The emerging role of valproate in bipolar disorder and other psychiatric disorders.
Although valproate, a simple branched-chain fatty acid, is generally considered to be an antiepileptic agent, a large literature dating back to 1966 describes its use in primary psychiatric disorders. The significant role that gamma-aminobutyric acid plays in mood provided the rationale to examine valproate in this regard. Numerous uncontrolled as well as placebo- and lithium-controlled studies verified the drug's efficacy in the short-term management of bipolar and schizoaffective disorders. The response appears to be independent of response to traditional therapies such as lithium, neuroleptics, and carbamazepine, and may be maintained for extended periods of time. Valproate should be considered not only in patients with mood disorders who are intolerant of or nonresponsive to traditional therapies, but also in those with rapid cycling, electroencephalographic abnormalities, head trauma antedating the onset of psychiatric illness, or any other factor suggesting an organic component. Preliminary uncontrolled studies suggest that the drug may also eventually play a role in the management of panic disorder and behavioral dyscontrol (agitation, aggression, temper outbursts). Its adverse event profile is well known from years of experience in the management of epilepsy and does not appear to be altered in the presence of psychiatric disorders. Similarly, the drug-drug interaction potential of valproate is reasonably well known, although further research into interactions with psychotropic agents is warranted.


Caspase-1 and Gasdermin D Afford the Optimal Targets with Distinct Switching Strategies in NLRP1b Inflammasome-Induced Cell Death.
Inflammasomes are essential complexes of innate immune system, which form the first line of host defense against pathogens. Mounting evidence accumulates that inflammasome signaling is highly correlated with coronavirus disease 2019 (COVID-19). However, there remains a significant gap in our understanding of the regulatory mechanism of inflammasome signaling. Combining mathematical modeling with experimental analysis of NLRP1b inflammasome signaling, we found that only the expression levels of caspase-1 and GSDMD have the potential to individually switch cell death modes. Reduction of caspase-1 or GSDMD switches cell death from pyroptosis to apoptosis. Caspase-1 and GSDMD present different thresholds and exert distinct pathway choices in switching death modes. Pyroptosis switches to apoptosis with an extremely low threshold level of caspase-1, but with a high threshold of GSDMD. Caspase-1-impaired cells employ ASC-caspase-8-dependent pathway for apoptosis, while GSDMD-impaired cells primarily utilize caspase-1-dependent pathway. Additionally, caspase-1 and GSDMD can severally ignite the cooccurrence of pyroptosis and apoptosis. Landscape topography unravels that the cooccurrence is dramatically different in caspase-1- and GSDMD-impaired cells. Besides pyroptosis state and apoptosis state, a potential new "coexisting" state in single cells is proposed when GSDMD acts as the driving force of the landscape. The "seesaw model" is therefore proposed, which can well describe the death states that are controlled by caspase-1 or GSDMD in single cells. Our study sheds new light on NLRP1b inflammasome signaling and uncovers the switching mechanisms among various death modes, providing potential clues to guide the development of more rational control strategies for diseases.


Induction of ear wiggling in the estrous female rat by gonadectomized rats treated with androgens and estrogens.
Intact and gonadectomized male and female rats treated with estradiol and/or dihydrotestosterone were introduced into the cage of estrous female rats. For 3 min the number of periods with ear wiggling displayed by the estrous female and the total duration of the periods with ear wiggling were recorded. It was found that estrous females showed about twice as much ear wiggling in the presence of intact males as in the presence of gonadectomized male and female rats. However, gonadectomized male and female rats treated with dihydrotestosterone induced as much ear wiggling as intact males did. In contrast, administration of estradiol to the gonadectomized stimulus rats did not affect the rate of ear wiggling of the estrous females. Estrous females showed the lowest rate of ear wiggling in the presence of intact female rats. It has been suggested that dihydrotestosterone-treated male and female rats have an odor which sexually excites estrous female rats.


Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy.
While existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.


Role of IL-4 in delayed type hypersensitivity.
IL-4 plays a key role in the contact sensitivity skin reaction. This has several implications. First, the view that contact sensitivity (CS) is only mediated by cells with a Th1 profile of cytokine secretion needs modification, in the light of the essential role of IL-4 at the effector stage. Second, the concept of a single cell involved in the systemic transfer of CS is no longer tenable, as it is known that both alpha beta and gamma delta cells are required. Studies with the cell lines (which contain both alpha beta and a few gamma delta cells) suggest that this double requirement may involve the action of IL-4 on gamma delta cells, which bear receptors for IL-4. Finally, the view that T cell lines only transfer CS when injected locally, but not when injected intravenously (systemic transfer), is correct but incomplete, as T cell lines actually give systemic transfer of CS, providing the cell line or the recipient is treated with IL-4.


Nanomechanical properties of desmin intermediate filaments.
Desmin intermediate filaments play important role in the mechanical integrity and elasticity of muscle cells. The mechanisms of how desmin contributes to cellular mechanics are little understood. Here, we explored the nanomechanics of desmin by manipulating individual filaments with atomic force microscopy. In complex, hierarchical force responses we identified recurring features which likely correspond to distinct properties and structural transitions related to desmin's extensibility and elasticity. The most frequently observed feature is an initial unbinding transition that corresponds to the removal of approximately 45-nm-long coiled-coil dimers from the filament surface with 20-60 pN forces in usually two discrete steps. In tethers longer than 60 nm we most often observed force plateaus studded with bumps spaced approximately 16 nm apart, which are likely caused by a combination of protofilament unzipping, dimer-dimer sliding and coiled-coil-domain unfolding events. At high stresses and strains non-linear, entropic elasticity was dominant, and sometimes repetitive sawtooth force transitions were seen which might arise because of slippage within the desmin protofilament. A model is proposed in which mechanical yielding is caused by coiled-coil domain unfolding and dimer-dimer sliding/slippage, and strain hardening by the entropic elasticity of partially unfolded protofilaments.


[Stomach cancer mortality and nutrition intake in northern Japan--especially on relation to sodium chloride].
There is a big difference on the stomach cancer (SC) mortality between the north-western and the north-eastern parts of Honshu (mainland of Japan) although not much differences on cerebrovascular disease (CVD) mortality can be observed between these two areas while both of these diseases are said to be related to high-salted diets. The relation between diet and age-adjusted mortality of SC and CVD in northern Honshu was examined here, based on the results of the nutrition survey carried out by prefecture office (1971-87, 6 prefectures, total of 18 data sets). The results are summarized as follows: 1. There are no significant differences on salt intake between the north-western and the north-eastern parts of Honshu. 2. Intake of milk and dairy products is negatively related to SC. 3. Intake of animal protein is negatively related to CVD.


Endoscopy-Assisted Diagnosis and Revision of a Malpositioned Screw.
Pedicle screw insertion is a common procedure in spine surgery, and freehand, fluoroscopic, and robotic-assisted techniques all are used. These are indirect methods that use fluoroscopy, and direct visualization of canal involvement has not been possible. However, owing to the development of high-definition imaging modalities, delicate procedures that use endoscopy are possible. A 47-year-old man presented with severe radiating pain in his leg after undergoing L5-S1 level endoscopic transforaminal lumbar interbody fusion and percutaneous pedicular screw fixation. The patient then underwent an endoscopy-assisted technique for violated spinal canal and screw revision in which the misplaced screw was directly visualized using endoscopy and the trajectory of the misplaced screw was changed. With 30° endoscopy, we directly visualized the screw thread and root compression. Then with 0° endoscopy, we changed the screw trajectory inside the pedicle with an anatomic landmark. The patient's radiating pain was completely relieved after revision of the malpositioned screw. Postoperative imaging showed the revised screw trajectory inside the pedicle. Endoscopy-assisted pedicle screw insertion does not require an additional incision, and early recovery after the procedure is possible. Accurate diagnosis of canal pathology and treatment are possible with direct visualization using endoscopy.


pH-responsive Ag-Phy@ZIF-8 nanoparticles modified by hyaluronate for efficient synergistic bacteria disinfection.
Zeolitic imidazolate framework-8 (ZIF-8) is a type of Metal-organic frameworks (MOFs), which shows promising application in the field of bacterial infection, owing to its excellent biocompatibility. Here, we report the encapsulation of silver nanoparticles (Ag NPs) in ZIF-8, accompanied with embedding of physcion (Phy) to obtain Ag-Phy@ZIF-8 with efficient and intelligent synergistic antimicrobial capabilities. Due to the micro-acidic environment around the bacteria, the release of silver and Phy shows a controlled released. Further, the Ag-Phy@ZIF-8 is modified by hyaluronate (HA), denoted as Ag-Phy@ZIF-8@HA, which has a strong inhibitory effect on the growth of both E. coli (99.1%) and S. aureus (99.5%), with no impacting on cell growth, showing good biocompatibility. Thus, these pH-responsive biocomposites have the potential application on smart wound excipients for bacterial infections.


Cadmium-metallothionein-induced kidney dysfunction increases magnesium excretion in the rat.
Urinary excretion of the major minerals, calcium (Ca), magnesium (Mg), sodium (Na), and potassium (K), as well as of protein and metallothionein, was studied following the injection of cadmium-metallothionein (CdMT) in rats. Animals were given vehicle (saline) and 0.4 and 0.8 mg Cd/kg body wt as CdMT. A marked, relatively early, and reversible increase in Mg excretion was seen. The increase was dose-related, indicating a close connection to the typical Cd-derived cellular damage in the renal tubular epithelium, including an early reversible Ca excretion and a late reversible protein excretion. The increase in Mg excretion was similar in magnitude to the one for Ca and much more prominent than that recorded for Na and K. The appearance of Mg and Ca excretion peaks at an early stage after CdMT injection makes it likely that this effect is an early event in the process of development of cellular damage and does not merely represent unspecific cellular damage giving rise to proteinuria.


Features of mixed medullary thyroid tumors: An NCDB analysis of clinicopathologic characteristics and survival.
Mixed medullary-papillary thyroid carcinoma (MMPTC) and mixed medullary-follicular thyroid carcinoma (MMFTC) are rare variants with little known regarding behavior and prognosis. Using the National Cancer Database (NCDB), demographics, clinicopathologic features, treatment, and overall survival (OS) from patients with MMPTC and MMFTC were compared to more prevalent subtypes. There were 296,101 patients: 421 MMPTC (0.14%), 133 MMFTC (0.04%), 263,140 PTC (88.87%), 24,208 FTC (8.18%) and 8,199 MTC (2.77%). Compared to PTC, MMPTC and MMFTC patients were older (p < 0.001) with a higher Charlson-Deyo comorbidity index (p < 0.001). Mixed tumors exhibited lower rates of nodal disease but more distant metastases compared to PTC (p < 0.001). MMPTC demonstrated lower estimated 10-year OS than PTC and FTC (76.04%vs 89.04% and 81.95%,p < 0.001), yet higher than MTC (70.29%,p < 0.001). MMFTC had a worse OS compared to all groups (63.32%,p < 0.001). Patients with MMFTC had significantly worse OS compared to DTC, portending a worse prognosis.


[Growth of the lower limbs in normal children. Results of 10 years' exclusively orthopedic pediatrics].
Ten years of exclusive pediatric orthopedic consults show that growth of lower limb in normal children goes in four distinct clinic forms. This view of growth and evolution in normal children allows to avoid orthopedically unjustified treatments and shows where the potential problems are for making easy therapeutic decisions.


Lentiviral vector-mediated RBM5 overexpression downregulates EGFR expression in human non-small cell lung cancer cells.
RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. Our previous studies suggested that RBM5 expression was negatively correlated with the expression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues. This study was aimed at determining whether RBM5 is able to regulate EGFR expression. Both in vitro and in vivo studies were carried out to determine the effect of RBM5 on the expression of EGFR. Lentiviral vector-mediated RBM5 overexpression was employed in lung adenocarcinoma cell line A549. A549 xenograft mice were treated with recombinant RBM5 plasmid carried by attenuated Salmonella typhi Ty21a. Real-time quantitative polymerase chain reaction and Western blot were carried out to detect RBM5 and EGFR expression. Both in vivo and in vitro studies indicated that the expression of EGFR mRNA and protein was decreased significantly in the RBM5 overexpression group compared to control groups as shown by real-time PCR and Western blot analysis. We identified that RBM5 overexpression inhibited EGFR expression both in A549 cells and in A549 xenograft mice model. Our study demonstrated that EGFR expression is regulated by RBM5 in lung adenocarcinomas cells either in a direct or indirect way, which might be meaningful with regards to target therapy in lung cancer.


Use of octadecasilyl-silica for the extraction and purification of peptides in biological samples. Application to the identification of circulating metabolites of corticotropin-(1-24)-tetracosapeptide and somatostatin in vivo.
Peptides can be adsorbed on octadecasilyl-silica from large volumes of aqueous solution and eluted with aqueous solvent mixtures containing methanol or acetonitrile. These properties may be used for the extraction and purification of peptide fragments in plasma samples collected from rats. After intravenous injection of Synacthen [corticotropin-(1-24)-tetracosapeptide], it was shown that within 2 min the main circulating products were intact peptide and its sulphoxide. In addition, a number of fragments indicative of cleavage at the N- and C-termini were present. Most of the products formed from Synacthen have low biological activity. Somatostatin was rapidly cleaved in vivo and in vitro to a single product, which probably retains biological activity. The absence of other circulating products suggests that somatostatin is only inactivated once it leaves the circulation.


WISC-V motor-free cognitive profile and predictive factors in adolescents with cerebral palsy.
The most commonly used intelligence tests - the Wechsler Scales - do not provide standardised procedures for assessing children with motor impairment, and as a result, may underestimate the intelligence quotient (IQ) of young people with CP. To characterise a motor-free cognitive profile of adolescents with CP using the Wechsler Intelligence Scale for Children - Fifth edition (WISC-V) and explore the influence of clinical factors on cognitive abilities. The WISC-V was used to assess cognitive abilities in 70 adolescents (M = 14 years 6 months, SD = 10 months). Sixty-six adolescents (Gross Motor Function Classification System (GMFCS) Level I, n = 26 ; II, n = 23; III, n = 15; IV, n = 1; V, n = 1) obtained either a Motor-free IQ or index score using the motor-free method. MFIQ and index scores fell below the normative data and rates of borderline and impaired cognitive abilities were significantly higher in the CP group. Scores showed an uneven cognitive profile with a relative strength in verbal abilities. Severity of motor impairment and small for gestational age (SGA) were associated with lower IQ scores. A history of seizures was related to lower verbal abilities. Cognitive abilities of adolescents with CP are significantly below expectation compared to normative data. Severity of motor impairment, SGA, and seizures need to be recognised by health professionals as risk factors for cognitive impairment. A substantial proportion of adolescents showed borderline cognitive abilities, constituting a group with CP which are relatively neglected in the literature.


Suppressed TSH levels secondary to thyroxine replacement therapy are not associated with osteoporosis.
Recent studies have suggested that patients receiving thyroxine are at increased risk of osteoporosis. We set out to measure bone mineral densities in two groups of post-menopausal women receiving thyroxine replacement therapy (those with serum TSH levels persistently suppressed or non-suppressed) and to compare the results in both groups with those of the local control population. Cross-sectional study. Seventy-eight post-menopausal women who had been treated with thyroxine for primary autoimmune or idiopathic hypothyroidism for a minimum of 5 years, 44 with TSH persistently suppressed and 34 non-suppressed. One hundred and two control subjects. Forearm bone mineral density at proximal and distal sites as measured by single-photon absorptiometry. Results were expressed as Z-scores, i.e. number of standard deviations from the mean of a 5-year age-band from the local control population. Mean Z-scores at proximal and distal sites for the non-suppressed patients were -0.03 and -0.07 and for the suppressed patients were -0.20 and -0.25, representing a decrease in bone mineral density of at most 5% in the suppressed patients. The differences between the three groups were not statistically significant. In this patient population, the reduction in bone mineral density due to thyroxine is small. It is unlikely to be of clinical significance and should not on its own be an indication for reduction of thyroxine dose in patients who are clinically euthyroid.


The effect of low molecular weight heparin thromboprophylaxis on bleeding complications after gastric cancer surgery.
Low molecular weight heparin (LMWH) has been widely used to prevent venous thromboembolism in cancer surgical patients. However, relatively few studies have examined the safety aspects related to the use of LMWH after abdominal cancer surgery. This study was designed to investigate the relationship between bleeding complications and LMWH thromboprophylaxis after gastric cancer surgery. From March to July in 2009, 179 consecutive patients who underwent gastric cancer surgery at our institution were administered LMWH (3200 U once daily from 2 to 6 h before surgery until discharge) perioperatively. A total of 182 patients consecutively treated before the introduction of LMWH prophylaxis were selected as controls. There were 234 men and 127 women (mean age, 60 +/- 12 years). No significant intergroup differences were observed with respect to clinicopathological features and operative procedures. No patient in the LMWH or control group developed symptomatic venous thromboembolism postoperatively. However, the LMWH group had a significantly higher surgical complication rate (27.4 versus 15.4%, P = 0.005). Among the surgical complications, postoperative bleeding and wound complications were significantly higher in the LMWH group, whereas other complications were similar in the two study groups. Multivariate analysis showed that LMWH administration was an independent risk factor (odds ratio, 2.83; 95% confidence interval, 1.28-6.23, P = 0.009) of postoperative bleeding. LMWH thromboprophylaxis was found to increase significantly the risk of bleeding complications after gastric cancer surgery. Optimal LMWH prophylaxis regimens, including the dosage and timing of treatment commencement, for gastric cancer surgery should be determined in further clinical trials.


EUS changes diagnosis from pancreatic to gallbladder carcinoma.
A patient was referred for endoscopic ultrasound (EUS) for preoperative staging of what was believed to be pancreatic cancer, based on minimal findings on computed tomography (CT) and highly elevated CA19-9. EUS imaged a normal pancreas, but a tumor mass was identified in the gallbladder, and proven to be adenocarcinoma using EUS-guided fine-needle aspiration (FNA). Open cholecystectomy was curative. CA19-9 is not a highly specific marker. EUS is emerging as a highly sensitive and specific test for pancreatic cancer. EUS can complement other imaging modalities, and reveal unsuspected pathologies, such as in the patient described in this report, with major clinical impact.


Wireless Light-emitting Marker Using Magnetic Field Resonance for Laparoscopic Gastrointestinal Surgery.
In laparoscopic gastrointestinal surgery, the location of the tumor is identified mainly with marking methods, such as ink tattooing and intraoperative gastrointestinal endoscopy and marking with a metal clip followed by confirmation with intraoperative x-ray fluoroscopy. Each method has disadvantages, such as complexity, instability of ink sticks, and radiation exposure. Thus, a simple and less-invasive marking method is needed. We developed a wireless light-emitting marker with a miniature light-emitting diode that uses a magnetic field resonance mechanism. It emits 4 individual colors-red, blue, green, and white. We confirmed the usefulness of this marker system in ex vivo and in vivo animal experiments. In the ex vivo experiment in porcine intestines, use of the wireless marker was successful, as each color of emitted light was recognized from outside the intestine. In the live animal experiment, it was confirmed that the light emitted by the marker system was visible in the porcine intestinal tract during laparoscopic surgery. The light emitted by the wireless marker in the intestinal tract was confirmed with a laparoscope in a simulated animal surgery. We have developed an innovative, radiation-free and reliable light-emitting marker system that uses a magnetic field resonance mechanism that emits four colors of light during laparoscopic surgery.


Cornea fluid dynamics. II. Evidence for transport of radiolabelled albumin in rabbits by bulk flow.
Transport of radiolabelled albumin in vivo has been measured in cornea. In anaesthetized rabbits, a 1-10 nl mixture of either 125I- or 131I-labelled human serum albumin and fluorescinthiocarbamoyldextran was injected with micropipettes under guidance of a fluorescent microscope. The injection sites were a spot 3 mm from limbus and the cornea centre, and the sites were localized by a template fitting the cornea exactly. Four, 12, 20 and 30 hr after the injection, the rabbits were reanaesthetized, and enucleated after being killed with an overdose of anaesthetic. The bulbi were frozen, and dissection of cornea performed in the cold room using the template described above and a stereomicroscope. Numbered samples were obtained, and isotope distribution measured. In the experiments lasting for 20 hr, about 55% of the isotope was recovered, giving a transfer coefficient of 0.4-0.5 per day. A common pattern of isotope distribution was observed independent of duration of isotope equilibration; peripherally injected isotope moved preferentially in central direction, indicating that fluid is transported by bulk flow and diffusion from peripheral to central cornea. Centrally injected isotope moved symmetrically from the injection point, as expected from transport by diffusion alone. Data from experiments with isotope injection in the cornea centre allowed the calculation of a diffusion coefficient for albumin along cornea of 2.19 x 10(-7) cm2 sec-1.


Blood Magnesium Level and Selected Oxidative Stress Indices in Lead-Exposed Workers.
Occupational exposure to lead is one of the important hazards to human global population. Lead interferes with divalent cations, such as calcium, magnesium, and iron. Magnesium is the fourth most common mineral in the human body and a cofactor in more than 325 enzymes. There are many disorders associated with magnesium deficiency. It has been postulated that hypomagnesemia promotes oxidative stress. Study population included 232 male employees of lead-zinc works and was divided into two sub-groups based on the median of magnesium serum level: low magnesium level (L-Mg) group and high magnesium level (H-Mg) group. Magnesium level was significantly higher in the H-Mg group than in the L-Mg group due to the study design. The level of zinc protoporphyrin was significantly higher in the L-Mg group than in the H-Mg group by 13%, while the blood lead levels were similar in the examined groups. The serum level of MDA was significantly higher in the L-Mg group than in the H-Mg group by 12%, while the serum levels of thiol groups, TAC, and bilirubin were significantly lower in that group by 6%, 3%, and 27%, respectively. Similarly, the erythrocyte SOD activity was lower in the L-Mg group than in the H-Mg group by 5%. Low serum magnesium levels contribute to lead-induced oxidative stress, result in unfavorable modification of antioxidant system function, and promote lead-induced impairment of heme synthesis. Obtained results indicate that prevention of hypomagnesemia should be regarded as an important step in ensuring adequate prophylaxis of chronic lead poisoning.


Electron-nuclear cross polarization.
We describe the coherent polarization transfer from an unpaired electron to neighboring nuclei via electron-nuclear cross polarization (eNCP) in a doubly, tilted rotating frame. Although the experiment superficially resembles the well-known Hartmann-Hahn cross polarization (CP) process introduced by Pines et al., that is widely used in solid-state nuclear magnetic resonance (SSNMR), it differs in significant respects. In particular, eNCP requires an alternative treatment due to the very different sizes of the specific terms in the spin Hamiltonian. We derive analytical expressions for the matching condition for optimal polarization transfer and verify their correctness with experimental results obtained with electron detected CP experiments performed on powder samples of BDPA radical dispersed in a protonated polystyrene matrix and with numerical simulations. We use fully protonated BDPA as an example of polarization transfer to strongly coupled nuclei. In contrast, perdeuterated BDPA serves as an example of the transfer of polarization from electrons to weakly coupled nuclei. In addition, we performed CP on a paramagnetic crystal to determine the influence of resolved hyperfine structure on the CP process. It is shown that almost no structure is observed in the corresponding electron-(1)H CP matching curve. It appears that only a restricted number of hyperfine coupled (1)H's contribute to the observed signal intensities in the CP experiment.


Plaque modification and stabilization after drug-coated balloon angioplasty for intracranial atherosclerotic lesions.
A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). We aimed to evaluate changes of vessel wall features of ICAD lesions after DCB treatment by using vessel wall MRI (VWMRI). We retrospectively included patients with symptomatic ICAD who underwent DCB angioplasty alone. The incidences of stenosis of the lumen area, vessel wall thickening, hyperintense plaques, and prominent wall enhancement were compared between the baseline and follow-up VWMRI. There were 29 ICAD lesions from 29 patients, of which 22 were stenosis and 7 were occlusion. The median interval between DCB treatment and follow-up VWMRI was 4.1 [3.3, 6.7] months. After DCB treatment, follow-up VWMRI showed a significant decrease in the stenosis degree of the lumen area (83% [71%, 96%] vs 15% [3%, 41%], p < 0.001). Thirty-eight percent (11/29) of the patients observed normal appearance of the target vessel wall on follow-up VWMRI. In the stenosis group, the prevalence of hyperintense plaques decreased from 66.7% (14/21) at baseline to 23.8% (5/21) at follow-up, and prominent wall enhancement decreased from 66.7% (14/21) at baseline to 19.0%(4/21) at follow-up. The incidence of hyperintense plaques (p = 0.028) and vessel wall thickening (p = 0.018) tended to decrease with follow-up time. Although not significant (p = 0.106), a similar trend was observed between the incidence of prominent wall enhancement and follow-up time. Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions. • A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). • Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions.


Inline Progesterone Monitoring in the Dairy Industry.
An inline progesterone monitoring system that works automatically and provides real-time physiological information about lactating dairy cows for making farm management decisions is not only a novel tool for scientific research but also improves productivity, food safety, animal well-being, the environment, and the public perception of the dairy industry.


Radiologic search for embolized leaflets of prosthetic heart valves: a report of two cases.
In a radiologic search for embolized leaflets of Edwards-Duromedics bileaflet valves in 2 patients, the embolized fragments were localized in the iliac vessels using computed tomography. Sonography was successful in one case and standard X-ray films of the abdomen were negative in both cases. In vitro investigations with Björk-Shiley and Edwards-Duromedics leaflets suggested that standard X-ray films of the abdomen and pelvis should be considered as the first investigational technique. If negative, computed tomography of the lower abdomen should be done.


Origin of the response to adrenal and sex steroids: Roles of promiscuity and co-evolution of enzymes and steroid receptors.
Many responses to adrenal and sex steroids are mediated by receptors that belong to the nuclear receptor family of transcription factors. We investigated the co-evolution of these vertebrate steroid receptors and the enzymes that synthesize adrenal and sex steroids through data mining of genomes from cephalochordates [amphioxus], cyclostomes [lampreys, hagfish], chondrichthyes [sharks, rays, skates], actinopterygii [ray-finned fish], sarcopterygii [coelacanths, lungfishes and terrestrial vertebrates]. An ancestor of the estrogen receptor and 3-ketosteroid receptors evolved in amphioxus. A corticoid receptor and a progesterone receptor evolved in cyclostomes, and an androgen receptor evolved in gnathostomes. Amphioxus contains CYP11, CYP17, CYP19, 3β/Δ5-4-HSD and 17β-HSD14, which suffice for the synthesis of estradiol and Δ5-androstenediol. Amphioxus also contains CYP27, which catalyzes the synthesis of 27-hydroxy-cholesterol, another estrogen. Lamprey contains, in addition, CYP21, which catalyzes the synthesis of 11-deoxycortisol. Chondrichthyes contain, in addition, CYP11A, CYP11C, CYP17A1, CYP17A2. Coelacanth also contains CYP11C1, the current descendent from a common ancestor with modern land vertebrate CYP11B genes, which catalyze the synthesis of cortisol, corticosterone and aldosterone. Interestingly, CYP11B2, aldosterone synthase, evolved from separate gene duplications in at least old world monkeys and two suborders of rodents. Sciurognathi (including mice and rats) and Hystricomorpha (including guinea pigs). Thus, steroid receptors and steroidogenic enzymes co-evolved at key transitions in the evolution of vertebrates. Together, this suite of receptors and enzymes through their roles in transcriptional regulation of reproduction, development, homeostasis and the response to stress contributed to the evolutionary diversification of vertebrates. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'.


Metal ions as allosteric regulators of calmodulin.
Previously we have shown that the fluorescence of the dihydropyridine calcium antagonist felodipine provides an accurate means of monitoring the formation of an allosterically potentiated conformer of calmodulin (Mills, J. S., and Johnson, J. D., (1985) Biochemistry 24, 4897-4903). Characteristic of this conformer is the abolition of cooperativity among the two felodipine-binding sites on calmodulin and a 20-fold increase in the apparent affinity of calmodulin for felodipine. In the present study, we find that the metal cations La3+, Tb3+, Pb2+, and Cd2+ are all capable of abolishing the cooperativity (Hill coefficient = 2.0) among the two felodipine-binding sites on calmodulin and can increase the apparent affinity of calmodulin for felodipine by approximately 20-fold. These effects are seen either in the presence or absence of calcium and are half-maximal at 8, 12, 22, and 1000 microM, respectively. Zinc and H+ are capable of producing similar potentiations of felodipine binding (half-maximal at 570 microM, and pH 5.8), but only in the presence of calcium. In each case, the calcium-binding sites of calmodulin must be occupied (by calcium, La3+, Tb3+, Pb2+, or by Cd2+) before these metals can bind to sites which are distinct from the calcium-binding sites to produce the active conformer of calmodulin which exhibits enhanced affinity for felodipine. Mercury and copper can compete with these potentiating metal cations on calmodulin and produce an inactivation of this active calmodulin conformer. These studies suggest that some metals including La3+, Tb3+, Pb2+, Cd2+, Zn2+ and protons are capable of binding to a calcium-calmodulin complex and forming an allosterically active species of calmodulin which cannot be maintained by physiological concentrations of calcium ions alone. Mercury and copper, on the other hand, are capable of inactivating this active calmodulin conformer independent of the presence of calcium on calmodulin. These findings are examined in terms of the mechanism of action of calmodulin and its possible role in heavy metal toxicity.


Enhanced performance of a submerged membrane bioreactor with powdered activated carbon addition for municipal secondary effluent treatment.
The aim of this study was to investigate the feasibility of PAC-MBR process treating municipal secondary effluent. Two laboratory-scale submerged MBRs (SMBR) with and without PAC addition were continuously operated in parallel for secondary effluent treatment. Approximately 63%TOC, 95% NH(4)(+)-N and 98% turbidity in secondary effluent were removed by the PAC-MBR process. Most organics in the secondary effluent were found to be low molecular weight (MW) substances, which could be retained in the reactor and then removed to some extent by using PAC-MBR process. Parallel experiments showed that the addition of PAC significantly increased organic removal and responsible for the largest fraction of organic removal. Membrane fouling analysis showed the enhanced membrane performance in terms of sustainable operational time and filtration resistances by PAC addition. Based on these results, the PAC-MBR process was considered as an attractive option for the reduction of pollutants in secondary effluent.


A novel technology with precise oxygen-input control: Application of the partial nitritation-anammox process.
Reliable and accurate oxygen-input control, which is critical to maintaining efficient nitrogen removal performance for partial nitritation-anammox (PN-A) process, remains one of the main operational difficulties. In this study, a novel, yet simple system (a simple process for autotrophic nitrogen-removal, SPAN) with precise oxygen-input control was developed to treat ammonium-rich wastewater via PN-A process. SPAN brings oxygen to biomass by circulating water and creating water spray (shower) at the water-air interface, and effectively balances the activities of core functional microorganisms through precise oxygen-input control. The oxygen-input rate is decided by the water circulation rate and shower rate and is measurable and predictable. Therefore, the required amount of oxygen for ammonium oxidation can be precisely delivered to the biomass by adjusting the circulation rate and shower rate. The results of two parallel SPAN reactors demonstrated that during long-term operation, the required oxygen input was precisely and reliably controlled. More than 99% of NH4+-N and 81% - 85% of total nitrogen were stably removed, with anammox bacteria contributing to more than 96% of total nitrogen removal. Anammox bacteria were efficiently enriched to the highest level among the key nitrogen-converting microbial groups, both in terms of abundance (8.17%) and nitrogen-conversion capacity, while ammonium oxidizing bacteria were well controlled to provide sufficient ammonium-oxidizing capacity. Nitrite oxidizing bacteria were maintained stable (relative abundance of 1.08%-1.88%) and their activity was effectively suppressed. This study provided a novel technology, SPAN, to precisely control oxygen input in PN-A system, and proved that SPAN was effective and reliable in achieving long-term high-efficiency nitrogen removal.


The hypothalamic-pituitary-thyroid axis.
Although recent investigations have contributed greatly to our understanding of the function and regulation of the hypothalamic-pituitary-thyroid axis, much remains unclear. The influence of suprahypothalamic areas of the brain on hypothalamic function, the nature of thyroid hormone feedback on the hypothalamus, and the physiologis sugnificance of prolactin release by TRH are all topics requiring further study. The extensive experience which has been accululated in the use of TRH as a diagnostic tool has led to its acceptance as a safe, convenient, rapid method of assessment of pituitary and thyroid function. It appears that TRH testing is useful in evaluation of pituitary TSH and prolactin reserve in patients with pituitary lesions; in the differentiation of pituitary and hypothalamic causes of hypothyroidism; in diagnosis of euthyroid Graves' disease; in the evaluation of the adequacy of TSH suppression in thyroid hormone therapy of nodular goiter; and possibly in the diagnosis of mild primary hypothyroidism.


Appearance of D2O in sweat after oral and oral-intravenous rehydration in men.
Intravenous (IV) rehydration is common in athletics, but its thermoregulatory benefits and ergogenicity have not been elucidated. Availability of orally ingested fluid is dependent on gastric emptying and intestinal absorption rate. Deuterium oxide (D2O) has been used to demonstrate that fluid ingested during exercise appears in sweat within 10 minutes. The purpose of this study was to determine the effect of concurrent IV rehydration on D2O appearance in sweat samples after per ora rehydration with D2O labeled fluid. We hypothesized that the combination method would not be superior to the oral method. Ten fit men (age 23 ± 4, VO2max 59.49 ± 4.09 L·min(-1)) underwent 20 hours of fluid restriction resulting in 1.95 ± 0.25% body weight loss before beginning treadmill exercise and cycling. Exercise was performed in an environmental chamber (35.6 ± 0.2° C, 35.0 ± 1.8% relative humidity) for 2 hours at 55% VO2max, and the participants exhibited a mean body weight deficit of 4.50 ± 0.04%. Thermoregulatory measures were recorded while subjects were rehydrated with oral (OR) or oral combined with intravenous (IVO) fluid traced with D2O. After 30 minutes of rehydration and 30 minutes of seated recovery, the subjects began treadmill exercise at 55-60% VO2max. Forehead sweat samples were collected 0, 5, 10, 20, and 75 minutes from the start of rehydration. The samples were analyzed for D2O via isotope ratio mass spectrometry. D2O did not appear in the sweat within 20 minutes of rehydration; however, it did appear during the subsequent exercise bout. There was no significant difference between rehydration modes. Plasma volume increases and decreased volume of orally ingested fluid did not significantly alter transit time from ingestion to appearance in excreted sweat. The IVO method does not appear to be superior to the traditional OR method of rehydration.


mRNA-Seq reveals the quorum sensing system luxS gene contributes to the environmental fitness of Streptococcus suis type 2.
Streptococcus suis type 2 (SS2) is an important zoonotic pathogen. We have previously reported the structure of LuxS protein and found that the luxS gene is closely related to biofilm, virulence gene expression and drug resistance of SS2. However, the mechanism of luxS mediated SS2 stress response is unclear. Therefore, this experiment performed stress response to luxS mutant (ΔluxS) and complement strain (CΔluxS), overexpression strain (luxS+) and wild-type SS2 strain HA9801, and analyzed the differential phenotypes in combination with transcriptome data. The results indicate that the luxS gene deletion causes a wide range of phenotypic changes, including chain length. RNA sequencing identified 278 lx-regulated genes, of which 179 were up-regulated and 99 were down-regulated. Differential genes focus on bacterial growth, stress response, metabolic mechanisms and drug tolerance. Multiple mitotic genes were down-regulated; while the ABC transporter system genes, cobalamin /Fe3+-iron carrier ABC transporter ATPase and oxidative stress regulators were up-regulated. The inactivation of the luxS gene caused a significant reduction in the growth and survival in the acid (pH = 3.0, 4.0, 5.0) and iron (100 mM iron chelator 2,2'-dipyridyl) stress environments. However, the mutant strain ΔluxS showed increased antioxidant activity to H2O2 (58.8 mmol/L). The luxS gene in SS2 appears to play roles in iron metabolism and protective responses to acidic and oxidative environmental conditions.


Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents.
Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. Longitudinal cohort study. Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32-3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89-4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: -0.05; 95% CI: -0.08 to -0.02; P < .001) and frailty (β: -0.22; 95% CI: -0.33 to -0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.


Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients.
Resistance to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in some patients with locally advanced breast cancer remains one of the main obstacles to first-line treatment. We investigated clinical and pathological responses to FAC neoadjuvant chemotherapy in Mexican women with breast cancer and their possible association with SNPs present in ABC transporters as predictors of chemoresistance. A total of 102 patients undergoing FAC neoadjuvant chemotherapy were included in the study. SNP analysis was performed by RT-PCR from genomic DNA. Two SNPs were analyzed: ABCB1 rs1045642 (3435 C > T) and ABCG2 rs2231142 (421 G > T). In clinical response evaluation, significant associations were found between the ABCB1 C3435T genotype and breast cancer chemoresistant and chemosensitive patients (p < 0.05). In the early clinical response, patients with genotype C/C or C/T were more likely to be chemosensitive to neoadjuvant therapy than patients with genotype T/T (OR = 4.055; p = 0.0064). Association analysis between the ABCB1 gene polymorphism and the pathologic response to FAC chemotherapy showed that the C/C + C/T genotype was a protective factor against chemoresistance (OR = 3.714; p = 0.0104). Polymorphisms in ABCG2 indicated a lack of association with resistance to chemotherapy (p = 0.2586) evaluating the clinical or pathological response rate to FAC neoadjuvant chemotherapy. The early clinical response and its association with SNPs in the ABCB1 transporter are preserved until the pathological response to neoadjuvant chemotherapy; therefore, it could be used as a predictor of chemoresistance in locally advanced breast cancer patients of the Mexican population.


Body mass index and body composition measures by dual x-ray absorptiometry in patients aged 10 to 21 years with spinal cord injury.
To determine the body composition of adolescents with spinal cord injury (SCI) and to assess whether established cutoff values for obesity determined by body mass index (BMI) are valid for this population. Sixty patients, aged 10-21 years, with traumatic SCI (50 with paraplegia and 10 with tetraplegia) were compared with 60 gender-, age-, and BMI-matched controls (CTRL). Dual-energy x-ray absorptiometry was used to estimate regional and total bone mineral content, lean tissue mass, fat tissue mass, and body fat percentage. BMI was calculated from measured weight and stature (kg/m2). Total percent body fat was significantly higher in the paraplegia group (31.4% +/- 1.2%; mean +/- SE) than in the tetraplegia and CTRL groups (25.7% +/- 2.7% and 22.9% +/- 1.1%, respectively). This change in percent total body fat was associated with a reduction of lean tissue mass in the paraplegia (37.6 +/- 1.1 kg; mean +/- SE) and tetraplegia (32.8 +/- 2.5 kg) subjects as compared to the CTRL group (46.2 +/- 1.0 kg; P < 0.001). Total fat mass was significantly greater in the paraplegia group (19.3 +/- 1.3 kg) than the CTRL and tetraplegia groups (14.9 +/- 1.2 kg and 11.7 +/- 3.0 kg, respectively). Regional measurements revealed that the greatest reduction of lean tissue mass in the SCI subjects occurred in the lower extremities, followed by the trunk. As a result of these changes in body composition, the optimal BMI for classifying obesity (trunk fat percent >30 in males and >35 in females) in subjects with SCI was 19 kg/m2 as compared to 25 kg/m2 in able-bodied subjects. Patients aged 10 to 21 years with SCI have significantly decreased lean tissue mass and bone mineral content, and increased fat mass. As a result, traditional BMI cutoff criteria significantly underestimate obesity in this population. New clinically applicable criteria to define obesity should be established for SCI children and adolescents with SCI.


Clinical values of transrectal ultrasound in judging GTV of cervical cancer.
To investigate the clinical value of transrectal ultrasound in judging the Gross Target Volume (GTV) of cervical cancer (CC). A total of 196 CC patients admitted to the Department of Radiotherapy, China-Japan Union Hospital, Jilin University, from January 2016 to June 2019 were selected as the study subjects. The GTVs before and after applicator insertion were determined by transrectal ultrasound and compared with those judged by MRI. All 196 patients were successfully undergoing applicator insertion according to the pretreatment plan. The GTV doses reached the clinical requirements during treatment. There was no significant difference between the GTVs judged by MRI and ultrasound before insertion in terms of upper/lower diameter (MRI Before 1 vs. Ultrasound Before 1) (MB1 vs. UB1), left/right diameter (MB2 vs. UB2), or ventral/dorsal diameter (MB3 vs. UB3), and the intragroup correlation coefficients (ICC) were 0.59, 0.77, and 0.66, respectively; moreover, there was no significant difference between the GTVs judged by MRI and ultrasound after insertion in terms of MRI After one vs. Ultrasound After one (MA1 vs. UA1), MA2 vs. UA2, and MA3 vs. UA3, and the ICC values were 0.62, 0.79, and 0.76, respectively. Transrectal ultrasound can satisfactorily determine the GTV of CC and has certain value in brachytherapy for CC.


Inclusion of shape parameters increases the accuracy of 3D models for microplastics mass quantification.
As microplastics may bring about adverse effects on living organisms, it is important to establish more precise quantification approaches to better understand their dynamics. One method to determine the concentration of microplastics is to estimate their mass using three-dimensional (3D) models, but its accuracy is not well known. In this study, we evaluated the shape of the particles and verified the accuracy of a 3D model-based mass estimation using samples from a tidal flat facing Tokyo Bay. The particle shape evaluation suggested that the microplastics were flat and irregular in shape; based on these data, we created two types of models to estimate their mass. As a result, an accuracy of mass estimation by our model was higher than other models that consider the slenderness and flatness of particles. The optimization of mass estimation methods based on 3D models may improve the reliability of microplastic evaluation in monitoring studies.


Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19.
The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. We sought to identify biomarkers for disease severity and progression of COVID-19. Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-γ-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-γ-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.


Late-Presenting Sagittal Craniosynostosis: An Update to a Standardized Treatment Protocol.
The authors previously published their protocol to treat patients who present with sagittal craniosynostosis after the age of 1 year. The purpose of this article is to present a follow-up and update of this cohort to evaluate outcomes of their treatment protocol. Patients with isolated sagittal craniosynostosis who presented after the age of 1 year between July of 2013 and April of 2021 were included. A total of 108 patients met inclusion criteria. The average age at presentation was 5.2 ± 3.4 years, and 79 patients (73.1%) were male. The indications for imaging were head shape (54.6%), headache (14.8%), trauma (9.3%), seizure (4.6%), papilledema (2.8%), and other (13.9%). Of the 108 patients, 12 (11.1%) underwent surgery following their initial consultation: five for papilledema, four for elevated intracranial pressure, two for severely scaphocephalic head shapes, and one for abnormal funduscopic findings. Two of these patients underwent additional reconstructive surgery, one for the recurrence of papilledema and headache and the other for progressive scaphocephaly. The average length of time between operations was 4.9 years. Of the 96 patients who were managed conservatively, four (4.2%) underwent surgery at an average of 1.2 ± 0.5 years later (average age, 4.4 ± 1.5 years) for brain growth restriction ( n = 2), aesthetic concerns ( n = 1), and refractory headaches ( n = 1). The average follow-up of all patients with craniofacial surgery was 2.7 ± 2.3 years (median, 2.1 years; interquartile range, 3.7 years). Patients with late-presenting sagittal craniosynostosis require surgical correction less often than younger patients, likely because of milder phenotype. Few patients in the conservative treatment arm ultimately required surgery (4%). Therapeutic, IV.


An overview of the clinical pharmacokinetics of x-ray contrast media.
Pharmacokinetic studies of contrast media are usually performed as preclinical trials in anaesthetised animals; however, results in humans have also been reported for this type of compounds. This paper reviews the existing data about x-ray contrast media in humans. In some cases, animal data are used in areas where no human data are available. The administration of contrast media is generally made via the intravenous, intra-arterial or intrathecal route. Diagnostic procedures are based on differential distribution to organs and between normal and abnormal tissue. Data are available for iodixanol, iohexol, iopamidol, iopromide, iothalamate and ioxaglate, but the kinetic distribution of all contrast media is similar. With the exception of biliary contrast agents, all compounds display limited plasma protein binding and do not undergo biotransformation. From the pharmacokinetic viewpoint, the main area of interest for these compounds is elimination. The majority of the data were obtained with iopamidol (of which 66 to 72% of the dose is excreted in the urine), iohexol, ioxaglate and iopromide. Some studies were performed in patients with renal impairment: in this case, metabolic clearance was abnormally elevated, suggesting the existence of significant compensatory factors such as hepatic metabolism, enterohepatic circulation and biliary elimination. New compounds, such as iodinated polymers for x-ray perfusion imaging and iopromide- or metrizamide-containing liposomes allowing liver enhancement are discussed.


Enhance the resistance of probiotics by microencapsulation and biofilm construction based on rhamnogalacturonan I rich pectin.
Microcapsules were always used as functional material carriers for targeted delivery and meanwhile offering protection. However, microcapsule wall materials with specific properties were required, which makes the choice of wall material a key factor. In our previous study, a highly branched rhamnogalacturonan I rich (RG-I-rich) pectin was extracted from citrus canning processing water, which showed good gelling properties and binding ability, indicating it could be a potential microcapsule wall material. In the present study, Lactiplantibacillus plantarum GDMCC 1.140 and Lactobacillus rhamnosus were encapsulated by RG-I-rich pectin with embedding efficiencies of about 65 %. The environmental tolerance effect was evaluated under four different environmental stresses. Positive protection results were obtained under all four conditions, especially under H2O2 stress, the survival rate of probiotics embedded in microcapsules was about double that of free probiotics. The storage test showed that the total plate count of L. rhamnosus encapsulated in RG-I-rich pectin microcapsules could still reach 6.38 Log (CFU/mL) at 25 °C for 45 days. Moreover, probiotics embedded in microcapsules with additional incubation to form a biofilm layer inside could further improve the probiotics' activities significantly in the above experiments. In conclusion, RG-I-rich pectin may be a good microcapsule wall material for probiotics protection.


Migratory birds have higher prevalence and richness of avian haemosporidian parasites than residents.
Individuals of migratory species may be more likely to become infected by parasites because they cross different regions along their route, thereby being exposed to a wider range of parasites during their annual cycle. Conversely, migration may have a protective effect since migratory behaviour allows hosts to escape environments presenting a high risk of infection. Haemosporidians are one of the best studied, most prevalent and diverse groups of avian parasites, however the impact of avian host migration on infection by these parasites remains controversial. We tested whether migratory behaviour influenced the prevalence and richness of avian haemosporidian parasites among South American birds. We used a dataset comprising ~ 11,000 bird blood samples representing 260 bird species from 63 localities and Bayesian multi-level models to test the impact of migratory behaviour on prevalence and lineage richness of two avian haemosporidian genera (Plasmodium and Haemoproteus). We found that fully migratory species present higher parasite prevalence and higher richness of haemosporidian lineages. However, we found no difference between migratory and non-migratory species when evaluating prevalence separately for Plasmodium and Haemoproteus, or for the richness of Plasmodium lineages. Nevertheless, our results indicate that migratory behaviour is associated with an infection cost, namely a higher prevalence and greater variety of haemosporidian parasites.


A systematic review and meta-analysis to determine the effect of oral anticoagulants on incidence of dementia in patients with atrial fibrillation.
To assess the effect of oral anticoagulant (OAC) administration on incidence of dementia in patients with atrial fibrillation (AF) with Systematic review and meta-analysis. We systematically searched the electronic databases including Pubmed, Embase, Cochrane library and ClinicalTrails.gov for relevant articles. The primary outcome was the incidence of dementia. The adjusted risk ratio (RR), odds ratio or hazard ratio were extracted and pooled by the random-effects models. Subgroup analysis was performed according to the setting observational window. Risk of bias was assessed using the Newcastle-Ottawa Scale, while publication bias was assessed by the Begg's and Egger's tests. Nine studies were included in this review (2 prospective and 7 retrospective observational studies, including 613,920 patients). The results presented the significant association between OAC therapy and the reduced risk of dementia compared with no treatment (RR [95% CI] = 0.72 [0.60, 0.86], I2 = 97.2%; P = .000). In the subgroup analysis with an observational window, the pooled RR became statistically non-significant (including four studies, RR [95% CI] = 0.75 [0.51, 1.10], I2 = 98.8%; P = .000). There is no significant risk of bias and publication bias. This study indicated the protective effect of OAC therapy for dementia in patients with AF. However, the results are limited because of high heterogeneity, inconsistent direction of effect in subgroup analysis with an observational window. Further prospective well-designed study is needed with longer follow-up duration in younger patients.


Dietary exposure to potentially toxic elements through sushi consumption in Catalonia, Spain.
Although sushi is considered as a healthy food, it can also be a route of exposure to chemical contaminants such as potentially toxic trace elements. In this study, we analysed the concentration of Cd, I, Ni, Pb and total Hg, as well as iAs and MeHg in sushi samples. Iodine levels were higher in samples containing seaweed, while iAs concentrations were greater in rice-containing sushi. In turn, total Hg and MeHg were significantly higher in sushi samples with tuna. Health risks of sushi consumption were assessed for three population groups: children, adolescents and adults. Considering an average intake of 8 sushi pieces for adults and adolescents, and 3 sushi pieces for children, the estimated exposure to MeHg by adolescents exceeded the tolerable daily intake set by EFSA, while MeHg intake by children and adults was below, but close to that threshold. A relatively high daily exposure of Ni and Pb was also found, especially for adolescents. Since this study focused only on the consumption of sushi, the contribution of other food groups to the overall dietary exposure should not be disregarded. It might lead to an exposure to MeHg and other trace elements above the health-based guideline values.


Amelioration of salmonellosis in pre-weaned dairy calves fed Saccharomyces cerevisiae fermentation products in feed and milk replacer.
Salmonellosis is an insidious and potentially epidemic problem in pre-weaned dairy calves. Managing this disease, or any other diarrheal disease, is a financial burden to producers. Calf mortalities and medicinal treatments are overt costs of salmonellosis, while hidden costs include hampered weight gains and persistent intestinal colonization of the pathogen. In this study, we examined the anti-Salmonella effects of Saccharomyces cerevisiae fermentation products (SCFP) incorporated into both the milk replacer and the starter grain. In a blinded study, 2-8 day-old calves were fed SCFP (n=20 calves) or an SCFP-free Control (n=20 calves) for two weeks before and three weeks after experimental challenge with Salmonella enterica serotype Typhimurium. Following the challenge, calves were monitored for clinical signs and parameters associated with salmonellosis. Calves were then euthanized and examined for rumen development and intestinal Salmonella colonization. When compared to calves that received milk replacer and feed lacking SCFP, calves fed SCFP had fewer bouts of diarrhea and fever. Rumens from these calves were more developed, as measured by the length of papillae, which is consistent with the enhanced weight gain observed in this treatment group. Additionally, Salmonella intestinal colonization was reduced in SCFP-fed calves and Salmonella fecal shedding disappeared at an earlier stage in these calves. This study revealed that the combination of two proprietary S. cerevisiae fermentation products provide marked benefit for preventing the negative effects of salmonellosis in pre-weaned dairy calves, while also boosting productivity. The mechanism of action needs to be clarified, but it may be related to the observed decrease in colonization by the pathogen and increase in rumen development.


Decorin and chondroitin-6 sulfate inhibit B16V melanoma cell migration and invasion by cellular acidification.
In vivo, cells are embedded in an environment generated and maintained by multiple cell-cell and cell-matrix interactions. While transiting the dermis metastasizing melanoma cells interact with the extracellular matrix (ECM) and fibroblasts. To study the roles of ECM components and fibroblasts in melanoma (B16V) cell migration and invasion, we established a co-culture system consisting of fibroblasts, their collagen-rich matrix and B16V cells. The crosstalk between B16V cells and fibroblasts was indicated by a clear increase in release and activity of matrix-metallo-protease-2. Time-lapse microscopy revealed that in B16V cells exposed to either decorin or chondroitin sulfates migration and invasion decreased by more than 50%. Decorin led to a reversible, chondroitin-6-sulfate to an irreversible, cytosolic acidification of B16V cells. Interestingly, decorin lowered NHE1 activity whereas chondroitin-6-sulfate did not. Furthermore, decorin and chondroitin-6-sulfate also acidified the pH at the cell surface which might prevent migration due to strong adhesion. In conclusion, the present co-culture system is an appropriate tool to analyze migration, invasion, and MMP release depending on cell-matrix interactions and the crosstalk between the invasive cells and those surrounded by their self-made matrix. We show a so far unknown function of decorin and chondroitin-6-sulfate: their ability to inhibit B16V cell migration by intracellular acidification.


[Linear IgA bullous dermatosis of children].
Linear IgA bullous dermatosis is an acquired autoimmune subepidermal blistering disease, characterized by linear IgA deposits at the basement membrane zone. Described in both children and adults, it occurs as tense pruritic vesicles and bullae in a "cluster of jewels" configuration with central crusting on an inflammatory elevated base. It is typically located on the face, anogenital region and trunk. Whilst the adult manifestations can be chronic, in children a spontaneous remission has often been reported. Our patient showed a spontaneous remission after 8 weeks of symptomatic topic treatment with methylprednisolone and oral cetirizine dihydrochloride.


A monoclonal antibody to viral glycoprotein blocks virus-immune effector T cells operating at H-2Dd but not at H-2Kd1.
A particular monoclonal antibody that binds to the influenza virus HA molecule inhibits HA-specific thymus-derived lymphocytes mediating cytotoxicity in the context of H-2Dd but not of H-2Kd. Another monoclonal antibody blocks both sets of HA-specific effector T cells. This observation, together with related findings from other laboratories, is considered to support the idea that T cell recognition is directed against some association of viral and H-2 glycoproteins, as proposed in the original formulation of the "altered self" concept.


Tissue-selective actions of estrogen analogs.
The biological actions of estrogen analogs have frequently confounded prevailing views regarding the mechanism of estrogen action. Agents originally intended as antifertility drugs are now used clinically to promote ovulation. The early work with antiestrogens as antifertility agents lead to the realization that triphenylethylene antiestrogens suppressed the growth of breast tumors. The subsequent ubiquitous clinical use of tamoxifen for adjuvant breast cancer therapy is a direct result of this research. Basic studies using tamoxifen and related antiestrogens revealed the previously unsuspected tissue selective actions of these compounds. This peculiar property is being taken advantage of to gain new insight into the molecular mechanisms of estrogen action. This property also forms the basis for an exciting new approach to hormone replacement therapy to prevent postmenopausal osteoporosis and cardiovascular disease. The laboratory rat played an integral and essential part in each of these developments. The success of the ovariectomized rat model in predicting the tissue selective effects of tamoxifen in women greatly increases confidence that this animal model will be useful in development of a new generation of estrogen analogs designed specifically for postmenopausal hormone replacement.


Altered phase-encoding order for reduced sensitivity to motion in three-dimensional MR imaging.
A method of reordering phase and slab encoding that can be used to address some of the inherent problems due to motion in three dimensional imaging is described and implemented. The method is shown to be more robust with respect to reducing artifacts resulting from several fundamental types of motion. It can be readily implemented on a standard magnetic resonance imager with essentially no increase in total imaging time. Results of simulations and phantom and in vivo experiments are presented.


Treatment technologies for selenium contaminated water: A critical review.
Selenium is an indispensable trace element for humans and other organisms; however, excessive selenium in water can jeopardize the aquatic environment. Investigations on the biogeochemical cycle of selenium have shown that anthropogenic activities such as mining, refinery, and coal combustion mainly contribute to aquatic selenium pollution, imposing tremendous risks on ecosystems and human beings. Various technologies thus have been developed recently to treat selenium contaminated water to reduce its environmental impacts. This work provides a critical review on the applications, characteristics, and latest developments of current treatment technologies for selenium polluted water. It first outlines the present status of the characteristics, sources, and toxicity of selenium in water. Selenium treatment technologies are then classified into three categories: 1) physicochemical separation including membrane filtration, adsorption, coagulation/precipitation, 2) redox decontamination including chemical reduction and catalysis, and 3) biological transformation including microbial treatment and constructed wetland. Details of these methods including their overall efficiencies, applicability, advantages and drawbacks, and latest developments are systematically analyzed and compared. Although all these methods are promising in treating selenium in water, further studies are still needed to develop sustainable strategies based on existing and new technologies. Perspectives on future research directions are laid out at the end.


A hunger for warmth.
Humans and animals alike perform behaviors-like putting on a sweater or building a warm nest-to regulate body temperature. In this issue of Neuron, Jung et al. (2022) reveal a parabrachial nucleus-to-lateral hypothalamus circuit that regulates thermoregulatory behavior, a circuit distinct from that which governs motivated feeding behavior.


Astrocytes-derived exosomes pre-treated by berberine inhibit neuroinflammation after stroke via miR-182-5p/Rac1 pathway.
Our previous studies have shown that berberine can improve the nerve function deficits in ischemic stroke by inhibiting inflammation. The cellular communication between astrocytes and neurons via exosomes might affect neurological function after ischemic stroke, which plays a vital role in the therapy of ischemic stroke. The present study focused on the effects of exosomes released from astrocytes induced by the glucose and oxygen deprivation model with berberine pretreatment (BBR-exos) treatment for ischemic stroke and its regulatory mechanism. Oxygen-glucose-deprivation/Reoxygenation (OGD/R)-treated primary cells were used to mimic cerebral ischemia/reperfusion conditions in vitro. With the treatment of BBR-exos and exosomes released from primary astrocytes induced by the glucose and oxygen deprivation model (OGD/R-exos), the cell viability was detected. C57BL/6J mice were used to establish middle cerebral artery occlusion/reperfusion (MCAO/R) model. The anti-neuroinflammation effects of BBR-exos and OGD/R-exos were evaluated. Subsequently, the key miRNA in BBR-exos was identified by exosomal miRNA sequencing and cell validation. miR-182-5p mimic and inhibitors were provided to verify the effects in inflammation. Finally, the binding sites between miR-182-5p and Rac1 were predicted online and verified by using a dual-luciferase reporter assay. BBR-exos and OGD/R-exos both improved the decreased activity of OGD/R-induced neurons, and decreased the expression of IL-1β, IL-6 and TNF-α (all P < 0.05), which reduced neuronal injury and inhibited neuroinflammation in Vitro. And BBR-exos showed better effects (P < 0.05). The same effect has been verified in vivo experiments: BBR-exos and OGD/R-exos both reduced cerebral ischemic injury and inhibited neuroinflammation in MCAO/R mice (all P < 0.05). Likewise, BBR-exos showed better effects (P < 0.05). The exosomal miRNA sequencing results showed that miR-182-5p was highly expressed in BBR-exos and inhibited neuroinflammation by targeting Rac1 (P < 0.05). BBR-exos can carry miR-182-5p to injured neurons and inhibit the expression of Rac1, which could inhibit neuroinflammation and improved brain injury after ischemic stroke.


[Therapeutically active dressings--biomaterials in a study of collagen glycation].
Active dressings (biomaterials, hydrogels) are cross-linked three-dimensional macromolecular networks. One of the most important properties of active dressings, is their ability for controlled uptake, release and retention of molecules. The formation of advanced glycation end products AGEs progressively increases with normal aging. However, AGE products are formed at accelerated rates in age and stress-related diseases (burns, in wound healing) and also in vitro. The aim will be also to develop a series of gels showing ability of controlled uptake, release and retention of molecules. The hydrogels can be used as biologically and therapeutically (antibacterial and anticancer) active biomaterials. The following materials and reagents were used in the examination: dried plants: Equisetum arvense L., Pulmonaria officinalis L., Agropyron repens. Non-defatted films were extracted from the dried plants. The suspension was stirred and extracted. Temperature was controlled using a water bath. The filtrate was vacuum condensed. The gelling precipitate was poured onto Petri plates and dried. The swelling ratio and the percent loading were calculated. The released amount of CaCl2 at different time intervals was determined by measuring the conductivity. The extent of glycation in collagen was measured. Novel types of swelling hydrogels have been prepared from dried plants and alginic acid. The active dressings showed swelling in aqueous medium, swelling characteristics were dependent on the chemical composition of hydrogel. The hydrogels were also loaded with CaCl2 and their potential for release was judged by measuring conductivity. The activity of hydrogels--active dressings on collagen incubated with glucose showed an decrease in glycation. So, hydrogels--active dressings, a known antiglycating agent which have therapeutic role in wound healing.


Structural characterization of a novel diglycosyl diacylglyceride glycolipid from Rhizobium trifolii ANU843.
A novel glycolipid was isolated by chloroform-methanol extraction of Rhizobium trifolii ANU843 cells. Compositional analysis, methylation studies, 1H NMR and spectroscopies led to the identification of a diglycosyl diacylglyceride: 1,2-di-O-acyl-3-O-[alpha-D-glucopyranosyl-(1----3)-O-alpha-D- mannopyranosyl]glycerol. Iso-hexadecanoic and anteiso-heptadecanoic acids were the predominant fatty acids esterifying the glyceryl moiety, but a microheterogeneity in fatty acid composition was found, resulting in at least five distinct molecular species of the glycolipid. Although widespread in plants, animals and Gram-positive bacteria, glycosyl glycerides have been seldom reported in Gram-negative bacteria and this work is the first evidence of their occurrence in the bacterial family Rhizobiaceae.


Primary care providers' bereavement care practices: recommendations for research directions.
Bereaved patients are often seen in primary care settings. Although most do not require formal support, physicians may be called upon to provide support to some bereaved, particularly those with bereavement-related mental health disorders like complicated grief and bereavement-related depression. Research evidence on physician bereavement care is scant. We make recommendations for future research in this area. Literature review focuses on studies conducted between 1996 and 2013 in the United States. Searches of Medline and PsychInfo, along with hand searches of reference sections, were conducted. The limited existing research indicates substantial gaps in the research literature, especially in the areas of primary care physician skill and capacity, patient-level outcomes, and the quality of research methodology. No US studies have focused specifically on care for bereavement-related mental health disorders. We provide recommendations about how to improve research about primary care bereavement care. The primary care sector offers ample opportunities for research on bereavement care. With greater research efforts, there may be improvements to quality of bereavement care in primary care, in general, and also to the accurate detection and appropriate referral for bereavement-related mental health conditions.


Current Guidelines for Integration of Palliative Care in Oncology.
Multiple cancer societies and professional medical organizations recommend integration of palliative care into routine oncology care. A growing body of literature supports the benefits of palliative care in patients with cancer. Palliative care improves pain and other symptoms, enhances quality of life, and reduces depression. The best method and timing for integration of palliative care is unclear. Multiple barriers exist that prevent optimal palliative care integration; these barriers will require additional education and research to overcome.


A metabolic data-driven systems pharmacology strategy for decoding and validating the mechanism of Compound Kushen Injection against HCC.
Compound Kushen Injection (CKI) is a widely used TCM formula for treatment of carcinomatous pain and tumors of digestive system including hepatocellular carcinoma (HCC). However, the potential mechanisms of CKI for treatment of HCC have not been systematically and deeply studied. A metabolic data-driven systems pharmacology approach was utilized to investigate the potential mechanisms of CKI for treatment of HCC. Based on phenotypic data generated by metabolomics and genotypic data of drug targets, a propagation model based on Dijkstra program was proposed to decode the effective network of key genotype-phenotype of CKI in treating HCC. The pivotal pathway was predicted by target propagation mode of our proposed model, and was validated in SMMC-7721 cells and diethylnitrosamine-induced rats. Metabolomics results indicated that 12 differential metabolites, and 5 metabolic pathways might be involved in the anti-HCC effect of CKI. A total of 86 metabolic related genes that affected by CKI were obtained. The results calculated by propagation model showed that 6475 shortest distance chains might be involved in the anti-HCC effect of CKI. According to the results of propagation mode, EGFR was identified as the core target of CKI for the anti-HCC effect. Finally, EGFR and its related pathway EGFR-STAT3 signaling pathway were validated in vivo and in vitro. The proposed method provides a methodological reference for explaining the underlying mechanism of TCM in treating HCC.


Use of aerobic granules for treating synthetic high-strength ammonium wastewaters.
In this work, two identical sequencing batch reactors (SBRs) with mature aerobic granules were utilized to treat synthetic high-strength ammonium wastewaters with chemical oxygen demand (COD)/total nitrogen (TN) ratios of 3.9-6.9. The contributions of various mechanisms to the removal of ammonium were determined. Ammonium levels of 600-2000 mg-N l-1 had little adverse effect on the COD removal rate (91.6%-95.3%) with an influent COD of 4490-9860 mg l-1. The TN removal rate was slightly reduced from 71.3% to 59.6% as the influent ammonium concentration was increased from 600 to 2000 mg-N l-1. Experimental results indicated that aerobic granules removed 94.5% of COD and 59.6% of TN in the treatment of synthetic high-strength wastewater (9860 mg-COD l-1 and 2000 mg NH+4-Nl-1) during a 12 h cycle. Granular adsorption, air stripping and conversion by nitrification/denitrification were responsible for removing 9%, 15% and 76%, respectively, of the total removed NHf -N. Dissolved oxygen (DO) was a useful process indicator of the biological reactions in the treatment of high-level ammonium wastewaters.


Temporal arteritis causing admission to hospital in Auckland.
A restrospective eight year review of patients hospitalised with temporal arteritis in Auckland shows that the features of the disease were headache, tender swollen temporal arteries, weight loss and fever very common, and blindness occurred in a quarter of the patients with definite temporal arteritis. The importance of making the diagnosis is discussed.


Adenocarcinoma of the anal transitional zone after double stapled ileal pouch-anal anastomosis for ulcerative colitis.
The development of adenocarcinoma in the anal transitional zone, after restorative proctocolectomy for ulcerative colitis, is rare. We report the first Asian and sixth known case. A 41-year-old Indian lady had a long standing history of ulcerative colitis. Restorative proctocolectomy and stapled ileal pouch-anal anastomosis without mucosectomy was performed. She remained asymptomatic until 3 years later when she complained of discomfort on defecation. A poorly differentiated adenocarcinoma in the anal transition zone was diagnosed and she subsequently underwent an abdomino-perineal resection. The previously reported cases in the literature are reviewed. We also discuss the suggested surveillance for high-risk patients who have undergone an ileal-anal pouch anastomosis.


Intravascular mucinosis with mucin emboli and thrombosis accompanying adenocarcinomas.
Three cases of adenocarcinoma that were complicated by nonbacterial thrombotic endocarditis and disseminated intravascular coagulation are described. In two of these cases mucin was demonstrable within vascular channels as well as within the thrombotic vegetations of the cardiac valves. This intravascular mucin was also responsible for vascular occlusion with resultant infarction in such organs as heart and brain. Intravascular mucin of this magnitude has not been previously recorded and mucinous accumulations behaving as thromboemboli with infarcts have not been heretofore described.


Timing of salvage hormonal therapy in prostate cancer patients with unfavorable prognosis treated with radiotherapy: a secondary analysis of Radiation Therapy Oncology Group 85-31.
Radiation Therapy Oncology Group 85-31 was a randomized trial comparing radiotherapy (RT) alone vs. RT plus adjuvant androgen suppression for life in unfavorable-prognosis carcinoma of the prostate. We examined the impact of early initiation of salvage hormonal therapy (HT) in relapsing patients randomized to RT alone arm. Patients were divided into two groups: early salvage HT and late salvage HT. The early salvage group was defined as receiving HT with a prostate-specific antigen (PSA) level of less than 10 ng/mL, and the late salvage HT group had a PSA level of 10 ng/mL or greater. The outcomes were overall survival (OS), cause-specific mortality (CSM), and local failure (LF). The Kaplan-Meier estimation and log-rank test were used for OS, and the cumulative incidence estimation and Gray's test were used for CSM and LF. Proportional hazards regression models were used to compare the outcomes adjusted for other covariates. The median follow-up times of surviving patients in the early and late salvage HT groups were about 11 and 13 years, respectively. The late salvage HT group had significantly more post-prostatectomy patients and patients with high Gleason scores. After adjustment for all covariates, OS was significantly longer in the early salvage HT group (hazard ratio, 1.5; p = 0.01). However, there were no statistically significant differences in LF or CSM between the groups. The early introduction of salvage HT resulted in improved OS but not improved CSM and LF. A randomized trial to define the optimal salvage hormonal timing is warranted in this group of patients with PSA recurrence after RT.


Remote proctoring for high-risk coronary interventions with mechanical circulatory support during COVID-19 pandemic and beyond.
Remote proctoring by advanced digital technologies may help to overcome pandemic, geographic, and resource-related constraints for mentoring and educating interventional cardiology skills. We present a case series of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with mechanical circulatory support (MCS) guided by remote proctoring to gain insights into a streaming technology platform with regard to video/audio quality, visibility of all structural and imaging details, and delay in transmission. According to our experience, remote proctoring appears to be a reliable, quick, and resource-conserving way to disseminate, educate and improve MCS-supported HR-PCI with implications far beyond the COVID-19 pandemic.


On unsteady 3D bio-convection flow of viscoelastic nanofluid with radiative heat transfer inside a solar collector plate.
Nanoparticles are used in industrial and engineering by allowing for faster heat transfer rates in microchips, vehicle cooling, food processing, and nuclear reactors. This research aims to scrutinize the three-dimensional bioconvectional flow performances of viscoelastic nanofluids through a elongating sheet with motile microorganisms. Radiative impact and solutal boundary conditions are studied here. The impacts of thermophoresis, Brownian motion, and bioconvection are also considered. By using suitable similarity transformations, the PDEs are converted into ODEs. The numerical and graphical results are calculated with the help of shooting scheme built-in function Bvp4c in computational tool MATLAB. The graphical and numerical importance of physical engineering parameters like local skin friction, local Nusselt, local Sherwood, and local motile microorganism numbers are discussed here. The thermal profile is enhanced for the higher estimations of the Brownian motion and thermophoresis parameter. The heat profile is boosted up for the increasing variations of the thermal radiation and the thermophoresis parameter. The energy profile is improved by increasing the estimations of solutal Biot number while declining for mixed convection parameter and unsteadiness parameter. The microorganism profile decays for Peclet and bioconvection Lewis number while rising for buoyancy ratio parameter and bioconvection Rayleigh number.


Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models.
Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis. The current, exploratory study evaluates a multiparametric MRI protocol including sodium imaging (23 Na-MRI) to determine the opportunities within this modality to assess kidney injury as a surrogate endpoint of fibrosis. The study includes 43 pigs exposed to ischemia-reperfusion injury (IRI) or unilateral ureteral obstruction (UUO), or serving as healthy controls. Fibrosis was determined using gene expression analysis of collagen. The medulla/cortex ratio of 23 Na-MRI decreased in the injured kidney in the IRI pigs, but not in the UUO pigs (p = 0.0180, p = 0.0754). To assess the combination of MRI parameters in estimating fibrosis, we created a linear regression model consisting of the cortical apparent diffusion coefficient, ΔR2*, ΔT1, the 23 Na medulla/cortex ratio, and plasma creatinine (R2 = 0.8009, p = 0.0117). The 23 Na medulla/cortex ratio only slightly improved the fibrosis prediction model, leaving 23 Na-MRI in an ambiguous place for evaluation of intrarenal fibrosis. Use of multiparametric MRI in combination with plasma creatinine shows potential for the estimation of fibrosis in human kidney disease, but more translational and clinical work is warranted before MRI can contribute to earlier diagnosis and evaluation of treatment for acute kidney injury and CKD.


The beta error and sample size determination in clinical trials in emergency medicine.
In the analysis of a clinical trial an investigator may fail to discern a statistically significant difference in outcome between control and experimental groups, when in fact one exists. Failure to demonstrate such a difference when it actually exists is known as "type II" error, and its probability of occurring is termed "beta." The purpose of our study was to determine the distribution of beta errors in negative trials in the Journal of the American College of Emergency Physicians (JACEP) (1972-1979) and Annals of Emergency Medicine (1980-1984). All negative comparative clinical trials appearing in JACEP and Annals from volume 1 (1972) to volume 13 (1984) were surveyed and were eligible for inclusion in the study. A trial was defined as negative if the investigator specifically stated that there was no significant difference in outcome between the experimental and control groups. For each negative trial the following parameters were calculated: beta error, based on the sample size used and the difference determined to be important to detect clinically; sample size required to detect a clinically meaningful difference as determined by the authors of this study; and minimum true difference that had to be detected in the trial at a beta equal to 0.20, to discern a statistically significant result. For the 13 years surveyed, we found 21 endpoints in 14 negative trials that were analyzable. Only one of the trials (7.1%) addressed the issues of beta errors and sample size determination. In the remaining 13 negative trials, the calculated beta error ranged from .60 to .97. For the endpoints analyzed, a sample size of up to 450 times larger than that used would have been required to detect a clinically important difference.(ABSTRACT TRUNCATED AT 250 WORDS)


Divergent lymphocyte signalling revealed by a powerful new tool for analysis of time-lapse microscopy.
We describe a new approach for interactive analysis of time-lapse microscopy, and apply this approach to elucidating whether polarity regulation is conserved between epithelial cells and lymphocytes. A key advantage of our analysis platform, 'TACTICS', is the capacity to visualize individual data points in the context of large data sets, similar to standard approaches in flow cytometry. Scatter plots representing microscopic parameters or their derivations such as polarity ratios are linked to the original data such that clicking on each dot enables a link to images and movies of the corresponding cell. Similar to flow cytometric analysis, subsets of the data can be gated and reanalyzed to explore the relationships between different parameters. TACTICS was used to dissect the regulation of polarization of the cell fate determinant, Numb, in migrating lymphocytes. We show here that residues of Numb that are phosphorylated by atypical protein kinase C (aPKC) to mediate apicobasal polarity in epithelial cells are not required for polarization of Numb in T cells, indicating that the role of aPKC is not conserved between lymphocytes and epithelia.


Synthesis and in vitro Anticancer Activity of Novel Heterocycles Utilizing Thiophene Incorporated Thioureido Substituent as Precursors.
Ethyl 2-(3-allylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) was used as a building block for synthesis of new heterocycles. Pyrimidine and thiazole moieties were achieved upon condensation of compound 1 with various reagents such as chloroacetic acid, dietyl malonate, ninhydrin, 2,3-epoxy-2,3-dihydro-1,4-naphthoquinone, and hydrazine hydrate. The structures of the newly synthesized compounds were confirmed using spectral measurements. The prepared products were evaluated for their anticancer activity against colon HCT-116 human cancer cell line. Compounds 6, 9, 10a, 11, 12, 15 have displayed potent activity.


Hypothalamic supraoptic neurones: rates and patterns of action potential firing during water deprivation in the unanaesthetized monkey.
Extracellularly recorded action potentials were obtained from hypothalamic supraoptic neurones in unanaesthetized rhesus monkeys. Rates and patterns of firing were studied during an initial control period, during 5 successive days of water deprivation and during 4 further days when drinking water was again available. During water deprivation, plasma osmolarity increased progressively from about 300 mOsmoles/kg to about 340 mOsmoles/kg; control values were again reached after 3 days of rehydration. Systematic changes in action potential firing accompanied the changes in plasma osmolarity. Under control conditions, the majority of cells fire slowly and irregularly (type i), whilst a few cells exhibited phases of alternating activity and silence (type p). As dehydration progresses, the frequency of neuronal firing increase and the pattern of firing changes. By the third day the majority of cells are type p with few type i cells being found. By the fourth day, the population consists of type p cells with some others showing a high continuous rate of firing (type c). By the fifth day, these two cell types are found in approximately equal proportions. Rehydration of the animal reverses the situation. We propose that type i cells contribute little, if at all, to hormone secretion, while type p and type c cells would be in a more actively secreting state. According to this view, the three firing patterns would represent different activity states of the same functional population stimulated by the unspecific stimulus of water deprivation rather than functionally different neurones. However, the use of stimuli which selectively release either oxytocin or vasopressin may be needed to answer this problem.


Chromatin structure as a mediator of aging.
The aging process is characterized by gradual changes to an organism's macromolecules, which negatively impacts biological processes. The complex macromolecular structure of chromatin regulates all nuclear processes requiring access to the DNA sequence. As such, maintenance of chromatin structure is an integral component to deter premature aging. In this review, we describe current research that links aging to chromatin structure. Histone modifications influence chromatin compaction and gene expression and undergo many changes during aging. Histone protein levels also decline during aging, dramatically affecting chromatin structure. Excitingly, lifespan can be extended by manipulations that reverse the age-dependent changes to chromatin structure, indicating the pivotal role chromatin structure plays during aging.