Functionality Enhancement of Pea Protein Powder via High-Intensity Ultrasound: Screening in-vitro Digestion, o/w Emulsion Properties and Testing in Gluten-Free Bread.
Structural modification of protein prior to food application is an emergent approach to improve functionalization. The effectiveness of high-power ultrasound at varying amplitudes (0-100%) on the properties of pea protein powder was investigated in this study. The resulting modification was also tested with model gluten-free bread formulation and by screening the emulsion properties within vegetable oil. The 50% and beyond amplitude levels had significant impact on protein solubility, viscosity, Fourier Transform Infrared (FTIR) spectra, emulsion activity and stability. Foaming capacity and stability were enhanced with 75 and 100% amplitudes while the 25% amplitude exhibited the highest absolute zeta-potential. There was a concomitant increase in ultrasound amplitude and oil-binding capacity (2.83-6.43 g/g) where the water-holding capacity gradually decreased (5.78-3.61 g/g) with the increase in ultrasound power. The increase in ultrasound power led to decrease in L* values but progressively increased the total color difference (ΔE). Sonication (50% amplitude) also promoted the in-vitro digestibility of proteins by 22% as compared to the untreated sample. Scanning electron microscopy (SEM) fairly depictured the structural modification and FTIR spectra clearly demonstrated conformational changes in protein powders. The fortification with restructured pea protein powder significantly affected the volume and adhesiveness of glutenfree bread.


Decontamination and/or revegetation of fly ash dykes through naturally growing plants.
Present study is focused on the decontamination and/or revegetation of fly ash dykes through naturally growing plants, namely Calotropis procera, Cassia tora, Chenopodium album, Sida cardifolia, Blumea lacera. The results of sequential extraction study showed that maximum amount of metals (Na, K, Fe, Mn, Cr, Pb, Ni, Cd) were associated with residual and Fe-Mn fractions. Diethylenetriamine penta acetic acid (DTPA)-triethanolamine (TEA) extraction assessed the bioavailability of the metals. The total metal accumulation in tested plants was found in the order; C. album>S. cardifolia>C. tora>C. procera>B. lacera. The maximum bioconcentration factor (BCF) was recorded in S. cardifolia for the metals (Na, Fe, Zn, Cd), in C. procera for the metals (Mn, Cu, Ni, Cr) and in C. album for the metals (Co, Pb). However, the translocation factor (TF) of most of the metals was found more in S. cardifolia followed by C. album than other plants. Among all the plants, C. album have shown high BCF and low TF values for toxic metals (Pb, Cd) and suitable for phytostabilization of these metals. Principal component analysis was used to predict translocation behavior of the metals in different parts of the plants which was found similar for the metals (Cu, Zn, Mn, Cr). All examined plants are suitable for revegetation (naturally grows on fly ash dykes) and S. cardifolia and C. album may be used for decontamination purposes.


Efficacy of orally toxic sugar baits against contact-insecticide resistant culex quinquefasciatus.
In recent years, attractive toxic sugar bait has been used in the mosquito control in nature, and achieved good control effects. However, the current researches about toxic sugar bait did not focus on whether the wild mosquito population used for control is resistant or not. The purpose of this study was to evaluate the effectiveness of the toxic sugar bait against mosquito resistant populations to test the effects of bait on the control of mosquitoes with different levels of resistance. Boric acid, dinotefuran and deltamethrin were separately formulated into toxic sugar bait to test their anti-mosquito activity against Culex quinquefasciatus. Using the sugar baits formulated with boric acid and dinotefuran, the mortality of Cx. quinquefasciatus resistant populations was significantly higher than that of sensitive populations at the same concentration. Conversely, with the use of sugar baits formulated with deltamethrin, the mortality of Cx. quinquefasciatus resistant populations was significantly lower than that of sensitive populations at the same concentration. The results suggested that toxic sugar baits might have a good application prospect in high resistant mosquito management.


Faecal incontinence--Willis Home Bowel Washout Programme.
A simple procedure for managing bowel incontinence among children with spina bifida and other disabilities is described. The results of treatment offered to 100 children shows that the majority achieved reliable continence.


Catalytic oxidation of ibuprofen over bulk heterojunction photocatalysts based on conjugated donor-acceptor configured benzoselenadiazole molecule.
The use of photocatalysts for acquiring direct photon energy from sunlight is a promising way to clean the environment, particularly the remediation of contaminants from water. In this work, firstly π-conjugated organic semiconductor configuring benzoselenadiazole, 4-(3,5-bis(trifluoromethyl) phenyl)-7-(5'-hexyl-[2,2'-bithiophen]-5-yl)-benzo [c] (Kümmerer, 2009; Chen et al., 2018; Randeep et al., 201) selenadiazole, abbreviated as (RTh-Se-F), was synthesized. The designed RTh-Se-F with an extended π-conjugation showed good optical properties in the visible region and estimated a low optical band gap of ∼2.02 eV . The molecular orbitals i.e. HOMO (-5.33 eV) and LUMO (-3.31 eV) for RTh-Se-F organic semiconductor were suitably aligned to energy levels of (Madhavan et al., 2010Madhavan et al., 2010)-Phenyl-C71-butyric acid methyl esters (PC71BM) which resulted in the broadening of absorption and covering of entire visible region. RTh-Se-F was integrated with varied weight percentages (wt %) of PC71BM to obtain bulk heterojunction (BHJ) and applied as efficient visible light driven BHJ photocatalyst for an effective oxidation of ibuprofen. RTh-Se-F@PC71BM (1:2, wt %) BHJ photocatalyst showed the superior ibuprofen degradation of ∼93% within 90 min under visible light illumination. The maximum degradation rate by BHJ photocatalyst might be accredited to the broadening of absorption capacity and improved lifetime of photogenerated electron-hole pairs which might be resulted from high absorption properties of RTh-Se-F organic semiconductor.


Genome-wide identification and expression pattern analysis of the MATE gene family in carmine radish (Raphanus sativus L.).
Carmine radish (Raphanus sativus L.) is famousforcontaininganaturalredpigment(redradishpigment) that grown in Fuling, Chongqing City, China. MATE (multidrug and toxic compound extrusion), as an integral member of the multidrug efflux transporter family, has various functions in plants. However, noinformationhasbeenavailableaboutcharacteristicsoftheMATEgenefamily in carmine radish. In this study, total of 85 candidate MATE gene family members classifiedinto 4 groups were identified and foundtobewidelyandrandomlydistributedindifferent genome. Synteny analysis revealed that twenty-one segmental and ten tandem duplications acted as important regulators for the expansion of RsMATE genes. The Ka/Ks ratios of RsMATE indicated that RsMATE may have undergone intense purification in the radish genome. Cis-acting element analysis of RsMATE in the promoter region indicated that RsMATE were mainly related to the abiotic stress response and phytohormone. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that RsMATE40-b, RsMATE16-b and RsMATE13-a genes were significantly expressed under ABA (abscisic acid) and NaCl stress treatments respectively. In addition, the expression patterns of fifteen key RsMATE genes were investigated in 'XCB' (Xichangbai) and 'HX' (Hongxin) roots under Cadmium (Cd) stress for different treatment times using qRT-PCR, of those, RsMATE49-b, RsMATE33 and RsMATE26 transcripts were strongly altered at different time points in XCB responsive to Cd stress,compared to HX. This study will provide valuable insights for studying the functional characterization of the MATE gene in carmine radish and other plants.


Intranasal oxytocin administration facilitates the induction of long-term potentiation and promotes cognitive performance of maternally separated rats.
Maternal separation (MS) is known to induce permanent changes in the central nervous system and is associated with increased levels of anxiety and cognitive impairments. The neuropeptide oxytocin (OT) has been implicated in a broad spectrum of social and nonsocial and behaviors. Since it plays a significant role in learning and memory and enhances synaptic plasticity, we hypothesized that OT may affect MS-induced changes in synaptic plasticity and cognitive performance. Rat pups underwent MS protocol for 180 min/day from postnatal day (PND) 1-21. OT was administered intranasally (2 μg/μl, 7 days) to control and MS groups from PND 22-34. Plasma corticosterone (CORT) levels, anxiety-like behavior, sociability, learning and memory were measured in adolescent rats. In addition, extracellular evoked field excitatory postsynaptic potentials (fEPSP) were also recorded from hippocampal slices. MS induced higher plasma CORT levels and impaired social interaction, learning and memory. Moreover, MS reduced locomotor activity and increased anxiety-like behavior. Intranasal OT could overcome MS-induced deficits and promoted sociability, learning and memory of MS rats. OT also enhanced locomotor activity in the open field and decreased anxiety-like behavior. Obtained results showed that long term potentiation (LTP) was not induced in MS animals. However, OT injection overcame the MS-induced impairment in LTP generation in CA1 area of the hippocampus.


Validation of diagnosis codes for chorioamnionitis in medical encounter data, 2013-2018.
Chorioamnionitis refers to intrauterine infection/inflammation that can be diagnosed clinically or from laboratory testing. This study aimed to validate chorioamnionitis International Classification of Diseases (ICD) codes using reference standards for clinical and histologic cases. Department of Defense Birth and Infant Health Research program data identified a cohort of live deliveries at two United States military hospitals from 2013 to 2018. Deliveries were screened for chorioamnionitis using ICD codes from maternal delivery records; a sample of screen positive and negative deliveries was selected for chart review. Primary analyses validated deliveries using a reference standard for clinical chorioamnionitis; secondary analyses employed a reference standard that also included histologic cases, but were limited by temporal differences in availability of laboratory data. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated with 95% confidence intervals (CIs). Overall, 1857 deliveries (465 screen positive, 1392 screen negative) were eligible for analysis and 336 met the reference standard for clinical chorioamnionitis, yielding a PPV of 0.68 (95% CI 0.63, 0.72) and sensitivity of 0.76 (95% CI 0.72, 0.81). In secondary analyses, 390 deliveries met the reference standard for clinical or histologic chorioamnionitis, resulting in an overall PPV of 0.75 (95% CI 0.71, 0.79); in 2018, when more laboratory results were available, the PPV was 0.91 (95% CI 0.84, 0.97). NPV and specificity were ≥0.97 across reference standards. Chorioamnionitis ICD codes exhibited moderate correlation with clinical disease, suggesting challenges in using medical encounter data to isolate clinical cases from those only identified through laboratory testing.


Methods and software in NGS for TE analysis.
The recent development of next-generation sequencing (NGS) technologies allowed various authors to imagine, test, and validate new approaches for TE analysis, in their nature, type, activity, or quantity. In this chapter, we describe briefly the technologies used, then the various approaches and methods used already, and finally some potential new methods. In contrast to the more molecular chapters of the book, the approaches described here are purely bioinformatics, and have a set of NGS data as a starting point. Moreover, as these analyses are quite recent in the field, most of them were only performed once, and we cannot be sure that they could be reused in other species or context than the original one. However, there are a lot of interesting approaches and results that NGS can provide in the TE field.


Right and left ventricular function after the Mustard procedure in transposition of the great arteries.
Right and left ventricular function was assessed at cardiac catheterization in 33 asymptomatic patients 0.5 to 11 years (mean 4.6) after the Mustard operation for complete transposition of the great arteries. Ages at operation had ranged from 0.5 to 16 years (mean 4.2 years). Right ventricular function was assessed using videodensitometric determination of ejection fraction and ventricular volume data. Ventricular volumes were obtained by computerized video analysis utilizing Simpson's rule. The right ventricular ejection fraction was 37 +/- 11 percent (standard deviation), as assessed with videodensitometry and 42 +/- 10 percent as assessed with ventricular volume--both values less than normal (P less than 0.001). Right ventricular end-diastolic volume was significantly greater than normal (P less than 0.001) and averaged 202 +/- 70 percent, but left ventricular end-diastolic volume averaged only 125 +/- 53 percent. These observations after the Mustard operation indicate that right ventricular function is seriously decreased with relatively preserved left ventricular function. They support efforts for surgical correction utilizing the left ventricle as the systemic ventricle.


Background identification in cryogenic calorimeters through α - α delayed coincidences.
Localization and modeling of radioactive contaminations is a challenge that ultra-low background experiments are constantly facing. These are fundamental steps both to extract scientific results and to further reduce the background of the detectors. Here we present an innovative technique based on the analysis of α - α delayed coincidences in 232 Th and 238 U decay chains, developed to investigate the contaminations of the ZnSe crystals in the CUPID-0 experiment. This method allows to disentangle surface and bulk contaminations of the detectors relying on the different probability to tag delayed coincidences as function of the α decay position.


Management of the Vertebral Artery in Craniovertebral Junction Stabilization Surgery.
The vertebral artery (VA) has an intimate relationship with the bones of the craniovertebral junction. An exact understanding of the VA anatomy in general and in the specific surgical case in particular is absolutely necessary in order to avoid intraoperative vascular injury. The course of the VA on the inferior aspect of the superior facet of the C2 vertebra makes it susceptible to damage during transarticular and interarticular fixation with the screw insertion in the adjacent lateral mass. The consequences of the intraoperative VA injury will depend on the patency of other arteries supplying the brain. In case of this complication, quick decision-making is essential to avoid excessive blood loss and to preserve adequate cerebral blood flow.


Constitutional pericentric inversion of chromosome 9 and acute leukemia.
In view of the recent reports demonstrating delayed engraftment after autologous and allogeneic transplantation from donors with constitutional pericentric inversion of chromosome 9, [inv(9)], we conducted a retrospective study on six patients with acute leukemia and inv(9) to investigate if there is an impaired engraftment potential of the inv(9) hematopoietic stem cells. All but one of our patients had poor outcome. The hematopoietic recovery after induction chemotherapy was not prolonged. It is possible that the hematopoietic defects of inv(9) become more apparent after repeated courses of chemotherapy. Alternatively, the number of patients in our series may have been too small to detect a partial hematopoietic defect in patients with constitutional inv(9). Larger studies are required to confirm our findings.


Learning curves in laparoscopic distal pancreatectomy: a different experience for each generation.
Learning curves of laparoscopic distal pancreatectomy (LDP) are mostly based on 'self-taught' surgeons who acquired sufficient proficiency largely through self-teaching. No learning curves have been investigated for 'trained' surgeons who received training and built on the experience of the 'self-taught' surgeons. This study compared the learning curves and outcome of LDP between 'self-taught' and 'trained' surgeons in terms of feasibility and proficiency using short-term outcomes. Data of consecutive patients with benign or malignant disease of the left pancreas who underwent LDP by four 'self-taught' and four 'trained' surgeons between 1997 and 2019 were collected, starting from the first patient operated by a contributing surgeon. Risk-adjusted cumulative sum (RA-CUSUM) analyses were performed to determine phase-1 feasibility (operative time) and phase-2 proficiency (major complications) learning curves. Outcomes were compared based on the inflection points of the learning curves. The inflection points for the feasibility and proficiency learning curves were 24 and 36 procedures for 'trained' surgeons compared to 64 and 85 procedures for 'self-taught' surgeons, respectively. In 'trained' surgeons, operative time was reduced after completion of the learning curves (230.5-203 min, P= 0.028). In 'self-taught' surgeons, operative time (240-195 min, P ≤0.001), major complications (20.6-7.8%, P= 0.008), and length of hospital stay (9-5 days, P ≤0.001) reduced after completion of the learning curves. This retrospective international cohort study showed that the feasibility and proficiency learning curves for LDP of 'trained' surgeons were at least halved as compared to 'self-taught' surgeons.


[Lung cancer: Stereotactic body radiation therapy and surgery].
Stereotactic body radiation therapy for lung cancer is now well established for patients who are not eligible to surgery. These patients can benefit from a curative treatment, which is a new therapeutic indication. Protocols are effective and well tolerated even for the most fragile patients. Three randomized trials comparing stereotactic body radiation therapy and surgery failed due to poor accrual. However, taking into account the favourable available data, the choice of stereotactic body radiation therapy in first intention arises. The treatment decision has to be discussed in a multidisciplinary way, while considering the opinion of the patient, who must be clearly informed about the principle of both therapeutic options.


Turanecio hypochionaeus: Determination of Its Polyphenol Contents, and Bioactivities Potential Assisted with in Silico Studies.
The aim of this study was to identify and quantify the phenolic composition of Turanecio hypochionaeus Bosse and determine the anti-urease, anti-lipase, antidiabetic, anti-melanogenesis, antibacterial, and anti-Alzheimer properties. IC50 results for all enzymes were obtained between 0.234-116.50 μg/mL and this plant inhibited HMG_CoA R and glucosidase enzymes more with IC50 values of 0.234 and 116.50 μg/mL, respectively. Among the 11 secondary metabolites identified in T. hypochionaeus extract, chlorogenic acid 255.459±1.17 μg g-1 ), benzoic acid (56.251±1.98 μg g-1 ), and catechin (29.029±0.27 μg g-1 ) were determined as the most abundant phenolic compounds. According to the results of the tested microorganisms, the plant extracts showed antimicrobial and antifungal properties in a dose-dependent manner. In molecular docking study, the interactions of active compounds extracted from Turanecio hypochionaeus plant and showing activity against diverse metabolic enzymes were examined. The most active compound 1, (chlorogenic acid) has -12.80, -12.80, -12.60 and -12.00 kcal/mol binding energy value against HMG_CoA R, and α-amylase, α-glucosidase, and lipase, respectively.


Quantum DFT methods to explore the interaction of 1-Adamantylamine with pristine, and P, As, Al, and Ga doped BN nanotubes.
Nanostructures, nowadays, found growing applications in different scientific and industrial areas. Nano-coins, nanosheets, and nanotubes are used in medical applications as sensors or drug delivery substances. The aim of this study is to explore the adsorption of 1-Adamantylamine drug on the pristine armchair boron nitride nanotubes (BNNTs) with BNNT(5,5), BNNT(6,6), and BNNT(7,7) chirality along with the P, As, Al and Ga-doped BNNTs, using the quantum mechanical density functional methods. Considering the fact that dispersion effects are important in the case of weak Van der Waals interactions, computations have been done using B3LYP hybrid functional with the implementation of the D3(BJ) empirical dispersion correction methods. Quantum theory of atoms in molecules, natural bonding orbitals, and Kohn-Sham orbitals were used to investigate the nature and type of the adsorption process. The results showed that, while the adsorption of 1-Adamantylamine on the outer surface of pristine BNNT is physical in nature, doping can improve the ability of detracted BN to adsorb the drug through chemical bonds. Also, it was found that, by increasing the radius of the BNNT the adsorption energy was decreased. In conclusion, results of the present work suggest that, Ga doped nanotube, due the chemisorption, is not an ideal nanotube in drug delivery of 1-Adamantylamine drug, whereas, the other studied cases physiosorbed the drug, and may not have serious problem in release of the 1-Adamantylamine drug.


Clinical diagnosis from digital displays: preliminary findings of the St Mary's Evaluation Project.
Image quality is a fundamental issue in the introduction of picture archiving and communications systems (PACS), and one that has hitherto been eclipsed by other aspects of the considerable technological challenge facing scientists and manufacturers involved in its development. We conducted a formal evaluation of clinical radiological diagnosis from a commercially available PACS viewing station, using subperiosteal resorbtion in renal osteodystrophy as the test pathological diagnosis, with receiver operating characteristic (ROC) analysis of the results. We conclude that the displayed, digitised images were inferior to film using the apparatus tested and believe that careful, objective clinical evaluation of such systems is of paramount important.


Plecoglossus altivelis as a new fish intermediate host of Heterophyopsis continua.
P. altivelis from Korea republic is recorded as a new host for H. continua which is described and figured.


Numerical Study of Three Ventilation Strategies in a prefabricated COVID-19 inpatient ward.
Prefabricated inpatient wards have been proven to be an efficient alternative to quickly extend the caring capacity for patients. In this study, three typical ventilation strategies were studied using computational fluid dynamics in a prefabricated Coronavirus disease 2019 double-patient ward. Pollutants are the respiratory droplets and aerosols injected from two manikins. They are modelled as particles with different diameters (3 μm, 6 μm, 12 μm, 20 μm, 45 μm and 175 μm) by the Eulerian-Lagrangian model. Three ventilation strategies with an identical air change rate of 12.3 h-1 but different layouts of inlets and outlets are implemented. The flow field, flow structures and particle trajectories have been analysed and compared among the three ventilation strategies. The fate of particles is analysed and compared quantitatively. It is found that small particles (<20 μm) can move along with the main flow streams. Most of them are removed by ventilation to the outlet(s). Large particles (>45 μm) cannot move with the flow streams over a long path. Most of them deposit on solid surfaces in different regions of the ward in each ventilation strategy. Health workers should pay close attention to these polluted areas. Targeted cleaning of the polluted areas is necessary in a prefabricated inpatient ward. To promote the removal of some large particles (e.g., 45 μm) by the outlet(s), the outlet(s) should be installed inside the landing area of large particles and close to the polluted source(s).


Assessment of compression and strength of divergent screws mounted on miniplates for fixation of mandibular fractures: an in vitro experimental study.
An efficient band of tension is critical for the adequate fixation of mandibular fractures, so fixation devices that compress are helpful. We aimed to evaluate the possibility of creating compression using screws inserted divergently into miniplates placed in the tension zone of mandibular fractures and record the effects on the strength of fixation. For this in vitro experimental study we prepared 20 sheep hemimandibles. After angle fractures had been created, the specimens were divided into standard and study groups (n=10 in each). In the standard group the tension zones were fixed in the standard manner with 4-hole miniplates and 4 parallel screws. Those in the study group were fixed as for the standard group but with 4×45° divergent screws. The differences in the gap in the fracture line before and after fixation were measured as indicators of compression. The strength of fixation was also assessed with a universal testing machine in vitro. The amount of compression was significant only in the study group (p<0.001), and there was no difference in the strength of fixation between the two groups (p=0.7). We conclude that divergent drilling and insertion of screws creates more horizontal force when miniplates are used, and results in reduction in the size of the probable gap in the fracture line. Insertion of divergent screws in miniplates may create compression between fractured segments without jeopardising the strength of fixation.


Search for proteomic markers for stunning stress and stress-induced textural tenderization in silver carp (Hypophthalmichthys molitrix) fillets using label-free strategy.
A differential proteome analysis using label-free strategy was conducted to elucidate the stunning stress-induced proteome changes and its relationship to textural softening in silver carp (Hypophthalmichthys molitrix) fillets. Compared with the muscle proteome of fillets stunned by percussion, ice/water and gill cut stunning resulted in 43 differentially abundant proteins (DAPs) that were involved in muscle contraction, energy metabolism, antioxidant defense, protein turnover, etc., and gill cut-stunned fillets showed the most significant proteome changes with 28 up- and down-regulated DAPs. In addition, textural softening was more obvious in ice/water- and gill cut-treated fillets and was closely correlated to 21 DAPs including fast muscle troponin T, fragments of myosin, superoxide dismutase [Cu-Zn], ribosomal protein L38, isoform 2 of heat shock cognate 70, two subunits of proteasome, etc., and those DAPs were selected as potential proteomic markers to trace the accelerated textural softening in stunning-stressed fillets.


Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord.
Exogenous NGF or saline was delivered to the detrusor smooth muscle of female rats for a two-week period using osmotic mini-pumps. We then determined: (1) bladder function using conscious cystometry; (2) organization of micturition reflexes using Fos protein expression in lumbosacral (L5-S1) spinal cord neurons; (3) calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) in lumbosacral spinal cord segments. An osmotic pump infused 0.9% NaCl (n = 6) or NGF (n = 6)(2.5 microg/microl solution; 0.5 microl/hr) for two weeks into the bladder wall. NGF bladder content was determined by enzyme-linked immunoassays. Bladder function was assessed with conscious cystometry. Immunohistochemical and imaging techniques were used to determine the distribution of Fos-IR cells and CGRP expression in the L5-S1 spinal cord in saline and NGF-treated rats two hours after intravesical saline distention. Fos expression and CGRP-IR in NGF-treated rats with bladder distention was compared to that observed in cyclophosphamide (CYP; 75 mg/kg; i.p.) treated rats with bladder distention. Two-week infusion of NGF into the bladder wall increased bladder weight, reduced bladder capacity (60%), reduced the intercontraction interval (60%) and increased the amplitude of non-voiding contractions. NGF treatment and intravesical saline distention (2 hr) increased expression of Fos protein in L6-S1 spinal cord and altered the distribution pattern of Fos-IR cells. CGRP-IR in the lumbosacral spinal cord was also increased after NGF treatment. These data suggest that NGF infusion into the bladder wall induces bladder overactivity, can reveal a "nociceptive" Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus and increases CGRP-IR in the lumbosacral spinal cord.


Long-term high-dose L-arginine supplementation in patients with vasculogenic erectile dysfunction: a multicentre, double-blind, randomized, placebo-controlled clinical trial.
The current randomized, double-blind, placebo-controlled clinical trial addressed the effects on penile erectile function of relatively high daily oral doses (6 g/day) of L-ARG for 3 months (N = 51) compared to placebo (N = 47), in patients with vasculogenic ED, with comparison between mild-moderate and severe vasculogenic ED. The outcome measures included IIEF-6 score and cavernous arteries peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography (PDU). L-ARG supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p < 0.0001) and in subgroups of patients with mild-moderate (p < 0.0001) and severe (p = 0.007) vasculogenic ED; PSV was significantly increased in the overall cohort (p < 0.0001) and in patients with mild-moderate (p < 0.0001), but not severe vasculogenic ED. At study completion, 74% of patients improved ED degree category, although only 24% of patients, mainly belonging to the baseline category of mild ED, reached IIEF-6 scores compatible with absence of ED; moreover, 20% of patients, exclusively belonging to the baseline category of mild-moderate vasculogenic ED, reached PSV values compatible with absence of ED. The results of the current study demonstrated that supplementation with relatively high doses of L-ARG as a single compound for 3 months significantly improved penile erectile function, assessed by both IIEF-6 score and PSV at dynamic PDU in patients with mild-moderate, and improved IIEF-6 score, but not PSV, in patients with severe vasculogenic ED, therefore suggesting that L-ARG might be an alternative treatment in mild-moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5i compounds.


Inhibitory effects of 5-azapyrimidine nucleosides on cellular immunity.
The effect of 5-azacytidine (5-AzCR) and 5-aza-deoxycytidine (5-AzCdR) on the survival of skin grafts in mice and rats, the action of these drugs on regional GVH reaction, as well as the formation of haemopoietic colonies (CFU-5) in the spleen were studied. Both drugs prolonged the life span of skin grafts when administered 24 hr before transplantation, or on the 4th post-transplantation day. However, they were little effective when injected 24 hr after skin grafting, or after induction of the regional GVHR. Following intraperitoneal administration, they inhibited CFU-5 formation. Two-hour incubation in vitro of cells with 5-AzCR significantly reduced their GVH reactivity and capacity to form CFU-5; 5-AzCdR under the same conditions was ineffective.


Modifications of the isonipecotic acid fragment of SNS-032: analogs with improved permeability and lower efflux ratio.
Modifications of the isonipecotic acid fragment of SNS-032 results in analogs which are more permeable and lower effluxed than SNS-032. The enantiomerically pure synthesis and the in vivo profile of analog 20 is described.


Epstein-Barr virus infection controls the concentration of the intracellular antioxidant glutathione by upregulation of the glutamate transporter EAAT3 in tumor cells.
Epstein-Barr virus or human herpesvirus 4 (EBV/HHV-4) is an omnipresent oncovirus etiologically associated with various B-cell lymphomas and epithelial cancers. The malignant transformation associated with the persistent expression of viral proteins often deregulates the host cellular machinery and EBV infection is coupled to elevated levels of reactive oxygen species. Here, we investigated the role that the glutamate transporter EAAT3 plays in regulating the antioxidant system as a protective mechanism of EBV-infected cells against the virus-induced oxidative stress. Our study demonstrated that the expression of EAAT3 was upregulated and localized to the plasma membrane in EBV latently infected and de novo EBV-infected cells. EAAT3 was regulated by the transcription factor NFAT5 in the infected cells. Membrane localized EAAT3 was found to be involved in the transportation of glutamate from the extracellular space into the cell, as EAAT3 and NFAT5 inhibitors markedly reduced the levels of intracellular glutamate levels in EBV latently infected cells. Additionally, our data demonstrated a notable decrease in the intracellular glutathione levels following treatment with an EAAT3 inhibitor. Collectively, our results suggest that upregulation of the glutamate transporter EAAT3 is an adaptation of EBV-infected cells to maintain cellular redox homeostasis against the virus-induced oxidative stress, and that this cellular balance could be therapeutically destroyed by targeting EAAT3 to impede EBV-associated cancers.


Clinical and cytogenetic findings in monocyte--macrophage system malignancies with initial spontaneous regression.
Clinical and cytogenetic features are described in two patients with rare monocyte-macrophage malignancy. Their conditions clinically were different, but initial spontaneous regression was observed, and in both patients a No. 15 anomaly was involved.


Poly-ɛ-caprolactone nanocapsules loaded with copaiba essential oil reduce inflammation and pain in mice.
Diverse drugs have been used for the management of inflammation disorders and pain. However, they present many side effects and stimulate the search for new pharmacotherapeutic alternatives. Plant-derived products such as copaiba essential oil (CO) offer beneficial pharmacological effects. On the other hand, essential oil's low water solubility and physical instability hinder its in vivo application. Thus, poly-ɛ-caprolactone (PCL)-based nanocarriers have been used to increase their stability and efficacy. This work aimed to encapsulate CO in PCL nanocapsules and evaluate their effect on inflammation models and pain. The polymeric nanocapsules loading CO (CO-NC) were prepared by nanoprecipitation technique, characterized, and analyzed for their anti-inflammatory effect in vitro and in vivo. The results showed that CO-NC presented a spherical shape, 229.3 ± 1.5 nm diameter, and a negative zeta potential (approximately -23 mV). CO and CO-NC presented anti-inflammatory and antioxidant effects by LPS-activated macrophages (J774 cells). In addition, CO-NC significantly reduced TNF-α secretion (3-fold) compared to CO. In vivo, pre-treatment with CO or CO-NC (50, 100, 200 mg/kg, intraperitoneal; i.p) reduced the mechanical allodynia, paw edema, and pro-inflammatory cytokines induced by intraplantar (i.pl) injection of carrageenan in mice. Specifically, CO-NC (200 mg/kg; i.p.) reduced the production of TNF-α similar to the control group. Our results support using polymeric nanocapsules for CO delivery in inflammatory conditions.


Promoter methylation of genes in bronchial lavages: a marker for early diagnosis of primary and relapsing non-small cell lung cancer?
A prospective screening program, including CT, autofluorescent bronchoscopy, biopsies and bronchial lavage (BL) collection, was initiated with the specific goal of identifying biomarkers for the early detection of non-small cell lung cancer. We report and discuss the results of p16, DAPK, MGMT, FHIT and APC methylation analysis in the 126 first patients: 77 at high risk of cancer and 49 followed up after primary cancer resection. Positive results were found in 49% of BLs, 53% in current smokers and 43% in former smokers. In presence of peripheral tumours, only 38% of BLs were abnormal versus 73% in presence of central tumours, 50% in presence of preneoplasic lesions and 47% in absence of lesions. FHIT methylation was an early event, observed in one-third of the BLs from patients with or without lesions as well as in tumours. APC methylation was a late event observed in 33% of tumours but rarely in BLs. p16 was methylated in 17% of BLs but in 48% of tumours; DAPK in 15% of BL and 22% of tumours. MGMT methylation was rare. Among patients followed up after cancer surgery, 14 were in remission with normalised BL, whereas three had positive BLs and relapsed with a central tumour. Thus, gene methylation in BL might help to detect central tumours but a CT is crucial for peripheral cancer detection.


Operation Homefront: Meeting Clerkship Competencies with Home Visits to Families of Children With Special Needs.
We assessed how third-year medical students' written reflections on home visit experiences with families of children with special needs demonstrate evidence of exposure to 9 selected competencies for pediatric clerkships designated by the Council on Medical Student Education in Pediatrics. We reviewed written reflections from 152 third-year medical students. For each competency (2 related to communication were combined), we tabulated the number of reflections in which a given competency was demonstrated. Within each competency, themes are described and presented with exemplary quotes to provide a more robust picture of students' exposure and experience. Of 152 reflections, 100% demonstrated at least 1 of the 8 expected competencies. Each reflection exhibited an average of 3 (3.1) competencies (range: 1-7). The competencies most frequently mentioned were demonstration of respect for patient, parent, and family attitudes, behaviors, and lifestyles (90%) and demonstration of positive attitude toward education (76%). Less frequently mentioned competencies included demonstration of behaviors and attitudes that promote patients' and families' best interests (41%), demonstration of effective verbal and nonverbal communication skills (a combination of 2 communication-related competencies) (33%), and description of barriers that prevent children from accessing health care (37%). The following competencies were least often mentioned: description of a pediatrician's role and responsibility in advocating for patients' needs (10%), description of the important role of patient education (8%), or description of the types of problems that benefit from a community approach (17%). Our analysis demonstrates that community-based home visits can provide medical students with opportunities to meet required pediatric clerkship competencies.


Ligand-based virtual screening under partial shape constraints.
Ligand-based virtual screening has proven to be a viable technology during the search for new lead structures in drug discovery. Despite the rapidly increasing number of published methods, meaningful shape matching as well as ligand and target flexibility still remain open challenges. In this work, we analyze the influence of knowledge-based sterical constraints on the performance of the recently published ligand-based virtual screening method mRAISE. We introduce the concept of partial shape matching enabling a more differentiated view on chemical structure. The new method is integrated into the LBVS tool mRAISE providing multiple options for such constraints. The applied constraints can either be derived automatically from a protein-ligand complex structure or by manual selection of ligand atoms. In this way, the descriptor directly encodes the fit of a ligand into the binding site. Furthermore, the conservation of close contacts between the binding site surface and the query ligand can be enforced. We validated our new method on the DUD and DUD-E datasets. Although the statistical performance remains on the same level, detailed analysis reveal that for certain and especially very flexible targets a significant improvement can be achieved. This is further highlighted looking at the quality of calculated molecular alignments using the recently introduced mRAISE dataset. The new partial shape constraints improved the overall quality of molecular alignments especially for difficult targets with highly flexible or different sized molecules. The software tool mRAISE is freely available on Linux operating systems for evaluation purposes and academic use (see http://www.zbh.uni-hamburg.de/raise ).


Water-Dispersible Silica-Coated Upconverting Liposomes: Can a Thin Silica Layer Protect TTA-UC against Oxygen Quenching?
Light upconversion by triplet-triplet annihilation (TTA-UC) in nanoparticles has received considerable attention for bioimaging and light activation of prodrugs. However, the mechanism of TTA-UC is inherently sensitive for quenching by molecular oxygen. A potential oxygen protection strategy is the coating of TTA-UC nanoparticles with a layer of oxygen-impermeable material. In this work, we explore if (organo)silica can fulfill this protecting role. Three synthesis routes are described for preparing water-dispersible (organo)silica-coated red-to-blue upconverting liposomes. Their upconversion properties are investigated in solution and in A549 lung carcinoma cells. Although it was found that the silica offered no protection from oxygen in solution and after uptake in A549 cancer cells, upon drying of the silica-coated liposome dispersion in an excess of (organo)silica precursor, interesting liposome-silica nanocomposite materials were obtained that were capable of generating blue light upon red light excitation in air.


Overexpression of KIFC1 and its association with spheroid formation in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most common human cancers. We previously reported that KIFC1 is involved in gastric cancer pathogenesis and that KIFC1 plays an important role in gastric cancer spheroid colony formation. However, the significance of KIFC1 in ESCC has not been examined. In the present study, we analyzed the expression and distribution of KIFC1 in 132 ESCC cases by immunohistochemistry. In contrast to weak or no staining of KIFC1 in non-neoplastic mucosa, ESCC tissue showed stronger, more extensive KIFC1 staining. In total, 95 (72%) of 132 ESCC cases were positive for KIFC1. Immunostaining of ALDH1 was also performed, and KIFC1-positive ESCC cases were significantly frequently found in ALDH1-positive ESCC cases compared with ALDH1-negative ESCC cases. Spheroid colony formation is an effective method to characterize CSCs, thus we analyzed sphere number and size at 15days in ESCC cells downregulated for KIFC1 by siRNA transfection. Both the number and size of sphere from TE-1 cells were significantly reduced in KIFC1 siRNA-transfected TE-1 cells than in negative control siRNA-transfected cells. These results suggest that KIFC1 plays an important role in ESCC pathogenesis.


Role of puberty in multiple sclerosis risk and course.
Multiple sclerosis (MS) overwhelmingly presents during the reproductive years, and is more common in females than males. The sexual dimorphism observed in post-pubertal cases is absent in pre-pubertal cases, suggesting that puberty is a key risk period for development of disease, particularly in females. Research has identified several risk factors for MS that occur during the adolescent, or post-pubertal reproductive years, which are associated with clinical presentations later in life. These observations necessitate examination of the biological changes associated with puberty, their interactions with MS risk factors, and potential effects on disease immunopathogenesis. Pediatric and adolescent presentations of MS provide a unique opportunity to study the effects of neuroendocrine changes occurring during puberty and its effect on disease development and disease course. Reviewed is the relationship of MS risk factors and puberty, and differences in disease presentation of pre- and post-pubertal children with MS. Further avenues of research are discussed.


Identification of TPS family members in apple (Malus x domestica Borkh.) and the effect of sucrose sprays on TPS expression and floral induction.
Trehalose (α-D-glucopyranosyl α-D-glucopyranoside) is a non-reducing disaccharide that serves as a carbon source and stress protectant in apple trees. Trehalose-6-phosphate (T6P) is the biosynthetic precursor of trehalose. It functions as a crucial signaling molecule involved in the regulation of floral induction, and is closely related to sucrose. Trehalose-6-phosphate synthase (TPS) family members are pivotal components of the T6P biosynthetic pathway. The present study identified 13 apple TPS family members and characterized their expression patterns in different tissues and in response to exogenous application of sucrose during floral induction. 'Fuji' apple trees were sprayed with sucrose prior to the onset of floral induction. Bud growth, flowering rate, and endogenous sugar levels were then monitored. The expression of genes associated with sucrose metabolism and flowering were also characterized by RT-quantitative PCR. Results revealed that sucrose applications significantly improved flower production and increased bud size and fresh weight, as well as the sucrose content in buds and leaves. Furthermore, the expression of MdTPS1, 2, 4, 10, and 11 was rapidly and significantly up-regulated in response to the sucrose treatments. In addition, the expression levels of flowering-related genes (e.g., SPL genes, FT1, and AP1) also increased in response to the sucrose sprays. In summary, apple TPS family members were identified that may influence the regulation of floral induction and other responses to sucrose. The relationship between sucrose and T6P or TPS during the regulation of floral induction in apple trees is discussed.


Correction: Diffusion of methyl oleate in hierarchical micro-/mesoporous TS-1-based catalysts probed by PFG NMR spectroscopy.
[This corrects the article DOI: 10.1039/C8RA07434H.].


Improved isolation of proteins tagged with glutathione S-transferase.
A common affinity tag used to express and purify fusion proteins is glutathione S-transferase. However, many researchers have reported difficulty eluting GST-tagged proteins from the affinity matrix. This report demonstrates that the problem likely is due to the propensity of glutathione S-transferase to dimerize combined with a propensity of the tagged protein to oligomerize, which results in formation of large oligomers of fusion protein that are chelated by the affinity matrix. The solution to the problem is to use S-butylglutathione instead of glutathione to elute, as S-butylglutathione binds more tightly to glutathione S-transferase and overcomes the chelate effect. Moreover, in contrast to glutathione, S-butylglutathione has no reducing capability that might inactivate a tagged protein.


Calcitonin receptor gene and breast cancer: quantitative analysis with laser capture microdissection.
There is a growing body of evidence indicating that calcitonin (CT) and its receptor (CTR) is involved in cell growth, differentiation and tissue development. Using laser capture microdissection (LCM) and real-time reverse transcription polymerase chain reactions (RT-PCR), we have investigated CTR mRNA expression in 60 primary breast cancers, including 14 pairs of matched cancers and unaffected ductal epithelia from the same patients. Our results demonstrate that CTR mRNA was constantly expressed in normal ductal epithelium and in breast cancer. In the 14 cases where matched samples were available, a decrease in CTR mRNA expression was found in 9 breast cancers (64.3%), an increased CTR expression in 2 cases (14.3%) and no significant change in 3 cases (21.4%). In 60 cases of primary breast cancers, decreased CTR expression was found in 44 (73.3%), increased CTR expression was detected in 10 cases (16.7%) and no change was observed in 6 cases (10%). Decreased CTR expression was found more often in cases with lymph node metastasis (p = 0.0498) and lymphatic invasion (p = 0.0179). Also there was a decreased CTR expression in cases with an extensive intraductal component (p = 0.0543) and a high nuclear grade (p = 0.1934), although this was not statistically significant. Overall, we conclude that CTR mRNA was constantly expressed in unaffected ductal epithelium, whereas decreased CTR mRNA expression was frequently found in breast cancers, particularly in cases with lymph node metastasis and lymphatic invasion. These results suggest that CTR might be of great potential significance in breast cancer progression.


Consequences of fluid absorption during transurethral resection of the prostate using distilled water or glycine 1.5 per cent.
This prospective and randomized study compared the consequences of two irrigating fluids, distilled water and glycine for transurethral prostatectomy. Forty-nine consecutive unselected patients undergoing transurethral resection of the prostate with spinal anaesthesia were investigated. The irrigating fluid was either distilled water (group A, 24 patients) or glycine 1.5 per cent (group B, 25 patients). The absorption of irrigating fluid was measured, all surgical events and any clinical signs of TURP syndrome during and after surgery were recorded. Early signs of TURP syndrome were observed in one patient in group A and in four in group B without further consequence. From all the biological variables, only plasma protein concentration, haematocrit, free plasma haemoglobin and free bilirubin concentrations were found to have changed. Plasma protein concentration and haematocrit decreased significantly during and after surgery in the two groups. Free plasma haemoglobin increased significantly with time: a significantly higher concentration was observed in group A than group B. Free bilirubin concentration increased with time in the two groups and was statistically greater in group A. With the two irrigating fluids, we observed a significant amount of haemolysis and haemodilution without clinical consequences. A low irrigating fluid pressure, a short resection time, and the use of spinal anaesthesia seems to us to be essential. Close observation of patients following transurethral prostatectomy is needed but the choice of the irrigating fluid does not seem to be important.


PpsR, a regulator of heme and bacteriochlorophyll biosynthesis, is a heme-sensing protein.
Heme-mediated regulation, presented in many biological processes, is achieved in part with proteins containing heme regulatory motif. In this study, we demonstrate that FLAG-tagged PpsR isolated from Rhodobacter sphaeroides cells contains bound heme. In vitro heme binding studies with tagless apo-PpsR show that PpsR binds heme at a near one-to-one ratio with a micromolar binding constant. Mutational and spectral assays suggest that both the second Per-Arnt-Sim (PAS) and DNA binding domains of PpsR are involved in the heme binding. Furthermore, we show that heme changes the DNA binding patterns of PpsR and induces different responses of photosystem genes expression. Thus, PpsR functions as both a redox and heme sensor to coordinate the amount of heme, bacteriochlorophyll, and photosystem apoprotein synthesis thereby providing fine tune control to avoid excess free tetrapyrrole accumulation.


Evaluating the etiology of mechanical valve obstruction: use of clinical parameters, fluoroscopy, and echocardiography.
Prosthetic valve obstruction is a life-threatening complication most commonly caused by thrombus, pannus, or both. We report a St. Jude tricuspid valve obstruction, initially treated with thrombolytic therapy, found to be caused by pannus on pathologic examination. Clinical evaluation and diagnostic evaluation with fluoroscopy and echocardiography in distinguishing pannus from thrombus are reviewed.


Nuclear reactor pulse calibration using a CdZnTe electro-optic radiation detector.
A CdZnTe electro-optic radiation detector was used to calibrate nuclear reactor pulses. The standard configuration of the Pockels cell has collimated light passing through an optically transparent CdZnTe crystal located between crossed polarizers. The transmitted light was focused onto an IR sensitive photodiode. Calibrations of reactor pulses were performed using the CdZnTe Pockels cell by measuring the change in the photodiode current, repeated 10 times for each set of reactor pulses, set between 1.00 and 2.50 dollars in 0.50 increments of reactivity.


Functional defects of cancer-associated MDC1 mutations in DNA damage repair.
Mediator of DNA damage checkpoint protein 1 (MDC1) serves as a docking platform to promote the localization of various DNA damage response (DDR) components to DNA double-strand break (DSB) sites. MDC1 is vital in controlling proper DDR and maintaining genomic stability. In cancers, genomic instability results from mutations in DNA repair genes and drives cancer development. The mutations of MDC1 in human cancers have not been systematically examined and little is known about the molecular phenotypes caused by these genetic changes. Here, we summarized cancer-associated mutations of MDC1 including insertion/deletion mutations as well as missense mutations in key functional domains of MDC1 from ICGC, TCGA and COSMIC databases. We analyzed 711 somatic mutations of MDC1 across 26 types of human cancers and examined the functional defects of these cancer-associated mutations of MDC1 in the context of DNA damage repair. 6 truncation mutations and 7 missense mutations of MDC1 were chosen for further study. 6 truncation mutations which abolish MDC1-γH2AX interaction abrogate its biological functions in DNA damage repair. 2 missense mutations in FHA domain impaired ATM (ataxia telangiectasia mutated) phosphorylation. 5 missense mutations in BRCT domain also abolished its interaction with γH2AX, resulting in defects in foci formation of MDC1, 53BP1 and BRCA1 as well as defects in G2/M checkpoints. We further used structural modeling to analyze the potential molecular mechanism by which the 7 missense mutations cause the DNA damage repair defects. Taken together, our results reveal these cancer-associated MDC1 mutations can result in functional defects in DNA damage response and may serve as biomarkers for cancer diagnostics in future.


The ABC of Flower Development in Monocots: The Model of Rice Spikelet.
The initial seminal studies of flower developmental genetics were made from observations in several eudicot model species, particularly Arabidopsis and Antirrhinum. However, an increasing amount of research in monocot model and crop species is finally giving the credit that monocots deserve for their position in the evolutionary history of Angiosperms, their astonishing diversification and adaptation, their diversified floral structures, their pivotal function in most ecosystems on Earth and, finally, their importance in agriculture and farming, economy, landscaping and feeding mankind. Rice is a staple crop and the major monocot model to study the reproductive phase and flower evolution. Inspired by this, this chapter reviews a story of highly conserved functions related to the ABC model of flower development. Nevertheless, this model is complicated in rice by cases of gene neofunctionalization, like the recruitment of MADS-box genes for the development of the unique organs known as lemma and palea, subfunctionalization, and rewiring of conserved molecular pathways.


Hypotension in normotensive pregnant women treated with nifedipine as a tocolytic drug.
To determine hypotensive effect of nifedipine in the treatment of preterm labor. A descriptive analytic study was conducted on pregnant women treated with nifedipine as tocolytic drug for preterm labor. Maternal blood pressure before and at 15, 30, 45 and 60 min after administration of nifedipine was evaluated and analyzed. Hypotension was defined as a decrease in systolic or diastolic blood pressure of 15 mmHg or more. A total of 157 pregnant women met the inclusion criteria. The mean systolic and diastolic blood pressure before treatment was 109.4 and 72.5 mmHg, respectively. The blood pressure following treatment with nifedipine was significantly decreased both systolic and diastolic blood pressure (p < 0.05) at 30, 45 and 60 min. Of 157 patients, 28 (17.8%) and 27 (17.2%) had systolic and diastolic hypotension, respectively. Of the patients with decreased blood pressure, the mean decrease of systolic and diastolic blood pressure was 16.3 and 14.5 mmHg, respectively. Nifedipine was associated with a minimal but significant decrease in blood pressure. 17% of cases have hypotension. However, hypotension secondary to nifedipine was not associated with significant clinical symptoms, suggesting that nifedipine is relatively safe in terms of hypotensive effect.


Palliative care volunteer roles in Nordic countries: qualitative studies-systematic review and thematic synthesis.
Given limited palliative care resources, volunteers can be viewed as essential. To better understand the contribution of volunteers, it is useful to look at their roles in care systems with high level of financed public welfare, such as those found in Nordic countries. To develop research-based knowledge of experiences related to volunteer roles in palliative care in Nordic countries with similar welfare systems. Systematic review and thematic synthesis of qualitative studies. Cinahl, APA PsycInfo, SocINDEX, Idunn, Cristin, SwePub, SweMed+, Doria and Danish Research Database from 2005 to 2020. Qualitative peer-reviewed studies reporting first-hand experience of volunteers in palliative care in hospital, community (homecare and nursing home) and hospice settings (hospice institution and hospice home care); English abstract and available full text. Of 1521 citations, 11 articles were included in the review: seven Norwegian articles, three Swedish articles and one Danish article. Three overall themes emerged from analysis: (1) volunteers offered something different than professionals, (2) volunteering took place in professionals' domain, (3) volunteers were motivated by personal gains. Volunteers provide valuable support to patients and next of kin that differs from professionals' support. Volunteers are motivated by direct interaction with patients and next of kin. Opportunities for interactions depend on the healthcare setting and professionals' understandings of volunteers' role. Formal training of volunteers is limited and supportive available professionals important to volunteers. Professionals' understandings of volunteers' role should be improved to strengthen volunteers' role in palliative care in Nordic countries. CRD42020222695.


Impact of Size Thresholds on the Diagnosis of Incidental Adrenal Lesions: A Systematic Review and Meta-Analysis.
Preferred size-threshold recommendations for management of incidental adrenal lesions remain controversial. This meta-analysis aimed to compare the diagnostic accuracy of different size thresholds for detecting malignancy in patients with incidental adrenal lesions on imaging. A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature, covering the period from inception to September 2021, was performed. Studies with >10 patients evaluating the diagnostic accuracy of imaging size thresholds for detecting malignancy in patients with incidental adrenal lesions and no prior history of cancer were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. From 2,690 citations, 40 studies (9,794 patients with mean age ranging from 41 to 66 years) were included. Most (36 of 40) were retrospective single-center studies. CT+/- MRI served as the index test(s). Sensitivity and specificity values, respectively, by size threshold used in the included studies were as follows: 85% (95% confidence interval [CI] 74%-91%) and 39% (95% CI 23%-57%) for 3-cm thresholds; 85% (95% CI 78%-90%) and 75% (95% CI 62%-85%) for 4-cm thresholds; 70% (95% CI 56%-81%) and 74% (95% CI 59%-85%) for 5-cm thresholds; and 75% (95% CI 67%-82%) and 77% (95% CI 62%-87%) for 6-cm thresholds. No cause for variability in sensitivity or specificity was identified on subgroup analysis of the 4-cm threshold. Nearly half of the studies (19 of 40) had at least one QUADAS-2 domain with a high risk of bias. A 4-cm size threshold demonstrates the highest combined sensitivity and specificity, with a preserved specificity compared to higher size thresholds, but with a trend toward improved sensitivity. Future research reevaluating 4-5 cm size thresholds while excluding characteristically benign lesions by imaging may help redefine a size threshold that has improved specificity but preserved sensitivity, compared to the existing 4-cm threshold.


Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.
The comparative impact of histologic variants and grade has not been well described. Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.


Laparoscopic gastric banding in the rat model as a means of videolaparoscopic training.
The development of laparoscopy in bariatric surgery has attracted a large number of surgeons. Learning this method for future clinical practice requires intensive training with inert tissues, simulators and experimental surgery in animals. Performing these procedures in small animals, with the same equipment used in humans, is feasible, allowing familiarization with and comprehension of the basic techniques. Wistar rats weighing 300-600 g were used. The animals were kept in standard laboratory conditions. A laparoscopic video-system, Veress needle, three ports, a 0 degree optic, a laparoscopic needle-holder, two 5-mm graspers, a 5-mm dissection clamp and a 5-mm scissors were used. An orogastric catheter with three 4-0 nylon sutures and one 6-0 nylon suture were also utilized. For the gastric band, we used a plastic device similar to the human gastric band. The present study describes a simple, inexpensive and reproducible technique for laparoscopic gastric banding in a rat model utilizing the same instruments developed for humans. The experimental rat model is more motivating than simulators, requires less space, and has easier maintenance compared with bigger animals, and consequently allows the use of more animals for teaching, training and application in many scientific studies.


A taxonomic study on the species of the genus Furcilarnaca (Orthoptera, Gryllacrididae, Gryllacridinae).
A taxonomic study of the genus Furcilarnaca Gorochov, 2004 is presented. Four new species are described: F. affinis sp. nov., F. hirta sp. nov., F. fractiflexa sp. nov., F. brachyptera sp. nov.. Two new combinations F. fallax (Liu et al., 2010) comb. nov. and F. pulex (Karny, 1928) comb. nov. are given. A key to the species and the distributional data of Furcilarnaca are provided.


ARSH 10: Adolescent immunization revisited.
The emerging epidemiological shift in the incidence of vaccine preventable diseases like diphtheria, whooping cough and measles and the recent introduction of the attenuated combination vaccines (Tdap) and human papillomavirus (HPV) vaccine have necessitated the introduction of new vaccination schedules for the adolescents. On the back of this success in the west, it is timely to consider these schedules for the Indian scenario. The details of these vaccines as suggested by IAP COI and its programatic difficulties are discussed. The importance of providing evidence based, accurate information regarding adolescent immunization is emphasized.


Eosinophils in Helminth Infection: Defenders and Dupes.
Eosinophilia is a central feature of the host response to helminth infection. Larval stages of parasitic worms are killed in vitro by eosinophils in the presence of specific antibodies or complement. These findings established host defense as the paradigm for eosinophil function. Recently, studies in eosinophil-ablated mouse strains have revealed an expanded repertoire of immunoregulatory functions for this cell. Other reports document crucial roles for eosinophils in tissue homeostasis and metabolism, processes that are central to the establishment and maintenance of parasitic worms in their hosts. In this review, we summarize current understanding of the significance of eosinophils at the host-parasite interface, highlighting their distinct functions during primary and secondary exposure.


Relationship between (123)I-MIBG scintigrams and REM sleep behavior disorder in Parkinson's disease.
Uptake of (123)I-labeled meta-iodobenzylguanidine (MIBG) in myocardial scintigrams has been shown to be as low in patients with idiopathic RBD as in Parkinson's disease (PD) patients. AIM FOR STUDY: To clarify whether the existence of RBD accelerates autonomic dysfunction in PD, we investigated the association between MIBG scintigraphic findings and RBD measures among non-dementia PD patients. We conducted clinical interviews to assess REM sleep behavior disorder (RBD) symptoms, and performed polysomnograms (PSG) recordings and MIBG scintigrams on 49 PD patients. The patients were divided into three groups (PD with clinical RBD, PD with subclinical RBD, and PD with normal REM sleep). PD patients with clinical RBD had reduced MIBG uptake as determined by heart-to-mediastinum ratios of the delayed image compared to those with subclinical RBD and those with normal REM sleep. Multiple linear regression analysis revealed that only the existence of RBD symptoms was significantly associated with reduced MIBG uptake among PD patients without dementia after adjusting for demographic and PD symptom-related variables. PD patients with clinical RBD might suffer from a wider α-synuclein pathology, including reduced cardiac sympathetic ganglia function as reflected by a lowered MIBG uptake.


[Compressive optic neuropathy secondary to a pituitary macroadenoma].
Pituitary adenoma is a common benign tumor representing 8 to 10% of intracranial mass lesions. The compressive optic neuropathy associated with a pituitary adenoma can be clinically indistinguishable from glaucomatous optic neuropathy. A 56-year-old man with no significant past medical history had noticed a rapid decrease in visual acuity for 6 months. Funduscopic examination revealed glaucoma-like bilateral, asymmetric optic cupping. Brain MRI examination revealed a pituitary tumor compressing the optic chiasm. The diagnosis of a compressive optic neuropathy associated with a pituitary adenoma can be difficult, since it often simulates chronic glaucoma. However, several features should alert the clinician to the possibility of a compressive optic neuropathy and prompt neuroimaging, in order to obtain earlier diagnosis and treatment.


Selective attention in Alzheimer's disease: characterizing cognitive subgroups of patients.
Picture recognition was studied in 20 patients with AD and in 20 control subjects, using a procedure that matched these groups for initial performance. The groups did not differ significantly in overall forgetting, although 10 patients displayed improved recognition performance 72 hr after learning. These same patients were impaired in a test of attentional focusing, as revealed by post hoc analyses. A predictive experiment involving 20 new patients with AD confirmed the initial findings: a subgroup of patients displayed improved recognition performance 72 hr after learning and impairments in attentional focusing. Neuropsychological tests thus identify a subgroup of patients with impaired selective attention, perhaps related to locus coeruleus neuropathology.


Long term behavioral effects of functional dopaminergic neurons generated from human neural stem cells in the rat 6-OH-DA Parkinson's disease model. Effects of the forced expression of BCL-X(L).
Parkinson's disease (PD) motor symptoms are caused by the progressive degeneration of ventral mesencephalic (VM) dopaminergic neurons (DAn) in the Substantia Nigra pars compacta (SNpc). Cell replacement therapy for PD is based on the concept that the implantation of DAn in the striatum can functionally restore the dopamine levels lost in the disease. In the current study we have used an immortalized human VM neural stem cell line (hVM1) that generates DAn with the A9 phenotype. We have previously found that the forced expression of Bcl-X(L) in these cells enhances DAn generation and improves, short-term, d-amphetamine-induced rotation after transplantation in the 6-OH-DA rat model of PD 2-month post-grafting. Since functional maturation of human A9 DAn in vivo requires long survival times, in the present study we investigated the behavioral amelioration induced by the transplantation of these precursors (naïve and Bcl-X(L)-modified) in the striatum of Parkinsonian rats for up to 5 months. The main findings observed are an improvement on drug-induced behaviour and importantly, in spontaneous behavior tests for both cell-transplanted groups. Finally, we have also tested whether the grafts could ameliorate cognitive performance in PD, in addition to motor deficits. Significant difference was observed for T-maze alternation test in the cell-transplanted animals as compared to sham operated ones. To our knowledge, this is the first report showing an amelioration in spontaneous motor behavior and in cognitive performance in Parkinsonian animals after receiving human VM neural stem cell grafts. Histological studies confirmed that the grafts generated mature dopaminergic cells.


Piloting cognitive-behavioral therapy for insomnia integrated with prolonged exposure.
Approximately 35-61% of individuals with posttraumatic stress disorder (PTSD) report insomnia. Further, upward of 70% report clinically significant insomnia following PTSD treatment. There are converging lines of evidence suggesting that insomnia not only independently affects daytime functioning and worsens PTSD symptoms but also may compromise response to PTSD treatment, such as prolonged exposure (PE). Taken together, integrated insomnia and PTSD treatment may increase client-centered care and treatment outcomes. This article reviews the theory and evidence for treating sleep prior to PTSD treatment, describes the key elements of integrated cognitive-behavioral treatment for insomnia (CBT-I) and PE (2NITE protocol), and presents pilot data from a sample of 12 treatment-seeking veterans with PTSD and insomnia who completed the 2NITE protocol. Sleep data were collected with sleep diaries and actigraphy watches. The Client Satisfaction Questionnaire indicated high satisfaction with the 2NITE protocol (mean score 29.66 out of 32 points). On average, there were statistical and clinically significant changes in all measures, including a 20.17-point decrease in the PTSD Checklist DSM-5, a 11.75-point decrease in the insomnia severity index, an 18.58-point increase in the World Health Organization Quality of Life index, a 11% increase in sleep efficiency, and a 51-min increase in total sleep time from the actigraphy data. Among individuals with insomnia and PTSD, integrating CBT-I and PE with the 2NITE protocol represents a logical, innovative, and empirically informed method for augmenting existing treatments and optimizing outcomes that justifies further investigation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Targeted deletion of growth hormone (GH) receptor in macrophage reveals novel osteopontin-mediated effects of GH on glucose homeostasis and insulin sensitivity in diet-induced obesity.
We investigated GH action on macrophage (MΦ) by creating a MΦ-specific GH receptor-null mouse model (MacGHR KO). On a normal diet (10% fat), MacGHR KO and littermate controls exhibited similar growth profiles and glucose excursions on intraperitoneal glucose (ipGTT) and insulin tolerance (ITT) tests. However, when challenged with high fat diet (HFD, 45% fat) for 18 weeks, MacGHR KO mice exhibited impaired ipGTT and ITT compared with controls. In MacGHR KO, adipose-tissue (AT) MΦ abundance was increased with skewing toward M1 polarization. Expression of pro-inflammatory cytokines (IL1β, TNF-α, IL6, and osteopontin (OPN)) were increased in MacGHR KO AT stromal vascular fraction (SVF). In MacGHR KO AT, crown-like-structures were increased with decreased insulin-dependent Akt phosphorylation. The abundance of phosphorylated NF-κB and of OPN was increased in SVF and bone-marrow-derived MΦ in MacGHR KO. GH, acting via an NF-κB site in the distal OPN promoter, inhibited the OPN promoter. Thus in diet-induced obesity (DIO), lack of GH action on the MΦ exerts an unexpected deleterious effect on glucose homeostasis by accentuating AT inflammation and NF-κB-dependent activation of OPN expression. These novel results in mice support the possibility that administration of GH could have salutary effects on DIO-associated chronic inflammation and insulin resistance in humans.


Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial.
Insomnia is a common complaint that is closely related to gastrointestinal symptoms, which is consistent with the traditional Chinese medicine classical theory of "stomach disharmony leading to restless sleep." Acupuncture is an effective complementary and alternative medicine therapy to improve gastrointestinal function and restore the normal sleep-wake cycle. However, studies on the effectiveness of acupuncture for insomnia due to spleen-stomach disharmony syndrome are limited to case reports and few randomized controlled trials; deeper research on its mechanism is still lacking. This randomized controlled trial aims to assess the treatment efficacy of "harmonizing stomach to tranquilize mind" acupuncture for insomnia and its influence on the intestinal microbiome. This is a randomized, single-blind, parallel-group study. Sixty eligible patients with insomnia due to spleen-stomach disharmony syndrome will be randomly divided into two groups (1:1 allocation ratio). The intervention group will use "harmonizing stomach to tranquilize mind" acupuncture, and the control group will receive sham acupuncture. Participants will receive 5 acupuncture treatment sessions per week for 4 consecutive weeks. The Pittsburgh Sleep Quality Index will be used to evaluate the clinical efficacy of acupuncture treatment by making assessments at baseline, the end of treatment and the end of the follow-up. High-throughput 16S ribosomal ribonucleic acid gene sequencing will be performed to detect changes in the intestinal microbial composition before and after treatment. The results of this trial are expected to confirm that "harmonizing stomach to tranquilize mind" acupuncture can effectively relieve insomnia and alter the intestinal microbiome. Chinese Clinical Trials Registry: ChiCTR1800017092.


Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study.
On Sept 1, 2008, Scotland launched routine vaccination for human papillomavirus (HPV) types 16 and 18, targeted at 12-13-year-old girls, of whom 92·4% were fully vaccinated in 2008-09. In this study, we report on vaccine effectiveness of the bivalent vaccine in these vaccinated women who attended for routine cervical screening at age 20-21 years. In this 7-year cross-sectional study (covering birth cohorts 1988-1995), we sampled approximately 1000 samples per year from those attending cervical screening at age 20-21 years and tested each for HPV. By linkage to vaccination records we ascertained prevalence by birth cohort and vaccination status. Estimates of vaccine effectiveness for HPV types 16 and 18, HPV types 31, 33, and 45, other high-risk types, and any HPV were calculated using logistic regression. In total, 8584 samples were HPV genotyped. Prevalence of HPV types 16 and 18 reduced substantially from 30·0% (95% CI 26·9-33·1) in the 1988 cohort to 4·5% (3·5-5·7) in the 1995 cohort, giving a vaccine effectiveness of 89·1% (85·1-92·3) for those vaccinated at age 12-13 years. All cross-protective types showed significant vaccine effectiveness (HPV type 31, 93·8% [95% CI 83·8-98·5]; HPV type 33, 79·1% [64·2-89·0]; HPV type 45, 82·6% [61·5-93·9]). Unvaccinated individuals born in 1995 had a reduced odds of HPV types 16 and 18 infection compared with those born in 1988 (adjusted odds ratio 0·13 [95% CI 0·06-0·28]) and reduced odds of HPV types 31, 33, and 45 (odds ratio 0·45 [0·23-0·89]). Bivalent vaccination has led to a startling reduction in vaccine and cross-protective HPV types 7 years after vaccination. There is also evidence of herd protection against the vaccine-specific and cross-protective types in unvaccinated individuals born in 1995. These findings should be considered in cost-effectiveness models informing vaccine choice and models to shape the future of cervical screening programmes. Scottish Government and Chief Scientists Office.


Cystic fibrosis in young children: A review of disease manifestation, progression, and response to early treatment.
Studies have described illness associated with cystic fibrosis (CF) early in life, but there is no comprehensive accounting of the prevalence and ages of disease manifestation and progression described in individual studies. We searched for peer-reviewed English-language studies of the health of children ≤6years old with CF (published 1990-2014). Structural abnormalities and dysfunction of the digestive and respiratory systems were summarized across relevant studies by system and age group. Primary studies (125 total) from 22 countries described abnormalities, dysfunction, and disease progression in infancy and early childhood. Improved health was consistently observed in association with diagnosis via newborn screening compared with cohorts diagnosed later by symptomatic presentation. The peer-reviewed literature is remarkably consistent: CF-associated growth impairment and airway abnormalities are reported at birth, and disease progression is reported in infancy and throughout childhood. Earlier access to routine CF management is associated with improved subsequent health status.


Aberrant metabolite trafficking and fuel sensitivity in human pluripotent stem cell-derived islets.
Pancreatic islets regulate blood glucose homeostasis through the controlled release of insulin; however, current metabolic models of glucose-sensitive insulin secretion are incomplete. A comprehensive understanding of islet metabolism is integral to studies of endocrine cell development as well as diabetic islet dysfunction. Human pluripotent stem cell-derived islets (SC-islets) are a developmentally relevant model of human islet function that have great potential in providing a cure for type 1 diabetes. Using multiple 13C-labeled metabolic fuels, we demonstrate that SC-islets show numerous divergent patterns of metabolite trafficking in proposed insulin release pathways compared with primary human islets but are still reliant on mitochondrial aerobic metabolism to derive function. Furthermore, reductive tricarboxylic acid cycle activity and glycolytic metabolite cycling occur in SC-islets, suggesting that non-canonical coupling factors are also present. In aggregate, we show that many facets of SC-islet metabolism overlap with those of primary islets, albeit with a retained immature signature.


Updating the Y-chromosomal phylogenetic tree for forensic applications based on whole genome SNPs.
The Y-chromosomal phylogenetic tree has a wide variety of important forensic applications and therefore it needs to be state-of-the-art. Nevertheless, since the last 'official' published tree many publications reported additional Y-chromosomal lineages and other phylogenetic topologies. Therefore, it is difficult for forensic scientists to interpret those reports and use an up-to-date tree and corresponding nomenclature in their daily work. Whole genome sequencing (WGS) data is useful to verify and optimise the current phylogenetic tree for haploid markers. The AMY-tree software is the first open access program which analyses WGS data for Y-chromosomal phylogenetic applications. Here, all published information is collected in a phylogenetic tree and the correctness of this tree is checked based on the first large analysis of 747 WGS samples with AMY-tree. The obtained result is one phylogenetic tree with all peer-reviewed reported Y-SNPs without the observed recurrent and ambiguous mutations. Nevertheless, the results showed that currently only the genomes of a limited set of Y-chromosomal (sub-)haplogroups is available and that many newly reported Y-SNPs based on WGS projects are false positives, even with high sequencing coverage methods. This study demonstrates the usefulness of AMY-tree in the process of checking the quality of the present Y-chromosomal tree and it accentuates the difficulties to enlarge this tree based on only WGS methods.


Kluyvera cryocrescens finger infection: case report and review of eighteen Kluyvera infections in human beings.
We report a case of soft tissue infection with Kluyvera cryocrescens and a critical review of Kluyvera infections. A 31-year-old diabetic man used a new chemical for stripping the floor with his bare hands. Two days later he developed a blister on a finger which progressed to tenosynovitis in spite of intravenous nafcillin therapy. After 11 days culture and sensitivity results dictated treatment with intravenous ticarcillin/clavulanic acid. The wound was debrided twice, and later a skin flap was done. Wound cultures became sterile after 7 days of treatment with ticarcillin/clavulanic acid, and he recovered. This case represents the fourth clinical infection with K. cryocrescens and the eighteenth of Kluyvera to be reported. Four others were K. ascorbata, and the remaining ten Kluyvera infections in humans were not identified beyond genus. Our case and review of the 17 previous cases emphasize that while Kluyvera rarely cause disease, these opportunistic Gram-negative bacilli may be virulent in a variety of sites under as yet poorly defined host conditions. Sites of infection varied, but the brain and meninges were not among them. Two patients had diabetes mellitus, none had AIDS, and four died. Once shown clinically to be the cause of an infection, Kluyvera deserve aggressive treatment which acknowledges their ampicillin resistance.


Maximizing the subtonsillar transcerebellomedullary approach to suprasellar cistern: how I do it.
The subtonsillar transcerebellomedullary approach (STA) has been well established as one of the surgical options to access lesions in the foramen of Luschka. The middle cerebellar peduncle has been defined as the superior limit of this corridor, and tumors extending beyond this landmark were often approached through combined accesses. We illustrate the access to the suprasellar cistern, from a purely STA for a large tumor arising from the foramen of Luschka. This manuscript demonstrates the STA as a valid alternative for certain tumors of the foramen of Luschka, which extend into crural and suprasellar cisterns.


[Isolated ventricular inversion associated with complete atrioventricular septal defect with total anomalous pulmonary venous drainage].
Based upon the description of the clinico-pathological characteristic of a case with isolated ventricular inversion plus other cardiac malformations, the clinical, diagnostic and embryo-pathological implications of this entity are reviewed.


Structural basis for plastic glycolipid recognition of the C-type lectin Mincle.
Mincle (macrophage-inducible C-type lectin, CLEC4E) is a C-type lectin immune-stimulatory receptor for cord factor, trehalose dimycolate (TDM), which serves as a potent component of adjuvants. The recognition of glycolipids by Mincle, especially their lipid parts, is poorly understood. Here, we performed nuclear magnetic resonance analysis, revealing that titration of trehalose harboring a linear short acyl chain showed a chemical shift perturbation of hydrophobic residues next to the Ca-binding site. Notably, there were split signals for Tyr201 upon complex formation, indicating two binding modes for the acyl chain. In addition, most Mincle residues close to the Ca-binding site showed no observable signals, suggesting their mobility on an ∼ ms scale even after complex formation. Mutagenesis study supported two putative lipid-binding modes for branched acyl-chain TDM binding. These results provide novel insights into the plastic-binding modes of Mincle toward a wide range of glycol- and glycerol-lipids, important for rational adjuvant development.


[Complications of laparoscopic procedures of inguinal hernias, diagnosed on colonoscopy].
The aim was to assess significance of colonoscopy in detection of inguinal hernias - dislocation of the mesh into the lumen of the large intestine, following inguinal hernia laparoscopic procedures (TAPP). From 01-01-2004 to 31-12-2006, the authors performed 3 colonoscopies in 3 subjects after TAPP inguinal hernia laparoscopic procedures. The subjects included 2 males and 1 female, 4 to 9 months after the laparoscopic procedure, colonoscopy was performed, which was indicated for the lower abdominal pain and enterorrhagia. However, no signs of a relapsing hernia were recorded. Endoscopy detected irritation and bleeding of the sigmoid, and a mesh, which passed through the intestinal wall was detec ted in the sigmoid lumen. The subjects were then reoperated and the mesh was removed. In one subject, resection of the sigmoid had to be performed as well. The subject recovered. The postoperative complications of the TAPP procedure included dislocation of the mesh into the intestinal lumen. Detection of the mesh dislocation into the lumen of the large intestine facilitates indication for surgical management.


Combined chemotherapy and pembrolizumab salvages multi-chemotherapy agent and avelumab resistant choriocarcinoma: A case report.
Gestational trophoblastic neoplasia (GTN) including choriocarcinoma (CC) frequently requires multi-agent chemotherapy to achieve cure. In chemotherapy-resistant GTN, immunotherapy with the checkpoint inhibitors pembrolizumab, avelumab and camrelizumab are potential new treatment options previously described in small case series, phase 2 trials and case reports. A 32-year-old woman was diagnosed with gestational choriocarcinoma (FIGO score 5). Prior administered therapy regimes included methotrexate, actinomycin-D followed by open hysterectomy with bilateral salpingectomy (histology without GTN) as well as multi-agent chemotherapy and avelumab single-agent. After detection of a suspicious pulmonary mass video- assisted thoracoscopic left lung segmentectomy was performed confirming CC. The patient experienced an intracerebral haemorrhage and was treated with an emergency decompressive craniotomy. The cerebrospinal fluid showed an increased ratio of hCG compared to serum. Therapy with combined escalated etoposide and cisplatin with pembrolizumab was commenced followed by maintenance pembrolizumab achieving a complete hCG response and negative PET CT. In the management of multi drug- resistant GTN, application of checkpoint inhibitor pembrolizumab is a new therapeutic strategy. In this heavily pre-treated patient incorporation of pembrolizumab resulted in complete long-term response in a patient who had also failed avelumab therapy.


Structural analysis of Centrolobium tomentosum seed lectin with inflammatory activity.
A glycosylated lectin (CTL) with specificity for mannose and glucose has been detected and purified from seeds of Centrolobium tomentosum, a legume plant from Dalbergieae tribe. It was isolated by mannose-sepharose affinity chromatography. The primary structure was determined by tandem mass spectrometry and consists of 245 amino acids, similar to other Dalbergieae lectins. CTL structures were solved from two crystal forms, a monoclinic and a tetragonal, diffracted at 2.25 and 1.9 Å, respectively. The carbohydrate recognition domain (CRD), metal-binding site and glycosylation site were characterized, and the structural basis for mannose/glucose-binding was elucidated. The lectin adopts the canonical dimeric organization of legume lectins. CTL showed acute inflammatory effect in paw edema model. The protein was subjected to ligand screening (dimannosides and trimannoside) by molecular docking, and interactions were compared with similar lectins possessing the same ligand specificity. This is the first crystal structure of mannose/glucose native seed lectin with proinflammatory activity isolated from the Centrolobium genus.


Construction and characterization of recombinant fowlpox virus coexpressing HIV-1(CN) gp120 and IL-2.
The acquired immunodeficiency syndrome (AIDS) has now become one of the most serious infectious disease in the world, the safe and effective AIDS vaccines would be the best tools to control the disease. Fowlpox virus has been studied recently as a potential vector for the delivery of heterologous vaccine antigen. In this study, a recombinant fowlpox virus coexpressing gp120 of Chinese prevalent HIV-1 strain and IL-2 was constructed and the cellular immune responses against HIV-1 gp120 in BALB/c mice were evaluated. Chinese vaccine strain 282E4 of fowlpox virus was used as the vector to construct the recombinant fowlpox virus (rFPV) coexpressing HIV-1 gp120 and IL-2 via homologous recombination, and the recombinant virus was identified by PCR and Western blotting. The specific DNA fragment was amplified by PCR from the genomes of rFPV. Western blotting analysis showed that HIV-1 gp120 and IL-2 was expressed not only in chicken embryo fibroblast (CEF) cells infected by rFPV, but also in mammalian cells infected by rFPV. After the recombinant fowlpox virus was inoculated into BALB/c mice, specific CTL activities in the immunized mice were detected in the spleen. The results demonstrated that rFPV had good immunogenicity and could induce BALB/c mice to produce specific cellular immunity. IL-2 played a role of immunoadjuvant and enhanced the cellular immune response. The study provides the basis for the preparation of a Chinese vaccine candidate against HIV-1.


A single bolus of high dose levothyroxine (L-T4) as a test in cases of suspected poor compliance to L-T4 therapy.
Though compliance (or adherence) problems, as well as inappropriate levothyroxine (L-T4) intake (e.g. with meal, other drugs or certain foods that can significantly affect absorption) are very common, the issue is often either not mentioned or even frankly denied by patients. We describe three cases of patients who presented with high TSH (ranging from about 30 to 200 mIU/l), with concomitantly either high, normal or low free thyroxine (FT4), despite treatment with high doses of L-T4. The above mentioned problems with adjustment of L-T4 dose persisted for several months or even years. Coeliac disease screen was negative in all cases. In all these patients administration of a single bolus of L-T4 (1000 μg) or two doses of 1000 μg of L-T4 within 48 h resulted in a quick increase in FT4 (thus confirming proper absorption) and in normalization of TSH within a week. No adverse effects of administration of these high doses of L-T4 were observed. Our data support the efficacy, as well as safety of administration of single bolus of high dose L-T4 as a test for possible compliance/adherence problems.


A preliminary investigation of the role of the transcription co-activators YAP/TAZ of the Hippo signalling pathway in canine and feline mammary tumours.
Breast cancer is the most common cancer in women worldwide. Cancer metastases are responsible for the high mortality rate. A small but distinct subset of cells, cancer stem cells (CSCs), have the capacity to self-renew, initiate tumour formation, and develop metastases. The CSC content in human breast cancer correlates with the Hippo tumour suppressor signalling pathway. Specifically, the activity of YAP/TAZ, transcription co-activators of the Hippo pathway, sustains the self-renewal and tumour-initiation capacities of CSCs. Little is known about YAP/TAZ in canine and feline mammary tumours, which are very common tumours. The preliminary aim of the study was to investigate the expression of YAP/TAZ in canine and feline mammary tumours by Western blot and immunohistochemistry. Increased cytoplasmic and nuclear expression of YAP/TAZ was observed in all carcinomas compared to normal tissues, indicating neoplastic deregulation of the Hippo pathway. Nuclear expression significantly increased in grade III (high grade carcinomas) compared to grade I (low grade carcinomas) tumours, suggesting that YAP/TAZ play a role in the increased aggressiveness of these tumours. Moreover, different scoring systems for immunohistochemical analyses were compared and the H index and the Allred scores were the most significant. In conclusion, YAP/TAZ are expressed in aggressive canine and feline mammary tumours as reported in some human cancers. Further studies might better elucidate the role of the Hippo pathway in prognosis and as a target for new therapies. In addition, tumours in dogs and cats may be a useful model to study this pathway.


A novel tumor-specific human single-chain Fv selected from an active specific immunotherapy phage display library.
A colon tumor-associated antigen, CTAA 28A32-32K (CTA # 2E), related to the annexin family of proteins, was initially identified by its reactivity with a low affinity human IgM monoclonal antibody (mAb), 28A32. Both in vitro lymphoproliferative assays with human peripheral blood lymphocytes and delayed type hypersensitivity responses in patients immunized with autologous colon tumor cells indicated that CTA # 2E elicits potent T cell mediated responses and may be an important antigen in the development of a generic colorectal vaccine (Pomato et al. Vaccine Res 1994;3:145-161). A CTA # 2E-specific, murine hybridoma-derived mAb, 5-11A, which recognizes the amino-terminus of the tumor-associated antigen, exhibited qualitative human colon tumor-specific immunohistochemical reactivity. To rapidly develop a human mAb with similar antigen specificity and tumor reactivity as the murine 5-11A mAb, antibody phage display technology was employed. Two human antibody phage display libraries with 3.1 x 10(7) and 2.3 x 10(8) members were prepared from the variable region genes expressed by circulating B cells of patients undergoing active specific immunotherapy (ASI) with autologous tumor cells, predominantly from the colon, admixed with Bacille Calmette-Guerin (BCG). A CTA # 2E-reactive human single-chain (sc)Fv was selected by panning the larger library on decreasing concentrations of biotinylated tumor-associated antigen in solution. It exhibited similar antigen specificity as the murine hybridoma-derived 5-11A scFv, requiring the presence of the CTA # 2E amino-terminus for reactivity. This human scFv exhibited qualitative human colon tumor-specific immunohistochemical reactivity when displayed as a gene III fusion protein on phage. When reconstructed and expressed as an intact human IgG1, K mAb, its qualitative colon tumor-specificity was unaltered. Two other CTA # 2E-reactive human scFvs were selected from the smaller library by panning initially on decreasing concentrations of CTA # 2E coated to polystyrene and then on biotinylated CTA # 2E in solution. These human scFvs, which exhibited modest reactivity with different epitopes on the CTA # 2E antigen, did not exhibit human colon tumor-specific immunohistochemical reactivity.


Stromal infiltration as a predictor of tumor invasion in breast fine-needle aspiration biopsy.
Clinical management of in situ carcinoma of the breast is different from invasive carcinomas. Thus, it is important to find cytomorphologic criteria to distinguish between these two entities. The current study is designed to assess whether, by applying strict cytologic criteria, the status of stromal invasion can be predicted. In this retrospective study, 223 consecutive nonpalpable tumors sampled by ultrasound-guided breast fine-needle aspirates with diagnosis of in situ and invasive carcinoma with histologic follow-up evaluation were retrieved. Ten cytologic parameters were evaluated, which included cellular clustering, eosinophilic differentiation, necrosis, tubular structures, dirty background, nuclear anisonucleosis, cellular pleomorphism, cribriform pattern, tubular structures, and stromal infiltration. Among all the parameters examined, stromal infiltration was the most powerful predictor of status of invasion. Stromal infiltration was significantly higher in invasive (88%) than in situ (11%), P < 0.0001. In contrast, cribriform pattern (16% vs 36%) and necrosis (19% vs 59%) were more frequently seen in situ than in invasive carcinomas with P-values of 0.0008 and <0.0001, respectively. This study demonstrates that stromal infiltration defined by strict criteria may predict the status of tumor invasion in breast fine-needle aspirates. The combination of stromal infiltration and cribriform pattern and necrosis in aspirates may provide an opportunity in introducing a "predictive index" to differentiate between an in situ versus an invasive process.