Effectiveness of Kabasura Kudineer tablets in the management of asymptomatic and mild cases of COVID-19: A pilot double-blinded, randomized controlled trial.
COVID-19 was declared a pandemic in 2020. It has had a devastating effect on human life and the global economy. To date, there is no proven therapy for COVID-19, even though rigorous research is ongoing to test multiple compounds across all systems of medicine. A need was felt to systematically explore the Indian system of medicine to assess its efficacy against COVID-19. The objective of the present study was to examine the effect of Kabasura Kudineer as a standalone therapy on the following: time required to achieve symptom relief & resolution, virological clearance, and levels of IL6, CRP and IgG, and compare it to the standard therapy available for treatment of COVID-19. A double-blinded randomized controlled trial was conducted in 110 participants. 55 participants were enrolled in the Kabasura Kudineer arm and 55 in the control (standard therapy + Kabasura Kudineer placebo) arm. Study participants were randomly allocated into the two study arms. They were assessed for symptoms at baseline, and on Day 5 and Day 10. RT PCR, CRP, IL6 and IgG levels were measured at baseline, Day 5 and Day 10. On day 28, participants were interviewed telephonically for symptom assessment alone. A per-protocol approach was used. Significant difference between two groups was assessed at baseline, day 5 and day 10 using the Chi-square and Mann Whitney test. A total of 110 patients participated in study. Four patients in the Kabasura Kudineer arm and 9 in the Standard therapy arm were lost to follow-up. Baseline characteristics for both the groups were matched at baseline. 83.9% and 93.9% patients were relieved of all symptoms by the 10th day in Kabasura and standard therapy groups respectively. Decrease in CRP level was more pronounced in the Kabasura group compared to standard therapy viz. 3 mg/l and 1.26 mg/l. No significant difference was found in IgG level and IL6 levels in both the study groups. However, it was noticed that among the unvaccinated group, the surge in IgG levels was much higher in Kabasura Kudineer group than the standard therapy group. Kabasura Kudineer as a standalone therapy was as effective and safe as the standard therapy among patients with asymptomatic to mild COVID-19.


A new type of exo-beta-glucuronidase acting only on non-sulfated glycosaminoglycans.
Using chondroitin as a substrate, a new type of exo-beta-glucuronidase (EC 126.96.36.199) from rabbit liver was purified using a combination of ammonium sulfate fractionation, DEAE-cellulose chromatography, gel filtration on Sephracryl S-300, affinity chromatography through heparin-Sepharose CL-6B, and preparative polyacrylamide gel electrophoresis. This enzyme acts only on non-sulfated glycosaminoglycans and their oligosaccharides and was shown to be quite different from exo-beta-glucuronidase, which does act on p-nitro-phenyl-beta-D-glucuronide with regard to the following properties. 1) Neither sulfated glycosaminoglycanoligosaccharides nor p-nitrophenyl-beta-D-glucuronide were substrates for the enzyme. 2) The molecular weight was found to be about 130,000 by gel filtration, compared with a molecular weight of 280,000-300,000 for beta-glucuronidase, which acts on p-nitro-phenyl-beta-D-glucuronide. 3) The enzyme showed maximal activity at pH 5.0, compared with an optimum pH of 4.5 for beta-glucuronidase, which acts on p-nitro-phenyl-beta-D-glucuronide. 4) The enzyme showed maximal activity in 0.075 M NaCl but no activity above 0.25 M NaCl. 5) The enzyme was inhibited strongly by compounds bearing a sulfate group. 6) The enzyme did not react with an antibody against beta-glucuronidase acting on p-nitrophenyl-D-glucuronide. It is suggested that the enzyme may be involved in the catabolism of glycosaminoglycans, acting especially on chondroitin after the desulfation reaction and/or hyaluronic acid, but showing little involvement with the detoxification system.


Amyloid pseudotumor treated by tracheal resection.
Primary amyloidosis is a rare disease, and even more so when it appears as a tumorlike formation in the lung or tracheobronchial tree. On rare occasions it has been treated by pulmonary resection but never before by tracheal or bronchial sleeve resection. A case of tracheal sleeve resection for tumorlike amyloidosis is reported. If the lesion is well circumscribed to a relatively short tracheal or bronchial segment, sleeve resection appears to be a satisfactory and economical solution. However, the problem of a mucosa undermined by amyloid deposits above and below the tumorlike lesion entails the risk of anastomotic stenosis. For this reason in future cases, particularly those with extensive involvement, piecemeal endoscopic removal should be considered as the method offering the best prognosis and least risk.


Characterizing the preventable emergency department visit after bariatric surgery.
Patients who present to the emergency department (ED) after bariatric surgery may incur significant costs with no additional benefit. To characterize patients who presented to the ED but could have been treated in an alternative setting. University hospital, United States. We identified 131 patients who underwent primary bariatric surgery at a single-center academic institution between 2006 and 2016 who also presented to the ED within 30 days of surgery. Preventable ED visits were identified by excluding patients with life-threatening presentations and/or use of emergent ED-specific resources. Patients with preventable ED visits were matched 1:1 to controls (no ED visit) based on procedure type and preoperative patient characteristics. Independent risk factors among patients with preventable ED visits were identified. A total of 80 patients (61%) were identified as having a preventable ED visit after bariatric surgery. After multivariable logistic regression, independent risk factors associated with preventable ED visits included anxiolytic prescription at discharge (odds ratio [OR] 5.4 [95% confidence interval 1.6-18.6]; P = .007), electrolyte abnormalities (OR 4.3 [1.9-9.6]; P < .0001), and leukocytosis (OR 2.2 [1.0-4.9]; P = .048) at discharge, and number of ED visits preoperatively (OR 2.0 [1.3-3.1]; P = .001). Severe complications, reoperation rates, and 1-year patient reported outcomes did not differ between patients with preventable ED visits and their matched cohort. Preventable ED visits are common after bariatric surgery and are associated with risk factors that can be identified perioperatively. Identifying and triaging patients at risk for preventable ED visits may decrease unnecessary and costly visits to the ED after bariatric surgery.


Intracavitary physiotherapy combined with acupuncture mediated AMPK/mTOR signalling to improve endometrial receptivity in patients with thin endometrium.
To explore the mechanism of intracavitary physiotherapy combined with acupuncture to improve the receptivity of thin endometrium. From October 2020 to April 2021, 40 patients diagnosed with thin endometrium and preparing for hormone replacement cycle freeze-thaw embryo transfer in our centre for Reproduction were included, 40 patients were randomized to treatment group and control group. 20 patients with normal endometrium during the same period were selected as the normal group.All patients underwent freeze-thaw embryo transfer using hormone replacement cycles.The treatment group added endovascular physiotherapy combined with acupuncture. The endometrial receptivity of the patients with thin endometrium was significantly lower than that of the normal group(P < 0.01). Endovascular therapy combined with acupuncture can significantly increase endometrial thickness in patients with thin endometrium and the proportion of patients with type A endometrium, reduce bilateral Uterine arterial pulsatilityindex (PI), Uterine arterial resistance index (RI), and peaksystolicvelocity/diastolicvelocity (S/D), upregulate the expression of HOXA10 protein and mRNA in endometrium tissue, and improve the rate of embryo implantation and clinical pregnancy(P < 0.01).there was no significant difference between the treatment group and the normal group (P > 0.05). This may be related to the regulation of the AMPK/mTOR signalling pathway by intracavitary physiotherapy combined with acupuncture, downregulation of the expression of the AMPK gene and protein and upregulation of the expression of the mTOR gene and protein. 1. Abnormal energy metabolism is present in the endometrium of patients with thin endometrium, which affects the autophagy process and leads to a decrease in the receptivity of thin endometrium. 2. Intracavitary physiotherapy combined with acupuncture mediated the AMPK/mTOR pathway to improve energy metabolism, promote the autophagy process, improve endometrial morphology and ultrasonic indicators of patients, upregulate the expression of endometrial receptivity-related HOXA10 genes and proteins, and improve the embryo implantation rate and clinical pregnancy rate.


Case-control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India.
Congenital Heart diseases (CHDs) account for 1/3rd of all congenital birth defects. Etiopathogenesis of CHDs remain elusive despite extensive investigations globally. Phenotypic heterogeneity witnessed in this developmental disorder reiterate gene-environment interactions with periconceptional factors as risk conferring; and genetic analysis of both sporadic and familial forms of CHD suggest its multigenic basis. Significant association of de novo and inherited variants have been observed. Approximately 1/5th of CHDs are documented in the ethnically distinct Indian population but genetic insights have been very limited. This pilot case-control based association study was undertaken to investigate the status of Caucasian SNPs in a north Indian cohort. A total of 306 CHD cases sub-classified into n = 198 acyanotic and n = 108 cyanotic types were recruited from a dedicated tertiary paediatric cardiac centre in Palwal, Haryana. 23 SNPs primarily prioritized from Genome-wide association studies (GWAS) on Caucasians were genotyped using Agena MassARRAY Technology and test of association was performed with adequately numbered controls. Fifty percent of the studied SNPs were substantially associated in either allelic, genotypic or sub-phenotype categories validating their strong correlation with disease manifestation. Of note, strongest allelic association was observed for rs73118372 in CRELD1 (p < 0.0001) on Chr3, rs28711516 in MYH6 (p = 0.00083) and rs735712 in MYH7 (p = 0.0009) both on Chr 14 and were also significantly associated with acyanotic, and cyanotic categories separately. rs28711516 (p = 0.003) and rs735712 (p = 0.002) also showed genotypic association. Strongest association was observed with rs735712(p = 0.003) in VSD and maximum association was observed for ASD sub-phenotypes. Caucasian findings were partly replicated in the north Indian population. The findings suggest the contribution of genetic, environmental and sociodemographic factors, warranting continued investigations in this study population.


Fulminating hypercalcemia and markedly increased nephrogenous cyclic AMP in a patient with transitional cell carcinoma of the bladder.
Refractory hypercalcemia developed suddenly in a patient who had undergone a radical cystectomy for an anaplastic transitional cell carcinoma of the bladder. A normal serum parathyroid hormone (PTH) value was obtained by immunoassay while the patient had hypercalcemia and unimpaired renal function. This normal PTH value in the presence of hypercalcemia was consistent with his hypercalcemia being secondary to excessive amounts of circulating PTH. The finding of increased nephrogenous cyclic AMP, however, provided the definitive diagnosis of hyyperparathyroidism. Since autopsy revealed that there was no residual tumor in the bladder area, only evidence of metastatic disease, and since the parathyroid glands were not hyperplastic or adenomatous, we attributed this patient's hypercalcemia to hyperparathyroidism due to the ectopic production of PTH by a metastasis from the transitional cell carcinoma of the bladder.


Risk Factors for Surgical Site Infections After Lower Extremity Open Revascularization.
Surgical site infection (SSI) is a serious complication of lower extremity open revascularization and is associated with increased morbidity, increased healthcare costs, and decreased postoperative quality of life. The objective of this study was to determine factors associated with an increased risk of developing postoperative SSI in patients undergoing lower extremity revascularization. Associations between SSI and postoperative complications were also identified. Patients who underwent lower extremity open revascularization from 2014-2017 were identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). A multivariate logistic regression analysis was used to determine risk factors associated with SSIs within 30 days of the operation and postoperative complications. Odds ratios (ORs) were adjusted for demographics, preoperative comorbidities, procedure type, and intraoperative variables. Ten thousand nine hundred ten patients who underwent lower extremity open revascularization were identified, with a mean age of 67.24 years and of whom 7,318 (67%) were male. Of the 10,910 patients, 922 (8.45%) had an SSI within 30 days of the operation. Risk factors associated with developing SSI included body mass index 25-29.9 (OR, 1.34; 95% confidence interval [CI], 1.08-1.67), body mass index ≥ 30 (OR, 2.12; 95% CI, 1.71-2.62), history of severe chronic obstructive pulmonary disease (OR, 1.47; 95% CI, 1.18-1.84), preprocedural beta-blocker use (OR, 1.25; CI 95%, 1.05-1.49), procedure time > 214 minutes (OR, 1.44; 95% CI, 1.22-1.70), and creatinine > 1.2 (OR 1.03; 95% CI, 0.87-1.21). One factor associated with a decreased risk of developing SSI was male gender (OR, 0.71; 95% CI, 0.60-0.84). Patients who developed an SSI were more likely to have adverse outcomes such as myocardial infarction/stroke, major amputation, bleeding requiring transfusion or secondary procedure, or require a reintervention in the treated segment. There are various patient-related and operative factors that increase the likelihood of developing an SSI after lower extremity open revascularization. These findings indicate that addressing modifiable perioperative SSI risk factors may be beneficial in decreasing rates of SSI and improving postoperative outcomes.


Factors determining the prey size of the orb-web spider, Argiope amoena (L. Koch) (Argiopidae).
Argiope amoena is a common web spider in southwestern Japan. Surveys were made of prey size by use of prey traps and by direct observations, and of potential prey size by use of the sweeping method. The web size, web mesh size, spider size, and spider's effective size on prey capture were also measured. Hymenoptera, Coleoptera, and Hemiptera were important as prey for female A. amoena which is far larger than male. Small insects such as dipterans, which are numerous in the surrounding vegetation, were excluded as prey of the female. It seems that small insects pass through the web mesh. A. amoena caught prey nearly twice its own length. The upper limit of prey size coincided with the distance between the first and third legs of A. amoena; these legs are used for prey handling and silk-wrapping. It seems that large insects above the upper limit escape by defeating the spider or by breaking the web.


Muscle contributions to center of mass acceleration adapt to asymmetric walking in healthy subjects.
Symmetrical limb movement requires complex muscle coordination patterns. Consequently, coordination impairments lead to asymmetric gait patterns, as often seen in stroke subjects. Split-belt walking has previously been used to induce limping-like walking in able-bodied adults. The goal of this study is to analyze how muscle coordination patterns that control the centre of mass are modulated during an asymmetric gait pattern imposed on healthy subjects. These modulations can be uniquely related to the biomechanics of limping as no pathology is present. Forward simulations of limping-like walking (split-belt) and corresponding symmetric conditions (tied-belt) were generated for twelve healthy subjects. Our results show that the differences between 'fast' and 'slow' leg contributions during split-belt walking are not attributable to simple differences in speed between the belts, because most split-belt muscle contributions differ from tied-belt walking. Different types of modulations, inducing increased, decreased or even reversed asymmetry (e.g. plantarflexors, biceps femoris short head, and quadriceps respectively), underlie limping-like walking in healthy subjects. In general, these patterns present large similarities with adaptations previously described in hemiplegic subjects. However, differences were found with gluteus medius and biceps femoris short head contributions in hemiplegic subjects, suggesting that the latter are not just related to limping, but to concomitant deficits.


The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism.
The altered metabolic programme of cancer cells facilitates their cell-autonomous proliferation and survival. In normal cells, signal transduction pathways control core cellular functions, including metabolism, to couple the signals from exogenous growth factors, cytokines or hormones to adaptive changes in cell physiology. The ubiquitous, growth factor-regulated phosphoinositide 3-kinase (PI3K)-AKT signalling network has diverse downstream effects on cellular metabolism, through either direct regulation of nutrient transporters and metabolic enzymes or the control of transcription factors that regulate the expression of key components of metabolic pathways. Aberrant activation of this signalling network is one of the most frequent events in human cancer and serves to disconnect the control of cell growth, survival and metabolism from exogenous growth stimuli. Here we discuss our current understanding of the molecular events controlling cellular metabolism downstream of PI3K and AKT and of how these events couple two major hallmarks of cancer: growth factor independence through oncogenic signalling and metabolic reprogramming to support cell survival and proliferation.


Allergic contact dermatitis due to the liquid skin adhesive Dermabond® predominantly occurs after the first exposure.
The clinical characteristics of patients with allergic contact dermatitis (ACD) due to a skin adhesive containing 2-octyl cyanoacrylate, Dermabond®, have not yet been elucidated. To investigate the clinical characteristics of patients with ACD caused by Dermabond® application. In this retrospective study, 577 patch tested patients were included. We identified patients with positive patch test results for Dermabond® and evaluated their results concerning (meth)acrylates and ethyl cyanoacrylate adhesive. Nine patients had positive patch test results to Dermabond®; six had developed secondary generalization.The mean time between Dermabond® application and ACD onset was 34 days (range, 27-44) in six patients with ACD after the first use, whereas, in the other three patients, it was 5.6 days (range, 4-8) after the second use. The time was significantly different between the two groups (P < .01). Positive reactions to ethyl cyanoacrylate adhesive (Aron Alpha) occurred in seven of nine patients, to ethyl cyanoacrylate 10% pet. in four of eight patients tested, and to 2-hydroxyethyl methacrylate in one of eight patients tested. Dermabond®-induced ACD is apparently characterized by a high prevalence of primary sensitization at first exposure to Dermabond®, secondary generalization is frequent, and most patients show cross-reactivity to ethyl cyanoacrylate.


Immediate and long-term impacts of potassium permanganate on photosynthetic activity, survival and microcystin-LR release risk of Microcystis aeruginosa.
The immediate and long-term impacts of potassium permanganate (KMnO(4)) as pre-oxidant on Microcystis aeruginosa and microcystin-LR (MC-LR) release risk were investigated. The cell density and the integrity of M. aeruginosa were determined by a flow cytometry, and typical photosynthetic parameters were measured by a pulse amplitude modulated fluorometer. The photosynthetic parameters were reduced to different degrees, accompanied with slight cytoclasis and complete degradation of extracellular MC-LR immediately after various dosages KMnO(4) oxidation (2-20 mg L(-1)). In a 6-d cultivation following 5 mg L(-1) KMnO(4) oxidation, the cell density decreased from 3.9×10(6) to 0.6×10(6) cells mL(-1), and then increased to 0.9×10(6) cells mL(-1), while the extracellular MC-LR increased from 0 to 51.2 μg L(-1). In the cultivation after 10 mg L(-1) KMnO(4) treatment, the intracellular MC-LR and cell activity significantly declined, while significant cytoclasis (cell density from 3.8×10(6) to 0 cells mL(-1)) and MC-LR release (increase from 0 to 15.2 μg L(-1)) were observed. The photosynthetic parameters were found to be useful tools to predict the recovery tendency of M. aeruginosa cells, and the MC-LR release risk should be considered during KMnO(4) pre-oxidation in water-treatment plants.


Experienced and skilled nurses' narratives of situations where caring action made a difference to the patient.
Forty-five skilled and experienced nurses working at long-term, medical and surgical care clinics narrated 88 caring situations. The aim of the study was to interpret these narratives concerning the nurses' caring actions and the type of situations where they experienced that their caring made a difference to the patient. There were eight types of caring actions that were then condensed into three interaction and intervention approaches; 1) deliberate distanced interaction and intervention with the patient; 2) deliberate providing of prerequisites for interaction and intervention with the patient; and 3) deliberate deep interaction with the patient when intervening. These approaches were used when the nurses dealt with the following three types of caring situations: caring focusing on the nurse-patient relationship, on medical intervention, and on practical problem solving. The first two approaches occurred in situations focusing on acute medical intervention and on practical problem solving. All approaches occurred in situations focusing on the nurse-patient relationship. The finding that experienced and skilled nurses described situations where the depth of their contact with the patient varied can be expressed in the phrase "how I act depends on the situation." The skill to find the right level of involvement seems important.


Production of rat monoclonal antibody from rat x mouse hybridoma cell lines using microencapsulation technology.
The cell growth and monoclonal antibody production characteristics of two rat x mouse heterohybridoma cell lines, designated 187.1 and M1/9.3, were investigated using a biocompatible microencapsulation technology. Both cell lines, derived from the fusion of immunized rat spleen cells with either the NS1 or X63Ag8.653 myeloma cell lines, were found to reach a maximum intracapsular cell density of 1.3 to 1.5 X 10(7) cells/ml during a 27-d culture period. During this period, rat monoclonal antibody accumulated in the intracapsular space of both cultures to a final concentration of 2.0 to 2.8 mg/ml. Comparison of the concentration of rat monoclonal antibody in the extracapsular vs. the intracapsular space of both cultures indicated that significantly less than 1% of the antibody produced by the encapsulated hybridoma cells was capable of transiting the microcapsule membrane during the culture period. Due to the partition of the rat monoclonal antibody within the intracapsular space, the initial purity of the antibody harvested from 21-d microcapsule cultures of 187.1 and M1/9.3 cells was approximately 48 and 75% by weight, respectively. Analysis of the intracapsular protein by sodium dodecyl sulfoxide gel electrophoresis at different times during the culture period demonstrated that the principal contaminant associated with the unpurified antibody was bovine serum albumin.


Limited diagnostic value of lymphocytic karyotype in primary amenorrhea with streak gonads.
Cytogenetic data represent a first line diagnostic aid in gonadal dysgenesis. Generally, the results of a peripheral blood examination reflect the genotypic alteration of the patient. Nevertheless, on occasion one may encounter cases in which clinical and hormonal evidence suggestive of dysgenesis is not accompanied by an anomalous chromosomal finding, upon cytogenetic analysis of the peripheral blood. In these cases, a cytogenetic alteration may be present in cellular components of the ovary and the cutis. In the light of the above, two patients presenting with primary hypergonadotropic amenorrhea, streak gonads and normal peripheral karyotype are described. In one patient presenting with phenotype alterations, ovarian wedge biopsy via laparotomy followed by cytogenetic analysis of ovarian tissue and tissue from the cutis revealed a 45,X/46,XX-type mosaicism. In the other patient, the ovarian cytogenetic findings were unremarkable. Extending chromosomal analysis to several tissues, beyond the peripheral level, in selected cases, is discussed.


NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition: implications for Huntington's disease.
Nuclear factor-kB (NF-kB) is a family of DNA-binding proteins that are important regulators involved in immune and inflammatory responses, as well as in cell survival and apoptosis. In the nervous system NF-kB is activated under physiological and pathological conditions including learning and memory mechanisms and neurodegenerative diseases. NF-kB is activated in neurons in response to excitotoxic, metabolic and oxidative stress and there is a body of evidence to suggest that glutamate induces NF-kB by the main ionotropic glutamate receptors. In the present study, 3 nitroproprionic acid (3NP), an irreversible inhibitor of succinate dehydrogenase (SD, complex II) has been employed to provide an experimental model of Huntington's disease (HD). Specifically, we described 3NP-induced activation of NF-kB and of iNOS and nNOS genes in striatal treated slices. To aim to better understand the relationship between these identified dysregulated genes and mitochondrial dysfunction, we investigated in SK-N-MC human neuroblastoma cells following 3NP treatment, whether NF-kB nuclear translocation and activation might be involved in the mechanisms by which 3NP leads to transcriptional activation of NOS genes. These results are relevant to more precisely define the role of NF-kB in neuronal cells and better understand its putative involvement in neurodegeneration.


Evaluation of antimicrobial activity of ethanol extract and compounds isolated from Trichodesma indicum (Linn.) R. Br. root.
The roots are reportedly used to treat diarrhoea, dysentery, leprosy, skin diseases and fever. The aim of present study was to investigate the in vitro antimicrobial potential of ethanol extract of Trichdesma indicum root, and its purified compounds and to validate scientifically its use in traditional medicine. The root of Trichdesma indicum was extracted with ethanol and subjected to chromatographic separation for isolation of phytochemical compounds. Structures of isolated compounds were elucidated by spectroscopic methods. The antimicrobial activities of the ethanol extract of T. indicum and isolated compounds were primarily evaluated by a disc diffusion test. The anti-microbial efficacy of the ethanol extract or isolated compounds was then assessed in vitro by determining minimal inhibition concentration (MIC) and minimal bactericidal or fungicidal concentration (MBC/MFC). n-Decanyl laurate (1), n-tetradecanyl laurate (2), n-nonacosanyl palmitate (3), stigmast-5-en-3β-ol-21(24)-olide (4), n-pentacos-9-one (5), n-dotriacont-9-one-13-ene (6), stigmast-5-en-3β-ol-23-one (7) and lanast-5-en-3β-D-glucopyranosyl-21 (24)-olide (8) were isolated from ethanol extract of T.indicum. The ethanol extract and isolated compounds (1-8) showed varying degrees of antimicrobial activities. The ethanol extract exhibited potent growth inhibitory activity against S. aureus, B. subtilis and C. albicans with an MIC value of 19.2 μg/ml. Among all the isolated compounds, lanast-5-en-3β-D-glucopyranosyl-21 (24)-olide (8) displayed strongest antibacterial activity against S. aureus with MIC value of 2.4 μg/ml. The results of present study provide ground basis for the potential use of the ethanol extract Trichodesma indicum root as well as the some of the isolated compounds in the treatment of infections associated with the studied microorganisms.


Neuroendocrine manifestations of congestive heart failure.
Congestive heart failure is a complex clinical syndrome characterized by a number of neuroendocrine responses. These responses are probably an evolutionary vestige of mechanisms designed to defend volume and maintain circulatory homeostasis. Activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and the release of vasopressin have been clearly documented in patients with heart failure. Unlike the normal ventricle, the failing ventricle responds to peripheral vasoconstriction and sodium retention with further hemodynamic embarrassment and circulatory congestion. Certain vasorelaxant natriuretic substances are also released during heart failure, perhaps in an attempt to offset excessive peripheral constriction and sodium retention. Prostaglandin E2, atrial natriuretic peptide (or atrial natriuretic factor) and plasma dopamine are found to be increased in some patients with heart failure. However, peripheral constriction and sodium retention appear to be dominant, particularly in the advanced stages of heart failure. An understanding of these neuroendocrine responses has led to new developments in therapy. Angiotensin-converting enzyme inhibitors have emerged as distinctly useful drugs in the treatment of heart failure. Agents designed to block excessive sympathetic drive and inhibit vasopressin are under investigation. Infusion of atrial natriuretic factors and the use of selective dopamine agonists are also undergoing clinical trials in patients with heart failure. Increased knowledge of the neuroendocrine responses will likely result in even newer and more imaginative therapy.


Risk factors and outcome of seizures after spontaneous aneurysmal subarachnoid hemorrhage.
Seizures are important neurologic complications of spontaneous aneurysmal subarachnoid hemorrhage (SAH). A better understanding of the risk factors of seizures following aneurysmal SAH is needed to predict those who will require treatment. A total of 137 adult patients were enrolled in this two-year retrospective study. Baseline prognostic variables were analyzed based on Cox's proportional hazards model after a minimum of one-year follow-up. Seizures occurred in 21 patients who had SAH, including acute symptomatic seizures in 11.7% (16/137) and unprovoked seizures in 3.6% (5/137). None progressed to status epilepticus during hospitalization. After a minimum of one-year follow-up, the mean Glasgow Outcome Score was 3.5 +/- 1.4 for patients with seizures and 3.1 +/- 1.1 for those without. Higher mean World Federation of Neurological Societies grade on presentation was predictive of seizure, but seizure itself was not a significant prognostic predictor after a minimum of one-year follow-up. Regarding potential side effects of anti-epileptic drugs, anti-epileptic therapy should be carefully administered to patients with seizures after aneurysmal SAH.


Expression of regulatory receptors on γδ T cells and their cytokine production in Behcet's disease.
Behcet's disease (BD) is a multi-systemic disorder with muco-cutaneous, ocular, arthritic, vascular or central nervous system involvement. The role of γδ T cells is implicated in BD. The activation status of γδ T cells and their cytokine secretion against phosphoantigens are evaluated in BD. NKG2A, NKG2C, NKG2D, CD16 and CCR7 molecules on γδ T cells were analyzed in 70 BD, 27 tuberculosis (TB) patients and 26 healthy controls (HC). Peripheral γδ T cells were expanded with a phosphoantigen (BrHPP) and IL-2, restimulated with BrHPP and a TLR3 ligand, and cytokine production was measured. γδ T cells were not increased in both BD and TB patients, but the proportions of TCRVδ2+ T cells were lower (58.9 and 50.7 vs. 71.7%, P=0.04 and P=0.005) compared to HC. Higher proportion of TCRVδ2+ T cells were CD16+ (26.2 and 33.9 vs. 16.6%, P=0.02 and P=0.001) and CCR7- (32.2 and 27.9 vs. 17.7%, P<0.0001 and P=0.014) in BD and TB patients compared to HC. NKG2C+ γδ+ T cells were relatively increased (0.5 and 0.6 vs. 0.3%, P=0.008 and 0.018), whereas NKG2D positivity was decreased in patients with BD and TB (77.7 and 75.8 vs. 87.5%, P=0.001 and 0.004). Expansion capacity of γδ T cells in BD and TB as well as production of IL-13, IFN-γ, granulocyte monocyte colony stimulating factor (GM-CSF), TNF-α, CCL4 and CCL5 in BD was lower compared to HC, when restimulated by TLR3 ligand and BrHPP. The changes on γδ T cells of BD as well as TB patients implicate that γδ T cells have already been exposed to regulatory effects, which changed their activity. Lower cytokine response of γδ T cells implicates down modulation of these cells in BD.


Post-intestine transplant graft-vs-host disease associated with inclusion of a liver graft and with a high mortality risk.
This study reports the incidence, anatomic location, and outcomes of graft-vs-host disease (GVHD) at a single active intestine transplant center. Records were reviewed for all patients receiving an intestine transplant from 2003 to 2015. Pathology reports and pharmacy records were reviewed to establish the diagnosis, location, and therapeutic interventions for GVHD. A total of 236 intestine transplants were performed during the study period, with 37 patients (16%) developing GVHD. The median time to onset of disease was 83 days, with 89% of affected patients diagnosed in the first year post-transplant. Mortality for affected patients was 54% in the 1 year after GVHD diagnosis. Skin lesions were the most common manifestation of GVHD. Other sites of disease included lungs, bone marrow, oral mucosa, large intestine, and brain. The incidence of GVHD was 16% in adult patients, and slightly lower in pediatric recipients (13%). In adults, increasing graft volume (isolated vs multi-organ) and liver inclusion were associated with increasing risk of GVHD, though this was not seen in pediatric patients. Overall, 16% of intestine transplant recipients developed GVHD. GVHD is associated with high mortality, and disease in the lungs, brain, and bone marrow was universally fatal.


Prediction of mortality in type 2 diabetes from health-related quality of life (ZODIAC-4).
To investigate the relationship between health-related quality of life (HRQOL) and mortality in type 2 diabetes. In 1998, 1,143 primary care patients with type 2 diabetes participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. At baseline, HRQOL was assessed with the RAND-36 and, after almost 6 years, life status was retrieved. Cox proportional hazards modeling was used to investigate the association between HRQOL (continuous data) and mortality with adjustment for selected confounders (smoking, age, sex, diabetes duration, A1C, renal function, BMI, blood pressure, HDL cholesterol, and macrovascular complications). The Physical Component Summary of the RAND-36 was inversely associated with mortality (hazard ratio [HR] 0.979 [95% CI 0.966-0.992]), as were two separate RAND-36 dimensions. This study found that HRQOL is an independent marker of mortality and emphasizes the importance of looking beyond clinical parameters in patients with type 2 diabetes.


Prevention of damage in acute spinal cord injury by peptides and pharmacologic agents.
Cats were used as models of traumatic spinal cord injury. Each experimental animal received a 500 g-cm force to the exposed dura at the level of thoracic fourth vertebra. Somatosensory evoked potentials (SEPs), carotid arterial blood pressure (BP), and abdominal aorta blood flow in the treated groups were compared with those of the control group. The three treated groups received naloxone (5 mg/kg), TRH (5 mg/kg), and a combination of methyl-prednisolone sodium succinate (MP, 35 mg/kg) and epsilon-aminocaproic acid (EACA, 350 mg/kg). The SEPs which were done only in the naloxone treated group approached "normalcy" 24-26 hours after trauma as compared with the absence of SEPs in traumatized untreated group. In all three groups, the treatment increased the blood flow in abdominal aorta significantly. Morphine sulfate increased substance P (SP) immunoreactivity in the dorsal and ventral gray matter. Naloxone not only reversed this effect, it depleted SP below the saline control level. In order to establish that lipid free radicals are responsible for damage to biological membranes, their effects were also investigated in vitro: 14C-GABA uptake by mouse cortical slices which had decreased by 33% in the presence of superoxide (. O-2) generating system, horseradish peroxidase (HRP), was reduced only by 9% when superoxide dismutase was added to the medium. The latter also protected the nerve endings from damage by (. O-2) as examined by electron microscopy. It is concluded that the agents used in this study produce their ameliorating effects by virtue of their anti-inflammatory, anti-oxidant, and membrane stabilizing properties in addition to their effect on enhancing the regional microcirculation. The release of SP by naloxone may be responsible for the increase in blood flow. The consequences of traumatic injury as depicted in Fig. 1 are discussed at length.


Ethyl 2-(4-hy-droxy-3-meth-oxy-phen-yl)-1-[3-(2-oxopyrrolidin-1-yl)prop-yl]-1H-benzimidazole-5-carboxyl-ate monohydrate.
In the title compound, C(24)H(27)N(3)O(5)·H(2)O, the essentially planar benzimidazole ring system [maximum deviation = 0.020 (1) Å] forms dihedral angles of 54.10 (11) and 67.79 (6)°, respectively, with the mean plane of pyrrolidin-2-one ring and the benzene ring. The pyrrolidin-2-one ring adopts an envelope conformation with one of the methylene C atoms at the flap. An intra-molecular C-H⋯π inter-action is observed. In the crystal, O-H⋯O and O-H⋯N hydrogen bonds link the two components into a double-tape structure along the a axis. The crystal packing is further stabilized by weak π-π stacking [centroid-centroid distance = 3.6632 (9) Å] and C-H⋯O inter-actions.


Altered surfactant synthesis and function in rats with diet-induced hyperlipidemia.
Altered lung function in hyperlipidemic patients has been reported by many authors. An alteration of surfactant synthesis has been suggested. Isolated lungs of rats rendered hyperlipidemic by suitable diets display an increased distensibility at maximal inflation and a higher degree of alveolar stability during deflation. These alterations are related to modifications of surfactant properties. Lung lavage fluid obtained from hyperlipidemic rats displays an increase in percent content of phosphatidylglycerol and a decrease of phosphatidylethanolamine. The percent content of phosphatidylglycerol correlates with the circulating levels if free fatty acids (FFA). It is suggested that FFA might affect the activity of enzymes operating in lung phospholipid synthesis. The reported increase of surfactant phosphatidylglycerol might explain the increment of alveolar stability observed in hyperlipidemic rats.


Special Issue: Advanced Science and Technology of Polymer Matrix Nanomaterials.
Polymer matrix nanomaterials have revolutionized materials science due to their unique properties resulting from the incorporation of nanoscale fillers into polymer matrices [...].


The possible role of fungal infections in AIDS.
The acquired immunodefficiency syndrome (AIDS) is characterized by a gross defect in the cell-mediated immune response. However, infection with human immunodeficiency virus (HIV), which is the generally accepted etiological factor of AIDS, cannot explain by itself the following problems: why do not some of the seropositive subjects develop AIDS or AIDS-related complex; why are some of the patients with AIDS seronegative for HIV and its corresponding antibodies; what is the reason why some of the healthy seronegative subjects from groups at a high risk for AIDS (homosexuals, hemophiliacs and drug abusers) have low T-helper to T-suppressor ratios. We suggest that some additional factor is necessary for the development of AIDS. We propose that the factor needed is a 'partial functional thymectomy'. We suspect that slow fungal infections, producing thymotoxic metabolites, may be a major cause for the latter.


Gastrectomy Versus Esophagectomy for Gastroesophageal Junction Tumors: Short- and Long-Term Outcomes From the Dutch Upper Gastrointestinal Cancer Audit.
Investigate long-term survival, morbidity, mortality, and pathology results in patients following esophagectomy or total gastrectomy for gastroesophageal junction (GEJ) cancer. Both a total gastrectomy and an esophagectomy may be valid treatment options in patients with GEJ cancer. Which procedure results in the most optimal patient outcome is not well studied. The aim of this study was to investigate the long-term survival, morbidity, mortality, and pathology results in patients following esophagectomy or total gastrectomy for GEJ cancer. A retrospective comparative cohort study of prospectively collected data from the Dutch Upper GI Cancer Audit combined with survival data of the Dutch medical insurance database was performed. Patients with GEJ cancer in whom a total gastrectomy or an esophagectomy was performed between 2011 and 2016 were compared. The primary outcome was 3-year overall survival. Postoperative morbidity, mortality, 3-year conditional survival, radicality of resection, and lymph node yield were secondary endpoints. A total of 871 patients were included: 790 following esophagectomy and 81 following gastrectomy. The 3-year overall survival was 35.8% after esophagectomy and 28.4% after gastrectomy (hazard ratio 1.2, 95% confidence interval 0.721-1.836, P = 0.557). Postoperative morbidity, mortality, radicality of resection, lymph node yield, and 3-year conditional survival did not differ significantly between groups. A total gastrectomy and an esophagectomy for GEJ cancer show largely comparable results with regard to long-term survival, postoperative morbidity, mortality, and pathology results. If both procedures are feasible, other parameters such as surgeon's experience and quality of life should be considered when planning for surgery.


High-affinity binding of beta-carbolines to imidazoline I2B receptors and MAO-A in rat tissues: norharman blocks the effect of morphine withdrawal on DOPA/noradrenaline synthesis in the brain.
This study was designed to determine the affinity and binding profile of beta-carbolines for imidazoline I2 receptors and catalytic sites of monoamine oxidase (MAO)-A/B in rat brain and liver. The aim was also directed to assess the in vivo effects of norharman (beta-carboline) and LSL 60101 (I2 ligand) on brain 3,4-dihydroxyphenylalanine (DOPA) synthesis in morphine-dependent rats. Competition experiments against [3H]2-BFI revealed that beta-carbolines recognize the high- and low-affinity components of the brain imidazoline I2 receptor with the rank order of potency (K(iH) in nM): noreleagnine (12)>norharman (20)>harmalol (82)>harmaline (177)>>harmine (630)>harman (700)>>FG-7142 (>100,000). In liver, this rank was different: harmine (51)>harmaline (103)=noreleagnine (103)>>harmalol (1290)>harman (2000)>>norharman (12,382)>>FG-7142 (>100,000). In brain and liver, competition curves for beta-carbolines against [3H]Ro41-1049 (MAO-A) and [3H]Ro19-6327 (MAO-B) were monophasic and resulted in different drug potencies for the two MAO isozymes (higher affinities for MAO-A) and in similar pharmacological profiles in both tissues. In morphine-dependent rats, naloxone (2 mg/kg, 2 h)-precipitated withdrawal increased the synthesis of DOPA in the cerebral cortex and hippocampus (50%). Pretreatment with norharman (20 mg/kg) or LSL 60101 (20 mg/kg) (30 min before naloxone) fully prevented the stimulatory effect of opiate withdrawal on DOPA synthesis. Norharman and LSL 60101 also attenuated the severity of the withdrawal syndrome. The results indicate that beta-carbolines bind with high affinity to imidazoline I2B receptors, and similarly to I2 ligands (LSL 60101) can block the behavioural and biochemical effects of opiate withdrawal.


Conventional-dose Versus Half-dose Sulfamethoxazole-trimethoprim for the Prophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Disease: A Non-blind, Randomized Controlled Trial.
Pneumocystis pneumonia (PCP) due to Pneumocystis jirovecii infection is the leading cause of fatal opportunistic infections in immunocompromised patients. We will determine whether a daily sulfamethoxazole-trimethoprim (SMX/TMP) dose of 200/40 mg was non-inferior to 400/80 mg for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. This is a randomized, open-label, multicenter controlled trial. The primary outcome is the rate of PCP prevention at 52 weeks. The secondary outcome is the discontinuation rate of SMX/TMP. The trial will evaluate the optimal dose of SMX/TMP for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy.


Influence of socioeconomic factors on the adherence of alendronate treatment in incident users in Norway.
To examine whether socioeconomic factors influence adherence to alendronate drug treatment among incident users in Norway during 2005-2009. The study included 7610 incident alendronate users in 2005 (40-79 years), followed until 31 December 2009. Mean age was 66.6 years, and 86.7% of the patients were women. Data were drawn from the Norwegian Prescription Database and linked to marital status, education and income. Adherence was measured by the medication possession ratio (MPR). MPR was defined as the number of dispensed defined daily doses divided by the number of days each patient was included in the study. A patient was adherent if MPR ≥ 80%. ORs with 95%CI were estimated using logistic regression. Among all patients, 45.5% was adherent throughout 4.2 years. A slightly higher proportion of women than men were adherent. Adjusted for all covariates, women aged 70-79 years had an OR of 1.27 (95%CI 1.10-1.45) for adherence compared with those 40-59 years. In women, high household income predicted adherence of alendronate use. In men, a middle educational level compared with a low level, predicted adherence (adjusted OR = 1.47 (95%CI 1.10-1.96)). After adjustments, previous marriage reduced the odds of being adherent compared with present marriage, in both men and women. In women, the most important factors for being adherent were high age and high income. In men, a middle educational level predicted adherence. Previous marriage reduced the odds of being adherent in both women and men.


Value of probe-based confocal laser endomicroscopy (pCLE) and dual focus narrow-band imaging (dNBI) in diagnosing early squamous cell neoplasms in esophageal Lugol's voiding lesions.
Lugol's chromoendoscopy provides excellent sensitivity for the detection of early esophageal squamous cell neoplasms (ESCN), but its specificity is suboptimal. An endoscopy technique for real-time histology is required to decrease the number of unnecessary biopsies. This study aimed to compare the ESCN diagnostic capability of probed-based confocal laser endomicroscopy (pCLE) and dual focus narrow-band imaging (dNBI) in Lugol's voiding lesions. Patients with a history of head and neck cancer without dysphagia were recruited. Lugol's voiding lesions larger than 5 mm were sequentially characterized by dNBI and pCLE by two independent operators. Finally, all lesions larger than 5 mm were biopsied followed by histological analysis, which is considered to be the gold standard in cancer diagnosis. The primary outcomes were the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of the two techniques. In total, 44 patients were enrolled with a mean age of 60 years; 80 % were male. Twenty-one Lugol's voiding lesions larger than 5 mm were detected in 12 patients. Seven lesions (33 %) from four patients were histologically diagnosed as ESCNs (four with high grade dysplasia and three with low grade dysplasia). The other 14 lesions were histologically confirmed as non-neoplastic: active esophagitis, glycogenation with inflammation, acute ulcer, inlet patch, and unremarkable changes. The sensitivity, specificity, PPV, NPV, and accuracy of pCLE vs. dNBI were 83 % vs. 85 %, 92 % vs. 62 %, 83 % vs. 54 %, 92 % vs. 89 %, and 89 % vs. 70 %, respectively (NS). Asymptomatic patients with a history of head and neck cancer underwent Lugol's chromoendoscopy based ESCN surveillance. Further characterization of the Lugol's voiding lesions by advanced imaging showed that both pCLE and dNBI provided good sensitivity in diagnosing ESCN, and pCLE tended to provide higher specificity, PPV, and accuracy than dNBI. Perhaps the trend of lower specificity of dNBI in this study was possibly because of the interference from Lugol's stain on the interpretation of intrapapillary capillary loops (IPCLs). Further study is required to seek a significant difference in the performance of dNBI and pCLE in a larger group of patients.


Trypsin-pancreatic secretory isoinhibitor A from bovine pancreas (Kazal type). Spectroscopic study on structure and stability.
The secondary and tertiary structure of isoinhibitor A from bovine pancreas secretion (Kazal inhibitor) was investigated by circular dichroism (CD) and fluorescence measurements. The protein shows noteworthy thermal stability as seen by the temperature dependence of the CD spectra and the intensity of emission fluorescence at different pH values.


Hypercapnia modulates synaptic interaction of cultured brainstem neurons.
CO(2) is an important metabolic product whose concentrations are constantly monitored by CO(2) chemoreceptors. However, the high systemic CO(2) sensitivity may not be achieved by the CO(2) chemoreceptors without neuronal network processes. To show modulation of network properties during hypercapnia, we studied brainstem neurons dissociated from embryonic rats (P17-19) in multielectrode arrays (MEA) after initial period (3 weeks) of culture. Spike trains of 33,622 pairs of units were analyzed using peri-event histograms (PEH). The amplitude of peri-central peaks between two CO(2)-stimulated units increased and the peak latency decreased during hypercapnia. Similar enhancement of synaptic strength was observed in those sharing a common input. These phenomena were not seen in CO(2)-unresponsive neurons. The amplitude of peri-central peaks between two CO(2) inhibited units also increased without changing latency. Over 60% CO(2)-stimulated neurons studied received mono-/oligosynaptic inputs from other CO(2)-stimulated cells, whereas only approximately 10% CO(2)-unresponsive neurons had such synaptic inputs. A small number of brainstem neurons showed electrical couplings. The coupling efficiency of CO(2)-stimulated but not CO(2)-unresponsive units was suppressed by approximately 50% with high PCO(2). Inhibitory synaptic projections were also found, which was barely affected by hypercapnia. Consistent with the strengthening of excitatory synaptic connections, CO(2) sensitivity of post-synaptic neurons was significantly higher than presynaptic neurons. The difference was eliminated with blockade of presynaptic input. Based on these indirect assessments of synaptic interaction, our PEH analysis suggests that hypercapnia appears to modulate excitatory synaptic transmissions, especially those between CO(2)-stimulated neurons.


Pneumoperitoneum as a complication of cardiopulmonary resuscitation.
A case of pneumoperitoneum following cardiopulmonary resuscitation (CPR) is reported and 11 cases in the literature are reviewed. Four patients had laparotomies failing to demonstrate any visceral perforation or evidence of peritonitis in spite of the massive pneumoperitoneum present. Operative intervention immediately after resuscitation is associated with potentially high morbidity and mortality. Several diagnostic tools are used, including peritoneal lavage and contrast media tests, to accurately diagnose perforated viscus. To avoid an unnecessary celiotomy a clinical treatment protocol has been developed for patients with pneumoperitoneum secondary to CPR. Such diagnostic tools as peritoneal lavage and water-soluble contrast medium test are reviewed and included in this protocol. A nonsurgical approach to patient management may be reasonable if certain criteria are met.


Use of drug-coated balloons in the management of a recalcitrant postsurgical hepatic vein stenosis in a pediatric patient.
Drug-coated balloons (DCB) are a treatment alternative to conventional angioplasty in arterial, hemodialysis fistulas, and venous stenoses. This case report describes a child with the diagnosis of hepatoblastoma treated with chemotherapy and a right extended hepatectomy with venous reconstruction. The patient presented with signs and symptoms of portal hypertension due to a hepatic venous outflow obstruction secondary to stenosis of the surgical anastomosis. The response to conventional angioplasty was limited with frequent recurrence of symptoms. DCBs were used as an alternative prior to stent consideration aiming to assess if these devices could provide improvement of the symptoms and as a long-term therapy. The use of DCBs increased the time interval of reinterventions in comparison with conventional angioplasty. The patient eventually required stents due to recurrence of the primary disease. While this report does not provide an in-depth evaluation in terms of the efficacy and safety of DCB, this case illustrates a potential novel treatment modality to be considered for children, when stenotic venous lesions not amenable for stenting are present.


The determinants of mortality and morbidity after multiple-valve operations.
The factors predictive of hospital mortality and morbidity after contemporary multiple-valve surgical procedures were identified to develop strategies to improve the results of such procedures. Preoperative, intraoperative, and postoperative information was collected prospectively on 90 consecutive patients undergoing surgical procedures between 1982 and 1984. The operative mortality was 5.6%, and the incidence of postoperative low-output syndrome was 16.7%. Multivariate logistic regression analysis identified tricuspid regurgitation (p less than .03, improvement-of-fit chi square) and the aortic valve lesion (p less than .03) as the independent predictors of postoperative complications (mortality or low-output syndrome). Patients with tricuspid regurgitation and right ventricular decompensation and those with aortic stenosis and left ventricular hypertrophy had limited ventricular functional reserve and faced an increased risk. Improved methods of myocardial protection may reduce the risk in these patients.


Mucus penetrating properties of soft, distensible lipid nanocapsules.
Designing nanomaterials to release their drug pay-load upon exposure to an exogenous trigger can help to direct drug delivery, but how the triggered release, which often modifies the nanomaterial properties, influences the biological fate of these systems is currently unknown. The aim of this study was to investigate how the triggered drug release from PEG coated, soft, 50 nm distensible lipid nanocapsules (LNC) influenced their diffusion across a mucus barrier. The translocation speed of the non-triggered LNC across a 35 µm thick purified gastric mucin (PGM) barrier was 3 times faster (30.08 ± 2.49 × 10-10 cm2 s-1) compared to equivalent-sized negatively charged polystyrene particles (9.87 ± 0.61 × 10-10 cm2 s-1, p < 0.05). In cystic fibrosis mucus (CFM), harvested from patient primary cells, the non-triggered LNC translocation speed was similar to the PGM, but the polystyrene particle diffusion was so slow it could not be measured. The trigger induced LNC distension process had no effect on the particle diffusion rate in both PGM and CFM (p > 0.05) in a static mucus barrier, but when shear was applied to the barrier the distended LNCs diffused more slowly (3.97 ± 1.38 × 10-8 cm2 s-1, p < 0.05) compared to the non-distended materials (4.94 ± 0.04 × 10-8 cm2 s-1). This data suggested the rapid mucus penetration of the distended LNCs, despite their increased size, was a consequence of their capacity to take a less tortuous path through the barrier, i.e., they experienced less steric hinderance, compared to the non-distended LNC.


Surgical margin follow-up after nephron-sparing surgery: the possible role of CEUS.
To evaluate the possible role of CEUS in the management of patients who underwent nephron-sparing surgery (NSS) and presented questionable findings on the surgical margins at the CECT follow-up exam. In our retro-prospective study, we included 952 patients with small renal masses (SRMs) treated with NSS between 2012 and 2015 and followed with CECT for at least 3 years at Careggi University Hospital. Twenty-two of them presented solid masses on the site of surgery with questionable enhancement at CECT and were further studied with CEUS. This examination was followed by a quantitative analysis of the enhancement pattern. Out of the 22 masses, 18 were considered possible granulomas, presenting slow wash-in and low enhancement peaks compared to the surrounding parenchyma and persistent delayed wash-out at CEUS. Four lesions presented a suspicious malignant enhancement pattern, with rapid wash-in, high peak and rapid wash-out. In accordance with instructions from the urologist, the first group of 18 patients was strictly monitored, revealing that the mass dimensions and enhancement pattern were stable for at least 3 years of follow-up, while the other 4 patients underwent a second intervention and their masses were confirmed as tumor recurrence at the histopathological evaluation. CEUS can play a key role in the surgical margin follow-up after NSS when a suspicious enhancing mass is detected by CECT, giving an accurate depiction of the enhancement pattern and thus helping the clinician in the management of the patient.


The effect of oxoguanine glycosylase 1 rs1052133 polymorphism on colorectal cancer risk in Caucasian population.
Human oxoguanine glycosylase 1 (OGG1) is an important part of the base excision repair pathway in the DNA repair. Numerous epidemiological studies have evaluated the association between OGG1 rs1052133 polymorphism and the risk of colorectal cancer, but the results of these studies from the Caucasian population were conflicting. To derive a more precise assessment on the association between OGG1 rs1052133 polymorphism and risk of colorectal cancer in Caucasian population, we performed a meta-analysis. The odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the association. Thirteen case-control studies with a total of 4,103 cases and 5,400 controls were finally included into the meta-analysis. Meta-analysis of all 13 studies showed that OGG1 rs1052133 polymorphism was significantly associated with the risk of colorectal cancer in Caucasian population (Cys versus Ser OR = 1.20, 95% CI = 1.03-1.39, P = 0.02; CysCys versus SerSer OR = 1.44, 95% CI = 1.04-2.00, P = 0.03; CysCys versus SerSer/SerCys OR = 1.39, 95% CI = 1.15-1.67, P = 0.0005). In the sensitivity analysis, omitting each study one at a time had no obvious influence on the pooled OR, which confirmed the stability of meta-analysis. The meta-analysis suggests that OGG1 rs1052133 polymorphism is significantly associated with the risk of colorectal cancer in Caucasian population.


The potential clinical advantages of charged particle radiotherapy using protons or light ions.
The increasing use of charged particle radiotherapy (CPT) in many countries will require British oncologists to establish their personal viewpoints on this subject in order to advise their patients regarding the merits or otherwise of obtaining such treatment abroad. This paper covers the advantages and some disadvantages of CPT in many anatomical locations on the basis of the achievable dose distributions as a consequence of the Bragg peak effect. The advantages in terms of normal tissue effects should follow the reduction of tissue volumes exposed to low/moderate dose: significant reductions in acute tissue effects are expected and experienced. For late reacting tissues, the predicted benefits are in the reduction of chronic low-grade symptoms and so improving the quality of life. For tumour control, dose escalation beyond what is achievable with X-ray therapy is possible only for some tumour types. Also, some tumours not presently treated by X-rays can be treated by CPT instead of radical surgery. Many of the available publications about CPT are at 'proof of principle' stage, as the treatment technique continues to be optimised: this is a similar situation to mega-voltage radiotherapy around 50 years ago. Oncologists in the UK need to familiarise themselves with CPT dose distributions, continually educate themselves by following the results of clinical studies as these emerge with time and hopefully visit CPT centres for direct experience.


Complete dissociation branching fractions and Coulomb explosion dynamics of SO2 induced by excitation of O 1s pre-edge resonances.
Fragmentation processes of SO2 following excitation of the six main O 1s pre-edge resonances, as well as above the ionization threshold and below the resonances, are studied using a position-sensitive time-of-flight ion imaging detector, and the associated dissociation branching ratios and break-up dynamics are determined. In order to distinguish between the O(+) and S(2+) fragments of equal mass-to-charge ratio, the measurements have been performed with the isotopically enriched S(18)O2 sample. By analysis of the complete set of the fragment momentum vectors, the β values for the fragments originating from the SO(+) + O(+) break-up and the kinetic energy release for fragmentation channels of both SO2 (2+) and SO2 (3+) parent ions are determined. We also present results on the three-body break-up dynamics.


Codium isthmocladum lectin 1 (CiL-1): Interaction with N-glycans explains antinociceptive and anti-inflammatory activities in adult zebrafish (Danio rerio).
Inflammation and oxidative stress are processes associated with different human diseases. They are treated using drugs that have several side effects. Seaweed are sources of potentially relevant natural compounds for use as treatment of these disorders. Lectins are able to reversibly interact with complex carbohydrates and modulate cell membrane glycosylated receptors through this interaction. This study aimed to determine the antinociceptive and anti-inflammatory potential of CiL-1 in adult zebrafish by modulation of TRPA1 through lectin-glycan binding. Possible neuromodulation by TRPA1 channel was also evaluated by camphor pretreatment. CiL-1 was efficacious at all tested doses, revealing anti-nociceptive and anti-inflammatory effects in adult zebrafish. This galactose-binding lectin was also able to reduce the content of ROS in brain and liver. In silico analyses showed CiL-1 interactions with both ligands tested. LacNac2 presents the most favorable binding energy with the protein. The interaction occurs at 4 subsites as an extended conformation at the site. LacNac2-Sia had a less favorable curved-shape interaction energy. Based on the predictions made for the oligosaccharides, a tetra-antenate putative glycan was schematically constructed, illustrating an interaction between TRPA1 N-glycan and CiL-1. This binding seems to be related to CiL-1 anti-inflammatory activity as result of receptor modulation.


Corticosteroid therapy for cardiac sarcoidosis: a systematic review.
There are no published clinical consensus guidelines or systematic evaluation supporting the use of corticosteroids for the treatment of cardiac sarcoidosis. The purpose of this study was to systematically review the published data on corticosteroid treatment of cardiac sarcoidosis. Studies were identified from MEDLINE, EMBASE, Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and National Institutes of Health Clinical Trials.gov database. The quality of included articles was rated using Scottish Intercollegiate Guidelines Network 50. Outcomes examined were atrioventricular (AV) conduction, left ventricular function, ventricular arrhythmias, and mortality. A total of 1491 references were retrieved and 10 publications met the inclusion criteria. There were no randomized trials and all publications were of poor to fair quality. In the 10 reports, 257 patients received corticosteroids and 42 patients did not. There were 57 patients with AV conduction disease treated with corticosteroids, with 27/57 (47.4%) improving. In contrast, 16 patients were not treated with corticosteroids and 0/16 improved. Four publications reported on left ventricular function recovery, 2 reported on ventricular arrhythmia burden, and 9 reported on mortality. However, the data quality were too limited to draw conclusions for any of these outcomes. Our systematic review identified 10 publications reporting outcomes after corticosteroid therapy. The best data relates to AV conduction recovery and corticosteroids appeared to be beneficial. It is not possible to draw clear conclusions about the utility of corticosteroids for the other outcomes. There is a clear need for large multicentre prospective registries and trials in this patient population.


The relationship between lymphocyte-to-monocyte ratio and saphenous vein graft patency in patients with coronary artery bypass graft.
A lower lymphocyte count and a high monocyte count give important clues about the prognosis of various cardiovascular diseases. We hypothesized that lymphocyte-to-monocyte ratio (LMR) was associated with the saphenous vein graft disease (SVGD) in patients with coronary artery bypass graft (CABG). A total of 218 patients with previous history of CABG surgery, who underwent coronary angiography due to stable angina symptoms, were investigated, retrospectively. LMR levels were significantly lower in the SVGD group. Multiple logistic regression analyses showed that LMR levels were independent predictors of SVGD (OR: 0.648; 95% CI: 0.469-0.894; p = 0.008). Our results suggested that LMR levels may provide useful information for the relevant risk evaluation of SVGD in CABG patients.


Racial/ethnic inequities in continuity and site of care: location, location, location.
To examine how continuity of care with the same provider varies by race/ethnicity and by site of care. Secondary data analyses of the 1996-97 Community Tracking Study household survey, a representative cross-sectional sample of 34,858 U.S. adults (aged 18 to 64 years), were employed. Logistic regression analyses were conducted to explore relationships between respondents' race/ethnicity and having a regular site of care, type of site, and continuity with the same provider at this site. Racial/ethnic minority group members were less likely than whites to identify a regular site of care. Among respondents who identified a regular site, minorities, particularly Spanish-speaking Hispanics, reported less continuity of care with the same provider. However, these disparities in continuity were largely explained by racial/ethnic differences in the types of places where care was obtained. Compared to those who were seen in physicians' offices, continuity with the same provider was much lower among respondents who were seen in hospital out patient departments or health centers or other clinics. Racial and ethnic minority group members receive less continuity of care for reasons including lack of a regular site of care and less continuity with the same provider. Greater use of hospital clinics and community health centers by minorities also contributes to this discontinuity.


Transplacental kanamycin ototoxicity in the guinea pig.
The effect of kanamycin on the cochlear sensory epithelium of albino guinea pig fetuses was studied histologically following the administration of 200 or 400 mg/kg body weight kanamycin sulfate to the pregnant mothers for 8 consecutive days at different stages of gestation. Surface view analysis of Corti's organ revealed slight damage following treatment in the middle trimester of gestation and marked damage due to treatment in the last trimester. The pattern of hair cell loss induced during and after the functional differentiation of the cochlea resembled the pattern of ototoxic lesions in the adult ear. The assumed mechanisms for induction of teratogenesis by kanamycin in the fetal organ of Corti are discussed.


Increased aneurysm wall permeability colocalized with low wall shear stress in unruptured saccular intracranial aneurysm.
Aneurysm wall permeability has recently emerged as an in vivo marker of aneurysm wall remodeling. We sought to study the spatial relationship between hemodynamic forces derived from 4D-flow MRI and aneurysm wall permeability by DCE-MRI in a region-based analysis of unruptured saccular intracranial aneurysms (IAs). We performed 4D-flow MRI and DCE-MRI on patients with unruptured IAs of ≥ 5 mm to measure hemodynamic parameters, including wall shear stress (WSS), oscillatory shear index (OSI), WSS temporal (WSSGt) and spatial (WSSGs) gradient, and aneurysm wall permeability (Ktrans) in different sectors of aneurysm wall defined by evenly distributed radial lines emitted from the aneurysm center. The spatial association between Ktrans and hemodynamic parameters measured at the sector level was evaluated. Thirty-one patients were scanned. Ktrans not only varied between aneurysms but also demonstrated spatial heterogeneity within an aneurysm. Among all 159 sectors, higher Ktrans was associated with lower WSS, which was seen in both Spearman's correlation analysis (rho = - 0.18, p = 0.025) and linear regression analysis using generalized estimating equation to account for correlations between multiple sectors of the same aneurysm (regression coefficient = - 0.33, p = 0.006). Aneurysm wall permeability by DCE-MRI was shown to be spatially heterogenous in unruptured saccular IAs and associated with local WSS by 4D-flow MRI.


Metal-organic frameworks for wastewater treatment: Recent developments, challenges, and future prospects.
Wastewater treatment is critically important for the existence of life on earth; however, this approach involves the removal of toxic metal contaminants and organic pollutants, requiring efficient adsorbent materials. Within this agenda, metal-organic frameworks (MOFs) appear to be potential materials due to their unique properties as efficient adsorbents, effective photocatalysts, and reliable semi-permeable membranes. Therefore, MOFs have undergone various modifications over the years without desirable success to improve adsorption capacity, hydro-stability, reaction kinetics, and reusability. Therefore, scientists around the world got engaged in MOF research for novel modifications, including defect engineering, carbonization, and membrane fabrication, at the laboratory scale. This review focuses on developing MOF-based adsorbents, photocatalysts, and semi-permeable membranes for wastewater treatment since 2015, emphasizing their structural-functional relationships. Finally, the challenges and opportunities with MOFs in wastewater treatment are also underlined for future efforts.


Modeling of ozone decomposition, oxidant exposures, and the abatement of micropollutants during ozonation processes.
This study demonstrates new empirical models to predict the decomposition of ozone (O3) and the exposures of oxidants (i.e., O3 and hydroxyl radical, OH) during the ozonation of natural waters. Four models were developed for the instantaneous O3 demand, first-order rate constant for the secondary O3 decay, O3 exposure (∫[O3]dt), and OH exposure ((∫[OH]dt)), as functions of five independent variables, namely the O3 dose, concentration of dissolved organic carbon (DOC), pH, alkalinity, and temperature. The models were derived by polynomial regression analysis of experimental data obtained by controlling variables in natural water samples from a single source water (Maegok water in Korea), and they exhibited high accuracies for regression (R2 = 0.99 for the three O3 models, and R2 = 0.96 for the OH exposure model). The three O3 models exhibited excellent internal validity for Maegok water samples of different conditions (that were not used for the model development). They also showed acceptable external validity for seven natural water samples collected from different sources (not Maegok water); the IOD model showed somewhat poor external validity. However, the OH exposure model showed relatively poor internal and external validity. The models for oxidant exposures were successfully used to predict the abatement of micropollutants by ozonation; the model predictions showed high accuracy for Maegok water, but not for the other natural waters.


Obesity Management and Chronic Kidney Disease.
Obesity is one of the risk factors for the development and progression of chronic kidney disease (CKD). Several studies have shown the association between increased body mass index and kidney function decline. Obesity leads to CKD directly by acting as an independent risk factor and indirectly through increasing risks for diabetes, hypertension, and atherosclerosis, a group of well-established independent risk factors for CKD. Alterations in renal hemodynamics, inflammation, and in hormones and growth factors results in hyperfiltration injury and focal segmental glomerulosclerosis. In recent years, many studies have shown that the gut microbiome may play a role in the pathogenesis of obesity. Dysbiosis has been noted in obese subjects in both human and animal studies. Changes in the gut microbiome in obese patients promote weight gain by effectively extracting energy from diet, and induction of low-grade inflammation. Evidence also points to the role of inflammation within the adipose tissue in obesity as a key factor in the pathogenesis of obesity-related complications. Thus, obesity is the net result of complex interactions between behavioral, genetic, and environmental factors. In terms of management, conservative approaches are often the first option, but they often are unsuccessful in achieving and/or maintaining weight loss, particularly in severe obesity. Consequently, nonmedical management with bariatric surgery is the most effective treatment option for morbid obesity and has shown mitigation of multiple risk factors for the progression of CKD. The most frequently performed interventions are vertical sleeve gastrectomy and Roux-en-Y gastric bypass. Studies have shown that bariatric surgery is associated with beneficial effects on CKD by mitigating its risk factors by weight loss, reducing insulin resistance, hemoglobin A1c, and proteinuria, in addition to positive long-term outcomes. Because of the epidemic of obesity, the prevalence of obesity in kidney transplant recipients also is increasing. The maximal body mass index (BMI) threshold for kidney transplantation is not clear. The Organ Procurement Transplant Network/Scientific Registry of Transplant Recipients 2019 annual data report showed that the proportion of kidney transplant recipient candidates with a BMI of 30 kg/m2 or greater is increasing steadily. Morbid obesity is linked to adverse graft outcomes including delayed graft function, primary nonfunction, and decreased graft survival. Obesity is also an independent risk factor for cardiovascular death in kidney transplant recipients, suggesting that these patients should not be excluded from transplantation based on their BMI because transplantation is associated with lower mortality compared with dialysis. However, many centers exclude obese patients (with different BMI cut-off values) from transplantation to avoid postoperative complications. To minimize the surgical complications of kidney transplantation in obese patients, our center has adopted the robot-assisted kidney transplantation procedure. Our data show that this approach is comparable with historical nonobese controls in the United Network for Organ Sharing database in terms of patient and graft survival. Another surgical option for this group of patients at our center is a combined robotic sleeve gastrectomy and robotic-assisted kidney transplant. In a recent study, this approach showed promising results in terms of weight loss, patient survival, and graft survival, and might become more common in the future.


Dialysis membrane-enforced microelectrode array measurement of diverse gut electrical activity.
A variety of electrical activities occur depending on the functional state in each section of the gut, but the application of microelectrode array (MEA) is rather limited. We thus developed a dialysis membranes-enforced technique to investigate diverse and complex spatio-temporal electrical activity in the gut. Muscle sheets isolated from the gastrointestinal (GI) tract of mice along with a piece of dialysis membrane were woven over and under the strings to fix them to the anchor rig, and mounted on an 8×8 MEA (inter-electrode distance=150µm). Small molecules (molecular weight <12,000) were exchanged through the membrane, maintaining a physiological environment. Low impedance MEA was used to measure electrical signals in a wide frequency range. We demonstrated the following examples: 1) pacemaker activity-like potentials accompanied by bursting spike-like potentials in the ileum; 2) electrotonic potentials reflecting local neurotransmission in the ileum; 3) myoelectric complex-like potentials consisting of slow and rapid oscillations accompanied by spike potentials in the colon. Despite their limited spatial resolution, these recordings detected transient electric activities that optical probes followed with difficulty. In Addition, propagation of pacemaker-like potential was visualized in the stomach and ileum. These results indicate that the dialysis membrane-enforced technique largely extends the application of MEA, probably due to stabilisation of the access resistance between each sensing electrode and a reference electrode and improvement of electric separation between sensing electrodes. We anticipate that this technique will be utilized to characterise spatio-temporal electrical activities in the gut in health and disease.


Vascularized bone flaps versus nonvascularized bone grafts for mandibular reconstruction: an outcome analysis of primary bony union and endosseous implant success.
Functional restoration following resection or traumatic injury to the mandible depends on the reliability of the bony reconstruction to heal primarily and support endosseous implants. Although vascularized bone flaps (VBF) and nonvascularized bone grafts (NVBG) are both widely used to reconstruct the mandible, indications for each remain ill-defined. The purpose of this study was to compare bone graft/flap healing and success of implant placement in patients reconstructed with VBF versus NVBG. Over the past 10 years, 75 consecutive mandibular reconstructions were performed (26 free bone grafts, 49 vascularized bone flaps). Etiology of the defect, history of irradiation, bone defect size, number of operations, graft/flap success, and dental implant success rates were determined and compared. Bone graft/flap success was defined as complete bony union. Implant success was defined as complete osseointegration. Mean follow-up was 3 years. Free flaps were used primarily for malignant disease (78%, 38/49). Bone grafts were used primarily for benign disease (88%, 23/26). History of prior irradiation: 11% (3/26) NVBG versus 45% (22/49) VBF. Length of bony defect (mean): 8.1 cm NVBG versus 9.4 cm VBF. Successful bony union, any size defect: 69% (18/26) NVBG versus 96% (47/49) VBF (p < .0005); lateral defects only: 75% (15/20) NVBG versus 100% (17/17) VBF (p < .05). Number of operations to achieve bony union (mean), any size defect: 2.3 NVBG versus 1.1 VBF (p < .001); lateral defects only: 1.9 NVBG versus 1.0 VBF (p < .005). Twenty-two patients (29%) had a total of 104 endosseous implants placed (NVBG: 8 patients, 33 implants; VBF: 14 patients, 71 implants). Immediate implants placed: 0/33 NVBG versus 54% (38/71) VBF. Overall implant success: 82% (27/33) NVBG versus 99% (70/71) VBF (p < .0001). Implant success in VBF patients with a history of RT: 100% (15/15). Despite the fact that patients reconstructed with VBFs were older, had larger defects, and were treated primarily for malignant disease and therefore had a higher incidence of irradiation to the affected mandible than in patients treated with NVBGs, the incidence of bony union was higher, requiring fewer operations to achieve union, and the implant success rate was significantly greater than for NVBG patients. Results were similar when considering lateral defects only. Based on these results, VBFs are indicated in most cases of mandibular reconstruction; NVBGs are effective for short bone defects (<5-6 cm), in nonirradiated tissue, and/or in patients determined to be too medically compromised to tolerate the additional operative time required for a free-flap reconstruction.


[Camillo Golgi and the "Accademia di Scienze Mediche e Naturali in Ferrara"].
Drawing from sources and documents preserved in Ferrara, the Author proposes to add to the literature concerning Camillo Golgi some probably original data about the presence of Golgi within the Academy of Ferrara: honours, commemorations, scholarships, contributions of local scholars spurred by Golgi's researches accomplished in the field of histology, neurology and malariology.


Addressing the System-Size Dependence of the Local Approximation Error in Coupled-Cluster Calculations.
Over the last two decades, the local approximation has been successfully used to extend the range of applicability of the "gold standard" singles and doubles coupled-cluster method with perturbative triples CCSD(T) to systems with hundreds of atoms. The local approximation error grows in absolute value with the increasing system size, i.e., by increasing the number of electron pairs in the system. In this study, we demonstrate that the recently introduced two-point extrapolation scheme for approaching the complete pair natural orbital (PNOs) space limit in domain-based pair natural orbital CCSD(T) calculations drastically reduces the dependence of the error on the system size, thus opening up unprecedented opportunities for the calculation of benchmark quality relative energies for large systems.


Recovery of poly(3-hydroxybutyrate) from coagulated Ralstonia eutropha using a chemical digestion method.
For economic recovery of poly(3-hydroxybutyrate) (PHB) from culture broths of Ralstonia eutropha containing PHB, Al-based and Fe-based coagulants were used in the pretreatment step. The coagulated cells were then separated by centrifugation, and PHB was extracted by chemical digestion with a sodium hypochlorite/chloroform dispersion solution. The practical upper limits of dosage were found to be 1, 500 mg-Al/L and 1,000 mg-Fe/L, respectively, for Al- and Fe-based coagulants. When the harvested cells were treated with a 50% sodium hypochlorite/chloroform dispersion solution, PHB recovery and purity were 90-94% and 98-99%, respectively. The influence of the use of coagulants on the PHB recovery process was found to be insignificant. Despite the residual Al and Fe in the recovered PHB (less than 450 mg-Al/kg-PHB and 750 mg-Fe/kg-PHB, respectively), no detectable amounts of Al and Fe were leached from films made of the recovered PHB under acidic conditions. The use of Fe-based coagulants is less recommended because the Fe impurity can cause an unwanted colorization problem in the final product.


Species, sex and geographic variation in chlamydial prevalence in abundant wild Australian parrots.
Chlamydia psittaci (order: Chlamydiales) is a globally distributed zoonotic bacterium that can cause potentially fatal disease in birds and humans. Parrots are a major host, yet prevalence and risk factors for infection in wild parrots are largely unknown. Additionally, recent research suggests there is a diverse range of novel Chlamydiales circulating in wildlife. We therefore sampled seven abundant parrot species in south-eastern Australia, taking cloacal swabs and serum from n = 132 wild adults. We determined C. psittaci and Chlamydiales prevalence and seroprevalence, and tested for host species, sex, geographical and seasonal differences, and temporal changes in individual infection status. Across all species, Chlamydiales prevalence was 39.8% (95% CI 31.6, 48.7), C. psittaci prevalence was 9.8% (95% CI 5.7, 16.3) and C. gallinacea prevalence was 0.8% (95% CI 0.1, 4.5). Other Chlamydiales species were not identified to species level. We identified two C. psittaci strains within the 6BC clade, which is highly virulent in humans. Seroprevalence was 37.0% (95% CI 28.5, 46.4). Host species (including crimson rosellas, galahs, sulphur-crested cockatoos and blue-winged parrots) differed in seroprevalence and Chlamydiales prevalence. Galahs had both highest Chlamydiales prevalence (54.8%) and seroprevalence (74.1%). Seroprevalence differed between sites, with a larger difference in males (range 20-63%) than females (29-44%). We reveal a higher chlamydial prevalence than previously reported in many wild parrots, with implications for potential reservoirs, and transmission risks to humans and other avian hosts.


Successful Embolization of Posterior Inferior Pancreaticoduodenal Artery Pseudoaneurysm on the Grounds of Chronic Pancreatitis-Case Report and Literature Review.
Pancreatic pseudoaneurysm is a rare but life-threatening clinical entity. In this paper, we present a case of a 74-year-old man, who was admitted to our clinic with a diagnosis of an acute on chronic pancreatitis complicated by walled-off-pancreatic-necrosis, with subsequent development of peripancreatic pseudoaneurysm. After initial conservative management, the patient recovered and was discharged from the hospital. However, he soon returned feeling anxious due to a pulsatile abdominal mass. Abdominal Color-Doppler examination, CT scan, and angiography revealed large pancreatic necrotic collection in the total size of 9 cm, with centrally enhancing area of 3.5 cm that corresponded to pseudoaneurysm originating from the posterior pancreaticoduodenal vascular arcade. Considering the size, location of the pseudoaneurysm, feeding vessel, and poor general patients condition, we opted for minimally invasive treatment. Pseudoaneurysm was successfully managed by endovascular coil embolization, i.e., "sandwich technique".


Efficient nonreciprocal mode transitions in spatiotemporally modulated acoustic metamaterials.
In linear, lossless, time-invariant, and nonbiased acoustic systems, mode transitions are time reversible, consistent with Lorentz reciprocity and implying a strict symmetry in space-time for sound manipulation. Here, we overcome this fundamental limitation by implementing spatiotemporally modulated acoustic metamaterials that support nonreciprocal sound steering. Our mechanism relies on the coupling between an ultrathin membrane and external biasing electromagnetic fields, realizing programmable dynamic control of the acoustic impedance over a motionless and noiseless platform. The fast and flexible impedance modulation of our metamaterial imparts an effective unidirectional momentum in space-time to realize nonreciprocal transitions in k-ω space between different diffraction modes. On the basis of these principles, we demonstrate efficient nonreciprocal sound steering, showcasing unidirectional evanescent wave conversion and nonreciprocal upconversion focusing. More generally, our metamaterial platform offers opportunities for generation of nonreciprocal Bloch waves and extension to other domains, such as non-Hermitian topological and parity-time symmetric acoustics.


Environmental noise, brain structure, and language development in children.
While excessive noise exposure in childhood has been associated with reduced language ability, few studies have examined potential underlying neurobiological mechanisms that may account for noise-related differences in language skills. In this study, we tested the hypotheses that higher everyday noise exposure would be associated with 1) poorer language skills and 2) differences in language-related cortical structure. A socioeconomically diverse sample of children aged 5-9 (N = 94) completed standardized language assessments. High-resolution T1-weighted magnetic resonance imaging (MRI) scans were acquired, and surface area and cortical thickness of the left inferior frontal gyrus (IFG) and left superior temporal gyrus (STG) were extracted. Language Environmental Analysis (LENA) was used to measure levels of exposure to excessive environmental noise over the course of a typical day (n = 43 with complete LENA, MRI, and behavioral data). Results indicated that children exposed to excessive levels of noise exhibited reduced cortical thickness in the left IFG. These findings add to a growing literature that explores the extent to which home environmental factors, such as environmental noise, are associated with neurobiological development related to language development in children.


Nutritional and technological behavior of stabilized iron-gluconate in wheat flour.
Food fortification has been shown to be an effective strategy to overcome iron malnutrition. When a new iron compound is developed for this purpose, it must be evaluated from a nutritional and technological point of view before adding it into foods. In this way, we have evaluated ferrous gluconate stabilized by glycine as a new iron source to be used in wheat flour fortification. We performed biological studies in rats as well as sensory perceptions by human subjects in wheat flour fortified with this iron source. The productions of pentane as a rancidity indicator as well as the change of the sensorial properties of the biscuits made with stabilized ferrous gluconate-fortified wheat flour were negligible. Iron absorption in water from this iron source was similar to the reference standard ferrous sulfate. Nevertheless, because of the phytic acid content, iron absorption from fortified wheat flour decrease 40% for both iron sources. The addition of zinc from different sources did not modify iron absorption from ferrous sulfate and stabilized ferrous gluconate in water and wheat flour. The iron absorption mechanism as well as the biodistribution studies demonstrate that the biological behavior of this iron source does not differ significantly from the reference standard. These results demonstrate that the iron source under study has adequate properties to be used in wheat flour fortification. Nevertheless, more research is needed before considering this iron source for its massive use in food fortification.


Complexation with beta-cyclodextrin confers oral activity on the flavonoid dioclein.
Dioclein is a flavonoid reported to have many beneficial effects on the cardiovascular system such as vasorelaxant, hypotensive, antioxidant and antiarrythmogenic activities. However, use as pharmaceuticals is limited due to the lack of oral activity and low water solubility. In this work, intending to improve its oral activity, we performed a 1:1 inclusion complex (IC) between dioclein and beta-cyclodextrin (beta-CD). The IC was characterized by nuclear magnetic resonance and infrared spectroscopy and its vasodilator and hypotensive effects were evaluated in mice. The inclusion of dioclein in beta-CD increased the water solubility 44% compared to free dioclein. The IC (2.5mgkg(-1)) produced a higher and long lasting change in systolic blood pressure (SBP) after intraperitoneal administration compared to free dioclein. When given orally, free dioclein (10mgkg(-1)) showed no hypotensive effect while the IC induced a pronounced decrease in SBP. The in vitro vasodilator effect of dioclein was unchanged by its inclusion in beta-CD showing that the IC does not change the interaction between dioclein and its cellular targets. In conclusion, our results show that the new complex prepared by inclusion of dioclein in beta-CD improves the hypotensive effect of the flavonoid by increasing its bioavailability and enables dioclein to be effective after oral administration. The mechanism underling the increase in bioavailability is probably a consequence of a protective effect of beta-CD against in vivo biodegradation by enzymes and possibly increased water solubility.


Effect of season on the fatty acid composition and free amino acid content of the sardine Sardinops melanostictus.
The purpose of this study was to clarify the seasonal variation of fatty acid composition and free amino acid content in the Japanese sardine (Sardinops melanostictus) from the sea of Hyuga-Nada, and the relationship between the fatty acid composition of this sardine and that of plankton in the area. The lipid content of sardines at the sea of Hyuga-Nada was low in February (1.8%) and high (7.2%) from July to September. The major fatty acids in the total lipids from sardine were myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1 n-7), oleic acid (18:1 n-9), eicosapentaenoic acid (20:5 n-3), and docosahexaenoic acid (22:6 n-3). The characteristics of the fatty acids isolated from sardines in July were similar to those from plankton in the same season. This reflects the deposition of plankton fatty acids in sardine depot fat. The season of high free histidine content in the ordinary meat corresponded with that of high lipid content. These results suggested that both the fatty acid composition of sardines and the high concentrations of certain amino acids in free form are influenced by the intake and seasonal variation of composition of plankton.


Imbalance in cytokines from interleukin-1 family - role in pathogenesis of endometriosis.
To assess whether interleukin (IL)-1beta, IL-18 and interleukin-1 converting enzyme (ICE) are involved in the pathogenesis of endometriosis. Peritoneal fluid (PF) was obtained from 85 women with and without endometriosis. Peritoneal macrophages were cultured and the culture media collected. IL-1beta, IL-18 and ICE levels were measured by the enzyme-linked immunosorbent assay (ELISA). Levels of IL-1beta and ICE in PF of women with endometriosis were higher than those in the control group. However, PF level of IL-18 was significantly lower in the study group than in the controls. Higher secretion of IL-1beta by peritoneal macrophages and lower IL-18 and ICE in endometriosis patients than in control were observed. Following lipopolysaccharide (LPS) stimulation, the macrophages secreted more IL-1beta, IL-18 and ICE in all groups. The results pointed to impairment of the secretion of the IL-1 cytokine family in endometriosis. Invalid IL-1beta and IL-18 maturation by ICE may be an important pathogenic factor in endometriosis.


Distortion-product emissions in rabbit: I. Altered susceptibility to repeated pure-tone exposures.
An important issue in understanding the development of noise-induced hearing loss is whether prior acoustic overstimulation alters the susceptibility of the cochlea to further damage. The present work was designed to establish a model of activity-dependent changes in the susceptibility of the cochlea to acoustic overstimulation by regularly exposing the ear to a low-frequency pure tone. As a quantitative index of cochlear function, 2f1-f2 distortion-product otoacoustic emissions (DPOAEs) were monitored systematically over time in three groups of rabbits, with each group experiencing a unique paradigm that incorporated repeated exposure to the low-frequency tone. Common to each rabbit's exposure protocol was that a given experimental session consisted of two exposure episodes, separated by a 40-min period. Experimental sessions were repeated three times, with 2- to 3-day recovery periods interposed between sessions. The rate of decrement in DPOAE amplitude over a prescribed time period was utilized as a measure of susceptibility to the acoustic trauma. The overall results indicated that ears were more susceptible to exposure 40 mins after the first exposure of a session than they were initially. A series of control experiments indicated that the robustness of the acoustic middle-ear reflex (AMR) did not change between the exposure episodes. Consequently, changes in the AMR could not account for the increased susceptibility seen following the first exposure. However, in awake rabbits with stronger AMRs, higher pure-tone exposure levels were needed to produce increased susceptibility to the second exposure. After 2-3 days of intersession recovery, susceptibility to the effects of excessive sound returned close to its original baseline level. The outcome of these studies demonstrated a reduced capacity for the ear to resist the harmful effects of exposure to a moderately intense tone, which was repeated twice over a brief 40-min period, but little change in susceptibility when identical exposures were repeated over longer intersession intervals of several days.