Short-term toxicity of allyl alcohol in rats.
Groups of 15 male and 15 female rats were give 0 (control), 50, 100, 200 or 800 ppm allyl alcohol in the drinking water for 15 weeks. There were no effects attributable to allyl alcohol in the results of the haematological examinations or analyses of serum. There was a dose-related reduction in the fluid intake at all treatment levels in both sexes, while growth and food consumption were reduced in both sexes given 800 ppm and in males give 200 ppm. Males given 100 ppm or above and females given 200 or 800 ppm produced less urine than the controls in a period without water or following a water load. The only changes in organ weight that could be attributed to treatment were increased values for the relative weights of liver, spleen and kidney. All 3 organs were affected in both sexes given 800 ppm and the kidneys were also affected in both sexes given 200 ppm and in females given 100 ppm. No effects attributable to allyl alcohol treatment were seen at autopsy or in the histopathological examination. The no-untoward-effect level established in this study was 50 ppm of the drinking water, a level equivalent to an intake in rats of between 4.8 and 6.2 mg allyl alcohol/kg/day.


Major and trace metals in suspended and bottom sediments of the Mandovi and Zuari estuaries, western India: distribution, source, and pollution.
Major elements and trace metals in suspended sediments along transect stations of the Mandovi and Zuari estuaries showed three types of distribution: (a) high concentrations of most metals (Al, Fe, Mn, Cr, Pb, Cu, Ni, Zn, Co, Sc, Mo, and U) in the upper estuary and their decreasing concentrations seaward in every season, (b) lower concentrations of some metals (Mg, Cr, Zr, V, Al, Th) in the upper estuary and bay and their increased concentrations in the lower estuary, and (c) higher concentrations of some metals (Cu, Ni, Zn, Pb, and Cr) in the upper estuary and bay and their decreased concentrations in the lower estuary. Mn was the most significant pollutant in both the estuaries. The Zn, Cr, Fe, and Mo in Mandovi during the monsoon and post-monsoon and, Pb, Ni, and Cr in Zuari during the post- and pre-monsoons were in the range "moderately to heavily polluted." The pollution load index of metals was high at upstream stations, with higher values in Mandovi during monsoon and Zuari during the post- and pre-monsoons. Most trace metals were correlated with Fe and Mn indicating their association primarily with Fe-Mn ore material. The principal component analysis indicated natural and anthropogenic inputs and the latter was predominantly related to ore material in both the estuaries. The distribution factor was high for Al, Mg, Zr, Th, and U in < 2-μm fraction and Cr, Cu, Ni, Zn, Co, V, Sc, and Zr in 2-4-μm size fraction sediments suggesting two sources of sediments. More than 60% concentrations of all trace metals were associated with < 2-μm fraction sediments. The distribution of trace metals along transect was affected by the physico-chemical conditions of the estuary, grain size of sediments, and anthropogenic contribution of metals.


Neural correlates of incidental memory in mild cognitive impairment: an fMRI study.
Behaviour and fMRI brain activation patterns were compared during encoding and recognition tasks in mild cognitive impairment (MCI) (n=14) and normal controls (NC) (n=14). Deep (natural vs. man-made) and shallow (color vs. black and white) decisions were made at encoding and pictures from each condition were presented for yes/no recognition 20 min later. MCI showed less inferior frontal activation during deep (left only) and superficial encoding (bilaterally) and in both medial temporal lobes (MTL). When performance was equivalent (recognition of words encoded superficially), MTL activation was similar for the two groups, but during recognition testing of deeply encoded items NC showed more activation in both prefrontal and left MTL region. In a region of interest analysis, the extent of activation during deep encoding in the parahippocampi bilaterally and in left hippocampus correlated with subsequent recognition accuracy for those items in controls but not in MCI, which may reflect the heterogeneity of activation responses in conjunction with different degrees of pathology burden and progression status in the MCI group.


Obstructive uropathy from endometriosis after hysterectomy and oophorectomy; two case reports.
Two patients with obstructive uropathy as a result of post menopausal endometriosis are reported. They both illustrate the potential problems of hormone replacement therapy after bilateral salpingo-oophorectomy and hysterectomy in patients who have had extensive endometriosis. It is suggested that in such patients the potential of reactivation of the disease with hormone-replacement therapy should be recognised and ureteric involvement be excluded by intravenous urography or renograms.


Fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric cancer with peritoneal metastasis.
There are few data on the efficacy of combination chemotherapy with a fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric cancer (AGC) complicated by peritoneal metastasis, especially massive ascites. We retrospectively evaluated the efficacy and safety of a fluoropyrimidine (S-1 or capecitabine) plus cisplatin as first-line chemotherapy in 120 patients with AGC and peritoneal metastasis. Ascites was detected in 50 patients, with 11 patients having massive ascites. Median progression-free survival (PFS) and overall survival (OS) of all patients was 6.1 and 15.9 months, respectively. The PFS and OS were shorter in patients with massive ascites (n = 11; 3.7 and 9.5 months) compared with patients with small or moderate ascites (n = 39; 5.8 and 13.5 months) or patients without ascites (n = 70; 6.9 and 18.1 months). The objective response in terms of ascites was similar whether ascites was massive (4 of 11 patients; 36.4%) or small or moderate (16 of 39 patients; 41%). The frequencies of grade 3 or higher toxicity or treatment discontinuation due to toxicity are relatively similar across ascites groups. Fluoropyrimidine plus cisplatin appears to be tolerated in selected patients with peritoneal metastasis.


Synthesis, preliminary structure-activity relationships, and in vitro biological evaluation of 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives as potential anti-inflammatory agents.
In our previous study, a series of 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives exhibited potent antiproliferative activities and an unique hepatocellular carcinoma (HCC)-specific anticancer activity was also observed. In further anti-inflammatory research, thienopyridine derivative 1a showed potent inhibition of nitric oxide (NO) production. So a series of thienopyridine analogues of 1a were synthesized and evaluated for anti-inflammatory activities. The structure-activity relationships (SARs) revealed that the most potent analogues 1f and 1o were identified as potent inhibitors of NO production with IC50 values of 3.30 and 3.24 μM, respectively. These results suggest that these 6-aryl-3-amino-thieno[2,3-b]pyridine derivatives might potentially constitute a novel class of anti-inflammatory agents, which require further studies.


Association between dietary folate intake and severe headache among adults in the USA: a cross-sectional survey.
Folate, also known as vitamin B9, is a water-soluble vitamin. Previous studies on dietary folate intake in severe headache patients were equivocal. Therefore, we conducted a cross-sectional study to elucidate the relationship between folate intake and severe headache. This cross-sectional study used data from participants over 20 years old who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The diagnosis of severe headache was made through participants' self-report in the NHANES questionnaire section. We performed multivariate logistic regression and restricted cubic spline (RCS) regression to explore the relationship between folate intake and severe headache. A total of 9859 participants took part in the study, 1965 of whom were severe headache patients and the rest were non-severe headache. We found that dietary folate intake was significantly and inversely associated with severe headache. Compared with participants with lower folate intake Q1 (≤ 229·97 ug/d), the adjusted OR values for dietary folate intake and severe headache in Q2 (229·98-337 ug/d), Q3 (337·01-485 ug/d) and Q4 (≥ 485·01 ug/d) were 0·81 (95 % CI: 0·67, 0·98, P = 0·03), 0·93 (95 % CI: 0·77, 1·12, P = 0·41) and 0·63 (95 % CI: 0·49, 0·80, P < 0·001), respectively. For women aged 20-50 years, there was a non-linear association between folate intake and severe headache in the RCS. Women aged 20-50 years should have higher awareness of dietary folate and increase their dietary intake of folate, which may aid in preventing severe headache.


Adenovirus-mediated RNA interference targeting FOXM1 transcription factor suppresses cell proliferation and tumor growth of nasopharyngeal carcinoma.
The Forkhead Box M1 (FOXM1) transcription factor, which regulates the expression of genes essential for cell proliferation and transformation, is implicated in tumorigenesis and tumor progression. FOXM1 has attracted much attention as a potential target for the prevention and/or therapeutic intervention in human carcinomas. The levels of FOXM1 expression in clinical tissue specimens and cell lines of human malignant nasopharyngeal carcinoma (NPC) were measured. Knockdown of FOXM1 expression was performed by small interfering RNA in NPC cells. An adenovirus vector (named AdFOXM1shRNA) was constructed to express a short hairpin RNA specific to FOXM1. The efficacy of AdFOXM1shRNA for tumor gene therapy in NPC cells and an in vivo NPC grafting model was assessed. A strong expression of FOXM1 was observed in clinical tissue specimens and cell lines of human NPC. Knockdown of FOXM1 expression by FOXM1 specific small interfering RNA diminished the NPC cell proliferation. The infection of AdFOXM1shRNA in NPC cells resulted in the knockdown of FOXM1 mRNA and protein levels, correlated with the reduction of proliferation and anchorage-independent growth of the cancer cells. The growth of NPC tumors was significantly suppressed when inoculated mice were injected with AdFOXM1shRNA in the tumor. Together, our results suggest that FOXM1 is a potential therapeutic target for NPC and AdFOXM1shRNA may be an additional gene therapeutic intervention to be evaluated in future treatment strategies for patients with NPC.


A unique AA5 alcohol oxidase fused with a catalytically inactive CE3 domain from the bacterium Burkholderia pseudomallei.
Copper radical oxidases (CROs) are redox enzymes able to oxidize alcohols or aldehydes, while only requiring a single copper atom as cofactor. Studied CROs are found in one of two subfamilies within the Auxiliary Activities family 5 (AA5) in the carbohydrate-active enzymes database. We here characterize an AA5 enzyme outside the subfamily classification from the opportunistic bacterial pathogen Burkholderia pseudomallei, which curiously was fused to a carbohydrate esterase family 3 domain. The enzyme was shown to be a promiscuous primary alcohol oxidase, with an activity profile similar to enzymes from subfamily 2. The esterase domain was inactive on all tested substrates, and structural predictions revealed this being an effect of crippling substitutions in the expected active site residues.


Targeted expression of redesigned and codon optimised synthetic gene leads to recrystallisation inhibition and reduced electrolyte leakage in spring wheat at sub-zero temperatures.
Antifreeze proteins (AFPs) adsorb to ice crystals and inhibit their growth, leading to non-colligative freezing point depression. Crops like spring wheat, that are highly susceptible to frost damage, can potentially be made frost tolerant by expressing AFPs in the cytoplasm and apoplast where ice recrystallisation leads to cellular damage. The protein sequence for HPLC-6 alpha-helical antifreeze protein from winter flounder was rationally redesigned after removing the prosequences in the native protein. Wheat nuclear gene preferred amino acid codons were used to synthesize a recombinant antifreeze gene, rAFPI. Antifreeze protein was targeted to the apoplast using a Murine leader peptide sequence from the mAb24 light chain or retained in the endoplasmic reticulum using C-terminus KDEL sequence. The coding sequences were placed downstream of the rice Actin promoter and Actin-1 intron and upstream of the nopaline synthase terminator in the plant expression vectors. Transgenic wheat lines were generated through micro projectile bombardment of immature embryos of spring wheat cultivar Seri 82. Levels of antifreeze protein in the transgenic lines without any targeting peptide were low (0.06-0.07%). The apoplast-targeted protein reached a level of 1.61% of total soluble protein, 90% of which was present in the apoplast. ER-retained protein accumulated in the cells at levels up to 0.65% of total soluble proteins. Transgenic wheat line T-8 with apoplast-targeted antifreeze protein exhibited the highest levels of antifreeze activity and provided significant freezing protection even at temperatures as low as -7 degrees C.


Target Selection during Protein Quality Control.
Protein quality control (QC) pathways survey the cellular proteome to selectively recognize and degrade faulty proteins whose accumulation can lead to various diseases. Recognition of the occasional aberrant protein among an abundant sea of similar normal counterparts poses a considerable challenge to the cell. Solving this problem requires protein QC machinery to assay multiple molecular criteria within a spatial and temporal context. Although each QC pathway has unique criteria and mechanisms for distinguishing right from wrong, they appear to share several general concepts. We discuss principles of high-fidelity target recognition, the decisive event of all protein QC pathways, to guide future work in this area.


A rare case of coiling of the brachial artery: a description of the sonographic features.
We report the case of a patient with 360° coiling of the brachial artery that had been previously misdiagnosed as aneurysms of the right brachial artery on sonography performed at another institution. The previous misdiagnosis occurred due to sonographic pitfalls in gray-scale and color imaging, which led the operator to make a false interpretation. Knowledge of Doppler analysis and sonographic interpretation of arterial coiling may improve the diagnostic accuracy for this condition.


Caffeine and muscarinic antagonists act in synergy to inhibit haloperidol-induced catalepsy.
The possible synergism between caffeine and muscarinic antagonists to inhibit haloperidol-induced catalepsy was investigated with the bar test in rats. Pretreatment with low doses of caffeine (1-3 mg/kg), a non-selective adenosine antagonist, dose dependently reduced the intensity and increased the onset latency of catalepsy induced by haloperidol (0.5-2 mg/kg). Similar effects were produced by the muscarinic antagonists atropine (4.1 mg/kg), and trihexyphenidyl (THP, 0.01-3 mg/kg). THP inhibited catalepsy intensity with an ED(50) of 0.38 mg/kg, and increased its onset latency with an ED(50) of 0.52 mg/kg. The anticataleptic effect of anticholinergics was potentiated when a low dose of caffeine (1 mg/kg) was applied simultaneously. In the presence of caffeine, THP inhibited catalepsy intensity with an ED(50) of 0.19 mg/kg, and prolonged the latency with an ED(50) of 0.30 mg/kg. The synergism was more evident when THP was administered at subthreshold doses that were unable to modify haloperidol-induced catalepsy when applied alone, but produced a clear inhibition of catalepsy when injected with caffeine. To assess whether repeated administration of caffeine could induce tolerance to the synergism with THP, a group of rats was pretreated with three daily doses of caffeine (1 mg/kg) for seven days, and the catalepsy test was performed on the eighth day. In these animals, caffeine was still able to enhance the anticataleptic actions of THP, suggesting that repeated administration of 1 mg/kg caffeine does not induce tolerance to the synergism with anticholinergics. These results indicate that low doses of caffeine enhance the anticataleptic actions of muscarinic antagonists, and leave open the possibility of using caffeine as adjunctive therapy to reduce the doses and the adverse effects of anticholinergics in Parkinson's disease.


Maternal sepsis.
Maternal sepsis is relatively common. Most of these infections are the result of tissue damage during labor and delivery and physiologic changes normally occurring during pregnancy. These infections, whether directly pregnancy-related or simply aggravated by normal pregnancy physiology, ultimately have the potential to progress to severe sepsis and septic shock. This article discusses commonly encountered entities and septic shock. The expeditious recognition of common maternal sepsis and meticulous attention to appropriate management to prevent the progression to severe sepsis and septic shock are emphasized. Also discussed are principles and new approaches for the management of septic shock.


Can advanced edge enhancement software improve image quality to visualise tubes, catheters and wires in digital chest radiographs?
This study aimed to test whether Advanced Edge Enhancement (AEE) software could improve the localisation of tubes, catheters or wires, while also affecting the overall image quality in chest x-rays (CXR). In total, 50 retrospective CXRs were included. All images were obtained utilising the Canon X-ray system (CANON/Arcoma Precision T3 DR System, Canon Europe, Amsterdam, NL) with a CXDI-810C wireless detector. A clinical image, plus three additional AEE algorithms were applied using post processing (two intensity variations 1 and 4) on all CXRs totalling 350 different images. Three radiologists evaluated the images using a subjective Absolute Visual Grading Analysis (VGA). The clinical images used in post processing were not applied as reference in the analysis. Each radiologist graded the images separately in a randomized order, with a score of three indicating suitability for diagnostic assessment. The three AEE algorithms contributed to an overall improvement (average 16-49%) in visualisation of tube, catheter or wire on CXR images. The Mann-Whitney U tests showed a statistically significant (p < 0.05) improvement in contrast resolution and sharpness, indicating an increased ability to differentiate tubes, wires or catheters tips from surrounding tissues. For the noise criterion, not applying any AEE algorithm showed a significantly higher homogeneity in soft tissue (p < 0.001), reducing the ability to visualise soft tissue. The high-intensity catheter algorithm was the only algorithm to achieve a statistically significant (p = 0.017) increase in the ability to differentiate pulmonary tissues of similar density. An overall improvement in the visualisation of tube, catheter and wire placement was obtained using the three AEE-algorithms. The bone and catheter algorithms showed the highest consistency, with the small structure algorithm underperforming in resolution and low contrast resolution. In general, image noise increased regardless of algorithm type or applied intensity. The AEE-algorithms should therefore be seen as a supplementary tool to the clinical image protocol, while having the potential to improve image quality to specific clinical situations. AEE filtered images appear to be a supplement to the current practice of using CXRs in the diagnosis in placement of catheters, tubes and wires in the chest region. The use of AEE-algorithms has the potential to improve the daily work in clinical practice, which serves the basis for further investigation of its effect on radiographic practices.


A review on 129I analysis in air.
A review of literature focused on (129)I determination in air is provided. (129)I analysis in the environment represents a vital tool for tracing transport mechanisms, distribution pathways, safety assessment and its application as environmental tracer. To achieve that, specific chemical extraction methods and high sensitivity analytical techniques have been developed. This paper is intended to give an overview about the sample collection, extraction and distribution of (129)I in the air. Sensitivity of available measurement techniques for the determination of (129)I is compared. The article also provides the summary of current worldwide distribution of (129)I in air and respective radiation exposure of man.


U.S. trends in prescription nonsteroidal anti-inflammatory drug use among patients with cardiovascular disease, 1988-2016.
Nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased risk of adverse cardiovascular events prompting labeling revisions cautioning their use among patients with cardiovascular disease (CVD). However, little is known regarding long-term trends in real-world prescribing of NSAIDs within the CVD population. We aimed to characterize the use of prescription NSAIDs among U.S. adults with CVD from 1988 to 2016. We used the National Health and Nutrition Examination Survey cross-sectional data from 1988-1994 and 19992016 to identify participants aged greater than or equal to 18 years with hypertension (defined by self-report, mean blood pressure ≥ 140/90 mm Hg, or antihypertensive medication use), or aged greater than or equal to 20 years with self-reported congestive heart failure (CHF), coronary heart disease (CHD), angina, myocardial infarction (MI), or stroke. Prevalence of prescription NSAID use was analyzed in 6-year examination periods. Weighted logistic regression was performed to test time trends in prescription NSAID use. Overall, prescription NSAID use declined among all CVD populations. The highest prevalence of overall prescription NSAID use was observed during the 1999-2004 examination years, thereafter declining through the 2005-2010 and 2011-2016 examination years: in patients with hypertension (13.9% [1999-2004] to 8.5% [2011-2016]), CHF (14.6%-8.5%), CHD (16.3%-7.4%), angina (17.6%-8.5%), MI (16.1%-9.0%), and stroke (15.7%-7.9%). Decreased use of COX-2-selective inhibitors was observed during the same period; whereas, nonselective NSAID use remained relatively stable. Trends in prescription NSAID use were reflective of the general adult population. Prescription NSAID use among patients with CVD appears to have declined from 1988 to 2016, primarily due to reduced COX-2-selective inhibitor use. Nonetheless, the prevalence of prescription NSAIDs has persisted among a subset of high-risk CVD populations.


Room temperature removal of high-space-velocity formaldehyde boosted by fixing Pt nanoparticles into Beta zeolite framework.
Catalytic oxidation of volatile organic compounds like formaldehyde (HCHO) over the noble metals catalysts at room temperature is among the most promising strategies to control indoor pollution but remains one challenge to maximize the efficiency of noble metal species. Herein, we demonstrated the straightforward encapsulation of highly dispersive Pt nanoparticles (NPs) within BEA zeolite and adjacent with the surface hydroxyl groups to reach the synergistic HCHO oxidation at 25 °C. High efficiency and long-term stability was reached under large space velocity (∼100% conversion at 180,000 mL (gcat × h)-1 and >95% at 360,000 mL (gcat × h)-1), affording rapid elimination rate of 129.4 μmol (gPt × s)-1 and large turnover frequency of 2.5 × 10-2 s-1. This is the first synergy example derived from the hydroxyl groups and confined noble metals within zeolites that accelerated the rate-determining step, the formate transformation, in the HCHO elimination.


Atopic dermatitis guidelines: Diagnosis, systemic therapy, and adjunctive care.
Atopic dermatitis is an important and chronic skin condition that has recently been the subject of enormous volumes of basic science, clinical, and epidemiologic research. This field is undergoing rapid expansion, making it vitally important to integrate the emerging data with our current body of knowledge. In 2014, the American Academy of Dermatology published Guidelines of Care for the Management of Atopic Dermatitis, composed of four parts, reflecting the work of 17 experts from North America and the United Kingdom.1-4 It uses a patient-oriented system, SORT (Strength of Recommendation Taxonomy), to provide evidence-based guidance in the management of this common, vexing dermatitis. These guidelines join a series of similar efforts published recently across the world, reflecting universal interest in distilling the tremendous volume of basic scientific and clinical data previously generated.5-7 With new therapies rapidly emerging, clinicians require a current understanding of the field to be able to incorporate new treatments in their practice.


Benign osteoblastoma of the odontoid process of the axis with secondary aneurysmal bone cyst component: a case report.
The authors report their experience on one patient with osteoblatoma of the odontoid process of the axis with secondary aneurysmal bone cyst. According to their knowledge, this is the first case, reported in the literature, of this kind of lesion in that particular anatomical region. Because of the rarity of this lesion, it was difficult to have a certain preoperative diagnosis. Therefore, the patient underwent a biopsy via a transoral route. The biopsy was performed over the noncalcified component of the lesion. The intraoperative histological examination showed the benign nature of the lesion. Thereafter, the lesion was totally removed, succeeding in preserving the remaining part of the odontoid process and the anterior arch of C1. In the follow-up, there was no evidence of cranio-vertebral instability. The histological examination revealed an osteoblastoma of the odontoid process of the axis with a secondary aneurysmal bone cyst. To the best of our knowledge, this is the first case reported in the literature.


The management of exfoliative glaucoma.
Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues and is the most common identifiable cause of open-angle glaucoma worldwide. XFS plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract, and retinal vein occlusion. It is accompanied by an increase in serious complications at the time of cataract extraction, such as zonular dialysis, capsular rupture, and vitreous loss. It is associated systemically with an increasing number of vascular disorders, hearing loss, and Alzheimer's disease. XFS appears to be a disease of elastic tissue microfibrils. The characteristic fibrils, composed of microfibrillar subunits surrounded by an amorphous matrix comprising various glycoconjugates, contain predominantly epitopes of elastic fibers, such as elastin, tropoelastin, amyloid P, vitronectin, and components of elastic microfibrils, such as fibrillin-1, fibulin-2, vitronectin, microfibril-associated glycoprotein (MAGP-1), and latent TGF-beta binding proteins (LTBP-1 and LTBP-2), the proteoglycans syndecan and versican, the extracellular chaperone clusterin, the cross-linking enzyme lysyl oxidase, and other proteins. A recent milestone study showed that two common single nucleotide polymorphisms in the coding region of the lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically associated with XFS and XFG. LOXL1 is a member of the lysyl oxidase family of enzymes, which are essential for the formation, stabilization, maintenance, and remodeling of elastic fibers and prevent age-related loss of elasticity of tissues. LOXL1 protein is a major component of exfoliation deposits and appears to play a role in its accumulation and in concomitant elastotic processes in intra- and extraocular tissues of XFS patients. This discovery should open the way to new approaches and directions of therapy for this protein disorder.


Boosting B Cell and Macrophage-Mediated Humoral Immunity with Fusion Nanovesicles for Triple-Negative Breast Cancer Combined Therapy.
Cell-derived nanovesicles are widely utilized as therapeutic agents for cancer therapy. Current research mostly focuses on their ability to activate antitumor cellular immunity. However, whether they can activate and participate in antitumor humoral immunity is rarely studied. Here, doxorubicin-loaded hybrid cell nanovesicles (DNVs) are designed for boosting antitumor humoral and cellular immunity. The hybrid cell nanovesicles are generated through fusion of nanovesicles derived from M1-type macrophages and 4T1 tumor cells. It is found that DNVs can accumulate at tumor tissues and draining lymph nodes effectively, which results in the activation of antitumor immune response and significant inhibition of tumor progression. During this process, dendritic cells are effectively activated, subsequently inducing cytotoxicity T lymphocytes-mediated cellular immunity. Furthermore, DNVs elicit the antitumor humoral immunity through boosting T follicular helper cells and germinal center B cells. By analyzing the mechanism behind humoral immunity activation, it is found that M1-type macrophages repolarized by DNVs play an important role. In general, besides antitumor cellular immunity, the proposed hybrid nanovesicles provide a promising strategy for enhancing antitumor humoral immunity by macrophages repolarization and germinal center B cells activation.


[Alterations of Rous virus and polyoma virus during their synthesis in the cells of unnatural hosts].
The line of human embryo fibroblasts transformed by Rous sarcoma virus (strain Schmidt-Ruppin) contained and produced Rous sarcoma virus; this was shown by the complement fixation test, immunofluorescent test, electron microscopy and labelling with 3H-uridine peak in sucrose gradient. Biological properties of the new synthesized virus differed from that of the parent Schmidt-Ruppin strain; the range of the sensitive cells and the protein envelope antigens altered in particular. Analogous results by the change of the viral biological properties produced in the unnatural host tissue were obtained for polioma virus synthesized in the human embryo fibroblasts transformed by this virus.


Child abuse and neglect in Greece: sociomedical aspects.
Fifty-four abused and neglected children have been referred to our multidisciplinary team for assessment and treatment. There were many more boys than girls (36 vs 18) and the mean age was 3.3 years. Half of the children were admitted for medical reasons and abuse or neglect were secondary findings. The medical findings included bruises and fractures, head injuries, knife wounds, and failure to thrive. The children's main characteristics were: "difficult children," unwanted pregnancies, difficult pregnancies and deliveries and half of them were separated from their mothers during the first months of life due to illness. The families were characteristic of multiproblem families of low social level. Almost all parents were young when married and half were unemployed or had unsteady employment. In most cases the parents were socially isolated and had poor relations with their families of origin. Most mothers and half of the fathers had an unhappy childhood while almost half of the mothers had a psychiatric problem. In general, our findings were in accordance with those described in other nations. Nevertheless, there were some characteristics which seem to be of relevance within the Greek ethnic and cultural context. The legal problems as well as those pertaining to child protection are discussed.


Heat-air-moisture modeling for prediction of interior surface condensation of lift-and-slide window - Case study.
Metal - aluminium windows have an important position in residential architecture. High thermal conductivity, as the main material disadvantage of aluminium, is solved by decoupling the thermal bridge. With the improved geometry of the frames and the appropriate break of the thermal bridge, high-performance systems are achieved, used for all-glazed facades of various building categories around the world. Mathematical modelling methods enable highly accurate prediction of the system's behaviour, thereby achieving shape and material optimization of the frame and glazing concept. Despite this, there are products on the market that show defects of a thermal technical nature, which is caused, among other things, by the absence of a standard requirement for the minimum surface temperature of the window in some countries (e.g. the Czech Republic). The subject of the study is condensation on the surface of the glazing bead of aluminium lift-and-slide windows in a residential complex in eastern Slovakia. The occurrence of condensation is conditioned by operating boundary conditions - air temperature, relative air humidity, heating and ventilation mode. Through experimental measurements and subsequent modelling, the cause of the structural failure was determined, alternative solutions were proposed, and the optimal solution for adjusting the glazing bead was selected. The modelling methodology used is derived for use in determining condensation risk. With external boundary conditions from Typical Meteorological Year - ASHRAE 2.0 (TMY) for the Prešov (SK) location, the annual decrease in the amount of condensation and condensation time after the adjustment of the glazing bead compared to the original construction was determined.


Low speed limits in residential areas in Melbourne, Australia.
Objective: This study set out to provide pretrial data for use in evaluating the benefits of lower speed limits in a local residential area in Melbourne.Methods: An online survey was conducted to assess community views among residents to the proposed trial on a number of relevant issues, along with speed measurements at more than 70 road sites in the region.Findings: The findings showed a degree of support for reducing the speed in local streets in the trial region, even though most respondents thought the current speed limit (40 km/h, 25 mph) was about right. Most agreed that reducing the speed limit in the region was good for safety and would make the area more pleasant. The average travel speed was 28.3 km/h (17.7 mph) and the 85th percentile speed was 35.0 km/h (21.9 mph) from onsite speed measurement (42% of the individual speeds recorded at the test sites were over 30 km/h or 18.75 mph).Conclusions: These findings give support to the expectation that lower speed limits on local streets may be possible with good community support.


Effect of metformin in addition to an antenatal diet and lifestyle intervention on fetal growth and adiposity: the GRoW randomised trial.
The infants born to women who are overweight or obese in pregnancy are at an increased risk of being born macrosomic or large for gestational age. Antenatal dietary and lifestyle interventions have been shown to be ineffective at reducing this risk. Our aim was to examine the effects of metformin in addition to a diet and lifestyle intervention on fetal growth and adiposity among women with a BMI above the healthy range. Women who had a body mass index ≥25 kg/m2 in early pregnancy, and a singleton gestation, were enrolled in the GRoW trial from three public maternity hospitals in metropolitan Adelaide. Women were invited to have a research ultrasounds at 28 and 36 weeks' gestation at which ultrasound measures of fetal biometry and adiposity were obtained. Fetal biometry z-scores and trajectories were calculated. Measurements and calculations were compared between treatment groups. This secondary analysis was pre-specified. Ultrasound data from 511 women were included in this analysis. The difference in femur length at 36 weeks' gestation was (0.07 cm, 95% CI 0.01-0.14 cm, p = 0.019) and this was was statistically significant, however the magnitude of effect was small. Differences between treatment groups for all other fetal biometry measures, z-scores, estimated fetal weight, and adiposity measures at 28 and 36 weeks' gestation were similar. The addition of metformin to dietary and lifestyle advice in pregnancy for overweight and obese women has no clinically relevant effect on ultrasound measures of fetal biometry or adiposity. Australian and New Zealand Clinical Trials Registry ( ACTRN12612001277831 ).


Genetic analysis of the low responsiveness to dextran B512 in CBA/N and C57BL/10ScCr mice.
CBA/N and C57BL/10ScCr mice are low responders to the antigen dextran B512. This is due to the Xid gene in CBA/N mice and to unknown genes in C57BL/10ScCr mice, although this strain is unresponsive to lipopolysaccharide (LPS) due to a defective gene in the fourth chromosome. The female F1 hybrids (C57BL/10ScCr X CBA/N) and (CBA/N X C57BL/10ScCr) were low responders to dextran, although the Xid gene is not expressed in these hybrids, indicating lack of genetic complementation. In contrast, female F1 hybrids between the dextran high-responder strains CBA or C57BL/10 as one parental strain and the low-responder strains CBA/N or C57BL/10ScCr as the other parental strain, respectively, were responders to dextran. The C57BL/10ScCr mice did not appear to have an X-linked gene determining low responsiveness to dextran. The findings suggest that the only defect in CBA/N mice cannot be the Xid gene and the only defect in C57BL/10ScCr mice cannot be the gene determining unresponsiveness to LPS.


Thoracic Outlet Syndrome: Diagnostic Accuracy of MRI.
Thoracic outlet syndrome (TOS) is challenging to diagnose, as the physical findings and investigations lack sensitivity and/or specificity. Magnetic resonance imaging (MRI) with dynamic manoeuvres can rule out a tumour and detect anatomical abnormalities potentially responsible for compression. The objective of this study was to assess the sensitivity and specificity of MRI for identifying anatomical structures responsible for compression in TOS, using intra-operative findings as the diagnostic reference standard. MRI is effective in diagnosing the source of compression in TOS, notably within the scalene triangle and at the pleural apex. We retrospectively included 48 patients who underwent surgery for TOS after a work-up that included MRI (1.5-T, n=29 and 3-T, n=19). The MRI scans were reviewed for the study by a specialised radiologist who was unaware of the intra-operative findings. The sensitivity and specificity of MRI for diagnosing TOS were estimated using the intra-operative findings as the reference standard. MRI identified a structure potentially responsible for TOS in 34 (71%) patients; thus, the false-negative rate was 14/48 (29%). The sensitivity of MRI was 28% for compression at the suspensory ligament of the pleural dome, 81% for hypertrophy of the anterior scalene muscle, and 50% for an accessory scalene muscle. For diagnosing a cervical rib, MRI had 100% sensitivity and 100% specificity. MRI can contribute to the diagnosis of TOS. Specificity is sufficiently high to provide guidance for planning the surgical procedure. Sensitivity, however, is too low for MRI to be useful as a screening test. MRI should be used in combination with the clinical assessment and other investigations to assist in the diagnosis of TOS. IV, retrospective cohort study.


Prognostic factors for adult sarcomas of head and neck.
The optimal management of adult soft-tissue sarcomas is not clearly established. To assess prognostic factors and survival, the experience of 45 recent successive cases was reviewed. Data were collected from a retrospective database (1993-2005) and statistically analyzed. Rhabdomyosarcomas were excluded. The mean age was 50.1 years; there were 24 men and 21 women. The main histological subtypes were undifferentiated sarcoma (14) and angiosarcoma (10); 21 tumours were grade 3 (46%). The most frequent primary sites were neck muscles (15, 33%) and scalp (11, 24%). At presentation, 5 (20%) cases with lymph-node involvement and another 11 cases (24%) with distant metastasis were observed. The treatment was with curative intent in 33 cases (73%). This entailed surgery, with adjuvant radiotherapy in 15 cases and adjuvant chemotherapy in 5 cases. The 5-year overall survival was 52% (+/-8%). In univariate analysis, the poor prognostic factors were high grade, initial metastasis or lymph nodes, absence of surgery, and number of surgical procedures. In multivariate analysis, two factors remained significant: grade (P=0.006) and absence of surgery (P=0.005). After taking into account grade and metastasis at presentation, quality of surgery has prognostic value. The primary aim of a multidisciplinary approach to these tumours must favour complete resection.


Reciprocal modulation between microglia and astrocyte in reactive gliosis following the CNS injury.
Reactive gliosis, also known as glial scar formation, is an inflammatory response characterized by the proliferation of microglia and astrocytes as well as astrocytic hypertrophy following injury in the central nervous system (CNS). The glial scar forms a physical and molecular barrier to isolate the injured area from adjacent normal nervous tissue for re-establishing the integrity of the CNS. It prevents the further spread of cellular damage but represents an obstacle to regrowing axons. In this review, we integrated the current findings to elucidate the tightly reciprocal modulation between activated microglia and astrocytes in reactive gliosis and proposed that modification of cellular response to the injury or cellular reprogramming in the glial scar could lead advances in axon regeneration and functional recovery after the CNS injury.


Differential effects of main error correction versus secondary error correction on motor pattern of running.
The aim of this study was to gain a better understanding of how the run pattern varies as a consequence to main error correction versus secondary error correction. Twenty-two university students were randomly assigned to one of two training-conditions: 'main error' (ME) and 'secondary error' (SE) correction. The rear-foot strike at touchdown was hypothesized as the 'main error', whereas an incorrect shoulder position (i.e., behind the base of support) as the 'secondary error'. In order to evaluate any changes in run pattern at the foot touchdown instant, the ankle, knee and hip joint angles, the height of toe and heel (with respect to the ground), and the horizontal distance from the heel to the projected center of mass on the ground were measured. After the training-intervention, the ME group showed a significant improvement in the run pattern at the foot touchdown instant in all kinematic parameters, whereas no significant changes were found in the SE group. The results support the hypothesis that the main error can have a greater influence on the movement patterns than a secondary error. Furthermore, the findings highlight that a correct diagnosis and the correction of the 'main error' are fundamental for greater run pattern improvement.


Heart failure and airway obstruction.
We investigated 60 patients with severe left-sided heart failure before and after cardiac recompensation. We observed that the cardiac insufficiency had a marked effect on dynamic ventilatory parameters. The "effort independent part" of the flow-volume curve was changed significantly by means of cardiac therapy.


Immunopathological events surrounding IL-6 and IFN-α: A bridge for anti-lupus erythematosus drugs used to treat COVID-19.
With the outbreak and rapid spread of COVID-19, the world health situation is unprecedentedly severe. Systemic lupus erythematosus (SLE) is a common autoimmune disease, which can cause multiple organ damage. Numerous studies have shown that immune factors have important roles in the pathogenesis of both COVID-19 and SLE. In the early stages of COVID-19 and SLE pathogenesis, IFN-α expression is frequently increased, which aggravates the virus infection and promotes SLE development. In addition, increased IL-6 levels, caused by different mechanisms, are observed in the peripheral blood of patients with severe COVID-19 and SLE, stimulating a series of immune cascades that lead to a cytokine storm, as well as causing B cell hyperfunction and production of numerous of antibodies, aggravating both COVID-19 and SLE. In this review, we explore the background immunopathological mechanisms in COVID-19 and SLE and analyze the advantages and disadvantages of commonly used SLE drugs for patients with COVID-19, to optimize treatment plans for patients with SLE who develop COVID-19.


Advances in 3D culture systems for therapeutic discovery and development in brain cancer.
This review focuses on recent advances in 3D culture systems that promise more accurate therapeutic models of the glioblastoma multiforme (GBM) tumor microenvironment (TME), such as the unique anatomical, cellular, and molecular features evident in human GBM. The key components of a GBM TME are outlined, including microbiomes, vasculature, extracellular matrix (ECM), infiltrating parenchymal and peripheral immune cells and molecules, and chemical gradients. 3D culture systems are evaluated against 2D culture systems and in vivo animal models. The main 3D culture techniques available are compared, with an emphasis on identifying key gaps in knowledge for the development of suitable platforms to accurately model the intricate components of the GBM TME.


The effect of complete and incomplete revascularization on exercise variables in patients undergoing coronary angioplasty.
To investigate the effects of complete and incomplete revascularization on the response to exercise, 25 patients underwent symptom-limited exercise testing with continuous assessment of gas exchange a mean of 5 +/- 4 days prior to and 18 +/- 12 days following percutaneous transluminal coronary angioplasty. All antianginal medications were discontinued for testing. Revascularization was considered complete if all stenoses were reduced to less than 50% diameter (13 patients), and incomplete if one or more stenoses remained (12 patients). Consistent improvements in ST-segment depression were observed after angioplasty at matched submaximal exercise levels (mean range 0.5-0.8 mm; p less than 0.05), and were accompanied by a reduction in angina. Significant increases in heart rate and systolic blood pressure were observed at peak exercise following angioplasty in both groups. Gas exchange variables were significantly improved at maximal exercise, with a similar increase in oxygen uptake observed in both groups following angioplasty (mean increase 3.3-3.7 ml/kg/min; p less than 0.01). Thus, incomplete revascularization following coronary angioplasty resulted in hemodynamic, electrocardiographic, symptomatic, and gas exchange responses to exercise that were comparable to complete revascularization.


Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis--the CaVenT study: rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771).
The conventional treatment of acute deep vein thrombosis (DVT) is anticoagulation and compression therapy, as recommended in the international guidelines. Anticoagulation prevents recurrent venous thrombosis, pulmonary embolism, and death. Compression therapy reduces the risk of developing long-term sequelae, that is, postthrombotic syndrome (PTS). Evaluation of systemic thrombolysis has shown effective thrombolysis and a likely reduction in PTS but at the cost of increased risk of bleeding complications. Catheter-directed thrombolysis (CDT) was introduced for rapid removal of thrombi and salvage of venous valves with less systemic thrombolytic effect, and is being offered to selected patients with iliofemoral DVT to prevent development of PTS. Case series have shown technical and thrombolytic success; however, no randomized studies have evaluated the long-term clinical effects of venous CDT. The aim of the CaVenT study is to investigate the role of adjunctive CDT by evaluating its clinical efficacy and safety compared with conventional treatment alone in patients with acute iliofemoral DVT. The CaVenT study is an open, randomized, controlled, clinical trial. We plan to include 200 patients who will receive either CDT, in addition to conventional treatment, or conventional treatment alone. The primary outcome measures are patency at 6 months and prevalence of PTS at 2 years. Implementation of the CaVenT study will be a contribution toward evidence-based medicine in the treatment of acute proximal DVT of the leg. Any documentation of improved functional outcome will have a significant impact on clinical practice for this patient group and may lead to a modification of existing international guidelines.


Fragile sites still breaking.
Rare fragile sites on chromosomes are the archetypal dynamic mutations. They involve large expansions of the microsatellite CCG or AT-rich minisatellites. The mutation process is an increase in repeat-unit number from within a normal range, through a premutation range, up to full mutation where the fragile site is expressed. Full mutations can inactivate genes and are regions of genomic instability. Common fragile sites, in particular, might have a role in oncogensis by facilitating gene inactivation through chromosomal deletion or amplification, but this requires further exploration. The mechanisms behind the changes that give rise to the cytogenetic manifestation of chromosomal fragility are now beginning to be understood.


Building Blocks of Functioning Brain: Cytoskeletal Dynamics in Neuronal Development.
Neural connectivity requires proper polarization of neurons, guidance to appropriate target locations, and establishment of synaptic connections. From when neurons are born to when they finally reach their synaptic partners, neurons undergo constant rearrangment of the cytoskeleton to achieve appropriate shape and polarity. Of particular importance to neuronal guidance to target locations is the growth cone at the tip of the axon. Growth-cone steering is also dictated by the underlying cytoskeleton. All these changes require spatiotemporal control of the cytoskeletal machinery. This review summarizes the proteins that are involved in modulating the actin and microtubule cytoskeleton during the various stages of neuronal development.


High temporal resolution transparent thermoelectric temperature sensors for photothermal effect sensing.
We propose inkjet-printed high-speed and transparent temperature sensors based on the thermoelectric effect for direct monitoring of the photothermal effect. They consist of highly transparent organic thermoelectric materials that allow excellent biocompatibility and sub-ms temporal resolution, simultaneously. Our transparent thermoelectric temperature sensors can be used to advance various photothermal biomedical applications.


Lung cancer in chromate workers: high-risk group for multiple lung cancer.
We diagnosed eight (8.9%) lung cancer patients in 90 workers exposed to chromate compounds. The duration of exposure ranged from 8 to 31 years, with a mean value of 18 +/- 8 years. The histological classification was squamous-cell carcinoma in seven patients and adenocarcinoma in one patient. The site of origin of the primary tumors was located peripherally in two (25%) and centrally in six (75%). All but one of these patients underwent surgery. In three (37.5%) of these patients, lung cancer foci were detected during the postoperative follow-up by sputum cytology and bronchoscopy. Two of these three patients had multicentric cancer foci: double primary early squamous-cell carcinoma in one and early squamous-cell carcinoma + small-cell lung cancer in the other. In a high-risk group such as chromate workers, we should emphasize early detection of lung cancer by serial sputum cytology, chest x-rays, and bronchoscopy. Lung cancer patients with chromate exposure should be treated with due regard to the possibility of synchronous or metachronous cancer.


Antimicrobial mixtures used by tissue banks for harvested skin: comparative in vitro activity.
The activities of antimicrobial combinations from three geographically diverse skin/tissue banks used in the processing of skin/ tissue were compared using bacteria and yeast isolated from burn patients. All formulations showed 90% or more effectiveness against bacteria generally susceptible to antibiotics but were less effective (60-80%) when tested against bacteria resistant to specific antimicrobials. Anti-yeast activity was present when an appropriate antifungal agent was included in the combination. All formulations were stable for at least six weeks. Results of this study raise certain questions about the use of these antimicrobial combinations in contemporary skin/tissue banking and point the way toward areas for future study.


Core promoter analysis of porcine Six1 gene and its regulation of the promoter activity by CpG methylation.
Six1, an evolutionary conserved transcription factor, has been shown to play an important role in organogenesis and diseases. However, no reports were shown to investigate its transcriptional regulatory mechanisms. In the present study, we first identified porcine Six1 gene core promoter region (+170/-360) using luciferase reporter assay system and found that promoter activities were significantly higher in the mouse myoblast C2C12 cells than that in the mouse fibroblast C3H10T1/2 cells, implying that Six1 promoter could possess muscle-specific characteristics. Moreover, our results showed that promoter activities of Six1 were decreased as induction of differentiation of C2C12 cells, which was accompanied by the down-regulation of mRNA expression of Six1 gene. In addition, we found that the DNA methylation of Six1 promoters in vitro obviously influences the promoter activities and the DNA methylation level of Six1 promoter core region was negatively correlated to Six1 gene expression in vivo. Taken together, we preliminarily clarified transcriptional regulatory mechanisms of Six1 gene, which should be useful for investigating its subtle transcriptional regulatory mechanisms in the future. On the other hand, based on Six1 involved in tumorigenesis, our data also provide a genetic foundation to control the generation of diseases via pursuing Six1 as therapeutic target gene.


Silencing Srsf6 does not modulate incomplete splicing of the huntingtin gene in Huntington's disease models.
We have previously shown that the incomplete splicing of exon 1 to exon 2 of the HTT gene results in the production of a small polyadenylated transcript (Httexon1) that encodes the highly pathogenic exon 1 HTT protein. There is evidence to suggest that the splicing factor SRSF6 is involved in the mechanism that underlies this aberrant splicing event. Therefore, we set out to test this hypothesis, by manipulating SRSF6 levels in Huntington's disease models in which an expanded CAG repeat had been knocked in to the endogenous Htt gene. We began by generating mice that were knocked out for Srsf6, and demonstrated that reduction of SRSF6 to 50% of wild type levels had no effect on incomplete splicing in zQ175 knockin mice. We found that nullizygosity for Srsf6 was embryonic lethal, and therefore, to decrease SRSF6 levels further, we established mouse embryonic fibroblasts (MEFs) from wild type, zQ175, and zQ175::Srsf6+/- mice and transfected them with an Srsf6 siRNA. The incomplete splicing of Htt was recapitulated in the MEFs and we demonstrated that ablation of SRSF6 did not modulate the levels of the Httexon1 transcript. We conclude that SRSF6 is not required for the incomplete splicing of HTT in Huntington's disease.


Self-control, cultural animals, and Big Gods.
As Norenzayan et al. cogently argue, religions that proliferated most successfully did so because they facilitated prosociality and cooperation in large-scale, anonymous groups. One important way that religion promotes cooperation may be through improving self-control. In this comment, we cover some potential obstacles to implementing self-control and how religion can overcome them.


Amelioration of myocarditis by statin through inhibiting cross-talk between antigen presenting cells and lymphocytes in rats.
Statins, inhibitors of 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, have been recognized as a new type of immunomodulator and reported to have anti-inflammatory effect. To investigate the effect of simvastatin, a lipophilic statin, on myocarditis, we explored whether simvastatin is able to inhibit experimental autoimmune myocarditis (EAM) and adoptive transfer of EAM in rats. We found that administration of simvastatin not only interfered with the development of EAM, but also inhibited the transfer. Antigen presenting cells (APCs) were proved to be important for the development of EAM. The ability of myocarditic splenocytes to transfer myocarditis was enhanced after co-culture with APCs. During co-culture of the myocarditic splenocytes and the APCs, simvastatin not only decreased percentages of CD28 expression in CD4-positive myocarditic splenocytes, and CD80 and CD86 expressions in APCs, but also inhibited the production of tumor necrosis factor (TNF)-partial differential in the CD4-positive myocarditic splenocytes and the APCs. These results indicate that simvastatin was able to ameliorate EAM through the inhibition of cross-talk between lymphocytes and APCs, suggesting beneficial role of simvastatin in the treatment of autoimmune myocarditis.


Endovascular Treatment of 2 True Degenerative Aneurysms of Superficial Femoral Arteries.
We report the rare observation of a 58-year-old patient presenting 2 degenerative aneurysms of the superficial femoral arteries, with a rupture of the right aneurysm, treated by covered stents, with a satisfying midterm follow-up. The endovascular approach is a minimally invasive procedure which should be proposed as the first-line treatment to all the patients presenting aneurysms of the superficial femoral arteries, both asymptomatic as complicated.


Long-term monitoring of clodronate in equine hair using liquid chromatography-tandem mass spectrometry.
Given the potential for long-term inhibition of bone remodeling/healing and detrimental effects to horses in training, bisphosphonates are tightly regulated in horseracing. Hair has proven to be an effective matrix for detection of drug administration to horses and has been particularly effective in detecting drugs for a long period of time post administration. Thus, hair may prove to be a useful matrix for detection of administration of this class of drugs. The objective of the current study was to develop an assay and assess the usefulness of hair as a matrix for long-term detection of clodronate to horses. Seven horses received a single intramuscular administration of 1.8 mg/kg clodronate. Hair samples were collected prior to and up to 6 months post administration. A liquid chromatography-tandem mass spectrometry method was developed and concentrations of clodronate measured in hair samples. The drug was first detected on day 7 in 4/7 horses, and on days 14, 28 and 35 in the remaining three horses. In 4/7 horses, clodronate was still detectable 6 months post administration. Results of this study demonstrate that, although there was significant inter-individual variability in detection times (63 to 180 days) and several intermediate times where the drug could not be detected but was subsequently detected in later timepoints, clodronate administration was detectable in hair for a prolonged period in most of the horses (4/7) studied.


Single-cell transcriptomics of the ventral posterolateral nucleus-enriched thalamic regions from HSV-1-infected mice reveal a novel microglia/microglia-like transcriptional response.
Microglia participate in the immune response upon central nervous system (CNS) infections. However, the role of these cells during herpes simplex encephalitis (HSE) has not been fully characterized. We sought to identify different microglia/microglia-like cells and describe the potential mechanisms and signaling pathways involved during HSE. The transcriptional response of CD11b+ immune cells, including microglia/microglia-like cells, was investigated using single-cell RNA sequencing (scRNA-seq) on cells isolated from the ventral posterolateral nucleus (VPL)-enriched thalamic regions of C57BL/6 N mice intranasally infected with herpes simplex virus-1 (HSV-1) (6 × 105 PFUs/20 µl). We further performed scanning electronic microscopy (SEM) analysis in VPL regions on day 6 post-infection (p.i.) to provide insight into microglial functions. We describe a novel microglia-like transcriptional response associated with a rare cell population (7% of all analyzed cells), named "in transition" microglia/microglia-like cells in HSE. This new microglia-like transcriptional signature, found in the highly infected thalamic regions, was enriched in specific genes (Retnlg, Cxcr2, Il1f9) usually associated with neutrophils. Pathway analysis of this cell-type transcriptome showed increased NLRP3-inflammasome-mediated interleukin IL-1β production, promoting a pro-inflammatory response. These cells' increased expression of viral transcripts suggests that the distinct "in transition" transcriptome corresponds to the intrinsic antiviral immune signaling of HSV-1-infected microglia/microglia-like cells in the thalamus. In accordance with this phenotype, we observed several TMEM119+/IBA-I+ microglia/microglia-like cells immunostained for HSV-1 in highly infected regions. A new microglia/microglia-like state may potentially shed light on how microglia could react to HSV-1 infection. Our observations suggest that infected microglia/microglia-like cells contribute to an exacerbated CNS inflammation. Further characterization of this transitory state of the microglia/microglia-like cell transcriptome may allow the development of novel immunomodulatory approaches to improve HSE outcomes by regulating the microglial immune response.


"You can tell by the way I use my walk." Predicting the presence of cognitive load with gait measurements.
There is considerable evidence that a person's gait is affected by cognitive load. Research in this field has implications for understanding the relationship between motor control and neurological conditions in aging and clinical populations. Accordingly, this pilot study evaluates the cognitive load based on gait accelerometry measurements of the walking patterns of ten healthy individuals (18-35 years old). Data points were collected using six triaxial accelerometer sensors and treadmill pressure reports. Stride and window extraction methods were used to process these data points and separate into statistical features. A binary classification was created by using logistic regression, support vector machine, random forest, and learning vector quantization to classify cognitive load vs. no cognitive load. Within and between subjects, a cognitive load was predicted with accuracy values ranged of 0.93-1 by all four models. Various feature selection methods demonstrated that only 2-20 variables could be used to achieve similar levels of accuracies. Coupling sensors with machine learning algorithms to detect the most minute changes in gait patterns, most of which are too subtle to identify with the human eye, may have a remarkable impact on the potential to detect potential neuromotor illnesses and fall risks. In doing so, we can open a new window to human health and safety prevention.


On the use of one-sided statistical tests in biomedical research.
There is a tendency to automatically use two-sided tests to assess the statistical significance of experimental results. Yet if a theory predicts the direction of an experimental outcome, or if for some practical (eg clinical) reason an outcome in that direction is the only one of interest, then it makes sense to use a one-sided test. The use of a two-sided test in these situations will lead to too many false negatives. Consequently treatment effects that corroborate a theory or that are of practical importance may be missed. This problem becomes particularly acute in the case of borderline results. Following a nonsignificant one-sided test, the possibility of an effect in the direction opposite to that predicted or required can be assessed in an exploratory fashion by computing the odds in favour of such an effect. Anyone is then at liberty to pursue this possibility as they see fit. The question of whether to use a one-sided or two-sided statistical test should always be decided on logical grounds not statistical ones, and suspicions regarding the motives of the investigator(s) should be disregarded. On the other hand, this choice can be avoided altogether by assuming that a treatment always has some effect (however small) and then computing the strength of the evidence in favour of the observed or predicted/required effect (ie 1-P, where P is the one-sided significance level of the test). With this approach one-sided and two-sided tests yield identical results, and so there is effectively only one type of test.


Increased visceral fat and decreased energy expenditure during the menopausal transition.
This study assessed longitudinal changes in body composition, fat distribution and energy balance in perimenopausal women. We hypothesized that total fat and abdominal body fat would increase at menopause due to decreased energy expenditure (EE) and declining estrogen, respectively. Observational, longitudinal study with annual measurements for 4 years. Healthy women (103 Caucasian; 53 African-American), initially premenopausal. During follow-up, lack of menstruation for 1 year and follicle-stimulating hormone >30 mIU ml(-1) defined a subject as postmenopausal. Fat and lean mass (dual-energy X-ray absorptiometry), visceral (VAT) and subcutaneous abdominal fat (SAT) (computed tomography), dietary intake (4-day food record), serum sex hormones and physical activity (tri-axial accelerometry). Twenty-four hour EE was measured by whole-room calorimeter in a subset of 34 women at baseline and at year 4. Body fat and weight increased significantly over time only in those women who became postmenopausal by year 4 (n=51). All women gained SAT over time; however, only those who became postmenopausal had a significant increase in VAT. The postmenopausal group also exhibited a significant decrease in serum estradiol. Physical activity decreased significantly 2 years before menopause and remained low. Dietary energy, protein, carbohydrate and fiber intake were significantly higher 3-4 years before the onset of menopause compared with menopause onset. Twenty-four hour EE and sleeping EE decreased significantly with age; however, the decrease in sleeping EE was 1.5-fold greater in women who became postmenopausal compared with premenopausal controls (-7.9 vs -5.3%). Fat oxidation decreased by 32% in women who became postmenopausal (P<0.05), but did not change in those who remained premenopausal. Middle-aged women gained SAT with age, whereas menopause per se was associated with an increase in total body fat and VAT. Menopause onset is associated with decreased EE and fat oxidation that can predispose to obesity if lifestyle changes are not made.


Tracking the ends: a dynamic protein network controls the fate of microtubule tips.
Microtubule plus-end tracking proteins (+TIPs) are a diverse group of evolutionarily conserved cellular factors that accumulate at the ends of growing microtubules. They form dynamic networks through the interaction of a limited set of protein modules, repeat sequences and linear motifs that bind to each other with moderate affinities. +TIPs regulate different aspects of cell architecture by controlling microtubule dynamics, microtubule interactions with cellular structures and signalling factors, and the forces that are exerted on microtubule networks.


Applying Mindfulness Techniques to the Management of Depressive Tendencies in Women in Taiwan in the Perinatal Period: A Qualitative Study.
Perinatal distress, especially depression, commonly occurs during pregnancy and the first year postpartum, but this medical condition are often undiagnosed and untreated. The present study explored how women with depressive symptoms during the perinatal period who had participated in a mindfulness course applied the training and perceived its effects. This descriptive qualitative study included 16 women with probable perinatal depression who had participated in an 8-week mindfulness-based childbirth and parenting program during their pregnancy and agreed to be interviewed. One-to-one in-depth interviews were conducted and recorded following the completion of the mindfulness course, approximately 1 month after childbirth. Verbatim transcripts were analyzed using content analysis. We proposed three themes and six subthemes relating to first-time mothers' experiences during and after the group mindfulness-based intervention: learning to be aware of the body and mind (confronting awareness of physical change, managing negative feelings differently), building positive family relationships (strengthening the mother-baby bond, developing a satisfactory marital partnership), and overcoming ongoing challenges (conquering childbirth pain with confidence, accepting unexpected situations). Three main themes were generated to demonstrate how women experience the effects of mindfulness training. Mindfulness-based interventions helped the participants develop insight into their mood and physical changes and accept their childbirth process. Therefore, mindfulness education programs can be incorporated into prenatal care to enhance the management of the depressive symptoms of perinatal women.


[Impact of simvastatin on microthrombosis in cortical after subarachnoid hemorrhage in rats and its mechanism].
Accumulating evidence demonstrates that subarachnoid hemorrhage (SAH)-induced microthrombosis plays important roles in the pathogenesis of delayed cerebral ischemia. The purpose of the present study was to determine the impact of simvastatin on microthrombi formation and cerebral vasospasm after SAH and explore its mechanism. A total of 24 adult male SD rats were divided into 4 groups: (1) control group (n = 6); (2) SAH group (n = 6); (3) SAH + vehicle group (n = 6) and (4) SAH + simvastatin group (n = 6). SAH was induced by injecting 0.3 ml of fresh arterial, non-heparinized blood into prechiasmatic cistern in 20 sec with a syringe pump. In the SAH + simvastatin group, simvastatin was administered ip at a dose of 20 mg×kg(-1)×d(-1) after SAH. Brain samples were excised after perfusion fixation at 7 days post-SAH. Microclots were evaluated by H&E staining. Microthrombi formation was measured by fibrinogen immunostaining. The number of microthrombi was 1 ± 1, 25 ± 5, 24 ± 4 and 5 ± 2 in control, SAH, vehicle and simvastatin groups respectively. The number of microthrombi significantly increased in cerebral cortex at 7 days post-SAH (P < 0.01). The treatment of simvastatin down-regulated the formation of microclots in the SAH model and the number of microthrombi decreased significantly in the SAH + simvastatin group as compared with the SAH or SAH + vehicle groups (P < 0.01). The administration of simvastatin alleviates microthrombosis in late phase of SAH in this prechiasmatic blood injection model.


Mortality from prostate cancer in Italy: 1950-1979. Cross-sectional rates and cohort analysis.
This paper studies prostate cancer mortality in Italy from 1950-1979 to evaluate its importance in relation to total cancers, examine the time trend for forecasting future mortality trends, and makes an attempt to interpretate mortality by analyzing demographic and risk factors. In the Authors' opinion findings from cross-sectional rates, cohort analysis and Devesa-Schneiderman method, indicate that in Italy even if the age-adjusted mortality rate has nearly doubled over the period, as in many other countries, mortality can be expected to remain constant or decrease in the future, since the data to hand show a decreasing trend in some age cohorts.


Immunopathogenesis of chronic pyelonephritis.
Immunopathologic responses to urinary Tamm-Horsfall protein in the development of chronic pyelonephritis were examined by four different approaches. First, in a rabbit model, tubulointerstitial nephritis developed in 64 of 102 rabbits injected intravenously with urine or rabbit Tamm-Horsfall protein as compared with only one of 17 rabbits in two control groups. Circulating cytotoxic lymphocytes plus immunoglobulin G (IgG) antibodies against Tamm-Horsfall protein were found in 51 percent of challenged (urine or Tamm-Horsfall protein) rabbits with tubulointerstitial nephritis as compared with only 8 percent of those without it (p less than 0.001). Second, in a porcine model of reflux nephropathy, 16 of 21 pigs with pyelographic findings indicative of reflux had elevated serum titers of anti-Tamm-Horsfall protein antibody as compared with 0 of 13 with normal pyelograms. Five of 10 refluxing pigs tested also had circulating lymphocytes that were cytotoxic in the presence of Tamm-Horsfall protein as compared with 0 of 13 with normal pyelograms. Third, in human studies, 12 of 49 patients with recurrent nephrolithiasis demonstrated abnormal elevations in anti-Tamm-Horsfall protein antibody; 13 of 49 had an abnormality in one of two assays of cell-mediated immunity to Tamm-Horsfall protein as compared with 0 of the normal control subjects. These abnormalities were not associated with overt obstruction or bacteriuria, but appeared to be more common in patients with recent onset and active recurrent nephrolithiasis. Lastly, an inhibitor of the binding reaction between human Tamm-Horsfall protein and its IgG antibody was detected in extracts of three uropathic coliforms. The inhibitors were partially purified by chromatographic means. Preliminary immunoautoradiographic studies revealed three or less protein-containing subunits of Escherichia coli that cross-reacted with anti-Tamm-Horsfall protein antibody. These studies suggest that autoimmune responses to Tamm-Horsfall protein may occur after exposure to Tamm-Horsfall protein by intravenous challenge, urinary reflux, or recurrent nephrolithiasis. This autoimmune response to Tamm-Horsfall protein may be the pathogenetic mechanism by which these factors, including bacteriuria, contribute to chronic pyelonephritis.


Genetic Analysis of Prosaposin, the Lysosomal Storage Disorder Gene in Parkinson's Disease.
Recent genetic studies clearly indicate that variants in several lysosomal genes act as risk factors for idiopathic Parkinson's disease (PD). Variants in the co-activator of glucocerebrosidase gene (GBA) and the four active saposins (Sap A-D) which are encoded by the prosaposin gene (PSAP) are of particular interest; however, their genetic roles in PD are unknown. Whole-exome sequencing and Sanger sequencing were used to assess the genetic etiology of 400 autosomal dominant inherited PD (ADPD) and 300 sporadic PD (SPD) patients. Variants from public databases, including Genome Aggregation Database-East Asian (GnomAD_EAS) and Chinese Millionome Database (CMDB), were used as control groups. Burden analysis based on gene and domains level were performed to investigate the role of rare PSAP variants in PD. Six rare and likely pathogenic variants, located in the Sap A-D domains, were identified and accounted for 0.75% (3/400) of ADPD and 1.33% (4/300) of SPD in the Chinese population. Based on the gene or domain, burden analysis showed that damaging missense variants in SapC had statistical significance on the risk of developing PD. Interestingly, rs4747203, an intronic variant potentially linked to PSAP expression, was associated with reduced risk for PD (p = 8.6e-7 in GnomAD EAS and p = 0.002 in Chinese). Clinically, patients carrying the likely pathogenic variants presented typical PD motor symptoms and responded well to levodopa treatment. Six out of seven patients carrying the likely pathogenic variants of PSAP presented slow disease progression, and none of the patients developed cognitive impairment. Our study expands the spectrum of mutations associated with the risk of developing PD and enhances the understanding of the relationship of the clinical phenotype of PD with PSAP variants.


A gel-free proteomic analysis of Taenia solium and Taenia crassiceps cysticerci vesicular extracts.
The taeniasis/cysticercosis complex is a zoonosis caused by the presence of the parasite Taenia solium in humans. It is considered a neglected disease that causes serious public health and economic problems in developing countries. In humans, the most common locations for the larval form are the skeletal muscles, ocular system, and the central nervous system, which is the most clinically important. Several glycoproteins of T. solium and Taenia crassiceps cysticerci have been characterized and studied for their use in the immunodiagnosis of neurocysticercosis and/or the development of synthetic or recombinant vaccines against cysticercosis. The aim of this study was to perform a gel-free shotgun proteomic analysis to identify saline vesicular extract (SVE) proteins of T. solium and T. crassiceps cysticerci. After solubilization of the SVE with and without surfactant reagent and in-solution digestion, the proteins were analyzed by LC-MS/MS. Use of a surfactant resulted in a significantly higher number of proteins that were able to be identified by LC-MS/MS. Novel proteins were identified in T. solium and T. crassiceps SVE. The qualitative analysis revealed a total of 79 proteins in the Taenia species: 29 in T. solium alone, 11 in T. crassiceps alone, and 39 in both. These results are an important contribution to support future investigations and for establishing a Taenia proteomic profile to study candidate biomarkers involved in the diagnosis or pathogenesis of neurocysticercosis.


Structural and adsorptive properties of activated carbons prepared by carbonization and activation of resins.
Four activated carbons (S1-S4) possessing different structural characteristics were prepared by carbonization of commercial resins (used for ion exchange) and subsequent activation. Their textural parameters were determined on the basis of nitrogen adsorption-desorption at 77.4 K, analyzed by applying several local and overall adsorption isotherm equations. The nature of carbon surface functionalities was analyzed by FTIR spectroscopy. The GC and solid-phase extraction (SPE) techniques were applied to study the influence of the texture of carbonaceous materials on their adsorptive properties. The adsorption efficiency of synthesized carbons with respect to alkylhalides used as probe compounds in the GC measurements varied over a range from 28% (C(2)H(3)Cl(3)/S2) to 85% (CHBr(3)/S1) depending on the type of adsorbates and adsorbents. The concentrating efficiency of these carbons in SPE of explosive materials changed over a larger range from 12% (trinitroglycerin/S4) and 13% (trinitrotoluene/S2) up to 100% (octogen/S1). Active carbon prepared using Zerolite 225x8 as a precursor demonstrated better results than other carbons in two types of adsorption with average values of the efficiency of 75.4% for explosives and 60.8% for alkylhalides.


Direct enrichment of phenols in lake and sea water by stir bar sorptive extraction based on poly (vinylpyridine-ethylene dimethacrylate) monolithic material and liquid chromatographic analysis.
A poly (vinylpyridine-ethylene dimethacrylate) monolithic material was synthesized and selected as stir bar sorptive extraction (SBSE) medium. The influences of polymerization conditions on the extraction efficiency were investigated using phenol and p-nitrophenol as target analytes. Based on this, six strongly polar phenols in water were directly concentrated by the new SBSE and determined with high performance liquid chromatography equipped with diode array detector. To achieve the optimum extraction performance, several main parameters, including extraction and desorption time, pH value and contents of inorganic salt in the sample matrix were investigated. The method showed good linearity and acceptable recoveries, as well as advantages such as sensitivity, simplicity, low cost and high feasibility. The proposed method was successfully applied to the determination of phenolic compounds in lake and sea waters.


Topographic differences of slow event-related brain potentials in blind and sighted adult human subjects during haptic mental rotation.
Twelve blindfolded sighted, nine congenitally blind, and seven adventitiously blind subjects were tested in a haptic mental rotation task while slow event-related brain potentials in the EEG were recorded from 17 scalp locations. The overall topography of the slow wave pattern which prevailed during the task differed for sighted and for blind, but not for congenitally and adventitiously blind subjects. While the tactile stimuli were encoded, the blind showed a pronounced occipital and the sighted a pronounced frontal activation. The task-specific amplitude increment of a negative slow wave which can be understood as a manifestation of the process of mental rotation proper, showed a different topography for sighted and for blind subjects too. It had its maximum over central to parietal cortical areas in both groups, but it extended more towards occipital regions in the blind. In both groups, the effects were very similar to those observed in former studies with visual versions of the mental rotation task, i.e. the slow wave amplitude over central to parietal areas increased monotonously with an increasing angular disparity of the two stimuli to be compared. These results are discussed with respect to the question of whether visual deprivation in the blind can cause a reorganization of cortical representational maps.


Laser cataract surgery: technique and clinical results.
To study the effectiveness of an erbium:YAG (Er:YAG) laser in removing nuclei of various densities. University clinic. This nonrandomized prospective clinical study included 147 consecutive cataractous eyes: Group 1 (n = 71) had conventional ultrasound, and Group 2 (n = 76) had surgery with the Er:YAG laser. The 2 groups were further classified by cataract density. Patients were examined 6 months postoperatively to evaluate surgical time, intraocular pressure (IOP), pachymetry, endothelial cell loss, and visual acuity. With ultrasound cataract surgery, there were no significant changes in IOP compared with the preoperative measurements. Laser treatment of 3+ and 4+ cataracts resulted in IOP increases of 12.6% and 18.2%, respectively, compared with 1+ and 2+ cataracts (P<.001). Slight endothelial cell losses occurred in all cases. With ultrasound, the mean decrease was 2.8%, and with laser surgery, the results were similar except for a significant decrease of 13.4% with 4+ cataracts. There was a correlation between pachymetry and surgical time when the trauma related to surgical time and hydrodynamic flow in the anterior chamber was assessed. With ultrasound, the visual acuity was similar with all types of cataract; with the laser, similar normal values were seen with 1+ and 2+ cataracts but decreased values were seen with 3+ cataracts and lower values with 4+ cataracts-0.43 compared to 0.84 best corrected visual acuity with same-density cataracts treated with ultrasound (P<.0005). Patients with 4+ cataracts treated with the laser developed more complications than those treated with ultrasound. The Er:YAG laser was as effective and reliable as ultrasound in removing soft and medium-density cataracts. With dense cataracts, the surgical length produced more trauma and complications during laser treatment than during ultrasound treatment.


The landscape of international oral and maxillofacial surgery collaborations from 1996 to 2020: a scoping review of the published literature.
The emerging field of global oral and maxillofacial surgery (OMS) aims to improve worldwide access to safe, timely, and affordable OMS care. However, there exists a dearth of literature thoroughly detailing the scope of academic global OMS collaborations between high-income countries (HICs) and low- and/or lower middle-income countries (LICs/LMICs). This scoping review was performed to characterize the landscape of global academic OMS collaborations between HICs and LICs/LMICs. A five-stage methodological framework was used. Academic global OMS collaborations from 1996 to 2020 were identified via an electronic database and grey literature review. A total 1318 articles were identified on December 17, 2020. Following the application of inclusion and exclusion criteria, 71 articles describing 81 unique global OMS academic collaborations were included in the final analysis. The most common HIC was the United States (44.4%); the majority of LIC/LMICs were within Africa (45.8%). Of the total interventions, 89.6% improved LIC/LMIC capacity development, and surgical (43.8%) interventions were the most common. By serving as a central report on current and past academic collaborations in global OMS, this review helps identify areas in need of surgical capacity building, lays the foundation for future research efforts on the topic, and serves as a resource for individuals aiming to become involved in global OMS.


hhLIM is a novel F-actin binding protein involved in actin cytoskeleton remodeling.
Human heart LIM protein (hhLIM) is a newly cloned protein. In vitro analyses showed that green fluorescent protein (GFP)-tagged hhLIM protein accumulated in the cytoplasm of C2C12 cells and colocalized with F-actin, indicating that hhLIM is an actin-binding protein in C2C12 cells. Overexpression of hhLIM-GFP in C2C12 cells significantly stabilized actin filaments and delayed depolymerization of the actin cytoskeleton induced by cytochalasin B treatment. Expression of hhLIM-GFP in C2C12 cells also induced significant changes in the organization of the actin cytoskeleton, specifically, fewer and thicker actin bundles than in control cells, suggesting that hhLIM functions as an actin-bundling protein. This hypothesis was confirmed using low-speed co-sedimentation assays and direct observation of F-actin bundles that formed in vitro in the presence of hhLIM. hhLIM has two LIM domains. To identify the essential regions and sites for association, a series of truncated mutants was constructed which showed that LIM domain 2 has the same activity as full-length hhLIM. To further characterize the binding sites, the LIM domain was functionally destructed by replacing cysteine with serine in domain 2, and results showed that the second LIM domain plays a central role in bundling of F-actin. Taken together, these data identify hhLIM as an actin-binding protein that increases actin cytoskeleton stability by promoting bundling of actin filaments.


Rehabilitation of the dysfunctional bladder in children: method and 3-year followup.
A rehabilitation program has been developed for children with functional, nonneurogenic bladder disturbance. The basis for the program is a bladder regimen supplemented by biofeedback training if needed. Results in the first 70 children (64 girls and 6 boys) are presented. After 1 and 3 years 36 and 53 children, respectively, had completely normalized voiding patterns, that is they were continent, had no urgency, voided 3 to 6 times a day and emptied the bladder completely in 1 portion with a normal flow rate. The training program is applicable in children with varying urodynamic diagnoses and it has been used in children as young as 4 years old.


A deeper understanding about the role of uranium toxicity in neurodegeneration.
Natural deposits and human-caused releases of uranium have led to its contamination in the nature. Toxic environmental contaminants such as uranium that harm cerebral processes specifically target the brain. Numerous experimental researches have shown that occupational and environmental uranium exposure can result in a wide range of health issues. According to the recent experimental research, uranium can enter the brain after exposure and cause neurobehavioral problems such as elevated motion related activity, disruption of the sleep-wake cycle, poor memory, and elevated anxiety. However, the exact mechanism behind the factor for neurotoxicity by uranium is still uncertain. This review primarily aims on a brief overview of uranium, its route of exposure to the central nervous system, and the likely mechanism of uranium in neurological diseases including oxidative stress, epigenetic modification, and neuronal inflammation has been described, which could present the probable state-of-the-art status of uranium in neurotoxicity. Finally, we offer some preventative strategies to workers who are exposed to uranium at work. In closing, this study highlights the knowledge of uranium's health dangers and underlying toxicological mechanisms is still in its infancy, and there is still more to learn about many contentious discoveries.


The Multidimensional, Intersecting Impacts of COVID-19 on Young People's Lives: Evidence From Cross-Sectional Surveys in Mexico, India, and Kenya.
Studies have documented diverse adverse effects of the COVID-19 pandemic on young people's lives-for instance on mental health, education/employment prospects, and intrafamily violence. We sought to generate much-needed evidence regarding whether, and which, young people are experiencing multiple intersecting effects. Data come from cross-sectional surveys with young people ages 15-25 years in Mexico (nationwide, n = 55,692), Kenya (four counties, n = 2,750), and India (two states, n = 3,537), collected from late 2020 to early 2022. We used latent class analysis to identify subgroups based on multiple adverse effects, then examined associations between these subgroups and COVID-19 infections/family deaths, and sociodemographic characteristics. We found prevalent adverse impacts overall and two distinct subgroups in each country-one experiencing higher levels of all impacts, such as on mental health (44%-78% across countries), education/employment (22%-84%), intrafamily violence (22%-49%), and friendships (66%-86%). This subgroup comprised 40% of the sample in Mexico, 25% in Kenya, and 35% in India. In multivariate analyses, this group consistently had greater odds of experiencing COVID-19-related infections and deaths of loved ones. They were more likely socioeconomically disadvantaged, older, urban residents. Associations with other characteristics were country-specific. This study provides novel cross-country evidence that a subgroup of young people has experienced intersecting adverse impacts of COVID-19 on their lives. Findings also confirm prior evidence of multiple elevated vulnerabilities in general. Expanded provision of multiple layers of support is required, particularly for the most vulnerable subgroup, as are multi-sectoral policies and interventions to prevent intersectional effects in future times of crisis.


Primary adenocarcinoma of the ileostomy after colectomy for ulcerative colitis.
A fifth case of adenocarcinoma arising at an ileostomy site many years after total colectomy for ulcerative colitis is reported with a review of the literature. The patient is a 79-year-old white man who presented with a bleeding, locally invasive exophytic mass at his ileostomy site 36 years after total colectomy for ulcerative colitis; he is the oldest patient, with the longest interval from creation of his ileostomy to diagnosis of adenocarcinoma. Careful gross and histopathologic examination of any mass arising at an ileostomy site is recommended. Early detection of such a slowly growing malignancy arising in a long-standing ileostomy may result in cure.


Statistical inference on categorical variables.
Categorical data are data that capture a characteristic of an experimental unit (such as a tissue specimen) rather than a numerical value. In this chapter, we first describe types of categorical data (nominal and ordinal) and how these types of data are distributed (binomial, multinomial, and independent multinomial). Next, methods for estimation and making statistical inferences for categorical data in commonly seen situations are presented. This includes approximation of the binomial distribution with a normal distribution, estimation and inference for one and two binomial samples, inference for 2 x 2 and R x C contingency tables, and estimation of sample size. Relevant data examples, along with discussions of which study designs generated the data, are presented throughout the chapter.


Function-preserving gastrectomy for early gastric cancer.
The number of early gastric cancer (EGC) cases has been increasing because of improved diagnostic procedures. Applications of function-preserving gastric cancer surgery may therefore also be increasing because of its low incidence of lymph node metastasis, excellent survival rates, and the possibility of less-invasive procedures such as laparoscopic gastrectomy being used in combination. Pylorus-preserving gastrectomy (PPG) with radical lymph node dissection is one such function-preserving procedure that has been applied for EGC, with the indications, limitations, and survival benefits of PPG already reported in several retrospective studies. Laparoscopy-assisted proximal gastrectomy has also been applied for EGC of the upper third of the stomach, although this procedure can be associated with the 2 major problems of reflux esophagitis and carcinoma arising in the gastric stump. In the patient with EGC in the upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a preserved very small stomach may provide a better quality of life for the patients and fewer postoperative complications. Finally, the laparoscopy endoscopy cooperative surgery procedure combines endoscopic submucosal dissection with laparoscopic gastric wall resection, which prevents excessive resection and deformation of the stomach after surgery and was recently applied for EGC cases without possibility of lymph node metastasis. Function-preserving laparoscopic gastrectomy is recommended for the treatment of EGC if the indication followed by accurate diagnosis is strictly confirmed. Preservation of remnant stomach sometimes causes severe postoperative dysfunctions such as delayed gastric retention in PPG, esophageal reflux in PG, and gastric stump carcinoma in the remnant stomach. Moreover, these techniques present technical difficulties to the surgeon. Although many retrospective studies showed the functional benefit or oncological safety of function-preserving gastrectomy, further prospective studies using large case series are necessary.


Importance of diagnostic aspects in ostertagism.
Diagnostic methods which reveal only the presence or absence of Ostertagia in grazing animals are of little importance since all will acquire some degree of infection when grazed in the temperate regions of the world. Ostertagia infections may be (1) light--no disease or performance losses occur; (2) moderate--disease may or may not be overtly visible but performance losses occur or (3) heavy--disease is overt with or without death loss. The differentiation of these levels of infection is a quantitative matter insofar as the number of parasites correlates with the degree of pathology and is much less certain than is the presence or absence of infection. Historically, the quantitative parasite egg count in feces (eggs per gram (e.p.g.)), combined with the usual subjective and objective information obtained in clinical examinations has been the procedure used to obtain a quantitative estimate of the level of infection. More recently, the use of plasma pepsinogen levels as an indication of gastric pathology has been adopted by some laboratories. Neither of these methods have met with the desired level of accuracy, but they do have considerable value when their limitations are recognized. In the present era of emphasis on epidemiologically based control programs we are faced with yet another aspect of diagnosis, namely that of a quantitative estimate of numbers of infective stages (L3) on herbage. Methods to assess the number of L3 on forage are not satisfactory for routine clinical use. This paper evaluates the primary objectives of diagnosis as applied to the herd and flock. It briefly evaluates current methodology insofar as the diagnosis of parasitic gastroenteritis is concerned. The use of e.p.g. counts in clinical practice is discussed. Examples applicable to herds of weaner and stocker cattle are presented.


Characterization of water-in-oil microemulsion for oral delivery of earthworm fibrinolytic enzyme.
Earthworm fibrinolytic enzyme (EFE-d, Mr 24177), a water-soluble protein, is clinically used for the management of cardiovascular diseases. However, this protein drug has a very low oral bioavailability because of its low oil/water partitioning, low membrane permeability and unstable nature in harsh gastric juice. This study explored the possibility of absorption and efficacy enhancement for EFE-d through the delivery of the water-in-oil (w/o) microemulsions. The w/o microemulsion consisting of Labrafac CC, Labrasol, Plurol Oleique CC 497 and saline (54/18/18/10, % w/w) was developed and characterized, including conductivity, viscosity, particle size and in vitro membrane permeability. The w/o microemulsion and the control solution of EFE-d were administered intraduodenally (or orally) to rats. The w/o microemulsion possessed a higher intestinal membrane permeability in vitro as well as a higher absorption and efficacy in vivo, when compared to control solution. The intraduodenal bioavailability of EFE-d for microemulsions was 208-fold higher than that of control solution and the absolute bioavailability was 17.55%. Meanwhile, there was no tissue damage of the intestinal mucosa found after oral multiple-dose administration of the EFE-d microemulsion to rats. These findings indicated that the w/o microemulsion may represent a safe and effective oral delivery system for hydrophilic bioactivity macromolecules.