Thermally induced percolational transition and thermal stability of silver nanowire networks studied by THz spectroscopy.
Great demand toward flexible optoelectronic devices finds metal nanowires (NWs) the most promising flexible transparent conducting material with superior mechanical properties. However, ultrathin metal nanowires suffer from relatively poor thermal stability and sheet conductance, attributed to the poor adhesivity of the ohmic contact between nanowires. Thermal heating and annealing at 200 °C increase the conductivity of the metal network, but prolonged annealing accelerates the breakage of NWs near the NW junction and the formation of Ag droplets. In this study, the thermal stability of silver NW (AgNW) films is investigated through the in situ measurements of sheet resistance and terahertz (THz) conductivity. With the improved ohmic contact at the NW junctions by heating, a characteristic transition from the subpercolative to percolative network is observed by in situ THz spectroscopy. It is found that stamp-transferred graphene incorporated with a near-percolative AgNW network can dramatically enhance the thermal stability of the graphene-AgNW (GAgNW) hybrid film. In both in situ measurements, little variation of physical parameters in GAgNW film is observed for up to 3 h of annealing. The presented results offer the potential of graphene-incorporated metal nanowire film as a highly conductive electrode that also has high thermal stability and excellent transparency for next-generation electronics and optoelectronics on flexible substrates.


Pulmonary vein isolation for chronic atrial fibrillation associated with mitral valve disease: the midterm results.
The Cox Maze procedure is widely performed for the surgical treatment of atrial fibrillation. However it requires numerous incision lines and therefore is a time-consuming operation. We report a simplified operation for chronic atrial fibrillation associated with mitral valve disease. Pulmonary vein isolation procedure was performed on atrial fibrillation associated with mitral valve disease in thirteen patients. This simple procedure consisted of isolation of the four pulmonary veins only. Combined mitral valve surgery involved mitral valve plasty, mitral valve replacement with or without aortic valve replacement and tricuspid annuloplasty. Eleven patients returned to sinus rhythm (84.6%). Mean follow-up time is 32.7 +/- 11.7 months. Three patients required a DDD pacemaker implant for sick sinus syndrome but two out of these three resumed sinus rhythm most of the time recently. Left atrial contraction was detected in eight cases by trans-esophageal echo. One patient died of liver failure two months postoperatively. Eight patients had no blood transfusion. Twelve patients are classified as New York Heart Association class I. Compared with the Maze procedure, this operation was less invasive and preserved the atrial appendage and was thought to have a normal level of secretion of atrial natriuretic peptide. This study suggests that the pulmonary vein isolation procedure may be an effective and simple maneuver for atrial fibrillation associated with mitral valvular disease.


Association of postdoctoral programs in clinical neuropsychology: update and new directions.
This paper provides an update on the Association of Postdoctoral Programs in Clinical Neuropsychology (APPCN), which was formed in 1992. The paper summarizes the historical background of APPCN, reports on contemporary influences on APPCN and its role in postdoctoral education and training in neuropsychology, and provides an update on APPCN's most recent initiatives. The paper includes a list of current members in APPCN and explains how other postdoctoral residency programs in clinical neuropsychology may apply for membership.


Nerve Stimulator Guided Axillary Block in Painless Reduction of Distal Radius Fractures; a Randomized Clinical Trial.
Given the high prevalence of upper extremity fractures and increasing need to perform painless reduction in the emergency departments, the use of analgesic methods with fewer complications and more satisfaction appears to be essential. The aim of this study is comparison the nerve stimulator guided axillary block (NSAB) with intravenous sedation in induction of analgesia for painless reduction of distal radius fractures. In the present randomized clinical trial, 60 patients (18-70 years of age) suffered from distal radius fractures, were divided into two equal groups. One group received axillary nerve block by nerve stimulator guidance and the other procedural sedation and analgesia (PSA) using midazolam/fentanyl. Onset of analgesia, duration of analgesic effect, total procedure time and pain scores were recorded using visual analogue scale (VAS) and the outcomes were compared. Chi-squared and student t test were performed to evaluate differences between two groups. Sixty patients were randomly divided into two groups (83.3% male). The mean age of patients was 31 ±0.7 years. While the onset of analgesia was significantly longer in the NSAB group, the mean total time of procedure was shorter than PSA (p<0.001). The NSAB group needed a shorter post-operative observation time (P<0.001). Both groups experienced equal pain relief before, during and after procedure (p>0.05). It seems that shorter post-operative monitoring time and consequently lesser total time of procedure, make nerve stimulator guided axillary block as an appropriate alternative for procedural sedation and analgesia in painless reduction of distal radius fractures in emergency department.


[Patients classification according the intensity of care in an Emergency Department].
. Patients classification according the intensity of care in an Emergency Department. The increasing number of Emergency Department (ED) admittances coupled with the limited availability of hospital beds requires a patients classification according their intensity of care. Among the available classification systems the Tri-Co (Corridor triage) system, could fit ED patients and was therefore progressively adapted and tested to be used in the ED. To assess the correct allocation of patients according to the intensity of care. Eight versions of the Tri-Co were progressively modified and tested. The Final Modified Tri-Co system was used in 111 randomly selected index days, in different time slots, on all adult patients admitted to ED from May to November 2017 and allocated according to the traditional system (1008 observations). The vast majority of patients (88%) was placed in a section adequate to their intensity of care; 8% in a sector with higher and 4% with lower intensity of care compared to their needs. The comparison between the allocation based on clinical assessment and Tri-Co scores highlighted the reliability of the Tri-Co. The alpha Crombach of the modified IDA scale was 0.724. The Modified Tri-Co system allows the early classification of patients and their assignment to the adequate level of care.


Pain and sedation management and monitoring in pediatric intensive care units across Europe: an ESPNIC survey.
Management and monitoring of pain and sedation to reduce discomfort as well as side effects, such as over- and under-sedation, withdrawal syndrome and delirium, is an integral part of pediatric intensive care practice. However, the current state of management and monitoring of analgosedation across European pediatric intensive care units (PICUs) remains unknown. The aim of this survey was to describe current practices across European PICUs regarding the management and monitoring of pain and sedation. An online survey was distributed among 357 European PICUs assessing demographic features, drug choices and dosing, as well as usage of instruments for monitoring pain and sedation. We also compared low- and high-volume PICUs practices. Responses were collected from January to April 2021. A total of 215 (60% response rate) PICUs from 27 European countries responded. Seventy-one percent of PICUs stated to use protocols for analgosedation management, more frequently in high-volume PICUs (77% vs 63%, p = 0.028). First-choice drug combination was an opioid with a benzodiazepine, namely fentanyl (51%) and midazolam (71%) being the preferred drugs. The starting doses differed between PICUs from 0.1 to 5 mcg/kg/h for fentanyl, and 0.01 to 0.5 mg/kg/h for midazolam. Daily assessment and documentation for pain (81%) and sedation (87%) was reported by most of the PICUs, using the preferred validated FLACC scale (54%) and the COMFORT Behavioural scale (48%), respectively. Both analgesia and sedation were mainly monitored by nurses (92% and 84%, respectively). Eighty-six percent of the responding PICUs stated to use neuromuscular blocking agents in some scenarios. Monitoring of paralysed patients was preferably done by observation of vital signs with electronic devices support. This survey provides an overview of current analgosedation practices among European PICUs. Drugs of choice, dosing and assessment strategies were shown to differ widely. Further research and development of evidence-based guidelines for optimal drug dosing and analgosedation assessment are needed.


Calcium receptor signaling and citrate transport.
The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells. This calcium-sensitive process has the potential to modulate the amount of citrate available to complex increased urinary calcium. Using isotope labeled succinate uptake in OK cells along with various pharmacologic tools we examined whether the CaSR alters apical dicarboxylate transport and through which signal transduction pathways this occurs. Our results indicate that in the proximal tubule CaSR adjusts apical dicarboxylate transport, and does so via a CaSR → Gq → PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.


An unusual 3D coordination polymer based on bridging interactions of the nucleobase adenine.
The first 3D coordination polymer containing a nucleobase as a bridging ligand, [[Cu2(mu-ade)4(H2O)2][Cu(ox)(H2O)]2 x approximately 14H2O]n (1), has been synthesized by reaction of adenine (Hade) with a basic solution of K2[Cu(ox)2] x 2H2O (ox = oxalato dianion). Compound 1 crystallizes in the trigonal space group R3 with a = b = 31.350(1) angstroms, c = 14.285(1) angstroms, V = 12158.7(10) angstroms3, and Z = 9. X-ray analysis shows a covalent 3D network in which the copper(II) centers are bridged by tridentate mu-N3,N7,N9 adeninate ligands. The compound has relatively large, nanometer-sized tubes associated with the self-assembly process directed solely by metal-ligand interactions. The covalent 3D framework remains intact upon removal of the guest water molecules trapped in the nanotubes. Magnetic measurements indicate an overall antiferromagnetic behavior of the compound.


Gastroenterology - Evolution of specialty choice in recent years.
Gastroenterology is one of the medical specialties offered to residency training candidates each year. This project analyzes the data associated with the choice of a Gastroenterology residency program in recent years. Data related to specialty selection were obtained from official reports with regard to the allocation of residency places by the Spanish Ministry of Health, Social Services and Equality. Information was collected from various teaching centers via their training guides, the Spanish National Catalogue of Hospitals and the National Transplant Organization. The median consecutive number involved in the choice of Gastroenterology training has decreased year after year, and this specialty is now positioned among the five most commonly selected residency programs in 2015. The median number of hospitals with a higher number of beds, adult liver transplantation activities and dedicated GI bleeding units is significantly lower. This is also true when centers are analyzed according to the presence of specific Gastroenterology on-call shifts for residents or their association with medical schools. Data from the past five years highlight Madrid, Aragón and the Basque Country as the autonomous communities where Gastroenterology is the most popular. Centers selected by candidates with the lowest median consecutive numbers from 2011-2015 included the university hospitals Ramón y Cajal, Santiago de Compostela and Gregorio Marañón. Gastroenterology has gradually escalated in the ranking of residency choices and is now one of the five most popular options. Potential residents prefer larger centers with complex-care patients and more research activity.


Masterless soft lithography: patterning UV/ozone-induced adhesion on poly(dimethylsiloxane) surfaces.
A novel microreactor-based photomask capable of effecting high resolution, large area patterning of UV/ozone (UVO) treatments of poly(dimethylsiloxane) (PDMS) surfaces is described. This tool forms the basis of two new soft lithographic patterning techniques that significantly extend the design rules of decal transfer lithography (DTL). The first technique, photodefined cohesive mechanical failure, fuses the design rules of photolithography with the contact-based adhesive transfer of PDMS in DTL. In a second powerful variation, the UVO masks described in this work enable a masterless soft lithographic patterning process. This latter method, UVO-patterned adhesive transfer, allows the direct transfer of PDMS-based polymer microstructures from a slab of polymer to silicon and other material surfaces. Both methods exploit the improved process qualities that result from the use of a deuterium discharge lamp to affect the UVO treatment to pattern complex, large area PDMS patterns with limiting feature sizes extending well below 1 microm (> or = 0.3 microm). The use of these structures as resists is demonstrated for the patterning of metal thin films. A time-of-flight secondary ion mass spectroscopy study of the process provides new insights into the mechanisms that contribute to the chemistry responsible for the interfacial adhesion of DTL transfers.


Synthesis of fused bicyclic piperidines: potential bioactive templates for medicinal chemistry.
An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.


Transgenic approaches in medical entomology: 2022 highlights.
Transgenesis has emerged as a powerful tool to control arthropod vectors and the diseases they transmit. Here, we highlight the latest developments on transgenic approaches in ticks, Anopheles and Aedes mosquitoes, based on recent findings and significant papers from 2022. We survey topics ranging from population replacement, population suppression, gene drive, sex ratio distortion, public engagement and capacity building, and gene editing in ticks. While presenting these advancements, we discuss the current challenges surrounding the application of arthropod transgenesis for the development of novel vector control strategies.


It is not "Just Circumcision".
Circumcision is one of the most commonly performed operations during childhood. The procedure is often underestimated in areas where it is frequently executed due to social and religion-based indications. In fact it might be an opportunity to detect and to correct any existing penile anomaly. The aim of the study was to retrospectively evaluate the boys who were admitted to a hospital for circumcision and the outcome of the procedure. The boys who were brought to outpatient clinics for circumcision between 2009-2015, were retrospectively evaluated. The indications for hospital admission and the presence of associated penile anomalies were searched. All the boys were examined and operated by a single surgeon of the institution. Nine hundred forty four boys were brought to pediatric surgery outpatient clinics in order to be circumcised. The operation was performed in 318 of them. The physical examination revealed penile anomalies in 29 of the 318 cases. The detected anomalies were webbed penis, penile torsion, hypospadias, chordee without hypospadias and meatal stenosis. The proper examination of the boys by a physician prior to circumcision provides the detection of penile anomalies which can be corrected at the same session. The arrangements for performing circumcision in hospitals by the medical staff should be favored. The misleading perception of underestimation of the procedure where it is ritually performed, should be corrected.


[Treatment outcome of peptide vaccination for advanced colorectal cancer].
Complementary DNA( cDNA) microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen (HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different cancer-testis antigens, ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34( TOMM34). We conducted a clinical trial of colorectal cancer-specific peptide( RNF43, TOMM34) vaccines with uracil/tegafur( UFT)+Leucovorin( LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any serious adverse events. There were long-term survivors in the group showing cytotoxic T lymphocyte (CTL) responses against both RNF43 and TOMM34, as well as in the group showing CTL responses against either RNF43 or TOMM34. A new study has been planned to obtain more immunological responses. We started a clinical trial of vaccines against multiple peptides (RNF43, TOMM34, forkhead box protein M1 [FOXM1], maternal embryonic leucine zipper kinase [MELK], holliday junction recognition protein[HJURP], vascular endothelial growth factor receptor 1[VEGFR1], and VEGFR2) for the treatment of advanced or recurrent colorectal cancer.


[Development of salivary gland tumors in pleomorphic adenoma gene 1 transgenic mice].
Activation and overexpression of pleomorphic adenoma (PLAG1) gene due to t(3;8)(p21;q12) translocation are associated with the development of human pleomorphic adenomas of the salivary glands. This study was conducted to generate ubiquitously-expressed or tissue-specific expressed PLAG1 transgenic mice and to elucidate the role of PLAG1 gene in tumorigenesis in vivo. Human PLAG1 cDNA was cloned from salivary gland tumor or placenta tissues by RT-PCR. Ubiquitous expression vector pCMV-EGFP/PLAG1 driven by CMV promoter and tissue-specific expression vector pMMTV-PLAG1 driven by MMTV LTR were constructed. NIH3T3 cells transiently transfected with pCMV-EGFP/PLAG1 showed high expression of PLAG1 in nucleus. Transgenes were microinjected into pronucleus of zygotes to generate transgenic mice. It was found that the human PLAG1 cDNA cloned from several salivary gland tumor and normal placenta tissues consistently showed a variation of a single nucleotide at the same position when compared with the human PLAG1 cDNA sequence in Genbank (Accession No. U65002), which led to T458P at protein level. It might be a single nucleotide polymorphism (SNP)locus. Fused EGFP/PLAG1 protein was found to be localized in the nucleus of NIH3T3 cells transiently transfected with pCMV-EGFP/ PLAG1. Several pCMV-EGFP/PLAG1 and pMMTV-PLAG1 transgenic mouse lines were obtained respectively. As might be expected, pMMTV-PLAG1 transgenic mice spontaneously developed salivary gland tumors in three independent lines, among which, line 42 showed tumorigenic phenotype in 100% of transgenic mice within three months after birth. Overexpression of PLAG1 gene plays a crucial role in tumorigenesis of salivary gland tumors.


EVOLUTIONARY ORIGIN OF A PARTHENOFORM, THE AMAZON MOLLY POECILIA FORMOSA, ON THE BASIS OF A MOLECULAR GENEALOGY.
The appearance of vertebrate species that reproduce without genetic recombination has been explained by their origin from a rare hybridization event between members of two distantly related species. For the first recognized vertebrate unisexual, the Amazon molly Poecilia formosa, mostly morphological and biochemical genetic information has been available so far with respect to its evolutionary origin. DNA sequence analyses of transcribed portions of the genome (tyrosine kinase proto-oncogenes) demonstrated its hybrid state unequivocally. Both alleles can be traced in a DNA sequence-based phylogenetic tree to extant species that represent the parental species or that are closely related to the corresponding extinct forms, namely P. mexicana limantouri and a so far taxonomically ill-defined north Mexican subspecies of the P. latipinna/P. velifera complex. A rough estimate from the mutation rates dates the hybridization event further back than would have been predicted on the basis of "Muller's ratchet" for an ecologically successful species.


T cell-selective deletion of Oct1 protects animals from autoimmune neuroinflammation while maintaining neurotropic pathogen response.
Treatments for autoimmune diseases aim to dampen autoreactivity while preserving normal immune function. In CD4+ T cells, the transcription factor Oct1/Pou2f1 is a dispensable transcription factor for T cell development and response to primary infection, but promotes expression of target genes, including Il2 and Ifng, under conditions of antigen reencounter. As a result, they are more strongly expressed upon secondary stimulation. Such repeated antigen encounters occur in memory recall responses, in autoimmunity where self-antigen can be recognized multiple times, and in chronic infection where foreign antigen is persistent. Based on these previous findings, we hypothesized that Oct1 loss would protect animals from autoimmunity but maintain normal responses to pathogens in the CNS. We used a conditional mouse Oct1 (Pou2f1) allele and a CD4-Cre driver to determine the effect of T cell-specific Oct1 loss on autoimmune- and viral-induced neuroinflammation using an autoantigen-driven EAE model of autoimmunity and a JHMV model of viral infection. Oct1 conditional deletion mitigated clinical scores and reduced infiltrating T cells and cytokine production in the EAE model. Consistently, Oct1-deficient CD4+ T cells stimulated in vitro showed increased expression of markers associated with T cell anergy, particularly in the absence of co-stimulatory signals. In contrast, anti-viral T cell effector functions are intact in the absence of Oct1, with no changes in neuroinflammation, infiltrating T cells or cytokine production. Our findings uncover a significant difference between the effect of Oct1 loss on autoimmune and anti-pathogen responses, which potentially could be exploited for therapeutic benefit.


Digital tools in polysomnography.
Recent advances in the computing power and storage devices have made computer-based recording of polysomnograms (PSGs) very attractive. Digital PSGs offer the possibility of automating many tedious and time-consuming tasks of identifying sleep related events. Automation not only alleviates these laborious tasks, but also introduces a measure of objectivity in the scoring of various discrete events. In this paper we briefly review some automatic methods that have been previously developed by the authors. Automatic sleep staging methods is emphasized with some illustrative results on inter-scorer variations. We also discuss the leg movement event, respiratory event, sleep spindle and rapid-eye-movement detection methods.


Consensus of the Brazilian Headache Society (SBCe) for prophylactic treatment of episodic migraine: part II.
Migraine affects 1 billion people worldwide and > 30 million Brazilians; besides, it is an underdiagnosed and undertreated disorder. The need to disseminate knowledge about the prophylactic treatment of migraine is known, so the Brazilian Headache Society (SBCe, in the Portuguese acronym) appointed a committee of authors with the objective of establishing a consensus with recommendations on the prophylactic treatment of episodic migraine based on articles from the world literature as well as from personal experience. Meetings were held entirely online, with the participation of 12 groups that reviewed and wrote about the pharmacological categories of drugs and, at the end, met to read and finish the document. The drug classes studied in part II of this Consensus were: antihypertensives, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, calcium channel blockers, other drugs, and rational polytherapy. From this list of drugs, only candesartan has been established as effective in controlling episodic migraine. Flunarizine, venlafaxine, duloxetine, and pizotifen were defined as likely to be effective, while lisinopril, enalapril, escitalopram, fluvoxamine, quetiapine, atorvastatin, simvastatin, cyproheptadine, and melatonin were possibly effective in prophylaxis of the disease. Despite an effort by the scientific community to find really effective drugs in the treatment of migraine, given the large number of drugs tested for this purpose, we still have few therapeutic options.


CD44 promotes cell proliferation in non-small cell lung cancer.
Cluster of differentiation 44 (CD44), a marker for cancer stem cells, has been reported to be associated with poor prognosis in non-small cell lung cancer (NSCLC), but its involvement in tumor growth has not fully been elucidated. The present study explored the associations between CD44 expression and clinicopathological features using immunohistochemistry in 94 NSCLC cases, as well as proliferation in cells with aberrant expression of this protein. Overexpression of CD44 was achieved by transfecting H1299 cells with CD44 expression vectors, and inhibition of CD44 expression was performed by transfecting small interfering RNAs into A549 cells. Cell proliferation was measured using Cell Counting Kit-8 assays and flat plate colony formation assay was performed to confirm the cellular anchorage growth in vitro. In total, 64 (68.1%) of the 94 NSCLC cases stained positive for CD44 expression. High expression of CD44 was associated with advanced T stage in NSCLC. Overexpression of CD44 in H1299 cells promoted cell proliferation and colony formation in vitro. Meanwhile, knockdown of CD44 expression in A549 cells suppressed cell proliferation and colony formation in vitro. High expression of CD44 may promote NSCLC progression by increasing cancer cell proliferation; therefore, it may serve as a potential biomarker for diagnosis or target therapy.


Highly recurrent H3F3A mutations with additional epigenetic regulator alterations in giant cell tumor of bone.
Recurrent H3F3A and IDH2 mutations have been reported in giant cell tumor of bone (GCTB). However, the reported incidences have varied, and other molecular genetic alterations have not been identified due to the small number of cases analyzed with comprehensive methods. Moreover, the relative sensitivities of Sanger sequencing and next-generation sequencing (NGS) for the detection of H3F3A mutations in DNA extracted from archival formalin-fixed paraffin-embedded (FFPE) samples for clinical diagnosis have not been assessed. To address these issues, we conducted whole-exome sequencing of 7 GCTBs and integrated the previously published genomic sequencing data of 6 GCTBs. We subsequently performed targeted sequencing of an additional 39 GCTBs, including 2 atypical cases and an extremely rare case of primary malignant transformation of GCTB. We also evaluated the sensitivity of Sanger sequencing for detecting H3F3A mutations in FFPE samples that are usually used for clinical diagnosis. H3F3A glycine hotspot mutations were the most frequently detected mutations (96%) in the 52 GCTBs by NGS. Of the 50 hotspot mutations, p.G34W was observed in 48 cases and p.G34L/G34R was detected in one. One of two atypical GCTB cases with wild-type H3F3A had a H3F3B mutation (p.G34V). Other mutated genes were not recurrent. Sanger sequencing did not detect H3F3A mutations in 10 of 15 H3F3A NGS mutation-positive FFPE samples. In conclusion, we confirmed that H3F3A is the most frequently mutated GCTB driver gene, and that H3F3A mutations are not present in atypical GCTBs. Sanger sequencing was much less sensitive than targeted NGS for detecting H3F3A mutations in FFPE samples.


Sensory Impairments and Cognitive Function in Middle-Aged Adults.
Hearing, visual, and olfactory impairments have been associated with cognitive impairment in older adults but less is known about associations with cognitive function in middle-aged adults. Sensory and cognitive functions were measured on participants in the baseline examination (2005-2008) of the Beaver Dam Offspring Study. Cognitive function was measured with the Trail Making tests A (TMTA) and B (TMTB) and the Grooved Peg Board test. Pure-tone audiometry, Pelli-Robson letter charts, and the San Diego Odor Identification test were used to measure hearing, contrast sensitivity, and olfaction, respectively. There were 2,836 participants aged 21-84 years with measures of hearing, visual, olfactory, and cognitive function at the baseline examination. Nineteen percent of the cohort had one sensory impairment and 3% had multiple sensory impairments. In multivariable adjusted linear regression models that included all three sensory impairments, hearing impairment, visual impairment, and olfactory impairment were each independently associated with poorer performance on the TMTA, TMTB, and Grooved Peg Board (p < .05 for all sensory impairments in all models). Participants with a sensory impairment took on average from 2 to 10 seconds longer than participants without the corresponding sensory impairment to complete these tests. Results were similar in models that included adjustment for hearing aid use. Hearing, visual and olfactory impairment were associated with poorer performance on cognitive function tests independent of the other sensory impairments and factors associated with cognition. Sensory impairments in midlife are associated with subtle deficits in cognitive function which may be indicative of early brain aging.


Mitochondrial toxicity: myths and facts.
Nucleoside analogue reverse transcriptase inhibitors (NRTIs) represent key components of the antiretroviral combinations used to manage HIV infection. A range of nucleoside analogues are currently available which differ in their convenience of administration, frequency of dosing, resistance profile and frequency and severity of adverse effects. Many of the important and treatment limiting side-effects of nucleoside analogues have been suggested to be related to the impact of these agents on mitochondrial DNA polymerase gamma. Depletion of mitochondrial DNA or impacts of these agents on mitochondrial enzymes during chronic nucleoside analogue therapy may lead to cellular respiratory dysfunction and both generalised and tissue specific toxicities. In particular, fatal lactic acidosis represents a rare but clinically important manifestation of nucleoside analogue induced mitochondrial dysfunction. Other potentially severe toxicities which are well-characterised include peripheral neuropathy (PN) and myopathy. Management of potentially mitochondrial toxicity during nucleoside analogue therapy remains a challenge. A range of nutritional supplements, both as treatments and prophylaxes have been proposed and some investigated in vitro but not as yet in vivo. At present, therefore, interruption of nucleoside analogue therapy, or substitution of the probable causative agent with nucleoside analogues which appear better tolerated represent the mainstay of management.


Microfilamentous carcinoid of the thymus: correlation of ultrastructural study with Grimelius stain.
We observed a carcinoid of the thymus that was remarkable for the presence of intracytoplasmic inclusions-readily visible by light microscopy-in the majority of tumor cells. The inclusions were best seen in Grimelius-stained preparations, which also revealed argyrophilic granules present within or close to the masses. On electron microscope examination the inclusions were found to be composed of aggregates of filaments, probably of the intermediate type, which were at times accompanied by neurosecretory granules. The observed incompatibility between the presence of such inclusions and a homogeneous distribution of secretory granules in the cytoplasm is suggestive of a dysfunction of intracellular movements. Microfilamentous carcinoids may represent a class of tumor having a pathologic excretory process.


Evaluation of metabolic response with 18F-FDG PET-CT in patients with advanced or recurrent thymic epithelial tumors.
Patients with advanced or recurrent thymic epithelial tumors (TETs) often need several consecutive lines of chemotherapy. The aim of this retrospective monocentric study was to test whether 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) is able to monitor standard chemotherapy efficacy in those patients and whether metabolic response correlates with morphovolumetric response as assessed by Response Evaluation Criteria in Solid Tumor (RECIST). We evaluated 27 consecutive patients with advanced (16 patients) or recurrent (11 patients) TETs. All patients underwent 18F-FDG PET-CT before and after at least 3 cycles of chemotherapy. Maximum standardized uptake value (SUVmax) of all detected lesions was recorded and the most 18F-FDG avid lesion in each patient was selected for determination of percentage change of SUVmax (ΔSUVmax) in pre- and post-treatment scans. Tumor response was assessed by contrast-enhanced computed tomography (CE-CT) using RECIST criteria. Receiver operating characteristic (ROC) curve analysis was performed to define the optimal threshold of ΔSUVmax discriminating responders from non-responders. Metabolic response expressed as ΔSUVmax was significantly correlated with morphovolumetric response (Spearman's rank correlation, r = 0.64, p = 0.001). ROC curve analysis showed that a ΔSUVmax value of -25% could discriminate responders from non-responders with a sensitivity of 88% and a specificity of 80%. Conversely, basal SUVmax values were not predictive of morphovolumetric tumor response. Our findings indicate that metabolic response assessed by 18F-FDG PET-CT, through evaluation of ΔSUVmax, may allow identification of responders and non-responders thus guiding adaptation of therapy in patients with advanced or recurrent TETs.


Instability-enhanced collisional friction can determine the Bohm criterion in multiple-ion-species plasmas.
A generalized Lenard-Balescu theory that accounts for instability-enhanced collective responses is used to calculate the collisional friction between ion species in the plasma-boundary transition region (presheath). Ion-ion streaming instabilities are shown to cause such a strong frictional force that the relative flow speed between ion species cannot significantly exceed the critical threshold value (DeltaV(c)) at which instability onset occurs. When combined with the Bohm criterion, this condition uniquely determines the flow speed of each ion species at the plasma-sheath boundary. For cold ions, DeltaV(c) --> 0 and each ion species leaves the plasma at a common system sound speed c(s).


Cell wall integrity modulates RHO1 activity via the exchange factor ROM2.
The essential phosphatidylinositol kinase homologue TOR2 of Saccharomyces cerevisiae controls the actin cytoskeleton by activating a GTPase switch consisting of RHO1 (GTPase), ROM2 (GEF) and SAC7 (GAP). We have identified two mutations, rot1-1 and rot2-1, that suppress the loss of TOR2 and are synthetic-lethal. The wild-type ROT1 and ROT2 genes and a multicopy suppressor, BIG1, were isolated by their ability to rescue the rot1-1 rot2-1 double mutant. ROT2 encodes glucosidase II, and ROT1 and BIG1 encode novel proteins. We present evidence that cell wall defects activate RHO1. First, rot1, rot2, big1, cwh41, gas1 and fks1 mutations all confer cell wall defects and suppress tor2(ts). Second, destabilizing the cell wall by supplementing the growth medium with 0.005% SDS also suppresses a tor2(ts) mutation. Third, disturbing the cell wall with SDS or a rot1, rot2, big1, cwh41, gas1 or fks1 mutation increases GDP/GTP exchange activity toward RHO1. These results suggest that cell wall defects suppress a tor2 mutation by activating RHO1 independently of TOR2, thereby inducing TOR2-independent polarization of the actin cytoskeleton and cell wall synthesis. Activation of RHO1, a subunit of the cell wall synthesis enzyme glucan synthase, by a cell wall alteration would ensure that cell wall synthesis occurs only when and where needed. The mechanism of RHO1 activation by a cell wall alteration is via the exchange factor ROM2 and could be analogous to signalling by integrin receptors in mammalian cells.


Nutrition and human milk.
The nutritional composition of human milk is specifically suited to the needs of the human infant. In addition to eliminating the chance for contamination, human milk provides active protection against infection, and breast-fed babies have fewer metabolic anomalies and are less subject to allergy than formula-fed babies.


The Relationship Between Core Members' Social Capital and Perceived and Externally Evaluated Prestige and Cooperation Among HIV/AIDS-Related Civil Society Organizations in China.
The purpose of this study was to investigate whether the core members' social capital was associated with individually perceived and externally evaluated prestige and cooperation among the HIV/AIDS-related civil society organizations (CSOs). To accomplish this, a cross-sectional study using multistage sampling was carried out in eight provinces of China. Data were collected from the 327 core members via questionnaires and self-evaluated performance of the respondents were evaluated and measured. The interviews were conducted with all core members and the supervisory staff of the local Centers for Disease Control and Prevention. Multivariate logistic regression analysis indicated that social support (adjusted odds ratio [a OR] = 1.87) and organizational commitment (a OR = 1.57) were significantly associated with a higher odds of prestige performance in self-evaluation. Furthermore, social support (a OR = 1.65), trust (a OR = 1.33), and organizational commitment (a OR = 1.52) were significantly correlated with cooperation performance. Trust was positively associated with the cooperation performance on external evaluation. These findings may provide a new perspective on challenges that the CSOs face in response to a growing HIV/AIDS epidemic in China. Social capital may increase performance and accelerate organizational growth, ultimately improving HIV/AIDS prevention and care.


Drug entrapment in silica microspheres through a single step sol-gel process and in vitro release behavior.
A single step sol-gel process was used to precipitate silica microspheres containing ibuprofen or naproxen for controlled drug delivery applications. The drug release behavior from these systems was analyzed in vitro. Pure ibuprofen and naproxen exhibited linear release with time, while sol-gel silica entrapped drugs were released with a logarithmic time dependence starting with an initial burst effect followed by a gradual decrease. Microscopic analysis combined with gravimety and infrared spectroscopy indicated that some of the drug is entrapped as large crystals attached to silica microspheres while the rest is encapsulated inside the microspheres. Drug-loaded silica microspheres with no open porosity and with a narrow particle size distribution were obtained. Both erosion of the microspheres and diffusion through them contributed to drug release. Sol-gel precipitation of silica microspheres is a promising method for drug entrapment and controlled release.


Chiral Lithiated Allylic α-Sulfonyl Carbanions: Experimental and Computational Study of Their Structure, Configurational Stability, and Enantioselective Synthesis.
X-ray crystal structure analysis of the lithiated allylic α-sulfonyl carbanions [CH2 CHC(Me)SO2 Ph]Li⋅diglyme, [cC6 H8 SO2 tBu]Li⋅PMDETA and [cC7 H10 SO2 tBu]Li⋅PMDETA showed dimeric and monomeric CIPs, having nearly planar anionic C atoms, only OLi bonds, almost planar allylic units with strong CC bond length alternation and the s-trans conformation around C1C2. They adopt a C1S conformation, which is similar to the one generally found for alkyl and aryl substituted α-sulfonyl carbanions. Cryoscopy of [EtCHCHC(Et)SO2 tBu]Li in THF at 164 K revealed an equilibrium between monomers and dimers in a ratio of 83:17, which is similar to the one found by low temperature NMR spectroscopy. According to NMR spectroscopy the lone-pair orbital at C1 strongly interacts with the CC double bond. Low temperature (6) Li,(1) H NOE experiments of [EtCHCHC(Et)SO2 tBu]Li in THF point to an equilibrium between monomeric CIPs having only OLi bonds and CIPs having both OLi and C1Li bonds. Ab initio calculation of [MeCHCHC(Me)SO2 Me]Li⋅(Me2 O)2 gave three isomeric CIPs having the s-trans conformation and three isomeric CIPs having the s-cis conformation around the C1C2 bond. All s-trans isomers are more stable than the s-cis isomers. At all levels of theory the s-trans isomer having OLi and C1Li bonds is the most stable one followed by the isomer which has two OLi bonds. The allylic unit of the C,O,Li isomer shows strong bond length alternation and the C1 atom is in contrast to the O,Li isomer significantly pyramidalized. According to NBO analysis of the s-trans and s-cis isomers, the interaction of the lone pair at C1 with the π* orbital of the CC double bond is energetically much more favorable than that with the "empty" orbitals at the Li atom. The C1S and C1C2 conformations are determined by the stereoelectronic effects nC -σSR * interaction and allylic conjugation. (1) H DNMR spectroscopy of racemic [EtCHCHC(Et)SO2 tBu]Li, [iPrCHCHC(iPr)SO2 tBu]Li and [EtCHC(Me)C(Et)SO2 tBu]Li in [D8 ]THF gave estimated barriers of enantiomerization of ΔG(≠) =13.2 kcal mol(-1) (270 K), 14.2 kcal mol(-1) (291 K) and 14.2 kcal mol(-1) (295 K), respectively. Deprotonation of sulfone (R)-EtCHCHCH(Et)SO2 tBu (94 % ee) with nBuLi in THF at -105 °C occurred with a calculated enantioselectivity of 93 % ee and gave carbanion (M)-[EtCHCHC(Et)SO2 tBu]Li, the deuteration and alkylation of which with CF3 CO2 D and MeOCH2 I, respectively, proceeded with high enantioselectivities. Time-dependent deuteration of the enantioenriched carbanion (M)-[EtCHCHC(Et)SO2 tBu]Li in THF gave a racemization barrier of ΔG(≠) =12.5 kcal mol(-1) (168 K), which translates to a calculated half-time of racemization of t1/2 =12 min at -105 °C.


A Meta-Analysis of Randomized Controlled Trials Concerning the Efficacy of Transversus Abdominis Plane Block for Pain Control After Laparoscopic Cholecystectomy.
Background and Purpose: Transverse abdominis plane (TAP) block has been suggested to reduce post-operative pain after laparoscopic cholecystectomy (LC). However, the literature is divided on whether ultrasound (USG)-guided TAP block is effective for pain control after LC. The present meta-analysis therefore evaluated the efficacy of USG-guided TAP block vs. controls and port site infiltration for pain control after LC. Methods: A comprehensive literature search of online academic databases was performed for published randomized controlled trials (RCTs) for studies published to January 31, 2021. The primary outcome analyzed was post-operative pain score at 0, 6, 12, and 24 h post-surgery, both during rest and while coughing. Secondary outcomes included morphine consumption and post-operative nausea and vomiting (PONV) incidence. Results: A total of 23 studies with data on 1,450 LC patients were included in our meta-analysis. A reduction in pain intensity at certain post-operative timepoints was observed for USG-guided TAP block patients compared to control group patients. No reduction in pain intensity was observed for patients receiving USG-guided TAP block patients vs. conventional Port site infiltration. Conclusion: This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings.


Low isolated ferritin levels without anemia: is gastrointestinal tract endoscopy sufficient to explain the cause?
The present study assesses the diagnostic significance of low ferritin levels in gastrointestinal diseases by evaluating the endoscopic findings of patients with low ferritin levels without anemia. The study included patients aged 0-18 years who underwent an upper and lower gastrointestinal system endoscopy in the Pediatric Gastroenterology Department of our hospital. The patients were divided into three groups based on hemoglobin, and ferritin levels at the time of initial presentation and endoscopic and histopathological findings were recorded retrospectively. In the present study, 2391 pediatric patients were reviewed, among which 29% (n = 699) had anemia, 23% (n = 549) had low ferritin levels without anemia, and 48% (n = 1143) did not have anemia. The most common symptoms were abdominal pain, dyspepsia, and growth retardation. When the endoscopy findings were compared with those of patients with non-anemic group, Helicobacter pylori gastritis (24%/17.6%) and celiac disease (6%/2.2%) were more common in low ferritin levels without anemia, which indicated a statistically significant difference (p = 0.000/p = 0.04). Helicobacter pylori gastritis and celiac disease were more commonly observed in association with low ferritin levels. Low ferritin levels without anemia can be an early and silent sign of celiac disease.


Should we apply sorafenib in hepatocellular carcinoma patients with microvascular invasion after curative hepatectomy?
Microvascular invasion (MVI) has been proved to be an independent risk factor for the recurrence of HCC. If promptly treated, the recurrence rate can be reduced and the total survival time can be prolonged. The aim of this study is to analyze the effect of sorafenib on the clinical outcomes in HCC patients with MVI after curative hepatectomy. HCC patients who underwent hepatectomy and were pathologically diagnosed with MVI were retrospectively analyzed. Patients were divided into sorafenib group and control group. Sorafenib 400 mg, twice daily, was administered orally after surgery in the sorafenib group. The recurrence-free survival (RFS) and overall survival (OS) were observed during follow-up, and associated factors were analyzed using univariate and multivariate COX regression. There was no significant difference in demographics, clinical staging, and tumor index between sorafenib group (16 patients) and control group (33 matched patients). The RFS and OS were both longer in the sorafenib group, and the 3-years RFS rates of the sorafenib group and control group were 56.3% (9 of 16) and 24.2% (8 of 33), respectively (P=0.027). The 3-year OS rate of the sorafenib group was 81.3% (13 of 16), which was significantly higher than that of the control group (39.4%, P=0.006). The results of multivariate COX regression indicated that treatment with sorafenib was an independent associated factor for RFS and OS. We believe that using sorafenib therapy after curative hepatectomy in HCC patients with MVI is effective and beneficial as it can reduce recurrence and prolong the survival time.


Recurrent Laryngeal Nerve Injury In Total Versus Subtotal Thyroidectomy.
Both Total and Subtotal Thyroidectomy are correct treatment options for symptomatic Euthyroid Multinodular Goitre. The choice depends upon surgeon's preference due to consideration of disadvantages like permanent hypothyroidism in Total Thyroidectomy and high chances of recurrence in Subtotal Thyroidectomy. Many surgeons believe that there is a higher incidence of Recurrent Laryngeal nerve injury in Total Thyroidectomy which affects their choice of surgery. This study aimed to compare the incidence of recurrent laryngeal nerve injury in total versus subtotal thyroidectomy. This non randomized controlled trial was carried out at Department of Surgery and ENT of Ayub Teaching Hospital Abbottabad, and Combined Military Hospital Rawalpindi from 1st September 2013 to 30th August 2014. During the period of study, patients presenting in surgical outpatient department with euthyroid multinodular goitre having pressure symptoms requiring thyroidectomy were divided into two groups by convenience sampling with 87 patients in group 1 and 90 patients in group 2. Group-1 was subjected to total thyroidectomy and Group -2 underwent subtotal thyroidectomy. All the patients had preoperative Indirect Laryngoscopy examination and it was repeated postoperatively to check for injury to the recurrent laryngeal nerve. A total of 177 patients were included in the study. Out of these, 87 patients underwent total thyroidectomy (Group-1). Two of these patients developed recurrent laryngeal nerve injury (2.3%). In group-2 subjected to subtotal thyroidectomy, three of the patients developed recurrent laryngeal nerve injury (3.3%). The p-value was 0.678. The overall risk of injury to this nerve in both surgeries combined was 2.8%. There is no significant difference in the risk of recurrent laryngeal nerve damage in patients undergoing total versus subtotal thyroidectomy.


Evolution of a rare vaccine-derived multirecombinant poliovirus.
Recombination is one of the mechanisms by which viral genomes evolve. A vaccine-derived multirecombinant poliovirus strain was isolated from a 5-month-old child with vaccine-associated paralytic poliomyelitis after oral poliovirus vaccine administration. The isolate had an S2/S1/S2/S1 primary genomic structure as revealed by restriction fragment length polymorphism and sequencing analysis. Recombination of the middle S1/S2 region is extremely rare and one of the few characterized types of recombination with Sabin type 1 as a 5' partner. An attempt was made to perform evolutionary analysis of the contributing sequences using the identified mutations in comparison with the original Sabin sequences. A hypothesis is proposed for the order in which the identified recombination events occurred.


Development of a system to study CD4+-T-cell responses to transgenic ovalbumin-expressing Toxoplasma gondii during toxoplasmosis.
The study of the immune response to Toxoplasma gondii has provided numerous insights into the role of T cells in resistance to intracellular infections. However, the complexity of this eukaryote pathogen has made it difficult to characterize immunodominant epitopes that would allow the identification of T cells with a known specificity for parasite antigens. As a consequence, analysis of T-cell responses to T. gondii has been based on characterization of the percentage of T cells that express an activated phenotype during infection and on the ability of these cells to produce cytokines in response to complex mixtures of parasite antigens. In order to study specific CD4(+) T cells responses to T. gondii, recombinant parasites that express a truncated ovalbumin (OVA) protein, in either a cytosolic or a secreted form, were engineered. In vitro and in vivo studies reveal that transgenic parasites expressing secreted OVA are able to stimulate T-cell receptor-transgenic OVA-specific CD4(+) T cells to proliferate, express an activated phenotype, and produce gamma interferon (IFN-gamma). Furthermore, the adoptive transfer of OVA-specific T cells into IFN-gamma(-/-) mice provided enhanced protection against infection with the OVA-transgenic (but not parental) parasites. Together, these studies establish the utility of this transgenic system to study CD4(+)-T-cell responses during toxoplasmosis.


Multi-segment analysis of spinal kinematics during sit-to-stand in patients with chronic low back pain.
While alterations in spinal kinematics have been frequently reported in patients with chronic low back pain (CLBP), a better characterization of the kinematics during functional activities is needed to improve our understanding and therapeutic solutions for this condition. Recent studies on healthy subjects showed the value of analyzing the spine during sit-to-stand transition (STST) using multi-segment models, suggesting that additional knowledge could be gained by conducting similar assessments in CLBP patients. The objectives of this study were to characterize three dimensional kinematics at the lower lumbar (LLS), upper lumbar (ULS), lower thoracic (LTS) and upper thoracic (UTS) joints during STST, and to test the hypothesis that CLBP patients perform this movement with smaller angle and angular velocity compared to asymptomatic controls. Ten CLBP patients (with minimal to moderate disability) and 11 asymptomatic controls with comparable demographics (52% male, 37.4±5.6 years old, 22.5±2.8kg/m(2)) were tested using a three-dimensional camera-based system following previously proposed protocols. Characteristic patterns of movement were identified at the LLS, ULS and UTS joints in the sagittal plane only. Significant differences in the form of smaller sagittal-plane angle and smaller angular velocity in the patient group compared to the control group were observed at these three joints. This indicated a more rigid spine in the patient group and suggested that CLBP rehabilitation could potentially be enhanced by targeting movement deficits in functional activities. The results further recommended the analysis of STST kinematics using a pelvis-lumbar-thoracic model including lower and upper lumbar and thoracic segments.


How Essential Is to Focus on Physician's Health and Burnout in Coronavirus (COVID-19) Pandemic?
An infection of novel coronavirus (COVID-19) that originated from Wuhan city of China in December 2019 converted rapidly into pandemic by March 11, 2020. To date, the number of confirmed cases and deaths has risen exponentially in more than 200 countries, with an estimated crude mortality ratio of at least over 2%. The unpreparedness to tackle the unprecedented situation of coronavirus has contributed to the rising number of cases, which has generated an immense sense of fear and anxiety amongst the public. It has further resulted in the inadequacy and unavailability of essential medical supplies, physicians, and healthcare workers (HCW). Although the chief focus is on minimizing transmission through prevention, combating infection, and saving lives by ramping up the development of treatment and vaccines, very little attention is on the critical issue of physician burnout, resident burnout, and the psychological well-being of HCW. Until now, no significant steps have been taken by the authorities to minimize the COVID-19 specific contributing factors for burnout. The COVID-19 has posed strain on the entire healthcare system already, and it is vital to remediate the issue of physician and resident burnout urgently with concrete actions to avoid subsequent potential short-term and long-term adverse implications.


Mental health of Automobile Transportation Troop personnel stationed in the Western Sichuan Plateau of China.
This study investigated the mental health of military transport personnel in the Western Sichuan Plateau of China, and factors that correlate with their mental health.The Symptom Checklist 90 (SCL-90) was used to investigate the mental health status of the subjects. Their scores were compared with the national and military norm in China. Demographic factors were analyzed for associations with SCL-90 scores.Psychological problems were detected in 28.90% of total 1076 male officers and soldiers surveyed. The SCL-90 scale somatization score of these servicemen was higher than the national and military norms in China, while other scores were comparable. The reported physical health symptoms and being an only child were strongly associated with the SCL-90 scores.The mental health of military transport personnel in the China Western Sichuan Plateau should receive more attention.


Indications and alternatives to hysterectomy.
Hysterectomy is the commonest major operation performed by gynaecologists and is the definitive cure for many of it's indications which include dysfunctional uterine bleeding, fibroids, utero-vaginal prolapse, endometriosis and adenomyosis, pelvic inflammatory disease, pelvic pain, gynaecological cancers and obstetric complications. It is a successful operation in terms of relieving women of their presenting symptoms and high levels of satisfaction are reported by patients. However, it has a high risk of complications, involves a prolonged convalescence, is expensive and to some women represents a loss of femininity. It should only be employed after trying conservative treatments first if appropriate. If this fails, currently only endometrial ablation and myomectomy are valid alternatives to hysterectomy. If ultimately hysterectomy is required, there is considerable evidence that patient care can be improved by increasing the proportion of operations that are done vaginally and laparoscopically and decreasing the number of laparotomies.


Five year maintenance of the inducible expression of anthranilate synthase in Catharanthus roseus hairy roots.
Transgenic hairy root cultures have the potential to be an industrial production platform for a variety of chemicals. This report demonstrates the long-term stability of a transgenic Catharanthus roseus hairy root line containing the inducible expression of a feedback-insensitive anthranilate synthase (AS). After 5 years in liquid culture, the presence of the inserted AS gene was confirmed by genomic PCR. The inducible expression of AS was confirmed by enzyme assay and by changes in terpenoid indole alkaloid concentrations. This report also demonstrates that it may take as long as 2 years for the metabolite profile to stabilize.


[Clinical picture and treatment of the Raynaud syndrome of the upper extremities].
Raynaud's disease occurs in different clinical forms, which are not specific to the vascular spasm which characterizes the disease. This spasm virtually always develops in the same manner. Clinical aspects depend on the underlying pathology, which will define treatment. Therapeutic efficacy in Raynaud's disease is discussed. Current interest focuses on serotonin antagonists.


The impact of team-based primary care on health care services utilization and costs: Quebec's family medicine groups.
We investigate the effects on health care costs and utilization of team-based primary care delivery: Quebec's Family Medicine Groups (FMGs). FMGs include extended hours, patient enrolment and multidisciplinary teams, but they maintain the same remuneration scheme (fee-for-service) as outside FMGs. In contrast to previous studies, we examine the impacts of organizational changes in primary care settings in the absence of changes to provider payment and outside integrated care systems. We built a panel of administrative data of the population of elderly and chronically ill patients, characterizing all individuals as FMG enrollees or not. Participation in FMGs is voluntary and we address potential selection bias by matching on GP propensity scores, using inverse probability of treatment weights at the patient level, and then estimating difference-in-differences models. We also use appropriate modelling strategies to account for the distributions of health care cost and utilization data. We find that FMGs significantly decrease patients' health care services utilization and costs in outpatient settings relative to patients not in FMGs. The number of primary care visits decreased by 11% per patient per year among FMG enrolees and specialist visits declined by 6%. The declines in costs were of roughly equal magnitude. We found no evidence of an effect on hospitalizations, their associated costs, or the costs of ED visits. These results provide support for the idea that primary care organizational reforms can have impacts on the health care system in the absence of changes to physician payment mechanisms. The extent to which the decline in GP visits represents substitution with other primary care providers warrants further investigation.


[Isolation and structure of 6'-O-caffeylerigeroside from Erigeron multiradiatus].
The plant, Erigeron multiradiatus (Wall.) Benth(Family: Compositae), is a perennial herb distributed abundantly in the mountainous area of the southwestern part in China. It is used in folk medicine for the treatment of common cold, panting cough, rheumatic, enteritis and toothache. In this paper, we report a new glycoside named as 6'-O-caffeylerigeroside isolated from Erigeron Multiradiatus (Family: Compositae) together with four known compounds. The known compounds were identified as pyromeconic acid(I), scopoletin(II), 4-hydroxybenzoic acid(III) and vanillic acid(IV). The structure of 6'-O-caffeylerigeroside was elucidated as gamma-pyrone-3-O-[6"-(3',4'-dihydroxy-cinnamoyl)]-beta-D-glucoside(V) on the basis of chemical evidence and spectral data.


[Thrombotic thrombocytopenic purpura in patients with systemic lupus erythematosus].
Although not common, thrombotic thrombocytopenic purpura (TTP) is one of the most serious complications in patients with systemic lupus erythematosus (SLE). This study aimed to characterize the association between SLE and TTP by examining clinical features and treatment outcomes. We evaluated eight patients diagnosed over two years in our hospital. The mean disease duration of SLE until TTP onset was 13.2 years. One patient had a simultaneous diagnosis of SLE and TTP. CNS lupus and lupus nephritis were involved in 6 patients, respectively. The mean value of the SLE disease activity index was 40.5. Five out of 7 patients who have been examined the von Willebrand factor cleaving protease showed moderately decreased activity. Seven out of the 8 patients were treated with plasmapheresis, and 7 received immunosuppressive therapy including cyclophosphamide and rituximab. Seven patients recovered, but one died from an exacerbation of the disease. These data indicated that plasmapheresis and immunosuppressive therapy improved prognosis of TTP associated with SLE.


A perspective on paper-based microfluidics: Current status and future trends.
"Paper-based microfluidics" or "lab on paper," as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors' point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system may take in its development.


Carcinogen exposure enhances cancer immunogenicity by blocking the development of an immunosuppressive tumor microenvironment.
Carcinogen exposure is strongly associated with enhanced cancer immunogenicity. Increased tumor mutational burden and resulting neoantigen generation have been proposed to link carcinogen exposure and cancer immunogenicity. However, the neoantigen-independent immunological impact of carcinogen exposure on cancer is unknown. Here, we demonstrate that chemical carcinogen-exposed cancer cells fail to establish an immunosuppressive tumor microenvironment (TME), resulting in their T cell-mediated rejection in vivo. A chemical carcinogen-treated breast cancer cell clone that lacked any additional coding region mutations (i.e., neoantigen) was rejected in mice in a T cell-dependent manner. Strikingly, the coinjection of carcinogen- and control-treated cancer cells prevented this rejection, suggesting that the loss of immunosuppressive TME was the dominant cause of rejection. Reduced M-CSF expression by carcinogen-treated cancer cells significantly suppressed tumor-associated macrophages (TAMs) and resulted in the loss of an immunosuppressive TME. Single-cell analysis of human lung cancers revealed a significant reduction in the immunosuppressive TAMs in former smokers compared with individuals who had never smoked. These findings demonstrate that carcinogen exposure impairs the development of an immunosuppressive TME and indicate a novel link between carcinogens and cancer immunogenicity.


Derealization during utricular stimulation.
Feelings of unreality have been provoked in healthy subjects undergoing stimulation of the semicircular canals, but no studies have assessed the influence of otoliths stimulation on depersonalization/derealization (DD) symptoms. To assess DD symptoms during unilateral centrifugation in healthy adults. 100 subjects participated in the study. They completed a standardized questionnaire of symptoms related to balance (Jáuregui-Renaud 2003), the 17-item Hamilton Depression Rating Scale, the Zung Instrument for Anxiety Disorders and the Cox & Swinson 28-item DD inventory. After unilateral centrifugation (300°/s at 3.5 cm), subjects completed the DD inventory again. Centrifugation provoked symptoms which subjects denied ever experiencing before. The items most frequently reported were "Body feels strange or different in some way" (56%) and "Time seems to pass very slowly" (55%). The DD total score was related to the score of symptoms related to balance and to the depression inventory with no influence from the general characteristics of the subjects or the responses to vestibular tests. The individual scores of symptoms of vestibular function and derealization were related to the report of the other DD symptoms. In healthy subjects, unilateral centrifugation provokes DD symptoms. The results support that distorted vestibular signals may create a misleading frame of reference which mismatch with the other senses, giving rise to 'unreal' perceptions.


Diffuse pneumocephalus in neonatal Citrobacter meningitis.
Pneumocephalus, intracranial air or gas collection, associated with neonatal meningitis is extremely rare. We report the first case in the United States and the second case in the world of intracranial gas accumulation in a neonate with Citrobacter koseri meningitis. The clinical presentation was acute with pneumocephalus demonstrated by cranial sonography and computed tomography. The clinical course was fatal despite the prompt administration of antibiotics.


A proposal for teaching basic clinical skills for mastery: the case against vertical integration.
The authors argue that medical school faculty should (1) make a distinction among competencies that they feel need to be taught for mastery (i.e., at a level of proficiency expected from a practicing physician) and those that should be taught at lower levels of proficiency, and (2) impart the former competencies in single teaching units. The authors propose that the skills that students should be expected to master include patient interviewing, physical examination, patient counseling on health promotion and disease prevention (HP/DP), and self-directed learning. The concepts of a hypothetical teaching unit that aims to impart these skills are described. By the end of this unit, the students would be expected to (1) examine simulated and real patients to detect risk indicators and physical findings for the diseases that are the most common causes of death in the patient's gender and age group, and to look for risk indicators and physical findings for diseases where early diagnosis and treatment have been shown to reduce mortality for such patients, and (2) provide counseling for lifestyle changes and future clinical examinations. The authors believe that the objective of acquiring an ability to counsel a patient on HP/DP at the level of competence of a practicing physician will motivate students to acquire the skills of patient interviewing, physical examination, and self-directed learning more effectively than would a succession of reinforcements of these subjects throughout the curriculum.


Volume and characteristics of inpatient and ambulatory medical care for neck pain in the United States: data from three national surveys.
Secondary analysis of national survey data. To describe the volume and characteristics of outpatient visits to physician offices, hospital outpatient departments and emergency departments, and inpatient hospital utilization for neck pain in the United States. We also examined the use of pathology-based versus symptom-based diagnoses on a national scale. Descriptions of the epidemiology of neck pain will assist policy makers and clinicians in understanding the impact of neck pain on society. Analysis of combined survey data from the 2001 and 2002 National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey, and National Hospital Discharge Survey, from the Centers for Disease Control and Prevention/National Center for Health Statistics. During 2001 and 2002, an average of 10.2 million visits were made annually. At 64% of visits, a symptom-based diagnosis was used. An annual average of 179,000 hospital discharges for neck pain was recorded and 94% received a pathology-based diagnosis. Most (79%) had surgery for the neck problem. Outpatient visits for neck pain are common in the United States, and the majority are given symptom-based rather than pathology-based diagnoses. An alternative diagnostic taxonomy may be needed to guide treatment, particularly for patients with vague, symptom-based diagnoses. Hospitalizations for neck pain often include surgical procedures, but 21% received no surgery.


A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish.
Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is, however, not expressed in systemic tissues, where there is high affinity RBP4 binding and ROL uptake. We tested the hypothesis that the second retinol binding protein 4 receptor 2 (Rbpr2), which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR-generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, which were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatment rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.


Dysregulation of TMPRSS3 and TNFRSF11B correlates with tumorigenesis and poor prognosis in patients with breast cancer.
The present study was carried out to investigate the clinical significance of TMPRSS3 and TNFRSF11B in breast cancer. Thus, the expression levels of TMPRSS3 and TNFRSF11B and the correlation with prognosis in patients with breast cancer were analyzed in silico using gene microarray and hierarchical clustering analysis. Then, the differential expression in breast cancer vs. normal breast tissue was explored in the Oncomine platform and verified in our independent samples using IHC technique. Our results indicated that TMPRSS3 was upregulated and TNFRSF11B was downregulated in breast cancer tissues compared with the levels in the human normal breast tissues. TMPRSS3 and TNFRSF11B were confirmed to be correlated with distant organ metastasis of breast cancer. Moreover, upregulation of TMPRSS3 accompanied by downregulation of TNFRSF11B was found to be associated with a shorter median overall survival and indicated a poor prognosis. In conclusion, TMPRSS3 and TNFRSF11B may have potential prognostic value to be used as tumor biomarkers in breast cancer patients.


Electrical Characteristics of Top-Gated Graphene Field Effect Transistors Fabricated on Stainless Steel (STS) Substrate.
Top-gated Graphene transistors with Al2O3 gate-dielectric on the flexible stainless steel substrate have been demonstrated. Graphene was synthesized on copper foil using a chemical vapor deposition method and transferred onto the stainless steel substrate by wet transfer technique. The stainless steel substrate was polished by chemical mechanical polishing method and the spin-on-glass layer was coated on the surface to improve the surface roughness. The average surface roughness R(a) was as low as 5.9 nm from the AFM measurement. The measured hole and electron mobilities from the current-voltage characteristics at room temperature were calculated as high as 310 and 45 cm2/Vs, respectively. In addition, the effect of surrounding temperature up to 355 K on the electrical variations was investigated. The mobility was inversely proportional to the temperature with negligible hysteresis where the temperature coefficient was calculated as low as -0.65 %/K.


Repetitive Deep TMS for Parkinson Disease: A 3-Month Double-Blind, Randomized Sham-Controlled Study.
To study the effects of a repetitive deep transcranial magnetic stimulation (rDTMS) in patients with Parkinson disease using the H5 coil for the low-frequency stimulation of the primary motor cortex, followed by the high-frequency rDTMS of the prefrontal cortex. The main outcome measures were the total and motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). Secondary measures included rating of depression and quantitative motor tasks. Forty-eight patients were randomized 1:1 into real or sham rDTMS treatment arms. Analyses (n = 42) of both UPDRS scores revealed a significant main effect for time between baseline and day 90 (end of treatment), indicating that there was an improvement of both scores over time in the whole sample. Although effects of treatment and time-by-treatment were insignificant, simple effects analysis of both measures was significant in the rDTMS group and reached a P-value of 0.06 in the sham group. The response rate was higher in patients with longer disease duration and higher motor UPDRS scores. Side effects were more common in the rDTMS group but were transient and tolerable. Although rDTMS treatment exhibited some motor improvements, we could not demonstrate an advantage for real treatment over sham. Further research is required to establish stimulation parameters that may induce potentially more beneficial outcomes, probably in patients with longer and more sever disease.


The faculty of pain medicine of the Australian and New Zealand college of anaesthetists - history and strategic plan.
Since its formation, the Faculty of Pain Medicine (FPM) has grown into an organization with 369 fellows. It has 29 accredited pain medicine training units in Australia, New Zealand, Hong Kong, and Singapore. This article reviews the history of its birth and subsequent growth. The FPM fellowship is widely recognized as a high-quality qualification, based on a sound curriculum, excellent clinical exposure, and robust continuing professional development. But how does the Faculty position itself for the future? The Faculty's 5-year Strategic Plan (from 2013 to 2017) sets out its vision "to reduce the burden of pain in society through education, advocacy, training and research."


Contrasting Effects of Inhibitors Li+ and Be2+ on Catalytic Cycle of Glycogen Synthase Kinase-3β.
Ionic lithium shows rare effectiveness for treating bipolar disorder and is a potential drug for neurodegenerative diseases. Unfortunately, lithium suffers from significant drawbacks, mainly a narrow therapeutic window. Among the targets of lithium, glycogen synthase kinase 3β (GSK-3β) may be responsible for its therapeutic effects. The development of alternative, selective inhibitors of this kinase could prevent lithium side effects, but such efforts have met little success so far. An atomistic understanding of Li+ inhibition and the GSK-3β phosphorylation reaction would therefore facilitate the development of new drugs. In this study, we use extensive sampling of catalytic states with our mixed quantum-classical dynamics method QM/DMD and binding affinities from a competitive metal affinity (CMA) approach to expand the atomistic picture of Li+ GSK-3β inhibition. We compare Li+ action with Be2+ and find our results in agreement with in vitro kinetics studies. Ultimately, our simulations show that Li+ inhibition is driven by decreasing the phosphorylation reaction rate, rather than reducing catalytic turnover through tight binding to different GSK-3β states like Be2+ inhibition. The effect of these metals derive from electrostatic differences and especially their smaller atomic radii compared to the native Mg2+ and thus provide insight for the development of GSK-3β inhibitors based on other paradigms.


Effectiveness of acupuncture and physiotherapy on myogenic headache: a comparative study.
Twenty-two tension-neck and headache patients were divided into acupuncture and physiotherapy groups. The quantity of muscle tension (motor unit potential spikes per time unit) was estimated three times before the beginning of the therapy, four times during a therapy period of four weeks, and two times during the follow-up period of 28 weeks. Pain level was also estimated using a visual analogue scale. In both of the groups a significant reduction of muscle tension was observed during the therapy period. After a follow-up period of 28 weeks, there was still a significant reduction of EMG activity in both groups. Also, the subjective level of headache decreased in these groups during the therapy period, and it was also significantly lowered after 28 weeks of follow-up. It is concluded that either acupuncture therapy or physiotherapy relieves pain in tension-neck and headache patients.


Steerable Induction of the Thymosin β4/MRTF-A Pathway via AAV-Based Overexpression Induces Therapeutic Neovascularization.
Viral vectors have been frequently used in a variety of preclinical animal models to deliver genetic constructs into tissues. Among the vectors used, adeno-associated viral vectors (AAVs) may be targeted to specific tissues, depending on the serotype used. Moreover, they show robust expression for prolonged periods of time and have a low immunogenic potential. Furthermore, AAVs, unlike other vector systems, only display a low rate of genomic integration. However, to ensure efficient transgene production, expression is typically driven by constitutively active promoters, such as the cytomegalovirus (CMV) promoter. Tetracyclin responsive promoters represent a promising alternative to unregulated promoters. The present study compares AAVs encoding either constitutively active CMV or tet-off promoter regions in the preclinical models of hindlimb and chronic myocardial ischemia. Therapeutically, mediators regulating vessel maturation, specifically thymosin beta 4 (Tβ4) and the downstream signaling molecule myocardin-related transcription factor A (MRTF-A) as well as the endothelial activator angiopoietin-2 (Ang2) were overexpressed via AAVs using both promotors. In the model of rabbit hindlimb ischemia, temporary (tet-off) expression of Tβ4 improved capillary density, collateralization, and perfusion in the ischemic hindlimb, with no detectable difference to constitutive Tβ4 overexpression. Similarly, constitutive overexpression of MRTF-A alone was able to improve capillarization, collateralization and perfusion. Temporary expression of Ang2 for 7 days further increased capillary density and pericyte coverage compared with MRTF-A alone, without further improving collateralization or perfusion. In the pig model of chronic myocardial ischemia constitutive expression of Tβ4 for 4 weeks induced capillary and collateral growth similarly to a pulsed expression (2 day expression per week for 3 weeks). Taken together these findings demonstrate for two models of preclinical interventions that temporary gene expression may lead to similar results as constitutive expression, highlighting the potential of controlled temporary gene expression for induction of vascular growth as a therapeutic approach.


The role of ethnic-racial and national identities on U.S. Latino adolescents' global identity coherence and adjustment.
Ethnic-racial minoritized adolescents are tasked with concurrently developing and balancing their ethnic-racial and national identities. The present study investigated the extent to which these two social identities were simultaneously associated with U.S. Latino adolescents' psychological adjustment via their associations with global identity coherence. This cross-sectional study included 370 self-identified Latino middle-to-late adolescents (Mage = 16.14 years; SD = 1.12; range: 14-18; 52.8% female; 96.2% U.S.-born; 50% had at least one foreign-born parent) who completed paper surveys in class. Structural equation path analyses with bias-corrected bootstrapping were conducted to test a theoretical mediational model of identity and adjustment. Findings indicated that each social identity component explained significant variance in adolescent psychological adjustment (i.e., lower depressive symptoms; higher life satisfaction and self-esteem) via its unique association with identity coherence (i.e., synthesis and confusion). Results generalized across adolescent gender but were qualified by family immigrant status (i.e., having no foreign-born parent vs. having at least one foreign-born parent). Additionally, there was no support for an alternate model with the order of predictors and mediators reversed. This study highlights the importance of multifaceted, multicomponent social identity development and exemplifies ways in which social position factors may set adolescents onto different developmental pathways. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Human colorectal malignancy and oral UFT.
Thymidylate synthase (EC 220.127.116.11) and thymidine kinase (EC 2.71.21) are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis. Both enzyme activities are increased in rapidly proliferating normal, fetal and neoplastic tissues. In a previous study, the activities of thymidylate synthase and thymidine kinase were relatively predominant in the poorly-and well-differentiated types of a gastric cancer. In the present study of patients with colorectal cancer, the serum thymidine kinase activities are elevated in cases at a clinically late stage, and in cases with a recurrence and a distant metastasis associated with abundant blood supply, i.e. metastasis to the liver, lung and bone. Well-differentiated colorectal cancer shows higher thymidine kinase activity than moderately-well-differentiated type as was previously shown in gastric cancer patients. Furthermore, neoadjuvant chemotherapy using the 5-fluorouracil derivative UFT demonstrates a stronger suppression of increased activities of thymidylate synthase in the tumorous tissues than in the non-tumorous mucosa.


Treating the brain dead for the benefit of the family.
The law -- and almost all medical ethicists and physicians -- insists upon an exclusively patient-centered ethics. There is virtual unanimity within medical ethics that treatment must serve the interests of the patient, at least within limits posed by the just distribution of scarce medical resources. A patient-centered ethics means that the interests of the patient cannot be sacrificed to promote the interests of others -- not the interests of society, not the interests of other patients, not the interests of the family, and certainly not the interests of the hospital staff or the physician.


The Effect of Pitch Auditory Feedback Perturbations on the Production of Anticipatory Phrasal Prominence and Boundary.
Purpose In this study, we investigated how the direction and timing of a perturbation in voice pitch auditory feedback during phrasal production modulated the magnitude and latency of the pitch-shift reflex as well as the scaling of acoustic production of anticipatory intonation targets for phrasal prominence and boundary. Method Brief pitch auditory feedback perturbations (±200 cents for 200-ms duration) were applied during the production of a target phrase on the first or the second word of the phrase. To replicate previous work, we first measured the magnitude and latency of the pitch-shift reflex as a function of the direction and timing of the perturbation within the phrase. As a novel approach, we also measured the adjustment in the production of the phrase-final prominent word as a function of perturbation direction and timing by extracting the acoustic correlates of pitch, loudness, and duration. Results The pitch-shift reflex was greater in magnitude after perturbations on the first word of the phrase, replicating the results from Mandarin speakers in an American English-speaking population. Additionally, the production of the phrase-final prominent word was acoustically enhanced (lengthened vowel duration and increased intensity and fundamental frequency) after perturbations earlier in the phrase, but more so after perturbations on the first word in the phrase. Conclusion The timing of the pitch perturbation within the phrase modulated both the magnitude of the pitch-shift reflex and the production of the prominent word, supporting our hypothesis that speakers use auditory feedback to correct for immediate production errors and to scale anticipatory intonation targets during phrasal production.


Inundation and Fire Shape the Structure of Riparian Forests in the Pantanal, Brazil.
Inundation and fire can affect the structure of riparian vegetation in wetlands. Our aim was to verify if there are differences in richness, abundance, basal area, composition and topographic preference of woody species in riparian forests related to the fire history, flooding duration, or the interaction between both. The study was conducted in the riparian forests of the Paraguay River some of which were burned three times between 2001 and 2011. We sampled trees with a girth of at least 5 cm at breast height in 150 5 × 10 m plots (79 burned and 71 unburned). We also measured height of the flood mark and estimated the flooding duration of each plot. We performed Generalized Linear Mixed Models to verify differences in richness, basal area, and abundance of individuals associated to interaction of fire and inundation. We used an analysis of similarity (ANOSIM) and indicator species analysis to identify differences in composition of species and the association with burned and unburned area according to different levels of inundation. Finally, we used a hierarchical set of Generalized Linear Models (GLM), the so-called HOF models, to analyse each species' specific response to inundation based on topography and to determine their preferred optimal topographic position for both burned as well as unburned areas. Richness was positively associated with elevation only in burned areas while abundance was negatively influenced by inundation only in burned areas. Basal area was negatively associated with time of inundation independent of fire history. There were 15 species which were significant indicators for at least one combination of the studied factors. We found nine species in burned areas and 15 in unburned areas, with response curves in HOF models along the inundation gradient. From these, five species shifted their optimal position along the inundation gradient in burned areas. The interaction of fire and inundation did not appear to affect the basal area, but it did affect the richness, number of individuals, success of some species, and seemed to shape the boundary of these forests as shown by the difference in the positioning of these species along the inundation gradient.


Short communication: Dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.


Spousally Bereaved Elders With Subsyndromal Depression: A Descriptive Analysis and Comparison With Major Depression.
The authors compared the frequency and severity of symptoms in subsyndromal and major depression after spousal bereavement in later life, as well as measures of social support, functional status, and grief intensity. Subsyndromal subjects (n = 25, mean age = 68.1) experienced fewer and less severe depressive symptoms and less functional impairment and anxiety than subjects with major depression (n = 25, mean age = 68.5). In a multivariate discriminant-function analysis (taking into account both symptom frequency and severity), mood, anxiety, early morning awakening, and weight loss correctly identified 92% of subsyndromal subjects and 92% of those with major depression. Further longitudinal study is under way to document the relationship of the current differences in symptomatology and clinical status to clinical outcome.


Standardized versus open-ended assessment of psychosocial and medical concerns among African American breast cancer patients.
Standardized quality of life measures have been developed and used primarily with Caucasian and middle-class cancer patients. This study assessed the ability of several widely used standardized measures to capture the concerns and problems of 89 African American breast cancer patients. Concerns and problems were assessed using both an open-ended format and standardized measures. The degree of overlap in responses from these two formats was examined. The most frequently reported problems in the open-ended format included physical (43%), financial (40%), and worry about others (30%). Overall, standardized measures had significant overlap with open-ended concerns and problems. The Cancer Rehabilitation Evaluation System-Short Form subscales/items were associated with corresponding open-ended physical, financial, and social problems (R2 change = 0.07-0.16, p's < or = 0.02), the Interpersonal Support Evaluation List-Short Form was associated with open-ended social problems (R2 change = 0.11, p = 0.004), and the Mental Health Inventory was associated with open-ended psychological distress problems (R2 change = 0.08, p = 0.01). One category of open-ended problems, worry about others, was not captured by standardized measures. With the exception of associations between open-ended physical problems and psychological distress measures, there were few significant correlations between standardized measures and dissimilar problem categories. These findings suggest that the standardized measures in this study reflected the concerns and problems of African American breast cancer patients. Additional studies are needed to evaluate the utility of other widely used standardized measures that have not been developed or standardized among non-white samples.


[Expression changes of tumor metastasis-related genes after overexpression of KAI1 in retinoblastoma Y79 cells].
To investigate the expression changes of tumor metastasis-related genes after overexpression of KAI1 in retinoblastoma Y79 cells. Experimental study. Y79 cells were transfected with a lentivirus vector containing KAI1 and enhanced green fluorescent protein (EGFP) fusion gene, or a control lentivirus vector containing EGFP. Positive transfectants stably expressing high levels of KAI1 were named Y79-KAI1 and control transfectants were named Y79-KAI1/zero. These transfectants were selected by puromycin resistance and analysis with fluorescent microscopy. The expression of KAI1 mRNA and its protein among Y79, Y79-KAI1 and Y79-KAI1/zero were detected by fluorescent quantitative RT-PCR and Western blot. Differential expression of tumor metastasis-related genes in Y79-KAI1 and Y79-KAI1/zero was analyzed with human tumor metastasis PCR array. One-way ANOVA was used to analyze the differences of KAI1 mRNA and protein expression among the three groups. The stably transfected cell lines of Y79-KAI1 and Y79-KAI1/zero were established. The result of fluorescent quantitative real-time PCR showed that the relative quantification of mRNA level of KAI1 gene in the three kinds of cells above was 183.67 ± 21.20, 1.42 ± 0.55, 1.00 ± 0.00, respectively. And the expression level of KAI1 mRNA in Y79-KAI1 cells was significantly higher than those in Y79-KAI1/zero and Y79 cells (F = 108.74, P = 0.000). The results of Western blot showed that the expression level of the KAI1 protein in Y79-KAI1 cells was significantly higher than those in Y79-KAI1/zero and Y79 cells (F = 34.36, P = 0.001). Immunofluorescent staining showed that Y79 and Y79-KAI1/zero cells had no detectable KAI1 expression, while Y79-KAI1 cells expressed KAI1 in the cytoplasm surrounding the nuclei. Among the 84 tumor metastasis-related genes examined, 7 genes were up-regulated more than 2 folds and 6 genes were down-regulated over 50%. Over-expression of KAI1 may result in differential expression of tumor metastasis-related genes in Y79 cells, which may be related to the inhibitory effect on the tumor metastasis of retinoblastoma.