Hot melt extrusion as an approach to improve solubility, permeability and oral absorption of a psychoactive natural product, piperine.
The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology. Piperine 10-40% w/w and Eudragit(®) EPO/Kollidon(®) VA 64 or Soluplus(®) were mixed, and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus(®) , and pure piperine to study the permeability characteristics. Dissolution studies demonstrated enhancement in piperine per cent release of 10% and 20% w/w piperine/Soluplus(®) extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus(®) increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus(®) extrudates up to 158.9 μg/5 ml compared with pure piperine at 1.3 μg/5 ml within 20 min. These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study.


Programmed cell death of myelin basic protein-specific T lymphocytes is reduced in patients with acute multiple sclerosis.
We investigated the apoptosis of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) patients with acute (AMS) or stable (SMS) MS by evaluating the expression of apoptosis markers on peripheral cells. Cells of healthy controls (HC) were evaluated as well. Results showed that mitogen-stimulated apoptosis was comparable among patients and controls, whereas MBP-stimulated CD4+ and CD8+ 7-AAD+ and 7-AAD+ Fas+ cell (apoptotic cells) were significantly reduced in AMS patients. A reduction of the apoptotic rate of myelin-specific CD4+ and CD8+ T lymphocytes could be involved in the immune-mediated destruction of the myelin sheath seen in AMS patients.


Operationalizing and evaluating the Frascati criteria for functional decline in diagnosing HIV-associated neurocognitive disorders in adults.
The Frascati criteria for HIV-associated neurocognitive disorders (HAND; Antinori et al. 2007) outlines a classification scheme for functional decline that-despite being over a decade old-has not heretofore been examined systematically. Participants included 307 HIV+ and 183 HIV- participants who completed self-report, clinician-rated, and performance-based measures of functional status, along with neurocognitive, psychiatric, and medical/laboratory assessments. Using the Frascati criteria, we classified participants with (1) no functional declines, (2) mild functional declines, or (3) major functional declines. A multivariable logistic regression showed that HIV serostatus was associated with higher rates of major (33.2 vs. 13.7%) but not mild (38.8 vs. 31.7%) Frascati-defined functional decline. Within the HIV+ group, individuals with global neurocognitive impairment and affective disorders were at highest risk of Frascati-defined functional decline. Findings provide some empirical support for the sensitivity and validity of the Frascati criteria for functional declines in the context of HAND. Future work is needed to determine the reliability, stability, cross-cultural validity, and downstream health-related consequences of the Frascati-defined functional classifications.


Inhibitory effect of insulin and cytoplasmic factor(s) on brain (Na(+) + K+) ATPase.
(Na+ + K+)ATPase activity in cerebral cortex was modulated by insulin action depending on the Mg2+ concentration. Thus, in homogenates in the presence of 1-3 mM Mg2+, insulin stimulated the enzyme, whereas in the presence of 4-6 mM Mg2+ inhibition was observed. Exposure of synaptosomal membranes to the soluble fraction resulted in inhibition of ATPase activity in a dose-dependent manner. The inhibitory effect of insulin was regulated by a cytoplasmic factor in a dose-dependent manner. Similar variations to those obtained with a crude synaptosomal fraction were obtained by using a partially purified ATPase. These results indicated the importance of soluble factors in the modulation of ATPase by insulin and add more evidence in support for a role of insulin as a neuromodulator.


Acute cardiac side effects after COVID-19 mRNA vaccination: a case series.
Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©). Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography. Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset. Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.


Evaluation of the teratogenic effects of Tri-ortho-cresyl phosphate in the Long-Evans hooded rat.
The developmental toxicity of tri-ortho-cresyl phosphate (TOCP) was evaluated in Long-Evans rats. Pregnant rats were treated with 87.5, 175, and 350 mg/kg/day TOCP throughout organogenesis from gestation Days 6 through 18 (Day of sperm = Day 0). The highest dose tested (350 mg/kg) was lethal in 28% of the dams; no maternal deaths or toxicity were observed in the 87.5 or 175 mg/kg dose groups. There were no significant differences noted among the experimental and control groups for preimplantation loss or resorption. Fetal weights for both sexes in the TOCP groups were significantly greater than in the control group; however, no difference among the TOCP groups was observed. Malformation rates were too low to warrant statistical analysis. Numerous soft tissue and skeletal variations were observed in both control and TOCP-treated groups; there were no significant differences in the frequency of variations among the dose groups. The results of this study indicate that TOCP is not teratogenic in the Long-Evans rat.


Synthesis, assembly and organization of the cytoskeleton during early amphibian development.
All eukaryotic cells undergo changes in three-dimensional organization which are controlled by the cytoskeleton. Early embryos execute cytoskeletal-mediated changes in a rapid and dramatic fashion and are therefore useful cytoskeletal model systems. This review highlights similarities and differences between somatic cell cytoskeletons and those of amphibian oocytes, eggs and zygotes.


The role of everyday activities on likelihood of dietary lapse: an ecological momentary assessment study.
Developing a more nuanced understanding of factors predicting risk of dietary lapse (i.e., instances of non-adherence to a reduced calorie diet) is important, because dietary lapses contribute to suboptimal weight outcomes. The study investigated, for the first time, how various everyday activities affected likelihood of dietary lapses at two timescales-both in-the-moment, and in the hours after engaging in an activity. Participants (N = 107) with overweight/obesity in a behavioral weight loss program completed ecological momentary assessment surveys on dietary adherence and daily activities for 3 weeks at mid-treatment. Generalized estimating equations revealed that socializing predicted greater concurrent lapse risk, while work/school, doing chores, cooking, or practicing a spiritual activity/prayer/meditation were associated with reduced lapse risk. In terms of subsequent effects, cooking and indoor hobbies were associated with greater lapse risk in the next few hours, whereas spiritual activity/meditation was associated with reduced risk. Certain activities may have affected concurrent and subsequent lapse risk due to: their influence on the presence of tempting food, the compatibility of engaging in the activity and eating simultaneously, and the reward reaped from the activity (potentially reducing desire for food-related reward). Findings speak to the importance of attending to the timescale of relationships between activities and lapses, which has clinical implications for providing nuanced and optimally timed interventions for overweight/obesity.


Three cooperative mechanisms required for recovery after brain damage.
Stroke is one of the main causes of human disabilities. Experimental observations indicate that several mechanisms are activated during the recovery of functional activity after a stroke. Here we unveil how the brain recovers by explaining the role played by three mechanisms: Plastic adaptation, hyperexcitability and synaptogenesis. We consider two different damages in a neural network: A diffuse damage that simply causes the reduction of the effective system size and a localized damage, a stroke, that strongly alters the spontaneous activity of the system. Recovery mechanisms observed experimentally are implemented both separately and in a combined way. Interestingly, each mechanism contributes to the recovery to a limited extent. Only the combined application of all three together is able to recover the spontaneous activity of the undamaged system. This explains why the brain triggers independent mechanisms, whose cooperation is the fundamental ingredient for the system's recovery.


Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse.
Biochemical parameters in the brains of olfactory bulbectomized male and female mice were studied in two experiments, followed by three experiments in which 5-HTP was injected into bulbectomized males and females to try to block abnormal behaviors. In Experiment 1 bulbectomized male and female mice had significantly less tryptophan hydroxylase in their brains than did sham controls. Neither 5-hydroxtryptophan decarboxylase nor tyrosine hydroxylase activity was affected. In Experiment 2 the rate of synthesis of 5-HT was significantly less in bulbectomized males and females. Since bulbectomy leads to increased pup killing by female mice, the objective of Experiments 3 and 4 was to see whether the injection of 5-HTP into bulbectomized females could block this behavior. The incidence of pup killing was not influenced, but in both studies the latency to kill was significantly prolonged. Olfactory bulbectomy eliminates aggressive behavior in male mice, and the purpose of Experiment 5 was to determine whether 5-HTP treatment could restore normal levels of aggression. No significant effect was found. The data suggest that a dual mechanism is needed to explain the behavioral abnomalities seen in the two sexes; the mechanism in the female appears to be serotonergic while that in the male is still unknown.


Factors correlated with excessive daytime sleepiness in patients with Parkinson's disease: A polysomnography study.
To explore the factors correlated with excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD). A total of 239 PD patients were divided into two groups based on the presence of EDS (Epworth Sleepiness Scale score≥10) (PD-EDS vs. PD-non-EDS). Participants underwent an extensive assessment to determine demographic features, disease severity, polysomnography characteristics, and nonmotor symptoms. Of the 239 patients, 56 patients (23.4%) were classified as having PD combined with EDS. Binary logistic regression analysis showed that fatigue (Fatigue Severity Scale [FSS] score ≥4) (odds ratio [OR] [95% CI] = 4.897 [2.376-10.095], p < .001) and the respiratory-related microarousal index (OR [95% CI] = 2.063 [1.085-3.923], p = .027) were independent risk factors for EDS in PD patients. A priori-determined stratified analysis showed that after adjustment for confounding factors, the association of the respiratory-related microarousal index with EDS was significant (OR = 4.404, 95% CI 1.673-11.592, p trend = .036) in patients with respiratory arousal index scores in the highest quintile compared with those with scores in the lowest quintile. Our data revealed a close association among the respiratory-related microarousal index, FSS scores, and EDS. It can be speculated that fragmented sleep and pathological abnormalities of the central nervous system resulting in changes in arousal are major influencing factors of EDS in PD.


Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.
Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology. We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies. ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05). Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment. Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.


Impact of pre-burn statin use on metabolic and cardiovascular disorders.
Statins are among the most widely prescribed medications with proven effectiveness in patients with hyperlipidemia and atherosclerotic cardiovascular diseases. We investigated the relationship between statin use, metabolic and cardiovascular outcomes after burn. We utilized data from the TriNetX electronic health database. Burn patients with prior statin use were compared to patients without prior use and analyzed the occurrence of metabolic and cardiovascular disorders. Prior statin use burn patients were 1.33 times as likely to develop hyperglycemia, 1.20 times for cardiac arrhythmia, 1.70 times for coronary artery disease (CAD), 1.10 times for sepsis, and 0.80 times for death. High percent TBSA burn, male sex, and lipophilic statin use were associated with higher odds of outcome development. Prior statin use in severely burned patients is associated with an increased risk of developing hyperglycemia, arrhythmias, and CAD, with higher odds in males, higher TBSA burn, and lipophilic statin users.


Abnormal morphological features of osteocyte lacunae in adolescent idiopathic scoliosis: A large-scale assessment by ultra-high-resolution micro-computed tomography.
Abnormal osteocyte lacunar morphology in adolescent idiopathic scoliosis (AIS) has been reported while the results were limited by the number of osteocyte lacunae being quantified. The present study aimed to validate previous findings through (a) comparing morphological features of osteocyte lacunae between AIS patients and controls in spine and ilium using a large-scale assessment, and (b) investigating whether there is an association between the acquired morphological features of osteocyte lacunae and disease severity in AIS. Trabecular bone tissue of the facet joint of human vertebrae on both concave and convex sides at the apex of the scoliotic curve were collected from 4 AIS and 5 congenital scoliosis (CS) patients, and also at the same anatomic site from 3 non-scoliosis (NS) subjects intraoperatively. Trabecular bone tissue from ilium was obtained from 12 AIS vs 9 NS subjects during surgery. Osteocyte lacunae were assessed using ultra-high-resolution micro-computed tomography. Clinical information such as age, body mass index (BMI) and radiological Cobb angle of the major curve were collected. There was no significant difference between density of osteocyte lacuna and bone volume fraction (BV/TV) between groups. A total of 230,076 and 78,758 osteocyte lacunae from facet joints of apical vertebra of scoliotic curve and iliac bone were included in the analysis, respectively. In facet joint bone biopsies, lacunar stretch (Lc.St) was higher, and lacunar equancy (Lc.Eq), lacunar oblateness (Lc.Ob), and lacunar sphericity (Lc.Sr) were lower in AIS and CS groups when compared with NS group. CA side was associated with higher Lc.St when compared with CX side. In iliac bone biopsies, Lc.Ob was higher and lacunar surface area (Lc.S) was lower in AIS group than NS group. Median values of Lc.St, Lc.Eq and Lc.Sr were significantly associated with radiological Cobb angle with adjustment for age and BMI (R-squared: 0.576, 0.558 and 0.543, respectively). This large-scale assessment of osteocyte lacunae confirms that AIS osteocyte lacunae are more oblate in iliac bone that is less influenced by asymmetric loading of the deformed spine than the vertebrae. Shape of osteocyte lacunae in iliac bone is associated with radiological Cobb angle of the major curve in AIS patients, suggesting the likelihood of systemic abnormal osteocyte morphology in AIS. Osteocyte lacunae from concave side of scoliotic curves were more stretched in both AIS and CS groups, which is likely secondary to asymmetric mechanical loading.


Telomeres and telomerase in endocrine pathology.
Telomeres representing repetitive DNA sequences of chromosome ends are necessary for maintaining chromosomal integrity. The enzyme telomerase synthesizes de novo telomeric repeats and incorporates them onto the DNA 3'-ends of chromosomes. Stability of chromosome ends and activation of telomerase are elementary requirements for cell immortalization and tumor progression. The telomeric length and telomerase activity have been recently studied in several human neoplasms, including those of endocrine tissues. Assessment of telomerase activity may help to distinguish normal or hyperplastic from neoplastic tissues. Inhibition or inactivation of telomerase activity may provide novel strategies for cancer therapy.


Xanthelasma Palpebrarum: More than Meets the Eye.
Xanthelasma palpebrarum (XP) is the most common form of cutaneous xanthomata, and is important aesthetically, because of its close relation to the eyes, as well as medically for its association with cardiovascular disease (CVD). To provide avant-garde review discussing the various aspects of XP, including its aetio-pathogenesis and various treatment modalities. A structured Pubmed and Medline were searched for relevant articles. The finding of recent research has strongly espoused the link between XP and CVD, and mechanisms have been suggested for its formation. The new technologies have led to a multitude of treatment options for XP. XP is a multi-faceted entity; other than simple treatment of the cosmetic aspect of the disease, one must be cognizant of its cardiovascular implications.


Author Correction: Revealing the air pollution burden associated with internal Migration in Peru.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Simple and robust near-infrared spectroscopic monitoring of indium-tin-oxide (ITO) etching solution using Teflon tubing.
The ability to monitor etching solutions using a spectroscopy directly through existing Teflon lines in electronic industries is highly beneficial and offers many advantages. A monitoring method was developed using near-infrared (NIR) measurements with Teflon tubing as a sample container for the quantification of components in the indium-tin-oxide (ITO) etching solution composed of hydrochloric acid (HCl), acetic acid (CH3COOH) and water. Measurements were reproducible and it was possible to use the same calibration model for different Teflon tubings. Even though partial least squares (PLS) calibration performance was slightly degraded for Teflon cells when compared to quartz cells of the similar pathlength, the calibration data correlated well with reference data. The robustness of Teflon-based NIR measurement was evaluated by predicting the spectra of 10 independent samples that were collected using five different Teflon tubes. Although, two Teflon tubes were visually less transparent than the other three, there was no significant variation in the standard error of predictions (SEPs) among the five Teflon tubes. Calibration accuracy was successfully maintained and highly repeatable prediction results were achieved. This study verifies that a Teflon-based NIR measurement is reliable for the monitoring of etching solutions and it can be successfully integrated into on-line process monitoring.


MinION sequencing from sea ice cryoconites leads to de novo genome reconstruction from metagenomes.
Genome reconstruction from metagenomes enables detailed study of individual community members, their metabolisms, and their survival strategies. Obtaining high quality metagenome-assembled genomes (MAGs) is particularly valuable in extreme environments like sea ice cryoconites, where the native consortia are recalcitrant to culture and strong astrobiology analogues. We evaluated three separate approaches for MAG generation from Allen Bay, Nunavut sea ice cryoconites-HiSeq-only, MinION-only, and hybrid (HiSeq + MinION)-where field MinION sequencing yielded a reliable metagenome. The hybrid assembly produced longer contigs, more coding sequences, and more total MAGs, revealing a microbial community dominated by Bacteroidetes. The hybrid MAGs also had the highest completeness, lowest contamination, and highest N50. A putatively novel species of Octadecabacter is among the hybrid MAGs produced, containing the genus's only known instances of genomic potential for nitrate reduction, denitrification, sulfate reduction, and fermentation. This study shows that the inclusion of MinION reads in traditional short read datasets leads to higher quality metagenomes and MAGs for more accurate descriptions of novel microorganisms in this extreme, transient habitat and has produced the first hybrid MAGs from an extreme environment.


Remnant saphenous veins after aortocoronary bypass grafting: analysis of 3,394 centimeters of unused vein from 402 patients.
To assess the status of a saphenous vein (SV) excised for coronary artery bypass grafting (CABG), 3,394 cm of remnant SV from 402 patients who underwent CABG were examined. The SV remnants were 0.5 to 52 cm long (mean 8.4). They were sectioned into 5-mm-long segments, and the resulting 6,788 five-millimeter segments were examined histologically: 5,896 (87%) were narrowed 0 to 25% in cross-sectional area by fibrous tissue; 853 (12%) were narrowed 26 to 50%; 23 (0.6%), 51 to 75%, and 16 (0.4%) segments were narrowed 76 to 100%. Of the 16 segments severely narrowed, 7 (44%) were nearly totally occluded by fibrous tissue. In 17 patients who died within 24 hours of CABG, similar degrees of luminal narrowing were observed in remnant segments and in utilized segments of SV. Thus, significant preexisting luminal narrowing of SV used for CABG is infrequent. The intimal fibrous thickening is variable within the same vein when each 5-mm-long segment is analyzed; it is variable from 1 vein to another in the same patient, and it varies among patients.


Magnetic resonance imaging the velocity vector components of fluid flow.
Encoding the precession phase angle of proton nuclei for Fourier analysis has produced accurate measurement of fluid velocity vector components by MRI. A pair of identical gradient pulses separated in time by exactly 1/2 TE, are used to linearly encode the phase of flow velocity vector components without changing the phase of stationary nuclei. Two-dimensional Fourier transformation of signals gave velocity density images of laminar flow in angled tubes which were in agreement with the laws of vector addition. These velocity profile images provide a quantitative method for the investigation of fluid dynamics and hemodynamics.


Local consideration of polymorphisms for populations coexisting in stable ecosystems.
The stability problem for multiallelic genetic polymorphisms for n populations coexisting in stable ecosystems is considered. Taking into account only density-dependent interactions a generalization of Fisher's theorem is obtained. Specifically, the average fitness of a population must be locally maximized subject to the constraint that the equilibrium population sizes are fixed if the polymorphism is stable. Further, the quasi-equilibrium population sizes Ni corresponding to fixing the genetic structure of all populations in the ecosystem at various values have extrema at the equilibrium point. Such an equilibrium can be a maximum, minimum or saddle point depending upon the type of ecosystem under consideration. A simple test separating these cases on the basis of the so-called ecosystem matrix is suggested. The general equilibrium problem is reformulated as a maximization problem under some restrictions. Conditions under which the maximized function can be expressed as sigma ni=1 Ni are formulated.


Tackling the challenges to health equity in China.
In terms of economic development, China is widely acclaimed as a miracle economy. Over a period of rapid economic growth, however, China's reputation for health has been slipping. In the 1970s China was a shining example of health development, but no longer. Government and public concerns about health equity have grown. China's health-equity challenges are truly daunting because of a vicious cycle of three synergistic factors: the social determinants of health have become more inequitable; imbalances in the roles of the market and government have developed; and concerns among the public have grown about fairness in health. With economic boom and growing government revenues, China is unlike other countries challenged by health inequities and can afford the necessary reforms so that economic development goes hand-in-hand with improved health equity. Reforms to improve health equity will receive immense popular support, governmental commitment, and interest from the public-health community worldwide.


Toxoplasmosis after allogeneic stem cell transplantation--a single centre experience.
Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.


The vascular biology of peroxisome proliferator-activated receptors: modulation of atherosclerosis.
Accumulating evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists possess powerful antiatherosclerotic properties, by both directly affecting the vascular wall and indirectly affecting systemic inflammation and insulin sensitivity. The PPARs are ligand-activated transcription factors, which play a number of important physiological roles in lipid and glucose homeostasis. Activation of PPARgamma appears to exert a vasculoprotective effect by limiting endothelial dysfunction, impairing atherogenesis and preventing restenosis, while simultaneously and favourably modulating adipokine expression and lipid metabolism. Several experimental and clinical studies have demonstrated the potential of the PPAR agonist drug class in terms of treating atherosclerotic disease. In the present review, the vascular biology of PPARs, and how the modulation of these molecular pathways may serve as a therapeutic strategy to prevent atherosclerosis, vascular inflammation and restenosis are discussed.


Rural-Urban Disparities in Health Access Factors Over Time: Implications for Cancer Prevention and Health Equity in the Midwest.
Population-level environmental and socioeconomic factors may influence cancer burden within communities, particularly in rural and urban areas that may be differentially impacted by factors related to health care access. The University of Kansas (KU) Cancer Center serves a geographically large diverse region with 75% of its 123 counties classified as rural. Using County Health Rankings data and joinpoint regression, we examined trends in four factors related to the socioeconomic environment and health care access from 2009 to 2017 in rural and urban counties across the KU Cancer Center catchment area. The adult health uninsurance rate declined significantly in rural and urban counties across the catchment area (rural annual percent change [APC]=-5.96; 95% CI=[-7.71 to -4.17]; urban APC=-5.72; 95% CI=[-8.03 to -3.35]). Childhood poverty significantly decreased in rural counties over time (APC=-2.94; 95% CI=[-4.52 to -1.33]); in contrast, urban childhood poverty rates did not significantly change before 2012 (APC=3.68; 95% CI=[-15.12 to 26.65]), after which rates declined (APC=-5.89; 95% CI=[-10.01 to -1.58]). The number of primary care providers increased slightly but significantly in both rural and urban counties (APC=0.54; 95% CI=[0.28 to 0.80]), although urban counties had more primary care providers than rural areas (76.1 per 100K population vs. 57.1 per 100K population, respectively; p=0.009). Unemployment declined significantly faster in urban counties (APC=-10.33; 95% CI=[-12.16 to -8.47]) compared with rural counties (APC=-6.71; 95% CI=[-8.22 to -5.18]) (p=0.02). Our findings reveal potential disparities in systemic factors that may contribute to differences in cancer prevention, care, and survivorship in rural and urban regions.


A Pilot Study to Examine Exposure to Residential Radon in Under-Sampled Census Tracts of DeKalb County, Georgia, in 2015.
While DeKalb County, Georgia, offers free radon screening for all eligible residents, portions of the county remain relatively under-sampled. This pilot study focused on 10% of the census tracts in the county with the lowest proportion of radon testing; most were in southern DeKalb County. In total, 217 households were recruited and homes were tested for indoor radon concentrations on the lowest livable floor over an eight-week period from March-May 2015. Tract-level characteristics were examined to understand the differences in socio-demographic and economic factors between the pilot study area and the rest of the county. The pilot study tracts had a higher proportion of African Americans compared to the rest of DeKalb County (82% versus 47%). Radon was detected above 11.1 Bq/m³ (0.3 pCi/L) in 73% of the indoor samples and 4% of samples were above 148 Bq/m³ (4 pCi/L). Having a basement was the strongest predictive factor for detectable and hazardous levels of radon. Radon screening can identify problems and spur homeowners to remediate but more research should be done to identify why screening rates vary across the county and how that varies with radon levels in homes to reduce radon exposure.


A simulator for teaching visual field techniques on Goldmann or Goldmann-type perimeters.
We developed a visual field simulator for teaching perimetry on a Goldmann-type perimeter. It can present reproducible normal and defective visual fields, is portable and can be used without being attached to the perimeter, and will provide an easier way to train individuals in the correct techniques of perimetry.


Activation of anthocyanin synthesis genes by white light in eggplant hypocotyl tissues, and identification of an inducible P-450 cDNA.
Eggplant seedlings (Solanum melongena) grown under red light irradiation showed a normal morphology with green, fully expanded cotyledons. When the seedlings grown under red light were irradiated with ultraviolet-containing white light, anthocyanin synthesis was induced in the hypocotyl tissues, especially when a UV light supplement was added. The accumulation of pigments was closely associated with the expression of genes involved in flavonoid synthesis. These genes include chalcone synthase (CHS) and dihydroflavonol 4-reductase (DFR). Using subtracted probes, which had been enriched for the accumulated mRNA, one white light-responsive cDNA was identified as being a P450 gene by comparison with database sequences. The maximal amino acid homology this cDNA had with other P450s was 36%. This was with CYP71 from avocado (Persea americana). Thus it represents a new P-450 family, which has been named CYP75. The mRNA of this gene was localized in the hypocotyl tissues of eggplant seedlings, which had been white light-irradiated. The transcript was accumulated by changing the light source, as in the case of other flavonoid biosynthesis genes. In delphinidin producing petunia plants, the mRNAs corresponding to the eggplant P-450 and flavonoid biosynthesis genes such as CHS and DFR were most abundant during the mid stage of flower bud development, but could not be detected in leaf tissues. These results suggest that this P-450 gene encodes a hydroxylating enzyme involved in flavonoid biosynthesis.


A Scoping Review on Para Judo.
This scoping review aimed to summarize the literature on Para judo comprehensively. A systematic search on WOS, PubMed, SPORTDiscus, and Scopus was carried out up to July 2022, combining the key words "judo" and "visual impairment," "visual disability," "visual deficiency," "visually handicapped," "low vision," "sight loss," "blind," "disability," "deficiency," and "Paralympic." The research question was focused on athletes with visual impairment who practiced judo at a competitive level. The following five methodological phases were followed: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, and (5) collating, summarizing, and reporting the results. A total of 44 studies were analyzed. Three lines of research emerged: physical fitness ( n = 18), performance and/or sport class ( n = 15), and physical and mental health ( n = 11). Findings indicated that judokas with visual impairment showed a similar fitness level to able-sighted judokas. In addition, it was observed that Para judo shows a considerable injury incidence, which is not influenced by the degree of visual impairment. The temporal structure of the combats, together with the studies focused on the optimal cutoff points between sports classes, confirmed the appropriateness of the recent changes in the regulations by which partially sighted judokas and functional blind judokas compete separately.


Severity of Unilateral Coronal Synostosis Linked to Intracranial Volume.
Severity of unilateral coronal synostosis (UCS) varies and can affect intracranial volume (ICV), and intracranial pressure. Correlation between ICV and severity according to Utrecht Cranial Shape Quantifier and presence of papilledema as sign of raised intracranial pressure is determined. The authors included patients with UCS (≤18 months). Intracranial volume was calculated on preoperative CT scans by manual segmentation (OsiriX [Fondation OsiriX, Geneva, Switzerland]). Calculated ICV was compared to Lichtenberg normative data for control patients. When present, papilledema was noted. Utrecht Cranial Shape Quantifier was used to quantify severity using the variables: asymmetry ratio of frontal peak and ratio of frontal peak gradient. Severity of UCS was correlated to ICV using Pearson correlation coefficient. Mean age at CT scan of patients with UCS was 7 months (1-18 months). Mean calculated ICV was 870.96 mL (617.31-1264.46 mL). All patients had ICV between ± 2 SD curves of Lichtenberg; 10 had an ICV between -1 SD and +1 SD. Majority of ICV in girls was at or larger than normative mean, in boys ICV was mostly lower than normative mean. Pearson correlation coefficient between severity of UCS and ICV was negligible (r = -0.28). Preoperative papilledema during fundoscopy was found in 4.5% (1/22; ICV 1003.88 mL; severe UCS). Therefore, severity of UCS does not correlate to ICV. Despite varying severity of UCS, ICV remains within normal ranges.


Impact of the creation of a specialized clinic for prenatal blood sampling and follow-up care in pregnant women.
To evaluate (1) the effect on gestational diabetes mellitus (GDM) screening rates of having a specialized clinic for pregnant women offering blood sampling and screening for GDM, and (2) the impact on perinatal outcomes of having early GDM screening and follow-up provided by the specialized clinic. We performed a retrospective cohort study, based on electronic health records. We compared data from women who delivered during a period when the Blood Sampling in Pregnancy (BSP) clinic was operating (2008-2009; n = 2780) to a time period before the clinic was established (2006-2007; n = 2591). During the 2008-2009 period, we compared data from women who had GDM screening in the first trimester with women who had screening during the second trimester and with women who were not screened. Following the creation of the BSP clinic, overall GDM screening rates reached 72.4% in 2008-2009, compared with 48.9% in 2006-2007 (P < 0.001) and GDM screening was more likely to be performed in the first trimester (36.7% vs. 0.4%; P < 0.001). During the period when the BSP clinic was operating (2008-2009), women who had GDM screening in the first trimester had lower rates of Caesarean section (15.7% vs. 22.1%; P < 0.001) and neonatal complications (bradycardia: 3.6% vs. 6.8%; P = 0.003; respiratory distress: 9.6% vs. 13.2%; P = 0.02; and admission to NICU: 15.4% vs. 26.8%; P < 0.001) than women who did not perform GDM screening. In our population, creation of a clinic offering specialized care to pregnant women improved GDM screening rates. With the support of the BSP clinic, women who had early GDM screening were less likely to undergo Caesarean section and their offspring had fewer perinatal complications.


Genetic characterization and fine mapping of the blast resistance locus Pigm(t) tightly linked to Pi2 and Pi9 in a broad-spectrum resistant Chinese variety.
The identification and utilization of broad-spectrum resistance genes have been proven the most effective and economical approach to control rice blast disease. To understand the molecular mechanism of broad-spectrum resistance to rice blast, we conducted genetic and fine mapping analysis of the blast resistance gene in a Chinese rice variety: Gumei 4 (GM4) identified with broad-spectrum resistance and used in rice breeding for blast resistance for more than 20 years. Genetic and mapping analysis indicated that blast resistance to nine isolates of different Chinese races in GM4 was controlled by the same dominant locus designated as Pigm(t) that was finely mapped to an approximately 70-kb interval between markers C5483 and C0428 on chromosome 6, which contains five candidate NBS--LRR disease resistance genes. The allelism test showed that Pigm(t) was either tightly linked or allelic to Pi2 and Pi9, two known blast resistance genes. Mapping information also indicated that another blast resistance gene Pi26(t) might also be located at the same region. Candidate genes were identified by sequence analysis of the Nipponbare and Pi9 locus and the corresponding region in GM4. Sequence divergence of candidate genes was observed between GM4 and model varieties Nipponbare and 9311, and Pi9. Our current study provides essential information and new genetic resource for the cloning of functional resistance gene(s) and for marker-assisted selection in rice breeding for broad-spectrum blast resistance.


The value of dual mating data in estimating genetic parameters.
It is shown that matings between two affected individuals provide important information on the parameters of a single locus model with incomplete penetrance.


Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3.
Hepatocellular carcinoma (HCC) is a common cancer worldwide, and sorafenib is a first-line drug for the treatment of advanced liver cancer. Resistance to sorafenib has become a major challenge in the treatment of hepatocellular carcinoma, however, studies have shown that metformin can promote ferroptosis and sorafenib sensitivity. Therefore, the aim of this study was to investigate the promotion of ferroptosis and sorafenib sensitivity by metformin via ATF4/STAT3 in hepatocellular carcinoma cells. Hepatocellular carcinoma cells Huh7 and Hep3B and induced sorafenib resistance (SR) Huh7/SR and Hep3B/SR cells were used as in vitro cell models. Cells were injected subcutaneously to establish a drug-resistant mouse model. CCK-8 was used to detect cell viability and sorafenib IC50. Western blotting was used to detect the expression of relevant proteins. BODIPY staining was used to analyze the lipid peroxidation level in cells. A scratch assay was used to detect cell migration. Transwell assays were used to detect cell invasion. Immunofluorescence was used to localize the expression of ATF4 and STAT3. Metformin promoted ferroptosis in hepatocellular carcinoma cells through ATF4/STAT3, decreased sorafenib IC50, increased ROS and lipid peroxidation levels, decreased cell migration and invasion, inhibited the expression of the drug-resistant proteins ABCG2 and P-GP in hepatocellular carcinoma cells, and thus inhibited sorafenib resistance in hepatocellular carcinoma cells. Downregulating ATF4 inhibited the phosphorylated nuclear translocation of STAT3, promoted ferroptosis, and increased the sensitivity of Huh7 cells to sorafenib. Metformin was also shown in animal models to promote ferroptosis and sorafenib sensitivity in vivo via ATF4/STAT3. Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3, and it inhibits HCC progression.


The Challenging World of Biofilm Physiology.
Worldwide, infectious diseases are one of the leading causes of death among children. At least 65% of all infections are caused by the biofilm mode of bacterial growth. Bacteria colonise surfaces and grow as multicellular biofilm communities surrounded by a polymeric matrix as a common survival strategy. These sessile communities endow bacteria with high tolerance to antimicrobial agents and hence cause persistent and chronic bacterial infections, such as dental caries, periodontitis, otitis media, cystic fibrosis and pneumonia. The highly complex nature and the rapid adaptability of the biofilm population impede our understanding of the process of biofilm formation, but an important role for oxygen-binding proteins herein is clear. Much research on this bacterial lifestyle is already performed, from genome/proteome analysis to in vivo antibiotic susceptibility testing, but without significant progress in biofilm treatment or eradication. This review will present the multiple challenges of biofilm research and discuss possibilities to cross these barriers in future experimental studies.


Virtual bronchoscopy versus thin section computed tomography in evaluation of moderate and low grade stenoses: receiver operating characteristic curve analysis.
To evaluate the impact of virtual bronchoscopy, under proper threshold settings, on observer level of confidence in the assessment of bronchial abnormalities producing stenoses < or = 75% compared to interpretation of thin section computed tomography (CT) images. Sixty-five patients with fiberoptic bronchoscopy positive for tracheobronchial abnormalities were evaluated in a blinded observer study using a commercially available virtual endoscopy software package. The findings of virtual endoscopy were compared with those of fiberoptic bronchoscopy using receiver operating characteristic curves (ROCs) and other statistical tools. A total of 102 lesions were identified by fiberoptic bronchoscopy, with 44 of these producing bronchial stenoses < or = 75%. Concerning the latter lesions, for virtual bronchoscopy the areas under the ROCs were 0.93 and 0.96 for the two observers, respectively, while for thin section CT the corresponding values were 0.86 and 0.88; the differences observed were statistically significant. Contrary to thin section CT, virtual bronchoscopy did not show statistically significant differences from fiberoptic bronchoscopy regarding estimation of degree of stenosis. Virtual bronchoscopy under proper threshold settings has a statistically significant impact on observer performance where moderate and low-grade bronchial stenoses are concerned and gives an estimate of the degree of stenosis more precisely than thin section CT.


Role of Halloween genes in ecdysteroids biosynthesis of the swimming crab (Portunus trituberculatus): Implications from RNA interference and eyestalk ablation.
Molting, including metamorphosis molting in arthropods are controlled by the ecdysteroids that are synthesized and secreted by the crustacean Y-organ (YO) or the insect prothoracic gland (PG). The Halloween genes encoding the enzymes mainly involved in the biosynthesis of ecdysteroids are well studied in insects but not in crustaceans. Given the importance of Halloween genes in ecdysteroids biosynthesis, we have previously reported the cDNA cloning of disembodied (Dib) in P. trituberculatus. Here, cDNA sequences of another two Halloween genes, Spook (Spo) and Shadow (Sad), were further identified and characterized. The predicted amino acid sequences for these two Halloween genes of Portunus trituberculatus were compared to those of several other arthropods, and several typical domains of the cytochrome P450 mono-oxygenase (CYP) were identified. Similar to the tissue distribution of Dib, the Spo and Sad also showed high specificity to the YO. RNA interference (RNAi) of these 3 genes indicated they all play essential role in ecdysteroids biosynthesis. To investigate the relationships of the Halloween genes to the eyestalk neuropeptides such as molt-inhibiting hormone (MIH), effects of eyestalk ablation (ESA) on the expression of Dib, Spo and Sad were detected. Expression of Dib and Sad, but not Spo, was significantly induced by ESA. The result indicated that the inhibition of MIH in ecdysteroids biosynthesis may be partly through the transcriptional regulation of certain Halloween genes, such as Dib and Sad, while the Spo might not be the target for MIH signal.


Effect of dietary butylated hydroxytoluene on the in vivo distribution, metabolism and DNA-binding of 7,12-dimethylbenz[a]anthracene.
The effect of dietary intake of butylated hydroxytoluene (BHT) (0.6%) on the in vivo distribution, metabolism and DNA-binding of intragastrically administered 7,12-dimethylbenz[a]anthracene (DMBA) was evaluated. Urinary excretion of DMBA increased, blood content of metabolized DMBA increased and blood content of non-metabolized DMBA decreased for rats fed the diet containing BHT as compared to rats fed the control diet. The binding of DMBA to both liver and mammary DNA decreased for rats fed the diet containing BHT as compared to controls. The liver activities of glutathione-S-transferase (GST), epoxide hydrolase (EH) and NAD(P)H-quinone reductase (QR) increased in response to BHT feeding. However, no increase in the mammary tissue activities of these enzymes was observed. These results suggest that the ability of dietary BHT to inhibit the initiation of DMBA-induced mammary carcinogenesis partly may be due to decreased binding of DMBA to mammary DNA. This effect of BHT is not due to an increase in mammary tissue activities of GST, EH and QR, enzymes involved in carcinogen detoxification, but may involve increased liver metabolism of DMBA to products that do not bind to DNA.


Hyperbaric oxygen therapy effects on tissue lesions in acute pancreatitis. Experimental study in rats.
To study the effects of hyperbaric oxygen therapy on tissue lesions in an experimental model of acute pancreatitis induced by pancreatic duct ligation. Forty-eight adult female Wistar rats were randomized into two groups (n=24): control group and hyperbaric oxygen therapy group. The second group was treated with a two-hour daily session of hyperbaric oxygen therapy at 2.5 ATA started 6 hours after pancreatic duct ligation. The two groups were divided into 3 subgroups of 8 rats each undergoing euthanasia on days 1, 3, and 7 after the acute pancreatitis induction. The pancreas was evaluated according to the following histopathologic criteria: edema, hemorrhage, acinar necrosis and leukocyte infiltration. Hyperbaric oxygen therapy was efficient in significantly reducing acinar necrosis on the first day (P=0.049) and the foci of hemorrhage on the seventh day (P=0.050). The edema and leukocyte infiltration did not show the expected reduction. The utilization of a daily session of hyperbaric oxygen therapy at 2.5 ATA is efficient in reducing the hemorrhage and acinar necrosis but is not sufficient to reduce edema and leukocyte infiltration.


Directed evolution of diacetylchitobiose deacetylase via high-throughput droplet sorting with a novel, bacteria-based biosensor.
Numerous biological disciplines rely on high-throughput cell sorting. Flow cytometry, the current gold standard, is capable of ultrahigh-throughput cell sorting, but measurements are primarily limited to cell size and surface marker. Droplet sorting technology is gaining increasing attention with the ability to provide an individual environment for the analysis of single-cell secretion. Although various droplet detecting methods, such as fluorescence, absorbance, mass spectrum, imaging analysis, have been developed for droplet sorting, it remains challenging to establish high-throughput sorting methods for numerous analytes. We aim to develop a high-throughput sorting system based on the glucosamine (GlcN) measurement for the directed evolution of diacetylchitobiose deacetylase (Dac), the key enzyme for GlcN production. To overcome the limitation that no high-throughput sorting system existed for GlcN, we designed a novel bacteria-based biosensor capable of converting GlcN to a positively correlated fluorescence signal. Through characterization and optimization, it was possible to detect GlcN in droplets for high-throughput droplet sorting. We recovered the best Dac mutant S60I/R157T/F168S after sorting ∼0.2 million Dac mutants; its activity was 48.6 ± 1.5 U/mL, which was 1.8-times that of our previously discovered Dac mutant R157T (27.2 ± 1.8 U/mL). This result successfully demonstrated the combination of high-throughput droplet sorting technology and a bacteria-based biosensor, which could facilitate the industrial production of GlcN and serve as a model for similar droplet sorting applications.


[Orbital pseudotumor].
The orbital pseudotumour is an inflammatory infiltration, which ranges from a lymphoid, through a granulomatous to a sclerosing type, depending on its stage of maturity. Its simulataneous appearance with autoimmune-reaction-induced diseases might indicate an immune-allergic aetiology. After clinical diagnostic procedures including imaging techniques (of which magnetic resonance is particularly important) as much of the tissue as possible should be removed by orbitotomy. Therapy with cortisone and/or radiation is indispensable, but seems to be effective only in the early stages. The case histories of three patients over periods of 1.5-12 years are analysed and compared with the currently available results in the literature.


Vacuum-assisted sternal closure after a 'depression induced ischemic test' in severe mediastinitis.
We present a case of a 71-year-old patient with arterial myocardial revascularization and postoperative course complicated with sternal wound diastasis and subsequent mediastinitis. The patient underwent double revision of the mediastinum: the first in 13th and the second in 27th with total sternectomy. Although the resulting external exposure of pericardial cavity and grafts is a contraindication for using vacuum-assisted closure (VAC), we used it after a 'depression induced ischemic test' (DIIT) to evaluate ischemic threshold. After the VAC therapy period (from 32nd to 112th postoperative day), the sternal wound was ready to close. We think that VAC-therapy is a safe and economic approach in the treatment of serious substance loss even with pericardial cavity and graft exposure.


Porcine nuclei in early growing stage do not possess meiotic competence in matured oocytes.
To determine whether the nuclei of early growing stage porcine oocytes can mature to the MII stage, we examined meiotic competence of nuclei that had been fused with enucleated GV oocytes using the nuclear transfer method. In vitro matured oocytes were enucleated and then fused with early growing oocytes (30-40 μm in diameter) from 5 to 7-wk-old piglets using the hemagglutinating virus of Japan (HVJ). Reconstructed oocytes were cultured for 24 h to the MII stage. Although these oocytes extruded the first polar body, they did not contain normal haploid chromosomes, and the spindles were misaligned or absent at the metaphase II (MII) stage. Furthermore, maturation promoting factor (MPF) activity levels were low in oocytes reconstructed with early growing oocytes at metaphase I (MI) and MII. In contrast, mitogen-activated protein kinase (MAPK) activity was detected between the MI and MII stages, although at slightly lower levels. In conclusion, the nuclei of early growing oocytes did not accomplish normal meiotic division in matured oocytes due to misaligned or absent spindle formation.


Persistent Use of Prescription Opioids Before and After Lumbar Spine Surgery: Observational Study With Prospectively Collected Data From Two Norwegian National Registries.
Prospective pharmacoepidemiologic study. To investigate clinical and sociodemographic factors associated with persistent opioid use in the years following spine surgery among patients with persistent opioid use preceding lumbar spine surgery. It is unknown whether successful spine surgery leads to a cessation of preoperative persistent opioid use. Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked for patients operated for degenerative lumbar spine disorders between 2007 and 2017. The primary outcome measure was persistent opioid use in the second year after surgery. Functional disability was measured with the Oswestry Disability Index (ODI). Factors associated with persistent opioid use in the year before, and two years following, surgery were identified using multivariable logistic regression analysis. The variables included in the analysis were selected based on their demonstrated role in prior studies. The prevalence of persistent opioid use was 8.7% in the year before surgery. Approximately two-thirds of patients also met the criteria for persistent opioid use the second year after surgery. Among patients who did not meet the criteria for persistent opioid use the year before surgery, 991 (3.3%) patients developed persistent opioid use in the second year following surgery. The strongest association was exhibited by high doses of benzodiazepines in the year preceding surgery (OR 1.7, 95% CI 1.26 to 2.19, P <0.001). Among patients without persistent opioid use, the most influential factor associated with new-onset persistent opioid use in the second year after surgery was the use of high doses of benzodiazepines (OR 1.8, 95% CI 1.26 to 2.44, P <0.001), high doses of z -hypnotics (OR 2.6, 95% CI 2.10 to 3.23, P <0.001) and previous surgery at the same lumbar level (OR 1.37, 95% CI 1.11 to 1.68, P =0.003). A substantial proportion of patients reported sustained opioid use after surgery. Patients with persistent opioid use before surgery should be supported to taper off opioid treatment. Special efforts appear to be required to taper off opioid use in patients using high doses of benzodiazepines. 2; Prospective observational study.


Cardiovascular mortality in the Federal Republic of Germany, 1970-79, and the evaluation of the German Cardiovascular Prevention Study: results from a geographic mortality study.
The primary endpoint of the German Cardiovascular Prevention Study (GCP), cardiovascular mortality, has to be based on the official mortality statistics. In the scope of a geographic mortality study trends and regional variations of ischemic heart disease (ICD-9, 410-414) and cerebrovascular disease (ICD-9, 430-438) mortality were investigated. During the study period from 1970 to 1979 a relevant decline of cerebrovascular diseases in men and women was observed, whereas ischemic heart disease mortality figures remained relatively stable. Over time the importance of ischemic heart disease mortality has increased. The geographic analysis points to relevant problems concerning the validity of mortality data due to the particularities of the German mortality statistics (separately signed in the 11 statistical offices of the 11 federal states). The mortality rates of the four intervention regions of the "Kooperative Prävention" (corresponding data of "Kommunale Prävention" not available) indicate that the intervention regions are at a considerably lower level than the FRG, the mortality patterns, however, paralleling those of the FRG. As far as mortality structures are concerned, ischemic heart diseases are more important in the intervention regions than in the FRG as a whole.


Effects of nucleoside analogs on Epstein-Barr virus-induced transformation of human umbilical cord leukocytes and Epstein-Barr virus expression in transformed cells.
Two methods of assay, measuring (i) stimulation of host cell DNA synthesis by [(3)H]thymidine incorporation and (ii) morphological transformation in microtiter plates, were employed to determine what effect treatment during infection with adenine arabinoside or 5-iodo-5'-amino-2',5'-dideoxyuridine has on Epstein-Barr virus (EBV) (B95-8)-induced transformation of human umbilical cord leukocytes. It was found that adenine arabinoside inhibited EBV-induced transformation in a dose-dependent manner in both assays, beginning at drug concentrations (<2 mug/ml) which had little effect on either spontaneous or phytohemagglutinin-induced host cell DNA synthesis. Adenine arabinoside was more effective in inhibiting morphological transformation than EBV-induced host DNA synthesis. Adenine arabinoside treatment was also effective in reducing both EB viral capsid antigen expression and production of biologically active extracellular transforming virus in EBV-transformed cells. In contrast, 5-iodo-5'-amino-2',5'-dideoxyuridine, which inhibited herpes simplex virus replication, had little effect on EBV-induced transformation as measured by either method of assay. However, 5-iodo-5'-amino-2',5'-dideoxyuridine was found to be effective in inhibiting viral capsid antigen expression and production of extracellular transforming virus in EBV-transformed cells.


Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance.
Previous studies identified the functional polymorphism 1858C/T in the gene PTPN22 in association with several autoimmune diseases and with resistance to tuberculosis (TB). This study is the first to investigate the association between pulmonary TB and the PTPN22 1858C/T polymorphism in the Brazilian Amazon. We conducted a case-control study involving a group of 413 individuals, comprised of 208TB carriers and 205 controls. No significant association between the PTPN22 1858T allele frequency in controls (2.4%) and TB carriers (2.7%, p=0.982, odds ratio (OR)=0.89, 95% confidence interval=0.37-2.13) was identified in the Brazilian Amazon population. An additional evaluation by meta-analysis, however, suggested a protective role of the T allele in relation to TB (pooled OR=0.44, p=0.011). These results suggest that the PTPN22 1858T allele serves as a protective genetic factor for TB in those individuals who carry this minor allele.


Replication of baboon endogenous virus in human cells. Kinetics of DNA synthesis and integration.
For the baboon endogenous virus to infect human cells a specific region on chromosome 6 is required for viral DNA replication and integration. In studying the kinetics of baboon endogenous virus DNA replication we show that linear DNA was synthesized as the predominant species after infection and that unintegrated DNA persisted after many cell passages. Examination of integrated DNA revealed the failure of the virus to integrate at early passages. With continuous replication, however, virus integration was observed, but at multiple sites in the host cell.


Curcumin loaded waste biomass resourced cellulosic nanofiber cloth as a potential scaffold for regenerative medicine: An in-vitro assessment.
This article demonstrates the development of nanofibrous cloths by electrospinning of renewable materials, i.e., curcumin-loaded 90% cellulose acetate (CA)/10% poly(ε-caprolactone) (PCL), for applications in regenerative medicine. The CA is derived from the biomass waste of the oil palm plantation (empty fruit bunch). The nanofiber scaffolds are characterized for the fiber morphology, microstructure, thermal properties, and wettability. The optimized smooth and bead-free electrospun fiber cloth contains 90% CA and 10% PCL in two curcumin compositions (0.5 and 1 wt%). The role of curcumin is shown to be two-fold: the first is its function as a drug and the second is its role in lowering the water contact angle and increasing the hydrophilicity. The hydrophilicity enhancements are related to the hydrogen bonding between the components. The enhanced hydrophilicity contributed to improve the swelling behavior of the scaffolds; the CA/PCL/Cur (0.5%) and the CA/PCL/Cur (1.0%) showed swelling of ~700 and 950%, respectively, in phosphate-buffered saline (PBS). The drug-release studies revealed the highest cumulative drug release of 60% and 78% for CA/PCL/Cur (0.5%) and CA/PCL/Cur (1.0%) nanofibers, respectively. The in-vitro studies showed that CA/PCL/Cur (0.5 wt%) and CA/PCL/Cur (1.0 wt%) nanofiber scaffolds facilitate a higher proliferation and expression of actin in fibroblasts than those scaffolds without curcumin for wound healing applications.


Inactivation of internalized and surface contaminated enteric viruses in green onions.
With increasing outbreaks of gastroenteritis associated with produce, it is important to assess interventions to reduce the risk of illness. UV, ozone and high pressure are non-thermal processing technologies that have potential to inactivate human pathogens on produce and allow the retention of fresh-like organoleptic properties. The objective of this study was to determine if UV, ozone, and high pressure are effective technologies compared to traditional chlorine spray on green onions to reduce enteric viral pathogens and to determine the effect of location of the virus (surface or internalized) on the efficacy of these processes. Mature green onion plants were inoculated with murine norovirus (MNV), hepatitis A virus (HAV) and human adenovirus type 41 (Ad41) either on the surface through spot inoculation or through inoculating contaminated hydroponic solution allowing for uptake of the virus into the internal tissues. Inoculated green onions were treated with UV (240 mJ s/cm(2)), ozone (6.25 ppm for 10 min), pressure (500 MPa, for 5 min at 20°C), or sprayed with calcium hypochlorite (150 ppm, 4°C). Viral inactivation was determined by comparing treated and untreated inoculated plants using cell culture infectivity assays. Processing treatments were observed to greatly affect viral inactivation. Viral inactivation for all three viruses was greatest after pressure treatment and the lowest inactivation was observed after chlorine and UV treatment. Both surface inoculated viruses and viruses internalized in green onions were inactivated to some extent by these post-harvest processing treatments. These results suggest that ozone and high pressure processes aimed to reduce the level of microbial contamination of produce have the ability to inactivate viruses if they become localized in the interior portions of produce.


The stress response to induced hypotension for cerebral aneurysm surgery: a comparison of two hypotensive techniques.
Plasma epinephrine (PE), plasma norepinephrine (PNE), plasma renin activity (PRA), mean arterial pressure (MAP) and heart rate (HR) were measured before, during and after induced hypotension in two groups of patients undergoing cerebral aneurysm surgery. In Group I isoflurane was used to maintain anaesthesia and induce hypotension. Mean PE fell significantly during hypotension and remained reduced after hypotension, mean PNE remained unchanged, while mean PRA rose slightly but not significantly during hypotension, falling again after hypotension. In Group II halothane was used to maintain anaesthesia and sodium nitroprusside to induce hypotension. During anaesthesia and surgical stimulation PNE and PRA were significantly greater compared to Group I. Mean PE, PNE and PRA all rose during hypotension and remained elevated after hypotension. The rise in PNE and PRA was statistically significant. After hypotension the MAP in Group II was significantly higher when compared to Group I. There was no significant change in HR during the study in either group. In conclusion, isoflurane-induced hypotension with isoflurane anaesthesia unlike sodium nitroprusside-induced hypotension with halothane anaesthesia attenuated the stress response.


[Atomic absorption in mercury determination by "Julia-2" analyzer and urine mercury level in children of Moscow suburbs].
The authors report on atomic absorption method determining mercury in urine. Being sensitive, with lower determination threshold of 10 nmole/l and correctness of 95.5%, the method was tested on children living in two districts of Moscow suburb.


Discrimination between red blood cell and platelet components of blood clots by MR microscopy.
Magnetic resonance imaging (MRI) of pulmonary emboli obtained ex vivo, verified by immunohistochemistry, showed that platelet layers display brighter signal intensity than areas containing predominantly red blood cells (RBC) in T1-weighted MRI. These results were surprising since platelets do not contain paramagnetic haemoglobin that would enhance magnetic relaxation. Our assumption was that the fibrin meshwork areas with entrapped RBC retain abundant extracellular space filled with serum, whereas platelets regroup into tight aggregates lacking serum, essentially mimicking solid tissue structure, rich with cellular proteins that enhance T1-relaxation. Our hypothesis was examined by MRI and NMR relaxometry of in vitro RBC suspensions and sedimented platelets, as well as by MRI of model clots and pulmonary emboli obtained ex vivo. Pure sedimented platelets exhibited shorter proton spin lattice relaxation times (T1 = 874 +/- 310 ms) than those of venous blood of a healthy male with 40% haematocrit (T1 = 1277 +/- 66 ms). T1-values of RBC samples containing high haematocrit (> or = 80%) resembled T1 of platelet samples. In T1-weighted spin-echo MRI echo time and repetition time (TE/TR = 10/120 ms) the ratio of signal intensities between a non-retracted whole blood clot (with a haematocrit of 35%) and a pure platelet clot was 3.0, and the ratio between a retracted whole blood clot with an estimated haematocrit of about 58% and a pure platelet clot was 2.6. We conclude that T1-weighted MRI can discriminate between platelet layers of thrombi and RBC-rich areas of thrombi that are not compacted to a haematocrit level of > or = 80%.


Yeast influence on the formation of stable pigments in red winemaking.
The anthocyanin profile of a wine greatly varies over time depending on many factors. In addition to color modifications due to changes in the chemical composition of wine, there may be some influence of the yeast strain used in fermentation. The main aim of this study is to identify and quantify the different ways in which yeast may influence on wine color and its stability, during red winemaking. Hydroxycinnamate decarboxylase activity was measured by the ability to transform the p-coumaric acid (HPLC-DAD). Acetaldehyde (GC-FID) and pyruvic acid (Y15 enzymatic autoanalyser) contents were monitored along fermentation. Stable pigments formation, including vitisins, vinylphenolic pyranoanthocyanins and flavanols-anthocyanins adducts, were analyzed by HPLC-DAD/ESI-MS. Moreover, the ability of adsorbing color molecules by yeasts' cell walls was assessed. It could be concluded that the strain used has substantial influence on the formation of stable pigments, and therefore, proper yeast selection is important to ensure the stability of the wine coloring matter.


Increasing Access to Diabetes Care in Underserved Populations Using Mobile Medicine: How Point-of-Care Testing on Mobile Clinics Strengthens Hemoglobin A1c Adherence in Vulnerable and Underserved Populations.
The Center for Disease Control and Prevention (CDC) reported 26.9 million individuals a diabetes diagnosis rate of 9.4% in the United States had diabetes in 2018, equivalent to 8.2% of the population (CDC, 2020). Key government organizations have developed clinical quality indicators (CQIs) to ensure patients receive adequate care. The CQIs for comprehensive diabetes care are complex and often indicate a gap-in-care among vulnerable populations. To evaluate if the availability of point-of-care (POC) hemoglobin A1c (HbA1c) testing in a mobile clinic increases CQIs adherence in vulnerable populations. This evidence-based clinical practice change project (EBCPCP) focused on improving diabetic CQIs in vulnerable populations by implementing POC HbA1c testing on a federally qualified health centers (FQHC) mobile clinic. The results, 125 individuals having received HbA1c results, indicate having POC HgbA1c testing available on the mobile unit increased HbA1c testing. No patients had an HbA1c lab completed prior to the availability of POC testing. The availability of POC testing on a mobile clinic increases access to HbA1c for vulnerable populations which improves practice outcomes and increased CQI adherence. The results of this EBCPCP indicate POC testing increases access to diagnostics and care.


Activity of selected phytochemicals against Plasmodium falciparum.
According to the WHO, in 2008, there were 247 million reported cases of malaria and nearly one million deaths from the disease. Parasite resistance against first-line drugs, including artemisinin and mefloquine, is increasing. In this study the plant-derived compounds aglafolin, rocaglamid, kokusaginine, arborine, arborinine and tuberostemonine were investigated for their anti-plasmodial activity in vitro. Fresh Plasmodium falciparum isolates were taken from patients in the area of Mae Sot, north-western Thailand in 2008 and the inhibition of schizont maturation was determined for the respective compounds. With inhibitory concentrations effecting 50%, 90% and 99% inhibition (IC(50), IC(90) and IC(99)) of 60.95 nM, 854.41 nM and 7351.49 nM, respectively, rocaglamid was the most active of the substances, closely followed by aglafoline with 53.49 nM, 864.55 nM and 8354.20 nM. The activity was significantly below that of artemisinin, but moderately higher than that of quinine. Arborine, arborinine, tuberostemonine and kokusaginine showed only marginal activity against P. falciparum characterized by IC(50) and IC(99) values higher than 350 nM and 180 μM, respectively, and regressions with relatively shallow slopes S>14.38. Analogues of rocaglamid and aglafoline merit further exploration of their anti-plasmodial activity.


Risk of Rehospitalization and Death in Patients Hospitalized Due to Asthma.
Asthma is a heterogeneous inflammatory airway disease that continues to cause considerable morbidity across the world, with poor asthma control leading to hospitalizations. The present study investigated the risk of rehospitalization, mortality, and the management of patients with asthma who had been hospitalized because of an asthma exacerbation. National Swedish health registries were linked for patients 6 years or older who were admitted to hospital because of asthma (index date) between January 1, 2006, and December 31, 2015. Exacerbations were defined as asthma-related hospitalization, emergency visits, or collection of oral steroids. Patients were followed for rehospitalizations 12 months after the index date, health care resource utilization and treatment for 36 months, and mortality to study end. Regression models for time-to-event analyses were applied to assess risk factors for rehospitalization and mortality. A total of 15,691 patients (mean age, 51.5 years; 63% females) were included, of whom 1,892 (12%) were rehospitalized for asthma within 12 months. Rehospitalized patients had a markedly increased risk of subsequent asthma-related mortality (adjusted hazard ratio, 2.80; 95% CI, 1.95-4.01) compared with those not rehospitalized. Two-third of the patients were not followed up by a hospital-based specialist, and 60% did not collect enough inhaled corticosteroid doses to cover daily treatment the year postindex. In this study, more than 1 in 10 patients were rehospitalized because of asthma within 12 months, and rehospitalizations were associated with asthma-related mortality. Few patients were seen by a hospital-based specialist, and few used inhaled corticosteroid continuously. Closer monitoring after hospitalization is needed.


Neutrophil priming as a surgery-related risk factor for postoperative infectious complications in patients with ulcerative colitis.
The present study was designed to assess whether preoperative neutrophil priming under surgical stress has causal effects on the postoperative clinical outcomes of ulcerative colitis (UC) patients. In 63 consecutive UC patients, perioperative changes in cytokines and neutrophil elastase (NE) were quantified and their relationships to postoperative infectious complications (PICs) were evaluated. A preoperative increase in NE (high group: Group H) was associated with longer disease duration and greater preoperative total amount of steroids administered. Patients in Group H developed more PICs than those in the low NE group when they underwent surgery >240 min. In Group H, the NE level remained high after longer duration surgery, but decreased rapidly after shorter duration surgery. Multivariate analyses revealed that the total amount of steroids used and preoperative NE level were independent risk factors for predicting PICs in the longer operation group. Preoperative neutrophil activation may become a risk factor for postoperative morbidity when the patients undergo intense surgical stress. The most important procedures for preventing postoperative morbidity in high-risk UC patients may be reducing surgical stress and/or controlling neutrophil activation perioperatively.


Role of intracellular calcium on the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes.
The role of intracellular calcium in the modifications of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes was examined. Naloxone-precipitated withdrawal jumping was significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. Intracerebroventricular (i.c.v. ) pretreatment with ryanodine attenuated naloxone-precipitated withdrawal jumping in morphine-dependent non-diabetic mice. However, naloxone-precipitated withdrawal jumping in morphine-dependent diabetic mice was not affected by i.c.v. pretreatment with ryanodine. Moreover, i.c.v. pretreatment with thapsigargin, a Ca2+-ATPase inhibitor, enhanced naloxone-precipitated withdrawal jumping in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice. The noradrenaline (NA) turnover in the frontal cortex in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was significantly increased by naloxone injection. Naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was blocked by i.c.v. pretreatment with ryanodine. In contrast to ryanodine, thapsigargin enhanced naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice. These results suggest that increased intracellular calcium augmented naloxone-precipitated withdrawal jumping and the turnover rate of NA in the frontal cortex in morphine-dependent non-diabetic mice. Furthermore, it seems likely that the attenuation of naloxone-precipitated withdrawal jumping in morphine-dependent diabetic mice may be due, in part, to the dysfunction of intracellular calcium store.


Web tools for molecular epidemiology of tuberculosis.
In this study we explore publicly available web tools designed to use molecular epidemiological data to extract information that can be employed for the effective tracking and control of tuberculosis (TB). The application of molecular methods for the epidemiology of TB complement traditional approaches used in public health. DNA fingerprinting methods are now routinely employed in TB surveillance programs and are primarily used to detect recent transmissions and in outbreak investigations. Here we present web tools that facilitate systematic analysis of Mycobacterium tuberculosis complex (MTBC) genotype information and provide a view of the genetic diversity in the MTBC population. These tools help answer questions about the characteristics of MTBC strains, such as their pathogenicity, virulence, immunogenicity, transmissibility, drug-resistance profiles and host-pathogen associativity. They provide an integrated platform for researchers to use molecular epidemiological data to address current challenges in the understanding of TB dynamics and the characteristics of MTBC.


Occlusal wear of teeth and restorative materials. A review of classification, etiology, mechanisms of wear, and some aspects of restorative procedures.
This paper is a literature review of various aspects of the wear of occluding tooth surfaces. It presents classification and terminology of occlusal tooth wear, and discusses etiology and differential diagnosis. It may be difficult to differentiate among abrasion, attrition, and erosion because there is nearly always a combination of the various processes. These processes of wear are described, and the in vitro and in vivo wear of some restorative materials is discussed. Treatment of severe tooth wear is considered difficult; prophylactic measures are therefore important. Some guidelines for restorative treatment of patients with extensive occlusal tooth wear are given, with special emphasis on the type of treatment, the vertical dimension of occlusion, the space available, and choice of material for the restorations.


Early-Onset Gastric Cancer from a Geographic Area of High Gastric Cancer Incidence in North-East India: a Retrospective Study.
We aim to report about the clinico-pathological characteristics of early-age gastric cancer in North-East India. It is a retrospective and observational study conducted in a tertiary care cancer centre in North-East India. We reviewed physical case records and the hospital electronic medical record system. The study population included all patients of age 40 years or less, with a confirmed diagnosis of gastric adenocarcinoma, who received treatment in the institute. The duration of the study was from 2016 to 2020. Data was collected using a pre-designed proforma, and the results were presented as percentages, ratios, median values and range. A total of 79 patients with early-age gastric cancer were found during the study period. There was female preponderance (45:34). Out of the total, 43% presented in stage IV. Most of them had good performance status (87.3% had ECOG 0-2), and none of them had documented co-morbid illness. Poorly differentiated adenocarcinoma and signet ring cell carcinoma were seen in 36.7% and 25.3% patients, respectively. Only 25 patients (31.6%) underwent definitive surgery, and they had a high nodal burden with a median metastatic lymph nodal ratio of 0.35 (range 0 to 0.91). Out of them, 40% developed systemic recurrence within a short span of time (median time to recurrence being 9.5 months). Peritoneal recurrence was the most common site of failure (80%). Early-age gastric cancer has been associated with aggressive pathological features and poor clinical outcomes in North-East India.


Plant-Based Diets and All-cause and Cardiovascular Mortality in a Nationwide Cohort in Spain: The ENRICA Study.
To investigate the associations of a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) with all-cause and cardiovascular disease (CVD) mortality in Spanish adults. We analyzed data from 11,825 individuals 18 years of age or older, representative of the Spanish population, recruited between 2008 and 2010 and followed-up to 2020. Food consumption was collected at baseline using a validated dietary history, which served to calculate two plant-based diet indices based on 18 major food groups (range, 18-90 points). For (1) hPDI only the consumption of healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea/coffee) received positive scores; whereas for (2) uPDI, only the consumption of less healthy plant foods (fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts) received positive scores. Multivariable-adjusted Cox models were used to estimate HRs and their 95% CIs. After a median follow-up of 10.9 and 9.8 years, 699 all-cause and 157 CVD deaths were ascertained, respectively. Each 10-point increase in hPDI was associated with 14% lower risk of all-cause death (HR, 0.86; 95% CI, 0.74 to 0.99), and 37% lower risk of CVD death (HR, 0.63; 95% CI, 0.46 to 0.85). No significant associations were found for uPDI. Higher adherence to an hPDI diet, but not to a uPDI, was associated with lower all-cause and CVD mortality. This suggests that the quality of the plant food consumed is paramount to achieve diet-related benefits in mortality. clinicaltrials.gov Identifier: NCT02804672.


Shortened analog of the gramicidin A channel argues for the doubly occupied channel as the dominant conducting state.
A shortened analog of the gramicidin A transmembrane channel has been synthesized and its transport characterized in planar lipid bilayer membranes. General considerations of a shorter diffusional length and a shorter distance over which the voltage drop occurs (i.e., an increased electric field) would contribute to an increase in single-channel conductance. The finding of a decreased single-channel conductance supports the perspective that the dominant conducting state is the doubly occupied channel wherein distance-dependent repulsion due to the first ion in the channel impedes entry of the second ion in the shorter channel.


Clinical and radionuclide evaluation of Roux-Y diversion for postgastrectomy dumping.
From 1973 to 1986, 22 patients underwent Roux-Y gastrojejunostomy for the early postgastrectomy dumping syndrome. In the early years, five patients underwent Roux-Y conversion with the addition of a 10 cm antiperistaltic jejunal segment interposed between the Roux-Y limb and the stomach. Within 4 years, all five patients had the jejunal segment removed due to severe symptoms of gastric retention. These patients underwent reconstruction to create Roux-Y limb only and joined the pool of 17 patients who underwent Roux-Y diversion only for the dumping syndrome. Overall, 19 of 22 patients (86 percent) had almost complete resolution of their dumping symptoms on long-term follow-up. Three patients showed no improvement, two with severe gastric retention and one with recurrent dumping symptoms. Overall, 5 of 22 patients (23 percent) had moderate to severe early and late postoperative gastric retention necessitating medical treatment in three and subsequent near-total gastrectomy in two. Although other procedures such as pyloric reconstruction or the addition of isoperistaltic or antiperistaltic jejunal interpositions have been reported to be equally successful in delaying gastric emptying and resolving dumping symptoms, we have preferred Roux-Y diversion for the treatment of combined alkaline reflux gastritis and dumping or the pure early vasomotor postgastrectomy dumping syndrome. As reported, we have abandoned the use of an antiperistaltic jejunal segment interposed between the stomach and the Roux-Y limb due to the high rate of postoperative gastric retention.


Synthesis of alkenyldiarylmethanes (ADAMs) containing benzo[d]isoxazole and oxazolidin-2-one rings, a new series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
As a continuation of efforts to replace the metabolically labile methyl esters of lead alkenyldiarylmethanes (ADAMs) with stable bioisosteres, compounds bearing benzo[d]isoxazole and oxazolidine-2-one rings were designed and evaluated as a new series of potent HIV-1 non-nucleoside reverse transcriptase inhibitors with anti-HIV activity. All of the resulting ADAMs were found to inhibit HIV-1 RT with poly(rC) x oligo(dG) as the template primer. The most promising compound in this series was ADAM 3, with EC(50) values of 40 nM (vs HIV-1(RF)) and 20 nM (vs HIV-1(IIIB)). Compound 3 also inhibited HIV-1 reverse transcriptase with an IC(50) of 0.91 microM. ADAM 4 has an antiviral EC(50) of 0.6 microM in CEM-SS cells and a plasma half-life of 51.4 min.


Pineal parenchymal tumor of intermediate differentiation with marked elevation of MIB-1 labeling index.
We report a case of pineal parenchymal tumor (PPT) in an 11-year-old girl. Brain magnetic resonance imaging (MRI) revealed a large tumor (48 mm) located in the pineal region with heterogeneous enhancement after gadolinium administration. The patient underwent tumor removal with craniotomy; only partial tumor resection could be performed because of massive intratumoral bleeding. Histopathological examination of the tumor showed lobular proliferation of round cells with moderate atypia. Cellularity varied by area, and focal Homer Wright rosettes were identified. Examination of tumor cells revealed a few mitoses (two mitotic figures per 10 high-powered fields), and immunohistochemical staining revealed positivity for synaptophysin, slight positivity for neurofilament protein (NFP) with antibody clone 2F11, and strong positivity for NFP with clone NF-M+H. The pathological diagnosis was pineal parenchymal tumor of intermediate differentiation grade II according to World Health Organization criteria despite a high (22%) MIB-1 labeling index (LI). The patient had a favorable clinical course after an intensified chemotherapy regimen designed for pineoblastoma and radiotherapy administered to the entire neuraxis, followed by stereotactic radiotherapy. In conclusion, MIB-1 LI could be a useful tool for deciding therapeutic strategies for PPT treatment when there is a discrepancy between clinical findings and pathological grading.


The impact of pre-donation viral markers screening of new blood donors on blood safety.
The risk of transfusion-transmissible infections (TTIs) remains a concern in transfusion medicine. Since the rate of infection among first-time blood donors is higher than repeated donors, strategies to enhance blood safety can focus on new donors. The aim of the study was to investigate the effect of pre-donation viral screening of new donors on blood safety. The pre-donation screening of new donors was implemented in the Kurdistan blood center. In this program, new donors who met the blood donation criteria were informed about the program and only a blood sample was donated for HBs Ag, HCV Ab, and HIV Ab testing. New donors with negative results were invited to donate blood after 12 weeks. A unit of blood was collected from eligible returned donors. Laboratory tests were performed again using the same methods. Finally, the prevalence of confirmed positive TTI results among donated blood in Kurdistan blood center was compared before and after the establishment of program. During the study, 4,434 new donors were screened for viral markers. A total of 41 new donors (0.92%, 95% CI, 0.007-0.13) had repeatedly reactive results and infection was confirmed in blood sample of 24 donors (0.54%, 95% CI, 0.003-0.008). Overall, 56% of new donors returned for blood donation. Prevalence of confirmed TTIs markers in collected blood units was 0.27% and 0 before and after implementing program, respectively. This study indicated that Pre-donation screening can reduce the risk of TTI transmission by identifying infected donors at the pre-donation phase.


Exercise-derived skeletal myogenic exosomes as mediators of intercellular crosstalk: a major player in health, disease, and exercise.
Exosomes are extracellular membrane vesicles that contain biological macromolecules such as RNAs and proteins. It plays an essential role in physiological and pathological processes as carrier of biologically active substances and new mediator of intercellular communication. It has been reported that myokines secreted by the skeletal muscle are wrapped in small vesicles (e.g., exosomes), secreted into the circulation, and then regulate the receptor cells. This review discussed the regulation of microRNAs (miRNAs), proteins, lipids, and other cargoes carried by skeletal muscle-derived exosomes (SkMCs-Exs) on the body and their effects on pathological states, including injury atrophy, aging, and vascular porosis. We also discussed the role of exercise in regulating skeletal muscle-derived exosomes and its physiological significance.


Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age.
The mean wall thickness (MWT) of packets of trabecular bone was measured in undecalcified iliac crest bone samples of 36 normal subjects (14 female and 22 male) under polarized light. The mean wall thickness was 49.7 +/- 8.7 microns at a mean age of 50.9 years. There existed a significant decrease of MWT with advancing age. With an appositional rate of 0.72 micron/day, the mean formation time of iliac trabecular bone packets is 69 days. The decrease of MWT with age corresponds to a decrease in bone formation at the basic multicellular unit (BMU) level with aging and can partly explain the physiological senile osteopenia.


Patients' Experiences of Cardiovascular Health Education and Risk Communication: A Qualitative Synthesis.
Coronary heart disease (CHD) has no cure, and patients with myocardial infarction are at high risk for further cardiac events. Health education is a key driver for patients' understanding and motivation for lifestyle change, but little is known about patients' experience of such education. In this review, we aimed to explore how patients with CHD experience health education and in particular risk communication. A total of 2,221 articles were identified through a systematic search in five databases. 40 articles were included and synthesized using thematic analysis. Findings show that both "what" was communicated, and "the way" it was communicated, had the potential to influence patients' engagement with lifestyle changes. Communication about the potential of lifestyle change to reduce future risk was largely missing causing uncertainty, anxiety, and, for some, disengagement with lifestyle change. Recommendations for ways to improve health education and risk communication are discussed to inform international practice.


Osmolarity changes can enhance the release of renin from human chorion.
Sections of human chorion were perfused with an aerated buffer for 5 hours. Samples were collected every 20 minutes and the concentration of active and total renin in the perfusate was measured. Substitution of the initial bicarbonate buffer (281 mosm/L) with a buffer of 251 mosm/L doubled the rate at which active and inactive renin were released into the perfusate. When the osmolarity of the solution was reduced by 60 mosm/L, a threefold rise in the concentration of active renin and a sixfold rise in that of total renin was seen. However, these effects were transient, and renin secretion decreased before osmolarity was raised to the previous value.


Medication use in a rural gynecologic population: prescription, over-the-counter, and herbal medicines.
The purpose of this study was to document current medication use by a rural female population. Over a 42-month period, nonpregnant women were interviewed about medication use. When applicable, interviews on subsequent visits provided a longitudinal study of medication usage and discontinuation, and data were analyzed according to the number of drugs used, age, and payment status. Five hundred sixty-seven participants had 776 interviews. Ninety-two percent of the participants took prescription medications, 96.5% of the participants self-medicated with over-the-counter medications, and 59.1% of the participants used herbal medications. Usage of prescription medications increased with age and, in some instances, varied with payment status. A database query for potential interacting drugs found several instances of coadministration, including herbal medicines that were not prescribed by the physician. Medication usage (all types) by rural women is substantial, and the frequency of usage varies on the basis of both age and payment status. Patients should also be queried concerning medications that are not prescribed by the physician for an assessment of potential drug interactions.


Sites of photosensitization by protoporphyrin and tin protoporphyrin in leukemia L1210 cells.
Studies with protoporphyrin (PP) and tin protoporphyrin (SnPP) were carried out to assess the effects of tin insertion on the sites of dye localization. Fluorescence emission spectra and studies on the sites of photodamage were consistent with a concentration of PP at membrane loci. In contrast, SnPP photodamage involved an intracellular site.


An automated learning apparatus for classical conditioning of Lymnaea stagnalis.
The pond snail Lymnaea stagnalis is capable of taste avoidance classical conditioning (TAC) with sucrose as the conditional stimulus (CS) and mechanical prodding as the unconditional stimulus (US). After successful training, feeding behavior is significantly suppressed in response to CS presentation. An automated apparatus is described for the training of multiple snails up to 10 snails at the same time. The new apparatus employs an electrical shock obtained from a 9-V dry cell to deliver a consistent and effective current amplitude of 0.4μA (i.e., the US). Using this apparatus, 10 snails can be conditioned simultaneously. We found that the optimal parameters to result in both short (STM) and long-term memory (LTM) were 15 paired presentations of the CS and US with a 5-min inter-trial interval (ITI) and 0.2-s current duration. However, both STM and LTM were observed with other ITIs tested. Successful TAC with only a single pairing of the CS-US occurred with a CS of 100mM sucrose solution for 60s followed by a US of 9V with 0.4μA for 5s. The use of automated training apparatus for TAC will enable us to better examine the relationship between strength of CS and US.