Photosynthetic gas exchange of the mangrove, Rhizophora stylosa Griff., in its natural environment.
Photosynthetic gas exchange properties of leaves of the mangrove, Rhizophora stylosa Griff., were investigated in order to assess its productivity and gain some insight into the constraints set upon it by the saline habitat. Mature trees of this dominant species were studied in their natural, tidal-forest environment at Hinchinbrook Is., North Queensland for two periods during the dry season. Individual leaves were enclosed in a chamber wherein environmental conditions were varied. CO2 assimilation, transpiration and environmental parameters were monitored during daylight hours by instrumentation housed in a mobile laboratory mounted on a barge. Analysis of the daily course of leaf gas exchange revealed a CO2 assimilation capacity comparable with that of many glycophytic trees. Photosynthesis was strongly influenced by leaf temperature as well as photon flux density. There was a strong and steadily increasing inhibition of gas exchange as leaf temperatures and, consequently, the leaf to air VPD increased. CO2 assimilation rates and leaf conductances to water vapour diffusion were strongly correlated, resulting in nearly constant internal CO2 concentrations in the leaves under the full range of conditions. The effect of leaf orientation in minimizing the leaf-to-air temperature difference was striking. The close coordination between stomatal conductance and CO2 assimilation rate in this mangrove results in high water use efficiency. This sparing use of water may be an important factor underlying the high salinity tolerance of mangroves.


Impact of propofol anesthesia induction on cardiac function in low-risk patients as measured by intraoperative Doppler tissue imaging.
Despite a few experimental studies showing a dose-dependent myocardial depressive effect of propofol anesthesia induction, few clinical data are available to determine its precise impact on myocardial function, probably because of its brevity and a lack of appropriate evaluation tools. The purpose of this study was to examine the impact of propofol-based anesthesia induction on left ventricular (LV) function using Doppler tissue and speckle-tracking imaging. In 19 low-risk patients with normal LV systolic and diastolic function undergoing noncardiac surgery (all women; mean age, 42 years), propofol bolus (2.0 mg/kg) was administered intravenously for anesthesia induction. LV ejection fraction, global peak systolic longitudinal strain, and tissue Doppler-derived indices of mitral annular velocity during systole (S'), early diastole (e'), and atrial contraction (a') were determined by intraoperative transthoracic echocardiography before and 1, 3, and 5 min after propofol bolus (T0, T1, T2, and T3, respectively). The following at T1, T2, and T3 were significantly less in magnitude than at T0: septal S' (5.61, 5.61, and 5.51 vs 7.60 cm/sec, P < .001), lateral S' (5.75, 5.89, and 5.94 vs 8.12 cm/sec, P < .001), septal e' (10.10, 10.26, and 10.07 vs 11.4 cm/sec, P < .01), septal a' (6.70, 6.21, and 6.13 vs 8.58 cm/sec, P < .01), lateral a' (7.29, 6.81, and 6.85 vs 9.01 cm/sec, P < .01), and longitudinal strain (-19.36%, -19.71%, and -19.61% vs -22.28%, P < .001). LV ejection fraction was not significantly changed (P = .361). Propofol anesthesia induction diminished LV and atrial contraction in low-risk patients with prior normal LV function. Further studies are needed to understand the clinical implications, particularly for higher risk populations.


An Analysis of Long-Term Outcomes in Patients Treated by Extensive Bowel Resection Due to Advanced Ovarian Cancer Relative to the Effectiveness of Surgery.
Surgery for advanced ovarian cancer (AOC) often requires bowel resections. However, the impact of bowel surgery on patient overall survival (OS) has not yet been precisely determined. The aim of the study was to analyze the OS rates in a group of AOC patients undergoing bowel resection. We carried out a retrospective analysis of patients who had undergone low anterior resection of the rectum (LAR) during primary or interval debulking surgery for AOC. We divided the patients into 2 groups: Group 1 included 69 patients who underwent only LAR; Group 2 included 66 patients who underwent LAR and additional bowel resection. The control group included 71 AOC patients who did not required bowel resection. In the subgroup of patients with no gross residual disease (NGR), there were no differences in OS between Groups 1 and 2. In the subgroup of "optimally" (tumors <1 cm) debulked patients, Group 1 patients had a higher median OS than Group 2 patients. Additionally, there was no difference between Groups 1 and 2 as far as the number of severe adverse events. Multiple bowel resections seem to improve OS in patients when NGR is achieved but should be avoided when complete resection is not possible.


The effect of body mass index on recovery and return to work after onset of work-related low back pain.
To assess the effect of body mass index (BMI) on pain and function outcomes in the acute and subacute stages of work-related low back pain (LBP). A prospective cohort of working-age patients (410 male, 197 female) with recent onset LBP (≤14 days' duration) provided height and weight as part of a study of prognostic factors for back disability. Self-reported pain, functional limitation, and work status were assessed at 1- and 3-month follow-ups. BMI (kg/m) was used to categorize participants as normal (31%), overweight (40%), or obese (29%). In prediction analyses, outcomes of pain, functional limitation, and return to work showed no significant variation (P > 0.05) by BMI, with or without controlling for potential confounds. BMI is not a useful prognostic factor during the acute and subacute stages of work-related LBP.


MRI 'magic angle' imaging of finger tendons.
The value of using the technique of magic angle MR imaging to demonstrate finger tendons is explored. Images of fresh frozen cadaveric specimens are presented and the structures that can be visualized in the finger are described. The results suggest that magic angle MR imaging may be a useful non-invasive technique of visualizing the details of the tendons and their surrounds in the hand.


NF-κB-dependent signals control BOB.1/OBF.1 and Oct2 transcriptional activity in B cells.
The transcriptional co-activator BOB.1/OBF.1 is crucial for Octamer-driven transcription in B cells. BOB.1/OBF.1-deficiency leads to tremendous defects in B-cell development and function. Therefore, in the past research focused on the identification of BOB.1/OBF.1 target genes. However, the regulation of BOB.1/OBF.1 expression itself is poorly understood. Here we show that in B cells NF-κB as well as to some extent NFAT proteins are involved in the activation of basal as well as inducible BOB.1/OBF.1 expression by direct binding to the BOB.1/OBF.1 promoter. Moreover, the analysis of different inducers of NF-κB, like several TLR ligands, TNF-α, BAFF, or LTα1β2, revealed that both the canonical and noncanonical NF-κB pathways are involved in the induction of BOB.1/OBF.1 gene. The identification of so far unknown inducers that regulate BOB.1/OBF.1 expression in B cells provides novel insights in the potential function of BOB.1/OBF.1 during different aspects of B-cell development and function.


Design and synthesis of 4-alkynyl pyrazoles as inhibitors of PDE4: a practical access via Pd/C-Cu catalysis.
The design and synthesis of 4-alkynyl pyrazole derivatives has led to the identification of new class of PDE4 inhibitors. All these compounds were accessed for the first time via a facile Pd/C-CuI-PPh(3) mediated C-C bond forming reaction between an appropriate pyrazole iodide and various terminal alkynes. In vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized indicated that 4-alkynyl pyrazole could be a promising template for the discovery of novel PDE4 inhibitors.


Simultaneous determination of pesticide residues in pomegranate whole fruit and arils using LC-MS/MS.
An analytical method in pomegranate whole fruits and arils was developed in LC-MS/MS and validated as per SANTE/12682/2019. Samples were extracted following acetonitrile-based modified QuEChERS protocol. The method was linear and the coefficient of determination ranged between 0.998 and 0.999. Through this method, all the pesticides were detected and quantified at 10 µg kg-1. The accuracy test at 10, 50, and 100 µg kg-1 spiking level recorded recovery between 70 and 120% and RSD less than 15% in both matrices. No significant matrix effect was observed for most pesticides. Intra (RSDr) and inter-day (RSDwr) precision estimated at 50 µg kg-1 found acceptable RSD in both matrices. Measurement uncertainty at 50 µg kg-1 was in the range of 4.02 to 16.12 µg kg-1. Quantifying pesticides in pomegranate whole fruits, peel, and arils using the proposed method is highly suitable and reproducible for 74 pesticides in a short run time of 25.00 min.


Functional coupling of diverse voltage-gated Ca(2+) channels underlies high fidelity of fast dendritic Ca(2+) signals during burst firing.
In neurons, the Ca(2+) signal associated with the dendritic back-propagating action potential codes a chemical message to the different dendritic sites, playing a crucial role in electrical signalling, synaptic transmission and synaptic plasticity. The study of the underlying Ca(2+) current, mediated by different types of voltage-gated Ca(2+) channels, cannot be achieved by using the patch clamp technique. In this article, we used a recently developed cutting-edge optical technique to investigate the physiological behaviour of local Ca(2+) currents along the apical dendrite of CA1 hippocampal pyramidal neurons. We directly measure, for the first time, the synergistic activation and deactivation of the diverse dendritic voltage-gated Ca(2+) channels operating during bursts of back-propagating action potentials to precisely control the Ca(2+) signal. We demonstrate that the Ca(2+) loss via high-voltage-activated channels is compensated by the Ca(2+) entry via the other channels translating in high fidelity of Ca(2+) signalling. In CA1 hippocampal pyramidal neurons, the dendritic Ca(2+) signal associated with somatic firing represents a fundamental activation code for several proteins. This signal, mediated by voltage-gated Ca(2+) channels (VGCCs), varies along the dendrites. In this study, using a recent optical technique based on the low-affinity indicator Oregon Green 488 BAPTA-5N, we analysed how activation and deactivation of VGCCs produced by back-propagating action potentials (bAPs) along the apical dendrite shape the Ca(2+) signal at different locations in CA1 hippocampal pyramidal neurons of the mouse. We measured, at multiple dendritic sites, the Ca(2+) transients and the changes in membrane potential associated with bAPs at 50 μs temporal resolution and we estimated the kinetics of the Ca(2+) current. We found that during somatic bursts, the bAPs decrease in amplitude along the apical dendrite but the amplitude of the associated Ca(2+) signal in the initial 200 μm dendritic segment does not change. Using a detailed pharmacological analysis, we demonstrate that this effect is due to the perfect compensation of the loss of Ca(2+) via high-voltage-activated (HVA) VGCCs by a larger Ca(2+) component via low-voltage-activated (LVA) VGCCs, revealing a mechanism coupling the two VGCC families of K(+) channels. More distally, where the bAP does not activate HVA-VGCCs, the Ca(2+) signal is variable during the burst. Thus, we demonstrate that HVA- and LVA-VGCCs operate synergistically to stabilise Ca(2+) signals associated with bAPs in the most proximal 200 μm dendritic segment.


Severe episodic viral wheeze in preschool children: High risk of asthma at age 5-10 years.
In population studies, most children with episodic viral wheeze (EVW) become symptom free by 6 years. We studied the outcome of children with severe EVW, treated and followed up in hospital. We followed up 78 children <4 years, managed by paediatricians for severe EVW, to the age of 5-10 years. We recorded respiratory symptoms, spirometry and exhaled nitric oxide (FeNO). At follow-up, 42 children (54%) had current wheeze or dyspnoea, and 52 (67%) had current asthma. There was no significant difference between children with and without current asthma in FEV1 (p = 0.420), but FeNO was higher in children with current asthma (median (interquartile range) 14.5 (11.25-21.50) ppb) than in those without (12.0 (10.0-13.8) ppb, p = 0.020). Positive family history of asthma was the only factor associated with current asthma (odds ratio 8.77, 95% CI 2.88-26.69, p < 0.001). This remained significant after adjustment for duration of follow-up, gender and parental smoking. Conclusion. Severe EVW at preschool age has a high risk of asthma at age 5-10 years, and this is reinforced by a positive family history of asthma and to elevated FeNO levels.


Hepatitis B reactivation: A possible cause of coronavirus disease 2019 vaccine induced hepatitis.
Coronavirus disease 2019 (COVID-19) vaccines were rapidly implemented globally and vaccine-associated immune-related hepatitis was recently reported. We aim to investigate its impact in regions endemic of chronic hepatitis B (CHB). We retrospectively collected patients who developed hepatitis within 90 days after COVID-19 vaccination in Taiwan. The mechanisms of hepatitis included vaccine induced liver injury (VILI) and immune-related hepatitis, which are direct liver injuries defined as aspartate or alanine aminotransferase (AST or ALT) increased ≥ 5-fold upper limit of normal (ULN) and/or AST or ALT ≥ 3-fold of ULN with concurrent total bilirubin ≥ 2-fold of ULN. Indirect liver injury due to HBV reactivation was defined as HBsAg reverse seroconversion or significant rise in HBV DNA level. The demographics, clinical data, and course of hepatitis were compared statistically. Twenty-five patients were included with a median age of 54. The culprit vaccines were ChAdOx1 nCoV-19 (n = 9), mRNA-1273 (n = 12), and BNT162b2 (n = 4). The characteristics of hepatitis were comparable regardless of vaccine subtypes. The median onset of hepatitis was 25 days post vaccination, with a peak of 10-fold ALT-increase. The etiologies included HBV reactivation (n = 10), VILI (n = 10), and immune-related hepatitis (n = 5). HBV reactivation accounts for 90% of vaccine-induced hepatitis in patients of CHB (n = 10), and two patients died. Patients with initial AST levels >500 U/L increased 27-fold risks of liver injury greater than moderate severity compared with those without. COVID-19 vaccine induced hepatitis is a clinical significant complication, and HBV reactivation may account for a possible mechanism.


Establishing a reliable gait evaluation method for rodent studies.
CatWalk is one of the most popular tools for evaluating gait recovery in preclinical research, however, there is currently no consensus on which of the many gait parameters captured by CatWalk can reliably model recovery. There are conflicting interpretations of results, along with many common but seldom reported problems such as heel walking and poor compliance. We developed a systematic manual classification method that overcomes common problems such as heel walking and poor compliance. By correcting automation errors and removing inconsistent gait cycles, we isolated stretches of recordings that are more reliable for analysis. Recovery outcome was also assessed by quantitative histomorphometric analysis of myelinated axons. While 40-60% of runs were erroneously classified without manual intervention, we corrected all errors with our new method, and showed that Stand Time, Duty Cycle, and Swing Speed are able to track significant differences over time and between experimental groups (all p<0.05). The usability of print area and intensity parameters requires further validation beyond the capabilities of CatWalk. There is currently no strategy that addresses problems such as heel walking and poor compliance, and therefore no standard set of parameters that researchers can rely on to report their findings. Manual classification is a crucial step to generate reliable CatWalk data, and Stand Time, Duty Cycle, and Swing Speed are suitable parameters for evaluating gait recovery. Static parameters such as print area and intensity should be used with extreme caution.


Peripheral natural killer cells exhibit qualitative and quantitative changes in patients with psoriasis and atopic dermatitis.
Psoriasis and atopic dermatitis are the most recurrent skin inflammatory disorders. Despite their distinct aetiology and clinical aspects, these diseases share several immunological features. Besides the largely documented role of T cells, emerging literature supports a potential involvement of innate immune effectors, the natural killer (NK) cells, in both pathologies. In the peripheral blood, NK cells consist of CD3-CD56dim and CD3-CD56bright cell subsets, harbouring a distinct cell surface phenotype, but both endowed with the main NK-cell effector functions: cytotoxicity and cytokine production. To determine whether the frequency, the cell surface phenotype and the functional properties of peripheral NK cells were affected in patients with psoriasis or atopic dermatitis. Peripheral blood mononuclear cells were isolated from 11 patients with psoriasis, nine patients with atopic dermatitis and 16 healthy individuals. By using flow cytometry, we analysed the following parameters of peripheral NK cells: the frequency, the cell surface expression of several NK-cell receptors (NKR) and the activation of the effector functions upon various in vitro stimuli. Peripheral NK cells were significantly reduced in both skin diseases. The cell surface expression of various NKR was differently modified in peripheral NK cells of the two cohorts of patients. Finally, NK-cell natural cytotoxicity was affected only in atopic dermatitis, while interferon-γ production was defective in both groups of patients. Psoriasis and atopic dermatitis are associated with quantitative and qualitative changes of peripheral NK cells, mostly shared by both diseases, supporting a common process implicating these innate effectors in skin inflammation.


Role of intratumoral infiltrating macrophages after transarterial immunoembolization for hepatocellular carcinoma.
Preoperative transarterial immunoembolization (TIE) for hepatocellular carcinoma (HCC) is effective for preventing recurrence. We aimed to investigate the intratumoral and peritumoral M1 macrophage-induced immune response following TIE treatment. We compared 13 patients treated with TIE between 2003 and 2009 (TIE group) and 13 patients treated with surgery alone during the same period of time at our institute (control group) using an immunohistological study with CD68 and CD163 antibodies. No significant differences in clinicopathological characteristics, except for surgical time, were observed between the two groups. The 3-year recurrence-free survival outcome of the TIE group was quite different from that of the control group (100% vs. 38.5%, P = 0.034). In the histological investigation, lytic necrosis and coagulation necrosis of the main tumor along with the presence of multinuclear giant cells were observed in 10 of the 13 patients in the TIE group. The immunohistological study showed that not only the numbers of intratumoral CD68(+) cells, but also the numbers of intratumoral and peritumoral CD8(+) cells were significantly increased in the TIE group. The suppression of tumor recurrence induced by preoperative TIE might be induced by intratumoral M1 macrophages that are activated by OK-432 and fibrinogen.


Leptospirosis as the most frequent infectious disease impairing productivity in small ruminants in Rio de Janeiro, Brazil.
Despite the importance of small ruminants breeding in developing countries, milk/meat productivity remains unsatisfactory. Infectious diseases, such as leptospirosis, brucellosis, and small ruminant lentiviruses (SRLVs), contribute to this scenario. The objective of the present study was to determine the role of each of these diseases in the productivity of small ruminants breeding in Rio de Janeiro, Brazil. In goats, 343 samples were tested for leptospirosis, 560 for Brucella abortus, and 506 for caprine arthritis-encephalitis (CAE), whereas in sheep, 308 samples were tested for leptospirosis, 319 for B. abortus, 374 for Brucella ovis, and 278 for Maedi-Visna (MV). Regarding leptospirosis, 25.9% of goats and 47.4% sheep were seroreactive, with serovar Hardjo the most prevalent in both species. Anti-B. abortus agglutinins were found in 0.7% of all samples, exclusively in goats. In relation to SRLVs, 8.6% of goats and 3.2% of sheep samples were positive for CAE and MV, respectively. Leptospirosis was the major infectious problem in the small ruminants sampled and may contribute to impaired productivity of these animals.


Drug-induced changes in the plasma membrane of Microsporum canis. A preliminary freeze--fracture study.
Commercial solutions of clotrimazole, tolnaftate and tolcyclate were tested for 12 h in cultures of Microsporum canis. They induced modifications in particle distribution, a blebbing of particle-free areas and the appearance of lamellar figures on the plasma membrane of fungus cells. The first two changes in the plasma membrane might be ascribed to a modification of the spectrin-like meshwork, while the third could be the result of a crystalline organization of membrane lipids.


Studies on the dopamine-dependent modulation of amino acid-gated currents in cone horizontal cells of the perch (Perca fluviatilis).
The whole-cell patch-clamp technique was employed to record membrane currents from isolated horizontal cells in culture. Concentration-response relationships for currents induced by L-glutamate, kainate and quisqualate were measured. Preincubation with dopamine changed the parameters of the concentration-response curves in a particular way for each agonist. The maximum currents induced by glutamate increased by 50-100% and the EC50-values were slightly shifted to higher values. The increase of kainate-induced maximum currents after dopamine incubation did not exceed 30% but the EC50-values were clearly shifted to lower concentrations. Quisqualate-induced maximum currents were not enhanced by dopamine preincubation but the EC50-values were shifted to lower concentrations. The dopamine-dependent modulation was affected by removal of magnesium and preincubation with concanavalin A and aniracetam. The concentration-response relation and the time-course of the dopamine effect on glutamate-induced currents is described.


Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage.
It has been suggested that DNA methylation/demethylation is involved in regulating V(D)J rearrangement. Although methylated DNA is thought to induce an inaccessible chromatin structure, it is unclear whether DNA methylation can directly control V(D)J recombination independently of chromatin structure. In this study, we tested whether DNA methylation directly affects the reactivity of the RAG1/RAG2 complex. Specific methylation within the heptamer of the recombination signal sequences (RSS) markedly reduced V(D)J cleavage without inhibiting RAG1/RAG2-DNA complex formation. By contrast, methylation at other positions around the RSS did not affect the reactivity of the RAG proteins. The presence of a methyl-CpG binding-domain protein inhibited the binding of the RAG1/RAG2 complex to all the methylated CpG sites that were tested. Our findings suggest that DNA methylation around the RSS may have a previously unexpected function in regulating V(D)J recombination by directly inhibiting V(D)J cleavage, in addition to its general function of inducing an inaccessible chromatin configuration.


Early infantile epileptic encephalopathy with suppression burst: Ohtahara syndrome.
Eleven infants with neonatal onset of intractable epilepsy are described, who showed the clinical and electroencephalographic features of Ohtahara syndrome. With time, transition to West and Lennox-Gastaut syndromes occurred. No cause could be found in eight cases. All nine survivors are severely mentally and physically handicapped and continue to have seizures. Early infantile epileptic encephalopathy represents the earliest of the age-dependent epileptic encephalopathies.


[Efficacy of basiliximab in the treatment of 87 cases of steroid-refractory or steroid-dependent acute graft-versus-host disease].
Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: ①There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. ②Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . ③The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. ④The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . ⑤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . ⑥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.


Prevalence and predictors for clinical attachment loss in adolescents in Latin America: cross-sectional study.
To describe the prevalence, severity and extension of clinical attachment loss (CAL) and to study the predictors in 15- to 19-year-old adolescents from high schools in the Latin America. A cross-sectional, epidemiological study was performed. The sample included 1070 high school adolescents 15-19 years of age from Santiago de Chile (Chile), Buenos Aires, Córdoba, Mendoza (Argentina), Montevideo (Uruguay), Quito (Ecuador) and Medellín (Colombia). Calibrated examiners performed full mouth, six sites per tooth clinical examination. There was a response rate of 100%. The prevalence of CAL ≥3 mm in ≥1 site was 32.6%, probing pocket depth ≥4 mm was 59.3% and bleeding on probing (BoP) ≥25% was 28.6%. The logistic regression analysis adjusted for cities revealed that smoking (OR = 1.6), attending public school (OR = 2.3) and having a BoP ≥25% (OR = 4.2) were positively associated with CAL ≥3 mm in ≥ 1 site. Clinical attachment loss was prevalent in Latin America adolescents and it is associated with smoking, attendance public school and BoP.


Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics.
This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor β((ERβ) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics.


Crystal packing in two pH-dependent crystal forms of rhamnogalacturonan acetylesterase.
The glycoprotein rhamnogalacturonan acetylesterase from Aspergillus aculeatus has been crystallized in two crystal forms, an orthorhombic and a trigonal crystal form. In the orthorhombic crystal form, the covalently bound carbohydrate at one of the two N-glycosylation sites is involved in crystal contacts. The orthorhombic crystal form was obtained at pH 5.0 and the trigonal crystal form at pH 4.5. In one case, the two crystal forms were found in the same drop at pH 4.7. The differences in crystal packing in the two crystal forms can be explained by the pH-dependent variation in the protonation state of the glutamic acid residues on the protein surface.


Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos.
The dual-luciferase assay has been widely used in cell lines to determine rapidly but accurately the activity of a given promoter. Although this strategy has proved very useful, it does not allow the promoter and gene function to be analyzed in the context of the whole organism. Here, we present a rapid and sensitive assay based on the classical dual-luciferase reporter technique which can be used as a new tool to characterize the minimum promoter region of a gene as well as the in vivo response of inducible promoters to different stimuli. We illustrate the usefulness of this system for studying both constitutive (telomerase) and inducible (NF-kappaB-dependent) promoters. The flexibility of this assay is demonstrated by induction of the NF-kappaB-dependent promoters using simultaneous microinjection of different pathogen-associated molecular patterns as well as with the use of morpholino-gene mediated knockdown. This assay has several advantages compared with the classical in vitro (cell lines) and in vivo (transgenic mice) approaches. Among others, the assay allows a rapid and quantitative measurement of the effects of particular genes or drugs in a given promoter in the context of a whole organism and it can also be used in high throughput screening experiments.


[Discussion of leigong 17 processing methods].
"Seventeen Methods" plays an important role in the field of processing medicinal herbs, and also makes a notable impact on modern ages. However, some problems among it are still existed. According to the origin of "17 Methods" and interrelating records, a simple description about its objections was given.


Serum lipoprotein abnormalities in renal allograft recipients.
Detailed lipid composition of serum and isolated lipoprotein fractions in male and female transplant recipients has been determined. Results have been compared with appropriate controls and a number of abnormalities have become apparent: (i) Serum total cholesterol, triglyceride and phospholipid levels were significantly elevated in transplant recipients. (ii) All lipid classes VLDL were significantly increased in both male and female patients. (iii) LDL-total cholesterol, triglyceride and phospholipid were significantly raised in female transplant patients, but this was true only for LDL-triglyceride in male patients. (iv) In female patients, HDL-total cholesterol and -triglyceride were significantly elevated, while in male patients, HDL-total cholesterol, but not HDL-triglyceride, was significantly greater than in controls. (v) The ratio of esterified to free cholesterol was significantly reduced in HDL of female transplant recipients. Results from correlation analysis suggest a relationship between some of the lipid abnormalities and renal function in female patients, while in male patients only immunosuppressive therapy is implicated.


Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease.
Sites of early neuropathologic change provide important clues regarding the initial clinical features of Alzheimer's disease (AD). We have shown significant reductions in hippocampal synaptic density in participants with AD, consistent with the early degeneration of entorhinal cortical (ERC) cells that project to hippocampus via the perforant path. In this study, [11C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) and [18F]flortaucipir binding to tau were measured via PET in 10 participants with AD (5 mild cognitive impairment, 5 mild dementia) and 10 cognitively normal participants. In the overall sample, ERC tau was inversely associated with hippocampal synaptic density (r = -0.59, p = 0.009). After correction for partial volume effects, the association of ERC tau with hippocampal synaptic density was stronger in the overall sample (r = -0.61, p = 0.007) and in the AD group where the effect size was large, but not statistically significant (r = -0.58, p = 0.06). This inverse association of ERC tau and hippocampal synaptic density may reflect synaptic failure due to tau pathology in ERC neurons projecting to the hippocampus.


Importance of DJ-1 in autophagy regulation and disease.
Autophagy is a highly conserved biological process that has evolved across evolution. It can be activated by various external stimuli including oxidative stress, amino acid starvation, infection, and hypoxia. Autophagy is the primary mechanism for preserving cellular homeostasis and is implicated in the regulation of metabolism, cell differentiation, tolerance to starvation conditions, and resistance to aging. As a multifunctional protein, DJ-1 is commonly expressed in vivo and is associated with a variety of biological processes. Its most widely studied role is its function as an oxidative stress sensor that inhibits the production of excessive reactive oxygen species (ROS) in the mitochondria and subsequently the cellular damage caused by oxidative stress. In recent years, many studies have identified DJ-1 as another important factor regulating autophagy; it regulates autophagy in various ways, most commonly by regulating the oxidative stress response. In particular, DJ-1-regulated autophagy is involved in cancer progression and plays a key role in alleviating neurodegenerative diseases(NDS) and defective reperfusion diseases. It could serve as a potential target for the regulation of autophagy and participate in disease treatment as a meaningful modality. Therefore, exploring DJ-1-regulated autophagy could provide new avenues for future disease treatment.


PP2A fulfills its promises as tumor suppressor: which subunits are important?
Reversible phosphorylation of proteins, catalyzed by kinases and phosphatases, is a key regulatory mechanism in the control of multiple cellular signal transduction pathways. Uncontrolled regulation by the altered phosphorylation state of the components of these pathways often leads to increased cell proliferation and cell transformation. Many viruses encode oncogenic proteins, required for their efficient viral replication, which deregulate the activity of host cell proteins. This might program cells to a malignant state, underlying the molecular mechanism of tumor formation and cancer development. Recent studies reveal a role for a specific form of protein phosphatase 2A (PP2A) in viral-induced cell transformation by interaction with the small t antigen (ST) of the DNA tumor simian virus 40 (SV40).


Amniocentesis performed at 14 weeks' gestation or earlier: comparison with first-trimester transabdominal chorionic villus sampling.
To compare our initial experiences with early amniocentesis and transabdominal chorionic villus sampling (CVS). We compared the diagnostic and pregnancy outcomes of our initial 250 patients undergoing early amniocentesis (at or before the 14th completed week of gestation) or transabdominal CVS (performed between 9.5-12.9 weeks' gestation). In both groups, the indication for prenatal diagnosis was advanced maternal age (35 years or older at estimated date of delivery). No diagnostic errors were made using either technique, and the culture failure rate for both methods was 0.8% (two of 250). Seven cytogenetic abnormalities in the early amniocentesis group and seven in the transabdominal CVS group were detected. Nine of the 250 women undergoing early amniocentesis reported spontaneous miscarriages following the procedure, compared to five in the transabdominal CVS group. The loss rates were 3.8% in the early amniocentesis group and 2.1% in the transabdominal CVS group among continuing pregnancies. Frequencies of premature delivery, small for gestational age infants, and associated structural defects in both groups were comparable. At this time, early amniocentesis cannot be assumed to be equal to conventional transabdominal CVS or amniocentesis with regard to safety or accuracy; only a large cohort randomized study will adequately determine the safety and efficacy of early amniocentesis.


Long noncoding RNA Nespas inhibits apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway.
Epilepsy is one of the most common neurological diseases with spontaneous recurrent seizures. Long noncoding RNAs (lncRNAs) are crucial modulators in numerous diseases, including epilepsy. However, the functional role and potential mechanism of lncRNA Nespas in epilepsy remain unknown. Our study clarified that Nespas was underexpressed in epileptiform hippocampal tissues and neurons. Furthermore, Nespas promoted hippocampal neuron viability and proliferation, and inhibited hippocampal neuron apoptosis. Mechanistically, Nespas interacted with microRNA 615-3p (miR-615-3p) in epileptiform hippocampal neurons. 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) was a downstream target of miR-615-3p, and Nespas elevated Psmd11 expression via competitively binding to miR-615-3p in epileptiform hippocampal neurons. In addition, rescue assays suggested that Nespas promoted hippocampal neuron viability and proliferation, and suppressed hippocampal neuron apoptosis by upregulation of Psmd11. Furthermore, Nespas suppressed the PI3K/Akt/mTOR pathway via upregulating Psmd11 in epileptiform hippocampal neurons. This report explored the function and regulatory mechanism of Nespas in epileptiform hippocampal neurons for the first time. Our findings revealed that Nespas suppressed the apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway via upregulation of Psmd11 at a miR-615-3p dependent way, indicating that Nespas may offer a new direction for the treatment of epilepsy.


Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells.
The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 µm Alexa Fluor dye, but not 10 µm, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 µm Alexa Fluor 594 did not alter the I-V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I-V relationship of EPSCs at GluA2-lacking AMPAR synapses.


Transpulmonary lactate gradient after hypothermic cardiopulmonary bypass.
Several studies demonstrated that the lungs could produce lactate in patients with acute lung injury (ALI). Because after cardiopulmonary bypass (CPB) some patients develop ALI, the effect of CPB on pulmonary lactate release was investigated. Prospective observational clinical study. Twenty-beds, surgical ICU at a university hospital. Sixteen deeply sedated, ventilated and post-cardiac surgery patients, all equipped with a pulmonary artery catheter. Lactate concentration was measured using a lactate analyser in simultaneously drawn arterial (A) and mixed venous (V) blood samples. Three measurements per patients were taken at 30-min interval, after body temperature reached 37 degrees C. Concomitantly, measurements of cardiac output were also obtained. Pulmonary lactate release was calculated as the product of transpulmonary A-V lactate and cardiac index. The mean cardiopulmonary bypass duration was 100+/-44 min (SD), and the aortic cross-clamping time was 71+/-33 min. After CPB, lactate release was 0.136+/-0.210 mmol/min m(-2). These values were not correlated with cardiopulmonary bypass duration. The present study shows that in patients receiving mechanical ventilation after CPB, the lung is a source of lactate production. This pulmonary release was not dependent on cardiopulmonary bypass duration.


The influence of dexamethasone on the proliferation and apoptosis of pulmonary inflammatory cells in bleomycin-induced pulmonary fibrosis in rats.
The aim of this study was to investigate the inhibitory effect of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in a rat pulmonary fibrosis model induced by bleomycin. Seventy-five pathogen-free Sprague-Dawley (SD) rats were randomly divided into three groups: control, bleomycin (BLM) and dexamethasone (DXM) groups with 25 rats in each group. Each group was then divided into five subgroups based on time of study (1-, 3-, 7-, 14- and 28-days). BAL fluid was obtained, the cells were counted and a differential was performed. A lower DNA content in apoptotic cells was detected and quantitated by flow cytometry. Haematoxylin and eosin staining was performed to observe the extent of alveolitis and fibrosis of lung tissue; the morphological changes in apoptotic cells were discerned by transmission electron-microscopy and a semi-quantitative assessment of apoptotic cells in lung tissue was performed using in situ TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling). The total number of inflammatory cells and the percentage of neutrophils in BAL fluid in almost every subgroup of the DXM group were significantly lower than those in corresponding subgroups of the BLM group (P < 0.01). The percentages of apoptotic cells in BAL fluid in the 14-day and 28-day subgroups of the DXM group were higher than those in corresponding subgroups of the BLM group (P < 0.05). The peak of alveolitis in the DXM group shifted backward and the extent of fibrosis was less than that in the BLM group. The apoptosis index (AI) of inflammatory cells in each of the DXM subgroups was higher than that in corresponding BLM subgroups except for day 14. Dexamethasone can induce apoptosis of pulmonary inflammatory cells and reduce the extent of alveolitis and fibrosis in bleomycin-induced pulmonary fibrosis of rats.


On the time-dependence of amphiphile-induced haemolysis.
The time-course of haemolysis induced by alkyltrimethylammonium bromides, alkyl sulphates, octaethyleneglycol alkyl ethers, and ZWITTERGENT detergents (C10-C16) was studied. A considerable lag in the development of haemolysis was observed for the C10 and C12 derivatives. The lag exceeded 30 min at low or moderate concentrations of the surfactants. Most of the C14 and C16 derivatives showed no lag but the time-course of the haemolytic reaction of these derivatives indicated biphasic kinetics of haemolysis. With those surfactants showing a lag the critical micelle concentration (cmc) of the surfactants was above the concentrations used in the experiments, whereas cmc in the case of those surfactants showing no lag was close to or slightly below. It is concluded that the differences in the time-course of the haemolytic reaction shown by different derivatives are not connected with the occurrence of micelles in the bulk solution, but that the differences in time-course of the haemolytic reaction reflect differences in the rate of those changes in the membrane molecular organization which precede haemolysis.


SIRT1 attenuates neuroinflammation by deacetylating HSPA4 in a mouse model of Parkinson's disease.
As a deacetylase, SIRT1 plays essential roles in various physiological events, from development to lifespan regulation. SIRT1 has been shown neuroprotective effects in neurodegeneration disorders such as Parkinson's disease (PD). However, the underlying molecular mechanisms are still not well understood. Here, we generated transgenic mice with increased expression of Sirt1 in the brain and examined the potential roles of SIRT1 in PD. Our data showed that SIRT1 repressed proinflammatory cytokine expression both in microglia and astrocytes. In MPTP induced PD model mice, lower levels of microglia and astrocyte activation were observed in SIRT1 transgenic mice. Moreover, the tyrosine hydroxylase (TH) loss in the substantia nigra pars compacta (SNpc) and striatum induced by MPTP was also attenuated by SIRT1. As a consequence, the behavioral defects induced by MPTP were largely prevented in SIRT1 transgenic mice. Mechanistically, SIRT1 interacts with heat shock 70 kDa protein 4 (HSPA4) and deacetylates it at 305, 351 and 605 lysine residues. This deacetylation modification induces the nuclear translocation of HSPA4 and thus to repress proinflammatory cytokine expression. On the contrary, mutated HSPA4, in which 305/351/605 lysine residues were replaced with arginine, was mainly localized in the cytoplasm and losses its repression on proinflammatory cytokine expression. Taken together, our data indicate that SIRT1 plays beneficial roles in PD model mice, which is likely due to, at least in part, its anti-inflammation activity in glial cells by deacetylating HSPA4. Furthermore, HSPA4 might be a druggable target for developing novel agents for treating neuroinflammation associated disorders such as PD.


Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats.
Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).


Umbilical hernia with cholelithiasis and hiatal hernia: a clinical entity similar to Saint's triad.
We experienced two cases involving the simultaneous presence of cholelithiasis, hiatal hernia, and umbilical hernia. Both patients were female and overweight (body mass index of 25.0-29.9 kg/m(2)) and had a history of pregnancy and surgical treatment of cholelithiasis. Additionally, both patients had two of the three conditions of Saint's triad. Based on analysis of the pathogenesis of these two cases, we consider that these four diseases (Saint's triad and umbilical hernia) are associated with one another. Obesity is a common risk factor for both umbilical hernia and Saint's triad. Female sex, older age, and a history of pregnancy are common risk factors for umbilical hernia and two of the three conditions of Saint's triad. Thus, umbilical hernia may readily develop with Saint's triad. Knowledge of this coincidence is important in the clinical setting. The concomitant occurrence of Saint's triad and umbilical hernia may be another clinical "tetralogy."


Performance evaluation of traveling wave ultrasonic motor based on a model with visco-elastic friction layer on stator.
A new visco-elastic contact model of traveling wave ultrasonic motor (TWUSM) is proposed. In this model, the rotor is assumed to be rigid body and the friction material on stator teeth surface to be visco-elastic body. Both load characteristics of TWUSM, such as rotation speed, torque and efficiency, and effects of interface parameters between stator and rotor on output characteristic of TWUSM can be calculated and simulated numerically by using MATLAB method based on this model. This model is compared with that one of compliant slider and rigid stator. The results show that this model can obtain bigger stall torque. The simulated results are compared with test results, and found that their load characteristics have good agreement.


Radical retropubic prostatectomy: 59 cases.
Our results with radical retropubic prostatectomy in 59 patients are described. This is the largest retropubic series outside a university setting that we could find. We discuss the reasons that we believe our technique is beneficial. Our blood loss has been less than the loss in most series, with 48 per cent of our patients receiving no units of blood and, over-all, 64.5 per cent receiving 0 or 1 unit. None of our patients had total urinary incontinence or required a collecting device. Of the 59 patients 5 (9 per cent) are potent. A discussion of the method, complications and 5 and 10-year results is presented. Our statistics compare favorably to those of other series and we believe that this operation is beneficial for the patient.


The role of DMSA scans in evaluation of the correlation between urinary tract infection, vesicoureteric reflux, and renal scarring.
The correlation between urinary tract infection (UTI), vesicoureteric reflux (VUR) and renal scarring was studied in 89 patients (177 renal units; 1 solitary kidney) during the period 1997-2000. There were 63 males and 26 females; ages ranged from neonates to 14 years. UTI was diagnosed on the basis of a positive urine culture, VUR was diagnosed and graded by micturating cystourethrogram (MCU), and renal scarring was assessed by technetium 99 m Tc-dimercaptosuccinic acid (DMSA) scan. Ultrasonography (US) was done to evaluate renal tract dilatation and other structural abnormalities. A follow up DMSA scan was performed approximately 6 months after the initial scan. VUR was present in 106 of the 171 renal units in which it was studied and absent in 65 units. The majority of the VUR was grade V. Renal scars were seen in 90 of 177 renal units at presentation and in 72 of the 163 renal units studied at follow-up. Some information was lacking in 31 patients; hence, the correlation between UTI, VUR, and renal scarring was done in 58 patients. The majority of the suspected scars at presentation were not seen at follow-up, but most of the established scars persisted. Only 2 renal units showed scars for the first time on follow-up. On US, approximately 50% of normal kidneys showed either suspicious or established scars on DMSA scan, and patients with bilateral abnormality on US showed renal scars. Renal scars were seen in 15 of 23 children without VUR, 17 of 18 with unilateral VUR, and 16 of 17 with bilateral VUR. Thus, there is a cause-and-effect relationship between UTI and renal scarring that is made worse by VUR. DMSA scans have been shown to be the most reliable method of assessing renal scarring, and an abnormal US scan showing upper-tract dilatation or a structural abnormality may have a predictive value in the detection of renal scarring.


Seasonal changes in testicular contents and plasma concentrations of androgens in the desert gerbil (Gerbillus gerbillus).
Gerbils were caught in the Béni-Abbès area (Algeria). Testicular endocrine activity was highest in spring (testicular wt 298 +/- 10 mg; seminal vesicle wt 603 +/- 62 mg; testicular testosterone and androstenedione content 9.2 +/- 1.7 and 0.5 +/- 0.1 ng/testis; plasma testosterone 832 +/- 200 pg/ml). Values decreased in summer, were lowest in late summer and in autumn (84 +/- 17 mg; 40 +/- 14 mg; 0.20 +/- 0.06 and 0.02 +/- 0.01 ng/testis; 228 +/- 54 pg/ml, respectively) and increased again in winter (December-January). The onset of testicular endocrine activity was concomitant with the lowest temperatures and the shortest photoperiod; it increased when temperatures and daylength were increasing and began to decline when temperatures and photoperiod were still maximal. These seasonal changes in the endocrine activity of the testis of the gerbil differ from those of the sand rat inhabiting the same area.


Environment contamination and intra-hospital spread of COVID-19 in a tertiary care Hospital in Taiwan.
The role of environmental contamination in COVID-19 transmission within hospitals is still of interest due to the significant impact of outbreaks globally. However, there is a scarcity of data regarding the utilization of environmental sampling for informing infection control measures during SARS-CoV-2 outbreaks. This retrospective study analyzed incident event investigations conducted at a single center from May 1, 2021, to August 31, 2021. Investigations were initiated following the identification of a COVID-19 confirmed case (referred to as the index case) who had stayed in a hospital area outside the dedicated COVID-19 ward/bed and without specific COVID-19 precautions. Measures to prevent intra-hospital spread included contact tracing, adjusted testing policies, isolation of confirmed cases, quarantine of close contacts, environmental disinfection, and PCR testing of environmental samples. Among the 18 incident events investigated, the index case was a healthcare personnel in 8 events, a patient in 8 events, and a caregiver in 2 events. The median number of confirmed COVID-19 cases within 14 days was 13 (IQR, 7-31) for events with SARS-CoV-2 RNA detected on environmental surfaces, compared to only one (IQR, 1-1.5) for events without surface contamination (P = 0.04). Environmental contamination was independently associated with a higher number of COVID-19 cases (P < 0.001). This study highlights environmental contamination as an indicator of the severity of incident events and provides a framework for incident event management, including a protocol for environmental sampling. Implementing these measures can help prevent the spread of COVID-19 within healthcare facilities.


Substance, use in relation to COVID-19: A scoping review.
We conducted a scoping review focused on various forms of substance use amid the pandemic, looking at both the impact of substance use on COVID-19 infection, severity, and vaccine uptake, as well as the impact that COVID-19 has had on substance use treatment and rates. A scoping review, compiling both peer-reviewed and grey literature, focusing on substance use and COVID-19 was conducted on September 15, 2020 and again in April 15, 2021 to capture any new studies. Three bibliographic databases (Web of Science Core Collection, Embase, PubMed) and several preprint servers (EuropePMC, bioRxiv, medRxiv, F1000, PeerJ Preprints, PsyArXiv, Research Square) were searched. We included English language original studies only. Of 1564 articles screened in the abstract and title screening phase, we included 111 research studies (peer-reviewed: 98, grey literature: 13) that met inclusion criteria. There was limited research on substance use other than those involving tobacco or alcohol. We noted that individuals engaging in substance use had increased risk for COVID-19 severity, and Black Americans with COVID-19 and who engaged in substance use had worse outcomes than white Americans. There were issues with treatment provision earlier in the pandemic, but increased use of telehealth as the pandemic progressed. COVID-19 anxiety was associated with increased substance use. Our scoping review of studies to date during COVID-19 uncovered notable research gaps namely the need for research efforts on vaccines, COVID-19 concerns such as anxiety and worry, and low- to middle-income countries (LMICs) and under-researched topics within substance use, and to explore the use of qualitative techniques and interventions where appropriate. We also noted that clinicians can screen and treat individuals exhibiting substance use to mitigate effects of the pandemic. Study was funded by the Institution for Social and Policy Studies, Yale University and The Horowitz Foundation for Social Policy. DH was funded by a NIDA grant (R01DA048860). The funding body had no role in the design, analysis, or interpretation of the data in the study.


Structural analysis of inter-genus complexes of V-antigen and its regulator and their stabilization by divalent metal ions.
Gram-negative bacteria like Yersinia, Pseudomonas, and Aeromonas need type III secretion system (T3SS) for their pathogenicity. V-antigen and its regulator are essential for functioning of T3SS. There is significant functional conservation amongst V-antigen and its regulator belonging to the Ysc family. In this study, we have structurally characterized the inter-genus complexes of V-antigen and its regulator. ConSurf analysis demonstrates that V-antigens belonging to the Ysc family show high structural identity predominantly confined to the two long helical regions. The regulator of V-antigen shows high conservation in its first intramolecular coiled-coil domain, responsible for interaction with V-antigen. ∆LcrG(1-70) localizes within the groove formed by long helices of LcrV, as observed in PcrV-∆PcrG(13-72) interaction. Inter-genus complexes of LcrV-PcrG and PcrV-LcrG exhibited elongated conformation and 1:1 heterodimeric state like the native complex of PcrV-PcrG and LcrV-LcrG. Both native and inter-genus complexes showed rigid tertiary structure, solvent-exposed hydrophobic patches, and cooperative melting behavior with high melting temperature. LcrV-PcrG and PcrV-LcrG showed nanomolar affinity of interaction, identical to PcrV-PcrG interaction, but stronger than LcrV-LcrG interaction. Calcium (a secretion blocker of T3SS) propels all the complexes towards a highly monodisperse form. Calcium and magnesium increase the helicity of the native and inter-genus complexes, and causes helix-helix stabilization. Stabilization of helices leads to a slight increase in the melting temperature by 1.5-2.0 °C. However, calcium does not alter the affinity of interaction of V-antigen and its regulator, emphasizing the effect of divalent of cations at the structural level without any regulatory implications. Therefore, the structural conservation of these inter-genus complexes could be the basis for their functional complementation.


Consumers decrease variability across space and turnover through time during coral reef succession.
Consumers play an integral role in mediating ecological succession-the change in community composition over time. As consumer populations are facing rapid decline in ecosystems around the world, understanding of their ecological role is becoming increasingly urgent. Increased understanding of how changes in consumer populations may influence community variability across space and turnover through time during succession is particularly important for coral reefs, which are among the most threatened ecosystems globally, and where fishes play vital roles in structuring benthic succession. Here, we examine how consumers influence coral reef succession by deploying 180 paired settlement tiles, caged (to exclude fishes larger than approximately 15 cm) and uncaged, within Palmyra Atoll, a remote marine wildlife refuge with previously documented high fish abundance, and monitored benthic community development one and three years after deployment. We found that excluding large fishes lead to lower alpha diversity and divergent community states across space (i.e.,, high beta diversity among caged tiles), suggesting that benthic fish feeding maintains local diversity but tends to homogenize community composition with dominance by crustose coralline algae. In addition, when fish were experimentally excluded, the developing benthic community exhibited a greater change in species composition over time (i.e., high temporal beta diversity), indicating that fish feeding tends to canalize community successional trajectories. Finally, the caged and uncaged tiles became more similar over time, suggesting that fish feeding plays a more important role during early succession. Our results demonstrate that the loss of large fishes, for example from overfishing, may result in benthic communities that are more variable across space and time. Increased variability could have important implications for ecosystem function and coral reef resilience in the face of escalating global stressors.


Switching Excited State Distribution of Metal-Organic Framework for Dramatically Boosting Photocatalysis.
Photosensitization associated with electron/energy transfer represents the central science of natural photosynthesis. Herein, we proposed a protocol to dramatically improve the sensitizing ability of metal-organic frameworks (MOFs) by switching their excited state distribution from 3 MLCT (metal-to-ligand charge transfer) to 3 IL (intraligand). The hierarchical organization of 3 IL MOFs and Co/Cu catalysts facilitates electron transfer for efficient photocatalytic H2 evolution with a yield of 26 844.6 μmol g-1 and CO2 photoreduction with a record HCOOH yield of 4807.6 μmol g-1 among all the MOF photocatalysts. Systematic investigations demonstrate that strong visible-light-absorption, long-lived excited state and ingenious multi-component synergy in the 3 IL MOFs can facilitate both interface and intra-framework electron transfer to boost photocatalysis. This work opens up an avenue to boost solar-energy conversion by engineering sensitizing centers at a molecular level.


Regulation and rate limiting mechanisms of Ca2+ ATPase (SERCA2) expression in cardiac myocytes.
Involvement of the calcineurin/NFAT pathway in transcription of cardiac sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) was demonstrated (Prasad and Inesi, Am J Physiol Heart Circ Physiol 300(1):H173-H180, 2011) by upregulation of SERCA2 following calcineurin (CN) activation by cytosolic Ca(2+), and downregulation of SERCA2 following CN inhibition with cyclosporine (CsA) or CN subunits gene silencing. We show here that in cultured cardiac myocytes, competitive engagement of the CN/NFAT pathway is accompanied by downregulation of SERCA2 and Ca(2+) signaling alterations. In fact, SERCA2 downregulation occurs following infection of myocytes with adenovirus vectors carrying luciferase or SERCA1 cDNA under control of NFAT-dependent promoters, but not under control of CMV promoters that do not depend on NFAT. SERCA2 downregulation is demonstrated by comparison with endogenous transcription and protein expression standards such as GAPDH and actin, indicating prominent SERCA2 involvement by the CN/NFAT pathway. Transcription of genes involved in hypertrophy, triggered by adrenergic agonist or by direct protein kinase C (PKC) activation with phorbol 12-myristate 13-acetate (PMA), is also prominently dependent on CN/NFAT. This is demonstrated by CN inhibition with CsA, CN subunits gene silencing with siRNA, displacement of NFAT from CN with 9,10-Dihydro-9,10[1',2']-benzenoanthracene-1,4-dione (INCA-6), and myocyte infection with vectors carrying luciferase cDNA under control of NFAT-dependent promoter. We show here that competitive engagement of the CN/NFAT pathway by endogenous genes involved in hypertrophy produces downregulation of SERCA2, reduction of Ca(2+) transport and inadequate Ca(2+) signaling. It is most interesting that, in the presence of adrenergic agonist, specific protein kinase C (PKC) inhibition with 3-[1-[3-(dimethylamino)propyl]-5-methoxy-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione (Gö 6983) prevents development of hypertrophy and maintains adequate SERCA2 levels and Ca(2+) signaling.


Recurrent gastric carcinoma--analysis of 100 in-patients--.
Between 1964 and 1981, 100 in-patients with recurrent gastric carcinoma following curative resection were investigated in the Second Department of Surgery, Kyushu University Hospital. The disease-free interval after initial operation and the advancement of the carcinoma correlated. The mean disease free interval of cases with local recurrence was 4 years and 1 month, that is 2 years longer than in cases of peritoneal dissemination or hematogenous metastasis. The disease free interval and the survival time after recurrence also correlated. Patients with a relapse more than 2 years after initial operation survived statistically longer than did those with a relapse in less than 2 years (p less than 0.01). One and 2 year survival rates after recurrence in the second resection group was 41.4 per cent and 17.2 per cent, respectively. Almost all patients in the other group died within one year after recurrence. The average survival in patients on a combination of chemotherapy and resection of the recurrent tumor was about 2 years and longer than in cases of resection but without chemotherapy.


Conformational changes and inactivation of calf intestinal alkaline phosphatase in trifluoroethanol solutions.
The changes in activity and unfolding of calf intestinal alkaline phosphatase (CIP) during denaturation in different concentrations of trifluoroethanol (TFE) have been investigated by far-ultraviolet circular dichroism and fluorescence emission spectra. Unfolding and activation rate constants were measured and compared, the activation and inactivation courses were much faster than that of unfolding, which suggests that the active site of CIP containing two zinc ions and one magnesium ion is situated in a limited and flexible region of the enzyme molecule that is more fragile to the denaturant than the protein as a whole. However, compared to other metalloenzymes, CIP is inactivated at higher concentrations of TFE as denaturant.


Potential effects of gut microbiota on host cancers: focus on immunity, DNA damage, cellular pathways, and anticancer therapy.
The symbiotic bacteria that live in the human gut and the metabolites they produce have long influenced local and systemic physiological and pathological processes of the host. The gut microbiota are increasingly being recognized for its impact on a range of human diseases, including cancer, it may play a key role in the occurrence, progression, treatment, and prognosis of many types of cancer. Understanding the functional role of the gut microbiota in cancer is crucial for the development of the era of personalized medicine. Here, we review recent advances in research and summarize the important associations and clear experimental evidence for the role of the gut microbiota in a variety of human cancers, focus on the application and possible challenges associated with the gut microbiota in antitumor therapy. In conclusion, our research demonstrated the multifaceted mechanisms of gut microbiota affecting human cancer and provides directions and ideas for future clinical research.


Discovery and Engineering of a Novel Baeyer-Villiger Monooxygenase with High Normal Regioselectivity.
Baeyer-Villiger monooxygenases (BVMOs) are remarkable biocatalysts for the Baeyer-Villiger oxidation of ketones to generate esters or lactones. The regioselectivity of BVMOs is essential for determining the ratio of the two regioisomeric products ("normal" and "abnormal") when catalyzing asymmetric ketone substrates. Starting from a known normal-preferring BVMO sequence from Pseudomonas putida KT2440 (PpBVMO), a novel BVMO from Gordonia sihwensis (GsBVMO) with higher normal regioselectivity (up to 97/3) was identified. Furthermore, protein engineering increased the specificity constant (kcat /KM ) 8.9-fold to 484 s-1 mM-1 for 10-ketostearic acid derived from oleic acid. Consequently, by using the variant GsBVMOC308L as an efficient biocatalyst, 10-ketostearic acid was efficiently transformed into 9-(nonanoyloxy)nonanoic acid, with a space-time yield of 60.5 g L-1 d-1 . This study showed that the mutant with higher regioselectivity and catalytic efficiency could be applied to prepare medium-chain ω-hydroxy fatty acids through biotransformation of long-chain aliphatic keto acids derived from renewable plant oils.


Incidence and predictors of common bile duct stones in patients with acute cholecystitis: a systematic literature review and meta-analysis.
Acute cholecystitis (AC) is a surgical condition that is usually managed by emergency surgery. The presence of common bile duct stones (CBDS) in this setting mandates definitive treatment to avoid complications such as cholangitis. The incidence of CBDS in the setting of AC is poorly defined. A systematic English literature search was conducted in PubMed, MEDLINE and Embase to determine the incidence of CBDS in patients presenting with AC. Outlier studies identified by funnel plot analysis were excluded and the incidence of CBDS was identified. The mean CBD diameter and liver function test values of patients with AC and CBDS were calculated. Data were extracted from 19 studies representing a total 4057 patients with AC. Routine biliary imaging was not performed in all studies. The pooled incidence of CBDS was 13.7% (95% confidence interval 11.8-15.9). The incidence of unsuspected retained CBDS was 1.1%. Histologically confirmed cases of AC had a similar rate of CBDS compared to those diagnosed clinically. The mean CBD diameter of patients with AC and CBDS was 7.2 mm compared to 5.8 mm without. Liver function test values in the presence of CBDS were more likely to be deranged, with gamma-glutamyltransferase the most sensitive and specific marker for CBDS in the setting of AC. CBDS is present in a significant proportion of patients presenting with AC. Routine biliary imaging is advised in all patients presenting with AC where possible.


Adult tethered cord syndrome. A case report.
A patient with adult onset of the tethered cord syndrome is described. The significance of the clinical presentation and the myelographic and computed tomographic findings are discussed.


Nonmucosa-associated lymphoid tissue lymphomas of gastric and intestinal origin differ in their clinical features: a single institute experience.
The treatment policy and disease process of mucosa-associated lymphoid tissue (MALT) lymphomas are different from those of other gastrointestinal lymphomas. Chemotherapy has replaced curative surgery as the treatment of choice in gastric lymphomas but the optimal frontline treatment of intestinal lymphomas has yet to be defined. Hence, we attempted to identify the difference in features between gastric and intestinal nonMALT lymphomas. Patients who were newly diagnosed with nonMALT lymphomas of gastrointestinal origin in our hospital between January 2001 and February 2010 were included in our study. Patient characteristics and outcomes were retrospectively analyzed. Among 59 gastric lymphoma patients and 25 intestinal lymphoma patients, the intestinal group were significantly younger and had better performance (p=0.002 and 0.042). Whereas gastrointestinal obstruction and intussusception were more common in the intestinal group (p=0.024 and 0.024), more bleeding episodes were displayed in the gastric counterpart (p=0.042). Histologically, diffuse large B-cell lymphoma was more prevalent in the stomach, and enteropathy associated T-cell lymphoma was found only in the intestine (p=0.006 and 0.024). Despite more intestinal lymphoma patients receiving surgery (p=0.002), the response rate, overall survival and progression-free survival were similar to the gastric counterpart (p=0.1060, 0.7758 and 0.1248). In the multivariate analysis of overall survival, chemotherapy (hazard ratio [HR] 0.2; 95% confidence interval [CI] 0.091-0.440; p<0.001) and International Prognostic Index (HR 1.7; 95% CI 1.181-2.448; p=0.004) proved prognostic in gastric lymphomas. Furthermore, T-cell lineage (HR 8.615; 95% CI 2.165-34.288; p=0.002) and poor performance (HR 9.374; 95% CI 1.497-58.712; p=0.017) were poor predictors in the intestinal counterpart. Intestinal lymphomas differ from gastric lymphomas in manifestation, histology, management and prognosis. Surgery still plays a role in intestinal lymphomas because presentations of surgical emergencies are more common. In addition, the outcome of gastric lymphomas compared with intestinal lymphomas is no longer superior if patients with MALT lymphomas are excluded. Because of the limited number of enrolled patients, further large-scale studies are warranted to validate these results.


The good, the bad and the twisted: a survey of ligand geometry in protein crystal structures.
The protein databank now contains the structures of over 11,000 ligands bound to proteins. These structures are invaluable in applied areas such as structure-based drug design, but are also the substrate for understanding the energetics of intermolecular interactions with proteins. Despite their obvious importance, the careful analysis of ligands bound to protein structures lags behind the analysis of the protein structures themselves. We present an analysis of the geometry of ligands bound to proteins and highlight the role of small molecule crystal structures in enabling molecular modellers to critically evaluate a ligand model's quality and investigate protein-induced strain.


Personalized persuasion: tailoring persuasive appeals to recipients' personality traits.
Persuasive messages are more effective when they are custom-tailored to reflect the interests and concerns of the intended audience. Much of the message-framing literature has focused on the advantages of using either gain or loss frames, depending on the motivational orientation of the target group. In the current study, we extended this research to examine whether a persuasive appeal's effectiveness can be increased by aligning the message framing with the recipient's personality profile. For a single product, we constructed five advertisements, each designed to target one of the five major trait domains of human personality. In a sample of 324 survey respondents, advertisements were evaluated more positively the more they cohered with participants' dispositional motives. These results suggest that adapting persuasive messages to the personality traits of the target audience can be an effective way of increasing the messages' impact, and highlight the potential value of personality-based communication strategies.


Myocardial immediate early gene activation after cardiopulmonary bypass with cardiac ischemia-reperfusion.
The inflammatory process after cardiopulmonary bypass is accompanied by alterations in gene expression for various inflammatory mediators. To analyze differential gene expression after myocardial ischemia-reperfusion, subtraction hybridization was used to discover induction of TIS7/PC4, an immediate early gene heretofore not observed in the heart. This prompted characterization of the related immediate early genes c-fos and c-jun, by Northern analysis and in situ hybridization in human and lamb myocardium subjected to cardiopulmonary bypass with myocardial ischemia. For comparison, we analyzed expression of inducible nitric oxide synthase (iNOS), which requires cytokine-activation, resulting in a "delayed" response. In ischemic-reperfused myocardium at endcardiopulmonary bypass, c-fos, c-jun, and TIS7/PC4 were induced, whereas iNOS transcripts were undetectable. Expression patterns of c-fos and c-jun by in situ hybridization were markedly different; myocardial c-fos expression was diffuse and homogeneous, whereas c-jun expression was patchy with areas of intense focal localization. Cardiopulmonary bypass with myocardial ischemia rapidly induces the immediate early genes TIS7/PC4 (discovered by subtraction hybridization), and c-fos and c-jun (precursors to the transcriptional regulator AP-1). Immediate early genes presumably contribute to activation of inflammatory mediators after cardiopulmonary bypass and differences in their tissue expression patterns, as observed for c-fos and c-jun, presumably modulate their effect upon downstream gene activation.


The pemoline model of self-injurious behaviour.
Traditional models of neuropsychiatric disorders consist of attempts to replicate the broad spectrum of behavioural and neurochemical sequelae that characterize a specific disorder. However, these disorders comprise complex constellations of symptoms, including emotional instability, perseverative thoughts, and aberrant behaviours. Close examination often reveals heterogeneity of symptom expression within patient groups and homogeneity in expression of specific symptoms across diagnostic categories. Accordingly, it may not be possible to model the entire spectrum of characteristics for any one of these disorders in any single animal model. A focus on one or more specific behavioural characteristics (e.g. self-injury) may be a more fruitful strategy. Development of behaviourally focused models yields increased understanding of the genetic basis and biochemical abnormalities that underlie specific psychiatric dysfunctions. Furthermore, by revealing pathophysiology that underlies specific disease characteristics, behaviourally focused models improve translational power and help to identify targets for effective pharmacotherapies. One such behaviourally focused animal model is the pemoline model of self-injurious behaviour.


Recognition imaging of chromatin and chromatin-remodeling complexes in the atomic force microscope.
Atomic force microscopy (AFM) can directly visualize single molecules in solution, which makes it an extremely powerful technique for carrying out studies of biological complexes and the processes in which they are involved. A recent development, called Recognition Imaging, allows the identification of a specific type of protein in solution AFM images, a capability that greatly enhances the power of the AFM approach for studies of complex biological materials. In this technique, an antibody against the protein of interest is attached to an AFM tip. Scanning a sample with this tip generates a typical topographic image simultaneously and in exact spatial registration with a "recognition image." The latter identifies the locations of antibody-antigen binding events and thus the locations of the protein of interest in the image field. The recognition image can be electronically superimposed on the topographic image, providing a very accurate map of specific protein locations in the topographic image. This technique has been mainly used in in vitro studies of biological complexes and reconstituted chromatin, but has great potential for studying chromatin and protein complexes isolated from nuclei.


Past and present of beta arrestins: A new perspective on insulin secretion and effect.
Beta arrestins had been known as intracellular adaptors that uncouple and inactivate the G protein-coupled receptors that they interact with. Their roles as signal initiators for some receptors have recently been recognized. In this review, we focused on their role in mediating metabolic modulation primarily in relation to insulin signaling. Commenced by the upstream receptor, they seem to act like intracellular hubs that divert the metabolic profile of the cell. The amount of metabolic substrates in circulation and their usage/deposition by tissues are controlled by the contribution of all systems in the organism. This control is enabled by the release of hormones such as insulin, glucagon and glucagon-like peptide-1. Intriguingly, some ligands -either agonists or antagonists-of different classes of receptors have preferential properties mediated by β arrestins. This is not surprizing considering that substrate supply and usage should parallel physiological function such as hormone release or muscle contraction. Available data indicate that β arrestins conduct the regulatory role in insulin secretion and action. They may be good candidates to target when the upstream signal demands the function that may compromise the cell. An example is carvedilol that is protective by preventing the stimulatory effects of excessive catecholamines, stimulates mitochondrial function and has preferential clinical outcomes in metabolic disorders.


Esophagobronchial fistula and mediastinal tuberculosis.
A 59-year-old man was seen with what preoperatively was thought to be an acquired esophagobronchial fistula secondary to an old burned-out infection with tuberculosis. At operation the gross and microscopic findings were most compatible with a congenital H-shaped esophagobronchial fistula. However, cultures of calcified lymph nodes grew Mycobacterium tuberculosis. The need for culturing calcified tissue to assure proper treatment is emphasized.


Procedures and Outcomes of Surgical Aortic Valve Replacement in Adults.
The ideal aortic valve substitute remains elusive. Bioprosthetic valves are the replacement option of choice in elderly patients undergoing aortic valve replacement (AVR). When implanted in young and middle-aged adults, both bioprosthetic and mechanical valves are associated with excess mortality compared with the age- and sex-matched general population. The Ross procedure is the only operation that can restore normal life expectancy in young and middle-aged adults undergoing AVR. In this article, the authors review the various options for surgical AVR and examine their contemporary applications and outcomes.


[Histologic changes in peripheral nerves in rats with chronic copper poisoning].
The results of histochemical and histopathologic tests of a periphery nerve in rats which were chronically poisoned with copper, are presented. The tests were performed on 45 albino Wistar female rats, which were poisoned with pure copper powder in an inhalation chamber for one year. The control group consisted of 16 rats. By histochemical test the copper pigment was found in 46.66% of the poisoned rats. It was located in epineurium and perineurium, cells and less in the endoneurium. It was also found in cells of the blood vessel media of a periphery nerve. Histopathological changes in a periphery nerve were discrete and they appeared in the form of certain swollen axones.


Radiological approach to interstitial lung disease: a guide for the nonradiologist.
Articles in the past have described the radiological appearances of different interstitial lung diseases (ILDs) in varying levels of detail. However, these articles have generally been written for radiologists with a background in basic chest computed tomography (CT) interpretation. This article summarizes a basic approach for diagnosing ILDs on high-resolution CT (HRCT) for the nonradiologist clinician and discusses the most common HRCT features of common ILDs.


Neurorescue effects of VEGF on a rat model of Parkinson's disease.
Vascular endothelial growth factor (VEGF) has been shown to display neuroprotective effects on dopaminergic (DA) neurons. Here, we investigated the neurorescue effects of VEGF on 6-hydroxydopamine (6-OHDA)-treated DA neurons in vitro and in vivo. Initially, we examined in vitro whether 1, 10, or 100 ng/ml of VEGF administration at 2 or 4 h after 6-OHDA treatment rescued DA neurons derived from E14 murine ventral mesencephalon. The earlier treatment of VEGF suppressed 6-OHDA-induced loss of DA neurons more than the delayed treatment. Next, we examined whether the continuous infusion of VEGF had neurorescue effects in a rat model of Parkinson's disease. We established a human VEGF secreting cell line (BHK-VEGF) and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally transplanted into the striatum of adult rats at 1 or 2 weeks after 6-OHDA lesions, and animals subsequently underwent behavioral and immunohistochemical evaluations. Compared to lesioned rats that received BHK-Control capsules, lesioned rats transplanted with BHK-VEGF capsules showed a significant reduction in the number of amphetamine-induced rotations, a significant preservation of TH-positive neurons in the substantia nigra pars compacta, and a remarkable glial proliferation in the striatum, with the earlier transplantation exerting much more benefits than the delayed transplantation. Parallel studies revealed that the observed in vitro and in vivo neurorescue effects were likely mediated by VEGF's angiogenic and glial proliferative effects, as well as its direct effects on the neurons. Our results suggest that VEGF is a highly potent neurorescue molecule for Parkinson's disease therapy.


Dual function of sialic acid in gastrointestinal SARS-CoV-2 infection.
Recent analysis concerning the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- angiotensin converting enzyme (ACE) receptor interaction in enterocytes, the definition of gut-lung axis, as well as the molecular basis of sialic acid-related dual recognition concept in gastrointestinal SARS-CoV-2 infection, have brought a new perspective to potential therapeutic targets. In this review evolving research and clinical data on gastrointestinal SARS-CoV-2 infection are discussed in the context of viral fusion and entry mechanisms, focusing on the different triggers used by coronaviruses. Furthermore, it is emphasized that the viral spike protein is prevented from binding gangliosides, which are composed of a glycosphingolipid with one or more sialic acids, in the presence of chloroquine or hydroxychloroquine. In gastrointestinal SARS-CoV-2 infection the efficiency of these repositioned drugs is debated.


The First 50 Years of Postnatal Neurogenesis in the Cerebellum: a Long Journey Across Phenomena, Mechanisms, and Human Disease.
The discovery by Altman and coworkers of adult-born microneurons in the olfactory bulb and dentate gyrus has triggered a long stream of studies and many attempts to harness adult neurogenesis, promote regeneration after injury, and contrast cognitive decline in the elderly. Likewise, the discovery of postnatal neurogenesis in the cerebellum has provided the framework for many subsequent molecular studies, including investigations of developmental processes and the assessment of GC progenitor (GCP) clonal expansion in the context of human disease. Here, I will briefly discuss some of the discoveries made in the field of cerebellar development over the years building upon the findings of Altman and his colleagues, touching upon signaling pathways that regulate granule cell neurogenesis and their involvement in developmental and neoplastic disorders of the cerebellum.


Evidence for spontaneous serial refreshing in verbal working memory?
Working memory (WM) keeps information temporarily accessible for ongoing cognition. One proposed mechanism to keep information active in WM is refreshing. This mechanism is assumed to operate by bringing memory items into the focus of attention, thereby serially refreshing the content of WM. We report two experiments in which we examine evidence for the spontaneous occurrence of serial refreshing in verbal WM. Participants had to remember series of red letters, while black probe letters were presented between these memory items, with each probe to be judged present in or absent from the list presented so far, as quickly as possible (i.e., the probe-span task). Response times to the probes were used to infer the status of the representations in WM and, in particular, to examine whether the content of the focus of attention changed over time, as would be expected if serial refreshing occurs spontaneously during inter-item pauses. In sharp contrast with this hypothesis, our results indicate that the last-presented memory item remained in the focus of attention during the inter-item pauses of the probe-span task. We discuss how these findings help to define the boundary conditions of spontaneous refreshing of verbal material in WM, and discuss implications for verbal WM maintenance and forgetting.


Dose-response relationships between dairy intake and non-communicable chronic diseases: an NHANES-based cross-sectional study.
The purpose of this study was to explore the possible association between dairy and NCDs and identify possible dairy types that could lower the odds of NCDs. Data were from the 2003-2016 NHANES, a cross-sectional study with 20,297 adults. Multivariable logistic regression analyses and restricted cubic spline (RCS) models were conducted. In the highest intake group (>250 g/d, 1 daily serving), yogurt and milk were inversely associated with the odds of general obesity and central obesity [OR (95% CI), general obesity, 0.74 (0.60-0.91) and 0.75 (0.68-0.83); central obesity, 0.70 (0.56-0.87), and 0.77 (0.70-0.86), respectively, p < 0.05]. Higher milk intake is inversely associated with diabetes, and higher cream intake is associated with a lower likelihood of hyperlipidaemia. The intake of yogurt, milk, cheese, and butter was 0-308 g/d (0-1.2 daily servings), 0-887 g/d (0-3.5 daily servings), <75 g/d (1.7 daily servings), and <15 g/d (0.5 daily servings), respectively.


The Two-Operon-Coded ABC Transporter Complex FpvWXYZCDEF is Required for Pseudomonas aeruginosa Growth and Virulence Under Iron-Limiting Conditions.
Iron is essential for all organisms. Bacteria have devolved sophisticated systems to maintain intracellular iron homeostasis. FpvCDEF(PA2407-2410) has been reported as an ABC transporter involved in pyoverdine-Fe uptake which does not affect growth under iron-limiting condition, when it is deleted in PAO1. In this study, we proved that fpvCDEF and fpvWXYZ(PA2403-2406) constituted an ABC transporter complex containing two operons: fpvWXYZCDE and fpvF. The operon fpvWXYZCDE was regulated by iron negatively and the single gene operon fpvF was constitutively expressed. Inactivation of any one of the components, fpvW, fpvC, fpvD, fpvE, and fpvF, led to increased expression of fpvWXYZCDE suggesting that each component of fpvWXYZCDEF could be involved in iron uptake. The ABC transporter complex encoded by fpvWXYZCDEF plays important roles in growth, oxidative stress resistance, and virulence, since the deletion of fpvWXYZCDEF resulted in defective growth, increased sensitivity to H2O2, and decreased virulence compared with PAO1(ΔfpvCDEF) and the wild type PAO1 under iron-limiting condition.


Rumenotomy.
If performed correctly, the rumenotomy procedure can be a safe and effective way to retrieve ingested foreign bodies and address other problems of the ruminant forestomachs. In the author's practice, rumen surgery has been associated with few postoperative complications. Morbidity and mortality in cases that have had a previous rumenotomy have mostly been associated with complications related to the original presurgical condition or from causes unrelated to the rumen surgery.


Novel Prognostic Implications of DUPAN-2 in the Era of Initial Systemic Therapy for Pancreatic Cancer.
This study aimed to explore the impact of serum tumor markers on survival for patients with pancreatic cancer (PC) who received initial systemic therapy (IST) followed by surgery. Between April 2010 and July 2018, 285 consecutive patients who underwent curative intent surgery for PC were enrolled in the study. The relation between carbohydrate antigen 19-9 and duke pancreatic monoclonal antigen type 2 (DUPAN-2) after IST was analyzed as well as PC prognosis. The study identified 95 patients who underwent systemic chemotherapy with or without radiotherapy as IST from the our prospectively maintained database at the Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. Survival analysis of the 95 patients showed significant differences in recurrence-free survival (RFS) and overall survival (OS) between the DUPAN-2-normalized (D-normalized) and DUPAN-2-unnormalized (D-unnormalized) groups (median RFS, 24.1 vs. 14.2 months, p = 0.003; median OS, not reached vs. 29.6 months, p = 0.003). In addition, a tendency of differences in survival was observed between the D-normalized and D-unnormalized groups with borderline resectable PC (RFS, 20.1 vs. 14.2 months, p = 0.052; OS, not reached vs. 29.6 months, p = 0.081), and significant differences in survival were observed between the D-normalized and D-unnormalized groups with unresectable PC (RFS, 25.1 vs. 12.1 months, p < 0.001; OS, not reached vs. 11.4 months, p < 0.001). Furthermore, multivariate analysis demonstrated that normalized DUPAN-2 independently predicted survival of resected PC [RFS: hazard ratio (HR) 2.180; 95% confidence interval (CI) 1.16-4.08, p = 0.015; OS: HR 2.806; 95% CI 1.19-6.62, p = 0.018]. During IST, DUPAN-2 normalization may potentially predict prolonged survival for PC patients and optimal timing for conversion surgery in IST.


[Clinico-morphologic analysis of human amyotrophic leukospongiosis reproduced in guinea pigs].
Fourteen guinea pigs were infected with brain suspension obtained from a patient who died from amyotrophic leukospongiosis. Eight animals (57.7%) developed the disease in 2-4 months (2 of 4 with intracerebral and 6 of 10 with intramuscular infection). Morphological CNS changes in the patient and the guinea pigs were very similar.


Simultaneous spatial updating in nested environments.
When one moves, the spatial relationship between oneself and the entire world changes. Spatial updating refers to the cognitive process that computes these relationships as one moves. In two experiments, we tested whether spatial updating occurs automatically for multiple environments simultaneously. Participants turned relative to either a room or the surrounding campus buildings and then pointed to targets in both the environment in which they turned (updated environment) and the other environment (nonupdated environment). The participants automatically updated the room targets when they moved relative to the campus, but they did not update the campus targets when they moved relative to the room. Thus, automatic spatial updating depends on the nature of the environment. Implications for theories of spatial learning and the structure of human spatial representations are discussed.


Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation.
Transgenic expression in medaka of the Xiphophorus oncogene xmrk, under a pigment cell specific mitf promoter, induces hyperpigmentation and pigment cell tumors. In this study, we crossed the Hd-rR and HNI inbred strains because complete genome information is readily available for molecular and genetic analysis. We prepared an Hd-rR (p53+/-, p53-/-) and Hd-rR HNI hybrid (p53+/-) fish-based xmrk model system to study the progression of pigment cells from hyperpigmentation to malignant tumors on different genetic backgrounds. In all strains examined, most of the initial hyperpigmentation occurred in the posterior region. On the Hd-rR background, mitf:xmrk-induced tumorigenesis was less frequent in p53+/- fish than in p53-/- fish. The incidence of hyperpigmentation was more frequent in Hd-rR/HNI hybrids than in Hd-rR homozygotes; however, the frequency of malignant tumors was low, which suggested the presence of a tumor suppressor in HNI genetic background fish. The effects on tumorigenesis in xmrk-transgenic immature medaka of a single 1.3 Gy irradiation was assessed by quantifying tumor progression over 4 consecutive months. The results demonstrate that irradiation has a different level of suppressive effect on the frequency of hyperpigmentation in purebred Hd-rR compared with hybrids.