Slow hydrogel matrix degradation enhances salivary gland mimetic phenotype.
We recently developed a salivary gland tissue mimetic (SGm), comprised of salivary gland cells encapsulated in matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) hydrogels within arrays of ∼320 µm diameter spherical cavities molded in PDMS. The SGm provides a functional and physiologically relevant platform well-suited to high-throughput drug screening for radioprotective compounds. However, the utility of the SGm would benefit from improved retention of acinar cell phenotype and function. We hypothesized that tuning biochemical cues presented within the PEG hydrogel matrix would improve maintenance of acinar cell phenotype and function by mimicking the natural extracellular matrix microenvironment of the intact gland. Hydrogels formed using slower-degrading MMP-sensitive peptide crosslinkers showed >2-fold increase in sphere number formed at 48 h, increased expression of acinar cell markers, and more robust response to calcium stimulation by the secretory agonist, carbachol, with reduced SGm tissue cluster disruption and outgrowth during prolonged culture. The incorporation of adhesive peptides containing RGD or IKVAV improved calcium flux response to secretory agonists at 14 days of culture. Tuning the hydrogel matrix improved cell aggregation, and promoted acinar cell phenotype, and stability of the SGm over 14 days of culture. Furthermore, combining this matrix with optimized media conditions synergistically prolonged the retention of the acinar cell phenotype in SGm. STATEMENT OF SIGNIFICANCE: Salivary gland (SG) dysfunction occurs due to off-target radiation due to head and neck cancer treatments. Progress in understanding gland dysfunction and developing therapeutic strategies for the SG are hampered by the lack of in vitro models, as salivary gland cells rapidly lose critical secretory function within 24 hours in vitro. Herein, we identify properties of poly(ethylene glycol) hydrogel matrices that enhance the secretory phenotype of SG tissue mimetics within the previously-described SG-microbubble tissue chip environment. Combining slow-degrading hydrogels with media conditions optimized for secretory marker expression further enhanced functional secretory response and secretory marker expression.


The effect of glucocorticosteroids on in vitro motility of the ureter of the sheep.
1. The effects of three glucocorticosteroids, hydrocortisone, methylprednisolone and dexamethasone, as well as two non-steroidal anti-inflammatory agents (NSAIDs) indomethacin and diclofenac sodium were tested in vitro on the spontaneously rhythmic contracting ureteral preparation of the sheep. 2. The NSAIDs and the steroids methylprednisolone (10(-7)-10(-4) M) and dexamethasone (10(-8) - 10(-4) M), dose-dependently inhibited ureteral motility. Hydrocortisone caused a cessation of spontaneous contractions only at the high concentration of 10(-4) M. 3. Pretreatment of ureteral strips with the protein synthesis inhibitor cycloheximide (10(-6) M) abolished the inhibitory action of the corticosteroids on peristalsis, consistent with the suggestion that the action of steroids on the ureter is mediated via the synthesis of the anti-phospholipase protein, lipocortin. 4. The potency of the steroids in descending order was found to be dexamethasone greater than methylprednisolone greater than hydrocortisone.


Heterostrain-enabled dynamically tunable moiré superlattice in twisted bilayer graphene.
The ability to precisely control moiré patterns in two-dimensional materials has enabled the realization of unprecedented physical phenomena including Mott insulators, unconventional superconductivity, and quantum emission. Along with the twist angle, the application of independent strain in each layer of stacked two-dimensional materials-termed heterostrain-has become a powerful means to manipulate the moiré potential landscapes. Recent experimental studies have demonstrated the possibility of continuously tuning the twist angle and the resulting physical properties. However, the dynamic control of heterostrain that allows the on-demand manipulation of moiré superlattices has yet to be experimentally realized. Here, by harnessing the weak interlayer van der Waals bonding in twisted bilayer graphene devices, we demonstrate the realization of dynamically tunable heterostrain of up to 1.3%. Polarization-resolved Raman spectroscopy confirmed the existence of substantial heterostrain by presenting triple G peaks arising from the independently strained graphene layers. Theoretical calculations revealed that the distorted moiré patterns via heterostrain can significantly alter the electronic structure of twisted bilayer graphene, allowing the emergence of multiple absorption peaks ranging from near-infrared to visible spectral ranges. Our experimental demonstration presents a new degree of freedom towards the dynamic modulation of moiré superlattices, holding the promise to unveil unprecedented physics and applications of stacked two-dimensional materials.


Team-Based Approach to Reduce Malignancies in People with Diabetes and Obesity.
Numerous observations have indicated an increased risk of developing various types of cancers, as well as cancer-related mortality, among patients with diabetes and obesity. The purpose of this review is to outline multiple-cancer screening among these patients through a team-based approach and to present the findings of a pioneering integrated care program designed for patients with obesity with a specific emphasis on cancer prevention. A community-based multi-cancer prevention program, which provides all services in one location and utilizes team-based approaches, is reported to be feasible and has the potential to enhance the uptake rate of multiple cancers screening among patients with diabetes and obesity. The team-based approach is a commonly utilized method for managing patients with diabetes, obesity, and cancer, and has been shown to be efficacious. Nevertheless, research on team-based cancer screening programs for patients with diabetes and obesity remains limited. Providing a comprehensive screening for colorectal, prostate, and breast cancer, as well as metabolic syndrome, during a single clinic visit has been proven effective and well-received by participants.


"Breath holding" as a thermoregulation strategy in the deep-diving scalloped hammerhead shark.
Fish moving between different thermal environments experience heat exchange via conduction through the body wall and convection from blood flow across the gills. We report a strategy of preventing convective heat loss at the gills during excursions into deep, cold water by the tropical scalloped hammerhead shark (Sphryna lewini). Adult scalloped hammerhead sharks dive rapidly and repeatedly from warm (~26°C) surface waters to depths exceeding 800 meters with temperatures as low as 5°C. Biologgers attached to adult sharks show that warm muscle temperatures were maintained throughout the deepest portion of each dive. Substantive cooling only occurred during the latter stages of the ascent phase and, once initiated, was rapid. Heat transfer coefficient modeling indicated that convective heat transfer was suspended, probably by suppressing gill function during deep dives. This previously unobserved strategy has broad similarities to marine mammal "breath hold" diving.


Overall and net survival of patients with sarcoma between 2005 and 2010: Results from the French Network of Cancer Registries (FRANCIM).
Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors. Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population-based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar-Perme method. Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5-year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5-year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5-year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5-year NS (74%); those with MDM2-amplified sarcomas had the worst NS (45%). NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population-based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.


Potentilla fulgens (Family Rosaceae), a medicinal plant of north-east India: a natural anthelmintic?
The cestode parasite, Raillietina echinobothrida and the trematode, Gastrothylax crumenifer were exposed to the ethanolic root peel extract of Potentilla fulgens, an antiparasitic local medicinal plant of Meghalaya, India, to evaluate the anthelmintic efficacy of the plant. The parasites were incubated in 1, 5, 10, 20, 50 and 100 mg crude alcoholic extract per ml of phosphate buffered saline (PBS) at a temperature of 37 ± 1°C. Paralysis and death were observed at 2.00 ± 0.05 and 2.80 ± 0.06 h for the cestode and 1.21 ± 0.06 and 2.18 ± 0.04 h for the trematode parasites at the highest test concentration of the plant extract. The commercial anthelmintic, Praziquantel (PZQ) showed higher activity at the tested concentration (0.02 mg/ml). To further investigate the efficacy of the plant extract, vital tegumental enzymes of the parasite viz. Acid phosphatase (AcPase), Alkaline phosphatase (AlkPase) and Adenosine triphosphatase (ATPase) were studied. Quantitatively, the total enzyme activity of AcPase, AlkPase and ATPase was found to be reduced significantly by 69.20, 66.43 and 29.63% for R. echinobothrida and 47.96, 51.79 and 42.63% for G. crumenifer, respectively compared to the respective controls; histochemical study also showed reduction in the visible staining of the enzymes. The reference drug, PZQ also showed more or less similar effect like that of the plant extract. The result suggests that phytochemicals of P. fulgens have anthelmintic potential.


Analgesic potential of standardized methanol stem bark extract of Ficus platyphylla in mice: Mechanisms of action.
Extracts of the stem bark of Ficus platyphylla (FP) have been used in traditional the Nigerian medicine to treat psychoses, depression, epilepsy, pain and inflammation. Previous studies have revealed the analgesic and anti-inflammatory effects of FP in different assays including acetic acid-induced writhing, formalin-induced nociception, and albumin-induced oedema. In this study, we assessed the effects of the standardised extract of FP on hot plate nociceptive threshold and vocalisation threshold in response to electrical stimulation of the tail root in order to confirm its acclaimed analgesic properties. We also investigated the molecular mechanisms underlying these effects, with the focus on opiate receptor binding and the key enzymes of eicosanoid biosynthesis, namely cyclooxygenase (COX) and 5-lipoxygenase (5-LO). FP (i) increased the hot plate nociceptive threshold and vocalisation threshold. The increase in hot plate nociceptive threshold was detectable over a period of 30min whereas the increase in vocalisation threshold persisted over a period of 90min. (ii) FP showed an affinity for µ opiate receptors but not for δ or κ opiate receptors, and (iii) FP inhibited the activities of COX-2 and 5-LO but not of COX-1. We provided evidence supporting the use of FP in Nigerian folk medicine for the treatment of different types of pain, and identified opioid and non-opioid targets. It is interesting to note that the dual inhibition of COX-2 and 5-LO appears favourable in terms of both efficacy and side effect profile.


Flow cytometric analysis of phosphatidylcholine metabolism using organelle-selective click labeling.
Here, we present a protocol to analyze phosphatidylcholine (PC) metabolism in mammalian cells using organelle-selective click labeling coupled with flow cytometry (O-ClickFC). We describe steps for the metabolic incorporation of azide-choline into PC. We then detail fluorescent labeling of the azide-modified PC with organelle-targeting clickable dyes in the ER-Golgi, plasma membrane, and mitochondria, and by flow cytometry. This protocol is optimized for flow cytometric quantification of the labeled PC at the organelle level within single live cells. For complete details on the use and execution of this protocol, please refer to Tsuchiya et al. (2023).1.


Screening of sera and tumor extracts of cancer patients using a monoclonal antibody directed against human placental alkaline phosphatase.
A sensitive endogenous enzyme immunoassay involving an anti-human placental alkaline phosphatase (PLAP) monoclonal antibody was used in the screening of sera and tumor extracts of patients with various types of cancer. In sera of breast cancer patients an incidence of 5.2% was recorded. This value rose to 43% when tumor extracts were analyzed. For lung and bronchial cancers we found 11.2% seropositive patients. On several occasions a good correlation was observed between the PLAP determinations and the histopathological staging of tumor tissue.


Self-Assembled and Size-Controllable Oligonucleotide Nanospheres for Effective Antisense Gene Delivery through an Endocytosis-Independent Pathway.
The development of efficient gene delivery vectors has faced two major challenges, namely endo- and lysosomal escape and intracellular release. To address these problems, we developed an oligonucleotide (ON)-template-assisted polymerization approach to create ON nanospheres as gene vectors. Guanidinium-containing disulfide monomers were organized on the ON templates to increase their effective local concentrations. Consequently, ring-opening disulfide-exchange polymerization between monomers was accelerated, further facilitating the self-assembly of ON nanospheres. The size of these nanospheres was controlled by varying the length of the ON templates. Importantly, the nanospheres can be directly delivered into the cytosol through an endocytosis-independent pathway, which is followed by intracellular depolymerization in the reductive cytosolic environment to release the packaged ONs, resulting in efficient gene silencing. The ON nanospheres thus hold great promise as candidates for gene therapy.


Crosstalk relationship between adiponectin receptors, PPAR-γ and α-adrenoceptors in renal vasculature of diabetic WKYs.
Hypoadiponectinemia is associated with renal dysfunctions. Irbesartan and pioglitazone activate Peroxisome proliferator-activated gamma receptor (PPAR-γ) as partial and full agonists. We investigated a crosstalk interaction and synergistic action between adiponectin receptors, PPAR-γ agonists in attenuating renal hemodynamics to adrenergic agonists in diabetic Wistar Kyoto rats (WKY). Streptozotocin (40 mg/kg) was used to induce diabetes, whereas, pioglitazone (10 mg/kg/day), irbesartan (30 mg/kg/day) administered orally for 28 days and adiponectin intraperitoneally (2.5 μg/kg/day) for last 7 days. Metabolic and plasma samples were analyzed on days 0, 8, 21, and 28. During the acute study (day 29), renal vasoconstrictor actions to adrenergic agonists and angiotensin-II were determined. Diabetic WKYs had lower plasma adiponectin, higher creatinine clearance, urinary and fractional sodium excretion but were normalized to a greater extent in pioglitazone and adiponectin combined treatment. Responses to intra-renal administration of adrenergic agonists including noradrenaline (NA), phenylephrine (PE), methoxamine (ME), and angiotensin-II (ANG-II) were larger in diabetic WKY, but significantly blunted with adiponectin treatment in diabetic WKYs to 35-40%, and further reduced by 65-70% in combination with pioglitazone. Attenuation to ANG-II responses in adiponectin and combination with irbesartan was 30-35% and 75-80%, respectively (P < 0.05). Pharmacodynamically, a crosstalk interaction exists between PPAR-γ, adiponectin receptors (adipo R1 & R2), alpha adrenoceptors, and angiotensin-I (ATI) receptors in the renal vasculature of diabetic WKYs. Exogenously administered adiponectin with full PPAR-γ agonist substantially attenuated renal hemodynamics and improved excretory functions, signifying their renoprotective action. Additionally, a degree of synergism exists between adiponectin and pioglitazone to a large extent compared to combination therapy with irbesartan (partial PPAR-γ agonist) in attenuating the renal vascular receptiveness to adrenergic agonists.


["Clumping factor"-reactions using staphylococci after their extraction with guanidiniumchloride (author's transl)].
Staphylococci of strain K 807 (ATCC: 31243) have much "clumping factor" (CF) on their surface. Extraction of the staphylococci with 6 M guanidinium chloride, removed all soluble substances, including coagulase, without reduction in CF-activity. The extracted staphylococci proved to be most suitable for the quantitative determination of fibrinogen and fibrin degradation products in a microtiter procedure (fig. 2). The CF-test with staphylococci of strain K 807 was more sensitive compared with the hitherto used strain Newman D2C (table 1). After staining with "Astrazonrot (BBL)" no loss of CF occurred. With the stained staphylococci the CF-reactions became more distinctly visible and gave sharp endpoints.


Paradoxical implication of BAX/BAK in the persistence of tetraploid cells.
Pro-apoptotic multi-domain proteins of the BCL2 family such as BAX and BAK are well known for their important role in the induction of mitochondrial outer membrane permeabilization (MOMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. Human or mouse cells lacking both BAX and BAK (due to a double knockout, DKO) are notoriously resistant to MOMP and cell death induction. Here we report the surprising finding that BAX/BAK DKO cells proliferate less than control cells expressing both BAX and BAK (or either BAX or BAK) when they are driven into tetraploidy by transient exposure to the microtubule inhibitor nocodazole. Mechanistically, in contrast to their BAX/BAK-sufficient controls, tetraploid DKO cells activate a senescent program, as indicated by the overexpression of several cyclin-dependent kinase inhibitors and the activation of β-galactosidase. Moreover, DKO cells manifest alterations in ionomycin-mobilizable endoplasmic reticulum (ER) Ca2+ stores and store-operated Ca2+ entry that are affected by tetraploidization. DKO cells manifested reduced expression of endogenous sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (Serca2a) and transfection-enforced reintroduction of Serca2a, or reintroduction of an ER-targeted variant of BAK into DKO cells reestablished the same pattern of Ca2+ fluxes as observed in BAX/BAK-sufficient control cells. Serca2a reexpression and ER-targeted BAK also abolished the tetraploidy-induced senescence of DKO cells, placing ER Ca2+ fluxes downstream of the regulation of senescence by BAX/BAK. In conclusion, it appears that BAX/BAK prevent the induction of a tetraploidization-associated senescence program. Speculatively, this may contribute to the low incidence of cancers in BAX/BAK DKO mice and explain why human cancers rarely lose the expression of both BAX and BAK.


Advancement of differentiation of oligodendrocyte progenitor cells by a cascade including protein kinase A and cyclic AMP-response element binding protein.
A transcription factor, cyclic AMP-response element binding protein (CREB), which is phosphorylated by protein kinases (PKA and PKC), is known to be involved in the regulation of oligodendrocyte differentiation. However, it is still unclear whether protein kinase A (PKA) and protein kinase C (PKC) are used simultaneously or at different time points to phosphorylate CREB in oligodendrocytes and whether CREB phosphorylation advances oligodendrocyte differentiation or vise versa. Our previous experiments have shown that in the differentiation process from immature to mature cells, CREB phosphorylation depends on PKC activity and leads to the progression of differentiation. In order to gain a better understanding of the process of differentiation from progenitor to immature cells, we identified which protein kinase, i.e., PKA or PKC, regulates CREB phosphorylation and we determined whether CREB phosphorylation advances differentiation or the reverse. Our results showed that CREB phosphorylation is principally regulated by PKA activity in progenitor cells but not by PKC activity, and that this phosphorylation advances the differentiation of progenitor cells to immature cells in oligodendrocytes.


Heart failure and sleep-disordered breathing: susceptibility to reduced muscle strength and preclinical congestion (SICA-HF cohort).
Increased sympathetic activation in patients with heart failure (HF) and sleep-disordered breathing (SDB) provokes cardiac decompensation and protein degradation and could lead to muscle wasting and muscle weakness. The aim of this study was to investigate the differences in body composition, muscle function, and the susceptibility of preclinical congestion among patients with HF and SDB compared with those without SDB. We studied 111 outpatients with stable HF who were enrolled into the Studies Investigating Co-morbidities Aggravating Heart Failure. Echocardiography, short physical performance battery (SPPB), cardiopulmonary exercise testing, dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), tests of muscle strength, and polygraphy were performed. SDB was defined as apnoea/hypopnoea index (AHI) >5 per hour of sleep. Central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) were defined as AHI >50% of central or obstructive origin, respectively. A total of 74 patients (66.7%) had any form of SDB [CSA (24 patients, 32.4%), OSA (47 patients, 63.5%)]. Patients with SDB showed increased muscle weakness (chair stand), reduced muscle strength, and lower values of SPPB score (P < 0.05). Patients with SDB did not show overt clinical signs of cardiac decompensation compared with those without SDB (P > 0.05) but had increased amounts of water (total body water, intracellular, and extracellular) measured using BIA (P < 0.05). Increased amounts of total body water were associated with the severity of SDB and inversely with muscle strength and exercise capacity measured by anaerobic threshold (P < 0.05). Altogether, 17 patients had muscle wasting. Of these, 11 (65%) patients had SDB (statistically not significant). SDB is highly prevalent in patients with HF. Patients with SDB have lower muscle strength and tend to be more susceptible to preclinical congestion.


[Comparison of the action of powerful pulses of ultrashort UV on the DNA replication and transcription functions in proliferating and resting HeLa cells].
It was established that the response of proliferating and resting HeLa cells to irradiation with single powerful UV-pulses (lambda = 266 nm, the pulse duration 3.10(-11) sec) is different. In the proliferating cells, the rate of DNA synthesis is markedly changed (accelerated or retarded) while the rate of RNA synthesis changes slightly. In the resting cells, RNA synthesis is stimulated while DNA synthesis remains at the control level. In all cases, the processes observed depend upon the intensity and the number of pulses.


Effect of cell-penetrating peptides on the nasal absorption of insulin.
The goal of this study was to evaluate whether cell-penetrating peptides (CPPs) affect the nasal absorption of insulin. L- or D-forms of penetratin, or the L- or D-forms of octaarginine (L- or D-R8), was used as first time for nasal insulin delivery. Furthermore, the concentration of lactate dehydrogenase (LDH) in nasal lavage fluid was determined and a histopathological study of nasal respiratory epithelium was conducted. CPPs dramatically increased nasal insulin absorption, and it was more pronounced for L- and D-penetratin than L- or D-R8. L-penetratin was the most effective promoter of insulin absorption compared with others CPPs. A dose-dependent relationship of L-penetratin and insulin bioavailability was statically significant. The pharmacological availability and bioavailability of nasally administered insulin was up to 76.7% and 50.7% relative to the subcutaneous route, respectively. In contrast, increasing the D-penetratin concentration decreased the efficiency of nasal insulin absorption. There was no significant difference in the release of LDH in nasal lavage fluid and the integrity of nasal respiratory epithelium when L-penetratin was present. In conclusion, these data demonstrate that L-penetratin markedly increased the permeability of insulin across the nasal membrane without causing detectable damage to the integrity of cells in the nasal respiratory mucosa.


Antiapoptotic and protective effects of roscovitine on ischemia-reperfusion injury of the rat liver.
This study was designed to investigate the role of apoptosis on liver IR injury and to determine the effects of roscovitine on this process. Rat livers pretreated with roscovitine received 60 min right lobe ischemia followed by 4 h (n=8) and 24 h (n=8) reperfusion. Tissue injury was evaluated by serum alanine aminotransferase, aspartate aminotransferase, tissue malondialdehyde, myeloperoxidase measurements and histological examination. Dead (apoptotic and necrotic) hepatocytes were determined by trypan blue dye and apoptosis was evaluated with M30 monoclonal antibody. Administration of roscovitine significantly decreased both apoptotic and dead hepatocyte counts compared to controls (P<0.01). Liver transaminase levels were decreased significantly in the roscovitine-pretreated groups (P<0.05). In the groups evaluated 24 h after reperfusion, MPO levels (P<0.02) and leukocyte infiltration on histologic sections were decreased significantly in the roscovitine-administered group compared to its control. This study indicates that hepatocyte apoptosis may play a role in the development of IR injury of the liver. Administration of roscovitine may be beneficial in preventing this injury.


Nurse managers implementing the lean management system: A qualitative study in Western Canada.
This study explores the perceptions and experiences of nurse managers involved in implementing the Lean management system in a Western Canadian province. The provincial government of Saskatchewan, Canada, implemented a multimillion-dollar investment in the Lean management system to transform health care delivery by reducing waste and increasing efficiency of processes and outcomes. This qualitative exploratory study employed semi-structured interviews with 14 nurse managers in urban and rural health regions in one Canadian province. Six themes outline the difficulties nurse managers experienced in juggling role responsibilities alongside a poorly implemented change system with scarce resources. The results showed tensions in the implementation of a Lean model adapted in the context of health care organisations. The expectations for nurse managers to be pivotal players in the implementation of transformative health care practices that promote and sustain strategies to reduce waste, improve coordination and increase patient safety require investment in leadership development. Lean management systems significantly impact the roles of nurse managers who require adequate resources and training to successfully adapt. The results of this study may be used for more effective support mechanisms for nurse managers.


Non-invasive quantitative analysis of human blood components in renal three items using spectral compensation method based on spectral data and component content correlation.
The non-invasive measurement of the blood component contents in humans using spectroscopic methods has important clinical application value. In the absorption spectrum of human blood, for a target component with a small content, the absorption spectrum line is low, the absorption spectrum line of the target component changes weakly at different wavelengths, and the absorption spectrum lines of the target and non-target components overlap. The above reasons cause the spectral line difference between the target and non-target components to be small. However, non-target components also have physical properties such as scattering, which will reduce the contribution of the target component in the absorption spectrum of blood, that is, the spectral line difference between the target and non-target components becomes smaller, thus making the accuracy of the target component model lower. To increase the accuracy of modeling analysis, according to the correlation between spectral data and the content of the target component, this paper proposes a spectral compensation method. The method compensates for the influence caused by the non-target components on the target components through the mathematical relations between the data of the spectrum and the contents of the target components. Thus, a high-precision, non-invasive quantitative analysis system of human blood components is obtained. Taking the analysis of the three components of urea nitrogen, creatinine, and uric acid as examples, the experiment used spectral data before and after spectral compensation and partial least squares (PLS) methods to build two models and used them to predict the content of the target component. When the models of different components established by the spectral compensation method respectively predict the all samples' contents of urea, creatinine, and uric acid, the three correlation coefficients can reach more than 0.9700. It can be obtained from the experimental results that the spectral compensation method can greatly increase the performance of each component model. Spectral compensation is a new and comprehensive method for improving the quality of spectral data. Therefore, this paper obtains a non-invasive quantitative analysis system of human blood components with higher precision, and can quantitatively analyze blood urea nitrogen, creatinine, and uric acid in human blood with high precision, which has great practical application value in clinical practice.


Real-time imaging of hydrogen peroxide dynamics in vegetative and pathogenic hyphae of Fusarium graminearum.
Balanced dynamics of reactive oxygen species in the phytopathogenic fungus Fusarium graminearum play key roles for development and infection. To monitor those dynamics, ratiometric analysis using the novel hydrogen peroxide (H2O2) sensitive fluorescent indicator protein HyPer-2 was established for the first time in phytopathogenic fungi. H2O2 changes the excitation spectrum of HyPer-2 with an excitation maximum at 405 nm for the reduced and 488 nm for the oxidized state, facilitating ratiometric readouts with maximum emission at 516 nm. HyPer-2 analyses were performed using a microtiter fluorometer and confocal laser scanning microscopy (CLSM). Addition of external H2O2 to mycelia caused a steep and transient increase in fluorescence excited at 488 nm. This can be reversed by the addition of the reducing agent dithiothreitol. HyPer-2 in F. graminearum is highly sensitive and specific to H2O2 even in tiny amounts. Hyperosmotic treatment elicited a transient internal H2O2 burst. Hence, HyPer-2 is suitable to monitor the intracellular redox balance. Using CLSM, developmental processes like nuclear division, tip growth, septation, and infection structure development were analyzed. The latter two processes imply marked accumulations of intracellular H2O2. Taken together, HyPer-2 is a valuable and reliable tool for the analysis of environmental conditions, cellular development, and pathogenicity.


Health physics activities in support of the thermal shield removal/disposal and core support barrel repair at the St. Lucie Nuclear Power Plant.
The health physics activities related to the removal and disposal of a thermal shield at a nuclear power plant and subsequent repairs to the core support barrel required increased planning relative to a normal refueling/maintenance outage. The repair of the core support barrel was a "first" in the nuclear power industry. Pre-job planning was of great concern because of extremely high radiation levels associated with the irradiated stainless steel thermal shield and core support barrel. ALARA techniques used in the preparation of the thermal shield for removal and shipment to the disposal site are discussed.


Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity.
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio. Here, we report the effect of this heterozygous intragenic deletion in CNTNAP2 on global gene expression and neuronal activity in the same cohort. Our findings suggest that heterozygous CNTNAP2 deletions affect genes involved in neuronal development and neuronal activity; however, these data reflect only one family trio and therefore more deletion carriers, with a variety of genetic backgrounds, will be needed to understand the molecular mechanisms underlying CNTNAP2 deletions.


Novel whole blood transcriptome signatures of changes in maximal aerobic capacity in response to endurance exercise training in healthy women.
Maximal aerobic exercise capacity [maximal oxygen consumption (V̇o2max)] is one of the strongest predictors of morbidity and mortality. Aerobic exercise training can increase V̇o2max, but inter-individual variability is marked and unexplained physiologically. The mechanisms underlying this variability have major clinical implications for extending human healthspan. Here, we report a novel transcriptome signature related to ΔV̇o2max with exercise training detected in whole blood RNA. We used RNA-Seq to characterize transcriptomic signatures of ΔV̇o2max in healthy women who completed a 16-wk randomized controlled trial comparing supervised, higher versus lower aerobic exercise training volume and intensity (4 training groups, fully crossed). We found significant baseline gene expression differences in subjects who responded to aerobic exercise training with robust versus little/no ΔV̇o2max, and differentially expressed genes/transcripts were mostly related to inflammatory signaling and mitochondrial function/protein translation. Baseline gene expression signatures associated with robust versus little/no ΔV̇o2max were also modulated by exercise training in a dose-dependent manner, and they predicted ΔV̇o2max in this and a separate dataset. Collectively, our data demonstrate the potential utility of using whole blood transcriptomics to study the biology of inter-individual variability in responsiveness to the same exercise training stimulus.


Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients.
Aspiration due to an age-related reduction in cough is a major cause of pneumonia in elderly persons. Because the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE) has been associated with the cough reflex, we studied whether this genetic polymorphism was also associated with the risk of pneumonia. We studied 1011 elderly inpatients (221 men and 790 women, mean [+/- SD] age of 82 +/- 7 years) in a long-term care hospital. The association between the ACE I/D polymorphism and the incidence of pneumonia (defined using specific criteria that included radiographic abnormalities) was assessed during an 8-month period that excluded the winter. Data were analyzed using proportional hazards models, with adjustment for age, sex, and other potential confounders. During follow-up, 87 cases (9%) of pneumonia occurred, 38 of which were fatal. The ACE DD allele (vs. ID + II) was associated with an increased risk of pneumonia (relative risk [RR] = 2.9; 95% confidence interval [CI]: 1.7 to 4.8, P < 0.001) and fatal pneumonia [RR = 4.4; 95% CI: 2.1 to 9.0; P < 0.0001). The ACE D allele is an independent risk factor for pneumonia in elderly persons.


[Late metabolic effects of the neo natal andogenisation or oestrogenisation of the rat (author's transl)].
Neo natal androgenisation of the female rat provoke at 3 months : 1) an accentuation of the insulin secretion at the glucose loading with the diet rich in saturated fat an a reduction with the diet rich in sucrose or rapesced oil; 2) Hypercholesterolemia with all the diets and 3) hypertriglyceridemia with diet rich in saturated fat or sucrose. Neo natal oestrogenisation of the male rata provoke at 3 months : 1) a reduction of the insulin secretion at the glucose loading with all the diets 2) hypercholesterolemia with the diet rich in saturated fats 3) hypertriglyceridemia with diets rich in M.C.T. or sucrose.


A Room-Temperature Stable Distonic Radical Cation.
Distonic radical cations (DRCs) with spatially separated charge and radical sites have, so far, largely been observed by gas-phase mass spectrometry and/or matrix isolation spectroscopy work. Herein, we disclose the isolation of a crystalline dicarbondiphosphide-based β-distonic radical cation salt 3.+ (BARF) (BARF=[B(3,5-(CF3 )2 C6 H3 )4 )]- ) stable at room temperature and formed by a one-electron-oxidation-induced intramolecular skeletal rearrangement reaction. Such a species has been validated by electron paramagnetic resonance (EPR) spectroscopy, single-crystal X-ray diffraction, UV/Vis spectroscopy and density functional theory (DFT) calculations. Compound 3.+ (BARF) exhibits a large majority of spin density at a two-coordinate phosphorus atom (0.74 a.u.) and a cationic charge located predominantly at the four-coordinate phosphorus atom (1.53 a.u.), which are separated by one carbon atom. This species represents an isolable entity of a phosphorus radical cation that is the closest to a genuine phosphorus DRC to date.


Alkylating agents from sugars: synthesis of chlorambucil derivatives carried by chiral glycosyl glycerols derived from D-glucosamine.
Chlorambucilamide derivatives involving chiral glycosyl glycerols derived from D-glucosamine were synthesized in good yield by coupling the chlorambucil moiety to the amino group of omega-amino-(omega-1)-hydroxyalkyl 2-acylamino-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosides, and subsequent hydrolysis of the benzylidene group. The starting material was easily available from 2-acetamido-2-deoxy-D-glucose. The bonding of 2,3,4,6-tetra-O-pivaloyl-beta-D-galactopyranosylamine to chlorambucil by formation of an amide function is also described.


Current principles of dietary therapy of diabetes mellitus.
"Diet therapy" is a term with multiple implications. Current concepts, and the principles upon which they are based, are examined, and an attempt is made to elaborate diet therapy in the context of the pathogenesis of diabetes.


Dietary acid load is associated with waist circumference in university students with low adherence to the Mediterranean diet: The potential role of ultra-processed foods.
Dietary acid load (DAL), as expressed by potential renal acid load (PRAL) and net acid production (NEAP), is connected to cardiometabolic disorders and obesity. Mediterranean diet relates to lower, while western diets to higher DAL values. The present study aimed to assess the association of PRAL and NEAP with adiposity measures in young adults (19.61 ± 3.15 years, mean ± standard deviation) and explore the implication of Mediterranean diet adherence and ultra-processed foods (UPF) intake in this relation. 346 students (269 women) participated. Anthropometry was performed, and a food frequency questionnaire was administered. The MedDietScore was calculated, UPF consumption was calculated based on the NOVA classification and PRAL/NEAP was estimated from published equations. Waist Circumference (WC) was transformed to WC-1 (1/WC) in order to achieve normality and run linear regression models. In subjects with MedDietScore ≤ 28.00, PRAL and NEAP were negatively associated with 1/WC (B = -1.594 × 10-5± 8 × 10-6, p = 0.044 for PRAL and B = -2.84 × 10-5 ± 1 × 10-5, p = 0.048 for NEAP). Moreover, in this subgroup, subjects with medium to high UPF intake i.e., in the 2nd or 3rd tertile of UPF intake representing more than 34.16% of energy, PRAL (2nd tertile B = -0.00007, SE = 0.00003, p = 0.018; 3rd tertile B = -0.00002, SE = 0.00001, p = 0.024) and NEAP (2nd tertile B = -0.00004, SE = 0.00002, p = 0.040; 3rd tertile B = -0.00007, SE = 0.00004, p = 0.055) were connected to central obesity. In similar models, PRAL and NEAP were not significant predictors of BMI. The DAL may be related to central obesity, especially in individuals with worse dietary quality, as reflected by lower adherence to the Mediterranean diet, and high intake of UPF. Nutrition guidance aiming at the reduction of DAL may be useful in the reduction of central obesity in these subgroups.


Molecular dynamics study on the hydrogen bond formation between α-hydrogen atom of L-Phe and N5 atom of FAD in the enzyme-substrate complex of the L-Phe oxidase reaction.
It is difficult to observe the structure of the enzyme-substrate complex (ES complex) experimentally, since the complex changes to the enzyme and its product during observation. The molecular dynamics (MD) approach is ideal to observe the structural change of enzyme and of substrate in the ES complex. Analyses on the complex of L-Phe oxidase with L-Phe by MD showed 1) the distance between the α-hydrogen atom of L-Phe and the N5 atom of isoalloxazine ring of FAD to be 2.64 ± 0.19 Å, and 2) the angle CA-HA-N5 atoms to be 141.5 ± 10.7°. This result clearly showed that the α-hydrogen atom forms the hydrogen bond with the N5 atom of isoalloxazine ring of FAD in the enzyme-substrate complex. Thus, the complex is ready for the hydrogen transfer from substrate to FAD in the key step of the oxidation of substrate by the enzyme.


Nonmedical personnel requirements for a pediatric radiology department.
The primary goal of a successful pediatric radiology department is to arrive at the correct clinical diagnosis as soon as possible. This responsibility is shared by radiologists, technologists, nurses, secretaries and clerks. The goal of this study was to determine the optimum number and type of nonmedical staff required to correctly and efficiently perform these examinations. The secondary purpose of our study was to evaluate the effectiveness of technologists, nurses, secretaries and clerks regarding: 1) patient waiting time, 2) performance of multiple examinations, 3) actual time for completion of examination(s), and 4) time required for the radiology report to be in the patient's medical history. Our study analyzed the number and type of radiological examinations performed for a variety of patients (emergency room patients, outpatients and inpatients) examined in the Radiology Department of Childrens Hospital of Los Angeles, a 345 bed metropolitan pediatric teaching hospital. The results of these evaluations will be discussed in this paper. Our data suggests that the time spent by the technologists in psychological support of the parents and the patient is inversely proportional to the time required to complete the test. Based on our study and the conclusions it presented, significant changes were implemented in our pediatric radiology department; specifically, the number of clerical positions was reduced from three to one with the use of computer-assisted check-in and chart follow-up within the department. Childrens Hospital of Los Angeles is a 345-bed metropolitan pediatric teaching hospital affiliated with the USC School of Medicine.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus.
Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention. The purpose of this study was to develop a risk model for atherothrombosis in patients with T2DM. We developed and validated a risk model for myocardial infarction (MI) or ischemic stroke (IS) in a pooled cohort of 42,181 patients with T2DM from 4 TIMI (Thrombolysis In Myocardial Infarction) clinical trial cohorts. Candidate variables were assessed with multivariable Cox regression, and independent variables (P < 0.05) were retained in the final model. Discrimination and calibration were assessed. Treatment interactions with dapagliflozin (sodium-glucose cotransporter-2 inhibitor) and evolocumab (proprotein convertase subtilisin/kexin type 9 inhibitor) were explored in the DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis In Myocardial Infarction 58) and FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trials, respectively. Sixteen variables were independent predictors of MI or IS. The model identified a >8-fold gradient of MI or IS rates between the top vs bottom risk quintiles in the validation cohort (3-year Kaplan-Meier rate: 14.9% vs 1.4%; P < 0.0001). C-indexes were 0.704 and 0.706 in the derivation and validation cohorts, respectively. The model was well-calibrated in both primary and secondary prevention. Absolute reduction in the rates of MI or IS tended to be greater in patients with higher baseline predicted risk for both dapagliflozin (absolute risk reduction: 2.1% vs 0.2%) and evolocumab (absolute risk reduction: 3.2% vs 1.0%). We developed and validated a risk score for atherothrombotic events, leveraging 16 routinely assessed clinical variables in patients with T2DM. The score has the potential to improve risk assessment and inform clinical decision-making.


Study on the gas desorption law and indicator influencing factors of fixed-size coal samples.
The prediction of dangerous hazards in working faces is an important link to prevent coal and gas outbursts. Improving the accuracy of predictive indicators is of great significance for reducing the phenomenon of being prominently below the critical value and ensuring safe production. The fixed-size desorption index K1 is one of the important indicators for coal face and gas outburst prediction. Based on the diffusion theory and the physical meaning of fixed-size coal samples, the mathematical expression of K1 is established by the self-developed high/low temperature pressure swing adsorption-desorption experimental system. According to the equation, the effects of gas pressure, loss time, coal particle size and diffusion coefficient on K1 are studied. The results show that the K1 index is logarithmically related to the gas pressure. Under the same conditions, the longer the loss time is, the smaller the measured K1 is, and the smaller the particle sizes of the drill cuttings are, the more notable the performance is; the diffusion coefficient represents the ability of gas to bypass micropores and the coal matrix. The greater the ability to bypass the matrix is, the larger the diffusion coefficient under the same conditions is, and the larger K1 is; the coal particle size has a greater influence on K1, and the smaller the size is, the more likely it is that the phenomenon of being prominently below the critical value occurs. Therefore, the particle size composition of coal during on-site measurements is crucial for obtaining the true K1 and the exact critical values.


Structural brain abnormalities in adult males with clefts of the lip and/or palate.
To evaluate brain morphology of adult males with nonsyndromic clefts of the lip and/or palate (NSCLP) in comparison to a matched healthy control group. Brain structure was measured using quantitative analysis of magnetic resonance images. Subjects with NSCLP had significant abnormalities in brain morphology consisting of abnormally enlarged anterior regions of the cerebrum, and decreased volumes of the posterior cerebrum and cerebellum. Overall, the most severely affected region was the left temporal lobe. Furthermore, these structural abnormalities were directly related to cognitive dysfunction. These findings highlight the important relationship and interplay between face and brain development.


De Novo Molecular Design with Chemical Language Models.
Artificial intelligence (AI) offers new possibilities for hit and lead finding in medicinal chemistry. Several instances of AI have been used for prospective de novo drug design. Among these, chemical language models have been shown to perform well in various experimental scenarios. In this study, we provide a hands-on introduction to chemical language modeling. A technique based on recurrent neural networks is discussed in detail, together with a step-by-step guide to applying this AI method for focused compound library design. The program code is freely available at URL: github.com/ETHmodlab/de_novo_design_RNN .


Calcification of the large bowel in schistosomiasis demonstrated by computed tomography.
Four cases are described in which large bowel calcification was demonstrated on CT. All four patients had mixed infection by Schistosoma haematobium and mansoni, the latter being responsible for this abnormality. Intestinal calcification by S. mansoni is unusual, but is especially well demonstrated by computed tomography.


[Flash electroretinography and pattern-type visual evoked potentials in early glaucoma].
The aim of this prospective study was to evaluate diagnostic sensitivity of flash-erg, oscillatory potentials (OPs), and pattern-visual evoked potentials (pVEP) in early glaucoma. Erg, OPs and pVEP were registered in 416 eyes primary open angle glaucoma (120 eyes), normal tension glaucoma (137), ocular hypertension (74), glaucoma-like discs (86) in age-matched groups, by Tomey 400. There were no statistically significant differences between parameters of flash-erg and pVEP of examined population and control group. Significant reduction in OPs amplitude in NTG patients were found. Flash erg and pVEP have low diagnostic value in early glaucoma. OPs could be useful in scientific research on pathogenesis of glaucomatous neuropathy.


[Primary and secondary neutropenia].
Severe chronic neutropenia (SCN) comprises a heterogeneous group of disorders with a common hematological and clinical phenotype characterized by absolute neutrophil counts (ANC) below 0,5 • 10(9)/l and increased risk of severe bacterial infections. The differentiation between primary and secondary neutropenia and the identification of causative gene mutations is of great importance for the estimation of prognosis. During childhood primary autoimmune neutropenia is the most frequent diagnosis, while secondary neutropenia predominates in adulthood. Despite the rarity, congenital, genetic neutropenias are of great value for research on normal and pathological hematopoiesis and have a fundamental impact on the current knowledge on hematopoiesis. To date mutations in more than 10 genes have been described which are mainly associated with an increased risk for leukemia.The treatment with hematopoietic growth factors has improved the long-term prognosis of SCN patients dramatically: Bacterial infections can be prevented and a normal participation in everyday life is possible.


Farnesylated proteins and cell cycle progression.
Post-translational modification of proteins by the addition of a farnesyl group is critical for the function of a number of proteins involved in signal transduction. Farnesylation facilitates their membrane association and also promotes protein-protein interaction. Recently, progress has been made in understanding the biological significance of farnesylation. First, effects of farnesyltransferase inhibitors (FTIs) on cancer cells have been examined using a variety of human cancer cells. This study showed that one of the major effects of FTIs is to alter cell cycle progression. Both G0/G1 enrichment and G2/M accumulation were observed depending on the cell line examined. Second, a number of novel farnesylated proteins have been characterized. Of these, Rheb and CENP-E,F are of particular interest. Rheb, a novel member of the Ras superfamily G-proteins, may play a role in the G1 phase of the cell cycle. CENP-E,F are centromere associated motors that play critical roles in mitosis. These results suggest important contributions of farnesylated proteins in the regulation of cell cycle progression.


Thermodynamic changes associated with the formation of the hydrated electron after photoionization of inorganic anions: a time-resolved photoacoustic study.
The enthalpy and volume changes, deltaH and deltaV, associated with the 266 nm laser-induced photoionization reactions of aqueous ferrocyanide and iodide ions, to yield the hydrated electron, e(-)aq, and oxidized products were determined by temperature-dependent time-resolved photoacoustics. The photoionization quantum yield as function of temperature (9-30 degrees C) was determined by laser flash photolysis actinometry. The obtained values were used for the calculation of thermodynamic parameters associated with the formation of e(-)aq, such as the apparent partial molar volume, V(o)e = 26 cm3 mol(-1), and the standard formation enthalpy and entropy changes, deltaH(o)f,e = 31 kJ mol(-1) and TdeltaS(o)f,e = 338 kJ mol(-1). These results indicate that the formation of the aqueous excess electron solution is governed by the increase in entropy in the three-dimensional hydrogen-bonding network of water.


Two pharmacologically distinct sodium- and chloride-coupled high-affinity gamma-aminobutyric acid transporters are present in plasma membrane vesicles and reconstituted preparations from rat brain.
Electrogenic sodium- and chloride-dependent gamma-aminobutyric acid (GABA) transport in crude synaptosomal membrane vesicles is partly inhibited by saturating levels of either of the substrate analogues cis-3-aminocyclohexanecarboxylic acid (ACHC) or beta-alanine. However, both of them together potently and fully inhibit the process. Transport of beta-alanine, which exhibits an apparent Km of about 44 microM, is also electrogenic and sodium and chloride dependent and competitively inhibited by GABA with a Ki of about 3 microM. This value is very similar to the Km of 2-4 microM found for GABA transport. On the other hand, ACHC does not inhibit beta-alanine transport at all. Upon solubilization of the membrane proteins with cholate and fractionation with ammonium sulfate, a fraction is obtained which upon reconstitution into proteoliposomes exhibits 4- to 10-fold-increased GABA transport. This activity is fully inhibited by low concentrations of ACHC and is not sensitive at all to beta-alanine. GABA transport in this preparation exhibits an apparent Km of about 2.5 microM and it is competitively inhibited by ACHC (Ki approximately 7 microM). These data indicate the presence of two GABA transporter subtypes in the membrane vesicles: the A type, sensitive to ACHC, and the B type, sensitive to beta-alanine.


PERT in patient placement.
The use of PERT as a standardized process for the placement of patients in community facilities is illustrated and advocated by the authors.


Variable life history characteristics along an altitudinal gradient in three species of Australian grasshopper.
Variation in life history characteristics was examined in three closely related species of univoltine grasshopper, Praxibulus sp., Kosciuscola cognatus and K. usitatus, along three altitudinal transects in South East Australia. With increasing altitude females lay fewer eggs in total over the summer season but lay their eggs in larger clutches. This pattern of variation, which is not related to variation in egg size, is observed both between and within species. The relationship between clutch size and altitude is similar in all three species but quite distinct reproductive strategies are maintained between species even where different species are found together at the same altitude. It is proposed that both the length and predictability of the summer growing season could be impratant in determining the evolution of life history characteristics along the altitudinal gradient.


Reply to comment on "Ultrasonographic scores for ileal Crohn's disease assessment: better, worse or the same as contrast‑enhanced ultrasound?
We read the comments by Nylund K et al. regarding our paper "Ultrasonographic scores for ileal Crohn's disease assessment: Better, worse or the same as contrast‑enhanced ultrasound?". Intestinal ultrasound has become one of the most valuable developments in the past decade, a non-invasive, well-tolerated exam, with an easy repeatability, and absence of sedation, ionizing radiation, or preparation. Particularly for inflammatory bowel disease, where there is a lack of agreement of patient's symptoms with disease activity, in an era where the paradigm of mucosal healing is changing to transmural healing, and with the emergence of several therapies leading to repeated imaging surveillance, it is essential to highlight the role of intestinal ultrasound. Although intestinal ultrasound is an increasingly used tool to monitor inflammatory bowel disease activity, there is no widely accepted reproducible activity index, since the methodology for the development of the scores was shown to be insufficient in most studies and none have been adequately validated (Bots et al., J Crohns Colitis 12:920-9, 2018). In our study, we showed that the contrast-enhanced ultrasound (CEUS) peak enhancement derived from the time-intensity curve (TIC) is a promising non-invasive emerging method with a good accuracy to correlate clinical and endoscopic activity in the terminal ileum, superior to intestinal ultrasound scores relying on bowel wall thickness and colour Doppler.


Combined procedures with laparoscopic cholecystectomy.
With advancement in laparoscopic surgery a number of surgical procedures can be performed combined with laparoscopic cholecystectomy in a single surgery. We evaluate the safety & efficacy of such surgeries. A retrospective review of all patients who had undergone combined procedures with laparoscopic cholecystectomy during January 2005 to June 2009 was performed. 3144 laparoscopic cholecystectomies were performed in the period from January 2005 to June 2009. Of these, 401 cases were combined with another procedure. The mean operative time was 80 min (range 50-270 min). The mean hospital stay was 3.2 days (range 1-5 days). The mean no. of days injectable analgesics was required was 2 days (range 1 day-4 days). Combined procedures provide patients with all the benefits of minimal invasive surgery and also give the benefit of single time anaesthesia without adding to post operative morbidity & hospital stay.


Central distribution of trigeminal and upper cervical primary afferents in the rat studied by anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin.
Injections of WGA-HRP were made in the rat trigeminal ganglion and C1-3 dorsal root ganglia (DRGs) to study the central projection patterns and their relations to each other. Trigeminal ganglion injections resulted in heavy terminal labeling in all trigeminal sensory nuclei. Prominent labeling was also observed in the solitary tract nucleus and in the medial parts of the dorsal horn at C1-3 levels, but labeling could be followed caudally to the C7 segment. Contralateral trigeminal projections were found in the nucleus caudalis and in the dorsal horn at C1-3 levels. The C1 DRG was found to be inconstant in the rat. When it was present, small amounts of terminal labeling were found in the external cuneate nucleus (ECN) and the central cervical nucleus (CCN). No dorsal horn projections were seen from the C1 DRG. Injections in the C2 DRG resulted in heavy labeling in the ECN, nucleus X, CCN, and dorsal horn, where it was mainly located in lateral areas. Labeling could be followed caudally to the Th 7 segment. C2 DRG projections also appeared in the cuneate nucleus (Cun), in all the trigeminal sensory nuclei, and in the spinal, medial, and lateral vestibular nuclei. A small C2 DRG projection was observed in the ventral cochlear nucleus. C3 DRG injections resulted in heavy labeling in both medial middle and lateral parts of the dorsal horn, in the ECN, and in nucleus X, whereas the labeling in the CCN was somewhat weaker. Smaller projections were seen to trigeminal nuclei, Cun, and the column of Clarke. Comparisons of the central projection fields of trigeminal and upper cervical primary afferents indicated a somatotopic organization but with a certain degree of overlap.


Early onset of overweight and obesity among low-income 1- to 5-year olds in New York City.
Early-childhood obesity has reached epidemic proportions, particularly among low-income, minority, urban children. Understanding the progression of obesity prevalence rates from infancy through early childhood can inform public health efforts to combat this epidemic and create developmentally appropriate strategies. In this study, we assessed the prevalence of overweight and obesity among urban 1- to 5-year olds and estimated risk by age and gender. We surveyed the medical records of a random sample of 1,713 children seen at a New York City primary-care network. Outcome measures were weight-for-length for <2-year olds and body mass index for 2- to 5-year olds. Overweight was defined as percentiles >or=85% to <95%, obesity >or=95%. Analysis utilized chi-square, logistic regression, and z tests. Between 1 and 5 years of age, overweight increased 3.7% to 20.8% and obesity 7.5% to 29.8% (p < 0.01). Risk increased with age: compared with 1-year olds, 5-year olds were 8.2 times as likely (95% confidence interval (CI) = 5.5-12.21) to be overweight or obese. Boys were more likely to be obese than girls (adjusted odds ratio = 1.3; 95% CI = 1-1.64). Significant increases in overweight and obesity occurred between ages 1 and 3 years (overweight, 3.7% to 16%, p < 0.01; obesity, 7.5% to 30.2%, p < 0.01). Among urban children, more than half were overweight or obese by age 5. Overweight and obesity rates increased dramatically between the ages of 1 and 3 years. Interventions aimed at this age period may have the greatest impact at preventing childhood obesity.


A Retrospective Study on the Eye-Related Quality of Life, Functional Vision, and Their Determinants Among Children Following Congenital and Developmental Cataracts Surgery and Its Impact on Their Families Using the PedEyeQ.
To evaluate the eye-related quality of life (ER-QOL), functional vision, and their determinants in children following congenital and developmental cataract surgery, as the impact on their families, using the Pediatric Eye Questionnaire (PedEyeQ). This was a retrospective cross-sectional study involving 107 children (aged 0-11 years) with congenital and developmental cataracts who had undergone surgery, as well as 59 visually healthy controls (aged 0-11 years). One parent for each child completed either the Proxy 0-4 PedEyeQ, the Proxy 5-11 PedEyeQ, or the Parent PedEyeQ, depending on their child's age. Mann-Whitney U and Kruskal-Wallis tests were then conducted to compare the differences between groups and to analyze their determinants. PedEyeQ scores were found to be lower in postoperative children with congenital and developmental cataracts compared with the control group across all study domains. The PedEyeQ Proxy 0 to 4 years' greatest mean difference was 27 points worse in the Functional Vision domain (95% CI -34 to -19; p < 0.001). We also found that the occurrence of nystagmus (p < 0.005) and strabismus (p < 0.005) were the major factors affecting participants' functional vision. The PedEyeQ Proxy 5 to 11 years' greatest mean difference was 23 points worse in this same domain (95% CI -30 to -15; p < 0.001), with nystagmus (p < 0.05) being the main determinant herein. Parent PedEyeQ 0 to 4 years' greatest difference was 46 points worse on the Worry about their Child's Eye Condition domain (95% CI -57 to -36; p < 0.001). Similarly, parents of children with ophthalmologic abnormalities, including nystagmus (p < 0.001) and strabismus (p < 0.05), were significantly more worried about their children's eye condition. Parent PedEyeQ 5 to 11 years' greatest difference was also found to be 30 points worse on the Worry about their Child's Eye Condition domain (95% CI -43 to -17; p < 0.005). Children who have undergone congenital and developmental cataract surgery experience a lower quality of life and reduced functional vision. Their families are also significantly and adversely affected herein. Thus, more attention is needed on these groups, with more focused measures being administered to both children and their families.


A systematic review and meta-analysis on the prevalence of antibiotic-resistant Listeria species in food, animal and human specimens in Iran.
The aim of this study was to determine the antimicrobial resistance characteristics of Listeria species isolated from foods and food processing environments, animal and human specimens in Iran. A systematic review of the papers published in Persian and English languages up to 20th May 2019 and indexed in the Scientific Information Database, PubMed, Scopus and Google Scholar databases using related keywords was conducted. Eligible articles were selected based on the predefined inclusion and exclusion criteria, followed by data extraction and meta-analysis using random-effects or fixed-effects models. A total of 27 articles were found reporting antibiotic resistance patterns of different Listeria species using disk diffusion method. Among Listeria species, Listeria monocytogenes resistance to commonly used antibiotics i.e. penicillin, ampicillin and gentamicin was as follows: 34.5%, 26.4%, 8.9% in isolates from foods and food processing environments, 47.1%, 29.5%, 9.2% in isolates from animal specimens and 56.8%, 29.5%, 32.4% in human strains, respectively. A high prevalence of L. monocytogenes strains resistant to penicillin, ampicillin and gentamicin was observed in Iran. Our findings suggested that trimethoprim/sulfamethoxazole, vancomycin and ciprofloxacin can be used as alternatives in the treatment of human listeriosis in Iran due to their low resistance rates.


Usage of removable partial dentures in Saudi male patients after 1 year telephone interview.
The success of removable partial dentures (RPDs) is partly dependent on patients' acceptance and compliance in using them. The purpose of this study was to describe the usage of removable partial dentures (RPDs) by patients 1 year after insertion and to evaluate the factors that influence their denture usage. Forty-seven patients who received 75 new RPDs at the undergraduate clinic of College of Dentistry, King Saud University, were contacted by telephone 1 year later for an interview. The questions covered denture usage, patient's satisfaction and reasons for non-use. Results showed that 36% of patients discarded or occasionally used their RPDs. There was no significant association between denture usage and RPD experience, location or Kennedy classification. A significantly more RPD rejection was found when it was opposed by natural teeth or complete denture. The most quoted reason for RPD rejection was pain and discomfort. Despite the short follow-up period, RPDs were poorly accepted by patients treated by undergraduate students.


Isolation of purified insoluble aortic collagen.
The chemistry of collagen from major blood vessels, such as the aorta, is poorly defined because of problems encountered in solubilization techniques. Normal extraction of calf aorta with acetic acid and/or pepsin does not yield significant quantities of collagen. However, treatment of the aorta with purified pancreatic elastase results in a residue containing a significant portion of the collagen. The amino acid analysis, the acrylamide gel electrophoretic patterns and the electron micrographs of this residue display characteristics consistent with relatively pure collagen. Using this purified collagen preparation approximately 90% of the collagenous material present can be solubilized by pepsin treatment.


Changes in rates of early exclusive breast feeding in South Africa from 2010 to 2013: data from three national surveys before and during implementation of a change in national breastfeeding policy.
Between 1998 and 2009 reported exclusive breastfeeding (EBF) rates in South African infants, aged 0-6 months, ranged from 6.2% to 25.7%. In 2011, the National Minister of Health shifted policy to promote 'exclusive' breast feeding for all women in South Africa irrespective of HIV status (Tshwane Declaration of Support for Breastfeeding in South Africa). This analysis examines early EBF prior to and through implementation of the declaration. Data from the three South Africa national, cross-sectional, facility-based surveys, conducted in 2010, 2011-12 and 2012-13, were analysed. Primary health facilities (n=580) were randomly selected after a stratified multistage probability proportional-to-size sampling to provide valid national and provincial estimates. A national sample of all infants attending their 6 weeks vaccination at selected facilities. The number of caregiver-infant pairs enrolled were 10 182, 10 106 and 9120 in 2010, 2011-12, and 2012-13, respectively. Exclusive breast feeding as measured using structured 24 hours recall plus prior 7 days (8 days inclusive prior to day interview) and WHO definition. The adjusted OR comparing EBF prevalence in 2011-12 and 2012-13 with 2010 were 2.08 and 5.51, respectively. Mothers with generally higher socioeconomic status, HIV-positive, unplanned pregnancy, primipara, postcaesarean delivery, resided in certain provinces and women who did not receive breastfeeding counselling had significantly lower odds of EBF. With what seemed to be an intransigently low EBF rate since 1998, South Africa saw an increase in early EBF for infants aged 4-8 weeks from 2010 to 2013, coinciding with a major national breastfeeding policy change. These increases were seen across all provinces and subgroups, suggesting a population-wide effect, rather than an increase in certain subgroups or locations. While these increases in EBF were significant, the 59.1% prevalence is still below desired levels of early EBF. Further improvements in EBF programmes are needed.


The box A domain of high mobility group box-1 protein as an efficient siRNA carrier with anti-inflammatory effects.
High mobility group box-1 (HMGB-1) is a DNA binding nuclear protein and pro-inflammatory cytokine. The box A domain of HMGB-1 (rHMGB-1A) exerts an anti-inflammatory effect, inhibiting wild-type HMGB-1 (wtHMGB-1). In this study, HMGB-1A was evaluated as an siRNA carrier with anti-inflammatory effects. HMGB-1A was expressed and purified by consecutive nickel chelate chromatography, cationic exchange chromatography, and polymixin B chromatography. Purified rHMGB-1A demonstrated an anti-inflammatory effect, reducing tumor necrosis factor-α (TNF-α) in wtHMGB-1 or lipopolysaccharide (LPS) activated macrophages. In gel retardation assay, rHMGB-1A formed a stable complex with siRNA at or above a 1:2 weight ratio (siRNA:rHMGB-1A). A heparin competition assay showed that an siRNA/rHMGB-1A complex released siRNA more easily than an siRNA/polyethylenimine (PEI, 25 kDa) complex. Luciferase siRNA/rHMGB-1A reduced firefly luciferase expression at a similar level as luciferase siRNA/PEI complex. Furthermore, TNF-α siRNA/rHMGB-1A synergistically reduced TNF-α expression in LPS activated macrophages. Therefore, rHMGB-1A may be useful as an siRNA carrier with anti-inflammatory effects in siRNA therapy for various inflammatory diseases.


Overexpression, purification and properties of alcohol dehydrogenase IV from Saccharomyces cerevisiae.
We have purified ADHIV, a novel alcohol dehydrogenase (ADH) isozyme in the yeast Saccharomyces cerevisiae, after increasing the normally low amount of ADHIV protein in laboratory strains. This was done by overexpression of the structural gene (ADH4) on a 2micro-based multicopy vector. Characterization of the purified enzyme revealed a dimeric structure as well as a different substrate specificity and pH profile as compared to other alcohol dehydrogenase isozymes. On the other hand, we could demonstrate that ADHIV is activated by zinc ions, like the other yeast alcohol dehydrogenase isozymes, and not by ferrous ions, like a structurally similar alcohol dehydrogenase from the bacterium Zymomonas mobilis.


[Methodological studies on the hemolytic anti-bovine gamma globulin plaque technic].
Sheep red blood cells (SRBC) coated with specific bovine antibodies are suitable to detect anti-bovine gammaglobulin (BGG)-antibody-forming cells with the hemolytic plaque technique. The number of the definable anti-BGG-plaque-forming cells is dependent on the antibody density per SRBC. The developed plaques are specific for BGG. They are to inhibit with BGG only not with other proteins. The cellular kinetics of the anti-BGG response is to follow up in the spleen and poplitea lymph nodes of the immunized mice with this modification of the hemolytic plaque technique. The results are discussed.


NIST radiochemistry intercomparison program: a summary of four-year performance evaluation study. National Institute of Standards and Technology.
This paper summarizes the methods currently applied by the National Institute of Standards and Technology (NIST) for the preparation and verification of environmental and radiobioaasay performance evaluation materials for the traceability testing of low-level radioactivity measurements. The evaluation of measurement quality of the all participants indicated that over 90% of the intercomparison results complied with ANSI N42.22 and/or HPS N13.30 standards. Overall, the differences from the NIST values observed for all test nuclides and matrices are less than -7%, with a typical measurement precision better than 10% (1 s). The dependency of measurement quality on the test radionuclides, sample matrices, and radiochemical methods is identified by statistical analyses.


The effect of Expanding Maternal and Neonatal Survival interventions on improving the coverage of labor monitoring and complication prevention practices in hospitals in Indonesia: A difference-in-difference analysis.
To assess whether the Expanding Maternal and Neonatal Survival (EMAS) program was associated with improved care provided during hospital-based childbirth. A quasi-experimental study with two rounds of data collection examined whether EMAS interventions improved facility-based labor and childbirth care. Direct clinical observations were conducted for 1208 deliveries across 13 hospitals in 12 districts. Primary outcome measures included implementation of standard practices to reduce the risk of complications during labor and childbirth for both women and newborns. Adjusted difference-in-difference analysis compared the mean difference in quality scores between EMAS intervention hospitals and comparison sites and consistently found significantly better performance in EMAS sites: 14 points higher for labor monitoring (β-coefficient 14.1; 95% confidence interval [CI], 7.1-21.0); 38 points higher for newborn resuscitation readiness (β-coefficient 38.1; 95% CI, 31.1-45.2); and 33 points higher for infection prevention practices (β-coefficient 32.6; 95% CI, 28.5-36.8). EMAS approaches emphasizing facility readiness and adherence to performance standards significantly improved labor monitoring and complication prevention practices during childbirth.


Serum selenium concentrations correlate significantly with inflammatory biomarker high-sensitive CRP levels in Hungarian gestational diabetic and healthy pregnant women at mid-pregnancy.
Selenium is an essential trace element and a component of various enzymes with antioxidant functions. High-sensitive C-reactive protein (hsCRP) is an early indicator of increased lipid peroxidation. The serum selenium concentration, lipid parameters, and hsCRP values of gestational diabetic pregnant women (GD), control pregnant women (CP), and healthy nonpregnant controls (HC) were compared. Blood was taken between the 24th and the 28th week of pregnancy when the oral glucose tolerance test was performed. Selenium concentration was determined by atomic absorption spectrometry after hydride generation. HsCRP was measured by immunturbidimetry. HC had significantly higher serum selenium concentrations than GD and CP women (HC = 77.4 +/- 14.82, GD = 51.7 +/- 11.62, and CP = 40.5 +/- 8.03 microg/l, respectively). HsCRP values of both GD and nondiabetic pregnant women were significantly higher compared to controls. Significant negative correlations were found between serum selenium and total cholesterol, low-density lipoprotein cholesterol, and hsCRP values indicating that low selenium levels are associated with increased lipid peroxidation. Serum selenium concentrations of Hungarian pregnant women are low compared to internationally published data.


The identification, adaptive evolutionary analyses and mRNA expression levels of homeobox (hox) genes in the Chinese mitten crab Eriocheir sinensis.
Arthropods are the largest group in the animal kingdom and are morphologically characterized by heterorhythmic segments. Brachyuran decapod crustaceans undergo brachyurization metamorphosis in the early developmental process, characterized by a reduced abdomen that is folded beneath the cephalothorax and inserted between the pereiopods or in a special cavity. As the main cause of major alterations in the evolution of animal body plans, Hox genes encode transcription factors and are involved in bilaterian anterior-posterior axis patterning. We found eight Hox genes (labial, proboscipedia, Deformed, zerknüllt, Sex combs reduced, Antennapedia, Ultrabithorax, fushi tarazu, abdominal-A and Abdominal-B) in Eriocheir sinensis. The phylogenetic topology of 13 arthropod Hox genes was closely related to traditional taxonomic groupings. Genome collinearity analysis was performed using genomic data and chromosomal location data of E. sinensis and Portunus trituratus. We found that their chromosomes were highly collinear, and there was a corresponding collinear relationship between the three Hox genes (lab, ftz and Abd-B). The mRNA expression levels of Scr and Antp fluctuated significantly in different developmental stages of E. sinensis, especially in the brachyurization stages. Evolutionary analysis indicated the presence of positively selected sites in Ubx. In this study, we used genome-wide analysis to identify and analyze all members of the Hox genes in E. sinensis. Our data will contribute to a better understanding of Hox genes in E. sinensis and provide useful molecular evolutionary information for further investigation on their roles in the brachyurization of crabs.


Effect of school feeding program on academic performance of primary school adolescents: A prospective cohort study.
School Feeding Programs (SFPs) in low-income countries help vulnerable children learn better and maintain their health through the provision of nutritious food to school children. Ethiopia scaled up the implementation of SFP in Addis Ababa. We aimed at evaluating the effect of the SFP on the school performance of primary school adolescents in Addis Ababa, Central Ethiopia. A prospective cohort study design was employed on 322 SFP-beneficiary and equal-size non-beneficiary adolescents. SPSS version 24 and multivariable linear regression models were used. In linear regression, unadjusted model (Model 1), compared with the non-school-fed adolescent, the mean difference in difference of average academic scores of school-fed adolescents was higher by 2.11 (β 2.11, 95% CI 1.39-2.83). The beta coefficient remained positive after adjusted for age and sex (Model 2: β 2.11, 95% CI 1.39-2.83), sociodemographic variable (Model 3: β 2.16, 95% CI 1.45-2.88), health and lifestyle variable (Model 4: β 2.21, 95% CI 1.38-3.04). In the final model, adjusted for model five, school absenteeism, there was a significant difference in favor of school-fed adolescents on GPA-score (Model 5: β 2.32, 95% CI 1.47-3.17). Furthermore, being adolescents in middle tertile wealth index families decrease GPA by 1.22 (β -1.22, 95% CI -2.19 to -0.26) as compared to high tertile wealth index. School feeding was positively associated with academic performance. However, these changes may not be meaningful to generate a firm conclusion on the utility of school feeding in improving the academic performance of adolescents.


Functional role of the olivo-cochlear bundle: a motor unit control system in the mammalian cochlea.
A fiber optic lever is applied to the measurement of the motion of the basilar membrane motion in guinea pigs. In response to intense tones from either ear, the motion includes a substantial summating shift in the mean position in addition to a travelling wave originally described by von Békésy. His stroboscopic technique and most techniques used since have been concentrated upon measuring vibrations of the basilar membrane synchronous with the stimulus and have been insensitive to variations in the baseline position such as a summating component of motion analogous to the extracellular summating potential. In addition to the role of the outer hair cells in providing normal hearing sensitivity, they evidently play a role in regulating the mean position of the basilar membrane. For a fixed frequency, the polarity of the mean position varies systematically with sound level and place and summates with time since onset. Since these cells are the target cells for the olivocochlear bundle, homeostasis in the cochlea would appear to be linked efferent function and involve cochlear mechanics. The negative damping hypothesis asserts that hair cell activity is necessary for low thresholds. The results presented here demonstrate that OHC activity exists independent of neural thresholds. The discussion develops the concept that threshold losses are due to a mismatch of opposing tonic forces which normally maintain the mean position of the basilar membrane. Structure is examined in relation to function and the group of outer hair cells innervated by a single medial efferent neuron is identified as a motor unit. Implications of central control of individual motor units include peripheral involvement in selective attention tasks.


Second-trimester cardiovascular biometry in growth-restricted fetuses; a multicenter cohort study.
Intrauterine growth restriction is associated with an increased risk of cardiovascular changes neonatally. However, the underlying pathways are poorly understood, and it is not clear whether the dysfunction is already present in the fetus. This study aimed to investigate fetal cardiac dimensions assessed from images at the second trimester anatomy scan from fetuses classified postnatally as small for gestational age and intrauterine growth restricted and compare them with appropriate for gestational age fetuses. This was a substudy from The Copenhagen Baby Heart Study, a prospective, multicenter cohort study including fetuses from the second trimester of pregnancy in Copenhagen from April 2016 to October 2018. The mothers were recruited at the second trimester anatomy scan that included extended cardiovascular image documentation followed by consecutively measured heart biometry by 2 investigators blinded for the pregnancy outcome. The fetuses were classified postnatally as small for gestational age and intrauterine growth restricted according to the International Society of Ultrasound in Obstetrics and Gynecology 2020 guidelines using birthweight and with a retrospective assessment of Doppler flow. The mean differences in the cardiovascular biometry were adjusted for gestational age at the time of the second trimester scan and the abdominal circumference. The z-scores were calculated, and the comparisons were Bonferroni corrected (significance level of P<.005). Receiver operating characteristic curves were computed after performing backward regression on several maternal characteristics and biomarkers. We included 8278 fetuses, with 625 (7.6%) of them being small for gestational age and 289 (3.5%) being intrauterine growth restricted. Both small for gestational age and intrauterine growth restricted fetuses had smaller heart biometry, including the diameter at the location of the aortic valve (P<.005), the ascending aorta in the 3-vessel view (P<.005), and at the location of the pulmonary valve (P<.005). The intrauterine growth restricted group had significantly smaller hearts with respect to length and width (P<.005) and smaller right and left ventricles (P<.005). After adjusting for the abdominal circumference, the differences in the aortic valve and the pulmonary valve remained significant in the intrauterine growth restricted group. Achievement of an optimal receiver operating characteristic curve included the following parameters: head circumference, abdominal circumference, femur length, gestational age, pregnancy associated plasma protein-A multiples of median, nullipara, spontaneous conception, smoking, body mass index <18.5, heart width, and pulmonary valve with an area under the curve of 0.91 (0.88-0.93) for intrauterine growth restricted cases. Intrauterine growth restricted fetuses had smaller prenatal cardiovascular biometry, even when adjusting for abdominal circumference. Our findings support that growth restriction is already associated with altered cardiac growth at an early stage of pregnancy. The heart biometry alone did perform well as a screening test, but combined with other factors, it increased the sensitivity and specificity for intrauterine growth restriction.


The Impact of Establishing a Dedicated Liver Surgery Program at a University-affiliated Hospital on Workforce, Workload, Surgical Outcomes, and Trainee Surgical Autonomy and Academic Output.
To detail the implementation of a dedicated liver surgery program at a university-affiliated hospital and to analyze its impact on the community, workforce, workload, complexity of cases, the short-term outcomes, and residents and young faculties progression toward technical autonomy and academic production. Due to the increased burden of liver tumors worldwide, there is an increased need for liver centers to better serve the community and facilitate the education of trainees in this field. The implementation of the program is described. The 3 domains of workload, research, and teaching were compared between 2-year periods before and after the implementation of the new program. The severity of disease, complexity of procedures, and subsequent morbidity and mortality were compared. Compared with the 2-year period before the implementation of the new program, the number of liver resections increased by 36% within 2 years. The number of highly complex resections, the number of liver resections performed by residents and young faculties, and the number of publications increased 5.5-, 40-, and 6-fold, respectively. This was achieved by operating on more severe patients and performing more complex procedures, at the cost of a significant increase in morbidity but not mortality. Nevertheless, operations during the second period did not emerge as an independent predictor of severe morbidity. A new liver surgery program can fill the gap between the demand for and supply of liver surgeries, benefiting the community and the development of the next generation of liver surgeons.


Social Enhancement of Adult Neurogenesis in Zebrafish is Not Regulated by Cortisol.
In Mammals adult neurogenesis is influenced by environmental conditions, and the glucocorticoid hormones (GC) play a major role in this regulation. In contrast in fish, the study of the effects of cortisol on the regulation of environmental driven adult neurogenesis has produced conflicting results. While in some species elevated cortisol levels impair cell proliferation, in others, it promotes cell proliferation and differentiation. This lack of consistency may be explained by methodological differences across studies, namely in the stimuli and/or cortisol treatments used. Here, we tested the effects of the social environment on adult neurogenesis, considering a positive and a negative social context, and different durations of cortisol exposure. We hypothesise that there is an interaction between the valence of the social environment and cortisol, such that elevated acute cortisol experienced during social interactions only have a detrimental effect on neurogenesis in negative social contexts. Therefore, fish were exposed to a positive (conspecific shoal) or negative (predator) social experience, and the interaction between the valence of the social context and cortisol exposure (acute and chronic) was tested. Our results indicate that adult neurogenesis is modulated by the social environment, with the number of newly generated cells being dependent on the valence of the social information (positive > negative). These effects were independent of cortisol, either for acute or chronic exposure, highlighting the social environment as a key factor in the modulation of cell proliferation in the adult zebrafish brain, and rejecting a role for cortisol in this modulation.


Missense mutations near the N-glycosylation site of the A2 domain lead to various intracellular trafficking defects in coagulation factor VIII.
Missense mutation is the most common mutation type in hemophilia. However, the majority of missense mutations remain uncharacterized. Here we characterize how hemophilia mutations near the unused N-glycosylation site of the A2 domain (N582) of FVIII affect protein conformation and intracellular trafficking. N582 is located in the middle of a short 310-helical turn (D580-S584), in which most amino acids have multiple hemophilia mutations. All 14 missense mutations found in this 310-helix reduced secretion levels of the A2 domain and full-length FVIII. Secreted mutants have decreased activities relative to WT FVIII. Selected mutations also lead to partial glycosylation of N582, suggesting that rapid folding of local conformation prevents glycosylation of this site in wild-type FVIII. Protease sensitivity, stability and degradation of the A2 domain vary among mutants, and between non-glycosylated and glycosylated species of the same mutant. Most of the mutants interact with the ER chaperone BiP, while only mutants with aberrant glycosylation interact with calreticulin. Our results show that the short 310-helix from D580 to S584 is critical for proper biogenesis of the A2 domain and FVIII, and reveal a range of molecular mechanisms by which FVIII missense mutations lead to moderate to severe hemophilia A.


Molecular wires, switches, and memories.
Design and measurements of molecular wires, switches, and memories offer an increased device capability with reduced elements. We report: Measurements on through-bond electronic transport properties of nanoscale metal-1,4-phenylene diisocyanide-metal junctions are reported, where nonohmic thermionic emission is the dominant process, with isocyanide-Pd showing the lowest thermionic barrier of 0.22 eV; robust and large reversible switching behavior in an electronic device that utilizes molecules containing redox centers as the active component, exhibiting negative differential resistance (NDR) and large on-off peak-to-valley ratio (PVR) are realized; erasable storage of higher conductivity states in these redox-center-containing molecular devices are observed; and a two-terminal electronically programmable and erasable molecular memory cell with long bit retention time is demonstrated.


Displaced scapular fractures: indication and long-term results of open reduction and internal fixation.
Displaced scapular fractures are often found in polytraumatized patients. In emergency treatment they assume a minor role. Advances in dealing with severely injured patients in most instances allow us to perform an operation on the fractured scapula within the first 2 weeks after injury. A differentiated approach is necessary as exclusively conservative treatment does not always bring about good results. From 1981-1991 we performed open reduction and internal fixation (ORIF) in 25 patients with displaced fractures of the scapula. The long-term results could be assessed in 20 patients after an average of 6.1 years. The different types of fractures were classified according to Habermeyer/Ideberg, and the Constant score was used in the evaluation of results. Some 64% of patients were involved in road accidents, and 64% suffered concomitant injuries. Articular fractures (n = 6) were the most common ones, followed by fractures of the coracoid process (n = 5) and the neck of the scapula (n = 2). There was no early postoperative complication, and follow-up showed a breakage of K-wires in one patient (fracture of the acromion). Thirteen patients obtained a very good, two patients a good, four a fair and one a poor result (according to the Constant score). Fractures of the scapular neck had the best results in terms of pain, daily activity, range of motion, and strength) as compared with fractures of the glenoid and apophyseal fractures.(ABSTRACT TRUNCATED AT 250 WORDS)


Delivery to the gut microbiota: A rapidly proliferating research field.
The post genomic era has brought breakthroughs in our understanding of the complex and fascinating symbiosis we have with our co-evolving microbiota, and its dramatic impact on our physiology, physical and mental health, mood, interpersonal communication, and more. This fast "proliferating" knowledge, particularly related to the gut microbiota, is leading to the development of numerous technologies aimed to promote our health via prudent modulation of our gut microbiota. This review embarks on a journey through the gastrointestinal tract from a biomaterial science and engineering perspective, and focusses on the various state-of-the-art approaches proposed in research institutes and those already used in various industries and clinics, for delivery to the gut microbiota, with emphasis on the latest developments published within the last 5 years. Current and possible future trends are discussed. It seems that future development will progress toward more personalized solutions, combining high throughput diagnostic omic methods, and precision interventions.


Value of ¹⁸F-FDG-PET/CT in the detection of recurrent hepatocellular carcinoma after hepatectomy or radiofrequency ablation: a comparative study with contrast-enhanced ultrasound.
To evaluate the role of positron emission tomography/computer tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG-PET/CT) in detecting hepatocellular carcinoma (HCC) recurrence after hepatectomy and/or radiofrequency ablation (RFA) and to compare its efficacy with contrast-enhanced ultrasound (CEUS). A total of 36 HCC patients were included in this study. All patients underwent both (18) F-FDG-PET/CT and CEUS at least once for the diagnosis of HCC recurrence. The time interval between PET/CT and CEUS was 14 ± 3 days. All patients were followed up for at least 24 months. In all, 32 patients were confirmed to have HCC recurrence by pathology and clinical follow-up. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18) F-FDG-PET/CT for intrahepatic HCC recurrence were 96.7%, 83.3%, 96.7%, 83.3% and 94.4%, respectively. The corresponding values of CEUS were 56.7%, 100%, 100%, 31.6% and 63.9%, respectively. The sensitivity and accuracy of (18) F-FDG-PET/CT for the diagnosis of HCC recurrence were significantly higher than those of CEUS (P < 0.01, respectively). Compared with CEUS, (18) F-FDG-PET/CT has higher sensitivity and accuracy in detecting the local recurrence of HCC after hepatectomy and/or RFA. It can be used to detect recurrent extrahepatic lesions of HCC effectively.


Olfactory marker protein regulates adipogenesis via the cAMP-IκBα pathway.
Olfactory marker protein (OMP) regulates olfactory transduction and is also expressed in adipose tissue. Since it serves as a regulatory buffer for cyclic AMP (cAMP) levels, we hypothesized that it plays a role in modulating adipocyte differentiation. To determine the role of OMP in adipogenesis, we examined the differences in body weight, adipose tissue mass, and adipogenic or thermogenic gene expression between high-fat diet-fed control and Omp-knockout (KO) mice. cAMP production, adipogenic gene expression, and cAMP response element binding protein (CREB) phosphorylation were measured during the differentiation of 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). RNA sequencing was performed to determine the gene expression patterns responsible for the reduction in adipogenesis when Omp was deleted. Body weight, adipose tissue mass, and adipocyte size decreased in Omp-KO mice. Furthermore, cAMP production and CREB phosphorylation reduced during adipogenesis induced in Omp-/- MEFs, and the Nuclear factor kappa B was activated due to significantly reduced expression of its inhibitor. Collectively, our results suggest that loss of OMP function inhibits adipogenesis by affecting adipocyte differentiation.