The cause of leg cramps and knee pains: an hypothesis and effective treatment.
Cramps and pains of the lower extremities along with stiffness and pains in the knees are common complaints in the general population. Because the etiology and development of these disorders are poorly understood, treatment has been haphazard, for the most part unsuccessful, and occasionally dangerous. The diagnosis of "arthritis" is often incorrect; when osteoarthritis is present it is frequently not the cause of the pain. We name these maladies the "stiff leg syndrome" and hypothesise that they are caused by muscle and tendon shortening which came about as a direct result of modern civilization; the popular practice of squatting close to the ground to defecate, cook and eat was replaced by a more "civilized" practice of sitting high on toilets and chairs. We discuss several simple stretching exercises which mimic the effects of squatting and frequently result in immediate and dramatic relief of symptoms.


Effect of sleep state on the QT interval in normal infants.
Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied.


Pigment epithelium-derived factor alleviates depressive-like behaviors in mice by modulating adult hippocampal synaptic growth and Wnt pathway.
Pigment epithelium-derived factor (PEDF, also known as SERPINF1) is a secreted glycoprotein with neuroprotective effects. However, the potential role of PEDF in major depressive disorder (MDD) remains largely unknown. Here, applying two-dimensional gel electrophoresis (2-DE) proteomics, we found that PEDF levels were significantly decreased in the plasma of 12 first-episode treatment-naïve MDD patients (FETND) compared to the levels in 12 healthy controls (HCs). PEDF levels were especially lower in MDD patients than in HCs and patients with bipolar disorder (BD) and schizophrenia (SCZ), and elevated PEDF were consistent with decreased HAM-D scores in patients given antidepressant therapy (ADT). Animal research indicated that PEDF was decreased in the periphery and hippocampus of two well-known depression rodent models (the chronic unpredictable mild stress (CUMS) rat model and chronic social defeat stress (CSDS) mouse model). Decreased PEDF levels in the hippocampus led to depressive-like behaviors, synaptic impairments and aberrant Wnt signaling in C57BL mice, while increased PEDF resulted in the opposite results. Mechanistic studies indicated that PEDF contributes to dendritic growth and Wnt signaling activation in the hippocampus of adult mice. Taken together, the results of our study demonstrate the involvement of PEDF and its related mechanism in depression, thus providing translational evidence suggesting that PEDF may be a novel therapeutic target for depression.


Prospective randomized controlled trial in the treatment of lateral epicondylitis with a new dynamic wrist orthosis.
In the treatment of lateral epicondylitis (LE), the role of a new dynamic wrist orthosis is unclear. Patients suffering from a LE longer than 3 months were multicentrically and prospectively randomized into a physiotherapeutic group (PT group) and in a physiotherapy group plus wrist orthosis (PT + O group). Physiotherapy consisted of daily eccentric strengthening exercises under initial professional supervision. Inclusion criteria were a Placzek score greater than 4. Exclusion criteria were previous surgery, rheumatic arthritis, elbow instability, radicular symptoms, higher-grade extensor tendon rupture, or cervical osteoarthritis. The clinical evaluation was performed after 12 weeks and 12 months. The Patient-Rated Tennis Elbow Evaluation (PRTEE) scale, Placzek Score, the pain rating (VAS), range of motion and the Subjective Elbow Score were evaluated. Of the initially 61 patients, 31 were followed up after 12 weeks and 22 after 12 months. Twenty-nine patients (43%) were male, the mean age was 46, and 44 patients (66%) had the right elbow involved. At 12 weeks, there was a pain reduction on the VAS in both groups (PT + O: 6.5-3.7 [p = .001]; PT: 4.7-4.1 [p = .468]), albeit it was only significant for the PT + O group. At 12 months, reduction was significant in both groups (PT + O: 1.1 [p = .000]; PT: 1.3 [p = .000]). The painless maximum hand strength in kg improved in both groups significant after 3 and 12 months. The Placzek score was reduced from 8.25 to 3.5 [p = .001] after 12 weeks for the PT + O group and from 8.1 to 3.8 [p = .000] in the PT group, as well as after 12 months in the PT + O group to 0 [p = .000] and in the PT group to 2.0 [p = .000]. The PRTEE improved in both groups after 12 weeks (PT + O: 52.8--31.3 [p = .002]; PT: 48.6-37.6 [p = .185]) and 12 months (PT + O: 16.15 [p = .000]; PT: 16.6 [p = .000]), although the reduction at 12 weeks was not significant for the PT group. The elbow orthosis appears to accelerate the healing process with respect to the PRTEE and pain on the VAS (12 weeks follow-up), although there is an adjustment after 12 months in both groups and a significant improvement of symptoms is achieved in all endpoints.


Transcriptional profiling of native inner medullary collecting duct cells from rat kidney.
Vasopressin acts on the inner medullary collecting duct (IMCD) in the kidney to regulate water and urea transport. To obtain a "parts list" of gene products expressed in the IMCD, we carried out mRNA profiling of freshly isolated rat IMCD cells using Affymetrix Rat 230 2.0 microarrays with approximately 31,000 features; 7,913 annotated transcripts were found to be expressed above background in the IMCD cells. We have created a new online database (the "IMCD Transcriptome Database;" http://dir.nhlbi.nih.gov/papers/lkem/imcdtr/) to make the results publicly accessible. Among the 30 transcripts with the greatest signals on the arrays were 3 water channels: aquaporin-2, aquaporin-3, and aquaporin-4, all of which have been reported to be targets for regulation by vasopressin. In addition, the transcript with the greatest signal among members of the solute carrier family of genes was the UT-A urea transporter (Slc14a2), which is also regulated by vasopressin. The V2 vasopressin receptor was strongly expressed, but the V1a and V1b vasopressin receptors did not produce signals above background. Among the 200 protein kinases expressed, the serum-glucocorticoid-regulated kinase (Sgk1) had the greatest signal intensity in the IMCD. WNK1 and WNK4 were also expressed in the IMCD with a relatively high signal intensity, as was protein kinase A (beta-catalytic subunit). In addition, a large number of transcripts corresponding to A kinase anchoring proteins and 14-3-3 proteins (phospho-S/T-binding proteins) were expressed. Altogether, the results combine with proteomics studies of the IMCD to provide a framework for modeling complex interaction networks responsible for vasopressin action in collecting duct cells.


Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease.
Parenteral magnesium has been used for several decades in the empiric treatment of various arrhythmias, but the data on its electrophysiologic effects in man are limited. We evaluated the electrophysiologic effects of magnesium sulfate (MgSO4) administration in eight normomagnesemic patients with normal mononuclear cell magnesium content, who had no clinically significant heart disease and had normal baseline electrophysiologic properties. After administration of intravenous MgSO4, serum magnesium rose significantly from 1.9 +/- 0.1 to 4.4 +/- 1.7 mg/dl (p less than 0.02). During a maintenance magnesium infusion, we observed significant prolongation of the ECG PR interval (145 +/- 18 to 155 +/- 26 msec, p less than 0.05), AH interval (77 +/- 27 to 83 +/- 26 msec, p less than 0.002), antegrade atrioventricular (AV) nodal effective refractory period (278 +/- 67 to 293 +/- 67 msec, p less than 0.05), and sinoatrial conduction time (60 +/- 34 to 76 +/- 32 msec, p less than 0.02). No significant effect was observed on sinus cycle length, sinus node recovery time, intra-atrial or intraventricular conduction times, QRS duration (during both sinus rhythm and ventricular pacing), QT interval, HV interval, paced cycle length resulting in AV nodal Wenckebach block, AV nodal functional refractory period, retrograde ventriculoatrial (VA) effective refractory period, or atrial and ventricular refractory periods. These findings, in conjunction with the demonstrated ability of magnesium to block slow channels for sodium movement, may provide an explanation of the mechanism by which magnesium exerts its effect in the treatment of atrial and junctional arrhythmias.


Opioid Agonist Therapies and Pregnancy Outcomes for Pregnant People With Opioid Use Disorder: Protocol for a Systematic Review.
Opioid use disorder (OUD) during pregnancy presents a significant risk to maternal, fetal, and neonatal health, increasing the likelihood of adverse events, such as maternal overdose, pregnancy loss, stillbirth, preterm birth, low birth weight, and neonatal abstinence syndrome. In order to reduce the risk of these outcomes, the standard of care for OUD during pregnancy in many jurisdictions within the United States and Canada is opioid agonist therapy (OAT). OAT refers to prescription medications that alleviate or eliminate opioid withdrawal symptoms, so that opioid use can be managed more safely. Although OAT has been recognized as a safe option for pregnant people with OUD, many jurisdictions do not have treatment guidelines regarding pharmacological options, dosing recommendations, side effect management, and individual preferences. There is currently a lack of systematic evidence on the impacts of different OAT regimens on pregnancy outcomes. We aim to evaluate the impacts of specific OAT agents on pregnancy outcomes and inform recommendations for practitioners treating pregnant people with OUD. The MEDLINE, Embase, CINAHL, and PsycINFO databases will be searched for published quantitative studies assessing pregnancy outcomes for individuals on OAT. Given the substantially increased risk of preterm birth, low birth weight, small for gestational age, and stillbirth among pregnant people with OUD, these four end points will comprise our primary outcomes. Database searches will not be restricted by date, and conference abstracts will be restricted to the past 2 years. Titles, abstracts, and full-text articles will be independently screened by 2 reviewers. Data will be extracted independently and in duplicate, using a data extraction form to reduce the risk of reviewer bias. The risk of bias within individual studies will be assessed by using the appropriate CASP (Critical Appraisal Skills Programme) checklists. For studies that consider the same research questions, interventions, or outcomes, meta-analyses will be conducted to synthesize the pooled effect size. In the event that studies cannot be compared directly, results will be synthesized in a narrative account. Between-study heterogeneity will be measured by using the τ2 statistic. If more than 10 studies are available for pooling, publication bias will be evaluated by using the Egger regression test. As of January 2023, a total of 3266 abstracts have been identified for screening. Data extraction is expected to commence in February 2023. The topic of OAT and its effect on pregnancy is an understudied area that has the potential to improve health outcomes, clinical practice, education, and community advocacy. The results of our review will be used to inform clinical practice guidelines and improve health outcomes for pregnant people. Findings will be disseminated to diverse groups of stakeholders, including policy makers, clinicians, community partners, and individuals with lived experience of drug use. PROSPERO CRD42022332082; https://tinyurl.com/2p94pkx5. DERR1-10.2196/42417.


Evidence that natural benzodiazepine-like compounds increase during spontaneous labour.
Natural benzodiazepine-like compounds (NBDZ) are present in the blood of normal people free of commercial benzodiazepine medication. In this work, we evaluated the levels of NBDZ in maternal/foetal serum during delivery after spontaneous labour (VD) or caesarean section (CS). For both the VD (n=11) and the CS (n=11) groups (VD+CS=22), three blood samples were collected at three different times: the first was collected three days before labour, the second immediately after delivery or at fetal abdominal extraction and the third one was obtained at second day post-partum. NBDZ were measured by radioreceptor binding assay after HPLC extraction and purification while cortisol was measured through radioimmunoassay. In the VD group, a significant increase of NBDZ levels occurred at labour in comparison with the levels found in pre- and post-partum periods. By the contrary, no differences in NBDZ levels were found in the CS group at the three different times. The levels of cortisol in the VD group were found to be higher at labour than that determined at pre- and post-partum. Again no significant changes were found in the CS group. These findings suggest for the first time that labour is associated with a marked increase of NBDZ which could be envisaged as a stress-related event.


Pretreatment Proteinuria Predicts the Prognosis of Patients Receiving Systemic Therapy for Unresectable Hepatocellular Carcinoma.
Proteinuria is a common adverse event in systemic therapy for hepatocellular carcinoma (HCC). However, whether the presence of pretreatment proteinuria affects the clinical course is still unclear. From 2011 to 2022, 321 patients with unresectable HCC who were treated with systemic therapy as first-line treatment were enrolled in this study. We retrospectively analyzed the presence of pretreatment proteinuria and the treatment course of systemic therapy. In the cohort, 190 patients were tested for proteinuria qualitatively within 3 months before systemic therapy; 75 were treated with sorafenib, 72 were treated with lenvatinib, and 43 were treated with atezolizumab plus bevacizumab. Overall survival tended to be longer for patients treated with lenvatinib and significantly longer with atezolizumab plus bevacizumab in patients without pretreatment proteinuria but not for those treated with sorafenib. Further analysis was performed in 111 patients treated with lenvatinib or atezolizumab plus bevacizumab who had proteinuria measured quantitatively. Multivariate analysis including proteinuria, liver function, and HCC stage revealed that the severity of proteinuria was an independent predictor of prognosis. Pretreatment proteinuria predicts a poorer prognosis in patients with unresectable HCC treated with lenvatinib or atezolizumab plus bevacizumab but not in those treated with sorafenib.


Bedside nutrition evaluation and physical assessment techniques in critical illness.
The purpose of this review is to highlight emerging techniques used to determine body composition early in ICU stay, their prediction of poor outcome, and what is required before they can be more widely used. Opportunistic use of imaging techniques to assess muscle mass shows promise with regard to predicting patient outcomes; however, some of these techniques are expensive. Mid-arm muscle circumference and physical assessments of muscle wasting and subcutaneous fat loss using the subjective global assessment (SGA) are simple cheap tools that can be undertaken at the ICU patient bedside. Furthermore, each of these simple measures is a better predictor of patient outcome than BMI. Mid-arm muscle circumference, SGA fat loss, and SGA muscle wasting have each been found to be better predictors of poor outcome than BMI in ICU patients.Mid-arm muscle circumference, SGA fat loss, and SGA muscle wasting may be able to identify patients who are most likely to benefit from enhanced nutrition support.We need further research incorporating the use of these simple measures to evaluate their ability to accurately identify patients most likely to benefit from enhanced nutritional support.


Effects of Local Administration of Iron Oxide Nanoparticles in the Prefrontal Cortex, Striatum, and Hippocampus of Rats.
Iron oxide nanoparticles (IONPs) are used for diverse medical approaches, although the potential health risks, for example adverse effects on brain functions, are not fully clarified. Several in vitro studies demonstrated that the different types of brain cells are able to accumulate IONPs and reported a toxic potential for IONPs, at least for microglia. However, little information is available for the in vivo effects of direct application of IONPs into the brain over time. Therefore, we examined the cellular responses and the distribution of iron in the rat brain at different time points after local infusion of IONPs into selected brain areas. Dispersed IONPs or an equivalent amount of low molecular weight iron complex ferric ammonium citrate or vehicle were infused into the medial prefrontal cortex (mPFC), the caudate putamen (CPu), or the dorsal hippocampus (dHip). Rats were sacrificed 1 day, 1 week, or 4 weeks post-infusion and brain sections were histologically examined for treatment effects on astrocytes, microglia, and neurons. Glial scar formation was observed in the mPFC and CPu 1 week post-infusion independent of the substance and probably resulted from the infusion procedure. Compared to vehicle, IONPs did not cause any obvious additional adverse effects and no additional tissue damage, while the infusion of ferric ammonium citrate enhanced neurodegeneration in the mPFC. Results of iron staining indicate that IONPs were mainly accumulated in microglia. Our results demonstrate that local infusions of IONPs in selected brain areas do not cause any additional adverse effects or neurodegeneration compared to vehicle.


In Vitro Regeneration of Miscanthus x giganteus through Indirect Organogenesis: Effect of Explant Type and Growth Regulators.
Miscanthus x giganteus is a spontaneous sterile hybrid therefore the creation of useful genetic diversity by conventional breeding methods is restricted. Plant regeneration through indirect organogenesis may be a useful approach to create genetic variability of this important agricultural crop. The present study aimed to evaluate the effect of the explant type and growth regulators on indirect organogenesis of Miscanthus x giganteus and to determine the ploidy level of plant regenerants by flow cytometry. On average, the highest percentage of morphogenic callus tested explants formed in the medium supplemented with 2.5 mg L-1 IBA + 0.1 mg L-1 BAP + 4.0 mg L-1 l-proline. The most intensive secondary differentiation of callus cells was observed in the medium supplemented with 4.0 mg L-1 ZEA + 1.0 mg L-1 NAA. The highest root formation frequency with the highest number of roots was determined in the MS nutrient medium supplemented with 0.4 mg L-1 IBA, where more than 95% of plant regenerants survived and were growing normally.


A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2.
Increasing evidence suggests that pre-mRNA splicing can take place cotranscriptionally in vivo. However, insight into how these two processes are linked has been lacking. Here, we describe that a novel transcriptional coactivator, p52, interacts not only with transcriptional activators and general transcription factors to enhance activated transcription but also with the essential splicing factor ASF/SF2 both in vitro and in vivo to modulate ASF/SF2-mediated pre-mRNA splicing. Furthermore, immunofluorescence studies indicate that the majority of endogenous p52 is colocalized with ASF/SF2 in the nucleoplasm of HeLa cells. Together, these observations suggest that, in addition to functioning as a transcriptional coactivator, p52 may also act as an adaptor to coordinate pre-mRNA splicing and transcriptional activation of class II genes.


Comparative effects of cotrimoxazole (trimethoprim-sulphamethoxazole) and spiramycin in pregnant mice infected with Toxoplasma gondii (Beverley strain).
The effects of cotrimoxazole (CTX) and spiramycin (Spir) in mice infected in midpregnancy with the Beverley (Bev) strain of Toxoplasma gondii were compared. Therapeutic effectiveness was determined according to the following parameters: rate of successful delivery, litter size, offspring weight and survival. When compared with the uninfected untreated control group, CTX showed a more beneficial therapeutic effect than Spir, with a statistically significant increase in the rate of both successful delivery and offspring survival. Results based on antitoxoplasma antibody determinations in the offspring indicated a better in utero control of congenital infection by CTX than by Spir.


Onecut factors control development of the Locus Coeruleus and of the mesencephalic trigeminal nucleus.
The Locus Coeruleus (LC), the main noradrenergic nucleus in the vertebrate CNS, contributes to the regulation of several processes including arousal, sleep, adaptative behaviors and stress. Regulators controlling the formation of the LC have been identified but factors involved in its maintenance remain unknown. Here, we show that members of the Onecut (OC) family of transcription factors, namely HNF-6, OC-2 and OC-3, are required for maintenance of the LC phenotype. Indeed, in embryos lacking any OC proteins, LC neurons properly differentiate but abnormally migrate and eventually lose their noradrenergic characteristics. Surprisingly, the expression of Oc genes in these neurons is restricted to the earliest differentiation stages, suggesting that OC factors may regulate maintenance of the LC in a non cell-autonomous manner. Accordingly, the OC factors are present throughout development in a population directly adjacent to the LC, the rhombencephalic portion of the mesencephalic trigeminal nucleus (MTN). In the absence of OC factors, rhombencephalic MTN neurons fail to be generated, suggesting that OC proteins cell-autonomously control their production. Hence, we propose that OC factors are required at early developmental stages for differentiation of the MTN neurons that are in turn necessary for maintenance of the LC.


Distinct chemokinetic and chemotactic responses in neutrophil granulocytes.
Evidence has been presented to show that chemokinesis and chemotaxis of human neutrophil granulocytes can be controlled by distinct cellular mechanisms and by different chemicals. Materials such as human serum albumin or fibrinogen had chemokinetic but no chemotactic properties. Highly purified preparations of serum-derived peptides containing classical anaphylatoxin had detectable chemotactic activity only. Chemokinetic as well as chemotactic substances were required for the expression of chemotaxis in the form of efficient directional locomotion. The roles of chemokinesis and chemotaxis in the regulation of directional locomotion have been analyzed. Further experiments showed that the chemotactic response conforms to the law of Weber-Fechner. The number of cells which had accumulated in response to a chemotactic simulus was proportional to the logarithm of the concentration of the chemical substance. Readaptation from high to low chemotactic stimulus occurred only to a limited extent.


An analysis of the stimulant effects of 5-hydroxytryptamine on isolated, blood-perfused rat heart.
In rat isolated hearts perfused at a fixed low rate, single injections of 5-hydroxytryptamine (5-HT) (0.1--3 microgram) into the coronary perfusion produced dose-dependent increases in left ventricular (LV) dP/dt max and perfusion pressure (PP), but no clear changes in heart rate. The increases in the LVdP/dt max and PP were not significantly affected by treatment with propranolol, while they were abolished by methysergide. The present study indicates that the positive inotropic and vasoconstrictor responses of the rat heart to 5-HT are not mediated by endogenous catecholamine release, but are induced by a direct action on 5-HT receptors.


Tumor-specific antibody-mediated targeted delivery of Doxil reduces the manifestation of auricular erythema side effect in mice.
A mucocutaneous reaction in mice associated with Doxil treatment was identified as auricular erythema (AE). Given that the immuno-targeting of Doxil to tumors was found to influence also its systemic biodistribution pattern, the attempt was made to exploit a specific targeting of Doxil to reduce the manifestation of this adverse reaction. This problem is of general significance, since cutaneous reactions often lead to alterations of Doxil dosing regimen in patients and might subsequently compromise the therapeutic outcome of cancer treatment. Tumor-bearing mice were used to study the biodistribution and skin-tissue accumulation effects of the tumor-targeted Doxil (the clinically used anti-cancer formulation) coupled with the anti-cancer monoclonal 2C5 antibody (mAb 2C5) as well as AE caused by Doxil application. The modification of Doxil with mAb 2C5 resulted in a significant decrease in the normal skin accumulation of doxorubicin compared to original Doxil and substantially reduced AE. The frequency of AE was decreased by three to fourfold with the mAb 2C5-modified doxorubicin-loaded long-circulating liposomes. Thus, targeting of Doxil with the anti-cancer mAb 2C5 not only can increase the tumor-specific accumulation of the drug, but also diminishes the cutaneous side effect of the original Doxil therapy.


Open Partial Nephrectomy for Wilms' Tumor in a Cross-fused Pelvic Ectopic Kidney.
Wilms' tumor is the most common pediatric solid renal tumor. Cross-fused renal ectopia is a rare congenital anomaly in which the left and right kidneys become fused and fail to ascend from the pelvis and abdomen. We report a case of a 5-year-old girl that underwent open partial nephrectomy on a cross-fused ectopic kidney, "pancake kidney," after incidental discovery of a solid renal mass found to be a Wilms' tumor. Thorough review of the literature shows that this combination of Wilms' tumor in the setting of cross-fused renal ectopia has only been reported twice previously.


A dual function of Drosophila capping protein on DE-cadherin maintains epithelial integrity and prevents JNK-mediated apoptosis.
E-cadherin plays a pivotal role in epithelial cell polarity, cell signalling and tumour suppression. However, how E-cadherin dysfunction promotes tumour progression is poorly understood. Here we show that the actin-capping protein heterodimer, which regulates actin filament polymerization, has a dual function on DE-cadherin in restricted Drosophila epithelia. Knocking down capping protein in the distal wing disc epithelium disrupts DE-cadherin and Armadillo localization at adherens junctions and upregulates DE-cadherin transcription. In turn, DE-cadherin provides an active signal, which prevents Wingless signalling and promotes JNK-mediated apoptosis. However, when cells are kept alive with the Caspase inhibitor P35, the activity of the JNK pathway and of the Yorkie oncogene trigger massive proliferation of cells that fail to stably retain associations with their neighbours. Moreover, loss of capping protein cooperates with the Ras oncogene to induce massive tissue overgrowth. Taken together, our findings argue that in some epithelia, the dual effect of capping protein loss on DE-cadherin triggers the elimination of mutant cells, preventing them from proliferating. However, the appearance of a second mutation that blocks cell death may allow for the development of some epithelial tumours.


Impact of pre-operative coronary artery disease on the clinical outcomes of patients with aortic aneurysms.
Aortic aneurysm is an increasingly important public health problem with high morbidity and mortality. It is associated with coronary artery disease (CAD), which is a comorbidity of high incidence that is reported to worsen perioperative complications and long-term clinical outcomes in patients with an aortic aneurysm. Patients with significant coronary artery stenosis may require coronary revascularization and/or optimal medical therapy in the perioperative period of aneurysm surgery. However, the prognostic impact of non-significant coronary artery stenosis not indicated for coronary revascularization on clinical outcomes of patients with aortic aneurysms remains unclear. We performed coronary angiography on 239 consecutive patients with thoracic and abdominal aortic aneurysms before endovascular aortic repair or surgical repair. The patients were divided into the following 3 groups according to the severity of stenosis of major coronary arteries: non-CAD group (with < 25% stenosis), non-significant CAD group (with ≥ 25% but < 75% stenosis), and significant CAD group (with ≥ 75% stenosis). CAD was diagnosed in 133 (56%) patients consisting of 48 (20%) patients with non-significant CAD and 85 (36%) patients with significant CAD. Thirty-nine major adverse cardiovascular and cerebrovascular events (MACCEs) occurred in a median follow-up period of 723 days. Kaplan-Meier analysis revealed that the risk of MACCEs was higher in the significant and non-significant CAD groups than in the non-CAD group. Multivariate Cox proportional hazard regression analysis showed that the risk of MACCEs was equally high in the non-significant CAD and significant CAD groups compared to that in the non-CAD group after adjustment for confounding factors. CAD is significantly associated with poor outcomes in patients with aortic aneurysms, irrespective of the significance of CAD.


Vitamin D modulates airway smooth muscle function in COPD.
COPD is a disease manifested as persistent airflow obstruction with an enhanced inflammatory response in the airways and lungs to noxious particles and gases which evokes symptoms of dyspnea on exertion, cough and mucus production. Airway smooth muscle plays a central role in the COPD diathesis and is implicated in many aspects of COPD pathogenesis. Vitamin D deficiency has been associated with COPD severity and studies suggest a role for Vitamin D as a treatment for COPD. In this review, we describe the effects of 1,25-dihydroxyvitamin D on airway smooth muscle function, including agonist-induced shortening, secretion of inflammatory mediators, and myocyte hypertrophy and hyperplasia.


Noncausal effects between tea intake and migraine risk: a Mendelian randomization study.
Observational studies have yielded conflicting results regarding the relationship between tea intake and migraine risk. Residual confounders and potential reverse causality are unavoidable in traditional observational studies. To provide evidence for establishing viable disease screening and prevention strategies, a Mendelian randomization study (MR) was conducted to determine the causal inference between tea intake and migraine. We obtained 28 single-nucleotide polymorphisms (SNPs) for any migraine (AM), 25 SNPs for migraine with aura (MA), and 27 SNPs for migraine without aura (MO) associated with tea intake derived from a large genome-wide association study (GWAS) of the UK Biobank (UKBB) (containing 447,485 samples). The largest migraine GWAS performed by the International Headache Genetics Consortium (IHGC), including 29,209 cases and 172,931 controls, provided data on migraines and their subtypes (MA and MO). We used the method of inverse variance weighting (IVW) with fixed effects as the first-string MR selection. Sensitivity analysis and MR-pleiotropy residual sum and outlier (MR-PRESSO) method further assessed the robustness of the findings. Based on the conclusion of IVW in the fixed effects model, we found that tea intake had no causal relationship with AM risk (odds ratio (OR), 0.94; 95% confidence interval (CI), 0.70-1.25; P = 0.65), MA risk (OR, 0.93; 95% CI, 0.51-1.72; P = 0.83), or MO risk (OR, 0.90; 95% CI, 0.52-1.54; P = 0.69). Sensitivity analyses and MR-PRESSO showed no directional pleiotropy or heterogeneity. Our two-sample MR investigation found no causality between tea intake and migraine risk in European populations, implying that attempts to change tea drinking habits may not lead to a reduced risk of migraine.


[Rhinoscleroma in black Africa. Apropos of a case in a Malian observed in Paris].
Rhinoscleroma, an inflammatory tumour due to Klebsiella rhinoscleromatis, is rare in France but the few known cases have been observed among immigrants. A case of a Malian is reported here; to our knowledge this is the first described case from Mali. The clinical, histological and epidemiological aspects of the disease in Africans is reviewed.


MR diffusion - "diffraction" phenomenon in multi-pulse-field-gradient experiments.
Using pulsed-field-gradient (PFG) experiments, the sizes of the pores in ordered porous media can be estimated from the "diffraction" pattern that the signal attenuation curves exhibit. A different diffraction pattern is observed when the experiment is extended to a larger number (N) of diffusion gradient pulse pairs. Simulations to calculate signal values from arbitrary gradient waveforms are performed for diffusion in restricted geometries using a matrix operator formalism. The simulations suggest that the differences in the characteristics of the attenuation curves are expected to make it possible to measure smaller pore sizes, to improve the accuracy of pore size measurements and potentially to distinguish different pore shapes using the N-PFG technique. Moreover, when an even number of PFG pairs is used, it is possible to observe the diffraction pattern at shorter diffusion times and measure an approximation to the average pore size even when the sample contains pores with a broad distribution of sizes.


Photochemistry studied with ab initio orbital-correlation and state-correlation plots: Classic cyclobutene ring opening, and the reaction of N2 with photoexcited O2.
Pericyclic reaction theory arose from ideas presented in 1965, based on orbital-energy correlation diagrams (Woodward and Hoffmann) and state-energy correlation diagrams (Longuet-Higgins and Abrahamson). Here we have used ab initio complete-active-space self-consistent field (CASSCF) calculations to generate such diagrams. First we present diagrams for the classic case of cyclobutene ring opening, to demonstrate agreement between the CASSCF results and the classic diagrams of both Woodward/Hoffmann and Longuet-Higgins/Abrahamson. Then we present diagrams for the more difficult cases of N(2) + photoexcited O(2), to produce either 2 NO or NNO + O. These N(2) + O(2) cases feature significant electron reorganization, for which elementary pencil-and-paper diagrams are less accurate. Finally, the benefits and limitations of such diagrams for predicting photochemistry are briefly discussed.


Aboriginal and non-Aboriginal health differentials in Australian prisoners.
Compare the self-reported physical and mental health of Aboriginal and non-Aboriginal prisoners in New South Wales (NSW). Cross-sectional random sample. Twenty-nine correctional centres (27 male and two female) in NSW. 747 men (227 Aboriginal) and 167 women (29 Aboriginal) in full-time custody. Face to-face interviews were used to record self-reported health status. Aboriginal prisoners differed significantly from non-Aboriginal inmates in several socio-demographic and criminographic factors. However, few differences were observed in health status between Aboriginal and non-Aboriginal men and women. After adjusting for age, Aboriginal men were more likely to report high blood pressure and diabetes. No differences were found in chronic health conditions in the female group. Aboriginal men had higher SF-36 scores than non-Aboriginal men on general health, vitality, and mental health. Aboriginal women had lower scores than non-Aboriginal women on social functioning and role-emotional but scored higher on the role-physical dimension. Aboriginal inmates were more likely to report seeing certain health professionals (doctors, dentists, drug and alcohol counsellors, and optometrists) in prison compared with the community. The health of Aboriginal and non-Aboriginal prisoners is remarkably similar in this population group. Few differences were observed in self-reported chronic health conditions. Aboriginal prisoners report using prison health services more while in prison compared with the community. This highlights that for many, prison is a rare opportunity to contact health services.


Extracorporeal photochemotherapy in heart transplant rejection: A single-center experience.
The addition of extracorporeal photochemotherapy (ECP) to standard immunosuppressive therapy has been suggested to be beneficial in the treatment of recurrent/persistent heart rejection. We reviewed medical data of heart transplant recipients who received ECP between 2010 and 2016 at our institution. During the study period, eight patients underwent nine ECP courses. The median time from transplant to ECP was 18 months (range 9-54). Indications for ECP were recurrent rejection in 6 patients, persistent rejection in 1 patient and mixed rejection with hemodynamic compromise in 1 patient. Additional criteria for patients' selection were represented by relevant comorbidities limiting the increase of immunosuppressive therapies. ECP was performed on an outpatient basis in 6 out of 8 patients. The median ECP duration was 12 months (range 1-18). Three out of 8 patients responded to ECP showing negative endomyocardial biopsies at the end of treatment. No additional rejection episodes were observed at their follow up (at 44, 72 and 31 months). Four of 8 patients failed to respond to ECP treatment, one patient has been judged not evaluable. Reduction of immunosuppressive therapies was obtained in all 3 responsive patients but also in 3 patients with a stable grade of rejection. The median duration of the follow up was 26 months (range 6-80). Two patients died at 6 and 21 months after beginning ECP. Survival after ECP was 78.2% at 26 months. No adverse effect or infectious complications associated with ECP were reported. The low response rate (37.5%) in our case series could be partially explained by patient selection, the treated patients representing a high-risk sub-set group. Further studies to provide evidence of a role for ECP in heart rejection treatment or prophylaxis are needed.


The use of intraluminal manometry to assess upper esophageal sphincter function.
The UES is a striated muscular structure that exhibits substantial variation in tone in response to a wide variety of stimuli as well as during deglutition. It is an asymmetric structure subject to substantial axial movement. Hence the findings on UES manometry are highly dependent upon the manometry equipment used, positioning of this equipment in relation to the UES, and external stimuli. There is considerable intrasubject and intersubject variation in some parameters from UES pressure recordings. These factors must be taken into accout in the clinical use of UES manometry.


Hydrological, mineralogical and geotechnical characterisation of soils from Douala (coastal, cameroon): potential used in road construction.
The life span of pavements in coastal areas is diminutive due to high traffic levels. In this study, soils from different localities (Dibamba, Bekoko and Lendi) in the Douala coastal area were investigated, for their hydrological, mineralogical and geotechnical properties. This is to determine their potential used as raw material in the sub-base or base layer for road construction. Hydrological analysis of data for the past twenty years revealed that the average annual temperature stood at 27.5 °C with average precipitation of about 433.1mm. Average relative humidity was 82% throughout the year. XRD/XRF analysis were carried on the different soil samples and revealed quartz ranges from 52 -72%, kaolinite (20-35%); goethite (4-5%), anatase (3-4%) and feldspar (0-4%). The mineralogical content of these soils was similar to silico-aluminous-ferruginuos-titanous soils characterized by high silica content (43.52-66.4%), moderate alumina (13.5-31%), low content of Fe2O3 (2.5-3.2%) and TiO2 (1.2-2.02%). The silica/sesquioxide ratio of the various sample ranged from 1:1 to 1:3 indicating that the samples from Bekoko are non-lateritic, those of Dibamba are lateritic while the soils from Lendi are true laterite soils. The laterites are suitable for the sub base layer of road pavements. Specific density of investigated samples ranges between 2.12 and 2.32 g/cm3 a result of low degree of laterization. The percentage of clay in the fine fraction for samples from Bekoko, Dibamba and Lendi stood at 24.5%, 19.0% and 14.9% respectively. These values are lower than 35% which is the standard value recommended for sub-base material by the CEBTP. The Atterberg limits range from 11.50 to 22.4% hence samples from Lendi are the low plasticity while those of Bekoko and Dibamba have a moderate plasticity with low swelling potentials. Soil samples from Dibamba and Bekoko were of the A-7-6 group while Lendi soil samples were of the A-7-5 group which correspond to clayey soils and hence classified as poor materials for road construction according to American Association of State Highway and Transportation Officials (AASHTO) classification. The Unified Soil Classification System (USCS) revealed that, the majority of samples collected in the study area belonged to the SM group (silty sand) except DIB1 and LEN1 samples which pertain to SC group (clayey sand). The average of the maximum dry density (MDD) values stood at 1.9 g/cm3 with an average moisture content of 11% corresponding to the lower limit recommended for the use as sub-base materials. The value of CBR range between 8.6 and 28,2% which correspond to class S4 and can be used as raw material for the foundation layer of low traffic (T1) in the CEBTP standard. If those materials are treated with coarse gravel, cement and/or bitumen, they can be used on sub-base and base layer of high traffic (T2/T3).


Patterns of uterine enhancement with helical CT.
The purpose of this study was to evaluate the enhancement characteristics of the normal uterine body and cervix using dynamic contrast-enhanced helical CT. Thirty-eight women scheduled for pelvic CT for non-gynecologic malignancies underwent dynamic contrast-enhanced helical CT of the pelvis. Data acquisition was during the arterial phase (30-45 s after the start of injection), the parenchymal phase (90-120 s after the start of injection), and delayed phase (3-9 min after the start of injection). The images were evaluated by four radiologists for the pattern of myometrial and cervical enhancement. Correlation was made with the age and menstrual status of the patients. In the uterine body, three types of enhancement were observed. Type 1 enhancement, seen in 16 patients (42%), was characterized by the visualization of a subendometrial zone of enhancement, 30-120 s after the start of injection. Eight of these patients also showed an enhancing zone in the outer myometrium. Both zones were transitory, and in all cases, the uterus became homogeneous in the delayed phase. This pattern was seen predominantly in premenopausal women with a mean age of 34 years. Type 2 enhancement, seen in 17 cases (45%), was defined by the absence of subendometrial enhancement in the early phase. Enhancement was either diffuse from the outset or originated in the outer myometrium. This pattern was seen nearly equally in premenopausal and postmenopausal women with a mean age of 40 years. Type 3 enhancement was seen in five postmenopausal patients (13%) with a mean age of 53 years and was characterized by faint diffuse enhancement. In the cervix, a zonal pattern of enhancement defining inner and outer stroma was seen in 23 patients (61%). Fifteen patients were premenopausal and eight were postmenopausal. In this study, we have shown a transitory zonal distribution of the contrast in the myometrium and cervix using dynamic contrast-enhanced helical CT. The demonstration of these patterns is not constant and depends on individual variables. Of these, the menopausal status and/or age of the patient appear to be most important. While CT is not the primary imaging modality to evaluate the uterus, knowledge of these normal findings might help when confronted with unusual uterine enhancement during routine studies obtained with spiral CT.


Femoral artery necrosis due to parenteral intravascular drug misuse: a case report and literature review.
Accidental intra-arterial injection as a consequence of drug misuse has been described in both the upper and lower limbs. We present a case in which a drug abuser injected heroin into his femoral artery. This resulted in necrosis of the femoral artery requiring an autologous graft. A life threatening haemorrhage necessitated ligation of the common femoral artery. His limb survived.


South Africans and Mexicans in Florida: intergroup conflict.
Newly arriving immigrants from Southern Africa and Mexicans do not get on well in the sunbelt state of Florida. A persistent theme emerging from discussions with South Africans on their relationship with Mexicans is that both sides perceive the other as culturally ethnocentric. The antagonistic relationship between both social groups is due to strong ethnic bonds and the clash of cultures.


Sunbird pollination of Strelitzia nicolai.
The role of sunbirds (Nectariniidae) in the pollination ecology of Strelitzia nicolai (Musaceae) was studied for one year in a coastal dune forest in Zululand, South Africa. It was found that S. nicolai produced large quantities of low quality nectar (1.74 j/μl); that nectar production was highest during the day-time; and that the flowers displayed several characteristics attractive to bird-visitors. The flowers were large, conspicuous and provided the birds with a perch, facilitating easy access to the nectar. Flowers were visited by four species of sunbirds: Olive Sunbird Nectarinia olivacea, Grey Sunbird N. veroxii, Black Sunbird N. amethystina, and Collared Sunbird Anthreptes collaris. Sunbirds visited the flowers throughout the year, and apparently cued into changes in the flower angle as an indication of nectar flow rates. Sunbirds perched on the flowers in a manner which effected pollination, the pollen being transferred to the stigma via the birds' feet. Besides the sunbirds, there were other visitors (bushbabies, monkeys and insects) to the flowers, but they did not visit the flowers frequently nor did they appear to be significant pollinators. The high seed set of S. nicolai in the study area attests to the efficacy of the sunbirds as pollinators.


NMR determination of protein partitioning into membrane domains with different curvatures and application to the influenza M2 peptide.
The M2 protein of the influenza A virus acts both as a drug-sensitive proton channel and mediates virus budding through membrane scission. The segment responsible for causing membrane curvature is an amphipathic helix in the cytoplasmic domain of the protein. Here, we use (31)P and (13)C solid-state NMR to examine M2-induced membrane curvature. M2(22-46), which includes only the transmembrane (TM) helix, and M2(21-61), which contains an additional amphipathic helix, are studied. (31)P chemical shift lineshapes indicate that M2(21-61) causes a high-curvature isotropic phase to both cholesterol-rich virus-mimetic membranes and 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayers, whereas M2(22-46) has minimal effect. The lamellar and isotropic domains have distinct (31)P isotropic chemical shifts, indicating perturbation of the lipid headgroup conformation by the amphipathic helix. (31)P- and (13)C-detected (1)H T(2) relaxation and two-dimensional peptide-lipid correlation spectra show that M2(21-61) preferentially binds to the high-curvature domain. (31)P linewidths indicate that the isotropic vesicles induced by M2(21-61) are 10-35 nm in diameter, and the virus-mimetic vesicles are smaller than the 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles. A strong correlation is found between high membrane curvature and weak drug-binding ability of the TM helix. Thus, the M2 amphipathic helix causes membrane curvature, which in turn perturbs the TM helix conformation, abolishing drug binding. These NMR experiments are applicable to other curvature-inducing membrane proteins such as fusion proteins and antimicrobial peptides.


Development of a protocol for monitoring status and trends in forest soil carbon at a national level.
The national Forest Health Monitoring (FHM) program requires protocols for monitoring soil carbon contents. In a pilot study, 30 FHM plots loblolly shortleaf (Pinus taeda L./Pinus echinata Mill.) pine forests across Georgia were sampled by horizon and by depth increments. For total soil carbon, approximately 40% of the variance was between plots, 40% between subplots and 20% within subplots. Results by depth differed from those obtained by horizon primarily due to the rapid changes in carbon content from the top to the bottom of the A horizon. Published soil survey information overestimated bulk densities for these forest sites. The measurement of forest floor depths as a substitute to sampling did not provide reliable estimates of forest floor carbon. Precision of replicate samples was approximately 10-30% for field duplicates and 5-10% for laboratory duplicates. Based on national indicator evaluation criteria, sampling by depth using bulk density core samplers has been recommended for national implementation. Additional procedures are needed when sampling organic soils or soils with a high percentage of large rock fragments.


Hen egg white fractionation by ion-exchange chromatography.
Major hen egg white proteins have been widely studied for their functional properties but these studies still are unable to explain, alone, all of the biological properties of hen egg white. Hence, it is still interesting to produce pure and non-altered proteins to improve our knowledge on the biological properties of hen egg white. Presently, identification and characterization of both bioactive peptides and minor proteins from hen egg white is essential work for progressing in the understanding of hen egg white biological properties. With this objective in mind, a new process for a complete "mucin free" hen egg white fractionation based on ion exchange chromatography is proposed. "Mucin free" egg white is fractionated into six different fractions. Four of them are high-recovery yield purified fractions of lysozyme, ovotransferrin, ovalbumin and flavoprotein. The two other fractions are enriched in recently detected minor proteins in hen egg white.


Catalytic Conversion of 5-Hydroxymethylfurfural to High-Value Derivatives by Selective Activation of C-O, C=O, and C=C Bonds.
With increasing concern for reducing CO2 emission and alleviating fossil resource dependence, catalytic transformation of 5-hydroxymethylfurfural (HMF), a vital platform compound derived from C6 sugars, holds great promise for producing value-added chemicals. Among several well-established catalytic systems, hydrogenation and oxidation processes have been efficiently adopted for upgrading HMF. This Review covers recent advances in the development of thermocatalytic conversion of HMF into value-added chemicals. The advances of metal-catalyzed hydrogenation, hydrogenolysis, ring-opening, decarbonylation, and oxidation involving selective activation of C-O, C=O, and C=C groups are described. The roles played by nature of metals, supports, additives, synergy of metal-acid sites, and metal-support interaction are also discussed at the molecular level. Finally, an outlook is provided to highlight major challenges associated with this huge research area.


Protein assay sensitive at nanogram levels.
A simple, fast protein assay which utilizes the affinity of colloidal gold for proteins is described. This assay is sensitive at the 20-ng level when a visible light spectrophotometer is used to measure absorbance. Few chemicals interfere with the assay. Interfering reagents include those that are strongly alkaline, contain high levels of salt, or contain sodium dodecyl sulfate. The problem of alkaline interference can be overcome by acidifying the protein solution before performing the assay. Purified proteins have different capacities to interact with the colloidal gold but this variability is not greater than that seen with the Bradford protein assay.


Sarcoidosis-associated small fiber neuropathy in a large cohort: Clinical aspects and response to IVIG and anti-TNF alpha treatment.
Small fiber neuropathy commonly affects patients with sarcoidosis and is often refractory to standard immunosuppressive therapies used for systemic disease. The clinical features of sarcoidosis-associated small fiber neuropathy (SSFN) and its response to medical therapy have not been described in a large population. We performed a retrospective review of patients with SSFN seen at the Cleveland Clinic over a 4-year period. SSFN was identified in 143 individuals although other causes of neuropathy were found in 28 cases. Of the remaining 115 patients, 100 (87%) were Caucasian and 72 (63%) were female. Median age at reported neuropathy onset was 46 years (range 19-77 years), while median age of systemic diagnosis was 41 years. Pain and paresthesias were the most common symptoms, of which 54% were nonlength-dependent. Dysautonomia was seen in 61 patients with cardiac symptoms (orthostasis, palpitations) as the most common presentation followed by gastrointestinal and sweating dysfunction. Symptomatic improvement with treatment was seen in 47 of 62 patients that received IVIG, 8 of 12 patients that received anti-TNF and 10 of 14 patients who received combination therapy. Of 27 patients who were untreated, 4 improved. The most common presentation of SSFN in our series was a painful non-length dependent polyneuropathy with the highest overall incidence in Caucasian females. In most patients, neuropathy symptoms developed within 3 years of systemic sarcoidosis diagnosis. IVIG appeared beneficial in treating SSFN symptoms while nearly 2/3 of subjects also responded favorably to anti-TNF with or without IVIG. Further prospective studies are needed.


Do the benefits of polyandry scale with outbreeding?
There have been many potential explanations put forward as to why polyandry often persists despite the multiple costs it can inflict on females. One such explanation is avoidance of costs associated with mating with genetically incompatible males. Genetic incompatibility can be thought of as a spectrum from individuals that are genetically too similar (inbreeding) to those that are too dissimilar (outbreeding or hybridization). Here we look for evidence that the level of outbreeding influences the benefits of polyandry in the seed bug Lygaeus equestris. Our system allows us to test for benefits of polyandry at levels of genetic similarity ranging from full siblings to heterospecifics, both in terms of egg production and hatching success. We found that while outbreeding level appeared to have no effect on fitness for intraspecific matings, and polyandry did not appear to result in any increase in fertility or fecundity, hybridization with a closely related species, Lygaeus simulans, carried considerable fitness costs. However, these costs could be rescued with a single mating to a conspecific. Thus, polyandry may be beneficial in populations that co-occur with closely related species and where there is reproductive interference. However, within-species genetic incompatibility is unlikely to be the driving force behind polyandry in this species. Furthermore, the mechanism underlying this rescue of fertility remains unclear as manipulation of male cuticular hydrocarbon profile, a possible mechanism by which females can assess male identity, had no effect on female offspring production.


Feasibility and mechanism of recycling carbon resources from waste cyanobacteria and reducing microcystin toxicity by dielectric barrier discharge plasma.
Recycling carbon resources from discarded cyanobacteria is a worthwhile research topic. This study focuses on the use of dielectric barrier discharge (DBD) plasma technology as a pretreatment for anaerobic fermentation of cyanobacteria. The DBD group (58.5 W, 45 min) accumulated the most short chain fatty acids (SCFAs) along with acetate, which were 3.0 and 3.3 times higher than the control. The DBD oxidation system can effectively collapse cyanobacteria extracellular polymer substances and cellular structure, improve the biodegradability of dissolved organic matter, enrich microorganisms produced by hydrolysis and SCFAs, reduce the abundance of SCFAs consumers, thereby promoting the accumulation of SCFAs and accelerating the fermentation process. The microcystin-LR removal rate of 39.8% was obtained in DBD group (58.5 W, 45 min) on day 6 of anaerobic fermentation. The toxicity analysis using the ECOSAR program showed that compared to microcystin-LR, the toxicity of degradation intermediates was reduced. The contribution order of functional active substances to cyanobacteria cracking was obtained as eaq- > •OH > 1O2 > •O2- > ONOO-, while the contribution order to microcystin-LR degradation was eaq- > •OH > •O2- > 1O2 > ONOO-. DBD has the potential to be a revolutionary pretreatment method for cyanobacteria anaerobic fermentation.


Spatial interpolation methods and geostatistics for mapping groundwater contamination in a coastal area.
Mapping groundwater contaminants and identifying the sources are the initial steps in pollution control and mitigation. Due to the availability of different mapping methods and the large number of emerging pollutants, these methods need to be used together in decision making. The present study aims to map the contaminated areas in Richards Bay, South Africa and compare the results of ordinary kriging (OK) and inverse distance weighted (IDW) interpolation techniques. Statistical methods were also used for identifying contamination sources. Na-Cl groundwater type was dominant followed by Ca-Mg-Cl. Data analysis indicate that silicate weathering, ion exchange and fresh water-seawater mixing are the major geochemical processes controlling the presence of major ions in groundwater. Factor analysis also helped to confirm the results. Overlay analysis by OK and IDW gave different results. Areas where groundwater was unsuitable as a drinking source were 419 and 116 km2 for OK and IDW, respectively. Such diverse results make decision making difficult, if only one method was to be used. Three highly contaminated zones within the study area were more accurately identified by OK. If large areas are identified as being contaminated such as by IDW in this study, the mitigation measures will be expensive. If these areas were underestimated, then even though management measures are taken, it will not be effective for a longer time. Use of multiple techniques like this study will help to avoid taking harsh decisions. Overall, the groundwater quality in this area was poor, and it is essential to identify alternate drinking water source or treat the groundwater before ingestion.


A new ground beetle (Carabidae, Protorabinae) from the Lower Cretaceous of Inner Mongolia, China.
Cretorabus rasnitsynisp. n., belonging to the extinct subfamily Protorabinae of Carabidae, was described based on a well-preserved specimen from the Lower Cretaceous Yixian Formation of Yangshuwanzi, Inner Mongolia. The diagnostic characters forCretorabus are revised, and the key to species of the genus was presented. The fossil record of Protorabinae was summarized. Sinocarabus Hong, 1982 and Obesofemoria Hong, 1982 cannot be attributed to Protorabinae.


[Expression of BRMS1 gene protein in nasal and paranasal sinus carcinomas].
To investigate the role and clinical significance of the expression of BRMS1 gene in development and progression of nasal and paranasal sinus carcinomas. The expression of BRMS1 protein was detected by immunohistochemistry method in the 53 nasal and paranasal sinus carcinomas and 24 nasal polyp tissues and 10 normal mucosa. The expression of BRMS1 was analyzed in nasal and paranasal sinus carcinomas with different clinicopathological parameters. The expression of BRMS1 in normal tissues (90.0%) and nasal polyp tissues (79.2%) was statistically significantly higher than that in nasal and paranasal sinus carcinomas (39.6%) (P < 0.01). There was a positive correlation between BRMS1 expression and TNM staging and lymph node metastasis; but not associated with pathological grade. The loss of BRMS1 expression may be involved in the development and progression of nasal and paranasal sinus carcinomas.


[Increased arterial pressure in negative emotions as one of the functions of the baroreceptor reflex].
An experimental study in conscious rats with intact and denervated sinoaortic baroreceptor zones has been concerned with arterial BP changes in response to negative and positive emotions. Negative emotions are shown to suppress both the cardiochronotropic and the vasomotor components of the baroreceptor reflex. The role of the baroreceptor reflex in the provision of BP changes in response to negative and positive emotions is discussed.


Plasma status of retinol, alpha- and gamma-tocopherols, and main carotenoids to first myocardial infarction: case control and follow-up study.
Epidemiologic studies have suggested that dietary intake and plasma concentrations of antioxidants have an inverse relation with coronary heart disease. To test whether fat-soluble antioxidants can play a role against the occurrence of myocardial infarction (MI), we measured plasma levels of retinol, tocopherols, and individual carotenoids in MI patients. A case-control and follow-up study of patients in the Móstoles area (Madrid, Spain). One hundred six patients (62 after 1 y) and 104 control subjects participated in the study. Blood samples were collected after overnight fast or during the first 24 h of MI onset for biochemical profiles of retinol, alpha- and gamma-tocopherols, and carotenoid by means of a quality-controlled high-performance liquid chromatography. During the acute phase after MI onset, plasma levels of retinol, gamma-tocopherol, and xanthophylls (lutein/zeaxanthin and beta-cryptoxanthin) decreased, whereas alpha-tocopherol, alpha-carotene, beta-carotene, and lycopene showed levels similar to those of control subjects. Logistic regression analysis showed low concentrations of gamma-tocopherol (and retinol) in plasma as the only statistically significant factor associated with MI, after adjusting for traditional risk factors. However, 1 y later, the MI patients showed a general improvement in plasma lipids and fat-soluble antioxidant status, and none of the analytes was associated with MI. The decreased plasma status of retinol, gamma-tocopherol, and xanthophylls during the acute phase of MI normalized the year after the MI event, suggesting that most subjects had followed an overall healthier lifestyle and dietary pattern. The results also raise concerns on the usefulness of these plasma compounds as specific, relevant, and predictive markers in relation to coronary heart disease.


Yolk sac carcinoma: an immunohistochemical and clinicopathologic review.
The records of 14 children with yolk sac carcinoma were reviewed to determine if the production of specific proteins by the tumor could be used to predict the biologic potential of the neoplasm. Several marker proteins were identified by immunohistochemical staining of tissue specimens. The presence or absence of these proteins (periodic acid, Schiff-positive and diastase-resistant globules, alpha-1-antitrypsin, alpha-fetoprotein, beta-subunit of human chorionic gonadotropin and albumin) was of no prognostic significance when survivals free of disease were compared. Six patients underwent retroperitoneal node dissection as part of initial staging (group A), 1 (17 per cent) of whom had retroperitoneal lymphatic metastasis. Eight patients were not subjected to lymphadenectomy initially (group B). Retroperitoneal node dissection did not produce an increase in survival free of disease. Our findings suggest that retroperitoneal node dissection should not be used routinely in all children with yolk sac tumors. Adjunctive chemotherapy has proved extremely effective in salvaging patients in whom metastatic disease develops.


A completely automated sample preparation instrument and consumable device for isolation and purification of nucleic acids.
Molecular diagnostic analysis and life science studies are dependent on the ability to effectively prepare samples for analysis. We report the development of a system that enables robust sample preparation of nucleic acids. To enable completely automated sample preparation, a consumable cartridge and consumable module system were developed to emulate every step of the sample preparation process. This included enzyme and reagent addition, temperature-controlled incubations, noncontact mixing of enzymes and reagents, buffer exchanges, and sample elution. Using this system, completely automated methods were developed for the purification of viral RNA and DNA from plasma and whole blood and of bacterial genomic DNA from water and whole blood. Extracted nucleic acids were detected and quantified using real-time PCR. The data indicate that automated viral DNA extraction was more efficient than sample extractions performed using a manual process, whereas automated total RNA extraction from the same samples was equivalent to controls. Additionally, we found that the process for bacterial genomic DNA extraction from either water or whole blood was equivalent to the manual extraction processes. We conclude the instrument, consumable cartridge, and reagent system enables easy, cost-effective, and robust sample preparation regardless of the experience of the operator.


Editorial: Beyond the Prior Authorization: Multimodal Efforts to Reduce Antipsychotic Medication Prescribing in Foster Care Youth.
When it comes to efforts to reduce the overprescribing of psychiatric medications, the first thing that comes to mind for many clinicians is burdensome prior authorizations or generic letters from insurance companies telling you things you already know. Most psychiatrists and primary care clinicians are well aware of the potential risks associated with drugs such as antipsychotic medications, and many wonder if these intrusions into the doctor-patient relationship go beyond saving money and actually contribute to improved care.


StarMap: a user-friendly workflow for Rosetta-driven molecular structure refinement.
Cryogenic electron microscopy (cryo-EM) data represent density maps of macromolecular systems at atomic or near-atomic resolution. However, building and refining 3D atomic models by using data from cryo-EM maps is not straightforward and requires significant hands-on experience and manual intervention. We recently developed StarMap, an easy-to-use interface between the popular structural display program ChimeraX and Rosetta, a powerful molecular modeling engine. StarMap offers a general approach for refining structural models of biological macromolecules into cryo-EM density maps by combining Monte Carlo sampling with local density-guided optimization, Rosetta-based all-atom refinement and real-space B-factor calculations in a straightforward workflow. StarMap includes options for structural symmetry, local refinements and independent model validation. The overall quality of the refinement and the structure resolution is then assessed via analytical outputs, such as magnification calibration (pixel size calibration) and Fourier shell correlations. Z-scores reported by StarMap provide an easily interpretable indicator of the goodness of fit for each residue and can be plotted to evaluate structural models and improve local residue refinements, as well as to identify flexible regions and potentially functional sites in large macromolecular complexes. The protocol requires general computer skills, without the need for coding expertise, because most parts of the workflow can be operated by clicking tabs within the ChimeraX graphical user interface. Time requirements for the model refinement depend on the size and quality of the input data; however, this step can typically be completed within 1 d. The analytical parts of the workflow are completed within minutes.


Nuclear DNA content variation and evolution in liverworts.
Across embryophytes there is a significant range in DNA content, both in regards to genome size (total DNA in an unreduced chromosome complement) and degree of endoreduplication (when DNA replication not followed by division resulting in various ploidy levels within the same individual). However, there is little information available on DNA content evolution in liverworts, the likely sister group to all other living plants. This study seeks to detect a phylogenetic structure in the variation in genome size and degree of endopolyploidy within liverworts. Furthermore, we test the hypothesis that shifts in breeding systems and genome size are correlated, as polyploidy is suggested to be a possible mechanism for the evolution of monoecy in liverworts and could therefore be associated with larger genome sizes. Genome size was determined for 67 liverwort species from 33 families using flow cytometry. Estimates for 48 species and 16 families are new to science. A phylogeny was reconstructed using the plastid gene rbcL. Over all taxa analyzed, there was a considerable range in genome size estimates with 1C-values from 0.27 pg (Jungermannia rubra) to 20.46 pg (Phyllothallia fuegiana). Large genome sizes were also found in the Haplomitriopsida. None of the liverwort species showed evidence of endopolyploidy. Although some taxa may be polyploids, a correlation between shifts in genome size and breeding system is lacking. Importantly, genome size variation in liverworts exhibits strong phylogenetic signal (Pagel's λ=0.99955).


Low-set umbilicus in a pregnant woman with bladder pseudoexstrophy: A case report.
Bladder pseudoexstrophy is a rare form of bladder exstrophy. Bladder exstrophy occurs in 1 in every 30,000 to 50,000 live births. Because bladder pseudoexstrophy is asymptomatic, it may be undiagnosed even in adulthood. A 31-year-old woman with uterus bicornis unicollis and a low-set umbilicus underwent emergency cesarean delivery during the 37th week of pregnancy for chorioamnionitis. Perioperatively, asymptomatic anatomical abnormalities were identified, which included separated rectus abdominis muscles and diastasis of the symphysis pubis. The urinary tract was normal. The patient was diagnosed with bladder pseudoexstrophy. A low-set umbilicus may be a potential marker for the diagnosis of bladder pseudoextrophy.


A Simple Technique for Reconstruction of the Medial Patellofemoral Ligament With Patellar Soft-Tissue Fixation Using Synthetic Suture Tape Internal Bracing.
Recurrent patellar dislocation is most commonly treated with an isolated medial patellofemoral ligament reconstruction using autograft tissue. Harvest and fixation of these grafts have some theoretical disadvantages. With this Technical Note, we aim to describe a simple reconstruction of the medial patellofemoral ligament using high-strength suture tape with a soft-tissue fixation on the patellar side and an interference screw fixation on the femoral side, avoiding some of these possible disadvantages.


Insight into the binding model of new antagonists of kappa receptor using docking and molecular dynamics simulation.
PF-4455242 and its analogues represent a new series of kappa opioid selective antagonists that demonstrate high selectivity and potency. We investigated their binding mode to the κ-receptor via docking and molecular dynamics simulations. The ranking of the predicted binding free energies is consistent with experimental results. Detailed binding free energies between antagonists and individual protein residues were calculated, and key residues involved in binding were identified. Deviation of the active site residues was investigated, and the results show that Gln115, Leu135, Tyr139, Trp287 and Tyr313 deviate greatly from the reference structure. Information obtained from molecular modeling studies will aid in the design of potent kappa receptor antagonists.


Comparative analysis of microbial diversity in Longitarsus flea beetles (Coleoptera: Chrysomelidae).
Herbivorous beetles comprise a significant fraction of eukaryotic biodiversity and their plant-feeding adaptations make them notorious agricultural pests. Despite more than a century of research on their ecology and evolution, we know little about the diversity and function of their symbiotic microbial communities. Recent culture-independent molecular studies have shown that insects possess diverse gut microbial communities that appear critical for their survival. In this study, we combined culture-independent methods and high-throughput sequencing strategies to perform a comparative analysis of Longitarsus flea-beetles microbial community diversity (MCD). This genus of beetle herbivores contains host plant specialists and generalists that feed on a diverse array of toxic plants. Using a deep-sequencing approach, we characterized the MCD of eleven Longitarsus species across the genus, several of which represented independent shifts to the same host plant families. Database comparisons found that Longitarsus-associated microbes came from two habitat types: insect guts and the soil rhizosphere. Statistical clustering of the Longitarsus microbial communities found little correlation with the beetle phylogeny, and uncovered discrepancies between bacterial communities extracted directly from beetles and those from frass. A Principal Coordinates Analysis also found some correspondence between beetle MCD and host plant family. Collectively, our data suggest that environmental factors play a dominant role in shaping Longitarsus MCD and that the root-feeding beetle larvae of these insects are inoculated by soil rhizosphere microbes. Future studies will investigate MCD of select Longitarsus species across their geographic ranges and explore the connection between the soil rhizosphere and the beetle MCD.


Investigation of an F-18 oxytocin receptor selective ligand via PET imaging.
The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vivo via PET imaging using rat and cynomolgus monkey models. PET imaging studies in female Sprague-Dawley rats suggested [F-18]1 reached the brain and accumulated in various regions of the brain, but washed out too rapidly for adequate quantification and localization. In vivo PET imaging studies in a male cynomolgus monkey suggested [F-18]1 had limited brain penetration while specific uptake of radioactivity significantly accumulated within the vasculature of the cerebral ventricles in areas representative of the choroid plexus.


Estimated daily per capita intakes of phenolics and antioxidants from coffee in the Korean diet.
This study evaluated the daily per drinker intakes of total phenolics, total flavonoids, and antioxidants from coffee in the Korean diet. Four types of coffee (instant coffee, decaffeinated instant coffee, roasted coffee, and coffee mix) were selected and analyzed. Based on the Korea National Health and Nutrition Examination Survey in 2012, the daily intakes per coffee drinker were estimated to be 348.6 mg gallic acid equivalents for phenolics, 222.5 mg catechin equivalents for flavonoids, and 370.8 mg vitamin C equivalents (DPPH assay) or 546.7 mg vitamin C equivalents (ABTS assay) for antioxidants. Men had higher intakes of instant coffee and coffee mix, while women had a higher intake of roasted coffee. Regarding age categories, over 58% of the coffee consumers were 30-59 years old. This study revealed that, in Korea, approximately half of the people drank about 1.4 cups of roasted coffee or 2.0 cups of instant coffee every day.


A review and discussion of platelet nitric oxide and nitric oxide synthase: do blood platelets produce nitric oxide from L-arginine or nitrite?
The NO/sGC/cGMP/PKG system is one of the most powerful mechanisms responsible for platelet inhibition. In numerous publications, expression of functional NO synthase (NOS) in human and mouse platelets has been reported. Constitutive and inducible NOS isoforms convert L-arginine to NO and L-citrulline. The importance of this pathway in platelets and in endothelial cells for the regulation of platelet function is discussed since decades. However, there are serious doubts in the literature concerning both expression and functionality of NOS in platelets. In this review, we aim to present and critically evaluate recent data concerning NOS expression and function in platelets, and to especially emphasise potential pitfalls of detection of NOS proteins and measurement of NOS activity. Prevailing analytical problems are probably the main sources of contradictory data on occurrence, activity and function of NOS in platelets. In this review we also address issues of how these problems can be resolved. NO donors including organic nitrites (RONO) and organic nitrate (RONO2) are inhibitors of platelet activation. Endogenous inorganic nitrite (NO2 (-)), the product of NO autoxidation, and exogenous inorganic nitrite are increasingly investigated as NO donors in the circulation. The role of platelets in the generation of NO from nitrite is also discussed.


Screening extremely obese pregnant women for obstructive sleep apnea.
Obesity is prevalent among pregnant women in the United States; obstructive sleep apnea is highly comorbid with obesity and is associated with adverse pregnancy outcomes. Screening for obstructive sleep apnea in pregnant women has remained a challenge because of a lack of validated screening tools. The purpose of this study was to evaluate established obstructive sleep apnea screening tools, a sleepiness scale, and individual component items in a cohort of pregnant women with extreme obesity in mid pregnancy with the use of objective testing to determine obstructive sleep apnea status and to describe the prevalence of obstructive sleep apnea among women with extreme obesity. Adult pregnant subjects, between 24 and 35 weeks gestation, with a body mass index ≥40 kg/m2 at the time of enrollment completed obstructive sleep apnea screening tools (Berlin Questionnaire, American Society of Anesthesiologists checklist, and STOP-BANG questionnaire) and the Epworth Sleepiness Scale; they also underwent physical examination of the neck, mouth, and airway. The published obstructive sleep apnea in pregnancy prediction score was calculated for each subject. Obstructive sleep apnea status for each subject was determined by the results of an overnight, unattended type III home sleep apnea test. Twenty-four percent of pregnant women with extreme obesity had obstructive sleep apnea on home sleep apnea testing in mid pregnancy (Apnea-Hypopnea Index, ≥5 events per hour]. Established obstructive sleep apnea screening tools performed very poorly to screen for obstructive sleep apnea in this cohort. Age, body mass index, neck circumference, frequently witnessed apneas, and highly likely to fall asleep while driving were associated most strongly with obstructive sleep apnea status in this cohort. We found that 24% of pregnant women with body mass index ≥40 kg/m2 between 24 and 35 weeks gestation have obstructive sleep apnea, defined as Apnea-Hypopnea Index ≥5 events per hour on an overnight type III home sleep apnea test. We found the Berlin Questionnaire, American Society of Anesthesiologists checklist, STOP-BANG, obstructive sleep apnea in pregnancy score by Facco et al, and the Epworth Sleepiness Scale were not useful screening tools for obstructive sleep apnea in a cohort of obese pregnant women. However, age, body mass index, neck circumference, frequently witnessed apneas, and likely to fall asleep while driving were associated with obstructive sleep apnea in this cohort. Further studies are needed to adjust the criteria and thresholds within the available screening tools to better predict obstructive sleep apnea in pregnant women with obesity.


Membrane antigens of human bronchial epithelial cells identified by monoclonal antibodies.
Subpopulations of normal bronchial epithelial cells were identified using a series of murine monoclonal antibodies. These antibodies were used to stain intact bronchial epithelial cells in culture by indirect immunofluorescence. LAM 2 reacted with 80%, LAM 6 with 75%, LAM 7 with 60%, and LAM 8 with 5% of these cells. Sections of human bronchial epithelium were also stained with these antibodies by immunoperoxidase methods. LAM 2 was found to bind with 80%, LAM 6 with 65%, LAM 7 with 50%, and LAM 8 with less than 1% of bronchial epithelial cells. LAM 2 stained both columnar epithelial cells and basal cells; LAM 6 stained mainly basal cells and only a small proportion of columnar cells; LAM 7 showed specificity for basal cells; LAM 8 distinctly stained single cells in the basal cell layer. These antibodies were previously shown to react with the surface membrane of human lung carcinomas, ranging from the broad reactivity of LAM 2 with small cell and non-small cell lung cancers to the highly restricted reactivity of LAM 8 with small cell carcinomas of the lung. Thus, membrane antigens have been identified in bronchial epithelial cells by monoclonal antibodies which exhibit a similar range of cellular reactivity in vitro as in vivo. Inasmuch as these antibodies recognize subsets of cells which could not be easily distinguished by morphologic characteristics, these reagents may be useful in classifying bronchial epithelial cells.


The Universal Prescription for Parkinson's Disease: Exercise.
Over the past two decades, aerobic exercise has emerged as a mainstream recommendation to aid in treating Parkinson's disease (PD). Despite the acknowledgement of the benefits of exercise for people with PD (PwPD), frequently, exercise recommendations lack specificity in terms of frequency, intensity and duration. Additionally, conflating physical activity with exercise has contributed to providing vague exercise recommendations to PwPD. Therefore, the beneficial effects of exercise may not be fully realized in PwPD. Data provided by animal studies and select human trials indicate aerobic exercise may facilitate structural and functional changes in the brain. Recently, several large human clinical trials have been completed and collectively support the use of aerobic exercise, specifically high-intensity aerobic exercise, in improving PD motor symptoms. Data from these and other studies provide the basis to include aerobic exercise as an integral component in treating PD. Based on positive clinical findings and trials, it is advised that PwPD perform aerobic exercise in the following dose: 3x/week, 30-40-minute main exercise set, 60-80% of heart rate reserve or 70-85% of heart rate max. In lieu of heart rate, individuals can achieve an intensity of 14-17 on a 20-point RPE scale. Ongoing clinical trials, SPARX3 and CYCLE-II, have potential to further develop patient-specific exercise recommendations through prognostic modeling.


Revision of the genus Scopoides Platnick, 1989 from China, with description of a new genus (Araneae, Gnaphosidae).
The genus Scopoides Platnick, 1989 from China is revised. A new genus, Platnickusgen. nov., is established with the type species Scopoidesxizangensis Hu, 2001, and a new species is described, Platnickusrenisp. nov. Three new combinations are proposed: Allozelotesgyirongensis (Hu, 2001), comb. nov., Platnickuswanglangensis (Yuan, Zhao & Zhang, 2019), comb. nov., and Platnickusxizangensis (Hu, 2001), comb. nov.


Elevated Peak Systolic Velocity and Velocity Ratio from Duplex Ultrasound are Associated with Hemodynamically Significant Lesions in Arteriovenous Access.
Duplex ultrasound (DUS) is reliably used to detect lesions in the peripheral and carotid arterial beds and venous system. Although commonly used in clinical practice, duplex criteria to define lesions in arteriovenous access are not well characterized. This study will define the optimal Doppler-derived peak systolic velocity (PSV) and velocity ratio (VR) to identify >50% lesions in arteriovenous fistulas (AVF) and arteriovenous grafts (AVG). This retrospective analysis includes patients with both DUS and fistulogram within 30 days. DUS-derived PSV and VR were recorded for 3 segments of each access and compared with fistulograms of the same 3 segments of each AV access. Receiver operating characteristic (ROC) was used to determine the optimal DUS criteria for diagnosis of >50% stenosis. Fifty pairs of imaging in 40 patients were available for analysis. Mean PSV and VR for segments with greater than 50% stenosis were significantly greater than those without; mean PSV of 480 cm/sec vs. 297 cm/sec (P < 0.001) and mean VR of 3.81 vs. 2.09 (P < 0.001). The ROC analysis demonstrated an optimal PSV of 404 and VR of 2.2 to diagnose >50% stenosis with area under the curve of 0.825 and 0.821 for PSV and VR, respectively. PSV of 500 had sensitivity (Se) of 0.60, specificity (Sp) of 0.86, positive predictive value (PPV) of 0.72, and negative predictive value (NPV) of 0.78. VR of 3.0 had Se of 0.52, Sp of 0.91, PPV of 0.77, and NPV of 0.75. DUS-derived PSV of 400 cm/sec and VR of 2.25 have good discrimination to predict greater than 50% stenosis in AVFs and AVGs. Given the broad range of velocities in AV accesses, a threshold of PSV greater than 500 cm/sec and VR greater than 3.0, will reliably identify graft-threatening lesions. Se and Sp of PSV 500 are 0.596 and 0.854, respectively. Se and Sp for VR 3.0 are 0.519 and 0.894, respectively.


Health-related quality of life and associated factors among prisoners in Gondar city prison, Northwest Ethiopia: Using structural equation modeling.
Prisoners usually need more comprehensive health and social support than the general population. Due to the growing number of prisoners in Ethiopia and limited access to health service, quality of life is a key concern. Compromised health-related quality of life imposes short and long-term consequences on the prisoners, their families, and the healthcare system. In Ethiopia, there are limited studies that investigate health outcomes and health-related quality of life in this particular population. Therefore, this study aimed to assess the magnitude of health-related quality of life and associated factors among prisoners considering the multidimensional nature of health related quality of life. An institution-based cross-sectional study was conducted on 1,246 prisoners who were enrolled using simple random sampling. The World Health Organization Quality of Life (WHOQoL-BREF-26) and Patient Health Questionnaire (PHQ-9) tools were used to assess the HRQoL and depression among prisoners, respectively. The relationships between exogenous, mediating, and endogenous variables were identified using structural equation modeling. As the mediation of effects were present, then the direct, indirect, and total effects were determined. General fit indices of the final model were acceptable (x2/df = 1.76, p < 0.001, RMSEA = 0.06, TLI = 0.90, CFI = 0.91, and SRMR = 0.06). The mean (standard deviation) score of the overall health related quality of life was 53.25 (15.12). Having an underlying medical condition had negative total effect on health related quality of life while visits in prison had positive total effect. Having income-generating work in prison had only a direct positive effect. Whereas, older age, being married, longer duration of imprisonment, and depression all had only a negative direct effect on one or more domains of quality of life (p<0.05). Inmates in Gondar Prison have very poor and compromised levels of physical and psychological health despite having a modest degree of overall HRQoL. The result of this study is significant for people who work in and research the prison environment because it can assist in recognizing prisoners' health needs and devising treatment procedures that take into consideration physical, psychological, environmental, and social relationship aspects.


Uncovering the shared molecule and mechanism between ulcerative colitis and atherosclerosis: an integrative genomic analysis.
Ulcerative colitis (UC) and atherosclerosis (AS) are closely related. However, the pathologic mechanisms underlying the co-occurrence of UC and AS are not well understood. To reveal the hub molecule and mechanism involved in the co-occurrence of UC and AS. Differentially expressed genes (DEGs) of UC and AS were obtained, and the shared DEGs of UC and AS were explored for biological function. Next, the hub genes were explored using the cytoHubba plugin. The predictive ability of the hub genes was measured by constructing the receiver operating characteristic curve. Analyses of immune infiltration and the single-gene gene set enrichment analysis (GSEA) for the hub genes were further carried out. Identification of 59 DEGs (55 were upregulated and four were downregulated) shared by both UC and AS was performed. Enriched pathways of the shared DEGs were mainly related to immunity and inflammation. Protein tyrosine phosphatase, receptor type, C (PTPRC) was identified as the hub crosstalk gene for the comorbidity of UC and AS. The upregulation of PTPRC was correlated with mast cells resting, T cells CD4 memory resting, macrophages M0, and macrophages M1. Pathways of immune and inflammatory processes, including NF-kappa B, viral protein interaction with cytokine and cytokine receptor, and cytokine-cytokine receptor interaction, were significantly correlated with high expression of PTPRC in UC and AS. At the transcriptional level, our study reveals that imbalanced inflammatory and immune responses are the key pathological mechanisms underlying the comorbidity of UC and AS and that PTPRC is a key biomarker for the comorbidity of UC and AS.


[Parasites as a cause of urticaria. Helminths and protozoa as triggers of hives?].
Urticaria is one of the most prevalent disorders in dermatological practice. The disease can be incapacitating. There are clear pathophysiological and epidemiological hints that helminths and protozoa are rare but treatable causes of acute and chronic urticaria. Doctors and patients are often not aware that parasitic diseases are increasingly common even in industrialized countries due to a steep rise in migration and international travel. This review presents the most important parasitic causes of urticaria and provides relevant details regarding personal history, clinical presentation, diagnosis and therapy.


Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A.
The posttranscriptional mechanisms that control the cycling of circadian clock protein levels are not known. Here we demonstrate a role for protein phosphatase 2A (PP2A) in the cyclic expression of the PER protein. PP2A regulatory subunits TWS and WDB target PER and stabilize it in S2 cells. In adult fly heads, expression of tws cycles robustly under control of the circadian clock. Hypomorphic tws mutants show delayed accumulation of PER, while overexpression of tws in clock neurons produces shorter, weaker rhythms. Reduction of PP2A activity reduces PER expression in central clock neurons and results in long periods and arrhythmia. In addition, overexpression of the PP2A catalytic subunit results in loss of behavioral rhythms and constitutive nuclear expression of PER. PP2A also affects PER phosphorylation in vitro and in vivo. We propose that the posttranslational mechanisms that drive cycling of PER require the rhythmic expression of PP2A.


VWF release and platelet aggregation in human melanoma after perfusion with TNF alpha.
Twenty-nine stage IIIA/B melanoma patients treated by isolated limb perfusion (ILP) with a high dose of recombinant human tumour necrosis factor alpha (rHuTNF alpha), interferon gamma (IFN gamma), and melphalan were histologically documented with emphasis on therapy-induced changes of the tumour vasculature. Sequential biopsies were taken at various intervals before and after the treatment to compare the morphological change. In order to visualize microvascular changes, immunostaining was performed for von Willebrand factor (VWF), type IV collagen, alpha-smooth muscle actin, endothelial antigen PAL-E, tissue factor, CD41 (thrombocyte marker), and fibrin. In biopsies prior to perfusion, necrosis, haemorrhage, and fibrin thrombi were not found. Within 3 h following triple combination therapy, a change in the distribution of VWF staining occurred, from a discrete endothelial pattern in the untreated lesions to a fuzzy perivascular and subepidermal pattern in the treated lesions. Within 24 h, this was accompanied by intravascular thrombocyte aggregation and erythrostasis, in the absence of tissue factor and fibrin deposits. These findings indicate that the thrombocyte aggregation observed is not caused by local procoagulant activity, but is rather the result of the therapy-associated vascular damage or haemostasis. Although it is difficult to derive the dynamics of this process from static images, we assume that TNF alpha induced endothelial cell damage, leading to VWF release. Release VWF may play a role in the adhesion between thrombocytes and the damaged endothelium or the denuded subendothelium. As a consequence, the blood flow is impaired, leading to congestion and oedema, compatible with an early stage of haemorrhagic infarction.


Bacterial adherence to extended wear soft contact lenses.
The authors studied the adherence of Pseudomonas aeruginosa and Staphylococcus aureus to extended wear soft contact lenses (EWSCLs) with and without focal deposits using both a radiolabeling technique and electron microscopy. P. aeruginosa showed significant adherence to contact lenses in vitro. In contrast, S. aureus failed to show significant adherence to contact lenses in vitro (i.e., the radioactive uptake was not significantly above background). The extent of adherence of Pseudomonas was proportional to the number of focal deposits on the lenses. Results of electron microscopic examination showed the bacteria to be adherent primarily to large focal deposits (greater than or equal to 150 microns). There was no pseudomonal adherence to the small focal deposits (less than or equal to 50 microns) and little adherence to the areas in between the focal deposits. The authors hypothesize that worn lenses, especially those with large focal deposits, serve as a vehicle for the transport of P. aeruginosa to the cornea. This hypothesis could be a partial explanation for the high incidence of keratitis caused by P. aeruginosa in EWSCL patients.


Mussel-inspired polysaccharide-based sponges for hemostasis and bacteria infected wound healing.
Effective bleeding control and wound protecting from infection play critical roles in the tissue healing process. However, local hemostats are not involved in the whole healing processes to promote the final healing efficiency. Here, a multi-functional mussel-inspired polysaccharide-based sponge with hemostatic, antibacterial and adhesive properties was fabricated via cryopolymerization of oxidized dextran (OD), carboxymethyl chitosan (CC) and polydopamine nanoparticles (PDA-NPs), followed by lyophilization. Combining with the adsorbed thrombin, the sponges yielded a considerably lower amount of blood than the commercially available hemostatic dressings. Benefiting from the high photo-thermal transition efficiency of PDA-NPs, the sponges exhibited excellent antibacterial activity to both gram positive and negative bacteria. Owing to the rapid hemostatic activity and effective infection resistance, the sponges illustrated the significantly acceleratory wound healing efficiency compared with the control group. The thrombin-loaded OD/CC-PDA polysaccharide-based sponge has great potential for future clinical use as wound dressing.


Is surgery the best treatment for sporadic small (≤2 cm) non-functioning pancreatic neuroendocrine tumours? A single centre experience.
There is currently there is substantial controversy regarding the best management of non-functioning pancreatic neuroendocrine tumours ≤2 cm. Retrospective study involving 102 surgically treated patients affected by non-functioning pancreatic neuroendocrine tumours. Patients having small tumours (≤2 cm) (Group A) and those having large tumours (>2 cm) (Group B) were compared regarding demographics, clinical and pathological factors with the aim of evaluating the risk of malignancy and survival times. The small tumours were T3-4 in 11% and G2-3 in 36.6% of cases; lymph node and distant metastases were present in 31% and 8% of the cases, respectively. When small and large tumours were compared, significant differences were found in relation to the presence of symptoms (P = 0.012), tumour status (P > 0.001), grading (P > 0.001) and years lost due to disability (P = 0.002). Multivariate analysis of the factors predicting malignancy and survival times showed that tumour size was related only to grading (P < 0.001). The years of life lost and disability adjusted life years were influenced by age at of diagnosis, the presence of symptoms and years lost due to disability only by grading. Tumour size alone did not seem to be reliable in predicting malignancy because, first, small tumours (≤2 cm) could present lymph node or distant metastases, and could be G2-3 in a non-negligible percentage of cases and second, their risk of malignancy and survival time are similar to large tumours. Additional parameters have to be considered in order to establish the proper management of small tumours, such as age at diagnosis, presence of symptoms and grading.