Inosine biosynthesis in transfer RNA: a postulated role in immune regulation.
A hypothesis is put forth describing a role in immune regulation for inosine biosynthesis in the anticodon of tRNA. The enzymatic insertion of hypoxanthine into the tRNA wobble base position is predicted to be a control point for the translation of proteins and peptides required for normal immune function. The substrate for inosine biosynthesis in tRNA, hypoxanthine, is an intermediate in the purine catabolic pathway, and defects in this pathway are associated with inherited immunodeficiency diseases. Therefore, a role for aberrant inosine biosynthesis in tRNA is postulated in causing the immunodeficient conditions, and it may be a relevant molecular defect in leukemia as well.


A computer program for multivariate ratio analysis (MISCAT).
Analysts must deal frequently with missing data in multivariate analysis. In such cases, estimating the covariance maxtrix V of the dependent variables usually involves initial estimation and iterative adjustment of imputed missing data values, and/or smoothing of an estimate V which is not necessarily positive semi-definite. This paper presents an alternative procedure for computing estimates of relevant multivariate parameters in situations where missing data occur at random and with small probability. MISCAT is a computer program which computes multivariate ratio estimates of the means and a corresponding positive semi-definite estimate of the covariance matrix. It is an extension of GENCAT, which is a program for the generalizaed least squares analysis of categorical data. Thus, one advantage of dealing with missing data in this manner is that variation among the ratio estimates may be conveniently analyzed within MISCAT using asymptotic regression methodology, provided that sample sizes are sufficiently large. An example is given to illustrate such analysis for longitudinal data from a multicenter clinical trial.


Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species.
1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis.


Anti-OX40L alone or in combination with anti-CD40L and CTLA4Ig does not inhibit the humoral and cellular response to a major grass pollen allergen.
IgE-mediated allergy is a common disease characterized by a harmful immune response towards otherwise harmless environmental antigens. Induction of specific immunological non-responsiveness towards allergens would be a desirable goal. Blockade of costimulatory pathways is a promising strategy to modulate the immune response in an antigen-specific manner. Recently, OX40 (CD134) was identified as a costimulatory receptor important in Th2-mediated immune responses. Moreover, synergy between OX40 blockade and 'conventional' costimulation blockade (anti-CD40L, CTLA4Ig) was observed in models of alloimmunity. We investigated the potential of interfering with OX40 alone or in combination with CD40/CD28 signals to influence the allergic immune response. The OX40 pathway was investigated in an established murine model of IgE-mediated allergy where BALB/c mice are repeatedly immunized with the clinically relevant grass pollen allergen Phl p 5. Groups were treated with combinations of anti-OX40L, CTLA4Ig and anti-CD40L. In selected mice, Tregs were depleted with anti-CD25. Blockade of OX40L alone at the time of first or second immunization did not modulate the allergic response on the humoral or effector cell levels but slightly on T cell responses. Administration of a combination of anti-CD40L/CTLA4Ig delayed the allergic immune response, but antibody production could not be inhibited after repeated immunization even though the allergen-specific T cell response was suppressed in the long run. Notably, additional blockade of OX40L had no detectable supplementary effect. Immunomodulation partly involved regulatory T cells as depletion of CD25(+) cells led to restored T cell proliferation. Collectively, our data provide evidence that the allergic immune response towards Phl p 5 is independent of OX40L, although reduction on T cell responses and slightly on the asthmatic phenotype was detectable. Besides, no relevant synergistic effect of OX40L blockade in addition to CD40L/CD28 blockade could be detected. Thus, the therapeutic potential of OX40L blockade for IgE-mediated allergy appears to be ineffective in this setting.


Development of the retina.
As in other vertebrate species, the zebrafish retina is simpler than other regions of the central nervous system. This relative simplicity along with rapid development, and accessibility to genetic analysis make the zebrafish retina an excellent model system for studies of neurogenesis in the vertebrate CNS. Several genetic screens have led to the isolation of an impressive collection of mutants affecting the retina and the retinotectal projections in zebrafish. A variety of techniques and markers are available to study the isolated mutants. These include several antigen- and transcript-detection methods, retrograde and anterograde labeling of neurons, blastomere transplantations, H3 labeling, and others. As past genetic screens have achieved a rather low level of saturation, the current collection of mutants can only grow in the future. Morphological and behavioral criteria have been successfully applied in zebrafish to search for defects in spinal development. In future genetic screens, progressively more sophisticated screening approaches will make it possible to detect very subtle changes in the retinal development. The remarkable evolutionary conservation of the vertebrate eye provides the basis for using the zebrafish as a model system for the detection and analysis of genetic defects potentially related to human eye disorders. Some of the genetic defects of the zebrafish retina indeed resemble human retinopathies. As the genetic analysis of the vertebrate visual system is far from being complete and new techniques are being introduced at a rapid pace, the zebrafish embryo will become increasingly useful as a model for studies of the vertebrate retina.


Determinant-specific regulation of T helper cell responses to murine lambda light chains by both H-2 and non-H-2 genes.
Previous work has revealed that the T helper cell (Th) responses to an antigenic determinant of V lambda 2(315) (called lambda 2.1) is regulated by both H-2 and non-H-2 genes. In the present study this was confirmed and extended to two other determinants, one shared between free lambda 2(315) and lambda 1(J558) (called lambda 2.2) and one unique for free lambda 1(J558) (called lambda 1.1). H-2 genes regulate the responses to the latter determinants, because BALB.B (H-2b) mice were low responders and BALB/c (H-2d) mice were high responders. Thus, the H-2d haplotype on BALB/c background was associated with high responder status. However, when the H-2d haplotype was examined on other genetic backgrounds than BALB/c, the animals could be classified as either intermediate or low responders, depending upon the non-H-2 background. This demonstrated that non-H-2 genes also influenced Th responses. Furthermore, C3H-H-2o, DBA/2 and B10.D2 mice (all H-2d) responded to only one (lambda 2.1) but not the other (lambda 2.2) of two determinants physically linked on the same polypeptide chain (lambda 2(315)). This indicated that the non-H-2 gene effect is capable of fine discrimination, i.e. the non-H-2 gene-mediated low responder phenotype may at least in part be due to failure of recognition of certain antigenic sites, like the H-2-linked Ir-gene defect. F1 hybrids responded to the same determinants as their parental strains; e.g., the BALB/c non-H-2 background exerted a dominant influence over the low responder background of C3H, B10 and DBA/2 strains.


Beyond amyloid: a diverse portfolio of novel drug discovery programs for Alzheimer's disease and related dementias.
Although the molecular mechanisms underlying the pathogenesis of Alzheimer's disease and other related neurodegenerative diseases remain unclear, accumulation of misfolded proteins, neuroinflammation, mitochondrial dysfunction and perturbed calcium homeostasis have been identified as key events leading to neuronal loss during neurodegeneration. Evidence for 'druggable' targets for each of these key mechanisms was presented by the Alzheimer's Drug Discovery Foundation-funded investigators at the 12th International Conference on Alzheimer's Drug Discovery, Jersey City, NJ, 26-27 September 2011 http://www.worldeventsforum.com/addf/addrugdiscovery.


Arthroscopic reconstruction of triangular fibrocartilage complex (TFCC) with tendon graft for chronic DRUJ instability.
To report the 10-years' experience of a novel arthroscopic assisted anatomical TFCC reconstruction in treatment of chronic DRUJ instability resulting from irreparable TFCC injuries. 15 patients (7 males, 8 females) with mean age of 37 (17-49) suffering from irreparable TFCC injuries received arthroscopic assisted reconstruction using palmaris longus graft. Three skin incisions were made with creation of one radial and one ulna tunnel for passage of graft following the path of dorsal and palmar radio-ulnar ligaments under fluoroscopic and arthroscopic guidance. The joint capsule was kept intact. Early mid-range forearm rotation was started since 4th week postoperatively. The mean follow-up was 85.53 months (32-138). Mayo wrist score improved from 62.5 to 88 (p<0.05). Comparing contralateral side, total prono-supination range increased from 76.6% to 92.1% and grip strength increased from 56.1% to 76.9%. Twelve patients resumed previous jobs. No evidence of DRUJ arthritis was noticed. Complications included 2 late graft ruptures and one unexplained dystonia. Our arthroscopic assisted approach on TFCC reconstruction is safe, produces comparable results as the standard technique and may achieve better range of motion with less soft tissue dissection and earlier mobilization.


The association between restless legs syndrome and premotor symptoms of Parkinson's disease.
Previous studies regarding the association between restless legs syndrome (RLS) and Parkinson's disease (PD) have produced contradictory results. However, the time frame between them has varied across these studies, and also, the longitudinal trajectroy of RLS symptoms has not been considered. To investigate if transient or continuous/recurrent RLS identified by questionnaire are associated with the premotor symptoms of PD. The study population comprised 16,636 men in the Health Professional Follow-Up Study, who answered questions regarding RLS symptoms in both 2002 and 2008, and were not diagnosed with PD. Outcomes were self-reported constipation, possible REM sleep behavior disorder (pRBD) in 2012 and smell identification test score in 2014. RLS was associated with increased odds of constipation, but only continuous/recurrent RLS status was associated with higher odds of having pRBD. RLS was not significantly associated with olfactory scores. In this large-scale longitudinal study, we found moderate associations between the presence of RLS and increased odds of having constipation and pRBD.


Prevalence of co-morbidities and their association with mortality in patients with COVID-19: A systematic review and meta-analysis.
To estimate the prevalence of both cardiometabolic and other co-morbidities in patients with COVID-19, and to estimate the increased risk of severity of disease and mortality in people with co-morbidities. Medline, Scopus and the World Health Organization website were searched for global research on COVID-19 conducted from January 2019 up to 23 April 2020. Study inclusion was restricted to English language publications, original articles that reported the prevalence of co-morbidities in individuals with COVID-19, and case series including more than 10 patients. Eighteen studies were selected for inclusion. Data were analysed using random effects meta-analysis models. Eighteen studies with a total of 14 558 individuals were identified. The pooled prevalence for co-morbidities in patients with COVID-19 disease was 22.9% (95% CI: 15.8 to 29.9) for hypertension, 11.5% (9.7 to 13.4) for diabetes, and 9.7% (6.8 to 12.6) for cardiovascular disease (CVD). For chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cerebrovascular disease and cancer, the pooled prevalences were all less than 4%. With the exception of cerebrovascular disease, all the other co-morbidities presented a significantly increased risk for having severe COVID-19. In addition, the risk of mortality was significantly increased in individuals with CVD, COPD, CKD, cerebrovascular disease and cancer. In individuals with COVID-19, the presence of co-morbidities (both cardiometabolic and other) is associated with a higher risk of severe COVID-19 and mortality. These findings have important implications for public health with regard to risk stratification and future planning.


Born of animal magnetism: 150 years of psycho-physiology.
The historical beginnings of the scientific discipline of psychophysiology are traced back to the first published English definition by Dr. Samuel Adams, M.D.


A domain responsible for the transformation suppressor activity in Krev-1 protein.
Krev-1 cDNA encodes a ras-related protein and exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when introduced into a v-K-ras-transformed mouse NIH3T3 cell line, DT. To explore the functional organization of Krev-1 protein, we constructed a series of chimeric genes consisting of fragments of H-ras and Krev-1 cDNAs, and tested their biological activities in DT cells. The results indicated that the determinant for the transformation suppressor activity resides in the N-terminal one-third of the Krev-1 encoded polypeptide within which a highly conserved, putative effector-binding domain is present.


Changes in liver histology as a "surrogate" end point of antiviral therapy for chronic HBV can predict progression to liver complications.
The modified histology activity index (HAI) score has been extensively used as an additional primary or secondary end point in most phase III pivotal therapeutic clinical trials on chronic hepatitis B. Improvement in modified HAI after antiviral therapy has usually been defined as a 2-point reduction in modified HAI score. We studied whether a 2-point change in modified HAI score after antiviral therapy for chronic hepatitis B is associated with progression to liver complications (decompensated cirrhosis or hepatocellular carcinoma). Eighty-nine patients treated with interferon-alpha with liver biopsy before and at 6 to 12 months after the end of therapy were followed-up for a median 119.4 months. At the time of analysis, 11 patients (12.4%) had liver complications. Liver complications were higher in patients with a 2-point increase in modified HAI score [8 of 19 patients (42.1%) vs. 3 of 70 patients (4.3%), P=0.0002] and in those with severe fibrosis at end of therapy [6 of 19 patients (31.6%) vs. 5 of 70 patients (7.1%), P=0.010]. On Cox regression analysis, a 2-point increase in modified HAI score was associated with increased liver complications (relative risk 5.564, P=0.036). A 2-point increase in modified HAI score after antiviral therapy is associated with increased progression to liver complications.


Genome-wide identification and expression pattern profiling of the ATP-binding cassette gene family in tea plant (Camelliasinensis).
The ATP-binding cassette (ABC) gene family is one of the largest and oldest protein families, consisting of ATP-driven transporters facilitating substrate transportation across cell membranes. However, little is known about the evolution and biological function of the ABC gene family in tea plants. In this study, we performed a genome-wide identification and expression analysis of genes encoding ABC transporter proteins in Camellia sinensis. Our analysis of 170 ABC genes revealed that CsABCs were unevenly distributed across 15 chromosomes, with an amino acid length ranging from 188 to 2489 aa, molecular weight ranging from 20.29 to 277.34 kDa, and an isoelectric point ranging from 4.89 to 10.63. Phylogenetic analysis showed that CsABCs were divided into eight subfamilies, among which the ABCG subfamily was the most abundant. Furthermore, the subcellular localization of CsABCs indicated that they were present in various organelles. Collinearity analysis between the tea plant and Arabidopsis thaliana genomes revealed that the CsABC genes were homologous to the AtABC genes. Large gene fragment duplication analysis identified ten gene pairs as tandem repeats, and interaction network analysis demonstrated that CsABCs interacted with various types of target genes, with protein interactions also occurring within the family. Tissue expression analysis indicated that CsABCs were highly expressed in roots, stems, and leaves and were easily induced by drought and cold stress. Moreover, qRT-PCR analysis of the relative expression level of the gene under drought and cold stress correlated with the sequencing results. Identifying ABC genes in tea plants lays a foundation for the classification and functional analysis of ABC family genes, which can facilitate molecular breeding and the development of new tea varieties.


Polypharmacy at discharge in older hospitalised patients in Vietnam and its association with frailty.
To investigate the prevalence of polypharmacy and the common drugs prescribed at discharge in frail and non-frail older inpatients, and to examine whether frailty is significantly associated with polypharmacy. Cross-sectional analysis from data of a study about the prevalence of frailty in older inpatients in Vietnam in 2015. Polypharmacy was defined as using ≥5 medications. Frailty was defined by Fried's frailty criteria. There were 382 participants, mean age 76.4, 56.5% female and 35.9% frail. At discharge, 59.2% had polypharmacy (62.8% in the frail and 57.1% in the non-frail). Vitamin/supplements were the most common drugs prescribed, followed by antiplatelets. Frailty was not significantly associated with polypharmacy (adjusted OR 1.45, 95% CI 0.89-2.34). The prevalence of polypharmacy at discharge was high in both frail and non-frail participants. The association between frailty and polypharmacy needs to be investigated further in multicentre studies with larger sample sizes in Vietnam.


Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene.
KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance.


Epilepsy: A bibliometric analysis (1968-2020) of the Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suarez" in Mexico.
The Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez" (INNN) is one of the main institutions in Latin America treating epilepsy; and bibliometric analysis has an increasing role in analyzing the literature, acting as a Google Maps of medical research. We tracked the scientific output in Scopus and the impact of the institution from its foundation to July 2020 in the field of epilepsy. We roughly separated this group by clinical and experimental approach, identifying core journals, type of article, increase with time, and number of citations. A total of 228 papers, from a total of 3,034 produced by the INNN in that period, were found. Additionally, we identified that neurocysticercosis, pharmacology, genetics, and proteins involved in epilepsy were the most investigated topics. Also, there is a sustained growth in the number of papers per year since 1985. The number of authors per paper ranges from one to 15, and neuroscience journals are the preferred target of researchers, with a predilection for "Epilepsy and Behavior".


The role of seed depth, litter, and fire in the seedling establishment of amphicarpic peanutgrass (Amphicarpum purshii).
Amphicarpum purshii is an annual grass which mostly grows in disturbed areas of the New Jersey Pine Barrens, USA. It is amphicarpic, producing spikelets (and seeds) both above and below the soil surface. Previous research has shown that subterranean seed production ensures reproduction in the event of a major disturbance such as fire and results in rapid post-burn colonization of these sandy habitats. The effects of fire, litter, and seed depth were further examined by planting subterranean seeds at four depths in 16 litter-covered flats buried at ground level and comparing plants arising from burned flats with those in undisturbed litter-covered flats. At 0 and 1 cm depth, rates of seedling emergence were lowest in burned flats. Surface-sown seeds produced seedlings more likely to desiccate. Sowing depth had a greater influence on most measured characters than burning treatments. The mean depth of subterranean seed placement by Amphicarpum is 3.5 cm and this coincides with the seed depth from which plants showed the greatest height growth, shoot biomass, and reproductive output. In a second experiment, subterranean seeds on the bare soil surface in clay pots were more likely to lose viability and less likely to germinate than seeds protected by litter or burial in soil. In addition to providing protection from fire, placement of seeds below ground in the sandy habitat of peanutgrass provides conditions more suitable for seed survival and subsequent seedling establishment.


Diazepam inhibition of phorbol ester tumor promotion.
Diazepam (Valium) had previously been shown to enhance the growth rate of some transplantable tumors although studies in other systems have suggested an inhibitory effect. Skin tumor promotion studies were therefore carried out to determine the effect of diazepam on 12-O-tetradecanoyl phorbol-13-acetate (TPA) promotion in SENCAR mice. A sex-independent dose response inhibition occurred over a dose range of 100 g to 5 mg, both in number of papillomas and percent of mice bearing tumors. Furthermore, a dose-response reduction in tumor size was observed. By itself, diazepam had no tumor promoting activity.


Investigation of the usefulness of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function.
Military operation personnel often suffer from sleep difficulty because of their work requirements. In this study, we investigated the efficacy of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function; we subsequently established the optimal dosage regimen for military operation personnel. Twenty-two healthy young male volunteers were recruited for the study. Eight subjects took 10 mg or 15 mg of zaleplon and placebo alternately and then were exposed to noise. Changes in polysomnography (PSG) indices, including sleep latency (SL), sleep efficiency (SE) and sleep structure, were recorded after drug administration. After awakening, the volunteers' subjective judgments of sleep quality and sleepiness were measured. Eight volunteers underwent 3 psychomotor performance tests at a one-week interval, and the psychomotor performance tests were conducted before and after taking zaleplon and placebo. Six volunteers participated in the vestibular function test session, and parameters, including optokinetic nystagmus (OKN), vestibular ocular reflex (VOR), visual-vestibular ocular reflex (VVOR) and vestibular ocular reflex fixation suppression (VOR-Fix), were detected by the same experimental design as described above. The data of sleep observations were subjected to one-way variance analysis. Compared with the placebo group, SL was shortened significantly, and the scores of subjective sleep quality and sleep depth were clearly increased in the zaleplon 10 mg group (P < 0.05). Moreover, the SE and the percent of REM (rapid eye movement) sleep were increased remarkably in the zaleplon 15 mg group (P < 0.01). Furthermore, the SE, percent of REM sleep and scores of subjective sleep depth in the zaleplon 15 mg group were significantly higher than in the zaleplon 10 mg group (P < 0.05). The psychomotor performance did not change significantly after ingestion of 10 mg or 15 mg of zaleplon, whereas the OKN and VOR gains were lower in the two dose groups of zaleplon (P < 0.05) and restored to normal 3 h after drug ingestion. Zaleplon is an ideal hypnotic for military personnel, and its hypnotic efficiency is dose-related under noise interference; a 15 mg dose of zaleplon could provide significantly better sleep than a 10 mg dose of zaleplon.


Do spinal cord-injured individuals with stronger sense of coherence use different psychological defense styles?
Although the importance of sense of coherence (SOC) and psychological defense mechanisms (PDMs) in the process of coping has been demonstrated, it has not yet been clarified whether individuals with stronger SOC use specific PDMs. Cross-sectional. Iran. Demographic and injury-related variables including injury level, time since injury, American Spinal Cord Association (ASIA) Scale and Spinal cord independence measure-III were collected among individuals with spinal cord injury (SCI). SOC was assessed by the Short-form Sense of Coherence Scale. PDMs were identified using 40-version of the Defense Style Questionnaire. Neurotic defense style was the most commonly used style especially. The overall most commonly used PDM was 'rationalization', which was used by 95%. Individuals with stronger SOC used more mature style (P=0.001, r=0.52), particularly 'humor' and 'suppression' mechanisms (P<0.0001 and 0.024, respectively). There was a negative correlation between stronger SOC and the use of immature defenses including passive aggression (P=0.001, r=-0.51), acting out (P=0.001, r=-0.48), isolation (P=0.009, r=-0.50), autistic fantasy (P=0.010, r=-0.30) and somatization (P<0.0001, r=-0.62). Married individuals had significantly stronger SOC (P=0.01). Age, gender, age at the time of injury incidence, time since injury, ASIA score and cause of injury were not determinants of SOC. In this study, PDMs, which are more probable to be used by individuals with stronger SOC, have been identified. Mature defenses including 'humor' and 'suppression' are used by stronger SOC more often, whereas immature mechanisms are less likely to be used.


Cerebrovascular occlusive disease: hydatidosis.
We reviewed six patients with cerebral hydatid embolism from the heart. Although hydatid disease is becoming less common in the world as a whole, it should be considered in the differential diagnosis of embolic stroke in children, especially in the infested areas where hydatidosis is endemic.


Day case hemithyroidectomy is safe and feasible: experience in Scotland.
We aimed to analyse the safety and feasibility of day case hemithyroidectomy. We reviewed all hemithyroidectomies led by two surgeons across two sites between 2010 and the end of 2013. Patients were divided into 'planned inpatient' or 'planned day case'. Day of discharge, conversion to inpatient procedure, intraoperative and postoperative complications and postoperative presentations or readmission to hospital were analysed. Age, gender, American Society of Anaesthesiologists score and indication for surgery were also recorded. One-hundred and eighty hemithyroidectomy cases were analysed, 35 (19.5%) were planned as inpatient procedures. Of the remaining 145 (80.5%) planned day case: 106 (73.1%) were successfully discharged on the same day and 39 (26.9%) were not; 11 (7.6%) were converted to inpatient procedures perioperatively; 8 (5.5%) had additional procedures; 6 (4.1%) had wound infections; 7 (4.8%) presented to ER; 1 (0.7%) of which required readmission to hospital for a reason unrelated to the surgery. None had laryngeal nerve palsy, compressive haematoma or symptomatic hypocalcaemia. This study showed that hemithyroidectomy by experienced surgeons can be performed safely as a day surgery. No 'planned day case patients' in this study developed laryngeal nerve palsy, compressive haematoma or symptomatic hypocalcaemia.


Β-endorphin-immunoreactive perikarya appear to receive innervation from NPY-immunoreactive fiber varicosities in the human hypothalamus.
Morphological and pharmacological studies indicate that hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons communicate with each other in rats and regulate a variety of hypothalamic and extrahypothalamic functions. Indeed, electron microscopic studies revealed NPY-immunoreactive (NPI-IR) synapses on β-endorphin-IR neurons in the hypothalamus. However, no such connections have been reported in humans. Here, we studied the putative NPY-β-endorphin associations with high-resolution light microscopic double-label immunocytochemistry in the human hypothalamus. The majority of β-endorphin-IR perikarya appear to be innervated by abutting NPY-IR fibers in the infundibulum/median eminence, receiving more than 6 contacts (38% of the counted neurons) or three to six contacts (42% of the counted neurons). The rest of the β-endorphin-IR neurons are lightly innervated by NPY fibers (14%, one-three contacts) or do not receive any detectable NPY-IR axon varicosities (6% of the counted neurons). Since β-endorphin is cleaved from the proopiomelanocortin (POMC) precursor, the NPY-β-endorphin connections also provide the foundation for NPY-α-MSH and NPY-ACTH connections and their subsequent physiology. The close anatomical connections between NPY-IR nerve terminals and β-endorphin-IR neurons reported herein may represent functional synapses and provide the foundation for NPY-stimulated β-endorphin release. By interacting with β-endorphin, NPY may have a more widespread regulatory capacity than acting alone on different neurotransmitter systems.


Targeting HSP90 with picropodophyllin suppresses gastric cancer tumorigenesis by disrupting the association of HSP90 and AKT.
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Thus, the development of safe and effective therapeutic compounds for GC treatment is urgently required. Here, we aimed to examine the role of picropodophyllin (PPP), a compound extracted from the rhizome of Dysosma versipellis (Hance) M. Cheng ex Ying, on the proliferation of GC cells. Our study revealed that PPP inhibits the proliferation of GC cells in a dose-dependent manner by inducing apoptosis. Moreover, our study elucidated that PPP suppresses the growth of GC tumor xenografts with no side effects of observable toxicity. Mechanistically, PPP exerts its effects by blocking the AKT/mammalian target of rapamycin (mTOR) signaling pathway; these effects are markedly abrogated by the overexpression of constitutively active AKT. Furthermore, drug affinity responsive target stability (DARTS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) revealed that heat shock protein 90 (HSP90) may be a potential target of PPP. Surface plasmon resonance and immunoprecipitation assay validated that PPP directly targets HSP90 and disrupts the binding of HSP90 to AKT, thereby suppressing GC cell proliferation. Thus, our study revealed that PPP may be a promising therapeutic compound for GC treatment.


Application of the independent molecule model to elucidate the dynamics of structure I methane hydrate: a second report.
Two model systems of methane hydrate are constructed. One has a small cage surrounded by 12 large cages. The other has a large cage surrounded by four small cages and ten large cages. Three different H-bonding network patterns between waters are formed, and three random configurations of methane in each cage are chosen. A new method called the surface water fixed model is presented in which the energy minimum conformations for both model systems are preserved close to the X-ray crystallized structure. With normal mode analysis, we calculated frequencies of 2916.6 cm(-1) for a small cage at a centre, 2915.9 cm(-1) not at a centre, and 2911.7 cm(-1) for a large cage at a centre, and 2911.3 cm(-1) not at a centre. These frequencies are in moderate agreement with the corresponding Raman spectra, though not adequate. With our new method, however, it should be possible to improve agreement with the Raman spectra, if a model system vastly larger than the present model systems were constructed.


[Enzymes of carbohydrate and lipid metabolism in dependence on age (author's transl)].
The levels of the rat liver enzymes glucose-6-phosphate-dehydrogenase, alpha-glycerophosphate-dehydrogenase and citrate cleavage enzyme decrease between the age groups of 3 and 18 months. The half-life time of these enzymes is uneffected by age and the diminished levels of the enzymes in the liver of old rats can be ascribed to a reduced rate of enzyme synthesis. The half-life time of malic enzyme decreases as a function of age and this increased enzyme destruction may contribute to the diminished malic enzyme level of old rat liver.


Adverse effect propensity: A new feature of Gulf War illness predicted by environmental exposures.
A third of 1990-1 Gulf-deployed personnel developed drug/chemical-induced multisymptom illness, "Gulf War illness" (GWI). Veterans with GWI (VGWI) report increased drug/exposure adverse effects (AEs). Using previously collected data from a case-control study, we evaluated whether the fraction of exposures that engendered AEs ("AE Propensity") is increased in VGWI (it was); whether AE Propensity is related to self-rated "chemical sensitivity" (it did); and whether specific exposures "predicted" AE Propensity (they did). Pesticides and radiation exposure were significant predictors, with copper significantly "protective"-in the total sample (adjusted for GWI-status) and separately in VGWI and controls, on multivariable regression. Mitochondrial impairment and oxidative stress (OS) underlie AEs from many exposures irrespective of nominal specific mechanism. We hypothesize that mitochondrial toxicity and interrelated OS from pesticides and radiation position people on the steep part of the curve of mitochondrial impairment and OS versus symptom/biological disruption, amplifying impact of new exposures. Copper, meanwhile, is involved in critical OS detoxification processes.


The wolf in sheep's clothing: Microtomographic aspects of clinically incipient radiation-related caries.
Radiation related caries (RRC) can cause rapid progression, with a high potential for dental destruction affecting mainly cervical and incisal areas. Unlike the injuries that occur in the conventional caries, incipient RRC present in unusual surfaces have difficult diagnosis and classification stages of cavitation. Evaluate the radiographic patterns of demineralization of RRC by using micro-CT. Ten teeth with incipient RRC and 10 teeth with incipient conventional caries (control group) matched by anatomic teeth group and caries affected surfaces were evaluated by X-ray microtomography (micro-CT) Skyscan 1174V2 (50Kv, 1.3 megapixel, Kontich, Belgium). Teeth were placed in a standard position for micro-CT (coronal, transaxial and sagittal sections) during images acquisition. Lesions were classified according to the depth of invasion and relationship with enamel, dentin and pulp. RRC samples presented deeper lesions with higher involvement of enamel and dentin. Control group presented focal and superficial lesions with lower involvement of enamel and dentin. Incipient RRC present aggressive microtomographic patterns of demineralization when compared to conventional caries, as indicated by deep lesions, regardless of its clinically incipient aspects.


Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16.
Oncolytic herpes simplex viruses (HSVs), in clinical trials for the treatment of malignant gliomas, are assumed to be selective for tumor cells because their replication is strongly attenuated in quiescent cells, but not in cycling cells. Oncolytic selectivity is thought to occur because mutations in viral ICP6 (encoding a viral ribonucleotide reductase function) and/or gamma34.5 function are respectively complemented by mammalian ribonucleotide reductase and GADD34, whose genes are expressed in cycling cells. However, it is estimated that only 5-15% of malignant glioma cells are in mitosis at any one time. Therefore, effective replication of HSV oncolytic viruses might be limited to a subpopulation of tumor cells, since at any one time the majority of tumor cells would not be cycling. However, we report that an HSV with defective ICP6 function replicates in quiescent cultured murine embryonic fibroblasts obtained from mice with homozygous p16 deletions. Furthermore, intracranial inoculation of this virus into the brains of p16-/- mice provides evidence of viral replication that does not occur when the virus is injected into the brains of wild-type mice. These approaches provide in vitro and in vivo evidence that ICP6-negative HSVs are 'molecularly targeted,' because they replicate in quiescent tumor cells carrying specific oncogene deletions, independent of cell cycle status.


Expression of growth hormone and its receptor in the lungs of embryonic chicks.
The lung is well established as being a postnatal target site for growth hormone (GH) action, since pathophysiological states of GH excess and deficiency are both associated with impaired pulmonary function. Pituitary GH is therefore probably involved in normal lung growth or development, although perinatal lung development occurs prior to the differentiation of pituitary somatotrophs and the ontogeny of pituitary GH secretion. The lung itself may, however, be a site of GH production during prenatal development, since a specific GH-response gene (a marker of GH activity) is expressed in the lungs of early chick embryos, in which GH immunoreactivity is widespread in many other peripheral tissues. We have assessed this possibility in embryonic chicks. A 690-bp cDNA, identical in size and nucleotide sequence to the full-length pituitary GH transcript, was amplified by reverse transcription/polymerase chain reaction from total RNA extracted from the lungs of embryos at 11, 13, 15, and 18 days of the 21-day incubation period. This transcript was localized by in situ hybridization to mesenchymal and epithelial cells of the developing lungs, in which specific GH immunoreactivity was similarly located. Intense GH immunoreactivity was also present after embryonic day 15 (ED15) in the smooth muscle surrounding blood vessels in the lung and surrounding the bronchioles. Lung GH immunoreactivity was primarily associated with a 15-kDa protein, rather than the 26-kDa protein in the pituitary gland. After the onset of pituitary GH secretion (at ED17), GH mRNA was barely detectable in the lungs of ED20 embryos, at the start of lung breathing. GH immunoreactivity was, however, still present in some cells in the lungs of ED20 embryos. GH-receptor mRNA and immunoreactivity were also widespread and abundant within the embryonic lung. Lung GH may thus have autocrine or paracrine roles in lung development or in pulmonary function prior to the ontogeny of the pituitary gland and the appearance of GH in peripheral plasma.


Patient-Reported Testing Burden of Breast Magnetic Resonance Imaging Among Women With Ductal Carcinoma In Situ: An Ancillary Study of the ECOG-ACRIN Cancer Research Group (E4112).
The use of magnetic resonance imaging (MRI) in pretreatment planning of ductal carcinoma in situ (DCIS) remains controversial. Understanding changes in short-term health-related quality of life associated with breast MRI would allow for a more complete comparative effectiveness assessment. To assess whether there are changes in patient-reported quality of life associated with breast MRI among women diagnosed with DCIS. This cohort study was a substudy of a nonrandomized clinical trial conducted at 75 participating US institutions from March 2015 to April 2016. Women recently diagnosed with unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. A total of 355 women met the eligibility criteria and underwent the study MRI. Data analysis was performed from June 3, 2020, to July 1, 2021. Participants underwent bilateral breast MRI within 30 days of study registration and before surgery. Information on patient-reported testing burden for breast MRI was collected after MRI and before surgery. The primary outcome of this substudy was the patient-reported testing burden of breast MRI, measured by the Testing Morbidities Index (TMI) summated scale score. The TMI is a 7-item instrument that evaluates the temporary changes in quality of life associated with imaging before, during, and after the test (0 represents the worst possible, 100 the hypothetical ideal test experience). Of the 355 women who met the eligibility criteria, 244 (69%) completed both questionnaires and were included in this analysis. The median age was 59 years (range, 34-85 years). The mean MRI TMI summated scale score was 85.9 (95% CI, 84.6-87.3). Of the 244 women, 142 (58%) experienced at least some fear and anxiety before the examination, and 120 women (49%) experienced fear and anxiety during the examination. A total of 156 women (64%) experienced pain or discomfort during the examination. In multivariable analyses, greater test-related burden was associated with higher levels of cancer worry (regression coefficient, -2.75; SE, 0.94; P = .004). In this cohort study, a clinically meaningful breast MRI testing burden among women with DCIS was revealed that was significantly associated with cancer worry. Understanding the potential quality-of-life reduction associated with MRI, especially when used in combination with mammography, may allow development of targeted interventions to improve the patient experience.


Safety impacts of signal-warning flashers and speed control at high-speed signalized intersections.
For many years, to reduce the crash frequency and severity at high-speed signalized intersections, warning flashers have been used to alert drivers of potential traffic-signal changes. Recently, more aggressive countermeasures at such intersections include a speed-limit reduction in addition to warning flashers. While such speed-control strategies have the potential to further improve the crash-mitigation effectiveness of warning flashers, a rigorous statistical analysis of crash data from such intersections has not been undertaken to date. This paper uses 10-year crash data from 28 intersections in Nebraska (all with intersection approaches having signal-warning flashers; some with no speed-limit reduction, and the others with either 5 mi/h or 10 mi/h reduction in speed limit) to estimate a random parameters negative binomial model of crash frequency and a nested logit model of crash-injury severity. The estimation findings show that, while a wide variety of factors significantly influence the frequency and severity of crashes, the effect of the 5 mi/h speed-limit reduction is ambiguous-decreasing the frequency of crashes on some intersection approaches and increasing it on others, and decreasing some crash-injury severities and increasing others. In contrast, the 10 mi/h reduction in speed limit unambiguously decreased both the frequency and injury-severity of crashes. It is speculated that, in the presence of potentially heterogeneous driver responses to decreased speed limits, the smaller distances covered during reaction time at lower speeds (allowing a higher likelihood of crash avoidance) and the reduced energy of crashes associated with lower speed limits are not necessarily sufficient to unambiguously decrease the frequency and severity of crashes when the speed-limit reduction is just 5 mi/h. However, they are sufficient to unambiguously decrease the frequency and severity of crashes when the speed-limit reduction is 10 mi/h. Based on this research, speed-limit reductions in conjunction with signal-warning flashers appear to be an effective safety countermeasure, but only clearly so if the speed-limit reduction is at least 10 mi/h.


Effect of infection by Babesia spp. on the development and survival of free-living stages of Boophilus annulatus.
Oviposition, egg hatching and survival of newly-hatched larvae of Boophilus annulatus were studied in relation to infection by Babesia species and different temperature regimens. Infection of female ticks by Babesia bigemina or B. bovis had no effect on the time elapsed between engorgement and oviposition. The duration of oviposition was shorter in infected females incubated at 25 degrees C or 35 degrees C and infected females laid fewer eggs than the controls. No larvae hatched at 16 degrees C. B. bigemina-infected eggs hatched more quickly than uninfected eggs at 35 degrees C. The hatching percentage of B. bigemina-infected eggs was reduced by 50% at an incubation temperature of 25 degrees C and by 75% at 35 degrees C. At 16 degrees C there was no difference in the duration of survival of infected and non-infected larvae but at 25 degrees C and 35 degrees C the mean survival period of infected larvae was significantly lower than those of controls.


Psychological distress, drug and alcohol use as correlates of condom use in HIV-serodiscordant heterosexual couples.
To investigate the relationship between psychological distress, alcohol, drug and condom use in HIV-serodiscordant heterosexual couples. Structured interviews were conducted to collect demographic information, detailed data on psychological distress, drug and alcohol use and sexual behavior. Analyses were based on 106 pairs of sexually active discordant couples. Significant differences among heterosexual condom users and non-users varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use and combining sex with drugs or alcohol. Employment was strongly associated with condom use in HIV-negative women whose regular sexual partners were HIV-positive men. The risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research on the effect of employment of HIV-negative women is required.


Small Non-Coding RNAs in Leukemia.
In 2020, more than 60,500 people were diagnosed with leukemia in the USA, and more than 23,000 died. The incidence of leukemia is still rising, and drug resistance development is a serious concern for patients' wellbeing and survival. In the past two decades, small non-coding RNAs have been studied to evaluate their functions and possible role in cancer pathogenesis. Small non-coding RNAs are short RNA molecules involved in several cellular processes by regulating the expression of genes. An increasing body of evidence collected by many independent studies shows that the expression of these molecules is tissue specific, and that their dysregulation alters the expression of genes involved in tumor development, progression and drug response. Indeed, small non-coding RNAs play a pivotal role in the onset, staging, relapse and drug response of hematological malignancies and cancers in general. These findings strongly suggest that small non-coding RNAs could function as biomarkers and possible targets for therapy. Thus, in this review, we summarize the regulatory mechanisms of small non-coding RNA expression in different types of leukemia and assess their potential clinical implications.


Survival and genetic stability of Dendranthema grandiflora Tzvelev shoot apices after cryopreservation by vitrification and encapsulation-dehydration.
The aim of this study was to compare the genetic stability of chrysanthemum (cv. Pasodoble) apices cryopreserved using two different methods: encapsulation-dehydration and vitrification. The assessment of the genetic stability was developed using RAPDs markers. Assessment of stability was evaluated in pot-cultivated mother plants (from which buds were excised for micropropagation), in shoots (leave tissue) from which apices were extracted for cryopreservation, and in shoots regenerated from cryopreserved apices 30 days after recovery and after further 3 months in culture. Throughout the process the origin of the apices (in vitro-shoot from which they were excised) was recorded. Twenty one regenerants cryopreserved by vitrification and 25 by encapsulation-dehydration were assessed. Only one cryopreserved regenerant from the encapsulation-dehydration method showed a different band pattern. These results support the necessity of monitoring the genetic stability of the regenerants obtained after cryopreservation, as this is a very useful technique for the conservation of plant genetic resources.


Colonization and Spatial Distribution of Boll Weevil in Commercial Cotton Fields.
The departure and arrival of boll weevil in cotton fields have fostered major control decisions against this pest over time. Field colonization and distribution of boll weevil were evaluated using cotton fields from 93.7 to 154 ha each, located in Serra da Petrovina and Campo Verde, both in the Cerrado biome of Mato Grosso State, Brazil, as a function of cotton field bordering vegetation and crop phenology. The monitoring of adult weevils was carried out using traps containing sex and aggregation pheromone. The traps were set up considering the four coordinates of the field, bordering vegetation, and distances from the field margin. Six traps were set in each direction with three representing the field margin (0 m, 60 m, and 120 m from the borderline) and the other three set up equidistant from the center of the field (> 200 m). Traps were evaluated weekly beginning 10 days after plant emergence (DAE) throughout the cotton phenology until harvesting. Boll weevils were caught in the first evaluation 10 DAE, irrespective of the vegetation bordering the cotton field and distance of trap from field margin. The average weevils per trap was relatively low throughout the crop development but increased significantly through the maturation and harvesting periods. Furthermore, the bordering vegetation was not the only determinant factor for boll weevil colonization and distribution throughout the cotton field. Based on these data, boll weevil exhibited early colonization, already occurring beyond the border of the field.


A suicide by thiopentone injection.
Post-mortem tissues from a thiopentone suicide were analysed by ultraviolet spectrometry and gas chromatography. The thiopentone concentrations found (0.6 mg/100 ml of blood and 2 6 mg/100 g of tissue) are consistent with those reported for 'anaesthetic' deaths where only thiopentone and other anaesthetic agents were present. The gas chromatographic method gave more accurate result with the tissues.


Water turbidity dynamics using random forest in the Yangtze River Delta Region, China.
Turbidity is a water quality indicator that is essential for the sustainable development of aquatic ecosystems and the protection of biodiversity. The turbidity of different water surfaces and its response mechanisms to regional climatic factors and human activities in the Yangtze River Delta Region (YRDR), an important rapid economic development region in China, remain poorly understood. To enhance the knowledge of turbidity variations and dominant drivers of YRDR water surfaces, a complete long-term turbidity series was obtained using Landsat images from 1990 to 2020. The results show that the turbidity trend differed from -1.3 NTU/yr to 0.7 NTU/yr in different water surfaces. Turbidity decreased significantly in the mainstream of the Yangtze River (MYR), aquaculture ponds (AP) and other water bodies, whilst increasing significantly in the medium lakes (ML) and mainstream of the Qiantang River (MQR). Meanwhile, no significant changes in turbidity were observed in the great lakes (GL) and small lakes (SL). Rather than climatic factors, urbanisation and decreasing wastewater discharge were the dominant drivers of turbidity trends during the study period. In addition, ecological engineering in AP increased water transparency. The Three Gorges Dam also decreased turbidity in MYR. Increasing turbidity in the downstream of MQR was driven by increasing seasonal water surfaces and reclamation projects near Hangzhou Bay. GL faced no significant increase in turbidity due to the offset of afforestation to urbanisation-induced turbidity increase. These findings provide important information for government decision-making for subsequent aquatic environmental protection and restoration in the YRDR.


Successful treatment of epilepsy and celiac disease with a gluten-free diet.
Celiac disease is a gluten-sensitive enteropathy, which recently has been described in association with epilepsy or other neurologic disturbances. This study describes a case of a 7-year-old female with intractable-to-treatment epilepsy and late-onset celiac disease, who was treated successfully with a gluten-free diet plus antiepileptic therapy. It is important for children with intractable cases of epilepsy and weight loss to undergo screening for celiac disease.


[Differential diagnosis of anorexia nervosa and depression. A case report of Addison's disease in a female patient].
Similar symptoms make the differential diagnosis of anorexia nervosa and Addison's disease difficult at times: vomiting, weight loss, hypotension, depressed mood, reduced drive, and increased irritability can occur in both disorders. Psychological factors are then frequently presumed to be causative, so that the diagnosis of Addison's disease is made only years after the onset of the disease. Against this background, our case report presents important differential features, particularly with regard to consultative psychiatry.


Ruthenium(II)-Catalyzed Alkene C-H Bond Functionalization on Cinnamic Acids: A Facile Synthesis of Versatile α-Pyrones.
An inexpensive ruthenium(II) complex enabled oxidative annulation of alkynes by using cinnamic acid derivatives to provide diversely decorated multisubstituted α-pyrones.


Anaphylaxis in laboratory workers because of rodent handling: two case reports.
Occupational allergy to rodents among laboratory animal workers is common. Most patients generally experience allergic symptoms after the first few years of work. Associated symptoms are usually mild, such as rhinoconjunctivits, urticaria, and asthma. Anaphylaxis, although rare, could be severe and life threatening. We have described in this study two cases of laboratory workers that developed skin and respiratory reactions following laboratory rat and mouse bites, consistent with anaphylaxis. Skin testing was found positive for rat epithelium in the patient with anaphylaxis due to rat bite. Elevated levels of specific IgE antibodies against rat and mouse epitheliums were also detected in both the patients. These cases illustrate a severe hypersensitivity reaction that could potentially occur in occupational workers that are in close contact with rodents. Reduction of allergen exposure, regular screening, and job modification could be beneficial for affected individuals. Health care workers should be made aware that anaphylaxis could be a serious consequence of laboratory animal bites, particularly in those already sensitized.


Substrate-induced conformational changes in the S-component ThiT from an energy coupling factor transporter.
Energy coupling factor (ECF) transporters are a recently discovered class of ABC transporters that mediate vitamin uptake in prokaryotes. Characteristic for ECF-type ABC transporters are small integral membrane proteins (S-components) that bind the transported substrates with high affinity. S-components associate with a second membrane protein (EcfT) and two peripheral ATPases to form a complete ATP-dependent transporter. Here, we have used EPR spectroscopy, stopped-flow fluorescence spectroscopy, and molecular dynamics simulations to determine the structural rearrangements that take place in the S-component ThiT from Lactococcus lactis upon binding of thiamin. Thiamin-induced conformational changes were confined to the long and partially membrane-embedded loop between transmembrane helices 1 and 2 that acts as a lid to occlude the binding site. The results indicate that solitary ThiT functions as a bona fide high-affinity substrate binding protein, which lacks a translocation pathway within the protein.


Light and electron microscopical studies of the location of Strongyloides ratti in the mouse intestine.
This study was designed to define the precise anatomical location of Strongyloides ratti in the intestinal mucosa of the mouse. Light microscopy showed adult worms in vacuoles in close relationship with the columnar epithelium. Serial sections indicated that the adults wound their way circuitously through the mucosa, usually close to the crypts. Portions of worms were sometimes seen in the intestinal lumen. Electron microscopy demonstrated that adult worms were situated between the epithelial cells. They were never observed to penetrate the basement lamina and enter the lamina propria. Enterocytes were in close proximity to the cephalic end of worms, suggesting that the head of the moving worm forced the cells apart. More posteriorly along the worm, a fluid-filled vacuole surrounded the nematode. The surrounding epithelial cells were compressed and distorted but there was never any evidence of syncytial cell formation. The external cortical layer of worms was seen in some vacuoles, suggesting that ecdysis may occur in tunnels in the epithelium. It appears that S. ratti may create epithelial tunnels through which it moves, moults and deposits eggs. Since S. ratti is a mucosal-dwelling parasite, it is susceptible to attack by cellular elements of the host's defences.


Lens implant exchanges for incorrect power: results of an informal survey.
Despite the introduction of ultrasonic axial length measurements and a variety of intraocular lens implant prediction formulas, postoperative predicted errors greater than 2 diopters occur in approximately 5% to 10% of lens implantations, and occasional errors of 5 diopters to 7 diopters or greater are still encountered. An informal survey revealed successful lens implant exchanges for initial postoperative refractive errors of +4.37 to -14.00 diopters in eight eyes.


Stroke Prevention in Patients with Patent Foramen Ovale.
Patent foramen ovale (PFO) is widely prevalent and studies have suggested an association with ischemic stroke. In this review, we aim to highlight current management of patients with ischemic stroke in the setting of PFO and discuss some areas of controversy. Upon reviewing the literature, we have found that the evidence regarding the management of patients with cryptogenic stroke and PFO has come a long way in the past several years, and many uncertainties remain in clinical practice. The Risk of Paradoxical Embolism (RoPE) score helps to predict the probability of a pathogenic PFO, and recent trial data confirms the benefit of closure in carefully selected patients. The benefit of closure in older patients and in patients with alternate, competing mechanisms is still uncertain, and the long-term risks of closure are not known. Finally, the efficacy of direct oral anticoagulants (DOACs) in this patient population as compared to other medical therapy or mechanical closure has not yet been investigated. Randomized data is needed to help answer these questions. PFO closure is a safe and effective strategy in reducing stroke risk in carefully selected patients with cryptogenic stroke in the setting of a PFO. More studies are needed to test optimal medical treatment strategies and the safety and efficacy of PFO closure in patient subgroups not included in prior PFO closure trials.


Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy.
There is growing evidence that the brain gamma-aminobutyric acid (GABA) system is involved in depression. Lowered plasma GABA levels were identified as a traitlike abnormality found in patients with remitted unipolar depression and in healthy first-degree relatives of patients with unipolar depression. Major depressive disorder has been associated with neuroimaging and neuropathological abnormalities in the prefrontal cortex by various types of evidence. As a result, the current study investigates whether GABA levels in the prefrontal cortex differ between unmedicated subjects with remitted major depressive disorder (rMDD) and healthy control subjects. Sixteen rMDD subjects and 15 healthy control subjects underwent magnetic resonance spectroscopy. We used a 3 Tesla GE whole body scanner with a homogeneous resonator coil providing a homogenous radiofrequency field and capability of obtaining measurement from the prefrontal cortex. Gamma-aminobutyric acid levels were measured in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. There was no difference in GABA concentrations between rMDD subjects and healthy control subjects in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. Secondary analyses provided preliminary evidence for a negative relationship between the glutamate/glutamine (Glx)/GABA ratio and age of onset of major depression in the ventromedial prefrontal cortex. This result suggests that GABA levels in the prefrontal cortex, if found to be reduced in symptomatic depression, do not represent a persistent characteristic of major depression. Further research is needed to determine brain GABA levels in different brain regions, in different stages of depressive illness, and in different depressive subtypes.


A histochemical and ultrastructural study of adenocarcinoma of the lung.
Twenty-five cases of solitary nodular adenocarcinoma of the human lung were studied histochemically and ultrastructurally and their morphological characteristics were compared to the cells observed in the control lungs. Adenocarcinoma cells of the human lung may be classified into following four types: Type A--cells resembling the bronchial goblet cell; Type B--cells resembling the mucous cell of the bronchial gland; Type C--cells resembling the type II alveolar lining cell; and Type D--cells resembling the nonciliated bronchiolar cell. Twenty-one cases belonging to Type D (84%) and two cases to Type B (8%), and one case each to Types A (4%) and C (4%). For the histogenesis of adenocarcinoma of the human lung, nonciliated bronchiolar epithelium may be the most important. A comparison of 10 cases of bronchiolo-alveolar carcinoma with 15 cases of ordinary (acinar and papillary) adenocarcinoma revealed no clear differences either histochemically or ultrastructurally.


Unintentional arterial puncture during cephalic vein cannulation: case report and anatomical study.
The cephalic antebrachial vein is often used for venous access. However, superficial radial arteries of the forearm are known and unintentional arterial puncture can result from attempts to cannulate the lateral veins of the arm. Accidental puncture of a superficial radial artery during peripheral venous cannulation prompted us to study the anatomy of 26 specimens and to assess the relationship between the radial artery and the cephalic vein in the forearm. In two cases, we found accessory branches of the radial artery close to the cephalic forearm vein. Venous cannulation at the lateral wrist carries a small risk of arterial puncture if arterial anomalies are present. If venous cannulation is attempted at the radial side of the wrist, palpation for pulsation should reduce the danger of arterial puncture.


Is sustainable extensive green roof realizable without irrigation in a temperate monsoonal climate? A case study in Beijing.
A strategy to combat the adverse effects of urbanization involves the installation of green roofs under different climatic conditions. The design and maintenance of green roof systems need to be tailored to the local climate. However, there is a scarcity of reports on the performance of plants under temperate monsoonal climatic conditions. This study follows the growth pattern of 28 species (18 non-succulent forbs and 10 succulents) grown at three substrate depths (10, 15, and 20 cm) over three years on an unirrigated extensive green roof, located in Beijing, China. The results of this study revealed that sustainable extensive green roof was realizable without irrigation in Beijing. In terms of plant adaptive strategies, the most successful plants in this study were the stress-tolerant species, followed by the ruderal species. While deeper substrate could facilitate the survival and performance of plants, substrate moisture content was more significant for the survival of plants in the dry and cold winter in Beijing. This study recommended the use of a substrate depth, which was at least 15 cm deep for unirrigated green roofs in Beijing.


Novel Repositioning Therapy for Drug-Resistant Glioblastoma: In Vivo Validation Study of Clindamycin Treatment Targeting the mTOR Pathway and Combination Therapy with Temozolomide.
Multimodal therapy including surgery, radiation treatment, and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to examine the signal activation patterns in GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose-dependent manner. These effects on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of the O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1)-positive cells within the tumor. These results suggest that CLD suppressed GBM cell growth by inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.


Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature.
DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10-30%) and of varying intensity (1+ to 2+). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.


Can deep learning on retinal images augment known risk factors for cardiovascular disease prediction in diabetes? A prospective cohort study from the national screening programme in Scotland.
This study's objective was to evaluate whether deep learning (DL) on retinal photographs from a diabetic retinopathy screening programme improve prediction of incident cardiovascular disease (CVD). DL models were trained to jointly predict future CVD risk and CVD risk factors and used to output a DL score. Poisson regression models including clinical risk factors with and without a DL score were fitted to study cohorts with 2,072 and 38,730 incident CVD events in type 1 (T1DM) and type 2 diabetes (T2DM) respectively. DL scores were independently associated with incident CVD with adjusted standardised incidence rate ratios of 1.14 (P = 3 × 10-04 95 % CI (1.06, 1.23)) and 1.16 (P = 4 × 10-33 95 % CI (1.13, 1.18)) in T1DM and T2DM cohorts respectively. The differences in predictive performance between models with and without a DL score were statistically significant (differences in test log-likelihood 6.7 and 51.1 natural log units) but the increments in C-statistics from 0.820 to 0.822 and from 0.709 to 0.711 for T1DM and T2DM respectively, were small. These results show that in people with diabetes, retinal photographs contain information on future CVD risk. However for this to contribute appreciably to clinical prediction of CVD further approaches, including exploitation of serial images, need to be evaluated.


Isolation and nephrotoxic studies of orellanine from the mushroom Cortinarius speciosissimus.
A nephrotoxic substance has been isolated from Cortinarius speciosissimus. The 1H-NMR and 13C-NMR mass spectra indicated the chemical structure to be 3,3',4,4'-tetrahydroxy-2,2'-bipyridine-N-N'-dioxide. The toxin was quantitated using reversed phase high performance liquid chromatography (HPLC) with electrochemical detection. The detection limit of this method was 500 pg, corresponding to a signal-to-noise ratio of 2.5. The toxin had an LD50 in mice of approximately 20 mg/kg i.p. Light microscopic examination of the kidneys of mice surviving treatment with the toxin showed interstitial nephritis and tubular necrosis.


Oxidative mechanisms of fish hepatocyte toxicity by the harmful dinoflagellate Cochlodinium polykrikoides.
Harmful Algal Blooms caused by the marine ichthyotoxic dinoflagellate Cochlodinium polykrikoides are responsible for mass mortalities of wild and farmed fish worldwide. In this research, we investigated the cytotoxic mechanisms of aqueous extract of C. polykrikoides on isolated Rainbow trout (Oncorhynchus mykiss) liver hepatocytes. Algal extract exposure with isolated trout hepatocytes caused hepatocyte membrane lysis, reactive oxygen species (ROS) formation, glutathione depletion, lysosomal membrane rupture, collapse of mitochondrial membrane potential, ATP depletion and increase in ADP/ATP ratio, cytochrome C release into the hepatocyte cytosol, and activation of caspases cascade. Anti-oxidants, free radical scavengers, mitochondrial permeability transition (MPT) pore sealing agents, microsomal oxidases inhibitors, ATP generators and lysosomotropic agents protected fish hepatocytes against C. polykrikoides. Fish hepatocyte toxicity was also associated with mitochondrial and lysosomal membrane injury. These events caused cytochrome C release from the mitochondrial intra-membrane space into cytosol. The cytochrome C release could trigger activation of caspase-3 and apoptosis.


Partial splenectomy: the preferred alternative for the treatment of splenic cysts.
We report six pediatric patients who had a partial splenectomy for splenic cysts and a seventh patient who had a total splenectomy. There were six epidermoid cysts and one traumatic cyst. All patients had benign postoperative courses. All patients who underwent partial splenectomy had a significant postoperative rise in platelet count that subsequently returned toward baseline. This rise implies a loss of splenic function, although the exact meaning of this is unclear. All patients had late postoperative liver-spleen scans that showed mean spleen size and function to be normal. We have described several methods of partial splenectomy used at Children's Hospital of Philadelphia. Recommendations for patients undergoing partial splenectomy include preoperative pneumococcus and Hemophilus influenzae vaccinations and prophylactic antibiotics postoperatively. The antibiotics are terminated if a liver-spleen scan and platelet count at the end of 3 months' time are normal.


Instant rice made from white and pigmented giant embryonic rice reduces lipid levels and body weight in high fat diet-fed mice.
With the growing health problem on obesity and its associated metabolic disorders, functional foods with hypolipidemic and body fat-lowering effects are greatly needed. The effects of instant rice made from a combination of pigmented giant embryonic rice (Keunnunjami) and white rice, in comparison with those of instant non-pigmented giant embryonic brown rice and instant ordinary brown rice, on the lipid metabolism and body weight in mice under high fat diet condition were investigated. Male C57BL/6N mice (n=48) were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal brown rice (HF-NB), non-pigmented giant embryonic brown rice (HF-GB), and white rice with 8% Keununnjami (HF-KJ8) or 18% Keunnunjami (HF-KJ18). Their body weight gain, plasma lipid profile, adipokine level, lipid-regulating enzymes activities, and mRNA expressions of peroxisome proliferator-activated receptors (PPARs) were determined. At the end of the experimental period, the HF mice exhibited significantly higher body weight and fat, plasma triglyceride and total cholesterol levels, and atherogenic index and lower high-density lipoprotein cholesterol concentration than the NC group. However, diet supplementation of instant rice counteracted this high fat-induced body weight gain and hyperlipidemia through inhibition of lipogenesis and adipokine production and alteration of PPARs expressions. The instant KJ8 and KJ18 rice showed generally similar hypolipidemic and body weight-lowering effects to instant NB and GB rice. These findings demonstrate that instant white rice with added 8% Keunnunjami may be beneficial as functional food with strong hypolipidemic and anti-obesity properties.


Histone modifications accompanying the onset of developmental commitment.
In the sea urchin, Strongylocentrotus purpuratus, three cell types comprise the 16-cell stage embryo: micromeres, macromeres, and mesomeres. We have analyzed these three cell types for nuclear proteins that were synthesized during the earliest stages of embryonic development. The most striking differences in composition of newly synthesized proteins were found between the micromeres, which are the most committed cell type, and the macromeres and mesomeres. First, the micromeres lacked triply modified forms of histone H3; the levels of doubly modified forms of H3 were also greatly reduced. In contrast, micromeres were enriched in a band which migrated at the position of unmodified, unacetylated, histone H3 protein. Second, the overall distribution of H2A histone variants differed among the three cell types. Compared with macromeres and mesomeres, micromeres had a higher ratio of alpha-stage to cleavage-stage (CS) histone H2A; the micromere nuclei were depleted by 50 and 35%, respectively, in embryonically synthesized histone CS-H2A. Third, micromeres displayed different profiles of H1 histones. (a) They contained a cleavage-stage H1 histone which migrated faster than that of macromeres and mesomeres. This protein displays the electrophoretic behavior expected for a protein with reduced levels of posttranslational covalent modification. (b) Micromeres also had reduced levels of an H1 histone (designated H1 alpha a) band found in the alpha-H1 region of macromeres and mesomeres. These changes in chromatin modification correlate with the degree of commitment of cells in the developing embryo; they may reflect differing activities of the chromatin modifying enzymes in the various cell types at the 16-cell stage. Thus, the newly synthesized chromatin proteins of the individual blastomere types already differ in the developing sea urchin by the 16-cell stage. We suggest that variations in histone subtypes and in the levels of activity of chromatin modifying enzymes, e.g., acetylases and phosphorylases, could be involved in commitment and differentiation of different cell types.


Editorial comments on patch size and mechanics in the surgery for post-infarction ventricular septal perforation.
Finite element analysis method (FEM) provides suitable methodology to analyze a target with complex shape such as VSP patch. In this study, by employing the FEM, Ito and colleagues showed the importance of using a large patch to eliminate the dead space between the patch and LV endocardium. Intuitionally many surgeons believed the same way, but it now has been proven mathematically. Although the FEM model has some limitation in part due to too much simplified model, I believe that the study provides useful information to the patch mechanics for VSP closure and that it will help improving the outcome of surgical treatment of VSP.


IHGA: An interactive web server for large-scale and comprehensive discovery of genes of interest in hepatocellular carcinoma.
Mining gene expression data is valuable for discovering novel biomarkers and therapeutic targets in hepatocellular carcinoma (HCC). Although emerging data mining tools are available for pan-cancer-related gene data analysis, few tools are dedicated to HCC. Moreover, tools specifically designed for HCC have restrictions such as small data scale and limited functionality. Therefore, we developed IHGA, a new interactive web server for discovering genes of interest in HCC on a large-scale and comprehensive basis. Integrative HCC Gene Analysis (IHGA) contains over 100 independent HCC patient-derived datasets (with over 10,000 tissue samples) and more than 90 cell models. IHGA allows users to conduct a series of large-scale and comprehensive analyses and data visualizations based on gene mRNA levels, including expression comparison, correlation analysis, clinical characteristics analysis, survival analysis, immune system interaction analysis, and drug sensitivity analysis. This method notably enhanced the richness of clinical data in IHGA. Additionally, IHGA integrates artificial intelligence (AI)-assisted gene screening based on natural language models. IHGA is free, user-friendly, and can effectively reduce time spent during data collection, organization, and analysis. In conclusion, IHGA is competitive in terms of data scale, data diversity, and functionality. It effectively alleviates the obstacles caused by HCC heterogeneity to data mining work and helps advance research on the molecular mechanisms of HCC.


[Abductor digiti minimi-plasty: a local muscle flap for treatment of calcaneus fractures with limited soft tissue injuries].
Wound healing complications and osteitis following calcaneus fractures are common problems due to compromised local soft-tissue perfusion. Transposition of the M. abductor digiti minimi was successfully performed in 12 cases. The problem of soft tissue coverage could be solved by this procedure. Up to now, no negative influence on the myo-osseous architecture of the feet could be observed.


Integrated care model and point of care diagnostics facilitate Hepatitis C treatment among patients receiving opioid agonist therapy: a retrospective review of medical records.
Hepatitis C virus (HCV) is common among individuals in opioid agonist therapy (OAT). HCV treatment has previously been unavailable for most HCV positive OAT patients in Finland. The removal of treatment restrictions and attempts to reach HCV elimination goals have increased the number of OAT patients needing HCV treatment. The objectives of this study were 1) to characterize Finnish HCV positive OAT patients and evaluate their eligibility for HCV treatment at addiction service units, and 2) to retrospectively review the outcomes of treated patients. The study focused on HCV positive OAT patients (n = 235). Demographics and clinical parameters were retrospectively reviewed using the patients' medical records. The eligibility of providing HCV treatment to patients at addiction service units were evaluated based on patients' clinical characteristics, such as liver function and patterns of substance use. The outcomes of patients receiving HCV treatment were reviewed. Of HCV antibody positive OAT patients, 75% had chronic HCV. Of 103 HCV patients screened for liver fibrosis either with Fibroscan or APRI (aspartate aminotransferase to platelet ratio index), 83 patients (81%) had no indication of severe liver damage. Point of care (POC) HCV tests were used for 46 patients to lower the threshold of attending laboratory testing. All patients preferred POC testing to conventional blood testing. Twenty patients had received HCV treatment, 19 completed the treatment and achieved sustained virologic response (SVR) at the end of the treatment. Of the 18 patients available for evaluation of SVR at 12 weeks after the treatment (SVR12), 17 achieved SVR12. The integrated model consisting of HCV diagnostics and treatment at the addiction service unit was successfully implemented within normal OAT practice.


Crystallizing amino acids as bulking agents in freeze-drying.
Bulking agents as mannitol (Man) and glycine (Gly) require high bulking agent to stabilizer ratios to ensure their crystallization during the freeze-drying process. The aim of this study was to investigate several amino acids (AA) as potential alternative bulking agents in low AA to sucrose (Suc) ratios. A fast freeze-drying process was performed above the collapse temperature (Tc) of the amorphous phase challenging the crystalline AA scaffold. Lyophilizates and liquid formulations were characterized by differential scanning calorimetry. Karl-Fischer titration and X-ray powder diffraction as well as macroscopic cake appearance and reconstitution times were evaluated. Stability of a monoclonal antibody was investigated by UV-Vis spectroscopy, light obscuration and size exclusion chromatography. Phenylalanine (Phe), leucine (Leu) and isoleucine (Ile) crystallized upon freeze-drying at 5/45 and 10/40 AA/Suc ratios. 2.5/47.5 AA/Suc ratio showed less pronounced crystallization. Crystallization peaks were not suppressed by 2 or 50 mg/mL antibody in Leu and Ile lyophilizates. Reconstitution times could be improved by addition of surfactant. No signs of protein aggregation were detected after freeze-drying. Man and Gly yielded inacceptable cake appearance when dried with the fast freeze-drying cycle in such low bulking agent to Suc ratios. Leu, Ile and Phe can be used as alternate bulking agents at lower bulking agent to Suc ratios compared to Man or Gly. The selected AAs provided promising cake characteristics and good protein process stability.


RNF213 p.Arg4810Lys Heterozygosity in Moyamoya Disease Indicates Early Onset and Bilateral Cerebrovascular Events.
The relationship between RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variants and clinical manifestation in patients with Moyamoya disease (MMD) remains unclear. We performed a retrospective cohort analysis to clarify the genotype-phenotype correlation of this RNF213 hotspot variant in MMD patients, especially between wild-type (GG) and heterozygous (GA) genotypes. Clinical and genetic data were obtained from patients diagnosed with MMD in our institutions between October 2011 and November 2020. Clinical data included age, sex, neurological status at diagnosis, medical history, smoking history, alcohol intake, and family history. Of the 225 enrolled patients, 160 (71.1%) were symptomatic, 3 (1.3%) had the homozygous variant, and 149 (66.2%) had the heterozygous variant (GA). Analysis of all enrolled patients showed that the GA group was prone to present bilateral symptoms (p = 0.008) and progressive status (Suzuki grade ≥ 4; p = 0.017). Analysis limited to symptomatic patients revealed that the GA group had bilateral symptoms (p = 0.017), younger age at onset (p = 0.043), and, in particular, a higher proportion of onset before 25 years of age (p = 0.021). Multivariate logistic regression analysis of overall patients revealed that earlier age at diagnosis (p < 0.001, OR 0.936, 95% CI 0.914-0.959) and GA group (p = 0.017, OR 3.326, 95%CI 1.237-8.941) were significantly associated with bilateral symptoms. MMD patients diagnosed at a young age with the RNF213 heterozygous variant should be followed up with consideration of possible contralateral stroke if one hemisphere is already symptomatic or of early cerebrovascular events if bilateral hemispheres are asymptomatic.


White matter hyperintensities influence distal cortical β-amyloid accumulation in default mode network pathways.
Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults. Regional standard uptake value ratios (SUVr) from Aβ-PET and white matter hyperintensity (WMH) volumes from three-dimensional magnetic resonance imaging FLAIR images were analyzed across a sample of 72 clinically unimpaired (mini-mental state examination ≥26), older adults (mean age 74.96 and standard deviation 8.13) from the Alzheimer's Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aβ-PET SUVr in the connected cortical DMN regions was analyzed using linear regression models adjusted for age, sex, ApoE, and total brain volumes. The regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus were associated with increased regional SUVr in the inferior parietal lobule (p = .011). The findings suggest that the relation between Aβ in parietal cortex is associated with SVD in downstream white matter (WM) pathways in preclinical AD. The biological relationships and interplay between Aβ and WM microstructure alterations that precede overt WMH development across the continuum of AD progression warrant further study.


In vivo measurement of the elastic properties of the human vocal fold.
The ability to measure the biomechanical properties of the vocal fold in vivo is both an aid to diagnosis and enhances our knowledge of how the vocal folds operate. This paper details a new instrument that is capable of taking readings of the spring rate of the vocal fold in a repeatable manner. We also present three sets of readings taken from two volunteer patients. Patient 1 was suffering from polyp growth, and the data presented are taken from both the damaged vocal fold and the healthy vocal fold. The third set of readings was obtained from a similar volunteer and taken from a healthy vocal fold. It can be seen that the data obtained from the healthy vocal folds are similar and that the data obtained from the diseased vocal fold is at variance.


Non-invasive respiratory volume monitoring identifies opioid-induced respiratory depression in an orthopedic surgery patient with diagnosed obstructive sleep apnea: a case report.
Obstructive sleep apnea and opioid-induced respiratory depression can unpredictably threaten respiratory competence in the post-anesthesia care unit. Current respiratory monitoring relies heavily on respiratory rate and oxygen saturation, as well as subjective clinical assessment. These assessments have distinct limitations, and none provide a real-time, objective, quantitative direct measurement of respiratory status. A novel, non-invasive respiratory volume monitor uses bioimpedance to provide accurate, quantitative measurements of minute ventilation, tidal volume and respiratory rate continuously in real time, providing a direct measurement of ventilation. The case describes an orthopedic surgery patient (54-year-old Caucasian man, body mass index 33.7 kg/m(2)) with diagnosed obstructive sleep apnea in whom the respiratory volume monitor data depicted persistent apneic behavior undetected by other monitoring. The monitor was able to detect a sudden reduction in minute ventilation after initial opioid administration in the post-anesthesia care unit. The patient had sustained low minute ventilation until discharge. Neither respiratory rate data from the hospital monitor nor oxygen saturation readings reflected the respiratory decompensation, remaining within normal limits even during sustained low minute ventilation. The events of this case illustrate the limitations of current respiratory rate monitoring and pulse oximetry in the evaluation of post-surgical respiratory status. Our patient displayed stable respiratory rate and no evidence of desaturation, despite sustained low minute ventilation, and he received opioids in the post-anesthesia care unit despite already compromised ventilation. Because the available monitoring did not indicate the patient's true respiratory status, he was treated with additional opioids, markedly increasing his risk for further respiratory decline.


Rh/Cr2 O3 and CoOx Cocatalysts for Efficient Photocatalytic Water Splitting by Poly (Triazine Imide) Crystals.
In situ photo-deposition of both Pt and CoOx cocatalysts on the facets of poly (triazine imide) (PTI) crystals has been developed for photocatalytic overall water splitting. However, the undesired backward reaction (i.e., water formation) on the noble Pt surface is a spontaneously down-hill process, which restricts their efficiency to run the overall water splitting reaction. Herein, we demonstrate that the efficiency for photocatalytic overall water splitting could be largely promoted by the decoration of Rh/Cr2 O3 and CoOx as H2 and O2 evolution cocatalysts, respectively. Results reveal that the dual cocatalysts greatly extract charges from bulk to surface, while the Rh/Cr2 O3 cocatalyst dramatically restrains the backward reaction, achieving an apparent quantum efficiency (AQE) of 20.2 % for the photocatalytic overall water splitting reaction.


Effect of trehalose and melibiose on crystallization of amorphous paracetamol.
This paper investigates the solid-state behavior of two-phase solid dispersions involving small molecules. The effect of two sugars, trehalose and melibiose, on the recrystallization of amorphous paracetamol, and vice versa, was investigated. The solid dispersions were prepared via heating and quench-cooling, and then stored at a temperature of 38.5 ± 0.5 °C and relative humidities of 3 ± 1% and 75 ± 1%. X-ray powder diffraction (XRPD) confirmed that the solid dispersions were amorphous, while Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) revealed that the solid dispersions were two-phase systems with drug-rich and excipient-rich regions. XRPD was used to qualitatively and quantitatively study the crystallization of the components, and revealed that, despite the existence of two phases, the sugars hindered the crystallization of paracetamol. In contrast, once the paracetamol crystallization started, it accelerated the crystallization of the sugars. Overall, the study demonstrates that small-molecule solid-dispersions need not be single-phase to observe mutual influences between the components in crystallization behavior, and that these effects are likely mediated through interactions at the phase interfaces, as well as alterations in water sorption and mechanical effects.


Swelling of mucoadhesive electrospun chitosan/polyethylene oxide nanofibers facilitates adhesion to the sublingual mucosa.
Mucoadhesive chitosan-based electrospun nanofibers are promising candidates for overcoming challenges associated with sublingual drug delivery, yet studies focusing on evaluating the mucoadhesive properties of nanofibers for sublingual administration are limited. The aim was to elucidate the mucoadhesive properties of chitosan/polyethylene oxide (PEO) nanofibers focusing on how the degree of deacetylation (DDA, 53-96 %) of chitosan influenced their morphological and mucoadhesive properties. The mechanism of mucoadhesion was explained by the intermolecular interactions of chitosan with mucin from bovine submaxillary glands using quartz-crystal microbalance with dissipation monitoring and by adhesion of the nanofibers to ex vivo porcine sublingual mucosa. An increase in chitosan DDA improved the morphological stability of the nanofibers in water, but did not contribute to altered mucoadhesive properties. This study demonstrates excellent mucoadhesive properties of chitosan/PEO nanofibers and shows that the strong mucoadhesiveness of the nanofibers is attributed to their swelling ability.


[The role of hybrid zones in speciation: a case study on chromosome races of the house mouse Mus domesticus and common shrew Sorex araneus].
Although diverse complexes of chromosome races are of rather rare occurrence in mammals, that does not reduce its importance to insignificant phenomenon not worthy of studying as some unique case without direct analogy. Moreover, these complexes present virtually ideal models for estimation of the impact of hybridization on the process of microevolution. The chromosome races are characterized by almost zero level of genetic differentiation and well-defined distinctions, usually induced by chromosome rearrangements only. The presented review shows the valuable contribution of the studies on Sorex araneus and Mus domesticus chromosome Robertsonian systems into our understanding of varied impacts of hybridization on the speciation process. Particularly, it promotes better understanding of such evolutionary phenomena as "reinforcement" of reproductive isolation in secondary contact zones between divergent populations, speciation without geographic separation ("divergence with gene flow"), and "zonal raciation".


Tinnitus as a plastic phenomenon and its possible neural underpinnings in the dorsal cochlear nucleus.
Tinnitus displays many features suggestive of plastic changes in the nervous system. These can be categorized based on the types of manipulations that induce them. We have categorized the various forms of plasticity that characterize tinnitus and searched for their neural underpinnings in the dorsal cochlear nucleus (DCN). This structure has been implicated as a possible site for the generation of tinnitus-producing signals owing to its tendency to become hyperactive following exposure to tinnitus inducing agents such as intense sound and cisplatin. In this paper, we review the many forms of plasticity that have been uncovered in anatomical, physiological and neurochemical studies of the DCN. Some of these plastic changes have been observed as consequences of peripheral injury or as fluctuations in the behavior and chemical activities of DCN neurons, while others can be induced by stimulation of auditory or even non-auditory structures. We show that many parallels can be drawn between the various forms of plasticity displayed by tinnitus and the various forms of neural plasticity which have been defined in the DCN. These parallels lend further support to the hypothesis that the DCN is an important site for the generation and modulation of tinnitus-producing signals.