they provide a consistent and sound body of evidence tochallenge the current clinical practice recommendations. As a medical community, we needto embrace these changes and to challenge ourselves whether there is any rationale notto consider CCTA as a first line strategy for the investigation of individuals withsuspected obstructive CAD.The recent NICE guidelines from the United Kingdom delineates CCTA as a first line testfor the investigation of suspected CAD, regardless of the pretest probability ofdisease.


Operating in series, they constitute a soluble electron transport chain of one-electron transfers between FeS clusters. They fulfil the same function—redox balance—served by two electron-transfers in the NADH- and O2-dependent respiratory chains of mitochondria. Although they possess O2-sensitive FeS clusters, PFO, Fd and [Fe]-HYD are also present among numerous algae that produce O2. The evolutionary persistence of these enzymes among eukaryotic aerobes is traditionally explained as adaptation to facultative anaerobic growth. Here, we show that algae express enzymes of anaerobic energy metabolism at ambient O2 levels (21% v/v), Chlamydomonas reinhardtii expresses them with diurnal regulation. High O2 environments arose on Earth only approximately 450 million years ago. Gene presence/absence and gene expression data indicate that during the transition to high O2 environments and terrestrialization, diverse algal lineages retained enzymes of Fd-dependent one-electron-based redox balance, while the land plant and land animal lineages underwent irreversible specialization to redox balance involving the O2-insensitive two-electron carrier NADH.Pyruvate : ferredoxin oxidoreductase (PFO) and iron only hydrogenase ([Fe]-HYD) are common enzymes among eukaryotic microbes that inhabit anaerobic niches. Their function is to maintain redox balance by donating electrons from food oxidation via ferredoxin (Fd) to protons, generating H From about 2.7–2.5 billion years ago onwards, cyanobacteria started using H2O as the electron donor for a photosynthetic electron transport chain consisting of two photosystems connected in series -HYD, which donates the electrons to protons, generating H2 gas that leaves the cell as a waste product. Fdred generated by PFO is a low potential one-electron carrier (Fdox/FdredE0 = −420 mV) that can readily transfer a single electron to O2 generating the superoxide radical, O2–·-HYD are irreversibly inactivated by O2. Accordingly, eukaryotes that employ PFO and [Fe]-HYD in energy metabolism typically inhabit low oxygen environments, with their possession of these enzymes being interpreted as niche specialization [The enzymatic backbone of redox balance in anaerobic energy metabolism in unicellular eukaryotes is pyruvate : ferredoxin oxidoreductase (PFO) and [Fe-Fe] hydrogenase ([Fe]-HYD), which were first described for eukaryotes in studies of carbon and energy metabolism in trichomonad hydrogenosomes . The ecocal, O2–·,23 and rlization ,25.2. Their presence in algae is known to enable facultative anaerobic growth in low oxygen environments -HYD and a larger suite of enzymes associated with anaerobic energy metabolism are also present in algae ,26–28, pronments ,28, and ronments ,30, in tronments . However2.2-producing enzymatic activity in several eukaryotic lineages and has assumed different functions. The [Fe]-HYD homologues IOP1/NAR1 repress the hypoxia-inducible factor-1α subunit (HIF1-α) in humans -HYD enzymes can be trimeric , with 24urcation , affordisubunits , which aoduction , which wion . In all algae studied, including algae with secondary plastids (a), we were able to detect the expression of at least a subset of the corresponding genes. It is well known that other algae such as Vitrella brassicaformis and Chromera velia encode a set of anaerobic enzymes that is as complete as that of C. reinhardtii -HYD expression, typically in the context of biohydrogen applications -HYD are localized in the plastid -HYD and in response to the ROS generating potential PFO of Fdred. Once on land, both the plant and animal lineages were subsequently confronted again with hypoxic environments in adaptations to aquatic environments. The corresponding adaptations did not, however, involve gene acquisitions via LGT, merely novel expression regulation for NADH-dependent enzymes involved in redox balance during hypoxic response. In plants, these responses include mainly ethanol fermentations in waterlogged roots [The transition to life on land approximately 450 Ma marked the advent of life in very high Onditions ,10. Plannditions . Massiveed roots ,69,70. Ied roots ,72, and ed roots ,74. In aed roots  to rhodoed roots . The lanSynechocystis [2 in the transition to life on land [red, the stromal levels of which are monitored in some photosynthetic lineages by the flavodiiron (FLV) proteins [2 levels. Algae retained the Fd-dependent pathway for Fd-dependent, one-electron-based redox balance in plastids, not for anaerobic growth.The retention of the chloroplast encoded NADH dehydrogenase complex (cpNDH) specifically in the land plant lineage  is notewhocystis  and in lhocystis ,79. Amonhocystis . Their rhocystis ,68, becahocystis . Land plhocystis  and a cyhocystis  to plast on land . Land plproteins . Our fin5.(a)e-value of less than 10−10 were considered and provided in the electronic supplementary material, table S2. All the sequences that were used to identify the EPCs and perform the BLAST search are provided in the electronic supplementary material, file S1 along with the BLAST hits.As part of a larger study , sequenc(b)™ reagent  or the Spectrum™ Plant Total RNA Kit  according to the manufacturer's protocols. Then, samples were DNase treated  and RNA-Seq was performed at the Beijing Genome Institute  using an Illumina HiSeq2000 resulting in 150 bp paired-end reads. For each sample, three individual runs were performed and pooled. Raw reads were subjected to several cleaning steps. First, adapter sequences as well as reads containing more than 5% of unknown nucleotides or more than 20% of nucleotides with quality scores less than 10 were removed. Further, reads were processed using Trimmomatic (v. 0.35) [rinseq-lite (v. 0.20.4) [rinity (v. 2.2.0) [ransdecoder (v. 3.0.1) (https://github.com/TransDecoder/TransDecoder/wiki). These ORFs were used for a BLAST with an identity cut-off of 30% against the genome of the respective organisms to verify their presence in the genome and to remove possible contaminations. Transcriptomes are available via the Sequence Read Archive of NCBI (https://www.ncbi.nlm.nih.gov/sra) with the accession number PRJNA509798.All algae were grown in their respective media (see SAG Göttingen or ncma.bigelow.org) in aerated flasks under controlled conditions at 22°C and illuminated with 50 µE under a 12L : 12D cycle. RNA was isolated from cells growing in the exponential phase and at 6 h into the day and 6 h into the night. RNA was isolated using either Trizolv. 0.35)  by remov 0.20.4) . Finally. 2.2.0)  and resu


The presentation of Kaposi sarcoma is divided into four known clinical subtypes. In this case report we describe classic Kaposi sarcoma in an African-American heterosexual, diabetic, seronegative human immunodeficiency virus male. Classic Kaposi sarcoma is rare in this patient demographic and can be easily misdiagnosed.The patient presented with a lesion between the fourth and fifth digits of his right foot which was initially diagnosed as a diabetic foot ulcer. Despite local wound care, the lesion did not resolve. A shave biopsy was performed and histopathology findings were consistent with classic Kaposi sarcoma.The patient tolerated local radiotherapy well and had complete resolution of his pedal lesion. There have been emerging associations between diabetes and Kaposi sarcoma. As such, clinicians should have a low threshold when considering the biopsy of suspicious pedal lesions in patients with diabetes. The utilization of appropriate biopsy technique may lead to the diagnosis of classic KS tumors in populations outside of the current four widely accepted clinical subtypes. Classic KS, typically benign and mostly limited to the hands and the feet, is seen primarily in elderly men of Eastern European and Mediterranean origin [Endemic or African KS is most commonly seen in indigenous Sub-Saharan Africans and is independent of the human immunodeficiency virus (HIV) [Iatrogenic KS is associated with recipients of organ transplants and patients undergoing immunosuppression therapy [Epidemic or acquired immune deficiency syndrome (AIDS) KS is the most common tumor seen in people infected with HIV. This subtype is most frequently described in HIV seropositive homosexual and bisexual men [Kaposi sarcoma (KS) is a vascular tumor caused by the proliferation of spindle cells in the endothelium of blood vessels . In the n origin . Endemicus (HIV) . Iatroge therapy . Epidemixual men , 5. Eachxual men . We presAn 80-year-old African-American male presented to the University of Michigan Hospital and Health Systems Comprehensive Wound Center for ongoing care of a painful right foot fifth digit wound. He first noticed the lesion after stubbing the digit 2 months prior. He presented to his primary care doctor 1 month after the injury and the lesion was diagnosed as a diabetic foot ulcer (DFU). The lesion improved minimally with local wound care. Due to stagnation of the suspected DFU the patient presented to the wound center for further care. Upon initial wound center presentation, a granulomatous mass was noted to the medial aspect of the right fifth digit (Fig. The patient’s past medical history was significant for type 2 diabetes mellitus T2DM, hypertension, hyperlipidemia, asthma, and dementia. He denied a family history of skin lesions and cancer. He did not take any immunosuppressive medication. The patient was a lifelong non-smoker and denied alcohol and illicit drug use. He was married, heterosexual and monogamous. At the time of presentation his last recorded hemoglobin A1c was 6.1%. Clinical examination revealed palpable pedal pulses with triphasic flow to the bilateral dorsalis pedis artery and posterior tibialis artery. His right hallux toe pressure was 126 mmHg and his left hallux toe pressure was 184 mmHg. He had diminished protective sensation, 2 out of 4 sites bilaterally, as tested with 10-g 5.07 Semmes-Weinstein monofilament as per American Diabetes Association guidelines [After obtaining written informed consent a #15 blade was used to perform a shave biopsy of both the right fifth digit proximal and distal papules. The two specimens were labeled appropriately and sent separately to the University of Michigan Hospital and Health Systems pathology laboratory for assessment. The pathology report identified the specimen obtained from the distal papule as the superficial aspect of a hemorrhagic vascular lesion. The specimen from the proximal papule was identified as Kaposi sarcoma, nodular stage, transected at the deep margin. Hematoxylin and eosin stain demonstrated dermal nodules with haphazard spindle cell proliferation of endothelial cells forming vascular spaces which is diagnostic of classic KS Fig. . The tumAfter the resulting classic KS diagnosis, the patient was referred to the Surgical Oncology Clinic at the University of Michigan Hospital and Health Systems. He underwent a series of blood tests to assess for underlying immunosuppression including HIV testing and a complete blood count with platelet and differential. He was determined to be HIV seronegative without any other clinical findings of immunosuppression. His case was reviewed by the University of Michigan Sarcoma Medical Oncology Department as well as the Multidisciplinary Sarcoma Tumor Board. The consensus of the combined board was local therapy with radiation without surgical intervention. The patient underwent 30 Gy of radiation in 10 fractions directed to the right foot fifth digit. The patient tolerated radiotherapy well and upon finishing his course of therapy, the KS lesion to the right foot had completely resolved. Upon a 10 month follow-up from initiation of radiation, the patient was disease free.KS is rare in the general population. The disease represents about 1% of all diagnosed cancers worldwide . The casThough the patient in our case study had peripheral neuropathy, classic KS lesions can occur in diabetic patients independent of neuropathy or ischemia. The lesions are usually on the soles and arches of the foot . Pedal iThe case presented serves as an example of the necessity to biopsy pedal lesions that do not respond to standard therapy. In addition to DFUs classic KS lesions can mimic other conditions such as pyogenic granuloma, melanoma, melanocytic nevi, arteriovenous malformations or severe stasis dermatitis . The acrIn general patients with diabetes are more susceptible to pathogen infection and tumor growth , 20. SevThe patient’s demographic designation is another interesting component of this case. As stated previously, classic KS is most commonly seen in elderly Mediterranean men. In recent years KS in African-American males has been linked to an HIV seropositive status . AfricanThe patient did report that his right fifth digit lesion was precipitated by stubbing the digit. Interestingly, pedal trauma induced KS has been discussed in the literature. Berkowitz et al. described a case in which a 48-year-old HIV positive man developed KS of the right hallux after dropping a piece of wood on the digit . The autIn clinical practice punch biopsy is the most accepted biopsy technique for definitive diagnosis of a classic KS. Punch biopsy provides a full-thickness specimen, which allows for adequate depth for proper diagnosis , 33. In Treatment for KS depends on the type and number of lesions, the extent of the disease, as well as the overall patient health. . There iThis case is atypical as it shows classic KS in a heterosexual, HIV-seronegative African-American male. Though KS is common in indigenous Africans, classic KS has been described as rare in the American black heterosexual and HIV-seronegative population. Growing literature suggests an association between diabetes and KS, though the specifics of the association are unclear. Given the current perceived rareness of KS in some populations, the clinician should be astute when examining suspicious pedal lesions in patients with diabetes to avoid misdiagnoses and delayed treatment.


To report our experience with incarcerated femoral hernia procedure, which allows laparotomy through same inguinal skin incision, inspection and resection of compromised bowel, and preperitoneal tension-free transabdominal repair with Ventralex™ Hernia Patch. n = 3) or for inspection of viability (n = 2).  The suprainguinal laparotomy was performed via same groin incision without compromising iliopubic tract. The femoral ring was sealed with Ventralex™ Hernia Patch pulled through the abdominal cavity and secured outside. Five consecutive patients diagnosed with incarcerated femoral hernias were operated. All of them required laparotomy, either for bowel resection ( All patients tolerated the procedure well. There were no wound or mesh infections, incisional hernias, or recurrences during follow-up.  Our easy-to-master operative approach to incarcerated femoral hernia allows easy access to abdominal cavity through same groin incision without compromising iliopubic tract or midline laparotomy. Reduction of incarcerated bowel and its inspection and resection can be safely performed. The femoral ring defect can be effectively obliterated with Ventralex™ Hernia Patch. Femoral hernias are less frequently encountered in general surgical practice than other types of primary groin hernias. They comprise less than five percent of all inguinal hernias. Because of its anatomically complex surrounding, challenging repair options, and lack of experience, it has been coined “the bête noire of hernias” , 2. MoreYoung surgeons fear femoral hernia not only because of their lack of experience with this type of a hernia but also because of numerous horror stories told them by their senior colleagues about this beast. Nevertheless, most of us approach incarcerated femoral hernia with some degree of apprehension.We would like to describe incarcerated femoral hernia procedure, utilizing novel technique which allows small laparotomy through same skin incision, inspection and resection of compromised bowel, and durable tension-free transabdominal repair with Ventralex™ Hernia Patch.The patient is placed in supine position, and after induction of general anesthesia, the patient was prepped and draped in regular surgical fashion. The oblique incision is made slightly above the inguinal ligament and carried medially to the pubic tubercle . This inThe procedure is performed only when laparotomy is needed for resection or viability assessment. The skin incision is undermined upwards to expose the aponeurosis of external oblique muscle 4–5 cm above inguinal ligament. The aponeurosis is divided transversely or obliquely above the inguinal canal. Muscle-splitting gridiron-type incision is made to enter the abdominal cavity. This approach allows 4–6 cm laparotomy incision. The incarcerated bowel is then pulled to the abdominal cavity and eviscerated for viability assessment .We try to avoid violation of iliopubic tract during hernia gate incision. The femoral ring is released by incision of a small portion of inguinal ligament in the cranial direction and/or the lacunar ligament of Gimbernat, just to ensure appropriate relaxation of the hernia gate for the release of the strangulated bowel.If the incarcerated bowel loop is undoubtedly nonviable, it may be resected with linear stapler first and then the stumps are pushed back to the abdominal cavity and retrieved through the laparotomy incision.This suprainguinal laparotomy allows enough room for manipulation with incarcerated bowel, viability assessment, resection, anastomosis, and subsequent hernia repair.The repair of the femoral ring opening is performed from the abdominal cavity. Long Kelly clamp is passed from outside through the femoral canal to the abdominal cavity. Ventralex™ Hernia Patch straps are grasped and pulled through the femoral canal until the disc of the patch is tightly tugged against the pelvic wall. This maneuver not only allows complete obliteration of the hernia opening but also forms a wide intraperitoneal coverage of the entire myopectineal orifice of Fruchaud . The strThe suprainguinal laparotomy is closed by approximation of muscle and fascia.The first author of this paper (DA) used this technique since 2007, in 5 consecutive patients, three males and two females. Short-term follow-up was performed at regular clinic visits up to three months postoperatively. Long-term follow-up was performed with the universal electronic database system at the time of manuscript preparation.In three patients, incarcerated small bowel was reduced back to the abdominal cavity through the suprainguinal laparotomy and then resected. In one patient, ischemic small bowel was resected at the incarceration site with a linear stapler and its stumps are retrieved through the suprainguinal laparotomy and then anastomosed. In one patient, the incarcerated bowel regained its vitality after being released into the abdominal cavity. No recurrences, mesh, or wound infections were observed.Incarcerated femoral hernia poses several distinctive surgical challenges. Its treacherous anatomy is explained by intricacy of the femoral inlet, which creates a rigid circle, limited by the pubic crest and Cooper's ligament posteriorly, the inguinal ligament anteriorly, the lacunar ligament medially, and the femoral vein laterally. This tense environment around the hernia neck creates limited options for hernia gate incision and further exposure of the hernia content to allow safe inspection and resection of the incarcerated bowel. To overcome these obstacles, several techniques are generally used. Wide incision of the iliopubic tract can achieve a good exposure for bowel inspection and resection. But this method creates a large defect in the myopectineal orifice with inguinal floor violation, which is rather difficult to repair because of the flimsy tissues in the groin area and loss of natural support of intact iliopubic tract. If the bowel viability is put in question or resection is required, midline laparotomy or laparoscopy is generally employed for viability assessment and resection of the bowel. Emergency surgery for incarcerated femoral hernia has been associated with up to 25% complication rate . The mosThe Ventralex™ Hernia Patch is a self-expanding polypropylene and EPTFE (expanded polytetrafluoroethylene) patch that allows for an intra-abdominal retrofascial placement through relatively small incisions without the need of extensive lateral dissection. These composite polypropylene/EPTFE hernia patches have been proved to be an effective solution for small umbilical, epigastric, and ventral hernias with good long-term results and low recurrence rates –13.In this article, we describe another option to approach incarcerated femoral hernia, utilizing one skin incision for both hernia sac exploration, suprainguinal laparotomy for bowel viability assessment, and/or resection. We perform limited incision of the hernia gate just to allow its relaxation for relief of strangulation and content inspection. Furthermore, Ventralex™ Hernia Patch pulled from within the abdominal cavity and lodges in an extremely favorable preperitoneal position obliterating the entire myopectineal orifice. We believe that this procedure offers a simple option for dealing with incarcerated femoral hernias.


Interactions between hyaluronan (A-) and phospholipids play a key role in many systems in the human body. One example is the articular cartilage system, where the synergistic effect of such interactions supports nanoscale lubrication. A molecular dynamics simulation has been performed to understand the process of formation of hydrogen bonds inside the hyaluronan network, both in the presence and absence of phospholipids. Additionally, the effect of the molecular mass of (A-) was analyzed. The main finding of this work is a robust demonstration of the optimal parameters  influencing the facilitated lubrication mechanism of the articular cartilage system. Simulation results show that the presence of phospholipids has the greatest influence on hyaluronan at low molecular mass. We also show the specific sites of H-bonding between chains. Simulation results can help to understand how hyaluronan and phospholipids interact at several levels of articular cartilage system functioning. Surface active phospholipids play a vital role in biologic tissue systems, in large part due to an amphiphilic nature that allows for varied structural properties. In synovial joint organ systems, a surface active phospholipid layer (SAPL) covers normal articular surfaces in an oligolamellar structural formation ,2,3,4,5.During normal functioning, the SAPL serves as a sacrificial perturbation layer, whereby it can reform by self-assembly mechanisms after dissipation of incipient perturbation loads. In pathological synovial fluid, the hyaluronan structure changes ,21,22 toN-acetyl hexosamine ring contribute to chain stiffness [As has been presented in several studies, to some extent, the flexibility of hyaluronan chains in solution is determined by the restricted rotation about the various glycosidic linkages . On the tiffness   moieties between hyaluronan with molecular weights of 10, 40, and 160 kDa and phospholipid were performed.The purpose of this study was to evaluate molecular interactions by hydrogen bonding between hyaluronan (A-) and dipalmitoylphosphatidylcholine (DPPC) molecules. Molecular dynamic simulations of the hydrogen bond formation  was cA− = 10−6M—much higher than in SF; however, we focus more on the dense network region of SF, rather than the overall concentration. For molecular mass dependence on (-A···PL) interactions, two types of samples were tested: (i) (A-) only, and (ii) (A-) with phospholipid.All atom molecular dynamic simulations were performed using AMBER03 force field in YASARA Structure Software  to evaluate interactions between hyaluronan macro-ion and phospholipid molecules. A- and PL structures were downloaded from PubChem . The lipid used for this study was dipalmitoylphosphatidylcholine (DPPC). The hyaluronan macro-ion was modified to obtain longer chains by using YASARA Structure Software. The final molecular masses of (A-) were: 10, 40 and 160 kDa; additionally, a TIP4P water model was used. The isobaric-isothermal ensemble, all atom simulations were performed under the same conditions: temperature 310 K, at pH = 7.0 and at 0.9% NaCl aqueous solution, with a time step of 2 fs. Berendsen barostat and thermostat with a relaxation time of 1 fs were used to maintain constant temperature and pressure. Then the DPPC solution was mixed and added at a concentration of The concentrations of dipalmitoylphosphatidylcholine were taken to show the effect of . To Rg is defined by Equation (1) as the root mean square distance of the atoms from the center of mass as Radius of gyration We consider total and intermolecular bonds separately: total is a sum of interactions between all atoms of (A-), whereas intermolecular is a sum of interactions between separate chains; thus, it does not exist for long (A-), because all interactions take place within a single chain. Thus, hydrogen bond energy is defined as ented in ,29. The Hydrogen is formed between two oxygen atoms if: (i) the distance between the hydrogen and adjacent oxygen atoms is smaller than ented in . If the The presented results are divided into three parts, describing separate effects of (-A···PL) interactions. Namely, (i) (A-) cross-linking dependence on its molecular mass; (ii) cross-linking of (A-) dependence of its concentration; (iii) influence of those two effects on (-A···PL) hydrogen bond formation of hyaluronan-hyaluronan molecular (-A···A-) interaction. Final structures for different molecular masses (MM) are presented in rH₋bond < 1.5) and weak (rH₋bond > 2.2) H-bonds represent ~10% of all bonds, strong H-bonds (1.5 < rH₋bond < 2.2) represent 80% of all bonds. The addition of PL changes characteristics of specific H-bonds as presented in Geometrical properties are presented in 4−), as presented in Finally, we look at the bond creation between A- and PL, namely, hydrogen bonds formation between  interaction in normal and pathological conditions. The bonding of (A-) with PL presented in 4−) of PLs along the chain. Rheopexy of SF, an anomalous viscoelastic phenomenon of stress increase upon time raising at shear rate stationarity, has also been addressed in terms of protein aggregations by [The changes in the setting of synovial fluid are predominantly outcomes of the latter process . The changes influence the existence of friction regimes in joint systems . For furtions by .4−) as dependent on (A-) molecular mass. Negatively charged DPPC were tested for their interaction with long, medium and short chains of hyaluronan (A-) M.W. 160, 40 and 10 kDa at pH ~ 7. The formation of phospholipid membrane structures has been shown to be supported by (A-) long molecules; in the presence of low molecular (or short chain) (A-), formation of liposomes and lamellar phases may be less efficient. The decreased friction coefficient demonstrated by some investigators indicates that DPPC could complement the boundary-lubricating ability of long molecules of hyaluronan in joints, which is demonstrated in this work. We also explained how hyaluronan (A-) could have a carrier function for insoluble phospholipid, in the molecular bonding of (A-) and DPPC; namely, hydrogen bond formation between (–OH···PO4−) groups.In this study, we have shown the interaction between (–OH···PO


In this study, the physical properties and the biocompatibility of electrospun silicone-modified polyurethane (PUSX) nanofibers were discussed and compared with PUSX films. To investigate the effects of different structures on the physical properties, tensile strength, elongation at break, Young’s modulus, water retention, water contact angle (WCA) and thermal conductivity measurements were performed. To prove the in vitro biocompatibility of the materials, cell adhesion, cell proliferation, and cytotoxicity were studied by NIH3T3 mouse embryonic fibroblasts cells following by lactate dehydrogenase (LDH) analysis. As a conclusion, the mechanical properties, water retention, and WCA were proven to be able to be controlled and improved by adjusting the structure of PUSX. A higher hydrophobicity and lower thermal conductivity were found in PUSX nanofibers compared with polyurethane (PU) nanofibers and films. An in vitro biocompatibility evaluation shows that the cell proliferation can be performed on both PUSX nanofibers and films. However, within a short period, cells prefer to attach and entangle on PUSX nanofibers rather than PUSX films. PUSX nanofibers were proven to be a nontoxic alternative for PU nano-membranes or films in the biomedical field, because of the controllable physical properties and the biocompatibility. Electrospun nanofibers have been used in various fields such as filtration, catalysis, clothing, and biomedical applications, because of their submicron size and high surface area, along with their porous architecture ,2. EspecAmong various kinds of nanofibers, polyurethane nanofibers were selected as one of the most suitable choices for biomedical applications, thanks to the unique properties of polyurethane. Electrospun polyurethane nanofibers have been successfully used in wound dressing, due to an excellent oxygen permeability and barrier properties . Water pHowever, there are still several limitations and disadvantages of polyurethane nanofibers to be applied in the biomedical field, such as poor thermal capability, poor weatherability, and flammability. In order to improve the properties of polyurethane nanofibers, silicone groups were introduced into polyurethane polymer chains to fabricate silicone-modified polyurethane (PUSX) and to optimize the electrospinning parameters. In this study, PUSX nanofibers were evaluated by physical properties and cell culture studies, and they were compared with the films. The advantages of polyurethane, silicone, and nanofibers are very attractive for this work. This new material is expected to be applied in many fields as an improved alternative for polyurethane nanofibers, such as wound dressing and tissue engineering, due to the biocompatibility of silicone. Before going for the in vitro cell attachment and proliferation applications, all of the prepared nanofibers were analyzed in detail by various methods, and compared with films. To investigate the effects of different structure (block and graft type), chain lengths, and silicone concentration, evaluation of the physical properties was performed. Tensile tests were performed to investigate mechanical properties such as tensile strength, elongation at break, and Young’s modulus. The water contact angle (WCA) measurement and water retention tests were carried out to determine the hydrophobicity of the PUSX material. The thermal conductivity was analyzed in order to discuss the heat retention ability of the PUSX nanofibers and films. In order to reveal the potential for cell adhesion and proliferation, NIH3T3 mouse embryonic fibroblasts cells were cultured on all the samples, followed by lactate dehydrogenase (LDH) activity. The toxicity of the PUSX nanofibers and films were evaluated by using direct contact based on ISO 10993-5. Therefore, as the purpose of our research, the influence of PUSX structures on the physical properties and biocompatibility is investigated. PUSX nanofibers might be expected as an ideal alternative for PU nanofibrous membranes or films in the biomedical fields.N,N-dimethylformamide/ ethyl methyl ketone (DMF/MEK) standardized a solid content of 30 wt%. The structures of two types of PUSX are shown in N,N-dimethylformamide (DMF) and ethyl methyl ketone (MEK) were purchased from Wako Pure Chemical Industries., Ltd., and used as received.The 12 kinds of PUSX solutions and films were kindly synthesized and provided by Shin-Etsu Chemical Co., Ltd., and Dainichiseika Color & Chemicals Mfg. Co., Ltd. These synthesized PUSX solutions in All the electrospinning solutions were prepared by diluting the PUSX solutions (30 wt%) in DMF/MEK mixed solvent (v/v = 64:36), and stirring at room temperature for 48 h in order to obtain homogeneous solutions. All electrospinning experiments were performed at room temperature (22 °C) under the optimized parameters of our previous study , and theThe surface morphology of the nanofibers was investigated by scanning electron microscope  at an accelerating voltage of 10 kV. Before SEM analysis, the prepared samples were coated by using a platinum sputter coater  under 30 mA for 60 s. The diameters of the nanofibers were measured by ImageJ . The average fiber diameters were calculated from data of at least 50 measurements per sample.Tensile tests were performed by a compact tabletop universal tensile tester  for samples 10 mm long and 5 mm wide, at a crosshead speed of 10 mm/min. At least 10 specimens were tested for each sample. To compare the mechanical properties of the PUSX nanofibers with PUSX films, the same tests were performed on the PUSX films.2) were then placed on the water box, and the heat plate of the bottom temperature box (B. T. box) was placed on the upper surface of the samples. After reaching a constant value, the heat flow loss W (watts) of the B.T. was recorded using a panel meter. Steady heat flow lost was calculated as the following equation:2), △T is the temperature difference of sample (°C), and K is the thermal conductivity. The thermal conductivity K was calculated by the following equation: Thermal conductivities were determined by a KES-F7 Thermal LaboⅡB precision rapid thermal property measurement unit . The temperature of the water box was set to room temperature. Samples  after randomly dripping 2 μL of purified water on the surfaces of the samples. The droplets on the samples were captured after 1000 ms through an image analyzer, and the WCA, θ, was calculated by the software through analyzing the shape of the drop. When depositing a droplet onto the material, the water will form a droplet shape. The point where the surface, the water, and the vapor meet, is called the three-face point, and it determines the contact angle. The relationship between the contact angle, the surface free energy, the liquid surface tension, and the interfacial tension between solid and liquid is defined by the Young equation:Usually, when the WCA is less than 90°, the material can be considered to be hydrophilic while the material is hydrophobic. It is worth mentioning that if the WCA is between 150° and 180°, it shows the high water-repellency of the material.Before using the samples for in vitro cell culture, it is essential to remove the DMF/MEK mixed solvents because of the possible cytotoxicity. All of the samples were washed with distilled water for 48 h and dried in oven at 80 °C overnight. Then, the nanofibers and films were cut into round shapes with a diameter of 10 mm, with three replicates per sample prepared. Sterilization was performed by deeply soaking the samples in 70% ethanol aqueous solution in a multi-well tissue culture polystyrene (TCPS) dish for 1 h, followed by rinsing three times in phosphate buffer saline (PBS) to remove all traces of ethanol.NIH3T3 mouse embryonic fibroblasts were used to measure the cell adhesion and proliferation. For the cell adhesion test, 50,000 cells (in 1 mL of medium) were mixed well into the sample. After 3 h, the cells were harvested in 1 mL of 0.5% Triton X-100/PBS solution, and evaluated by LDH assay for adhesion evaluation of the cells.The cell proliferation test was a quantitative investigation of the capacity for the cells to grow on the electrospun nanofibers and films. At the seeding step of the proliferation culture, 5000 cells were added into the sample. The experiment lasted for a total of seven days, and the results of the first, third, fifth, and seventh days were compared.The LDH activity was immediately measured by ultraviolet absorption at a wavelength of 340 nm, using the Thermo Scientific Multiskan FC microplate photometer  with a recorder. The enzyme activity of LDH can be measure from chemical reaction of LDH, when it is released into the cells’ medium from the damaged or dead cells, due to cell membrane damage. LDH converts lactate using NAD as a coenzyme, and produces pyruvic acid and NADH. The number of cells was calculated from the calibration curve obtained by the relation between the known number of cells, and the absorbance value at 340 nm of NADH in the assay supernatant.The shape of the cells was observed by SEM to qualitatively investigate the cell reactions when in contact with the electrospun nanofibers. After each incubation period, the sample was fixed with paraformaldehyde (PFA) as a cross-linking fixation agent, to stop the proliferation of cells, and to preserve their shapes. The sample was further dehydrated by serially using ethanol gradient solutions of 50, 70, 95, and 99.5% for 30 min each, over a continuous process. Then, the sample was coated with platinum for SEM analysis.The toxicities of the PUSX nanofibers and films were evaluated by using direct contact based on ISO 10993-5. Briefly, cells were seeded evenly over the surface of each plate and incubated at 37 °C until the cells covered the whole surface. The samples were then placed on the cell layers in the center of the plates, and the culture medium was replaced. In order to determine the toxicity in accordance with Grade 0 (nontoxic) to Grade 4 (severe toxic) evaluation, Trypan blue was added after 24 h in each plate, and observed by morphological changes. This is the most obvious and direct way to reflect the impact of testing the materials on the cell .p < 0.05 to identify which groups were significantly different from the other groups.Significance in vitro biocompatibility and physical properties were statistically analyzed by a one-way analysis of variance (ANOVA) using R free software. Statistical significance was set at In the previous study , we succRepresentative SEM images of PUSX nanofibers are shown in When the silicone concentration increased, the low cohesive force changed the tensile strength of the material. On the other hand, the increase of silicone concentration caused the decrease of the ratio of PU in the polymer, and the weight percent of PU as well, which means there was a lack of the higher mechanical structure (PU). The tensile strengths of the films did not show much statistical significance because of the random orientation of the molecular chains.In the graph of graft-type PUSX nanofibers and films c, Si08 nIn this case, the silicone groups on the side chain were not able to influence the properties much, because the tensile strength was mainly determined by the high mechanical properties of PU in the main chain.The tensile stress–strain curves of the electrospun PUSX nanofibers and the PUSX films are shown in Referring to Referring to For both block- and graft-type PUSX nanofibers, all of the tensile test results showed that PUSX films have higher tensile strengths than nanofibers. This phenomenon can be explained by the orientation of the polymer chain, and the different structures of the nanofibers and films (porosity and density).It is worth mentioning that in solid objects, heat is transferred via conduction. For electrospun structures, much of the volume is made of empty spaces between fibers. Usually, the conduction along the fiber as part of the whole volume is negligible. But if the fibers becomes too compact, the packing density will be increased beyond an optimum standard, heat transfer via conduction through the solid fiber becomes significant, and the overall insulation property will be decreased. The insulation properties of the electrospun nanofibers are made more controllable due to their packing density compared to the films, to meet the demands of the market. As an ideal alternative to PUSX films, PUSX nanofibers provides good heat insulating properties and lightness in weight.p < 0.05).In Block-type PUSX nanofibers showed a decreasing trend in water retention with the increase of both silicone chain length and silicone concentration, because of the hydrophobicity of silicone. This also means that the water repellency of the PU nanofibers are able to be improved by introducing the silicone groups into the main chain. Meanwhile, compared with films, since nanofibers have a high porosity for holding water, the water retentions of the nanofibers are higher than films. Both the PU nanofibers and films have the highest water retentions. Higher hydrophobicity of silicone structure and moisture permeability were proven.Meanwhile, for graft-type PUSX nanofibers, the silicone groups on the side-chain are not able to increase the hydrophobicity of the material, so that the water retention did not show any difference between the PU nanofibers and the graft-type PUSX nanofibers.It is worth mentioning that for graft-type PUSX nanofibers, the water retention appeared to be higher compared with the block-type PUSX nanofibers, but the results of the water contact angle were similar. This might be caused by the different surfaces of the block-type and graft-type nanofibers. It is supposed that the silicone groups were distributed differently on the graft-type PUSX nanofibers than on the block-type PUSX nanofibers.To investigate the in vitro biocompatibility of the blended nanofibers, NIH3T3 cells were cultivated on to PUSX nanofibers and films of different structures. Cell attachment results were obtained and calculated after 3 h, and are showed in The results as displayed in There was no obvious difference between the PUSX and PU materials, because of the biocompatibility of silicone. To the best of our knowledge, silicone has been extensively used in medical areas, in several products such as breast implants, contact lenses, lubricants, sealers, artificial cardiac tubes and valves, urethral and venous catheters, membranes for blood oxygenation, dialysis tubes, orthopedic applications, and facial reconstructions, because of its high biocompatibility ,13. The Therefore, our novel nanofibrous membranes favored fibroblast cell attachment and growth by providing a stereo-structure environment that mimics the ECM, and which is considered to be biofriendly after toxicity evaluation. Indeed, there are a large amount of studies for developing biomedical materials for wound dressing and tissue engineering. For instance, Fenghua Xu et al. suggested tannic acid/chitosan/pullulan composite nanofibers, which showed synergistic antibacterial activity and the potential for deep and intricate wound healing. Compared with these materials, PUSX nanofibers show the controllable tensile strength of PU, which suggests potential applications for long-term tissue engineering, and hydrophobicity that is influenced by the silicone groups. As we know, wound infection is one of the main areas of concern in the management of the wound environment. Infection complicates treatment, and it impedes the healing process by damaging tissue, reducing wound tensile strength and inducing an undesirable inflammatory response ,15,16. PIn the present study, the physical properties and biocompatible properties of PUSX nanofibers were investigated and compared with films. As a conclusion, for all of the analyses, physical properties, mechanical properties, water retention, and water contact angle (WCA) can be controlled and improved by adjusting the structure. Unfortunately, the graft-type PUSX did not show obvious changes in mechanical strength, because the side chains of silicone could not have as much influence as the main chain of PU does. Conversely, the graft-type PUSX nanofibers were the most similar alternatives to PU nanofibers in terms of mechanical properties, but with better water repellency according to the water contact angle results. Higher hydrophobicity and lower thermal conductivity were also found in the PUSX nanofibers, due to the unique advantages of nanofibers compared with films. This material can be expected to be applied in various fields. For instance, by controlling the silicone chain length and the concentration of block-type PUSX nanofibers, it can be applied in the medical field as bandages or scaffolds, the apparel field as outdoor goods and sportswear, and it can also be used for air or water filters.In vitro biocompatible evaluation shows that cell proliferation can be performed on both the PUSX nanofibers and films. However, for cell attachment, the cells are not able to attach onto the PUSX films in a short time, nor entangle in the material, PUSX nanofibers were proven to be more appropriate for cell culture study. As we know, PU nanofibers have been developed as biomedical materials for several years. For instance, Lakshmi R. Lakshman et al.  and AfeeIn this research, the physical properties and the biocompatibility of PUSX nanofibers were discussed and compared with PUSX films. Tensile strength increased with the increase of silicone chain length, and decreased with the increase of silicone concentration. The elongation at break decreased with the increase of both the silicone chain length and the silicone concentration in block-type PUSX nanofibers, while the Young’s modulus showed the entirely opposite trend. Higher hydrophobicity and lower thermal conductivity were found in PUSX nanofibers, compared with PU nanofibers and films. An in vitro biocompatible evaluation shows that PUSX nanofibers are able to be applied in the cell culture field, and that it shows very little toxicity. Compared with films, PUSX nanofibers shows better cell attachment over a short period of time. Therefore, electrospun PUSX nanofibers with highly controllable physical properties can be expected as ideal alternatives to PU membranes applications of the biomedical field, such as for wound dressings and tissue engineering.


Many physiological and pathological changes in brain function manifest in eye-movement control. As such, assessment of oculomotion is an invaluable part of a clinical examination and affords a non-invasive window on several key aspects of neuronal computation. While oculomotion is often used to detect deficits of the sort associated with vascular or neoplastic events; subtler  effects on neuronal processing also induce oculomotor changes. We have previously framed oculomotor control as part of active vision, namely, a process of inference comprising two distinct but related challenges. The first is inferring where to look, and the second is inferring how to implement the selected action. In this paper, we draw from recent theoretical work on the neuromodulatory control of active inference. This allows us to simulate the sort of changes we would expect in oculomotor behaviour, following pharmacological enhancement or suppression of key neuromodulators—in terms of deciding where to look and the ensuing trajectory of the eye movement itself. We focus upon the influence of cholinergic and GABAergic agents on the speed of saccades, and consider dopaminergic and noradrenergic effects on more complex, memory-guided, behaviour. In principle, a computational approach to understanding the relationship between pharmacology and oculomotor behaviour affords the opportunity to estimate the influence of a given pharmaceutical upon neuronal function, and to use this to optimise therapeutic interventions on an individual basis. Oculomotor behaviour relies upon the coordination of a distributed network of regions throughout the brain (Parr and Friston We have previously argued for an association (i) between acetylcholine and beliefs about how precisely hidden variables in the world give rise to sensory data, (ii) between noradrenaline and beliefs about how hidden variables in the present cause those in the future, and (iii) between dopamine and beliefs about how we will act upon the world —give rise to sensory  data , and in the decision processes leading to a saccade (e.g. inappropriate saccade targets). For the purposes of this paper, we adopt a single oculomotor task  model of discrete states . At all stages, the proprioceptive outcome is generated through an identity mapping from the fixation location (i.e. the subject has precise sensory evidence about where she is looking). We do not explicitly model free free-viewing during inter-trial intervals and assume that feedback is given immediately following the response. Equipped with this model, we can now examine the effects of changing the precisions (i.e. simulated neuromodulators) on task performance.A receptor and facilitate action of the endogenous neurotransmitter. They are commonly used in clinical practice to treat a range of conditions including, but not limited to, anxiety disorders, insomnia, and (in an acute setting) epilepsy. Oculomotor changes during use of these agents are sufficiently robust that they have been proposed as biomarkers for the pharmacological effects , an antimuscarinic (anticholinergic) drug   policies. If we are able to infer, based upon early observations, the course of action we will pursue, performance becomes robust to the degradation of memories about those observations. In other words, if I know I have to perform a saccade to the left location, whether I believe that this is the target location or not has no influence over my task performance. This illustrates the dissociation between beliefs about states of the world and beliefs about ‘how I will act’. This explanation, and the redundancy it implies, lends itself to an empirical hypothesis. Under a noradrenergic blockade, the sensitivity of task performance to dopamine depletion should increase. Similarly, increasing noradrenaline or dopamine signalling should be able to rescue impaired performance due to depletion of the other transmitter. This sort of hypothesis, concerning an interaction between precision terms, highlights an important future research direction. While, for simplicity, we have highlighted the behavioural or physiological responses that build an intuition about the role of precision parameters, these quantitative behaviours also enable us to plot the responses shown above alongside any of the manipulations employed here. This affords an opportunity to investigate the interaction between neuromodulators and the influence of, for example, noradrenergic modulations on dopamine firing.Interestingly, selective noradrenaline uptake inhibitors have been shown to be efficacious in treating anxiety disorders  agents in individual patients  via a graphical user interface by typing in >>DEM and selecting ‘Decisions to movements’ and associated demos.Although the generative model changes from application to application, the belief updates described in this article are generic and can be implemented using standard routines (here spm_MDP_VB_X.m). These routines are available as Matlab code in the SPM academic software:


The article deals with the preparation and possibilities of using combined filtration sorption systems usable for the construction of folded filters or respirators. The studied materials are made of several structural layers—a filter membrane made of polymeric nanofibers, an adsorbent containing active carbon or porous silicon dioxide nanofibers, and a supporting or cover nonwoven bicomponent fabric. The layers are connected only by pressure at an elevated temperature without the use of binders, according to utility model PUV 31 375. The result is a compact fabric material of textile character with a high permeability, good mechanical resistance, which effectively catches the submicron particles and the gases of the organic substances. The prepared samples of the filter sorptive material have been evaluated not only from the point of view of morphology and microstructure, but also from the point of view of the capture of pollutants. It is generally known that decreasing the dimensions of basic components of filtration and sorptive materials in barrier layers of filters leads to increasing the efficiency of capture for even gaseous harmful substances ,2. The pIn the scope of filters that are designed to capture the particles made of fibrous components, this problem is usually solved by enlarging the exposed area of the microfibrous material by folding it into the form of folders . The dimHowever, barrier filtration layers made of polymeric nanofibers are usually not self-supporting, and a suitable textile or other substrate that functions not only as carrier material but also as a pre-filter must be applied. It is often necessary to use a nanofiber layer fix to the carrier for practical use. There are a number of ways to use it. Fusing powders, hot grids or fusing, or ultrasonic pointing are most often used. The microcapsules of the melt polymer applied to the underlying textile material can be used for the connection . These bThe filtration sorptive materials described in this paper have been made by applying a nanofiber filtration layers to a textile carrier from a nonwoven or nonwoven bicomponent fabric. Only pressure and temperature, and no binders, have been used to connect the single layers . This me2/g), with a different grain size and different internal pore distribution prepared by carbonization and activation from natural or polymeric precursors in powdered, granulated, spherical, or spherical fibrous form is used [−1) on adsorbents with a large specific surface without chemisorption treatment is a fast and universal process that can run in multiple layers, even at low temperatures. The physical adsorption efficiency, at which the adsorbed substance is bound to the surface of the adsorbent relatively weakly by the Van der Waals forces, is reduced with increasing temperature, and this process can be reversible (the adsorbent can be regenerated by raising the temperature). Within chemisorption, electrons are shared between the adsorbed molecule and the surface of the adsorbent because of a chemical reaction specific to the particular adsorbate (reaction heat to 400 kJ mol−1). Chemisorption occurs in one layer only, is not reversible, and exponentially increases with temperature [Within adsorbents, the situation is a bit different. In general, nowadays activated charcoal with a large specific surface area , a typical turbostratic structure, and good physical and mechanical properties. Adsorption carbon fabric is usually composed of threads containing about 150 monofilaments, with a thickness of 10–25 μm. For this reason, the formed sorption layer is very breathable with a low pressure loss, high sorption dynamics, and considerable sorption capacity. A certain disadvantage is the small size of the accessible micropores (nm units), which makes it difficult to effectively impregnate them with chemisorbents and, moreover, is of a relatively high price. However, there is also a mesoporous Filtration Activated Carbon (FAC). An advantage of this is the lower influence of moisture on the capture of gaseous pollutants in comparison with other types of adsorbents. The active carbon fiber adsorptive fabrics can be successfully combined with polymeric or inorganic nanofibers [As a preferred material for the capture of gaseous pollutants in areal filters, carbon fiber sorption layers prepared by textile or paper technology are also now considered. They may take the form of a woven or nonwoven fabric or felt . Textile2 nanofibers, with a large specific surface (up to 900 m2/g) [Another interesting sorbent is the porous SiO00 m2/g) . A surfa2 nanofibers. For their connection, the adhesive properties of bicomponent fibers without binders’ employment can be used.The aim of our research was to apply this knowledge in the development of new filtering sorption materials. We have tried to use newly developed permeable filter membranes, made of polymeric nanofibers, and surface adsorbents, based on powdered, spherical, or fibrous activated carbon or porous SiO2 nanofibers are modern construction materials used in addition to glass fibers and classical adsorbents in the production and development of new filters and filtration equipment [2 nanofibers, and a carrier cover nonwoven textile from bicofibers. The layers are connected only by pressure in increased temperature without the use of binders, according to utility model PUV 31375. The result is a compact fabric material of a textile character with a high permeability and good mechanical resistance, which effectively catches the submicron particles and vapors of organic substances.Polymeric nanofibers, active carbon fibers, spherical activated carbon, and porous SiOquipment ,28. The 2 has been made by the company PARDAM, Ltd.  from PA-6 and polyvinylidene difluoride (PVDF) polymer nanofibers by centrifugal spinning. To achieve antimicrobial and antifungal properties, these polymeric nanofibers are subsidized by silver nanoparticles. The size of silver nanoparticles moved from 40–60 nm. Its concertation has been stabilized in the amount of 160 ppm/g. In the case of the presented products, silver particles are firmly anchored in a polymeric nanomembrane, so the user’s body cannot by contaminated, even if their antibacterial effect is undisputed [The filtration membrane for particle filtration with areal weight of 1–10 g/mdisputed ,30,31. V2 and the air permeability moves in the range of 40 to 500 L/min/dm2. The melting point of the PA-6 nanofibers is 220 °C and the softening point is >204 °C. The PA-6 nanomembrane can have antibacterial and photocatalytic properties with doping functionalized particles . Hydrophobic, oleophobic, or hydrophilic post treatment with plasma spray is possible. PA-6 nanofibers are possible for using in the environment, because of their biodegradability [The PARDAM PA-6 nanofibers  are chemdability .2, and air permeability moves in range of 40 to 500 L/min/dm2. The melting point of the PVDF nanofibers is 130 °C. The PVDF nanomembrane can have antibacterial and photocatalytic properties with doping functionalized particles . Their small pore size and high specific surface makes PVDF nanomembranes suitable for hightech applications, like chemically resistant filters, carriers, and separators.The PVDF nanofibers  have exc2, from PARDAM, Ltd., has been also verified. The connection of single constructive layers of one-sided smelting nonwoven fabric of polyester bicofibers, VIGONAIR 1516, with an areal weight of 150 g/m2 and a 30% share of bicofibers, is made by Fibertex Nonwovens, public limited corporation (PLC), with thermal bonding.Several types of constructive materials have been used to form the adsorbent layer. The adsorption fabric based on powdered activated carbon has been made by Fibertex Nonwovens, PLC. The ACC 8092 15 active carbon fiber adsorption textile is produced by Kynol, Ltd. company,  and the adsorption fabric, SARATOGA Pyjama, based on spherical activated carbon is from the Blücher company . The use of the filtration sorption layer of the porous nanofibers of SiO2 SORBENT  can also be employed for similar purposes. Fibrous NnF CERAM, SiO SORBENT , is a stThe appearance of the used adsorptive textile ACC 509215 from activated carbon fiber, from Kynol Ltd., and the example of the permeation of toluene through this material is evident from As a carrier and binder material, thermally nonwoven fabrics with a 30% bicofiber content have been used by Fibertex Nonwovens, PLC, and JILANA, PLC. The thermal bonding technology is based on the heat treatment of the nonwoven fibrous layer, prepared by mixing the mixture of the basic and connective bicofibers. Within hot-air bonding, this layer passes through the hot-air connecting chamber. After melting the binder fibers, solid connections are formed between the fibers to form a flexible and stable nonwoven fabric. A schematic cut of the bicofibers is shown in For the connection and calibration of all construction layers with pressure and temperature, a special laminating device was used, whose principle is evident from the schema on Themicroshots of the studied materials were taken by a scanning microscope Phenom G2 Pure, and their specific surface area was measured by the Brunauer, Emmett, Teller (BET) method on the equipment of Quantachrome NOVA 4000 e by PARDAM, Ltd. . The filtration efficiency and pressure loss were evaluated on the LORENZ filter measuring system at SIGMA GROUP, PLC. The resistance of the studied materials against the permeation of the vapors of volatile organic compounds were evaluated on the SORPTEST device from Gryf, Ltd. , in cooperation with the NBC Defense Institute of the University of Defense  .The prepared sample of the filtration sorptive materials with a filtration membrane from the polymeric PA-6, and the PVDF nanofibers were evaluated from the point of the efficiency of the particle capture within the filtration from an aqueous solution. Selected combinations of used materials are listed in An example of an evaluation of good (sample No. IV) and poor (sample No. V) particle recovery from the solution is shown in The selected samples of the filtration sorptive materials were further evaluated for the efficiency of the capture of submicron particles from the gas phase, by SIGMA GROUP, PLC ,37. The 2 adsorption layer. These materials were then used to make folded filters and respirators  based on PAC, SAC, and FAC, optionally with a porous SiOpirators .Filter membranes made of polymeric nanofibers were also combined with a 30% part of the bicofibers. The appearance of the used struto textile of JILANA Elastic Universal and the manufactured respirator inserts is shown in ® PRO 8038, by the TSI company for the measurement of the respiratory protective factor, depending on the conditions of use, according to the standard methodology. The results of this evaluation are shown in Selected respirators were further evaluated by the State Institute for Nuclear, Chemical, and Biological Protection, from the point of view of the effectiveness of the submicron particle capture on the equipment, PortaCount® PRO 8038 measures the sum of solid particles, such as the condensation cores, from 20 nm to more than 1 μm. When measured, it switches between sampling concentrations of particles in the surroundings and in the protected area (under the respirator). It can also observe the influence of people and their grimaces on the leakage quality (if required). The result is the so-called Fit factor (cF), which gives the particle number ratio, around on, to the particle number n, under the respirator in the exhaled air. The measurement results are shown in The PortaCount2 SORBENT nanofibers are visible in 2 was also verified by the suction from an aqueous slurry or fixation in open polyurethane (PU) foam (The appearance and microstructure of the porous NnF CERAM-SiOPU) foam .2 nanofibers, comparison of water vapor sorption and desorption with silica gel, and the ability to adsorb selected organic vapors are shown in The basic parameters of porous SiOAs a result of the antibacterial and antifungal treatment with silver nanoparticles, the resistance to the long-term exposure of them olds has been tested for the filter membrane made of polymeric nanofibers. Aspergillus niger fungus resistance testing has been carried out in cooperation with the Military High School in Belgrade, according to the European Standard SRPS EN 60068-2-38 . For botDuring the implementation of the studied filtration sorptive systems, modern construction materials have been used, enabling the combination of both surface and spatial structures to capture both the submicron particles and industrial pollutant vapors. The advantage of this research direction is that most of these materials are commercially available and can be further modified as required. The connection of individual constructive layers without the use of binders, utilizing the good adhesion properties of bicofibers, maintains a high permeability of the product and does not affect the effectiveness of the trapping of pollutants. The obtained results show the practical applicability of the developed filtration sorptive systems in various fields of a human activity, especially in the protection of people against toxic particles, aerosols, molds, and gaseous pollutants.2 nanofibers, it is possible to prepare interesting design materials that are useful in the manufacture of filters, respirators, and similar devices. Centrifugal spinning has been shown to produce flexible, compact, and homogeneous filtration membranes with good separation properties for submicron particles. Their overlapping with nonwoven bicofiber textiles enhances their mechanical resistance and improves their further workability. The great advantage of this is that the nanofibrous layer can be applied directly onto the bicofibers textile without the need for a transfer textile. This textile can then be combined not only with bicofiber cover fabrics, but also with other layers with adsorption properties. The elasticity and good mechanical resistance of these combined materials makes it easy to fold or heat-shape without the use of binders, while maintaining the filtration sorptive properties of the initial substrates. The advantage is even the resistance of the polymeric nanofibrous membrane to bacteria and fungi.Based on the results of the recent research of filtration sorptive materials made from nanofibrous membranes with silver nanoparticles, nonwoven, or struto textile from bicofibers, as well as the sorption layers based on the powdered, spherical or fibrous activated carbon, or porous SiO