CNS stem and progenitor cell differentiation into functional neuronal circuits in three-dimensional collagen gels.
The mammalian central nervous system (CNS) has little capacity for self-repair after injury, and neurons are not capable of proliferating. Therefore, neural tissue engineering that combines neural stem and progenitor cells and biologically derived polymer scaffolds may revolutionize the medical approach to the treatment of damaged CNS tissues. Neural stem and progenitor cells isolated from embryonic rat cortical or subcortical neuroepithelium were dispersed within type I collagen, and the cell-collagen constructs were cultured in serum-free medium containing basic fibroblast growth factor. The collagen-entrapped stem and progenitors actively expanded and efficiently generated neurons, which developed neuronal polarity, neurotransmitters, ion channels/receptors, and excitability. Ca2+ imaging showed that differentiation from BrdU+/TuJ1- to BrdU-/TuJ1+ cells was accompanied by a shift in expression of functional receptors for neurotransmitters from cholinergic and purinergic to predominantly GABAergic and glutamatergic. Spontaneous postsynaptic currents were recorded by patch-clamping from precursor cell-derived neurons and these currents were partially blocked by 10-microM bicuculline, and completely blocked by additional 10 microM of the kainate receptor antagonist CNQX, indicating an appearance of both GABAergic and glutamatergic synaptic activities. Staining with endocytotic marker FM1-43 demonstrated active synaptic vesicle recycling occurring among collagen-entrapped neurons. These results show that neural stem and progenitor cells cultured in 3D collagen gels recapitulate CNS stem cell development; this is the first demonstration of CNS stem and progenitor cell-derived functional synapse and neuronal network formation in a 3D matrix. The proliferative capacity and neuronal differentiating potential of neural progenitors in 3D collagen gels suggest their potential use in attempts to promote neuronal regeneration in vivo.


Effectiveness of esophagus detection by three-dimensional electroanatomical mapping to avoid esophageal injury during ablation of atrial fibrillation.
Esophageal-left atrial (LA) fistula during atrial fibrillation (AF) ablation is a fatal event. We explored the relation of the esophagus-to-ablated point distance and esophageal temperature rise. Consecutive patients (n=106) underwent complex fractionated atrial electrogram-guided AF ablation using CartoMerge; the pulmonary veins were isolated in 23 patients. Maximum radiofrequency (RF) power near the esophagus was 15 W. Ablated points with esophageal temperature rise (monitored with a probe) to ≥38.0°C were tagged; if ≥39.0°C, RF was discontinued. Of 1647 ablated points near the esophagus, 274 were associated with a temperature rise to 38.0-38.9°C and 241 points to ≥39.0°C. Distances (mm) from points to esophagus were 5.1 ± 0.6 (no rise), 4.2±3.1 (38.0-38.9°C), 2.9 ± 2.5 (≥39.0°C). Altogether, 15.5% of points in the upper LA posterior wall, 41.5% in the middle, and 30.2% in the lower caused rises to ≥38.0°C; 8.7%, 24.6%, and 11.0% caused rises to ≥39.0°C. The middle wall was most affected (p<0.01), as shown by multiple logistic regression analysis (both temperatures). Points causing a rise increased significantly as distance decreased (p<0.001). The odds ratio for rise to ≥38.0°C compared with <4.0 to >5.0 mm distance was 2.28 (p=0.004). The longest distance for ≥38.0°C rise was 18.5 mm. Distance is an important predictor of esophageal temperature rise. The middle LA posterior wall is most vulnerable. A dose of 15 W is too high for ablation, especially <4.0 mm from the esophagus. Points >20.0 mm away are relatively safe.


Associations between local government expenditures and low birth weight incidence: Evidence from national birth records.
Local governments play an integral role in providing public services to their residents, yet the population health benefits are frequently overlooked, especially when services are outside the traditional health domain. With data from the U.S. Census of Governments and national birth records (spanning from 1992 to 2014), we examined whether local government expenditures on parks and recreation services (PRS) and housing and community development (HCD) predicted county low birth weight outcomes (population incidence and black-white disparities). Hypotheses were tested using bias-corrected county-by-period fixed effects models in a sample of 956 U.S. counties with a total of 3619 observations (observations were defined as three-year pooled estimates), representing 24 million births. Adjusting for prior county low birth weight incidence, levels of total operational, health, and hospital expenditures, and time-varying county sociodemographics, an increase in per capita county PRS expenditures of $50 was associated with 1.25 fewer low birth weight cases per 1000. Change in county HCD expenditures was not associated with low birth weight incidence, and, contrary to hypotheses, neither expenditure type was linked to county black-white disparities. Further examination of the benefits to birth outcomes from increasing parks and recreation services is warranted.


Symptoms mimicking dementia in a 60-year-old woman with bipolar disorder: a case report.
Dementia is generally considered an irreversible process of cognitive decline that can be caused by different neurodegenerative diseases. However, in some cases, dementia is caused by a non-neurodegenerative disease, such as an affective disorder. In these cases, the dementia can be reversible. Nevertheless, cognitive symptoms due to an affective disorder are often difficult to distinguish from a depressed mood due to a neurodegenerative disease. Especially in elderly patients with a history of affective disorder, a potentially reversible cause can be missed. We describe a 60-year-old white woman with bipolar disorder, depressive symptoms, a movement disorder and severe cognitive impairment, in whom a neurodegenerative disease was seriously considered. She was referred to our clinic for further investigation because initial treatment of the depressive episode with antidepressants, mood stabilizers and electroconvulsive therapy (ECT) had not been successful. However, despite extensive evaluation, we could not find evidence for a neurodegenerative disease and the patient mostly recovered after discontinuation of different psychotropic medications and treatment with nortriptyline. Our case shows that improvement of severe cognitive impairment in individual cases is possible. In our opinion, this underlines the necessity of a careful re-evaluation of the patient's symptoms at presentation and the course of the disease as well as a critical review of the prescribed medications.


Identification and characterization of a novel chitinase-like gene cluster (AgCht5) possibly derived from tandem duplications in the African malaria mosquito, Anopheles gambiae.
Insect chitinase 5 (Cht5), a well-characterized enzyme found in the molting fluid and/or integument, is classified as a group I chitinase and is usually encoded by a single gene. In this study, a Cht5 gene cluster consisting of five different chitinase-like genes (AgCht5-1, AgCht5-2, AgCht5-3, AgCht5-4 and AgCht5-5) was identified by a bioinformatics search of the genome of Anopheles gambiae. The gene models were confirmed by cloning and sequencing of the corresponding cDNAs and gene expression profiles during insect development were determined. All of these genes are found in a single cluster on chromosome 2R. Their open reading frames (ORF) range from 1227 to 1713 bp capable of encoding putative proteins ranging in size from 409 to 571 amino acids. The identities of their cDNA sequences range from 52 to 66%, and the identities of their deduced amino acid sequences range from 38 to 53%. There are four introns for AgCht5-1, two for AgCht5-2 and AgCht5-3, only one for AgCht5-4, but none for AgCht5-5 in the genome. All five chitinase-like proteins possess a catalytic domain with all of the conserved sequence motifs, but only AgCht5-1 has a chitin-binding domain. Phylogenetic analysis of these deduced proteins along with those from other insect species suggests that AgCht5-1 is orthologous to the Cht5 proteins identified in other insect species. The differences in expression patterns of these genes at different developmental stages further support that these genes may have distinct functions. Additional searching of the genomes of two other mosquito species led to the discovery of four Cht5-like genes in Aedes aegypti and three in Culex quinquefasciatus. Thus, the presence of a Cht5 gene cluster appears to be unique to mosquito species and these genes may have resulted from gene tandem duplications.


Observation of Magnetic Domains in Amorphous Magnetic Wires with a Diameter of 10 μm Used in GSR Sensors.
The core of a Gigahertz Spin Rotation (GSR) sensor, a compact and highly sensitive magnetic sensor, is composed of Co-Fe-based amorphous magnetic wire with a diameter of 10 μm. Observations of the magnetic domain structure showed that this magnetic wire has unusual magnetic noise characteristics. Bamboo-shaped magnetic domains a few hundred micrometers in width were observed to form inside the wire, and smaller domains a few micrometers across were observed to form inside these larger domains. The magnetic domain pattern changed abruptly when an external magnetic field was applied to the wire. Herein is shown how these changes may be a source of magnetic noise in the wire.


Regulation of ptsH and ptsI gene expression in Streptococcus salivarius ATCC 25975.
The transcriptional regulation of the Streptococcus salivarius ptsH and ptsI genes coding for the general energy-coupling proteins HPr and enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system were investigated. These genes form an operon with the gene order ptsH-ptsI. Three distinct mRNA species were detected: a 0.5 kb transcript specific for ptsH, and two long transcripts (2.2 and 2.4 kb) covering the whole pts operon. Transcription of all these mRNAs initiated at the same nucleotide located 9 bp downstream from a promoter located immediately upstream from the ptsH gene. The presence of a high-energy stem-loop structure (T0) located at the beginning of ptsI was responsible for the premature transcription termination generating the 0.5 kb ptsH-specific transcript. The long transcripts ended in the poly(U) region of two rho-independent-like terminators (T1 and T2) at the 3' end of ptsI. Studies with a 2-deoxyglucose-resistant spontaneous mutant of S. salivarius (L26) that produces an HPr-EI fusion protein suggest that the regulation of HPr and EI expression involves transcriptional as well as translational mechanisms.


Categorization of voice disorders with six perceptual dimensions.
To obtain a perceptual reference for acoustic feature selection, 94 male and 124 female voices were categorized using the ratings of 6 clinicians on visual analog scales for pathology, roughness, breathiness, strain, asthenia, and pitch. Partial correlations showed that breathiness and roughness were the main determinants of pathology. The six-dimensional ratings (the six median scores for each voice) were categorized with the aid of the Sammon map and the self-organizing map. The five categories created differed with respect to the breathiness/roughness ratio and the degree of pathology.


Microcuff Pediatric Endotracheal Tubes: Evaluation of Cuff Sealing Pressure, Fiber-optic Assessment of Tube Tip, and Cuff Position by Ultrasonography.
Use of uncuffed tubes causes lots of morbidity, and there is a surge in the use of microcuff pediatric endotracheal tubes. These tubes are not evaluated in the Indian population. The study aimed to evaluate the pediatric microcuff endotracheal tubes in terms of cuff sealing pressure, fiber-optic assessment of tube tip, and cuff position to assess postextubation airway morbidity. Study design involves follow-up analytical study. Thirty-four children in the age group of 2-12 years were studied. Patients with leak pressure >20 cm H2O were exchanged with smaller size tube and excluded. Cuff pressure, fiber-optic assessment of tube tip to carina distance in neutral and flexion, ultrasound assessment of cuff position, and postextubation airway morbidity were assessed. Parameters expressed as the median with the interquartile range. Nonparametric data were analyzed using the Wilcoxon signed-rank test. The tracheal leak pressure was <20 cm H2O (median 14.5 cm H2O) in 30 children. Tube exchange was required in four patients. A complete seal was achieved in 30 patients with cuff pressures ranging from 6 to 8.25 cm of H2O (median 8 cm of H2O). The median caudal displacement is 0.8 cm (0.47-1.22 cm) with flexion. There was no airway-related morbidity in any of these patients. The microcuff pediatric endotracheal tubes when used according to the age-based formula had a higher tube exchange rate in our study population. However, in children in whom the tube size was appropriate, the tubes provided good sealing without increasing airway morbidity. Further studies with a larger sample size might be required to confirm the findings.


Impact of Foam-Mat Drying on Plant-Based Foods Bioactive Compounds: a Review.
Plant-based foods are recognized by their remarkable content of bioactive compounds. In an attempt to increase plant-based foods shelf-life, technologies like drying can be used. Foam-mat drying is a mild drying technology that removes water, usually by using hot air, from a foam obtained by the whipping of a liquid or semi-liquid food added with a foaming agent. There are several reports on the use of foam-mat drying for extending plant-based foods shelf-life, including reports on the effect of drying on their bioactive compounds. Therefore, this study aimed at reviewing the literature on the impact of foam-mat drying on plant-based foods bioactive compounds published in the last 10 years. Results show that short foam-mat drying time is beneficial to bioactive compounds retention. In addition, hot air temperature between 40-65 °C, foam thickness between 0.2 and 1 cm and the use of egg white as one of the foaming agents leads to high bioactive retention. Egg white is also the most used foaming agent. Regarding the mathematical models used for fitting the foam-mat drying kinetics, the Page model was shown as the most proper model. Foaming agent concentration is a delicate parameter, as its increase in foam formulation may beneficially enhance drying rates but, at the same time, it dilutes bioactive compounds and may cause their loss by oxidation. In conclusion, foam-mat drying stands out as a suitable technology for producing food powders with high bioactive retention.


Some properties of polylysine-accessible DNA.
DNA regions in rat liver chromatin which are accessible to polylysine were isolated using three molecular weights of polylysine so as to overcome possible artefacts in measuring the DNA size. Sucrose gradient centrifugation showed a series of peaks or shoulders corresponding to sizes of 65, 110, 210, 370, 600 and 1,200 base pairs. Accessible DNA was enriched in and co-sedimented with rapidly synthesized RNA but the RNA was digestible by RNAase A, indicating that most of each RNA molecule was single-stranded (possibly hybridised to DNA at one end). The reassociation rate of accessible DNA was similar to that of whole DNA up to about Cot 50, but was slower at higher cost values.


The role of the lymphatic system in vaccine trafficking and immune response.
The development and improvement of vaccines has been a significant endeavor on the part of the medical community for more than the last two centuries, and the success of these efforts is obvious when one considers the millions of lives that have been saved. Recent work in the field of vaccines, however, indicates that vaccines may be developed for even more challenging diseases than those previously addressed. It will be important in achieving this feat to account for the physical and chemical processes related to vaccine trafficking, rather than solely relying on our knowledge of the pathogen and our empirical experience. A thorough understanding of the lymphatic system is essential considering the role it plays in antigen trafficking and all immunological activity. This review describes the results of recent work that provides insight into the physiological processes of the lymphatic system and its various components with an emphasis on vaccine antigen trafficking from the administration site to secondary lymphoid tissues and the ensuing immune response. The review also discusses current challenges in designing vaccines and presents modern strategies for designing vaccines to better interface with the lymphatic system.


Erratum to "Case report on babesiosis associated pre-hepatic jaundice in a Malabari goat" [3C (June 2017) 1-3].
[This corrects the article DOI: 10.1016/j.vas.2017.01.001.].


Backyard conservation in traditionally owned lands.
Backyard conservation is a community-based approach aiming to weave traditional knowledge, management practices, customary land ownership, and Indigenous-driven solutions with other scientific knowledge to enhance conservation. The islands of Papua New Guinea (PNG) provide an important example towards understanding the role of backyard conservation in culturally diverse and complex societies.


Alterations in crystallin gene expression during subculture of chick lens cells.
We report here on the changes in crystallin gene expression during serial subculture of lens epithelial cells derived from day-old post-hatch chicks. Total cellular RNA from mass cultures were analysed by in vitro cell-free translation and by RNA blot (Northern) hybridization using a cloned delta-crystallin cDNA. Our results indicate that following subculture, lens epithelial cells which still retain the capacity for lens fibre differentiation (lentoid body formation) show a selective loss of delta-crystallin synthesis, and that this is related to the loss of delta-crystallin mRNA. The data suggest that older epithelial-cell populations give rise to lentoid bodies which in terms of crystallin gene expression closely resemble the later-formed cortical fibres of the adult chick lens. Tertiary cultures had an accelerated growth rate, formed no lentoids, contained no translatable alpha- or delta-crystallin mRNAs but still contained translatable beta-crystallin mRNAs.


Mental health after childbirth and the impact on postpartum weight retention and body composition. Data from the INTER-ACT randomized controlled trial.
To study the evolution of maternal mental health during the first year after childbirth in women with previous excessive gestational weight gain, and the relationship with postpartum weight retention and body composition. Anthropometric and mental health data of 505 women of the INTER-ACT RCT control group were collected and assessed using descriptive statistics and mixed model analyses. At 6 weeks postpartum 28% of women reported depressive symptoms, 46% anxiety, 47% low sense of coherence and 48% low quality of life. From 6 weeks to 12 months postpartum there was a monthly increase (+0.38, p = .003) in anxiety and a monthly decrease (-0.39, p = .008) in quality of life. High levels of depressive symptoms at 6 weeks postpartum predicted higher body fat (+0.9%, p = .01) and higher waist circumference (+1.3 cm, p = .02) in the first year postpartum. High sense of coherence at 6 weeks postpartum predicted lower body fat (-0.8%, p = .01) the first year postpartum. In women with a history of excessive gestational weight gain, the first year after childbirth is characterized by a high prevalence of mental health problems in which levels of anxiety and quality of life deteriorate over time. Moreover, high levels of depressive symptoms and low sense of coherence in the first weeks postpartum predict unfavourable body composition outcomes in the year after childbirth.


In Silico Augmentation of the Drug Development Pipeline: Examples from the study of Acute Inflammation.
The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high-throughput and -content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are utilized in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. In this article, we present a Translational Systems Biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism.


Portable and sensitive quantitative detection of DNA based on personal glucose meters and isothermal circular strand-displacement polymerization reaction.
A portable and sensitive quantitative DNA detection method based on personal glucose meters and isothermal circular strand-displacement polymerization reaction was developed. The target DNA triggered target recycling process, which opened capture DNA. The released target then found another capture DNA to trigger another polymerization cycle, which was repeated for many rounds, resulting in the multiplication of the DNA-invertase conjugation on the surface of Streptavidin-MNBs. The DNA-invertase was used to catalyze the hydrolysis of sucrose into glucose for PGM readout. There was a liner relationship between the signal of PGM and the concentration of target DNA in the range of 5.0 to 1000 fM, which is lower than some DNA detection method. In addition, the method exhibited excellent sequence selectivity and there was almost no effect of biological complex to the detection performance, which suggested our method can be successfully applied to DNA detection in real biological samples.


Hearing loss among elderly people and access to hearing aids: a cross-sectional study from a rural area in Germany.
Hearing loss is common and associated with reduced quality of life, particularly among elderly people. However, many patients do not use hearing aids. We evaluated the use of hearing aids among people with hearing loss by health services availability near their residence in a rural area in the state of Brandenburg, Germany. Audiometry was performed in a convenience sample of subjects in ten towns and hearing loss was determined, defined as a threshold of ≥ 30 dB in at least one ear and at least one of the frequencies 0.5, 1.0, 2.0 and 4.0 kHz. For each participant, age and gender were collected and whether or not hearing aids were available. Among 186 persons with an average age of 74 years (interquartile range 71-81), 97% had hearing loss [95% confidence interval (CI) 95-100]. Among 121 patients with hearing loss who reported whether or not they have a hearing aid, 93 had no hearing aid (77%, 95% CI 69-84). The proportion of hearing-impaired persons who do not have a hearing aid significantly increased with the absence of a hearing aid specialist or ear nose throat (ENT) physician or both in the town where the tests were performed (p trend = 0.001). Hearing loss is common among elderly people in the study area and many people in rural areas in Germany may not be properly supplied with hearing aids due to lack of hearing aid specialists and/or ENT physicians close to their residence. Interventions to improve this situation are urgently required.


Effects of Nitrosyl Iron Complexes with Thiocarbamide and Its Aliphatic Derivatives on Activities of Ca2+-ATPase of Sarcoplasmic Reticulum and cGMP Phosphodiesterase.
We studied the effects of water-soluble cationic dinitrosyl iron complexes with thiocarbamide and its aliphatic derivatives, new synthetic analogs of natural NO donors, active centers of nitrosyl [1Fe-2S]proteins, on activities of Ca2+-ATPase of sarcoplasmic reticulum and cGMP phosphodiesterase. Nitrosyl iron complexes [Fe(C3N2H8S)Cl(NO)2]0[Fe(NO)2(C3N2H8S)2]+Cl- (I), [Fe(SC(N(CH3)2)2(NO)2]Cl (II), [Fe(SC(NH2)2)2(NO)2Cl×H2O (III), and [Fe(SC(NH2)2)2(NO)2]2SO4×H2O (IV) in a concentration of 10-4 M completely inhibited the transporting and hydrolytic functions of Ca2+-ATPase. In a concentration of 10-5 M, they inhibited active Ca2+ transport by 57±6, 75±8, 80±8, and 85±9% and ATP hydrolysis by 0, 40±4, 48±5, and 38±4%, respectively. Complex II reversibly and noncompetitively inhibited the hydrolytic function of Ca2+-ATPase (Ki=1.7×10-6 M). All the studied iron-sulphur complexes in a concentration of 10-4 M inhibited cGMP phosphodiesterase function. These data suggest that the studied complexes can exhibit antimetastatic, antiaggregation, vasodilatatory, and antihypertensive activities.


Inflammatory profile of apical periodontitis associated with liver fibrosis in rats: histological and immunohistochemical analysis.
To investigate the effects of liver fibrosis (LF) on the pro-inflammatory mediators and periapical bone resorption of apical periodontitis (AP) in rats. Forty male Wistar rats were distributed into four groups: C - control, AP - rats with AP, LF - rats with LF, AP + LF - rats with AP and LF. LF was induced by carbon tetrachloride administration for 8 weeks and surgical bile duct ligation for 4 weeks; AP was induced in the teeth of rats by dental pulp exposure to the oral environment for 30 days. Jaws and livers were removed after euthanasia. Haematoxylin and Eosin (H&E) and Picrosirius Red (PSR) staining were used to confirm fibrosis in the livers. The jaws were analysed using H&E staining, immunohistochemical assays of interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α). Student's t-test and Mann-Whitney's U-test were used for statistical analysis (P < 0.05). Inflammatory infiltrate was moderate in the AP group and severe in the AP + LF group (P < 0.05). Periapical bone resorption was significantly larger in the AP + LF group compared with the AP group (P < 0.05). IL-1β, IL-6 and TNF-α levels were significantly higher in AP + LF group when compared to the AP group (P < 0.05). More intense inflammatory infiltrate, greater amounts of pro-inflammatory cytokines and increased periapical bone resorption were observed in the presence of liver fibrosis in rats with exposed pulps.


["Even the best law will never replace reflection in the field"].
Implemented in 2006 by the French minister for health, the resource centres for people working with sex offenders (CRIAVS) provide support for professionals and non-professionals, concerned with transgressive sexual behaviour. They offer tools for legal, health and social professionals to facilitate the supervision of sex offenders. Florent Cochez, a psychiatrist and medical examiner, manager of the Aquitaine CRIAVS, describes in this interview the missions of these regional structures, their link with court-ordered therapy and his practice.


Expression of genetic markers of erythrocyte immunoglobulin G autoantibodies in autoimmune hemolytic anemia.
The Gm allotype constitution of the autoantibody molecules and the serum Gm phenotypes were determined in 19 patients with autiommune hemolytic anemia of IgG type. The results showed that the known heterogeneity of the antierythrocyte autoantibodies in this disease concerns not only the immunoglobulin class and the isotypic subclass, but also the genetic markers of these molecules. Evidence was obtained that the anomalous production of antierythrocyte autoantibodies is polyclonal, that thse autoantibodies belong mainly to the IgG1 isotypic subclass, and that they have a preference for the Gm(1) allotype. In addition, certain of the findings point to a preferential expression of the Gm(1,21) haplotype.


[CT scan evaluation of the syndesmotic diastasis in AO/OTA B and C ankle fractures].
There are anatomical variants of the tibiofibular syndesmosis that lead to changes in the radiographic criteria applied to its injury. To determine the syndesmotic diastasis using CAT scan in B and C (AO/OTA) ankle fractures and relate the anatomical variants of the tibial incisure with the separation from the fibula. Comparative, cross-sectional and prolective screening that included all patients with B and C (AO/OTA) ankle fractures who completed their X-ray and CAT scan assessment. The radiographic parameters included the tibiofibular clearance, tibiofibular overlapping and the internal clearance. The length, depth and shape of the tibial incisure were measured with CAT scan. The statistical method used was the chi2. The total number of patients was 17:8 females (47%) and 9 males (53%), with a mean age of 41 years. Fourteen (82%) had a syndesmotic fracture and 3 had suprasyndesmotic fractures. The CAT scan found 10 concave incisures, 4 irregular and 3 flat ones. The mean depth of the incisure was 2.82 +/- 0.89 mm, and the mean width was 22.18 +/- 3.04. No syndesmotic diastasis was detected radiographically in 6 cases (35.2%); the CAT scan only detected 3 of them (17.7%). The diagnosis of syndesmotic diastasis was made with plain X-rays in 11 cases (64.8%) and with CAT scan in 14 (82.3%) (p = 0.043). The X-rays are questionable to define the syndesmotic diastasis, so the CAT scan should be considered in cases of a doubtful diagnosis.


Substance P-induced changes in cell genesis following diffuse traumatic brain injury.
Inhibition of substance P (SP) activity through the use of NK1 receptor antagonists has been shown to be a promising neuroprotective therapy following traumatic brain injury (TBI). Conversely, recent research has implicated SP in the stimulation of neurogenesis, suggesting that the neuropeptide has the potential to promote recovery following TBI. This study characterised the effects of SP and the NK1 antagonist, n-acetyl tryptophan (NAT), on cell proliferation following diffuse TBI. Adult male Sprague-Dawley rats were injured using the impact acceleration model of TBI and randomly assigned to one of five treatment groups: sham, vehicle control, NAT alone, SP alone or SP with NAT. Cellular proliferation was assessed with immunostaining for bromodeoxyuridine (BrdU) and cell-specific markers. Infusion of SP (±NAT) promoted cellular proliferation in the subventricular zone and dentate gyrus following TBI. This increase was largely associated with microglial proliferation and did not correspond with functional improvements. These results suggest that NAT treatment results in neuroprotection following TBI, mediated in part via inhibition of microglia.


Activity, cardiac and respiratory responses of blindfold preterm infants in a neonatal intensive care unit.
The purposes of the present study were to examine 24-h periods in the life of preterm infants incubated in a Neonatal Intensive Care Unit (NICU) using indices of activity, cardiac and respiratory responses, and to examine the effects of blindfolding incubated infants upon these behavioural indices. Ten healthy preterm infants were individually observed for 2 days a week for a 24-h period, using a continuous video recording system. Each infant was blindfolded with an eye-mask and a black head-cap for approximately equal to 10 h during a night out of the 2 days. Analyses on activity, cardiac and respiratory responses were done for (1) 20 min sampled from every other hour during the 2 days, and (2) for 1 h during the night, both a blindfolded day and unblindfolded, respectively. The results showed that activity was less and respiration rate lower when blindfolded than when unblindfolded. Respiration rate was also found to be stable when blindfolded.


Agriculture and downstream ecosystems in Florida: an analysis of media discourse.
Environmental media discourse analysis allows researchers to explore thematic patterns in media coverage of environmental issues through qualitative observations and quantitative coding. In this paper, we review newspaper media coverage in Florida pertaining to the connections between agriculture, other non-point pollution sources, and downstream ecosystem health. We analyzed 930 articles from 2007 through 2019 to determine common patterns in how these issues are covered by Florida media, including patterns in the causes of environmental problems, potential solutions, and stakeholders mentioned. Findings suggest that water quality problems are often framed as unpredictable or episodic rather than chronic, and as requiring (and only potentially being remediated by) state-level centralized technological or infrastructural solutions. Stakeholder relationships are framed as adversarial, with environmentalists and the agricultural sector as opponents. This case study highlights key power dynamics, barriers, and opportunities for better managing and communicating about agricultural land use practices and associated downstream environmental impacts.


Levels of public awareness regarding cervical spine injury and the suitable first aid response among adults in Saudi Arabia.
To evaluate the level of public awareness regarding cervical spine injuries among adult residents of the Kingdom of Saudi Arabia (KSA). This descriptive cross-sectional study was carried out between June and November 2020. It involved structured questionnaires, collecting information on participant socio-demographic characteristics, first responder training status, and the awareness of cervical spine trauma and suitable first aid response. A total of 4914 respondents (age, 31.6 ± 11.8 years) completed the survey. Most participants (75.2%) reported road traffic accidents as a risk factor for cervical spine injury. Moreover, 79.4% of the participants reported that cervical spine injury may be accompanied by damage to the spinal cord. Motor and sensory disability, and trouble breathing were recognized as complications associated with cervical spine injuries by 52.1%, 39%, and 28.8% of the participants, respectively. Fewer than one in 3 participants was aware of cervical spine trauma or the suitable first aid response. Public awareness regarding cervical spine trauma is poor among the KSA residents, although most study participants were aware trauma victims should be immobilized at the site of the accident until the arrival of an emergency response team.


Tract-tracing in the nervous system of vertebrates using horseradish peroxidase and its conjugates: tracers, chromogens and stabilization for light and electron microscopy.
Surprisingly the first generation of tract-tracing techniques based on intra-axonal transport, that is the methods utilizing the uptake and transport of horseradish peroxidase (HRP), still rank among the most widely used neuroanatomical tracing techniques. The success of these methods can be ascribed to several characteristics. They are fast and easy to implement. Complicated injection apparatus is unnecessary. The reaction products are visualized through simple histochemical reactions, and they are permanent or can be stabilized into permanency. Most usefully, the reaction products are visible in the light and electron microscopes. HRP (mol. wt. 44 kDa) is extracted from the roots of the horseradish plant (Cochlearia armoracia L.). Uptake of HRP into cells occurs via a passive process of endocytosis. Since lectins like wheat germ agglutinin (WGA) and bacterial toxin fragments (subunit B of cholera toxin (CTB)) strongly induce active, receptor-mediated uptake mechanisms, conjugates of these substances with HRP have been successfully applied in sensitive tract-tracing HRP and its conjugates are transported both in anterograde and retrograde direction. Retrograde transport occurs in small vesicles that are incorporated in lysosome-like vacuoles and in the Golgi apparatus. These vesicles differ in membrane properties from the anterogradely transported HRP vesicles. The retrogradely transported vesicles tend to fuse and thus accumulate HRP at high densities, facilitating the visibility of the final reaction product. The anterogradely transported HRP does not accumulate directly in lysosome-like bodies and is distributed diffusely and therefore often requires specific visualization methods. HRP and WGA-HRP may therefore be used in anterograde and retrograde transneuronal (multineuron) transport studies. Even in fixed material, labeling through diffusion of HRP can provide details on neural connections. Visualization of transported HRP is achieved by means of using the oxidative enzymatic activity of HRP to precipitate a chromogen according to the following reaction: [symbol: see text] The final reaction product may be soluble in buffer or ethanol and may require stabilization to prevent fading. In this protocol we discuss the widely used chromogens 3,3'-diaminobenzidine tetrahydrochloride (DAB), 3,3',5,5'-tetramethylbenzidine (TMB), benzidine dihydrochloride (BDHC) and p-phenylenediamine dihydrochloride with pyrocatechol (PPD-PC). Other possible chromogens, not discussed here, are 4-chloro-1-naphthol (4C1N), 3-amino-9-ethylcarbazole (AEC) and o-phenylenediamine (OPD). The visualization of the reaction product can be further improved by intensification with metal salts. At the light microscopic level (LM) this intensification enables color differentiation between distinct markers. In the present protocol we provide an up-to-date guideline for the application of HRP and its conjugates in tracing with special emphasis on electron microscopic (EM) visualization. Some modifications for stabilization and of metal intensification to enhance visibility are incorporated in conjunction with specific methods for multiple labeling in combined tract-tracing experiments.


Subcapital femoral neck osteotomy without surgical hip dislocation in epiphyseolysis capitis femoris lenta with severe displacement.
Severe displacement in the lenta form of slipped capital femoral epiphysis leads to distinct joint incongruence with subsequent severe deformity, limitations of function and walking ability as well as early joint degeneration. Subcapital femoral neck osteotomy restores the congruence of the hip joint as far as possible. This procedure is a so-called secondary prophylactic intervention. Disimpaction of the slipped epiphysis in several planes by wedge-shaped osteotomy in the subcapital region of the femoral neck (slippage is in a posterior and caudal direction). Careful preservation of the nutrient vessels to the femoral head within the posterior capsule. Stabilization of the osteotomy with cannulated screws with a short thread. The data reported in the literature vary greatly with regard to frequency and extent of femoral head necrosis. The present author holds the opinion that this risk is minimal, if the surgeon proceeds with care. Nevertheless, the indications for this procedure should be chosen with great reservation.


The genetic and functional analysis of flavor in commercial tomato: the FLORAL4 gene underlies a QTL for floral aroma volatiles in tomato fruit.
Tomato (Solanum lycopersicum L.) has become a popular model for genetic studies of fruit flavor in the last two decades. In this article we present a study of tomato fruit flavor, including an analysis of the genetic, metabolic and sensorial variation of a collection of contemporary commercial glasshouse tomato cultivars, followed by a validation of the associations found by quantitative trait locus (QTL) analysis of representative biparental segregating populations. This led to the identification of the major sensorial and chemical components determining fruit flavor variation and detection of the underlying QTLs. The high representation of QTL haplotypes in the breeders' germplasm suggests that there is great potential for applying these QTLs in current breeding programs aimed at improving tomato flavor. A QTL on chromosome 4 was found to affect the levels of the phenylalanine-derived volatiles (PHEVs) 2-phenylethanol, phenylacetaldehyde and 1-nitro-2-phenylethane. Fruits of near-isogenic lines contrasting for this locus and in the composition of PHEVs significantly differed in the perception of fruity and rose-hip-like aroma. The PHEV locus was fine mapped, which allowed for the identification of FLORAL4 as a candidate gene for PHEV regulation. Using a gene-editing-based (CRISPR-CAS9) reverse-genetics approach, FLORAL4 was demonstrated to be the key factor in this QTL affecting PHEV accumulation in tomato fruit.


Incidence, clinicopathological features and genetics of in-situ follicular neoplasia: a comprehensive screening study in a Japanese cohort.
In-situ follicular neoplasia (ISFN) is a histologically recognizable neoplastic proliferation of follicular lymphoma (FL)-like B cells confined to the germinal centres. While some ISFNs are associated with overt FL, others are incidentally identified as isolated or pure forms in individuals without evidence of overt FL. The prevalence of incidentally found isolated ISFN is approximately 3% in Europe; however, no screening study has been conducted in Asia. To investigate the incidence and clinicopathological characteristics of ISFNs in the Japanese population, we conducted histopathological screening of the lymph nodes (LNs) resected for solid tumours or inflammatory conditions. We screened for ISFN in 5700 LNs from 340 individuals using immunohistochemistry for BCL2 and identified seven ISFNs, with an incidence of 2.1%. The median age of the individuals with ISFN was 67 years, none of whom developed overt FL, with a median follow-up of 59 months. Next-generation sequencing was performed in five ISFNs, and 10 variants in seven FL-associated genes were identified. The identified variants included HIST1H1E (n = 2), ARID1A (n = 2), KMT2D (n = 1), CARD11 (n = 1), BCL7A (n = 1), CREBBP (n = 1) and TNFRSF14 (n = 1). The incidence of isolated ISFN in the Japanese population is not significantly different from that in Europe, presumably reflecting the recent increase in FL in Japan. These incidentally found ISFNs have a low potential to transform into overt FL. Although mutations of FL-associated genes are already present in ISFNs, further molecular studies are needed to identify driver genes leading to the transformation of ISFN to overt FL.


Absence of AET protection against fast neutrons: cellular effects.
A series of experiments has been undertaken in order to test the biological properties of neutrons produced in the cyclotron of the Institute "Ruder Bosković" (IRB) in Zagreb. Protective effect of AET (2-amino ethylisothiuronium bromide hydrobromide) on survival of L cells irradiated by fast neutrons generated in the IRB cyclotron were studied by employing the single cell clonal growth method. For comparison the protective effect of AET after gamma irradiation has also been studied. The most important findings that have emerged from these experiments can be summarized as follows: (1) Protective effect of AET was present after gamma irradiation only. (2) The degree of protection was dependent on AET concentration in the growth medium. (3) No protective effect was found after neutron irradiation. These findings are in agreement with the generally less efficient protection of this compounds after high-LET irradiation.


Investigation of the beta-lactamase activity of Prototheca zopfii.
A total of 52 strains of Prototheca zopfii were studied with a series of beta-lactam compounds in order to test possible existence of beta-lactamase capable of inactivating these compounds. The method used was based on the iodimetric technique. Results showed the existence of beta-lactamase which worked in different degrees depending on the beta-lactam compounds.


Modulation of the tonic stretch reflex by monoamines.
The effects of L-DOPA and 5-HTP on the tonic stretch reflex (TSR) in the decerebrate rat were studied. L-DOPA facilitated the TSR in a dose-dependent manner. The facilitation of the TSR was blocked by pimozide. A sensitive electromygraphic (EMG) technique capable of recording single motor unit discharges was used. The EMG results suggest that gamma motoneuron sensitivity was increased to a greater degree than alpha motoneuron sensitivity during the facilitation by L-DOPA. The L-DOPA-induced facilitation persisted in animals partly depleted of 5-hydroxytryptamine (5-HT) by reserpine, p-chlorophenylalanine or 5,6-dihydroxytryptamine. 5-HTP inhibited the TSR in a dose-dependent manner. It is concluded that DA not 5-HT is the amine which normally mediates facilitation of the TSR after L-DOPA and that gamma motoneuron activation is more likely to be involved to a greater degree than alpha motoneuron activation in the neural mechanisms of the facilitation.


Coupled effects of climatic forcing and the human footprint on wildlife movement and space use in a dynamic floodplain landscape.
With climate change, terrestrial fauna in riparian floodplain ecosystems must adapt to a predicted increase in frequency and magnitude of fluvial perturbations. Seasonal migration to seek refuge from floodwaters represents a central adaptation strategy, but may entail risky navigation of anthropogenic spaces in heterogeneous landscapes. Here, we demonstrate the opportunities and constraints large-bodied mammalian herbivores face during an adaptive response of obligatory flood-driven refuge migration, across a human-dominated environment. Our study system, centred around a productive protected area--Kaziranga National Park in Assam, Northeast India--on the floodplains of the Brahmaputra River, is home to an abundance of large herbivores that undertake seasonal migrations in response to floods. We contrast species distribution data during a major flood event with those from the dry season to illustrate season-specific movement and space use decisions of large herbivores ranging in body mass from the 3000-kg Asian elephant Elephas maximus to the 20-kg muntjac Muntiacus muntjak. In the dry season, most large herbivores--a majority of which are endangered and threatened by anthropogenic pressures--avoided areas with a strong human footprint, while preferring spaces with high land-use diversity. During the floods, such species were pushed out of inundated habitats within the protected area, and they chose to move through woodlands and areas under bamboo cover on private lands, as they migrated to forested refugia on higher ground. Our results show how seasonal environmental constraints shaped by floods determine the internal motivation of animals to risk traversing a human-dominated space to seek refuge, which contextually defines how animals view and navigate the landscape. Such insights underscore the importance of dynamic and adaptive planning, and participatory conservation efforts, to facilitate connectivity in the changing environment and climate of the present Anthropocene.


Conduction velocity in peripheral nerve of foetal, newborn and adult sheep.
Measurements have been made of conduction velocity in tibial and peroneal divisions of the sciatic nerve in foetal, newborn and adult sheep. Foetal age ranged from 91 days after mating to term, at 145 days. Measurements on foetuses used chronically implanted electrodes in 6 animals and direct nerve recordings in two acute preparations. For chronic recordings, two pairs of stimulating electrodes were placed as far apart along the nerve as possible and recording electrodes measured the electromyogram of the lateral gastrocnemius muscle. In the nerve recordings stimulating electrodes were placed at several different sites and the latency of the nerve action potential at each site was plotted against electrode separation. Values of maximum conduction velocity in foetal tibial nerve ranged from 24 m/s at 91 days to 60 m/s at term. Conduction velocity increased by 0.6 m/s per day. In the newborn lamb conduction velocity was more than half of the adult value of 96 m/s, indicating the relative maturity of the sheep at birth compared with other mammals.


Endovascular treatment of extradural internal carotid artery aneurysm with a flow diverter stent.
Extradural internal carotid artery aneurysms are rare and the indications for treatment are not well defined. We report successful management of two high extradural internal carotid artery aneurysms treated with flow diverter stents. The endovascular repair of extradural internal carotid artery aneurysms is effective because with surgical treatment there is always the possibility of cranial nerve injury.


Motility depressed intestinal propulsion following selective jejunal myotomy in the rat.
The effect of segmentary sectioning of the proximal jejunal tunica muscularis on intestinal propulsion was studied in the rat. Care was taken to avoid damage to the mucosa. In no instance was perforation or occlusion of the intestine observed. Myotomy was followed by a significant slackening of the passage of a test meal during the first 15 min after feeding, while the total transit time was virtually unchanged. Sectioning the musculature of the intestinal wall is shown to be responsible for retardation of bowel passage.


Biopsy findings after detection of de novo donor-specific antibodies in renal transplant recipients: a single center experience.
De novo donor-specific antibodies (DSA) are associated with an increased risk of antibody-mediated rejection and a substantial reduction of allograft survival. We hypothesized that detection of DSA should prompt a biopsy even in the absence of proteinuria and loss of estimated glomerular filtration rate (eGFR). However, data on a population without proteinuria or loss of kidney function is scant, and this is the main novelty of our study design. Single center retrospective analysis on biopsy findings after detection of de novo DSA. One-hundred-thirty-two kidney and pancreas-kidney transplant recipients were included. Eighty-four of these patients (63.6%) underwent allograft biopsy. At the time of biopsy n = 50 (59.5%) had a protein/creatinine ratio (PCR) > 300 mg/g creatinine and/or a loss of eGFR ≥ 10 ml/min in the previous 12 months, whereas 40.5% did not. Diagnosis of rejection was performed according to Banff criteria. Seventy-seven (91.7%) of the biopsies had signs of rejection (47.6% antibody mediated rejection (ABMR), 13.1% cellular, 20.2% combined, 10.7% borderline). Among subjects without proteinuria or loss of eGFR ≥ 10 ml/min/a (n = 34), 29 patients (85.3%) showed signs of rejection (44.1% antibody mediated (ABMR), 14.7% cellular, 11.8% combined, 14.7% borderline). The majority of subjects with de novo DSA have histological signs of rejection, even in the absence of proteinuria and deterioration of graft function. Thus, it appears reasonable to routinely perform an allograft biopsy after the detection of de novo DSA.


Pulmonary artery-focused contrast echocardiography with supplemental oxygen(PCESO) for echocardiographic diagnosis of anomalous origin of left coronary artery from pulmonary artery: Novel use of an old technique.
Pulmonary artery-focused agitated saline contrast echocardiography unveils tricky cases of ALCAPA by the entry of microbubbles into the left coronary artery (LCA) during systole and retrograde flow from LCA into the main pulmonary artery during diastole. Associated pulmonary hypertension, if present, augments the former flow and supplemental oxygen increases the latter.


Skhodnya, Khvalynsk, Satanay, and Podkumok calvariae: possible Upper Paleolithic hominins from European Russia.
European Russia has been at the fringe of the hominin dispersal for most of the late Pleistocene. However, by about 20,000 BP this area was settled by modern humans who had highly sophisticated and sometimes unique technologies. Not many Upper Paleolithic human fossils have been described from this area and consequently the morphology of these people remains largely unknown. Here, we present descriptions and a comparative morphological analysis of four possibly late Pleistocene fossils from European Russia: Skhodnya, Khvalynsk, Satanay, and Podkumok. The frontal bone is chosen for study because it is preserved in all of these fossils and is known to provide good discrimination among groups of Pleistocene hominins. All four fossils have been previously claimed to possess 'archaic' features of frontal morphology, such as developed supraorbital relief and a flat frontal squama. The results of a 3D geometric morphometric analysis of frontal bone landmarks and semilandmarks indicate that these fossils indisputably belong to modern humans. However, there are good reasons to associate Khvalynsk, Skhodnya, and Podkumok with Upper Paleolithic fossils from central and western Europe, whereas Satanay is more similar to a pooled sample of recent modern humans.


Macrophage migration inhibitory factor - 794 CATT5-8 microsatellite polymorphism and susceptibility of tuberculosis.
The establishment of candidate genetic determinants associated with tuberculosis (TB) is a challenge, considering the divergent frequencies among populations. The objective of this study was to evaluate the association between MIF - 794 CATT 5-8 polymorphism and susceptibility to TB. Case-control study. Patients > 18 years, with pulmonary TB were included. The control group consisted of blood donors and household contacts, not relatives, healthy and > 18 years. MIF - 794 CATT 5-8 were genotyped using sequencing of PCR and capillary electrophoresis. 126 patients and 119 controls were included. The genotype 5/5 was more frequent among cases (15.1%) than in controls (5.9%) (p = 0.019). Cases had more frequently the allele 5 (29.4%) as compared with controls (19.3%) (p = 0.010). Prevalence of 7/X + 8/X genotypes was not different between cases and controls (p = 0.821). There was no difference between patients with alleles 7 and 8 and those with alleles 5 and 6 (p = 0.608). The genotype 5/5 and the allele 5 of MIF - 794 CATT 5-8 were more frequent among TB patients than in controls.


Attitude and perceptions of the other underrepresented minority in surgery.
To perform a national climate survey of general surgery residents regarding attitudes and perceptions of the influence of sexual orientation on the training experience. A cross-sectional voluntary online survey was distributed to all Accreditation Council for Graduate Medical Education-accredited general surgery programs. Residents self-identified as heterosexual, lesbian, gay, or bisexual. Descriptive statistics were performed. For the purposes of further analysis, respondents were classified as heterosexual or LGBT. Demographic characteristics and survey responses were examined by sexual orientation using the Fisher exact test. Of 388 resident respondents, 10 identified as lesbian (2.6%), 24 as gay (6.3%), and 9 as bisexual (2.4%). More than 30% of LGBT residents did not reveal their sexual orientation when applying for general surgery residency owing to fear of not being accepted. No statistical differences were found between LGBT and heterosexual residents regarding future career plans, happiness at work, good program fit, and rapport with fellow residents. Although no differences were found in relationship status between LGBT and heterosexual residents, more LGBT residents reported feeling uncomfortable openly discussing their spouse/partner with fellow residents (36% vs 3.0%, p < 0.001) and with surgical attending physicians (59% vs 9.3 %, p < 0.001) when compared with heterosexual peers. Additionally, LGBT residents felt more uncomfortable bringing their spouse/partner to formal surgery department events (42% vs 2.7%, p < 0.001). Among all respondents, 54% (n = 206) witnessed homophobic remarks by nurses and residents and 30% (n = 114) by surgical attending physicians. Of LGBT residents, 57% reported actively concealing their sexual orientation from fellow residents owing to fear of rejection and 52% from surgical attending physicians owing to fear of poor evaluations. LGBT residents reported experiencing targeted homophobic remarks by fellow residents (21%) and by surgical attending physicians (12%). None of the surgical residents who experienced directed homophobic remarks reported the event to their supervisors for reasons including fear of reprisal (13%-17%), not wanting to create more "trouble" (25%-50%), and a belief that nothing would be done about the event (17%-25%). Now, more than ever, issues related to sexual orientation have been at the forefront of political and public attention. No data exist that explore how these issues affect the training experience of general surgery residents. Our study showed that although there was no difference overall in reported work happiness or program fit, LGBT residents reported a greater need to conceal their personal lives from their surgery program peers and attending physicians. Whether these differences affect patient care, team work, career satisfaction, and personal cost of surgical training warrants further study.


Activation of the hypothalamo-anterior pituitary corticotropin-releasing hormone, adrenocorticotropin hormone and beta-endorphin systems during the estradiol 17 beta-induced plasma LH surge in the ovariectomized monkey.
The present work describes time-dependent changes in the content of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH), and beta-endorphin (beta-EP) in the hypothalamus (HT) and anterior pituitary (AP) and in the concentration of ACTH and beta-EP in the plasma during the 17 beta estradiol (E2) benzoate (E2B)-induced luteinizing hormone (LH) surge in ovariectomized cynomolgus monkeys. Monkeys were euthanized at 0, 30, 48, 72, and 96 hr post-E2B. HT and AP were rapidly dissected, extracted in 2 N acetic acid containing 1 mM phenylmethane sulfonyl fluoride at 4 degrees C, and centrifuged at 18,000g for 30 min. Peptide concentrations were measured in the supernatant by specific radioimmunoassays (RIAs). In the HT, there were significant (P < 0.05) decreases in ACTH and beta-EP content by 30 hr post-E2B and a significant (P < 0.05) decrease in HT CRH content 48 hr post-E2B. Thereafter, CRH, ACTH, and beta-EP content increased up to 72 hr post-E2B. In the AP, there was an almost linear decrease in the CRH content through 48 hr post-E2B followed by a marked 20-fold (P < 0.01) increase in the AP CRH content at 72 hr post-E2B, which corresponds to the time of the descending arm of the LH surge. The patterns of ACTH and beta-EP content were very similar in the AP, while that of CRH differed markedly. In contrast, in the HT CRH, ACTH, and beta-EP profiles were very similar. Significant (P < 0.05) increases in circulating levels of ACTH, beta-EP, and cortisol were evident at 30 hr (all 3 hormones), 48 hr (beta-EP and cortisol), and 72 hr (cortisol) post-E2B, which corresponds with the time of decreased hypothalamic content of CRH, ACTH, and beta-EP. These results suggest that there maybe a marked activation of the hypothalamo-anterior pituitary-adrenal axis during the negative and positive feedback phases of the E2B-induced LH surge in the ovariectomized monkey.


Metagenome-Assembled Genomes from Monte Cristo Cave (Diamantina, Brazil) Reveal Prokaryotic Lineages As Functional Models for Life on Mars.
Microbial communities have been explored in various terrestrial subsurface ecosystems, showing metabolic potentials that could generate noteworthy morphological and molecular biosignatures. Recent advancements in bioinformatic tools have allowed for descriptions of novel and yet-to-be cultivated microbial lineages in different ecosystems due to the genome reconstruction approach from metagenomic data. Using shotgun metagenomic data, we obtained metagenome-assembled genomes related to cultivated and yet-to-be cultivated prokaryotic lineages from a silica and iron-rich cave (Monte Cristo) in Minas Gerais State, Brazil. The Monte Cristo Cave has been shown to possess a high diversity of genes involved with different biogeochemical cycles, including reductive and oxidative pathways related to carbon, sulfur, nitrogen, and iron. Three genomes were selected for pangenomic analysis, assigned as Truepera sp., Ca. Methylomirabilis sp., and Ca. Koribacter sp. based on their lifestyles (radiation resistance, anaerobic methane oxidation, and potential iron oxidation). These bacteria exhibit genes involved with multiple DNA repair strategies, starvation, and stress response. Because these groups have few reference genomes deposited in databases, our study adds important genomic information about these lineages. The combination of techniques applied in this study allowed us to unveil the potential relationships between microbial genomes and their ecological processes with the cave mineralogy and highlight the lineages involved with anaerobic methane oxidation, iron oxidation, and radiation resistance as functional models for the search for extant life-forms outside our planet in silica- and iron-rich environments and potentially on Mars.


Unusual photodegradation reactions of Asteraceae and Poaceae grass pollen enzymatic extracts on P25 photocatalyst.
In previous studies, it was demonstrated that photocatalysis by TiO2 nanoparticles can be effective for decomposition of pollen grains and pollen allergen extracts (PAEs) for Cupressus arizonica and Platanus hybrida species. In this work, the chemical and photochemical processes of five types of PAEs belonging to family Asteraceae, tribe Astereae, and family Poaceae, tribes Poeae and Triticea, were studied. It was confirmed that the PAEs suffered almost complete decomposition, which likely led to gaseous final products. For the species of Poeae tribe, i.e., Poa pratensis, Festuca pratensis, and Avena sativa, an unusual surface chemical modification of the photocatalyst consisting in the appearance of new bands on fine core level spectra of Ti 2p, C 1s, and O 1s was observed. These changes were associated with possible doping of TiO2 with C and N by pollen extracts. This was accompanied by a red shift of absorption spectra. The results suggest that some components of Poeae pollen can be grafted on TiO2 surface and they can activate the photocatalyst in the visible range. These findings can open a new pathway to eco-friendly chemical engineering of photocatalysts using organic biological compounds.


Clinical Profile, Viral Load, Maternal-Fetal Outcomes of Pregnancy With COVID-19: 4-Week Retrospective, Tertiary Care Single-Centre Descriptive Study.
The COVID-19 pandemic raises a major concern about its severity in pregnancy, maternal-fetal outcomes, and risk of vertical transmission. We report a retrospective descriptive study of the clinical course and maternal-fetal outcomes of pregnant women with COVID-19. This is a single-centre, retrospective study performed in a tertiary care hospital for pregnant women with COVID-19 in India. The medical records of all women who delivered in the COVID19 facility from May 5, 2020, to June 5, 2020, were reviewed independently. Data extracted from the records included demographic characteristics, obstetric details, comorbidities, disease severity, investigations, management, and information on neonates (birthweight, Apgar score, and perinatal complications). Among 348 women tested for SARS-CoV-2, 57 women (16.3%) were confirmed as positive based on quantitative reverse transcriptase polymerase chain reaction of the nasopharyngeal specimen. Most women (45; 78.9%) had a mild infection with favourable maternal-fetal outcomes. Three maternal deaths were associated with comorbidities. Five neonates tested positive for SARS-CoV-2, remained hemodynamically stable, and were subsequently discharged. A majority of pregnant women with COVID-19 had mild disease and recovered with good perinatal outcomes. Women with comorbidities may have an increased risk of severe morbidity and mortality. The cycle threshold signifying the viral load and degree of infectivity can modify management during pregnancy. Long-term outcomes and the potential mother-to-child vertical/horizontal transmission need further study.


Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial.
Existing guidelines for management of type 2 diabetes recommend a patient-centred approach to guide the choice of pharmacological agents. Although glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly used as second-line agents, direct comparisons between these treatments are insufficient. In the SUSTAIN 8 trial, we compared the efficacy and safety of semaglutide (a GLP-1 receptor agonist) with canagliflozin (an SGLT2 inhibitor) in patients with type 2 diabetes. This was a double-blind, parallel-group, phase 3b, randomised controlled trial done at 111 centres in 11 countries. Eligible patients were at least 18 years old and had uncontrolled type 2 diabetes (HbA1c 7·0-10·5% [53-91 mmol/mol]) on stable daily metformin therapy. Patients were randomly assigned (1:1) by use of an interactive web response system to subcutaneous semaglutide 1·0 mg once weekly or oral canagliflozin 300 mg once daily. The primary endpoint was change from baseline in HbA1c, and the confirmatory secondary endpoint was change from baseline in bodyweight, both at week 52. The primary analysis population included all randomly assigned patients, using on-treatment data collected before initiation of rescue medication. The safety analysis was done on a population that included all patients exposed to at least one dose of trial product. The trial was powered for HbA1c and bodyweight superiority under reasonable assumptions. This trial is registered with ClinicalTrials.gov, NCT03136484. Between March 15, 2017, and Nov 16, 2018, 788 patients were randomly assigned to semaglutide 1·0 mg (394 patients) or canagliflozin 300 mg (394 patients). 739 patients completed the trial (367 in the semaglutide group and 372 in the canagliflozin group). From overall baseline mean, patients receiving semaglutide had significantly greater reductions in HbA1c and bodyweight than those receiving canagliflozin (HbA1c estimated treatment difference [ETD] -0·49 percentage points, 95% CI -0·65 to -0·33; -5·34 mmol/mol, 95% CI -7·10 to -3·57; p<0·0001; and bodyweight ETD -1·06 kg, 95% CI -1·76 to -0·36; p=0·0029). Gastrointestinal disorders, most commonly nausea, were the most frequently reported adverse events with semaglutide, occurring in 184 (47%) of 392 patients; whereas infections and infestations (defined using the Medical Dictionary for Regulatory Activities, version 21.0), most commonly urinary tract infections, occurred more frequently with canagliflozin, in 136 (35%) of 394 patients. Premature treatment discontinuation because of adverse events occurred in 38 (10%) of 392 patients with semaglutide and in 20 (5%) of 394 patients with canagliflozin. One fatal adverse event confirmed unlikely to be caused by treatment occurred in the semaglutide group. Once-weekly semaglutide 1·0 mg was superior to daily canagliflozin 300 mg in reducing HbA1c and bodyweight in patients with type 2 diabetes uncontrolled on metformin therapy. These outcomes might guide treatment intensification choices. Novo Nordisk.


Detection of adverse drug events in e-prescribing and administrative health data: a validation study.
Administrative health data are increasingly used to detect adverse drug events (ADEs). However, the few studies evaluating diagnostic codes for ADE detection demonstrated low sensitivity, likely due to narrow code sets, physician under-recognition of ADEs, and underreporting in administrative data. The objective of this study was to determine if combining an expanded ICD code set in administrative data with e-prescribing data improves ADE detection. We conducted a prospective cohort study among patients newly prescribed antidepressant or antihypertensive medication in primary care and followed for 2 months. Gold standard ADEs were defined as patient-reported symptoms adjudicated as medication-related by a clinical expert. Potential ADEs in administrative data were defined as physician, ED, or hospital visits during follow-up for known adverse effects of the study medication, as identified by ICD codes. Potential ADEs in e-prescribing data were defined as study drug discontinuations or dose changes made during follow-up for safety or effectiveness reasons. Of 688 study participants, 445 (64.7%) were female and mean age was 64.2 (SD 13.9). The study drug for 386 (56.1%) patients was an antihypertensive, and for 302 (43.9%) an antidepressant. Using the gold standard definition, 114 (16.6%) patients experienced an ADE, with 40 (10.4%) among antihypertensive users and 74 (24.5%) among antidepressant users. The sensitivity of the expanded ICD code set was 7.0%, of e-prescribing data 9.7%, and of the two combined 14.0%. Specificities were high (86.0-95.0%). The sensitivity of the combined approach increased to 25.8% when analysis was restricted to the 27% of patients who indicated having reported symptoms to a physician. Combining an expanded diagnostic code set with e-prescribing data improves ADE detection. As few patients report symptoms to their physician, higher detection rates may be achieved by collecting patient-reported outcomes via emerging digital technologies such as patient portals and mHealth applications.


Antihistamine activity, central nervous system and cardiovascular profiles of histamine H1 antagonists: comparative studies with loratadine, terfenadine and sedating antihistamines in guinea-pigs.
Sedation limits the clinical utility of classical H1 antihistamines, while newer antihistamines such as loratadine and terfenadine are non-sedating. However, clinical use of the terfenadine has been associated with rare but severe cardiac arrhythmias, in particular torsades de pointes. To establish a quantitative experimental model for assessing the sedating and cardiotoxicity potential of non-sedating and sedating antihistamines. Drugs were administered intravenously and the integrated amplitude of the cortical electroencephalogram (EEG) signal was recorded. The threshold dose that depressed EEG activity was compared with the dose required to inhibit by 50% the peripheral bronchospasm elicited by 10 micrograms/kg i.v., of histamine. In separate studies, the electrocardiogram (ECG) and cardiovascular effects of loratadine (30 and 100 mg/kg, i.v.), terfenadine (10 mg/kg, i.v.), promethazine (5 mg/kg, i.v.) and diphenhydramine (20 mg/kg, i.v.) were evaluated. The sedating antihistamines, diphenhydramine and promethazine, depressed the integrated EEG at doses between 0.6 and 2.0 times their peripheral antihistamine doses. Loratadine had no EEG depressant activity at 100 mg/kg, i.v., a dose more than 170 times its ED50 (0.58 mg/kg, i.v.) against histamine bronchospasm. We were unable to evaluate the EEG effects of terfenadine, because it produced cardiovascular collapse at 10 mg/kg, i.v. Loratadine and promethazine did not produce adverse cardiovascular effects, nor did they alter normal ECG activity. Diphenhydramine produced bradycardia followed by a transient hypertensive phase without affecting the QTc interval. In contrast, terfenadine elicited hypotension, bradycardia and significant arrhythmogenic activity, causing a prolongation of the QTc interval and a torsades de pointes--like ventricular arrhythmia. Pharmacokinetic studies after i.v. administration of loratadine (30 and 100 mg/kg) demonstrated plasma levels of loratadine and its major metabolite descarboethoxyloratadine to be several orders of magnitude greater than levels found in humans at the clinical dose of 10 mg. The CNS depressant effects of H1 antihistamines are promethazine approximately diphenhydramine >> loratadine = placebo. Of the non-sedating antihistamines, loratadine was devoid of adverse cardiovascular effects whereas terfenadine caused a pronounced disruption of the normal ECG, characterized by a torsades de pointes-like effect.


GABA and dopamine act directly on melanotropes of Xenopus to inhibit MSH secretion.
The release of melanophore stimulating hormone (MSH) from the pars intermedia of the amphibian Xenopus laevis is regulated by multiple factors of hypothalamic origin. The aim of this study was to determine if potential secretagogues function through a direct action on the melanotrope cell. For this purpose an in vitro superfusion system containing isolated melanotropes (cell suspension) was utilized. The viability of the cells in suspension was tested by examining their ability to synthesize, process and release pro-opiomelanocortin (POMC) related peptides. All biosynthetic functions appeared normal, with the exception that the isolated melanotropes are unable to N-terminally acetylate MSH. Release of immunoreactive-MSH from these cells was shown to be Ca2+-dependent, and high K+ stimulated release. Both the neurotransmitters dopamine and gamma-aminobutyric acid (GABA), which are thought to be physiologically important MSH-release inhibiting factors, were shown to inhibit MSH release from isolated melanotropes. Dopamine appeared to function through a dopamine D2 type receptor mechanism while for GABA, both a GABAa and GABAb receptor mechanism are involved.


Radiographic measurements for the prediction of dysphagia after occipitocervical fusion: a systematic review.
Occipitocervical fusion (OCF) is a procedure performed for multiple upper cervical pathologies. A common postprocedural complication of OCF is dysphagia, which has been linked to the narrowing of the pharyngeal space due to fixation in a hyper-flexed angle. Postoperative dysphagia is linked to reduced quality of life, prolonged hospital stay, aspiration pneumonia, and increased mortality. This has led to investigations of the association between sagittal radiographic angles and dysphagia following OCF. A systematic review of the literature was performed to explore the current evidence regarding cervical sagittal radiographic measurements and dysphagia following OCF. A search strategy was carried out using the PubMed, Embase, and Web of Science databases from their dates of inception until August 2022. Only original English-language studies were considered. Moreover, studies had to include the correlation between dysphagia and at least one radiographic measurement in the sagittal plane. The search and subsequent selection process yielded eight studies that were included in the final review, totaling 329 patients in whom dysphagia had been assessed and graded. The dysphagia score by Bazaz et al. (Spine 27, 22:2453-2458, 2002) was used most often. The pooled incidence of dysphagia, in the early postoperative period, was estimated at 26.4%. At long-term follow-up (range: 17-72 months), about one-third of patients experienced resolution of symptoms, which resulted in a long-term post-OCF dysphagia incidence of 16.5%. Across the studies included, six different radiographic parameters were used to derive several measures which were repeatedly and significantly associated with the occurrence of dysphagia. The high incidence of postoperative dysphagia following OCF warrants close monitoring of patients, especially in the short-term postoperative period. These patients may be assessed through standardized tools where the one by Bazaz et al. was the most commonly used. Moreover, there are several radiographic measurements that can be used to predict the occurrence of dysphagia. These findings may serve as a basis for strategies to prevent the occurrence of dysphagia after OCF.


Prognostic impact of percutaneous coronary intervention in octogenarians with non-ST elevation myocardial infarction: A report from SWEDEHEART.
Percutaneous coronary intervention (PCI) improves outcomes in non-ST elevation acute coronary syndromes (NSTE-ACSs). Octogenarians, however, were underrepresented in the pivotal trials. This study aimed to assess the effect of PCI in patients ≥80 years old. We used data from the SWEDEHEART registry for all hospital admissions at eight cardiac care centres within Västra Götaland County. Consecutive patients ≥80 years old admitted for NSTE-ACS between January 2000 and December 2011 were included. We performed instrumental variable analysis with propensity score. The primary endpoint was all-cause mortality at 30 days and one year after index hospitalization. During the study period 5200 patients fulfilled the inclusion criteria. In total, 586 (11.2%) patients underwent PCI, the remaining 4613 patients were treated conservatively. Total mortality at 30 days was 19.4% (1007 events) and 39.4% (1876 events) at one year. Thirty-day mortality was 20.7% in conservatively treated patients and 8.5% in the PCI group (adjusted odds ratio 0.34; 95% confidence interval 0.12-0.97, p = 0.044). One-year mortality was 42.1% in the conservatively treated group and 16.3% in the PCI group (adjusted odds ratio 0.97; 95% confidence interval 0.36-2.51, p = 0.847). PCI in octogenarians with NSTE-ACS was associated with a lower risk of mortality at 30 days. However, this survival benefit was not sustained during the entire study-period of one-year.


Insulin stimulates Akt translocation to mitochondria: implications on dysregulation of mitochondrial oxidative phosphorylation in diabetic myocardium.
Mitochondrial oxidative phosphorylation is the major source of energy in cardiac muscle. In the streptozotocin-induced diabetic (STZ-DM) mice, myocardial oxidative phosphorylation was perturbated and oxidative phosphorylation complex V (ATP synthase) activity was significantly reduced. To determine the independent effects of hyperglycemia and insulin deficiency on the changes of myocardial complex V, we used phlorizin (Ph) to normalize blood glucose in the diabetic mice. Ph treatment did not improve myocardial complex V activity in the STZ-DM mice, whereas insulin treatment normalized myocardial complex V activity in the diabetic mice. Therefore, the reduction of complex V activity was caused by insulin deficiency and not by hyperglycemia in STZ-DM myocardium. Acute insulin stimulation induced phosphorylation of Akt and translocation of Akt to mitochondria in myocardium. Translocation of phospho-Akt to mitochondria was enhanced in the STZ-DM mice and was blunted in the diet-induced diabetic mice. In parallel, insulin activation of complex V was enhanced in the STZ-DM myocardium and suppressed in the diet-induced diabetic myocardium. In vivo inhibition of Akt blocked insulin stimulation of phospho-Akt translocation and blunted activation of complex V. Insulin-activated Akt translocation to mitochondria in cardiac muscle is a novel paradigm that may have important implications on myocardial bioenergetics.


Peculiarities and systematics of microbial diglycosidases, and their applications in food technology.
Diglycosidases are endo-β-glucosidases that hydrolyze the heterosidic linkage of diglycoconjugates, thereby releasing in a single reaction the disaccharide and the aglycone. Plant diglycosidases belong to the glycoside hydrolase family 1 and are associated with defense mechanisms. Microbial diglycosidases exhibit higher diversity-they belong to the families 3, 5, and 55-and play a catabolic role. As diglycoconjugates are widespread in the environments, so are the microbial diglycosidases, which allow their utilization as nutritional source and carbon recycling. In the last 10 years, six microbial diglycosidases have been sequenced, and for two of them, the three-dimensional structure has been elucidated. This knowledge allowed the identification of their diverse phylogenetic origin, and gave insights into the understanding of the substrate specificity. Here, the last advances and the applications of microbial diglycosidases are reviewed. KEY POINTS: • Substrate specificity and phylogenetic relationships of diglycosidases are reviewed. • On-going and potential applications of diglycosidases are discussed.


The ultrastructure of the normal human thymus: a study of 36 cases.
Electron microscopy of the normal human thymus demonstrates a supporting framework of epithelial-reticular cells with long branchticular cell processes lie lymphocytes, macrophages, and rare myoid cells. Both small and large lymphocytes are evident. No desmosomes are observed between the lymphocytes and the epithelial-reticular cells. Macrophages are most numerous in the cort(x were they often contain phagocytized nuclear debris. The possible functional significance of the above-described fine structural features is discussed.


Critical Decisions in 22 Years of Outpatient Laparoscopy
More than 2400 single-incision outpatient laparoscopic operations for sterilization or diagnosis performed by the author over the past 22 years have been influenced by seven critical decisions which were made after reviewing all of the options: 1. Perform procedures on all cooperative patients in free-standing facilities, except in cases with serious medical disorders which require elaborate safeguards and the presence of an anesthesiologist. 2. Administer local anesthesia in all cases. 3. Use the Hasson cannula with blunt obturator for open abdominal entry in every case. 4. Abandon tubal coagulation for sterilization. Instead, perform mechanical tubal occlusion with the Hulka-Lexan Clip. 5. Instill low-volume filtered room air for pneumoperitoneum in place of nitrous oxide. 6. Enter the abdomen through the umbilical fossa in all obese women instead of through the lower rim of the umbilicus. 7. As preliminary steps in abdominal entry in every patient, perforate the partially incised fascia and the parietal peritoneum with a small Kelly clamp or hemostat instead of a scalpel. Each of these seven decisions has, in the author's opinion, improved the technique and safety of outpatient laparoscopy.


How to evaluate scar colour after burn injuries - A clinical comparison of the Mexameter® and the subjective scar assessment (POSAS/VSS).
Scarring after burn injuries remains one of the major challenges in burn medicine and is the subject of current research. Accurate and high-quality assessment of scars is needed to enable exact outcome evaluation of different treatments. Our aim was to evaluate the most common subjective scar evaluation scores-the POSAS (Patient and Observer Scar Assessment Scale) and VSS (Vancouver Scar Scale)-in comparison with the objective device Mexameter® for colour evaluation. A prospective monocentre study was performed, which included 120 examined scar areas of 60 patients with third degree burns who had received skin grafts between 1975 and 2018 with a total burned surface area (TBSA) > 2%. Two different scar areas in comparison with one healthy skin area concerning 'colour', 'pigmentation', and 'vascularization' were evaluated by the Mexameter® MX 18, the OSAS, and the VSS by the same examiner, as well as the PSAS by the patient. The mean TBSA of the 60 patients was 24.3%. In the OSAS, 61% of the scars were evaluated as 'hyper-', 19% as 'hypo-', and 19% as 'mix-pigmented'. Furthermore, 65% of the scars were estimated as highly vascularized. In the Mexameter®, the melanin index values of the scar areas compared to the healthy skin areas showed a small difference of 12 (p < 0.05). The mean difference of erythema between the scar and the healthy skin areas was 84 (p < 0.001). For the Mexameter®, moderate correlations were found when comparing 'erythema' with the OSAS category 'vascularization' (r = 0.33, p < 0.05) and 'melanin' with the OSAS parameter 'pigmentation' (r = 0.28, p < 0.05). When comparing the Mexameter® measurements to the OSAS questionnaire, 27% of the scars were wrongly evaluated as 'hyperpigmented' by the observer and 21% as 'hypervascularized', while showing low measurements in the device. Additionally, a novel Mexameter® ordinal scare scale was calculated. In this study, we were able to show on a relatively large patient population that with the Mexameter®, the subjectivity of the scar colour assessment by examiner/patient can be overcome, but precise differentiation can still be ensured with subjective evaluation tools. We further introduced a novel Mexameter® Scar Scale. It is necessary to further investigate the vast range of objective devices and develop scar panels for with an incorporation of objective and subjective devices to further improve reliability with reduced bias in terms of scar assessment.


The prevalence of anxiety symptoms and depressive symptoms in patients with somatic disorders in urban China: a multi-center cross-sectional study.
To assess the prevalence of anxiety and depressive symptoms among patients with somatic diseases in urban China. A hospital-based cross-sectional study was carried out in four major cities of China from June to August in 2004. There were 2111 eligible subjects with Stroke, Parkinson's Disease, Epilepsy, Irritable Bowel Syndrome, Functional Dyspepsia, and Menopausal Syndrome, and 317 Post-natal women were recruited from general hospitals. Self-completed hospital anxiety and depression scale (HAD) questionnaire was used for screening anxiety and/or depressive symptoms. Subjects with a HAD score of > = 9 were further assessed with Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) by certified psychologists or psychiatrists. The prevalence of "screened" depressive and anxiety symptoms using HAD were 11-19% and 11-22% respectively in patients with above somatic diseases and post-natal women. Assessed by HAMA/HAMD scale, the prevalence of "definite" depressive symptoms was 30%-59% in subjects with "screened" depressive symptoms, and 44%-84% in subjects with "screened" anxiety symptoms. About half of the subjects had co-morbidity depressive and anxiety symptoms. Less than one-fourth of these subjects had ever been diagnosed as depressive/anxiety disorders and been treated prior to the investigation. There is a high prevalence and low diagnosis and treatment rate of depressive and anxiety symptoms in patients with these somatic diseases in China.


Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients.
Hypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance) could be a common root for RHTN (resistant hypertension) or RHTN plus type 2 diabetes (T2D) comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D), and its relationship with serum adiponectin concentration. Twenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years) were evaluated using the following parameters: BMI (body mass index), biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV) in time and frequency domains stratified into three periods: 24 hour, day time and night time. Both groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone) and night periods (sympathetic > parasympathetic tone). T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m² - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04), lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04) and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r = 0.37 [95% CI -0.04 - 1.00] p = 0.03), negatively with HbA1c levels (r = -0.58 [95% CI -1.00 - -0.3] p = 0.00) and also adiponectin correlated negatively with HbA1c levels (r = -0.40 [95% CI -1.00 - -0.07] p = 0.02). Type 2 diabetes comorbidity is associated with greater autonomic imbalance, lower adiponectin levels and greater BMI in RHTN patients. Similar circadian disruption was also found in both groups indicating the importance of lifestyle behavior in the genesis of RHTN.


Research and development of drug delivery systems based on drug transporter and nano-formulation.
In recent years, the continuous occurrence of multi-drug resistance in the clinic has made people pay more attention to the transporter. Changes in the expression and activity of transporters can cause corresponding changes in drug pharmacokinetics and pharmacodynamics. The drug-drug interactions (DDI) caused by transporters can seriously affect drug effectiveness and toxicity. In the development of pharmaceutical preparations, people have increasingly concerned about the effects and regulation of transporters in drug effects. To improve the targeting and physicochemical properties of drugs, the development of targeted agents is very rapid. Among them, novel nano-formulations are the best. With the continuous innovation and development of nano-formulation, its application has become more and more extensive. Nano-formulation has exerted certain advantages in the drug development based on transporters, and is also involved in the combination of targeted transporters. This review focuses on the application of novel nano-agents targeting transporters and the introduction of drug-transporter-based nano-formulations.


Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by exposure to high-density 50-Hz magnetic fields.
Exposure to extremely low frequency magnetic field (ELFMF) of 50 Hz and 400 mT induced mutations in the hypoxanthine-guanine phosphoribosyl transferase gene of human melanoma MeWo cells. The mutant frequency was enhanced both by increasing the exposure period and the induced current intensity. Mutations induced by X-rays were enhanced by ELFMF exposure. No significant increase in mutant frequency occurred when DNA replication was inhibited during ELFMF exposure. DNA replication error is suspected of causing the mutations produced by ELFMF exposure.


Matrix vesicles in newly synthesizing bone observed after ultracryotomy and ultramicroincineration.
Matrix vesicles were observed in femurs of 8-day-old chick embryos prepared by ultracryotomy. Some of the sections were subjected to ultramicroincineration. The unfixed tissues never came into contact with solutions, and thereby artifacts due to dissolution, redistribution, or rearrangement of the mineral constituents were avoided. In the osteoid, electron dense objects with the size and appearance of matrix vesicles were seen, although limiting membranes were not visible. After ultramicroincineration the vesicles were observed to contain small crystals and a less dense amorphous mineral material which may te the precursor of bone mineral. In addition, a ring of ash enclosed the crystalline and amorphous mineral and appeared to occupy the position of the vesicle membrane as seen in conventionally prepared material.


For the Birds: Radiology Parallels, Finding Wellness, and Lessons Learned in Birding.
The popularity of birding has grown substantially during the COVID-19 pandemic. As an activity that can be performed year-round with social distancing in virtually any location, birding shares a striking resemblance to the practice of radiology - so much so that we feel it represents a unique wellness activity that may greatly appeal to radiologists. In this paper, we describe commonalities between birding and radiology, hopefully inspiring readers to get outdoors and commune with nature in this restorative wellness activity.


Non-penetrating deep sclerectomy without or with autologous scleral implant in open-angle glaucoma: medium-term results.
This study compares the medium-term success rate and complications of non-penetrating deep sclerectomy (NPDS) without and with autologous scleral implant in open-angle glaucoma. Retrospective review of 93 eyes of 93 patients with medically uncontrolled open-angle glaucoma who underwent NPDS without (n=69, group 1) or with (n=24, group 2) autologous scleral implant. The mean follow-up was 16 months (range 5-36) in group 1 and 15 months (range 4-28) in group 2. The mean intra-ocular pressures (IOP) pre- and postoperatively were, respectively, 23.8 and 16.1 mmHg in group 1, and 25.6 and 15.8 mmHg in group 2. The absolute success rate was 41% in group 1 and 54% in group 2. The qualitative success rate was 83% in group 1 and 75% in group 2. An IOP lower than 16 mmHg was obtained in 51% of patients in group 1 and 58% of patients in group 2. A Nd:YAG laser goniopuncture was performed in 30% of patients in group 1 and 50% of patients in group 2, and resulted in a better controlled IOP. NPDS without or with an autologous scleral implant is a safe procedure reducing the IOP significantly, but probably not sufficient when an IOP below 16 mmHg is required. We found no statistically significant difference between the two groups.


Erratum: Jiang, J.; et al. Expeditious Synthesis of Dianionic-Headed 4-Sulfoalkanoic Acid Surfactants. Molecules 2017, 22, 640.
The authors wish to make the following change to their paper [1]. [...].


Feasibility of interactive voice response methods in health behavior research with immigrant Latinos.
Determine the feasibility of using interactive voice response (IVR) for conducting daily diary research with immigrant Latinos. Baseline data containing demographic, health, and job-related characteristics were obtained from immigrant Latino construction workers (N=119). Participants also completed an IVR-based daily diary for 21 consecutive days. Over one third (37%) of the sample adhered to the 21-day protocol; a comparable percent-age (38.7%) initiated but did not adhere to the protocol; and 24% never began the diary protocol. Adherence was generally not predicted by demographic, health, or job-related characteristics. IVR technology makes diary studies with Latino samples feasible.


The influence of medium formulation on phosphomonoester and UDP-hexose levels in cultured human colon tumor cells as observed by 31P NMR spectroscopy.
High-resolution 31P NMR spectroscopy at 11.7 T was used to examine the influence of medium formulation (medium and serum type, and concentrations of glucose and inositol) on the cellular phosphate metabolism of CX-1 cells, a human colon cancer cell line derived from HT-29 cells. Striking differences in the 31P spectra of harvested CX-1 cells were observed. The largest variation was seen in the phosphocholine and UDP-hexose levels (up to seven-fold changes), with smaller differences in the levels of other phosphate metabolites. The major UDP-hexose species were found to be UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine (ca 2:1 ratio), which have been proposed in the literature to be markers of cell differentiation status. Medium-induced alterations in metabolite levels were much greater than the normal variations seen in CX-1 control samples grown under identical conditions. They even exceeded the characteristic differences observed between different human tumor cell lines grown under one set of culture conditions. The remarkable sensitivity of CX-1 cellular phosphate metabolism to the culture environment has implications for the comparison of in vitro vs in vivo spectra, and for the interpretation of effects due to growth and therapy.


Detection and characterization of volatile organic compounds from burned human and animal remains in fire debris.
Debris collected from various test sites where mammalian remains (human and porcine) had been burned in a variety of full-scale fire scenarios was evaluated for the presence of volatile residues that could be characteristic of those remains. Levels of volatiles were measured using the method commonly used for fire debris analysis: gas chromatography-mass spectrometry. Homologous n-aldehydes (from n-pentanal to n-nonanal) proved to be a significant indicator of the presence of burned animal tissue as they were observed in nearly all of the samples. Such aldehydes are created by the combustion of animal fats. One aldehyde, n-hexanal, appeared more frequently than the other aldehydes, n-pentanal, n-heptanal, n-octanal, and n-nonanal. Ethanol was detected in two-thirds of the samples, while acetone appeared in about three-fourths of the samples, but both were detected at much lower concentrations than n-hexanal. These appear to have been combustion products of the substrates on which each body burned, rather than originating from the combustion of the body. There appeared to be no qualitative distinction between volatile products produced from burned porcine carcasses and those from human cadavers. Since a homologous series of C5-C9n-aldehydes is not produced as a dominant species by the pyrolysis or combustion of any normally encountered substrate (carpet, bedding, wood products or upholstery), their detection by normal fire debris methods appears to be a valid indicator of the presence of burned animal remains. These data will also provide guidance to fire debris analysts as to the nature of volatiles associated with the combustion of human bodies in real-world fires.


Resolution of enzyme bands of Plasmodium knowlesi as a function of substrate concentration.
An extra band of isoenzyme lactate dehydrogenase (LDH) was obtained in case of Plasmodium knowlesi free parasite as compared to normal monkey blood. This extra band could be resolved due to the decreasing amount of substrate concentration. Agarose electrophoresis technique was used to separate the isoenzyme bands.