Peritoneal mesothelial cell injury factors in rat cancerous ascites.
To elucidate the mechanism of the peritoneal dissemination of cancer, the influence of cancerous ascites on peritoneal mesothelial cells was studied by scanning electron microscopy and light microscopy. We inoculated normal Donryu rats with AH100B ascites hepatoma cells and studied the influence of the supernatant from cancerous ascites on the normal rat peritoneal surface by i.p. injection. The mesothelial cells were damaged and exfoliated markedly, which is supposed to be a profitable condition for cancer cells to proliferate on the peritoneal surface. Therefore, the presence of mesothelial cell injury factors was noted. Subsequently, we divided the supernatant from rat cancerous ascites into four fractions by gel filtration and revealed the distribution of mesothelial cell injury factors by studying the influence of each fraction on the normal rat peritoneal surface. Although Fraction I (fibrin fraction) and Fraction II (IgG fraction) made no changes on the peritoneal surface, Fraction III (albumin fraction) and Fraction IV provoked damages on the mesothelial cells. We found that the mesothelial cell injury factors are present in the albumin fraction and in the fraction containing low-molecular-weight substances.


Risk of bacteremia in young children with pneumonia treated as outpatients.
Blood cultures are often obtained as part of the evaluation of children with pneumonia. There are few data regarding the risk of bacteremia with pneumonia in children since introduction of the Haemophilus influenzae type b vaccine. To evaluate the risk of bacteremia in young children with pneumonia who were treated as outpatients. A retrospective cohort study of 580 children aged 2 to 24 months who were evaluated by blood culture in a tertiary care children's hospital emergency department between February 1, 1993, and May 31, 1996, and discharged with the diagnosis of pneumonia. The mean patient age was 14.1 months; 339 patients (58.4%) were boys. Thirty-eight patients (6.6%) reported the use of oral antibiotics before initial emergency department evaluation. The prevalence of bacteremia was 1.6% (95% confidence interval, 0.7%-2.9%). Streptococcus pneumoniae was the causative organism in all 9 cases. The serotype was available for 8 of 9 cases. Six (75%) of 8 cases of S pneumoniae bacteremia were caused by serotypes included in the current heptavalent pneumococcal conjugate vaccine, which was not available at the time of this study. The contamination rate was 1.9% (95% confidence interval, 1.0%-3.4%). The mean +/- SD time to blood culture positive for organisms in a continuously monitored system was significantly shorter for pathogens (13.9 +/- 1.3 hours) than for contaminants (21.2 +/- 6.1 hours; P =.01). Children aged 2 to 24 months with pneumonia who are treated as outpatients are at low risk of bacteremia. Widespread use of the pneumococcal conjugate vaccine may further decrease the incidence of bacteremia in this population.


[Studies of the histomorphology and function of the uvula].
Alternations in pharyngeal structure and function are considered fundamental in the pathogenesis of snoring or obstructive sleep apnea (OSA). The physiological function of the uvula as a dynamic sealing of the nasopharynx prevents a "craniocaudal aspiration" during deglutition. The oropharyngeal soft tissues and the uvula are known to play an important role in affecting the oropharyngeal airflow resistance but studies about alterations in the histomorphological uvula structure are controversial. We studied the histomorphological tissue composition of the uvula (midsagittal and transversal sections) in 142 patients who underwent uvulopalatopharyngoplasty (UPPP) or uvulopalatoplasty (UPP) for snoring and by autopsy in 30 normal subjects not known to have been snoring. Statistical comparisons were controlled for differences caused by age and body mass index. The uvula was found to be significantly longer in patients with snoring than in control subjects. Patients with snoring had a significantly greater percentage of fat content and connective tissue in combination with a muscle atrophy in the uvula than did normal subjects. The disturbance of the specific muscular composition and formation causes a reduction of muscular tonus and a loss of muscular contraction. The uvula is destabilized on the basis of a missing skeletal and cartilaginous brace. The uvula destabilization causes a narrowing of the pharyngeal airway that could lead to an increased oropharyngeal airflow resistance with an intensified passive uvula movement and vibration during mouth breathing.


Blackbody heterodyne receiver for NEP measurements and wideband photodetector characterization.
A blackbody radiometer is designed to measure the noise equivalent power of 10.6-microm heterodyne-receiver front ends as a function of intermediate frequency from 100 to 6000 MHz. The system includes noise diode injection and IF response normalization, making it particularly useful for characterizing high-speed photo-detectors coupled to wideband preamplifiers. Experimental results for some 77-K HgCdTe photodiodes indicate amplifier-limited NEP values <2 x 10(-19) W/Hz at 4.0 GHz. The NEP data agree well with those obtained by the standard blackbody heterodyne technique.


Proteomic analysis of Haloferax volcanii reveals salinity-mediated regulation of the stress response protein PspA.
A proteomic survey of the halophilic archaeon Haloferax volcanii was performed by comparative two-dimensional gel electrophoresis in order to determine the molecular effects of salt stress on the organism. Cells were grown under optimal (2.1 M) and high (3.5 M) NaCl conditions. From this analysis, over 44 protein spots responsive to these conditions were detected. These spots were excised, digested in-gel with trypsin, subjected to QSTAR tandem mass spectrometry (LC/MS/MS) analysis, and identified by comparing the MS/MS-derived peptide sequence to that deduced from the H. volcanii genome. Approximately 40 % of the proteins detected (18 in total) displayed differential abundance based on the detection of at least two peptide fragments per protein and overall MOWSE scores of >or=75 per protein. All of these identified proteins were either uniquely present or 2.3- to 26-fold higher in abundance under one condition compared to the other. The majority of proteins identified in this study were preferentially displayed under optimal salinity and primarily involved in translation, transport and metabolism. However, one protein of interest whose transcript levels were confirmed in these studies to be upregulated under high salt conditions was identified as a homologue of the phage shock protein PspA. The pspA gene belongs to the psp stress-responsive regulon commonly found among Gram-negative bacteria where its transcription is stimulated by a wide variety of stressors, including heat shock, osmotic shock and prolonged stationary-phase incubation. Homologues of PspA are also found among the genomes of cyanobacteria, higher plants and other Archaea, suggesting that this protein may retain some aspects of functional conservation across the three domains of life. Given its integral role in sensing a variety of membrane stressors in bacteria, these results suggest that PspA may play an important role in hypersaline adaptation in H. volcanii.


The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells.
Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNA(Ile) gene. Importantly, we further demonstrate that the carboxy-terminal domain of human mt leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with these "mild" mutations or with the "severe" m.3243A>G mutation in the mt-tRNA(L)(eu(UUR)) gene. Furthermore, we provide evidence that this small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNA(Leu(UUR)) with high affinity and stability and, with lower affinity, with mt-tRNA(Ile). Taken together, our results sustain the hypothesis that the carboxy-terminal domain of human mt leucyl-tRNA synthetase can be used to correct mt dysfunctions caused by mt-tRNA mutations.


New type of heterometallic 3d-4f rhomblike core in Weakley-like polyoxometalates.
The first heterometallic copper-cerium polyoxometalate, [{Ce(IV)(OAc)}Cu(II)(3)(H(2)O)(B-α-GeW(9)O(34))(2)](11-) (1), is composed of an unprecedented copper(II)-trisubstituted Weakley-type tungstogermanate subunit stabilized by coordination of a {Ce(OAc)}(3+) group at the vacant position. The title species contains a central {Ce(IV)Cu(II)(3)O(18)} rhomblike cluster that belongs to a new {(4f(ext))(3d(ext))(3d(int))(2)} type and magnetically behaves as a triangular Cu(3) system with overall antiferromagnetic exchange affected by the structural distortions the vicinity of diamagnetic Ce(IV) induces.


Transcription Factor bHLH2 Represses CYSTEINE PROTEASE77 to Negatively Regulate Nodule Senescence.
Legume-rhizobia symbiosis is a time-limited process due to the onset of senescence, which results in the degradation of host plant cells and symbiosomes. A number of transcription factors, proteases, and functional genes have been associated with nodule senescence; however, whether other proteases or transcription factors are involved in nodule senescence remains poorly understood. In this study, we identified an early nodule senescence mutant in Medicago truncatula, denoted basic helix-loop-helix transcription factor2 (bhlh2), that exhibits decreased nitrogenase activity, acceleration of plant programmed cell death (PCD), and accumulation of reactive oxygen species (ROS). The results suggest that MtbHLH2 plays a negative role in nodule senescence. Nodules of wild-type and bhlh2-TALEN mutant plants at 28 d postinoculation were used for transcriptome sequencing. The transcriptome data analysis identified a papain-like Cys protease gene, denoted MtCP77, that could serve as a potential target of MtbHLH2. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis demonstrated that MtbHLH2 directly binds to the promoter of MtCP77 to inhibit its expression. MtCP77 positively regulates nodule senescence by accelerating plant PCD and ROS accumulation. In addition, the expression of MtbHLH2 in the nodules gradually decreased from the meristematic zone to the nitrogen fixation zone, whereas the expression of MtCP77 showed enhancement. These results indicate that MtbHLH2 and MtCP77 have opposite functions in the regulation of nodule senescence. These results reveal significant roles for MtbHLH2 and MtCP77 in plant PCD, ROS accumulation, and nodule senescence, and improve our understanding of the regulation of the nodule senescence process.


Immunofluorescent studies on chronic pneumonia in swine with experimentally induced African swine fever.
Chronic pneumonia experimentally produced in 14 pigs with African swine fever (ASF) virus was studied by immunofluorescene (IF) and histopathologic techniques. Frozen sections prepared from pulmonary tissues of the infected pigs were stained with fluorescein-conjugated antiserums against ASF viral antigen, porcine immunoglobulin G (IgG), procine complement (C), and porcine fibrinogen. The viral antigen(s) was mainly seen in macrophages and cell debris in alveolar walls and lumens. This finding indicates that the virus replicated in the cytoplasm of alveolar macrophages that subsequently degenerated and released the viral antigen. Diffuse immunoglobulin (Ig) deposition was found in necrotic cells and debris. Immunoglobulin also was seen bound to intracytoplasmic inclusion bodies in some degenerating alveolar macrophages. This finding indicates that antibody against ASF viral antigen(s) excluded from blood circulation or produced by local immunocytes (or both) reacted with viral antigen at intramacrophage and extramacrophage levels and resulted in the formation of insoluble antigen-antibody (Ag-Ab) complexes. The participation of C in the immune complex was evident in the early stage of the pneumonia, but was less evident in the subsequent extensive, progressive necrotic processes. Fibrin deposits were visible only in the early necrotic area of alveolar walls and lumens. Possible mechanisms inducing extensive necrosis are discussed.


High-speed line-scan confocal imaging of stimulus-evoked intrinsic optical signals in the retina.
A rapid line-scan confocal imager was developed for functional imaging of the retina. In this imager, an acousto-optic deflector was employed to produce mechanical vibration- and inertia-free light scanning, and a high-speed (68,000 Hz) linear CCD camera was used to achieve subcellular and submillisecond spatiotemporal resolution imaging. Two imaging modalities, i.e., frame-by-frame and line-by-line recording, were validated for the reflected light detection of intrinsic optical signals (IOSs) in visible light stimulus activated frog retinas. Experimental results indicated that fast IOSs were tightly correlated with retinal stimuli and could track visible light flicker stimulus frequency up to at least 2 Hz.


Effectiveness of herb-partitioned moxibustion combined with electroacupuncture on polycystic ovary syndrome in patients with symptom pattern of kidney deficiency and phlegm-dampne.
To observe the effect of herb-partitioned moxibustion combined with electroacupuncture on polycystic ovary syndrome (PCOS) in patients with symptom pattern of kidney deficiency and phlegm-dampness. Totally 62 PCOS patients who met the inclusion criteria were randomly divided into intervention group and control group. In the intervention group, acupoints were subjected to (43 ± 1) ℃ herb-partitioned moxibustion and electroacupuncture treatment. In the control group, acupoints were subjected to (37 ± 1) ℃ herb-partitioned moxibustion and sham electroacupuncture treatment. Treatment was provided 3 times per week for 12 weeks, and the treatment was stopped during menstruation. After the treatment, the clinical efficacy, the Traditional Chinese Medicine (TCM) symptom pattern score, basal body temperature (BBT) levels, menstrual cycle, and related sex hormone levels of the two groups were evaluated. Sixty patients were eventually included in the study (30 in the intervention group and 30 in the control group). There were not obvious between-group differences in the baseline efficacy parameters (all P > 0.05). (a) After treatment, the two groups have improved in terms of clinical efficacy, TCM symptom pattern score, menstrual cycle and, BBT (P < 0.01, < 0.05), and the intervention group was better than the control group (P < 0.01, < 0.05). (b) In the intervention group, the estradiol (E2) and P450 aromatase (P450arom) levels were increased (all P < 0.05), the testosterone (T) level was decreased (P < 0.05), and the luteotropic hormone (LH) and anti-Müllerian hormone (AMH) levels were significantly decreased (P < 0.01). In the control group, E2 level was increased (P < 0.05), and LH level was decreased (P < 0.05). After treatment, the T, LH, and AMH levels of the intervention group were decreased compared with those of the control group (all P < 0.05), and the P450arom level was increased (P < 0.05). Herb-partitioned moxibustion combined with electroacupuncture can effectively improve the related clinical symptoms of PCOS patients with kidney deficiency and phlegm-dampness. Herb-partitioned moxibustion combined with electroacupuncture may inhibit the overexpression of AMH to increase the expression level of P450arom in ovarian granulosa cells, thereby reconstructing the dependence of follicular development on FSH, and finally improving abnormal follicular development and hyperandrogenism in PCOS patients with kidney deficiency and phlegmdampness. ChiCTR1900024182.


Human visual skills for brain-computer interface use: a tutorial.
Background and objectives: Many brain-computer interfaces (BCIs) for people with severe disabilities present stimuli in the visual modality with little consideration of the visual skills required for successful use. The primary objective of this tutorial is to present researchers and clinical professionals with basic information about the visual skills needed for functional use of visual BCIs, and to offer modifications that would render BCI technology more accessible for persons with vision impairments.Methods: First, we provide a background on BCIs that rely on a visual interface. We then describe the visual skills required for BCI technologies that are used for augmentative and alternative communication (AAC), as well as common eye conditions or impairments that can impact the user's performance. We summarize screening tools that can be administered by the non-eye care professional in a research or clinical setting, as well as the role of the eye care professional. Finally, we explore potential BCI design modifications to compensate for identified functional impairments. Information was generated from literature review and the clinical experience of vision experts.Results and conclusions: This in-depth description culminates in foundational information about visual skills and functional visual impairments that affect the design and use of visual interfaces for BCI technologies. The visual interface is a critical component of successful BCI systems. We can determine a BCI system for potential users with visual impairments and design BCI visual interfaces based on sound anatomical and physiological visual clinical science.Implications for RehabilitationAs brain-computer interfaces (BCIs) become possible access methods for people with severe motor impairments, it is critical that clinicians have a basic knowledge of the visual skills necessary for use of visual BCI interfaces.Rehabilitation providers must have a knowledge of objectively gathering information regarding a potential BCI user's functional visual skills.Rehabilitation providers must understand how to modify BCI visual interfaces for the potential user with visual impairments.Rehabilitation scientists should understand the visual demands of BCIs as they develop and evaluate these new access methods.


Dominant-hemisphere arteriovenous malformations: therapeutic embolization with isobutyl-2-cyanoacrylate.
Embolization treatment of 16 patients with dominant-hemisphere arteriovenous malformations (AVMs) is described. This group was selected from 50 patients with brain AVMs embolized with isobutyl 2-cyanoacrylate (IBC-2) over a period of 3 years. All 16 AVMs were cortical in location; six involved the rolandic and speech areas, and four had a deep component. Ten AVMs were embolized through a transfemoral approach, an intraoperative approach was used for four cases, and a combined transfemoral/intraoperative approach was used in two cases. Complete obliteration of the AVM was obtained in one case. Partial obliteration and complete surgical resection was obtained in three cases. Obliteration of 70%-95% of the AVM was obtained in six cases and 45%-70% of the AVM was obliterated in six cases. IBC-2 embolization of the venous drainage was observed in three cases. After embolization, eight patients remained neurologically unchanged. Three patients had mild neurologic deficits that resolved completely within 48 hr; one had a deficit that cleared up 1 week later; and one had a deficit that disappeared within 6 months. In three patients a mild permanent neurologic deficit was evident 6 months after embolization.


Comorbid substance use disorder, major depression, and associated disability in a nationally representative sample.
Major depression episodes (MDE) and substance use disorders (SUDs) are commonly linked to disability, but there is a lack of research on the risk of disability among individuals who have both SUDs and MD in the general population. This study aimed to investigate the associated risk of disability in people with comorbid SUDs- specifically cannabis use disorder, alcohol use disorder, other drug (except cannabis) use disorder, and a major depressive episode using a nationally representative sample. The 2012 Canadian Community Health Survey- Mental Health (CCHS-MH) data were analyzed using multilevel logistic regression models. The survey included a nationally representative sample of Canadians aged 15 years and older (n = 25,113) residing in the ten Canadian provinces from January to December 2012. The diagnoses of MDE and the SUDs were derived from the DSM-IV diagnostic criteria using a modified WHO-CIDI instrument, while disability was assessed using the World Health Organization Disability Assessment Score (WHODAS) 2.0. The strongest predictor of disability was found to be comorbidity. Individuals diagnosed with both a SUD and MDE were respectively, 4 to 9 times more likely to experience disability, depending on substance used, compared to those without either diagnosis. The study's cross-sectional design limits causal inferences. Our research discovered that individuals who have both SUD and MDE are at a significantly higher risk of experiencing disability. This highlights the importance of integrating mental health and addiction services to mitigate the risk of disability and improve overall treatment outcomes.


Acyl chain specificity and kinetic properties of phospholipase A1 and A2 of bone marrow-derived macrophages.
The fatty acyl specificity of phospholipase A1 and A2 in homogenates of mouse bone marrow-derived macrophages was determined using phosphatidylcholine and phosphatidylethanolamine of different acyl chain composition. Phosphatidylcholine with arachidonoyl at position 2 was cleaved preferentially by an alkaline phospholipase A2 (pH-optimum 9.0) leading to selective liberation of arachidonic acid. In contrast, phosphatidylcholines with oleoyl or linoleoyl at position 2 were degraded mainly by an acid phospholipase A1 (pH-optimum 4-5) resulting in a conservation of these fatty acids esterified in lysophosphatides. Substrate kinetics of the alkaline phospholipase A2 revealed a 30 fold higher affinity (Km = 3.8 X 10(-7) M) for 1-acyl-2-arachidonoyl-glycerophosphocholine compared to 1-acyl-2-oleoyl-glycerophosphocholine. The kinetic data were not influenced by endogenous lipids indicating that exogenous substrates do not equilibrate with cellular lipids. These results are suitable to explain a selective liberation of arachidonic acid from a mixture of phospholipids.


Histopathology of Sanfilippo's syndrome.
A 19-year-old woman with Sanfilippo's syndrome had poor vision, a flat electroretinographic pattern, and fundus changes similar to those in retinitis pigmentosa. Histology of her eyes by phase-contrast and electron microscopy showed extensive intracellular accumulation of fibrillogranular and membranous lamellar vacuoles in cornea, trabecular meshwork, iris, lens, ciliary body, and sclera. Retinal ganglion cells, retinal pigment epithelium (RPE), and optic nerve glia were similarly involved. Retinal pigment epithelial hyperplasia and hypopigmentation, intraretinal RPE migration, vascular attenuation, and marked photoreceptor loss were notable and closely resembled that occurring in inherited retinitis pigmentosa. We assume that the patient's blindness was due to photoreceptor cell loss, since the ganglion cells and optic nerve seemed to be intact. Although the cause of photoreceptor loss is unclear, the massive storage of acid mucopolysaccharide and lipofuscin within the RPE might disturb its essential metabolic functions and lead to photoreceptor degeneration.


Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data.
Anogenital distance (AGD) in animals is a sensitive biomarker of fetal endocrine disruption and the associated testicular dysgenesis syndrome (TDS). However, AGD in human infants with cryptorchidism and hypospadias, which are potential manifestations of TDS during childhood, is not clearly described. Our aim was to compare AGD in boys with cryptorchidism or hypospadias against normative data. Boys with isolated cryptorchidism (n = 71, age 13.4 ± 5.8 months) or hypospadias (n = 81, age 11.4 ± 6.2 months) were recruited from a tertiary center for measurement of AGD and penile length; they were compared with 487 healthy full-term boys from a birth cohort by deriving age-specific standard deviation scores (SDS). Boys with cryptorchidism were older (p = 0.048) compared with boys with hypospadias. Boys with hypospadias had shorter mean AGD and penile length SDS than healthy boys (both p < 0.0001). Mean AGD and penile length SDS values in boys with cryptorchidism were longer than mean values in boys with hypospadias (both p < 0.01) and shorter than mean values in healthy boys (both p < 0.0001). Mean penile length SDS decreased as the severity of hypospadias increased (ptrend = 0.078). In the study population, AGD and penile length were reduced in boys with hypospadias or cryptorchidism relative to normative data derived from a longitudinal birth cohort. The findings support the use of AGD as a quantitative biomarker to examine the prenatal effects of exposure to endocrine disruptors on the development of the male reproductive tract.


[Induction of transposition and excision of mobile genetic elements in Drosophila during isogenization].
Localization patterns of mobile genetic element (MGE) Dm412 were compared in chromosomes of ten isogenic lines and a heterogeneous control line riC of Drosophila. Isogenization was shown to induce MGE transpositions and excisions. Rates of induced transpositions and excisions were, respectively, 0.35 and 0.13 per site per haploid genome per isogenization, which is significantly (by two to three orders of magnitude) higher than corresponding rates in the control line. These values are also higher by an order of magnitude than previously obtained rates of transposition induction by means of heat shock treatment and gamma-irradiation of isogenic lines. In the average haploid genome of the original line, nc = 22.14 of the occupied Dm412 sites correspond to 11.9 transpositions and 4.6 excisions generated by isogenization. Calculated for the genomic system of copia-like MGE, these rates are approximately 105 and 39 events per approximately 300 initial MGE positions. Apparently, these rates exceed the "catastrophic limit of transpositions and excisions." A hypothesis on the role of inbreeding as genomic stress in induction of transpositions and excisions was proposed. Inbreeding is assumed to increase cell concentration of defective proteins, acting via the system of heat shock response-a general system of cell response to external and physiological stresses.


Improving cardiovascular risk management: a randomized, controlled trial on the effect of a decision support tool for patients and physicians.
There is nonoptimal adherence of general practitioners (GPs) and patients to cardiovascular risk reducing interventions. GPs find it difficult to assimilate multiple risk factors into an accurate assessment of cardiovascular risk. In addition, communicating cardiovascular risk to patients has proved to be difficult. Improving primary prevention of cardiovascular disease (CVD) in primary care by enhancing patient involvement in the use of a decision support tool. Cluster randomized trial. Thirty-four GPs included patients (40-75 years old) without CVD. In an interactive, small group training session lasting 4 h, the GPs in the intervention group were trained to use the guidelines on cardiovascular risk and a decision support tool. The control group received educational materials about the guidelines on paper. GPs' clinical performance and patients' risk perception and self-reported lifestyles were measured at baseline and after 6 months. Thirty-four GPs recorded 490 consultations, 276 in the intervention and 214 in the control group. After 6 months, no significant effect of the intervention on the GPs' performance or the patients' risk perception was found. There was only an effect on self-reported lifestyle, in that more men in the intervention group than in the control group increased their physical activity (odds ratio 3.8, 95% confidence interval 1.7-8.7). The 4-h interactive, small group training did not guarantee correct application of the decision support tool and as such failed to improve GPs' performance or correct patients' risk perception. The positive effect on physical activity justifies further research on patient involvement.


Effects of short- or long-term infusions of acetate or propionate on luteinizing hormone, insulin, and metabolite concentrations in beef heifers.
Two trials were conducted to evaluate the effects of short- (Trial 1) or long-term (Trial 2) intraruminal isocaloric infusions of acetate or propionate on secretion of LH, insulin, and selected metabolites in short- or long-term energy-restricted beef heifers. In Trial 1, 16 Angus heifers were assigned on d 6 to 12 of a synchronized estrous cycle (estrus = d 0) to a body weight-maintenance (BWM; n = 4) or an energy-restricted, body weight-loss (BWL; n = 12) treatment. On d 12 of a synchronized estrous cycle, heifers received PGF2alpha to synchronize estrus, and 12 h later BWL heifers received intraruminal, isocaloric infusions of acetate, propionate, or vehicle for 6 h and BWM heifers received vehicle concurrently. Mean plasma LH and LH pulse frequencies and amplitudes were not affected by treatment (P > .05). In contrast, infusion of propionate increased plasma insulin (P < .05) and reduced plasma concentration of NEFA (P < .05). In Trial 2, six ovariectomized Angus heifers were energy-restricted for 30 d. On d 14 and 26 of restriction, heifers began receiving intraruminal isocaloric infusions of acetate or propionate for 96 h in a switchback approach. Intraruminal infusions of vehicle for 6 h preceded infusions of acetate or propionate. Jugular blood was collected at 12-min intervals during infusions of vehicle and during the last 6 h of infusion of acetate or propionate. Mean concentration of LH and amplitude of pulses of LH were lower during acetate vs propionate or vehicle infusion (P < .05). Infusion of propionate increased insulin relative to acetate or vehicle infusion (P < .05). Plasma NEFA were reduced by infusion of propionate (P < .05) and increased by infusion of acetate (P < .05).


Vildagliptin Enhances Differentiation of Insulin Producing Cells from Adipose-Derived Mesenchymal Stem Cells.
Type 1 diabetes is caused by destruction of beta cells of pancreas. Vildagliptin (VG), a dipeptidyl peptidase IV (DPP IV) inhibitor, is an anti-diabetic drug, which increases beta cell mass. In the present study, the effects of VG on generation of insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ASCs) is investigated. In this experimental study, ASCs were isolated and after characterization were exposed to differentiation media with or without VG. The presence of IPCs was confirmed by morphological analysis and gene expression (Pdx-1, Glut-2 and Insulin). Newport Green staining was used to determine insulin-positive cells. Insulin secretion under different concentrations of glucose was measured using radioimmunoassay method. In the presence of VG the morphology of differentiated cells was similar to the pancreatic islet cells. Expression of Pdx-1, Glut-2 and Insulin genes in VG-treated cells was significantly higher than the cells exposed to induction media only. Insulin release from VG-treated ASCs showed a nearly 3.6 fold (P<0.05) increase when exposed to a highglucose medium in comparison to untreated ASCs. The percentage of insulin-positive cells in the VG-treated cells was approximately 2.9-fold higher than the untreated ASCs. The present study has demonstrated that VG elevates differentiation of ASCs into IPCs. Improvement of this protocol may be used in cell therapy in diabetic patients.


Quality of reporting of randomised controlled trials of herbal interventions in ASEAN Plus Six Countries: a systematic review.
Many randomised controlled trials (RCTs) of herbal interventions have been conducted in the ASEAN Communities. Good quality reporting of RCTs is essential for assessing clinical significance. Given the importance ASEAN placed on herbal medicines, the reporting quality of RCTs of herbal interventions among the ASEAN Communities deserved a special attention. To systematically review the quality of reporting of RCTs of herbal interventions conducted in the ASEAN Plus Six Countries. Searches were performed using PubMed, EMBASE, The Cochrane Library, and Allied and Complementary Medicine (AMED), from inception through October 2013. These were limited to studies specific to humans and RCTs. Herbal species search terms were based on those listed in the National List of Essential Medicines [NLEM (Thailand, 2011)]. Studies conducted in the ASEAN Plus Six Countries, published in English were included. Seventy-one articles were identified. Thirty (42.25%) RCTs were from ASEAN Countries, whereas 41 RCTs (57.75%) were from Plus Six Group. Adherence to the recommended CONSORT checklist items for reporting of RCTs of herbal interventions among ASEAN Plus Six Countries ranged from 0% to 97.18%. Less than a quarter of the RCTs (18.31%) reported information on standardisation of the herbal products. However, the scope of our interventions of interest was limited to those developed from 20 herbal species listed in the NLEM of Thailand. The present study highlights the need to improve reporting quality of RCTs of herbal interventions across ASEAN Plus Six Communities.


Influence of mechanical stretch on growth and protein turnover of rat uterus.
A new technique has been developed and used to distend the uterus of nonpregnant rats for up to 5 days. Continuous distension of the saline-filled uterus induced rapid and extensive growth of the whole uterus and the myometrium by a combination of hyperplasia and hypertrophy. In both cases, 1 day after this imposition of mechanical stretch significant increases (25-50%) in the protein, RNA, and DNA contents were found, with larger changes (100-250%) being progressively expressed up to 5 days. This stretch-induced growth primarily results from a stimulation of protein synthesis (measured both in vivo and in vitro), with little or no change being evident in the rate of protein breakdown. These findings have been discussed in relation to the role of stretch in the growth of the uterus during pregnancy and stretch-induced responses found in other types of muscle.


Tibial plateau fracture as a measure of early estrogen-dependent bone fragility in rats.
The goals of this study were to develop a protocol to induce a compressive fracture at the tibial plateau of the rat knee in vitro and to determine if the biomechanical parameters provided a sensitive assessment of the early skeletal changes induced by estrogen deficiency. Sixty-one rats underwent an ovariectomy (n = 36) or sham operation (n = 25) and were maintained for 50 days after the procedure. Just before death, the proximal tibia of each animal was scanned with high-resolution x-ray tomography. From the three-dimensional images, the mean trabecular bone volume, thickness, and separation and the number of trabeculae were calculated. The knees were then harvested and mounted into a servohydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture. The fracture load of the ovariectomized rats was 24% less than that of the rats that had the sham operation. Similarly, the structural stiffness of the ovariectomized knees was decreased by 22%. Both of these differences were statistically significant (p < 0.01) and were explained by differences in trabecular bone volume (r = 0.56, p < 0.0001 and r = 0.42, p < 0.005, respectively). The other measures of trabecular bone structure were correlated with the volume and did not improve the prediction by the biomechanical parameters. These data demonstrate that biomechanical testing of the tibial plateau in rats can quantify the structural consequences of estrogen deficiency at an early time point before they become apparent at other bone sites, such as the lumbar spine.


In Vitro-In Silico Tools for Streamlined Development of Acalabrutinib Amorphous Solid Dispersion Tablets.
Amorphous solid dispersion (ASD) dosage forms can improve the oral bioavailability of poorly water-soluble drugs, enabling the commercialization of new chemical entities and improving the efficacy and patient compliance of existing drugs. However, the development of robust, high-performing ASD dosage forms can be challenging, often requiring multiple formulation iterations, long timelines, and high cost. In a previous study, acalabrutinib/hydroxypropyl methylcellulose acetate succinate (HPMCAS)-H grade ASD tablets were shown to overcome the pH effect of commercially marketed Calquence in beagle dogs. This study describes the streamlined in vitro and in silico approach used to develop those ASD tablets. HPMCAS-H and -M grade polymers provided the longest acalabrutinib supersaturation sustainment in an initial screening study, and HPMCAS-H grade ASDs provided the highest in vitro area under the curve (AUC) in gastric to intestinal transfer dissolution tests at elevated gastric pH. In silico simulations of the HPMCAS-H ASD tablet and Calquence capsule provided good in vivo study prediction accuracy using a bottom-up approach (absolute average fold error of AUC0-inf < 2). This streamlined approach combined an understanding of key drug, polymer, and gastrointestinal properties with in vitro and in silico tools to overcome the acalabrutinib pH effect without the need for reformulation or multiple studies, showing promise for reducing time and costs to develop ASD drug products.


Plasmapheresis in the management of acute severe hyperlipidemic pancreatitis: report of 5 cases.
Hyperlipidemic pancreatitis is an acute and potentially life-threatening complication of hypertriglyceridemia that can be provoked when triglyceride levels (TGL) exceed 11.3 mmol/l (1,000 mg/dl). Except for standard symptomatic treatment, plasmapheresis has been performed to rapidly reduce TGL and chylomicron levels in the blood. In 5 patients with hyperlipidemic pancreatitis, treatment with plasmapheresis was evaluated. Five male patients who suffered from acute pancreatitis with severe primary hyperlipidemia were studied. In addition to the standard treatment, they were treated with plasmapheresis. Plasma exchange lowered the lipid level and TGLs in all cases. It also improved abdominal pain, the clinical state of the patients, and signs and symptoms of the disease. Complications of treatment were not encountered, none of the patients died and only 1 patient underwent surgery. Follow-up of the patients lasted 4-28 months, and recurrence of pancreatitis was not noted. Our study showed that plasmapheresis was successfully applied in patients with hyperlipidemic pancreatitis, especially to improve the acute phase of the disease.


TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+ T cells.
Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved αβ T cell receptor (TCR) repertoire has not been comprehensively analyzed. We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naïve (CCR7+ CD45RA+) and memory (not naïve) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 µmol/L NiSO4 ., TCR α- and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Stimulation of PBMCs with NiSO4 induced CD154 expression on ~0.1% (mean) of naïve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the α-chain segment TRAV9-2 or a histidine in their α- or β-chain complementarity determining region 3 (CDR3) were highly overrepresented. Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests.


Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.
BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective.


Prediction of Negative Outcomes in Non-Surgical Treatment for Appendiceal Abscess in Adults.
Non-surgical treatment is an acceptable approach for managing appendiceal abscess in adults. However, it is only applicable for selected patients, and conversion to surgery is mandatory for failed conservative treatment. This study aimed to determine the predictive factors for unsuccessful outcomes. Of 594 patients with acute appendicitis, 34 (5.7%) diagnosed with appendiceal abscess were initially treated conservatively. Patients were divided into two groups: the conservative group, which was successfully treated with antibiotics and percutaneous abscess drainage, and the conversion group, which comprised patients who had surgical conversion despite conservative treatment. Risk factors for the conversion group were investigated by comparing clinical and radiological parameters between the two groups. Eight (23.4%) patients were converted to surgical management at an average of 5.5 days of non-surgical treatment. An abscess size greater than 40 mm and a lower rate of improvement in the white blood cell (WBC) count were significant factors for predicting conversion in multivariate analysis. The conversion group had a long operative time and high morbidity and operative conversion rates (change of proposed initial operation). Early conversion to operation group, i.e., less than 5 days of treatment, contributed to a significantly shorter hospital stay, lower hospital cost, and relatively shorter operative time (p = 0.02, p = 0.04, and p = 0.11, respectively). Contributing factors in predicting unsuccessful outcomes for non-surgical treatment include an abscess size greater than 40 mm and a low rate of improvement in WBC count on the first day of antibiotic treatment.


A rapid and reliable PCR method for genotyping the ABO blood group. II: A2 and O2 alleles.
PCR permits direct genotyping of individuals at the ABO locus. Several methods have been reported for genotyping ABO that rely on differentiating the A, B, and O alleles at specific base substitutions. However, the O allele as defined by serology comprises at least two alleles (O1 and O2) at the molecular level, and most current ABO genotyping methods only take into account the O1 allele. Determining the presence of the O2 allele is critical, as this not-infrequent allele would be mistyped as an A or a B allele by standard PCR typing methods. Furthermore, none of the methods to date distinguish between the A1 and A2 alleles, even though 10% of all white persons are blood group A2. We have developed a method for genotyping the ABO locus that takes the O2 and A2 alleles into account. Typing for A2 and O2 by diagnostic restriction enzyme digestion is a sensitive, nonradioactive assay that provides a convenient method useful for forensic and paternity testing and for clarifying anomalous serological results.


Finding alternatives when a major database is gone.
What to do when a major database ceases publication? An urban, academic health sciences library with four campuses serves a university health sciences system, a college of medicine, and five other health sciences colleges. Usage statistics of each e-book title in the resource were carefully analyzed. Purchase decisions were made based on the assessment of usage. Sustainable resources were acquired from other vendors, with perpetual access for library users. This systematic process of finding alternative resources is an example of librarians' persistence in acquiring perpetual electronic resources when a major resource is cancelled.


Beehive scale-free emergent dynamics.
It has been repeatedly reported that the collective dynamics of social insects exhibit universal emergent properties similar to other complex systems. In this note, we study a previously published data set in which the positions of thousands of honeybees in a hive are individually tracked over multiple days. The results show that the hive dynamics exhibit long-range spatial and temporal correlations in the occupancy density fluctuations, despite the characteristic short-range bees' mutual interactions. The variations in the occupancy unveil a non-monotonic function between density and bees' flow, reminiscent of the car traffic dynamic near a jamming transition at which the system performance is optimized to achieve the highest possible throughput. Overall, these results suggest that the beehive collective dynamics are self-adjusted towards a point near its optimal density.


Assessing biosynthetic potential of agricultural groundwater through metagenomic sequencing: A diverse anammox community dominates nitrate-rich groundwater.
Climate change produces extremes in both temperature and precipitation causing increased drought severity and increased reliance on groundwater resources. Agricultural practices, which rely on groundwater, are sensitive to but also sources of contaminants, including nitrate. How agricultural contamination drives groundwater geochemistry through microbial metabolism is poorly understood. On an active cow dairy in the Central Valley of California, we sampled groundwater from three wells at depths of 4.3 m (two wells) and 100 m (one well) below ground surface (bgs) as well as an effluent surface water lagoon that fertilizes surrounding corn fields. We analyzed the samples for concentrations of solutes, heavy metals, and USDA pathogenic bacteria of the Escherichia coli and Enterococcus groups as part of a long term groundwater monitoring study. Whole metagenome shotgun sequencing and assembly revealed taxonomic composition and metabolic potential of the community. Elevated nitrate and dissolved organic carbon occurred at 4.3m but not at 100m bgs. Metagenomics confirmed chemical observations and revealed several Planctomycete genomes, including a new Brocadiaceae lineage and a likely Planctomycetes OM190, as well novel diversity and high abundance of nano-prokaryotes from the Candidate Phyla Radiation (CPR), the Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaea (DPANN) and the Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota (TACK) superphyla. Pathway analysis suggests community interactions based on complimentary primary metabolic pathways and abundant secondary metabolite operons encoding antimicrobials and quorum sensing systems. The metagenomes show strong resemblance to activated sludge communities from a nitrogen removal reactor at a wastewater treatment plant, suggesting that natural bioremediation occurs through microbial metabolism. Elevated nitrate and rich secondary metabolite biosynthetic capacity suggest incomplete remediation and the potential for novel pharmacologically active compounds.


In silico, experimental, mechanistic model for extended-release felodipine disposition exhibiting complex absorption and a highly variable food interaction.
The objective of this study was to develop and explore new, in silico experimental methods for deciphering complex, highly variable absorption and food interaction pharmacokinetics observed for a modified-release drug product. Toward that aim, we constructed an executable software analog of study participants to whom product was administered orally. The analog is an object- and agent-oriented, discrete event system, which consists of grid spaces and event mechanisms that map abstractly to different physiological features and processes. Analog mechanisms were made sufficiently complicated to achieve prespecified similarity criteria. An equation-based gastrointestinal transit model with nonlinear mixed effects analysis provided a standard for comparison. Subject-specific parameterizations enabled each executed analog's plasma profile to mimic features of the corresponding six individual pairs of subject plasma profiles. All achieved prespecified, quantitative similarity criteria, and outperformed the gastrointestinal transit model estimations. We observed important subject-specific interactions within the simulation and mechanistic differences between the two models. We hypothesize that mechanisms, events, and their causes occurring during simulations had counterparts within the food interaction study: they are working, evolvable, concrete theories of dynamic interactions occurring within individual subjects. The approach presented provides new, experimental strategies for unraveling the mechanistic basis of complex pharmacological interactions and observed variability.


Self-setting bioceramic microscopic protrusions for transdermal drug delivery.
Microneedle (MN) technology offers both an efficient and a minimally invasive transdermal drug delivery strategy. The current MNs, made of silicon and metal, have poor biocompatibility and low drug loading, while the polymer MNs have some constraints related to mechanical strength and storage conditions. In this study, self-setting bioceramics were explored as substitutes for the current MN materials for the first time. Self-setting bioceramic microneedles were fabricated using a master mold by a procedure under mild conditions, which could minimize the drug degradation during fabrication and also facilitates a higher drug loading capability than the other current ceramic microneedles. The drug release and mechanical strength were correlated with the microstructure and porosity of the needles. As observed by SEM and microCT, the ceramic paste could fully fill the geometry of the mould and was cured into an array of micro-sized needles. The drug release study showed that the release rate from this type of MN array could be controlled by the bulk surface area, porosity and resorption rate of the ceramic needles. Applying the MNs to porcine skin indicated that the needles were able to pierce the stratum corneum of the skin. We successfully prepared the bioceramic needles that have high mechanical strength and are resorbable, which can promote safe, efficient and successful transdermal drug delivery.


Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia.
To determine whether prostaglandins are involved in circulatory homeostasis in congestive heart failure, we measured plasma levels of the metabolites of vasodilator prostaglandins I2 and E2 in 15 patients with severe chronic heart failure. Mean circulating levels of both metabolites were 3 to 10 times higher than those in normal subjects. Plasma levels of both metabolites correlated directly with plasma renin activity and plasma angiotensin II concentrations (r = 0.64 and 0.84, respectively). Individual serum sodium concentrations were inversely correlated with levels of prostaglandin E2 metabolites (r = -0.92, P less than 0.001) and plasma renin activity (r = -0.69, P less than 0.02). Of 23 patients with severe heart failure challenged with indomethacin (an inhibitor of prostaglandin synthesis), the 9 with hyponatremia had significant decreases in the cardiac index (1.99 +/- 0.12 to 1.72 +/- 0.13 liters per minute per square meter of body-surface area, P less than 0.001) and significant increases in the pulmonary capillary wedge pressure (17.4 +/- 2.0 to 24.0 +/- 1.9 mm Hg, P less than 0.001) and systemic vascular resistance (1882 +/- 239 to 2488 +/- 315 dyn x sec x cm-5, P less than 0.001), whereas the 14 patients with a normal serum sodium concentration had no significant hemodynamic changes. We conclude that both vasoconstrictor (renin-angiotensin) and vasodilator (prostaglandin) mechanisms are operative in patients with heart failure complicated by hyponatremia and that these mechanisms interact to modulate circulatory homeostasis.


Molecular Spectrum of α- and β-Thalassemia among Young Individuals of Marriageable Age in Guangdong Province, China.
Thalassemia is a group of genetically heterogeneous diseases characterized by hemolytic anemia. To investigate molecular characteristics of α- and β-thalassemia among young individuals of marriageable age in Guangdong Province, 24,788 subjects with suspected thalassemia were genetically tested for α- and β-thalassemia by Gap-PCR and reverse dot blot during 2018-2019. For suspected rare thalassemia cases, DNA sequencing was performed to identify rare and unknown thalassemia gene mutations. A total of 14,346 thalassemia carriers were detected, including 7,556 cases of α-thalassemia with 25 genotypes and 8 α-gene mutations identified, 5,860 cases of β-thalassemia with 18 genotypes and 18 β-gene mutations identified, and 930 cases of compound α/β-thalassemia. Among them, the frequency of -- SEA deletion was the highest in α-thalassemia (66.01%), followed by -α 3.7 (17.98%) and -α 4.2 (8.22%), and the frequency of CD41-42 (-TCTT) mutation was the highest in β-thalassemia (38.38%), followed by IVS-II-654 (C > T) (25.67%), -28 (A > G) (15.76%), and CD17 (10.01%). In addition, 5 rare mutations (--THAI and HKαα, CD113, -90, and CD56) were found in the study population. Our results revealed molecular epidemiological background of α- and β-thalassemia in Guangdong Province, which can support optimization of thalassemia prevention and control strategies. We demonstrated that thalassemia is heterogeneous with significant geographical differences and population specificity.


A comparative evaluation of the efficacy of intraoperative mitomycin C use after the excision of cobblestone-like papillae in severe atopic and vernal keratoconjunctivitis.
To evaluate the effect of intraoperative 0.02% mitomycin-C (MMC) use after excision of cobblestone-like papillae on preventing corneal recurrences compared with simple papillary resection. Thirteen cases of atopic keratoconjunctivitis (AKC) and 6 cases of vernal keratoconjunctivitis (VKC) with a mean age of 12.0 +/- 3.4 years participated in this study. All patients had cobblestone-like papillae on the upper tarsal conjunctiva and corneal ulcers or erosions that were refractory to conventional treatment. Seventeen eyes received simple papillary excision. Papillary excision with intraoperative application of MMC was performed in 7 eyes: 0.02% MMC was applied for 2 minutes to the upper palpebral conjunctiva immediately after papillary excision. Recurrence of corneal lesions and regrowth of papillae were evaluated and compared retrospectively between the 2 groups. Postoperative follow-up ranged from 12 to 18 months. Papillary regrowth was observed in 14 out of 17 eyes (82.4%) in the simple resection group, whereas regrowth was noted in 4 out of 7 eyes (57.1%) in the MMC group (P > 0.05). The recurrence of corneal lesions was observed in 8 out of 17 eyes (47.1%) in the simple resection group (mean onset 1.5 +/- 1.7 months) compared with 1 eye with corneal recurrence 6 months after surgery in the MMC group (14.3%). The difference was statistically significant (P < 0.05). No complications related to MMC use were observed during the follow-up period. MMC-aided papillary resection may be rewarding in well-selected severe AKC and VKC cases in preventing recurrence of corneal complications, but the potential complications of MMC use would suggest caution in its consideration.


Trends in smoking behaviour among Estonian physicians in 1982-2014.
Smoking surveys among physicians have proved useful in highlighting the importance of physicians as healthy life style exemplars and role models in tobacco control and smoking cessation. The aim of this study was to give an overview of smoking behaviour among Estonian physicians from 1982 to 2014. Three cross-sectional postal surveys using a self-administered questionnaire were carried out among all practising physicians in Estonia. The number of physicians participating in this study was 3786 in 1982, 2735 in 2002, and 2902 in 2014. Data analysis involved calculating the age-standardized prevalences of smoking, prevalences of smoking by age group and mean age of smoking initiation. A non-parametric test for trend was used to assess significant changes in smoking over time. Age-standardized prevalence of current smoking among men was 39.7% in 1982, 20.9% in 2002, and 14.3% in 2014 and among women 12.2%, 8.0%, and 5.2%, respectively (p < 0.0001 for trends). From 1982 to 2014, the biggest decline of current smoking among men and women was in age groups under 35 (from 55.2% to 16.7% and from 16.7% to 2.8%, respectively) and 35-44 (from 47.1% to 8.3% and from 19.5% to 5.1%, respectively) (p < 0.0001 for trends). Mean age of smoking initiation decreased from 20.4 to 19.3 among men and from 24.5 to 20.4 among women over the study period. In 1982-2014, smoking prevalence among Estonian physicians declined substantially. This may influence the willingness of society to recognize the health consequences of smoking which could give a support to the decline of the smoking epidemic in the country. Differences between smoking among male and female physicians persisted over the study period, but mean age of smoking initiation decreased. A further decline in smoking among Estonian physicians should be encouraged by special efforts targeted at physicians.


Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies.
To evaluate the clinical utility of a human immunodeficiency virus (HIV)-IgA serological assay for diagnosis of perinatally acquired HIV infection. Coded serum samples prospectively collected from children born to HIV-infected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot. A university hospital in Baltimore, Md, and an outpatient clinic in Port-au-Prince, Haiti. Five hundred thirty-nine serum samples were obtained sequentially from 278 children born to HIV-infected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince. Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity, and predictive values were calculated at different ages and collectively for children 3 months of age or older. The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age, and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7%, and the positive and negative predictive values were 99.4% and 98.7%, respectively. Although the HIV-IgA assay had a low sensitivity within the first months of life, the high sensitivity, specificity, and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries.


The sodium channel gene in Tetranychus cinnabarinus (Boisduval): identification and expression analysis of a mutation associated with pyrethroid resistance.
The carmine spider mite (CSM), Tetranychus cinnabarinus, is the most harmful mite pest of various crops and vegetable plants. Pyrethroid insecticide fenpropathrin has been used to control insects and mites worldwide, but CSM has developed resistance to this compound. Three synergists together eliminated about 50% resistance against fenpropathrin in the CSM. A point mutation was identified from the sodium channel gene of fenpropathrin-resistant CSM (FeR) by comparing cDNA sequences between FeR and susceptible (S) sodium channel genes, which caused a phenylalanine (F) to isoleucine (I) change at amino acid 1538 position in IIIS6 of the sodium channel and has been proven to confer strong resistance to pyrethroid in other species. The mRNA expression of the sodium channel gene in the FeR and abamectin-resistant strain (AbR), which was included as a control, were both relatively lower than in the S. These results demonstrate that a mutation (F1538I) is present in the sodium channel gene in FeR of CSM, likely playing an important role in fenpropathrin resistance in T. cinnabarinus, but that decrease in the abundance of sodium channel did not confer this resistance. The F1538I mutation could be used as a molecular marker for detecting kdr resistance in Arachnida populations.


Billing and Utilization Trends in Reconstructive Microsurgery Indicate Worsening Access to Care.
Within the last 20-years, Medicare reimbursements for microsurgery have been declining, while physician expenses continue to increase. As a result, hospitals may increase charges to offset revenue losses, which may impose a financial barrier to care. This study aimed to characterize the billing trends in microsurgery and their implications on patient care. The 2013-2020 Provider Utilization and Payment Data Physician and Other Practitioners Dataset was queried for 16 CPT codes. Service counts, hospital charges, and reimbursements were collected. The utilization, weighted mean reimbursements and charges, and charge-to-reimbursement ratios (CRRs) were calculated. The total and annual percent changes were also determined. 13 CPT codes (81.3%) were included. The overall number of procedures decreased by 15.0%. The average reimbursement of all microsurgical procedures increased from $618 to $722 (16.7%). The mean charge increased from $3,200 to $4,340 (35.6%). As charges had a greater increase than reimbursement rates, the CRR increased by 15.4%. At the categorical level, all groups had increases in CRRs, except for bone graft (-49.4%) and other procedures (-3.5%). The CRR for free flap breast procedures had the largest percent increase (47.1%). Additionally, lymphangiotomy (28.6%) had the second largest increases. Our analysis of microsurgical procedures billed to Medicare Part B from 2013 to 2020 showed that hospital charges are increasing at faster rate than that of reimbursements. This may be in part due to increasing physician expenses, cost of advanced technology in microsurgical procedures, and inadequate reimbursement rates. Regardless, these increased markups may limit patients who are economically disadvantaged from accessing care. Policy makers should consider legislation aimed at updating Medicare reimbursement rates to reflect the increasing complexity and cost associated with microsurgical procedures, as well as regulating charge markups at the hospital level.


Heterogeneous effects of IL-2 on collagen-induced arthritis.
IL-2 is generally considered a pro-inflammatory cytokine that exacerbates Th1-mediated disease states, such as autoimmune arthritis. Consistent with this role for IL-2, recent studies from our laboratory demonstrate that IL-2 mRNA is markedly increased during the acute stage of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. To further define the role of IL-2 in CIA, the levels of IL-2 protein and its receptor and the effects of IL-2 administration were analyzed during CIA. IL-2 protein and IL-2R were preferentially expressed at disease onset, compared with later stages of disease. Administration of recombinant human IL-2 (rhIL-2) at, or just before, disease onset exacerbated disease; surprisingly, rhIL-2 given before disease onset inhibited CIA, associated with reduced cellular and humoral responses to type II collagen. Determination of in vivo serum levels of Th1 and Th2 cytokines in response to rhIL-2 treatment demonstrated that IFN-gamma, but not IL-4, was markedly up-regulated in response to IL-2. In mice treated with anti-IFN-gamma Ab, both early and late IL-2 administration exacerbated CIA. Thus, IL-2 can have two opposite effects on autoimmune arthritis, a direct stimulatory effect and an indirect suppressive effect that is mediated by IFN-gamma.


Factors associated with alcohol use disorder: the role of depression, anxiety, stress, alexithymia and work fatigue- a population study in Lebanon.
International research showed that common mental disorders such as depression, anxiety, social anxiety, stress, alexithymia and having insecure attachment styles are risk factors for alcohol use disorder (AUD). Our objective was to study the factors associated withAUD in a sample of the Lebanese population. During the period lasting from November 2017 to March 2018, a sample of 789 Lebanese participants agreed to contribute to a cross-sectional study (53.23% males). Alcohol use disorder was assessed using the Alcohol Use Disorder Identification Test (AUDIT). A high risk of AUD was associated with higher alexithymia (ORa = 1.030; CI 1.009-1.051), depression (ORa = 1.076; CI 1.050-1.103) and suicidal ideation (ORa = 1.253; CI 1.026-1.531) in a significant manner. In opposition, a higher number of kids (ORa = 0.863; CI 0.752-0.991), being a female (ORa = 0.460; CI 0.305-0.694) and higher emotional management (ORa = 0.962; CI 0.937-0.988) were significantly associated with lower AUD risk. A cluster analysis derived three mutually exclusive clusters. Cluster 1 formed 45.4% of the sample and assembled people with psychological difficulties (work fatigue and high stress, high emotional work fatigue and low emotional intelligence, low self-esteem, high social phobia, high alexithymia); Cluster 2 formed 34.4% of the sample and assembled people with high wellbeing (low suicidal ideation, low emotional work fatigue, depression and anxiety, high emotional intelligence, high self-esteem and low social phobia); whereas cluster 3 formed 20.2% of the sample and represented people with mental dysfunction (high anxiety and depression, high suicidal ideation, low self-esteem and high social phobia, low emotional intelligence, high emotional work fatigue). People with psychological difficulties (cluster 1) (Beta = 5.547; CI 4.430-6.663), and people in distress (cluster 3) (Beta = 7.455; CI 5.945-8.965) were associated with higher AUDIT scores than those with high wellbeing (cluster 2). AUD seems to be influenced by several factors among the Lebanese population, including alexithymia, stress, anxiety and work fatigue. Healthcare professionals should spread awareness to reduce the prevalence of these factors.


Preemption in State Tobacco Minimum Legal Sales Age Laws in the US, 2022: A Policy Analysis of State Statutes and Case Laws.
Preemptive statutory language within tobacco minimum legal sales age (MLSA) laws has prohibited localities from enacting stricter laws than state statutes. With the recent uptake of state Tobacco 21 laws in the US, the current landscape of preempted MLSA laws is unknown. This study sought to update the status of preemption in MLSA laws enacted in US states between 2015-2022. A public health attorney reviewed state tobacco MLSA laws (n = 50) and state tobacco control codes, searching for language regarding preemption. When statutes were unclear, case law was reviewed by examining local ordinances that were invalidated by state court decisions. Overall, 40 states enacted Tobacco 21 laws, seven of which expanded or introduced preemption when they increased the MLSA; a total of 26 states (52%) included preemption. Six states (12%) retained 'savings clauses' included in the MLSA prior to Tobacco 21, and 18 states (36%) did not mention preemption. Based on the precedent set by state courts, eight of these 18 states may preempt localities from raising their MLSA. Historically, preemption has slowed the diffusion of best practices in tobacco control, and once implemented, the laws are difficult to repeal. The recent expansion of preemption could inhibit the evolution, development, and implementation of effective tobacco control policies.


Assessing Surface Adsorption in Cyclic Olefin Copolymer Microfluidic Devices Using Two-Dimensional Nano Liquid Chromatography-Micro Free Flow Electrophoresis Separations.
Surface interactions are a concern in microscale separations, where analyte adsorption can decrease the speed, sensitivity, and resolution otherwise achieved by miniaturization. Here, we functionally characterize the surface adsorption of hot-embossed cyclic olefin copolymer (COC) micro free-flow electrophoresis (μFFE) devices using two-dimensional nLC × μFFE separations, which introduce a 3- to 5 s plug of analyte into the device and measure temporal broadening that arises from surface interactions. COC is an attractive material for microfluidic devices, but little is known about its potential for surface adsorption in applications with continuous fluid flow and temporal measurements. Adsorption was minimal for three small molecule dyes: positively charged rhodamine 123, negatively charged fluorescein, and neutral rhodamine 110. Temporal peak widths for the three dyes ranged from 3 to 7 s and did not change significantly with increasing transit distance. Moderate adsorption was observed for Chromeo P503-labeled myoglobin and cytochrome c with temporal peak widths around 20 s. Overall, the COC surface adsorption was low compared to traditional glass devices, where peak widths are on the order of minutes. Improvements in durability, long-term performance, and ease of fabrication, combined with low overall adsorption, make the COC μFFE devices a practical choice for applications involving time-resolved continuous detection.


BAK1 is required for the attenuation of ethylene-inducing xylanase (Eix)-induced defense responses by the decoy receptor LeEix1.
Elicitor recognition plays a key role in the reaction of plants to pathogens and the induction of plant defense responses. Furthermore, plant-microbe interactions involve numerous regulatory systems essential for plant defense against pathogens. Ethylene-inducing xylanase (Eix) is a potent elicitor of plant defense responses in specific cultivars of tobacco (Nicotiana tabacum) and tomato (Solanum lycopersicum). The Eix receptors (LeEix1 and LeEix2) belong to a superclade of leucine-rich repeat receptor-like proteins (RLP) with a signal for receptor-mediated endocytosis, which was shown to be essential for proper induction of defense responses. Both receptors are able to bind Eix, while only LeEix2 mediates defense responses. Here we demonstrate that LeEix1 heterodimerizes with LeEix2 upon application of the Eix elicitor. We show that LeEix1 attenuates Eix-induced internalization and signaling of the LeEix2 receptor. Furthermore, we demonstrate, using yeast two-hybrid and in planta bimolecular fluorescence complementation assays, that the brassinosteroid co-receptor, BAK1, binds LeEix1 but not LeEix2. In BAK1-silenced plants, LeEix1 was no longer able to attenuate plant responses to Eix, indicating that BAK1 is required for this attenuation. We suggest that LeEix1 functions as a decoy receptor for LeEix2, a function which requires BAK1.


Defining incident chronic kidney disease in the research setting: The ARIC Study.
Deaths of participants and losses to follow-up pose challenges for defining outcomes in epidemiologic studies. The authors compared several definitions of incident chronic kidney disease (CKD) in terms of incidence, agreement, and risk factor associations. They used data from 14,873 participants in the community-based, multicenter, biracial Atherosclerosis Risk in Communities Study (1987-1999). The estimated glomerular filtration rate (eGFR) was based on serum creatinine at baseline and the 3- and 9-year follow-up visits. Hospitalizations were ascertained continuously. The authors compared 4 definitions of incident CKD: 1) low eGFR (<60 mL/minute/1.73 m(2)); 2) low and declining (> or =25%) eGFR; 3) an increase in serum creatinine (> or =0.4 mg/dL) at 3- or 9-year follow-ups; and 4) CKD-related hospitalization or death. From these definitions, they identified 1,086, 677, 457, and 163 cases, respectively. There was relatively good agreement among definitions 1-3, but definition 4 identified mostly different cases. Risk factor associations were consistent across definitions for hypertension and lipids. Diabetes showed weaker associations with definition 1 (incidence rate ratio = 1.5, 95% confidence interval: 1.2, 1.7) than with definition 4 (incidence rate ratio = 6.3, confidence interval: 4.4, 8.9). Associations with gender differed in direction and magnitude across definitions. Case definition can impact relative risk estimates for CKD risk factors.


Stabilization of the large T protein in temperature-independent (type A) FR 3T3 rat cells transformed with the simian virus 40 tsA30 mutant.
The stabilities of in vivo [35S]methionine-labeled large T and small t proteins, synthesized in temperature-sensitive (type N) and temperature-insensitive (type A) FR 3T3 rat cells transformed by an early temperature-sensitive mutant of simian virus 40 (SV40), tsA30, were analyzed at the permissive and restrictive temperatures. The two polypeptides, detected in greatly reduced amounts in cells of the N type at the restrictive temperature, were also unstable at the permissive temperature. However, both were made in similar amounts and were apparently stable in cells of the A type, irrespective of the temperature. The structures of the viral RNAs present at the permissive temperature were analyzed for transformants representative of each type, and containing a single integration of viral DNA. The two cell lines synthesized transcripts identical to the large T and small t mRNAs identified in SV40-infected monkey cells. Similar amounts of viral RNA were found in A and N transformants in active growth at the permissive and restrictive temperatures, which argued against a control at a transcriptional level. Assay of a defined function of the protein, namely, the binding of nucleotide detected by affinity labeling with periodate-oxidized [alpha-32P]ATP, clearly showed that the large T proteins from both types of transformants exhibited, at least for that particular biochemical function, the same in vitro temperature sensitivity. In transformants of the A type only could a reduced binding activity be detected in extracts from cells grown at the restrictive temperature. Thus, the temperature-independent behavior of the A transformants may result from an in vivo partial stabilization of the newly synthesized large T protein, probably through interaction with a cellular component(s).


Allergenic risk assessment of cowpea and its cross-reactivity with pea and peanut.
Novel protein sources can represent a risk for allergic consumers. The aim of this study was to evaluate the allergenicity of cowpea (Vigna unguiculata), an increasingly consumed legume and potential new industrial food ingredient which may put legume-allergic patients at risk. Children with allergy to legumes associated to peanut (LP group: n = 13) or without peanut allergy (L group: n = 14) were recruited and sensitization to several legumes including cowpea was assessed by prick tests and detection of specific IgE (sIgE). Cowpea protein extract was analyzed by SDS-PAGE and immunoblotting, IgE-reactive spots were subjected to mass spectrometry. IgE-cross-reactivity between cowpea, pea, and peanut was determined using ELISA inhibition assays. Basophil activation tests were performed to evaluate sensitivity and reactivity of patient basophils toward legumes. Prick tests and sIgE levels to cowpea were positive in 8/14 and 4/13 patients of the L group and in 9/13 and 10/13 patients of the LP group, respectively. Four major IgE-binding proteins were identified as vicilins and seed albumin. Cowpea extract and its vicilin fraction strongly inhibited IgE-binding to pea and peanut extract. Peanut, lentil, and pea were the strongest activators of basophils, followed by cowpea, soybean, mung bean, and lupin. A majority of patients with legume allergy were sensitized to cowpea proteins. Four novel allergens were identified in cowpea, among which storage proteins were playing an important role in IgE-cross-reactivity, exposing legume-allergic patients to the risk of clinical cross-reactivity to cowpea and thus adding cowpea to the group of nonpriority legumes that are not subjected to allergen labeling such as chickpea, pea, and lentil.


[Absolute strength of the muscles attached to the mandible].
In the course of an anatomical investigation of the muscles, securing movements of the mandible, performed on 10 human corpses, the muscle fibre length, volume and weight of each muscle has been estimated. Owing to the formula suggested by P. F. Leshaft (1880)--q = v/e, the physiological diameter of the muscles has been determined. Since the muscle with the diameter equal to 1 cm2 develops an absolute forse of 10 kg, the absolute muscle force value of the anterior group of muscles has been obtained for the first time (venter anterior musculi digastri--4.8 kg, musculus mylohyoideus--10.7 kg and musculus geniohyoideus--6.3 kg). The data on the absolute force of the posterior group of muscles has been verified (musculus masseter--24.2 kg, musculus temporalis--28 kg, musculus pterygoideus medialis--15.6 kg and musculus pterygoideus lateralis--15.5 kg). Analysing the interaction of forces of the muscles participating in the mandible movements, direction and value of displacements of the mandibular fragments have been explained and confirmed on some clinical examples. The data on the absolute force of the muscles studied can be used for investigating the displacement mechanism of the mandibular fragments after its resection and when its integrity is broken.


Intra-axonal transport and turnover of neurophysins in the rat. A proposal for a possible origin of the minor neurophysin component.
1. Radioactivity associated with the three neurophysins in the neural lobe of the rat was determined at intervals up to 5 weeks after an intracisternal injection of [(35)S]cysteine. 2. The radioactivity associated with the two major neurophysins (one supposedly associated with vasopressin and the other with oxytocin) increased linearly for 12h after the injection and the ratio of the rates of increase in the two proteins was very similar to the ratio of vasopressin to oxytocin in the gland. 3. From 12h onwards the radioactivity associated with each major neurophysin declined exponentially but the half-life of the supposed oxytocin-neurophysin (13.3 days) was shorter than that for the supposed vasopressin-neurophysin (19.8 days). 4. The kinetics of labelling of the minor neurophysin was quite different from that of the two major ones. It became slowly labelled during 3-5 days after injection and the radioactivity hardly decreased during the following 4 weeks. 5. The data could support the hypothesis that the minor neurophysin is a metabolic product of oxytocin-neurophysin. The exponential rate of disappearance of radioactivity from oxytocin-neurophysin and the minor component taken together has a rate constant similar to that for vasopressin-neurophysin (e.g. half-life=18.9 days).


Training the trainers: substance abuse screening and intervention.
Screening and brief intervention for substance abuse is effective yet underutilized by primary care physicians. This article reports on Project SAEFP (Substance Abuse Education for Family Physicians), which aimed to enhance the clinical and teaching skills and activities of U.S. family practice residency faculty. Ten five-day workshops were designed and administered for 165 participants. Evaluation data included measures of participant satisfaction and pre-workshop and twelve-month post-workshop measures of the frequency of teaching, consulting, and clinical activities, and the attainment of self-identified teaching goals. The participants were very satisfied with the workshops. They improved significantly in the key outcome measures. Several workshops may have contributed to the apparent success of Project SAEFP. Attributes of the workshops which might have facilitated their success were their duration, funding, frequency of offering, collegial learning environment, opportunities for active learning, emotionally moving exposure to recovering individuals, focus on how to modify curriculum at participant residency programs, availability of family physician role models as faculty, and readily usable instructional materials. Planners of interventions for physician educators might profit from similar attention to these attributes.


Sustained increases in heart rate induced by timed repetition of vagal stimulation in dogs.
We determined the influence of the "free-running cycle length" (tau FR) on chronotropic responses to one burst of right vagal stimuli per cardiac cycle in anesthetized dogs (tau FR, cycle length that prevailed in absence of right vagal stimulation). We varied tau FR by the following methods: 1) tonic left vagal stimulation in pentobarbital-anesthetized animals; 2) tonic left vagal stimulation plus sinus node cooling in pentobarbital-anesthetized animals; and 3) anesthesia with fentanyl, droperidol, and pentobarbital. When tau FR was less than a critical value [1,019 +/- 60 (SE) ms], right vagal stimulus bursts always had the expected negative chronotropic effect. However, when the tau FR was increased beyond critical value, right vagal stimulus bursts delivered within a specific portion of cardiac cycle actually had a positive chronotropic effect; i.e., cycle lengths diminished to values below tau FR. As tau FR was progressively increased beyond critical value, positive chronotropic response became greater and could be evoked by stimulus bursts delivered within a greater fraction of cardiac cycle. The right vagal stimuli that elicited the maximum positive chronotropic effect were those that were given approximately 235 ms prior to beginning of next atrial depolarization. This critical time probably occurs near the end of the period of phase 4 depolarization of sinus node automatic cells.


Satellite Imaging and Long-Term Mosquito Surveillance Implicate the Influence of Rapid Urbanization on Culex Vector Populations.
The ecology and environmental conditions of a habitat have profound influences on mosquito population abundance. As a result, mosquito species vary in their associations with particular habitat types, yet long-term studies showing how mosquito populations shift in a changing ecological landscape are lacking. To better understand how land use changes influence mosquito populations, we examined mosquito surveillance data over a thirty-four-year period for two contrasting sites in central Iowa. One site displayed increasing levels of urbanization over time and a dramatic decline in Culex pipiens group (an informal grouping of Culex restuans, Culex pipiens, and Culex salinarius, referred to as CPG), the primary vectors of West Nile virus in central Iowa. Similar effects were also shown for other mosquito vector populations, yet the abundance of Aedes vexans remained constant during the study period. This is in contrast to a second site, which reflected an established urban landscape. At this location, there were no significant changes in land use and CPG populations remained constant. Climate data (temperature, total precipitation) were compiled for each location to see if these changes could account for altered population dynamics, but neither significantly influence CPG abundance at the respective site locations. Taken together, our data suggest that increased landscape development can have negative impacts on Culex vector populations, and we argue that long-term surveillance paired with satellite imagery analysis are useful methods for measuring the impacts of rapid human development on mosquito vector communities. As a result, we believe that land use changes can have important implications for mosquito management practices, population modeling, and disease transmission dynamics.


[Correlation between Peripheral Blood PLR with Treg, Th17 in Newly Diagnosed Multiple Myeloma and Its Influence on Prognosis].
To investigate the correlation of peripheral blood platelet/lymphocyte ratio (PLR) with Treg and Th17 and its influence on prognosis in newly diagnosed multiple myeloma (MM). One hundred thirty-five newly diagnosed multiple myeloma patients admitted to the Department of Hematology of Zhengzhou People's Hospital from June 2015 to October 2022 were selected as MM group. Clinical data included sex, age, immune typing, ISS stage, blood calcium (Ca), albumin (ALB), hemoglobin (Hb), PLR, LDH, β2 microglobulin (β2-MG), Treg and Th17 levels. Sixty healthy volunteers who underwent physical examination in our hospital during the same period were selected as the control group. PLR, Treg and Th17 levels in MM group and control group were compared. Pearson was used to analyze the correlation between PLR and Treg, Th17. The relationship between MM patients with different PLR and clinical features and prognosis was analyzed. The PLR and Th17 of MM patients were significantly higher than that of control group, and Treg was significantly lower than that of control group (P<0.05). In MM patients, PLR was negatively correlated with Treg (r=-0.616), and PLR was positively correlated with Th17 (r=0.555). Using mean PLR=132.72 as the boundary, 135 MM patients were divided into high PLR group (n=54) and low PLR group (n=81). In MM patients with high PLR, ISS stage, ALB and Treg were significantly higher than those in low PLR group, while Th17 was significantly lower than those in low PLR group (P<0.05). By univariate and COX regression analysis, PLR was an independent prognostic risk factor for newly diagnosed MM patients (P<0.05). MM patients with high PLR had better PFS and OS, and the difference was statistically significant compared with MM patients with low PLR (P<0.05). 65 patients admitted from June 2015 to December 2018 were used as the training set, and 70 patients admitted from January 2019 to October 2022 were used as the validation set. The OS of MM patients with different PLR were compared respectively. The results showed that the conclusions of the training set and the validation set were consistent. PLR with high expression had higher OS (P<0.01). PLR is correlated with Treg and Th17 in newly diagnosed MM patients, and high PLR has better prognosis. PLR can be used to evaluate the prognosis of MM patients.


Label-free DNA sensor by boron-doped diamond electrode using an ac impedimetric approach.
An electrochemical biosensor using a boron-doped diamond (BDD) electrode is described for differentiating between gene sequences according to DNA hybridization events using an ac impedimetric approach. BDD electrodes were dipped into a 1% solution of polyethylenimine (PEI) to adsorb a thin layer of positively charged PEI on the surface of BDD, then PEI-modified BDD electrodes were used to immobilize negatively charged single-stranded PCR fragments from Exon 7 of human p53 gene. Alternating current impedimetric measurements were first performed on these systems in phosphate buffered saline (PBS) and then upon exposure to single-stranded DNA (ssDNA). When the ssDNA-immobilized BDD electrode and solution ssDNA were completely complementary, a large drop in impedance was measured. Complementary DNA could be clearly detected at concentrations down to 10 (-19) g mL (-1) at a fixed frequency (10 Hz). Higher concentrations of DNA gave faster hybridization with saturation occurring at levels above 1.0 pg mL (-1.) Responses were much lower upon exposure to noncDNA, even at higher concentrations. The results show it is possible to directly detect target DNA at a fixed frequency and without additional labeling.


Validation of the Gambling Refusal Self-Efficacy Questionnaire for Chinese Undergraduate Students.
Although research on self-efficacy in the gambling literature took place more than 25 years ago, only in the recent decade did researchers attempt to develop valid and reliable measures of gambling-related self-efficacy. Recently Casey et al. (J Gambl Stud 24:229-246, 2008) developed the Gambling Refusal Self-Efficacy Questionnaire (GRSEQ) in an Australian sample, which is a valuable tool for gambling research. The first objective of this study is to validate the measure in a new sample. Given that previous research on Chinese's gamblers' self-efficacy is lacking, and that related research often used ad-hoc measures of the construct, a second objective of this study is to evaluate whether the GRSEQ is suitable for Chinese people. A sample of 427 university students (56.4 % females, 50.7 % gamblers) answered a questionnaire with measures including the GRSEQ, subjective norms, intentions toward gambling, general self-efficacy, impulsiveness, and pathological gambling symptoms. Evidence was found for the four-factor structure, internal consistency, criterion-related validity, and discriminant validity of the Chinese version of the GRSEQ among this young Chinese group.


Attitudes Toward Computer Interventions for Partner Abuse and Drug Use Among Women in the Emergency Department.
Drug use and partner abuse often coexist among women presenting to the emergency department (ED). Technology offers one solution to the limited time and expertise available to address these problems. The aims of this study were to explore womens' attitudes about use of computers for screening and intervening in drug use and partner abuse. Seventeen adult women with recent histories of partner abuse and drug use were recruited from an urban ED to participate in one-on-one semi-structured interviews. A coding classification scheme was developed and applied to the transcripts by two independent coders. The research team collaboratively decided upon a thematic framework and selected illustrative quotes. Most participants used computers and/or mobile phones frequently and reported high self-efficacy with them. Women described emotional difficulty and shame around partner abuse experiences and drug use; however, they felt that reporting drug use and partner abuse was easier and safer through a computer than face-to-face with a person, and that advice from a computer about drug use or partner abuse was acceptable and accessible. Some had very positive experiences completing screening assessments. However, participants were skeptical of a computer's ability to give empathy, emotional support or meaningful feedback. The ED was felt to be an appropriate venue for such programs, as long as they were private and did not supersede clinical care. Women with partner abuse and drug use histories were receptive to computerized screening and advice, while still expressing a need for the empathy and compassion of a human interaction within an intervention.


The Electrical Response to Injury: Molecular Mechanisms and Wound Healing.
Significance: Natural, endogenous electric fields (EFs) and currents arise spontaneously after wounding of many tissues, especially epithelia, and are necessary for normal healing. This wound electrical activity is a long-lasting and regulated response. Enhancing or inhibiting this electrical activity increases or decreases wound healing, respectively. Cells that are responsible for wound closure such as corneal epithelial cells or skin keratinocytes migrate directionally in EFs of physiological magnitude. However, the mechanisms of how the wound electrical response is initiated and regulated remain unclear. Recent Advances: Wound EFs and currents appear to arise by ion channel up-regulation and redistribution, which are perhaps triggered by an intracellular calcium wave or cell depolarization. We discuss the possibility of stimulation of wound healing via pharmacological enhancement of the wound electric signal by stimulation of ion pumping. Critical Issues: Chronic wounds are a major problem in the elderly and diabetic patient. Any strategy to stimulate wound healing in these patients is desirable. Applying electrical stimulation directly is problematic, but pharmacological enhancement of the wound signal may be a promising strategy. Future Directions: Understanding the molecular regulation of wound electric signals may reveal some fundamental mechanisms in wound healing. Manipulating fluxes of ions and electric currents at wounds might offer new approaches to achieve better wound healing and to heal chronic wounds.


National hospital discharge survey: annual summary, 1994.
This report presents national estimates of the use of non-Federal short-stay hospitals in the United States during 1994. Estimates are provided by demographic characteristics of patients discharged, geographic region of hospitals, conditions diagnosed, and surgical and nonsurgical procedures performed. Measurements of hospital use include number and rate of discharges and days of care, and the average length of stay. The estimates are based on data collected through the National Hospital Discharge Survey for 1994. The survey has been conducted annually by the National Center for Health Statistics since 1965. In the 1994, data were collected for approximately 277,000 discharges. Of the 512 eligible non-Federal short-stay hospitals, 478 (93 percent) responded to the survey. Diagnoses and procedures are presented according to their code number in the International Classification of Diseases, 9th Revision, Clinical Modification, or ICD-9-CM. In 1994 there were an estimated 30.8 million discharges from non-Federal short-stay hospitals. These patients used a total of 177.2 million days of care and had an average length of stay of 5.7 days. Other data summarized in this report include estimates for diagnoses, procedures, expected source of payment, hospital deaths, and newborn infants.


Knowledge deficiency of work-related radiation hazards associated with psychological distress among orthopedic surgeons: A cross-sectional study.
Knowledge and concern degree about work-related radiation hazards remained unknown among orthopedic surgeons. The aim of the cross-sectional study is to investigate whether the knowledge degree of work-related radiation is associated with psychological distress among orthopedic surgeons. This cross-sectional study sent electronic questionnaire via WeChat to orthopedic surgeons nationwide. Concern and knowing degree over radiation exposure was evaluated by a single self-reported question. Professional evaluation of concern degree was reflected by general psychological distress, which was assessed with the Kessler 10 scale (K10) and depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D). Only 43.23% (115/266) respondents knew well about radiation and a total of 78.20% (208/266) respondents considered radiation exposure as a great concern. Among those who reported concerns about radiation exposure, a total of 57.69% (120/208) respondents reported knowing little about radiation. Respondents who reported concerns over radiation exposure were significantly associated with higher scores on CES-D and K10 (P < .05). Among respondents who reported concerns over radiation exposure, those who have fewer knowledge about radiation, had higher CES-D and K10 scores than those who knew well about radiation (P < .05). Among respondents who reported no concerns over radiation exposure, those who knew little about radiation still had higher CES-D and K10 scores (P < .05). Fewer radiation knowledge tends to induce more radiation concerns associated with higher psychological distress in orthopedic surgeons. Radiation knowledge should be enhanced for surgeons who daily work with radiation-related fluoroscopy.