Identification of an enolase gene and its physiological role in Spirometra mansoni.
Enolase is a crucial enzyme involved in the glycolytic pathway and gluconeogenesis in parasites. It also has been reported to function as a plasminogen receptor and may be involved in tissue invasion. In this study, the biochemical properties of the enolase of Spirometra mansoni (Smenolase) were investigated. The Smenolase gene was found to cluster closely with the enolase genes of Clonorchis sinensis and Echinococcus granulosus, and some functional motifs were identified as conserved. Smenolase was confirmed to be a component of the secretory/excretory products (ESPs) and a circulating antigen of spargana. Recombinant Smenolase expressed in vitro was able to bind to human plasminogen. Smenolase was detected in the eggs, testicles, and vitellaria of adult worms and the tegument of spargana. The transcription level of Smenolase was highest at the gravid proglottid stage. When spargana were cultured with glucose of different concentration in vitro, it was observed that the expression levels of Smenolase in the low-glucose groups were consistent with that of Smenolase in vivo. These results indicate that Smenolase is a critical enzyme involved in supplying energy to support the development and reproduction of the parasite, and it may also play a role in sparganum invasion.


Psychological assessment of torture survivors: essential steps, avoidable errors, and helpful resources.
This article provides ideas, information, and resources that may be helpful in conducting psychological evaluations of people who have been tortured. The first section discusses essential steps, including achieving competence; clarifying the purpose; selecting methods appropriate to the individual, the purpose, and the situation; addressing issues of culture and language; maintaining awareness of ways in which the presence of third parties and recording can affect the assessment; attending carefully to similarities, echoes, and triggers; and actively searching for ways to transcend our own limited experiences and misleading expectations. The second section discusses avoiding five common errors that undermine these evaluations: mismatched validity; confirmation bias; confusing retrospective and prospective accuracy (switching conditional probabilities); ignoring the effects of low base rates; and misinterpreting dual high base rates. The third section identifies resources on the web (e.g., major centers, legal services, online courses, information about asylum and refuge, networks of torture survivors, human rights organizations providing information and services, guides to assessment) that people working with torture survivors, refugees, and asylum-seekers may find helpful.


Transitive Versus Intransitive Complex Gesture Representation: A Comparison Between Execution, Observation and Imagination by fNIRS.
The aim of the present study was to examine cortical correlates of motor execution, motor observation and motor imagery of hand complex gestures, in particular by comparing meaningful gestures implying the use of an object (transitive action) or not (intransitive action). Functional near-infrared spectroscopy (fNIRS) was used to verify the presence of partial overlapping between some cortical areas involved in those different tasks. Participants were instructed to observe videos of transitive vs. intransitive gestures and then to execute or imagine them. Gesture execution was associated to greater brain activity (increased oxygenated hemoglobin levels) with respect to observation and imagination in motor areas (premotor cortex, PMC; primary sensorimotor cortex, SM1). In contrast, the posterior parietal cortex (PPC) was more relevantly involved in both execution and observation tasks compared to gesture imagination. Moreover, execution and observation of transitive gestures seemed primarily supported by similar parietal posterior areas when compared with intransitive gestures, which do not imply the presence on a object.


Interaction of a synthetic peptide based on the neutrophil-derived antimicrobial protein CAP37 with dipalmitoyl-phosphatidylcholine membranes.
CAP37, a cationic antimicrobial protein of Mr 37 kDa is constitutively expressed in human neutrophils. A synthetic peptide, CAP37 P20-44, corresponding to amino acid residues 20 through 44 of the native CAP37 molecule has been shown to mimic the antimicrobial activity of the native protein. An analog of peptide CAP37 P20-44 was synthesized in which the cysteine residues at positions 26 and 42 were replaced with serine residues (CAP37 P20-44Ser). This resulted in a peptide that no longer exhibited bactericidal activity. The effect of different concentrations of the active CAP37 peptide, CAP37 P20-44, and its inactive analog, CAP37 P20-44Ser, on artificial lipid membranes composed of dipalmitoyl phosphatidylcholine (DPPC) was studied using small-angle X-ray scattering and differential scanning calorimetry. The results indicated that CAP37 P20-44 perturbs the periodicity of the lamellar structure as shown by small angle X-ray diffraction, while the effect of the inactive peptide is not as strong. Differential scanning calorimetry further confirms that CAP37 P20-44 interacts with lipid membranes as indicated by increased width of the transition and decreased peak height. Moreover, it completely abolishes the pretransition temperature of the DPPC membranes. The effect of the inactive peptide, CAP37 P20-44Ser on the thermotropic properties of DPPC was small. These studies suggest that CAP37 perturbs the lamellar structure of lipid bilayers and further suggests that the antibiotic action of the molecule may be through its interactions with the lipid components of the Gram negative bacterial membrane.


Imaging update on musculoskeletal infections.
The clinical diagnosis of musculoskeletal infections can be challenging due to non-specific signs and symptoms on presentation. These infections include infectious myositis, necrotising fasciitis, septic arthritis, septic bursitis, suppurative tenosynovitis, osteomyelitis, spondylodiscitis and periprosthetic infections. Diagnostic imaging is routinely employed as part of the investigative pathway to characterise the underlying infectious disease pattern, allowing expedited and customised patient management plans to optimise outcomes. This article provides an update on the various imaging modalities comprising of radiography, computed tomography, ultrasonography, magnetic resonance imaging and radionuclide procedures, and incorporates representative images of key findings in the different forms of musculoskeletal infections.


Gerontological nursing leadership in the Advancing Excellence Campaign: moving interdisciplinary collaboration forward.
Nursing was not a part of the coalition of multiple nursing home stakeholders at the roll out of the Advancing Excellence Campaign (AEC). In January 2007, several nurse organizations proactively approached the AEC leadership, were welcomed and immediately began to volunteer for leadership positions such as committee chairs and conference coordinators. This paper presents an exemplar of how a proactive stance, even when not initially included, allowed nurses to secure chairs at the decision making table of this quality campaign and contribute to improved resident outcomes.


[Connections between the nucleus lateralis dorsalis of the thalamus and the limbic system in man. Study of 12 anatomo-clinical cases of vascular origin].
Lateralis dorsalis nucleus of thalamus belong to the limbic system of Papez more by its trigonal than cingular afferent pathways. Its parietal efferent pathways are probable, its cingular and trigonal ones possible but not proved. Neuropathologic studies provide informations to separate a latero-ventral part connected with parietal cortex and a mediodorsal part connected with limbic system.


RA175, which is the mouse ortholog of TSLC1, a tumor suppressor gene in human lung cancer, is a cell adhesion molecule.
RA175, a new immunoglobulin superfamily member, is preferentially expressed during differentiation of P19 embryonic carcinoma (EC) cells induced by retinoic acid. In the present study, we isolated mouse RA175 cDNA in its entirety and showed that RA175 is the mouse ortholog of TSLC1, a tumor suppressor gene in human lung cancer. RA175/TSLC1 was localized in the adherent region of human lung squamous carcinoma cells and in the differentiated P19 EC cells. RA175/TSLC1 showed homophilic trans-interaction activity in a Ca(2+)-independent manner. RA175/TSLC1 was preferentially expressed in the polarized cells lining the lumen of developing mouse lung epithelium. This suggests that RA175/TSLC1 is a cell adhesion molecule that is acting as a tumor suppressor gene in the metastasis of lung tumors. RA175/TSLC1 may be necessary for cells to remain tightly associated in the epithelium, thereby suppressing metastasis.


High-level itaconic acid (IA) production using engineered Escherichia coli Lemo21(DE3) toward sustainable biorefinery.
Itaconic acid (IA) serves as a prominent building block for polyamides as sustainable material. In vivo IA production is facing the competing side reactions, byproducts accumulation, and long cultivation time. Therefore, the utilization of whole-cell biocatalysts to carry out production from citrate is an alternative approach to sidestep the current limitations. In this study, in vitro reaction of IA was obtained 72.44 g/L by using engineered E. coli Lemo21(DE3) harboring the aconitase (Acn, EC 184.108.40.206) and cis-aconitate decarboxylase (CadA, EC 188.8.131.52) which was cultured in glycerol-based minimal medium. IA productivity enhancement was observed after cold-treating the biocatalysts in - 80 °C for 24 h prior to the reaction, reaching 81.6 g/L. On the other hand, a new seeding strategy in Terrific Broth (TB) as a nutritionally rich medium was employed to maintain the biocatalysts stability up to 30 days. Finally, the highest IA titer of 98.17 g/L was attained using L21::7G chassis, that has a pLemo plasmid and integration of GroELS to the chromosome. The high-level of IA production along with the biocatalyst reutilization enables the economic viability toward a sustainable biorefinery.


Donkey-derived anti-CDV IgG, as a passive immunotherapy agent, can effectively increase survival rates of the experimental CDV-infected dogs.
Humoral immunity plays an important role in the prevention of canine distemper. Anti-CD virus (CDV) antibody has strong antiviral activity and is widely used in the treatment of CD. However, with the increase of CD cases, the availability of therapeutic CD antibody fell short of the clinical needs. The high-titer antiserum with the high-titer neutralizing activity against CDV was obtained from the donkeys (Dezhou Donkey) immunized with the inactivated CDV vaccine. The donkey anti-CDV IgG was purified from the donkey serum, which was identified to significantly inhibit the CDV replication in the cultured Vero cells and effectively reduce the clinical symptoms and increase the survival rates (75%) of CDV-infected dogs (Shih-tzu Dog), similar to that treated with the dog-derived anti-CDV IgG. These results indicate that donkey-derived IgG is a potential substitute for dog-derived IgG to treat the CD in clinic. Administration of donkey-derived anti-CDV IgG can ameliorate clinical symptoms and inhibit virus replication, thereby increasing the survival of CDV-infected dogs. This study opens up a new source of therapeutic antibody for CD treatment.


High-level nitrogen removal by simultaneous partial nitritation, anammox and nitrite/nitrate-dependent anaerobic methane oxidation.
While the anaerobic ammonium oxidation (anammox) process has been applied for nitrogen removal from high-strength wastewater, nitrate accumulation in effluent still represents a major concern. Here, a novel process, named the one-stage PNAM, that integrates the Partial Nitritation (PN), Anammox and Methane-dependent nitrite/nitrate reduction reactions in a single membrane biofilm reactor (MBfR) is developed. With feeding of 1030 mg NH4+-N/L at a hydraulic retention time of 16 h, the proposed one-stage PNAM process achieved an average total nitrogen removal efficiency of 98% and a nitrogen removal rate of 1.5 kg N/m3/d (1.4-1.8 g N/m2/d) by using methane as the sole carbon-based electron donor. The N2O emission was determined to be 0.34% ± 0.01%. Microbial community characterization revealed that ammonia-oxidizing bacteria (AOB), anammox bacteria, nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) bacteria and archaea co-developed in the biofilm. Batch tests showed that AOB, anammox bacteria and n-DAMO microorganisms were indeed jointly responsible for the nitrogen removal. This one-stage PNAM process can potentially be applied to treating high-strength wastewater, such as anaerobic sludge digestion liquor or landfill leachate.


Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems.
Introducing small DNA molecules (Dbait) impairs the repair of damaged chromosomes and provides a new method for enhancing the efficiency of radiotherapy in radio-resistant tumors. The radiosensitizing activity is dependent upon the efficient delivery of Dbait molecules into the tumor cells. Different strategies have been compared, to improve this key step. We developed a pipeline of assays to select the most efficient nanoparticles and administration protocols before preclinical assays: (i) molecular analyses of complexes formed with Dbait molecules, (ii) cellular tests for Dbait uptake and activity, (iii) live zebrafish embryo confocal microscopy monitoring for in vivo distribution and biological activity of the nanoparticles and (iv) tumor growth and survival measurement on mice with xenografted tumors. Two classes of nanoparticles were compared, polycationic polymers with linear or branched polyethylenimine (PEI) and covalently attached cholesterol (coDbait). The most efficient Dbait transfection was observed with linear PEI complexes, in vitro and in vivo. Doses of coDbait ten-fold higher than PEI/Dbait nanoparticles, and pretreatment with chloroquine, were required to obtain the same antitumoral effect on xenografted melanoma. However, with a 22-fold lower 'efficacy dose/toxicity dose' ratio as compared with Dbait/PEI, coDbait was selected for clinical trials.


Validation of the orthogonal tilt reconstruction method with a biological test sample.
Electron microscopy of frozen-hydrated samples (cryo-EM) can yield high resolution structures of macromolecular complexes by accurately determining the orientation of large numbers of experimental views of the sample relative to an existing 3D model. The "initial model problem", the challenge of obtaining these orientations ab initio, remains a major bottleneck in determining the structure of novel macromolecules, chiefly those lacking internal symmetry. We previously proposed a method for the generation of initial models--orthogonal tilt reconstruction (OTR)--that bypasses limitations inherent to the other two existing methods, random conical tilt (RCT) and angular reconstitution (AR). Here we present a validation of OTR with a biological test sample whose structure was previously solved by RCT: the complex between the yeast exosome and the subunit Rrp44. We show that, as originally demonstrated with synthetic data, OTR generates initial models that do not exhibit the "missing cone" artifacts associated with RCT and show an isotropic distribution of information when compared with the known structure. This eliminates the need for further user intervention to solve these artifacts and makes OTR ideal for automation and the analysis of heterogeneous samples. With the former in mind, we propose a set of simple quantitative criteria that can be used, in combination, to select from a large set of initial reconstructions a subset that can be used as reliable references for refinement to higher resolution.


Curcumin induces differential expression of cytoprotective enzymes but similar apoptotic responses in fibroblasts and myofibroblasts.
Excessive extracellular matrix (ECM) deposition and tissue contraction after injury can lead to esthetic and functional problems. Fibroblasts and myofibroblasts activated by transforming growth factor (TGF)-β1 play a key role in these processes. The persistence of (myo)fibroblasts and their excessive ECM production and continuous wound contraction have been linked to pathological scarring. The identification of compounds reducing myofibroblast survival and function may thus offer promising therapeutic strategies to optimize impaired wound healing. The plant-derived polyphenol curcumin has shown promising results as a wound healing therapeutic in vivo; however, the exact mechanism is still unclear. In vitro, curcumin induces apoptosis in various cell types via a reactive oxygen species (ROS)-dependent mechanism. Here we treated human dermal fibroblasts with TGF-β1 to induce myofibroblast differentiation, and compared the responses of fibroblasts and myofibroblasts to 25 µM curcumin. Curcumin induced caspase-independent apoptosis in both fibroblasts and myofibroblasts in a ROS-dependent manner. Oxidative stress leads to the induction of several antioxidant systems to regain cellular homeostasis. We detected stress-induced induction of heme oxygenase (HO)-1 in fibroblasts but not in myofibroblasts following curcumin exposure. Instead, myofibroblasts expressed higher levels of heat shock protein (HSP)72 compared to fibroblasts in response to curcumin, suggesting that TGF-β1 treatment alters the stress-responses of the cells. However, we did not detect any differences in curcumin toxicity between the two populations. The differential stress responses in fibroblasts and myofibroblasts may open new therapeutic approaches to reduce myofibroblasts and scarring.


Predictive value of incidental right ventricular abnormalities identified on SPECT for mortality and pulmonary hypertension.
The clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH). We retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes. Of the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001). These data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.


Cellular suppression of murine ADCC and NK activities induced by Corynebacterium parvum.
Administration of a single dose of C. parvum (CP) induces depression of splenic NK activity in mice after a lag period of 3-5 days and this depression lasts about 2 weeks. The depressed levels of NK activity noted in this study depended on time of CP administration and were associated with the induction of suppressor cell activity. Neonatally thymectomized or sublethally irradiated mice had unimpaired ability to generate suppressor cells following CP treatment. Depletion of adherent/phagocytic cells by carbonyl iron plus magnetism, Sephadex G-10 filtration, or both neither enriched NK activity nor removed suppressor activity from the spleens of CP-treated mice. Antibody-dependent cellular cytotoxicity (ADCC) against lymphoma targets was also depressed in CP-treated mice, accompanied by a concomitant appearance of suppressor cells that interfere with ADCC at the effector level.


Life-threatening gastrointestinal haemorrhage requiring surgical resection caused by SARS-CoV-2 induced ANCA associated vasculitis: A case report.
SARS-CoV-2 infection has been linked to the de novo diagnosis of various autoimmune conditions as well as flares in pre-existing disease. With such high prevalence of SARS-CoV-2 in the community, it is important to consider rare manifestations of autoimmune conditions when patients present with severe symptoms. Multi-specialty care is required to ensure optimal outcomes and prompt diagnosis. A 28-year-old male presented to our tertiary referral centre with progressive debilitating polyarthritis, a purpuric rash on both flanks and aphthous ulcers 6 weeks after infection with SARS-CoV-2. On the second day of admission, he developed severe gastrointestinal haemorrhage requiring multiple blood transfusions. Attempted angioembolisation failed to identify a site of active haemorrhage. On failing trial of conservative management, the decision was made to perform an exploratory laparotomy. The small bowel was found to have an extensive vasculitis requiring resection to control haemorrhage. Autoimmune serology revealed c-ANCA positivity with anti-PR3 antibodies. Patients presenting with acute vasculitic pathologies related to SARS-CoV-2 have the potential to rapidly progress to severe life-threatening gastrointestinal haemorrhage. Prompt surgical management is appropriate in selected cases. In the current era of COVID-19, the differential diagnosis of SARS-CoV-2 induced ANCA vasculitis must be considered for such cases with gastrointestinal haemorrhage. Compilation of similar cases and further studies are required to determine an optimal management pathway for these patients.


Low molecular weight organic acids in the urine of the newborn.
The urinary excretion of seven selected low molecular weight organic acids in normal neonates was measured by gas chromatography. First and third to fourth day of life excretion of the following compounds was significantly unchanged: 3-OH-butyric acid (less than 13 mumol/mmol creatinine), succinic acid (approx. 43 mumol/mmol creatinine), adipic acid (approx. 12 mumol/mmol creatinine), 2-OH-glutaric acid (approx. 23 mumol/mmol creatinine), 3-OH-3-Me-glutaric acid (approx. 25 mumol/mmol creatinine) and citric acid (approx. 115 mumol/mmol creatinine). The excretion of 4-OH-phenyl-acetic acid increased during the first four days of life (from less than 8 mumol/mmol creatinine to approx. 20 mumol/mmol creatinine). It is postulated that urinary orgainc acid excretion in the neonate, which is clearly different from the adult urinary pattern, is a reflection of the specific neonatal metabolic situation, including a high fatty acid utilisation and a low protein catabolism.


Cognitive activation theory of stress (CATS).
The cognitive activation theory of stress (CATS) is based on a long series of experiments on animals and on humans, in the laboratory, and in real life situations. From the common sense coping concept formulated by Seymour Levine; coping is when my "tommy" does not hurt, we have advanced to a systematic theory for what is behind the relaxed and happy coping rat (and cat). We also cover the translational leap to humans, starting with the now classic parachutist study. The bridge is based on formal and symbolic definitions, a theoretical short cut that Levine actually never really accepted. The essential pathophysiological concept is the potential pathological effects of sustained activation, which may occur in the absence of coping (positive response outcome expectancy). We review the current status of CATS in Behavioural Medicine by discussing its potential explanatory power in epidemiology, prevention and treatment of "subjective health complaints".


An intraoral splint for the prevention of microstomia from facial burns.
Microstomia may be a disfiguring complication of severe burn injuries of the soft tissues of the face. The constriction of the perioral myocutaneous tissues following such trauma poses several problems and usually necessitates major plastic and reconstructive intervention. A novel technique is described which limited the anticipated constriction of perioral tissues in a 21-year-old female who suffered full skin thickness burns to 65 per cent of her body, including her face, following a self-induced petrol burn.


Traumatic stress, oxidative stress and post-traumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis.
Post-traumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may have in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD.


DNA restriction analysis of adenovirus prototypes 1 to 41.
DNA restriction patterns of all known human adenovirus prototypes (1 to 41), ordered according to subgenera A to F, are presented for restriction endonucleases BamHI, BglII, BstEII, HindIII, and SmaI. This catalogue is a prerequisite for typing of adenoviruses by DNA restriction analysis in diagnostic laboratories and for strain identification in reference laboratories. To determine the genetic relationship of human adenoviruses within a subgenus and between subgenera, a pairwise analysis of comigrating fragments was performed. Adenoviruses of subgenus C were closely related. Adenoviruses of subgenus B showed two related clusters of four types each, whereas the numerous serotypes of subgenus D did not show any corresponding clustering. Little comigration was observed between DNA restriction fragments from members of subgenus A or F respectively.


Very deep burns of the hand due to low voltage electrical laboratory equipment: a potential hazard for scientists.
A low voltage (24 V) electrical deep burn of the hand injured a professor of applied physics when performing an experiment in his laboratory. The potential hazard of the equipment is described, the injuries are reported and the literature is reviewed.


Evaluation of intraprostatic metabolism of 1,25-dihydroxyvitamin D(3) (calcitriol) using a microdialysis technique.
1,25-dihydroxyvitamin D(3) (calcitriol) inhibits prostate cancer growth in vitro and in vivo. We used a prostate microdialysis technique to better understand the intraprostatic pharmacokinetics of calcitriol, which in turn would facilitate planning for systemic calcitriol therapy in patients with prostate cancer. Male Sprague-Dawley rats were treated with 5 microg of calcitriol intravenously. Animals were either intact (group 1, n = 6) or castrated (group 2, n = 3). Prostate microdialysis was performed by perfusing Krebs solution through a 5-mm linear probe. Effluents were collected hourly from 0 to 20 hours or until death. Serum was collected at baseline and at the end of the experiment. Serum was also obtained from untreated rats at 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours after intraperitoneal injection of calcitriol. Calcitriol levels were measured by radioimmunoassay. The average baseline intraprostatic level of calcitriol in prostate dialysate in intact rats was 21.1 pg/mL (+/-7.5); it was 88 pg/mL (+/-98.4) after calcitriol administration. In castrated animals, the values were 16.6 pg/mL (+/-5.3) and 25.3 pg/mL (+/-10.7). Two peaks in intraprostatic calcitriol levels were observed after intravenous administration: at less than 6 hours after injection and at more than 13 hours after injection. The mean total calcitriol exposure (area under the concentration versus time curve) in the prostate was 297.6 (+/-159) pg/hr/mL (intact) and 272.7 (+/-123.6) pg/hr/mL (castrated). The baseline serum levels were 0.1 to 1 ng/mL and reached a peak of more than 100 ng/mL within 1 hour of intraperitoneal injection. This technique permits real-time measurement of intraprostatic pharmacokinetics of calcitriol. The ratio of the intraprostatic area under the concentration versus time curve to the serum area under the concentration versus time curve of calcitriol was less than 1:100. Hence, within 24 hours of calcitriol administration, only a fraction (less than 1%) of the serum level is detectable in prostatic tissue. A bimodal peak in intraprostatic calcitriol levels is observed. This technique could be used to determine the tissue levels of calcitriol more accurately and to conduct additional studies to better elucidate the effects of castration on the intraprostatic pharmacokinetics of calcitriol.


Topographic thickness of Bowman's layer determined by ultra-high resolution spectral domain-optical coherence tomography.
To characterize the thickness profile of the corneal epithelium and the Bowman's layer across the horizontal meridian. Forty-four eyes of 22 healthy subjects were investigated in this study. Ultra-high resolution anterior segment spectral domain-optical coherence tomography (SD-OCT) was used to assess the topographic thickness of the epithelium and the Bowman's layer across the cornea. Thicknesses at five locations, including the center, midperiphery, and periphery close to the limbus, on both the nasal and the temporal sides along the horizontal meridian, were analyzed. Mean epithelial thickness at the central cornea was 52.5 ± 2.4 μm. It increased gradually from the center to the periphery (P < 0.001). There was no significant difference between the nasal side and the temporal side for epithelial thickness. The central Bowman's layer thickness was 17.7 ± 1.6 μm, and it remained constant from the center to the midperiphery (P > 0.05). However, thicknesses at the nasal and temporal periphery, 20.0 ± 1.9 μm and 19.8 ± 2.2 μm, respectively, were significantly greater than the central and midperipheral thicknesses (P < 0.001). Nasal and temporal thicknesses were similar on either side of the center. The epithelium and the Bowman's layer were not evenly distributed across the horizontal meridian of the cornea. SD-OCT provided useful information about topographic thickness of the different corneal layers in vivo.


ESR correlation times of 2,2,6,6-tetramethyl piperidone-N-oxyl (Tempone) in solutions of hemoglobin A and hemoglobin S.
Correlation times for the tumbling motion of the spin probe 2,2,6,6,-tetramethyl piperidone-N-oxyl (Tempone) were obtained in the presence of different concentrations of oxyhemoglobin A, oxyhemoglobin S, and deoxyhemoglobin S and compared to the viscosity of non-gelling hemoglobin solutions. Reorientational motion (or tumbling) of Tempone in gelled solutions of deoxyhemoglobin S is as great as that in non-gelled hemoglobins of the same total concentration. It is concluded that the gel does not exclusively partition Tempone into an aqueous phase of lower solute concentration after gel formation. The gel at room temperature is a highly mobile and dynamic structure on the microscopic level.


Preliminary in vivo breast vibro-acoustography results with a quasi-2-d array transducer: a step forward.
We previously investigated the application of a novel imaging modality, vibro-acoustography (VA), using an annular confocal transducer (confocal VA) integrated into a clinical prone stereotactic mammography system, to detect various breast abnormalities. To shorten the scanning time and provide improved coverage of the breast, we have evolved our imaging system by implementing VA on a clinical ultrasound scanner equipped with a ''quasi-2-D'' array transducer. We call this technique ''quasi-2-D vibro-acoustography'' (Q2-DVA). A clinical ultrasound scanner (GE Vivid 7) was modified to perform both ultrasound imaging and VAusing an array transducer consisting of a matrix of 12 rows by 70 columns of ultrasound elements. The newly designed system was used to perform VA on patients with either benign or cancerous lesions. Our results indicate that benign and malignant solid breast lesions were easily detected using our newly modified VA system. It was also possible to detect microcalcifications within the breast. Our results suggest that with further development, Q2-DVA could provide high-resolution diagnostic information in the clinical setting and may be used either as a stand-alone or as a complementary tool in support of other clinical imaging modalities.


A-kinase interacting protein 1 might serve as a novel biomarker for worse prognosis through the interaction of chemokine (C-X-C motif) ligand 1/chemokine (C-X-C motif) ligand 2 in acute myeloid leukemia.
This study aimed to explore the association of A-kinase interacting protein 1 (AKIP1) with chemokine (C-X-C motif) ligand (CXCL) 1/CXCL2, and further investigate their correlation with clinical features and prognosis in acute myeloid leukemia (AML) patients. Totally 160 de novo AML patients were recruited, and their bone marrow samples were collected before treatment for detecting the expressions of AKIP1, CXCL1, and CXCL2 by the quantitative polymerase chain reaction. Complete remission (CR) was assessed after induction treatment, and event-free survival (EFS) and overall survival (OS) were calculated. AKIP1 expression was positively associated with CXCL1 (P < .001) and CXCL2 expression (P < .001). AKIP1 high expression was correlated with FAB classification (P = .022), monosomal karyotype (P = .001), and poor risk stratification (P = .013), while CXCL2 high expression was associated with monosomal karyotype (P = .001). As for treatment response, AKIP1 high expression exhibited a trend to be increased in non-CR patients compared with CR patients, while without statistical significance (P = .105). However, no correlation of CXCL1 (P = .418) or CXCL2 (P = .685) with CR achievement was observed. Most importantly, AKIP1 and CXCL1 were negatively correlated with accumulating EFS and OS (all P < .05), while CXCL2 only showed a trend to be negatively associated with accumulating EFS (P = .069) and OS (P = .055; but without statistical significance). AKIP1 might serve as a novel biomarker for worse AML prognosis through the interaction of CXCL1/CXCL2.


An associative analysis of object memory.
Different aspects of recognition memory in rodents are commonly assessed using variants of the spontaneous object recognition procedure in which animals explore objects that differ in terms of their novelty, recency, or where they have previously been presented. The present article describes three standard variants of this procedure, and outlines a theory of associative learning, SOP which can offer an explanation of performance on all three types of task. The implications of this for theoretical interpretations of recognition memory and the procedures used to explore it are discussed.


Pyrroloquinoline quinone delays inflammaging induced by TNF-α through the p16/p21 and Jagged1 signalling pathways.
Previous studies on the longevity effect of pyrroloquinoline quinine (PQQ) on nematode worms have revealed that PQQ can enhance the antioxidant capacity of nematode worms, thus extending the lifespan of the worms. The induction and development of cellular senescence are closely connected with inflammatory reactions. The aim of this study was to determine the effect of PQQ and ageing factors on senescent cells. To this end, we cultivated human embryonic lung fibroblasts in nutrient solution with or without tumour necrosis factor-alpha (TNF-α) to establish an inflammaging model in vitro. The cells were preincubated with or without PQQ to determine if PQQ had any anti-inflammaging effect. More senescent cells were detected with the addition of TNF-α than without (P < .01). The ratio of senescent cells to non-senescent cells in the TNF-α group was greater than that in the control group (P < .01). When cells were preincubated with PQQ prior to TNF-α treatment, there were fewer senescent cells than those in the control group, which was not pretreated with PQQ (P < .05). The same tendency was noted with regard to p21, p16, and Jagged1. In summary, we used TNF-α, a well-known pro-inflammatory cytokine associated with inflammaging, to establish an in vitro inflammaging model and provided evidence that PQQ delays TNF-α -induced cellular senescence and has anti-inflammaging properties.


ERK1/2 activation plays important roles in the opposite effects of Trichostatin A in non-cancer and cancer cells.
Histone deacetylase (HDAC) inhibitors are candidates of anti-cancer drugs as they can effectively kill cancer cells while have little or no toxicity to non-cancer cells, but the molecular mechanism underlying this process remains unclear. We previously reported that HDAC inhibitors could protect normal mouse hepatocytes from apoptosis induced by transforming growth factor-β1 (TGF-β1) with the requirement of extracellular signal-regulated kinase 1/2 (ERK1/2). In this study, we investigate the roles of trichostatin A (TSA), a typical HDAC inhibitor, on three non-cancer cell lines AML-12, MDCK and 3T3-L1, and four cancer cell lines Hep-3B, HeLa, A549 and MCF-7. TSA is a fermentation product of Streptomyces originally used as an antifungal agent. Our results showed that TSA blocked not only the TGF-β1-induced apoptosis but also serum starvation-induced apoptosis in all the non-cancer cells, whereas it could induce strong apoptosis in all the cancer cells. Further investigation revealed that TSA can induce the activation of ERK1/2 in the three non-cancer cells but not in the cancer cells. In summary, these findings indicated that TSA protect non-cancer cells from apoptosis via activating ERK1/2, providing a useful insight into the better application of HDAC inhibitors in cancer therapy.


Positions of polar amino acids alter interactions between transmembrane segments and detergents.
α-Helical transmembrane (TM) segments in membrane proteins are comprised primarily of hydrophobic amino acids that accommodate insertion from water into the nonpolar membrane bilayer. In many such segments, however, polar residues are also present for structural or functional reasons. These latter residues impair the local favorable acyl interactions required for solvation by hydrophobic media such as phospholipids in native bilayers or detergents used for in vitro characterization. Using a series of Lys-tagged designed TM-like peptides (typified by KK-YAAAIAAIAWAIAAIAAAIAA-KKK) in which single-Asn residue substitutions (from Ile or Ala) were made successively from the center of the hydrophobic region toward the C-terminus, we demonstrate that polar residues strongly alter the nature of the interaction between TM segments and the solvating detergent. Through the application of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism spectroscopy, and tryptophan fluorescence, we observed drastic differences in the structures of the detergent-peptide complexes that contain relatively minor sequence differences. For example, the blue shift of the Trp fluorescence (indicating local detergent solvation at this location) differs by as much as ~10 nm depending upon the position of a single Asn substitution in an otherwise identical segment. The overall results suggest that polar point mutations occurring in a biological membrane will elicit comparable effects, placing a significant refolding burden on the local protein structure and potentially leading to disease states through altered protein--lipid interactions in membrane proteins.


Geometric charges and nonlinear elasticity of two-dimensional elastic metamaterials.
Problems of flexible mechanical metamaterials, and highly deformable porous solids in general, are rich and complex due to their nonlinear mechanics and the presence of nontrivial geometrical effects. While numeric approaches are successful, analytic tools and conceptual frameworks are largely lacking. Using an analogy with electrostatics, and building on recent developments in a nonlinear geometric formulation of elasticity, we develop a formalism that maps the two-dimensional (2D) elastic problem into that of nonlinear interaction of elastic charges. This approach offers an intuitive conceptual framework, qualitatively explaining the linear response, the onset of mechanical instability, and aspects of the postinstability state. Apart from intuition, the formalism also quantitatively reproduces full numeric simulations of several prototypical 2D structures. Possible applications of the tools developed in this work for the study of ordered and disordered 2D porous elastic metamaterials are discussed.


iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis.
To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose. Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated. The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1 : 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD2 : 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.


Progress in understanding the structure-activity relationships of P-glycoprotein.
Efflux out of cells by P-glycoprotein (P-gp) represents a serious liability for pharmaceuticals, particularly for anti-cancer drugs. Consequently, identification of compounds as potential substrates is important for understanding their bioavailability. Also, the development of agents which reverse this multi-drug resistance phenotype has received considerable attention. Assays for determining these activities are reviewed. Recent literature and studies into the structure-activity relationships (SAR) of the resulting data are discussed. Multiple binding sites and other complicating factors have prevented the development of a truly general, conclusive SAR either for substrate or inhibitory activities. Consequently, many models have tended to address only very general properties, such as lipophilicity and size. However, progress has been made in the last few years toward more specific SAR suggesting well-defined structural features responsible for both activities. The future of understanding the details of P-gp SAR lies in more specific assays that target specific binding sites and mechanisms of action.


Schwann cell-like remyelination following transplantation of human umbilical cord blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord injury.
Human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) have significant therapeutic potential in cell-based therapies following spinal cord injury (SCI). To evaluate this potential, we conducted our preliminary investigations on the remyelination of injured spinal cords with hUCB-MSC transplantations and we observed its long term effects on dogs with SCI. Of the ten injured dogs, seven were transplanted with hUCB-MSCs 1 week after SCI, whereas the remaining three dogs were not transplanted. Two transplanted dogs died over the first month after transplantation because of urinary tract infection, bedsores and sepsis. The SCI dogs showed no improvement in motor and sensory functions and their urinary dysfunction persisted until they were euthanized (from 3 months to 1 year) while hind-limb recovery in 4 dogs among the five transplanted dogs was significantly improved. In the recovered dogs, functional recovery was sustained for three years following transplantation. Histological results from five transplanted dogs showed that many axons were remyelinated by P0-positive myelin sheaths after transplantation. Our results suggest that transplantation of hUCB-derived MSCs may have beneficial therapeutic effects. Furthermore, histological results provided the first in vivo evidence that hUCB-MSCs are able to enhance the remyelination of peripheral-type myelin sheaths following SCI.


In Vitro Models and Proteomics in Osteoarthritis Research.
This review summarizes and exemplifies the current understanding of osteoarthritis in vitro models and describes their relevance for new insights in the future of osteoarthritis research. Our friend and highly appreciated colleague, Prof. Alan Grodzinsky has contributed greatly to the understanding of joint tissue biology and cartilage biomechanics. He frequently utilizes in vitro models and cartilage explant cultures, and recent work also includes proteomics studies. This review is dedicated to honor his 75-year birthday and will focus on recent proteomic in vitro studies related to osteoarthritis, and within this topic highlight some of his contributions to the field.


Proteolysis of the bifunctional methionine-repressible aspartokinase II-homoserine dehydrogenase II of Escherichia coli K12. Production of an active homoserine dehydrogenase fragment.
The dimeric bifunctional enzyme aspartokinase II-homoserine dehydrogenase II (Mr = 2 X 88,000) of Escherichia coli K12 can be cleaved into two nonoverlapping fragments by limited proteolysis with subtilisin. These two fragments can be separated under nondenaturing conditions as dimeric species, which indicates that each fragment has retained some of the association areas involved in the conformation of the native protein. The smaller fragment (Mr = 2 X 24,000) is devoid of aspartokinase and homoserine dehydrogenase activity. The larger fragment (Mr = 2 X 37,000) is endowed with full homoserine dehydrogenase activity. These results show that the polypeptide chains of the native enzyme are organized in two different domains, that both domains participate in building up the native dimeric structure, and that one of these domains only is responsible for homoserine dehydrogenase activity. A model of aspartokinase II-homoserine dehydrogenase II is proposed, which accounts for the present results.


The regulation of NONO by USP11 via deubiquitination is linked to the proliferation of melanoma cells.
Ubiquitin-specific protease 11 (USP11) has been implicated in the regulation of DNA repair, apoptosis, signal transduction and cell cycle. It belongs to a USP subfamily of deubiquitinases. Although previous research has shown that USP11 overexpression is frequently found in melanoma and is correlated with a poor prognosis, the potential molecular mechanism of USP11 in melanoma remains indefinitive. Here, we report that USP11 and NONO colocalize and interact with each other in the nucleus of melanoma cells. As a result, the knockdown of USP11 decreases NONO levels. Whereas, overexpression of USP11 increases NONO levels in a dose-dependent manner. Furthermore, we reveal that USP11 protects NONO protein from proteasome-mediated degradation by removing poly-ubiquitin chains conjugated onto NONO. Functionally, USP11 mediated melanoma cell proliferation via the regulation of NONO levels because ablation of USP11 inhibits the proliferation which could be rescued by ectopic expression of NONO protein. Moreover, a significant positive correlation between USP11 and NONO concentrations was found in clinical melanoma samples. Collectively, these results demonstrate that USP11 is a new deubiquitinase of NONO and that the signalling axis of USP11-NONO is significantly involved in melanoma proliferation.


The nodI gene product of Rhizobium leguminosarum is closely related to ATP-binding bacterial transport proteins; nucleotide sequence analysis of the nodI and nodJ genes.
The nucleotide sequence of a 2-kb fragment immediately downstream of the nodABC genes of the Rhizobium leguminosarum symbiotic plasmid pRL1JI has been determined. Genes corresponding to the two open reading frames identified are named nodI and nodJ. Tn 5 insertions into these genes result in a "nodulation-delayed" phenotype. The predicted amino acid sequence of the nodI gene shows considerable homology to inner-membrane-located gene products involved in active transport systems in Escherichia coli and Salmonella typhimurium. The predicted product of the nodJ gene is very hydrophobic, suggesting that it may be an integral membrane protein.


[Neurotrophic corneal ulcer in an HIV patient].
We present the case of a 29 year-old man who came to the Emergency Department due to pain in the right eye. There was demonstrated a complete corneal de-epithelialisation. There was no clinical improvement after appropriate treatment, which was complicated by migraine and vomiting. The computerized tomography (CT) scan showed images suggestive of cerebral toxoplasmosis. After the complete tarsorrhaphy a restitution ad integrum was observed. The diagnosis of a neurotrophic corneal ulcer due to an affected trigeminal nerve in the context of a cerebral toxoplasmosis, tarsorrhaphy is an effective procedure to take in account in corneal epithelial defects resistant to other treatments.


Immunometabolism at the cornerstone of inflammaging, immunosenescence, and autoimmunity in COVID-19.
Inflammaging constitutes the common factor for comorbidities predisposing to severe COVID-19. Inflammaging leads to T-cell senescence, and immunosenescence is linked to autoimmune manifestations in COVID-19. As in SLE, metabolic dysregulation occurs in T-cells. Targeting this T-cell dysfunction opens the field for new therapeutic strategies to prevent severe COVID-19. Immunometabolism-mediated approaches such as rapamycin, metformin and dimethyl fumarate, may optimize COVID-19 treatment of the elderly and patients at risk for severe disease.


Characteristics of the normal central visual field measured with resolution perimetry.
The ring perimeter is an innovative device that measures the resolution threshold at 50 locations in the central visual field in approximately 6 min. This study was undertaken to define the characteristics of the resolution visual field in normal eyes using this instrument and to check the repeatability of the measurement. A total of 114 perimetrically naive, normal subjects aged from 20 to 79 years were prospectively enrolled; 55 randomly chosen subjects were tested twice, with a rest period of less than or equal to 60 s elapsing between examinations. The resolution threshold increased towards the periphery in all subjects. A small but significant decline in sensitivity occurred with age; this loss was greatest in the inner part of the field. Variability in threshold between subjects was not found to increase towards the periphery or in the upper field as compared with the lower. The field was highly repeatable when reexamined in the same subject. This study defines the resolution visual field in normal subjects, along with its inter- and intra-observer variability, and gives age-corrected predictive confidence intervals for each location of the field using the ring perimeter.


Motion of the multi-segmented spine in elite dancers during passé and arabesque.
The spinal biomechanics of dance tasks have received little study and no studies have used a multi-segmented spinal model. Knowledge of how the segments of the spine move may be useful to the dance clinician and dance educator. What is the direction and amount of motion of the primary segments of the spine in elite dancers during an arabesque and a passé? This observational study examined 59 elite dancers performing an arabesque and a passé using a three-dimensional motion analysis system with the trunk divided into a series of five segments: pelvis, lower lumbar, upper lumbar, lower thoracic and upper thoracic spine. For the arabesque, all spinal segments moved in the same direction within each plane and the majority of total spinal motion occurred in the thoracic spine. Thoracic segments were at or near end range position at completion of the arabesque. For the passé, the spinal segments moved in different directions within each plane and the majority of total spinal motion occurred in the lumbar spine. Dance clinicians and dance educators may benefit from the knowledge that thoracic hypomobility in any plane may limit arabesque performance and that attempts to instruct dancers to achieve a position of passé without flexion of the lumbar spine may be a valid aesthetic ideal but also an unrealistic functional expectation.


Calcium Channel Subunit α2δ-1 as a Potential Biomarker Reflecting Illness Severity and Neuroinflammation in Patients with Acute Ischemic Stroke.
Voltage-gated calcium channels (VGCCs) dysfunction is involved in the development of acute ischemic stroke (AIS). As a subunit of VGCC complexes, we detected the levels of α2δ-1 subunit in serum and cerebrospinal fluid (CSF) specimens from AIS patients. The study included 105 patients with first-ever AIS, who were admitted within 48 hours after stroke onset. The serum and CSF levels of α2δ-1 were measured with ELISA and the severity of AIS patients was evaluated according to the National Institutes of Health Stroke Scale (NIHSS) score. The cerebral infarct volume was calculated through the Pullicino formula based on the cranial CT or MRI scan. C-reactive protein (CRP) and serum amyloid A (SAA) were measured using the latex-enhanced immunoturbidimetric assay. Compared to the control subjects, the serum α2δ-1 level was significantly increased in AIS patients with large infarct volume and in severe AIS cases with high NIHSS score, which correlated positively with the inflammatory markers CRP and SAA. Furthermore, the concentration of α2δ-1 in CSF was elevated with the infarct volume, which was higher in severe AIS patients. Our study suggests that the increased α2δ-1 levels in serum and CSF specimens may be used as a potential marker for reflecting VGCCs dysfunction, illness severity and neuroinflammation in AIS patients.


Giant cell tumour of tendon sheath in a child: a case report.
Giant cell tumour of the tendon sheath is uncommon in children. We describe this tumour arising from the right ring finger in an eight-year-old girl. Plane radiographs showed a soft tissue mass with erosion of the distal phalanx. The tumour was treated by surgical excision with good outcome.


Dialogic linkage and resonance in autism.
We evaluated how children with autism make linguistic adjustments when talking with someone else. We devised two novel measures to assess (a) overall conversational linkage and (b) utterance-by-utterance resonance within dialogue between an adult and matched participants with and without autism (n = 12 per group). Participants with autism were less able to establish 'cognitive linkage' with an interlocutor. As predicted, only among children with autism was there a positive correlation between the ability to link in with speaker's meanings and ratings of emotional connectedness with the conversational partner. Participants with autism were not less likely to show a basic form of dialogic resonance across successive utterances (the 'frame grab'), but more often elaborated their responses in an atypical manner.


Care pathway of women with interval breast cancer in 2016, based on medico-administrative data.
Since 2004, an organised screening programme (OS) for breast cancer has been in place for 50-74 years women who are not at an increased risk. Despite this, 17% of cancers diagnosed within 24 months following an OS mammogram are interval cancers (IC), diagnosed even though the OS had not reported cancer. After identifying IC from the French administrative healthcare database (SNDS), our objective was to describe the care pathways of women with IC in 2016. The IC identification algorithm is based on breast imaging tests conducted in the 24 months prior to diagnosis and on the compatibility of their timeline with ACR3 lesion follow-up (BIRADS guidelines). The care pathways of 3 groups were compared: women with IC, diagnosed through the OS, and diagnosed outside the OS programme (personalised screening or based on clinical signs, PSCS group). Respectively, 12,965 (46%), 3433 (12%), and 11,761 women (42%) were classified in the OS, IC and PSCS groups, i.e. 20.9% IC cases among the women taking part in the OS programme. The women from the IC group presented with more forms with lymph node or metastatic involvement than those of the OS group. Their pathways were more complex than in the OS group: at an equivalent stage, more total mastectomies and more adjuvant or neoadjuvant chemotherapy regimens. The care pathways of women with IC are intermediate with respect to those of the OS or PSCS group.Cases of IC probably include several cancer prognosis profiles.


Quantitative diffusion-weighted and dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging analysis of T2 hypointense lesion components in pediatric diffuse intrinsic pontine glioma.
Focal anaplasia characterized by T2 hypointensity, signal-intensity enhancement on postcontrast T1-weighted MR imaging and restricted water diffusion has been reported in a patient with juvenile pilocytic astrocytoma. We identified T2(HOF) with these MR imaging characteristics in children with DIPG and hypothesized that these represent areas of focal anaplasia; and may, therefore, have increased perfusion properties and should be characterized by increased perfusion. Thus, we used DSC to investigate our hypothesis. We retrospectively reviewed the baseline MR imaging scans of 86 patients (49 girls, 37 boys; median age, 6.1 years; range, 1.1-17.6 years) treated for DIPG at our hospital (2004-2009). T2(HOF) with the described MR imaging characteristics was identified in 10 patients. We used a region of interest-based approach to compare the ADC, FA, rCBV, rCBF, and rMTT of T2(HOF) with those of the typical T2(HRT). The ADC of T2(HOF) with the specified MR imaging characteristics was significantly lower than that of T2(HRT) (range, 0.71-1.95 μm(2)/ms versus 1.36-2.13 μm(2)/ms; P < .01); and the FA (range, 0.12-0.34 versus 0.07-0.24; P = .03) and rCBV (range, 0.4-2.62 versus 0.23-1.57; P = .01) values of T2(HOF)s were significantly higher. Our data suggest that T2(HOF) in DIPG may represent areas of focal anaplasia and underline the importance of regional, rather than global, tumor-field analysis. T2(HOF) may be the ideal target when stereotactic biopsy of tumors that present with an inhomogeneous T2 signal intensity is considered.


Survival and infectivity of Toxoplasma gondii and Cryptosporidium parvum oocysts bioaccumulated by Dreissena polymorpha.
The study was aimed to understand the depuration process of Cryptosporidium parvum and Toxoplasma gondii oocysts by zebra mussel (Dreissena polymorpha), to consider the use of the zebra mussel as a bioremediation tool. Two experiments were performed: (i) individual exposure of mussel to investigate oocyst transfers between bivalves and water and (ii) in vivo exposure to assess the ability of the zebra mussel to degrade oocysts. (i) Our results highlighted a transfer of oocysts from the mussels to the water after 3 and 7 days of depuration; however, some oocysts were still bioaccumulated in mussel tissue. (ii) Between 7 days of exposure at 1000 or 10 000 oocysts/mussel/day and 7 days of depuration, the number of bioaccumulated oocysts did not vary but the number of infectious oocysts decreased. Results show that D. polymorpha can release oocysts in water via (pseudo)faeces in depuration period. Oocysts remain bioaccumulated and infectious oocyst number decreases during the depuration period in zebra mussel tissues. Results suggest a degradation of bioaccumulated C. parvum and T. gondii oocysts. This study highlighted the potential use of D. polymorpha as a bioremediation tool to mitigate of protozoan contamination in water resources.


NIR-emitting squaraine J-aggregate nanosheets.
Click chemistry and Yamamoto coupling afforded an S-shaped π-scaffold composed of two directly connected dicyanomethylene-substituted squaraine dyes. This bis(squaraine) self-assembles into nanosheets in a cooperative self-assembly process, affording an absorption maximum at 886 nm and a fluorescence peak at 904 nm due to strong J-type exciton coupling.


Mössbauer effect in hemoglobin and some iron-containing biological compounds.
The Mössbauer effect in Fe(57) has been used to study the molecules, hemoglobin, O(2)-hemoglobin, CO(2)-hemoglobin, and CO-hemoglobin (within red cells) and the molecules, hemin and hematin (in the crystalline state). Quadrupole splittings and isomeric shifts observed in the Mössbauer spectra of these molecules are tabulated. The temperature dependence of the quadrupole splitting and relative recoil-free fraction for hemoglobin with different ligands has been investigated. An estimate of the Debye-Waller factor in O(2)-hemoglobin at 5 degrees K is 0.83. An asymmetry in the quadrupole splitting observed in hemoglobin is attributed to a directional dependence of the recoil-free fraction which establishes the sign of the electric field gradient in the molecule and indicates that the lowest lying d orbital of the Fe atoms is |xy>. This asymmetry indicates that the iron atoms in hemoglobin are vibrating farther perpendicular to the heme planes than parallel to them, and, in fact, the ratio of the mean square displacements perpendicular and parallel to the heme planes in hemoglobin is approximately 5.5 at 5 degrees K. The temperature dependence of the quadrupole splitting in hemoglobin has been used to estimate a splitting between the lowest lying iron atom d orbitals of approximately 420 cm(-1).


The association of pre-existing mental health conditions and patient outcomes after lower extremity orthopaedic trauma: a scoping review.
Existing research has established a correlation between post-traumatic mental health conditions, including anxiety and depression, and various aspects of recovery, such as pain exacerbations, reduced functional recovery, and lowered patient satisfaction. However, the influence of pre-existing mental health conditions on orthopaedic trauma outcomes has not been thoroughly investigated. The objective of this study was to systematically review literature addressing the association between pre-existing mental health conditions and patient outcomes following surgical interventions for lower extremity fractures in non-geriatric populations. A systematic literature review was conducted using Medline, Embase, and Scopus databases following PRISMA-ScR guidelines to select studies that examined lower extremity orthopaedic trauma outcomes in relation to pre-existing mental health conditions. Studies that evaluated patients with surgically treated lower extremity fractures and a history of mental health conditions such as anxiety, depression, or mood disorders were included. Studies with a mean patient age above 65 years of age were excluded to focus on non-geriatric injury patterns. The systematic review identified 12 studies investigating the relationship between surgical outcomes of orthopaedic lower extremity fractures and pre-existing mental health disorders in non-geriatric populations. Studies included patients with pelvis, femur, tibia, and ankle fractures. A majority (83%) of these studies demonstrated that patients with pre-existing mental health diagnoses had inferior functional outcomes, heightened pain levels, or an increase in postoperative complications. The presence of pre-existing mental health conditions, particularly anxiety and depression, may predispose orthopaedic trauma patients to an elevated risk of suboptimal functional outcomes, increased pain, or complications after surgical intervention for lower extremity fractures. Future research should focus on interventions that mitigate the impact of mental health conditions on orthopaedic outcomes and patient wellness in this population.


The dark proteome of cancer: Intrinsic disorderedness and functionality of HIF-1α along with its interacting proteins.
The dark side of protein is the region (s) where molecular conformation is unknown. Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are the dark matter of biology due to inability to visualize them using standard structure elucidation technique such as X-ray crystallography due to lack in diffraction signal. IDPs are the functionally important class of proteins with entire protein or its parts lack ordered three-dimensional structure. Computational studies have predicted that nearly one-third of the human proteome is disordered, which gives the enormous flexibility and functional diversity to proteins. The conserved residues and elements in disordered proteins are critical for function and might be parts of peptide motifs or protein-protein interaction interfaces. For example, regions of proteins that are involved in disorder-based molecular recognition are known as molecular recognition features (MoRFs). Generally, MoRFs could undergo disorder to order transition or vice versa at interaction with specific partners. Hypoxia inducible factor 1α (HIF-1α) is a master transcriptional regulator involved in response to hypoxia, which is associated with many pathological conditions. Importantly, HIF-1α regulates various steps of cancer progression such as cell survival, tumor cell invasion, and metastasis. In this chapter, we have extensively analyzed the molecular recognition features and their relationship with disordered regions and associated structural islands of HIF-1α. We had also analyzed the disorderness and MoRFs of HIF-1α primary interaction partners that are enriched in IDPRs and MoRFs giving their role in protein-protein interaction and cancer regulation.


Phase II trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer.
We conducted a phase II trial of gemcitabine with S-1, oral fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, to evaluate the activity and toxicity of such a combination in metastatic pancreatic cancer (MPC) patients. Patients who had pathologically proven pancreatic cancer with metastatic lesions were eligible candidates for entry into the study. S-1 was given orally (30 mg m(-2)) b.i.d. for 14 consecutive days and gemcitabine (1000 mg m(-2)) was given on days 8 and 15. The cycle was repeated every 21 days. We enrolled 33 MPC patients. The median number of cycles was eight (range 1-20). Grade 3-4 toxicities were leucopenia (33%), neutropenia (55%), anaemia (9%), thrombocytopenia (15%), anorexia (6%), fever (9%), and interstitial pneumonia (6%). Objective responses were obtained in 16 patients (one complete response and 15 partial responses; response rate, 48%; 95% confidence interval (CI), 33-65). Median survival and 1-year survival rate were 12.5 months (95% CI, 5.9-19.1) and 54% (95% CI, 36-72), respectively. Combination chemotherapy with GEM and S-1 was well tolerated and yielded a significantly high response rate.


Cultivation of the bacterial strain Achromobacter delicatulus, producing an exocellular polyglucan-type polysaccharide in the fermentation tank FU-6.
Growth processes and biosynthesis of the exocellular polyglucan-type polysaccharide, produced by the bacteria Achromobacter delicatulus, were studied in the laboratory fermentation apparatus FU-6 under three completely different aeration systems. The purpose of this study was to find the most economical way of the polysaccharide biosynthesis. The growth rate and the synthesis of the exopolysaccharide were not limited either by the oxygen transfer or glucose content under the conditions examined. The best construction proved to be the fermentation tank with the lowspeed agitation system. In the case of the bacterial strain Achromobacter delicatulus, producing huge amounts of the thick slimy polyglucan exopolysaccharide, the industrial production may develop without any principal technical difficulties.


Calling behavior of mass-reared and wild Anastrepha serpentina (Diptera: Tephritidae).
The calling behavior of mass-reared and wild males of Anastrepha serpentina (Wiedemann) (Diptera: Tephritidae) was studied both in the laboratory and in field cage tests. In the laboratory, density (1, 5, and 10 males per container), age, and hour of day significantly affected calling behavior. Mass-reared males called independently of density, whereas wild males only called at densities of 5 and 10 individuals. Males of both strains started calling when they were 5-7 d old. The daily pattern of male calling was similar in both strains, starting at 0730 hours, and reaching a peak at 1330-1630 hours. Field cage tests showed that mass-reared males started calling when they were 5d old; the period of peak calling was when males were 8-9 d old. In contrast, wild males began calling when they were 10 d old, reaching peaks when males were 13, 15, and 18 d old. Wild males tended to form leks to call during each day of the experiment, whereas mass-reared males only formed leks during 2 d, both strains displaying very low levels. During field cage tests, males, independently of strain, displayed two calling peaks, one peak in the morning and one peak in the afternoon, whereas males observed in the laboratory only showed a single calling peak. The results are discussed in view of the effects of mass rearing A. serpentina males in relation to potential use of the sterile insect technique.


Microsurgical anatomy and operative technique for extreme lateral lumbar disc herniations.
The anatomy of the lateral aspect of the lumbar spine and our lateral microsurgical technique for extreme lateral lumbar disc herniations (ELLDH) is described. This study was based on the microdissection of 4 cadavers, on the morphometric evaluation of these as well as 6 dried cadaver spines and 8 lumbar CT scans, and on the use of this technique on over 200 cases. Level dependent changes in the posterior arch cause a shift of the disc space distally relative to the facet joint, an increasing amount of bone to overlie the intervertebral foramen, and a decreasing amount of working space within the exposure in the caudal direction. Therefore, more bone removal from the lateral aspect of the pars interarticularis and supero-lateral aspect of the facet joint is required in the lower lumbar spine. When the exposed ligamentum flavum is resected, the dorsal root ganglion is seen and access to the herniation and disc space is achieved. Level dependent changes in the pedicles and transverse processes lead to an alteration in the course and relationships of the nerves, thereby influencing the pathophysiology of and surgical technique for the ELLDH. The operative target is the lateral aspect of the pars interarticularis and not the intertransverse space as has been previously described. Our techniques allows for the early identification of the nerve with minimal risks of injury to it, to the adjacent vessels and to the structural integrity of the facet joint and pars interarticularis.


MACF1, Involved in the 1p34.2p34.3 Microdeletion Syndrome, is Essential in Cortical Progenitor Polarity and Brain Integrity.
1p34.2p34.3 deletion syndrome is characterized by an increased risk for autism. Microtubule Actin Crosslinking Factor 1 (MACF1) is one candidate gene for this syndrome. It is unclear, however, how MACF1 deletion is linked to brain development and neurodevelopmental deficits. Here we report on Macf1 deletion in the developing mouse cerebral cortex, focusing on radial glia polarity and morphological integrity, as these are critical factors in brain formation. We found that deleting Macf1 during cortical development resulted in double cortex/subcortical band heterotopia as well as disrupted cortical lamination. Macf1-deleted radial progenitors showed increased proliferation rates compared to control cells but failed to remain confined within their defined proliferation zone in the developing brain. The overproliferation of Macf1-deleted radial progenitors was associated with elevated cell cycle speed and re-entry. Microtubule stability and actin polymerization along the apical ventricular area were decreased in the Macf1 mutant cortex. Correspondingly, there was a disconnection between radial glial fibers and the apical and pial surfaces. Finally, we observed that Macf1-mutant mice exhibited social deficits and aberrant emotional behaviors. Together, these results suggest that MACF1 plays a critical role in cortical progenitor proliferation and localization by promoting glial fiber stabilization and polarization. Our findings may provide insights into the pathogenic mechanism underlying the 1p34.2p34.3 deletion syndrome.


Arthrogryposis-like signs in trisomy 18.
Two cases of newborn male infants afflicted with trisomy 18 and with signs of arthrogryposis multiplex congenita (AMC) are described. Anomalies occurring in most cases of trisomy 18 such as polyhydramnios, reduced foetal activity, and skeletal muscle hypoplasia decrease articular movements and, thus might cause AMC. Since AMC is rarely associated with trisomy 18, chromosomal aberration is not the only factor involved in these cases.


Impact of age on outcomes of midurethral sling procedures in women.
Trans-obturator tape (TOT) and tension-free vaginal tape (TVT) comprise minimally invasive surgical management for stress urinary incontinence (SUI). The aim of this retrospective cohort study was to investigate outcomes of TOT and TVT among different age groups of women. Medical records of patients who underwent TOT and TVT from January 2010 to December 2015 were reviewed. Patients were stratified into three groups according to age. All patients were interviewed routinely before and after surgery. The primary outcome was cure rate after surgery. Secondary outcomes included hospital stay, operative time, blood loss in surgery, and complication rate. A total of 616 patients diagnosed with SUI and 262 patients who had not undergone any concurrent surgery were eligible for study inclusion. A total of 616 patients diagnosed with SUI and 262 patients who had not undergone any concurrent surgery were eligible for study inclusion. There were 81 patients in group 1 (≤ 50 years), 97 patients in group 2 (51-59 years), and 84 patients in group 3 (≥ 60 years). After surgery, there were no significant differences in cure rates among the three groups (96.3% vs. 94.8% vs. 97.6%, P = 0.623). There were also no significant differences in operation time, blood loss, hospital stay, and complication rate among the three groups. When analyzing the TOT group (217 patients) and TVT group (45 patients) separately, primary and secondary outcomes did not differ significantly according to age group. As surgical management for SUI, midurethral sling procedures, both TOT and TVT, were found to be safe and effective among different age groups.


Synthesis, crystal structure, antitumor activity and DNA-binding study on the Mn(II) complex of 2H-5-hydroxy-1,2,5-oxadiazo[3,4-f]1,10-phenanthroline.
The complex [Mn(L)(NO(3))(2)(H(2)O)(2)] (1) (L=2H-5-hydroxy-1,2,5-oxadiazo[3,4-f]1,10-phenanthroline) was synthesized and characterized by elemental analysis, IR and UV. The crystal and molecular structure of 1 was determined by single-crystal X-ray diffraction; crystal data: light yellow, monoclinic, space group P2(1)/n, Z=4, a=7.432(2) A, b=9.582(3) A, c=23.445(7) A, beta=90.519(5) degrees. The Mn atom in 1 is hexa-coordinated in a distorted octahedral arrangement by two N atoms of the ligand L and four O atoms of two water molecules and two nitrate anions. Biological tests in vitro showed that 1 has significant antitumor activity against HL-60, KB, Hela and BGC-823 cells. The interaction of 1 with calf thymus DNA was investigated by absorption titration, thermal denaturation and viscosity measurements. The results suggest that 1 binds with DNA by intercalating via the ligand L.


Untargeted UHPLC-MS metabolic profiling as a valuable tool for the evaluation of eggs quality parameters after dietary supplementation with oregano, thyme, sideritis tea and chamomile on brown laying hens.
Bioactive constituents of medicinal-aromatic plants used as feed additives may affect the metabolic profile and oxidative stability of hen eggs. To determine the effects of dietary supplementation with a mixture of dried oregano, thyme, sideritis tea and chamomile on laying hen performance, egg quality parameters, and oxidative stability in the egg yolk were monitored. In this trial 432 hens were allocated in two treatments (unsupplemented vs. supplemented with the mixture) and fed for 42 days. Eggs were collected at the end of the trial period, egg yolk was separated, extracted, and the total phenolic content (TPC) and oxidative stability was measured. Furthermore, LC-MS metabolic profile of eggs was studied and pathway analysis was elaborated in MetaboAnalyst to facilitate annotation of features. Overall, egg production and feed conversion ratio were not affected by the supplementation. However, eggs from the supplemented treatment showed improved shell thickness and strength, and yolk resistance to oxidation. Moreover, LC-MS metabolomic analysis of egg yolk of supplemented and unsupplemented layers showed significant variations and tight clustering in unsupervised principal component analysis due to different chemical profiling of egg yolk. LC-MS study showed that secondary metabolites of aromatic plants did not transfer into yolk, nevertheless the feed supplementation impacted the pathway metabolism of tyrosine, phenylalanine, propanate, and the biosynthesis of aminoacyl-tRNA, phenylalanine, tyrosine and tryptophan. The dietary supplementation of layers with a mixture of dried medicinal aromatic plants affected shell thickness and strength, the lipid and protein oxidative stability and increased tyrosine and phenylalanine content in eggs.


Erratum: Emodin-Induced Autophagy Against Cell Apoptosis Through the PI3K/AKT/mTOR Pathway in Human Hepatocytes [Corrigendum].
[This corrects the article DOI: 10.2147/DDDT.S204958.].


Amniotic fluid embolism and leukotrienes.
Extracts of experimental amniotic fluid embolism from rabbit lungs showed the same biologic activities as leukotrienes and a peak on high-performance liquid chromatography at the same retention time as leukotriene D4. Acute death was prevented by administration of 5-lipoxygenase inhibitor. These results suggest the possibility that leukotrienes contribute to the clinical and pathophysiologic features of amniotic fluid embolism.


Fibrinogen γ' promotes host survival during Staphylococcus aureus septicemia in mice.
Staphylococcus aureus is a common gram-positive bacterium that is the causative agent for several human diseases, including sepsis. A key virulence mechanism is pathogen binding to host fibrinogen through the C-terminal region of the γ-chain. Previous work demonstrated that FggΔ5 mice expressing mutant fibrinogen γΔ5 lacking a S. aureus binding motif had significantly improved survival following S. aureus septicemia. Fibrinogen γ' is a human splice variant that represents about 10% to 15% of the total fibrinogen in plasma and circulates as a fibrinogen γ'-γ heterodimer (phFibγ'-γ). The fibrinogen γ'-chain is also expected to lack S. aureus binding function. Determine if human fibrinogen γ'-γ confers host protection during S. aureus septicemia. Analyses of survival and the host response following S. aureus septicemia challenge in FggΔ5 mice and mice reconstituted with purified phFibγ'-γ or phFibγ-γ. Reconstitution of fibrinogen-deficient or wildtype mice with purified phFibγ'-γ prior to infection provided a significant prolongation in host survival relative to mice reconstituted with purified phFibγ-γ, which was superior to that observed with heterozygous FggΔ5 mice. Improved survival could not be accounted for by quantitative differences in fibrinogen-dependent adhesion or clumping, but phFibγ'-γ-containing mixtures generated notably smaller bacterial aggregates. Importantly, administration of phFibγ'-γ after infection also provided a therapeutic benefit by prolonging host survival relative to administration of phFibγ-γ. These findings provide the proof-of-concept that changing the ratio of naturally occurring fibrinogen variants in blood could offer significant therapeutic potential against bacterial infection and potentially other diseases.


The incidence of occult paraumbilical hernias in patients undergoing primary umbilical hernia repair.
The primary goal of this study was to determine the incidence of occult paraumbilical hernias during open primary umbilical hernia repair. The secondary objective was to further characterize the clinical features of these patients and hernias. This was a retrospective chart review of patients undergoing primary umbilical hernia repair at Shouldice Hospital, from 2007 to 2017. Inclusion criteria were utilized to elucidate patients, where a concomitant occult paraumbilical hernia was found. Descriptive statistics were used throughout. 5850 patients underwent primary umbilical hernia repair, 459 (7.85%) patients had concomitant primary umbilical and paraumbilical hernias. There was a preoperative suspicion/diagnosis of a paraumbilical hernia in 166 (2.8%) of these patients. In 293 (5.01%) patients who had open primary umbilical hernia repair, at least one associated occult paraumbilical defect was found during surgery. Most of umbilical and concomitant occult paraumbilical hernias were small and medium size defects. The great majority of the reported occult paraumbilical hernias were found in the supraumbilical position at a distance of 3 cm or less from the top of the umbilical defect. The incidence of concomitant occult paraumbilical hernias in patients mildly overweight undergoing primary umbilical hernia repair is 5.01%, relevant to surgical decision-making. Since the great majority of these paraumbilical defects are superior to the umbilical defect, an adequate incision and dissection for at least 3 cm above the umbilical hernia may reduce the number of missed concomitant hernias and result in less presumed recurrences.


Phenoxyacetic acids as PPARδ partial agonists: synthesis, optimization, and in vivo efficacy.
A series of phenoxyacetic acids as subtype selective and potent hPPARδ partial agonists is described. Many analogues were readily accessible via a single solution-phase synthetic route which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of two potent exemplars which were further evaluated in vivo. Details of the SAR, optimization, and in vivo efficacy of this series are presented herein.


A compendium and review of pediatric pulmonary function testing assessment opportunities for asthma.
Standard spirograms are widely used in the respiratory disease management community to help diagnosis asthma and provide longitudinal information. Surprisingly, basic information obtained on the spirogram, beyond the FEV1 and change in FEV1 after bronchodilator is underutilized. We reviewed information on pulmonary function and bronchodilator response in children since 2016. We present here a discussion of other element of the standard spirogram that can be used for pediatric asthma management.Methods: Medline search of pulmonary function, children, adolescents, bronchodilator reversibility, small airway disease, small airway function, asthma, airflow limitation, bronchodilator response. Studies since 2016 that provide information on normal or asthmatic children bronchodilator response, and/or small airway or pulmonary function values after albuterol. Limited data has been published on FEV1 bronchodilator response in children since 2016. Other parameters of the pulmonary function test in children have had recent documentation. New data on FEV1 bronchodilator response in normal children is limited since 2016. However, other details of pulmonary function interpretation in asthmatic children has had considerable attention, and are reviewed here.


Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013-2015.
Crimean-Congo hemorrhagic fever (CCHF) is a viral disease, mainly transmitted through tick bite, of great importance in Public Health. In Spain, Crimean-Congo hemorrhagic fever virus (CCHFV) was detected for the first time in 2010 in Hyalomma lusitanicum ticks collected from deer in Cáceres. The aim of this study was to investigate the presence of CCHFV in ticks from Cáceres, and from other Spanish areas, and to evaluate the presence of antibodies against the virus in individuals exposed to tick bites. A total of 2053 ticks (1333 Hyalomma marginatum, 680 H. lusitanicum and 40 Rhipicephalus bursa) were analyzed using molecular biology techniques (PCR) for CCHFV detection. The determination of specific IgG antibodies against CCHFV in 228 serum samples from humans with regular contact with ticks (at risk of acquiring the infection) was performed by indirect immunofluorescence assay. The CCHFV was not amplified in ticks, nor were antibodies against the virus found in the serum samples analyzed. The absence of the CCHFV in the ticks studied and the lack of antibodies against the virus in individuals exposed to tick bites would seem to suggest a low risk of acquisition of human infection by CCHFV in Spain.


Impact of idiopathic pulmonary fibrosis on clinical outcomes of lung cancer patients.
The clinical characteristics of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) differ from those of lung cancer in patients without IPF. Thus, we aimed to evaluate the impact of IPF on the clinical course of patients with lung cancer. Clinical data of IPF patients with lung cancer (n = 122) were compared with those of patients with lung cancer without IPF (n = 488) matched by age, sex, histopathology, stage, and date of diagnosis of lung cancer. The median follow-up period after diagnosis of lung cancer was 16 months. Among patients with IPF, the mean age was 68 years, 95.9% were male, 93.2% were ever-smokers, and squamous cell carcinoma was the most common cancer type (48.4%). The IPF group had poorer lung function and lower lobe predominance of lung cancer than the no-IPF group. The IPF group showed a poorer prognosis than the no-IPF group (5-year survival rate: 14.5% vs. 30.1%, respectively; P < 0.001), even after adjusting for lung function and regardless of the treatment method. Among patients with IPF, 16.8% experienced acute exacerbation within 1 month after treatment of lung cancer. The treatment outcome of patients with lung cancer and IPF was generally unfavorable, and acute exacerbation triggered by treatment frequently occurred.


Should child protection services respond differently to maltreatment, risk of maltreatment, and risk of harm?
To examine evidence available in large-scale North American datasets on child abuse and neglect that can assist in understanding the complexities of child protection case classifications. A review of child abuse and neglect data from large North American epidemiological studies including the Canadian Incidence Study of Reported Child Abuse and Neglect (CIS), the National Child Abuse and Neglect Data System (NCANDS), and the National Incidence Studies of Reported Child Abuse and Neglect (NIS). The authors of this paper argue that recent evidence from large North American epidemiological studies examining the incidence of child abuse and neglect demonstrate that children and families identified as being at risk of maltreatment present with as many household and caregiver concerns as investigations that are substantiated. In order to continue to develop appropriate services and policies for vulnerable children the authors urge continue definitional clarity for research in child maltreatment that considers the exemplars or indicators of categories, in tandem with parental and child characteristics which can provide one source of evidence-basis to meaningful child protection case classifications. Continued monitoring, refined by the dilemmas faced in practice, are critical for a continued public health investment in children's well-being, predicated upon upholding children's rights.


Antidiabetic potential of dietary polyphenols: A mechanistic review.
Diabetes is a metabolic disorder that has caused enormous harm to the public health worldwide. In this study, we evaluated the potential of phenolic compounds on diabetes management, addressing their mechanisms of action, in addition to discussing the digestion, absorption, metabolism, bioavailability, and toxic effects of these compounds. The intake of phenolic compounds can play a fundamental role on diabetes management, since they can reduce blood glucose levels, oxidative stress, protein glycation, inhibit the activity of dipeptidyl peptidase - IV and other key enzymes related to carbohydrate metabolism, activate various biochemical pathways to improve pancreatic β-cell functions, increase insulin secretion, and improve insulin resistance. In this way, they can be considered a potential strategy in the development of pharmaceutical approaches that aim to reduce complications resulting from the progression of this metabolic pathology.


Structural organization of the tight junctions.
Tight junctions are the most apical organelle of the apical junctional complex and are primarily involved in the regulation of paracellular permeability and membrane polarity. Extensive research in the past two decades has identified not only the individual molecules of the tight junctions but also their mutual interactions, which are the focus of the present review article. While a complete map of the interactions among the tight junction molecules is probably far from being complete, the available evidence already allows outlining the general molecular architecture of the tight junctions. Here, with the aim of gaining deeper mechanistic understanding of tight junction assembly, regulation and function, we have subdivided the known molecular interactions into four major clusters that are centered on cell surface, polarity, cytoskeletal and signaling molecules.


Prioritizing Elective Surgery During the COVID-19 Pandemic Has Caused Age-Related Inequality: a Multicenter Study.
The concern has been that this prioritization has resulted in age-related inequality between patients, with the older population suffering the most. The aim of this multicenter study was to examine the differences in incidence and waiting times of elective surgeries by age during the SARS-CoV-2 coronavirus disease (COVID-19) pandemic in Finland. Data on elective surgery (88 716 operations) were gathered from three Finnish public hospitals for the years 2017-2020. Surgery incidence and waiting times stratified by age groups (younger than 18, 18 to 49, 50 to 69, and 70 or older) were examined, and the year 2020 was compared to the reference years 2017-2019. The mean annual, monthly, and weekly waiting times were calculated with 95% confidence intervals (CI). The first COVID-19 wave decreased surgery incidence most prominently in patients younger than 18 (incidence rate ratio [IRR] 0.64, CI 0.60-0.68) and 70 or older (IRR 0.68, CI 0.66-0.70). After the first wave, the incidence increased in patients aged 50 to 69 and 70 or older by 22% and 29%, respectively. Among patients younger than 18, the incidence in 2020 was 15% lower. In patients younger than 18, waiting times were at mean of 43% longer in June to December compared to the reference years. In patients aged 18 to 49, 50 to 69, and 70 or older, waiting times increased in May but recovered to normal level during fall 2020. COVID-19 decreased the incidence of surgery and led to increased waiting times. Clearing of the treatment backlog started with older patients which resulted in prolonged waiting times among pediatric patients.


4-amino-4-arylcyclohexanones and their derivatives: a novel class of analgesics. 2. Modification of the carbonyl function.
The effect on potency of modification of the carbonyl function of analgesics derived from 4-(dimethylamino)-4-arylcyclohexan-1-one was studied by reduction and by addition of nucleophiles. The resulting amino alcohols were separated and assigned structures on the basis of X-ray crystallography, NMR, and TLC mobility. The trans (OH and N) isomers were invariably more potent than the cis. Inclusion of flat lipophilic moieties (phenyl, cyclohexenyl) at a distance of at least two carbon atoms from the carbon bearing hydroxyl led to increases in potency by orders of magnitude. The possible significance of this on receptor interaction is discussed.


Change in onset age of first primary colorectal cancer in the USA.
Identifying the onset age of cancer is essential for its early intervention. The aim of this study was to characterize the features and investigate the variation tendency of first primary colorectal cancer (CRC) onset age in the USA. For this retrospective population-based cohort analysis, data on patients diagnosed with first primary CRC (n = 330,977) between 1992 and 2017 were obtained from the Surveillance, Epidemiology, and End Results dataset. Annual percent changes (APC) and average APCs were calculated to examine the changes in average age at CRC diagnosis using the Joinpoint Regression Program. From 1992 to 2017, the average age at CRC diagnosis decreased from 67.0 to 61.2 years, declining by 0.22% and 0.45% annually before and after 2000. The age at diagnosis was lower in the distal than in the proximal CRC cases and the age has the downward trends in all subgroups of sex, race, and stage. Over one-fifth of CRC patients were initially diagnosed with distantly metastatic CRC, with the age lower than that in localized CRC cases (63.5 vs 64.8 years). The first primary CRC onset age has decreased significantly in the USA over the last 25 years and the modern lifestyle may be responsible for the decline. Specifically, the age of proximal CRC is invariably higher than that of distal CRC. Moreover, the age of advanced stage is lower than that of the early stage. Clinicians should adopt earlier screening age and more effective screening techniques for CRC.


Diabetes mellitus and dental implants: a clinical study.
Diabetes mellitus is no longer considered to be a contraindication for implant-supported prostheses, provided that the patient's blood sugar is under control, and that there is motivation for oral hygiene procedures. This paper presents the experiences of treating diabetic patients using implants with good success rates.


Inpatient Hepatology Consultation: A Practical Approach for Clinicians.
Cirrhosis is the end-stage of chronic liver disease and constitutes a leading cause of potential years of working life lost, especially in the Americas and Europe. Its natural history is characterized by an asymptomatic phase called compensated cirrhosis, followed by a rapidly progressive phase characterized by liver-related complications termed decompensated cirrhosis. Complications could be related to portal hypertension and/or liver dysfunction, including ascites, portal hypertensive gastrointestinal bleeding, encephalopathy, and jaundice. This review will discuss some of the most important precipitants of hepatic decompensation, including acute variceal bleeding, spontaneous bacterial peritonitis, and hepatic encephalopathy.


Subjective response to antipsychotics in bipolar disorders: A review of a neglected area.
The term "subjective response to antipsychotic" (SRA) refers to changes in the subjective state experienced due to antipsychotic (AP) exposition that is independent of the therapeutic or physical side effects of these drugs. This dimension of analysis has been extensively explored in schizophrenic disorders, finding that negative SRA is an early and independent predictor of compliance as well as a successful pathway to construct current theoretical frameworks of these disorders. There is an increasing use of AP in bipolar disorders' treatment (BD) but no reviews on the topic have been published to date in this population. The aim of this work is to review published data of SRA in BD patients and to discuss their clinical and theoretical implications. An extensive search in online databases was performed. Reports were reviewed and included if they described SRA in BD or included instruments aimed to assess it. Reports of cognitive, sexual, motor autonomic side effects were excluded. Findings were summarized in a narrative fashion. Nine reports fulfilled the inclusion criteria and were included in the revision, reporting data from 1282 BD patients. Among these, three were prospective studies and three explored relations between SRA and treatment compliance. There is an asymmetry between the increase in the use of antipsychotics in BD and the lack of data regarding the SRA. Phenomenologically, SRA in BD is similar to that found in schizophrenic subjects. Some of these symptoms may be misdiagnosed as depressive symptoms. The existing data show that SRA has a strong correlation with treatment compliance as well as a promising way to develop theoretical paradigms for these disorders.