Novel pulmonary perfusion imaging using chest digital dynamic radiography for pulmonary artery sarcoma.
Chest digital dynamic radiography (DDR) is a novel method for evaluating pulmonary perfusion and ventilation. It could depict ventilation-perfusion mismatch in a pulmonary artery sarcoma with severe stenosis in the right pulmonary artery. This report is the first demonstration of ventilation-perfusion mismatch in a malignant neoplasm using DDR.


Scoliosis at less than 30 degrees. Properties of the evolutivity (risk of progression).
In an attempt to find prognostic factors for mild scoliosis, the first clinical and radiologic data of 159 subjects with idiopathic scoliosis less than 30 degrees were correlated with the annual speed of progression estimated graphically by further examinations. Thoracic and double major are more progressive than thoracolumbar and lumbar. The correlation with rate of progression is better for supine angle than for standing angle. Curves with low supine angles are those that have great relative collapse and low risk of progression. Only the rib hump of thoracic and thoracolumbar are correlated with evolutivity. Predictive equations give less approximation for individual prognosis than a previous graphic method, so they are not used. Approximately 73% of scoliosis have evolutivities less than 6 degrees per year and required nocturn corrective treatment.


Robotic-assisted laparoscopic cystectomy with ileal conduit for urinary diversion.
This case demonstrates the need for flexibility when approaching major abdominal surgery through a robotic approach. While the case was initiated with robotic technology, it ultimately had to be converted to an open procedure for reasons of patient safety and to ensure a good surgical outcome.


Coordination pattern and reactivity of two model peptides from porin protein P1.
It has been reported that numerous of Fusobacterium nucleatum outer membrane proteins take part in cancerogenesis. Therefore, it is very interesting to study their interactions with metal ions and the ability to produce reactive oxygen species, which may be involved in cancer progression. Since investigations of metal binding to proteins are often based on fragments that contain the metal-binding domains, designing model peptides should be very mindful. As was shown in this paper, very similar protein fragments may behave differentially. Herein, combined potentiometric, spectroscopic, and computational studies were performed to determine metal ion binding by ligands constituting fragments of porin protein P1. Two studied tetrapeptides (Ac-KEHK-NH2 and Ac-EHKA-NH2) that have common EHK motif have different coordination properties and reactivity. Therefore, we should be cautious when transferring the behavior of small peptide fragments to whole protein.


A Ceramic PZT-based PMUT Array for Endoscopic Photoacoustic Imaging.
In this paper, we present the design, fabrication, and characterization of a compact 4 × 4 piezoelectric micromachined ultrasonic transducer (pMUT) array and its application to photoacoustic imaging. The uniqueness of this pMUT array is the integration of a 4 μm-thick ceramic PZT, having significantly higher piezoelectric coefficient and lower stress than sol-gel or sputtered PZT. The fabricated pMUT array has a small chip size of only 1.8 × 1.6 mm2 with each pMUT element having a diameter of 210 μm. The fabricated device was characterized with electrical impedance measurement and acoustic sensing test. Photoacoustic imaging has also been successfully demonstrated on an agar phantom with a pencil lead embedded using the fabricated pMUT array.


Polyploid giant cancer cells and ovarian cancer: new insights into mitotic regulators and polyploidy†.
Current first-line treatment of patients with high-grade serous ovarian cancer (HGSOC) involves the use of cytotoxic drugs that frequently lead to recurrent tumors exhibiting increased resistance to the drugs and poor patient survival. Strong evidence is accumulating to show that HGSOC tumors and cell lines contain a subset of cells called polyploidy giant cancer cells (PGCCs) that act as stem-like, self-renewing cells. These PGCCs appear to play a key role in tumor progression by generating drug-resistant progeny produced, in part, as a consequence of utilizing a modified form of mitosis known as endoreplication. Thus, developing drugs to target PGCCs and endoreplication may be an important approach for reducing the appearance of drug-resistant progeny. In the review, we discuss newly identified regulatory factors that impact mitosis and which may be altered or repurposed during endoreplication in PGCCs. We also review recent papers showing that a single PGCC can give rise to tumors in vivo and spheroids in culture. To illustrate some of the specific features of PGCCs and factors that may impact their function and endoreplication compared to mitosis, we have included immunofluorescent images co-localizing p53 and specific mitotic regulatory, phosphoproteins in xenografts derived from commonly used HGSOC cell lines.


Moderate operation scales of agricultural land under the greenhouse and open-field production modes based on DEA model in mountainous areas of southwest China.
The identification of the moderate scale of agricultural land was recognized as one of the key measures promoting sustainable agriculture development. However, due to the research gap in mountainous areas, new agricultural business entities (NABE) in these areas usually either refer to the plain area or simply pursue large scale, resulting in low production efficiency and even posing a threat to their sustainable survival. In this study, the Data Envelopment Analysis (DEA) model and Tobit regression model tools were employed to quantitatively reveal the moderate scale and key driving factors of agricultural land under the scale operation modes of greenhouse and open-field types. It was based on 154 NABE questionnaires in the mountainous areas around the Sichuan Basin in China, where NABEs are flourishing. The findings show an approximately "inverted U-shaped" curve relationship between NABE's production efficiency and their planting scale. The primary reason for the failure of NABE to achieve an overall high level of production efficiency is scale inefficiency. The optimal scale intervals for the greenhouse and open-field types of scale operation modes are 3.0-4.3 ha and 3.3-5.0 ha, respectively. Business entities' age, land circulation scale, land rent, and agricultural insurance are common factors that influence the scale efficiencies of both the greenhouse and open-field types. Accordingly, policy interventions regarding the guidance of moderate-scale operation of agricultural land are proposed for achieving the dual goal of cultivating NABE and implementing the Rural Revitalization Strategy in mountainous areas of China. While contributing to the knowledge on scale efficiency of agricultural land, this research also enlightens the practice of policy-making targeted to the sustainable development of agricultural industry led by NABE worldwide.


Nitrogen liberated via allelopathy can promote harmful algal blooms.
Allelopathy is a biological mechanism that can promote harmful algal blooms (HAB) via the inhibition of sympatric phytoplankton. While nutrient loading can also promote HABs, the ability of allelopathy to stimulate HABs via the regeneration of nutrients has yet to be explored. To examine the impacts of allelopathically liberated N on HAB species, a series of experiments were performed using multiple allelopathic HAB species including the dinoflagellates Alexandrium catenella and Margalefidinium polykrikoides, and the pelagophyte, Aureoumbra lagunensis. These HAB species were paired with the cosmopolitan dinoflagellate, Akashiwo sanguinea, that was labeled with 15NO3- or 15NH4+, allowing the release and transfer of N to be traced as a time course during allelopathic interactions. During all experiments, the allelopathic inhibition of Akashiwo was accompanied by increases in cell densities, growth rates, and the δ15N content of the HAB species, evidencing the transfer of N liberated from Akashiwo. The cellular transfer of 15N and release of dissolved N was higher when Akashiwo was grown with 15NO3- compared to 15NH4+ suggesting a differential subcellular-compartmentalization of N sources. Regardless of the type of N, HAB species obtained 60 - 100% of their cellular N from lysed Akashiwo cells and there was an enrichment of the δ15N content of the dissolved NH4+ pool post-lysis of Akashiwo. Collectively, the results demonstrate that beyond facilitating species succession, allelopathy can supply HABs with N and, therefore, is likely important for promoting and sustaining HABs. Given that allelopathy is known to be a dose-dependent process, allelopathy may induce a positive feedback loop, whereby competitors are lysed, N is liberated, HABs are intensified and, in turn, become more strongly allelopathic.


Sec14l3 is specifically expressed in mouse airway ciliated cells.
Airway epithelium is a key component for airway integrity. Previously, we found that expression of the Sec14l3 gene that encodes a 45-kDa secretory protein is inversely associated with the progression of experimentally induced airway inflammation and degeneration/necrosis of alveolar epithelium. In this report, using in situ hybridization we demonstrated that the ciliated cells in mouse lung selectively express Sec14l3 mRNA. In a three-dimensional culture of mouse tracheal epithelial cells, levels of the Sec14l3 mRNA correlated with the differentiation of ciliated cells. Intranasal infection of adult mice with influenza virus resulted in a 20-fold, progressive decrease in Sec14l3 mRNA expression over 10 days post infection. These results enhance the potential value of Sec14l3 as a ciliated epithelial cell-specific biomarker for the progression of airway inflammations such as airway viral infection and asthma.


Delineating functional properties of a cello-oligosaccharide and β-glucan specific cellobiohydrolase (GH5_38): Its synergism with Cel6A and Cel7A for β-(1,3)-(1,4)-glucan degradation.
Cellulase cocktails formulated to degrade crystalline cellulose generally contain cellobiohydrolases (CBHs), referred to as CBHI (Cel7A) and CBHII (Cel6A), as the major constituents. The combined hydrolytic activities of CBHI and CBHII improve the release of fermentable sugars (β-1,4-cellobiose as the main product) from crystalline cellulose. In this study, a novel cellobiohydrolase (Exg-D) sourced from a metagenome of hindgut bacterial symbionts of a termite was heterologouly expressed, purified, and functionally characterised. Exg-D specific activity was higher on insoluble barley β-glucan (38.94 U/mg protein), soluble wheat flour β-glucan (12.71 U/mg protein) and oat β-glucan (8.89 U/mg protein) compared to cellulosic substrates; Avicel and CMC. We further explored Exg-D activity on the unpretreated or NaOH-pretreated (mercerised) Avicel and compared its activity to commercially available CBHI and CBHII on these celluloses. CBHI displayed the highest activity of 4.74 U/mg protein on mercerised cellulose followed by CBHII (2.14 U/mg protein), while Exg-D activity on untreated and mercerised cellulose was 1.66 and 1.67 U/mg protein, respectively. The high activity of CBHI was supported by binding assays, which revealed that CBHI has a higher binding capacity towards crystalline cellulose compared to Exg-D and CBHII. Only CBHI and CBHII showed synergism during the hydrolysis of mercerised Avicel, showing a degree of synergy (DS) of about 1.299 and yielded about 1.43 μmol/ml of reducing sugars higher than control. In contrast, Exg-D and CBHII displayed synergism during β-glucan degradation, displaying a DS of about 1.22. Thus, we propose that Exg-D should only be used synergistically with other CBHs to degrade mixed linked-β-(1,3)-(1,4)-glucan.


A promising evaluation method for dead leaves of Posidonia oceanica (L.) in the adsorption of methyl violet.
Posidonia oceanica (Linnaeus) Delile is an endemic species in the Mediterranean Sea. In the present study, dead leaves of P. oceanica (L.) which are accumulated on the beach seasonally were used as an alternative low cost biosorbent to remove methyl violet (MV) from aqueous solution. In order to explain the adsorption kinetics, pseudo first-order and pseudo second-order kinetic models were investigated. It was obtained that the pseudo second-order model was well in line with our experimental results. Equilibrium data were analyzed according to Langmuir, Freundlich, and Dubinin-Radushkevich equations. Langmuir isotherm model corresponded well with equilibrium data than the others, and the maximum adsorption capacity of the biomass was found to be 119.05 mg g⁻¹ at 45°C. Thermodynamic parameters, ΔG°, ΔH°, and ΔS°, were calculated according to van't Hoff equation. Negative values of Gibbs free energy imply that the process is spontaneous. Consequently, dried biomass of this species can be an alternative and low cost material for the removal of MV from wastewaters. Moreover, since the remarkable adsorption capacity of these dead leaves compared to other low cost adsorbents has been observed, this beach waste could provide an economic contribution to the countries in the Mediterranean region.


Biodiversity 2030: a road paved with good intentions: The new EU Commission's biodiversity Strategy risks to remain an empty husk without proper implementation.
The EU's Biodiversity Strategy for 2030 makes great promises about halting the decline of biodiversity but it offers little in terms of implementation.


Telenzepine inhibits electrically-stimulated, acetylcholine plus histamine-mediated acid secretion in the mouse isolated stomach by blockade of M1 muscarine receptors.
1. The muscarine receptor mediating electrically-stimulated acid secretion in the mouse isolated stomach was characterized using a variety of muscarine receptor antagonists confirming the M1 nature of the antagonist effect of telenzepine. 2. Field stimulation (7 V, 10 Hz, 0.5 ms) resulted in a plateau acid secretion over at least 90 min which was completely blocked by either 1 mumol/l TTX or H2 receptor antagonists (100 mumol/l cimetidine or 10 mumol/l lupitidine). Ranitidine, which is known to potently inhibit mucosal acetylcholine esterase, was ineffective. Compound 48/80 at 100 mumol/l, which depletes mucosal histamine stores, initially mimicked electrical stimulation but subsequently prevented it from inducing acid secretion. 3. 10 muscarine receptor antagonists with differing relative affinities for M1, M2 and M3 receptors were introduced at 1 mumol/l to inhibit electrically-stimulated acid secretion. The percentages inhibition were plotted against binding affinities of the antagonists at either M1, M2 or M3 binding sites. A statistically significant correlation between functional and binding data was detected only when based on M1 affinities. 4. It is concluded that field stimulation, which probably mimicks vagal drive, results in muscarinic M1 receptor activation on paracrine cells to release histamine. Histamine then stimulates parietal cells to secrete acid. Hence, according to the present and our previous data, telenzepine inhibits acid secretion under these conditions by blocking M1 receptors at least partially located on histamine-releasing paracrine cells.


Increased risk of postsurgical macular edema in high stage idiopathic epiretinal membranes.
To assess the rate of occurrence and the risk factors of postsurgical macular edema (PSME) in eyes with idiopathic epiretinal membrane (iERM) or full-thickness macular hole (FTMH). Retrospective longitudinal analysis of all subjects scheduled for vitrectomy with or without combined cataract surgery over a 6-month period. Electronic medical charts and imaging data were analyzed preoperatively and at 1, 3 and 6 months after surgery. From 101 patients diagnosed with iERM or FTMH, 71 patients were eligible for the study. Forty-nine eyes with iERM (69.0%) and 22 eyes with FTMH (31.0%) underwent vitrectomy either isolated (31.0%) or combined with cataract extraction (69.0%). The overall rate of PSME was 26.7%, without differences between the two groups (P = 0.9479). Combined cataract extraction did not affect the overall occurrence of PSME rate in both groups (P = 0.9255 in FTMH and P = 0.8658 in iERM). If grouped by stage, eyes with stage 4 iERM though disclosed an increased rate of PSME (57.1%) compared to lower (1 to 3) stages (14.3%, P = 0.0021), particularly when combined with cataract surgery (71.4% vs. 15.4% in stages ≤ 3, P = 0.0021). The PSME odds ratio for a stage 4 iERM is 8 (95% CI: 1.933-33.1; P = 0.0041) compared to stages 3 and below. PSME remains a clinically relevant and frequent event after surgery for iERM and FTMH. Patients with stage 4 iERM have an 8-fold higher likelihood of developing PSME in a 6-month postsurgical period compared to iERM in 1-3 stages, especially when combined with cataract extraction.


Reverse genetics in Chlamydomonas: a platform for isolating insertional mutants.
A method was developed to identify insertional mutants of Chlamydomonas reinhardtii disrupted for selected target genes. The approach relies on the generation of thousands of transformants followed by PCR-based screenings that allow for identification of strains harboring the introduced marker gene within specific genes of interest. Our results highlight the strengths and limitations of two independent screens that differed in the nature of the marker DNA used (PCR-amplified fragment containing the plasmid-free marker versus entire linearized plasmid with the marker) and in the strategies used to maintain and store transformants.


A thalamic-primary auditory cortex circuit mediates resilience to stress.
Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.


Measurement of short-term exposure to airborne soluble platinum in the platinum industry.
A number of cases of respiratory sensitization to soluble platinum have arisen in the U.K. over the last few years, despite measured 8 h TWA exposure levels below the current long-term exposure limit in most cases. One possible cause of sensitization may be as a result of high exposures over short periods. Short-term sampling has been hampered by inadequate sampling and analysis techniques. This investigation has used two types of personal inhalable sampler, with ICPMS analysis, to take 15 min TWA soluble platinum exposure measurements at three sites. The lower detection limit for soluble platinum salts was approximately 0.01 microgram m-3 for 15 min samples, allowing exposures two orders of magnitude below the exposure limit to be measured. It was found that the majority of short-term exposure levels were significantly below 0.006 mg m-3. No evidence was found for altered work practices during sampling, indicating that either sensitization is occurring at airborne exposure levels below the exposure limit, or there is an alternate route of exposure.


Autophagy regulates hypoxia-induced osteoclastogenesis through the HIF-1α/BNIP3 signaling pathway.
Previous studies have implicated that hypoxic stress could enhance osteoclast differentiation; however, the underlying mechanism remains poorly understood. Autophagy is a dynamic lysosomal degradation process that has emerged as an important regulator under hypoxic environment. In the present study, we demonstrate for the first time that autophagy regulates hypoxia-induced osteoclastogenesis in vitro. We found that exposure of RAW264.7 cells to hypoxia (0.2% oxygen) resulted in enhanced osteoclast differentiation, accompanied by the observation of several specific features of autophagy, including appearance of membranous vacuoles, formation of acidic vesicular organelles, cleavage and recruitment of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes, increase in autophagic flux, as well as up-regulation of autophagy-related gene (Atg) expression. Moreover, suppression of autophagy with DN-Atg5(K130R) or 3-methyladenine (3-MA) significantly attenuated the osteoclast differentiation under hypoxic conditions, indicating the functional significance of autophagy in hypoxia-induced osteoclastogenesis. The data also showed that the activation of autophagy under hypoxic conditions was caused by up-regulated expression of hypoxia-inducible factor-1α (HIF-1α)-dependent Bcl-2 adenovirus E1a 19 kDa interacting protein 3 (BNIP3). Importantly, knockdown of HIF-1α or BNIP3 obviously abrogated hypoxia-induced autophagy activation and osteoclastogenesis enhancement. Collectively, our results highlight the fact that autophagy is a pivotal regulator for hypoxia-induced osteoclast differentiation, which may provide new insight into the pathological processes of osteoclastogenesis under hypoxic stress and help develop new therapeutic strategies for abnormal osteoclastogenesis.


Improvement of Pulmonary Function in Arthrogryposis Multiplex Congenita Patients Undergoing Posterior Spinal Fusion Surgery for Concomitant Scoliosis: A Minimum of 3-Year Follow-up.
We sought to investigate the long-term outcome of pulmonary function for arthrogryposis multiplex congenita (AMC) patients undergoing posterior spinal fusion (PSF) and to further determine influential factors. Eighteen AMC patients with a minimum of 3-year follow-up after PSF were prospectively collected. All the patients underwent a pulmonary function test before surgery and at the final follow-up. The percentage predicted values of vital capacity (VC%) and forced vital capacity (FVC%) were recorded. The following radiographic parameters were collected including Cobb angle and thoracic kyphosis. The total lung volumes (TLV) were measured on the image of 3-dimensional computed tomography scan by the reconstruction software. There were 10 males and 8 females with a mean age of 13.8 ± 6.1 years. The mean preoperative VC% and FVC% were 40.5% ± 7.6% and 39.5% ± 4.7%, which were significantly increased to 52.0% ± 7.5% and 51.2% ± 6.8% at the final follow-up (P < 0.001). Besides, there was remarkable improvement in terms of TLV (1.57 ± 0.2 L vs. 2.39 ± 0.6 L, P < 0.001). Remarkable correlations were observed between TLV and pulmonary function tests (r = 0.79, P < 0.001 for VC%; r = 0.78, P < 0.001 for FVC%). Multiple regression analysis showed that 2 variables including Δ thoracic kyphosis and Δ Cobb angle were independently associated with the improvement of pulmonary function. The pulmonary function of AMC patients can be well improved through PSF surgery. It was remarkably associated with the correction of curve magnitude and restoration of thoracic kyphosis.


Histological investigation of physiologically resorbing primary teeth using Ag-NOR staining method.
The aim of this study was to investigate pulpal tissue of primary teeth in early and late stages of physiological resorption by means of silver-binding nucleolar organizer region (Ag-NOR) staining. Ten primary teeth in early, ten in the late stage of resorption and five sound premolar teeth pulps as the control group were investigated by means of silver-binding nucleolar organizer region (Ag-NOR) staining. The mean number of Ag-NOR's per nucleus increased with the continuing of the resorption process. The difference in the mean number of Ag-NORs was statistically significant both in the early and late stage of resorption compared with controls (P > 0.001). In the early stage of resorption calcific plates in the apical part of the pulps were observed. Odontoclasts, as well as inflammatory cells, were observed in the late stages of resorption. The increase in the mean number of Ag-NORs per nucleus with the progression of the resorption process in primary teeth suggests that metabolic cell activity in the early stages of resorption is enhanced and increased with the continuing of the process, thus showing the importance of the pulp tissue in the resorption process.


Endemic or regionally limited parasitic and fungal infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.
There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.


Strength of Excitation Is Negatively Associated with Aggressive Behavior after Interpersonal Rejection.
This study explored how the Pavlovian temperamental traits strength of excitation (SE) and strength of inhibition (SI) were related to rejection and aggression. We predicted that rejection would increase aggression, but that higher SE and SI would mitigate this effect. Participants (n = 117) completed Strelau and Zawadzki's (1998) Pavlovian Temperament Survey. A week later they were told that a peer wanted (acceptance) or did not want (rejection) to work with them and they were given a chance to react aggressively by damaging that person's chance of getting a job. We found that only high SE was negatively related to rejected individuals' aggression. The results are related to the diathesis-stress and catalyst models' accounts of the role of temperament in shaping experience of social stress.


Comparison of sulfamethoxazole alone and combined with trimethoprim in urinary tract infections.
In a double blind, randomized study, sulfamethoxazole was compared alone and in combination with trimethoprim as commonly used in therapeutic regimes for the treatment of uncomplicated acute urinary tract infections in out-patients. The cure of sulfamethoxazole alone was 92.2%, and for sulfamethoxazole plus trimethoprim 97.6%. The rate of side-effects for the former was 5%, for the latter 21.8%. If the failure rate plus the rate of occurrence of rash, which necessitated discontinuing the drug, are combined, it appears that 8.8% of the patients were at a disadvantage receiving sulfamethoxazole compared to 9.7% for the combination of sulfamethoxazole plus trimethoprim. When considering the cure rate and rate of side-effects together, therefore, the position of sulfamethoxazole alone as a suitable drug in this type of infection is defended.


[DNA Probes for Analysis of the Activity of Key Enzymes of the Base Excision DNA Repair Pathway in Human Cells].
The important role of DNA damage in the occurrence of various diseases, including cancer, has led to study of the mechanisms of genetic information stability, that have been carried out since the discovery of DNA repair systems. The question of the relationship between the accumulation of DNA damage, disorders in DNA repair pathways, and increased risk of disease development is still relevant. Over the past few years, significant efforts have been made to develop methods for analyzing the activity of DNA repair enzymes in human cells. In this work, we developed fluorescent DNA probes that allow us to determine the activity of key enzymes of base excision DNA repair in cell extracts, namely the DNA glycosylases UNG2, SMUG1, MBD4, TDG, AAG, NEIL1, NTHL1, and OGG1 and the AP endonuclease APE1. The sensitivity of DNA probes was determined on pure enzyme preparations. Determination of the activity of repair enzymes in cell extracts of the human ovarian tumor lines TOV112, 79, OVCAR3, MESOV, SCOV3, and TOV21 revealed significant variability in the level of enzyme activity in these cell lines. These results may become a test system platform for analyzing the activity of the base excision DNA repair system in the human body.


Luminescence of peptide-bound terbium ions. Determination of binding constants.
Luminescence of Tb3+ ions bound to a calmodulin fragment has been studied. It is shown that during their lifetime excited ions dissociate from the peptide. If concentration of free peptide is high enough they can be coordinated again. As a consequence, observed terbium luminescence lifetime and intensity depends not only on binding equilibrium, but also on concentration of free peptide molecules. In such a system terbium binding constant cannot be correctly determined by simple steady-state measurements of luminescence intensities. Instead, terbium luminescence decay curves measured at various peptide concentrations must be analysed. Such an analysis has been made for a fragment of the IIIrd calcium binding domain of rat testis calmodulin. Rate constant of terbium association and the equilibrium binding constant corresponding to the best fit of theoretical functions to experimental points have been determined.


[Identification of biomarkers in the serum of the patients with poorly differentiated gastric cancer].
To investigate the application of proteomics in the field of serology,and to screen the differential expression proteins related with poorly differentiated gastric carcinoma. Two-dimensional electrophoresis (2-DE) was applied to segregate the total proteins in the serum form gastric cancer patients and health volunteers. After staining,the differential expression proteins were analyzed using PDQuest software,and identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Electrophoresis figures with high resolution and reproducibility were obtained. Six differential expression proteins were found only in the serum from gastric cancer patients, while four other proteins from healthy volunteers. Protein expression is differential in the serum from the gastric cancer patients and health volunteers. It is hopeful to find the biomarkers related with poorly differentiated gastric carcinoma using proteomics.


The impact of a Critical Care Information System (CCIS) on time spent charting and in direct patient care by staff in the ICU: a review of the literature.
The introduction of a Critical Care Information System (CCIS) into an intensive care unit (ICU) is purported to reduce the time health care providers (HCP) spend on documentation and increase the time available for direct patient care. However, there is a paucity of rigorous empirical research that has investigated these assertions. Moreover, those studies that have sought to elucidate the relationship between the introduction of a CCIS and the time spent by staff on in/direct patient care activities have published contradictory findings. The objective of this literature review is to establish the impact of a CCIS on time spent documenting and in direct patient care by staff in the ICU. Five electronic databases were searched including PubMed Central, EMBASE, CINAHL, IEEE Xplore, and the Cochrane Database of Systematic Reviews. Reference lists of all published papers were hand searched, and citations reviewed to identify extra papers. We included studies that were empirical articles, published in English, and provided original data on the impact of a CCIS on time spent documenting and in direct patient care by staff in the ICU. In total, 12 articles met the inclusion criteria. Workflow analysis (66%) and time-and-motion analysis (25%) were the most common forms of data collection. Three (25%) studies found an increase in time spent charting, five (42%) found no difference, and four (33%) studies reported a decrease. Results on the impact of a CCIS on direct patient care were similarly inconclusive. Due to the discrepant findings and several key methodological issues, the impact of a CCIS on time spent charting and in direct patient care remains unclear. This review highlights the need for an increase in rigorous empirical research in this area and provides recommendations for the design and implementation of future studies.


The immunomodulatory activity of degradation products of Sesbania cannabina galactomannan with different molecular weights.
Galactomannan (GM) is widely recognized as an immune enhancer; however, the underlying molecular mechanism is still unknown. Herein, four products with molecular weights in descending order, namely GM40, GM50, GM65, and GMOS, were separated from incomplete degradation products of Sesbania cannabina GM by ethanol precipitation, followed by their immunomodulatory activity. Through FTIR and XPS spectra, the amount of free hydroxyl groups was shown to decrease in the following order: GM > GM50 > GMOS > GM40 > GM65. Moreover, the immunomodulatory activity of different products decreased in abovementioned order. The TNF-α, IL-6 and TLR4 content in RAW 264.7 cells treated with different GM products in the presence or absence of TAK-242 (TLR4 inhibitor) suggested that the immunomodulatory activity of GM and its degradation products is TLR4-dependent. Overall, the preliminary relationship indicated here between the hydroxyl groups or the possible deeper structural changes of GM and the immunomodulatory activity need to be further investigated.


Progress and Prospective of the Industrial Development and Applications of Eco-Friendly Colorants: An Insight into Environmental Impact and Sustainability Issues.
Color is the prime feature directly associated with the consumer's attraction and choice of their food. The flavor, safety, and nutritional value of any food product are directly associated with the food color. Natural and synthetic colorants (dyes and pigments) have diversified applications in various sectors such as food, feed, pharmaceutical, textiles, cosmetics, and others. Concerning the food industry, different types of natural and synthetic colorants are available in the market. Synthetic food colorants have gained popularity as they are highly stable and cheaply available. Consumers worldwide prefer delightful foodstuffs but are more concerned about the safety of the food. After its disposal, the colloidal particles present in the synthetic colorants do not allow sunlight to penetrate aquatic bodies. This causes a foul smell and turbidity formation and gives a bad appearance. Furthermore, different studies carried out previously have presented the toxicological, carcinogenic effects, hypersensitivity reactions, and behavioral changes linked to the usage of synthetic colorants. Natural food colorings, however, have nutraceutical qualities that are valuable to human health such as curcumin extracted from turmeric and beta-carotene extracted from carrots. In addition, natural colorants have beneficial properties such as excellent antioxidant properties, antimutagenic, anti-inflammatory, antineoplastic, and antiarthritic effects. This review summarizes the sources of natural and synthetic colorants, their production rate, demand, extraction, and characterization of food colorants, their industrial applications, environmental impact, challenges in the sustainable utilization of natural colorants, and their prospects.


Aggressive fluid hydration plus non-steroidal anti-inflammatory drugs versus non-steroidal anti-inflammatory drugs alone for post-endoscopic retrograde cholangiopancreatography pancreatitis (FLUYT): a multicentre, open-label, randomised, controlled trial.
Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs. FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1·5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155. Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0·84, 95% CI 0·53-1·33, p=0·53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0·99, 95% CI 0·59-1·64; p=1·00), ERCP-related complications (0·90, 0·62-1·31; p=0·62), intensive care unit admission (0·37, 0·07-1·80; p=0·22), and 30-day mortality (0·95, 0·50-1·83; p=1·00). Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. Netherlands Organisation for Health Research and Development and Radboud University Medical Center.


Silk-coated dexamethasone non-spherical microcrystals for local drug delivery to inner ear.
The local drug delivery systems play an important role in treating sudden sensorineural hearing loss. In this work, we synthesized dexamethasone microcrystals (DEX MCs) using precipitation technique followed by silk coating via layer-by-layer assembly. Compared to raw DEX, the physicochemical properties including shape, crystal form, dispersity, dissolution or sustained release, of DEX MCs or poly-l-lysine/silk fibroin (PLL/SF) multilayers-coated DEX MCs (DEX-(PLL/SF)3) were investigated. More importantly, after a single intratympanic administration in guinea pigs, DEX-(PLL/SF)3 was uniformly distributed on the round window membrane (RWM) in comparison with raw DEX and DEX MCs. And increased concentration of DEX treatment resulted in higher perilymph DEX levels. No significant morphological change and inflammatory responses on the cochlear tissue were observed. Thus, the DEX-(PLL/SF)3 formulation could be a novel local drug delivery strategy to realize safe, efficient and sustainable DEX delivery into inner ear across RWM.


The CYP3A4 *1B polymorphism and prostate cancer susceptibility in a Portuguese population.
Testosterone exposure has been implicated in prostate carcinogenesis, and genes that alter its metabolism, such as CYP3A4, have been associated with prostate cancer susceptibility. The aim of our study was to assess the relationship between the CYP3A4 *1B polymorphism and its possible role in the development of prostate cancer. DNA samples obtained from the peripheral blood cells of 414 individuals diagnosed with prostate cancer and 337 healthy male donors were used in this case-control study. The CYP3A4*1B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism methodology. We found no statistically significant differences in the distribution of the CYP3A4*1B genotypes between cases and controls (P = 0.470; odds ratio = 1.191; 95% confidence interval=0.740-1.918), as well as after the stratification of our analysis, according to important clinicopathologic parameters of prostate cancer. Our results suggest that the CYP3A4*1B polymorphism is not associated with prostate cancer risk within the Portuguese population.


Initial experience of temperature-controlled irrigated radiofrequency ablation for ischaemic cardiomyopathy ventricular tachycardia ablation.
The DiamondTemp ablation (DTA) catheter system delivers high power, open-irrigated, temperature-controlled radiofrequency (RF) ablation. This novel ablation system has not been previously used for ventricular tachycardia (VT) ablation. Feasibility of using the DTA catheter system for VT ablation in ischaemic cardiomyopathy (ICM) patients. Ten ICM patients with optimal anti-arrhythmic drug therapy and implantable cardiac defibrillators (ICD) were recruited. VT inducibility testing was performed at the end of the procedure. ICD data for device detected VT episodes and device treated VT episodes were collected for 6-months pre- and post-ablation. Substrate analysis demonstrated reductions in the borderzone area of 4.4 cm2 (p = 0.026) and late potential area of 3.5 cm2 (p = 0.0449) post-ablation, with reductions in the mean bipolar and unipolar voltages of the ablation target areas (0.14 mV (p = 0.0007); 0.59 mV (p = 0.0072) respectively). Complete procedural success was achieved in 9 procedures. Post-ablation VT inducibility testing was not performed in 1 procedure due to a steam pop complication resulting in pericardial tamponade requiring drainage. Mean follow-up of 214 ± 33 days revealed an 88% reduction in total VT episodes (n = 266 median 16 [IQR 3-57] to n = 33 median 0; p = 0.0164) and 77% reduction in ICD therapies (n = 128 median 5 [IQR 2-15] to n = 30 median 0; p = 0.0181). The DTA system resulted in adequate lesion characteristics with effective substrate modification, acute procedural success and improved outcomes at intermediate-term follow-up. Randomised controlled trials are required to compare the performance of the DTA system against conventional ablation catheters.


Late-onset BK viral nephropathy in a kidney transplant recipient.
BK polyoma viral infection occurs as an asymptomatic infection in a high proportion of normal hosts without obvious sequelae. In the kidney transplant population, the virus is reactivated because of reduced immunity and, if not appropriately managed, can lead to BK viral nephropathy, which has emerged as a common cause of acute kidney injury and progressive chronic kidney disease in renal transplant recipients. BK viremia almost always occurs during the first 2 years after transplantation, when immunosuppressive therapy is high, or at other periods when immunosuppression is intensified. BK viremia is now detected by routine screening of transplant patients for the first few years, and BK viral nephropathy is considered to be high in the differential diagnosis of acute kidney injury in recently transplanted patients. We report a case of BK viral nephropathy developing 10 years after transplantation and present the challenges of managing advanced disease.


Legionella pneumophila growth in macrophages from susceptible mice is genetically controlled.
Growth of the intracellular opportunistic bacterium Legionella pneumophila in macrophages from A/J mice is a vigorous as growth in macrophages from susceptible guinea pigs and human monocytes, whereas growth is inhibited in macrophages from other mouse strains, such as nonpermissive BALB/c mice. Permissiveness versus nonpermissiveness of macrophages from A/J versus BALB/c mice appeared to be controlled by a genetic mechanism dependent upon a single gene or a closely clustered family of genes. Susceptibility versus resistance of macrophages from F1 offspring of these two strains of mice and macrophages from backcrossed mice prepared from F1 hybrids and the original parental strain showed a segregation of permissiveness for growth of Legionella in vitro, consistent with genetic control.


Diffusion basis spectrum imaging measures anti-inflammatory and neuroprotective effects of fingolimod on murine optic neuritis.
To prospectively determine whether diffusion basis spectrum imaging (DBSI) detects, differentiates and quantitates coexisting inflammation, demyelination, axonal injury and axon loss in mice with optic neuritis (ON) due to experimental autoimmune encephalomyelitis (EAE), and to determine if DBSI accurately measures effects of fingolimod on underlying pathology. EAE was induced in 7-week-old C57BL/6 female mice. Visual acuity (VA) was assessed daily to detect onset of ON after which daily oral-treatment with either fingolimod (1 mg/kg) or saline was given for ten weeks. In vivo DBSI scans of optic nerves were performed at baseline, 2-, 6- and 10-weeks post treatment. DBSI-derived metrics including restricted isotropic diffusion tensor fraction (putatively reflecting cellularity), non-restricted isotropic diffusion tensor fraction (putatively reflecting vasogenic edema), DBSI-derived axonal volume, axial diffusivity, λ∥ (putatively reflecting axonal integrity), and increased radial diffusivity, λ⊥ (putatively reflecting demyelination). Mice were killed immediately after the last DBSI scan for immunohistochemical assessment. Optic nerves of fingolimod-treated mice exhibited significantly better (p < 0.05) VA than saline-treated group at each time point. During ten-week of treatment, DBSI-derived non-restricted and restricted-isotropic-diffusion-tensor fractions, and axonal volumes were not significantly different (p > 0.05) from the baseline values in fingolimod-treated mice. Transient DBSI-λ∥ decrease and DBSI-λ⊥ increase were detected during Fingolimod treatment. DBSI-derived metrics assessed in vivo significantly correlated (p < 0.05) with the corresponding histological markers. DBSI was used to assess changes of the underlying optic nerve pathologies in EAE mice with ON, exhibiting great potential as a noninvasive outcome measure for monitoring disease progression and therapeutic efficacy for MS.


Aeroembolism in left atrium during catheter ablation of atrial fibrillation in a patient with dextrocardia: a case report and review of the literature.
Air embolus penetrating into heart chamber as a complication during percutaneous radiofrequency catheter ablation has been infrequently reported. A 55-year-old man with dextrocardia who suffered from abdominal pain was suspected to have multiple arterial thromboembolisms, which might have originated from left atrium thrombosis since he had atrial fibrillation. He received oral anticoagulant therapy and catheter ablation of the arrhythmia. During the ablation procedure, an iatrogenic aeroembolism penetrated into the left atrium due to improper operation. Ultimately, the entire air embolus was extracted from the patient, who was free of any aeroembolism events thereafter. It is essential for an operator to pay full attention to all details of the procedure to avoid an aeroembolism during catheter ablation. In case of aeroembolism, removal by aspiration is an optimal and effective treatment.


Mutating BnEOD1s via CRISPR-Cas9 increases the seed size and weight in Brassica napus.
Seed weight, which is highly correlated to seed size, is a critical agronomic trait that determines the yield of Brassica napus. However, there have been limited researches on the genes involved in regulating seed size. In Arabidopsis thaliana, ENHANCER OF DA1 (EOD1), an E3 ubiquitin ligase gene, has been identified as a significant negative regulator in controlling organ size, but the function of its homologs in rapeseed remains unknown. Only two homologous of EOD1, BnaEOD1.A04 and BnaEOD1.C04, have been found in B. napus and were mutated using the CRISPR-Cas9 system. Three T-DNA-free lines, T2-157-1-C8, T2-390-2-B8, and T2-397-2-E2, were identified from the homozygous T2 mutant lines. The BnaEOD1.A04 showed a similar type of editing in these mutants, whereas the BnaEOD1.C04 in T2-397-2-E2 was only missing 26 amino acids, and the translation was not prematurely terminated, which was different from the other two mutants. In parallel, mutation of BnaEOD1s resulted in a noteworthy increase in both seed size and seed weight in the three editing lines. Additionally, there was a significant decline in the number of seeds per silique (SPS) and silique length (SL) in T2-157-1-C8 and T2-390-2-B8, but T2-397-2-E2 did not show any significant changes in the SPS and SL, possibly due to distinct types of editing in the three lines. The above results indicate the conserved function of EOD1 homologs and provides promising germplasm for breeding novel high-yield rapeseed varieties by improving seed size and thousand-seed weight. The online version contains supplementary material available at 10.1007/s11032-023-01430-z.


The role of antioxidant supplementation in occupational exposure to waste anaesthetic gases.
Although the genotoxicity related to waste anaesthetic gases is controversial, a consistent number of observations have provided evidence for an increased level of DNA strand breaks. The goal of the research was to investigate this hypothesis and estimate the genoprotective role of antioxidant supplementation in technical anaesthesiology staff working in operating theatres. Heparinized venous blood samples were collected from 17 exposed technical anaesthesiology staff (mean age 34.3 +/- 3.5 years) and non-exposed control group (mean age 32.2 +/- 3.4 years) and examined in the alkaline comet assay for DNA strand breakage. Vitamin E (300 mg/day) plus vitamin C (500 mg/day) were supplemented to the technical anaesthesiology staff for 12 weeks and blood samples were retaken and evaluated by comet assay. The DNA breakage observed in the lymphocytes of the technical anaesthesiology staff was 21.5 +/- 5.0, as calculated by total comet score (TCS). This score was significantly higher (P<0.001) than in the controls (8.6 +/- 4.7) before antioxidant treatment. Supplementation of vitamins E plus C significantly (P<0.01) reduced the mean TCS as 14.2 +/- 6.1. The results of our study indicate that occupational exposure to anaesthetic gases induces oxidative DNA damage. Supplementation of the diet for 12 weeks with vitamin C and vitamin E resulted in a significant decrease in the DNA damage.


KB-R7943 restores endothelium-dependent relaxation induced by advanced glycosylation end products in rat aorta.
The aims of this study were to examine the effects of KB-R7943, an inhibitor of Na(+)/Ca(2+) exchanger, on impaired endothelium-dependent relaxation (EDR) induced by advanced glycosylation end products (AGE) in isolated rat aorta. Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured after the rings were exposed to AGE in the absence and presence of KB-R7943. Co-incubation of aortic rings with AGE (0.1 g/L) for 24 h resulted in a significant inhibition of EDR, but had no effects on EIR. After incubation of the rings in the co-presence of KB-R7943 (0.1-10 μM) with AGE for 24 h, KB-R7943 (10 μM) significantly attenuated impaired EDR. Superoxide dismutase (200 U/mL) and l-arginine (3mM) could ameliorate the impairment of EDR caused by AGE, whereas d-arginine (3mM) had no effect on EDR. Similarly, AGE decreased superoxide dismutase (SOD) activity and the release of nitric oxide (NO), and increased superoxide anion (O(2)(.-)) production in aortic tissue. KB-R7943 (10 μM) significantly decreased O(2)(.-) production and increased SOD activity and the NO release. These results suggest that KB-R7943 attenuated the impairment of EDR elicited by AGE partially through scavenging oxygen free radicals.


Screening for gonorrhea and Chlamydia: a systematic review for the U.S. Preventive Services Task Force.
Previous research has supported screening for gonorrhea and chlamydia in asymptomatic, sexually active women (including pregnant women) who are younger than 25 years or at increased risk but not in other patient populations. To update the 2005 and 2007 systematic reviews for the U.S. Preventive Services Task Force on screening for gonorrhea and chlamydia in men and women, including pregnant women and adolescents. MEDLINE (1 January 2004 to 13 June 2014), Cochrane databases (May 2014), ClinicalTrials.gov, and reference lists. English-language trials and observational studies about screening effectiveness, test accuracy, and screening harms. Extracted study data were confirmed by a second investigator, and study quality and applicability were dual-rated using prespecified criteria. Screening a subset of asymptomatic young women for chlamydia in a good-quality trial did not significantly reduce the incidence of pelvic inflammatory disease over the following year (relative risk, 0.39 [95% CI, 0.14 to 1.08]); however, 1 previous trial reported a reduction. An observational study evaluating a risk prediction tool to identify persons with chlamydia in high-risk populations had low predictive ability and applicability. In 10 new studies of asymptomatic patients, nucleic acid amplification tests demonstrated sensitivity of 86% or greater and specificity of 97% or greater for diagnosing gonorrhea and chlamydia, regardless of specimen type or test. There were few relevant studies of screening benefits and harms. Only screening tests and methods cleared by the U.S. Food and Drug Administration for current clinical practice were included to determine diagnostic accuracy. Chlamydia screening in young women may reduce the incidence of pelvic inflammatory disease. Nucleic acid amplification tests are accurate for diagnosing gonorrhea and chlamydia in asymptomatic persons. Agency for Healthcare Research and Quality.


Internalization and down-regulation of mu opioid receptors by endomorphins and morphine in SH-SY5Y human neuroblastoma cells.
The human neuroblastoma cell line, SH-SY5Y, was used to examine the effects of morphine and the endogenous opioid peptides, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), on mu opioid receptor (MOR) internalization and down-regulation. Treatment for 24 h with EM-1, EM-2 or morphine at 100 nM, 1 microM and 10 microM resulted in a dose-dependent down-regulation of mu receptors. Exposure of cells to 10 microM EM-1 for 2.5, 5 and 24 h resulted in a time-dependent down-regulation of mu receptors. Down-regulation of mu receptors by morphine and EM-1 was blocked by treatment with hypertonic sucrose, consistent with an endocytosis-dependent mechanism. Sensitive cell-surface binding studies with a radiolabeled mu antagonist revealed that morphine was able to induce internalization of mu receptors naturally expressed in SH-SY5Y cells. EM-1 produced a more rapid internalization of mu receptors than morphine, but hypertonic sucrose blocked the internalization induced by each of these agonists. This study demonstrates that, like morphine, the endomorphins down-regulate mu opioid receptors in a dose- and time-dependent manner. This study also demonstrates that morphine, as well as EM-1, can induce rapid, endocytosis-dependent internalization of mu opioid receptors in SH-SY5Y cells. These results may help elucidate the ability of mu agonists to regulate the number and responsiveness of their receptors.


Concomitant enhancement of a cytoskeleton-associated 76,000-dalton protein and inhibition of fluid-phase pinocytosis by interferon-alpha in Fujinami sarcoma virus-transformed rat 3Y1 cells.
Addition of rat interferon-alpha (IFN-alpha) to Fujinami sarcoma virus-transformed rat 3Y1 cells progressively inhibited fluid-phase pinocytosis [10% inhibition at 3 h; maximal (60%) inhibition by 12 h]. Electrophoretic analysis of the cytoskeletal fraction from cultures exposed to IFN for 24 h revealed a novel 76,000-dalton protein (CKp76). The kinetics of its appearance paralleled the inhibition of fluid-phase pinocytosis. CKp76 was not detected in cultures pretreated with actinomycin D, or prelabeled with [35S]methionine, prior to IFN addition. However, the presence of cycloheximide during incubation with IFN had no effect on the synthesis of CKp76 after removal of both agents. These results suggest that the appearance of CKp76 was due to enhanced transcription of its gene in response to IFN. Subcellular fractionation revealed the presence of induced CKp76 in the nuclear pellet. From these results it is possible that CKp76 may be responsible at leat in part for the effects of IFN on fluid-phase pinocytosis.


Spectral measurements of stack effluents using a double-beam interferometer with background suppression.
The emission spectra of the effluents from four selected stacks were measured using a double-beam interferometer to provide real-time background suppression. The double-beam interferometer system, installed in a mobile van, provided the capability for field site measurements and near real-time graphical data display. The advantages of double-beam interferometric background suppression are discussed. Selected spectra were analyzed, and one, from a municipal incinerator, was compared with a FASCODE generated synthetic spectrum.


Corticotropin releasing factor receptor-mediated stimulation of adenylate cyclase activity in the rat brain.
Corticotropin releasing factor (CRF)-stimulated adenylate cyclase activity and receptor binding were examined in rat brain homogenates using a potent synthetic CRF analog--[D-Tyr3,D-Pro4,Nle18,21,alpha-helical]CRF3-41 (alpha-hel CRF3-41). Binding of alpha-hel CRF3-41 in the rat brain was saturable, reversible, of high affinity and exhibited relevant peptide specificity. This analog also stimulated adenylate cyclase activity of various brain regions; the greatest magnitude of stimulation was in the cerebral cortex followed by the septum, cerebellum and thalamus. Adenylate cyclase stimulation in the cerebral cortex was concentration-dependent with an ED50 of 2.5 +/- 0.4 nM for alpha-hel CRF3-41 and an ED50 of 16 +/- 2 nM for ovine and rat CRF. Maximal stimulation was comparable for all peptides. Agonist-stimulated adenylate cyclase activity was competitively blocked by the CRF antagonists. The inactive CRF analog, ovine CRF1-39, at concentrations less than 1 microM, did not significantly stimulate adenylate cyclase. Adrenalectomy, which has been reported to modulate CRF receptor number and CRF-stimulated adenylate cyclase activity in the anterior pituitary, had no effect on CRF receptor binding or CRF-stimulated adenylate cyclase activity in the cerebral cortex. These results suggest that, as in the anterior pituitary, at least some of the physiological responses mediated by CRF receptors in the brain utilize the cyclic nucleotide regulatory pathway as a post-receptor mechanism.


How to improve results with extracorporeal shock wave lithotripsy.
Shock wave lithotripsy (SWL) has greatly revolutionized the treatment of patients suffering from stone disease. There are a number of patient- and device-specific factors that can affect treatment outcome. Herein, we review practices that can increase the likelihood of SWL treatment success. A systematic literature review was performed to identify studies of SWL treatment parameters. Among the factors affecting the outcome of SWL were patient selection criteria, such as stone burden, stone location, and anatomic features. Additionally, technical aspects of the SWL procedure also can affect outcome; these factors include the acoustic output of the lithotripter, the coupling of the lithotripter to the patient, and the power, total number, and rate of shock wave delivery. The outcome of SWL can be optimized with close attention to patient selection criteria as well as the manner in which the treatment is performed.


Vitreous haemorrhage in children.
Vitreous haemorrhage in early childhood is rare and may cause few symptoms. Three children (aged 1, 2 and 6 years) with no history of trauma, presented with squint or unreactive pupil. Unilateral dense vitreous haemorrhage was found in all three children. Rapid clearing of the vitreous opacities within a few weeks made surgical intervention unnecessary in two children. A 6-year-old boy underwent a vitrectomy. Thorough investigations revealed angle recession, retinal pigment epithelium (RPE) scars and an orbital floor bone fracture, respectively, suggesting ocular trauma as the cause for the haemorrhage in all three cases. With early amblyopia treatment, the visual outcome was good. Trauma appears to be a likely cause for vitreous haemorrhage in small children. Even if there is a risk for the development of amblyopia, observation may be a reasonable approach in some cases, since even dense vitreous haemorrhage may resorb rapidly in young children.


Scintigraphic analysis as a diagnostic tool in canine experimental lung embolism.
Scintigraphic changes occurring after lung embolism induced by intravenous administration of agar were assessed in 10 anesthetized prone dogs. Using 99mTc aerosol inhalation combined with 99mTc perfusion scintigraphy, parameters quantifying the regional distribution of the inhalation-to-perfusion ratio (I/P) and the degree of intraregional I-P mismatching were calculated from dorsoventral views (DV) for 6 equidistant cranial-to-caudal left and right lung zones before (B) and after acute embolism (PE). Postmortem examination was performed in 7 dogs. Several perfusion defects could be detected in either the conventional or the functional (I-P) lung scintigrams. Nevertheless, PE did not induce significant changes in blood gases. On the scintigrams, the outer zones appeared to be the most heavily embolized. The regional I/P ratio was increased in the more caudal and cranial parts of both lungs. However, postmortem examination of the lungs showed the presence of emboli diffuse in all lobes. Their presence was revealed in all zones by a significant increase of an intraregional mismatching index rho and especially of an intraregional mismatching factor mean value of gamma. After acute embolism, blood was redistributed to perihilar regions, especially in the right lung. This redistribution process continued during the experiment. In conclusion, the use of combined aerosol inhalation/perfusion lung scintigraphy with quantitative analysis provides a sensitive method for the detection of pulmonary embolism.


How females become complex: cell differentiation in the gametophyte.
In contrast to animals, gametes in plants form a separate haploid generation, the gametophyte. The female gametophyte of flowering plants consists of just four different cell types that play distinct roles in the reproductive process. Differentiation of the distinct cell fates is tightly controlled and appears to follow regional cues that are arranged along a polar axis. Mutant analysis suggests that important aspects of gametophyte patterning are gametophytically regulated. Additionally, structural and molecular changes following misspecification indicate that the female gametophyte is a remarkably versatile structure with enormous respecification potential. Recently, new tools have been developed that open fascinating possibilities to access and analyze those processes that ultimately ensure successful fertilization.


Total endoscopic left ventricle lipoma removal.
Left ventricle (LV) lipoma is a very rare, benign cardiac tumor. Due to its rarity, LV lipoma is often misdiagnosed. Aspecific symptoms such as murmurs, arrhythmias, memory loss and palpitation may occur due to the mass effect. We report a case report of a 42 year old woman who was found to have left ventricle mass after check-up for arrhytmia. By a fully endoscopic approach, the mass was successfully resected from the left ventricle without the need for sternotomy. Total endoscopic removal of left ventricle lipoma's can be done safely and has several advantages to conventional sternotomy. Larger studies are needed to confirm this hypothesis.


Evaluation of serum interleukin-6 (IL-6), IL-13, and IL-17 levels and computed tomography finding in interstitial lung disease associated with connective tissue disease patients.
Interstitial lung disease (ILD) is one of the most severe complications which is associated with connective tissue disease (CTD) and causes to morbidity and mortality. So, we aimed to determine serum levels of interleukin-6 (IL-6), IL-13, and IL-17, to investigate whether these cytokines are related to CTD-ILD, and to find their possible contribution to determining the prognosis of the disease. A total of 150 participants, 80 patients diagnosed with CTD-ILD (mean age, 58.21 ± 12.36) and 70 healthy controls (mean age, 57.07 ± 9.60) were recruited from the rheumatology department between January 2016 and June 2019 in the study. High-resolution computed tomography (HRCT) findings were scored as similarly to previous studies. Serum IL-6, IL 13, and IL-17 levels were measured by ELISA test kits. The levels of IL-6, IL-13, and IL-17 in CTD patients were significantly higher than the healthy individuals (p < 001), but the HRCT score's relation were not determined. IL-6 was associated with disease duration and disease activity scores of DAS28, ESDAII, and dSSc. There was a significant relation between dSSc, HCRT fibrosis, and total score.CRP, hemoglobin, and platelets were associated with the HRCT inflammation pattern. At the study, it has been observed that serum IL-13, IL-6 and IL-17 levels are increased in patients with CTD-ILD. Besides, IL-6 was associated with disease activity scores of DAS28, ESDAII, and dSSc. Also, HRCT fibrosis score is associated with dSSc. Further and comprehensive studies are needed to understand better the complex intersection of lung disease with systemic autoimmunity. Key Points • Serum IL-13, IL-6, and IL-17 levels are increased in patients with CTD-ILD. • IL-6 was associated with disease activity scores of DAS28, ESDAII, and diffuse skin involvement. • HRCT fibrosis score is associated with diffuse skin involvement in patients with SSc-ILD. • HRCT inflammation score is associated with PAH.


A predictive framework based on brain volume trajectories enabling early detection of Alzheimer's disease.
We present a framework for constructing predictive models of cognitive decline from longitudinal MRI examinations, based on mixed effects models and machine learning. We apply the framework to detect conversion from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to Alzheimer's disease (AD), using a large collection of subjects sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging (AIBL). We extract subcortical segmentation and cortical parcellation from corresponding T1-weighted images using FreeSurfer v.6.0, select bilateral 3D regions of interest relevant to neurodegeneration/dementia, and fit their longitudinal volume trajectories using linear mixed effects models. Features describing these model-based trajectories are then used to train an ensemble of machine learning classifiers to distinguish stable CN from converters to MCI, and stable MCI from converters to AD. On separate test sets the models achieved an average of accuracy/precision/recall score of 69/73/60% for converted to MCI and 75/74/77% for converted to AD, illustrating the framework's ability to extract predictive imaging-based biomarkers from routine T1-weighted MRI acquisitions.


Supramolecular interactions between losartan and hydroxypropyl-β-CD: ESI mass-spectrometry, NMR techniques, phase solubility, isothermal titration calorimetry and anti-hypertensive studies.
In this work, low soluble supramolecular complex between the losartan potassium (Los) and hydroxypropil-β-cyclodextrin (HPβCD) were characterized throughout phase-solubility, NMR techniques ((1)H and 2D-ROESY) and isothermal titration calorimetry (ITC) in order to attain physical-chemical knowledge of the system. In addition, the hypertensive effect of composition Los/HPβCD was evaluated aiming to obtain a more efficient oral pharmaceutical composition. ESI mass spectrometry and ITC blank experiment demonstrate the presence of Los clusters at 30 mM pure solution. Phase-solubility experiments showed a "Bs" type system, due to the formation of a less soluble complex than pure Los. NMR demonstrated the short distance interactions between the Los and the cyclodextrin, where several possibilities of interactions were observed. ITC data suggest an average 1:1 stoichiometry of Los and the cyclodextrin. The complex demonstrated efficiency in hypertension control, presenting antagonist action on the pressure effect of angiotensin II within 30 h, as compared to Los alone, 6h, indicating that inclusion of Los in HPβCD enhanced the extent and duration of its antagonistic action. In this work, a model of interaction between Los and HPβCD was proposed based on dissociation of self-assembled Los followed by complexation with HPβCD.


Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis.
DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83-88%), the development of HCC 7% (95% CI 5-9%), and mortality 6% (95% CI 4-8%). Improvement in liver function was observed in 51% (95% CI 44-58%) of patients, and 16% (95% CI 5-40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.


A safe and successful capsulorhexis technique for the intumescent cataracts; modified two-stage continuous curvilinear capsulorhexis.
Capsulorhexis is the most important step in intumescent cataract due to the high risk of radial extension of the capsular tear during the cataract surgery. The aim of this study is to present modified the two-stage capsulorhexis technique for intumescent cataract. The two-stage capsulorhexis technique was used in this study. A small size capsulorhexis approximately 1.5-2 mm diameter was created in the first stage. Liquefied cortex was aspirated with a 25 G cannula to equalize anterior chamber pressure and intracapsular pressure after the small size capsulorhexis. In the second stage, a 5-6 mm capsulorhexis size was performed for a safe phacoemulsification. A total of 73 consecutive patients with intumescent cataract were evaluated in this study. There were 39 male cases and 34 female cases. Mean age was 66 years ± 8 (between 53 and 84 years). A well centered complete continuous curvilinear capsulorhexis approximately 5-6 mm size was achieved in 72 of 73 cases (98.6%). Peripheral extension of capsulorhexis occurred in one eye during the second stage capsulorhexis. In this case, the capsule was cut with Vannas scissors and the capsulorhexis was completed. The rest of surgery was continued with a standard procedure and in-the-bag IOL implantation was done. This technique facilitates the creation of a safe capsulorhexis compared to the one-stage capsulorhexis technique. Surgeons may consider this technique to perform a safe phacoemulsification in the intumescent cataracts.


Percutaneous transhepatic cholangiography (PTC) in biliary atresia with special reference to the structure of the intrahepatic bile ducts.
Percutaneous transhepatic cholangiography (PTC) was carried out in 30 cases of biliary atresia, 19 prior to surgery, and 11 following hepatic portoenterostomy. The intrahepatic biliary system was demonstrated in 47% of the patients prior to surgery and in all cases following surgery. Two distinct patterns of intrahepatic bile ducts were noted. The first shows changes similar to those noted by intrahepatic cholangiography in patients with choledochal cyst, as in type A. The second pattern shows collections of numerous narrow proliferated bile ducts that constitute the ducts within and outside the liver as in type B. In patients with recurrent ascending cholangitis or symptoms suggestive of stenosis of the hepatointestinal anastomosis following Kasai-type operations for biliary atresia, PTC is useful in determining the structure of the hepatobiliary ductal system prior to reexploration procedures.


Identification of two new D variants, DHMi and DHMii using monoclonal anti-D.
Fifteen examples of red cells are described which showed discrepant reactivity on routine grouping with two monoclonal anti-D typing reagents, HAM-A being negative and MAD-2 strongly positive. The reaction profile of these cells with a number of monoclonal anti-D characterised the samples into two new variant groups, DHMi and DHMii. DHMi was characterised by a negative reaction with BRAD-8 and DHMii by a negative reaction with BRAD-5. DHMi cells were found to have a papain-sensitive site, identified by Mab 21 G6, which was not detectable in DHMii. The presence of allo-anti-D in one case of DHMi suggests a partial D in these individuals. The positive reaction of HAM-A with sialidase- and endo-F-treated DHMii cells suggests that sialic acid and/or N-glycans could possibly be involved in blocking the reaction with untreated cells. All samples typed as C-E+. One was e negative while the rest had variable depression of the e and f antigens. Marginal depression of E was seen with those DHMi cells tested, but not with DHMii cells. Data from family studies suggest that the variant D in both DHMi and DHMii is inherited as a cDE gene complex and is controlled by the RH locus.


Proteogenomic Profiling of High-Grade B-Cell Lymphoma With 11q Aberrations and Burkitt Lymphoma Reveals Lymphoid Enhancer Binding Factor 1 as a Novel Biomarker.
High-grade B-cell lymphomas with 11q aberrations (HGBL-11q) represent a World Health Organization-defined group of lymphomas that harbor recurrent chromosome 11q aberrations involving proximal gains and telomeric losses. Although a limited number of HGBL-11q cases evaluated thus far appear to show a similar course and prognosis as Burkitt lymphoma (BL), many molecular differences have been appreciated, most notably the absence of MYC rearrangement. Despite biological differences between BL and HGBL-11q, histomorphologic and immunophenotypic distinction remains challenging. Here, we provide a comparative whole proteomic profile of BL- and HGBL-11q-derived cell lines, identifying numerous shared and differentially expressed proteins. Transcriptome profiling performed on paraffin-embedded tissue samples from primary BL and HGBL-11q lymphomas was additionally performed to provide further molecular characterization. Overlap of proteomic and transcriptomic data sets identified several potential novel biomarkers of HGBL-11q, including diminished lymphoid enhancer-binding factor 1 expression, which was validated by immunohistochemistry staining in a cohort of 23 cases. Altogether, these findings provide a comprehensive multimodal and comparative molecular profiling of BL and HGBL-11q and suggest the use of enhancer-binding factor 1 as an immunohistochemistry target to distinguish between these aggressive lymphomas.


Doing Genetic and Genomic Biology Using the Legume Information System and Associated Resources.
In this chapter, we introduce the main components of the Legume Information System ( https://legumeinfo.org ) and several associated resources. Additionally, we provide an example of their use by exploring a biological question: is there a common molecular basis, across legume species, that underlies the photoperiod-mediated transition from vegetative to reproductive development, that is, days to flowering? The Legume Information System (LIS) holds genetic and genomic data for a large number of crop and model legumes and provides a set of online bioinformatic tools designed to help biologists address questions and tasks related to legume biology. Such tasks include identifying the molecular basis of agronomic traits; identifying orthologs/syntelogs for known genes; determining gene expression patterns; accessing genomic datasets; identifying markers for breeding work; and identifying genetic similarities and differences among selected accessions. LIS integrates with other legume-focused informatics resources such as SoyBase ( https://soybase.org ), PeanutBase ( https://peanutbase.org ), and projects of the Legume Federation ( https://legumefederation.org ).


Anxiety- and activity-related effects of diazepam and chlordiazepoxide in the rat light/dark and dark/light tests.
We have investigated, through factor analysis, anxiety- and activity-related variables in rats placed in the light/dark box. Thus, vehicle-, diazepam (DZ)-, and chlordiazepoxide (CDP)-treated rats were submitted 30 min later to 5-min light/dark or dark/light tests (initial placements in light or dark, respectively). Following this test, the animals were tested for 5 min in an automated activity monitor. Doses of DZ (0.75-3.0 mg/kg) and CDP (2.5-10.0 mg/kg) were based on preliminary evidence for 1.5 mg/kg of DZ and 5 mg/kg of CDP being anxiolytic in the elevated plus-maze. In the light/dark test, DZ increased the number of visits to and duration in the light compartment, and locomotor activity in the dark compartment; moreover, DZ decreased the latency to enter the light compartment. These effects were, however, significant for the highest dose only. Although CDP yielded similar behavioural effects, only the highest dose had a significant effect, namely, on latency to enter the light side. Conversely, none of the other variables were benzodiazepine-sensitive. Locomotion in the activity cages was decreased by DZ and CDP, an effect significant for the highest doses of benzodiazepines (dark/light test condition only). In both tests, factor analyses revealed an anxiety-related factor (to which all variables related to the visits in the light and part of the locomotion in the dark contributed), and an activity-related factor (upon which the latency to enter the dark and part of the locomotion in the dark loaded) in the light/dark test only. It is suggested that although the light/dark and dark/light tests capture an approach/avoidance dimension, DZ and CDP are more effective in the former test. Compared to the light/dark test, however, the plus-maze may be more sensitive to the anxiolytic effects of DZ and CDP.


Calcium to magnesium intake ratio and non-alcoholic fatty liver disease development: a case-control study.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Adoption of sedentary life style and westernized diet are shown to be associated with development of NAFLD. Since previous studies suggested that calcium (Ca) to magnesium (Mg) ratio intake is associated with some chronic diseases including dyslipidemia and insulin resistance, we designed this study to find any possible association between this ratio and NAFLD development. The NAFLD was diagnosed using Fibroscan according to a CAP cut-off value of 263 dB/m. Dietary intakes of one hundred and ninety-six patients with incident NAFLD diagnosis, and eight hundred and three controls without NAFLD were assessed using a valid food frequency questionnaire (FFQ). Dietary nutrients were calculated using Nutritionist IV software. Age of the study population (57 % female) was 43.2 ± 14.1 years. In addition, energy-adjusted daily calcium to magnesium intake ratio was 2.34 ± 0.57 and 2.73 ± 0.69 for control and case groups, respectively. In the multivariable-adjusted model, after adjustment for potential confounding variables; including, age, gender, BMI, alcohol consumption, smoking, diabetes, physical activity, energy, dietary fiber, carbohydrate, fat, and protein intakes, participants in the third (Q3) and fourth (Q4) quartile of Ca/Mg ratio intake had a greater development of incidental NAFLD compared to the lowest quartile (Q1) [(OR = 2.86; 95 % CI: 1.20-6.81), (P-value = 0.017) and (OR = 5.97; 95 % CI: 2.54-14.01), (P-value < 0.001) for Q3 and Q4 compared to the Q1, respectively]. Moreover, energy-adjusted Ca to Mg intake ratio was positively correlated with plasma level of ALT (r = 0.18; P = 0.01); contrarily, it had no correlation with plasma levels of AST. The current study revealed that higher dietary Ca to Mg intake ratio is associated with a greater development of NAFLD. Further interventional studies are needed to confirm the causal relationship of the Ca/Mg ratio intake and development of NAFLD.


Characteristics and prognosis of rectal gastrointestinal stromal tumors: an analysis of registry data.
Rectal gastrointestinal stromal tumors (GISTs) are rare. Accordingly, their clinical features are not well-documented and optimal treatment has not been established. The objective of this study is to clarify the rates and patterns of recurrence after surgical resection of rectal GISTs, with a focus on outcomes and therapeutic modalities. The registry was designed to collect data on rectal GISTs recorded between January, 2003 and December, 2007 at 40 participating institutions of the Kinki GIST Study Group. The principal variables were the rates and patterns of recurrence of rectal GISTs. Other study variables were age, sex, tumor size, mitotic count, distance from the anal verge, tumor location, surgical procedures, surgical margins, and recurrence-free survival. Twenty-four cases were registered, 11 (45.8%) of which were classified as high-risk by the modified NIH criteria. Locoregional recurrence (7/23, 30.4%) was the predominant recurrence pattern after curative resection, with rates that did not differ after local excision (33.3%; 3/9) vs. extended resection (28.6%; 4/14). The recurrence rates were high (25.0%) even for patients with low-risk disease. There was only one case of recurrence among patients who received perioperative treatment with imatinib. Rectal GISTs showed high rates of local recurrence regardless of the surgical procedure. Perioperative treatment with imatinib may improve outcomes.


A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy.
Tau acetylation has recently emerged as a dominant post-translational modification (PTM) in Alzheimer's disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule (MT)-binding region (MTBR), suggesting acetylation could regulate both normal and pathological tau functions. Here, we combined biochemical and cell-based approaches to uncover a dual pathogenic mechanism mediated by tau acetylation. We show that acetylation specifically at residues K280/K281 impairs tau-mediated MT stabilization, and enhances the formation of fibrillar tau aggregates, highlighting both loss and gain of tau function. Full-length acetylation-mimic tau showed increased propensity to undergo seed-dependent aggregation, revealing a potential role for tau acetylation in the propagation of tau pathology. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds. Our study identifies a potential "two-hit" mechanism in which tau acetylation disengages tau from MTs and also promotes tau aggregation. Thus, therapeutic approaches to limit tau K280/K281 acetylation could simultaneously restore MT stability and ameliorate tau pathology in AD and related tauopathies.


Nursing interventions for patients with rheumatic and musculoskeletal diseases on biological therapies: a systematic literature review.
Investigating unmet needs and identifying the necessary interventions for patients affected by rheumatic and musculoskeletal diseases (RMDs) may help significantly to ensure the continuity and quality of the chronic care pathway. To this aim, the contribution of rheumatology nurses requires further evidence. The aim of our systematic literature review (SLR) was to identify the nursing interventions directed towards patients with RMDs undergoing biological therapy. To retrieve data, a search was carried out in the MEDLINE database, the Cumulative Index to Nursing and Allied Health Literature (CINAHL database), the APA PsycINFO database and the Excerpta Medica Database (EMBASE) from 1990 to 2022. The systematic review was carried out in accordance with the relevant PRISMA guidelines. Inclusion criteria were as follows: (I) adult patients with RMDs, (II) undergoing therapy with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs), (III) original and quantitative research papers in English with available abstract, (IV) specific to nursing interventions and/or outcomes. Two independent reviewers screened the identified records for eligibility according to their title and abstract, full texts were subsequently assessed and, finally, data was extracted. Critical Appraisal Skills Programme (CASP) tools were used to evaluate the quality of the studies included. Among the 2348 records retrieved, 13 articles met the inclusion criteria. These consisted of six randomised controlled trials (RCTs), one pilot study and six observational studies on RMDs. In a total population of 2004 patients, 43% (862/2004) of the cases concerned rheumatoid arthritis (RA) and 56% (1122/2004) of the cases concerned spondyloarthritis (SpA). Three major nursing interventions were identified, namely education, patient-centred care and data collection/nurse monitoring, which were correlated with high satisfaction rates regarding care, increased self-care capacity and treatment adherence among patients. All interventions followed a protocol defined in collaboration with rheumatologists. The large degree of heterogeneity in the interventions did not allow the performance of a meta-analysis. Rheumatology nurses are part of a multidisciplinary team caring for patients with RMDs. Following an accurate initial nursing evaluation, rheumatology nurses can plan and standardise their interventions focusing primarily on patient education and personalised care based on actual needs, such as psychological well-being and disease control. However, the training for rheumatology nurses should define and standardise, as much as possible, the competencies required for the detection of disease parameters. Key Points • This SLR provides an overview of nursing interventions for patients with RMDs. • This SLR considers the specific population of patients on biological therapies. • Training for rheumatology nurses should standardise, as much as possible, the knowledge and methods required for detecting disease parameters. • This SLR highlights the various competencies of rheumatology nurses.


Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment.
Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.


Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study.
Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9-10 year-old children, among whom 8,845 had 1-year follow-up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting-state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within- and between-network connectivities (DMN-DAN, DMN-DMN, DAN-DAN) mediated the relationship between baseline TSD and MP at 1-year follow-up and the relationship between baseline MP and TSD at 1-year follow-up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well-being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems.


Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miokamycin). Part I-1. Acute toxicity in mice.
Miokamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens. The objective of this study was to determine the acute toxicity of MOM, non-crystalline solid, in male and female mice (Jcl-ICR, SPF, 5-week-old) after single i.p., and p.o. administration of this material at a dose level of 5,000 mg/kg as the maximum physically applicable dose. MOM, non-crystalline solid, exhibited no acute toxicity in the present study. LD0 values were estimated as more than 5,000 mg/kg in each route of administration.


Effectiveness of preconditioned adipose-derived mesenchymal stem cells with photobiomodulation for the treatment of diabetic foot ulcers: a systematic review.
The primary goal of this systematic review article was to provide an outline of the use of diabetic autologous adipose-derived mesenchymal stem cells (DAAD-MSCs) in the treatment of wounds and ulcers in animal models and patients with diabetes mellitus (DM). The secondary goal was to present the outcomes of pretreatment of diabetic adipose-derived mesenchymal stem cells (DAD-MSCs) with probable different agents in the treatment of diabetic foot ulcers (DFUs) and wounds. In view of possible clinical applications of AD-MSC-mediated cell therapy for DFUs, it is essential to evaluate the influence of DM on AD-MSC functions. Nevertheless, there are conflicting results about the effects of DAAD-MSCs on accelerating wound healing in animals and DM patients. Multistep research of the MEDLINE, PubMed, Embase, Clinicaltrials.gov, Scopus database, and Cochrane databases was conducted for abstracts and full-text scientific papers published between 2000 and 2020. Finally, 5 articles confirmed that the usage of allogeneic or autologous AD-MSCs had encouraging outcomes on diabetic wound healing. One study reported that DM changes AD-MSC function and therapeutic potential, and one article recommended that the pretreatment of diabetic allogeneic adipose-derived mesenchymal stem cells (DAlD-MSCs) was more effective in accelerating diabetic wound healing. Recently, much work has concentrated on evolving innovative healing tactics for hastening the repair of DFUs. While DM alters the intrinsic properties of AD-MSCs and impairs their function, one animal study showed that the pretreatment of DAlD-MSCs in vitro significantly increased the function of DAlD-MSCs compared with DAlD-MSCs without any treatment. Preconditioning diabetic AD-MSCs with pretreatment agents like photobiomodulation (PBM) significantly hastened healing in delayed-healing wounds. It is suggested that further animal and human studies be conducted in order to provide more documentation. Hopefully, these outcomes will help the use of DAAD-MSCs plus PBM as a routine treatment protocol for healing severe DFUs in DM patients.


Open systems living in a closed biosphere: a new paradox for the Gaia debate.
While energetically open, the biosphere is appreciably closed from the standpoint of matter exchange. Matter cycling and recycling is hence a necessary and emergent property of the global-scale system known as Gaia. But how can an aggregate of open-system life forms have evolved and persisted for billions of years within a planetary system that is largely closed to matter influx and outflow? The puzzling nature of a closed yet persistent biosphere draws our attention to the course of evolution of fundamental metabolic strategies and matter-capture techniques. It suggests a facet of the Gaia hypothesis, framed in terms of persistence. The oceans, atmosphere, soils and biota constitute a complex system which maintains and adjusts matter cycling and recycling within the constraints of planetary closure such that open-system forms of life can persist. This weaker version of the Gaia hypothesis may be useful because it readily lends itself to at least one form of test. What is the solution to the closed biosphere puzzle, and does it indicate that Gaia merits status as a discrete entity? We suggest several disciplines within the field of biology that might provide tools and perspectives toward reaching a solution. These disciplines include artificial closed ecosystems, prokaryote evolution, the nexus of thermodynamics and evolutionary biology, and hierarchy theory in ecosystem modeling and evolution theory.


Diabetes and Cancer: The Epidemiological and Metabolic Associations.
Diabetes mellitus, commonly known as diabetes, and cancer are two of the most common diseases plaguing the world today. According to the Centers for Disease Control and Prevention (CDC), there are currently more than 20 million people with diabetes in the United States [1]. According to the International Agency for Research on Cancer (IARC), there were around 18 million people diagnosed with cancer, with approximately ten million deaths globally in 2018 [2]. Given the prevalence and deadliness of diabetes and cancer, these two diseases have long been the focus of many researchers with the goal of improving treatment outcomes. While diabetes and cancer may seem to be two very different diseases at first glance, they share several similarities, especially regarding their metabolic characteristics. This chapter discusses the similarities and relationships between the metabolism of diabetes, especially type 2 diabetes (T2D), and cancer, including their abnormal glucose and amino acid metabolism, the contribution of hyperglycemia to oncogenic mutation, and the contribution of hyperinsulinemia to cancer progression. Investigating the metabolic interplay between diabetes and cancer in an effort to exploit this connection for cancer treatment has the potential to significantly improve clinical efficacy.