Impact of dental caries and nutritional status on oral health related quality of life in young Indian adolescents.
A combination of poor oral health status and malnourishment ultimately affect the quality of life of the person. Hence, these tools may help in identifying individuals at risk of poor quality of life and malnutrition caused by oral problems especially in adolescents. To test the association between dental caries, nutritional status and Oral Health Related Quality of Life (OHRQoL) in 12-15 year-old school going adolescents. A cross sectional study was conducted on 12-15-year-old school going adolescents. A total of 1214 adolescents participated in the study. Data on quality of life was collected using OHIP-14 and clinical examination was done to assess the DMFT status and Body Mass Index (BMI) as measure of nutritional status of the subjects. DMFT was found to be positively correlated with total OHIP score, however BMI was negatively correlated with OHIP. Controlling for BMI, partial correlation analysis revealed that there is a weak association between OHIP and DMFT scores which was found to be statistically significant. Both caries experience and nutrition status had significant impact on Quality of Life. All the three parameters were found to be correlated to each other.


Measurement of fetal atrioventricular intervals in pregnant women with anti-SSA/Ro antibodies.
The objective of our study was to compare and consider reference values of fetal atrioventricular (AV) intervals as measured by four different pulsed Doppler wave techniques (left ventricular inflow/outflow [LV in/out], pulmonary vein/pulmonary artery [PV/PA], innominate vein/ascending aorta [InnV/AA], and supra vena cava/ascending aorta [SVC/AA]) in pregnant women with anti-SSA/Ro antibodies. Between March 2014 and September 2020, 52 pregnant women with anti-SSA antibodies were enrolled. No bradyarrhythmia was observed in the group. A pulsed Doppler examination of the fetal heart was performed to obtain measurements of the mechanical Doppler AV interval. Doppler measurements were performed using four methods: LV in/out, PV/PA, InnV/AA, and SVC/AA. A statistical analysis was performed to examine the mean, standard deviation, significant difference, and correlation of the four methods. The detection rate of each method was also calculated. There was no significant difference in the AV intervals between any of the four methods. There was also a positive correlation in the AV intervals of each of the four methods. The fetal heart rate and AV interval showed no correlation. The gestational age and AV interval also showed no correlation. The detection rate was highest for LV in/out (62.6%, 95% confidence interval: 56.5-68.4). All four pulsed Doppler methods are useful for measuring AV intervals. The most practical method is LV in/out.


Micro-Raman analysis of the pigments on painted pottery figurines from two tombs of the Northern Wei Dynasty in Luoyang.
The pigments on the painted pottery figurines from two tombs of Northern Wei Dynasty (AD 386-534) in Luoyang were analyzed by Raman microscopy. All the pigments were identified compared with the Raman spectra of standard pigments. The red pigments were identified as haematite, the blue pigment as lapis lazuli, the green pigment as malachite, the black pigment as carbon black and the white pigment as calcite. Similar pigments were used in the two tombs despite the pottery figurines were very different in artistic style. The use of lapis lazuli as blue pigment on Chinese painted pottery figurines was found for the first time. This pigment and the painted pottery figurine of Sogdians are of great archaeological significance because it demonstrated that the trade and cultural exchanges via the Silk Road had extended to Luoyang city in the Northern Wei Dynasty. The result also confirms that micro-Raman spectroscopy is a powerful analytical method for the identification of pigments on ancient artworks.


Ion-Mediated Recombination Dynamics in Perovskite-Based Memory Light-Emitting Diodes for Neuromorphic Control Systems.
Neuromorphic devices can help perform memory-heavy tasks more efficiently due to the co-localization of memory and computing. In biological systems, fast dynamics are necessary for rapid communication, while slow dynamics aid in the amplification of signals over noise and regulatory processes such as adaptation- such dual dynamics are key for neuromorphic control systems. Halide perovskites exhibit much more complex phenomena than conventional semiconductors due to their coupled ionic, electronic, and optical properties which result in modulatable drift, diffusion of ions, carriers, and radiative recombination dynamics. This is exploited to engineer a dual-emitter tandem device with the requisite dual slow-fast dynamics. Here, a perovskite-organic tandem light-emitting diode (LED) capable of modulating its emission spectrum and intensity owing to the ion-mediated recombination zone modulation between the green-emitting quasi-2D perovskite layer and the red-emitting organic layer is introduced. Frequency-dependent response and high dynamic range memory of emission intensity and spectra in a LED are demonstrated. Utilizing the emissive read-out, image contrast enhancement as a neuromorphic pre-processing step to improve pattern recognition capabilities is illustrated. As proof of concept using the device's slow-fast dynamics, an inhibition of the return mechanism is physically emulated.


Sudden cardiac death and substance abuse.
There has been a steady increase in the number of deaths occurring from volatile substance abuse per year. The majority of deaths are in males, the peak age group being 15-19 years. Fuel gases i.e. cigarette lighter refills (butane), propane and gasoline and other solvents such as typewriter correction fluid, dry-cleaning fluids (trichloroethane) and fire extinguishers (bromochlorodifluoromethane) are responsible for approximately 60% of these deaths. Volatile substances sensitise the heart to circulating catecholamines, such that sudden alarm or exercise may precipitate sudden death. The main mechanism of cardiac arrest is a cardiac arrhythmia, but anoxia, respiratory depression and vagal stimulation along with aspiration of vomit or trauma may be contributing factors to the sudden death. In addition, particularly butane gas inhalation may be associated with severe laryngeal oedema and laryngospasm. Resuscitation from sudden death associated with volatile substance abuse is rare, since the majority of deaths are unwitnessed. It is suggested that cardiac arrhythmias should be treated conventionally. Sympathomimetic drugs should be avoided. Early during the resuscitation process, beta-adrenergic blocking agents should be administered to protect the catecholamine-sensitised heart. Early intubation in the management of the cardiac arrest should be avoided, if the inhalational agent is known to be associated with laryngospasm.(ABSTRACT TRUNCATED AT 250 WORDS)


Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and tobacco withdrawal symptoms in adult smokers with ADHD.
Tobacco withdrawal symptoms may be confounded with attention-deficit/hyperactivity disorder (ADHD) symptoms among smokers with ADHD. (1) To assess overlap between ADHD symptoms and tobacco/nicotine withdrawal symptoms and craving; (2) to assess the relationship between craving or withdrawal symptoms and the effect of osmotic-release oral system methylphenidate (OROS-MPH) on ADHD symptoms; (3) to assess the association of ADHD symptoms, craving, and withdrawal symptoms with abstinence. Secondary analysis of a randomized, placebo controlled smoking cessation trial assessing the efficacy of OROS-MPH taken in addition to nicotine patch among individuals with ADHD. ADHD symptoms, withdrawal symptoms, and craving were assessed at baseline and 2, 4 and 6 weeks after a target quit day. Withdrawal symptoms and craving showed limited and modest overlap with ADHD symptoms prior to abstinence but more extensive and stronger correlation after quit day. Compared to placebo, OROS-MPH reduced ADHD symptoms; this effect was attenuated by controlling for withdrawal symptoms, but not by craving. Craving, but not ADHD symptoms and withdrawal symptoms, was associated with abstinence during the trial. When treating smokers with ADHD (1) craving, rather than tobacco withdrawal symptoms or ADHD symptoms may be the more effective therapeutic smoking cessation targets; (2) careful distinction of craving, withdrawal symptoms, and ADHD symptoms when assessing withdrawal phenomena is needed.


Relationship between chewing side preference and handedness and lateral asymmetry of peripheral factors.
To determine whether chewing side preference is related to handedness and lateral asymmetry of occlusal characteristics, muscular force and temporomandibular disorders (TMD) in a dentate population. One hundred and seventeen dentate adults participated in this cross-sectional study. Static and dynamic occlusal characteristics were determined at the maximal intercuspal position and at the lateral excursions by scanning interocclusal records and analysing them using image software. Unilateral maximum bite force and finger-thumb grip force were measured by means of a gnathodynamometer. TMD were assessed according to the Research Diagnostic Criteria for TMD. Chewing side preference and masticatory laterality were determined by observing the jaw's movement while each subject chewed silicone. Asymmetry or side difference of the variables was calculated. Correlation between side difference variables and masticatory laterality was studied using Spearman correlation coefficient. Fifty-nine subjects chewed on the right, 15 on the left and 43 chewed on both sides. There was no relationship between preferred chewing side and handedness, lateral asymmetry of TMD or side difference in finger-thumb grip force. Significant and positive correlations were observed between masticatory laterality and side differences in bite force and side differences in occlusal contact area at intercuspal position (P<0.01). Chewing side preference in a dentate population is related to lateral asymmetry of bite force and asymmetry of occlusal contact area at the intercuspal position but not to handedness.


Changes in mouse skin cyclic nucleotides during chemical carcinogenesis and tumor response to treatment with BCG, L-Dopa and cyclic DBAMP.
During chemical carcinogenesis by 9, 10-dimethyl 1,2-benzanthracene the cyclic AMP and GMP content was measured in the skin of mice. The tissue of the developing skin tumor is characterized by an elevated cyclic GMP- and a lowered cyclic AMP level. Consequently the quotient of cyclic AMP and GMP is greatly lowered and is discussed as a crucial factor of cell derangement. Complete regression of the tumor is to be achieved by increasing the cyclic AMP levels by means of cyclic DBAMP and L-Dopa in 20% of the experimental animals. Additional stimulation by BCG of the unspecific immune defence has a favourable effect on tumor regression (about 50%). In a different type of tumor (solid Ehrlich carcinoma) it was possible after pretreatment of the mice with L-Dopa, cyclic DBAMP and BCG and after treatment following tumor injection to prevent tumor development in 67% of the animals.


Prenatal diagnosis, fetal surgery, recurrence risk and differential diagnosis of neural tube defects.
Prenatal screening with alpha-fetoprotein (AFP) and ultrasonography have allowed the prenatal diagnosis of neural tube defects (NTDs) in current obstetric care, and open spina bifida has been considered a potential candidate for in utero treatment in modern pediatric surgery. This article provides an overview of maternal serum AFP screening, amniotic fluid AFP assays, amniotic fluid acetylcholinesterase immunoassays and level II ultrasound for NTDs, prenatal repair of fetal myelomeningocele, recurrence risk of NTDs, and differential diagnosis of NTDs on prenatal ultrasound.


Fluorescent multiplex PCR--fast method for autosomal dominant spinocerebellar ataxias screening.
Expansion of CAG trinucleotide repeats has been shown to cause a number of autosomal dominant spinocerebellar ataxias such as SCA1, SCA2, SCA3/MJD, SCA6 and SCA7. These disorders are characterized by a wide inter- and intrafamiliar variation in clinical features. The same mutation can result in different phenotypes and the very similar phenotypes can be caused by different mutations. Therefore it is necessary to investigate more SCA genes (according to prevalence) to identify the causal elongation. We developed a fast and efficient screening method based on touchdown multiplex PCR with fluorescent labelled primers for the most common types of SCAs (SCA 1, 2, 3 and 7). It has been reliable in 113 probands tested. Fragment analysis was performed by using 6% denaturing polyacrylamide gel and employing the automated DNA sequencer. This method considerably shortens the process of molecular genetic screening of SCAs and might be used as a tip for designing other SCA screening sets.


Making Treatment of Special Needs Patients an Important Part of Your Growing Dental Practice.
Today many young dentists want to find a way to make their practices satisfying in ways other than the financial rewards of dentistry. Some of these practitioners have gained additional training in diagnosis and treatment of medically and physically compromised patients in hospital-based, general practice residency programs. A hospital affiliation can create a unique niche that will allow dentists to differentiate themselves from other dentists. By welcoming those ongoing relationships for patients with special needs, and having the resources and desire to treat them, dentists will achieve greater visibility and a reputation as caring, capable practitioners in their community.


Pulmonate slug evolution is reflected in the de novo genome of Arion vulgaris Moquin-Tandon, 1855.
Stylommatophoran pulmonate land slugs and snails successfully completed the water-to-land transition from an aquatic ancestor and flourished on land. Of the 30,000 estimated species, very few genomes have so far been published. Here, we assembled and characterized a chromosome-level genome of the "Spanish" slug, Arion vulgaris Moquin-Tandon, 1855, a notorious pest land slug in Europe. Using this reference genome, we conclude that a whole-genome duplication event occurred approximately 93-109 Mya at the base of Stylommatophora and might have promoted land invasion and adaptive radiation. Comparative genomic analyses reveal that genes related to the development of kidney, blood vessels, muscle, and nervous systems had expanded in the last common ancestor of land pulmonates, likely an evolutionary response to the terrestrial challenges of gravity and water loss. Analyses of A. vulgaris gene families and positively selected genes show the slug has evolved a stronger ability to counteract the greater threats of external damage, radiation, and water loss lacking a protective shell. Furthermore, a recent burst of long interspersed elements in the genome of A. vulgaris might affect gene regulation and contribute to rapid phenotype changes in A. vulgaris, which might be conducive to its rapid adaptation and invasiveness.


Use of toe clips as a nonlethal index of mercury accumulation and maternal transfer in amphibians.
Nonlethal indices of contaminant exposure can facilitate research on the accumulation and effects of contaminants in wildlife. Here, we tested the efficacy of using amputated toes ("toe clips"), a common byproduct when marking amphibians in population and genetic studies, to determine mercury (Hg) concentrations in amphibians. We examined total mercury (THg) concentrations in American toads (Bufo americanus) collected along a contamination gradient at a Hg-contaminated field site. We found significant positive correlations between toe THg and blood THg concentrations in adult males and females collected in two different years. We also found that blood and toe clips could be used to predict maternal transfer of Hg, an important mechanism of reproductive toxicity in wildlife. Maternal toe THg concentrations were more highly correlated with egg THg concentrations than were maternal blood THg concentrations. Our results indicate that amputated toes are effective for identifying Hg concentrations in amphibians.


Synchronous pulmonary MALT lymphoma and squamous cell lung cancer: a case report.
Pulmonary B-cell lymphoma in the extranodal marginal zone of mucosa-associated lymphoid tissue (MALT), a rare tumor originating from bronchial mucosa-associated lymphoid tissue, is the major histologic type of primary pulmonary lymphoma. Combined lung squamous cell carcinoma with pulmonary MALT lymphoma is rare. A 63-year-old male patient presented to the hospital because of a dry cough, and chest CT showed soft tissue density nodules in the upper lobe of the right lung, the boundary was visible lobulation and spiculation, and the middle lobe of the right lung showed patchy shadow, moderate enhancement, associated with bronchial traction. After a multidisciplinary diagnosis and treatment (MDT) discussion, surgical resection was done for the patient, and postoperative pathological results showed pulmonary MALT lymphoma combined with lung squamous carcinoma. For complex pulmonary multiple lesions, judgment needs to be made after MDT discussion, and timely intervention is required for lesions suspicious of malignancy. There are no uniform recommendations for the management of mixed tumors of the lung, and an individualized treatment plan needs to be developed based on the patient's actual condition.


Monitoring of Multimode Imaging Devices by use of Optical Low-Coherence Reflectometers in Reflection and Transmission Modes.
The broadband source of a high-precision optical low-coherence reflectometer is simultaneously employed in conventional reflection and transmission modes to monitor the internal properties of multimode imaging (MMI) devices. Using two carefully chosen examples, we show that this new methodology should permit precise assessment of the performance of MMI devices, including backreflection and internal reflection as well as the imbalance between output waveguides.


Shifts in a fish's resource holding power during a contact paired interaction: the influence of a copper-contaminated diet in rainbow trout.
The influence of sublethal chronic dietary copper (Cu) exposure on the dominant-subordinate relationship between pairs of juvenile rainbow trout (Oncorhynchus mykiss) was examined. Fish were fed either a normal (11 mg Cu kg(-1) food) or Cu-contaminated (721 mg Cu kg(-1) food) diet for 8 wk. Paired interactions were observed--control versus control, Cu-exposed versus Cu-exposed, and control versus Cu-exposed fish--using a computer-aided video tracking system to measure duration of interactions, total distance moved, and the number of encounters during each contest. In concurrence with game theory, each interaction became escalated with a lesser size disparity between contestants. However, in Cu-exposed versus Cu-exposed fish interactions, the dominant-subordinate relationship was decided sooner and with less aggression than a control versus control fish interaction with fish of a similar relative body mass disparity. During control versus Cu-exposed fish interactions, control fish would normally dominate interactions (12 out of 16 bouts) unless the Cu-exposed fish had a 15% body mass advantage. Muscle glycogen and lactate levels after each contest reflected the duration of bouts and winners of the contests, irrespective of Cu exposure. We conclude that Cu-contaminated fish are less able to compete and have lower resource holding power than controls and will withdraw from a contest at a lower level of interaction, unless a size advantage in the Cu-exposed fish increases the probability of winning.


A survey of temporomandibular joint dislocation: aetiology, demographics, risk factors and management in 96 Nigerian cases.
A retrospective study of 96 cases of temporomandibular joint dislocation was undertaken. Patients' ages ranged from 9 to 85 years (mean+/-SD, 35.3+/-17.4 years) and peak incidence was at 20-29 years. Mean duration was 7.9 weeks (range, 1h to 3 years). Acute, chronic and recurrent dislocations were seen in 46 (47.9%), 29 (30.2%) and 21 (21.9%) patients, respectively. Males dominated in all three categories but this was not statistically significant (P = 0.8). Excessive mouth opening while yawning (44 cases) was the commonest cause of dislocation, followed by road traffic accidents (13 cases). Ten patients (10.4%) had an underlying systemic disease, the commonest being epilepsy (four cases); those with acute dislocation recorded the highest incidence of underlying illness. Bilateral anterior (86 cases) dislocations were the most frequent. Of the 96 patients, 89 (92.7%) were available for treatment. Manual reduction with or without anaesthesia proved effective for 38/45 acute, 5/24 chronic and 14/20 recurrent cases. Chronic dislocations were treated mainly by surgical osteotomy (13/24). Vertical subsigmoid and oblique ramus osteotomies were the commonest surgical techniques recorded. Treatment was satisfactory for all patients surgically handled except for one case of anterior open bite postoperatively. This study has shown that excessive mouth opening while yawning is the commonest cause of temporomandibular joint dislocation in Nigerians, and conservative approaches to management remain quite effective irrespective of the duration and clinical subtype. The best choice of surgical technique should be determined by proper clinical evaluation and the need to avoid or minimize postoperative morbidity.


Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38.
Spinocerebellar ataxia 38 (SCA38) is caused by mutations in the ELOVL5 gene, which encodes an elongase involved in the synthesis of polyunsaturated fatty acids, including docosahexaenoic acid (DHA). As a consequence, DHA is significantly reduced in the serum of SCA38 subjects. In the present study, we evaluated the safety of DHA supplementation, its efficacy for clinical symptoms, and changes of brain functional imaging in SCA38 patients. We enrolled 10 SCA38 patients, and carried out a double-blind randomized placebo-controlled study for 16 weeks, followed by an open-label study with overall 40-week DHA treatment. At baseline and at follow-up visit, patients underwent standardized clinical assessment, brain 18-fluorodeoxyglucose positron emission tomography, electroneurography, and ELOVL5 expression analysis. After 16 weeks, we showed a significant pre-post clinical improvement in the DHA group versus placebo, using the Scale for the Assessment and Rating of Ataxia (SARA; mean difference [MD] = +2.70, 95% confidence interval [CI] = +0.13 to + 5.27, p = 0.042). At 40-week treatment, clinical improvement was found significant by both SARA (MD = +2.2, 95% CI = +0.93 to + 3.46, p = 0.008) and International Cooperative Ataxia Rating Scale (MD = +3.8, 95% CI = +1.39 to + 6.41, p = 0.02) scores; clinical data were corroborated by significant improvement of cerebellar hypometabolism (statistical parametric mapping analyses, false discovery rate corrected). We also showed a decreased expression of ELOVL5 in patients' blood at 40 weeks as compared to baseline. No side effect was recorded. DHA supplementation is a safe and effective treatment for SCA38, showing an improvement of clinical symptoms and cerebellar hypometabolism. Ann Neurol 2017;82:615-621.


Pitfall of Light Transmission Aggregometry-Based Assessment of Platelet Function in Acute Ischemic Stroke Patients.
The utility of light transmission aggregometry (LTA)-based assessment of platelet function in acute ischemic stroke patients remains controversial. This study aimed to clarify why LTA failed to estimate platelet function in acute ischemic stroke patients. Using LTA, we evaluated the platelet aggregation abilities of citrated blood samples from 22 acute noncardiogenic ischemic stroke patients prior to treatment and compared them with those of 65 heathy volunteer controls. Platelet counts and mean platelet volumes (MPV) of citrated blood and platelet-rich plasma (PRP) prepared for LTA were evaluated simultaneously. Using a hematology analyzer, we also measured and compared the aggregation-prone properties of platelets in the hematology analysis process between patient and control samples. Although platelets aggregated more easily and frequently in patient samples (P < .01), the maximum aggregation rate (MA%) of LTA was paradoxically lower in patients than in controls (P < .05). The PRP/citrated blood ratio of platelet counts and MPV were significantly lower in patients than in controls (P < .05). Our results suggest that MA% of LTA is erroneously displayed as lower values than the actual status in patients with increased platelet aggregation ability such as acute ischemic stroke because activated large platelets are preaggregated and thus decreased in the PRP on LTA.


Hemopatch® is effective and safe to use: real-world data from a prospective European registry study.
Surgical procedures are often impeded by bleeding and/or leakage of body fluids. These complications cannot always be resolved by conventional surgical techniques. Hemopatch® is a hemostatic patch that also functions as a sealant. Here we document the effectiveness and safety of Hemopatch® for routine procedures of multiple surgical disciplines. To this end, we performed a prospective, multicenter, single-arm, observational registry study. Patients were eligible if they had received Hemopatch® during an open or minimally invasive procedure in one of these specialties: hepatobiliary, cardiovascular, urological, neurological/spinal, general, or lung surgery. Patients were excluded if they had a known hypersensitivity to bovine proteins or brilliant blue, intraoperative pulsatile or severe bleeding and/or infection at the target application site (TAS). The primary endpoint for intraoperative effectiveness was hemostasis assessed as the percentage of patients achieving hemostasis within 2 min and the percentage of patients achieving hemostasis without re-bleeding at the time of surgical closure. The registry enrolled 621 patients at 23 study sites in six European countries. Six hundred twenty patients had completed follow-up information. Hemostasis within 2 min was achieved at 463 (74.5%) of all 621 TASs. Hemostasis without re-bleeding was observed at 620 (99.8%) TASs. Adverse events were reported in 64 patients (10.3%). This Hemopatch® registry shows that Hemopatch® efficiently establishes hemostasis and sealing in a variety of surgical specialties, including minimally invasive procedures. Furthermore, we provide evidence for the safety of Hemopatch® across all the specialties included in the registry. This study is registered at clinicaltrials.gov: NCT03392662.


Effects of exercise on immune cells with tumor-specific activity in breast cancer patients and survivors: a systematic review and meta-analysis.
Exercise is effective for improving the physical and psychological health of breast cancer patients. However, there is still controversy around its role on the immune system. Therefore, this systematic review and meta-analysis is aimed to evaluate the effect of chronic exercise on the number and activity of the immune cells that can contribute to anti-tumor immune responses, such as natural killers (NK) cells, CD + 4, or CD + 8. The main hypothesis of this study was that exercise could improve the immune system or, at least, there will not be a reduction in the number or activity of immune cells because of exercise. The search was conducted in the PubMed and Web of Science databases. Out of 244 studies reviewed, 10 studies met the inclusion criteria. The studies included in the meta-analyses showed mixed results and no significant (p > 0.05) positive or negative effects of exercise interventions in women with breast cancer. Therefore, the current evidence indicates that exercise does not significantly improve or reduce the immune system; thus, the prescription of exercise must not be discouraged due to the effects on the number and activity of immune system cells, but should be recommended due to the well-known benefits in quality of life, physical function or fatigue, and the absence of negative effects on the immune system. Further studies are needed to evaluate the effects according to the type of exercise, the type of cancer, or the timing of the intervention.


[DEVELOPMENT RESEARCH OF PREVENTION OF PROSTHETIC JOINT INFECTION].
To summarize the recent progress in prevention of prosthetic joint infection (PJI) so as to provide clinical references. The publications concerning the etiology and surgical management of PJI were reviewed, analyzed, and summarized. The prevention of PJI is related to preoperative, intraoperative, and postoperative aspects of PJI, comprehensive treatment is considered to be the most common method for PJI. These prevention strategies that may be utilized in all phases of perioperative care, a multifaceted approach to the patient undergoing total joint replacement will have the greatest positive effect.


Enzyme immunoassay and characterization of pancreatic stone proteins in human urine.
An enzyme immunoassay of pancreatic stone protein (PSP) in human urine was developed. Mean analytical recovery of pure PSP-S2-5 added to urine was 102.3% (SD 5.9%), and the precision of the assay was 2.0-2.7% within an assay and 2.5-2.9% between assays. In healthy volunteers (age 20-55 years), the mean value of the PSP concentration, expressed as ratios to urine creatinine, was 129 +/- 88 (mean +/- SD) micrograms/g without any differences for sex. Urine PSP correlated with urine N-acetylglucosaminidase (NAG) (r = 0.354). The molecular forms of immunoreactive PSP in urine were characterized by using cation exchange chromatography (Mono S), SDS-PAGE, N-terminal sequence, and enzyme immunoassay analysis. The urine PSP, eluted at the position corresponding to PSP-S2-5 on cation exchange chromatography, was converted to PSP-S1 by trypsin digestion. The difference in mobility on SDS-PAGE between urine PSP and PSP-S2-5 seems to be due to a glycosylated undecapeptide (N-terminal 1-11). The proposed method offers a sensitive, specific, and reproducible tool for laboratory analysis of human urine PSP levels.


Cyto-protective and immunomodulating effect of Curcuma longa in Wistar rats subjected to carbon tetrachloride-induced oxidative stress.
A comparison of crude curcuminoid extract and purified curcumin was made to evaluate hepato- and immunoprotective effect of Curcuma longa (turmeric) Zingiberaceae. Carbon tetrachloride (CCl4) induced cellular hepatic damage was evaluated by transmission electron microscopy, hepatic enzymes and thiobarbituric acid reactive species (TBAR) values. A selective cytolytic effect of CCl4 was observed among immature (PNA+) thymocytes and peripheral helper (CD4+) T lymphocytes in spleen and was paralleled by a significant reduction in CD25, CD71 and Con A receptor expression. Treatment with curcuminoid crude extract at two different doses, showed a significant cellular recovery among hepatocytes, which was reflected in a reduction of hepatic enzymes and TBAR values. A significant restoration of lymphocyte viability and CD25, CD71 and Con A receptor expression in both immature (PNA+) thymocytes and splenic helper (CD4+) T lymphocytes was observed. Turmeric crude extract, at both low and high dose, was found to be more efficient as compared to purified curcumin.


A survey for torovirus in New Zealand cats with protruding nictitating membranes.
Faecal samples from 51 cats were examined by negative stain electron microscopy to investigate a possible association between the syndrome of bilateral protrusion of the nictitating membranes and torovirus infection. Although toroviruses were not observed in any sample, other viruses or virus-like particles were observed in faeces from one of 15 cats with the syndrome, six of 21 cats which had experienced prior episodes of the syndrome and four of 15 healthy control cats. The findings of this study do not support the hypothesis that the syndrome is associated with torovirus infection.


Diagnosis of copy number variation by Illumina next generation sequencing is comparable in performance to oligonucleotide array comparative genomic hybridisation.
Array comparative genomic hybridisation (aCGH) profiling is currently the gold standard for genetic diagnosis of copy number. Next generation sequencing technologies provide an alternative and adaptable method of detecting copy number by comparing the number of sequence reads in non-overlapping windows between patient and control samples. Detection of copy number using the BlueGnome 8×60k oligonucleotide aCGH platform was compared with low resolution next generation sequencing using the Illumina GAIIx on 39 patients with developmental delay and/or learning difficulties who were referred to the Leeds Clinical Cytogenetics Laboratory. Sensitivity and workflow of the two platforms were compared. Customised copy number algorithms assessed sequence counts and detected changes in copy number. Imbalances detected on both platforms were compared. Of the thirty-nine patients analysed, all eleven imbalances detected by array CGH and confirmed by FISH or Q-PCR were also detected by CNV-seq. In addition, CNV-seq reported one purported pathogenic copy number variant that was not detected by array CGH. Non-pathogenic, unconfirmed copy number calls were detected by both platforms; however few were concordant between the two. CNV-seq offers an alternative to array CGH for copy number analysis with resolution and future costs comparable to conventional array CGH platforms and with less stringent sample requirements.


Influence of gender on long-term mortality in patients presenting with non-ST-elevation acute coronary syndromes undergoing percutaneous coronary intervention.
Although an invasive strategy has predominately been studied in men with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), its role in low-risk women is unclear. We sought to examine gender differences in a real-world registry of patients with NSTE-ACS who underwent percutaneous coronary intervention (PCI). Patients with NSTE-ACS undergoing PCI at the Cleveland Clinic, Cleveland, Ohio from 2003 through 2007 (n = 1,874) were included. In-hospital and long-term mortalities were assessed. Cox proportional hazards models were constructed to study the influence of gender on mortality. Interactions with age and biomarker status were examined. Women were older and had a higher incidence of co-morbid conditions compared to men. They had a smaller reference vessel diameter compared to men. Despite these characteristics there was no overall difference in in-hospital (1.4% vs 1.6%) or long-term (14.6% vs 15.8%) mortality between men and women. However, there was evidence of a significant effect modification by age (p = 0.012) and troponin status (p = 0.0073) for long-term mortality such that women <60 years of age, especially those who were troponin negative, had more than a twofold increase in long-term mortality compared to men (p = 0.007). In conclusion, although overall mortality rates are similar between men and women undergoing PCI for NSTE-ACS, women <60 years old with negative biomarkers have a higher mortality than their men peers.


Discrepant acute effect of saline loading on blood pressure, urinary sodium and potassium according to salt intake level: EpiSS study.
Acute dietary salt intake may cause an elevation in blood pressure (BP). The study aimed to assess the acute effect of saline loading on BP in subjects with different levels of salt intake. This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. The sodium excretion in the 24-hour urine was calculated for estimating the level of salt intake. Subjects were performed an acute oral saline loading test (1 L), and data of 2019 participants were included for analyses. Multivariate linear regression and stratified analyses were performed to identify associations between 24-hour urinary sodium (24hUNa) with BP changes. Due to saline loading, systolic BP (SBP), pulse pressure, and urinary sodium concentration were significantly increased, while diastolic BP, heart rate, and urinary potassium concentration were significantly decreased. The SBP increments were more significant in subjects with lower salt intake, normotensives, elders, males, smokers, and drinkers. There was a significant linear negative dose-response association between SBP increment with 24hUNa (β = -0.901, 95% CI: -1.253, -0.548), especially in lower salt intake individuals (β = -1.297, 95% CI: -2.338, -0.205) and hypertensive patients (β = -1.502, 95% CI: -2.037, -0.967). After excluding patients who received antidiabetic or antihypertensive medicines, the effects of negative associations weakened but remained significantly. In conclusion, acute salt loading leads to an increment in SBP, and the increased SBP was negatively related with 24hUNa. This study indicated avoiding acute salt loading was important for escaping acute BP changes, especially in lower salt intake populations.


Inducible expression of catalytically active type 1 serine/threonine protein phosphatase in a human carcinoma cell line.
BACKGROUND: One of the major cellular serine/threonine protein phosphatases is protein phosphatase type 1 (PP1). Studies employing many eukaryotic systems all point to a crucial role for PP1 activity in controlling cell cycle progression. One physiological substrate for PP1 appears to be the product of the retinoblastoma susceptibility gene (pRB), a demonstrated tumor suppressor. The growth suppressive activity of pRB is regulated by its phosphorylation state. Of critical importance is the question of the in vivo effect of PP1 activity on pRB and growth regulation. As a first step towards addressing this question, we developed an inducible PP1 expression system to investigate the regulation of PP1 activity. RESULTS: We have established a cell line for inducing protein expression of the type 1, alpha-isotype, serine/threonine protein phosphatase (PP1alpha). A plasmid encoding a fusion protein of the catalytic subunit of PP1alpha with a 6-histidine peptide (6His) and a peptide from hemagluttinin (HA) was transfected into the UMUC3 transitional cell carcinoma cell line, previously transfected with the reverse tetracycline transactivator plasmid pUHD172-1neo. A stable cell line designated LLWO2F was established by selection with hygromycin B. 6His-HA-PP1alpha protein appeared in cell lysates within two hours following addition of doxycycline to the culture medium. This protein localizes to the nucleus as does endogenous PP1alpha, and was shown to associate with PNUTS, a PP1-nuclear targeting subunit. Like endogenous PP1alpha, immunocomplexed 6His-HA-PP1alpha is active toward phosphorylase a and the product of the retinoblastoma susceptibility gene, pRB. When forcibly overexpressing 6His-HA-PP1alpha, there is a concomitant decrease in endogenous PP1alpha levels. CONCLUSIONS: These data suggest the existence of an autoregulatory mechanism by which PP1alpha protein levels and activity remain relatively constant. RT-PCR analyses of isolated polysome fractions support the notion that this putative autoregulatory mechanism is exerted, at least in part, at the translational level. Implications of these findings for the study of PP1alpha function in vivo are discussed.


Do all patients attending genitourinary medicine services want to be seen within 48 hours?
At a time of high capacity almost 40% of patients declined an appointment within 48 hours. Data were collected prospectively on the reasons why, and the impact of demand exceeding capacity.


Outcomes of retinal pigment epithelial detachment in Vogt-Koyanagi-Harada disease: a longitudinal analysis.
The aim of this study was to report the clinical profile and outcomes of retinal pigment epithelial detachment (PED) in Vogt-Koyanagi-Harada (VKH) disease, and to evaluate the correlation between PED and the subsequent development of central serous chorioretinopathy (CSC) throughout the whole corticosteroid treatment course. The retrospective study enrolled a total of 470 eyes with VKH, and 12 eyes with VKH and PED were recruited. Patients were divided into two groups according to the CSC onset or not throughout the whole course (the CSC group and non-CSC group). Best-corrected visual acuity (BCVA) improvement, and PED angle (PEDA, the angle between the two lines of the vertex of the lifted retinal pigment epithelium to the two edge points of the Bruch membrane) were compared between the two groups. CSC developed at the site of the PED in 5 of the 12 eyes with PED, while in the remaining 7 eyes PED gradually resolved following therapy. The prevalence of PED and CSC in VKH was 2.55% (12/470) and 1.06% (5/470), respectively. BCVA improvement in the non-CSC group was greater than that in the CSC group, but without a statistical difference (P = 0.25). PEDA was significantly smaller in the CSC group than in the non-CSC group (P = 0.03). PEDA is an ideal parameter to reflect hydrostatic pressure and stretches for RPE. As PED predisposes to the development of CSC in selected VKH eyes, PEDA may be a valuable predictive factor for the development of classic CSC in VKH cases.


Reconstruction of the external ear using multiple burow's triangles.
Basal cell carcinoma of the auricle presents a challenge in both excision and reconstruction to the clinician. The folloing case report discusses and illustrates the use of controlled excision with assessment of margins and reconstruction using chondrocutaneous advancement flaps and multiple Burow's triangles.


Ligand similarity guided receptor selection enhances docking accuracy and recall for non-nucleoside HIV reverse transcriptase inhibitors.
Non-nucleoside reverse transcriptase inhibitors (NNRTI) are allosteric inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), a viral polymerase essential to infection. Despite the availability of >150 NNRTI-bound RT crystal structures, rational design of new NNRTI remains challenging because of the variability of their induced fit, hydrophobic binding patterns. Docking NNRTI yields inconsistent results that vary markedly depending on the receptor structure used, as only 27% of the >20k cross-docking calculations we performed using known NNRTI were accurate. In order to determine if a hospitable receptor for docking could be selected a priori, we evaluated more than 40 chemical descriptors for their ability to pre-select a best receptor for NNRTI cross-docking. The receptor selection was based on similarity scores between the bound- and target-ligands generated by each descriptor. The top descriptors were able to double the probability of cross-docking accuracy over random receptor selection. Additionally, recall of known NNRTI from a large library of similar decoys was increased using the same approach. The results demonstrate the utility of pre-selecting receptors when docking into difficult targets. Graphical Abstract Cross-docking accuracy increases when using chemical descriptors to determine the NNRTI with maximum similarity to the new compound and then docking into its respective receptor.


Effects of Sleep-Extend on glucose metabolism in women with a history of gestational diabetes: a pilot randomized trial.
Women with a history of gestational diabetes (GDM) are at 7-fold increase in the risk of developing diabetes. Insufficient sleep has also been shown to increase diabetes risk. This study aimed to explore the feasibility of a sleep extension in women with a history of GDM and short sleep, and effects on glucose metabolism. Women age 18-45 years with a history of GDM and actigraphy confirmed short sleep duration (<7 h/night) on weekdays were randomized at a ratio of 1 control (heathy living information) to 2 cases (6 weeks of "Sleep-Extend" intervention: use of a Fitbit, weekly digital content, and weekly coaching to increase sleep duration). An oral glucose tolerance test (OGTT), 7-day actigraphy recording, and questionnaires were obtained at baseline and 6 weeks. Mean differences between baseline and end-of-intervention parameters were compared using independent samples t-tests. Mean (SD) sleep duration increased within the Sleep-Extend group (n=9, +26.9 (42.5) min) but decreased within the controls (n=5, - 9.1 (20.4) min), a mean difference (MD) of 35.9 min (95% confidence interval (CI) - 8.6, 80.5). Fasting glucose increased, but less in Sleep-Extend vs. control groups (1.6 (9.4) vs 10.4 (8.2) mg/dL, MD - 8.8 mg/dL (95% CI - 19.8, 2.1), while 2-h glucose levels after an OGTT did not differ. Compared to controls, Sleep-Extend had decreased fatigue score (MD - 10.6, 95%CI - 20.7, - 0.6), and increased self-report physical activity (MD 5036 MET- minutes/week, 95%CI 343, 9729. Fitbit compliance and satisfaction in Sleep-Extend group was high. Sleep extension is feasible in women with a history of GDM, with benefits in fatigue and physical activity, and possibly glucose metabolism. These data support a larger study exploring benefits of sleep extension on glucose metabolism in these high-risk women. ClinicalTrials.gov , NCT03638102 (8/20/2018).


Argumentation schemes, fallacies, and evidence in politicians' argumentative tweets-A coded dataset.
This coded database presents a corpus of argumentative tweets published by four politicians (Matteo Salvini, Donald Trump, Jair Bolsonaro, and Joe Biden) within 6 months from their taking office, which corresponds to the official end of their election campaign. The coding is based on a threefold method of analysis based on the instruments of argumentation theory and pragmatics. First, the types of arguments are recognized and classified according to a systematic organization of the argumentation schemes developed in the literature. Second, arguments are evaluated considering the fallacies committed. Third, the uses and misuses of "emotive words" are assessed. Based on this theoretical framework, each tweet is thus attributed three categories of codes: 1) argument types (maximum two, corresponding to the most important ones); 2) fallacies (maximum two types of fallacies, plus a distinct indication of the lack of necessary evidence or false presupposition); and 3) emotive language (maximum three emotive words, plus the most important emotion expressed). A total of 2657 tweets are coded, providing a ground for comparative works and an instrument for training further coding of different corpora.


Predictive Value of C-Reactive Protein and Albumin for Temporal Within-Individual Pharmacokinetic Variability of Voriconazole in Pediatric Patients Undergoing Hematopoietic Cell Transplantation.
Voriconazole is a widely used antifungal agent in immunocompromised patients, but its utility is limited by its variable exposure and narrow therapeutic index. Population pharmacokinetic (PK) models have been used to characterize voriconazole PK and derive individualized dosing regimens. However, determinants of temporal within-patient variability of voriconazole PK were not well established. We aimed to characterize temporal variability of voriconazole PK within individuals and identify predictive clinical factors. This study was conducted as a part of a single-institution, phase I study of intravenous voriconazole in children undergoing hematopoietic cell transplantation (NCT02227797). We analyzed voriconazole PK study data collected at week 1 and again at week 2 after the start of voriconazole therapy in 59 pediatric patients undergoing HCT (age <21 years). Population PK analysis using nonlinear mixed effect modeling was performed to analyze temporal within-individual variability of voriconazole PK by incorporating a between-occasion variability term in the model. A 2-compartment linear elimination model incorporating body weight and cytochrome P450 2C19 phenotype described the data. The ratio of individual voriconazole clearance between weeks 1 and 2 ranged from 0.11 to 3.3 (-9.1 to +3.3-fold change). Incorporation of covariate effects by serum C-reactive protein and albumin levels decreased between-occasion variability of clearance as compared to the model without them (coefficient of variation, 41.2% and 59.5%, respectively) and improved the model fit (P < .05). As significant covariates on voriconazole PK, C-reactive protein and albumin concentrations may potentially serve as useful biomarkers as part of therapeutic drug monitoring.


Validation of the molecular international prognostic scoring system in patients with myelodysplastic syndromes defined by international consensus classification.
Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R). Overall, 42.5% of the patients were reclassified and 29.3% were up-staged from the IPSS-R. After the reclassification, 16.9% of the patients may receive different treatment strategies. The IPSS-M had greater discriminative potential than the IPSS-R and IPSS. Patients with high, or very high-risk IPSS-M might benefit from allogeneic hematopoietic stem cell transplantation. IPSS-M, age, ferritin level, and the 2022 ICC categorization predicted outcomes independently. After analyzing demographic and genetic features, complementary genetic analyses, including KMT2A-PTD, were suggested for accurate IPSS-M categorization of patients with ASXL1, TET2, STAG2, RUNX1, SF3B1, SRSF2, DNMT3A, U2AF1, and BCOR mutations and those classified as MDS, not otherwise specified with single lineage dysplasia/multi-lineage dysplasia based on the 2022 ICC. This study confirmed that the IPSS-M can better risk-stratified MDS patients for optimized therapeutic decision-making.


Impact of Eisenia fetida earthworms and biochar on potentially toxic element mobility and health of a contaminated soil.
This study aimed to evaluate the influence of Eisenia fetida (Savigny), added to an acidic soil contaminated with potentially toxic elements (PTEs; As, Sb, Cd, Pb, Zn) and amended with a softwood-derived biochar (2 and 5% w/w), on the mobility of PTEs and soil health (i.e. nutrient availability, enzyme activity and soil basal respiration). The PTEs bioaccumulation by E. fetida and the acute ecotoxicity effects of the amended soils were also evaluated. The interaction between earthworms and biochar led to a significant increase in soil pH, organic matter, dissolved organic carbon content, cation exchange capacity, and exchangeable Ca compared to the untreated soil. Moreover, the water-soluble and readily exchangeable PTE fraction decreased (with the exception of Sb) between 1.2- and 3.0-fold in the presence of biochar and earthworms. Earthworms, biochar, and their combination, led to a reduction of phosphomonoesterase activity which in soils amended with biochar and earthworms decreased between 2.2- and 2.5-fold with respect to the untreated soil. On the other hand, biochar and earthworms also enhanced soil basal respiration and protease activity. Although the survival rate and the weight loss of E. fetida did not change significantly with the addition of 2% biochar, adding the highest biochar percentage (5%) resulted in a survival rate that was ~2-fold lower and a weight loss that was 2.5-fold higher than the other treatments. The PTE bioaccumulation factors for E. fetida, which were less than 1 for all elements (except Cd), followed the order Cd > As>Zn > Cu > Pb > Sb and were further decreased by biochar addition. Overall, these results highlight that E. fetida and biochar, especially at 2% rate, could be used for the restoration of soil functionality in PTE-polluted environments, reducing at the same time the environmental risks posed by PTEs, at least in the short time.


Inter-Examiner Agreement of the National Upper Cervical Chiropractic Association Analysis of the Atlas Subluxation Complex in a 3-View Upper Cervical Radiographic Series.
The purpose of this study was to measure the inter-examiner agreement between radiograph markings of 2 National Upper Cervical Chiropractic Association board-certified chiropractors. Two chiropractic examiners who had standardized training marked and analyzed 254 conventional orthogonal radiographic film sets. The level of agreement and potential biases in their measurements were assessed using intraclass correlation coefficients for absolute agreement and Bland-Altman plot analyses. There was 96.1% agreement between the examiners in the measurements of the side of atlas laterality and 94.5% for atlas rotation. The intraclass correlation coefficient was 0.95 (95% CI, 0.93-0.96) for atlas laterality and 0.92 (95% CI, 0.89-0.94) for atlas rotation. The mean difference in the measurement between the 2 examiners was -0.11, P = .12 for atlas laterality and 0.05, P = .55 for atlas rotation. Neither atlas laterality nor atlas rotation measurements were significantly different from zero. Bland-Altman plots were not suggestive of any proportional biases in the 2 measurements. Results of this study show almost perfect agreement between 2 trained chiropractic examiners, with no apparent proportional bias in the analysis of conventional orthogonal radiographic film sets.


The intestine as an endocrine organ and the role of gut hormones in metabolic regulation.
Gut hormones orchestrate pivotal physiological processes in multiple metabolically active tissues, including the pancreas, liver, adipose tissue, gut and central nervous system, making them attractive therapeutic targets in the treatment of obesity and type 2 diabetes mellitus. Most gut hormones are derived from enteroendocrine cells, but bioactive peptides that are derived from other intestinal epithelial cell types have also been implicated in metabolic regulation and can be considered gut hormones. A deeper understanding of the complex inter-organ crosstalk mediated by the intestinal endocrine system is a prerequisite for designing more effective drugs that are based on or target gut hormones and their receptors, and extending their therapeutic potential beyond obesity and diabetes mellitus. In this Review, we present an overview of gut hormones that are involved in the regulation of metabolism and discuss their action in the gastrointestinal system and beyond.


Glaucoma in patients with ocular inflammatory disease.
Uveitic glaucoma can pose some of the most challenging management problems faced by the ophthalmologist. A better understanding of the pathogenesis of glaucoma associated with ocular inflammatory disease is an important key to making appropriate therapeutic decisions. This article provides an update on recent advances in understanding the epidemiology and pathogenesis of uveitic glaucoma, as well as developments in the diagnosis and management of this condition.


Detection of mutations in whole genome-amplified DNA from laser-microdissected neurons.
Laser microdissection allows removal of individual cells for DNA extraction, but obtaining reliably amplified DNA from the small numbers of cells that survive neurodegenerative diseases can be difficult. We therefore tested a recently-available technique to amplify genomic DNA to see if it could reliably detect a mutation in nervous system cells. Fifty cortical motor neurons were removed by laser microdissection from cases of motor neuron disease both with and without known mutations in the gene for superoxide dismutase 1 (SOD1). DNA was extracted and amplified with a linear genomic amplification kit (GenomiPhitrade mark). The PCR product of exon 4 of SOD1 from this DNA was then sequenced. The GenomiPhi kit amplified the extracted DNA approximately 70 times. When exon 4 of SOD1 from this DNA was amplified by PCR the E100G SOD1 mutation could be identified on sequencing. No errors in replication were found. In conclusion, the GenomiPhi method of genomic DNA amplification appears to result in reliable replication of mutations in neurons. This technique can be used to obtain increased amounts of genomic DNA to study mutations within cells of the nervous system.


Data reproducibility issues and their potential impact on conclusions from evidence syntheses of randomized controlled trials in sleep medicine.
In this study, we examined the data reproducibility issues in systematic reviews in sleep medicine. We searched for systematic reviews of randomized controlled trials published in sleep medicine journals. The metadata in meta-analyses among the eligible systematic reviews were collected. The original sources of the data were reviewed to see if the components used in the meta-analyses were correctly extracted or estimated. The impacts of the data reproducibility issues were investigated. We identified 48 systematic reviews with 244 meta-analyses of continuous outcomes and 54 of binary outcomes. Our results suggest that for continuous outcomes, 20.03% of the data used in meta-analyses cannot be reproduced at the trial level, and 43.44% of the data cannot be reproduced at the meta-analysis level. For binary outcomes, the proportions were 14.14% and 40.74%. In total, 83.33% of the data cannot be reproduced at the systematic review level. Our further analysis suggested that these reproducibility issues would lead to as much as 6.52% of the available meta-analyses changing the direction of the effects, and 9.78% changing the significance of the P-values. Sleep medicine systematic reviews and meta-analyses face serious issues in terms of data reproducibility, and further efforts are urgently needed to improve this situation.


The world prevalence, associated risk factors and mortality of hepatitis C virus infection in hemodialysis patients: a meta-analysis.
The worldwide burden of HCV infection among hemodialysis patients has not been systematically examined. A systematic literature search was conducted in MEDLINE and Scopus to determine the worldwide prevalence of HCV infection, risk factors, and clinical outcomes among hemodialysis patients. Random-effect models and meta-regressions were used to generate pooled estimates and assess heterogeneity. Four hundred and seven studies with 1,302,167 participants were analyzed. The pooled prevalence of HCV infection was 21%. The highest prevalence was observed in Africa (28%) and low-income countries (48.5%). A significant prevalence decline was observed following the publication year and was also inversely related to GDP and total population of each country. Factors associated with HCV positivity included younger age, longer dialysis duration, more blood transfusions, and dialyzer reuse. The pooled unadjusted hazard ratio for all-cause mortality was 1.12 (95% CI 1.03-1.22), and the adjusted hazard ratio was 1.21 (95% CI 1.12-1.30) in HCV-infected compared to non-HCV infected patients. HCV infection among hemodialysis patients is a worldwide shared burden and is associated with a higher risk of death. Avoiding unnecessary blood transfusion and dialyzer reuse should be encouraged to prevent HCV transmission in hemodialysis units.


Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm.
The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.


Immediate X-radiation induced contractions of the isolated guinea pig terminal ileum: the localization of the effect by drugs.
Tone and motility of the isolated guinea pig ileum were increased by irradiation with a dose of 10 krd. The maximal effect corresponds to that induced by 0.001 microng/ml acetylcholine or 0.3 microng/ml nicotine. The pharmacological analysis of this effect performed with acetylcholine and nicotine and several blocking agents including hexamethonium, atropine, tetrodotoxin, diphenhydramine, and verapamil suggests that radiation acts on the postganglionic parasympathetic neuron and the neuromuscular synapse. The mechanism of radiation is likely to consist of both an increased release of acetylcholine from the postganglionic neuron and a sensibilization of the cholinergic receptor site at the smooth muscle cell. The latter effect is thought to result from an increased contractile action induced by acetylcholine or nicotine in the irradiated ileal smooth muscle.


[Surgical treatment of patients with a postinfarction aneurysm of the left ventricle and postinfarction incompetence of the mitral valve].
The authors have analyzed results of treatment of 18 patients with postinfarction aneurysms of the left ventricle (PALV) and postinfarction insufficiency of the mitral valve (PIMV) operated upon after examination. It is considered that both the mitral valve (MV) replacement and some kind of plasty, which is more preferable, can be used in patients with PALV and PIVM in order to recover the closing function of MV. Dosed resection of PALV and its plasty by the Dor-II Jatene method allowed the LV cavity geometry to be reestablished and thus the MV fibrous ring sizes to be reduced as well as the degree of the valve insufficiency. It is expedient to use the method of cardioplagia in such patients and to fulfill proximal anastomoses with the aorta at the lateral pulled position on the working heart and then to start extracorporeal circulation.


Screening for neonatal hypothyroidism by thyroxine and thyrotrophin radioimmunoassays using dried blood samples on filter paper.
A routine and automatized methodology for thyroxine (T4) and thyrotrophin (TSH) radioimmunoassay (RIA) using dried blood samples on filter paper is described. T4-RIA was performed on one single dot (5 mm diameter equivalent to 4 microliters of serum) while two dots were necessary for TSH-RIA. Reference filter papers were introduced in each assay for quality control. In a preliminary study on 4,155 neonates, samples generally obtained between the 5th--7th day gave a mean 'dot-T4' of 97.95 +/- 36.04 nmol/l and a mean 'dot-TSH' of 10.19 mU/l +/- 8.25, corresponding to 2.47 mU/l of serum. Within an 18-month period (November 1976-April 1978), a total of 16.522 neonates have been screened allowing detection of three cases of congenital hypothyroidism (incidence 1 : 5507), two cases of congenitally low TBG and thirty-three cases of transient hypothyroidism.


[Ratio and experimentum: Johannes Bohn (1640-1718) and Italian experimental physiology].
The Bohn-Malpighi-Bellini debate over the existence of 'liquor nerveus' and the functions of the spleen, though far from reaching a positive solution, emphasizes an exchange between the concepts of ratio and 'experimentum', and that in spite of their use of experimental techniques.


A review of melanocortin receptor small molecule ligands.
The melanocortin system (MC) is implicated in the regulation of a variety of physiological pathways including pigmentation, steroid function, energy homeostasis, food intake, obesity, cardiovascular, sexual function, and normal gland regulation. The melanocortin system consists of five receptors identified to date (MC1-5R), melanocortin agonists derived from the pro-opiomelanocortin prohormone (POMC) and two naturally existing antagonists. Melanocortin receptor ligand structure-activity studies have been performed since the 1960s, primarily focused on the pigmentation aspect of physiology. During the 1990s, the melanocortin-4 receptor was identified to play a significant physiological role in the regulation of both food intake and obesity. Subsequently, a concerted drug design effort has focused on the design and discovery of melanocortin receptor small molecules. Herein, we present an overview of melanocortin receptor heterocyclic small molecules.


[Conservative treatment results of the acute and chronic mallet finger].
In the treatment of the acute ligamentous mallet finger, conservative therapy with a Stack or Winterstein splint is an established approach, though there are many different conservative therapy regimes. There are even more therapy options for the chronic mallet finger (more than 4 weeks old) including different operation techniques. In a retrospective study, 44 patients with an acute and 33 patients with a chronic ligamentous mallet finger treated with a Stack or Winterstein splint were investigated. The results in both groups are satisfactory (SD <10 degrees : 70.5% in the acute, 87.9% in the chronic lesions). The subjective satisfaction (scale 1-6) was high in both groups. It was even significantly higher in the group with the chronic lesions (acute: 2.55+/-1.63, chronic: 1.82+/-1.38). In both groups there was no correlation between an initially high extension deficit and a bad therapy outcome. Also in chronic ligamentous mallet finger, conservative therapy should be attempted before an operation, irrespective of the initial extension deficit, especially because the stress and the therapy risk for the patient with this therapy is small.


Separation of sulfated bile acids by high-performance liquid chromatography.
In order to establish a new method for stimultaneous determination of sulfated bile acids without deconjugation, separation of 3-sulfates of unconjugated, glyco- and tauroconjugated bile acids by high-performance liquid chromatography has been undertaken. The preliminary experiment indicated that reversed phase chromatography on an ODS SC-02 column using ammonium carbonate aqueous solution/acetonitrile as a mobile phase would be promising. The ratio of peak width to retention time was varied depending upon the salt concentration. The content of water in mobile phase exerted an influence on the capacity ratio to a certain extent, but not on the resolution. The use of 0.5% ammonium carbonate/acetonitrile (26:8 and 20:8, v/v) was found to be suitable for complete resolution of sulfated cholate, chenodeoxycholate, deoxycholate, lithocholate and their glyco- and tauro-conjugates.


Action of metallic ions on the precocious development by rabbit sperm of motion patterns that are characteristic of hyperactivated motility.
An earlier study demonstrated that rabbit sperm incubated for 16 hr under capacitation conditions acquire motility patterns identical to those seen in rabbit sperm capacitated in vivo. We now show that similar motion patterns develop after 0.5 hr incubation in a Tris-buffered medium, medium M. Development and decline of the motion patterns occurred in three phases each recognized by the character of the biphasic motion patterns. Hyperactivated sperm were objectively identified and quantified by a previously developed computer-directed model. The percentage of motile sperm that acquired hyperactivated motility and the period they remained in this state varied among sperm from different rabbits. The decline in hyperactivated motility was paralleled by a decrease in the average sperm curvilinear velocity (VCL) and average amplitude of lateral head displacement (AALH), but was not accompanied by a concomitant decrease in percentage of motile sperm. Pb2+ and Cd2+, at concentrations that did not inhibit motility, prevented development of hyperactivated motility. Inhibition of hyperactivated motility by Pb2+ was time- and concentration-dependent; the average percentage of hyperactivated sperm decreased from approximately 30% to < 5% (n = 5) in 1 hr at a Pb2+ concentration of 25 microM. Cd2+ inhibition of hyperactivation was dependent only on concentration of the cation. At a concentration of 100 microM, the decrease in the percent of hyperactivated sperm was approximately 50% (n = 3). Hg2+, Zn2+, and Cr6+ at sublethal concentrations had no effect on hyperactivated motility development. These results suggest that Pb2+ and Cd2+, by virtue of their ability to prevent the wide curvature flagella beating that is characteristic of hyperactivation, can compromise fertilization at concentrations that do not inhibit sperm motility and act as a reproductive toxicant at a level other than spermatogenesis.


Longitudinal phenotypes in patients with acute respiratory distress syndrome: a multi-database study.
Previously identified phenotypes of acute respiratory distress syndrome (ARDS) have been limited by a disregard for temporal dynamics. We aimed to identify longitudinal phenotypes in ARDS to test the prognostic and predictive enrichment of longitudinal phenotypes, and to develop simplified models for phenotype identification. We conducted a multi-database study based on the Chinese Database in Intensive Care (CDIC) and four ARDS randomized clinical trials (RCTs). We employed latent class analysis (LCA) to identify longitudinal phenotypes using 24-hourly data from the first four days of invasive ventilation. We used the Cox regression model to explore the association between time-varying respiratory parameters and 28-day mortality across phenotypes. Phenotypes were validated in four RCTs, and the heterogeneity of treatment effect (HTE) was investigated. We also constructed two multinomial logistical regression analyses to develop the probabilistic models. A total of 605 ARDS patients in CDIC were enrolled. The three-class LCA model was identified and had the optimal fit, as follows: Class 1 (n = 400, 66.1% of the cohort) was the largest phenotype over all study days, and had fewer abnormal values, less organ dysfunction and the lowest 28-day mortality rate (30.5%). Class 2 (n = 102, 16.9% of the cohort) was characterized by pulmonary mechanical dysfunction and had the highest proportion of poorly aerated lung volume, the 28-day mortality rate was 47.1%. Class 3 (n = 103, 17% of the cohort) was correlated with extra-pulmonary dysfunction and had the highest 28-day mortality rate (56.3%). Time-varying mechanical power was more significantly associated with 28-day mortality in Class 2 patients compared to other phenotypes. Similar phenotypes were identified in four RCTs. A significant HTE between phenotypes and treatment strategies was observed in the ALVEOLI (high PEEP vs. low PEEP) and the FACTT trials (conservative vs. liberal fluid management). Two parsimonious probabilistic models were constructed to identify longitudinal phenotypes. We identified and validated three novel longitudinal phenotypes for ARDS patients, with both prognostic and predictive enrichment. The phenotypes of ARDS can be accurately identified with simple classifier models, except for Class 3.


Self and other through the prism of AIDS: a literary examination of relationships with patients.
This article examines how the "non-ill," often formal or informal caregivers, structure their relationships with "the ill," using as a specific example the disease of AIDS; and as a specific analytic tool selections of fictional writing. An introductory rationale explores why literature may be well-suited to helping us understand value-laden issues such as relationship. Discussion then focuses on how the professional and personal Self is identified and defined in relation to the suffering Other, through the development of concepts such as threat and boundary work. The concluding section suggests alternative relational models derived from more fluid and permeable definitions of Self and Other.


Asymmetrical warming of growing/non-growing season increases soil respiration during growing season in an alpine meadow.
Soil respiration (Rs) is an important carbon flux in the global carbon cycle, and understanding the influence of global warming on Rs is critical for precise prediction future climate change. Actually, global warming is expected to be seasonally asymmetric, however, it is still unclear on the response of Rs to asymmetrical warming of growing/non-growing season in alpine regions. In this study, an experiment with asymmetrical warming of growing/non-growing season (including three treatments, CK: control; GLNG: warming magnitude of growing season lower than non-growing season; GHNG: warming magnitude of growing season higher than non-growing season) was performed in an alpine meadow of the Northern Tibet since June 2015. The 'GLNG' and 'GHNG' treatments increased mean Rs by 71.22% (1.89 μmol CO2 m-2 s-1) and 34.32% (0.91 μmol CO2 m-2 s-1) during growing season in 2019, respectively. However, the 'GLNG' and 'GHNG' treatments did not significantly affect mean Rs during growing season in 2015, 2016, 2017 and 2018, respectively. The variation coefficient of growing season mean Rs was 32.95% under the CK treatment in 2015-2019. Therefore, warming may have a lagging effect on Rs. The warming scene with a greater warming during non-growing season may have a stronger effect on Rs than the warming scene with a greater warming during growing season. Inter-annual variation of Rs may be greater than the warming effect on Rs in alpine meadows.


The functional anatomy of cognitive control: A domain-general brain network for uncertainty processing.
Cognitive control is the coordination of mental operations under conditions of uncertainty in accordance with goal-directed behaviors, and plays a key role in the domains of executive control, working memory, and decision-making. Although there is emerging evidence of common involvement of the cognitive control network (CCN) of the brain in these domains, this network has mostly been linked to the processing of conflict, which is just one case of an increase in uncertainty. Here, we conducted an activation-likelihood-estimation-based large-scale meta-analysis of 289 functional magnetic resonance imaging studies in the three domains to examine the common involvement of the CCN in uncertainty processing by contrasting the high-uncertainty versus low-uncertainty conditions. We found a general association between increase in uncertainty and an activation increase in regions of the CCN, including the frontoparietal network (comprising the frontal eye fields, the areas near and along the intraparietal sulcus, and the dorsolateral prefrontal cortex), the cingulo-opercular network (including the anterior cingulate cortex extending to the supplementary motor area, and the anterior insular cortex), and a subcortical structure (the striatum). These results demonstrate that the CCN is a domain-general construct underlying uncertainty processing to support goal-directed behaviors.


Localization of ovulation hormone-like neuropeptide in the central nervous system of the snail Lymnaea stagnalis by means of immunocytochemistry and in situ hybridization.
The caudo-dorsal cells (CDC) in the cerebral ganglia of the pond snail Lymnaea stagnalis synthesize the 36-amino acid ovulation hormone (CDCH). We have used immuno-cytochemistry and in situ hybridization to reveal the localization of neurons and axons containing CDCH-like material. A monoclonal antibody to a fragment of CDCH and a cDNA probe encoding CDCH reacted with the CDC-system, with specific cell groups in the cerebral and pleural ganglia, and with individually occurring neurons throughout the central nervous system. The cells in the pleural ganglia, which were found in about 50% of the preparations studied, are considered as "ectopic" CDC. They are morphologically similar to CDC in their somal dimensions and axonal organization. By means of immuno-electron microscopy it was shown that these neurons contain secretory vesicles that are similar to those of the CDC. The neurons of the bilateral groups occurring in the cerebral ganglia in addition to the CDC are smaller and more intensely stained than the CDC. Axons of these small neurons probably have varicosities located on the CDC axons in the neuropil of the cerebral ganglion, indicating synaptic contacts. Two major axon tracts could be followed from (or toward) the neuropil of the cerebral ganglion. One tract runs from the cerebral ganglion via the pleural and parietal ganglia to the visceral ganglion, giving off branches to most nerves emanating from these ganglia. The other tract could be traced through the cerebro-pedal connective to the pedal ganglia. Only in the right pedal ganglion was extensive axonal branching observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Motion aftereffects associated with pursuit eye movements.
Contrary to an earlier report [Anstis and Gregory, Q. Jl exp. Psychol. 17, 173-174 (1965)], we find that the sustained retinal motion caused by tracking a moving target over a stationary grating does not result in a motion aftereffect (MAE) which is equivalent to that resulting from comparable retinal motion caused by actual motion of a grating. The MAE associated with tracking generally occurs in elements falling on areas not previously exposed to retinal motion. It is in the same direction as the previous retinal motion in the display and is apparently an induced MAE caused by a weak, below threshold MAE in the elements stimulating areas that were previously exposed to retinal motion. Based on an analysis of eye movement records, we do not believe that the weakness of the tracking MAE is primarily a function of the poor quality of the tracking eye movements. Other possible reasons for the weakness of the MAE are suggested.


Copeptin, a surrogate marker of arginine8 vasopressin, has no ability to modulate human and mouse gastric motility.
Copeptin, a glycosylated peptide fragment derived from the C-terminal region of the precursor of arginine8 vasopressin (AVP), is co-secreted with AVP in equimolar amounts. Elevated plasma AVP modulates gastric motility so we investigated whether copeptin had a similar effect. Copeptin (10-9-10-7M), and AVP (10-12-10-5M), were evaluated for their ability to modulate spontaneous and electrically-evoked (EFS) contractions of human proximal and distal gastric circular muscle in vitro. Similar experiments were performed on the mouse stomach and we re-examined the published effect of copeptin on the mouse aorta. In the presence of tetrodotoxin (10-6M), atropine (10-6M) and L-NAME (3 × 10-4M), human proximal and distal stomach muscle contracted spontaneously and rhythmically as did mouse distal stomach. Copeptin (10-9-10-7M), had no effect on baseline muscle tone or myogenic spontaneous contractions of either human or mouse stomach. However, AVP concentration-dependently increased tone, amplitude and frequency of contractions in both regions of human stomach with similar potency (pEC50 9.0-9.5; n = 4) and threshold concentration (10-11-10-10M). AVP was similarly active in the mouse stomach. EFS-evoked cholinergic contractions (human and mouse) were unaffected by both peptides EFS-evoked relaxations of mouse stomach were unaffected by copeptin. In sub-maximally contracted mouse aorta the elevated tone was unaffected by copeptin (10-7M) (cf. previously published study) but was reduced by carbachol (10-6M) and sodium nitroprusside (10-3M). We conclude that in contrast to AVP, copeptin over a concentration range reported in the plasma has no direct ability to modulate the motility of the human and mouse stomach.


Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline.
To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug.


Polymer supported carbodiimide strategy for the synthesis of N-acylated derivatives of deoxy- and ribo purinenucleosides using active esters.
A cost-effective synthetic strategy has been used for the selective protection of the exocyclic amino function of purine nucleosides. Instead of using the common protecting groups in their chloride or anhydride forms, the less expensive and nontoxic acidic form was chosen. The acids were first activated to an active ester form using DCC and further successfully used for N-acylation of purine nucleosides. The contamination of the N-acylated product with DCU was inconvenient and was avoided by use of polymer supported-carbodiimide that has the additional advantage of reusability.


Reported sexual abuse and cognitive content in the morbidly obese.
This study investigated whether a reported history of childhood sexual abuse (CSA) in morbidly obese adults is associated with a higher level of negative core beliefs (unconditional, schema-level representations regarding the self, the world, and others), and whether those beliefs are significantly associated with weight levels and weight fluctuation. A cross-sectional design was used, with comparative and correlational elements. The participants were 30 morbidly obese patients (age range=27-61years; body mass index [BMI] range=40.8-73.5), awaiting surgical intervention. Each completed standardized self-report measures of childhood traumatic experiences, core beliefs, and weight history. BMI was obtained from clinical interview. In terms of weight variables, the individuals with a reported history of sexual abuse (n=10) did not differ from those with no such history (n=20). However, those with a reported abuse history had higher levels of specific negative core beliefs. This group also showed more extensive associations between their BMI and their core beliefs than the nonabused group. Core beliefs, which are often associated with personality disorder pathology, were associated with the reported presence of a history of sexual abuse among the morbidly obese. The group differences (in levels of core beliefs and in their association with weight variables) suggest that there might be different mechanisms to explain weight levels in those obese patients who do or do not have a history of CSA. When psychological interventions are used in support of other treatments (e.g., surgery), they might be most productively targeted on those with such an abuse history.


Psychomotor, physiological and cognitive effects of scopolamine and ephedrine in healthy man.
Three placebo-controlled double-blind studies in healthy volunteers were performed to reveal the psychophysiological effects of scopolamine, ephedrine and their combination. Single intravenous dose of scopolamine 6 micrograms/kg (scopolamine hydrobromide 7.4 micrograms/kg) impaired various psychomotor functions both subjectively and objectively. It caused sedation, impairment of coordinative and reactive skills, visual disturbances and impairment of shortterm memory. Oral scopolamine hydrobromide in single doses of 0.3 mg and 0.9 mg, or 0.9 mg b.d. for 3 days, had few effects. A slight impairment of shortterm memory and a decrease in the flicker fusion threshold were seen. The visual nearpoint and pupil diameter were increased and some subjects reported blurred vision and dizziness during treatment with scopolamine 0.9 mg b.d. Scopolamine showed clear cardiovascular effects in all studies: it decreased heart rate and systolic blood pressure. Ephedrine alone and in combination with scopolamine had no deleterious effects. On the contrary, it antagonized the scopolamine-induced impairment in the flicker fusion test and the decrease in blood pressure and heart rate. In sufficient doses scopolamine impairs various psychomotor and cognitive skills. An oral dose of scopolamine hydrobromide 0.9 mg on average has few effects, although they may be very striking in certain individuals. To avoid unwanted effects and diminution in performance by scopolamine, doses less than 0.9 mg should be used.


Unreimbursed expenses for medical care among urban elderly people.
Out-of-pocket medical expenditures were examined among a sample of 400 low-to-moderate income Medicare recipients living in the Bronx for a twelve month period in 1986-87. Using three different measures of magnitude, the most significant expenses were for Medicare and private insurance premiums, medications, and dental care. The mean percent of per capita income spent out-of-pocket for medical care (including health care premiums) was 11.0%. Elderly people who spend over 12% of their own income on medical care include those in the poorest health, those with annual incomes under $15,000, people living with spouses or others, and those using a private physician as a primary source of medical care.


Association of neighborhood-level social determinants and food environments with pediatric hypertension care.
Despite the apparent relationship between neighborhood characteristics and health, few studies of child health address neighborhood-level barriers, which may contribute to clinic no-show rates and difficulties following treatment plans in children and youth. We used longitudinal data from an outpatient hypertension clinic to examine neighborhood social disorganization, built environments, and their associations with patients' clinic attendance and the risk of obesity/hypertension using mixed-effects regression models. Patients from disorganized neighborhoods were less likely to attend a baseline visit, and more likely to develop overweight/obesity and hypertension during follow-up. High-level fast-food expenditures in the neighborhood were associated with higher BMI percentiles and SBP during follow-up.


Autophagy Regulation of Mammalian Immune Cells.
Autophagy is a fully competent cellular machinery able to carry out the clearance of macromolecules via fusion with the lysosome. Many studies conducted in recent years have revealed that autophagy not only plays a critical role in maintaining cell homeostasis, but can also promote bacterial elimination. Additionally, autophagy exists in most eukaryotic cells including immune cells, such as lymphocytes, neutrophils, eosinophils, mast cells, and natural killer cells. Presently, there are numerous studies focusing on the roles of autophagy in regulating immune response. Autophagy regulates the innate and adaptive immunity by modulating cell differentiation, survival, phagocytosis, antigen presentation, degranulation, and cytokine production. In this chapter, we will summarize how autophagy participates explicitly in the survival and function of the mammalian adaptive and innate immune cells.


Factors associated with gamblers: a population-based cross-sectional study of South Australian adults.
To determine, using a random telephone survey, the prevalence of various gambling activities among South Australian adults, the prevalence of adult problem gamblers using the South Oaks Gambling Screen (SOGS) instrument, and to examine the problem gamblers by demographic and health-related risk factors. A random representative sample of South Australian adults selected from the Electronic White Pages. Overall, 6045 interviews were conducted (73.1% response rate) using Computer Assisted Telephone Interviewing (CATI) technology. Overall, 75.6% (95% CI: 74.5-76.7) of respondents had participated in at least one gambling activity during the last 12 months and 2.0% (95% CI: 1.7-2.4) were identified to be problem gamblers. A wide range of factors was associated with problem gambling at a univariate level, when compared to frequent gamblers. The logistic regression analysis highlighted that problem gamblers were more likely to speak a language other than English, be employed part time and a smoker when compared to frequent gamblers. Problem gamblers were also more likely to have a mental health condition (according to the Kessler 10), have had suicidal thoughts and know of services for gambling problems. There is a wide range of characteristics associated with problem gambling in South Australia. All of these factors need addressing during policy development to assist problem gamblers.


Cytokine expression in colon carcinoma.
Cytokines reflect the activity of the immune system. We analyzed the local expression of characteristic cytokines indicating the level of activity of unspecific inflammatory cells, Th1-cells and Th2-cells in colon cancer. In 25 tumor/ mucosa pairs, IL-1alpha, IL-2, IL-4, IL-5, IL-15, TNF-alpha and IFN-gamma were measured by real-time PCR. There was a significant increase in IL-1alpha, IL-4, IL-5 and TNF-alpha and a significant decrease in IL-2 in tumor tissue compared to normal mucosa. The cytokine profile in colon cancer indicates a strong unspecific inflammatory reaction in the tumor tissue represented by high levels of IL-1 and TNF-alpha. The comparatively low level of IL-2 suggests suppression of a specific immunological reaction, namely Th1-cells. It can be hypothesized that this is a result and/or cause of local immune escape mechanisms. Furthermore, there is an activation of TH2 cells in the carcinomas.


Chemotaxis of human articular chondrocytes and mesenchymal stem cells.
Migration of chondrocytes and mesenchymal stem cells (MSCs) may be important in cartilage development, tissue response to injury, and in tissue engineering. This study analyzed growth factors and cytokines for their ability to induce migration of human articular chondrocytes and bone marrow-derived mesenchymal stem cells in Boyden chamber assays. In human articular chondrocytes serum induced dose- and time-dependent increases in cell migration. Among a series of growth factors and cytokines tested only PDGF induced a significant increase in cell migration. The PDGF isoforms AB and BB were more potent than AA. There was an aging-related decline in the ability of chondrocytes to migrate in response to serum and PDGF. Human bone marrow MSC showed significant chemotaxis responses to several factors, including FBS, PDGF, VEGF, IGF-1, IL-8, BMP-4, and BMP-7. In summary, these results demonstrate that directed cell migration is inducible in human articular chondrocytes and MSC. PDGF is the most potent factor analyzed, and may be useful to promote tissue integration during cartilage repair or tissue engineering.


State capture through indemnification demands? Effects on equity in the global distribution of COVID-19 vaccines.
State capture by the pharmaceutical industry is a form of corruption whereby pharmaceutical companies shift laws or policies about their products away from the best interest of the public and toward their private benefit. State capture often limits equitable access to pharmaceutical products by inflating drug prices and increasing barriers to entry into the pharmaceutical industry. During the COVID-19 pandemic, the high demand and low supply of COVID-19 vaccines has put governments that manage vaccine procurement at risk of capture by COVID-19 vaccine manufacturers, both through bilateral deals and the COVID-19 Vaccine Global Access (COVAX) Facility; this threatens equity in the global distribution of these products. The purpose of this study is to determine whether COVID-19 vaccine manufacturers have been engaging in state capture and, if so, to examine the implications of state capture on equitable access to COVID-19 vaccines. A targeted rapid literature search was conducted on state capture by the pharmaceutical industry. Results were limited to journal articles, books, and grey literature published between 2000 and 2021 in or translated to English. A literature search was also conducted for information about state capture during the COVID-19 pandemic. Results were limited to media articles published between March 2020 and July 2021 in or translated to English. All articles were qualitatively analyzed using thematic analysis. COVID-19 vaccine manufacturers have demanded financial indemnification from national governments who procure their vaccines. While most high-income countries are legislatively capable of indemnifying vaccine manufacturers, many low- and middle-income countries (LMICs) are not. A number of LMICs have thus changed their legislations to permit for manufacturers' indemnification demands. Amending legislation in this way is state capture and has led to delays in LMICs and vaccine manufacturers signing procurement contracts. This has critically stalled access to vaccines in LMICs and created disparities in access to vaccines between high-income countries and LMICs. COVID-19 vaccine manufacturers' indemnification demands constitute state capture in many LMICs though not in high-income countries; this has enhanced global COVID-19 vaccine inequities. Results underscore the need to find alternatives to financial indemnification that do not hinder critical efforts to end the pandemic.


An extended wavelet approach of the money-output link in the United States.
The paper examines the link between money and output in the U.S. by using wavelet analysis. The time span covers the period from 1960Q1 to 2021Q1. The main results evidence that money positively leads real output from the late 1960s to 1982, at medium frequency, with the interest rate playing an important role. In contrast, we reveal that real output negatively leads money, at the same medium frequency, but from the late 1990s to 2021. The COVID-19 pandemic generates significant co-movements in the short and medium frequencies, over the period from 2020 to 2021, with output negatively leading money. We underline that Federal Reserve monetary policy operating procedures play an essential role in explaining these findings. The results support using the federal funds rate operating procedure as countercyclical monetary policy measures and implementing unconventional monetary policy tools in times of the effective lower bound. Finally, no relationship between money and output is observed in the long term, while the short term (i.e. high frequency) reveals rather chaotic co-movements. The results remain robust to alternative wavelet tools, higher-frequency datasets, and a Hodrick-Prescott filtered quarterly sample. The online version contains supplementary material available at 10.1007/s00181-022-02294-6.


Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy.
Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb-IV). While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.