The mesopelagic anoxic Black Sea as an unexpected habitat for Synechococcus challenges our understanding of global "deep red fluorescence".
The Black Sea is the largest meromictic sea with a reservoir of anoxic water extending from 100 to 1000 m depth. These deeper layers are characterised by a poorly understood fluorescence signal called "deep red fluorescence", a chlorophyll a- (Chl a) like signal found in deep dark oceanic waters. In two cruises, we repeatedly found up to 103 cells ml-1 of picocyanobacteria at 750 m depth in these waters and isolated two phycoerythrin-rich Synechococcus sp. strains (BS55D and BS56D). Tests on BS56D revealed its high adaptability, involving the accumulation of Chl a in anoxic/dark conditions and its capacity to photosynthesise when re-exposed to light. Whole-genome sequencing of the two strains showed the presence of genes that confirms the putative ability of our strains to survive in harsh mesopelagic environments. This discovery provides new evidence to support early speculations associating the "deep red fluorescence" signal to viable picocyanobacteria populations in the deep oxygen-depleted oceans, suggesting a reconsideration of the ecological role of a viable stock of Synechococcus in dark deep waters.


Nonradioactive detection of differentially expressed genes using complex RNA or DNA hybridization probes.
The analysis of differential gene expression has become increasingly important in recent years. Typically, differentially expressed genes are identified in a primary screening procedure, yielding candidate genes whose differential expression has to be verified. We provide a highly sensitive, efficient and nonradioactive differential screening procedure to analyze numerous candidate genes in a single step. This comprises labeling of poly(A)+ RNA of the cell types analyzed with DIG Chem-Link and differential hybridization to the candidate genes fixed on dot blots. DIG Chem-Link allows, to our knowledge, for the first time efficient and direct nonradioactive labeling of RNA in vitro. Advantages of this method include extremely short exposure times and the feasibility to re-use the probes after prolonged storage. Using this procedure, we isolated several genes that are differentially expressed in maturing Langerhans cells.


Acute serous and hemorrhagic choroidal effusion associated with topical dorzolamide therapy.
To report a case of acute onset unilateral hemorrhagic and serous choroidal effusion associated with dorzolamide administration and antiplatelet use that recurred in a patient who experienced a dorzolamide-induced choroidal effusion ten years prior to presentation. A 78-year-old male with a history of POAG in both eyes presented with sudden onset decreased vision and flashes of light in the left eye two days after escalating from timolol maleate 0.5% twice daily in both eyes to fixed combination dorzolamide-timolol 22.3-6.8 mg/mL twice daily in both eyes. Systemic medication included daily aspirin 81 mg for primary prevention of cardiovascular disease. Dilated fundus examination and B-scan ultrasound of the left eye revealed a hemorrhagic choroidal effusion in the nasal retinal periphery and low lying serous choroidal effusion in the temporal periphery. Complete resolution of the choroidal detachment was achieved in four days following prompt cessation of dorzolamide, and treatment with topical prednisolone acetate 1% four times daily and atropine 1% two times daily. Topical dorzolamide may induce an idiosyncratic reaction leading to serous and hemorrhagic choroidal effusion, which can be exacerbated by antiplatelet use. Prompt recognition and management of drug-induced choroidal effusion can lead to improved visual outcomes and prevent long-term sequelae.


Urinary lead levels among farmers in non-polluted areas in Japan.
Urine samples, 1163 in total, were collected in the winters of 1982 and 1983 from 132 male farmers and 1031 female farmers in 6 non-polluted areas in various parts of Japan. The urine samples were analyzed for lead concentration by means of flameless atomic absorption spectrophotometry after wet digestion followed by solvent extraction in the presence of sodium diethyldithiocarbamate. The lead concentration in urine (Pb-U; adjusted for a specific gravity of 1.016) distributed log-normally with a geometric mean (GM) of 1.81 micrograms/l (GSD = 1.99) for men (n = 132) and 2.08 micrograms/l (1.95) for women (n = 1031). No age-related changes in Pb-U were observed in either sex in the 30-79 year age range, and there was no sex-related difference in Pb-U. Analyses of female smokers together with area- and age-matched non-smokers suggested that the smoking habit would cause a significant increase in Pb-U. Comparison of the present findings with Pb-U levels published in the literature disclosed that the current Pb-levels among the Japanese population appear to be lower than the levels in Western Europe and the U.S.A.


One-year postoperative skeletal stability of 3D planned bimaxillary osteotomies: maxilla-first versus mandible-first surgery.
Orthognathic surgery is carried out to correct jaw deformities and to improve facial aesthetics. However, controversy surrounds whether the maxilla- or mandible-first surgery approach leads to better surgical outcomes. In our previous study, we have shown that in most instances, the maxilla-first surgical approach yielded closer concordance with the 3D virtual treatment plan than a mandibular-first procedure. However, the post-operative stability of each approach has not been investigated. Therefore, this one-year follow-up study was set-up and investigated the postoperative skeletal stability of the 3D planned translations and rotations after either the maxilla- or mandible-first surgery. In total, 106 patients who underwent bimaxillary surgery and had an individualized 3D virtual operation plans, received either maxilla-first (n = 53) or mandible-first (n = 53) surgery. 3D printed interocclusal splints were used during surgery to position the jaws. One year postoperatively a cone-beam computed tomography (CBCT) scan was made to assess the effects using the OrthoGnathicAnalyser. The mean sagittal, vertical and transverse relapse was less than 1.8 mm and no significant differences were found in relapse between the maxilla-first or the mandibular-first surgical procedure. Overall, this study shows that 3D virtual planning in combination with an optimised sequencing of osteotomies provides predictable long-term results in bimaxillary surgery.


The conformation-independent QSPR approach for predicting the oxidation rate constant of water micropollutants.
In advanced water treatment processes, the degradation efficiency of contaminants depends on the reactivity of the hydroxyl radical toward a target micropollutant. The present study predicts the hydroxyl radical rate constant in water (k OH) for 118 emerging micropollutants, by means of quantitative structure-property relationships (QSPR). The conformation-independent QSPR approach is employed, together with a large number of 15,251 molecular descriptors derived with the PaDEL, Epi Suite, and Mold2 freewares. The best multivariable linear regression (MLR) models are found with the replacement method variable subset selection technique. The proposed five-descriptor model has the following statistics for the training set: [Formula: see text], RMS train = 0.21, while for the test set is [Formula: see text], RMS test = 0.11. This QSPR serves as a rational guide for predicting oxidation processes of micropollutants.


Cleft Palate Repair in Robin Sequence following Mandibular Distraction Osteogenesis Compared to Tongue-Lip Adhesion.
To evaluate the timing and safety of cleft palate (CP) repair in patients with Robin sequence (RS) treated with mandibular distraction osteogenesis (MDO) or tongue-lip adhesion (TLA) for airway obstruction. Retrospective cohort study. Tertiary Pediatric Hospital during 2004-2020. 148 patients with RS underwent MDO, 66 met inclusion by having MDO and followed by palatoplasty. 26 patients with RS underwent TLA, 14 met inclusion by having TLA and followed by palatoplasty. Patient characteristics, hospital/operative details, postoperative complications, and polysomnographic (PSG) data were compared. Groups were well-matched except more patients with syndromes underwent MDO (N = 27, 41%, P ≤ .002). In the MDO and TLA cohorts, mean CP repair age was 12.8 ± 1.9 months and 14.6 ± 1.6 months, respectively (P ≤ .002). Despite the earlier CP repair in the MDO group, there were no differences in peri-operative complication rates after palatoplasty in either group. All sleep respiratory parameters improved after MDO/TLA prior to palatoplasty P ≤ .050. All PSG parameters remained significantly improved after palatoplasty compared to preoperative values, P ≤ .043. Obstructive apnea hypopnea index and Oxygen saturation nadir further improved after palatoplasty within the MDO group, P ≤ .050, while no changes in the TLA group, P ≥ .500. MDO was associated with earlier age at palatoplasty than TLA with a similar perioperative risk profile. In those patients with pre- and post-palatoplasty PSG data, palatoplasty was not associated with a deterioration in PSG parameters, and in fact in the MDO group, PSG data improved.


The prevalence of antibiotic resistance genes in Bacteroides fragilis group strains isolated in different European countries.
From the 2008-2009 European Bacteroides antibiotic resistance survey, we selected 161 strains for detection of antibiotic resistance genes (cepA, cfxA, cfiA, nim, ermB, ermF, ermG, linA, mefA, msrSA, tetM, tetQ, tetX, tetX1, tet36 and bexA). To facilitate the throughput, the genes were detected by Real-Time PCR. The presence of the genes was correlated with the known MIC data of the strains for the appropriate antibiotics. For the β-lactams, the cepA gene was found in 70.8% of the tested strains (all resistant to ampicillin), but its presence did not correlate with the ampicillin MIC values. The cepA gene occurred at different frequencies among Bacteroides fragilis and non-fragilis Bacteroides strains. The cfxA gene was not a major factor in determining cefoxitin resistance and it was found with higher prevalence in non-fragilis Bacteroides strains than in B. fragilis. Among the five possible clindamycin resistance genes, ermF was the most common and had the highest effect on clindamycin resistance after linA. The ermG-mefA-msrSA combination was found in a set of strains and their linked occurrence implied that they were harbored by the conjugative transposon CTnGERM1. All strains tested were susceptible to metronidazole and none of them harbored nim genes. TetQ was prevalent among both the B. fragilis and non-fragilis Bacteroides strains (78.9 and 84.8%, respectively) and no gene could be clearly linked to tigecycline resistance other than tetQ. BexA, which codes for the fluoroquinolone efflux pump, was found in 7.5% of strains and occurred at different frequencies among B. fragilis and non-fragilis Bacteroides strains, but was represented only in a minor proportion of moxifloxacin-resistant strains.


Etiologic agents and outcome determinants of community-acquired pneumonia in urban children: a hospital-based study.
Etiologic clues and prognostic indicators of community-acquired pneumonia (CAP) were sought in a 30-month study of under-5 admissions for acute lower respiratory infections (ALRIs). Investigative tools included blood culture, hemogram, immunofluorescence and serology. Associations of variables were tested using standard statistical tools. Of 419 ALRI, 323 (77%) had pneumonia, 234 (72.4%) bronchopneumonia, 66 (20.4%) lobar pneumonia and 23 (7.1%) both. More than 70% had poor parental socioeconomic parameters, 56.8% were overtly malnourished, 37.8% lived in overcrowded homes and 16.7% had been potentially exposed to wood smoke. Despite preconsultation antimicrobial use in 35.6%, 59 (28.8%) of 205 blood cultures proved positive; Staphylococcus aureus accounted for 22 (37.3%), Klebsiella species nine (15.3%) and Streptococcus pneumoniae three (5.1%). Ninety-two viruses were identified in 61 (50%) of 122 analyses. Respiratory syncytial virus (RSV) accounted for 28 (30.4%), parainfluenza virus type 3 (PIV-3) for 18 (19.5%) and influenza type-A (flu-A) 16 (17.3%). Twenty (16.4%) had > or = 2 viruses, while 40% of bacteremic cases with positive viral identification(s) had PIV-3. Pathogen detection was neither associated with hematologic parameters nor the final respiratory diagnosis. There were 35 (10.8%) deaths. Mortality was associated with maternal illiteracy (p = 0.045), wood smoke exposure (p = 0.006), preconsultation antimicrobial use (p = 0.04), malnutrition (p = 0.0003), bacteremia (p = 0.006) and polymorphonuclear leucocytosis (p = 0.023/0.013). RSV, PIV-3, flu-A, S. aureus and Klebsiella species constitute the major pathogens of pediatric CAP in urban Nigeria, while malnutrition, wood smoke exposure and bacteremia are strong risk factors of mortality. The poor prognostic import of antimicrobial abuse, vis-a-vis the apparent selection of necrotizing pathogens, are compelling indications for a reappraisal of current regional antimicrobial policies and exploring newer frontiers of disease control, including vaccine prevention.


An ACAP1 coat complex acting in endocytic recycling.
A key function of coat proteins is the sorting of protein cargoes into intracellular transport pathways. For many years, however, it has been unclear whether this role of coat proteins would apply to pathways of endocytic recycling. This issue has been clarified in recent years through the identification of multiple coat complexes acting in the recycling pathways. Leading this charge have been studies on a coat complex defined by ACAP1 (adenosine diphosphate ribosylation factor GTPase-activating proteins with Coiled-coil, Ankryin repeat and PH domains 1), which acts in the sorting of cargoes at the recycling endosome for their return to the plasma membrane. This chapter describes the methods used to characterize this role of ACAP1.


Huge bilateral pulmonary and pleural metastasis from intracranial meningioma: a case report and review of the literature.
A case of recurrent meningioma with atypical features and extracranial metastases is reported. A 34-year-old female was operated in 1996, 2000, and 2002, and frontal parasagittal meningioma was extirpated. Histological diagnoses of all the resected tumors were meningotheliomatous meningioma, WHO Grade I. However, 2 years later, the tumor recurred in the frontal scalp and was removed again totally. Histological diagnosis was reported as an atypical meningioma; meningotheliomatous type; WHO Grade II. She received radiation therapy. But the tumor had metastasized to the lung and pleura. Transthoracic tru-cut biopsy was performed from large mass of the left lung. Cytopathology was consistent with malignant meningioma, metastasis from the patient's known intracranial meningioma. Ki-67 staining index at the primary and metastatic sites of the present cases were 7 and 5%, respectively. We reviewed and discussed the histopathological features and mechanisms of metastasizing meningioma.


Gasless transaxillary robotic versus endoscopic thyroidectomy: exploring the frontiers of scarless thyroidectomy through a preliminary comparison study.
Robot-assisted thyroidectomy has been associated with lengthy operative times due to fussy robot preparation and docking maneuvers. The authors propose an endoscopic transaxillary approach using a novel platform, comparing its results with those of the former approach. Eight patients (6 females and 2 males; mean age, 38.8 years) with a favorable body habitus (mean body mass index [BMI], 23.4 kg/m(2)) underwent robot-assisted thyroidectomy through a gasless transaxillary approach using the da Vinci S system. Another four female patients (mean age, 31 years) underwent an endoscopic procedure. The patients' demographic data, operative time, complications, hospital stay, postoperative visual analog pain score (VAPS), and costs were compared. Three lobectomies, two near-total thyroidectomies, two total thyroidectomies, and one total thyroidectomy with lateral lymph node dissection were performed in the robotic group. Two lobectomies and two near total thyroidectomies were performed in the endoscopic group. The mean diameter of the largest nodule in the robotic series was 26.5 mm compared with 42.5 mm in the endoscopic group. The mean total operative time was 211 min for the robotic series compared with 160 min for the endoscopic series. There was one temporary recurrent laryngeal nerve paralysis in the robotic group. Two patients in the robotic group exhibited transient symptomatic hypocalcemia compared with one patient in the endoscopic group. Hypoesthesia in the flap dissection area was experienced by three patients in the robotic group and two patients of the endoscopic group. The mean hospital stay was 1.5 days (range 1-3 days) in both groups. The postoperative VAPS also was similar in the two groups (3.1 vs 2.8). The cost was significantly less for the endoscopic approach. The preliminary comparison in this study shows that both approaches are safe and feasible, with similar results. They also afford an excellent view of the critical neck anatomy that allows precise tissue handling and dissection. However, the endoscopic approach results in a significantly faster and more convenient thyroidectomy.


Effect of uranyl nitrate on enzymes of carbohydrate metabolism and brush border membrane in different kidney tissues.
Uranium, the heaviest of the naturally occurring elements is widely present as environmental contaminant from natural deposits, industrial emissions and most importantly from modern weapons. Histopathological examinations revealed that uranyl nitrate (UN) exposure caused severe damage to pars recta of renal proximal tubule. However, biochemical events involved in cellular response to renal injury are not completely elucidated. We hypothesized that UN exposure would severely damage kidney tissues and alter their metabolic functions. Rats were treated with a single nephrotoxic dose of UN (0.5mg/kg body weight) i.p. After 5d, effect of UN was studied on the activities of various enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in different kidney tissues. Activity of lactate dehydrogenase increased whereas activities of isocitrate, succinate and malate dehydrogenases, glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly decreased by UN exposure. Activity of glucose-6-phosphate dehydrogenase decreased whereas that of NADP-malic enzyme increased. The activities of BBM enzymes were significantly lowered and after dissociation from BBM excreted in urine. Lipid peroxidation and the activities of superoxide dismutase and glutathione peroxidase increased whereas catalase activity decreased by UN. UN treatment caused specific alterations in the activities of metabolic and membrane enzymes and perturbed antioxidant defenses.


AKI persistence at 48 h predicts mortality in patients with acute on chronic liver failure.
Management of acute kidney injury (AKI) in cirrhotics has undergone a paradigm change. We evaluated the impact of AKI persistence at 48 h on outcome in patients with acute on chronic liver failure (ACLF). Consecutive patients with ACLF (n = 373) were prospectively followed. AKI was defined as increase in serum creatinine of 0.3 mg/dl or 1.5- to 2-fold from baseline. Persistent AKI was defined as nonresponsive AKI at 48 h with respect to admission serum creatinine. AKI at admission was present in 177 (47.5 %) patients. At 48 h, 73 % patients had persistent AKI and 27 % had responsive AKI. High Model for End-Stage Liver Disease (MELD) (≥26) [p, odds ratio (OR), 95 % confidence interval (CI)] [<0.001, 3.65 (2.1-3.67)], systemic inflammatory response syndrome (SIRS) [0.03, 1.6 (1.02-21.6)], and age (≥42 years) [0.03, 1.84 (1.19-2.85)] were significant predictors of AKI persistence. Persistent AKI was associated with significantly higher in-hospital mortality [p < 0.001, hazard ratio (HR) 1.7, 95 % CI 1.32-2.27]. We further found a lower cutoff for serum creatinine of 1.14 mg/dl at 48 h with better sensitivity of 61 %, specificity of 61 %, and likelihood ratio (LR+) of 1.6, correctly classifying 61 %, as against the conventional cutoff of 1.5 mg/dl with sensitivity of 37 %, specificity of 57 %, and LR+ of 3.3, correctly classifying 56 %. This new cutoff also predicted mortality with higher odds (OR 2.4, 95 % CI 1.3-4.8) as compared with the conventional cutoff (OR 2.1, 95 % CI 1.1-4.1). AKI persistence at 48 h predicts mortality better than serum creatinine of 1.5 mg/dl in patients with ACLF. Serum creatinine value of 1.14 mg/dl and smaller increases in its value should be considered for risk stratification of patients with ACLF for interventional strategies.


Acoustic pre-stimulation modulates startle and postural reactions during sudden release of standing support surface in aging.
Falls contribute to injuries and reduced level of physical activity in older adults. During falls, the abrupt sensation of moving downward triggers a startle-like reaction that may interfere with protective response movements necessary to maintain balance. Startle reaction could be dampened by sensory pre-stimulation delivered immediately before a startling stimulus. This study investigated the neuromodulatory effects of pre-stimulation on postural/startle responses to drop perturbations of the standing support surface in relation to age. Ten younger and 10 older adults stood quietly on an elevated computer-controlled moveable platform. At an unpredictable time, participants were dropped vertically to elicit a startle-like response. Reactive drop perturbation trials without a pre-stimulus (control) were alternated with trials with acoustic pre-stimulus tone (PSI). A two-way mixed design analysis of variance comparing condition (control vs. PSI) X group (younger vs. older) was performed to analyze changes in muscle activation patterns, ground reaction force, and joint angular displacements. Compared to younger adults, older adults showed lower neck muscle electromyography amplitude reduction rate and incidence of response. Peak muscle activation in neck, upper arm, and hamstring muscles were reduced during PSI trials compared to control trials in both groups (p < 0.05). In addition, knee and hip joint flexion prior to ground contact was reduced in PSI trials compared to control (p < 0.05). During post-landing balance recovery, increased knee and hip flexion displacement and time to peak impact force were observed in PSI trials compared to control condition (p < 0.05). PSI reduced startle-induced muscle activation at proximal body segments and likely decreased joint flexion during abrupt downward vertical displacement perturbations of the body. Older adults retained the ability to modulate startle and postural responses but their neuromodulatory capacity was reduced compared with younger adults. Further research on the potential of applying PSI as a possible therapeutic tool to reduce the risk of fall-related injury is needed.


Development and internal validation of prediction models for persistence of self-reported orofacial pain in the follow-up of patients with myofascial pain.
To identify predictors in patient profiles, and to develop, internally validate, and calibrate prediction models for the persistence of self-reported orofacial pain at the 6-month and 12-month follow-up in patients with myofascial pain. A cohort of 63 adult patients with moderate to severe chronic myofascial pain was included. Patient and disease characteristics at baseline were recorded as potential predictors. Patients` presence or absence of improvement of orofacial pain at follow-up was considered the outcome. Binary logistic regression analyses were used to develop the models. The performance and clinical values of the models were determined. Forty-three percent and 30% of the patients had persistence of orofacial pain at 6-month and 12-month follow-up, respectively. Pain elsewhere, depression, parafunctional activities, and mandibular function impairment (MFI) were significantly associated with persistence of the pain at 6-month follow-up, whereas depression, parafunctional activities, and MFI were significantly associated with persistence of the pain at 12-month follow-up. Both of the models showed good calibration and discrimination, with shrunken area under the curve (AUC) values of 0.73 and 0.76, respectively. The clinical added predictive values for ruling in the risk of the persistence were 0.30 and 0.31, respectively, and those for ruling it out were 0.25 and 0.20, respectively. Potential predictors for prediction of the persistence of self-reported orofacial pain at follow-up were identified. The calibration, discrimination, and clinical values of the models were acceptable. The models may assist clinicians in decision-making regarding the improvement of orofacial pain of individual patients during follow-up in clinical settings.


Single-crystal nanorings formed by epitaxial self-coiling of polar nanobelts.
Freestanding single-crystal complete nanorings of zinc oxide were formed via a spontaneous self-coiling process during the growth of polar nanobelts. The nanoring appeared to be initiated by circular folding of a nanobelt, caused by long-range electrostatic interaction. Coaxial and uniradial loop-by-loop winding of the nanobelt formed a complete ring. Short-range chemical bonding among the loops resulted in a single-crystal structure. The self-coiling is likely to be driven by minimizing the energy contributed by polar charges, surface area, and elastic deformation. Zinc oxide nanorings formed by self-coiling of nanobelts may be useful for investigating polar surface-induced growth processes, fundamental physics phenomena, and nanoscale devices.


The progressive breakdown of number processing and calculation ability: a case study.
We examined a retired Army General with Progressive Dementia whose initial major presenting complaint was dyscalculia. Our examinations revealed an orderly dissolution of calculation ability with differing dissociations in calculation ability apparent at progressive stages of cognitive decline. For example, we found that number reading and writing errors were qualitatively different from calculation errors. Numerosity knowledge and magnitude comparisons can remain intact even when other arithmetic knowledge and calculation abilities were grossly impaired. His decline in calculation abilities was first demonstrated on more complex problems (e.g., multiplication) and only in later stages on simpler (e.g., addition) problems. The patient was aware that aspects of his performance were impaired, but he was unable to state why--a dissociation between declarative and procedural knowledge.


Galectin-1 upregulates glucose transporter-1 expression level via protein kinase C, phosphoinositol-3 kinase, and mammalian target of rapamycin pathways in mouse embryonic stem cells.
Although galectin-1 is expressed in various stem cells, our understanding of the functional roles of galectin-1 in embryonic stem (ES) cells is still fragmentary and incomplete. Thus, this study investigated the effect of galectin-1 on the 2-deoxyglucose (2-DG) uptake and its related signal cascades. Galectin-1 significantly increased 2-deoxyglucose uptake time- and dose-dependently. In addition, galectin-1-induced 2-deoxyglucose uptake was inhibited by glucose transporter-1 siRNA. Moreover, galectin-1 increased glucose transporter-1 mRNA and protein expression levels, which were inhibited by a disruption in transcription by actinomycin D and translation by the cycloheximide. Subsequently, the galectin-1-induced 2-deoxyglucose uptake was attenuated by these inhibitors. In investigation of signal transduction involved in this process, galectin-1 increased intracellular Ca2+ concentration and the protein kinase C activation, which induced extracellular signal regulated kinase1/2 phosphorylation. On the other hand, phosphoinositol-3-kinase/Akt activated by galectin-1 was not involved in extracellular signal regulated kinase1/2 pathway. Moreover, mammalian target of rapamycin signal pathway was stimulated in response to galectin-1. Finally, galectin-1-induced increase of glucose transporter-1 expression and 2-deoxyglucose uptake were inhibited by blocking of Ca2+/protein kinase C/extracellular signal regulated kinase1/2, phosphoinositol-3-kinase/Akt, and mammalian target of rapamycin pathways. In conclusion, galectin-1 upregulates glucose uptake through Ca2+/protein kinase C/extracellular signal regulated kinase1/2, phosphoinositol-3-kinase/Akt, and mammalian target of rapamycin pathways in mouse ES cells.


Pathogenesis and prognosis of hepatocellular carcinoma at the cellular and molecular levels.
Different approaches predict the outcome for patients with hepatocellular carcinoma (HCC). The expression of biliary-hepatic progenitor cell markers generally correlates with poor prognosis. This article focuses on the pathogenesis of HCC, how differentiation or dedifferentiation leads to a phenotype switch, and heterogeneity in the same tumor. A tumor cell decides its fate based on a complex interplay of signaling pathways. Interaction with the microenvironment decides whether it will invade, proliferate, or enter survival mode. Several signaling pathways contribute to stemness features, reflecting a small chemoresistant subpopulation of the tumor that expresses biliary-hepatic progenitor cell markers.


High-pressure selectivity studies--a simple route to a homochiral wistarin precursor.
The cycloaddition of spirobutenolide 3 to the homochiral cyclopentadiene 1 at 6.5 kbar leads exclusively to cycloadduct 5. Subsequent Diels-Alder or Michael additions again favour the cyclohexenone double bond; this perfect chemo- regio- and face selectivity was employed for a short and efficient approach to the wistarin framework.


Hemorrhagic Fever Virus Budding Studies.
Independent expression of the VP40 or Z matrix proteins of filoviruses (marburgviruses and ebolaviruses) and arenaviruses (Lassa fever and Junín), respectively, gives rise to the production and release of virus-like particles (VLPs) that are morphologically identical to infectious virions. We can detect and quantify VLP production and egress in mammalian cells by transient transfection, SDS-PAGE, Western blotting, and live cell imaging techniques such as total internal reflection fluorescence (TIRF) microscopy. Since the VLP budding assay accurately mimics budding of infectious virus, this BSL-2 assay is safe and useful for the interrogation of both viral and host determinants required for budding and can be used as an initial screen to identify and validate small molecule inhibitors of virus release and spread.


Diagnostic techniques for COVID-19 and new developments.
COVID-19 pandemic is a serious global health issue today due to the rapid human to human transmission of SARS-CoV-2, a new type of coronavirus that causes fatal pneumonia. SARS -CoV-2 has a faster rate of transmission than other coronaviruses such as SARS and MERS and until now there are no approved specific drugs or vaccines for treatment. Thus, early diagnosis is crucial to prevent the extensive spread of the disease. The reverse transcription-polymerase chain reaction (RT-PCR) is the most routinely used method until now to detect SARS-CoV-2 infections. However, several other faster and accurate assays are being developed for the diagnosis of COVID-19 aiming to control the spread of infection through the identification of patients and immediate isolation. In this review, we will discuss the various detection methods of the SARS-CoV-2 virus including the recent developments in immunological assays, amplification techniques as well as biosensors.


A dual-route account for access to grammatical gender: evidence from functional MRI.
Research investigating the neural correlates of grammatical gender processing has provided contradictory evidence with respect to activation in the left inferior frontal gyrus (IFG). A possible account for these discrepancies is a dual-route model proposing explicit vs implicit access to the gender information. In this event-related fMRI experiment, we investigated this issue by taking into account different processing strategies reported by the subjects. The participants performed two tasks, a gender judgement of German nouns and a non-lexical baseline task (spacing of consonant letter strings). Depending on the reported strategy (silent production of the definite determiner or direct access to the gender information), different patterns of activation in the left IFG were observed. Direct access to gender information yielded activation in the inferior tip of BA 44, whereas the verbalisation strategy elicited activation in the superior portion of BA 44, BA 45/47, and the fronto-median wall. These results speak in favour of a dual-route account for modelling the access to grammatical gender information during language comprehension.


Semen quality remains stable during the chronic phase of spinal cord injury: a longitudinal study.
In a longitudinal study we examined changes in semen quality with time during the chronic phase of spinal cord injury. Included in this study were 87 men with spinal cord injury who underwent 2 or more semen retrieval procedures with a minimum of 3 years between the first and last procedures. Patients were selected from our database of 500 with spinal cord injury who were volunteers enrolled in the Male Fertility Research Program of the Miami Project to Cure Paralysis from January 1, 1991 through April 31, 2009. Semen was collected by masturbation, penile vibratory stimulation or electroejaculation. Semen analysis was done according to WHO criteria. We used a statistical generalized linear mixed model to analyze changes in sperm concentration, total sperm count, total motile sperm count and sperm motility with time. Mean patient age was 30.1 years (range 16 to 48) and mean time after injury at the initial sperm retrieval procedure was 7.1 years (range 1 to 26). Sperm concentration decreased slightly with time but all other parameters were unchanged, including total sperm count, indicating a stable, null pattern in measures with time. Semen quality does not show clinically significant progressive changes during years after injury in men with spinal cord injury. This information is relevant for urologists who counsel these patients on family planning. Also, routine sperm freezing for fertility preservation is not indicated in this patient population.


Cost and outcomes of assessing patients with chest pain in an Australian emergency department.
We sought to characterise the demographics, length of admission, final diagnoses, long-term outcome and costs associated with the population who presented to an Australian emergency department (ED) with symptoms of possible acute coronary syndrome (ACS). Prospectively collected data on ED patients presenting with suspected ACS between November 2008 and February 2011 was used, including data on presentation and at 30 days after presentation. Information on patient disposition, length of stay and costs incurred was extracted from hospital administration records. Primary outcomes were mean and median cost and length of hospital stay. Secondary outcomes were diagnosis of ACS, other cardiovascular conditions or non-cardiovascular conditions within 30 days of presentation. An ACS was diagnosed in 103 (11.1%) of the 926 patients recruited. 193 patients (20.8%) were diagnosed with other cardiovascular-related conditions and 622 patients (67.2%) had non-cardiac-related chest pain. ACS events occurred in 0 and 11 (1.9%) of the low-risk and intermediate-risk groups, respectively. Ninety-two (28.0%) of the 329 high-risk patients had an ACS event. Patients with a proven ACS, high-grade atrioventricular block, pulmonary embolism and other respiratory conditions had the longest length of stay. The mean cost was highest in the ACS group ($13 509; 95% CI, $11 794-$15 223) followed by other cardiovascular conditions ($7283; 95% CI, $6152-$8415) and non-cardiovascular conditions ($3331; 95% CI, $2976-$3685). Most ED patients with symptoms of possible ACS do not have a cardiac cause for their presentation. The current guideline-based process of assessment is lengthy, costly and consumes significant resources. Investigation of strategies to shorten this process or reduce the need for objective cardiac testing in patients at intermediate risk according to the National Heart Foundation and Cardiac Society of Australia and New Zealand guideline is required.


A ten-year numerical hindcast of hydrodynamics and sediment dynamics in the Loire Estuary.
A numerical hindcast of the macrotidal Loire Estuary (France) has been generated to provide a long-term dataset (2008-2018) of estuarine hydrodynamics, temperature, salinity, and sediment dynamics. This hindcast is based on simulations coupling water motion, wave and mixed sediment models, forced with realistic conditions and extensively validated in the salinity gradient and turbidity maximum areas. These data represent extremely valuable information for diverse scientific communities, providing (i) environmental parameters for ecosystemic studies along the Loire River-sea continuum, (ii) a singular estuarine configuration for inter-comparison of estuarine functioning, and (iii) a ten-year synoptical view of a major estuarine environment of the North Atlantic Ocean.


Presence of inducible DNA repair in Bacillus thuringiensis.
Weigle reactivation of ultraviolet-irradiated luminal diameter 8 bacteriophage was observed after ultraviolet treatment of Bacillus thuringiensis cells. A slight increased frequency of clear plaque mutants was detected among the survivors. The kinetics of induction of the phage reactivation and phage mutagenesis have been determined. The presence of chloramphenicol before and after irradiation abolished the induction of repair and mutagenesis. These experiments suggest that, in spite of the relatively small mutagenic response in bacteriophage progeny, B. thuringiensis has an inducible repair system responsible to the significant Weigle reactivation of irradiated phage.


Relationship Between Obesity and Driving.
Obesity, which has become epidemic throughout many parts of the world, is known to be a risk factor for a range of diseases including hypertension, diabetes, and vascular disease. Based on this review, it also appears that obesity is associated with increased crash risk and increased risk of serious or fatal injury in a crash. The problem is particularly an issue for commercial truck drivers. Data are presented showing the high prevalence of obesity in truck drivers. Inadequate sleep, poor nutrition, lack of exercise, and the sedentary nature of driving all contribute to the risk of obesity. The obesity related condition of obstructive sleep apnea (OSA) is known to increase crash risk. Treatment of this condition has been demonstrated to improve driving performance and to reduce crash risk. Screening truck drivers for obesity related health conditions, such as OSA, would be expected to result in public safety benefits.


Analysis of the cleft lip-nose in the submental-vertical view. Part II. Panel study: which is the most important deformity?
In part I, we presented an anthropometric measurement instrument that uses standardized facial pictures in the submental-vertical view, Adobe Photoshop 7.0, and Scion Software for Windows to determine both form and symmetry of the cleft nose. This instrument was found to be both reliable and universally suitable for comparing results of cleft rhinoplasties. However, the quality of the overall result needs to be based on weights assigned to different measurable parameters/deformities. Therefore, we carried out a panel study to evaluate the relative importance of the different parameters/deformities according to the parents of the patients. A questionnaire with both pictorial and textual representations of 10 distinct nasal cleft deformities was sent twice to the parents of 14 complete unilateral and 14 complete bilateral cleft lip-nose patients. The deformities were rank-ordered by the parents, and the responses were analyzed for intraobserver and interobserver reliabilities. The most important deformity according to both groups was the asymmetric position of the nose within the facial frame. Alar position was also important whereas nostril form was least important. There was fair test reliability for both intraobserver and interobserver rankings. Rankings of the different nasal cleft deformities by the parents of cleft patients are reproducible and, hence, a useful preparatory guide for surgeons.


Does a delay in transfer to a rehabilitation unit for older people affect outcome after fracture of the proximal femur?
To detemine the relationship between delay in transfer to rehabilitation wards and outcome for patients aged over 75 years with fracture of the proximal femur. An observational study in a district general hospital of all patients admitted to hospital aged over 75 years with fracture of the proximal femur over 3 1/2 years. Outcome data collected included the number of patients discharged back to their usual residence and total hospital length of stay related to age, gender, usual residence and delay in transfer to a rehabilitation ward. 58% of 455 patients were transferred to a rehabilitation ward. For those patients who were transferred to a rehabilitation ward only age predicted discharge to a more dependent residence. The relative risk for discharge to a more dependent residence for people aged over 85 years compared to younger people was 1.47 (95% CI 1.15-1.88). Delay in transfer to rehabilitation was associated with a longer total hospital length of stay of 0.64 (95% CI 0.23-1.05) days per day of delay in transfer. Delay in transfer to a rehabilitation ward was associated with a disproportionate increase in total hospital length of stay for patients aged over 75 with fracture of the proximal femur.


In vitro skin corrosion: Human skin model test - A validation study.
The present article is an attempt to validate the in vitro skin corrosion human skin model test as per the OECD test guidelines 431 as an alternative method for in vivo skin corrosion/irritation test. All over India, in vivo skin corrosion/irritation test is commonly used, rather than in vitro skin corrosion models. Hence, the present study was under taken with EpiSkinTM, SNC, Lyon, France to validate this in vitro model. Various corrosive and non corrosive chemicals with their known skin corrosive property were used to validate the study as specified under the guideline (OECD 431). The results obtained in this study were in accordance with the corrosive properties of the respective chemicals.


The mediating role of general self-efficacy in the association between perceived social support and oral health-related quality of life after initial periodontal therapy.
Although initial periodontal therapy can ease some physical and psychological discomforts from periodontitis and improve patients' oral health-related quality of life (OHRQoL), it is also vital to find positive resources from psychological and social aspects to promote the overall OHRQoL. This study aims to explore the associations of perceived social support (PSS) and general self-efficacy with OHRQoL and the mediating role of general self-efficacy in PSS-OHRQoL association after initial periodontal therapy. A prospective case series study was conducted among consecutive outpatients with chronic periodontitis during the period of July 2014-April 2015. A total of 145 eligible patients responded to OHRQoL questionnaire and periodontal examination at baseline. About 4 to 5 weeks after initial periodontal therapy, 120 patients completed the second OHRQoL measurement and periodontal examination, along with PSS and general self-efficacy measurement. The Wilcoxon matched-pairs signed-rank test was used to determine the difference between baseline and post-treatment OHRQoL scores and periodontal parameters. Hierarchical linear regression analysis was used to explore the associations of PSS and general self-efficacy with post-treatment OHRQoL after adjusting for some demographic and periodontal variables. Asymptotic and resampling strategies were performed to explore the mediating role of general self-efficacy. Initial periodontal therapy resulted in a significant improvement in the mean total score and all domains of OHRQoL and all periodontal parameters measured. In hierarchical linear regression analysis, clinical attachment loss (CAL) was significantly and positively associated with post-treatment OHRQoL score (β = 0.265, p < 0.01), while PSS (β = -0.303, p < 0.01) and general self-efficacy (β = -0.221, p < 0.01) were significantly and negatively associated with post-treatment OHRQL score, respectively. A significant mediating role of general self-efficacy (a*b = -0.139, BCa 95 % CI: -0.298, -0.011) in the association between PSS and post-treatment OHRQoL was revealed, and the proportion of the mediating role of general self-efficacy was 31.4 %. Initial periodontal therapy could significantly improve all aspects of OHRQoL. PSS and general self-efficacy could be the positive resources for improving OHRQoL after initial periodontal therapy among patients with periodontitis. General self-efficacy partly mediated the association between PSS and post-treatment OHRQoL.


Health Care Use During Transfer to Adult Care Among Youth With Chronic Conditions.
To compare health care use and costs for youth with chronic health conditions before and after transfer from pediatric to adult health care services. Youth born in Ontario, Canada, between April 1, 1989, and April 1, 1993, were assigned to 11 mutually exclusive, hierarchically arranged clinical groupings, including "complex" chronic conditions (CCCs), non-complex chronic conditions (N-CCCs), and chronic mental health conditions (CMHCs). Outcomes were compared between 2-year periods before and after transfer of pediatric services, the subjects' 18th birthday. Among 104,497 youth, mortality was highest in those with CCCs, but did not increase after transfer (1.3% vs 1.5%, P = .55). Costs were highest among youth with CCCs and decreased after transfer (before and after median [interquartile range]: $4626 [1253-21,435] vs $3733 [950-16,841], P < .001);Costs increased slightly for N-CCCs ($569 [263-1246] vs $589 [262-1333], P < .001), and decreased for CMHCs ($1774 [659-5977] vs $1545 [529-5128], P < .001). Emergency department visits increased only among youth with N-CCCs (P < .001). High-acuity emergency department visits increased CCCs (P = .04) and N-CCCs (P < .001), but not for CMHC (P = .59), who had the highest visit rate. Among the 11 individual conditions, costs only increased in youth with asthma (P < .001), and decreased (P < .05) in those with neurologic impairment, lupus, inflammatory bowel disease, and mood/affective disorders. Pediatric transfer to adult care is characterized by relatively stable short-term patterns of health service use and costs among youth with chronic conditions.


DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia-reperfusion in rats.
The transcription factor and immediate-early gene Egr-1 is widely viewed as a key upstream activator in a variety of settings within cardiovascular pathobiology. The role that Egr-1 plays in myocardial ischemia-reperfusion (IR) injury is unknown. We hypothesized that Egr-1 upregulation is of pathophysiologic importance in myocardial IR injury. First, abrogation of Egr-1 mRNA upregulation using Egr-1 targeting DNAzymes in a rat cardiomyocyte in vitro model was demonstrated. Egr-1 mRNA and protein upregulation following myocardial IR in rats were then selectively suppressed by locally delivered DNAzyme. Furthermore, myocardial neutrophil infiltration, intercellular adhesion molecule 1 mRNA and protein expression, and myocardial infarct size were all attenuated in DNAzyme-treated animals. These data support the hypothesis that Egr-1 is a key contributor to myocardial IR injury, and that Egr-1 targeting strategies have therapeutic potential in this context.


Pediatric Delayed Union in the Presence of WAGR Syndrome.
In this study, we present the management of an intra-articular fracture in a 13-year-old boy with WAGR syndrome, an extremely rare genetic disorder. The goal of this study was to provide possible solutions to the complex pain management requirements presenting in the setting of trauma to the right lower extremity. Given the scarcity of literature available with regard to this condition, we aim to not only increase awareness of the disease but also provide insight into trauma management and expected outcomes.


Laparoscopic radical prostatectomy: the value of intraoperative frozen sections.
To examine the clinical and pathological value of intraoperative frozen section (IFS) in patients undergoing laparoscopic radical prostatectomy (L-RPE) for clinically localized prostate cancer. The study includes 198 consecutive cases of L-RPE. After removal of the prostate, a 2-3mm circumferential specimen was obtained from the apical and bladder neck soft-tissue margin and submitted for IFS examination. In cases suspicious for capsular incision (n=57), IFS were taken from the neurovascular bundle/lateral pedicle. The IFS diagnosis from the apical, bladder neck, and neurovascular bundle/lateral pedicle soft-tissue margins was adenocarcinoma in 12 (6%), 1 (0.5%), and 2 (1%) cases, respectively. Patient age, clinical stage, and mean specimen weight were not associated with cancer at the apical IFS. The accuracy, sensitivity, specificity, positive and negative predictive value of the apical IFS to predict cancer in the permanent section of the apical soft-tissue margin was 96%, 70%, 97%, 58%, and 98%, respectively. All the patients (n=15) with cancer at IFS had wide resections of additional tissue in the area of positive soft-tissue margin and all had no cancer in the additional resected tissue. Especially at the apex, IFS decreases the overall PSM status on surgical specimen by 5.1% (apical PSM from 8.6% to 3.5%). Because of the low predictive value of IFS of bladder neck and neurovascular bundle/lateral pedicle their use is not recommended. IFS of the apex should be performed to reduce the PSM rate.


Influence of stathmin 1 (STMN1) expression on neoangiogenesis in colorectal adenocarcinoma.
Stathmin1 is a microtubular regulatory protein. The expression disorders of this protein result in significant changes in cell migration, invasion, adhesion and colony formation in many malignant tumors. The aim of our research was to investigate the effects of Stathmin1 expression on neoangiogenesis in colorectal adenocarcinoma. Biopsy material that was obtained by the resection of colorectal carcinoma was used. The experimental group consisted of operative biopsies of colorectal cancer (n = 72), and the control group (n = 72) consisted of biopsies of adjacent non-tumor colon tissue. The biopsy material was taken from an operative preparation submitted to the Department of Pathology. After histopathological treatment, classical Hematoxylin- Eosin and immunohistochemical ABC methods with anti-Stathmin1, anti-VEGF and anti CD105 antibodies were applied on 4 µm thick sections. High expression of Stathmin1 is associated with severe (91.9%) and moderate (8.1%) expression of VEGF in a significantly high number of cases. This relation is defined by a highly significant correlation coefficient (r = 0.768; p = 0.000). High expression of Stathmin1 is associated with a high microvascular density index (mvdIDX) in a significant number of cases (73.0%) while low expression of Stathmin1 is in relation with low mvdIDX in a significant 73.7% of cases. This relationship is also defined by a highly significant correlation coefficient (r = 0.566; p = 0.000). ROC analysis showed that the sensitivity for Stathmin1 was 97.4% and the specificity was 91.4%. Based on Stathmin1 expression, it is possible to differentiate patients with increased risk for metastatic disease. The highly significant association of Stathmin1 expression with VEGF expression and microvascular density (MVD) suggests that Stathmin1 may be a serious candidate for therapeutic target.


Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: a prospective multicentre study.
To assess local control after preoperative radiation and local excision and to determine an optimal radiotherapy regimen. Eighty-nine patients with G1-2 rectal adenocarcinoma <3-4 cm; unfavourable cT1N0 (23.6%), cT2N0 (62.9%) or borderline cT2/cT3N0 (13.5%) received 5 × 5 Gy plus 4 Gy boost (71.9%) or 55.8 Gy in 31 fractions with 5-FU and leucovorin (28.1%). Local excision (traditional technique 56.2%, transanal endoscopic microsurgery 41.6%, Kraske procedure 2.2%) was performed 6-8 weeks later. If patients were downstaged to ypT0-1 without unfavourable factors (good responders), this was deemed definitive treatment. Immediate conversion to radical surgery was recommended for remaining patients. Good response to radiation was seen in 67.2% of patients in the short-course group and in 80.0% in the chemoradiation group, p = 0.30. Local recurrence at 2 years (median follow-up) in good responders was 11.8% in the short-course group and 6.2% in the chemoradiation group, p = 0.53. In the total group, a lower rate of local recurrence at 2 years was observed in elderly patients (>69 years, median value) when compared to the younger patients; 8.3% vs. 27.7%, Cox analysis hazard ratio 0.232, p = 0.016. A total of 18 patients initially managed with local excision required conversion to abdominal surgery but either refused it or were unfit. In this group, local recurrence at 2 years was 37.1%. This study suggests an acceptable local recurrence rate after preoperative radiotherapy and local excision of small, radiosensitive tumours in elderly patients.


Presence of blaPER-1 and blaVEB-1 beta-lactamase genes among isolates of Pseudomonas aeruginosa from South West of Iran.
Pseudomonas aeruginosa isolates have acquired resistance to antibiotics such as novel beta-lactams. The aim of this study was to investigate the blaPER-1, blaVEB-1, and blaPSE-1 genes among isolates of P. aeruginosa among intensive care unit (ICU) patients. Sixty-five isolates were collected. The antibiotic susceptibility testing and combined disk tests were performed to detect the isolates producing extended spectrum beta-lactamases (ESBLs) among ceftazidime-resistant isolates. Polymerase chain reaction (PCR) amplification of blaPER-1, blaVEB-1, and blaPSE-1 genes was conducted. Ten (15.3%) isolates were ESBL-positive, of which 40% (n=4) belonged to males and 60% (n=6) were collected from females. Moreover, two and one isolates harbored blaPER-1 and blaVEB-1 genes, respectively.


Carcinoma developing in ectopic pancreatic tissue in the stomach: a case report.
The development of pancreatic tissue outside the confines of the main gland, without anatomic or vascular connections between them, is a congenital abnormality referred to as heterotopic pancreas. A heterotopic pancreas in the gastrointestinal tract is usually discovered incidentally and the risk of its malignant transformation is extremely low. In this study, we describe the first case of endoepithelial carcinoma arising in a gastric heterotopic pancreas of a 56-year old woman in Greece. She presented with epigastric pain, periodic nausea and vomiting. Esophagogastroduodenoscopy revealed an ulcerated lesion in the gastric antrum, biopsies of which showed intense epithelial dysplasia with incipient malignant degeneration. The pathology report of the distal gastrectomy specimen demonstrated a 2 cm in diameter ulcerative mass in the gastric antrum. Microscopically, an endoepithelial (in situ) carcinoma of the gastric antrum was determined, which in places turned into an microinvasive endomucosal adenocarcinoma. It also incidentally demonstrated heterotopic pancreatic ducts, detected within the mucosa to the muscularis propria of the same region of the stomach, in which an endoepithelial (in situ) carcinoma was evolving. The follow-up course was uneventful 6 months postoperatively.


Rhabdomyosarcoma of the orbit. Evaluation with MR imaging and CT.
Rhabdomyosarcoma is the most common primary orbital malignancy of childhood. It can present insidiously, mimicking other (benign) processes clinically and radiographically. CT and MR imaging are crucial in the diagnostic evaluation, treatment planning, and follow-up monitoring of the disease. Such imaging, especially when contrast is used, can accurately detect and state the extent of tumor involvement.


Hydrothermal conversion of waste cartons into a magnetic carbon-iron composite for use as an efficient and recyclable dye adsorbent.
Disposal of large quantities of waste cartons aggravates the burden of municipal solid waste treatment. Exploitation of the potential value of waste cartons and conversion of this waste stream into available materials is a hot research topic with practical application prospects. In this study, we successfully fabricated a magnetic carbon-iron composite from waste cartons via hydrothermal treatment and investigated its application as an efficient adsorbent for the removal of a disperse blue dye (DB 56) and reactive yellow dye (RY 3) from aqueous solution. The fabricated product was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and Brunauer-Emmett-Teller analysis. The effects of the composite dose, initial dye concentration, and solution pH on the dye removal efficiency were investigated. Under acidic conditions at pH 2, the removal efficiencies of DB 56 and RY 3 reached 81.53% and 96.77%, respectively. The adsorption processes followed pseudo-second-order kinetics and the Freundlich isotherm. The magnetic carbon-iron composite could be easily separated from the aqueous solution because of its magnetism, and could be regenerated by the Fenton reaction. After re-use in three cycles, the removal efficiencies for both dyes were still above 70%. The magnetic carbon-iron composite produced from waste cartons shows promise for application to effluent that contains dyes because of its low cost, high efficiency, and simple application.


Assessment of gamma radiation exposure of beach sands in highly touristic areas associated with plutonic rocks of the Atticocycladic zone (Greece).
This study aims to evaluate the activity concentrations of 238U, 226Ra, 232Th, 228Th and 40K along beaches close to the plutonic rocks of the Atticocycladic zone that ranged from 15 to 628, 12-2292, 16-10,143, 14-9953 and 191-1192 Bq/kg respectively. A sample from island of Mykonos contained the highest 232Th content measured in sediments of Greece. The heavy magnetic fraction and the heavy non-magnetic fraction as well as the total heavy fraction, were correlated with the concentrations of the measured radionuclides in the bulk samples. The heavy fractions seem to control the activity concentrations of 238U and 232Th of all the samples, showing some local differences in the main 238U and 232Th mineral carrier. Similar correlations have been found between 238U, 232Th content and rare earth elements concentrations. The measured radionuclides in the beach sands were normalized to the respective values measured in the granitic rocks, which at least in most cases are their most probable parental rocks, so as to provide data upon their enrichment or depletion. Since the Greek beaches are among the most popular worldwide the annual effective dose equivalent received due to sand exposure has been estimated and found to vary between 0.002 and 0.379 mSv y-1 for tourists and from 0.018 to 3.164 mSv y-1 for local people working on the beach. The values corresponding to ordinary sand samples are orders of magnitude lower than the limit of 1 mSv y-1, only in the case of heavy minerals-rich sands the dose could reach or exceed the recommended maximum limit.


Social anxiety in high-functioning children and adolescents with Autism and Asperger syndrome.
We examined social anxiety and internalizing symptoms using the Social Phobia and Anxiety Inventory for Children (SPAI-C), the Social Anxiety Scale for Children -Revised (SASC-R), and the Child Behavior Checklist (CBCL) in a sample of fifty-four high-functioning subjects with autism or Asperger syndrome (HFA/AS) (M = 11.2 +/- 1.7 years) and 305 community subjects (M = 12.2 +/- 2.2 years). Children and adolescents completed the SPAI-C and SASC-R, and their parents completed the CBCL Internalizing scale. Adolescents with HFA/AS scored higher than the community sample on all measures. Behavioural avoidance and evaluative social anxiety increased by age within the HFA/AS group, whereas behavioural avoidance decreased by age in control participants. Data support that HFA/AS in adolescents may be associated with clinically relevant social anxiety symptoms.


Author Correction: The choroid plexus is an important circadian clock component.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Retraction: Synthesis and characterization of novel silica-coated magnetic nanoparticles with tags of ionic liquid. Application in the synthesis of polyhydroquinolines.
[This retracts the article DOI: 10.1039/C5RA23670C.].


Role of mu-calpain in human decidua for recurrent miscarriage.
Earlier, we showed that calpain activated by increasing intracellular calcium ion concentration in endometrial cells, causes endometrial dysfunction for implantation and early pregnancy. In the present study, we investigated the existence and distribution of calpains, calpastatin, integrin beta3 and alpha-fodrin in decidua from patients with recurrent miscarriage. Deciduae were surgically collected from 29 patients with recurrent miscarriage and 20 healthy women with informed consent. Immunohistochemistry, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and western blot analysis were performed. Staining of mu-calpain, m-calpain, calpastatin, integrin beta3 and alpha-fodrin were observed in the cytoplasm of stromal and epithelial cells in decidua using immunohistochemistry. No significant differences were observed in staining patterns. Western blot analysis showed no significant differences in expression of m-calpain, calpastatin and alpha-fodrin, whereas mu-calpain was significantly higher and integrin beta3 was lower in subject. The results suggest that cleavage of integrin beta3 by mu-calpain may have an adverse effect on the mechanism of early pregnancy.


A UHF/UWB Hybrid RFID Tag With a 51-m Energy-Harvesting Sensitivity for Remote Vital-Sign Monitoring.
A novel ultra-high frequency (UHF)/ultra-wideband (UWB) hybrid RFID tag is reported for object-specific remote vital-sign monitoring application. The tag achieves a record energy-harvesting sensitivity at UHF band by codesigning a meander dipole antenna and a passive rectifier. The especially high quality-factor makes the frontend sensitive to near-field motions such as heartbeats and respiration in a wearable setting. The custom CMOS IC of approximately 1-μW power consumption builds around a low-power UWB transmitter and converts variations of the supply voltage to the impulse repetition rate. The tag consisting of the IC and UHF/UWB antennas requires no other discrete components and features a size of 4.2 cm × 2.9 cm and a weight of 0.93 g. A long-distance experiment verifies that the tag can be wirelessly powered up at 51 meters from a 4-W equivalent-isotropic-radiation-power (EIRP) UHF transmitter. Remote vital-sign monitoring is validated on a human subject, in which the UHF power source is placed 2 meters away from the subject with a power emission of less than 20 dBm. This work proposes a first-of-its-kind remote vital-sign monitoring scheme based on a noncontact wearable tag. The design of the far-field energy-harvesting frontend with a record sensitivity serves as a reference for future works on battery-free remote sensors.


Nortriptyline in knee osteoarthritis (NortIKA Study): study protocol for a randomised controlled trial.
Osteoarthritis (OA) is a common cause of pain and disability. Currently available analgesics are often insufficiently effective or have unacceptable adverse effects. Tricyclic antidepressants may offer a useful centrally-acting analgesic. Nortriptyline is a readily-available, cheap and comparatively well-tolerated tricyclic antidepressant. We will conduct a parallel group, two-arm, participant and investigator-blinded, randomised controlled superiority trial comparing nortriptyline with placebo. Two hundred participants with primary knee OA will be enrolled. Participants will take study medication for 14 weeks. The primary outcome is difference between treatment arms in mean pain score measured on the Western Ontario and McMaster Universities (WOMAC) pain scale at 14 weeks. This protocol describes the first randomised controlled trial of a tricyclic antidepressant in the treatment of OA. The results of the study may have significant implications for the management of this common and painful condition. The trial was registered with the Australian New Zealand Clinical Trials Registry on 27 June 2014. The trial registration number is: ACTRN12614000683639 .


Biophysical and functional assays for viral membrane fusion peptides.
Membrane fusion is a protein catalyzed biophysical reaction that involves the simultaneous intermixing of two phospholipid bilayers and of the aqueous compartments bound by their respective bilayers. In the case of enveloped virus fusogens, short hydrophobic or amphipathic fusion peptides that are components of the larger fusion complex are essential for the membrane merger event. The process of cell-cell membrane fusion and syncytium formation induced by the nonenveloped fusogenic orthoreoviruses is driven by the Fusion-Associated Small Transmembrane (FAST) proteins, which are similarly dependent on the action of fusion peptides. In this article, we describe some simple methods for the biophysical characterization of viral membrane fusion peptides. Liposomes serve as an ideal model system for characterizing peptide-membrane interactions because their size, shape and composition can be readily manipulated. We present details of fluorescence assays used to elucidate the kinetics of membrane fusion as well as complimentary assays used to characterize peptide-induced liposome binding and aggregation.


Vulvar Aphthous Ulcer Following Pfizer-BioNTech COVID-19 Vaccine - A Case Report.
In this case report, we describe a potential association between the Pfizer-BioNTech COVID-19 vaccine and development of a vulvar aphthous ulcer in a virginal 14-year-old girl. A 14-year-old patient reported vulvar pain and visible lesion. Exam findings were consistent with vulvar aphthous ulcers. Two days prior to the onset of her symptoms she received her second Pfizer-BioNTech COVID-19 vaccine. The evening of vaccine administration, she experienced several hours duration of fatigue, muscle aching and insomnia but had otherwise been recently healthy and testing for common viral associations of vulvar ulcers was negative. Vaccination, in general, has been associated with mucosal side-effects and oral ulceration has been reported in subjects who received Pfizer-BioNTech COVID-19 vaccine. It is reasonable to hypothesize that vulvar ulceration may be caused by a similar mechanism and should be considered a rare side effect of this vaccine.


Diazepam and pentobarbital dependence in the rat.
Diazepam (100-133 mg/kg/day), administered chronically through a gastric fistula, and pentobarbital (ca 692 mg/kg/day), administered chronically in food, were studied for their dependence producing properties in Sprague-Dawley female rats. The diazepam abstinence syndrome was apparent 10 to 20 hours after withdrawal, persisted for over 60 hours and consisted of poker tail, explosive awakenings, digging in sawdust, jerks, tremors, wet dog shakes, hostility, decreased food and water consumption and weight loss. The pentobarbital abstinence syndrome came on rapidly peaking within 10 hours and was largely over by 16 hours. The pentobarbital abstinence syndrome differed from diazepam's by the presence of grand mal, clonic and atypical convulsions. Diazepam completely and in a dose related way suppressed the diazepam abstinence syndrome. Similarly pentobarbital suppressed the pentobarbital abstinence syndrome. The signs which could be suppressed in a dose related manner were different for the diazepam and pentobarbital abstinence syndromes. Diazepam only partially suppressed the pentobarbital abstinence syndrome and pentobarbital only partially suppressed the diazepam abstinence syndrome. These data indicate that diazepam and pentobarbital produce different types of dependencies in the rat and are not equivalent in suppressing signs of abstinence.


Comparative evaluation of three tests for the detection of Escherichia coli cytotoxic necrotizing factors (CNF1 and CNF2) using filtrates of cultures treated with mitomycin C.
Necrotizing Escherichia coli (NTEC) strains grown in the presence of mitomycin C released cell associated necrotizing factors CNF1 and CNF2 to culture medium. Using culture filtrates from 96 mitomycin C treated E. coli strains, we have found that a modified HeLa cell assay was a more sensitive and specific method for the detection of CNF1 and CNF2 than the Vero cell assay and the rabbit skin test.


Complexes of sulfur-containing ligands. I. Factors influencing complex formation between D-penicillamine and copper (II) ion.
Complex formation and redox reactions between copper (II) ion and D-penicillamine were studied in detail as functions of the metal/-ligand ratio and the concentration of halide ions. It was established that a copper (I)- D-penicillamine polymeric complex of amphoteric character is formed when excess D-penicillamine is present. When the D-penicillamine/copper (II) ratio = 1.45 in the starting reaction mixture, a mixed valence complex with an intense red-violet color is formed. The formation of this compound, which contains 44% copper (II) ion, is greatly influenced by the experimental conditions, primarily by the concentration of halide ions. The main chemical and physical characteristics of the mixed valence complex were determined via magnetic and spectroscopic measurements. It was further established that a very intense blue complex is formed when the D-penicillamine/copper (II) ratio = 2 and halide ions are present. On the basis of the nature of the products formed under various conditions it was concluded that the copper (II)-D-penicillamine system may serve as a good model for studying the binding sites of copper-containing proteins.


Pharmacy provision of influenza vaccinations in medically underserved communities.
To demonstrate the extent to which a community pharmacy can provide influenza immunizations in communities designated as medically underserved. This retrospective study examined the number of influenza immunizations administered and populations served in areas with limited access to health care by Walgreens pharmacies during the 2009-10 influenza season. More than 43% of the U.S. population resides in medically underserved areas (MUAs), and our results show that Walgreens pharmacies served nearly one-half of this population. Nationwide, more than one-third of influenza immunizations were administered by pharmacies located in MUAs. In states with the highest proportion of their population in MUAs, the percentage of influenza vaccines provided in MUAs was much greater (up to 77.1%). Community pharmacies are convenient and accessible venues at which patients can obtain seasonal influenza vaccines and other immunizations. They are well-positioned throughout the country, including in areas that are otherwise medically underserved. These factors help community pharmacists eliminate one of the most important barriers to vaccination: accessibility.


Hepatocellular carcinoma invading the main portal vein: treatment with transcatheter arterial chemoembolization and portal vein stenting.
To retrospectively analyze the therapeutic results of percutaneous transhepatic portal vein stenting (PTPVS) and transcatheter arterial chemoembolization (TACE) treatment in 58 patients with hepatocellular carcinoma (HCC) invading the main portal vein (MPV). A total of 58 procedures of PTPVS were performed, immediately after which TACE was undertaken to control HCC. The clinical effects, complications, digital subtraction angiographic appearance, stent patency rates, cumulative survival rates, and predictive factors for survival were evaluated. The Kaplan-Meyer method and the log rank test were used for survival analysis. Multivariable analysis was also conducted by the Cox proportional hazard model. No patient died during stent placement or within the first 24 h. No severe procedure-related complications were observed. After stent placement, the mean +/- standard deviation portal venous pressure levels decreased from 41.43 +/- 8.56 cmH(2)O to 37.19 +/- 7.89 cmH(2)O (p < 0.01). At the time of analysis, 9 of the 58 patients survived. The 60-, 180-, 360-, and 720-day cumulative patency rates were 98.1%, 71.0%, 52.6%, and 42.1%, respectively, with a mean patency time of 552.9 +/- 88.2 days and a median patency time of 639.00 +/- 310.00 (95% confidence interval [95% CI], 31.40-1246.60) days. The 60-, 180-, 360-, and 720-day cumulative survival rates for the total study population were 74.1%, 27.1%, 17.2%, and 13.8%, respectively, with a median survival time of 113 +/- 27.29 (95% CI, 59.51-166.49) days. In the univariate analysis, the following six variables were significantly associated with the prognosis: (1) HCC type; (2) Child-Pugh grade; (3) MPV stenosis/occlusion; (4) arteriovenous shunt; (5) iodized oil deposition; and (6) number of TACE procedure. In addition, having diffuse-type HCC and Child-Pugh grade B disease were each independent factors associated with decreased survival time in the multivariate analysis. PTPVS-TACE is feasible and may be useful to control HCC invading the MPV.


Ras activity in the Drosophila prothoracic gland regulates body size and developmental rate via ecdysone release.
In Drosophila, each of the three larval instars ends with a molt, triggered by release of steroid molting hormone ecdysone from the prothoracic gland (PG). Because all growth occurs during the larval stages, final body size depends on both the larval growth rate and the duration of each larval stage, which in turn might be regulated by the timing of ecdysone release. Here, we show that the expression of activated Ras, PI3 kinase (PI3K), or Raf specifically in the PG reduces body size, whereas activated Ras or PI3K, but not Raf, increases PG cell size. In contrast, expression of either dominant-negative (dn) Ras, Raf, or PI3K increases body size and prolongs the larval stages, leading to delayed pupariation, whereas expression of dn-PI3K, but not of dn-Raf or dn-Ras, reduces PG cell size. To test the possibility that altered ecdysone release is responsible for these phenotypes, we measured larval ecdysone levels indirectly, via the transcriptional activation of two ecdysone targets, E74A and E74B. We found that the activation of Ras within the PG induces precocious ecdysone release, whereas expression of either dn-PI3K or dn-Raf in the PG greatly attenuates the [ecdysone] increase that causes growth cessation and pupariation onset. We conclude that Ras activity in the PG regulates body size and the duration of each larval stage by regulating ecdysone release. We also suggest that ecdysone release is regulated in two ways: a PI3K-dependent growth-promoting effect on PG cells, and a Raf-dependent step that may involve the transcriptional regulation of ecdysone biosynthetic genes.


Towards accurate exclusion of neonatal bacterial meningitis: a feasibility study of a novel 16S rDNA PCR assay.
PCRctic is an innovative assay based on 16S rDNA PCR technology that has been designed to detect a single intact bacterium in a specimen of cerebro-spinal fluid (CSF). The assay's potential for accurate, fast and inexpensive discrimination of bacteria-free CSF makes it an ideal adjunct for confident exclusion of bacterial meningitis in newborn babies where the negative predictive value of bacterial culture is poor. This study aimed to stress-test and optimize PCRctic in the "field conditions" to attain a clinically useful level of specificity. The specificity of PCRctic was evaluated in CSF obtained from newborn babies investigated for meningitis on a tertiary neonatal unit. Following an interim analysis, the method of skin antisepsis was changed to increase bactericidal effect, and snap-top tubes (Eppendorf™) replaced standard universal containers for collection of CSF to reduce environmental contamination. The assay's specificity was 90.5% in CSF collected into the snap-top tubes - up from 60% in CSF in the universal containers. The method of skin antisepsis had no effect on the specificity. All CSF cultures were negative and no clinical cases of neonatal bacterial meningitis occurred during the study. A simple and inexpensive optimization of CSF collection resulted in a high specificity output. The low prevalence of neonatal bacterial meningitis means that a large multi-centre study will be required to validate the assay's sensitivity and its negative predictive value.


Tolerability of risedronate in postmenopausal women intolerant of alendronate.
Bisphosphonates are effective treatments for osteoporosis, but some have been associated with upper gastrointestinal intolerance. This randomized, double-blind study assessed the upper gastrointestinal tolerability of risedronate in postmenopausal women who had discontinued alendronate treatment because of upper gastrointestinal adverse events. Sixty-six women who had previously discontinued treatment with alendronate 10 mg/day because of upper gastrointestinal symptoms received placebo (N=31) or risedronate 5 mg (N=35) daily for 3 months. The primary outcome was the rate of discontinuation due to upper gastrointestinal adverse events: 5/31 (16.1%) in the placebo group, and 4/35 (11.4%) in the risedronate group. Discontinuation rates were also similar in the two treatment groups among subgroups of patients with a history of gastrointestinal disorder, prior use of acid suppression drugs, and concomitant use of NSAIDs. The overall incidence of upper gastrointestinal events was comparable between the placebo (19.4%) and risedronate (20.0%) groups. Overall, risedronate 5 mg/day for 3 months was as well tolerated as placebo in patients who could not tolerate alendronate 10 mg. These results are consistent with, and complement those from previous studies showing that risedronate 5 mg has a gastrointestinal tolerability similar to that of placebo.


Pattern of Relapse in Hepatic Hydatidosis: Analysis of 238 Cases in a Single Hospital.
Hydatidosis is a chronic disease that is endemic and prevalent in certain regions of the world. Surgical treatment is the best option, although its main problem is that there is a high rate of recurrence. The objective of the present study was to assess its therapeutic management and the factors related to its postoperative morbidity and relapse. A descriptive and retrospective study was made of 238 patients with hepatic hydatidosis operated from January 2006 to December 2017 at our center. An analysis was made of the variables associated with postoperative morbidity and relapse, and of the temporal pattern of that relapse. Out of 238 patients, radical surgery was performed in 132 (55.5%) and partial cystectomy in 106 of them (44.3%). The postoperative morbidity was 42% (100/238) and the relapse rate was 7.2% (17/238). The factors associated with greater postoperative morbidity were partial cystectomy (OR, 2.83 (1.47-5.43); p = 0.002), ≥ 2 cysts (OR, 3.22 (1.51-6.86); p = 0.002), and biliary fistula (OR, 4.34 (2.11-8.91); p < 0.0001); and those associated with higher relapse rate were history of hydatidosis (OR, 4.98 (1.76-14.11); p = 0.003) and ≥ 2 cysts (OR, 3.23 (1.14-9.11); p = 0.027). The first relapses appeared after 14 months, with the greatest incidence between 14 and 36 months. The surgical procedure applied is associated with morbidity but not with that of relapse. The observed relapse pattern demonstrates the need to maintain long-term follow-up, but with no follow-up being necessary in the first year. Broader multicenter and prospective studies are needed to establish more precise recommendations.


IRF8 and BATF3 interaction enhances the cDC1 specific Pfkfb3 gene expression.
Dendritic cells (DCs) play central role in innate as well as adaptive immune responses regulated by diverse DC subtypes that vary in terms of surface markers, transcriptional profile and functional responses. Generation of DC diversity from progenitor stage is tightly regulated by complex molecular inter-play between transcription factors. We earlier demonstrated that Batf3 and Id2 expression have a synergistic effect on the Irf8 directed classical cDC1 development. In present study, Bi-molecular fluorescence complementation assay suggested that IRF8 interacts with BATF3, and ID2 may aid cDC1 development independently. Genome wide recruitment analysis of IRF8 and BATF3 from different DC subtypes led to identification of the overlapping regions of occupancy by these two transcription factors. Further analysis of overlapping peaks of IRF8 and BATF3 occupancy in promoter region within the cDC1 subtype specific transcriptional pattern identified a metabolically important Pfkfb3 gene. Among various immune cell types; splenic cDC1 subtype displayed enhanced expression of Pfkfb3. Analysis of Irf8-/-, Irf8R294C and Batf3DCKO DC confirmed direct regulation of Pfkfb3 enhanced expression specifically in cDC1 subtype. Further we show that inhibition of PFKFB3 enzymatic activity by a chemical agent PFK15 led to reduction in cDC1 subtype in both in vitro FLDC cultures as well as in vivo mouse spleens. Together, our study identified the direct regulation of cDC1 specific enhanced expression of Pfkfb3 in glycolysis and cDC1 biology.


Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome.
Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.


One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial.
Prior randomised trials have evaluated statins in patients with sepsis and acute respiratory distress syndrome (ARDS), but there has been no comprehensive evaluation of long-term effects, despite potential neuromuscular and mental health adverse effects of these drugs. To evaluate the effect of rosuvastatin versus placebo on survival, physical function and performance, and mental health outcomes in patients with sepsis-associated ARDS. Prospective follow-up evaluation of the ARDS Clinical Trials Network Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo in 568 mechanically ventilated patients with sepsis-associated ARDS, with blinded 6-month outcome assessment performed in the 272 eligible survivors for age-adjusted and sex-adjusted 36-Item Short Form Health Survey (SF-36) physical function and mental health domains, and in 84 eligible survivors for the 6 min walk test, along with secondary outcomes evaluations of survival, and additional patient-reported and performance-based measures at 6-month and 12-month follow-up. Over 1-year follow-up, there was no significant difference in cumulative survival in the rosuvastatin versus placebo groups (58% vs 61%; p=0.377), with survivors demonstrating substantial impairments in physical function and mental health. Rosuvastatin versus placebo had no effect (mean treatment effect (95% CI)) on SF-36 physical function (0 (-7 to 8), p=0.939) or mental health (-6 (-12 to 1) p=0.085) domains, 6 min walk distance (per cent predicted: 2 (-9 to 14), p=0.679) or the vast majority of secondary outcomes. Over 1-year follow-up, patients with sepsis-associated ARDS had high cumulative mortality, with survivors commonly experiencing impairments in physical functioning and performance, and mental health. Randomisation to rosuvastatin had no effect on these outcomes. NCT00979121 and NCT00719446.


In Vitro Models for Studying Tumor Progression.
Beyond cell proliferation, one of the most outstanding characteristics of the cancerous cells that promotes the tumoral progression is their high capacity to migrate and invade the surrounding healthy tissue. These cellular processes (migration and invasion) are critical steps to metastasis. Metastatic progression of the tumors is often the leading cause of morbidity and mortality in cancer patients. Critical genes and cell signaling pathways involved in cell migration and invasion of tumor cells have been identified, and several clinical efforts to alleviate cancer are focused on them; however, once the tumor has metastasized, it is extremely difficult to stop the progression of very aggressive forms of cancer such as glioblastomas. Therefore, it is crucial to elucidate the specific molecular mechanisms underlying tumor progression. In this chapter, we describe some methods to study tumor progression by assessing migration and cell invasion in 2D and 3D cell culture conditions.


Vegetable foods: a cheap source of proteins and peptides with antihypertensive, antioxidant, and other less occurrence bioactivities.
Despite less explored than foods from animal origin, plant derived foods also contain biologically active proteins and peptides. Bioactive peptides can be present as an independent entity in the food or, more frequently, can be in a latent state as part of the sequence of a protein. Release from that protein requires protein hydrolysis by enzymatic digestion, fermentation or autolysis. Different methodologies have been used to test proteins and peptides bioactivities. Fractionation, separation, and identification techniques have also been employed for the isolation and identification of bioactive proteins or peptides. In this work, proteins and peptides from plant derived foods exerting antihypertensive, antioxidant, hypocholesterolemic, antithrombotic, and immunostimulating capacities or ability to reduce food intake have been reviewed.


Supracallosal interhemispheric arachnoid cyst: resolution after intracystic hemorrhage and infection.
A case of a large, symptomatic, supracallosal interhemispheric arachnoid cyst is presented. Positive contrast-enhanced computed tomographic (CT) cystography after stereotactic puncture and aspiration demonstrated lack of communication between the cyst and the subarachnoid space or ventricular system. A cystoperitoneal shunt was successful in relieving the patient's symptoms for 5 years. A delayed shunt infection after gynecologic surgery necessitated removal of the shunt, and was complicated by asymptomatic intracystic hemorrhage. Thereafter, serial CT and magnetic resonance imaging scans showed eventual disappearance of the cyst.


Occurrence of alternariol and alternariol monomethyl ether in beverages from the Entre Rios Province market, Argentina.
One hundred and eighty five samples of red, white and rosé wines and different juices purchased in Entre Rios, Argentina, were analyzed for the Alternaria mycotoxins alternariol (AOH) and alternariol methyl ether (AME). White wines were analyzed after removal of alcohol by a nitrogen stream and concentrated. AOH in red wines was cleaned up by solid-phase extraction columns in series (octadecyl and amino propyl modified silica) and AME quantified directly on the sample. The juices were filtered and concentrated, and then all sample extracts were quantified by high performance liquid chromatography with photodiode array detector that allows confirmation through UV spectra. Method validation revealed a good sensitivity with adequate LOD and LOQ for AME and less sensitivity for AOH (i.e. white wine: AME 0.8 and 1.4 ng/mL, AOH 2 and 3.3 ng/mL; red wine: AME 0.1 and 0.2 ng/mL, AOH 4.5 and 7.5 ng/mL; apple juice: AME 1.7 and 2.8 ng/mL, AOH 5 and 9 ng/mL; other juices: AME 2.0 and 3.1 ng/mL, AOH 6 and 10 ng/mL). Recoveries in all cases were greater than 80 %. Four of 53 white wine samples were contaminated with AOH with a maximum level of 18 ng/mL, 6 of 56 samples of red wine had a maximum of 13 ng/mL, and 3 of 68 samples of juices had traces of AOH. AME was less frequently detected than AOH, and the LOD and LOQ for AME are smaller than for AOH. Only three samples of white wine and one of red wine were contaminated, but in only one white wine sample (AME 225 ng/mL) did the toxin level exceed the LOQ.


Control of diarrhoea and death in home-bred dairy calves by bucket feeding pooled colostrum.
The feeding of colostrum to newborn calves from a bucket was found to be more effective in ensuring immune globulin uptake than leaving cow and calf together for two days post partum. A marked seasonal variation in the immune globulin status of calves, which could not readily be explained by management factors, was noted during two consecutive seasons.


Epidemic within a pandemic: Alcohol-associated hepatitis and COVID-19.
There was an increase in alcoholic beverage sales during the peak of the COVID pandemic in the United States. However, little is known about the impact of SARS-CoV-2 infection among hospitalized alcohol-associated hepatitis (AH) patients. We analyzed the available National Inpatient Data (NIS) data from 2020 to determine mortality and healthcare utilization among hospitalized AH patients with and without COVID-19 in the United States. We observed a ~15.6% increase in cases of hospitalized AH patients from 136,620 in 2019 to 157,885 in 2020, a significant increase from an average of 5.5% per annum despite an 8.7% decline in US hospital admissions over the same time span. Men younger than 40 were the fastest growing AH group, with a 23% increase in 2020. Approximately 1.8% of hospitalized AH patients had a SARS-CoV-2 infection, which significantly worsened the mortality among patients with AH (11.4% vs. 4.1%, p < 0.0001). This was especially true among older AH patients with concomitant conditions such as clinically apparent cirrhosis, acute renal failure, upper gastrointestinal bleeding, and sepsis. AH patients with COVID-19 also had a longer length of stay (8.6 vs. 6.1 days, p < 0.0001) and higher hospital charges during the stay ($93,670 vs. $66,283, p < 0.0001) than those without COVID-19. Our study highlights the rise in AH cases during the COVID-19 pandemic. Screening and appropriate management of excessive alcohol use and preventive measures such as COVID-19 vaccination should be considered to reduce morbidity and mortality among patients with AH.


Long-term results of suture suspension platysmaplasty for neck rejuvenation: a 13-year follow-up evaluation.
Neck rejuvenation has been one of the most important components in treatment for the aging face because the neck frequently is the first feature to show signs of aging. Several techniques have been described, but assessment of the long-term effects, although limited, has shown frequent recurrence of neck ptosis and the need for reoperation. The suture suspension technique was introduced 13 years ago. This article presents the long-term results for this technique, illustrating the different neck types, their classification, and their outcomes. For this study, 100 patients who underwent neck rejuvenation using the suture suspension platysmaplasty technique were randomly selected. They represented the four patient groups examined: 5-year group (47 patients), 7-year group (28 patients), 10-year group (19 patients), and 13-year group (6 patients). The key anatomic points for each patient were evaluated preoperatively and postoperatively by five independent observers who analyzed the outcomes with a simplified scoring system (1 to 10 for each anatomic point). The scoring system was used for all the patient age groups and applied to all six key anatomic points of the neck: cervicomental angle depth, mandibular border definition, mandibular angle definition, labiomandibular fold prominence (jowling), mental prominence, and neck width. Patient satisfaction surveys were offered to all patients included in the study. All the patient groups showed significant aesthetic improvement (in terms of their scores) for all the anatomic points (1-6) evaluated. Specifically, the long-term effect of the procedure was the most impressive for the cervicomental angle (with improvement ranging from 82% to 95% for the four groups of patients). The least degree of improvement was noted for the labiomandibular fold (with improvement ranging from 12% to 53% for the four groups of patients). The remaining anatomic variables showed an overall improvement ranging from 61% to 85%. The suture suspension technique is a safe, reproducible technique that allows for a staged rejuvenation of the neck. As an alternative for the early rhytidectomy candidate, it produces excellent patient satisfaction outcomes with long-term corrections for the majority of patients. As compared with previously described platysmaplasty techniques, suture suspension platysmaplasty has the benefit of endurance. This article documents that the corrections can last at least 13 years with virtually unchanged aesthetic results.


[Myelopathy, polymyositis and systemic manifestations associated with the HTLV-I virus].
A case of HTLV-I associated myelopathy in a 51 year-old Haitian woman is reported. MRI showed high signals in the cerebral white matter on T2-weighted images. There also was clinical and electrophysiological evidence of myositis, and a biopsy of the quadriceps muscle showed dense inflammatory infiltrates surrounding several small perimysial blood vessels. The virus was not demonstrated in the muscle. The presence of several systemic abnormalities (polyclonal gammapathy, circulating immune complexes, Sjögren's syndrome) and the vasculitis suggest an immunopathological mechanism for this HTLV-I associated myositis.


FT-IR spectroscopy of methylmercury-exposed mouse lung.
Infrared spectroscopy which has traditionally been utilized by chemists and physicists for characterization and identification of the structural properties of chemical compounds is now becoming more relevant as a biodiagnostic tool. Recent reports suggest that arthritis and Alzheimer's disease can be diagnosed by using this technique. Changes associated with these diseases diagnosable with this technique are generally overt. In this study we have used 'Fourier transform infrared spectroscopy' (FT-IR) to analyze subtle changes in composition and structure of lipids and proteins in lung tissue, bronchoalveolar lavage and purified lamellar body fraction of mice exposed to methylmercury. Infrared measurements were made in attenuated total reflection mode using the Split Pea (Harrick Scientific Corporation, USA). Mice were treated with 4 doses of methylmercuric chloride (15 mg/kg body weight/dose), and control animals received an equivalent volume of physiological saline. Comparison of the control and experimental spectra revealed alterations in the intensities and frequencies of vibrational modes of lipids following methylmercury exposure. Results indicate that FT-IR spectral analyses may be a valuable tool for detecting subtle variations in biological components associated with drug exposure to lungs and, in particular may be very useful for assessing changes in bronchoalveolar lavage.


Enhancing the detection of proximal cavities on near infrared transillumination images with Indocyanine Green (ICG) as a contrast medium: In vitro proof of concept studies.
The use of near infrared transillumination for caries detection is gaining recognition in daily practice. Differentiation between cavitated and non cavitated proximal lesions is recognized as a threshold for restorative treatment. This investigation focused on the use of a near infrared absorbent dye which may enhance the detection of cavitation on near infrared transillumination images. 1: Natural teeth with artificial proximal cavitation were images with 3 different dyes to establish that near infrared absorbent dye can act like a contrast medium. 2: Natural teeth with natural cavitated lesions were used to investigate the contrast enhancing effect of indocyanine green (ICG) on near infrared transillumination images. 3: Artificial teeth with artificial cavitations were used to determine the best consistency of ICG as a contrast medium. 4: natural teeth with proximal lesions were used to confirm that ICG can differentiate between cavitated and non cavitated proximal lesions. 1: ICG enhanced the contrast of cavitations compared to other dyes (ANOVA; p < 0.05). 2: ICG enhanced the contrast of the cavitated area on natural lesions but not significantly (t-test; p > 0.05). 3: ICG in a gel form enhanced the detection of cavitated lesions when compared to liquid ICG (t-test; p < 0.05). 4: ICG gel was able to differentiate between cavitated and non cavitated proximal lesions (ANOVA; p < 0.05). ICG can potentially be used as a contrast medium to enhance the detection of cavitated proximal lesions in vitro on near infrared transillumination images. A clinical study is required to validate these results in vivo.