Pulsatile gonadotrophin releasing hormone therapy in patients with hyperandrogenaemia or hypothalamic amenorrhoea.
From 1984 to 1985, 18 patients with infertility and oligomenorrhoea were treated with pulsatile GnRH administration (Zyklomat). According to the hormone levels and the ultrasonographic observation of the ovaries, they could be divided into two categories, group A (n = 11), patients with hyperandrogenaemia, and group B (n = 7), patients with hypothalamic amenorrhoea. As in hyperandrogenaemic patients a pathological LH-secretion pattern was suspected, assessment of LH-pulsing (5 ml blood samples at 10 min intervals over 6 h) was performed in this group of patients followed by an oestrogen-gestagen (E-Ge) suppression. One day before discontinuation of this medication, the GnRH pump was applied intravenously. Ovulation induction was more successful in group B than in group A. Hyperandrogenaemic women, in whom ovulation could be induced by the GnRH pump, exhibited higher basal concentrations of FSH, LH, LH/FSH ratio, oestradiol- 17 beta and testosterone (T) than the women not responding to pulsatile GnRH administration. The suppression of T and LH/FSH ratio with E-Ge treatment was more pronounced, while the non-responders had higher basal prolactin concentrations as well as after E-Ge therapy and a significantly greater body weight. The results indicate that GnRH therapy in hypothalamic amenorrhoea is more successful than in hyperandrogenaemia. Overweight hyperandrogenaemic patients appeared to be unsuitable for GnRH treatment, even after previous suppression of the hypothalamic pituitary ovarian axis with E-Ge.


[Normal and pathological ultrasonography of the fetal brain].
Advanced ultrasonic technology enabled the bidimensional imaging of fetal brain throughout pregnancy. The number of visible structures increases with gestational age. In order to certify the described items they were compared to similar anatomical sections available from brain specimens or an atlas of anatomy. Real-time as well as automatic compound scanning machines were used to obtain echographic images of fetal brain anatomy in utero. Many different scans were collected along three orthogonal directions: every 2 mm, with the automated compound scan and as close from each other as possible with the linear array real-time scanner. The material included 59 normal fetuses between the 15th and 40th week of gestation. Eight typical sections are made but the only structures identified are those being visible on every section obtained at the same level. Brain structures such as grey and white matter, nuclei, vessels and ventricles have different sonic properties. They are subsequently distinguishable on the ultrasonic image if the equipment is capable of detecting and showing such differences. Grey matter is more echogenic than white, choroid plexuses are very reflective as are vessel walls which also pulsate. Four horizontal sections are described in detail (Figs. 2-7). The coronal planes are demonstrated at three different levels (Figs. 8-12) and the sagittal plane is represented by Fig. 13. Thirty five structures were identified (Table 2). In the second section some brain and skull anomalies are briefly described. The principal signs of the abnormalities and possible encountered variations are listed such as cranial defects in anencephaly, acrania, encephalocele, iniencephaly; the anomaly of size and shape of head and ventricle, as in hydrocephaly and microcephaly, cystic-like- and solid-tumor lesions and Dandy Walker syndrome and hydranencephaly. Attention is drawn to possible artifacts and pitfalls in the differential diagnosis between similar looking pictures. Examples are given such as noise in the near field, occurring more often in sectorscan machines, inadequate orientation of scan plane producing asymetrical display of the hemisphere and the Sylvian fissure described as if it was the lateral ventricle wall. Anomalies can also be confused such as exencephaly, anencephaly, iniencephaly, encephalocele. An excellent knowledge of normal brain anatomy and pathology, together with excellent equipment and a careful scrutiny of the echograms are required qualities for fetal brain examination.


Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.
Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19. Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo. For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo. Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597.


[Intrarectal administration of quinine: an early treatment for severe malaria in children?].
Delay for treatment of severe malaria is the cause of an important childhood mortality in Africa especially in rural zone when health facilities and accessibility are scarce. Intrarectal treatment is of particular interest in children as a non aggressive, painless and easy treatment. It can be used as early treatment and could decrease the lethality of severe malaria. We recently showed the kinetic profile, the optimal regimen and the clinical efficacy of intrarectal quinine (QIR) using Quinimax (Sanofi, Gentilly France) 20 mg/kg in solution with 2 ml of water. From 1994 to 1996 two open clinical trials were performed in Niger in children (2-15 years). QIR was compared with intraveinous infusion in cerebral malaria (n = 76) and with intramuscular quinine in severe malaria (n = 57). A three daily QIR administration (20 mg/kg followed by 15 mg/kg/8 h) was used in cerebral malaria; a two daily administration in severe malaria (30 mg/kg followed by 20 mg/kg/12 h). Symptomatic treatment was associated for hyperthermia, hypoglycemia, anemia and seizures. Results. In the cerebral malaria study 58 children presented a Blantyre coma score below 3. Four children in the IR group and 9 children in the infusion group died (P > 0.05). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 39.0 +/- 15.2 h and 37.1 +/- 16.5 h; return to consciousness 34.6 +/- 12.8 h and 33.0 +/- 14.1 h; decrease to 50% of the initial parasites count: 15.5 +/- 11.5 h and 13.8 +/- 10.0 h. Residual blood quinine concentrations at 48 hours were similar 7.4 +/- 3.7 mg/l and 7.2 +/- 2.9 mg/l. In the severe malaria study, the mortality was 0 and 7.6% in the QIR and IM group respectively (P > 0.005). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 38.7 +/- 22.8 h and 38.6 +/- 22.2 h; return to consciousness 26.8 +/- 13.9 h and 27.6 +/- 9.9 h for the 16 children in coma. The evolution under QIR treatment was also similar with that described with the other quinine routes. QIR allows an efficious treatment particularly when correct infusion cannot be performed. The efficacy, the simplicity and the good tolerance of QIR are of major concern to decrease the mortality of severe malaria due to delay for treatment and to decrease the side-effects due to intramuscular administrations of quinine in Africa.


Transanal total mesorectal excision (taTME) for rectal cancer: beyond the learning curve.
Transanal total mesorectal excision (taTME) is a surgical approach for low rectal cancer with a learning curve estimated at 40-50 cases. The experience among taTME surgeons beyond their learning curve is limited. A retrospective analysis of all taTME cases performed for rectal cancer at two tertiary care hospitals from 2014 to 2019 was conducted. Transanal surgeons had previously performed > 50 taTME cases. Demographic, perioperative, and short-term outcomes were analyzed. Among 54 taTME patients, 74.1% were male and 27.8% had a BMI ≥ 30. Tumors were stage I (8), II (13), III (29), and IV (4). Complex cases included 4 local recurrences, 4 prior liver resections, and 2 with prior prostate cancer. Thirty tumors were located ≤ 6 cm from the anal verge. On staging MRI, 12 had a positive predicted circumferential radial margin (+CRM), and 4 had internal anal sphincter involvement (+IAS). Forty-seven patients received neoadjuvant therapy. A 2-team approach was used in 51 patients with laparoscopic (83.3%) or robotic (16.7%) abdominal assistance with a 9.2% conversion rate. Low anterior resection with sphincter salvage was achieved in 87% with 8 patients requiring intersphincteric resection. Anastomoses were hand-sewn in 57.4% and all patients were diverted. Median LOS was 5 days with a 42.6% 30-day morbidity rate and 3 postoperative mortalities (ARDS, pulmonary embolism and pseudomembranous colitis). Complete and near complete TME grade was achieved in 94.4% with a 3.7% rate of +CRM. At a median follow-up of 28 months, local and distant recurrence rates were 3.9% and 17.6%, respectively, with no cancer-related mortality. Indications for taTME at experienced centers have expanded to include complex reoperative cases, local recurrences, metastatic cancer, and tumors with threatened CRM or IAS with evidence of post-treatment tumor regression. In the latter cases, taTME achieves good short-term outcomes and may facilitate R0 resection.


Two-year survival of glass ionomer sealants placed as part of proximal atraumatic restorative treatment restorations.
To evaluate after two years, the survival rate of glass ionomer cement (GIC) sealants placed in primary molars of six to eight year-olds and as part of proximal atraumatic restorative treatment (ART) restoration. A longitudinal clinical study. Matungulu/Kangundo rural divisions, Machakos district, Kenya. A total of 804 six to eight year-olds from rural Kenya received a sealant as part of a proximal restoration placed in a primary molar using the atraumatic restorative treatment (ART) approach. The two-year cumulative survival of the sealants was 10.9%, and the survival of the sealants was not significantly affected by the GIC material brand and the tooth-isolation method used. However, slightly more sealants survived when Fuji IX and rubber dam tooth- isolation method were used. The two-year survival rate of the sealants was poor and was not significantly influenced by the GIC material or the tooth-isolation method used.


Multiple concurrent anastomotic procedures in the management of moyamoya disease: a case report with review of literature.
It has already been proved by many studies that surgical revascularization definitely helps in curing the symptoms of moyamoya vasculopathy. In this regard, we present a case of moyamoya disease which was cured by concurrent multiple anastomotic procedures, namely superficial temporal artery (STA), middle cerebral artery (MCA) anastomosis, encephalomyosynangiosis (EMS) and encephalogaleosynangiosis (EGS). A 24-year-old woman presented with symptoms of cerebral ischemia. Thorough investigation with MRA and MRI revealed moyamoya vasculopathy and was confirmed by cerebral angiogram. Multiple concurrent combined anastomotic procedures on both sides relieved the symptoms, which was also confirmed angiographically. A Combination of multiple direct and indirect procedures covers the whole ischemic cortical area and provides effective neovascularization.


Diversification of the three-component coupling of 2-aminoheterocycles, aldehydes, and isonitriles: efficient parallel synthesis of a diverse and druglike library of imidazo- and tetrahydroimidazo[1,2-a] heterocycles.
Due to their diverse range of biological activities, imidazoheterocycles are recognized as privileged structures making these structural motifs attractive targets for library preparation. We report herein the synthesis of a sizable collection of imidazo[1,2- a]heterocycle scaffolds well-suited for divergent library preparation by virtue of amine functional handles with diverse positioning and connectivities. Partial reduction of imidazo[1,2- a]pyrazines to the tetrahydroimidazo[1,2- a]pyrazines and regiospecific Mannich-type bond formation at the C-3 of imidazo[1,2- a]pyridine under mild conditions achieved additional topological and connective diversity within the scaffold collection. Subsequent parallel reaction of the functionalized imidazoheterocycles with polystyrene-tetrafluorophenol esters and sulfonates produced a 7500 compound library in high purity.


Phylogenetic Analysis of the SQUAMOSA Promoter-Binding Protein-Like Genes in Four Ipomoea Species and Expression Profiling of the IbSPLs During Storage Root Development in Sweet Potato (Ipomoea batatas).
As a major plant-specific transcription factor family, SPL genes play a crucial role in plant growth, development, and stress tolerance. The SPL transcription factor family has been widely studied in various plant species; however, systematic studies on SPL genes in the genus Ipomoea are lacking. Here, we identified a total of 29, 27, 26, and 23 SPLs in Ipomoea batatas, Ipomoea trifida, Ipomoea triloba, and Ipomoea nil, respectively. Based on the phylogenetic analysis of SPL proteins from model plants, the Ipomoea SPLs were classified into eight clades, which included conserved gene structures, domain organizations and motif compositions. Moreover, segmental duplication, which is derived from the Ipomoea lineage-specific whole-genome triplication event, was speculated to have a predominant role in Ipomoea SPL expansion. Particularly, tandem duplication was primarily responsible for the expansion of SPL subclades IV-b and IV-c. Furthermore, 25 interspecific orthologous groups were identified in Ipomoea, rice, Arabidopsis, and tomato. These findings support the expansion of SPLs in Ipomoea genus, with most of the SPLs being evolutionarily conserved. Of the 105 Ipomoea SPLs, 69 were predicted to be the targets of miR156, with seven IbSPLs being further verified as targets using degradome-seq data. Using transcriptomic data from aboveground and underground sweet potato tissues, IbSPLs showed diverse expression patterns, including seven highly expressed IbSPLs in the underground tissues. Furthermore, the expression of 11 IbSPLs was validated using qRT-PCR, and two (IbSPL17/IbSPL28) showed significantly increased expression during root development. Additionally, the qRT-PCR analysis revealed that six IbSPLs were strongly induced in the roots under phytohormone treatments, particularly zeatin and abscisic acid. Finally, the transcriptomic data of storage roots from 88 sweet potato accessions were used for weighted gene co-expression network analysis, which revealed four IbSPLs (IbSPL16/IbSPL17/IbSPL21/IbSPL28) clusters with genes involved in "regulation of root morphogenesis," "cell division," "cytoskeleton organization," and "plant-type cell wall organization or biogenesis," indicating their potential role in storage root development. This study not only provides novel insights into the evolutionary and functional divergence of the SPLs in the genus Ipomoea but also lays a foundation for further elucidation of the potential functional roles of IbSPLs on storage root development.


Axial coordination and reduction potentials of the sixteen hemes in high-molecular-mass cytochrome c from Desulfovibrio vulgaris (Hildenborough).
A spectroelectrochemical study is described of the sixteen hemes in the high-molecular-mass, monomeric cytochrome c (Hmc) from the periplasmic space of Desulfovibrio vulgaris, strain Hildenborough. One of the hemes has special properties. In the oxidized state at pH 7 it is predominantly high-spin, S = 5/2, with a g perpendicular value of less than 6 indicative of quantum-mechanical mixing with a low-lying (800 cm-1) S = 3/2 state; the balance is probably a low-spin derivative. The high-spin heme has an Em.7.5 value of +61 mV. The fifteen other hemes are low-spin bis-histidine coordinated with Em.7.5 values of approximately -0.20 V. Two of these hemes exhibit very anisotropic EPR spectra with a g1 value of 3.65 characteristic for strained bis-histidine coordination. A previous proposal, namely that methionine is coordinated to one of the hemes [Pollock, W.B.R., Loufti, M. Bruschi, M. Rapp-Giles, B.J., Wall, J. & Voordouw, G. (1991) J. Bacteriol. 173, 220] is disproved using spectroscopic evidence. Contrasting electrochemical data sets from two previous studies [Tan, J. & Cowan, J.A. (1990) Biochemistry 29, 4886; Bruschi, M., Bertrand, P., More, C., Leroy, G., Bonicel, J., Haladjian, J., Chottard, G., Pollock, W.B.R. & Voordouw, G. (1992) Biochemistry 31, 3281] are not consistent with our EPR titration results and are not reproducible. Hmc can be reduced by D. vulgaris Fe-hydrogenase in the presence of molecular hydrogen.


Is fine needle aspiration cytology (FNAC) useful in skin adnexal masses? A study on 5 cases of pilomatixoma.
Superficial cutaneous/subcutaneous nodules, caused by a variety of inflammatory, benign and malignant pathology of diverse origin, are tempting lesion for fine needle aspiration cytology (FNAC). Amongst these, adnexal tumor show considerable overlap, both in clinical manifestation as well as in histopathology. Archieval records of clinical findings, FNAC smears and reports pertaining to 5 histologically proved cases of pilomatricoma (PMX) were analyzed. Different cytological findings were graded + to +++. Pre FNAC clinical diagnoses were sebaceous cyst, tuberculous lymphadenopathy, dermatofibroma, reactive lymphadenopathy and lipoma. PMX was diagnosed on FNAC in 3 cases on finding groups of basaloid cells, ghost epithelial cells, pink fibrillary material and calcium deposits. Other cases were diagnosed as epidermal inclusion cyst with the differential diagnosis of well differentiated squamous cell carcinoma and skin appendageal tumor of undetermined origin in one case each. In all the cases, FNAC established epithelial nature of the lesion, excluding clinically mimicking inflammatory/neoplastic lesions of other origin. FNAC should be followed by excision biopsy to accurately type the epithelial neoplasm.


Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages.
Rat peritoneal macrophages were incubated in the presence of cycloheximide or dexamethasone to inhibit the induction of cyclooxygenase (COX)-2 protein synthesis. Thereafter, when the macrophages were incubated in the presence of arachidonic acid, PGE2 production was increased. Western blot analysis demonstrated that COX-2 protein levels were low and were not affected by arachidonic acid treatment. COX-1 protein levels were not affected by arachidonic acid treatment either. The COX-2 inhibitors NS-398 and nimesulide only slightly inhibited PGE2 production, whereas the COX-1/COX-2 inhibitors indomethacin, piroxicam and tenoxicam strongly inhibited PGE2 production. This suggests that under these conditions, PGE2 production is dependent on COX-1. After the macrophages were treated with aspirin to inactivate existing COX-1 and COX-2, however, treatment with 12-0-tetradecanoylphorbol 13-acetate increased PGE2 production. Furthermore, COX-2 protein levels were markedly increased by 12-0-tetradecanoylphorbol 13-acetate treatment, whereas COX-1 protein levels did not change. In this case, both the COX-2 and the COX-1/ COX-2 inhibitors inhibited PGE2 production. This suggest that under these conditions, PGE2 production is dependent on COX-2. Effects of auranofin on COX-1-dependent and COX-2-dependent PGE2 production were examined. We found that auranofin stimulated COX-1-dependent PGE2 production but inhibited COX-2-dependent PGE2 production in a concentration-dependent manner. The latter effect was found to be due to the inhibition of COX-2 protein induction. These findings might explain the mechanism of the antirheumatic and anti-inflammatory activities of auranofin.


Combined effects of bucillamine and etanercept on a rat type II collagen-induced arthritis model.
The combined effects of bucillamine (Buc) and etanercept (ETN) on a rat model of type II collagen (CII)-induced arthritis (CIA) after treatment onset were investigated. In the combination treatment, rats received Buc 30 mg/kg orally administered once daily from the onset of arthritis or from 4 days after the onset of arthritis and ETN 0.3 mg/kg subcutaneously administered once on the day of onset. The effects of monotherapy with Buc and ETN, respectively, and of Buc + ETN combination therapy on the resulting polyarthritis were evaluated by histopathological analyses and measurements of hindpaw volumes, serum anti-collagen antibody and immunoglobulin levels, and cytokine levels. The Buc + ETN therapeutic combination reduced hindpaw swelling, synovial proliferation, bone destruction, new bone formation, and inflammatory cell infiltration in CIA. Montherapy with Buc showed a tendency to ameliorate these symptoms, while monotherapy with ETN reduced hindpaw swelling at 4 days after administration but did not maintain treatment efficacy toward the end of the experimental period. Histopathological findings did not reveal any efficacy of the ETN therapy. ETN alone increased the serum immunoglobulin levels, while its combination with Buc reduced these levels. Similar results were obtained for serum anti-CII antibody titers. The Buc + ETN combination treatment also reduced serum interleuking (IL)-1alpha and granulocyte macrophage colony-stimulating factor and tended to reduce serum IL-1beta and IL-6 levels. These results suggest that a combination therapy of Buc and ETN may be effective for the treatment of rheumatoid arthritis (RA).


Foreign body response within postoperative perfluoro-N-octane for retinal detachment repair: clinical features, grading system, and histopathology.
To describe the clinical and histopathologic characteristics of inflammatory deposits occurring within intermediate duration postoperative perfluoro-n-octane (PFO) for inferior retinal detachment repair. Prospective interventional case series of consecutive patients with inferior retinal detachment treated with intermediate duration postoperative vitreous cavity PFO endotamponade were analyzed by ophthalmoscopy for the presence of inflammation and white deposits. Ten consecutive samples developing white deposits were analyzed microscopically. Clinical variables were analyzed. One hundred and eighty-one eyes of 181 patients were included (mean age = 52.4 ± 14 years; mean follow-up = 29.7 ± 14 months). Fifty of 181 patients (28%) developed a characteristic foreign body response with abundant white deposits within indwelling PFO. Ten consecutive samples analyzed histologically contained abundant macrophages, the absence of additional inflammatory cells, and intracytoplasmic optically lucent inclusions. Foreign body response was associated with longer duration of PFO (P = 0.003). Perfluoro-n-octane foreign body response was not associated with age (P = 0.136), ethnicity (P = 0.101), visual outcome (P = 0.157), or persistent intraocular pressure elevation (P = 0.381). A stereotypical foreign body response occurs in ∼ 30% of patients with postoperative vitreous cavity PFO and becomes clinically apparent at 7 days to 10 days after initial placement for rhegmatogenous retinal detachment repair. The response consists almost exclusively of macrophages and does not seem to be related to either long-term intraocular pressure elevation or visual outcome. The response may be related to the duration of indwelling PFO and may limit visualization of the retina during PFO removal.


[The work situation and mental health. The results of a cross-sectional study].
The aim of the study is to assess the relationship between employment situation and mental health in the city of Valencia. Between May and July of 1992, a cross sectional study by means of personal interviews was carried out. The total sample was 411 people of these 101 were selected through a random sampling of the working population, the rest (310) consisted of people registered with INEM selected through a predetermined sampling according to age and sex. The variable dependent (psychological morbidity) was measured through the General Health Questionnaire (GHQ) consisting of 28 items. The results obtained show that 36.4% of the unemployed sample displayed psychological morbidity as opposed to 23.3% of those is employment (p = 0.01). The prevalence Odds Ratio (OR) was calculated by means of a logistic regression model. Those in causal employment had a OR of 8.62 (95% CI = 2.66-27.9) as opposed to those in regular employment after adjusting for age, sex and professional status. Those that had been unemployed for more than a year had a OR of 16.02 (95% CI = 4.60-55.75) as opposed to those employment after adjusting for the same variables. These results seem to confirm a greater psychological morbidity among those with casual employment and the unemployed as opposed to those in regular employment although the transversal design of the study does not highlight any relation of casualty that might exist among the variables.


Extracellular signal-regulated kinase regulates microglial immune responses in Alzheimer's disease.
The importance of mitogen-activated protein kinase (MAPK) pathway signaling in regulating microglia-mediated neuroinflammation in Alzheimer's disease (AD) remains unclear. We examined the role of MAPK signaling in microglia using a preclinical model of AD pathology and quantitative proteomics studies of postmortem human brains. In multiplex immunoassay analyses of MAPK phosphoproteins in acutely isolated microglia and brain tissue from 5xFAD mice, we found phosphorylated extracellular signal-regulated kinase (ERK) was the most strongly upregulated phosphoprotein within the MAPK pathway in acutely isolated microglia, but not whole-brain tissue from 5xFAD mice. The importance of ERK signaling in primary microglia cultures was next investigated using transcriptomic profiling and functional assays of amyloid-β and neuronal phagocytosis, which confirmed that ERK is a critical regulator of IFNγ-mediated pro-inflammatory activation of microglia, although it was also partly important for constitutive microglial functions. Phospho-ERK was an upstream regulator of disease-associated microglial gene expression (Trem2, Tyrobp), as well as several human AD risk genes (Bin1, Cd33, Trem2, Cnn2), indicative of the importance of microglial ERK signaling in AD pathology. Quantitative proteomic analyses of postmortem human brain showed that ERK1 and ERK2 were the only MAPK proteins with increased protein expression and positive associations with neuropathological grade. In a human brain phosphoproteomic study, we found evidence for increased flux through the ERK signaling pathway in AD. Overall, our analyses strongly suggest that ERK phosphorylation, particularly in microglia in mouse models, is a regulator of pro-inflammatory immune responses in AD pathogenesis.


Identification and expression of the CCAP receptor in the Chagas' disease vector, Rhodnius prolixus, and its involvement in cardiac control.
Rhodnius prolixus is the vector of Chagas' disease, by virtue of transmitting the parasite Trypanosoma cruzi. There is no cure for Chagas' disease and therefore controlling R. prolixus is currently the only method of prevention. Understanding the physiology of the disease vector is an important step in developing control measures. Crustacean cardioactive peptide (CCAP) is an important neuropeptide in insects because it has multiple physiological roles such as controlling heart rate and modulating ecdysis behaviour. In this study, we have cloned the cDNA sequence of the CCAP receptor (RhoprCCAPR) from 5(th) instar R. prolixus and found it to be a G-protein coupled receptor (GPCR). The spatial expression pattern in 5(th) instars reveals that the RhoprCCAPR transcript levels are high in the central nervous system, hindgut and female reproductive systems, and lower in the salivary glands, male reproductive tissues and a pool of tissues including the dorsal vessel, trachea, and fat body. Interestingly, the RhoprCCAPR expression is increased prior to ecdysis and decreased post-ecdysis. A functional receptor expression assay confirms that the RhoprCCAPR is activated by CCAP (EC50 = 12 nM) but not by adipokinetic hormone, corazonin or an extended FMRFamide. The involvement of CCAP in controlling heartbeat frequency was studied in vivo and in vitro by utilizing RNA interference. In vivo, the basal heartbeat frequency is decreased by 31% in bugs treated with dsCCAPR. Knocking down the receptor in dsCCAPR-treated bugs also resulted in loss of function of applied CCAP in vitro. This is the first report of a GPCR knock-down in R. prolixus and the first report showing that a reduction in CCAPR transcript levels leads to a reduction in cardiac output in any insect.


Physicochemical characterization, solubilization, and stabilization of 9-nitrocamptothecin using pluronic block copolymers.
Solid-state properties and physicochemical characteristics of 9-nitrocamptothecin (9NC) were investigated with a view of molecular and bulk level understanding of its poor aqueous solubility and hydrolytic instability that prevent efficient drug delivery and pharmacological activity. 9NC bulk drug substance was found to be a nonhygroscopic, yellowish crystalline solid with long rectangular prism-shaped particle morphology and a sharp melting point at 264°C. Hydrolysis of 9NC-lactone occurs above pH 4, whereas complete conversion of lactone to carboxylate was recorded above pH 8. At saturated conditions, appreciable concentrations of 9NC-lactone were detected at pH as high as 11. 9NC undergoes oxidation in the presence of dimethyl sulfoxide with formation of 9NC-N-oxide. The total solubility of lactone and carboxylate forms of 9NC in deionized water was found to be less than 5 μg/mL, whereas the solubility of 9NC-lactone in aqueous acidic media was determined to be approximately 2.5 μg/mL. Incorporation of 10% pluronic copolymers P123, F127, and F68 in 10 mM HCl increased 9NC solubility by 13-fold, eightfold, and fivefold, respectively. The thermodynamic stability of drug-loaded pluronic micelles was evaluated under isothermal variable volume conditions and found F127, among all poloxamers, to offer the best hydrolytic protection efficacy for 9NC.


A discrete area within the left dorsolateral prefrontal cortex involved in visual-verbal incongruence judgment.
The role of the frontal lobe in cross-modal visual-auditory processing has been documented in experiments using incongruent/congruent paradigms. In this study, 4 patients with left frontal World Health Organization Grade II glioma were assessed during pre-, intra-, and postoperative sessions with picture-naming and verbal-visual task requiring judgment of congruence between pictures and words. During awake brain surgery, the naming and cross-modal tasks were coupled with electrical stimulation inactivating restricted specific regions. For all patients, focal brain stimulation in the dorsolateral prefrontal cortex elicited picture-word matching disturbances but no naming impairment, and the elicited errors exclusively appeared in incongruent and not congruent conditions. The dissociation observed between correct picture naming and disturbed cross-modal judgment shows that electrical stimulation of a discrete cortical area within the left dorsolateral prefrontal cortex can inhibit the simultaneous processing of visual-verbal information without disturbing larger networks involved in the naming process.


The decrease in farnesoid X receptor, pregnane X receptor and constitutive androstane receptor in the liver after intestinal ischemia-reperfusion.
Intestinal ischemia-reperfusion (I/R) damages remote organs, including the liver, and promotes multi-organ failure (MOF). However, the molecular mechanisms underlying acute liver injury after intestinal I/R have not been completely elucidated. Farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate metabolizing enzymes and transporters, and coordinately prevent hepatotoxicity reflecting an inability of appropriate excretion of endogenous toxic compounds. In this study, we assessed FXR, PXR and CAR expression levels and their localization levels in nuclei in the liver after intestinal I/R. We also investigated the effect of IL-6 on FXR, PXR and CAR expression levels and their localization levels in nuclei in in vitro experiments. We used intestinal I/R model rats. Moreover, HepG2 cells were used in in vitro study. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Nuclear receptor localization in nuclei was analyzed by Western blotting using nuclear extracts. FXR and PXR expression levels began to be decreased at 3 h, and FXR, PXR and CAR expression levels were decreased at 6 h after intestinal I/R. The localization levels of FXR, PXR and CAR in nuclei began to be decreased at 3 h, and all of them were decreased at 6 h after intestinal I/R. In HepG2 cells, FXR, PXR and CAR expression levels were decreased by 0.5-1 ng/mL, 0.5-100 ng/mL and 100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR localization levels in nuclei were suppressed by 0.5-10 ng/mL, 10-100 ng/mL and 10-100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R. IL-6 is one of main causes the decreases in expressions of these receptors.


Determinants of energy intake in Central African populations experiencing nutrition transition.
Central Africa is experiencing rapid urbanisation, and this situation comes along with changes in food habits and an increased prevalence of obesity and associated health risks. Factors influencing dietary intake among the diverse African populations are not well understood. Our objective was to characterise the dietary intake and their determinants in the two main ethnic groups experiencing nutrition transition in Cameroon, the Bamiléké and the Béti. We sampled Bamiléké (381) and Béti (347) adults living in both rural and urban, collected socio-demographic variables, assessed dietary patterns by using a food portion photographs book to administrate a FFQ and a 24-h dietary recall technique and derived their BMI from measured weight and height. The dietary patterns of Bamiléké people were composed of more energy-dense foods than the Béti people, regardless of the living area. The energy intake (13·8 (sd 4·6)-15·4 (sd 4·8) MJ v. 9·7 (sd 3·5)-11·2 (sd 3·9 MJ) and the obesity (15-29 % v. 5-8 %) were therefore higher in Bamiléké than in Béti, respectively. Multivariable linear regression analyses showed strong associations of both ethnicities (4·02 MJ; P < 0·001), living area (0·21 MJ; P < 0·001) and education (0·59 MJ; P < 0·048) with energy intake, independently of each other and other socio-demographic factors. The ethnicity factor has been characterised as the more important determinant of diet. Our findings provide new insights and perspectives highlighting the importance of anthropological factors when building prevention campaigns against obesity in Central Africa.


Learning, Neurogenesis and Effects of Flavonoids on Learning.
Learning and memory are two of our mind's most magical abilities. Different brain regions have roles to process and store different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis which is a process, new neurons are produced and then transformed into mature neurons and integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network, this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can exert particularly powerful actions in mammalian cognition and improve hippocampaldependent learning and memory by positively affecting hippocampal neurogenesis.


Limited ankle dorsiflexion increases the risk for mid-portion Achilles tendinopathy in infantry recruits: a prospective cohort study.
Achilles tendinopathy (AT) is a prevalent condition among runners and military personnel. Although ankle dorsiflexion (DF) range of motion (ROM) as measured with the knee bent has not been previously associated with AT, the literature concerning its role is limited. In addition, the role of lower extremity movement pattern in the pathogenesis of AT has not been studied prospectively. The purpose of this study was to further explore the role of ankle DF ROM as measured with the knee bent and that of lower extremity movement pattern as risk factors for mid-portion AT. Seventy healthy male military recruits (mean ± SD age, height and body mass of 19.6 ± 1.0 years, 176.0 ± 10.0 cm, and 71.5 ± 7.4 kg) participated in this study. Ankle DF ROM as measured with the knee bent in weight-bearing (WB) and non-weight-bearing (NWB), as well as lower extremity quality of movement during a lateral step down (LSD) test were measured at baseline. Participants were then followed for a 6-month period of army basic training with recording of the development of AT. Five participants developed AT during training. Participants that developed AT had a more limited NWB ankle DF ROM (27.4(0) versus 21.1(0), p = 0.025). The quality of lower extremity movement did not differ between injured and uninjured participants (p = 0.361). A more limited ankle DF ROM as measured in NWB with the knee bent increases the risk of developing AT among military recruits taking part in intensive physical training.


A method of direct measurement for the enzymatic determination of cholesteryl esters.
A direct measurement method for the enzymatic determination of cholesteryl esters (CEs) without measuring total cholesterol (TC) and free cholesterol (FC) is described. In the first step, hydrogen peroxide generated by cholesterol oxidase from FC was decomposed by catalase. In the second step, CE was measured by enzymatic determination using a colorimetric method or a fluorometric method. The measurement sensitivity of the fluorometric method was more than 20 times that of the colorimetric method. Optimal conditions of the assay were determined, and examples of measured CE in human plasma, rat liver, and cultured cells are indicated. The method of directly measuring CE was simple and has exceptional reproducibility compared with the technique of subtracting FC from TC using each measured TC and FC.


First record of the occurrence of "gill disease" in Mytilus edulis trossulus from the Gulf of Gdańsk (Baltic Sea, Poland).
We are presenting the first report of the occurrence of "gill disease" in Mytilus edulis trossulus from the southern Baltic Sea, Gulf of Gdańsk (Poland). The disease preliminary diagnosis was based on the presence of white and yellow "spots" causing deep indentations in the gills with degeneration, destruction and necrosis of gill filaments. Average prevalence of gill erosion in the blue mussels population was 15.8%. According to other authors, gill erosion may affect over 80% of the bivalve population resulting in mortality rates of up to 40%. The origin of the gill erosion remains unknown, but viruses are most likely involved in the etiology of these pathological conditions. The disease as such may indicate a decrease in the immunological resistance of organisms to infections and inflammations directly or indirectly caused by harmful factors in the ambient environment. Furthermore, the occurrence of numerous pathologies in bivalves is a particular problem in the Gulf of Gdańsk being a low biodiversity ecosystem. Pathologies reduce bilvalves' reproduction ability, worsen their physiological condition and increase their mortality rate. Those factors may also pose a significant ecological danger and lead to negative alterations of the ecosystem.


The Influence of Climate Change Efficacy Messages and Efficacy Beliefs on Intended Political Participation.
Using an online survey experiment with a national sample, this study examined how changing the type and valence of efficacy information in news stories discussing global climate change may impact intended political participation through the mediators of perceived internal, external, and response efficacy. Overall, the results revealed that after a single exposure to a news story, stories including positive internal efficacy content increased perceived internal efficacy, while stories including negative external efficacy content lowered perceived external efficacy. There were limited impacts of other types of efficacy content on perceived efficacy. Perceived internal, external, and response efficacy all offered unique, positive associations with intentions to engage in climate change-related political participation. The results suggest that news stories including positive internal efficacy information in particular have the potential to increase public engagement around climate change. The implications for science communication are discussed.


A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.
Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.


Biotechnological production and application of fructooligosaccharides.
Currently, prebiotics are all carbohydrates of relatively short chain length. One important group is the fructooligosaccharides (FOS), a special kind of prebiotic associated to the selective stimulation of the activity of certain groups of colonic bacteria. They have a positive and beneficial effect on intestinal microbiota, reducing the incidence of gastrointestinal infections and also possessing a recognized bifidogenic effect. Traditionally, these prebiotic compounds have been obtained through extraction processes from some plants, as well as through enzymatic hydrolysis of sucrose. However, different fermentative methods have also been proposed for the production of FOS, such as solid-state fermentations utilizing various agro-industrial by-products. By optimizing the culture parameters, FOS yields and productivity can be improved. The use of immobilized enzymes and cells has also been proposed as being an effective and economic method for large-scale production of FOS. This article is an overview of the results considering recent studies on FOS biosynthesis, physicochemical properties, sources, biotechnological production and applications.


Integrating susceptibility into environmental policy: an analysis of the national ambient air quality standard for lead.
Susceptibility to chemical toxins has not been adequately addressed in risk assessment methodologies. As a result, environmental policies may fail to meet their fundamental goal of protecting the public from harm. This study examines how characterization of risk may change when susceptibility is explicitly considered in policy development; in particular we examine the process used by the U.S. Environmental Protection Agency (EPA) to set a National Ambient Air Quality Standard (NAAQS) for lead. To determine a NAAQS, EPA estimated air lead-related decreases in child neurocognitive function through a combination of multiple data elements including concentration-response (CR) functions. In this article, we present alternative scenarios for determining a lead NAAQS using CR functions developed in populations more susceptible to lead toxicity due to socioeconomic disadvantage. The use of CR functions developed in susceptible groups resulted in cognitive decrements greater than original EPA estimates. EPA's analysis suggested that a standard level of 0.15 µg/m(3) would fulfill decision criteria, but by incorporating susceptibility we found that options for the standard could reasonably be extended to lower levels. The use of data developed in susceptible populations would result in the selection of a more protective NAAQS under the same decision framework applied by EPA. Results are used to frame discussion regarding why cumulative risk assessment methodologies are needed to help inform policy development.


HPLC quantification of all five ginkgolic acid derivatives in Ginkgo biloba extracts using 13 : 0 ginkgolic acid as a single marker compound.
An HPLC quantification method for ginkgolic acid derivatives in Ginkgo biloba leaf extracts was developed. Using 13 : 0 ginkgolic acid as a marker compound, the relative correlation factors of the four other ginkgolic acid derivatives - namely, 15 : 0 ginkgolic acid, 15 : 1 ginkgolic acid, 17 : 1 ginkgolic acid, and 17 : 2 ginkgolic acid - to 13 : 0 ginkgolic acid were determined by HPLC and subsequently used for calculating their contents in ten hydro-ethanolic refined extract samples. In other words, the content of 13 : 0 ginkgolic acid in the extracts was determined using the isolated compound as an external standard. Subsequently the now known concentration of this compound functioned as an internal standard for the quantification of the other four ginkgolic acid derivatives via the described correlation factors. This HPLC method was validated by two independent control measurements, one with an external standard for every individual compound and one based on the present method with the single marker compound alone. The results did not differ significantly in any of the 10 tested extract samples. The protocol presented here thus not only uses the same reference substance for G. biloba extracts as the current Chinese Pharmacopoeia method but also incorporates the advantages of the current European Pharmacopoeia approach. It is simple, reproducible, and can be used to determine the total contents of ginkgolic acid derivatives in G. biloba leaf extracts.


Seroprevalence of Coxiella burnetii infections among cats in different living environments.
The seroprevalence of Coxiella burnetii infection among pet cats in Japan and Korea and stray cats in Japan was investigated by an indirect fluorescent antibody technique and PCR test. Forty-four (14.2%) of 310 pet cats in Japan were seropositive, as were 15 (41.7%) of 36 stray cats in Japan and 10 (8.6%) of 116 pet cats in Korea. The antibody positive rate in stray cats was significantly higher than that in pet cats, but there was no correlation between the rates in Japanese and Korean pet cats. In this study, the prevalence of C. burnetii infection among cats in different living environments was found and it is difficult to deny that stray cats would be one of the important sources of infection for human Q fever.


Relationship between serum cortisol levels and some physiological parameters following reining training session in horse.
The changes of cortisol, red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were evaluated after a reining training session in eight Quarter Horses. All parameters were measured before exercise (T0), immediately after exercise (T1), 1 h after exercise (T2), 2 h after exercise (T3) and 24 h after exercise (T4). One-way analysis of variance (ANOVA) for repeated measures, followed Bonferroni's post hoc test, showed a significant effect of the reining training session (P < 0.0001) on cortisol, RBC, Hb, Hct, HR, RR and RT. Simple linear regression analysis showed the positive correlation (P < 0.05) between cortisol changes and variations of studied parameters in T1, T3 and T4. Exercise-induced cortisol concentrations reflect the physiological response of reining training, suggesting that the changes observed are useful to assess the performance in reining horses and their reining training adaptability.


Educating patients with upper limb dysfunction on self-adjustment of the CPAP/NPPV mask: A case series.
We share our experiences of instructing three patients with severe upper limb dysfunction on how to self-adjust CPAP/NPPV masks. In Case 1, we simplified the procedure by suturing a part of the headband as the left forearm was amputated. In Case 2, the patient had congenitally short limbs with short stature; thus, we provided an additional belt to the headband to maintain the headband's configuration while wearing the mask. In Case 3, the patient had left hemiplegia due to stroke and, repetitive coaching was conducted during the recovery phase rehabilitation program. Difficulties with self-adjusting NPPV/CPAP masks can occur whenever there is limited hand mobility above the head, including upper limb dysfunction. Simplifying procedures and providing sufficient time for instruction could help achieve independence. There have been no previous reports describing similar training details. We believe that sharing this knowledge will be helpful to both patients and healthcare professionals.


Early and Late Endograft Limb Proximal Migration with Resulting Type 1b Endoleak following an EVAR for Ruptured AAA.
Introduction. Seal zone failure after EVAR leads to type 1 endoleaks and increases the risk of delayed aortic rupture. Type 1b endoleaks, although rare, represent a true risk to the repair. Case Presentation. We report the case of a 65-year-old female who underwent emergent endovascular repair for a ruptured infrarenal abdominal aortic aneurysm and developed bilateral type 1b endoleaks following proximal migration of both endograft limbs. The right-side failure was diagnosed within 48 hours from the initial repair and the left side at the 1-year follow-up. Both sides were successfully treated with endovascular techniques. A review of the literature with an analysis of potential risk factors is also reported. Conclusion. For patients undergoing EVAR for ruptured AAA and with noncalcified iliac arteries, more aggressive oversizing of the iliac limbs is recommended to prevents distal seal zone failures.


[Molecular heterogeneity of malignant melanomas].
Malignant melanomas make up a heterogeneous group of tumors characterized by particular genetic aberrations depending on their anatomic localization and UV exposure. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway is found in the majority of melanomas, with either somatic missense mutations of BRAF or, considerably more rarely, mutations of N-RAS. The loss of both products of the CDKN2A gene, proteins p16(ARF) and p14(INK4a), or amplification of microphthalmia-associated transcriptional factor (MITF) are also predisposing factors in the development of melanoma. BRAF mutations are observed mainly in melanomas on skin liable to intermittent UV exposure. Acral and mucosal melanomas, and also melanomas on skin damaged by chronic exposure to the sun are characterized by distinct patterns of chromosomal aberrations with frequent amplifications and alterations of the KIT gene, while BRAF mutations are rarely found in these sites. Uveal melanomas show recurrent chromosomal losses (1p, 3, 6q) and gains (6p, 8q), but mutations of BRAF are hardly ever found. So far, ancillary molecular studies are not regularly applied in the routine diagnostic procedures performed when malignant melanoma is suspected. In the future, however, the development of targeted molecular therapies will require that molecular pathological techniques are used to identify the melanoma patients who will most probably benefit from a particular therapy.


Current management of pediatric achalasia.
Achalasia is a rare condition affecting esophageal motility in children. In a manner similar to the disease found in the adult population, children experience symptoms of dysphagia, regurgitation, and chest pain due to a failure of relaxation of the lower esophageal sphincter. Standard diagnostic approaches include upper endoscopy and esophageal manometry. New developments in diagnosis include high-resolution esophageal manometry and the endoscopic functional lumen imaging probe. Therapies available include endoscopic balloon dilations and botulinum toxin injections into the lower esophageal sphincter, as well as surgical interventions. The Heller myotomy was first described in 1913; since then, there have been many modifications to the procedure to improve outcomes and lower morbidity. Currently, the most commonly performed surgical procedure is the laparoscopic Heller myotomy, in which the sphincter muscle is divided using longitudinal incisions with or without a partial fundoplication procedure. In recent years, per oral endoscopic myotomy (POEM) is gaining support as a viable natural orifice therapy for achalasia. Complications of POEM occur at a relatively low rate, and outcomes following the procedure have been promising. The treatment of end-stage achalasia however, may include partial or total esophagectomy with reconstruction if possible. Future research is focused primarily on increasing the efficacy, and lowering complications, of existing therapeutic modalities.


Multifusion-induced wall-super-thick giant multilamellar vesicles.
A polymeric multivesicular system was created by hydrating a film. This system underwent multifusion events and eventually evolved into giant multilamellar vesicles with extremely thick walls. The semi-permeable wall and large size make these vesicles suitable for encapsulating living cells.


Spatially monitoring oxygen level in 3D microfabricated cell culture systems using optical oxygen sensing beads.
Capability of measuring and monitoring local oxygen concentration at the single cell level (tens of microns scale) is often desirable but difficult to achieve in cell culture. In this study, biocompatible oxygen sensing beads were prepared and tested for their potential for real-time monitoring and mapping of local oxygen concentration in 3D micro-patterned cell culture systems. Each oxygen sensing bead is composed of a silica core loaded with both an oxygen sensitive Ru(Ph2phen3)Cl2 dye and oxygen insensitive Nile blue reference dye, and a poly-dimethylsiloxane (PDMS) shell rendering biocompatibility. Human intestinal epithelial Caco-2 cells were cultivated on a series of PDMS and type I collagen based substrates patterned with micro-well arrays for 3 or 7 days, and then brought into contact with oxygen sensing beads. Using an image analysis algorithm to convert florescence intensity of beads to partial oxygen pressure in the culture system, tens of microns-size oxygen sensing beads enabled the spatial measurement of local oxygen concentration in the microfabricated system. Results generally indicated lower oxygen level inside wells than on top of wells, and local oxygen level dependence on structural features of cell culture surfaces. Interestingly, chemical composition of cell culture substrates also appeared to affect oxygen level, with type-I collagen based cell culture systems having lower oxygen concentration compared to PDMS based cell culture systems. In general, results suggest that oxygen sensing beads can be utilized to achieve real-time and local monitoring of micro-environment oxygen level in 3D microfabricated cell culture systems.


Photophysical Study of Heteroatom-Doped Carbon Dots-MnO2-Based Nanosensor: Selective Detection of Glutathione in the Nanomolar Level.
Heteroatom doping on carbon dots (Cdots) has been developed as an efficient approach to modify its optical and electronic properties. The four different types of heteroatom-doped Cdots (undoped Cdots (u-Cdots, nitrogen-doped Cdots (N-Cdots), sulfur-doped Cdots (Cdots), nitrogen, sulfur codoped Cdots (N, S-Cdots)) have been synthesized through a simple heat treatment of 5 min. Among four different heteroatoms doped nanosensors, N, S-Cdots with MnO2 nanospheres (Mn NS) showed one of the best fluorescents "on-off-on" nanosensors for selective sensing of glutathione (GSH) and cell imaging. N, S-Cdots showed a high fluorescence quantum yield, good photostability, ionic strength, and pH stability. N, S-Cdots with Mn NS demonstrated extremely high fluorescence quenching efficiency and the maximum fluorescence recovery rate after adding GSH to the produced solution. The photophysical study of N, S-Cdots-Mn NS used as a sensor confirms the inner filter effect (IFE) quenching mechanism between them. The developed sensor has an 80 nM limit of detection (LOD) for GSH. The heteroatom-doped framework of Cdots plays a significant role in the sensitive detection of GSH. N, S-Cdots-Mn NS have good permeability, biocompatibility, and low toxicity, due to which it was used in the intracellular imaging of GSH in living cells. The prepared sensor is rapid, economical, less toxic, and highly applicable in diagnosing diseases.


Equine recurrent uveitis in western Canadian prairie provinces: A retrospective study (2002-2015).
The objectives of this study were to determine the demographics of horses with equine recurrent uveitis (ERU) presenting to the Western College of Veterinary Medicine and to describe and compare the prognosis of ERU in the Appaloosa with that in other breeds. Horses diagnosed with ERU by a veterinary ophthalmologist between 2002 and 2015 were included. Eye lesions were classified as mild, moderate, or severe based on clinical manifestations. Breed, age, severity, blindness, and final outcome were evaluated. Thirty-two horses fit the inclusion criteria; 62.5% were Appaloosas. Mean age at presentation was 12.13 ± 4.6 years. Equine recurrent uveitis was bilateral in 93.6% of horses and was severe in 59.4% of eyes at presentation. Bilateral blindness was present in 59.4% of horses at last follow-up. Of 27 horses available for follow-up, 63% were euthanized due to ERU. No significant differences in age, severity, blindness, or rate of euthanasia were noted between Appaloosas and other breeds. The Appaloosa is at increased risk for ERU, which is a devastating ocular disease.


Atomic structure of ABC rhombohedral stacked trilayer graphene.
We distinguish between Bernal and rhombohedral stacked trilayer graphene using aberration-corrected high-resolution transmission electron microscopy. By using a monochromator to reduce chromatic aberration effects, angstrom resolution can be achieved at an accelerating voltage of 80 kV, which enables the atomic structure of ABC rhombohedral trilayer graphene to be unambiguously resolved. Our images of ABC rhombohedral trilayer graphene provide a clear signature for its identification. Few-layer graphene interfaces with ABC:BC:BCAB structure have also been studied, and we have determined the stacking sequence of each graphene layer and consequently the 3D structure. These results confirm that CVD-grown few-layer graphene can adopt an ABC rhombohedral stacking.


The Respiratory Specimen Collection Trial (ReSpeCT): A Randomized Controlled Trial to Compare Quality and Timeliness of Respiratory Sample Collection in the Home by Parents and Healthcare Workers From Children Aged <2 Years.
Most acute respiratory infection (ARI) research focuses on severe disease and overlooks the burden of community-managed illness. For community-based studies, home-based specimen collection by parents could be a resource-saving alternative to collection by healthcare workers (HCWs). In this study, we compared parent and HCW groups for their likelihood to collect specimens and the timeliness and quality of such collection. In this unblinded randomized controlled trial, parents from Brisbane, Australia, were taught to identify new ARI episodes in their children aged <2 years. When their child had a new ARI, parents either collected a nasal swab from the child (P group) or contacted an HCW who visited to obtain a nasopharyngeal swab (HCW group). We compared the likelihood and timeliness of specimen collection and respiratory pathogen detection. A nested diagnostic study compared paired specimen collections from children in the HCW group. Included were 76 incident ARI episodes from 31 children and 102 episodes from 33 children in the P and HCW groups, respectively. The proportions of ARIs for which a specimen was collected were similar (P group, 69.7%; HCW group, 72.5%; P = .77), and pathogens were detected in 93.8% and 77.5% of the specimens, respectively (P = .03). The period between ARI onset and specimen collection was shorter in the P group than in the HCW group (mean difference, 1.9 days [95% confidence interval, 0.7-3.0 days]; P < .001). For the 69 paired specimens, viral loads were lower in the parent-collected swabs (mean cycle threshold difference, 4.5 [95% confidence interval, 3.1-5.9]; P < .001). Parents and HCWs obtained samples in similar proportions of ARI episodes, but the parents collected the samples fewer days after ARI onset and with a resulting higher likelihood of pathogen identification. This method can be used in population-based epidemiological studies of ARI as a resource-saving alternative. ClinicalTrials.gov identifier NCT00966069.


[Bordetella holmesii endocarditis in an asplenic patient].
The case of a 52-year-old female patient with a history of critical aortic stenosis, hypothyroidism and splenectomy as treatment for her Hodgkin's lymphoma is herein presented. In April 2011, the patient was admitted to the cardiology service due to global heart failure, fever and poor response to diuretic and vasodilator therapy. A transesophageal echocardiogram showed images compatible with vegetations in the aortic, pulmonary, and mitral valves. A diagnosis of infective endocarditis was made. Growth of gram-negative coccobacilli was observed in two blood culture sets. The microorganism was finally identified as Bordetella holmesii. The patient was treated with ceftriaxone 1 g every 12 hours for 28 days with favorable outcome.


Effects of Training-for-Transformation Program on TB/MDR-TB Developed by the International Council of Nurses in China.
This study evaluated the effects of the Training-for-Transformation (TFT) program on tuberculosis (TB)/multidrug-resistant TB (MDR-TB) in China. Participants who received training from 2009 to 2017 (n = 230) were invited to complete an online survey using a self-designed questionnaire. A total of 130 (56.5%) trainees completed the survey for a valid response rate of 70% (91 of 130). All of the participants created a schedule and offered a TFT program on TB/MDR-TB for health care providers, clients, and communities by a variety of methods that included brainstorming, group work, and role-play, in addition to lectures. The most important supporting factors to train others were related to opportunity and managers' support, and the biggest barriers were lack of space and time. Trainees also made changes to practices that influenced the way nurses worked within their institution, infection control, team cooperation, extended care, and nurses' attitudes toward patients. The TFT program led to ongoing training provision and practical improvements, and can transform attitudes, practices, and changes in patient care. [J Contin Educ Nurs. 2020;51(5):233-237.].


Spatio-temporal characterization of tightly focused femtosecond laser fields formed by paraboloidal mirrors with different F-numbers.
The focusing spatiotemporal property of a femtosecond laser pulse is presented under tight focusing conditions by using the frequency-resolved incident electric field and vector diffraction formulas with the wavefront correction term. In the ideal case, the focused laser intensity reaches its maximum at the F-number of ∼0.35 due to the strong diffraction effect under extremely tight focusing conditions. In spatio-temporal coupling distortion cases, their spatiotemporal Strehl ratios show a trend of improvement as the F-number decreases and this phenomenon is mainly concentrated along the y-direction. Based on the numerical calculation method used in this work, the precise information of tightly focused ultra-intense femtosecond laser fields can be obtained, which is crucial for assessing a focused intensity and describing the motion of charged particles under an extremely strong electric field. Moreover, the evolution law of focal fields with spatiotemporal distortions found in this paper can offer some theoretical guidance for realizing ultrahigh laser intensity in the near future.


Identification and Quantification of Polymethoxylated Flavonoids in Different Citrus Species Using UPLC-QTOF-MS/MS and HPLC-DAD.
Many species from the genus Citrus are used in traditional medicine and contain polymethoxylated flavonoids. These compounds show anti-inflammatory and chemopreventive activities, among others, and therefore have a big potential to be developed as therapeutic agents or dietary supplements. Citrus species are different in their profile and yield of polymethoxylated flavonoids. Therefore, polymethoxylated flavonoids were identified and quantified in seven different Citrus species, including wild-type and commercially available species. All species were profiled using UPLC-QTOF-MS/MS analysis combined with mass spectral molecular networking. A total of 38 polymethoxylated flavonoids were detected and 8 of them were present in every species. As the yield of polymethoxylated flavonoids was different for each species, a generally applicable HPLC-diode array detection method was developed and validated according to the ICH guidelines to quantify the amount of nobiletin and the total amount of polymethoxylated flavonoids expressed as nobiletin. Analysis of the seven samples showed evidence that wild-type Citrus species (e.g., Citrus depressa) contain higher yields of polymethoxylated flavonoids compared to commercially available species (e.g., Citrus limon). Qualitative analysis revealed the broadest variety of different PMFs in C. depressa, Citrus reticulata, and Citrus reticulata × Citrus sinensis, which makes them interesting sources of polymethoxylated flavonoids for future development as therapeutic agents or dietary supplements.


Disability is an Independent Predictor of Falls and Recurrent Falls in People with Parkinson's Disease Without a History of Falls: A One-Year Prospective Study.
Predictors of falls in people with Parkinson's disease (PD) who have not previously fallen are yet to be identified. We aimed to identify predictors of all falls and recurrent falls in people with PD who had not fallen in the previous year and to explore the timing of falls in a 12-month follow-up period. Participants with PD (n = 130) were assessed by disease-specific, self-report and balance measures. Falls were recorded prospectively for 12 months. Univariate and multivariate analyses were performed. Kaplan-Meier survival analysis was used to investigate time to falling. Forty participants (31%) had ≥1 fall during follow-up and 21 (16%) had ≥2 falls. Disability, reduced balance confidence and greater concern about falling were associated with ≥1 fall in univariate analyses. Additionally, PD duration and severity, freezing of gait and impaired balance were associated with ≥2 falls (p < 0.05). Disability (Schwab and England scale, Odds Ratio [OR] = 0.56 per 10 points increase; 95% confidence interval [CI] 0.39-0.80; p = 0.002) was associated with ≥1 fall in the final multivariate model (area under the receiver operating characteristic curve [AUC] = 0.65; 95% CI 0.55-0.76; p = 0.005). Disability (Unified Parkinson's Disease Rating Scale activities of daily living, OR = 1.20; 95% CI 1.07-1.34; p = 0.001) and levodopa equivalent dose (OR = 1.11 per 100 mg increase; 95% CI 0.95-1.30; p = 0.19) were associated with ≥2 falls in the final multivariate model (AUC = 0.72; 95% CI 0.60-0.84; p = 0.001). Recurrent fallers experienced their first fall earlier than single fallers (p < 0.05). Self-reported disability was the strongest single predictor of all falls and recurrent falls.


Guided Self-help for Eating Disorders: A Systematic Review and Metaregression.
Evidence-based self-help is a recommended first stage of treatment for mild-moderate eating disorders. The provision of guidance enhances outcome. The literature evaluating exclusively 'guided' self-help (GSH) has not been systematically reviewed. The aim was to establish the effectiveness of GSH for reducing global eating disorder psychopathology and abstinence from binge eating, compared with controls. Results were pooled using random effects meta-analysis and heterogeneity explored using metaregression. Thirty randomised controlled trials met the inclusion criteria. Results showed an overall effect of GSH on global eating disorder psychopathology (-0.46) and binge abstinence (-0.20). There was strong evidence for an association between diagnosis of binge eating disorder and binge abstinence. Current interventions need to be adapted to address features other than binge eating. Further research is required to help us understand the effectiveness of GSH in children and young people, invariably high dropout rates and how technology can enhance interventions. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.


Improving potato storage and processing characteristics through all-native DNA transformation.
The dominant potato (Solanum tuberosum) variety for French fry production in the United States is the 131-year-old Russet Burbank. Market penetration of the higher yielding and more uniform Ranger Russet variety is limited to about one-fifth of that of the Russet Burbank because of two storage deficits: black spot bruise sensitivity and high levels of cold-induced sweetening. Here, these trait weaknesses are turned into strengths by simultaneously lowering the expression of Ranger Russet's tuber-expressed polyphenol oxidase (Ppo), starch-associated R1, and phosphorylase-L (PhL) genes. This genetic modification was accomplished without inserting any foreign DNA into the plant genome. French fries from the intragenic potatoes also contained reduced amounts of the antinutritional compound acrylamide while, unexpectedly, displaying enhanced sensory characteristics.


Blunt traumatic hernia of diaphragm with late presentation.
Diaphragmatic hernia after blunt trauma is an uncommon and often undiagnosed condition. We aimed to review patients who presented with delayed blunt traumatic hernia of diaphragm. In this retrospective study, the medical records of six patients treated for blunt diaphragmatic hernias who were admitted to Kashan Shahid Beheshti hospital between June 2007 and June 2011 were analyzed. Six patients with mean age of 41 years were included in the study. Male to female ratio was 2:1. Mean duration between trauma and admission to the hospital was 6.5 years (2 - 26 years). Five patients had left-sided diaphragmatic hernia. Chest X-ray was obtained from all patients which was diagnostic in 50 percent of the cases (n = 4). Additional diagnostic imaging with computerized tomography (CT) was used in six patients and upper gastrointestinal (GI) contrast study was performed in one patient. All patients underwent thoracotomy incision. Mesh repair was utilized in one patient. The mean hospitalization time was 14.1 days. There was one postoperative death (16.7%). Late presentation of blunt diaphragmatic hernia is an uncommon and challenging situation for the surgeon. Prompt diagnosis and treatment prevent serious morbidity and mortality associated with complications such as gangrene and perforation of herniated organ.


Associations between homocysteine and B vitamins and stroke: a cross-sectional study.
Homocysteine (Hcy) is a predictor for stroke. B vitamins are required for the metabolism of Hcy. We designed a study to investigate the associations of plasma Hcy and B vitamins with the prevalence of stroke in adults. A total of 8,371 adults were included in the National Health and Examination Survey (NHANES) between 2003-2006 in the United States. Multivariate regression analysis and smooth curve fitting were conducted to evaluate the associations of stroke prevalence with Hcy, folate, vitamin B6, and B12. A segmented regression model was used to analyze the threshold effects. Sample weights were calculated to ensure the results' generalizability. The mean age of all participants was 46.43 years (51.8% women), and the prevalence of stroke was 2.72%. A nonlinear and positive association was found between plasma Hcy levels and the prevalence of stroke. Furthermore, L-shaped associations were found between plasma vitamin B6 and folate levels and stroke, with the turning point at 65.2 nmol/L for vitamin B6 and 26 nmol/L for folate, respectively. Vitamin B12 revealed a U-shaped relationship with stroke, with the turning points at 492.98 pmol/L for vitamin B12. Non-linear associations of plasma Hcy and B vitamins levels with stroke prevalence were found in American adults. These associations may have an implication that higher plasma Hcy levels should be reduced, and plasma vitamin B6, vitamin B12 and folate levels should be moderately improved in stroke prevention. Future studies are needed to verify the causality of these associations and elucidate the underlying mechanisms.


Development and validation of an immune-related prognostic signature in lung adenocarcinoma.
Lung adenocarcinomas (LUAD) is the most common histological subtype of lung cancers. Tumor immune microenvironment (TIME) is involved in tumorigeneses, progressions, and metastases. This study is aimed to develop a robust immune-related signature of LUAD. A total of 1774 LUAD cases sourced from public databases were included in this study. Immune scores were calculated through ESTIMATE algorithm and weighted gene co-expression network analysis (WGCNA) was applied to identify immune-related genes. Stability selections and Lasso COX regressions were implemented to construct prognostic signatures. Validations and comparisons with other immune-related signatures were conducted in independent Gene Expression Omnibus (GEO) cohorts. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ImmuCellAI and gene set enrichment analysis (GSEA). In Cancer Genome Atlas (TCGA) LUAD cohorts, immune scores of higher levels were significantly associated with better prognoses (P < .05). Yellow (n = 270) and Blue (n = 764) colored genes were selected as immune-related genes, and after univariate Cox regression analysis (P < .005), a total of 133 genes were screened out for subsequent model constructions. A four-gene signature (ARNTL2, ECT2, PPIA, and TUBA4A) named IPSLUAD was developed through stability selection and Lasso COX regression. It was suggested by multivariate and subgroup analyses that IPSLUAD was an independent prognostic factor. It was suggested by Kaplan-Meier survival analysis that eight out of nine patients in high-risk groups had significantly worse prognoses in validation data sets (P < .05). IPSLUAD outperformed other signatures in two independent cohorts. A robust immune-related prognostic signature with great performances in multiple LUAD cohorts was developed in this study.


Successful resuscitation of an ASA 3 patient following ropivacaine-induced cardiac arrest.
A patient with severe myocardial disease and acute-on-chronic renal failure was undergoing a brachial plexus block for formation of an arteriovenous fistula when accidental intravascular injection of ropivacaine resulted in ventricular fibrillation. Cardiopulmonary resuscitation was instituted immediately and the advanced life support algorithm was followed until the return of sinus rhythm. Although, in comparison with bupivacaine, ropivacaine appears to be a safer local anaesthetic agent in the setting of intravenous injection, the emphasis on safety should remain a priority. Awareness of the risk of central nervous system and cardiovascular toxicity and preparation for immediate commencement of resuscitation in the event of toxicity remain of paramount importance.


[Non-union].
A non-union is a fracture that fails to heal within the expected time frame and occurs in approximately 3 to 5% of all fractures. Non-union has a negative impact on mental and physical functioning and quality of life. The causes, clinical presentation and treatment for non-union differ strongly on a case-by-case basis. By presenting three cases we aim to give healthcare providers more insight into the clinical scenario of non-union. In addition, we elaborate on characteristics, etiology, diagnostics and treatment of non-union.


Learning to interpret one's own outcome as unjustified amplifies altruistic compensation: a training study.
Interpretational tendencies in ambiguous situations were investigated as causal mechanisms of altruistic compensation. We used a training procedure to induce a tendency to interpret one's own advantages as unjustified. In a subsequent mixed-game, participants had to decide whether to invest their own money to compensate a victim of a norm violation. The amount of one's own resources invested as an altruistic compensation was enhanced after the training procedure compared to controls. These findings suggest that interpretational patterns with regard to injustice determine prosocial behavior. The training procedure offers a potential intervention strategy for enhancing altruistic compensation in bystander situations in which people must invest their own resources to restore justice.


CFTR inhibitors.
The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl- channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretory diarrheas, such as cholera, and for cyst expansion in autosomal dominant polycystic kidney disease. High-throughput screening has yielded CFTR inhibitors of the thiazolidinone, glycine hydrazide and quinoxalinedione chemical classes. The glycine hydrazides target the extracellular CFTR pore, whereas the thiazolidinones and quinoxalinediones act at the cytoplasmic surface. These inhibitors have been widely used in cystic fibrosis research to study CFTR function at the cell and organ levels. The most potent CFTR inhibitor has IC50 of approximately 4 nM. Studies in animal models support the development of CFTR inhibitors for antisecretory therapy of enterotoxin-mediated diarrheas and polycystic kidney disease.


Review of Poecilimon species with inflated pronotum: description of four new taxa within an acoustically diverse group.
Poecilimon Fischer (Orthoptera, Tettigoniidae) consists of about 130 species and a functional taxonomy of the genus requires arranging species into phylogenetic groups. However, this is a task that requires detailed empirical testing. This paper documents data on Poecilimon species with an inflated pronotum. The Poecilimon (Poecilimon) inflatus group is a lineage ranging along a narrow zone in the south-west corner of Anatolia and in Crete plus some other Aegean islands. By producing data of morphology and calling songs of males and responding songs of females the composition and intra-group diversity of P. inflatus group are studied. Both morphology and male calling and female responding songs, exhibited a considerable intra-group diversity. In the light of data obtained the following nomenclatural changes were made. The genus Parapoecilimon Karabağ, 1975 syn. n. is synonymised with Poecilimon Fischer and Parapoecilimon antalyaensis Karabağ, 1975 is given a new combination, Poecilimon antalyaensis (Karabağ, 1975) comb. n. Four new taxa are described in the group: (i) Poecilimon isopterus sp.n.; (ii) Poecilimon inflatus lyciae subsp. n.; (iii) Poecilimon antalyaensis myrae subsp. n., and (iv) Poecilimon antalyaensis anemurium subsp. n. The Poecilimon (P.) inflatus species group consists of the following species: (i) Poecilimon inflatus Brunner von Wattenwyl, 1891; (ii) Poecilimon martinae Heller, 2004; (iii) Poecilimon cretensis Werner, 1903; (iv) Poecilimon antalyaensis (Karabağ, 1975) comb. n.; (v) Poecilimon bilgeri Karabağ, 1953 and (vi) Poecilimon isopterus sp.n. The species group is defined by a combination of characters including the pronotum inflated in metazona and a male cerci mostly black in their apical 1/2-1/3. The male calling song has typically two types of short syllables and the females respond acoustically with very short latency times. By using combination of morphology and song data we suggest three main lineages in the group: (i) P. bilgeri, (ii) P. antalyaensis and (iii) the other four species.


Visible Light-Induced Radical Mediated DNA Damage.
Light-responsive compounds have been used to manipulate biological systems with spatial and temporal control of the event of interest. Illumination of alkylcobalamins with green light (>500 nm) produces carbon-centered radicals, which have been demonstrated to effectively cause DNA damage. Molecules that cause DNA and RNA strand scission are useful for studying polynucleotide structure and the binding of small molecules and proteins to polynucleotides. Most molecules that cause DNA damage in a light-dependent manner require high energy, short wavelength ultraviolet light, which is readily absorbed by nucleotide bases causing damage to the polynucleotides. Therefore, using alkylcobalamins is advantageous for causing strand scission of polynucleotides, because they are activated by light wavelengths that are not absorbed by nucleotide bases. Green-light illumination of methylcobalamin effectively causes DNA strand scission based on gel mobility assays. This cleavage is due to the generation of carbon-centered radicals based on the results of a radical trapping study. In addition, synthesis of an alkylcobalamin with a DNA binding moiety, spermine, improves DNA cleavage efficacy by an order of magnitude in comparison with methylcobalamin.


Effect of edeine on primary immunologic response in mice.
The effect of edeine on primary immune response against sheep erythrocytes in mice was studied. The response intensity was evaluated on the cellular and humoral level. The results showed significant decrease in the number of spleen cells capable of synthesizing hemolysins, and the decrease in serum level of these antibodies.


The effects of semen dosage and insemination frequency on the fertility of brolier breeder hens.
Sexuality mature commerical broiler breeder pullets were housed singly in laying cages and artifically inseminated with one of three different levels of undiluted pooled semen (0.1, 0.05 and 0.025 ml.) at either of two different frequencies (once and twice a week) in three different trials. The best fertility was obtained by inseminating twice a week with 0.05 ml. of semen. Inseminating once a week with 0.1 ml. of semen did not provide maximum fertility in the stock used in this study.


Changes in rate and socioeconomic inequality of cervical cancer screening in northeastern China from 2013 to 2018.
Cervical cancer, the fourth leading cancer diagnosed in women, has brought great attention to cervical cancer screening to eliminate cervical cancer. In this study, we analyzed two waves of provincially representative data from northeastern China's National Health Services Survey (NHSS) in 2013 and 2018, to investigate the temporal changes and socioeconomic inequalities in the cervical cancer screening rate in northeastern China. Data from two waves (2013 and 2018) of the NHSS deployed in Jilin Province were analyzed. We included women aged 15-64 years old and considered the occurrence of any cervical screening in the past 12 months to measure the cervical cancer screening rate in correlation with the annual per-capita household income, educational attainment, health insurance, and other socioeconomic characteristics. A total of 11,616 women aged 15-64 years were eligible for inclusion. Among all participants, 7,069 participants (61.11%) were from rural areas. The rate of cervical cancer screening increased from 2013 to 2018 [odds ratio (OR): 1.06; 95% confidence interval (CI): 1.04-1.09, p < 0.001]. In total, the cervical cancer screening rate was higher among participants who lived in urban areas than rural areas (OR: 1.20; 95% CI: 1.03-1.39, p = 0.020). The rate was also higher among those with the highest household income per capita (OR: 1.30; 95% CI: 1.07-1.56, p = 0.007), with higher educational attainment (p < 0.001), and with health insurance (p < 0.05), respectively. The rate of cervical cancer screening was also significantly associated with parity (OR: 1.62; 95% CI: 1.23-2.41, p = 0.001) and marital status (OR: 1.45; 95% CI: 1.15-1.81, p = 0.001) but not ethnicity (OR: 1.41; 95% CI: 0.95-1.36, p = 0.164). Cervical cancer screening coverage improved from 2013 to 2018 in northeastern China but remains far below the target 70% screening rate proposed by the World Health Organization. Although rural-urban inequality disappeared over time, other socioeconomic inequalities remained.


Downregulated pseudogene CTNNAP1 promote tumor growth in human cancer by downregulating its cognate gene CTNNA1 expression.
Accumulating evidence indicates that deregulation of cancer-associated pseudogene is involved in the pathogenesis of cancer. In the study, we demonstrated that pseudogene CTNNAP1, for the CTNNA1 gene, was dysregulated in colorectal cancer and the degree of dysregulation was remarkably associated with tumor node metastasis (TNM) stage (P<0.05). The mechanistic experiments revealed that pseudogene CTNNAP1 played a pivotal role in the regulation of its cognate gene CTNNA1 by competition for microRNA-141. Moreover, gain-of-function approaches showed that overexpression of CTNNAP1 or CTNNA1 significantly inhibited cell proliferation and tumor growth in vitro and in vivo by inducing G0/G1 cell cycle arrest. Our findings add a new regulatory circuit via competing endogenous RNA (ceRNA) cross-talk between pseudogene CTNNAP1 and its cognate gene CTNNA1, and provide new insights into potential diagnostic biomarker for monitoring human colorectal cancer.


Sleep and psychiatric symptoms in young child psychiatric outpatients.
Sleep may underlie psychiatric symptoms in young children. However, not many studies have reported on sleep and its associations with symptoms in young child psychiatric patients. To assess the amount and quality of sleep and how sleep associates with psychiatric symptoms in young child psychiatric patients. Furthermore, we evaluated how sleep and daytime somnolence differed in patients and their age- and gender-matched controls. The sample consisted of 139 3- to 7-year-old child psychiatric outpatients and 139 age- and gender-matched controls from community. We evaluated sleep and daytime somnolence with the Sleep Disturbance Scale for Children in all children and psychiatric symptoms with Child Behaviour Checklist (CBCL) in the patient group. Family background information was collected from the patients. Of the patients, 31.6% had a significant sleep problem and 14.4% slept too little. The most typical sleep problems were restless sleep (31.7%), morning tiredness (21.6%) and difficulties getting to sleep at night (18.7%). All types of sleep problems were associated with CBCL total, internalising and externalising problems (all p-values < .01). We observed a strong association between all types of sleep problems and emotionally reactive subscale ( p-value < .001). Furthermore, parent-reported sleep problems increased significantly the risk of having high scores on total (odds ratio (OR) = 5.3, 95% confidence interval (CI) = [2.2, 12.6], p < .001), external (OR = 3.7, 95%, CI = [1.6, 8.5], p < .01) and internal (OR = 2.5, 95% CI = [1.1, 5.5], p < .05) scores after controlling for age, gender, family structure and parent's educational level. Even mild sleep disturbance increased the intensity of psychiatric symptoms. Compared to controls, patients slept less ( p < .001) and had significantly more frequent restless sleep, nightmares and morning and daytime somnolence. Sleep problems and too little sleep are prevalent in young child psychiatric patients, and they relate strongly to the intensity of psychiatric symptoms. Identification and treatment of sleep problems should be a routine part of the treatment plan for young child psychiatric patients. The results emphasise the need for assessing sleep in young child psychiatric patients, as treating the sleep problem may reduce psychiatric symptoms.


Anterior Tragal Crease Is Associated With SYNTAX Score in Non-ST-Segment Elevation Myocardial Infarction.
The main aim of this study was to investigate the relation between anterior tragal crease (ATC) and coronary artery lesion complexity and severity assessed using the SYNTAX score (SXscore) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). A total of 121 patients with a first-time diagnosis of NSTEMI were consecutively enrolled. ATC was defined as ≥1 crease that was close to the tragus and descended anteriorly. SXscore was calculated using the SXscore algorithm. The SXscore was higher in the ATC-positive group than in the ATC-negative group (11.85 ± 8.20 vs 7.52 ± 6.38, P = .003). In the univariate analysis, hemoglobin (male: 11.7-17.4 g/dL, female: 11.7-16.1 g/dL; P = .006), diabetes mellitus (P = .031), current smoking (P = .022), and presence of ATC (P = .022) were significantly associated with increased SXscore. Multivariate analysis revealed ATC (95% confidence interval [CI]: 1.313-7.800, P = .011), current smoking (95% CI: 2.034-13.893, P = .001), and hemoglobin (95% CI: 0.433-0.822, P = .002) as independent determinants of increased SXscore. Anterior tragal crease is easily detected by physical examination. Presence of ATC in patients with NSTEMI may be a warning signal of complexity and severity of coronary artery disease (CAD).


Alternative Weighting Approaches for Anchored Matching-Adjusted Indirect Comparisons via a Common Comparator.
Adjusted indirect comparisons (anchored via a common comparator) are an integral part of health technology assessment. These methods are challenged when differences between studies exist, including inclusion/exclusion criteria, outcome definitions, patient characteristics, as well as ensuring the choice of a common comparator. Matching-adjusted indirect comparison (MAIC) can address these challenges, but the appropriate application of MAICs is uncertain. Examples include whether to match between individual-level data and aggregate-level data studies separately for treatment arms or to combine the arms, which matching algorithm should be used, and whether to include the control treatment outcome and/or covariates present in individual-level data. Results from seven matching approaches applied to a continuous outcome in six simulated scenarios demonstrated that when no effect modifiers were present, the matching methods were equivalent to the unmatched Bucher approach. When effect modifiers were present, matching methods (regardless of approach) outperformed the Bucher method. Matching on arms separately produced more precise estimates compared with matching on total moments, and for certain scenarios, matching including the control treatment outcome did not produce the expected effect size. The entropy balancing approach was used to determine whether there were any notable advantages over the method proposed by Signorovitch et al. When unmeasured effect modifiers were present, no approach was able to estimate the true treatment effect. Compared with the Bucher approach (no matching), the MAICs examined demonstrated more accurate estimates, but further research is required to understand these methods across an array of situations.


Pancreatic enzyme autodigestion of an unresectable retroperitoneal liposarcoma.
This is a case of a 71-year-old man who had multiple synchronous retroperitoneal liposarcoma (LPS) foci composed of both well-differentiated and dedifferentiated histologies. In addressing this, the patient underwent a margin negative resection of a 11.8×8.8 cm right-sided dedifferentiated LPS requiring pancreaticoduodenectomy; however, a 13.1×7.2 cm left-sided well-differentiated LPS (WDLPS) was not resected due to its involvement of the proximal mesenteric vessels. The patient's postoperative course was complicated by grade B postoperative pancreatic fistula involving the anatomical territory of the residual WDLPS. Over the next 12 months, serial CT scans demonstrated a stepwise reduction in size of the WDLPS until it completely regressed. The authors hypothesise that enzymes shed from the pancreatic fistula initiated the autodigestion and subsequent necrosis of the WDLPS with associated tumour regression.


Argon laser trabeculoplasty five years on.
The results of argon laser trabeculoplasty (ALT) in a series of 252 patients are presented with follow-up of up to five years. The procedure is effective in chronic open-angle glaucoma (COAG), ocular hypertension and pseudoexfoliative (PXF) glaucoma. Most cases were treated initially over 180 degrees of the angle and repeat treatment of the remaining 180 degrees usually resulted in an additional fall in IOP which was maintained at two, three and four year follow-up with only a small number of these retreated cases having no fall on later follow-up. ALT was not very effective in further lowering IOP in eyes with IOP controlled to a low level before treatment or in low tension glaucoma. It was effective in most of a number of miscellaneous glaucomas including pigmentary glaucoma. Apart from the immediate high rise in IOP the main complication was a late high rise in IOP which was serious in degree and appeared mainly in PXF but also in two cases of ocular hypertension. The presence of a concomitant fall in IOP in the fellow untreated eye is important and probably due to better compliance with treatment. Almost all cases required medical treatment for glaucoma which could not be ceased after ALT. ALT should be seen as an adjunct to, but not a substitute for, medical treatment.


Imaging approaches to Parkinson disease.
Parkinson disease (PD) is associated with nigral degeneration and striatal dopamine deficiency. Demonstrating midbrain structural abnormalities with transcranial sonography or diffusion-weighted MRI or showing striatal dopamine terminal dysfunction with PET or SPECT supports the diagnosis and rationalizes the use of dopaminergic medications. In atypical PD variants, transcranial sonography can detect striatal hyperechogenicity, and diffusion-weighted imaging can detect increased putamen water diffusion, whereas (18)F-FDG PET reveals reduced lentiform nucleus glucose metabolism. PET and SPECT can detect changes in striatal dopamine levels after levodopa administration and relate these to motor responses. Loss of cortical dopaminergic and cholinergic function is present in demented PD and, on occasion, amyloid deposits can be detected. Loss of cardiac sympathetic innervation can be sensitively detected in PD with (18)F-dopamine PET or (123)I-metaiodobenzylguanidine SPECT. Finally, PET can detect widespread brain inflammation in PD. This review discusses the role of structural and functional imaging for diagnosing and managing different parkinsonian syndromes.