Mononuclear Cu Complexes Based on Nitrogen Heterocyclic Carbene: A Comprehensive Review.
During the last decade, organometallic, coordination, and catalytic chemistry of the three-dimensional metals such as copper (Cu) has been greatly affected by the emergence of nitrogen heterocyclic carbene (NHC) complexes. The NHCs, and in particular the mononuclear CuI-based ones, have been proven vastly useful in several applications such as in biosynthesis, catalysis, photochemistry, etc. This review tries to thoroughly describe a series of mononuclear CuI NHC complexes and their subcategories such as heteroleptics, and bidentate and tridentate heteroatom complexes, and give some detailed insights on their development, emergence, and applications. A brief outlook is also disclosed to enable other researchers to further develop a platform for future advances and studies in the field of CuI-based NHCs.


Characterizing temporal and spatial recruitment of systemically administered RPE65-programmed bone marrow-derived cells to the retina in a mouse model of age-related macular degeneration.
Previously, we reported that the intravenous injection of bone marrow-derived cells (BMDC) infected with lentivirus expressing the human RPE65 gene resulted in the programming of BMDC to promote visual recovery in a mouse model of age-related macular degeneration (AMD). The aim of this study was to characterize the spatial and temporal recruitment of these programmed BMDC to the retinal pigment epithelial (RPE) layer. C57BL/6J female mice received a subretinal injection of AAV1-SOD2 ribozyme to knock down (KD) superoxide dismutase 2 (SOD2) and induce AMD-like pathology. BMDC were isolated from GFP+ mice and infected with a lentivirus expressing RPE65. One month after SOD2 KD, fifty thousand GFP+ RPE65-BMDC were injected in the mouse tail vein. Animals were terminated at different time points up to 60 min following cell administration, and localization of GFP+ cells was determined by fluorescence microscopy of neural retina and RPE flat mounts and tissue sections. GFP+ RPE65- BMDC were observed in SOD2 KD neural retina and RPE as early as 1 min following administration. With increasing time, the number of cells in the neural retina decreased, while those in the RPE increased. While the number of cells in peripheral and central retina remained similar at each time point, the number of BMDC recruited to the central RPE increased in a time-dependent manner up to a maximum by 60 min post administration. Immunohistochemistry of cross-sections of the RPE layer confirmed the incorporation of donor GFP+ BMDC into the RPE layer and that these GFP+ human RPE65 expressing cells co-localized with murine RPE65. No GFP+ cells were observed in the neural retina or RPE layer of normal uninjured control eyes. Our study shows that systemically administered GFP+ RPE65-BMDC can reach the retina within minutes and that the majority of these BMDC are recruited to the injured RPE layer by 60 min post injection.


Montmorillonite immobilized Fe/Ni bimetallic prepared by dry in-situ hydrogen reduction for the degradation of 4-Chlorophenlo.
This study puts forward a new way to produce montmorillonite immobilized bimetallic nickel-iron nanoparticles by dry in-situ hydrogen reduction method in the non-liquid environment, which effectively inhibits the oxidation of iron and nickel during the synthesis process and improves the reactivity of the material. The degradation of 4-Chlorophenol (4-CP) was investigated to examine the catalytic activity of the material. The morphology and crystal properties of the montmorillonite-templated Fe/Ni bimetallic particles were explored by using scanning electron microscopy, transmission electron microscopy, X-ray diffraction studies, and energy dispersive X-ray spectroscopy analysis. Results suggest that Fe and Ni particles were homogeneously dispersed on the montmorillonite. The optimization of Ni content and reduction temperature over the degradation of 4-CP was also studied. The introduction of Ni intensely improved the degradation of 4-CP and reached over 90% when Ni content was 28.5%. The degradation rate increased significantly with the increase of reduction temperature and showed maximum activity at the reduction tempreature of 800 °C. This study offers a new method to fabricate montmorillonite immobilized Fe/Ni bimetallic nanoparticles in the non-liquid environment and the composites exhibited high degradation activity to chlorinated organic compounds.


Expanded Efficacy of Venovenous Extracorporeal Membrane Oxygenation Support for Deceased Donor Liver Transplantation.
Perioperative respiratory failure occurs frequently in liver transplantation (LT) recipients. Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been applied in patients with acute and potentially reversible life-threatening respiratory failure that is unresponsive to conventional therapies. VV-ECMO is used as a bridging device for lung transplantation. However, there are few reports on VV-ECMO as bridging therapy in LT patients with respiratory failure. This study assessed patient outcomes of VV-ECMO after LT and investigated its applicability and safety in LT surgery. From January 2017 to May 2019, VV-ECMO was applied in 8 deceased donor LT patients at Pusan National University Yangsan Hospital. Patients administered pre- or postoperative VV-ECMO showed a 50% 1-year survival rate and 75% success rate for ECMO weaning. Six patients were administered preoperative VV-ECMO for respiratory failure, of whom 4 patients survived for longer than a year. Two patients who received VV-ECMO for refractory hypoxia during LT died; 1 failed ECMO weaning, and the other was successfully weaned off ECMO but died of other causes. VV-ECMO could lower the risk of hypoxemia-related organ failure while awaiting and during LT via better controlled gas exchange without significant acute morbidity. VV-ECMO may expand operability in patients with severe respiratory failure awaiting LT.


Studies on the pathogenesis of hepatocellular carcinoma in HBV-negative alcoholic cirrhotics.
Ninety five cases of HBV marker-negative cirrhosis with excess alcohol intake were examined clinicopathologically to obtain some clues and insights into the pathogenesis of hepatocellular carcinoma (HCC). The following data were obtained: cases were divided morphologically into 37 cases of macronodular cirrhosis (MacCir), 16 mixed cirrhosis (MixCir), and 42 micronodular cirrhosis (MicCir), the mean age at death was the oldest in MacCir (61 yrs), the youngest in MicCir (51 yrs), and intermediate in MixCir (59 yrs), association of HCC was common both in MacCir and MixCir (78 and 63%, respectively) but infrequent in MicCir (17%), all livers of MicCir with HCC had broad collapse and a small number of macronodules in non-cancerous areas and the mean age of them was older than that of MicCir without both the collapse and macronodules (56 vs 48 yrs), in total cases, the mean age at death of patients with HCC was 7 years older than that without HCC (60 vs 53 yrs), the mean liver weight was the largest in MicCir (1,211 g), the smallest in MacCir (829 g), and intermediate in MixCir (1,022 g), the incidence of MacCir was significantly higher in patients who had given up alcohol for more than one year before death than those without abstinence, and neither the subtypes of cirrhosis nor the incidence of HCC was significantly related to the total amount of alcohol intake. These data indicate that the development of HCC in HBV-negative alcoholics with cirrhosis occurs in relation to the development of macronodules and loss of liver weight, most likely along with the prolongation of the life span.


Fusobacterium necrophorum- detection and identification on a selective agar.
Within the last decade, Fusobacterium necrophorum subsp. funduliforme has been considered a clinically important pathogen causing pharyngitis especially in adolescents and young adults. F. necrophorum pharyngitis can progress into Lemierre's syndrome, which is a severe and life-threatening infection. However, throat swabs are not cultured anaerobically in the routine and even if cultured anaerobically, it can be difficult to identify F. necrophorum from the normal flora of the throat. F. necrophorum is therefore often overlooked as the cause of pharyngitis. In our laboratory, a F. necrophorum selective agar has been developed containing vancomycin and nalidixin, which inhibit the growth of most Gram-positive and many Gram-negative bacteria, respectively. β-haemolysis of horse blood can be detected, which further facilitates the detection and identification of F. necrophorum. The F. necrophorum selective agar was evaluated against a quantitative real-time polymerase chain reaction assay and shown to have a significantly higher sensitivity for detecting F. necrophorum than the anaerobic agar commonly used in Denmark. Furthermore, the F. necrophorum selective agar does not require experienced laboratory technicians, require fewer subcultures, is probably less expensive and is faster to perform than other culture methods.


[Visceral adiposity index (VAI) and dysfunctional adiposity index (DAI). Relationship with obesity parameters].
Obesity is a global pandemic with a growing impact on morbidity and mortality. We assessed the associative strength of the Visceral Adiposity Index (VAI) and Dysfunctional Adiposity Index (DAI) in obesity and associated risk using different methods. Cross-sectional study in 418 343 workers from different autonomous communities in Spain, estimating prevalence of obesity with: waist circumference, waist/height index, BMI, CUN-BAE, ECORE-BF, RFM, PALAFOLLS, IMG, METS-VF calculated according to their specific formulas. Descriptive analysis of categorical variables and associative strength of VAI and DAI for obesity was performed with ROC curves considering high risk when the AUC value.0.8 and moderate with AUC.0.7 and.0.8. SPSS 27.0 was used, considering statistical significance p.0.05. The prevalence of obesity varied according to the method used, being high with Palafolls (72.92% in women and 86.98% in men) and low with METS-VF (1.31% in women and 8.54% in men). The mean values of VAI and DAI are always higher in men. The AUC of the ROC curve for VAI was high with METS-VF: in women 0.836 (95%CI 0.829-0.843), in men 0.848 (95%CI 0.845-0.850) and with waist circumference in men: 0.819 (95%CI 0.816-0.822). DAI was high for METS-FV in women: 0.809 (95%CI 0.801-0.817). The prevalence of obesity and related risk differs according to the assessment method used. VAI shows high strength of association with obesity and fat mass for METS-VF in both sexes and with waist circumference in men; DAI for METS-VF in women.


Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary.
Phosphatidylinositol 3-kinase (PI3K) signaling is a fundamental pathway for the regulation of cell proliferation, survival, migration, and metabolism in a variety of physiological and pathological processes. In recent years information provided by genetically modified mouse models has revealed that PI3K signaling plays vital roles in oogenesis, folliculogenesis, ovulation, and carcinogenesis in mouse ovary. In this review, we summarize (1) the physiological function of intra-oocyte PI3K signaling in regulation of primordial follicle survival and activation; (2) intra-granulosa cell PI3K signaling in regulation of cyclic follicular recruitment and ovulation; (3) intra-oocyte PI3K signaling in regulation of meiosis resumption and early embryogenesis; and also (4) the pathological function of PI3K signaling in ovarian diseases such as premature ovarian failure, granulosa cell tumors, and ovarian surface epithelium carcinomas. This updated info hopefully will lead to a better understanding of the human ovary and provide potential therapies for treating human infertility.


NMR investigations unveil phase composition-property correlations in Sr0.55Na0.45SiO2.775 fast ion conductor.
This paper reports results of 23Na and 29Si solid-state NMR investigations carried out on sodium strontium silicate ion conductor, Sr0.55Na0.45SiO2.775 and presents the first experimental evidence to show that different synthesis conditions induce multiple devitrified phases. Along with 1-dimensional NMR, 23Na MQMAS spectra have been used to identify the phases corresponding to polymorphs of Na2Si2O5, in addition to the crystalline SrSiO3 and the glass/amorphous Na2Si2O5 phases. The surprising observation of about an order of magnitude higher ionic conductivity achieved in devitrified samples is attributed to the growth of the crystalline δ-Na2Si2O5 phase within the amorphous Na2Si2O5 phase domains, identified using NMR. Together with XRD and conductivity measurement data, the study leads to the identification of the chemical phase composition and an understanding of the composition-property-structure correlation in this material. Present findings, while do not show any evidence of Na doping in the SrSiO3 phase confirming earlier reports, explain the large discrepancy in the conductivity reported in the literature.


Remdesivir.
Remdesivir, marketed under the brand name Veklury, is an antiviral drug with a broad spectrum of activity. There were various countries where the use of Remdesivir for the treatment of COVID-19 was authorized during the pandemic. Remdesivir was first designed to treat hepatitis C, but it was later tested for Ebola virus sickness and Marburg virus infections. Remdesivir is a prodrug designed to facilitate the intracellular transport of GS-441524 monophosphate and its subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase. The objective of this chapter is to provide a comprehensive review of Remdesivir (GS-5734), including its nomenclature, physiochemical properties, preparation methods, identification procedures, numerous qualitative and quantitative analytical techniques, ADME profiles, and pharmacological effects. In addition, the chapter provides a variety of chromatographic and spectroscopic techniques for separating brimonidine from other drugs in combination formulations.


Clinical relevance of the quantification of apolipoprotein E in cerebrospinal fluid.
Apolipoprotein E was measured in paired sera and cerebrospinal fluid samples from 483 neurological patients. The average apolipoprotein E concentration was 7.5 (+/- 3.1) mg/l in cerebrospinal fluid and 93.5 (+/- 29.7) mg/l in serum. Mean apolipoprotein B concentrations in 88 patients were 0.77 +/- 3.4 mg/l in cerebrospinal fluid and 1.06 +/- 0.31 g/l in serum. The apolipoprotein E concentration in cerebrospinal fluid was much greater than expected for passive diffusion from serum. By contrast to apolipoprotein B, there was no correlation between the apolipoprotein E cerebrospinal fluid/serum concentration quotient and the albumin concentration quotient. This suggests that apolipoprotein E in cerebrospinal fluid, unlike apolipoprotein B, is locally synthesized and that the use of a cerebrospinal fluid/serum concentration quotient is unnecessary. In a control group (n = 64) the mean cerebrospinal fluid apolipoprotein E value (+/- SD) was 5.9 (1.6) mg/l. Elevated cerebrospinal fluid apolipoprotein E concentrations were observed in acute (n = 22, 12.5 +/- 6.2 mg/l) and chronic inflammatory central nervous system diseases (n = 15, 10.4 +/- 2.4 mg/l).


Examination of the Factors That Encourage University Students to Sports Betting. A Q-Method Study.
This study aimed to examine the factors that motivate university students to sports betting through the Q-method. The study is designed with the Q-methodology. According to this method, qualitative and quantitative research methods are applied in the same study. Interviews were conducted with the participants of the study, question expressions were created and similar studies in the literature were used. With this feature, the current study has both structural and non-structural pattern features. In the study, the snowball sampling method, one of the purposeful sampling methods, was employed as a sampling method. The people recommended by the participants with at least five years of sports betting history were included in the study. A total of 29 university students constituted the study group. In the analysis of the data, basic components analysis was applied and it was concluded that the participants were gathered under two factors, and the value of 0.55 was reached as the significance value. As a result, it can be stated that different factors motivate the participants to bet, such as making money, seeking excitement, having social relations, sports betting as a profession, endeavor, killing time, and betting because of addiction.


C3 polymorphism in polyacrylamide-gel electrophoresis.
C3 polymorphism in polyacrylamide-gel electrophoresis was identified by crossed immunoelectrophoresis using anti-C3/C3c-serum. Through ageing, treatment of sera with cobra venom factor, endotoxin or with neuramindase, polymorphic bands were seen also in a conversion product and antigenically attributed to C3c. Rare phenotypes were observable in native C3 and in C3c.


An engineered amino-terminal domain of yeast phosphoglycerate kinase with native-like structure.
Previous studies have suggested that the carboxy-terminal peptide (residues 401-415) and interdomain helix (residues 185-199) of yeast phosphoglycerate kinase, a two-domain enzyme, play a role in the folding and stability of the amino-terminal domain (residues 1-184). A deletion mutant has been created in which the carboxy-terminal peptide is attached to the amino-terminal domain (residues 1-184) plus interdomain helix (residues 185-199) through a flexible peptide linker, thus eliminating the carboxy-terminal domain entirely. CD, fluorescence, gel filtration, and NMR experiments indicated that, unlike versions described previously, this isolated N-domain is soluble, monomeric, compactly folded, native-like in structure, and capable of binding the substrate 3-phosphoglycerate with high affinity in a saturable manner. The midpoint of the guanidine-induced unfolding transition was the same as that of the native two-domain protein (Cm approximately 0.8 M). The free energy change associated with guanidine-induced unfolding was one-third that of the native enzyme, in agreement with previous studies that evaluated the intrinsic stability of the N-domain and the contribution of domain-domain interactions to the stability of PGK. These observations suggest that the C-terminal peptide and interdomain helix are sufficient for maintaining a native-like fold of the N-domain in the absence of the C-domain.


Concentration of bovine placental lactogen in dairy and beef cows across gestation.
The concentration of bovine placental lactogen (bPL) was determined in five dairy heifers and five beef cows across gestation. Blood samples were collected beginning at day 45 post insemination and once every two weeks until two d postpartum. Concentrations of bPL in maternal serum ranged from undetectable (< .25 ng/ml) to 2.93 ng/ml and there were no significant differences between dairy and beef animals. Peak concentrations were observed at day 215 of gestation and remained high until just prior to parturition. These results suggest that bPL concentrations follow a pattern similar to that in other species that produce placental lactogen.


Nurse used online translator to communicate during nursing home shifts.
A nurse with 'little understanding' of English relied on Google's online translator service while working at a nursing home in Wales, inspectors found.


Graft Choice for Anterior Cruciate Ligament Reconstruction With a Concomitant Non-surgically Treated Medial Collateral Ligament Injury Does Not Influence the Risk of Revision.
To compare the risk of anterior cruciate ligament (ACL) revision and the patient-reported outcome after ACL reconstruction with a concomitant non-surgically treated medial collateral ligament (MCL) injury with regard to 3 ACL graft choices; the use of semitendinosus (ST), the use of semitendinosus-gracilis (ST-G), and the use of patellar tendon (PT) autograft. It was hypothesized that the use of ST-G would be associated with a greater risk of ACL revision and poorer patient-reported knee function. Patients older than 15 years of age registered for a primary ACL reconstruction with a concomitant non-surgically treated MCL injury in the Swedish National Knee Ligament Registry were assessed for eligibility. Three groups were created according to ACL autograft choice; the ST, the ST-G, and the PT group. The primary outcomes were ACL revision and the 1- and 2-year Knee injury and Osteoarthritis Outcome Score (KOOS), including the KOOS patient acceptable symptom state (PASS). Cox regression analysis was applied to determine the proportional hazard ratio (HR) of primary ACL reconstruction survival. The KOOS was compared using the Mann-Whitney U test and Fisher exact test. A total of 622 patients (mean age 29.7 years, 42.4% women) were included. There was no difference in the risk of ACL revision for either the ST group (HR 1.354; 95% confidence interval [CI] 0.678-2.702 or the PT group (HR 0.837; 95% CI 0.334-2.100), compared with the ST-G group. The ST group reported a greater mean 2-year KOOS sports and recreation (68.5, standard deviation [SD] 28.5) than the ST-G group (57.4 [SD 27.6], P = .010) and the PT group (54.1 [SD 30.3], P = .006). The ST group was superior in terms of achieving PASS in sports and recreation (55.3%; 95% CI 44.1-66.1%) compared with both the ST-G (37.4%; 95% CI 29.8-45.5%; P = .014) and the PT group (33.9%; 95% CI 22.1-47.4%; P = .009). The risk of ACL revision did not differ between HT and PT autografts in patients undergoing ACL reconstruction with a non-surgically treated MCL injury. However, the use of ST-G was associated with poorer 2-year patient-reported knee function compared with the ST. Retrospective comparative trial, Level III.


Carbon nanomaterial-based molecularly imprinted polymer sensors for detection of hazardous substances in food: Recent progress and future trends.
The presence of various harmful substances in food is significantly risky to human health. Therefore, simple, rapid, and selective food hazard analysis tools have become a focus of sensing research. At present, molecularly imprinted polymers (MIPs) have attracted more and more attention because of their easy preparation and high selectivity. Due to their simple preparation, low cost, large specific surface area, and high conductivity, carbon nanomaterial can be used as sensing substrate carriers. Therefore, the combination of carbon nanomaterial with MIPs has attracted great attention. This paper summarizes the development, composition, and preparation methods of MIPs, as well as the latest research progress in carbon nanomaterials for the detection of various food hazards using sensors. In addition, the practical applications of carbon nanomaterial-based MIP sensors, their current challenges and future trends, and the ongoing efforts devoted to developing new and efficient carbon nanomaterial-based MIP sensing platforms are also introduced.


Phosphatase 2A puts the brakes on mTORC1 nutrient signaling.
Nutrients such as amino acids (aa) and glucose mediate mammalian target of rapamycin complex 1 (mTORC1) signaling to control cell growth and metabolism. Recent studies (Yan et al., 2010) identify a contributor, PP2A phosphatase subunit PR61varepsilon, in regulating the aa-sensitive input to mTORC1.


Redescription of the male and first description of the female of Capillaria carioca Freitas et Lent, 1935 (Nematoda: Capillariidae), a parasite of the marine fish Sphoeroides testudineus.
A redescription of the male and the first description of the female of the intestinal nematode Capillaria carioca Freitas et Lent, 1935 are presented on the basis of specimens collected from the type host, the marine fish Sphoeroides testudineus (Linnaeus) (Teleostei, Tetraodontoidei), from the Lagoon of Yucalpetén in the northern coast of Yucatan (Gulf of Mexico), Mexico. This species is characterized by a well-sclerotized spicule and by the presence of two large ventrolateral lobe-like papillae on the male caudal end and, therefore, is assigned to the subgenus Neocapillaria Moravec, 1987. C. carioca is reported from Mexico for the first time.


The spectrum of acute vestibular neuropathy through modern vestibular testing: A descriptive analysis.
Acute vestibular neuropathy (AVN), often referred to as vestibular neuritis, is a cranial neuropathy responsible for a significant proportion of cases of acute vertigo. This study describes the spectrum of lesion patterns in AVN as identified by video head impulse testing (vHIT) which assesses the high frequency vestibulo-ocular reflex function of the semicircular canals, and cervical and ocular vestibular evoked myogenic potentials (VEMPs) which assess otolith function. We used vHIT and VEMPs to assess 35 patients with vestibular neuropathy in the acute stage. Unilateral superior division vestibular nerve involvement was the most common variant (57.1%), followed by unilateral superior and inferior division (28.5%), bilateral superior division (8.5%) and unilateral inferior division (5.7%). We observed a partial inverse correlation between the proportion of afferent fibers from an organelle, and the likelihood that the test of that organelle's function will be abnormal. vHIT and VEMPs provide more detailed characterization of lesion pattern in AVN than caloric testing. Comparison of lesion patterns from neuro-physiological testing with what is known about the proportional distribution of afferent fibers from the vestibular end-organelles suggests a new, neuro-anatomically based insight regarding susceptibility of these pathways to AVN.


Isolated Grauer's gorilla populations differ in diet and gut microbiome.
The animal gut microbiome has been implicated in a number of key biological processes, ranging from digestion to behaviour, and has also been suggested to facilitate local adaptation. Yet studies in wild animals rarely compare multiple populations that differ ecologically, which is the level at which local adaptation may occur. Further, few studies simultaneously characterize diet and gut microbiome from the same sample, despite their probable interdependence. Here, we investigate the interplay between diet and gut microbiome in three geographically isolated populations of the critically endangered Grauer's gorilla (Gorilla beringei graueri), which we show to be genetically differentiated. We find population- and social group-specific dietary and gut microbial profiles and covariation between diet and gut microbiome, despite the presence of core microbial taxa. There was no detectable effect of age, and only marginal effects of sex and genetic relatedness on the microbiome. Diet differed considerably across populations, with the high-altitude population consuming a lower diversity of plants compared to low-altitude populations, consistent with plant availability constraining dietary choices. The observed pattern of covariation between diet and gut microbiome is probably a result of long-term social and environmental factors. Our study suggests that the gut microbiome is sufficiently plastic to support flexible food selection and hence contribute to local adaptation.


Three-generation reproduction and dominant lethal mutagenesis studies of ethylene glycol in the rat.
To assess the possible effects of ethylene glycol (EG) on reproductive performance and mutagenesis, three-generation reproduction and dominant lethal mutagenesis studies were performed in the Fischer 344 rat. EG was included in the diet at approximate dosages of 1.0, 0.2, and 0.04 g/kg/day during three generations of reproduction. Each generation was bred once. In a dominant lethal mutagenesis study, the F2 males from the reproduction study were bred to three consecutive lots of untreated females at weekly intervals. Concomitantly, another group of untreated F2 males that received a single ip injection of 0.50 mg/kg triethylenemelamine (TEM) were bred similarly to serve as a positive control group. No evidence of reduced fertility or increased fetal death was observed in any of the groups receiving EG. Dominant lethal effects in the TEM group confirmed the susceptibility of the rats to a known mutagen. In conclusion, there were no reproductive or dominant lethal effects associated with the inclusion of as much as 1.0 g/kg/day of EG in the diet.


Vibrio parahaemolyticus cell biology and pathogenicity determinants.
Vibrio parahaemolyticus is a significant cause of gastroenteritis worldwide. Characterization of this pathogen has revealed a unique repertoire of virulence factors that allow for colonization of the human host and disease. The following describes the known pathogenicity determinants while establishing the need for continued research.


Role of surface functionalities of nanoplastics on their transport in seawater-saturated sea sand.
The transport and retention of nanoplastics (NP, 200 nm nanopolystyrene) functionalized with surface carboxyl (NPC), sulfonic (NPS), low-density amino (negatively charged, NPA-), and high-density amino (positively charged, NPA+) groups in seawater-saturated sand with/without humic acid were examined to explore the role of NP surface functionalities. The mass percentages of NP recovered from the effluent (Meff) with a salinity of 35 practical salinity units (PSU) were ranked as follows: NPC (19.69%) > NPS (16.37%) > NPA+ (13.33%) > NPA- (9.78%). The homoaggregation of NPS and NPA- was observed in seawater. The transport of NPA- exhibited a ripening phenomenon (i.e., a decrease in the transport rate with time) due to the high attraction of NP with previously deposited NP, whereas monodispersed NPA+ presented a low Meff value because of the electrostatic attraction between NPA+ and negatively charged sand. Retention experiments showed that the majority of NPC, NPS and NPA+ accumulated in a monolayer on the sand surface, whereas NPA- accumulated in multiple layers. Suwannee River humic acid (SRHA) could remarkably improve the transportability of NPC, NPS, and NPA- by increasing steric repulsion. The strong attraction between NPA+ and the deposited NPA+ in the presence of SRHA triggered the weak ripening phenomenon. As seawater salinity decreased from 35 PSU to 3.5 PSU, the increase in electrostatic repulsion of NP-NP and NP-sand enhanced the transport of NPC, NPS, and NPA-, and the ripening of NPA- breakthrough curves disappeared. In deionized water, NPC, NPS, and NPA- achieved complete column breakthrough because the electrostatic repulsion between NP and sand intensified. However, the Meff values of NPA+ in 3.5 PSU seawater and deionized water presented limited increments of 15.49% and 23.67%, respectively. These results indicated that the fate of NP in sandy marine environments were strongly affected by NP surface functionalities, seawater salinity, and coexisting SRHA.


A program evaluation of classroom data collection with bar codes.
A technology incorporating bar code symbols and hand-held optical scanners was evaluated for its utility for routine data collection in a special education classroom. A different bar code symbol was created for each Individualized Educational Plan objective, each type of response occurrence, and each student in the first author's classroom. These symbols were organized by activity and printed as data sheets. The teacher and paraprofessionals scanned relevant codes with scanners when the students emitted targeted behaviors. The codes, dates, and approximate times of the scans were retained in the scanner's electronic memory until they could be transferred by communication software to a computer file. The data from the computer file were organized weekly into a printed report of student performance using a program written with commercially available database software. Advantages, disadvantages, and costs of using the system are discussed.


Mechanism of prostaglandin (PG)E2-induced prolactin expression in human T cells: cooperation of two PGE2 receptor subtypes, E-prostanoid (EP) 3 and EP4, via calcium- and cyclic adenosine 5'-monophosphate-mediated signaling pathways.
We previously reported that prolactin gene expression in the T-leukemic cell line Jurkat is stimulated by PGE(2) and that cAMP acts synergistically with Ca(2+) or protein kinase C on the activation of the upstream prolactin promoter. Using the transcription inhibitor actinomycin D, we now show that PGE(2)-induced prolactin expression requires de novo prolactin mRNA synthesis and that PGE(2) does not influence prolactin mRNA stability. Furthermore, PGE(2)-induced prolactin expression was inhibited by protein kinase inhibitor fragment 14-22 and BAPTA-AM, which respectively, inhibit protein kinase A- and Ca(2+)-mediated signaling cascades. Using specific PGE(2) receptor agonists and antagonists, we show that PGE(2) induces prolactin expression through engagement of E-prostanoid (EP) 3 and EP4 receptors. We also found that PGE(2) induces an increase in intracellular cAMP concentration as well as intracellular calcium concentration via EP4 and EP3 receptors, respectively. In transient transfections, 3000 bp flanking the leukocyte prolactin promoter conferred a weak induction of the luciferase reporter gene by PGE(2) and cAMP, whereas cAMP in synergy with ionomycin strongly activated the promoter. Mutation of a C/EBP responsive element at -214 partially abolished the response of the leukocyte prolactin promoter to PGE(2), cAMP, and ionomycin plus cAMP.


Fibroblast Growth Factor Receptor Inhibitor-Associated Multifocal Serous Retinal Detachments: A Case Report.
This report aims to describe a case of bilateral, multifocal neurosensory retinal detachments that developed during erdafitinib therapy for metastatic urothelial carcinoma. A case report with color fundus imaging and spectral-domain optical coherence tomography imaging is presented. A 50-year-old man with metastatic urothelial carcinoma had an unremarkable baseline ophthalmic examination prior to starting erdafitinib. At 3-month follow up, an examination revealed bilateral, multifocal retinal detachments. Because the patient was asymptomatic and erdafitinib was the only drug to which his tumor had responded, he was kept on the medication with close ophthalmic monitoring. Erdafitinib, a fibroblast growth factor receptor inhibitor, can cause bilateral, multifocal retinal detachments. Continuation of erdafitinib may be considered in patients without significant visual impairment when the overall benefit of the medication appears to outweigh the risks.


Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice.
Ozone (O₃), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O₃-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O₃ exposure protocol consisting of 2 days of filtered air and 5 days of O₃ exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-β), the most potent profibrogenic cytokine. The results showed that O₃ exposure for 5 or 10 cycles increased the TGF-β protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-β-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O₃ exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O₃ exposure. Importantly, blockage of the TGF-β signaling pathway with IN-1233 suppressed O₃-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O₃ exposure increases TGF-β expression and activates TGF-β signaling pathways, which mediates O₃-induced lung fibrotic responses in vivo.


A scabies outbreak in the North East Region of Ghana: The necessity for prompt intervention.
There is a dearth of data on scabies from Ghana. In September 2019, local health authorities in the East Mamprusi district of northern Ghana received reports of scabies from many parts of the district. Due to on-going reports of more cases, an assessment team visited the communities to assess the effect of the earlier individual treatment on the outbreak. The assessment team furthermore aimed to contribute to the data on scabies burden in Ghana and to demonstrate the use of the International Alliance for the Control of Scabies (IACS) diagnostic tool in a field survey in a resource limited setting. This was a cross sectional study. Demographic information and medical history was collected on all participants using a REDCap questionnaire. A standardised skin examination of exposed regions of the body was performed on all participants. Scabies was diagnosed based on the criteria of the International Alliance for the Control of Scabies (IACS). Participants were mostly female (61.5%) and had a median age of 18.8 years (IQR 13-25). Two hundred out of 283 (71%) of participants had scabies with most (47%) presenting with moderate disease. Impetigo was found in 22% of participants with scabies and 10.8% of those without scabies [RR 2.27 (95% CI 1.21-4.27)]. 119 participants who received scabies treatment in the past months still had clinical evidence of the disease. 97% of participants reported a recent scabies contact. Scabies was commoner in participants ≤16 years compared to those >16 years [RR 3.06 (95% CI 1.73-5.45)]. The prevalence of scabies was extremely high. The lack of a systematic approach to scabies treatment led to recurrence and ongoing community spread. The IACS criteria was useful in this outbreak assessment in Ghana. Alternative strategies such as Mass drug administration may be required to contain outbreaks early in such settings.


Occurrence of D-serine in rice and characterization of rice serine racemase.
Germinated, unpolished rice was found to contain a substantial amount of D-serine, with the ratio of the D-enantiomer to the L-enantiomer being higher for serine than for other amino acids. The relative amount of D-serine (D/(D+L)%) reached approximately 10% six days after germination. A putative serine racemase gene (serr, clone No. 001-110-B03) was found in chromosome 4 of the genomic DNA of Oryza sativa L. ssp. Japonica cv. Nipponbare. This was expressed as serr in Escherichia coli and its gene product (SerR) was purified to apparent homogeneity. SerR is a homodimer with a subunit molecular mass of 34.5kDa, and is highly specific for serine. In addition to a serine racemase reaction, SerR catalyzes D- and L-serine dehydratase reactions, for which the specific activities were determined to be 2.73 and 1.42nkatal/mg, respectively. The optimum temperature and pH were respectively determined for the racemase reaction (35 degrees C and pH9.0) and for the dehydratase reaction (35 degrees C and pH9.5). SerR was inhibited by PLP-enzyme inhibitors. ATP decreased the serine racemase activity of SerR but increased the serine dehydratase activity. Kinetic analysis showed that Mg(2+) increases the catalytic efficiency of the serine racemase activity of SerR and decreases that of the serine dehydratase activity. Fluorescence-quenching analysis of the tryptophan residues in SerR indicated that the structure of SerR is distorted by the addition of Mg(2+), and this structural change probably regulates the two enzymatic activities.


An unusual complication after excision of a recurrent mucocele of the anterior lingual gland.
A case report of a recurrent mucous extravasation phenomenon in the anterior lingual gland is presented. Multiple surgical procedures were necessary to eradicate the lesion. Alginate impression material was used during one of the surgical procedures to aid in defining the margins of the lesion. A foreign-body reaction arose in the tongue as a result of residual alginate within the tissues, necessitating further surgery. The use of this technique cannot be recommended in areas where extension into surrounding tissue planes is possible.


Isoginkgetin synergizes with doxorubicin for robust co-delivery to induce autophagic cell death in hepatocellular carcinoma.
Doxorubicin (DOX) widely used in hepatocellular carcinoma (HCC) can induce serious side effects and drug resistance. Herein, we aimed to seek a strategy to improve the efficacy and reduce the side effects of DOX in HCC based on an autophagy inducer drug called isoginkgetin (ISO). The design of multifunctional nanocarriers based on hyaluronic acid-conjugated and manganese-doped mesoporous silica nanoparticles (HM) for the co-delivery of antitumor drugs against HCC provided an effective and promising antitumor strategy. Our results showed that HM@ISO@DOX could efficiently inhibit HCC cell proliferation through activating autophagy through AMPKa-ULK1 pathway. Moreover, intravenous injection of HM@ISO@DOX significantly suppressed HCC tumor progression in nude mouse HCC model. Collectively, our findings revealed an anti-HCC mechanism of HM@ISO@DOX through autophagy and provide an effective therapeutic strategy for HCC. STATEMENT OF SIGNIFICANCE: In our study, we constructed a co-delivery system by loading ISO and DOX in the mesoporous channels of manganese-doped mesoporous silica nanoparticles, which could be further conjugated with hyaluronic acid to obtain HM@ISO@DOX. The nanocarriers had been demonstrated to be biodegradable under the acidic and reducing tumor microenvironment, as well as to possess the tumor targeting capability via the conjugated hyaluronic acid. In addition, HM@ISO@DOX enhanced the therapeutic efficacy against human HCC tumor through the combinatorial therapies of chemotherapeutics, Mn2+-mediated chemodynamic therapeutics and autophagic cell death, which might be achieved through AMPK-ULK1 signaling. This work revealed that such a nanomedicine exhibited superior tumor accumulation and antitumor efficiency against HCC with extremely low systemic toxicity in an autophagy-boosted manner.


Exercise, nutrition, and aging.
Advancing adult age is associated with profound changes in body composition. Age-related loss in skeletal muscle has been referred to as sarcopenia and is a direct cause of the age-related decreased in muscle strength. Resistance training is an effective means of preserving or increasing skeletal muscle mass and functional status in the elderly. In addition, resistance training has been demonstrated to increase energy requirements, protein retention, bone mass, and levels of physical activity in healthy elders as well as the very old and frail.


Influence of Smoking on Disease Activity and Quality of Life in Patients With Rheumatoid Arthritis: Results From a Swedish Case-Control Study With Longitudinal Follow-Up.
Inconclusive findings have been reported regarding the influence of smoking on disease outcomes in established rheumatoid arthritis (RA). This study was undertaken to investigate the influence of smoking habits on disease activity and health-related quality of life (HRQoL) in RA patients. Patients with newly diagnosed RA (n = 1,531) from the population-based case-control Epidemiological Investigation of Rheumatoid Arthritis study were followed up for up to 3 years after recruitment. Using logistic regression models, the risks of unfavorable outcomes in patients with different smoking habits were compared using self-reported swollen and tender joint counts, the Short Form 36 health survey, the Health Assessment Questionnaire, and the Hospital Anxiety and Depression Scale by calculating odds ratios with 95% confidence intervals. At 1-year and 3-year follow-up, current smokers reported higher disease activity and lower HRQoL life compared to non-smokers, regarding both physical and mental aspects. Patients who stopped smoking within 1-year post-baseline had less disease activity measured as swollen joint counts at 1-year follow-up compared to those who continued smoking. Patients who stopped smoking after the 1-year follow-up had higher disease activity and lower HRQoL at baseline than smokers who did not quit, and late smoking cessation was not associated with more favorable outcomes compared to continued smoking. Current smoking is associated with increased disease activity and lower HRQoL among RA patients. Smoking cessation within the first year after baseline appears to have a favorable effect on disease activity.


Quantitation of the anticonvulsant cinromide (3-bromo-N-ethylcinnamamide) and its major plasma metabolites by thin-layer chromatography.
A quantitative thin-layer chromatography (TLC) procedure is described for the analysis of cinromide (3-bromo-N-ethylcinnamamide) and its two major metabolites, 3-bromocinnamamide and 3-bromocinnamic acid in plasma of the dog. These compounds were recovered from acidified plasma by extraction into benzene with a recovery of 95 +/- 5%. All three compounds were quantitated directly on a TLC plate by ultraviolet absorbance densitometry at 270 nm. The linear dynamic range for the quantitation of the compounds on a TLC plate ranged between 10 and 1000 ng. The complete procedure is useful in the working range of 50 ng/ml to 100 microgram/ml of plasma with a coefficient of variability of about 10%. Specificity of the method for parent drug and each of its plasma metabolites was confirmed by high-performance liquid chromatography. The method was used to determine the pharmacokinetics of cinromide and its two major plasma metabolites in dogs following a single oral dose of the drug.


Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties.
Biomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.


Non-Hemorrhagic Adrenal Infarction during Pregnancy: The Diagnostic Imaging Keys.
Background: non-hemorrhagic adrenal infarction (NHAI) is a rare cause of acute abdominal/flank pain during pregnancy; in order to ensure prompt and appropriate treatment, this diagnosis should not be overlooked. This case series highlights pertinent imaging findings, including ultrasounds (USs), computed tomography (CT), and magnetic resonance imaging (MRI) of recent NHAI cases. Methods: we compiled all consecutive NHAI cases from two university hospitals over a two-year period and checked the relevant clinical, laboratory, and imaging findings. Relevant articles on NHAI published from January 2010 to March 2021 were analyzed. Results: six cases were found in our database. CT-scans typically showed enlarged, hypodense, and non-enhanced adrenal glands. Unenhanced MRIs allowed for diagnoses and showed enlarged adrenal glands in the signal hyperintensity on T2 and diffusion-weighted imaging, without any signal hyperintensity on T1. In two of our six cases, USs showed swollen adrenal glands with fluid collection. Conclusion: NHAI and its differential diagnosis-in cases of acute pain during pregnancy-highlight the crucial roles of integrated radiological examination and cooperation between obstetricians and radiologists, both of whom should consider the location of the pain, the accessibility and tolerance of MRI, and the radiation exposure of CT. Despite its supposed poor sensitivity, an US performed because the patient reports pain should also be used to examine the adrenal gland regions. Non-enhanced MRI is clearly of value and access to it in emergencies is important to avoid radiation exposure.


A novel application of propensity score matching to estimate Alcoholics Anonymous' effect on drinking outcomes.
Randomized controlled trials (RCTs) of mutual aid, including Alcoholics Anonymous (AA), are notoriously difficult to conduct and correlational studies are problematic to interpret due to potential confounds. A secondary analysis was conducted of Project MATCH, a RCT of alcoholism treatments. Although MATCH did not randomly assign subjects to AA vs. no AA, the 12 step facilitation (TSF) condition did result in a higher proportion of subjects attending community AA meetings than in the other two treatment conditions. The key inference is that there exists a latent subgroup in MATCH who attended AA only because its constituents received TSF, not because of the "normal" factors leading to self-selection of AA. A novel application of propensity score matching (PSM) allowed four latent AA-related subgroups to be identified to estimate an unconfounded effect of AA on drinking outcomes. The study hypothesis was supported: subjects who consistently attended AA solely due to their exposure to TSF (the "Added AA" subgroup) had better drinking outcomes than equivalent subjects who did not consistently attend AA, but would have so attended, had they been exposed to TSF (the "Potential AA" subgroup); this indicates an AA effect on drinking. The analysis presents evidence that consistent AA attendance improves drinking outcomes, independent of "normal" confounding factors that make correlations between AA attendance and outcomes difficult to interpret.


Cortical current density magnitudes during transcranial direct current stimulation correlate with skull thickness in children, adolescent and young adults.
Transcranial direct current stimulation protocols are often applied with a fixed parameter set to all subjects participating in an interventional study. This might lead to considerable effect variation in inhomogeneous subject groups or when transferring stimulation protocols to different age groups. The aim of this study was to evaluate magnitude differences of the electric current density distribution on the gray matter surface in children, adolescent and adults in correlation with the individual volume conductor geometry. We generated individual six compartment finite element models from structural magnetic resonance images of four children (age: 10.95 a±1.32 a), eight adolescents (age: 15.10 a±1.16 a) and eight young adults (age: 21.62 a±2.45 a). We determined the skull thickness in the models as Euclidean distance between the surface of the cerebrospinal fluid compartment and outer skull boundary. For tDCS simulations, we modeled 5×7cm patch electrodes impressing 1mA current intensity as anode and cathode over the left M1 and the right fronto-polar orbit, respectively. The resulting current density was analyzed on the gray matter surface. Our results demonstrate higher cortical current density magnitudes in children compared to adults for a given tDCS current strength. Above the evaluated cortex, the skull thickness increased with age. In conclusion, we underline the importance of age-dependent and individual models in tDCS simulations.


Paclobutrazol improves surface water use efficiency by regulating allometric trait behavior in maize.
Paclobutrazol (PBZ) role in drought management of maize is least understood. In maize, root traits are linked with surface water management. Over three years, early and terminal deficit irrigation (EDI and TDI) with or without PBZ were imposed on DKC-9144 and PG-2475 maize varieties. Several allometric parameters viz. stem height, stem diameter, leaf area and root traits along with physiological processes were measured. Implication of these parameters in the management of soil surface irrigation in terms of water use efficiency (WUE) was demonstrated in maize. Increased number of lateral roots and root number density in DKC-9144 provided more surface area for water absorption for better management of EDI. Root growth rates showed a similar pattern with root length, root surface areas, and root numbers in EDI. Elevated expressions of ZmRTCL, ZmRTCS and ZmARF34 in EDI and EDI plus PBZ were associated with seminal roots and root laterals initiation. Under TDI alone or in combination with PBZ, root lengths (BRL, CRL, SRL) and root surface areas varied in DKC-9144 and PG-2475 over control. Furthermore, correlation analysis showed that decrease in WUE under TDI was significantly associated with a reduction in stem thickness and leaf surface area. For WUE_N in TDI and PBZ plus TDI, structural equation modelling proposed, brace root surface area (BRSA_N) as a positive contributor, while a negative contributor was seminal root surface area (SRSA_N). Present study explained the importance of specific root traits and their association with other allometric parameters for improving WUE in DKC-9144 variety of maize and the crop in general.


Diagnosis of brachial root and plexus lesions.
The diagnosis and management of lesions of the brachial roots and of the brachial plexus is improved by appropriate investigation, both in acute and chronic disorders. The choice of investigation should be determined by the clinical problem. Since they are relatively non-invasive, electrophysiological investigations are particularly useful. In this review the role of these investigations is considered in relation to diagnosis and management.


Myocardial Inflammation on FDG PET/MRI and Clinical Outcomes in Symptomatic and Asymptomatic Participants after COVID-19 Vaccination.
To evaluate potential cardiac sequelae of COVID-19 vaccination at 2-month follow-up and relate cardiac symptoms to myocardial tissue changes on fluorodeoxyglucose (FDG) PET/MRI, blood biomarkers, health-related quality of life, and adverse outcomes. In this prospective study (ClinicalTrials.gov: NCT04967807), a convenience sample of individuals aged ≥17 years were enrolled after COVID-19 vaccination and were categorized as symptomatic myocarditis (new cardiac symptoms within 14 days of vaccination and met diagnostic criteria for acute myocarditis), symptomatic no myocarditis (new cardiac symptoms but did not meet criteria for myocarditis), and asymptomatic (no new cardiac symptoms). Standardized evaluation was performed 2 months after vaccination, including cardiac fluorine 18 FDG PET/MRI, blood biomarkers, and health-related quality of life. Statistical analysis included Kruskal-Wallis and Fisher exact tests. Fifty-four participants were evaluated a median of 72 days (IQR: 42, 91) after COVID-19 vaccination, 17 symptomatic with myocarditis (36±[SD]15 years, 13 males), 17 symptomatic without myocarditis (42±12 years, 7 males), and 20 asymptomatic (45±14 years, 9 males). No participants in the symptomatic without myocarditis or asymptomatic groups had focal FDG-uptake, myocardial edema or impaired ventricular function. Two participants with symptomatic myocarditis had focal FDG-uptake, and three had high T2 on MRI. Health-related quality of life was lower in the symptomatic myocarditis group than the asymptomatic group. There were no adverse cardiac events beyond myocarditis in any participant. At two-month follow-up, FDG PET/MRI showed evidence of myocardial inflammation in 2/17 participants diagnosed with acute myocarditis early after COVID-19 vaccination, but not in symptomatic and asymptomatic participants without acute myocarditis.Keywords: Myocarditis, Vaccination, COVID-19, PET/MRI, Cardiac MRI, FDG-PET.


An immunohistochemical investigation of the relationship between neuronal nitric oxide synthase, GABA and presympathetic paraventricular neurons in the hypothalamus.
Functional studies suggest that nitric oxide (NO) modulates sympathetic outflow by enhancing synaptic GABAergic function. Furthermore, the paraventricular nucleus of the hypothalamus (PVN), an important site for autonomic and endocrine homeostasis constitutes an important center mediating NO actions on sympathetic outflow. However, the exact anatomical organization of GABA and NO releasing neurons with the PVN neurons that regulate autonomic activity is poorly understood. The present study addressed this by identifying PVN-presympathetic neurons in the rat with the retrograde tracer Fluorogold injected into T2 segment of the spinal cord or herpes simplex virus injected into the adrenal medulla (AM). GABAergic or nitric oxide cell bodies were identified by antibodies directed towards GABA or glutamate decarboxylase (GAD67) enzyme or neuronal nitric oxide synthase. This revealed a population of GABAergic neurons to be synaptically associated with a chain of pre-sympathetic neurons targeting the AM. Furthermore, this GABAergic population is not a cellular source of NO. Within the PVN, the majority of cellular nitric oxide was localized to non-spinally projecting neurons while for the PVN-spinally projecting neuronal pool only a minority of neuron were immunopositive for neuronal nitric oxide synthase. In summary, nitrergic and GABAergic neurons are associated with a hierarchical chain of neurons that regulate autonomic outflow. This anatomical arrangement supports the known function role of a NO-GABA modulation of sympathetic outflow.


Preparation and purification of antibodies specific to human neuronal voltage-dependent calcium channel subunits.
Neuronal voltage-dependent calcium channels (VDCCs) each comprising of alpha 1, alpha 2 delta, and beta subunits, are one mechanism by which excitable cells regulate the flux of calcium ions across the cell membrane following depolarisation Studies have shown the expression of several alpha 1 and beta subtypes within neuronal tissue. The comparative distribution of these in normal human brain is largely unknown. The aim of this work is to prepare antibodies directed specifically to selected subunits of human neuronal VDCCs for use in biochemical and mapping studies of calcium channel subtypes in the brain. Previous studies have defined DNA sequences specific for each subunit Comparison of these sequences allows the selection of unique amino acid sequences for use as immunogens which are prepared as glutathione-S-transferase (GST) fusion proteins in E. coli. Polyclonal antibodies raised against these fusion proteins are purified by Protein A chromatography, followed by immunoaffinity chromatography and extensive adsorptions using the appropriate fusion protein-GST Sepharose 4B columns. The resultant antibodies are analysed for specificity against the fusion proteins by ELISA, and by immunofluorescence and Western immunoblot analysis of recombinant HEK293 cells stably transfected with cDNAs encoding alpha 1, alpha 2 delta and beta subunits.


Antimicrobial cholic acid derivatives from the Pitch Lake bacterium Bacillus amyloliquefaciens UWI-W23.
Six cholic acid derivatives (1-6) were isolated from broth cultures of Bacillus amyloliquefaciens UWI-W23, an isolate from the Trinidad Pitch Lake. The compounds were extracted via solvent extraction and/or XAD resin adsorption and purified using silica gel column chromatography. Their structures were elucidated using 1D, 2D NMR and ESI-MS spectrometry and FT-IR spectrophotometry. One of the compounds, taurodeoxycholate (2) is for the first time being reported from a bacterial source while deoxycholate (4) is for the first time being reported from a Gram-positive bacterium. The other compounds have not been previously isolated from Bacillus spp. viz. cholate (1), taurocholic acid (3); glycodeoxycholic acid (5) and glycocholic acid (6). All six compounds exhibited antimicrobial activity against P. aeruginosa and B. cereus with MICs ranging from 7 to 250 µg/mL. Cholate (1) also showed activity against MRSA (MICs = 125 µg/mL) and glycocholic acid (6) against S. cerevisiae (MICs = 15.6 µg/mL).


Chitosan-caffeic acid-genipin films presenting enhanced antioxidant activity and stability in acidic media.
The use of chitosan films has been limited due to their high degradability in aqueous acidic media. In order to produce chitosan films with high antioxidant activity and insoluble in acid solutions caffeic acid was grafted to chitosan by a radical mechanism using ammonium cerium (IV) nitrate (60 mM). Genipin was used as cross-linker. This methodology originated films with 80% higher antioxidant activity than the pristine film. Also, these films only lost 11% of their mass upon seven days immersion into an aqueous solution at pH 3.5 under stirring. The films surface wettability (contact angle 105°), mechanical properties (68 MPa of tensile strength and 4% of elongation at break), and thermal stability for temperatures lower than 300 °C were not significantly influenced by the covalent linkage of caffeic acid and genipin to chitosan. Due to their characteristics, mainly higher antioxidant activity and lower solubility, these are promising materials to be used as active films.


Cellular and subcellular distribution and factors influencing the accumulation of atmospheric Hg in Tillandsia usneoides leaves.
Atmospheric Hg is a highly toxic heavy metal with bioaccumulative properties. However, relatively few studies have focused on the distribution of Hg in cellular and subcellular structures of plants and factors influencing its accumulation. In this study, we selected Tillandsia usneoides, which is a widely used bioindicator for Hg, to analyze the concentration of Hg in different cells (foliar trichomes, epidermal cells, mesophyll cells, and vascular bundle cells), different subcellular structures (cell wall, cell membrane, vacuoles, and organelles) and different cell wall components (pectin, hemicellulose 1, and hemicellulose 2). It was determined that Hg was present in different types of cells, but there was no significant difference, suggesting that atmospheric Hg circulates dynamically in the surface and internal structural cells of T. usneoides leaves. Subcellular analysis showed that as Hg concentration increased, more Hg accumulated in the vacuoles and cell wall through the compartmentalization mechanism. Hemicellulose had the highest content of Hg, indicating that it is the primary Hg-binding component of the cell wall. The FTIR analysis results showed that after the Hg treatment, the cell wall -OH and COO- absorption peaks changed most significantly, indicating that these functional groups play a vital role in the Hg accumulation process.


Measuring nanometer distances in nucleic acids using a sequence-independent nitroxide probe.
This protocol describes the procedures for measuring nanometer distances in nucleic acids using a nitroxide probe that can be attached to any nucleotide within a given sequence. Two nitroxides are attached to phosphorothioates that are chemically substituted at specific sites of DNA or RNA. Inter-nitroxide distances are measured using a four-pulse double electron-electron resonance technique, and the measured distances are correlated to the parent structures using a Web-accessible computer program. Four to five days are needed for sample labeling, purification and distance measurement. The procedures described herein provide a method for probing global structures and studying conformational changes of nucleic acids and protein/nucleic acid complexes.


Price Determinants of the Tendering Process for Pharmaceuticals in the Cyprus Market.
Tendering has been a promising approach for procuring pharmaceuticals. Significant price reductions have been well documented by several authors. To our knowledge, there are limited data detailing the impact of variables in the tendering process. In this article, our objective was to evaluate the impact of potentially exploratory variables, which included innovation status, total value and volume of sales of each product, health care setting administration (hospital/outpatient), patent status (branded/generic), tendering type, and wholesale price, on price reduction in the tendering process. Financial data of public sector sales during 2011 were analyzed. On the basis of these data, we selected 178 medicines with corresponding sales of €49 million, out of a total market value of €104 million. Medicines were selected according to volume, value, and therapeutic value across all therapeutic areas. We performed a beta regression for the assessment of impact of variables and applied the same methodology to different subgroups. The generic status of medicines is statistically significantly associated with a higher price reduction. Tendering type by alternative, high wholesale prices, and high volume are robust estimators for price reduction. Innovation status does not have any effect on price reduction. Outpatient medicines reach lower prices as compared with hospital medicines. A rather unexpected finding is the negative correlation of high sales value with price reduction. These findings will lead to better understanding of the tendering framework, enabling us to further evolve its operational capacity, aiming to generate more savings. Moreover, our study indicates areas in which a more optimized approach is needed.


Effects of oral exposure to arsenite on arsenic metabolism and transport in rat kidney.
Nephrotoxicity is within the recognized toxic effects of arsenic. In this study we assessed the effect of arsenite on the renal capacity to metabolize and handle arsenicals in rats exposed to drinking water with 0, 1, 5, or 10 ppm sodium arsenite for ten days. Arsenite treatment did not affect the gene expression of the main enzyme catalyzing methylation of arsenite, As3mt, while it reduced the expression of GSTO1 mRNA and protein. Arsenite decreased the expression of Aqp3, Mrp1, Mrp4, and Mdr1b (i.e., transporters and channels used by arsenic), but not that of Aqp7, Glut1, Mrp2, and Mdr1a. The protein abundance of AQP3 was also reduced by arsenite. Arsenite increased urinary NGAL and FABP3 and decreased Klotho plasma levels, without alteration of creatinine, which evidenced early tubular damage. Renal Klotho mRNA and protein expressions were also downregulated, which may exacerbate renal damage. No effect was observed in selected miRNAs putatively associated with renal injury. Plasma PTH and FGF23 were similar between groups, but arsenite decreased the renal expression of Fgfr1 mRNA. In conclusion, exposure to arsenite alters the gene expression of proteins involved in the cellular handling of arsenical species and elicits tubular damage.


[Effect of hormonal compounds on embryogenesis of the pond snail Lymnaea stagnalis (L., 1758)].
Effect of preparations ofa peptide nature (pituitrin and oxytocin) and of a steroid nature (progesterone and hydrocortisone) on embryonic development of freshwater gastropod Lymnaea stagnalis (Mollusca, Gastropoda, Pulmonata) is described. The hormonal preparations used, which differed in chemical nature and physiological activity, may render diverse effects on embryogenesis of the studied mollusk. Of neurohormones, pituitrin rendered the most noticeable and principally stimulating effect. Oxytocin was incorporated in regulatory processes much later and its effect on the rate of realization of particular stages depended more on the quality of occurring changes. In final stages of development, this hormone principally inhibited growth and development of embryos. The female sex hormone progesterone rendered an expressed stimulatory effect, especially notable in later developmental stages of embryos. The hormone hydrocortisone stimulated initial stages of embryogenesis. Its effect was almost not expressed in the final stages. The discovered differences seem to be related both to the functional specificity of the investigated compounds and to specific traits of mechanisms of realization of their effects. A hypothesis is formulated: in gastropods, similarly to vertebrates, the hormones are systemic embryonic and postnatal inducers of differentiation processes.


The beneficial or detrimental fluoride to gut microbiota depends on its dosages.
Fluoride, widely presented in drinking water and tea, may be detrimental or beneficial to the human health, depending on its dosages ingested. However, the relationship of different dosages of fluoride and gut microbiota is still unclear. In this work, the fermentation model using fecal samples provided by four volunteers was used to evaluate the effects of different dosages of fluoride (1, 2, 10 and 15 mg/L) on the gut microbiota in vitro. The result showed low dosages of fluoride (1 and 2 mg/L) had limited effect on the structure and functional Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of gut microbiota. Furthermore, the low dosage of fluoride could promote the growth of beneficial gut microbiota, including Faecalibacterium and Lactobacillus. Whereas, the high dosage of fluoride (10 and 15 mg/L) significantly changed the composition and functional KEGG pathway of gut microbiota. Moreover, the high dosage of fluoride could also reduce the beneficial gut microbiota, including Faecalibacterium and Phascolarctobacterium, and increase the harmful bacterium including Proteobacteria and Enterobacteriaceae. Both low and high dosages of fluoride showed limited effect on the productions of short-chain fatty acids (SCFAs). Thus, the beneficial or detrimental fluoride to gut microbiota depends on its dosages. The fluoride is expected to serve as a food additive in suitable dosage to improve human health through modulation of the gut microbiota. Moreover, more attention should be paid to toxicity of fluoride with high dosage to gut microbiota.


Mild vs severe pulmonary hypertension before heart transplantation: different effects on posttransplantation pulmonary hypertension and mortality.
Pulmonary hypertension (PH) is common in severe heart failure, but the effect of mild PH on posttransplantation PH and survival after heart transplantation has not been well described. This cohort study examined preoperative and postoperative hemodynamics in 172 heart transplant recipients at Johns Hopkins Hospital followed for up to 15.1 years. PH was defined as pulmonary vascular resistance > or =2.5 Wood units, as measured during routine right heat catheterization; mild to moderate PH was defined as PVR between 2.5 and 4.9 Wood units; and severe PH was defined as PVR > or =5.0 Wood units. Seventy-one patients (41.3%) had PH, mostly of mild/moderate severity (77.5%), at the last routine hemodynamic monitoring before transplantation (median time before transplantation, 2.7 months). During follow-up, 105 patients (62.9%) developed PH at some point after transplantation, and 48 patients died (cumulative incidence, 76.5%). Mild/moderate preoperative PH was associated with increased risk of posttransplantation PH at 1, 3, and 6 months, but not with later episodes of PH. Mild/moderate preoperative PH was not associated with a higher mortality rate, but each 1 Wood unit increase in preoperative PVR demonstrated a trend toward increased mortality. Severe preoperative PH was associated with death within the first year after adjusting for potential confounders, but not with overall mortality or mortality at other time points. Mild to moderate preoperative PH is associated with increased risk of developing early but not late posttransplantation PH and may suggest different management strategies. Although PH was not consistently associated with mortality, increasing severity of the preoperative PH suggests potentially worse prognosis.


[Hemostatic effects of the argon laser on the gastric wall of the dog. II. Effects of the laser on 53 hemorrhagic ulcers of the gastric mucosa].
The authors made a histopathological study of 53 haemorrhagic ulcers of the gastric mucosa of the dog, photocoagulated using an Argon laser apparatus (delivering a power of 6 watts at the tip of the fibre). Haemostasis was obtained in less than 10 sec. in all cases where photocoagulation was performed by small applications of 1.5 sec. to the edges of the ulcer. There were no cases of perforation or muscularis damage. Healing of the lesions was complete or well under way at 15 days.


A Systematic Review of Drink Specials, Drink Special Laws, and Alcohol-Related Outcomes.
The adverse health and safety consequences of heavy alcohol consumption are a leading problem around the world. While many risk factors have been extensively studied and presented in comprehensive summaries, not all questions regarding risk factors for problematic drinking behaviors have been answered and presented in systematic reviews. As of March 2020, no review has summarized studies assessing the role of promotional price practices at on-premises alcohol outlets, known as drink specials. Also missing was systematic information of policies that regulated these promotional practices. We aimed to synthesize the available research evidence of the effects that drink specials and drink special laws have on different alcohol-related outcomes. Twelve studies examined the effect of drink specials in seven countries between 1978 and 2018. Of these, 11 found a consistent positive association between drink specials and increased alcohol consumption, heavy drinking, and alcohol intoxication. Drink specials also increased reports of driving under the influence, fighting, and unprotected sex. Drink specials were also associated with expectations of higher consumption and modified attitudes and behaviors towards favorable views of drink specials. Effect sizes ranged from 1.80 to 4.43 increased odds for the examined alcohol-related outcomes. The only study examining the effects of a drink special law revealed mixed findings between prohibiting happy hours and three alcohol-related outcomes. Drink specials were consistently associated with alcohol-related adverse outcomes, but almost nothing is known about the effects of laws restricting drink specials.


Parenting for foster parents.
A parenting course for foster parents was described with a follow-up evaluation utilized to determine its effectiveness. The content of this broad-based course included learning theory, principles and techniques, communication skills, methods of conflict resolution, developmental considerations, and information about community services. Results of the evaluation suggested that most of the participants had found the course helpful and were using the knowledge acquired.


The association between health-related quality of life, self-reported characteristics and 1- and 3-year mortality amongst cardiac patients with and without type 2 diabetes.
The objectives amongst cardiac patients with and without type 2 diabetes were to (i) describe self-reported characteristics as health-related quality of life (HRQoL), health behaviour, body mass index (BMI) and physical shape and to (ii) investigate the association between self-reported characteristics and 1- and 3-year mortality. Adult patients (≥ 18 years) discharged with a cardiac diagnosis were invited to participate in a national survey, DenHeart. Self-reported characteristics included HRQoL (EQ-5D-5L and HeartQol), health behaviour (alcohol and smoking), BMI and physical shape. Data were linked to national registries. The association between self-reported characteristics and 1- and 3-year mortality were investigated using the Cox Proportional Hazard Regression model, reported as hazard ratios (HR) with 95% confidence intervals (CI). In total, 16,659 cardiac responders were included (n = 2,205 with type 2 diabetes, n = 14,454 without type 2 diabetes). Self-reported characteristics were worse amongst cardiac patients with type 2 diabetes compared to those without. After three years, the mortality rate was 14% amongst responders with diabetes and 7% amongst responders without type 2 diabetes (p ≤ 0.001). Better HRQoL was associated with a reduced risk of mortality amongst both groups. "Never been smoking" significantly reduced the risk of 1- and 3-year mortality amongst cardiac patients without diabetes, whereas good physical shape was associated with a reduced risk across both groups. HRQoL, health behaviour, BMI and physical shape are significantly worse amongst cardiac patients with type 2 diabetes. Better HRQoL was associated with a reduced risk of mortality amongst both groups, whereas other self-reported characteristics and the mortality risk varied.


Implementing Oral Care as a Nursing Intervention to Reduce Hospital-Acquired Pneumonia Across the United States Department of Veterans Affairs Healthcare System.
Hospital-acquired pneumonia is a preventable complication. The primary source of pneumonia among hospitalized and long-term care residents is aspiration of bacteria present in the oral biofilm. Reducing the bacterial burden in the mouth through consistent oral care is associated with a reduction in the incidence of hospital-acquired pneumonia. Following a significant reduction in pneumonia among non-ventilated patients in the research pilots, the Veterans Health Administration deployed the evidence-based, nurse-led oral care intervention called Hospital Acquired Pneumonia Prevention by Engaging Nurses as quality improvement nationwide. In this article, nursing informatics experts on the team describe the design and implementation of process and outcome measures of Hospital-Acquired Pneumonia Prevention by Engaging Nurses and outline lessons learned. The team used standardized terms and observations embedded within the EHR documentation templates to measure the oral care intervention in acute care areas. They also developed a tracking system for hospital-acquired pneumonia cases among non-ventilated patients. In addition to improving patient safety and care quality, Hospital-Acquired Pneumonia Prevention by Engaging Nurses links evidence-based practice with nursing informatics principles to generate numerous opportunities to measure the value of nursing at the point of care. This initiative was reported using SQUIRE 2.0: Standards for QUality Improvement Reporting Excellence.


Mental health problems of children and adolescents, with and without migration background, living in Vienna, Austria.
Compared to their indigenous peers, migrant children and adolescents are at increased risk for mental health problems. The aim of our study was to compare psychological disorders of children and adolescents with Turkish migration background and their native Austrian peers. We analysed 302 children and adolescents aged between 7 and 18 years. The sample consisted of 100 Austrian and 100 Turkish outpatients with mental health problems, and 102 healthy controls, 52 with Austrian and 50 with Turkish background, recruited from various Viennese local child and youth centres. Native patients had more frequently externalizing problems (42.1%) compared to the Turkish-speaking sample (28%). However, in the control group, Turkish-speaking children and adolescents had higher levels of internalizing, depressive and anxiety symptoms compared to their native peers. We found noticeable differences in psychological problems among children and adolescents with and without migration background. We assume that migration-related stress factors are responsible for these differences. Also, children and adolescents with migration background seek for psychological help less frequently than their indigenous peers.


Brine residues and organics in the Urvara basin on Ceres.
Ceres is a partially differentiated dwarf planet, as confirmed by NASA's Dawn mission. The Urvara basin (diameter ~170 km) is its third-largest impact feature, enabling insights into the cerean crust. Urvara's geology and mineralogy suggest a potential brine layer at the crust-mantle transition. Here we report new findings that help in understanding the structure and composition of the cerean crust. These results were derived by using the highest-resolution Framing Camera images acquired by Dawn at Ceres. Unexpectedly, we found meter-scale concentrated exposures of bright material (salts) along the crater's upper central ridge, which originate from an enormous depth, possibly from a deep-seated brine or salt reservoir. An extended resurfacing modified the southern floor ~100 Myr after crater formation (~250 Myr), long after the dissipation of the impact-generated heat. In this resurfaced area, one floor scarp shows a granular flow pattern of bright material, showing spectra consistent with the presence of organic material, the first such finding on Ceres beyond the vast Ernutet area. Our results strengthen the hypothesis that Ceres is and has been a geologically active world even in recent epochs, with salts and organic-rich material playing a major role in its evolution.


Functionality of endothelial cells on silk fibroin nets: comparative study of micro- and nanometric fibre size.
Biomimetic material design, such as mimicking nanostructured components of the extracellular matrix, is an actual challenge for biomaterial research with a high impact on tissue engineering and regenerative medicine. Thus, understanding the cellular response at the cell biological and molecular level and the consequences of various chemically or physically modified biomaterials is highly important. In the present study we assessed the response of human umbilical vein endothelial cells (HUVEC) and outgrowth endothelial cells (OEC) from endothelial progenitor cells to different variants of nanofibrous silk fibroin nets in comparison to microfibrous silk fibroin scaffolds with regard to cellular morphology, proliferation, formation of intercellular contacts as well as integrin-dependent adhesion. Endothelial cells (ECs) grown on nanometric nets formed a differentiated and interconnected endothelial monolayer with no significant changes in the expression of intercellular contact molecules or proliferation rates compared with cells grown on micrometric nets. Nevertheless, quantitative real-time PCR revealed a higher expression level of integrin-beta1 in ECs grown on nanofibrous fibroin nets compared to the microfibrous samples. In addition, single nano-fibres were recognised by the integrin-receptor mechanism supporting the formation of focal adhesion at the interface of ECs and nanometric nets. These findings indicate that the nanometric silk fibroin scaffolds did not interfere with the formation of a differentiated and interconnected EC layer. On the contrary, nanofibre variation of the fibroin net architecture induced changes in ECs at the molecular level in terms of the increased expression of adhesion molecules such as integrin-beta1.


Implementation of a checklist to assess factors relevant for work ability assessments of employees on long-term sick leave.
To implement the use of a checklist with factors relevant for work ability assessments of employees on long-term sick leave in daily practice of Dutch insurance physicians (IPs). Two hundred and twenty IPs were asked to participate in a nationwide implementation study. A context analysis identified the barriers and promoting factors for the implementation. Then, participants were asked to assess, identify and report the factors that hinder or promote return to work (RTW) of employees on long-term sick leave using the checklist during six work ability assessments in daily practice. The outcome measure was the percentage of IPs that used the checklist in at least three of six work ability assessments. The use of the checklist was defined as the assessment of at least one of nine factors from the checklist. A frequency analysis was performed. Official work ability assessment records were analysed to determine whether the IPs reported the assessed factors. Most identified barriers and facilitators were related to the potential users, the work environment and the characteristics of the checklist. The implementation goal was achieved. A total of 79 IPs participated. Almost all the IPs (96 %) assessed at least one factor; 89 % used the checklist in at least 3 work ability assessments. An analysis of 474 official work ability assessment records indicated that 90 % of the IPs reported at least one of the factors. The implementation of a checklist to assess barriers and facilitators for RTW of long-term sick-listed employees was successful.


Recurrent high grade glioma surgery with carmustine wafers implantation: a long-term nationwide retrospective study.
Widespread use of carmustine wafers (CW) to treat high-grade gliomas (HGG) has been limited by uncertainties about its efficacy. To assess the outcome of patients after recurrent HGG surgery with CW implantation and, search for associated factors. We processed the French medico-administrative national database between 2008 and 2019 to retrieve ad hoc cases. Survival methods were implemented. 559 patients who had CW implantation after recurrent HGG resection at 41 different institutions between 2008 and 2019 were identified. 35.6% were female and, median age at HGG resection with CW implantation was 58.1 years, IQR [50-65.4]. 520 patients (93%) had died at data collection with a median age at death of 59.7 years, IQR [51.6-67.1]. Median overall survival (OS) was 1.1 years, 95%CI[0.97-1.2], id est 13.2 months. Median age at death was 59.7 years, IQR [51.6-67.1]. OS at 1, 2 and 5 years was 52.1%, 95%CI[48.1-56.4], 24.6%, 95%CI[21.3-28.5] & 8%, 95%CI[5.9-10.7] respectively. In the adjusted regression, bevacizumab given before CW implantation, (HR = 1.98, 95%CI[1.49-2.63], p < 0.001), a longer delay between the first and the second HGG surgery (HR = 1, 95%CI[1-1], p < 0.001), RT given before and after CW implantation (HR = 0.59, 95%CI[0.39-0.87], p = 0.009) and TMZ given before and after CW implantation (HR = 0.81, 95%CI[0.66-0.98], p = 0.034) remained significantly associated with a longer survival. OS of patients with recurrent HGG that underwent surgery with CW implantation is better in case of prolonged delay between the two resections and, for the patients who had RT and TMZ before and after CW implantation.


Tau Diagnostics and Clinical Studies.
This short editorial provides our point of view of the first EURO TAU meeting focusing on tau diagnostics and clinical studies. We cover postmortem analyses toward the identification of new biomarkers, tau imaging as a diagnostic biomarker, cerebrospinal fluid (CSF) sampling with emphasis on tau fragments, blood tests and genetic evaluations for sporadic cases, treatment aspects, drug development and points for future developments toward disease modification of devastating tauopathies.


Regulation of Glial Function by Noncoding RNA in Central Nervous System Disease.
Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.


A case for immediate-release niacin.
Niacin is currently a favored drug for increasing high-density lipoprotein, especially in patients with ischemic heart disease or at high risk of developing it. In addition, niacin further decreases low-density lipoprotein in statin-treated patients and has been shown to reduce morbidity and mortality. Among the available niacin preparations, crystalline, immediate-release niacin is the most effective for increasing high-density lipoprotein and is relatively free of hepatic toxicity. We present the case of a patient who had an excellent clinical and laboratory response to 3 g daily of immediate-release niacin, but who later developed clinical hepatitis when he inadvertently switched to the same dose of slow-release niacin. We encourage the use of niacin in general, immediate-release niacin in particular, and caution that niacin is a drug and not a dietary supplement. We also present practical steps for starting niacin, including close patient contact and support, and beginning with a therapeutic dose of 2 g per day right from the start.


Parental Decision-Making for Children With Medical Complexity: An Integrated Literature Review.
Children with medical complexity (CMC) have multiple significant chronic health conditions that result in functional limitations and high health care utilization. The population of CMC is increasing and parent decision-making for this population is nuanced. To review the literature specifically related to the parent experience of medical decision-making for CMC from the parent perspective. A comprehensive, systematic approach was undertaken with the goal of identifying emergent themes in the existing literature as well as implications for clinical practice and future research. PubMed and PsycInfo databases were searched for English-language articles published between 1995-2020 that focused on parent experiences/perspectives using the search terms: children with medical complexity, children with serious illness, parent decision-making, parent experience, goals of care, parental priorities, advance care planning, and shared decision-making. The search yielded 300 unique manuscripts; including 32 empirical articles incorporated in this review. The synthesized findings were broken down into three main sections: 1. types of decisions that parents of CMC face, 2. key factors that influence parental decision-making for CMC, and 3. reasons that the decision-making process for parents of CMC is unique. The findings suggest that parents should be considered experts in their child's care and should be incorporated in shared decision-making in a culturally appropriate manner. CMC should have their personhood valued and providers require specialized training in communication. Parents of CMC have unique needs in their decision-making process and benefit from shared decision-making, continuity of care, collaborative communication and tailored, individualized care.


A novel calmodulin-like gene from the nematode Caenorhabditis elegans.
A novel gene from the nematode Caenorhabditis elegans was isolated by hybridization with a human calmodulin complementary DNA probe. This gene, cal-1, is present at one copy per haploid genome. In-situ hybridization of the cloned gene to metaphase chromosomes allowed us to assign it to the nematode linkage group IV. The polypeptide predicted from the sequence of this gene displays structural features of both calmodulin and troponin C.


Pilot Study of a Free Long-Acting Reversible Contraception Program on a Mobile Health Center in Miami Dade County, Florida.
In 2016, the NeighborhoodHELP mobile health centers (MHCs) started to provide free long acting reversible contraception (LARC) for uninsured patients who lacked access due to cost. All female patients with appointments from May 1st, 2016 through April 30th, 2017 were identified. LARC uptake rate, as well as demographics for patients aged 15-44 who underwent LARC insertion versus those who did not, were determined. Of the 520 female patients seen on the MHCs during the study period, 170 were of reproductive age. Seventeen (10%) patients opted for LARC; 100 % of these patients spoke Spanish or English and 82 % identified as White and Hispanic/Latino. Results show a 10% LARC uptake, which is slightly above the national rate, but lower than rates in other studies in which cost barriers were removed. Further investigation into barriers influencing LARC uptake in our patient population is warranted.


Extract and molecular-based early infant sensitization and associated factors-A PreventADALL study.
More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. From the Scandinavian antenatally recruited PreventADALL mother-child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA /L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA /L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16-0.81 kUA /L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53-8.68). Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants' sensitization.


Effect of degree of milling and defatting on proximate composition, functional and texture characteristics of gluten-free muffin of bran of long-grain indica rice cultivars.
Effect of different degrees of milling (DoM: 2%, 4%, 6% and 8%) and defatting on the proximate composition, protein characteristics, functional properties of bran of long grain rice cultivars and texture characteristics of bran (RB) supplemented muffins were evaluated. Protein, ash content, redness and yellowness increased while fat content decreased for RB by extended DoM and defatting. A higher proportion of β sheets, random coils, α-helix and β-turns for all fractions of RB of both cultivars after defatting were also observed. Defatting and extended DoM both improved the essential amino acid content in RB. A higher level of prolamines (15-18 kDa) in RB and DF-RB of PUSA1121 than PR111 was observed. Muffins made from 2% DoM bran from PUSA1121 showed improved texture characteristics and achieved the highest score for sensory attributes. Therefore, DoM and defatting improved the proximate, protein profiling, and functionality of the different fraction of RB.


Bis(μ-N-nitroso-N-phenyl-hydroxy-laminato)-κO,O':O';κO':O,O'-bis-[(N-nitroso-N-phenyl-hydroxy-laminato-κO,O')lead(II)].
The four cupferronate ions in the dinuclear title compound, [Pb(2)(C(6)H(5)N(2)O(2))(4)], O,O'-chelate to the two Pb(II) atoms; two of the four nitroso O atoms are also involved in bridging. The geometry of both five-coordinate Pb(II)atoms is distorted Ψ-octa-hedral; if another two longer inter-molecular Pb⋯O inter-actions [at 2.955 (1) and 3.099 (1) Å] are considered, the geometry is a distorted Ψ-square anti-prism.


DNA Methylation Age and Physical and Cognitive Aging.
DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect(s) of aging it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline. AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed, and forced expiratory volume in one second [FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed. AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n = 1,388-1,685). For example, a 1-year increase in AgeAccelPheno or AgeAccelGrim was associated with a 0.01 mL (95% confidence interval [CI]: 0.01, 0.02) or 0.03 mL (95% CI: 0.01, 0.05) lower mean FEV1 respectively. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p < .05). In a subset of NSHD participants (n = 482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance. We found little evidence to support associations between the first generation of DNAm-based biomarkers of aging and age-related physical or cognitive performance in midlife to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual's healthspan as proposed.