M-Triad: An improvement of the sediment quality triad.
The traditional sediment quality triad generally uses three lines of evidence (LOE) in the assessment, integrating environmental chemistry, ecology and ecotoxicology. However the assessment is performed without considering the multivariate structure within LOE. In order to improve the sediment quality assessment, the M-Triad is proposed. Instead of averaging the values within a LOE, the new approach is based on the Euclidean distance between each sampling station and the reference station (s) for each LOE. These distances are then plotted in a radar-chart to obtain the area of the triangle and the quality assessment is subsequently obtained from the difference between the triangle areas of the impacted and the reference station. Three studies were selected to test the applicability of the M-Triad. In two cases, the M-Triad returned a more realistic ranking of the stations as observed in the principal component analysis (PCA) from each LOE By including the Euclidean distance, the use of M-Triad is advantageous when multiple variables with negative or uncorrelated patterns within a LOE are analyzed simultaneously. The combination of the M-Triad and the results of the PCA allows one to identify multiple contamination gradients and how biota and bioassays respond to each of these gradients. In comparison to the traditional method, the M-Triad reduces the uncertainty of the final analysis, permitting a more comprehensive ecological assessment.


Clinical study of anogenital condyloma acuminata treatment with photodynamic therapy including immunocompromised conditions.
Human Papillomavirus (HPV) infection is highly prevalent worldwide, and one of its consequences is the external genital wart, or Condyloma Acuminata (CA). The present study used Photodynamic Therapy (PDT) to treat CA lesions. PDT treated 23 patients with a clinical diagnosis of multifocal and unifocal CA. Patients were divided into Group 1 (G1, Patients without pathologies associated with immunodeficiency) and Group 2 (G2, patients with pathologies associated with immunodeficiency). In the G1 group (19 patients), PDT resulted in a Complete Response in 68.4% (average 5 PDT cycles), Partial Response in 26.3% (average 10 PDT cycles), and No Response in 5.3% (average 6 PDT cycles). In the G2 group (4 patients), 100% of subjects showed a partial response (8 PDT cycles). These patients in the G2 and with partial response had associated pathologies, such as renal failure, breast cancer, and HIV. There was a slight decrease in lesions (20-40%) post-treatment in these cases. Four months after treatment, no new lesions or recurrence were observed in the entire area treated with PDT using low doses of PDT. Eighty-six percent of the patients tolerated the treatments well. We conclude that PDT is a promising and safe treatment for CA lesions compared to traditional treatments.


Study on Emission Characteristics and Emission Reduction Effect for Construction Machinery under Actual Operating Conditions Using a Portable Emission Measurement System (Pems).
With the acceleration of urban construction, the pollutant emission of non-road mobile machinery such as construction machinery is becoming more and more prominent. In this paper, a portable emissions measurement system (PEMS) tested the emissions of eight different types of construction machinery under actual operating conditions and was used for idling, walking, and working under the different emission reduction techniques. The results showed that the pollutant emission of construction machinery is affected by the pollutant contribution of working conditions. According to different emission reduction techniques, the diesel oxidation catalyst (DOC) can reduce carbon monoxide (CO) by 41.6-94.8% and hydrocarbon (HC) by 92.7-95.1%, catalytic diesel particulate filter (CDPF) can reduce particulate matter (PM) by 87.1-99.5%, and selective catalytic reduction (SCR) using urea as a reducing agent can reduce nitrogen oxides (NOx) by 60.3% to 80.5%. Copper-based SCR is better than vanadium-based SCR in NOx reduction. In addition, the study found that when the enhanced 3DOC + CDPF emission reduction technique is used on forklifts, DOC has a "low-temperature saturation effect", which will reduce the emission reduction effect of CO and THC. The use of Burner + DOC + CDPF emission reduction techniques and fuel injection heating process will increase CO's emission factors by 3.2-3.5 and 4.4-6.7 times compared with the actual operating conditions.


P wave duration ≥150 ms predicts poor left atrial function and ablation outcomes in non-paroxysmal atrial fibrillation.
It remains unknown whether P wave duration (PWD) ≥ 150 ms measured after extensive radiofrequency catheter ablation (RFCA) can identify non-paroxysmal atrial fibrillation (non-PAF) patients at increased risk of atrial tachyarrhythmia recurrence. We investigated the predicting power of PWD and its association with left atrial (LA) reverse remodeling in patients with non-PAF undergoing pulmonary vein isolation with LA linear ablation. We retrospectively evaluated 136 patients who underwent RFCA for drug-refractory non-PAF. Electroanatomic mapping was acquired during AF. Low-voltage area (LVA) was defined as an area with bipolar voltage ≤0.5 mV. Electrocardiography and echocardiography were performed during sinus rhythm 1 day and 3 months after RFCA. PWD was measured using amplified 12‑lead electrocardiography. Prolonged PWD was defined as maximum PWD ≥ 150 ms. Over a mean follow-up duration of 48 ± 35 months, 28 patients experienced atrial tachyarrhythmia recurrence. PWD was positively correlated with LVA (r = 0.527, p < 0.001) and inversely correlated with LA emptying fraction (r = -0.399, p < 0.001). PWD was shortened and LA emptying fraction (LAEF) was increased in patients without atrial tachyarrhythmia recurrence during follow-up. Atrial tachyarrhythmia-free survival was significantly more likely in patients without a prolonged PWD (83.5% vs 60.7%, p = 0.002). Multivariate analysis showed that LAEF and PWD were independent predictors of atrial tachyarrhythmia recurrence. PWD ≥ 150 ms measured after RFCA can identify patients with non-PAF at increased risk of atrial tachyarrhythmia recurrence. PWD is correlated with LVA and LAEF and reflects LA reverse remodeling.


Increase in C-reactive protein and lipids in adolescents with psychiatric disease.
Eighteen adolescent patients with severe psychiatric disorders were compared with healthy, eutrophics adolescents for the presence of inflammation and cardiovascular risk factors. We found significant differences in high-sensitivity C-reactive protein, total cholesterol, and triglycerides. Our results show, evidence of an inflammatory status and a deleterious lipid profile, in a very early state of psychiatric disease.


The inflammatory markers sST2, HSP27 and hsCRP as a prognostic biomarker panel in chronic heart failure patients.
The inflammatory markers sST2, HSP27 and hsCRP have already been identified as prognostic markers in chronic heart failure (HF). Though individual biomarkers have proven their value in mortality risk prediction, the role of a multimarker strategy needs further evaluation. This is an exploratory reanalysis in chronic HF patients. Plasma HSP27, sST2 and hsCRP in outpatients with chronic HF were analysed. Patients were followed for a minimum of twelve months for the endpoint cardiovascular mortality and unplanned HF associated hospitalisation (=event). 15 year overall mortality was assessed retrospectively. The prognostic impact was assessed using a Cox proportional hazard model. 113 chronic HF patients were included. Median follow up time was 614 days and 37 patients (32.7%) experienced an event. A Kaplan-Meier analysis revealed that patients with increased sST2, HSP27 and hsCRP levels have significantly worse prognosis (p < 0.001). The use of a three-biomarker combination was superior in an independent risk prediction of an event (one high vs. two high: HR = 4.5, 95% CI: 1.3-15.5, p = 0.018; and one high vs. all high: HR = 9.8, 95% CI: 2.8-34.3, p < 0.001) as shown in a multivariable cox proportional hazard model. However, the biomarker panel did not predict 15 year overall mortality, in contrast to elevated HSP27 levels (p = 0.012). The combination of all three markers is an independent predictor of cardiovascular death and unplanned HF associated hospitalisation but not overall mortality. Our findings suggest that adding those markers in combination to well established risk assessment parameters may improve risk stratification.


Synthesis, mutagenicity, binding to pBR 322 DNA and antitumour activity of platinum(II) complexes with ethambutol.
Platinum complexes with N,N'-bis(1-hydroxybut-2-yl)ethylenediamine, [PtCl2(ethambutol)] were prepared and the biological activity of three isomers [with (-), (+) and (+/-) ethambutol, respectively] investigated. All species interact with the Bam HI and Ava I recognition sequences showing a binding preference for GC rich sequences of DNA. The complex which showed the greatest interaction with adjacent guanines, [PtCl2[+/-)ethambutol)] was also found to be the most mutagenic of the three. On the other hand, only [PtCl2[+)ethambutol)] had a considerable antitumour activity against both P388 leukaemia and Lewis lung carcinoma, and this was not correlated either with restriction enzyme blocking activity or with mutagenicity.


Stress Myocardial Blood Flow Ratio by Dynamic CT Perfusion Identifies Hemodynamically Significant CAD.
The aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis. A comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia. Patients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ≤0.80. A total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 ml/100 ml/min vs. 142.5 ± 31.2 ml/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ≥50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ≥50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013). Calculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.


Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure.
Hyperlipidemia is common in chronic renal failure (CRF), but the underlying mechanisms are not clearly defined. Certain data points toward a potential role for the state of secondary hyperparathyroidism of CRF in its pathogenesis. We examined the effects of parathyroid hormone (PTH) on lipid metabolism utilizing intravenous fat tolerance test (IVFTT) and post-heparin lipolytic activity in five normal dogs, in six animals with CRF and secondary hyperparathyroidism (NPX) and in six normocalcemic-thyroparathyroidectomized dogs (NPX-PTX) with comparable degree and duration of CRF. NPX dogs had fasting hypertriglyceridemia (82 + 6.0 mg/dl vs. 49 +/- 2.7 mg/dl in normal dogs, P less than 0.01), abnormal IVFTT, and reduced post-heparin plasma LPL activity (151 +/- 10 vs. 275 +/- 15 mumol fatty acids/ml/min in normal dogs, P less than 0.01). The NPX-PTX dogs had normal fasting levels of serum triglycerides (42 +/- 0.6 mg/dl), normal IVFTT, and normal post-heparin plasma LPL (317 +/- 19 mumol fatty acids/ml/min) despite CRF. Post-heparin HL activity in plasma was not different between NPX and NPX-TPX dogs. The results show that excess blood levels of PTH and not other consequences of CRF are mainly responsible for the abnormalities in lipid metabolism. The data are consistent with the notion that excess PTH reduces post-heparin LPL activity in plasma, which in turn results in impaired lipid removal from the circulation and consequently hyperlipidemia.


Antivenom to the venom of the male Sydney funnel-web spider Atrax robustus: preliminary report.
A purified rabbit IgG (antivenom) has been isolated from rabbits immunized with male Atrax robustus venom. This preparation has been shown to neutralize in vitro, male venom in a ratio of 97 microgram of IgG to 1 microgram of male venom. The venoms of a number of other members of the Atrax genus are also neutralized in vitro by this antivenom. Of particular importance is the fact that the venom of the extremely dangerous female A. formidabilis is neutralized. A serum harvest of 55 mL from an immunized rabbit yielded a total of 1.1869 g of immune IgG using the Protein A-Sepharose procedure. This quantity is sufficient antivenom to neutralize in vitro the average yield of 67 spiders. These findings suggest the preparation of an antivenom for human use is now feasible. The antivenom was shown to effectively neutralize venom in monkeys either when it was premixed with the venom before injection or when it was injected separately 10 minutes after injection of venom. This is the first time in-vitro and in-vivo neutralization of this venom has been demonstrated in the monkey. In other studies, a range of non-immunized animal sera was shown to have no inherent ability to neutralize male A. robustus venom in vitro.


Foot pedal-activated injector for contrast-enhanced sonography.
We assessed the feasibility and convenience of an injector that is electrically activated by a foot pedal for contrast-enhanced sonography. Thirty-seven patients with liver lesions underwent contrast-enhanced sonography using an injector that is activated by a foot pedal. The contrast agent was injected by pressing the foot pedal. All the studies were successfully performed without complications. The device enables the sonologist to keep the probe stationary during the injection and avoids the need for additional personnel. Pedal activated injection is a safe, useful, and convenient method of contrast-enhanced sonography.


Studies on the structure behavior of triphenyldichlorophosphorane in different solvents.
Triphenyldichlorophosporane, which was prepared according to Appel reaction, was an efficient reagent for alkyl halide synthesis by virtue of having two replaceable groups on "pentavalent" phosphorus. The reaction of triphenylphosphine with hexachloroethane was investigated in different solvents and 31P NMR traced the processes of these reactions. As results, it was found that there was similar high coordinated phosphorus species formed in aromatic solvents and in ring ether type solvents, which had large 1J(P-C) (about 140 Hz) according to 13C NMR experiments. It is indicated that, for some solvent such as benzene or dioxane, solvent molecules might be locked in the high coordinated phosphorus compounds, which in turn would affect the triphenyl groups situated at the equatorial position.


Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin-induced type 1 diabetes in rats.
This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-β1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.


Psychiatric disorders among adults treated for deliberate self-harm in general hospital: A national register study.
Psychiatric disorders are common among individuals treated for deliberate self-harm (DSH) in general hospitals. However, few large-scale studies have explicitly addressed psychiatric disorders among adult DSH patients. To examine the presence of psychiatric disorders among adults presenting to general hospitals following DSH, and further to establish clinical and sociodemographic determinants of being diagnosed with a psychiatric disorder in this patient population. Data from several national registers were interlinked to identify all individuals aged 18 and older presenting to general hospital for DSH during the period 2008-2018. Logistic regression was used to examine the association between psychiatric disorders (ICD-10) and clinical and sociodemographic characteristics of the DSH patients. Altogether 39,534 subjects with 63,622 episodes of DSH were included in the study with a gender ratio (F:M) of 1.48. The majority were unmarried and had low income and education. Psychiatric disorders were present in 58.5 % of all episodes and in 54.3 % of the index episodes. Affective disorders displayed the highest prevalence (18.3 %), followed by alcohol use disorder (16.4 %). Personality disorders were highly prevalent among young females with multiple DSH episodes. Middle-aged individuals had the highest prevalence of psychiatric disorders. Presence of psychiatric disorders was significantly associated with DSH repetition. Data was restricted to variables available in the registers. Psychiatric disorders were common among DSH patients in the present cohort, but distributed differently between the genders. DSH repetition and middle-age was associated with being diagnosed with a psychiatric disorder.


Impact of neoadjuvant chemotherapy on breast cancer-related lymphedema after axillary lymph node dissection: a retrospective cohort study.
We aimed to evaluate whether neoadjuvant chemotherapy (NAC) could be a risk factor for breast cancer-related lymphedema (BCRL) associated with axillary lymph node dissection (ALND). A total of 596 patients with cT0-4N0-3M0 breast cancer who underwent ALND and chemotherapy were retrospectively analyzed between March 2012 and March 2022. NAC was administered in 188 patients (31.5%), while up-front surgery in 408 (68.5%). Univariate and multivariable Cox regression analyses were performed to determine whether NAC was an independent risk factor for BCRL. With propensity score matching (PSM), the NAC group and up-front surgery group were matched 1:1 by age, body mass index (BMI), molecular subtypes, type of breast surgery, and the number of positive lymph nodes. Kaplan-Meier survival analyses were performed for BCRL between groups before and after PSM. Subgroup analyses were conducted to explore whether NAC differed for BCRL occurrence in people with different characteristics. At a median follow-up of 36.3 months, 130 patients (21.8%) experienced BCRL [NAC, 50/188 (26.60%) vs. up-front surgery, 80/408 (19.61%); P = 0.030]. Multivariable analysis identified that NAC [hazard ratio, 1.503; 95% CI (1.03, 2.19); P = 0.033] was an independent risk factor for BCRL. In addition, the hormone receptor-negative/human epidermal growth factor receptor 2-negative (HR-/HER2-) subtype, breast-conserving surgery (BCS), and increased positive lymph nodes significantly increased BCRL risk. After PSM, NAC remained a risk factor for BCRL [hazard ratio, 1.896; 95% CI (1.18, 3.04); P = 0.007]. Subgroup analyses showed that NAC had a consistent BCRL risk in most clinical subgroups. NAC receipt has a statistically significant increase in BCRL risk in patients with ALND. These patients should be closely monitored and may benefit from early BCRL intervention.


Metabolite profiling and transcriptomic analyses reveal an essential role of UVR8-mediated signal transduction pathway in regulating flavonoid biosynthesis in tea plants (Camellia sinensis) in response to shading.
Tea is the most popular nonalcoholic beverage worldwide for its pleasant characteristics and healthful properties. Catechins, theanine and caffeine are the major natural products in tea buds and leaves that determine tea qualities such as infusion colors, tastes and fragrances, as well as their health benefits. Shading is a traditional and effective practice to modify natural product accumulation and to enhance the tea quality in tea plantation. However, the mechanism underlying the shading effects is not fully understood. This study aims to explore the regulation of flavonoid biosynthesis in Camellia sinensis under shading by using both metabolomic and transcriptional analyses. While shading enhanced chlorophyll accumulation, major catechins, including C, EC, GC and EGC, decreased significantly in tea buds throughout the whole shading period. The reduction of catechins and flavonols were consistent with the simultaneous down-regulation of biosynthetic genes and TFs associated with flavonoid biosynthesis. Of 16 genes involved in the flavonoid biosynthetic pathway, F3'H and FLS significantly decreased throughout shading while the others (PAL, CHSs, DFR, ANS, ANR and LAR, etc.) temporally decreased in early or late shading stages. Gene co-expression cluster analysis suggested that a number of photoreceptors and potential genes involved in UV-B signal transductions (UVR8_L, HY5, COP1 and RUP1/2) showed decreasing expression patterns consistent with structural genes (F3'H, FLS, ANS, ANR, LAR, DFR and CHSs) and potential TFs (MYB4, MYB12, MYB14 and MYB111) involved in flavonoid biosynthesis, when compared with genes in the UV-A/blue and red/far-red light signal transductions. The KEGG enrichment and matrix correlation analyses also attributed the regulation of catechin biosynthesis to the UVR8-mediated signal transduction pathway. Further UV-B treatment in the controlled environment confirmed UV-B induction on flavonols and EGCG accumulation in tea leaves. We proposed that catechin biosynthesis in C. sinensis leaves is predominantly regulated by UV through the UVR8-mediated signal transduction pathway to MYB12/MYB4 downstream effectors, to modulate flavonoid accumulation. Our study provides new insights into our understanding of regulatory mechanisms for shading-enhanced tea quality.


COVID-19 anti-Asian racism and race-based stress: A phenomenological qualitative media analysis.
News media has recently been replete with stories of anti-Asian rhetoric and racism related to the COVID-19 pandemic. Empirical literature, however, has yet to systematically analyze and document these experiences and their impact. Our study aimed to examine this phenomenon by analyzing news media coverage published between December 31, 2019-June 30, 2020 on COVID-related anti-Asian incidents. We utilized a phenomenological approach to conduct qualitative content analysis of 84 media articles reporting on coronavirus related anti-Asian incidents. We also present the emerging psychological framework of race-based stress and trauma to conceptualize the psychological impact of these race-based incidents reported in the media. Qualitative analysis revealed five primary themes: (a) pathologizing cultural practices; (b) alien in one's own land; (c) invalidation of interethnic differences; (d) ascription of diseased status; and (e) duality of frontline hero and virus carrier. We provide examples for each of these themes. These themes document stigmatizing narratives and demonstrate the phenomenology of race-based stress and trauma experienced by Asian individuals during the COVID era. We present potential implications for mental health of Asian individuals during and following the COVID-19 pandemic, as well as recommendations for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Toward an optimal contraception dosing strategy.
Anovulation refers to a menstrual cycle characterized by the absence of ovulation. Exogenous hormones such as synthetic progesterone and estrogen have been used to attain this state to achieve contraception. However, large doses are associated with adverse effects such as increased risk for thrombosis and myocardial infarction. This study utilizes optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous estrogen/progesterone dose, and timing of administration to induce anovulation. The mathematical model correctly predicts the mean daily levels of pituitary hormones LH and FSH, and ovarian hormones E2, P4, and Inh throughout a normal menstrual cycle and reflects the reduction in these hormone levels caused by exogenous estrogen and/or progesterone. Results show that it is possible to reduce the total dose by 92% in estrogen monotherapy, 43% in progesterone monotherapy, and that it is most effective to deliver the estrogen contraceptive in the mid follicular phase. Finally, we show that by combining estrogen and progesterone the dose can be lowered even more. These results may give clinicians insights into optimal formulations and schedule of therapy that can suppress ovulation.


[Predatory journals: A real threat for medical research. 1. Identify these journals and understand how they work].
The "author-pay" model of open access publication, which appeared in 2002, allocates to the author or his institution the costs of processing articles due to the journal after acceptance, for an amount of a few hundred to several thousand euros. New publishers emerged towards the end of the 2000s, which used this model but with purely commercial objectives, offering naive authors and/or wishing to quickly expand their curriculum vitae by publications in "predatory journals". They are characterized by aggressive e-mail solicitations, lack of ethics, lack of details about the publisher and the editorial board, poor peer review, unspecified and low fees for processing articles, a lack of indexing and the promise of rapid publication.


The opposing forces of the intestinal microbiome and the emerging pathobiome.
This article summarizes emerging concepts on the role of the intestinal microbiome in surgical patients. Revolutionary research over the past decade has shown that human beings live in close and constant contact with boundless communities of microbes. Recent innovations in the study of the human microbiome are reviewed. To demonstrate the applicability of these studies to surgical disease, the authors discuss what is known about the role of microbes in the pathogenesis of perioperative complications. Enhanced awareness of the human microbiome will empower clinicians to adopt novel practices in the prevention and treatment of a variety of surgical conditions.


The distribution of changes in local cerebral energy metabolism associated with brain stimulation reward to the medial forebrain bundle of the rat.
Using the quantitative 2-[14C]deoxyglucose autoradiographic method, local rates of glucose utilization were measured in rats during brain stimulation reward to the medial forebrain bundle. Metabolic activation was observed both rostral and caudal to the site of stimulation. These sites included the nucleus accumbens, olfactory tubercle, lateral septum, and ventral tegmental area. In many cases, increases in glucose utilization occurred bilaterally. These data suggest the involvement of both ascending and descending systems in brain stimulation reward. Furthermore, despite the unilateral nature of the electrical stimulation, increases in glucose utilization were observed both ipsilateral and contralateral to the site of stimulation.


Optical coherence tomographic angiography detects retinal vascular changes associated with pituitary adenoma.
To report the distinct pattern of retinal perfusion loss captured on optical coherence tomographic angiography (OCTA) in a case of compressive optic neuropathy associated with pituitary adenoma. A 51-year-old male had bitemporal hemianopia caused by a pituitary adenoma that compressed the optic chiasm. OCTA scans in both eyes showed peripapillary nerve fiber layer plexus defects in the nasal hemispheres and papillomacular corridors. On macular scans, the ganglion cell layer plexus showed papillomacular defects. The perfusion defects corresponded with thinning on structural OCT measurement and loss of sensitivity on visual field tests. Chiasm compression produces a characteristic pattern of perfusion loss that can be recognized OCTA. This knowledge may be useful in the diagnosis and classification of optic neuropathies.


Infusions of muscimol into the lateral septum do not reduce rats' defensive behaviors toward a cat odor stimulus.
The lateral septum (LS) is implicated in behavioral defense. We tested whether bilateral infusions of the GABAA receptor agonist muscimol into the LS suppress rats' defensive responses to cat odor. Rats received intra-LS infusions of either saline or muscimol (40 ng/rat) and were exposed to either a piece of a cat collar that had been previously worn by a cat or to a control (cat odor free) collar. Rats exposed to the cat odor collar displayed more head-out postures, while intra-LS application of muscimol reduced the number of head-out postures. However, this reduction was also present in rats exposed to a control (cat odor free) collar. This latter finding suggests that despite its involvement in other defensive behaviors (e.g., open arm avoidance in the elevated plus maze), the LS does not selectively regulate rats' receptor defensive responding to the olfactory cues present in our cat odor stimulus.


Predictive significance of joint plasma fibrinogen and urinary alpha-1 microglobulin-creatinine ratio in patients with diabetic kidney disease.
Although many biomarkers have high diagnostic and predictive power for diabetic kidney disease (DKD), less studies were performed for the predictive assessment in DKD and its progression with combined blood and urinary biomarkers. This study aims to explore the predictive significance of joint plasma fibrinogen (FIB) concentration and urinary alpha-1 microglobulin-creatinine (α1-MG/CR) ratio in DKD. A total of 234 patients with type 2 diabetes were enrolled, and their clinical and laboratory data were retrospectively assessed. A ROC curve analysis was performed to evaluate the power of plasma FIB and urinary α1-MG/CR ratio for identifying DKD and advanced DKD, respectively. The predictive power for DKD and advanced DKD was analyzed by regression analysis. Plasma FIB and urinary α1-MG/CR levels were higher in patients with DKD than with pure T2D (p<0.001). The multivariate-adjusted odds ratios (ORs) were 5.047 (95%CI: 2.276-10.720) and 2.192 (95%CI: 1.539-3.122) (p<0.001) for FIB and α1-MG/CR as continuous variables for DKD prediction, respectively. The optimal cut-off values were 3.21 g/L and 2.11mg/mmol for identifying DKD, and 5.58 g/L and 11.07 mg/mmol for advanced DKD from ROC curves. At these cut-off values, the sensitivity and specificity of joint FIB and α1-MG/CR were 0.95 and 0.92 for identifying DKD, and 0.62 and 0.67 for identifying advanced DKD, respectively. The area under curve was 0.972 (95%CI: 0.948-0.995) (p<0.001) and 0.611, 95%CI: 0.488-0.734) (p>0.05). The multivariate-adjusted ORs for joint FIB and α1-MG/CR at the cut-off values were 214.500 (95%CI: 58.054-792.536) and 3.252 (95%CI: 1.040-10.175) (p<0.05), respectively. The present study suggests that joint plasma FIB concentration and urinary α1-MG/CR ratio can be used as a powerful predictor for general DKD, but it is less predictive for advanced DKD.


Rapid administration of undiluted intravenous levetiracetam.
Operational delays have the potential to lead to suboptimal time to seizure control during status epilepticus. Levetiracetam (LEV) is an urgent control antiepileptic medication that offers relative lack of adverse effects and ease of monitoring. There are limited data published demonstrating safety and tolerability of undiluted rapid intravenous (IV) push of LEV in doses of 1000 mg or less. The purpose of this study was to evaluate the safety of IV push administration of LEV doses up to 4500 mg. This is a retrospective, observational, cohort analysis of adult patients who received at least one dose of undiluted IV push LEV from October 15, 2019 to August 31, 2020 at a large academic medical center in Phoenix, Arizona. Outcomes of interest include safety and tolerability of rapid administration of undiluted LEV. There were 953 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizure in 51.9% of patients, and 40.7% of patients had a documented history of epilepsy or seizure disorder. There were 8561 undiluted IV push LEV doses administered, 3674 (42.9%) of which were greater than 1000 mg. LEV was administered most often through a peripheral IV (79.1%). There were 12 patients with documented adverse drug events during the study period, with four potentially directly related to IV push LEV administration. These events were limited to local injection site reactions and included redness, burning, and loss of a peripheral IV line. Rapid IV administration of undiluted LEV is both safe and tolerable in doses of up to 4500 mg, allowing for rapid drug administration, which is paramount during neurologic emergencies.


Critical appraisal of serum urate targets in the management of gout.
Gout management involves two broad aspects: treatment of gout flares to provide rapid symptomatic relief and long-term urate-lowering therapy to lower serum urate sufficiently to prevent gout flares from occurring. All of the major rheumatology societies recommend a target serum urate of <5 mg/dl (<0.30 mmol/l) or <6 mg/dl (<0.36 mmol/l), both of which are below the point of saturation for urate and therefore lead to monosodium urate crystal dissolution. In this Review, we describe the rationale for treat-to-target urate approach in the long-term management of gout and the current evidence and controversy around the appropriate serum urate targets.


A new fibre optic pulse oximeter probe for monitoring splanchnic organ arterial blood oxygen saturation.
A new, continuous method of monitoring splanchnic organ oxygen saturation (SpO(2)) would make the early detection of inadequate tissue oxygenation feasible, reducing the risk of hypoperfusion, severe ischaemia, and, ultimately, death. In an attempt to provide such a device, a new fibre optic based reflectance pulse oximeter probe and processing system were developed followed by an in vivo evaluation of the technology on seventeen patients undergoing elective laparotomy. Photoplethysmographic (PPG) signals of good quality and high signal-to-noise ratio were obtained from the small bowel, large bowel, liver and stomach. Simultaneous peripheral PPG signals from the finger were also obtained for comparison purposes. Analysis of the amplitudes of all acquired PPG signals indicated much larger amplitudes for those signals obtained from splanchnic organs than those obtained from the finger. Estimated SpO(2) values for splanchnic organs showed good agreement with those obtained from the finger fibre optic probe and those obtained from a commercial device. These preliminary results suggest that a miniaturized 'indwelling' fibre optic sensor may be a suitable method for pre-operative and post-operative evaluation of splanchnic organ SpO(2) and their health.


Characterization of murine anti-human Fab antibodies for use in an immunoassay for generic quantification of human Fab fragments in non-human serum samples including cynomolgus monkey samples.
Generic immunoassay formats in animal serum have been described for pharmacokinetic (PK) analysis of human full-length antibodies, but not of human antigen binding fragment (Fab) proteins. Here we characterize two murine monoclonal antibodies (mAb) raised against human immunoglobulin G (IgG) which bind to unique epitopes in the Fab region of human IgG. mAb M-1.7.10 is directed against the constant domain of the kappa light chain and mAb M-1.19.31 binds to the constant domain 1 (CH1) of the heavy chain. Surface plasmon resonance analysis showed that mAb M-1.7.10 does not cross-react with sera from mouse, rat, rabbit, dog, marmoset, rhesus macaque, baboon and cynomolgus monkey, but binds to human and chimpanzee serum (dissociation constant K(D) of 6.8 × 10(-12) and 3.1 × 10(-11)M, respectively). mAb M-1.19.31 shows a higher K(D) for human and chimpanzee IgG (2.0 × 10(-9)M and 5.8 × 10(-10)M, respectively), but also does not bind to serum of the other species. Therefore, mAb M-1.7.10 was used as capture and mAb M-1.19.31 as detection reagent in a generic enzyme linked immunosorbent assay (ELISA) to quantify the human anti-IGF-1R Fab in mouse serum. The generic human Fab assay showed a limit of detection of 31.5 ng/mL anti-IGF-1R Fab. Intra- and inter-assay precision was less than 12% and the accuracy range for all controls was within ±20% of the target concentration. The generic human Fab ELISA was applied to determine serum levels of human anti-IGF-1R Fab after intravenous (iv) administration of 10mg/kg to mice. The resulting concentration-time profile was nearly identical to that obtained by analysis with a validated specific ELISA for anti-IGF-1R Fab. The mean relative concentration of anti-IGF-1R Fab analyzed by the generic assay was 82-118% of that of the specific assay. This equivalence was confirmed in a cynomolgus monkey study with the full length human mAb anti-TROP-2 IgG. Both specific ELISAs used mAb M-1.7.10 as detection reagent and their targets for capturing. In conclusion, the two murine anti-human Fabs are versatile tools as capture and detection reagents for human antibodies in generic and specific PK ELISA formats for animal studies. Their use in specific ELISAs as detection reagents allows the usage of Fc-fusion proteins as capture reagents.


Androgen receptors in the posterior bed nucleus of the stria terminalis increase neuropeptide expression and the stress-induced activation of the paraventricular nucleus of the hypothalamus.
The posterior bed nuclei of the stria terminalis (BST) are important neural substrate for relaying limbic influences to the paraventricular nucleus (PVN) of the hypothalamus to inhibit hypothalamic-pituitary-adrenal (HPA) axis responses to emotional stress. Androgen receptor-expressing cells within the posterior BST have been identified as projecting to the PVN region. To test a role for androgen receptors in the posterior BST to inhibit PVN motor neurons, we compared the effects of the non-aromatizable androgen dihydrotestosterone (DHT), the androgen receptor antagonist hydroxyflutamide (HF), or a combination of both drugs implanted unilaterally within the posterior BST. Rats bearing unilateral implants were analyzed for PVN Fos induction in response to acute-restraint stress and relative levels of corticotrophin-releasing hormone and arginine vasopressin (AVP) mRNA. Glutamic acid decarboxylase (GAD) 65 and GAD 67 mRNA were analyzed in the posterior BST to test a local involvement of GABA. There were no changes in GAD expression to support a GABA-related mechanism in the BST. For PVN neuropeptide expression and Fos responses, basic effects were lateralized to the sides of the PVN ipsilateral to the implants. However, opposite to our expectations of an inhibitory influence of androgen receptors in the posterior BST, PVN AVP mRNA and stress-induced Fos were augmented in response to DHT and attenuated in response to HF. These results suggest that a subset of androgen receptor-expressing cells within the posterior BST region may be responsible for increasing the biosynthetic capacity and stress-induced drive of PVN motor neurons.


Inadvertent intrathecal drug injection while treating low back pain: a case report and review of the literature.
Undesired intrathecal injections represent an important subset of medical errors, albeit rare. Clinical effects depend on the type and concentration of drug(s) injected. Here we report on the case of a healthy woman with persistent low back pain, treated with a paravertebral injection of lidocaine, thiocolchicoside, and L-acetylcarnitine at an orthopedic practice. A 42-year-old Caucasian woman, with no relevant past medical history, received a lumbar paravertebral injection of lidocaine, thiocolchicoside, and L-acetylcarnitine for persistent low back pain. Approximately 30 minutes after injection, she experienced quick neurological worsening. Upon arrival at the Emergency Department, she was comatose, with fixed bilateral mydriasis, trismus, and mixed acidosis; seizures ensued in the first hours; slow progressive amelioration was observed by day 6; retrograde amnesia was the only clinical relevant remaining symptom by 6 months. To our knowledge, this is the first reported case of inadvertent intrathecal thiocolchicoside injection in an adult patient, as well as the first in the neurosurgical literature. Our experience suggests that injection therapy for low back pain should be administered in adequate settings, where possible complications may be promptly treated.


Antidiabetic and antihyperlipidemic effects of Argyreia pierreana and Matelea denticulata: Higher activity of the micellar nanoformulation over the crude extract.
Herbal medicine combined with nanotechnology is widely proposed to improve the oral bioavailability, reduce the required dose and side effects, and improve the pharmacological efficacy of extracts. Thus, this study evaluated the in vivo antidiabetic and antihyperlipidemic activities of ethanolic leaf extracts of Argyreia pierreana (AP) and Matelea denticulata (MP) plants in comparison with their micellar nanoformulations. The mixed micelles (MMs) loaded with crude extracts (CEs) of AP and MD (AP-MMs and MD-MMs) were prepared using a film dispersion technique. Type 2 diabetes was induced in rats using high-fat diet (HFD) and low-dose (35 mg/kg) streptozotocin (STZ) injection. The pharmacological actions of CEs, AP-MMs and MD-MMs were determined in type 2 diabetic Sprague-Dawley rats. Oral treatments with low-dose AP-MMs and MD-MMs having a mean particle size of 163 ± 10 nm and 145 ± 8 nm respectively, resulted in significantly decreased fasting blood glucose level and increased serum insulin, glucokinase levels, and normalized the elevated levels of hemoglobin A1C and glucose-6-phosphatase. Both extracts significantly decreased serum total cholesterol, triglycerides, and low-density lipoprotein, as well as elevated high-density lipoprotein levels. Additionally, improvements in antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and malondialdehyde levels were evidenced clearly in tested vital organs (brain, heart, liver). This is the first report of the antidiabetic and antihyperlipidemic activities of ethanolic leaf extracts of AP and MP plants. Our findings indicate the potential utility of nanotechnology in improving the oral therapeutic efficacy of herbal extracts.


[Mechanism of action and clinical use of ticlopidine].
The literature review contains date on mechanisms of action, pharmacokinetics of ticlopidine, its antithrombotic efficacy in various clinical conditions (ischemic heart and brain diseases, diabetic microangiopathy, occlusive disease of arteries of lower extremities) as well as main adverse effects.


[Surgical Technique for Prevention of Incisional Hernia in Laparoscopic Small Bowel Resection in the Obese Patient].
A 67-year-old woman reporting lower abdominal pain and anemia was examined. Small intestinal tumor was diagnosed by small intestinal radiographic contrast study and small intestinal endoscopy, and we decided to perform a laparoscopic partial resection of the small bowel. Since she was obese patients(BMI 36.3, abdominal wall 6 cm)at high risk of postoperative incisional hernia, we devised a way to make the wound smaller. We judged thick abdominal wall make umbilical wound larger in single port surgery. We performed multi-port surgery by using one 15 mm trocar, and removed small intestinal tumor from 15 mm port incision. In addition, to prevent incisional hernia, we used a trocar with a wound closure assist function for securely closing the port wound in all layers. Histopathological diagnosis was neuroendocrine tumor. The patient is being followed up without recurrence and without incisional hernia. In partial small bowel resection of obese patient, the use of a 15 mm port to minimize wound site and the use of trocar with a wound closure assist function may lead to prevent incisional hernia.


Calculation methods for ventricular diffusion-weighted imaging thermometry: phantom and volunteer studies.
A method for the measurement of temperature in the lateral ventricle using diffusion-weighted imaging (DWI) has been proposed recently. This method uses predetermined arbitrary thresholds, but a more objective method of calculation would be useful. We therefore compared four different calculation methods, two of which were newly created and did not require predetermined thresholds. A rectangular polyethylene terephthalate bottle (8 × 10 × 28 cm(3)) was filled with heated water (35.0-38.8 °C) and used as a water phantom. The DWI data of 23 healthy subjects (aged 26-75 years; mean ± standard deviation, 50.13 ± 19.1 years) were used for this study. The temperature was calculated using the following equation: T(°C) = 2256.74/ln(4.39221/D) - 273.15, where D is the diffusion coefficient. The mean ventricular temperature was calculated by four methods: two thresholding methods and two histogram curve-fitting methods. As a reference, we used the temperature measured at the tympanic membrane, which is known to be approximately 1 °C lower than the brain temperature. The averaged differences in temperature between mercury thermometry and classical predetermined thresholding methods for the water phantom were 0.10 ± 0.42 and 0.05 ± 0.41 °C, respectively. The histogram curve-fitting methods, however, yielded temperatures a little lower (averaged differences of -0.24 ± 0.32 and -0.14 ± 0.31 °C, respectively) than mercury thermometry. There was very little difference in temperature between tympanic thermometry and classical predetermined thresholding methods (+0.01 and -0.07 °C, respectively). In humans, however, the histogram curve-fitting methods yielded temperatures approximately 1 °C higher (+1.04 °C and +1.36 °C, respectively), suggesting that temperatures measured in this way more closely approximate the true brain temperature. The histogram curve-fitting methods were more objective and better matched the estimated brain temperature than did classical predetermined thresholding methods, although the standard deviation was wider in the former methods.


Impact of wheel running on chronic ethanol intake in aged Syrian hamsters.
Alcohol dependence in aging populations is seen as a public health concern, most recently because of the significant proportion of heavy drinking among "Baby Boomers." Basic animal research on the effects of aging on physiological and behavioral regulation of ethanol (EtOH) intake is sparse, since most of this research is limited to younger models of alcoholism. Here, EtOH drinking and preference were measured in groups of aged Syrian hamsters. Further, because voluntary exercise (wheel-running) is a rewarding substitute for EtOH in young adult hamsters, the potential for such reward substitution was also assessed. Aged (24 month-old) male hamsters were subjected to a three-stage regimen of free-choice EtOH (20% v/v) or water and unlocked or locked running wheels to investigate the modulatory effects of voluntary wheel running on EtOH intake and preference. Levels of fluid intake and activity were recorded daily across 60 days of experimentation. Prior to wheel running, levels of EtOH intake were significantly less than levels of water intake, resulting in a low preference for EtOH (30%). Hamsters with access to an unlocked running wheel had decreased EtOH intake and preference compared with hamsters with access to a locked running wheel. These group differences in EtOH intake and preference were sustained for up to 10 days after running wheels were re-locked. These results extend upon those of our previous work in young adult hamsters, indicating that aging dampens EtOH intake and preference. Voluntary wheel running further limited EtOH intake, suggesting that exercise could offer a practical approach for managing late-life alcoholism.


Lineage tracing and analog recording in mammalian cells by single-site DNA writing.
Studying cellular and developmental processes in complex multicellular organisms can require the non-destructive observation of thousands to billions of cells deep within an animal. DNA recorders address the staggering difficulty of this task by converting transient cellular experiences into mutations at defined genomic sites that can be sequenced later in high throughput. However, existing recorders act primarily by erasing DNA. This is problematic because, in the limit of progressive erasure, no record remains. We present a DNA recorder called CHYRON (Cell History Recording by Ordered Insertion) that acts primarily by writing new DNA through the repeated insertion of random nucleotides at a single locus in temporal order. To achieve in vivo DNA writing, CHYRON combines Cas9, a homing guide RNA and the template-independent DNA polymerase terminal deoxynucleotidyl transferase. We successfully applied CHYRON as an evolving lineage tracer and as a recorder of user-selected cellular stimuli.


PCSK9, a novel immune and ferroptosis related gene in abdominal aortic aneurysm neck.
The gene expression profile of abdominal aortic aneurysm (AAA) neck is not fully understood. The etiology of AAA is considered to be related to atherosclerosis and the inflammatory response, involving congenital, genetic, metabolic, and other factors. The level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to those of cholesterol, oxidized low-density lipoprotein, and triglycerides. PCSK9 inhibitors have significant effects on lowering LDL-cholesterol, reversing atherosclerotic plaques, and reducing the risk of cardiovascular events and have been approved by several lipid-lowering guidelines. This work was aimed to investigate the potential role of PCSK9 in the neck of AAA. We extracted the expression dataset (GSE47472) containing 14 AAA patients and 8 donors and single-cell RNAseq (scRNA-seq) data (GSE164678) of CaCl2-induced (AAA) samples from the Gene Expression Omnibus dataset. Through bioinformatics methods, we found that PCSK9 was up-regulated in the proximal neck of human AAA. In AAA, PCSK9 was mainly expressed in fibroblasts. Additionally, immune check-point PDCD1LG2 was also expressed higher in AAA neck than donor, while CTLA4, PDCD1, and SIGLEC15 were down-regulated in AAA neck. The expression of PCSK was correlated with PDCD1LG2, LAG3, and CTLA4 in AAA neck. Additionally, some ferroptosis-related genes were also down-regulated in AAA neck. PCSK9 was also correlated with ferroptosis-related genes in AAA neck. In conclusion, PCSK9 was highly expressed in AAA neck, and may exert its role through interacting with immune check-points and ferroptosis-related genes.


Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities.
Pediatric solid and central nervous system tumors are the leading cause of cancer-related death among children. Identifying new targeted therapies necessitates the use of pediatric cancer models that faithfully recapitulate the patient's disease. However, the generation and characterization of pediatric cancer models has significantly lagged behind adult cancers, underscoring the urgent need to develop pediatric-focused cell line resources. Herein, we establish a single-site collection of 261 cell lines, including 224 pediatric cell lines representing 18 distinct extracranial and brain childhood tumor types. We subjected 182 cell lines to multi-omics analyses (DNA sequencing, RNA sequencing, DNA methylation), and in parallel performed pharmacological and genetic CRISPR-Cas9 loss-of-function screens to identify pediatric-specific treatment opportunities and biomarkers. Our work provides insight into specific pathway vulnerabilities in molecularly defined pediatric tumor classes and uncovers biomarker-linked therapeutic opportunities of clinical relevance. Cell line data and resources are provided in an open access portal.


Long-Term Efficacy and Safety of Subconjunctival/Perilesional 5-Fluorouracil Injections for Ocular Surface Squamous Neoplasia.
To investigate the effectiveness and safety of subconjunctival/perilesional 5-fluorouracil injections on ocular surface squamous neoplasia (OSSN) during a 3-year follow-up period. We followed up six patients with intraepithelial OSSN (in one eye each) that had regressed after subconjunctival/perilesional 5-fluorouracil injections. Conjunctival fluorescein angiography (FA) and indocyanine green angiography (ICGA), as well as anterior segment optical coherence tomography (AS-OCT), were performed to evaluate the OSSN status 3 years after initiation of treatment. The mean age of patients (five males, one female) at baseline was 62.3±11.6 years. The mean number of 5-fluorouracil injections was 17.0±8.6, with a mean treatment duration of 13.0±7.4 weeks. At the final visit, both intratumoral and conjunctival feeding vessels had disappeared on ICGA and FA, with no neovascularization-related leakage, in accordance with the results of AS-OCT. The period from complete tumor regression to final visit according to AS-OCT was 32.5±4.2 months, which was longer than that according to ICGA (31.3±3.2 months, p=0.034). The final best-corrected visual acuity was similar to that at baseline (p=0.128). No side effects were observed in any of the eyes. Subconjunctival/perilesional 5-fluorouracil injections are an effective and safe treatment for OSSN. Future studies with a larger sample size are warranted for confirmation of our findings, as well as investigation into the reasons for residual areas of non-perfusion in the conjunctiva.


Motion sickness on tilting trains.
Trains that tilt on curves can go faster, but passengers complain of motion sickness. We studied the control signals and tilts to determine why this occurs and how to maintain speed while eliminating motion sickness. Accelerometers and gyros monitored train and passenger yaw and roll, and a survey evaluated motion sickness. The experimental train had 3 control configurations: an untilted mode, a reactive mode that detected curves from sensors on the front wheel set, and a predictive mode that determined curves from the train's position on the tracks. No motion sickness was induced in the untilted mode, but the train ran 21% slower than when it tilted 8° in either the reactive or predictive modes (113 vs. 137 km/h). Roll velocities rose and fell faster in the predictive than the reactive mode when entering and leaving turns (0.4 vs. 0.8 s for a 4°/s roll tilt, P<0.001). Concurrently, motion sickness was greater (P<0.001) in the reactive mode. We conclude that the slower rise in roll velocity during yaw rotations on entering and leaving curves had induced the motion sickness. Adequate synchronization of roll tilt with yaw velocity on curves will reduce motion sickness and improve passenger comfort on tilting trains.


Residues of polychlorinated-dibenzodioxins, -dibenzofurans and -biphenyls in human milk samples collected in a continental town in Croatia, Yugoslavia.
The levels of several polychlorinated-dibenzodioxins (PCDDs), polychlorinated-dibenzofurans (PCDFs) and total polychlorinated-biphenyls (PCBs) were determined in pooled human milk samples. The samples were collected in a continental town of Croatia, Yugoslavia, during the years 1981/82 and 1985. The concentrations of seven PCDDs and nine PCDFs were within the range less than 0.2-116 ng/kg milk fat; the total PCBs were 0.47 and 0.32 mg/kg milk fat. The levels determined were about the same as those reported for the general population in other countries.


Folding zones inside the ribosomal exit tunnel.
Helicity of membrane proteins can be manifested inside the ribosome tunnel, but the determinants of compact structure formation inside the tunnel are largely unexplored. Using an extended nascent peptide as a molecular tape measure of the ribosomal tunnel, we have previously demonstrated helix formation inside the tunnel. Here, we introduce a series of consecutive polyalanines into different regions of the tape measure to monitor the formation of compact structure in the nascent peptide. We find that the formation of compact structure of the polyalanine sequence depends on its location. Calculation of free energies for the equilibria between folded and unfolded nascent peptides in different regions of the tunnel shows that there are zones of secondary structure formation inside the ribosomal exit tunnel. These zones may have an active role in nascent-chain compaction.


A cross-sectional approach including dog owner characteristics as predictors of visceral leishmaniasis infection in dogs.
Visceral leishmaniasis (VL) is relevant for human and animal public health. Several factors have been associated with the risk of Leishmania infantum infection in dogs. However, dog owner characteristics have been rarely explored. To estimate the prevalence and to identify the associated factors for VL infection including dog owners characteristics. A cross-sectional study was conducted including dogs from an endemic canine visceral leishmaniasis (CVL) region in the Federal District, Brazil. The infection was detected using parasitological, serological, and molecular methods. The associated factors were identified through Poisson regression modelling. The prevalence of infection was 26.25% [95% confidence interval (CI): 20.05 to 33.57]. The associated factors were: short coat prevalence ratio (PR) = 2.33 (95% CI: 1.02 to 5.22); presence of backyard with predominance of soil and/or vegetation PR = 4.15 (95% CI: 1.35 to 12.77); and highest gross family income score PR = 2.03 (95% CI: 1.16 to 3.54). This is the first study that relates higher socioeconomic status of dog owners as an independent factor associated with higher prevalence of VL infection, along with other strongly associated factors related to receptive environment for phlebotomines. Our findings strengthen the need for exploration of the biological and behavioural bases linking dog owner characteristics to the risk of canine infection in prospective cohort studies.


Clival prolactinoma masquerading as a chordoma: a case report.
Ectopic pituitary adenomas are a rare clinical entity and are frequently mistaken for other base of skull lesions on imaging. We report the clinical presentation and management of a woman presenting with an ectopic prolactinoma located in the clivus. A 66-year-old female presented with a 6-month history of headaches and light-headedness. Anatomical imaging demonstrated a clival lesion most suspicious for chordoma. Endocrinological assessment revealed modestly increased prolactin level with lower-than-expected gonadotrophins levels for her age. Surgical resection confirmed an ectopic prolactinoma. A skull base lesion in a patient with hormonal derangement should lend to a high clinical suspicion of an EPA as they may be treated with medications before surgery. Guidelines could assist clinicians investigating skull-based lesions to identify the rare, but important diagnosis of ectopic pituitary adenomas.


Hepcidin and inflammatory bowel disease: dual role in host defence and iron homoeostasis.
Hepcidin is an endogenous antimicrobial peptide with a key role in iron homoeostasis. Hepcidin is similar to defensin, the deficiency of which is associated with Crohn's disease. To date there has been no validated method to reliably assay serum hepcidin. We studied iron indices in inflammatory bowel disease (IBD) including hepcidin. We assessed serum hepcidin concentrations (using a newly developed competitive radioimmunoassay) and ferritin in patients with IBD. Haematinics including serum soluble transferrin receptor, serum iron, serum vitamin B12 and red cell folate levels were also measured. The hepcidin results were compared with a control group of healthy volunteers from the local community. This study was based in a hospital. Sixty-one patients with IBD (51 patients with ulcerative colitis and 10 with Crohn's disease). Their mean hepcidin results were compared with 25 healthy controls. hepcidin concentration in serum samples in IBD patients compared with normal volunteers. We found significantly low serum hepcidin levels in patients with IBD. The hepcidin levels were low in IBD patients without iron deficiency anaemia as evidenced by normal ferritin and serum iron levels (n=41, mean hepcidin 6.81 ng/ml, SEM 1.2) and in IBD patients with iron deficiency anaemia (n=18, mean hepcidin 4.14 ng/ml, SEM 0.72) compared with healthy controls (n=25, mean hepcidin 15.3 ng/ml, SEM 3.14) (P=0.0045 and P=0.0050 on unpaired t-tests, respectively). We also measured IL-6 (enzyme-linked immunosorbent assay method, Abcam plc) in 21 of the 61 patients with IBD and compared the results with samples from 10 healthy volunteers. The IL-6 level was significantly higher (P=0.0222 on unpaired t-tests) in this group of IBD patients (n=21, IL-6 mean 2.94 pg/ml, SEM 0.64) compared with controls (n=10, IL-6 mean 0.663 pg/ml SEM 0.14). A significant positive correlation (Pearson's correlation coefficient r=0.6331) was present between hepcidin and IL-6, but not between hepcidin and serum soluble transferrin receptor (r=-0.235). The low hepcidin results in IBD patients may reflect a causal or perpetuator effect on intestinal inflammation.


Metallo-β Lactamase Producing Non-Fermentative Gram-Negative Bacilli from Various Clinical Isolates in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.
Non-fermentative gram-negative bacilli are common causes of human infections especially nosocomial infections. These organisms are usually resistant to multiple antimicrobial agents including carbapenems. The study aimed to find out the prevalence of metallo-β-lactamase producing non-fermentative gram-negative bacilli among the samples which yielded growth of bacteria in a tertiary care hospital. This is a descriptive cross-sectional study conducted in a tertiary care hospital from February 2017 to May 2017. Convenience sampling method was used. Bacterial identification, characterization and antimicrobial susceptibility testing were done by following standard microbiological guidelines. Metallo-β-lactamase production was detected by using combined disk diffusion test and double-disc synergy test. Data were analyzed by using Statistical Package of Social Science software version 16. Point estimate at 95% confidence interval was calculated along with frequency and proportion for binary data. Among 628 samples which yielded growth of bacteria, 118 (18.79%) at 95% Confidence Interval (15.74-21.84) were metallo-β-lactamase producing non-fermentative gram-negative bacilli. Among them, 54 (45.76%) were Pseudomonas aeruginosa and 64 (54.24%) were Acinetobacter baumannii. A high prevalence of metallo-β-lactamase production was observed among the nonfermentative gram-negative bacilli than the study done in similar settings. It is mandatory to perform routine monitoring of metallo-β-lactamase producing isolates in clinical laboratories in order to help the clinicians prescribe proper antibiotics.


Interprofessional identity: an ethnography of clinical simulation learning in New Zealand.
This article explores the experiences of clinical healthcare students on an interprofessional simulation course in Auckland, New Zealand. The four-day course aims to provide a formative learning experience for final year medical, pharmacy, nursing, and paramedicine students. It focuses on building skills in professionalism, communication, leadership and interprofessional safe teamwork through structured learning activities and clinical simulation scenarios. In 2018, we commenced focused ethnographic research involving participant observation, field notes, interviews, photography and ethnographic film. A total of 112 students participated in this research from the disciplines of medicine (n = 53), nursing (n = 27), pharmacy (n = 17), and paramedicine (n = 15). In a revisit to Van Gennep's (1972) seminal work on liminality, we suggest that the course represents a liminal space where students' ideas about what it means to be a healthcare 'professional' are challenged, disrupted and reconstructed. We observed students emerging from the course with transformed professional and interprofessional identities. We posit that the ritualised and liminal nature of the course plays a role in the development of interprofessional identities by interrupting the reproduction of siloed biomedical culture. Students are challenged to become effective team members alongside other students and experts from other professions. We discuss these findings as they relate to medical and health sciences education.


Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1α/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents.
Sirtuin 1 (Sirt1) plays an important role in cellular redox balance and resistance to oxidative stress. Sirt1 exhibits oncogenic properties in wild-type p53 cancer cells, whereas it acts as a tumor suppressor in p53-mutated cancer cells. Here, we investigated the effects of metformin on Sirt1 expression in several cancer cell lines. Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53. Metformin-induced p53 protein levels in wild-type p53 cancer cells resulted in upregulation of microRNA (miR)-34a. The use of a miR-34a inhibitor confirmed that metformin-induced miR-34a was required for Sirt1 downregulation. Metformin suppressed peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (Pgc-1α) expression and its downstream target Nrf2 in MCF-7 cells. Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1α by metformin caused Nrf2 downregulation via suppression of PPARγ transcriptional activity. Metformin reduced heme oxygenase-1 and superoxide dismutase 2 but upregulated catalase expression in MCF-7 cells. Metformin-treated MCF-7 cells had no increase in basal levels of reactive oxygen species but were more susceptible to oxidative stress. Furthermore, upregulation of death receptor 5 by metformin-mediated Sirt1 downregulation enhanced the sensitivity of wild-type p53 cancer cells to TRAIL-induced apoptosis. Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1α/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis.


Florida neighborhood analysis of social determinants and their relationship to life expectancy.
Social determinants of health (SDOH) contribute to unequal life expectancy (LE). Only a handful of papers have analyzed these relationships at the neighborhood level as opposed to the county level. This study draws on both the SDOH and social vulnerability literature to identify relevant factors affecting LE. LE was calculated from mortality records for Florida from 2009 to 2013 for 3640 census tracts with reliable estimates. A spatial Durbin error model (SDEM) quantified the direction and magnitude of the factors to LE. The SDEM contains a spatial error term and jointly estimates both local and neighborhood associations. This methodology controls for non-independence between census tracts to provide unbiased statistical estimates. Factors significantly related to an increase in LE, include percentage (%) of the population who identify as Hispanic (beta coefficient [β]: 0.06, p-value [P] < 0.001) and % of age dependent populations (% population < 5 years old and % population > 65) (β: 0.13, P < 0.001). Conversely, the following factors exhibited significant negative LE associations, % of households with no automobile (β: -0.05, P < 0.001), % of mobile homes (β: -0.02, P < 0.001), and % of female headed households (β: -0.11, P < 0.001). Results from the SDEM demonstrate social vulnerability indicators account for additional geographic LE variability beyond commonly studied SDOH. Empirical findings from this analysis can help local health departments identify drivers of spatial health disparities at the local level.


New compound curved needle TG6-C PLUS.
The benefits of a compound curve needle design will be seen readily when used as suggested. The surgeon will be able to position the needle repeatedly and accurately between the wound edges from needle entry through tissue, to exit to the opposite side of the wound. Continuous or interrupted corneal wound closure can be done consecutively without varying more than a few tenths of a millimeter in the positioning of the needle from bite to bite. During retrieval the compound curve needle has yet another advantage. The flat curve of the distal needle body minimizes the tissue distortion as the needle body is pulled through. The wound remains in close apposition. In wound closure, though an important and essential attribute of a surgical needle is its "sharpness", sharpness eventually reaches a maximum. The very sharp needles such as the new EthiconTM TG PLUS needles, have such little tactile feedback that shape and needle strength as exemplified by the compound curvature design become of primary importance. These combinations provide the consistent and accurate needle passage necessary for corneal wound apposition, with all of its optical as well as anatomic consequences, in the final outcome of contemporary keratoplasty and cataract procedures.


Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits.
Myocardial infarction (MI) remains a common and deadly disease. Using tissue-engineered cardiac grafts to repair infarcted myocrdium is considered to be a therapeutic approach. This study tested the feasibility of using MSCs-seeded SIS to repair chronic myocardial infarction in a rabbit model. MI in rabbits was created by ligation of the left anterior descending artery. BrdU-labeled mesenchymal stem cells (MSCs) were seeded on the small intestinal submucosa and cultured for 5-7 days prior to implantation. Four weeks after myocardial infarction, cardiac grafts were implanted onto the epicardial surface of infarcted myocardium. Four weeks after implantation of the membranes, a serial of tests including echocardiography, hemodynamics, histology and immunohistochemistry were undertaken to evaluate the effect of the implanted grafts on recovery of the infarcted myocardium. It was shown that left ventricular contractile function and dimension, the capillary density of the infarcted region, and myocardial pathological changes were significantly improved in rabbits implanted either SIS or MSCs-seeded SIS. But the MSCs-seeded SIS was more effective. Immunofluorescence staining demonstrated the migration of Brdu-labeled MSCs from the membrane into the infarcted area and their differentiation to cardiomyocytes and smooth muscle cells. Taken together, these results suggest that MSCs-seeded SIS can be used to repair chronic myocardial infarction, which enhances myocardial regeneration.


Contact sensitization to cosmetic series of allergens in female patients with rosacea: A prospective controlled study in China.
Allergic contact dermatitis to cosmetics (ACDC) complicates the diagnosis and treatment of rosacea, and is increasingly observed in daily practice. The present study aimed to identify the contact allergens responsible for ACDC in Chinese female rosacea patients with or without suspected ACDC (SACDC). From a total of 1267 women with rosacea, 122 with SACDC, 145 without SACDC, and 100 age-matched healthy controls without rosacea or SACDC were examined on a voluntary basis. Skin patch tests with C-1000 cosmetic series (Chemotechnique Diagnostics, Malmo, Sweden) were conducted, including 20 selected allergens. Positive allergic reaction was found in 85.2% and 33.8% of SACDC and non-SACDC (P < .001), respectively, and 27.0% of healthy volunteers. Most reactions occurred at day 3, and the majority of all the examinees including normal controls reacted to more than 1 allergen. In SACDC patients, leading allergens were methylchloroisothiazolinone/methylisothiazolinone (28.7%), linalool hydroperoxide (27.1%), fragrance mix I (21.3%), methylisothiazolinone (17.2%), limonene hydroperoxides (16.4%), formaldehyde (14.8%), myroxylon pereirae (13.9%), and propolis (10.7%); the overall allergic reaction rate positively correlated with new onset of facial pruritus (P < .001). The occurrence of irritant contact reactions correlated with positive allergic reactions in rosacea patients with or without SACDC (P = .032 or P < .001, respectively). Preservatives and fragrances are primary culprits for ACDC in Chinese female rosacea patients. Patch testing should be considered in the suspected patients.


Genome Sequence of an Alkaliphilus Species Isolated from Historically Contaminated Sediments of the Gulf of Naples (Mediterranean Sea).
Here, we report the draft genome sequence of a metagenome-assembled genome (MAG) of a new Alkaliphilus bacterium, NP8, of the Clostridiaceae family. This bacterium was isolated from polluted sediment collected from an abandoned industrial site located in the Gulf of Naples (Mediterranean Sea) as part of a microbial consortium.


Evolutionary history and classification of Micropia retroelements in Drosophilidae species.
Transposable elements (TEs) have the main role in shaping the evolution of genomes and host species, contributing to the creation of new genes and promoting rearrangements frequently associated with new regulatory networks. Support for these hypotheses frequently results from studies with model species, and Drosophila provides a great model organism to the study of TEs. Micropia belongs to the Ty3/Gypsy group of long terminal repeats (LTR) retroelements and comprises one of the least studied Drosophila transposable elements. In this study, we assessed the evolutionary history of Micropia within Drosophilidae, while trying to assist in the classification of this TE. At first, we performed searches of Micropia presence in the genome of natural populations from several species. Then, based on searches within online genomic databases, we retrieved Micropia-like sequences from the genomes of distinct Drosophilidae species. We expanded the knowledge of Micropia distribution within Drosophila species. The Micropia retroelements we detected consist of an array of divergent sequences, which we subdivided into 20 subfamilies. Even so, a patchy distribution of Micropia sequences within the Drosophilidae phylogeny could be identified, with incongruences between the species phylogeny and the Micropia phylogeny. Comparing the pairwise synonymous distance (dS) values between Micropia and three host nuclear sequences, we found several cases of unexpectedly high levels of similarity between Micropia sequences in divergent species. All these findings provide a hypothesis to the evolution of Micropia within Drosophilidae, which include several events of vertical and horizontal transposon transmission, associated with ancestral polymorphisms and recurrent Micropia sequences diversification.


A sustainable approach to controlling oil spills.
As a result of the huge economic and environmental destruction from oil spills, studies have been directed at improving and deploying natural sorbents which are not only the least expensive but also the safest means of spill control. This research reviews the limitations and environmental impact of existing cleanup methods. It also justifies the need for concerted research effort on oil spill control using natural and sustainable technology concepts. The article proposes future guidelines for the development of a sustainable cleanup technology. Finally, guidelines for the development of a new technology for the Middle East are proposed, which is the use of an abundant resource--date palm fibers--for such techniques.


Adverse drug reaction detection on social media with deep linguistic features.
Adverse reactions caused by drugs are one of the most important public health problems. Social media has encouraged more patients to share their drug use experiences and has become a major source for the detection of professionally unreported adverse drug reactions (ADRs). Since a large number of user posts do not mention any ADR, accurate detection of the presence of ADRs in each user post is necessary before further research can be conducted. Previous feature-based methods focus on extracting more shallow linguistic features that are unable to capture deep and subtle information in the context, ultimately failing to provide satisfactory accuracy. To overcome the limitations of previous studies, this paper proposes a novel method that can extract deep linguistic features and then combine them with shallow linguistic features for ADR detection. We first extract predicate-ADR pairs under the guidance of extended syntactic dependencies and ADR lexicon. Then, we extract semantic and part-of-speech (POS) features for each pair and pool the features of different pairs to generate a holistic representation of deep linguistic features. Finally, we use the collection of deep features and several shallow features to train the predictive models. A series of experiments are performed on data sets collected from DailyStrength and Twitter. Our approach can achieve AUCs of 94.44% and 88.97% on the two data sets, respectively, outperforming other state-of-the-art methods. The results demonstrate the potential benefits of deep linguistic features for ADR detection on social data. This method can be applied to multiple other healthcare and text analysis tasks and can be used to support pharmacovigilance research.


Akebia saponin D acts via the PPAR-gamma pathway to reprogramme a pro-neurogenic microglia that can restore hippocampal neurogenesis in mice exposed to chronic mild stress.
Using drugs to modulate microglial function may be an effective way to treat disorders, such as depression, that involve impaired neurogenesis. Akebia saponin D (ASD) can cross the blood-brain barrier and exert anti-inflammatory and neuroprotective effects, so we wondered whether it might influence adult hippocampal neurogenesis to treat depression. We exposed C57BL/6 mice to chronic mild stress (CMS) as a model of depression and then gave them ASD intraperitoneally once daily for 3 weeks. We investigated the effects of ASD on microglial phenotype, hippocampal neurogenesis, and animal behavior. The potential role of the peroxisome proliferator-activated receptor-gamma (PPAR-γ) or BDNF-TrkB pathway in the pro-neurogenesis and anti-depressant of ASD was identified using there inhibitors GW9662 and K252a, respectively. The neurogenic effects of ASD-treated microglia were evaluated using conditioned culture methods. We found that CMS upregulated pro-inflammatory factors and inhibited hippocampal neurogenesis in dentate gyrus of mice, while inducing depressive-like behaviors. Dramatically, ASD (40 mg/kg) treatment reprogrammed an arginase (Arg)-1+ microglial phenotype in dentate gyrus, which increased brain-derived neurotrophic factor (BDNF) expression and restored the hippocampal neurogenesis, and partially ameliorated the depressive-like behaviors of the CMS-exposed mice. K252a or neurogenesis inhibitor blocked the pro-neurogenic, anti-depressant effects of ASD. Furthermore, ASD activated PPAR-γ in dentate gyrus of CMS mice as well as in primary microglial cultures treated with lipopolysaccharide. Blocking the PPAR-γ using GW9962 suppressed the ASD-reprogrammed Arg-1+ microglia and BDNF expression in dentate gyrus of CMS mice. Such blockade abolished the promoted effects of ASD-treated microglia on NSPC proliferation, survival, and neurogenesis. The pro-neurogenic and anti-depressant effects of ASD were blocked by GW9962. These results suggested that ASD acts via the PPAR-γ pathway to induce a pro-neurogenic microglia in dentate gyrus of CMS mice that can increase BDNF expression and promote NSPC proliferation, survival, and neurogenesis.


Epstein-Barr virus and carcinomas: rare association of the virus with gastric adenocarcinomas.
We have analysed 174 gastric carcinomas from the United Kingdom and from Japan for the presence of Epstein-Barr virus (EBV) using in situ hybridisation for the small EBV-encoded nuclear RNAs (EBERs). EBV was detected in the tumour cells in all of six undifferentiated gastric carcinomas with prominent lymphoid stroma (undifferentiated carcinomas of nasopharyngeal type, UCNT) but only in three of the remaining 168 typical gastric adenocarcinomas (1.8%). No differences were observed between the British and the Japanese cases. One case with an EBV-positive UCNT showed adjacent areas of EBV-negative typical adenocarcinoma. It is uncertain whether these patterns represent two independent carcinomas or whether they are the result of heterogeneous EBV infection in a single tumour. In the remaining EBV-positive carcinomas, viral transcripts were detected in virtually all tumour cells, indicating that EBV infection must have taken place early in the neoplastic process and suggesting that the virus is likely to be of pathogenetic significance for the virus-associated tumours. Immunohistology demonstrated absence of detectable levels of the EBV-encoded latent membrane protein, LMP1, and nuclear antigen, EBNA2. The BZLF1 protein which induces the switch from latent to lytic infection was demonstrated in a small proportion of the tumour cells in three cases. The close association of EBV with undifferentiated gastric carcinomas compared to the variable association with gastric adenocarcinomas suggests fundamentally different roles for the virus in the aetiology of these two malignancies.


Risk factors for early-onset colorectal cancer: a population-based case-control study in Ontario, Canada.
There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). A population-based case-control study was conducted in Ontario, Canada during 2018-2019. EO-CRC cases aged 20-49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47-3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02-3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57-5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01-3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31-0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39-0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11-0.76) were each associated with a reduced risk. Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.


Principles of selective inactivation of viral genome. I. UV-induced inactivation of influenza virus.
Photosensitivity of infectious, haemagglutinating and neuraminidase activities of influenza virus has been determined experimentally. The photosensitivity of infectious activity of type B (strain Hongkong/8/73) influenza virus ws found to be higher than that of type A strains NIB-4 (N3N2-3), Leningrad/399/76 (H3N2-3) and NIB-6 (H1N1). The data obtained may be used for the determination of conditions of UV-irradiation for preparation of UV-inactivated antiviral vaccines.


Analysis of composite endpoints with component-wise censoring in the presence of differential visit schedules.
Composite endpoints are very common in clinical research, such as recurrence-free survival in oncology research, defined as the earliest of either death or disease recurrence. Because of the way data are collected in such studies, component-wise censoring is common, where, for example, recurrence is an interval-censored event and death is a right-censored event. However, a common way to analyze such component-wise censored composite endpoints is to treat them as right-censored, with the date at which the non-fatal event was detected serving as the date the event occurred. This approach is known to introduce upward bias when the Kaplan-Meier estimator is applied, but has more complex impact on semi-parametric regression approaches. In this article we compare the performance of the Cox model estimators for right-censored data and the Cox model estimators for interval-censored data in the context of component-wise censored data where the visit process differs across levels of a covariate of interest, a common scenario in observational data. We additionally examine estimators of the cause-specific hazard when applied to the individual components of such component-wise censored composite endpoints. We found that when visit schedules differed according to levels of a covariate of interest, the Cox model estimators for right-censored data and the estimators for cause-specific hazards were increasingly biased as the frequency of visits decreased. The Cox model estimator for interval-censored data with censoring at the last disease-free date is recommended for use in the presence of differential visit schedules.


Association between tonsillectomy and oropharyngeal cancer risk: a retrospective cohort study.
The purpose of this retrospective cohort study is to describe the association between the history of tonsillectomy and the risk of oropharyngeal squamous cell carcinoma (OPSSC), using a large cohort of patients. We performed a retrospective cohort study with 3620 patients diagnosed with OPٍSCC from 2010 to 2021. We utilized the University of Florida patients' registry i2b2 system. Three subsets of OPSSC were defined, base of tongue(BOT) cancer, tonsillar cancer, and other OPSSC. Tumor demographics and history of tonsillectomy were collected. Odds ratio for OPSSC were assessed utilizing a logistic regression model with adjusting for gender, race, and age. P < 0.05 was deemed significant. Of the 3620 OPSSC patients were BOT cancer (N = 964), tonsillar cancer (N = 995), and other OPSSC (N = 1661). There was a statistically significant reduction in tonsillar cancer and BOT cancer odds ratio in patients with a history of tonsillectomy vs. patients without tonsillectomy (0.086 and 0.117), respectively, with a P value < .0001. The odds ratio of OPSSC in patients with a history of tonsillectomy vs. patients without tonsillectomy is 1.031. This study showed that the OPSSC and previous history of tonsillectomy are associated. Our results showed a significant reduction in BOT and tonsillar cancer risk in patients with a history of tonsillectomy and an insignificant decrease in other OPSSC. This study could emphasize the importance of the development of future clinical trials to investigate the role of prophylactic tonsillectomy as a secondary preventive strategy to reduce OPSSC.


Residual tumour detection in post-treatment granulation tissue by using advanced diffusion models in head and neck squamous cell carcinoma patients.
To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0-1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (Ds) obtained by the SDM. The multivariate analysis revealed that the Ds and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour. DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour.


The knee and running.
Forty per cent of all injuries in our series are related to the knee area. A great number of people in the United States, estimated at 20 million, are running regularly. Sixty to 70 per cent of the individuals who are running regularly are injured severely enough that they must temporarily stop running. A large number of individuals who are running regularly are seeking treatment for their knee problems. The significance of the data is related to the number not the type of injuries. An underlying biomechanical abnormality must be sought and treated or symptoms will return. Biomechanical understanding and anatomic evaluation can provide a rational basis for treatment that manages the acute problem and prevents future ones.


DNA fingerprinting by random amplified polymorphic DNA and restriction fragment length polymorphism is useful for yeast typing.
Random amplified polymorphic DNA (RAPD) analysis was applied to genomic DNA from nineteen yeast strains belonging to the genera Saccharomyces and Zygosaccharomyces. Results obtained with five primers indicated that this technique is a powerful tool for yeast differentiation and identification. The data were consistent with those derived from restriction fragment length polymorphism (RFLP) using two S. cerevisiae DNA probes. We conclude that RAPD fingerprinting, combined with the analysis of RFLP, can provide unambiguous type assignment in yeasts.


Effects of radiofrequency catheter ablation on left ventricular structure and function in patients with atrial fibrillation: a meta-analysis.
Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). This study was designed to investigate the effects of RFCA on left ventricular (LV) structure and function in AF patients. A systematic literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed to identify trials involving changes of LV structure and function in AF patients undergoing RFCA. Effect size was expressed as weighted mean difference (WMD) with 95% confidence interval (CI). LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were estimated. A total of 21 trials including 1,135 participants were qualified for this meta-analysis. Compared to the baseline values, there were significant decreases in LVEDV (WMD, -6.39 ml; 95%CI, -12.46 to -0.33) and LVESV (WMD, -6.39 ml; 95%CI, -11.35 to -1.42) and a significant improvement in LVEF (WMD, 6.23%; 95%CI, 3.70 to 8.75), but no significant changes were observed in LVEDD (WMD, -0.64 mm; 95%CI, -2.40 to 1.13) and LVESD (WMD, -0.38 mm; 95%CI, -1.32 to 0.56) after RFCA. Subgroup analysis demonstrated that patients with low LVEF (WMD, 11.90%; 95%CI, 9.16 to 14.64) gained more benefits than those with normal LVEF (WMD, 1.56%; 95%CI, 0.38 to 2.74). Besides, patients with chronic AF (WMD, 10.96%; 95%CI, 4.92 to 17.01) improved more than those with paroxysmal AF (WMD, 1.93%; 95%CI, -0.27 to 4.12). RFCA in AF patients could reverse LV structural remodeling and improve LV systolic function, especially in patients with low LVEF and chronic AF.


COX-2 Gene increases tongue cancer cell proliferation and invasion through VEGF-C pathway.
COX-2 induces the proliferation and invasion of oral squamous cell carcinoma. In the present study, the role of the COX-2 gene in the tongue cancer cell proliferation and invasion was investigated. A short hairpin RNA (shRNA)method was used to knock down COX-2 gene expression and investigate the relationship between COX-2 and VEGF-C, and the role of the COX-2 gene for proliferation and invasion was also investigated in the tongue cancer cell Tca8113. COX-2 gene overexpressed in tongue cancer cell line. Suppressing the expression of COX-2 by shRNA could decrease cell proliferation comparing with control shRNA. Nevertheless, depressing COX-2 gene expression by shRNA reduced VEGF-C expression on both mRNA and protein levels. VEGF-C gene expression could be regulated by COX-2 gene. Our results suggested that COX-2 played essential roles in the proliferation and metastasis of tongue cancer, and COX-2 could serve as a potential chemotherapy target for tongue cancer.


Apneic Oxygenation Versus Low-Tidal-Volume Ventilation in Anesthetized Cardiac Surgical Patients: A Prospective, Single-Center, Randomized Controlled Trial.
To compare the physiology of apneic oxygenation with low-tidal-volume (VT) ventilation during harvesting of the left internal mammary artery. Prospective, single-center, randomized trial. Single-center teaching hospital. The study comprised 24 patients who underwent elective coronary artery bypass grafting surgery. Apneic oxygenation (apneic group: 12 participants) and low-VT ventilation (low-VT group: 12 participants) (2.5 mL/kg ideal body weight) for 15 minutes during harvesting of the left internal mammary artery. The primary endpoint was an absolute change in partial pressure of arterial carbon dioxide (PaCO2). Secondary endpoints were changes in arterial pH, pulmonary artery pressures (PAP), cardiac index, and pulmonary artery acceleration time and ease of surgical access. The mean (standard deviation) absolute increase in PaCO2 was 31.8 mmHg (7.6) in the apneic group and 17.6 mmHg (8.2) in the low-VT group (baseline-adjusted difference 14.2 mmHg [95% confidence interval 21.0-7.3], p<0.001). The mean (standard deviation) absolute decrease in pH was 0.15 (0.03) in the apneic group and 0.09 (0.03) in the low-VT group baseline-adjusted difference 0.06 [95% confidence interval 0.03-0.09], p<0.001. Differences in the rate of change over time between groups (time-by-treatment interaction) were observed for PaCO2 (p<0.001), pH (p<0.001), systolic PAP (p = 0.002), diastolic PAP (p = 0.023), and mean PAP (p = 0.034). Both techniques provided adequate ease of surgical access; however, apneic oxygenation was preferred predominantly. Apneic oxygenation caused a greater degree of hypercarbia and respiratory acidemia compared with low-VT ventilation. Neither technique had deleterious effects on PAP or cardiac function. Both techniques provided adequate ease of surgical access.