Changes in non-surgical management of stage III non-small cell lung cancer at a single institution between 2003 and 2010.
Concurrent chemo-radiotherapy (CON-CRT) is recommended for selected patients with stage III non-small cell lung cancer (NSCLC), but utilization varies. We assessed the response to national guidelines introduced in 2004 and the impact on outcomes. Retrospective study of stage III NSCLC patients treated with radical intent non-surgical treatment during 2003-2010 in a university medical center characterized by multidisciplinary assessment, routine use of four-dimensional computed tomography for radiotherapy planning, and rapid implementation of radiotherapy advances. Between 2003 and 2010, 319/435 (73%) patients with stage III NSCLC received (chemo) radiotherapy. The number receiving CON-CRT in successive two-year periods increased from 13/48 (27%) - 40/80 (50%) - 63/90 (70%), to 74/101 (73%). Median overall survival (OS) from start of radiotherapy was 18.6 months for CON-CRT (190/319) and 17.4 months for sequential (SEQ), typically hypofractionated, CRT (90/319) (p = 0.78). Eleven months OS with radiotherapy alone (39/319) was significantly shorter (p = 0.006). OS did not differ between the four periods (p = 0.87). CON-CRT was not over-represented in the 16% of patients dying within five months of starting radiotherapy. Between 2003 and 2010, CON-CRT for stage III NSCLC was rapidly and safely increased. However, OS did not increase and, as practiced, did not differ between CON- or SEQ-CRT.


An economic evaluation of targeted case-finding strategies for identifying postnatal depression: A model-based analysis comparing common case-finding instruments.
Half of women with postnatal depression (PND) are not identified in routine care. We aimed to estimate the cost-effectiveness of PND case-finding in women with risk factors for PND. A decision tree was developed to represent the one-year costs and health outcomes associated with case-finding and treatment for PND. The sensitivity and specificity of case-finding instruments, and prevalence and severity of PND, for women with ≥1 PND risk factor were estimated from a cohort of postnatal women. Risk factors were history of anxiety/depression, age < 20 years, and adverse life events. Other model parameters were derived from published literature and expert consultation. Case-finding for high-risk women only was compared with no case-finding and universal case-finding. More than half of the cohort had one or more PND risk factor (57.8 %; 95 % CI 52.7 %-62.7 %). The most cost-effective case-finding strategy was the Edinburgh Postnatal Depression Scale with a cut-off of ≥10 (EPDS-10). Among high-risk women, there is a high probability that EPDS-10 case-finding for PND is cost-effective compared to no case-finding (78.5 % at a threshold of £20,000/QALY), with an ICER of £8146/QALY gained. Universal case-finding is even more cost-effective at £2945/QALY gained (versus no case-finding). There is a greater health improvement with universal rather than targeted case-finding. The model includes costs and health benefits for mothers in the first year postpartum, the broader (e.g. families, societal) and long-term impacts are also important. Universal PND case-finding is more cost-effective than targeted case-finding which itself is more cost-effective than not case-finding.


Echocardiographic diagnosis of atrioventricular septal perforation caused by an aortic valve vegetation.
A case of aortic valve endocarditis is presented in which a vegetation eroded through the atrioventricular septum and extended into the right atrium. This was diagnosed by echocardiography and confirmed at surgery.


Pain behavior without pain sensation: an epileptic syndrome of "symbolism for pain"?
"Asymbolia for pain" has shown the potentiality of diseased insular networks to dissociate sensory from affective-behavioral dimensions of pain, resulting in the lack of appropriate motor and affective responses despite preserved sensory aspect of pain. Here, we describe 4 patients with an inverse phenomenon of asymbolia for pain, namely an isolated "symbolism for pain" triggered by epileptic seizures, characterized by pain behavior without declarative pain sensation despite fully preserved contact and vigilance. Stereoelectroencephalography demonstrated in each case focal seizure discharges within the posterior insulo-opercular cortex, with little or no propagation to other cortical structures, especially those considered to drive subjective pain experiences. The pain behavior might reflect seizure propagation from the insula to brain networks serving for behavioral responses associated with pain, including the cingulate motor region and possibly also the basal ganglia. We propose that the isolated symbolism for pain is a novel epileptic syndrome of dissociation between pain perception and behaviors associated with the insular nociceptive-related networks.


Freehand technique with the predrilled hole method for ulnar-shortening osteotomy.
Ulnar shortening is a common and useful method for treating ulnar wrist pain from many causes. Many devices used to perform osteotomy have been introduced in the literature; however, the devices are not universally available. The standard freehand technique is still commonly used in clinical practice; however, it is associated with several complications and is time-consuming. We present a freehand technique for ulnar-shortening osteotomy using a predrilled hole method. From 2011 to 2013, we performed the predrilled hole method for ulnar shortening in 18 cases using the six-hole limited-contact dynamic compression plate (LC-DCP) and in two cases using the Acumed six-hole Locking Midshaft Ulna Plate. All patients had uneventful union, and the average operative time was 39.7 minutes (range, 32-50 minutes). The average follow-up period was 21 months (range, 12-30 months). There were no complications except in three patients in the LC-DCP group who complained of implant irritation. Good functional outcomes were achieved with this method. Our technique is easy and quick to use and can minimize soft-tissue manipulation. The union rate is high and complications are few.


Inter-rater reliability of a video-analysis method measuring low-back load in a field situation.
Valid and reliable low-back load assessment tools that can be used in field situations are needed for epidemiologic studies and for ergonomic practice. The aim of this study was to assess the inter-rater reliability of a low-back load video-analysis method in a field setting. Five raters analyzed 50 work site manual material handling tasks of 14 workers. Peak and mean moments at the level of L5S1, and segment angles were obtained using the video-analysis method. Intra-class correlation coefficients (ICCs) and median standard deviations across raters were calculated. ICCs revealed excellent inter-rater reliability (>0.9) for peak and mean moments, ICCs of segment angles were variable. Median standard deviations showed relatively small inter-rater variance for moments (standard deviation <10 Nm) and segment angle variation ranging from 0° to 20°. The proposed video-analysis method, provides a reliable tool for obtaining low-back loads from occupational field tasks.


Combined treatment of maxillofacial carcinoma by intra-arterial proliferation block and irradiation.
We investigated the possible potentiation of a regimen of combined cytostatic and radiation therapy for epidermoid carcinoma of the maxillofacial region. The described combined approach by intra-arterial infusion of ADR and BLM and cytokinetically controlled irradiation was able to produce CR in all treated primary tumors of the head and neck. Regional metastases are not definitely controlled and require surgical intervention.


Macular thickness and volume in the elderly: A systematic review.
Ageing leads to a number of changes in the body including the macula. Detailed imaging using optical coherence tomography have enabled in vivo studies of how macula changes with age. Here we systematically review 49 studies (9115 participants and 11,577 eyes) to provide an overview of how ageing manifests in the macula of the elderly focusing on clinical relevant measures that are thicknesses and volumes of different macular areas. Ageing seems to increase center point foveal thickness. Ageing does not seem to change the center subfield thickness significantly. Ageing decreases the inner and outer macular thickness, and the overall macular thickness and volume. Studies find that specific retinal layers at specific locations seem to be the contributor to these changes. These findings confirm that age-related changes suggested in histological studies are measurable in vivo on thickness and volume and differ depending on location. Studies are needed to explore reasons for the large variance in measurements and how ageing by itself contributes to development of macular disease.


Dental team member compliance with personal protective equipment and aerosol-generating procedure recommendations during the COVID-19 pandemic in Israel: An observational study.
Coronaviruses which have been responsible for numerous epidemics worldwide, share common transmission modalities and pose a risk within dental clinics. Updated, COVID-19-specific infection control and personal protective equipment (PPE) guidelines for dental settings, including minimizing aerosol-generating procedures (AGPs), were issued by the Israeli Ministry of Health (MoH) in spring 2020. This study investigated dental team members (dentists, dental assistants and hygienists) compliance with MoH recommendations exposed to asymptomatic COVID-19 positive patients. The MoH analysed exposure reports from dental clinics to asymptomatic SARS-CoV-2 positive patients following their reopening (April 2020). Exposure reports were verified against a COVID-19 national database. A cumulative transmission rate was calculated and compared to the rate in the population. One thousand three hundred twenty-third exposure reports were received (May 1-December 31, 2020) regarding dental team members who treated asymptomatic SARS-CoV-2 positive patients: 525 (39.7%) were dentists, 656 (49.6%) dental assistants and 126 (9.5%) hygienists. Practitioner type was not reported in 16 (1.2%) cases. Most dental team members reported full PPE use and performance of short/non-aerosol-generating procedures. Dentists and hygienists reported higher compliance compared with dental assistants. 8 (0.6%) dental team members (four dentists, four dental assistants) were positive post-exposure, with an average of 5.4 days (median 5 days, SD = 4.8) from dental treatment to a positive COVID-19 test. Most dental team members complied fully with the MoH recommendations. Differences were found between the dental team members (hygienists being most adherent). Further efforts are required to encourage full compliance.


Low level detection of acetone vapor by improvised design of high "Q" tunable frequency Helmholtz photoacoustic cell using UV, mid- IR and THz sources.
The paper reports the designing and fabrication aspects of a high "Q = 492.3" Helmholtz photoacoustic (PA) cell employed for the trace level detection of acetone, a biomarker by using 266 nm- UV, Mid-IR (5.4-10.6 micron) and 0.11 Terahertz (THz) sources. The designed Helmholtz PA cell is made of Aluminum and possesses a natural frequency tunable between 1.4 to 4.4 kHz range using a movable piston arrangement of the microphone sensor. Numerous types of disorders, including diabetes, asthma, lung cancer, etc., can be diagnosed using the acetone concentration obtained through breath analysis. The comparative study is related to the response of different types of excitation mechanisms contributed by electronics, vibrational and rotational modes of acetone. The low-level detection (LoD) limit for acetone is of the order of 5.06 & 7.92 ppbV, and 15.3 pptV, respectively, in UV, Mid-IR, and THz region. This study contributes to the development of a highly sensitive, non-invasive acetone detection and quantification modality.


Tonglian Decoction () arrests the cell cycle in S-phase by targeting the nuclear factor-kappa B signal pathway in esophageal carcinoma Eca109 cells.
To investigate the anti-tumor activity and molecular mechanism of Tonglian Decoction (, TLD) on esophageal carcinoma Eca109 cells. Eca109 cells were treated with TLD and its separated formulae, including the clearing-heat and detoxification formula (Q), activating-blood and promoting-qi formula (H) and nourishing-yin and blood formula (Z). Cell proliferation was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell morphology was observed using a microscope, the cell cycle was measured using flow cytometry and the activity of the nuclear factor-kappa B (NF-κB) signal pathway was detected by Western blot. The half maximal inhibitory concentrations of TLD, Q and H were 386, 771 and 729 mg/L, respectively. TLD, Q and H significantly inhibited cell proliferation, with 69.43%, 60.84% and 61.90% of treated cells in the G phase of the cell cycle. The percentage of cells in S phase increased significantly after treatment with TLD, Q, and H compared with the control group (P<0.05), and TLD showed the strongest effect. Z had no influence on the cell cycle compared with the control group (P>0.05). Western blot detection indicated slight differences in the inhibition of the NF-κB pathway by the different formulae. TLD formula strongly inhibited IKKβ, NF-κB, interleukin-6 and tumor necrosis factor-α expression compared with the control group. TLD inhibited Eca109 cell proliferation by arresting cells in S phase. The possible mechanism might be related to inhibiting the NF-κB transduction cascade. The combination of the herbs found in the three separate formulae, H, Q and Z, work synergistically in TLD to produce the inhibitory effects of TLD treatment on Eca109 proliferation.


cAMP modulates macrophage development by suppressing M-CSF-induced MAPKs activation.
M-CSF is a key cytokine in macrophage development by inducing MAPKs activation, and cAMP can inhibit MAPKs activation induced by inflammatory stimuli. To explore the effects of cAMP on M-CSF-induced MAPKs activation and on macrophage development, the model of bone marrow-derived murine macrophages (BMMs) was used. The effects of cAMP on M-CSF-induced MAPKs activation were analyzed by Western blotting assay, and the effects of cAMP on CD14 and F4/80 expression during macrophage development were examined by FACS analysis. Macrophage morphology showed the successful establishment of the model of macrophage development. Western blotting assay revealed that M-CSF activated ERK, JNK and p38 in both mature and immature macrophages, and cAMP inhibited M-CSF-induced ERK, JNK and p38 activation in a time-dependent manner. FACS analysis revealed that macrophage development was impaired with cAMP pretreatment. In conclusion, cAMP modulates macrophage development by suppressing M-CSF-induced MAPKs activation.


Experimental improvements in combining CARD-FISH and flow cytometry for bacterial cell quantification.
Flow cytometry and Fluorescence In Situ Hybridization are common methods of identifying and quantifying bacterial cells. The combination of cytometric rapidity and multi-parametric accuracy with the phylogenetic specificity of oligonucleotide FISH probes has been regarded as a powerful and emerging tool in aquatic microbiology. In the present work, tests were carried out on E. coli pure culture and marine bacteria using an in-solution hybridization protocol revealing high efficiency hybridization signal for the first one and a lower for the second one. Other experiments were conducted on natural samples following the established CARD-FISH protocol on filter performed in a closed system, with the aim of improving cell detachment and detection. The hybridized cells were then subsequently re-suspended from the membrane filters by means of an optimized detachment procedure. The cytometric enumeration of hybridized marine bacteria reached 85.7%±18.1% of total events. The quality of the cytograms suggests that the procedures described may be applicable to the cytometric quantification of phylogenetic groups within natural microbial communities.


A new oleanane triterpenoid from Gordonia ceylanica.
The chemical investigation of the hexane extract of the stem bark of Gordonia ceylanica afforded 3beta-acetoxy-11alpha(2',3'-epoxyferulyloxy)-olean-13(18)-ene as a new natural product and alpha-spinasterol for the first time from Gordonia.


Effect of the addition of extracts of thermophilic lactobacilli on acid production by Streptococcus thermophilus in milk.
Soluble extracts of 20 strains of thermophilic lactobacilli (Lactobacillus helveticus, L. lactis and L. bulgaricus) were prepared and added to milk for the culture of 10 strains of Streptococcus thermophilus. Acid production was stimulated in 64.5% of cases for 9 of these 10 strains. The L. helveticus extracts were the most stimulatory, but the same extracts did not always strongly stimulate each strain of Str. thermophilus. The stimulatory effects observed varied with the volume of extract and the strain of Str. thermophilus. The exception was Str. thermophilus 385, which was never stimulated. The stimulatory effects observed were due to aminopeptidases present in the lactobacillus extracts and were not related to a general caseinolytic activity. The possible addition of such extracts to milk for cooked hard cheese is discussed.


Distinct innate and adaptive immunity phenotypic profile at the circulating single-cell level in Psoriatic Arthritis.
Mass cytometry was employed to investigate 47 circulating leukocyte subsets in patients with active psoriatic arthritis (PsA, n = 16) compared to healthy controls (n = 13), seropositive (RF and/or anti-CCP, n = 12) and seronegative (n = 9) RA patients. Comparing PsA to controls, different cell frequencies were found in both innate and adaptive immunity cell subsets, as well as in cells bridging innate and adaptive immunity. In some T cell subsets increased costimulatory molecules' expression in PsA, was also noted.No changes were observed in patients who remained disease-active after 3 months of treatment, in contrast to those who achieved remission/low-disease activity. Comparing PsA to seropositive RA, elevated frequencies of naïve and activated CD8+ T cells, B cells, MAIT/iNKT and ILCs were found, while the opposite was the case for terminal effector, senescent, and Th2-like cells. Strikingly, the composition of the leukocyte pool in PsA was comparable to seronegative RA, providing evidence for the pathogenetic similarities between these two entities.


Acute pulmonary edema associated with transfusion of packed red blood cells.
We experienced a patient who suffered noncardiogenic acute pulmonary edema after transfusion of packed red blood cells which contained antigranulocyte antibodies. The data suggested that complement activation and the release of polymorphonuclear protease were involved in the pathogenesis of the complication in the present patient. Furthermore, blood coagulative system was also activated after the transfusion. The underlying mechanisms of the complication are discussed.


Evaluation of commercial EBV RecombLine assay for diagnosis of nasopharyngeal carcinoma.
In recent years a number of Epstein-Barr virus (EBV) proteins were defined as being immunodominant for either IgM, IgG or IgA immune responses, yielding promising markers for diagnostic serology. Specific reactivity patterns to these proteins have been described for infectious mononucleosis (IM), nasopharyngeal carcinoma (NPC), various types of lymphoma, and healthy EBV carriers. To compare the NPC-related diagnostic value of EBV RecombLine test (Mikrogen, Germany) with a standardized immunoblot assay [Fachiroh J, Schouten T, Hariwiyanto B, Paramita DK, Harijadi A, Haryana SM, et al. Molecular diversity of Epstein-Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison of Indonesian, Chinese, and European subjects. J Infect Dis 2004;190:53-62] and to define the diagnostic value of individual EBV marker proteins in a population with high incidence of NPC. Sera from Indonesian NPC patients taken at primary diagnosis (n=108) were analyzed for IgG and IgA reactivity and compared with regional healthy blood donors (n=62), non-NPC patient controls (n=10) and IM patients (n=10). Most NPC patients and controls showed strong IgG reactivity to VCA-p18, -p23, and EBNA1, limiting their diagnostic use. Few (<20%) healthy donors and patient controls showed IgG reactivity to EA proteins p47/54 and p138, yielding combined sensitivity/specificity and PPV/NPV values of 92.6%/98.3% and 99.0%/88.1%, for diagnosing NPC. NPC sera showed significantly more EBV reactive IgA antibody (>80% positive) than controls (<10% positive), although being less broadly reactive and significantly less strong compared to IgG. For IgA best results were observed for RecombLine EBNA1 with sensitivity/specificity and PPV/NPV values of 92%/89% and 93.4%/85.9%, respectively. In high incidence NPC regions with low incidence IM yet high prevalence of EBV infection, both RecombLine IgG and IgA tests provide a useful alternative to the more complex cell-extract based immunoblot assay as confirmation test for NPC diagnosis in particular when using EA and EBNA1 as discriminators in IgG and IgA testing, respectively.


Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles.
The aim of the present study is to design and characterize quercetin-loaded solid lipid nanoparticles (QT-SLNs), clarify the absorption mechanism of QT-SLNs and to evaluate the potential of using solid lipid nanoparticles (SLNs) as an oral delivery carrier for poorly water soluble drugs. QT-SLNs were prepared by an emulsification and low-temperature solidification method. The QT-SLNs presented as spherically shaped under transmission electron microscopy, with an average diameter of 155.3 nm. The average drug entrapment efficiency, drug loading and zeta potential were 91.1%, 13.2% and -32.2 mV, respectively. Drug release from QT-SLNs was fitted to a double phase kinetics model and the equation was as follows: 100-Q=98.87e(-0.1042t)+42.45e(-0.0258t). The absorption of QT-SLNs in the gastrointestinal (GI) tract was studied using an in situ perfusion method in rats. It was found that the absorption percent in the stomach for 2 h was only 6.20%, the absorption process of intestine was first-process with passive diffusion mechanism, and the main absorptive segments were ileum and colon. A pharmacokinetic study was conducted in rats after oral administration of quercetin at 50 mg/kg in the form of either QT-SLNs or suspension. The plasma concentration-time curves were both fitted to a one-compartment model. The relative bioavailability of QT-SLNs to quercetin suspension was 571.4%. The T(max) and MRT for quercetin in plasma were both delayed. Our studies provide evidence that SLNs are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, quercetin.


Benefits and Pitfalls of O-Arm Navigation in Cervical Pedicle Screw.
Cervical pedicle screw (CPS) with O-arm-based intraoperative navigation has demonstrated satisfactory results in recent studies. In this article, we introduce our experience and discuss important considerations for CPS placement with O-arm navigation. We retrospectively reviewed the data of 51 patients with 156 pedicle screws who underwent O-arm navigated CPS from July 2020 to October 2021. The accuracy of each screw placement was evaluated at the initial screw location using intraoperative 3D reconstructed O-arm images and the final screw location using postoperative computed tomography (CT). The screw accuracy was assessed in the axial image. The initial accuracy of screws on intraoperative 3D reconstructed O-arm images was 93.6% (146 of 156). The accuracies of the mid-cervical level (C3, C4, C5) were relatively low (83.3%-85.0%) compared with those of C2, C6, and C7 (93.3%-100.0%) at the initial screw due to the rotation of the vertebral body. Among 10 violated screws, 5 were converted to lateral mass screws or removed intraoperatively, and the other 5 were retained because the violations were minimal. After converting the screw, the final accuracy of the screws in postoperative CT was 96.7% (146 of 151). CPS with O-arm navigation showed relatively low accuracy at the mid-cervical level due to vertebral rotation. However, the opportunity to convert the screw from intraoperative 3D reconstructed O-arm images is the advantage of the O-arm navigation, and it showed excellent accuracy.


Variation patterns and driving factors of regional atmospheric CO2 anomalies in China.
Atmospheric CO2 anomaly (△XCO2) is essential in evaluating regional carbon balance. However, it is difficult to understand △XCO2 variation characteristics due to regional differences. This paper explored the inter-annual and inter-monthly variation patterns of △XCO2 in different regions of China based on satellite observations. The relation model between regional △XCO2 and anthropogenic emissions, gross primary productivity (GPP), wind speed, upwind region's emission, and upwind region's CO2 concentration was established. Results show that the annual average △XCO2 in the northwest and southeast regions is stable at around 0 and 1-2 ppm, respectively. Some municipalities directly under the central government and the southern coastal areas showed relatively intense inter-annual fluctuations. Four inter-monthly △XCO2 variation patterns were observed: the northern region has a stable change, the northeast region has the lowest in summer, the southwest region has the highest in summer, and the central region has no obvious change rule. Furthermore, △XCO2 in most areas can be explained by the emission-absorption-transportation model. Significant positive △XCO2 in the southern coastal region in summer may be related to the stable GPP seasonal variation and increased power generation. In the southwestern plateau region, it may be related to the low wind speed and increased soil emission with rising temperature. The stability of the plateau carbon sink and inter-regional cooperation cannot be ignored for improving regional atmospheric environments.


Judgments of Learning in Context: Backgrounds Can Both Reduce and Produce Metamemory Illusions.
Varying item-specific features such as size (Rhodes & Castel, 2008) or blur (Yue, Castel, & Bjork, 2013) often produces metamemory illusions in which one type of item receives higher judgments of learning (JOLs) without being recalled better. In this study, we explored how similar manipulations to context would influence JOLs. When to-be-recalled words varying in size (or blur) were accompanied by backgrounds also varying in size (or blur), the traditional JOL illusions were reduced (Experiments 1, 2, 4, and 5) compared to when there were no backgrounds (Experiments 3a, 3b, and 4). Thus, the item-specific and contextual cues were used interactively. Further, the background manipulations also sometimes themselves led to metamemory illusions regarding JOLs for the to-be-remembered items. In general, there were robust individual differences in how participants used the cues, including how they incorporated the contextual cues into their JOL decisions. In part, this may explain why interactive cue utilization did not always emerge at the group level. In sum, we showed that context may affect JOLs both directly and indirectly by influencing participants' use of item-specific cues. These findings broaden our understanding of how cues may be utilized (e.g., Koriat, 1997) and integrated (e.g., Undorf, Söllner, and Bröder, 2018) in JOLs.


Site-specific covalent labeling of His-tag fused proteins with N-acyl-N-alkyl sulfonamide reagent.
The ability to incorporate a desired functionality into proteins of interest in a site-specific manner can provide powerful tools for investigating biological systems and creating therapeutic conjugates. However, there are not any universal methods that can be applied to all proteins, and it is thus important to explore the chemical strategy for protein modification. In this paper, we developed a new reactive peptide tag/probe pair system for site-specific covalent protein labeling. This method relies on the recognition-driven reaction of a peptide tag and a molecular probe, which comprises the lysine-containing short histidine tag (KH6 or H6K) and a binuclear nickel (II)- nitrilotriacetic acid (Ni2+-NTA) complex probe containing a lysine-reactive N-acyl-N-alkyl sulfonamide (NASA) group. The selective interaction of the His-tag and Ni2+-NTA propeles a rapid nucleophilic reaction between a lysine residue of the tag and the electrophilic NASA group of the probe by the proximity effect, resulting in the tag-site-specific functionalization of proteins. We characterized the reactive profile and site-specificity of this method using model peptides and proteins in vitro, and demonstrated the general utility for production of a nanobody-chemical probe conjugate without compromising its binding ability.


Identification of conserved T cell receptor CDR3 residues contacting known exposed peptide side chains from a major histocompatibility complex class I-bound determinant.
We have analyzed the T cell receptor (TCR) repertoire found in the major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response to the protein ovalbumin (OVA). Despite skewing towards the expression of V beta 5.2+TCR by OVA-specific CTL from C57BL/6 mice, we found a relatively high degree of diversity in V(D)J usage in both TCR alpha- and beta-chains. Closer examination showed that the majority of these sequences encoded negatively and positively charged residues at their respective TCR alpha- and beta-chain VJ or VDJ junctions. These junctions form the third complementarity-determining regions (CDR3) of the TCR polypeptides involved in the direct interaction with the class I-bound peptide. Crystallographic analyses of Kb-peptide complexes predict that the major determinant from OVA, peptide OVA257-264 (SIINFEKL), contains two exposed charged side chains which can contact the TCR. These are the negatively charged glutamic acid at determinant position 6 (P6) and the positively charged lysine at P7. To examine whether the TCR alpha-chain makes contact with P7 lysine, we established a single chain TCR transgenic C57BL/6 mouse line where all T cells express a TCR beta-chain derived from the V beta 5.2+ clone B3. OVA-specific T cells derived from in vivo primed transgenic mice preferentially expressed TCR alpha-chains that also contained negatively charged junctional residues despite some further variation in V alpha and J alpha sequences. Stimulation of naive TCR beta-chain transgenic T cells with a P7 substitution peptide analogue induced a T cell response that was no longer cross-reactive with the wild-type OVA257-264 determinant, suggesting that the TCR alpha-chain from the T cell clone B3 can determine the specificity for this residue. Consequently, these results reveal the existence of conserved residues in the CDR3 of TCR alpha- and beta-chains specific for OVA257-264 and identify their possible orientation over the peptide-class I complex.


Metal-free synthesis of allylic amines by cross-dehydrogenative-coupling of 1,3-diarylpropenes with anilines and amides under mild conditions.
Dehydrogenative cross-coupling reaction of primary anilines, secondary anilines, carboxamides, and sulfonamides with 1,3-diarylpropenes to form a series of allylic amines promoted by DDQ have been realized. Both monoallylation and diallylation products can be selectively synthesized when primary anilines are used as the starting materials. The method may provide a wide scope of allylamines in scientific research including biologically active compound library construction.


Atorvastatin administration is associated with dose-related changes in IGF bioavailability.
IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins. We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (S.D.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg). Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: -3 (-21 to 14) ng/ml; IGF2: -23 (-65 to 18) ng/ml and IGFBP3: -0.34 (-0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant -0.41 (-0.69 to 0.13, P=0.004). IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.


Paralyzed eyelids reanimated with a closed-eyelid spring.
Implantation of gold weights and open wire springs to close the eyelid have provided good corneal protection in selected patients with eyelid paralysis. These techniques, however, do not overcome lower eyelid drooping. The closed-eyelid spring technique was developed to address this problem, and, to date, the author has implanted 27 closed-eyelid springs. This technique has reestablished a voluntary blink, provided corneal protection, and effectively held the lower lid in a relatively normal position in 25 of 27 patients. This report describes patient selection, surgical technique, and results of implanting closed-eyelid springs to reanimate paralyzed eyelids.


Relevance of Sociocultural Inequalities and Parents' Origins in Relation to the Oral Health of Preschoolers in Lanzarote, Spain.
Approaching inequalities to achieve health equity requires joint action. Early childhood caries affects disadvantaged population groups. The objective of this study was to determine the relevance of sociocultural inequalities and parental origin with respect to oral health in preschool children in Lanzarote. A transversal epidemiological study was carried out. Sociocultural data and information about parental origin were collected via a questionnaire. The decayed and filled teeth (dft), decayed teeth (dt), filled teeth (ft), restorative index (RI), plaque index (PI) and gingival index (GI) were obtained via an investigator's examination. Statistical analysis of the data indicated that children of semi-skilled manual workers (28.15%) had the highest prevalence of caries (46.9%). Additionally 43.7 of the mothers had second grade and first cycle studies. When relating the medium and high level of education, there were statistically significant differences in relation to the cod index (p = 0.046). When the origin was foreign (48.4%), preschoolers presented 10.7% more active or untreated caries than Spaniards (p = 0.038). Low socioeconomic cultural level and foreign origin is associated with a more deficient state of oral health in preschoolers. Oral health programs are needed to minimize social inequalities.


Mechanistic insights into extracorporeal photochemotherapy: efficient induction of monocyte-to-dendritic cell maturation.
Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma, as well as immunomodulation of graft-versus-host disease (GVHD) and transplanted organ rejection. ECP's mechanism encompasses large-scale physiologic platelet induction of dendritic cells (DCs). The normal bidirectional immunologic talents of DCs likely contribute heavily to ECP's capacity to immunize against tumor antigens, while also suppressing transplant immunopathology. Our understanding of how ECP physiologically induces monocyte-to-DC maturation can enhance the treatment's potency, potentially broaden its use to other cancers and autoimmune disorders and tailor its application to individual patients' diseases. ECP's next decade is filled with promise.


Decreased overall survival in patients with locally advanced head and neck cancer receiving definitive radiotherapy and concurrent cetuximab: National Cancer Database analysis.
Recently, randomized trials have questioned the efficacy of cetuximab-based bioradiotherapy compared to chemoradiation for patients with squamous cell carcinoma of the oropharynx, larynx, and hypopharynx (HNSCC). We compared the OS of patients treated with radiotherapy alone (RTonly), chemoradiotherapy (chemoRT), and bioradiotherapy (cetuxRT). Patients with stage III-IVB HNSCC treated with RTonly, chemoRT, or cetuxRT were identified in the National Cancer Database. OS was estimated using Cox proportional hazards. Analyses were conducted on the overall cohort and propensity matched cohorts. 31 014 patients were treated with RTonly (22%), chemoRT (72%), or cetuxRT (6%) from 2013 to 2016. The 2-year OS was 69% for RTonly, 79% for chemoRT, and 66% for cetuxRT (p < 0.001). In the overall and propensity-matched cohorts, chemoRT and RTonly were associated with improved OS as compared to cetuxRT (p ≤ 0.001). Compared to chemoRT or RTonly, cetuxRT is associated with decreased OS for patients with HNSCC, suggesting minimal benefit of bioradiotherapy in this population.


Exposure of the rat small intestine to raw kidney beans results in reorganization of absorptive cell microvilli.
A single exposure to raw kidney beans (RKB) results in vesiculation, shortening, and then regrowth of microvilli in the rat small intestine. This study investigated changes that occur in the structure of microvilli 2-10 hours after RKB exposure. Circumferences of microvilli from absorptive cells obtained sequentially after challenge with RKB or chow were assigned to one of three groups: small, intermediate, or large. The distribution and concentration of actin in intact mucosae or isolated epithelial sheets were determined by confocal laser scanning microscopy, immunocytochemistry, and immunoblot analysis with specific probes. Six hours after exposure to RKB, most microvilli were large, abnormal in shape, and contained significantly more actin filaments than large microvilli from control rats. In addition, the fluorescence intensity of F-actin increased within injured microvilli without changes in the total intracellular actin concentration. By 8-10 hours after challenge with RKB, some microvilli remained larger than those of control rats but had resumed their normal shape and contained fewer actin filaments than at 6 hours. Exposure of the rat small intestine to RKB results in enlargement of absorptive cell microvilli and reorganization of membrane and core actin filaments without changes in intracellular actin concentration. Enlarged microvilli are rapidly repaired.


[Mucormycosis: an unusual cause of unilateral exophthalmia].
Mucormycosis is an invasive fungal infection associated with high mortality. Orbital involvement was usually reported but was rarely isolated. We report the case of a 57-year-old patient who presented a proptosis associated to an ethmoid sinusitis. Inflammatory symptoms were late which was responsible for delayed diagnosis. Our patient died because of multi-organ failure.


Serum cystatin C level is associated with left atrial enlargement, left ventricular hypertrophy and impaired left ventricular relaxation in patients with stage 2 or 3 chronic kidney disease.
Cystatin C is an endogenous marker of kidney function that overcomes the limitations of serum creatinine. High serum cystatin C levels have been associated with increased cardiovascular mortality and morbidity. In this cross-sectional study, we aimed to determine the associations between serum cystatin C levels and structural and functional cardiac changes in patients with stage 2 or 3 chronic kidney disease (CKD). We enrolled 429 consecutive patients (aged 24-97 years) with CKD stage 2 or 3 and left ventricular (LV) ejection fraction (LVEF)>40%. Echocardiographic parameters, including LV mass index (LVMI), early diastolic mitral annulus velocity (e' velocity), left atrial volume index (LAVI), and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) were measured. Patients were categorized into quartiles according to serum cystatin C levels. Cystatin C was associated with LAVI (p=0.0055), LVEF (p=0.0432), LVMI (p=0.0409), e' (p=0.0051), E/e' (p=0.0027), and log-transformed NT-proBNP (p<0.0001) according to multivariate linear regression analysis, after adjustment for confounding factors including creatinine-based estimated glomerular filtration rate (eGFRcreat) and urinary albumin to creatinine ratio. Incidence of eccentric and concentric hypertrophy increased with increasing cystatin C (Q1, 38%; Q2 49%; Q3, 51%; Q4, 66%, p=0.0008), mainly because of increasing concentric hypertrophy (Q1, 30%; Q2, 39%; Q3, 39%; Q4, 51%, p=0.0187). A high serum cystatin C is strongly associated with structural cardiac abnormalities such as LVH and left atrial enlargement, impaired LV relaxation, and an increased NT-proBNP, independently of eGFRcreat in patients with stage 2 or 3 CKD.


Clinically Occult Pituitary Adenoma Can Appear as a Hypermetabolic Lesion on Whole Body FDG PET Imaging in a Patient with Lymphoma.
We report a case with Non-Hodgkin Lymphoma with a focus of intense hypermetabolism in the sellar region in the primary staging and posttreatment whole body F-18 FDG PET. Further evaluation with magnetic resonance imaging after posttreatment FDG PET revealed a pituitary adenoma. Endocrinologic workup was normal consistent with nonfunctioning pituitary adenoma and endocrinologists decided to follow up the patient by yearly magnetic resonance imaging. This case demonstrates a nonfunctioning pituitary adenoma by whole body FDG PET and emphasizes the importance of pursuing incidental findings detected in the sella on PET imaging. None declared.


Investigation of bone conditions for orthodontic anchorage plates in the anterior mandible.
The clinical success of orthodontic anchorage plates depends on the stability of the miniscrews used for fixation. For good stability, the application site must provide bone of good quantity and quality. This study was performed to analyze bone quantity for orthodontic anchorage plates in the anterior mandible. A total of 51 computed tomography (CT) scans of fully dentate patients (mean age 24.0±8.1 years; 27 men and 24 women) were evaluated. Measurements were taken to analyze the total orovestibular and vestibular cortical thickness of the mandibular jawbone at different anterior locations and levels. Vestibular cortical thickness is generally thinnest within the incisor area on the apex level. Its thickness increases in basal and distal directions. The total orovestibular thickness is also the least on the level of the anterior mandibular apices, becoming thicker toward more basal levels and the posterior teeth. We can reasonably assume that the stability of anchorage plates can be optimized by selecting a position well basal to the apices of the lower incisors, as this area offers enhanced cortical and total jawbone thickness.


An attention transfer entropy based causality analysis with applications in rooting short-term disturbances for chemical processes.
The transfer entropy (TE) based causality analysis is able to provide a typical solution for fault rooting of industrial processes. However, short-term disturbances that occur during nominal operations of chemical processes are usually neglected because of the fixed time window of TE for global data distributions. Inspired by the selective attention idea, we propose attention transfer entropy (ATE) that helps to locate prominent targets. Concerning temporal features of industrial time series, prior knowledge is employed for constructing an interpretable model. We verify the reliability and effectiveness of the method with coal gasification process data. Additionally, the algorithm is compared to conventional causality analysis methods, proving that ATE enjoys excellent performances in rooting short-term disturbances with lower calculation burden.


Influence of cortical bone thickness and implant length on implant stability at the time of surgery--clinical, prospective, biomechanical, and imaging study.
This clinical study is the first to quantitatively evaluate both regional bone structure by computed tomography preoperatively and dental implant stability by resonance frequency analysis at the time of surgery to explore the relation between local bone structure and dental implant stability in humans. Implant stability at the time of installation is often difficult to achieve in lower density bone and implant stability might influence treatment efficacy. Few clinical studies have reported detailed bone characteristics obtained using computed tomography prior to surgery and comprehensive implant stability measurements at the time of surgery. We hypothesized that thicker cortical bone would improve the stability of the dental implant at the time of placement. Before radiographic examination, diagnostic radiographic templates were made by incorporating radiopaque indicators. Computed tomography scans were obtained for 50 edentulous subjects prior to surgery. Preoperatively, the thickness of the cortical bone at the sites of implant insertion was measured digitally, and then implant insertion surgery was performed. A total of 225-implant stability measurements were made using a resonance frequency analyzer. There was a strong linear correlation between cortical bone thickness and resonance frequency (r = 0.84, P < 0.0001). The implant length had a weak negative correlation with stability (r = -0.25, P < 0.0005). These results suggest that the initial stability at the time of implant installation is influenced more by cortical bone thickness than by implant length. The cortical and cancellous ratio of local bone is extremely important for implant stability at the time of surgery and determining the local bone condition is critical for treatment success.


Temporal dynamics of parietal cortex involvement in visual search.
The functional-neuroanatomic relationship that describes the involvement of the parietal cortex in visual search was investigated using repetitive transcranial magnetic stimulation (rTMS; 10 Hz, 500 ms in duration). Twelve adult participants performed feature-based visual search for a unique letter-without eye movements-under conditions that involved manipulations of search efficiency (efficient versus inefficient) and target-selection demands (set-size: 4 versus 10). rTMS was applied over the right posterior parietal cortex at the onset of the search array for all factorial conditions (0-500 ms); stimulation was additionally administered at 500 ms post-array onset (500-1000 ms) during inefficient search (set-size 10). Stimulation over the primary sensorimotor cortex served as a within-subjects control condition, and eye movements were monitored continuously. Significant increases in reaction time were restricted to parietal stimulation during inefficient search (set-size 10), with interference observed when rTMS was administered at the onset of the search array and at 500 ms post-array onset. The early effect was confined to target-present trials and the late effect was confined to target-absent trials, which may indicate temporally dissociable parietal involvement in target detection and response-based selection and/or search termination, respectively. Error rates did not vary significantly as a function of any of the independent variables. Taken together, these results are consistent with evidence from functional magnetic resonance studies indicating that inefficient feature-based visual search requires an intact parietal cortex, and also indicate that the parietal cortex is involved in inefficient search later than has been previously reported.


Corrigendum: Identification of extremely GC-rich micro RNAs for RT-qPCR data normalization in human plasma.
[This corrects the article DOI: 10.3389/fgene.2022.1058668.].


The different kinds of group psychotherapy with patients with different diagnoses.
Group psychotherapy is a treatment method in which in addition to the therapist(s) the participating individuals are, autocentrically, active in attaining a therapeutic effect. The different kinds of group psychotherapy are described: 1) activity group psychotherapy, 2) analytic group psychotherapy, 3) directive-suggestive-group psychotherapy, 4) psychodrama, 5) accelerating/focal methods of group psychotherapy. Group psychotherapeutic techniques with patients of different diagnoses are discussed, e.g. group psychotherapy with drug dependants and alcoholics, in which it is not possible to use a pure analytic method of group psychotherapy. Their oral tendencies and narcissistic desires of undergoing a fusion with the therapist have to a certain degree to be fulfilled. Schizophrenics should encounter is group psychotherapy an unconditioned emotional response from the therapist. These patients on the one hand expect to be understood in their psychotic experience, but on the other hand they seem to be glad when the measures of the outside reality are maintained in the group. The relatives of schizoprenics wanting to co-operate are taken in a parallel group. Depressives, especially endogenous depressives, need a longer time to be integrated in a therapeutic group than other patients, but if they can be integrated, it helps them to tolerate their sufferings. To the neurotics, group psychotherapy offers insight and a chance to "translate" this insight into a new social behaviour. Analytic self-experience groups with staff members give them an opportunity to recognise from their own experience the conflicts and the behaviour patterns from which their patients suffer.


Late complications of pars plana vitreous surgery.
Late complications (following hospital discharge) occurring in 206 consecutive pars plana vitrectomy cases, comprising a subgroup of 100 consecutive cases for diabetic retinopathy, are reviewed. Ocular hypertension, occurring as neovascular glaucoma, was present in 18% of diabetic eyes, but other causes of ocular hypertension gave an overall incidence of 26%. Electron microscopy, scanning, and transmission photographs document the devastating ocular neovascularization occurring postvitrectomy.


Humor in high-functioning autistic adults.
This study examined the humor used by a group of autistic adults. Subjects were nine autistic adults who were participating in a Social Skills Group. The jokes they told during a designated joke time over 15 consecutive group sessions were analyzed according to their developmental levels. The participants told a total of 87 unique jokes, almost all of which were riddles. The most common types were preriddles and those having lexical and phonological ambiguity. Along with empirically examining the jokes used by this group of high level autistic adults, the study demonstrates that they enjoy a wide range of jokes and that humor seems to enrich their lives.


Diminished presentation of complement regulatory protein CD55 on red blood cells from patients with hereditary haemolytic anaemias.
Hereditary haemolytic anaemias (HHA) encompass a heterogeneous group of anaemias characterized by decreased red blood cell survival. The aim of this study was to evaluate the status of red blood cell (RBC) surface molecules known or previously proposed to participate in preventing premature RBC clearance, analysing erythrocytes from patients with two types of HHA: hereditary spherocytosis (HS) and microcytosis. Relative binding of five monoclonal antibodies (mAbs), anti-CD55, anti-CD59, anti-CD44, anti-CD47 and anti-CD58, was evaluated in erythrocytes of patients with HS and hereditary microcytosis, using flow cytometry. The amount of CD55 protein was assessed by semi-quantitative Western blots densitometry analysis. The majority of both HS and microcytic patients demonstrated significant reduction of anti-CD55 binding by erythrocytes (average 23% and 19%, respectively, P < .001), with no concomitant anti-CD59-binding deficiency. Anti-CD44, anti-CD47 and anti-CD58 binding was within the healthy control range or was slightly decreased. This study provides evidence supporting the presence of erythrocytes deficient in CD55 presentation in HS and hereditary microcytosis. Moreover, deficiency of CD55 antigen presentation on RBC does not correlate with the amount of CD55 in RBC membrane. Further studies using molecular techniques will clarify the exact participation of CD55 deficiency in premature RBC clearance in HHA.


A Case of Mesenteric Desmoid Tumor Causing Bowel Obstruction After Laparoscopic Surgery.
A desmoid tumor is a rare neoplasm that is derived from soft tissues. Although it shows benign characteristics pathologically, local recurrence can occur. We herein report the case of a patient with an intraabdominal desmoid tumor that developed 3 years after laparoscopic appendectomy for acute appendicitis. A 59-year-old male visited our emergency room with complaints of abdominal pain and fullness. Abdominal computed tomography revealed distention of the small intestine with a point of obstruction by an intraabdominal tumor-like region. Pathological findings showed that the tumor was compatible with desmoid fibromatosis. In cases with an intraabdominal tumor after laparoscopic surgery, it is important to consider the possibility of a desmoid tumor, since it is difficult to diagnose it accurately before surgery.


Effectiveness of telephone-based screening and triage during COVID-19 outbreak in the promoted primary healthcare system: a case study in Ardabil province, Iran.
Screening services for early detection of patients is one of the important capabilities of the health system with a proper referral system. In the crisis of respiratory infection of Covid-19, screening based on symptoms is one of the key measures. The aim of the current study was to evaluate the telephone-based screening and triage services in the promoted primary healthcare system with regard to the Covid-19 outbreak, in terms of reducing unnecessary referrals to the hospital. This is a descriptive cross-sectional study conducted in two stages on 1,406,635 households during March/April 2020 in Ardabil province for screening and early detection of Covid-19 disease. In the first stage, conducted by trained healthcare providers through telephone, individuals suspected of Covid-19 were identified. In the second stage, the individuals were referred to the second level of service in comprehensive healthcare centers (16- or 24-h centers) for clinical evaluation by a physician. The results showed that before establishing a screening and triage system for patients in comprehensive healthcare centers, all patients were referred directly to the hospital, while after the implementation of the program, a significant reduction in hospital visits was observed and a large number of patients undertook the care and triage services in comprehensive healthcare centers. The use of a grading system in referring patients with suspected cases, triage of patients according to symptoms at the comprehensive health centers, and activation of home isolation were the most important factors in reducing the burden of unnecessary referrals of patients to the hospital.


Equity in private insurance coverage for substance abuse: a perspective on parity.
Congress is considering enactment of comprehensive parity legislation. The intent of parity is to equalize private coverage of behavioral and general medical care, thereby improving efficiency and fairness in insurance markets. One issue is whether to extend parity to substance abuse (SA) benefits. In the past, inclusion of substance abuse has been a hurdle to passage of parity. We examine the politics of SA parity, compare coverage trends for substance abuse and mental health, and assess the rationale for equalizing benefits. We conclude that the justification for SA parity is as compelling as it is for mental health parity.


Complexity, contradictions, and conundrums: studying post-proteasomal proteolysis in HLA class I antigen presentation.
The vast majority of the peptides produced during protein degradation by the cytosolic proteasome-ubiquitin system are consecutively hydrolyzed to single amino acids by multiple cytosolic peptidases preferring intermediate length or short substrates. The small fraction of peptides surviving the aggressive cytosolic environment can be recruited for presentation by major histocompatibility complex (MHC) class I molecules. However, such peptides may frequently have to be adapted to the strict MHC class I-binding requirements by one or several N-terminal-trimming steps. A recent model proposes that an initial step, in which peptides of 15 or more residues are shortened by cytosolic tripeptidylpeptidase II, is followed by additional trimming by cytosolic or endoplasmic reticulum (ER) aminopeptidases. In humans, at least two ER resident aminopeptidases, ERAP1 and ERAP2, contribute to trimming of human leukocyte antigen class I ligands. These interferon-gamma-regulated metallopeptidases show distinct substrate preferences and may have to act in a concerted fashion to remove some complex or longer N-terminal extensions and to trim the full spectrum of precursor peptides. This task is likely facilitated by the formation of presumably heterodimeric ERAP1-2 complexes. RNA interference experiments suggest that both enzymes are important for normal antigen presentation, but precise determination of the extent and the cellular context of their requirement will be left to future experimentation.


Chagas disease: Importance of rats as reservoir hosts of Trypanosoma cruzi (Chagas, 1909) in western Mexico.
In Mexico, the role of most species of mammals involved in the transmission cycle of Trypanosoma cruzi Chagas, 1909 is poorly known. It was carried out a study to investigate the importance of rats as reservoir of T. cruzi in western Mexico, an area with important risk of transmission of T. cruzi to human. Thirty-eight human dwellings were searched on two representative towns of western Mexico along twelve months for collection of rats and triatomines. Study rats (Rattus norvegicus) Berkenhout, 1769 and triatomines (Meccus phyllosomus longipennis) (Usinger, 1939) were collected inside and outside human dwellings. Most rats (68.6%, n=312) and triatomines (68.7%, n=217) were collected along months of the hot season. Most rats (59.3%) were collected in peridomiciliary areas. From 312 examined rats, 71 (22.7%) were positive for T. cruzi on examination by Indirect Hemagglutination, which was confirmed by xenodiagnosis. From the 217 examined triatomines, 169 (77.9%) were infected by T. cruzi. The presence of infected rats and triatomines was highly related since on every studied human dwelling where infected triatomines were collected, infected rats were also found. Rats seem to constitute an important domiciliary and peridomiciliary reservoir for T. cruzi, furthering the risk of infection for human beings.


Histochemical demonstration of copper in LEC rat liver.
Livers of LEC rats were histochemically stained for copper according to the modified Timm's method, which includes trichloroacetic acid (TCA) treatment. TCA pretreatment was effective in removing zinc and iron, leaving as the major metal in the liver. Hepatocytes in 3-month-old rats were stained intensely by the modified Timm's method, both in frozen sections and in paraffin-embedded specimens. The centrilobular hepatocytes were usually stained, but positive cells were also randomly distributed in the hepatic lobes, showing a mosaic pattern. The staining was intensified in 8- compared to 3-month-old LEC rats. In contrast hepatocytes from LEA rats, the normal counterpart of LEC rats, were faintly stained for copper. Proliferating cholangioles found in older LEC rats were shown to lack copper deposition, and hepatocellular carcinoma showed less copper deposits than the hepatocytes surrounding the tumor. The copper staining was augmented in livers of LEC rats subjected to copper-loading, but was less intense in the livers treated with D-penicillamine. The staining intensity under the various experimental conditions showed good correlation with the copper concentration. Lysosomal deposition of copper in hepatocytes was demonstrated by electron microscopic analysis for copper. Thus the modified Timm's method was shown to produce valuable results in demonstrating copper in LEC rat livers, providing important information for an understanding of the mechanism of copper deposition and hepatic disease of the animal.


Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells.
During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta-gonad-mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso-ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.


Biosynthesis, characterization and anthelmintic activity of silver nanoparticles of Clerodendrum infortunatum isolate.
Over the past few decades, the green synthesis of nanoparticles has gained importance for their therapeutic efficacy and eco-friendly nature. Integrating green chemistry principles into multidisciplinary nanoscience research has paved the way for developing environmentally benign and sustainable methods for synthesizing gold and silver nanoparticles. In the present study, the flowers obtained from Clerodendrum infortunatum (L.), belonging to the family Verbenaceae, have been used for biosynthesizing silver nanoparticles (AgNPs) to evaluate the anthelmintic potential. UV-Vis spectroscopy, XRD, FTIR, SEM and TEM analyses were performed to ascertain the formation of AgNPs. Clerodendrum-derived AgNP (CLE-AgNP) has significantly affected the normal physiological functions of the poultry parasite Raillietina spp., a menace to the livestock industry. Our study manifests that CLE-AgNPs cause considerable distortion of the surface tegument of this cestode parasite leading to changes in the host-parasite interface. The histochemical localization studies of the tegument-associated enzymes viz. AcPase, AlkPase, ATPase and 5'-Nu, exposed to the drug, showed a substantial activity decline, thus establishing the anthelmintic potential of the CLE-AgNPs.


Partial protection against infectious bursal disease virus through DNA-mediated vaccination with the VP2 capsid protein and chicken IL-2 genes.
Several DNA vaccination experiments were performed to determine the protective capability of a plasmid DNA molecule encoding the VP2 capsid protein gene of infectious bursal disease virus (IBDV) injected into chickens in the presence or absence of chicken interleukin 2 (IL-2) plasmid DNA. The results of these experiments indicate that partial protection against IBDV can be achieved by using the VP2 gene of IBDV as a DNA vaccine. Furthermore, the simultaneous injection of chicken IL-2 plasmid DNA significantly increased the protection after challenge with the virulent strain. It was also found that immunological tolerance may have been induced in one of the chicken experiments by vaccination with plasmid DNA.


High-performance liquid chromatographic separation and partial characterization of human protamines 1, 2, and 3.
A method for separating the three human protamines by HPLC of underivatized, total protamine extracts on a Nucleosil RP-C18 column is described. The identities of the three proteins have been confirmed by a combination of disc gel electrophoresis, amino acid composition, and primary sequence analysis. The results show that human protamine 3 elutes first, closely followed by protamine 2. Protamine 1 elutes later. The amino acid compositions and partial amino terminal sequences of human protamines 2 and 3 indicate that these two proteins are very closely related and suggest that they differ only by three amino-terminal amino acids.


Influences of the Seasons of the Year and Physiographic Regions on the Levels of Calcium, Copper and Zinc in the Hoof Capsule of Foals Pre- and Postweaning Raised in Native Pasture.
This study evaluated the levels of calcium (Ca), copper (Cu) and zinc (Zn) in the hoof of Criollo foals, pre- and postweaning, correlating them with the concentrations of these inorganic chemical compounds in soil and pasture in the different seasons of the year. We used 41 preweaning foals and 28 postweaning foals. Seventeen forage samples were collected in four seasons, later 10 soil samples per property in five distinct physiographic regions (Santa Maria, Dilermando de Aguiar, Jaguarão, Arroio Grande and Pelotas). There was variability in Ca, Cu and Zn concentrations in the hoof foal between distinct physiographic regions (P < .05), and between seasons. There was no association of preweaning and postweaning Ca levels with forage in the different physiographic regions. The concentrations of Cu and Zn showed positive association (R = 0.69, 0.43; P < .05) with the native pastures in the different physiographic regions in preweaning. In postweaning, only Cu was positively associated (R = 0.74; P < .05). Different season and physiographic regions influence the levels of Ca, Cu and Zn in the hoof capsule and native pasture during the pre- and postweaning stages.


Retrospective evaluation of the influence of azotemia on plasma lactate concentrations in hypotensive dogs and cats (2008-2018): 337 cases.
To evaluate the relationship between azotemia and plasma lactate concentration in hypotensive dogs and cats presented to an emergency department. Retrospective case-control study. University veterinary teaching hospital. The electronic medical record database was searched for dogs and cats presented to the emergency department that had severe azotemia (creatinine ≥ 443.1 μmol/L [5 mg/dL]), hypotension (systolic blood pressure ≤ 90 mm Hg), and a plasma lactate measurement within 2 h of each another. Non-azotemic, normotensive dogs and cats; non-azotemic, hypotensive dogs and cats; and azotemic, normotensive dogs and cats that presented to the emergency department were used as control populations. None. Severely azotemic, hypotensive dogs (n = 10) and cats (n = 63) had a lower plasma lactate than non-azotemic, hypotensive dogs and cats (P = 0.031 and P < 0.001, respectively). Median plasma lactate concentrations in hypotensive dogs (1.75 mmol/L) and cats (1.90 mmol/L) with severe azotemia were within reference intervals. Hypotensive dogs and cats with severe azotemia have decreased plasma lactate concentrations as compared to hypotensive, non-azotemic dogs and cats. The median plasma lactate in azotemic, hypotensive dogs and cats was within reference intervals. This may be due to either decreased cellular production of lactate or increased excretion of lactate. Further research is needed to determine which of these mechanisms is responsible and the clinical significance of plasma lactate concentrations in azotemic, hypotensive dogs and cats.


Dysphagia in Parkinson's disease is responsive to levodopa.
The role of levodopa in the treatment of dysphagia in Parkinson's disease (PD) has recently been questioned. There are good reasons, however, to "question the question." In this essay, evidence from published literature and clinical experience is presented, as well as a critical review of the first meta-analysis to explore this issue. The evidence presented supports the traditional view that PD dysphagia is responsive to levodopa.


Two-incision push-pull capsulorhexis for pediatric cataract surgery.
Pediatric capsulorhexis is a challenging surgical technique because of the elasticity of the pediatric anterior capsule. This technique of manual capsulorhexis allows reliable and reproducible results for the size and centration of anterior and posterior capsulorhexes in pediatric cases. The technique is a modification of a previously reported method.


Phosphatase activity in testis and prostate of rats treated with embelin and Vinca rosea extract.
Daily administration of Vinca rosea Linn. extract orally and embelin s.c. to male albino rats caused significant rise in levels of acid and alkaline phosphatases of testis and prostate indicating altered metabolic function.


Release kinetics and mitogenic capacity of collagen barrier membranes supplemented with secretome of activated platelets - the in vitro response of fibroblasts of the periodontal ligament and the gingiva.
Platelet preparations can stimulate the healing process and have mitogenic properties. We hypothesized that collagen barrier membranes (CBM), clinically used in guided bone regeneration and guided tissue regeneration, can serve as carriers for platelet secretome. Secretome was generated from washed platelets and unwashed platelets (washed/unwashed PSEC) and lyophilized onto CBM. Overall appearance of CBM was evaluated by scanning electron microscopy. The impact of PSEC on cell attachment was measured based on fluorescence microscopy with DiI-labeled cells. To assess the release kinetics, supernatants of CBM were collected and medium was replaced at hour 1-48. The mitogenic effect was evaluated with periodontal fibroblasts. Furthermore, the release of total protein, platelet-derived growth factor (PDGF)-BB, and transforming growth factor (TGF) β1 was measured. CBM overall appearance and cell attachment was not modulated by PSEC. Supernatants taken after one hour induced a mitogenic response in fibroblasts and showed the highest levels of total protein, TGFβ1 and PDGF-BB. These effects decreased rapidly in subsequent supernatants. While supernatants of CBM loaded with unwashed PSEC induced a stronger mitogenic response than supernatants of CBM loaded with washed PSEC this difference between the PSEC preparations was not observed when cells were seeded on 48-hours-washed CBM. CBM release platelet-derived factors in continuously declining release kinetics.


Surgical Catastrophic Health Expenditure and Risk Factors for Out-of-Pocket Expenditure at a South African Public Sector Hospital.
Worldwide, 3.7 billion people risk financial catastrophe if they require surgery, mostly affecting the poorest populations. Surgical care associated with catastrophic health expenditure (CHE) has not been well-described in the South African context. The objectives of this study were to determine: (1) the proportion of surgical patients at a South African hospital who experienced CHE and impoverishing health expenditure (IHE); and (2) the risk factors for out-of-pocket (OOP) payments. A cross-sectional prospective questionnaire was administered to participants admitted for a surgical procedure at New Somerset Hospital, Cape Town. CHE was defined in three ways: (1) 40% or more of capacity-to-pay, (2) 25% of annual household expenditure, or (3) 10% of annual household expenditure. IHE was described as the number of participants who experienced new or worsening impoverishment after surgery. Two hundred and seventy-four participants were interviewed, and 263 were included in the analysis (4% attrition rate). Two (0.8%) participants experienced CHE. 98.5% of participants spent less than 10% of their annual household expenditure and 43 participants (16.7%) experienced IHE. Risk factors for OOP expenditure were cancer diagnosis (p = 0.0386), an elective procedure (p = 0.0001), and having a limited health insurance plan (p = 0.0492). Most participants undergoing a surgical procedure did not experience CHE. Participants were relatively protected from financial catastrophe owing to subsidized user fees and the provision of transport. However, 17% of patients experienced IHE, suggesting even small payments resulted in impoverishment. Ensuring low financial vulnerabilities around surgical care is an important consideration for national surgical planning in South Africa.


Between religious philanthropy and individualised medicine: situating inherited breast cancer risk in Greece.
This article explores cultural articulations of inherited breast cancer risk at the meeting-point between religious philanthropy and individualised medicine. Drawing on the particularities of the ethnographic context of Northern Greece, in a rural area among a population facing the uneven distribution of biotechnologies, this analysis intends to show how developments in the field of breast cancer prevention and genetics are interwoven with the challenges and possibilities of the modernisation and secularisation processes. Notions of 'control' or 'protection' are put to work in medical discourse and the religious domain, through a renewed repertoire of pre-existing meaning-systems that highlight often contrasting aspects of collectivity and individuality. For women with high-risk family history of breast cancer, these tensions are reflected in ways they negotiate articulations of their biology, inherited risk and female subjectivity. In effect, the issues of inequality and religious philanthropy bring forth a different terrain for thinking about the biosocial configurations and the image of individualised consumers that genetic knowledge has been said to enforce or endorse.


Structural insights into the interaction of IL-33 with its receptors.
Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.


Mood Disorders in Youth: Complementary and Integrative Medicine.
Omega-3 polyunsaturated fatty acids, probiotics, vitamin C, vitamin D, folic acid and L-methyl folate, broad-spectrum micronutrients, N-acetylcysteine, physical activity, herbs, bright light therapy, melatonin, saffron, meditation, school-based interventions, and transcranial photobiomodulation are reviewed, with a focus on their use for treating mood disorders in children and adolescents. For each treatment, all published randomized controlled trials are summarized.


Whole-pelvic irradiation with boost to involved nodes and prostate in node-positive prostate cancer-long-term data from the prospective PLATIN-2 trial.
Node-positive prostate cancer is a potentially curable disease. Definitive radiotherapy to the prostate and lymphatic drainage is an effective treatment option but prospective long-term outcome data are scarce. Thus, the current study aimed to evaluate the toxicity and efficacy of definitive radiation therapy for men with prostate cancer and nodal metastases using modern irradiation techniques. A total of 40 treatment-naïve men with node-positive prostate cancer were allocated to the trial. All patients received definitive radiation therapy at two German university hospitals between 2009 and 2018. Radiation was delivered as intensity-modulated radiation therapy (IMRT) with 51 Gy to the lymphatic drainage with simultaneous integrated boost (SIB) up to 61.2 Gy to involved nodes and 76.5 Gy to the prostate in 34 fractions. Feasibility and safety, overall and progression-free survival, toxicity, and quality of life measurements were analyzed. During a median follow-up of 79 months, median overall survival was 107 months and progression-free survival was 78 months. Based on imaging follow-up, no infield relapse was reported during the first 24 months of follow-up. There were 3 (8%) potentially treatment-related grade 3 toxicities. Common iliac node involvement was associated with a higher risk of progression (HR 15.8; 95% CI 2.1-119.8; p = 0.007). Definitive radiation to the lymphatic drainage with SIB to the involved nodes and prostate is a safe and effective treatment approach for patients with treatment-naïve, node-positive prostate cancer with excellent infield tumor control rates and tolerable toxicity. Location rather than number of involved nodes is a major risk factor for progression.


Drug-resistant tuberculosis in Zhejiang Province, China, 1999-2008.
To evaluate levels and trends in drug-resistant tuberculosis (TB) in Zhejiang Province, China, we conducted 1 survey in each of 3 years (1999, 2004, and 2008). We found that <5% of new cases were multidrug-resistant TB. The prevalence of multidrug-resistant TB has not increased in new or re-treated cases in this province.


Stereotactic body radiotherapy (SBRT) in metachronous oligometastatic prostate cancer: a systematic review and meta-analysis on the current prospective evidence.
In contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment. There is mounting evidence in support of the role of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer (OMPC). MEDLINE and EMBASE were queried for prospective cohort studies reporting the outcomes of metachronous OMPC treated with SBRT. The primary outcome was overall local control. Secondary outcomes included androgen deprivation therapy-free survival (ADTFS), biochemical recurrence free survival (BCFS), and progression-free survival (PFS). When appropriate, these endpoints were combined in a meta-analysis. We screened 356 abstracts and identified 10 studies to include in our analysis, with a total of 653 patients and 1,111 lesions. The maximum number of lesions included in any single study ranged from 3 to 5. PET-CT staging occurred in 92.4% of all patients. SBRT dose varied, with BED1.5 ranging from 152 to 408. Only one Grade 3 bone toxicity was observed. Meta-analysis reported an overall local control rate of 97% (95% CI, 94-100). Median ADTFS was 24.7 months (95% CI, 20.1-29.2 months). Two-year BCFS, PFS, and ADTFS were 33% (95% CI, 11-55), 39% (95% CI, 24-54), and 52% (95%CI, 41-62), respectively. Patients treated with SBRT were half as likely to experience PSA progression than those on observation when looking at randomized control trial data alone. SBRT appears to be effective in controlling overall disease burden in metachronous OMPC patients and is associated with minimal significant toxicity. The current prospective literature is scarce, and further prospective data are needed to guide treatment recommendations. This study provides a comprehensive summary of the prospective evidence reporting the outcomes of SBRT in the management of OMPC patients. We quantify the rates of local control, biochemical-free recurrence, progression-free survival, and ADT-free survival through meta-analysis.


Approaches to recognition and management of childhood psychiatric disorders in pediatric primary care.
Psychiatric disorders occur in 14% to 20% of American children and adolescents and are a leading cause of disability among them, yet fewer than one in five of these children are recognized. The most common psychiatric disorders presenting to pediatricians include ADHD, anxiety disorders, depression, substance-use disorders, and conduct disorder, Approaches to recognition include screening for psychosocial concerns using specific questions in the clinical interview, and using brief, written questionnaires. Case vignettes illustrate comprehensive treatment planning for children with psychiatric disorders in the primary care context. As psychopharmacologic treatments and the new subspecialty of pediatric psychopharmacology take on growing importance, the traditional oversight role of the pediatrician and effective communication among referring and consulting physicians remain critical to quality care.


New potential chemotherapy for ovarian cancer - Combined therapy with WP 631 and epothilone B.
Despite more modern therapeutics approaches and the use of new drugs for chemotherapy, patients with ovarian cancer still have poor prognosis and therefore, new strategies for its cure are highly needed. One of the promising ways is combined therapy, which has many advantages as minimizing drug resistance, enhancing efficacy of treatment, and reducing toxicity. Combined therapy has rich and successful history in the field of ovarian cancer treatment. Currently use therapy is usually based on platinum-containing agent (carboplatin or cisplatin) and a member of taxanes (paclitaxel or docetaxel). In the mid-2000s this standard regimen has been expanded with bevacizumab, monoclonal antibody directed to Vascular Endothelial Growth Factor (VEGF). Another drug combination with promising perspectives is WP 631 given together with epothilone B (Epo B). WP 631 is a bisanthracycline composed of two molecules of daunorubicin linked with a p-xylenyl linker. Epo B is a 16-membered macrolide manifesting similar mechanism of action to taxanes. Their effectiveness against ovarian cancer as single agents is well established. However, the combination of WP 631 and Epo B appeared to act synergistically, meaning that it is much more potent than the single drugs. The mechanism lying under its efficacy includes disturbing essential cell cycle-regulating proteins leading to mitotic slippage and following apoptosis, as well as affecting EpCAM and HMGB1 expression. In this article, we summarized the current state of knowledge regarding combined therapy based on WP 631 and Epo B as a potential way of ovarian cancer treatment.


[Discussion on the substitution of anterior crucial ligament in knee capsule instabilities (author's transl)].
The conventional methods of rehabilitation plasty of the insufficient anterior crucial ligament will usually display elasticity in course of time. Accurate reconstructions of all capsular ligament lesions and the reinforcement by threads of the requisite connective tissue transplants, show good stability and a good overall result four years after the operation in a relatively small number of patients.


TRAF4 deficiency leads to tracheal malformation with resulting alterations in air flow to the lungs.
TRAF4 is one of six identified members of the family of TNFR-associated factors. While the other family members have been found to play important roles in the development and maintenance of a normal immune system, the importance of TRAF4 has remained unclear. To address this issue, we have generated TRAF4-deficient mice. Despite widespread expression of TRAF4 in the developing embryo, as well as in the adult, lack of TRAF4 expression results in a localized, developmental defect of the upper respiratory tract. TRAF4-deficient mice are born with a constricted upper trachea at the site of the tracheal junction with the larynx. This narrowing of the proximal end of the trachea results in respiratory air flow abnormalities and increases rates of pulmonary inflammation. These data demonstrate that TRAF4 is required to regulate the anastomosis of the upper and lower respiratory systems during development.


Avian influenza viruses in wild birds: a moving target.
The long-standing evolutionary and ecological relationships between wild birds and influenza A viruses has created a broad pool of viral genetic diversity and a reservoir of potentially transmissible viruses. An understanding of these relationships can help us identify and modify critical control points to reduce transmission of avian influenza viruses into animal and human populations.


Revisiting outcomes of right congenital diaphragmatic hernia.
Studies comparing outcomes of right- and left-sided congenital diaphragmatic hernia (R-CDH and L-CDH) have yielded conflicting results. We hypothesized that R-CDH is associated with higher short-term pulmonary morbidity than L-CDH. We reviewed all CDH patients at a tertiary children's hospital over 10 y. In prenatally diagnosed CDH, the observed-to-expected total fetal lung volume and percentage liver herniation (%LH) were calculated using fetal magnetic resonance imaging-based measurements. Outcomes were compared in patients with isolated CDH. Patients were subsequently matched by %LH to compare outcomes. Of 189 CDH patients, 37 (20.1 %) were R-CDH and 147 (79.9%) were L-CDH. Those with R-CDH were prenatally diagnosed at a significantly lower rate (40.5% versus 73.5%; P < 0.001) and later gestational age (26.5 ± 7.7 versus 22.6 ± 5.65 wk; P = 0.062). There was no difference in observed-to-expected total fetal lung volume between those with R-CDH and L-CDH (30.2 ± 11.1% versus 33.1 ± 14.2%; P = 0.471). Fetuses with R-CDH had a higher %LH than those with L-CDH (37.5 ± 14.1% versus 18.6 ± 12.2%; P < 0.001). Patients with isolated R-CDH had a higher need for extracorporeal membrane oxygenation than L-CDH (48% versus 27%; P = 0.055). There was no difference in duration of tracheal intubation, hospital stay, need for supplemental oxygen at 30-d of life or 6-mo mortality between groups. There was no difference in mortality and pulmonary morbidity when patients were matched by %LH. Compared to those with L-CDH, fetuses with R-CDH are less likely to be diagnosed prenatally and have a higher need for extracorporeal membrane oxygenation. The sidedness of the hernia defect was not associated with differences in short-term pulmonary morbidity in this large, contemporary single-institution experience of neonates with CDH.


A comparative evaluation of the three different antioxidant treatments on the bond strength of composite resin to bleached enamel: An in vitro study.
Natural antioxidants have capacity to neutralize the action of free radicles, therefore, effective in reversal of compromised bond strength. The aim of this study was to investigate the effect of three different antioxidant treatments on the bond strength of composite resin to bleached enamel. Ninety extracted human anterior teeth were divided into five groups: Group I (n = 10) - control group no bleaching, Group II (n = 20) - bleaching with 35% carbamide peroxide gel, Group III (n = 20): bleaching with application of 10% sodium ascorbate, Group IV (n = 20): bleaching with application of 6.5% proanthocyanidin, and Group V (n = 20) - bleaching with application of 50% Aloe vera. These groups were further subdivided into two subgroups based on whether composite buildup was done immediately (Subgroup A) or after a delay of 2 weeks (Subgroup B). Shear bond strength of the specimens was tested under universal testing machine. Data were statistically analyzed using Student's unpaired t-test, ANOVA test, and Tukey's Kramer multiple comparison test. The mean bond strength of Group IVA was significantly higher (4.27 ± 1.86) which indicated that immediate application of proanthocyanidin showed higher bond strength after bleaching (P < 0.05). Within the limitations of this study, it can be concluded that immediate application of antioxidants on bleached enamel before composite restoration reversed the bond strength of composite restoration. The immediate application of proanthocyanidin proved superior followed by A. vera.


Modernising the National Health and Medical Research Council.
The NHMRC is at a fork in the road - which route will the government take?


Intraoperative ultrasonographic study of the liver. Methods and anatomic results.
In this study, we have reported our experience with the use of intraoperative ultrasonography in the field of liver surgery. Using the method, the intrahepatic segmental pedicles can be precisely located and thus, segmentectomies can be performed in an anatomic way. The technique allows the most economic parenchymal resection in cirrhotic patients which may be important for prevention of postoperative liver insufficiency.


Anterior pituitary corticotropes of adrenalectomized, leptin-administered rats.
Leptin (LEP), the product of the ob gene is an adipose-tissue secreted hormone that acts to decrease caloric intake and increase energy expenditure. Some observations suggest the mutual relationship between leptin and blood ACTH levels. In the rat acute LEP administration enhances blood ACTH levels while prolonged treatment lowers blood corticotropin concentrations. Since the pituitary-derived ACTH is an important element in functioning of that loop, studies were undertaken to investigate the effect of prolonged LEP administration on anterior pituitary ACTH cells of adrenalectomized rats. Studies were performed on bilaterally adrenalectomized adult female rats. They were administered for 3 or 6 days with 2.7 nmol/rat/day LEP (recombinant human leptin) or with the vehicle (0.9% NaCl). LEP administration did not affect the body weight of bilaterally adrenalectomized rats. During the whole experiment the average increase in body weight was 3.9-4.3 g/day. LEP administration into adrenalectomized rats had no effect on anterior pituitary weight. This treatment resulted in a significant increase in pituitary ACTH concentration and content, and these changes were accompanied by a potent decrease in blood corticotropin level. LEP administration into adrenalectomized rats only insignificantly lowered the quantity of anterior pituitary ACTH-immunoreactive cells and their average area. On the opposite, the average volume of pituitary corticotropes of LEP-treated rats was notably lower than that in adrenalectomized-vehicle administered ones. Results of performed experiments clearly demonstrate that prolonged LEP administration results in a notable inhibition of the growth and secretory activity of anterior pituitary corticotropes of the adrenalectomized rats.


Argosomes: membrane fragments on the run.
Any biology student will know that the plasma membrane separates the inside of a cell from the outside world. Indeed, the plasma membrane is the guardian of a cell's physiology. Fewer students will be aware that cells can export bits of plasma membrane to distant sites in a tissue. Recent work demonstrates the transfer of membrane fragments in a live epithelium and, importantly, suggests that these fragments might be used as a vehicle to transport morphogens in a developing tissue.


Soluble membrane attack complex in the blood and cerebrospinal fluid of HIV-infected individuals, relationship to HIV RNA, and comparison with HIV negatives.
The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV+ adults (12 of whom underwent a second visit at least 24weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV+ individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV+ individuals on cART compared to HIV negative controls. In HIV+ participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance.


Nearest-neighbor amino acids of specificity-determining residues influence the activity of engineered Cre-type recombinases.
The tyrosine-type site-specific DNA recombinase Cre recombines its target site, loxP, with high activity and specificity without cross-recombining the target sites of highly related recombinases. Understanding how Cre achieves this precision is key to be able to rationally engineer site-specific recombinases (SSRs) for genome editing applications. Previous work has revealed key residues for target site selectivity in the Cre/loxP and the related Dre/rox recombinase systems. However, enzymes in which these residues were changed to the respective counterpart only showed weak activity on the foreign target site. Here, we use molecular modeling and dynamics simulation techniques to comprehensively explore the mechanisms by which these residues determine target recognition in the context of their flanking regions in the protein-DNA interface, and we establish a structure-based rationale for the design of improved recombination activities. Our theoretical models reveal that nearest-neighbors to the specificity-determining residues are important players for enhancing SSR activity on the foreign target site. Based on the established rationale, we design new Cre variants with improved rox recombination activities, which we validate experimentally. Our work provides new insights into the target recognition mechanisms of Cre-like recombinases and represents an important step towards the rational design of SSRs for applied genome engineering.


Expression profile of circRNA in peripheral blood mononuclear cells of patients with rheumatoid arthritis.
Circular RNAs (circRNAs) is a newly discovered non-coding RNA that can be used as biomarkers in clinical blood samples. This study aims to screen differentially expressed circular RNAs in PBMCs of patients with rheumatoid arthritis (RA) to determine new biomarkers for the diagnosis of RA. The differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) of 4 RA patients and 4 healthy participants were screened and analyzed by gene microarray technology. We then validated some of the differentially expressed circRNAs in PBMCs of 20 RA patients, 10 systemic lupus erythematosus (SLE) patients and 20 healthy participants using reverse transcription-quantitative polymerase chain reaction amplification (RT-qPCR). Spearman correlation test was performed to analyze the correlation between differentially expressed circRNAs and clinical variables in RA patients. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic value of circRNAs. Differential analysis obtained 149 circRNAs with significant up-regulated expression and 250 circRNAs with significant down-regulated expression, which predicted the miRNA targets and binding sites. Compared with SLE and health control group, hsa_circ_101328 was found to be a common gene with differential expression of RA. Besides, correlation analysis revealed significant correlation between hsa_circ_101328 and positive CRP. ROC curve analysis showed that hsa_circ_101328 has the potential of RA diagnosis. We identified some dysregulated circRNAs in PBMCs from RA patients, and hsa_circ_101328 may be a novel and effective biomarker for early diagnosis of RA.


Expression profiling of long noncoding RNA identifies lnc-MMP3-1 as a prognostic biomarker in external auditory canal squamous cell carcinoma.
Our previous studies suggested external auditory canal squamous cell carcinoma (EACSCC) is a rare malignancy with heterogeneous outcomes. This study aimed to identify lncRNA profile of EACSCC and determine the clinical application. Differential expression genes (DEGs) were investigated in EACSCC by whole transcriptome lncRNA arrays (GPL23178). RT-PCR was used to quantify the microarray data. Bioinformatics analyses were performed to evaluate DEGs regulations in gene ontology and cellular pathways. Fluorescence in situ hybridization (FISH) was utilized to validate lncRNA expression. The overall survival was determined by Kaplan-Meier and log-rank analyses. Our microarrays data had been submitted to Gene Expression Omnibus (GSE98912). We identified 5621 DEGs (3185 mRNAs, 2436 lncRNAs) in EACSCC. Lnc-MMP3-1 was the top one upregulated lncRNA in EACSCC with fold change of 237.2 (P < 0.001). RT-PCR results showed similar expression levels as microarrays data. Bioinformatics analyses indicated development of EACSCC was involved in aberrant alternations of multiple biological processes and cellular pathways. FSIH assays also found lnc-MMP3-1 was significantly differentially overexpressed in EACSCC (P < 0.001). Tumor lnc-MMP3-1 levels were closely associated with differentiation degree (P = 0.016), tumor invasion (P = 0.015) and TNM stage (P = 0.015). Moreover, lnc-MMP3-1 expression was a significant prognostic factor in EACSCC (χ2 = 4.276, P = 0.039). The study is the first screening and analysis of lncRNAs profile in EACSCC and provides new insights into pathogenesis of this rare disease. Our findings offered convincing evidences that lnc-MMP3-1 is a novel survival predictor of EACSCC patients.