Predicting enzyme subclasses by using random forest with multicharacteristic parameters.
In order to predict enzyme subclasses, this paper builds a new enzyme database in term of previous ideas and methods. Based on protein sequence, by selecting increment of diversity value, low-frequency of power spectral density, matrix scoring values and motif frequency as characteristic parameters to describe the sequence information, a Random Forest algorithm for predicting enzyme subclass is proposed. Using the Jack-knife test, the overall success rate identifying the 18 subclasses of oxidoreductases, the 8 subclasses of transferases, the 5 subclasses of hydrolases, the 6 subclasses of lyases, the 6 subclasses of isomerases, and the 6 subclasses of ligases are 90.86%, 95.24%, 96.42%, 98.60%, 97.53% and 98.03%. Furthermore, the same way is used to the previous database, the better results are obtained.


Characterization of macular lesions in punctate inner choroidopathy with spectral domain optical coherence tomography.
Punctate inner choroidopathy (PIC) is an ocular inflammatory disease. Spectral domain optical coherence tomography (SD-OCT) allows detailed visualization of retinal and choroidal structures. We aimed to describe the retinal changes on SD-OCT associated with PIC lesions localized in the macula. Retrospective case series: PIC lesions not associated with choroidal neovascularization (CNV) and captured by macular SD-OCT scans were identified and characterized. Twenty-seven PIC lesions from seven patients (eight eyes) were identified and classified into four categories according to disease activity and temporal changes. Among clinically inactive patients, two main patterns were noted on OCT: (1) retinal pigment epithelium (RPE) elevation with sub-RPE hyper-reflective signals and (2) localized disruption of outer retinal layers with choroid and Bruch's membrane (BM) generally spared. Clinically active patients demonstrated lesions with intact BM with RPE elevation that fluctuated with disease activity and sub-RPE hyper-reflective signals. Photoreceptor-associated bands on SD-OCT (PRs) were not visible during active disease, but returned to normal visibility when lesions were clinically stable. Seven lesions in patients without clinically detected activity demonstrated alteration of RPE elevation. SD-OCT can provide detailed structural characteristics of PIC lesions. RPE elevation is noted in many lesions while BM and choroid are spared. Photoreceptor-associated bands on SD-OCT appear compressed during clinically active stages and are visible during stabilization. OCT may provide information on activity not detected clinically.


Further purification of industrial quartz by much milder conditions and a harmless method.
A much "greener" and harmless leaching method for removing impurity aluminum further from industrial quartz sands by very dilute mixed acids has been presented. With the help of supersonic, the percentage of removal aluminum reached up to 52.5%/53%, that is, 17.4 ppm/17.7 ppm at 30 °C/80 °C, respectively. These results are 4.4/4.7 ppm lower than that supplied by a world famous quartz sands supplier, and the leaching conditions are much milder compared with other comparable methods: the concentration of hydrogen chloride in the mixed acid is only 10% of the others, the leaching temperature is much lower; at the same time, the operating time is only 13-20% of the others, thereby pollution of industrial strong acids and thermo-scattering is reduced substantially.


Treponema denticola biofilm-induced expression of a bacteriophage, toxin-antitoxin systems and transposases.
Treponema denticola is an oral spirochaete that has been strongly associated with chronic periodontitis. The bacterium exists as part of a dense biofilm (subgingival dental plaque) accreted to the tooth. To determine T. denticola gene products important for persistence as a biofilm we developed a continuous-culture biofilm model and conducted a genome-wide transcriptomic analysis of biofilm and planktonic cells. A total of 126 genes were differentially expressed with a fold change of 1.5 or greater. This analysis identified the upregulation of putative prophage genes in the T. denticola 35405 genome. Intact bacteriophage particles were isolated from T. denticola and circular phage DNA was detected by PCR analysis. This represents the first, to our knowledge, functional bacteriophage isolated from T. denticola, which we have designated varphitd1. In biofilm cells there was also an upregulation of genes encoding several virulence factors, toxin-antitoxin systems and a family of putative transposases. Together, these data indicate that there is a higher potential for genetic mobility in T. denticola when growing as a biofilm and that these systems are important for the biofilm persistence and therefore virulence of this bacterium.


Structure of fibrin network of two abnormal fibrinogens with mutations in the αC domain on the human dermal microvascular endothelial cells 1.
There is evidence that clot structure can be modulated by endothelial cells, wherein the fibrinogen αC domain plays a major role in the fibrin-cell interaction. The spatial distribution of fibrin fibers from fibrinogen Caracas V and Caracas I, with heterozygous mutation in the αC domain (Aα Ser432Cys and Aα Ser466stop, respectively) on human dermal microvasculature endothelial cells (HMEC-1), was studied by laser scanning confocal microscopy. In order to assess fibrin-cell interaction and the role of the αC domain, preliminary experiments were done with inert microspheres and RGD peptide included in the clotting reaction, and forming clots with fibrinogen fragment X (fibrinogen without αC domain). Groups of stressed fibers were observed near the cell surface and were related to fibrin-cell interactions, which were abolished by the RGD peptide, and by the absence of the αC domain. The fibrin network of fibrinogen Caracas V and Caracas I was very different from that of normal fibrinogen. In general, patient's clots were characterized by very thin, tightly packed fibrin fibers, with a substantially reduced network porosity. Near the cell's surface, both abnormal fibrinogens formed a very fine meshwork, with stressed fibers 'anchored' to the cell surface, a pattern that was lost far from the cell surface. The structure of normal and patient clots performed in the absence of cells resembled that observed far from the cell surface, concluding that Caracas V and Caracas I fibrin was modulated by the presence of endothelial cells.


Activation of the human immunodeficiency virus type 1 long terminal repeat by transforming mutants of human p53.
We have studied the effects of human wild-type and mutant p53s on the long terminal repeat (LTR) promoter of human immunodeficiency virus type 1 (HIV). HeLa cells were cotransfected with a wild-type or mutant p53 expression plasmid and a plasmid containing a chloramphenicol acetyltransferase reporter gene under HIV LTR promoter control. As expected, expression of wild-type p53 inhibited promoter function. Expression of a p53 mutated at any one of the four amino acid positions 175, 248, 273, and 281 correlated with a significant increase of the HIV promoter activity. The HIV LTR was also significantly activated in Saos-2 cells that do not express endogenous p53. This finding suggests a gain-of-transactivation function by mutation of the p53 gene. Cotransfection of wild-type and mutant p53-281G expression plasmids indicated that either the wild type or the mutant was dominant in inhibiting or enhancing promoter activity, respectively, when transfected in excess of the other. Transfection experiments showed transactivation even when the Sp1, NF-kappa B, and TATA sites in the LTR were individually mutated. Synthetic minimal promoter constructs containing two Sp1 sites or two NF-kappa B sites or an ATF site are also significantly activated by the mutant p53-281G. Thus, the mutant protein may activate transcription through interaction with either a general transcription factor or a common factor that bridges the basal transcription machinery and the transcription factors Sp1, NF-kappa B, and ATF.


Personal continuous glucose monitoring (CGM) in diabetes management: review of the literature and implementation for practical use.
Despite recent advances in diabetes therapy including the new long- and rapid-insulin analogs, insulin intensification strategies such as basal/bolus or pump therapy and sophisticated methods for insulin titration derived from the principles of functional insulin therapy, many patients fail to reach or maintain target glycosylated hemoglobin (HbA1c) values, putting them at increased risk for vascular complications. Continuous glucose monitoring (CGM) systems represent an important advance in diabetes technology that can facilitate optimal glucose control in type 1 diabetes. This review focuses on the efficacy and safety of CGM systems in diabetes management. The different CGM devices available are also described, as the way to use them and the educational approach to the patient in a step-by-step progression toward optimal glycemic control. In type 1 diabetes, CGM systems are associated with 0.5-1% reduction in HbA1c without increased risk of hypoglycemia. CGM efficacy correlates with compliance to sensor wear, whatever the patient's age range. Efficacy of CGM systems is now proven but indications, terms of use and educational issues of this new technology still need to be specified.


Transforming a General Hospital to an Infectious Disease Hospital for COVID-19 Over 2 Weeks.
Pandemics like the coronavirus disease (COVID)-19 can cause a significant strain on the healthcare system. Healthcare organizations must be ready with their contingency plans for managing many patients with contagious infectious disease. Ideally, every large hospital should have a facility that can function as a high-level isolation unit. An isolation unit ensures that the healthcare staff and the hospital are equipped to deal with infectious disease outbreaks. Unfortunately, such facilities do not exist in several hospitals, especially in resource-limited settings. In such a scenario, healthcare setups need to convert their existing general structure into an infectious disease facility. Herein, we describe our experience in transforming a general hospital into a functional infectious disease isolation unit.


Conscious performance and arthroscopic findings in athletes with anterior cruciate ligament injuries treated via conservative therapy during the competitive season.
Athletes often receive conservative treatment for injured anterior cruciate ligaments (ACLs) so that they can continue to play to the end of their season. The purpose of this study was to examine the conscious performance and arthroscopic findings of athletes who received conservative therapy for ACL injuries. Forty-two patients with ACL injuries underwent conservative treatment. After the season ended, ACL reconstruction was performed. We examined the following parameters: (1) time required for return to competition after injury, (2) conscious performance after return to competition, (3) whether the injured knee gave way during conservative therapy or after return to competition, and (4) cause of performance deterioration if applicable. To determine conscious performance, patients were asked to rate their performance after therapy relative to their performance before injury. Thirty-eight of the 42 patients (90.5%) returned to competition after conservative treatment. The mean time to return was 13.8 ± 7.6 weeks, and the mean conscious performance score was 58.4 ± 16.5%. Thirty-eight patients (90.5%) experienced their knee giving way, of whom 36 (94.9%) stated that fear of their knee giving way hampered their performance. At the time of ACL reconstruction, 9 patients had chondral injuries and 22 patients had meniscus injuries. Most athletes with damaged ACLs returned to the field within the same season after conservative treatment. However, conscious performance was only about 60%. It is possible that knees giving way caused secondary meniscus and joint cartilage damage. Therefore, conservative treatment of individuals with ACL injuries should be considered carefully.


Electron-ion hybrid instability experiment upgrades to the Auburn Linear Experiment for Instability Studies.
The Auburn Linear EXperiment for Instability Studies (ALEXIS) is a laboratory plasma physics experiment used to study spatially inhomogeneous flows in a magnetized cylindrical plasma column that are driven by crossed electric (E) and magnetic (B) fields. ALEXIS was recently upgraded to include a small, secondary plasma source for a new dual source, interpenetrating plasma experiment. Using two plasma sources allows for highly localized electric fields to be made at the boundary of the two plasmas, inducing strong E × B velocity shear in the plasma, which can give rise to a regime of instabilities that have not previously been studied in ALEXIS. The dual plasma configuration makes it possible to have independent control over the velocity shear and the density gradient. This paper discusses the recent addition of the secondary plasma source to ALEXIS, as well as the plasma diagnostics used to measure electric fields and electron densities.


Resting-State fMRI in Predicting Response to Treatment With SSRIs in First-Episode, Drug-Naive Patients With Major Depressive Disorder.
For major depressive disorder (MDD), there has been a lack of neuroimaging markers of efficacy of pharmacological treatment. In this study, we aimed to explore the neuroimaging mechanisms in patients with first-episode MDD and identify markers that predict the efficacy of 5-hydroxytryptamine reuptake inhibitors (SSRIs) with the use of resting-state brain imaging technology. A total of 101 patients with first-episode MDD and 53 normal controls were finally included in this study. Based on the reduction rate of the score of Hamilton Depression Rating Scale (HAMD-17) during the 2-week SSRI treatment, 31 patients were assigned into the unresponsive group and 32 were assigned into the responsive group. The brain function was compared between patients with MDD and normal controls, and the diagnostic value of brain function was analyzed. With brain regions showing differences between patients with MDD and normal controls as a mask, and the brain function between the responsive and unresponsive groups were compared. Correlations between brain function the HAMD-17 score reduction rate during the 2-week SSRI treatment were analyzed. Compared to normal controls, patients with MDD showed increased ReHo in the left parahippocampal gyrus and right parahippocampal gyrus, decreased ReHo in the right middle occipital gyrus, and decreased functional connectivity between the right and left parahippocampal gyri, right middle occipital gyrus and middle temporal gyrus. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) was 0.544 (95% CI: 0.445-0.644) for ReHo and 0.822 (95% CI: 0.734-0.909) for functional connectivity. Logistic regression pooling of the differences in ReHo mean time series with the functional connectivity mean time series was performed for the ROC curve analysis, which showed an AUC of 0.832 (95% CI: 0.752-0.911). Compared to the responsive group, the unresponsive group showed elevated ReHo in the right parahippocampal gyrus and lower functional connectivity in the middle temporal gyrus. We also found that the ReHo value was negatively correlated with the HAMD-17 score reduction after 2 weeks of SSRI treatment. Altered resting-state brain function in some regions might be a neurobiological marker for the diagnosis of MDD, and ReHo values are expected to be predictors of patient response to treatment with SSRIs. [http://www.chictr.org.cn/], identifier [ChiCTR1900028722].


Heterogeneity of Abnormal RUNX1 Leading to Clinicopathologic Variations in Childhood B-Lymphoblastic Leukemia.
Abnormalities of the RUNX1 gene in childhood B-acute lymphoblastic leukemia (B-ALL) are manifested by ETV6-RUNX1 or RUNX1 amplification. A detailed comparison between the two regarding clinicopathologic features with genetic analysis has not been performed previously. This parallel study assessed how different RUNX1 abnormalities affect the clinicopathology of B-ALL. We compared clinicopathologic factors, including age, sex, WBC count, cerebrospinal fluid (CSF) involvement, immunophenotype, and blast proliferation rate between B-ALL with RUNX1 amplification (10 cases) and B-ALL with ETV6-RUNX1 translocation (67 cases) in childhood B-ALL. CD7 was often expressed in RUNX1 amplification but not in ETV6-RUNX1 (44% vs 0%, P = .0001) and appeared to correlate with CSF involvement in the former group (3/4 [75%]). CD13 was often detected in ETV6-RUNX1 with additional RUNX1 gain (38%) with an even higher frequency in double ETV6-RUNX1 translocation (77%), but was not detected in RUNX1 amplification (0%, P < .05). Children with RUNX1 amplification were older and more often CSF positive, while those with ETV6-RUNX1 were younger, more frequently had hyperleukocytosis, and had higher blast proliferation rates. RUNX1 copy numbers seem to be proportional to the age of B-ALL onset and the frequency of CSF involvement, while RUNX1 amplification vs translocation causes aberrant expression of CD7 and CD13, respectively.


Assessment of mechanisms involved in antinociception caused by myrsinoic acid B.
Myrsinoic acid B (AMB) is a prenylated-benzoic acid derivative isolated from the Rapanea genus. Recent studies suggest that AMB has antihyperalgesic and antinociceptive properties in different animal models. The present study was designed to investigate the mechanisms involved in antinociception elicited by AMB (60 mg/kg) when administered by intraperitonial route (i.p.) in mice. The antinociceptive response of the compound was characterized by a reduction in contractions of the abdominal muscle, together with stretching of the hind limbs in response to i.p. injection of acetic acid (0.6%, 0.45 ml/mouse). The antinociception caused by AMB in the acetic acid test was significantly attenuated by i.p. treatment of mice with nitric oxide precursor, (L-arginine, 600 mg/kg), alpha2 and alpha1-adrenoceptor antagonists (yohimbine, 0.2 mg/kg/prazosin, 0.2 mg/kg), p-chlorophenylalanine (PCPA) an inhibitor of serotonin synthesis (100 mg/kg), 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN 190), a 5-HT1(A) selective receptor antagonist (0.5 mg/kg) and a non-selective cholinergic antagonist (atropine, 10 mg/kg). Its action was also modulated by the adrenal-gland hormones. In contrast, antinociception was not affected by naloxone (non-selective opioid receptor antagonist, 1.0 mg/kg), phaclofen (2.0 mg/kg) and bicuculline (1.0 mg/kg) GABA(B) and GABA(A) receptor antagonists, respectively, ondansetron (0.3 mg/kg) and ketaserin (1.0 mg/kg), (5-HT3 and 5-HT2 receptors, respectively) and haloperidol (0.2 mg/kg), a non-selective dopaminergic receptor. The antinociceptive effects are not related to muscle-relaxant or sedative action. These results indicate that AMB produces antinociception through mechanisms that involve interaction with L-arginine-nitric oxide, the serotonergic and cholinergic systems, as well as interaction with the alpha-adrenoceptors.


Ba5Cu8In2S12: a quaternary semiconductor with a unique 3D copper-rich framework and ultralow thermal conductivity.
A novel quaternary sulfide, Ba5Cu8In2S12 (1), has been successfully synthesized via a high-temperature solid-state reaction. It contains Cu8S10S4/2 clusters as basic building blocks, which are connected to one another by discrete In3+ ions to generate a 3D copper-rich framework, where the Ba2+ cations reside. Interestingly, such large clusters that are fused by five crystallographically independent Cu sites with three different chemical environments result in the increase of phonon scattering, which is the crucial factor to the exceptionally low lattice thermal conductivity (ca. 0.28 W m-1 K-1 at 773 K) in 1.


Automated Solid Phase Extraction and Polarity-Switching Tandem Mass Spectrometry Technique for High Throughput Analysis of Urine Biomarkers for 14 Tobacco-related Compounds.
Tobacco use is the leading preventable cause of premature disease and death in the United States. Approximately, 34 million U.S. adults currently smoke cigarettes. We developed a method for automated sample preparation and liquid chromatography-tandem mass spectrometry quantitation of 14 tobacco-related analytes: nicotine (NICF), cotinine (COTF), trans-3'-hydroxycotinine (HCTF), menthol glucuronide (MEG), anabasine (ANBF), anatabine (ANTF), isonicoteine (ISNT), myosmine (MYOS), beta-nicotyrine (BNTR), bupropion (BUPR), cytisine (CYTI), varenicline (VARE), arecaidine (ARD), and arecoline (ARL). The method includes automated solid-phase extraction using customized positive-pressure functions. The preparation scheme has the capacity to process a batch of 96 samples within 4 h with greater than 88% recovery for all analytes. The 14 analytes, separated within 4.15 min using reversed-phase liquid chromatography, were determined using a triple-quadrupole mass spectrometer with atmospheric-pressure chemical ionization and multiple reaction monitoring in negative and positive ionization modes. Wide quantitation ranges, within 1.2-72,000 ng/mL, were established especially for COTF, HCTF, MEG, and NICF to quantify the broad range of biomarker concentrations found in the U.S. population. The method accuracy is above 90% while the overall imprecision is below 7%. Finally, we tested urine samples from 90 smokers and observed detection rates of over 98% for six analytes with urinary HCTF and MEG concentrations ranging from 200-14,100 and 60-57,100 ng/mL, respectively. This high throughput analytical process can prepare and analyze a sample in 9 min and along with the 14-compound analyte panel can be useful for tobacco-exposure studies, in smoking-cessation programs, and for detecting changes in exposure related to tobacco products and their use.


'Socialising' primary care? The Soviet Union, WHO and the 1978 Alma-Ata Conference.
In September 1978, the WHO convened a momentous International Conference on Primary Health Care in Alma-Ata, capital of the Soviet republic of Kazakhstan. This unprecedented gathering signalled a break with WHO's long-standing technically oriented disease eradication campaigns. Instead, Alma-Ata emphasised a community-based, social justice-oriented approach to health. Existing historical accounts of the conference, largely based on WHO sources, have characterised it as a Soviet triumph. Such reasoning, embedded in Cold War logic, contradicts both the decision-making processes in Geneva and Moscow that led the conference to be held in the Union of Soviet Socialist Republics (USSR) and the reality that the highest Soviet authorities did not consider it a significant ideological or political opportunity. To redress the omissions and assumptions of prior accounts, this article examines the Alma-Ata conference in the context of Soviet political and health developments, drawing from Soviet archival and published sources as well as WHO materials and interviews with several key Soviet protagonists. We begin by outlining the USSR's complicated relationship to WHO and the international health sphere. Next, we trace the genesis of the proposal for-and realisation and repercussions of-the primary healthcare (PHC) meeting, framed by Soviet, Kazakh, WHO and Cold War politics. Finally, we explore misjudgements and competing meanings of PHC from both Soviet and WHO perspectives, in particular focusing on the role of physicians, community participation and socialist approaches to PHC.


The effect of menopause and hormone replacement therapy on bone alkaline phosphatase.
We evaluated two different assays for the determination of bone-specific alkaline phosphatase (B-AP). One assay was a direct method using a two-site IRMA (AP(Hyb)). The other assay determined B-AP indirectly after precipitation with lectin (AP(BM)). The assays were compared to serum osteocalcin (levels) and total AP in 20 premenopausal women and in 40 early postmenopausal women before and after 9 months of treatment with hormone replacement therapy (HRT) (n = 20) or placebo (n = 20). Serum osteocalcin correlated with serum AP(Hyb) (r = 0.45), and with serum AP(BM) (r = 0.33) (both p < 0.001). The correlation between AP(Hyb) and AP(BM) was moderate, r = 0.71 (p < 0.001). When comparing postmenopausal to premenopausal women, serum osteocalcin had a t score (mean +/- SEM) of 2.30 +/- 0.29 followed by total AP(T-AP) (1.20 +/- 0.28), AP(Hyb) (1.05 +/- 0.33) and AP(BM) (0.64 +/- 0.21) (paired t-test: p < 0.01 for osteocalcin vs. other markers). After 9 months of HRT all markers had declined significantly to premenopausal levels (mean +/- SEM): osteocalcin with 44.5% +/- 6.1%; AP(BM) with 32.1% +/- 5.6%; AP(Hyb) with 36.4% +/- 4.4% and T-AP with 24.4% +/- 2.9%; p < 0.001. Of the markers, only serum osteocalcin correlated significantly with the rate of bone loss in the placebo group (r = 0.52, p < 0.02). We conclude that both assays for B-AP reflect bone turnover in postmenopausal women with and without HRT. Under controlled conditions they did not show any advantage of osteocalcin in diagnosing increased bone turnover or monitoring the effect of an anti-resorptive therapy in postmenopausal women.


Superior sagittal sinus thrombosis: a complication of gunshot wound injuries to the brain.
Superior sagittal sinus thrombosis (SSST) is a rare complication of non-penetrating brain injuries. However, this is not an uncommon event in those patients who have suffered a gun shot wound (GSW) to the head. Disturbances in blood flow, lead to development of SST, endothelial injury and clotting abnormalities. Complications include increased weakness, mental status changes, seizures and potential mortality. The purpose of this paper is to illustrate three cases of SSST and the need to be alert for this entity. Our cases involve three young female patients each of whom suffered a GSW to the head, with resultant severe brain injury. In each case, severe disability ensued and imaging studies revealed the presence of the superior sagittal sinus syndrome. The cases demonstrate three different presentations and time courses of this entity, along with the appropriate treatment choices. This condition may appear in the immediate post-injury period, in the post-acute rehabilitation period or even at distant follow-up; therefore, patients with TBI secondary to GSW need to be monitored for an extended time interval for clinical signs which may be indicative of SSST.


Frequency multiplexer for ultrasonic Doppler blood flow signals.
An instrument is described which uses single-sideband techniques to combine two channels of Doppler flow signals into a form suitable for simultaneous processing by a single-channel real-time spectral analyzer. The maximum input frequency range is 50 Hz to 10 kHz.


Van Gogh and lithium. Creativity and bipolar disorder: perspective of a writer/photographer.
Diana Dennison has suffered from manic depression since her teenage years in the 1960s but only realised that she had the condition when, in her 30s, she learnt that her uncle was manic depressive. Diana endured her low states with either no medication or with what was for her the unsatisfactory effect of tricyclic antidepressants. Her untreated hypomanic states cut a swathe through her life. She has never been hospitalised for her condition. Her marriage did not survive but her daughters did and she is now a proud and doting grandmother who skis and scuba dives. Only in the last 4 years did Diana seek help for the treatment of her condition. Diana is a free-lance writer, researcher and photographer.


Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury.
To determine whether proton magnetic resonance spectroscopy (MRS), a newer radiographic technology, would be useful in the evaluation of the thalamus of patients in vegetative states resulting from traumatic brain injury. 14 victims of severe traumatic brain injury who were in the vegetative state and whose magnetic resonance images of the thalamus were normal underwent bilateral thalamic proton (MRS) studies. The N-acetyl aspartate to creatine (NAA:Cr) and choline to creatine (Cho:Cr) ratios were obtained for each patient. The proton thalamic MRS findings of patients who were in a persistent vegetative state (n = 8) and in patients who had regained awareness after being in the vegetative state (n = 6) were compared with proton thalamic MRS findings in five healthy volunteers. While conventional magnetic resonance imaging suggested that each patient had a normal thalamus, proton MRS indicated that the thalamus of each patient in the series was damaged. The NAA:Cr ratio was significantly lower in the thalami of both the patients who remained in a persistent vegetative state for the duration of the study and in those who regained awareness after being in the vegetative state (p < 0.001). In addition, NAA:Cr ratios were lower in the group of patients who remained in a persistent vegetative state than in the group of patients who regained awareness after being in the vegetative state (p < 0.001). Results suggest that the NAA:Cr ratio within the thalamus is significant and that thalamic MRS may be helpful when attempting to determine the degree of severity of neuronal and axonal injury in patients in the vegetative state.


Stable isotopes determination in some Romanian fruit juices.
The characterisation of 45 Romanian single-strength fruit juices (apples, pears, plums and grapes) collected from different Transylvanian areas by means of stable isotope approach are presented and discussed in this study. We measured (2)H/(1)H, (18)O/(16)O ratios from water juice and (13)C/(12)C from pulp and compared these results with those already reported in the literature for single-strength juices, in order to see how the geographical and climatic conditions of Transylvania and the meteorological peculiarities of the year 2010 influence the isotopic composition of the investigated fruit juices. The δ(13)C mean values that we found for apple pulp picked up from different Transylvanian areas show slight differences, probably due to the environmental conditions of the plants. No significant correlation either between the variety of apple or the geographical origin and δ(13)C value was established.


Anticardiolipin antibodies and lipoprotein (a) levels in patients with chronic renal failure treated with dialysis: associations with atherothrombotic disease.
The present study evaluated the importance of anticardiolipin antibodies (ACA) and lipoprotein (a) (Lp(a)) as markers of atherothrombotic disease in a retrospective study of patients on maintenance hemodialysis (HD) or peritoneal dialysis (PD). ACA and Lp(a) were measured in 22 patients on PD, and 64 on HD. Three patients were ACA IgM seropositive, whereas none were ACA IgG seropositive. The mean number of previous atherothrombotic events was 2.0 (1-3) in ACA seropositive patients, as compared to 0.7 (0-4) in ACA seronegative patients. The mean Lp(a) level was 56.7 mg/dl (3.0-217.7) in PD patients and 38.8 mg/dl (2.0-255.6) in HD patients (n.s.). Levels of Lp(a) greater than 30 mg/dl were not significantly associated with a history of atherothrombotic events, but all patients who had suffered a myocardial infarction or cerebrovascular insult had Lp(a) levels above 30 mg/dl. We conclude that ACA seropositivity is rare. All ACA seropositive patients had suffered atherothrombotic disease in the current study, whereas all patients with myocardial infarction or cerebrovascular insult had Lp(a) levels above 30 mg/dl.


Factors associated with the development of acute general surgical pathology in medical inpatients.
Medical inpatients can develop acute general surgical conditions. However, this is rare. The presence of multiple acute pathologies delays diagnosis and these patients have poorer prognoses. To determine the incidence, risk factors and prognosis of medical inpatients developing acute general surgical conditions. A single-centre retrospective case-control study was conducted over 1 year in the United Kingdom. Medical patients developing acute surgical pathology were identified using the local referral system. For each case, two controls were selected from a pool of medical inpatients receiving no general surgical input during their admission. Patient records were used to collect hospital admission details, demographic and laboratory data. Univariate analysis and multivariable analysis were performed. The study included 42 cases and 84 controls. The incidence of general surgical pathology in medical inpatients was 2.3/1000 admissions/year. In multivariate analysis, risk factors associated with developing general surgical pathology were previous abdominal surgery (odds ratio (OR) =3.68; 95% confidence interval (CI): 1.43 to 9.48; P = 0.007) and doubling from baseline creatinine (OR = 18.9; 95% CI: 2.57 to 139; P = 0.004). Patients with surgical pathology had longer inpatient stays (22.8 vs 9.4 days; P < 0.001) and a higher inpatient mortality (23.8% vs 7.1%; P = 0.011). Development of surgical pathology was strongly associated with mortality (OR = 4.06; 95% CI: 1.36 to 12.1). The development of acute surgical pathology in medical inpatients is rare but associated with longer inpatient stays and higher mortality. We have identified risk-factors associated with the development of surgical pathology, which can be used to identify patients at risk of surgical pathology.


Cloning of a gene encoding 4-amino-3-hydroxybenzoate 2,3-dioxygenase from Bordetella sp. 10d.
Bordetella sp. 10d produces a novel dioxygenase catalyzing the meta-cleavage of 4-amino-3-hydroxybenzoic acid, 4-amino-3-hydroxybenzoate 2,3-dioxygenase (4A3HBA23D). A gene encoding 4A3HBA23D was cloned and named ahdA. The deduced amino acid sequence of ahdA showed 29.2-24.2% identities to those of prokaryotic and eukaryotic 3-hydoxybenzoate 3,4-dioxygenases in reported meta-cleavage dioxygenases. However, no identities were observed in the amino-terminal sequences of the first 29 amino acid residues. An ORF was found downstream of ahdA. The deduced amino acid sequence of the ORF showed identities to those of LysR family regulators involved in protocatechuate metabolism and contained motifs conserved in the regulators. On the basis of these results, the ORF was named ahdR encoding a putative LysR family regulator. The transcription start point of ahdA was localized 414-bp upstream of the start codon of ahdA. Two DNA-binding motifs of LysR family regulators were found upstream of the transcription start point. These observations suggest that a LysR family regulator encoded by ahdR regulates the expression of ahdA.


Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial.
The Cardiac Antiarrhythmic Suppression Trial (CAST) showed flecainide and encainide induced excess mortality compared with placebo. Labeling drugs as Class 1C is based on clinical observations, comprising measurements of the electrocardiographic parameters QRS. H-V and J-T intervals and of effective refractory period (ERP) as follows: 1--(QRS) wide, 2--(HV) long, 3--(ERP) unchanged, 4--(JT) unchanged. In vitro electrophysiology helped to explain the clinical findings. Flecainide and encainide rendered Na channels as nonconducting, but F and E were only slowly released from the channels after repolarization. At any given drug concentration, a proportion of total channels were eliminated, and the steady-state proportion increased at rising heart rate. It is not proven that the properties that lead to classification of a drug as 1C were those that caused excess deaths in the CAST. The proarrhythmic tendency of 1C drugs can be reduced by beta-blockade, and the mechanisms of adrenergic arrhythmogenicity are discussed. Propafenone is both a 1C drug and a beta-blocker, and its pharmacologic profile is reviewed to illustrate how it resembles and differs from flecainide and encainide. Some features of the CAST are assessed with particular reference to the extent to which conclusions drawn from the results may be justifiably extrapolated to other drugs classified as 1C.


Circadian patterns of sleep, sleepiness, and performance in older and younger adults.
To compare circadian patterns of sleep, subjective sleepiness, and psychomotor performance in older and younger adults. Controlled experimental laboratory study. General Clinical Research Center. Healthy older adults (n = 17, mean age 76 years) and healthy younger adults (n = 19, mean age 23 years). Subjects lived for 60 consecutive hours on a 90-minute sleep-wake cycle (30 minutes in bed, 60 minutes awake). Electroencephalographic recordings were conducted during bedrest periods. Self-ratings and psychomotor performance tests were conducted during 60-minute wake periods. Data were analyzed with cosinor and linear mixed models. Amplitude and phase of the core body temperature rhythm did not significantly differ by age group. Older adults had significantly reduced mean levels and amplitude of rhythms in total sleep time and sleep efficiency and increased mean levels and amplitude of rhythms in sleep latency and wake after sleep onset. Age groups did not differ in mean level of subjective sleepiness, but older adults had reduced amplitude. Older adults had worse overall psychomotor performance, with evidence of larger circadian amplitude in some of these rhythms. Age groups did not differ on the phase position of any rhythm. Older adults had a lower level and smaller circadian variation of sleep propensity compared with younger adults, whereas wakefulness and psychomotor performance rhythms tended to show increased circadian variation among older subjects. These findings likely result from a combination of age-related changes in cortical function, homeostatic sleep mechanisms, and circadian regulation.


Staphylococcus aureus Isolated From Retail Meat and Meat Products in China: Incidence, Antibiotic Resistance and Genetic Diversity.
This study was to estimate the prevalence and characteristics of Staphylococcus aureus from 1,850 retail meat and meat products in China during July 2011 to June 2016. The samples were collected covering most provincial capitals in China, including 604 raw meat, 601 quick-frozen meat, and 645 ready-to-eat meat. Using the qualitative and quantitative methods, all 39 cities had S. aureus-positive samples, and S. aureus was detected in 35.0% (647/1,850) of the samples. The levels of S. aureus in retail meat showed that the MPN value of the majority of the positive samples ranged from 0.3 to 100 MPN/g. Twenty-four antibiotics were used to test all 868 S. aureus isolates for antibiotic susceptibility. Only 11 isolates (1.26%) were susceptible to all antibiotics, whereas most isolates (821/868, 94.6%) showed resistance or intermediary resistance to more than three or more antibiotics. Of these strains, 104 (12.0%) were resistant to more than 10 antibiotics. However, the most frequent resistance was observed to ampicillin (85.4%), followed by penicillin (84.6%), erythromycin (52.7%), tetracycline (49.3%), kanamycin (45.3%), telithromycin (30.1%), clindamycin (29.6%), streptomycin (21.1%), norfloxacin (20.4%), gentamicin (19.4%), fusidic acid (18.4%), ciprofloxacin (16.9%), chloramphenicol (13.1%), amoxycillin/clavulanic acid (11.0%), and others (<10%). 7.4% of isolates (62/868) were confirmed as methicillin-resistance S. aureus (MRSA). By molecular typing analysis, there were 164 spa types and 111 STs were identified, including 15 novel spa types and 65 newly STs by multilocus sequence typing (MLST) and spa typing. Despite the wide genetic diversity observed among the 868 isolates, a great proportion of the population belonged to finite number of major clones: ST1-t127 (93/868, 10.7%) and ST7-t091 (92/868, 10.6%), ST5-t002 (42/868, 4.8%), ST398-t034 (40/868, 4.6%), ST188-t034 (38/868, 4.4%), ST59-t437 (30/868, 3.5%), ST6-t701 (29/868, 3.3%), and ST9-t899 (27/868, 3.1%) in China. This study reflects S. aureus was readily detected in Chinese retail meat and meat products but the level were not very excessive. In this study, the high antibiotic resistance is alarming and raising public health concern. In additions, most of molecular types of isolates have been linked to human infections around the world, indicating that these types of S. aureus in China have a theoretical pathogenic potential.


Undergraduate training in palliative medicine: is more necessarily better?
The General Medical Council's call to modernize medical education prompted the University of Liverpool Medical School to develop a new undergraduate programme, integrating palliative medicine as 'core' curricula. Following successful piloting, the palliative medicine training programme was further developed and expanded. This paper examines whether the additional investment produces improved outcomes. In 1999, fourth year undergraduate medical students (Cohort 1, n = 217) undertook a 2-week pilot education programme in palliative medicine. Subsequently, the training programme was refined and extended, incorporating advanced communication skills training, an ethics project and individual case presentations (Cohort 2, n = 443). Congruent with the study's theoretical driver of self-efficacy, both cohorts were surveyed pre- and post-programme with validated measures of: (i) self-efficacy in palliative care scale; (ii) thanatophobia scale. No significant differences between cohorts' pre-programme scores were identified. Within each cohort, statistically and educationally significant post-education improvements were recorded in both scales. Further post-education analysis indicated that the extended programme produces significantly greater improvements in all domains of the self-efficacy in palliative care scale (communication, t =-7.28, patient management, t =-5.96, multidisciplinary team-working t =-3.77 at p < 0.000), but not thanatophobia. Although improvements were recorded in both cohorts, participation in the extended education programme resulted in further statistically significant gains. Interpreted through the theoretical model employed, improved self-efficacy and outcome expectancies will result in behavioural change that leads to improved practice and better patient care.


Detection of Cervical Cancer through Visual Inspection of Cervix with Acetic Acid (VIA) and Colposcopy at Mymensingh Medical College Hospital.
Cervical cancer is the second most common cause of cancer related morbidity and mortality in women with 50% mortality rate. It is preventable if cervical cellular changes are detected and managed at early stage. This was a retrospective study conducted at VIA center of outpatient department and Colposcopy clinic at in-patient department of Mymensingh Medical College Hospital, Bangladesh covering a period from September 2013 to November 2014. Objective of this study was detection of cervical cancer and precancerous condition amongst patients reported to VIA center and Colposcopy clinic. In primary screening at VIA Center, total respondents were 3604, their mean age was 35.9 and highest were in the age group 31 to 40 years. At VIA center, 110(3.05%) were found positive and highest were between 31 to 40 years. In Colposcopy Clinic, out of 700 patients, 51.7% were CIN 1, 4.9% CIN 2, 1.4% CIN 3, invasive carcinoma was 0.3% and unsatisfactory or inconclusive were 34.3%. Most of the respondents were housewives and majority had poor monthly income. Amongst respondents, 72.1% were from rural area and Colposcopic findings revealed in 62.5% abnormal cervical changes, 46.5% were from rural area. Mean age at marriage or age at first coitus was found 16.25 years and 92.7% were in 11 to 20 years. Maximum abnormal cervical findings including CIN were between the ages ranged from 11 to 20 years of marriage age. In patients having 1 - 5 number of child having abnormal (58%) cervical changes, 48% were CIN 1. Histopathology reports found 19.6% CIN 1 (Total CIN 20.7%), cervical carcinoma 1.3%, inflammatory 7.0% and 0.42% cases were reported normal. Amongst 438 histopathology advised cases, 230 respondent's reports with patients were not available. VIA followed by Colposcopy has been a feasible, easy and reliable tools for screening cervical cancer in Bangladesh.


[Research on the polycrystalline CdS thin films prepared by close-spaced sublimation].
In the present paper, the factors of influence on the deposition rate of CdS films prepared by close-spaced sublimation (CSS) were first studied systematically, and it was found from the experiments that the deposition rate increased with the raised temperature of sublimation source, while decreased with the raised substrate temperature and the deposition pressure. The structure, morphology and light transmittance of the prepared samples were tested subsequently, and the results show: (1) The CdS films deposited under different oxygen partial pressure all present predominating growth lattice orientation (103), and further more the films will be strengthened after annealed under CdCl2 atmosphere. (2) The AFM images of CdS show that the films are compact and uniform in grain diameter, and the grain size becomes larger with the increased substrate temperature. Along with it, the film roughness was also augmented. (3) The transmittance in the shortwave region of visible light through the CdS films would be enhanced when its thickness is reduced, and that will help improve the shortwave spectral response of CdTe solar cells. Finally, the prepared CdS films were employed to fabricate CdTe solar cells, which have achieved a conversion efficiency of 10.29%, and thus the feasibility of CSS process in the manufacture of CdTe solar cells was validated primarily.


Long-term effects of gastric surgery for treating respiratory insufficiency of obesity.
The Pickwickian syndrome can be divided into two primary breathing disorders, which can affect patients alone or in combination: sleep apnea syndrome (SAS) and obesity hypoventilation syndrome (OHS). Between 1980 and 1990, 126 patients with respiratory insufficiency underwent gastric surgery for morbid obesity, 12.5% of the entire series. These patients weighed more (164 +/- 36 vs 135 +/- 25 kg, P less than 0.0001) and were more often men (62% vs 14%, P less than 0.001) than those without pulmonary dysfunction. Sixteen had OHS alone, 65 had SAS alone, and 45 had both. Of those with OHS, 38 have been followed for 5.8 +/- 2.4 y since surgery and 29 are currently asymptomatic. In the 12 patients in whom arterial blood gases were available greater than 5 y since surgery, the PaO2 increased from 54 +/- 10 to 68 +/- 20 mm Hg (P less than 0.0001) and PaCO2 fell from 53 +/- 9 to 47 +/- 11 mm Hg (P = 0.05). Of the 110 patients with SAS, 57 were available for follow-up an average of 4.5 +/- 2.3 y since surgery and 38 were completely asymptomatic, 15 had mild SAS, and 4 had both SAS and OHS. In 40 patients with pre- and post-weight reduction sleep polysomnograms, the sleep apnea index fell from 64 +/- 39 to 26 +/- 26 (P less than 0.0001). Although respiratory insufficiency of obesity patients had a higher operative mortality than did patients without pulmonary dysfunction (2.4% vs 0.2% after gastric bypass), weight loss was associated with significant improvements in sleep apnea, arterial blood gases, pulmonary hypertension, left ventricular dysfunction, lung volumes, and polycythemia.


Development of an Anatomical Silicone Model for Simulation-based Medical Training of Obstetric Anal Sphincter Injury Repair in Bangladesh.
Advancing global healthcare in developing countries has traditionally been an area of interest for many North American medical organizations, as they strive to improve patient outcomes by helping to control disease and death-related illnesses. Women's healthcare in developing countries, in particular, presents a unique set of complexities, revealing high maternal mortality statistics surrounding pregnancy, labor, and childbirth, which is often tied to home births without medically trained attendants. In September 2018, Team Broken Earth, a Canadian-based outreach initiative, hosted a three-day women's healthcare course in Dhaka, Bangladesh, which included simulation-based training stations, for the purpose of advancing clinical skills and education in regards to local labor and delivery. The training stations included the prevention of shoulder dystocia, helping babies breathe, the application of uterine compression sutures, and the repair of obstetric anal sphincter injuries (OASIS). The OASIS management station provided an opportunity to practice anal sphincter repair on anatomically accurate silicone models, which was a focus of the training course due to the high frequency of such injuries in rural Bangladesh. Evaluation surveys were supplied to workshop participants to capture their feedback about the use of the OASIS models and their efficacy as a training tool in Bangladesh. Overall, the models were considered superior as compared to pre-existing training methods, which traditionally involve textbook education and hands-on learning in emergency birthing scenarios by non-medically trained attendants. Two minor iterative improvements were suggested during the Team Broken Earth workshops in Dhaka, Bangladesh, with regards to improving the models for future use: (a) the ethnicity coloring of the models should be more inclusive, especially when delivering training in international countries, and (b) future silicone models should include the addition of mesh across the bottom layer to ensure participants fingers did not rupture the enclosed vaginal canal while suturing. The purpose of this technical report is to determine the efficacy of a silicone OASIS model, developed for practicing high-risk laceration repair that can occur during childbirth, which presents in higher frequency in developing countries, such as Bangladesh, due to the number of rural at-home deliveries. The original study in this series involved the investigation of silicone perineal repair models focusing on first- and second-degree lacerations, which were used at the Remote and Rural Conference in St. John's, Newfoundland, in April 2018. The facilitators distributed the first iteration of the models to conference participants and collected participant feedback, which concluded that several improvements were required to enhance the models for medical training purposes. With the iterative revisions complete, the model is now under further validation testing to determine its efficacy within simulation-based medical education (SBME) and clinical skill maintenance. This technical report is the second in the series and includes the most recent third and fourth-degree silicone models as well as all suggested improvements from previous clinical feedback.


Obesity epidemic: overview, pathophysiology, and the intensive care unit conundrum.
Obesity is one of the leading causes of preventable death in the United States, second only to smoking. The annual number of deaths attributed to obesity is estimated to be as high as 400,000. Nearly 70% of the adult U.S. population is overweight or obese. The historical viewpoint toward obesity has deemed it to be a lifestyle choice or characterological flaw. However, given the emerging research into the development of obesity and its related complications, our perspective is changing. It is now clear that obesity is a heterogeneous disease with many different subtypes, which involves an interplay between genetic and environmental factors. The current epidemic of obesity is the result of an obesogenic environment (which includes energy-dense foods and a lack of physical activity) in individuals who have a genetic susceptibility for developing obesity. The pathophysiology associated with weight gain is much more complex than originally thought. The heterogeneous nature of the disease makes the development of treatment strategies for obesity difficult. Obesity in general is associated with increased all-cause mortality and cause-specific mortality (from cardiovascular, diabetic, hepatic, and neoplastic causes). Yet despite increased overall mortality rates, current evidence suggests that when these same patients are admitted to the intensive care unit (ICU), the obesity provides some protection against mortality. At present, there is no clear explanation for this obesity conundrum in critical illness.


In vitro binding of Sorghum bicolor transcription factors ABI4 and ABI5 to a conserved region of a GA 2-OXIDASE promoter: possible role of this interaction in the expression of seed dormancy.
The precise adjustment of the timing of dormancy release according to final grain usage is still a challenge for many cereal crops. Grain sorghum [Sorghum bicolor (L.) Moench] shows wide intraspecific variability in dormancy level and susceptibility to pre-harvest sprouting (PHS). Both embryo sensitivity to abscisic acid (ABA) and gibberellin (GA) metabolism play an important role in the expression of dormancy of the developing sorghum grain. In previous works, it was shown that, simultaneously with a greater embryo sensitivity to ABA and higher expression of SbABA-INSENSITIVE 4 (SbABI4) and SbABA-INSENSITIVE 5 (SbABI5), dormant grains accumulate less active GA4 due to a more active GA catabolism. In this work, it is demonstrated that the ABA signalling components SbABI4 and SbABI5 interact in vitro with a fragment of the SbGA 2-OXIDASE 3 (SbGA2ox3) promoter containing an ABA-responsive complex (ABRC). Both transcription factors were able to bind the promoter, although not simultaneously, suggesting that they might compete for the same cis-acting regulatory sequences. A biological role for these interactions in the expression of dormancy of sorghum grains is proposed: either SbABI4 and/or SbABI5 activate transcription of the SbGA2ox3 gene in vivo and promote SbGA2ox3 protein accumulation; this would result in active degradation of GA4, thus preventing germination of dormant grains. A comparative analysis of the 5'-regulatory region of GA2oxs from both monocots and dicots is also presented; conservation of the ABRC in closely related GA2oxs from Brachypodium distachyon and rice suggest that these species might share the same regulatory mechanism as proposed for grain sorghum.


Melatonin attenuates hypertension-related proarrhythmic myocardial maladaptation of connexin-43 and propensity of the heart to lethal arrhythmias.
We hypothesized that the pineal hormone melatonin, which exhibits cardioprotective effects, might affect myocardial expression of cell-to-cell electrical coupling protein connexin-43 (Cx43) and protein kinase C (PKC) signaling, and hence, the propensity of the heart to lethal ventricular fibrillation (VF). Spontaneously hypertensive (SHR) and normotensive Wistar rats fed a standard rat chow received melatonin (40 μg/mL in drinking water during the night) for 5 weeks, and were compared with untreated rats. Melatonin significantly reduced blood pressure and normalized triglycerides in SHR, whereas it decreased body mass and adiposity in Wistar rats. Compared with healthy rats, the threshold to induce sustained VF was significantly lower in SHR (18.3 ± 2.6 compared with 29.2 ± 5 mA; p < 0.05) and increased in melatonin-treated SHR and Wistar rats to 33.0 ± 4 and 32.5 ± 4 mA. Melatonin attenuated abnormal myocardial Cx43 distribution in SHR, and upregulated Cx43 mRNA, total Cx43 protein, and its functional phosphorylated forms in SHR, and to a lesser extent, in Wistar rat hearts. Moreover, melatonin suppressed myocardial proapoptotic PKCδ expression and increased cardioprotective PKCε expression in both SHR and Wistar rats. Our findings indicate that melatonin protects against lethal arrhythmias at least in part via upregulation of myocardial Cx43 and modulation of PKC-related cardioprotective signaling.


Rickettsia felis, an emerging flea-transmitted human pathogen.
Rickettsia felis was first recognised two decades ago and has now been described as endemic to all continents except Antarctica. The rickettsiosis caused by R. felis is known as flea-borne spotted fever or cat-flea typhus. The large number of arthropod species found to harbour R. felis and that may act as potential vectors support the view that it is a pan-global microbe. The main arthropod reservoir and vector is the cat flea, Ctenocephalides felis, yet more than 20 other species of fleas, ticks, and mites species have been reported to harbour R. felis. Few bacterial pathogens of humans have been found associated with such a diverse range of invertebrates. With the projected increase in global temperature over the next century, there is concern that changes to the ecology and distribution of R. felis vectors may adversely impact public health.


Noncationic dipeptide mimic oligomers as cell penetrating nonpeptides (CPNP).
Small oligomers of constrained dipeptide mimics have been synthesized as new vectors for intracellular delivery. They are highly internalized by cells and delivered to the lysosomes by an energy-dependent pathway. This new class of vectors referred to as cell penetrating nonpeptides (CPNP) possess the distinctive feature of being noncationic.


Who is More Likely to Report Medical Insurance Fraud in the Two Scenarios of Whether It Results in a Direct Loss of Individual Benefit? A Cross-Sectional Survey in China.
An individual's willingness to report is largely related to whether he or she is a direct victim. This study takes two scenarios of whether medical insurance fraud results in a direct loss of personal benefit and explores the differences in individuals' willingness to report and influencing factors in the two scenarios. In this study, questionnaires were used and participants were selected from 571 individuals in eastern, central, and western China. Analysis was performed using descriptive statistics and logistic regression models. 51.0% of individuals were willing to report when no direct loss of personal benefit was caused, and conversely, 78.3% of individuals were willing to report when direct loss of personal benefit was caused. The factors influencing the attitude dimension of individuals toward whistleblowing behavior were consistent in the two scenarios. In contrast, there were significant differences among the influences in the perceived behavioral control, consequence perception, and subjective norm dimensions. There were significant differences in the willingness of individuals to report medical insurance fraud and the factors influencing it in both scenarios. The most significantly influencing factor difference was perceived behavioral control, a dimension that had an effect only when it did not result in a direct loss of personal benefit. When an individual's direct interests are at stake, the individual's fear for his or her safety is not a deterrent to his or her willingness to report. And when there is no loss of direct personal benefit, individuals care more about government measures to protect whistleblowers. There are differences in the subjects that influence individuals' willingness to report in the two scenarios. The factors influencing the attitude dimension are the same in both scenarios, and the more supportive the attitude toward the whistleblower, the stronger the individual's willingness to report will be.


Diarrhea associated with lorazepam solution in a tube-fed patient.
A 43-year-old patient with adult respiratory distress syndrome, alcoholic hallucinosis, and delirium required significant amounts of lorazepam, morphine, and midazolam for management of agitation and increased peak airway pressures. Broad-spectrum antibiotics and intermittent pancuronium therapy were instituted. A nasoenteral feeding tube was placed for nutrition and medication administration during mechanical ventilation. Tube feedings were well tolerated except for intermittent bouts of large amounts of diarrhea. Clostridium difficile culture and toxin results were negative. Lorazepam and morphine administration were converted from the IV to enteral route to decrease the amount of fluid administered. The tube feeding was changed to an electrolyte rehydration solution and eventually discontinued. A search for drug-related contributing factors to the diarrhea revealed polyethylene glycol present in the lorazepam solution. It was postulated that this could be a contributing cause to the diarrhea. The lorazepam solution was changed to enterally administered crushed tablets with subsequent resolution of diarrhea.


Complete genome sequence of the BTEX-degrading bacterium Pseudoxanthomonas spadix BD-a59.
Pseudoxanthomonas spadix BD-a59, able to metabolize all six BTEX (benzene, toluene, ethylbenzene, and o-, m-, and p-xylene) compounds, was isolated from gasoline-contaminated sediment. Here, we report the complete 3.45-Mb genome sequence and annotation of strain BD-a59. These advance the understanding of strain BD-a59's genomic properties and pollutant metabolic versatility.


Sinonasal Chondrosarcoma Presenting With Isolated Severe Vision Loss.
A 24-year-old man presented with a 2-month history of progressive, painless vision loss in the right eye, with no history of headache, nasal congestion, rhinorrhea, or epistaxis. His visual acuity was counting fingers at 1 ft in the right eye and 20 of 20 in the left eye with a right relative afferent pupillary defect and mild temporal optic disc pallor. MRI of the brain and orbits showed a mass involving bilateral ethmoid and sphenoid sinuses and right nasal cavity. He underwent urgent extended endoscopic endonasal transsphenoidal approach for resection of the sinonasal skull base tumor and photon radiation therapy. Pathology revealed a well-differentiated cartilaginous neoplasm with focal areas of entrapped native bone, consistent with a chondrosarcoma WHO grade I/III. At 6-month follow-up after surgery, he had a visual acuity of 20/40 in the right eye and 20/20 in the left eye. Malignant tumors from the sinonasal area should be kept in the differential diagnosis for compressive optic neuropathies and may present with vision loss even in the absence of nasal or sinus symptoms.


Genotypic diversity of an emergent population of Borrelia burgdorferi at a coastal Maine island recently colonized by Ixodes scapularis.
The recent range expansion of Ixodes scapularis has been accompanied by the emergence of Borrelia burgdorferi. The development of genetic diversity in B. burgdorferi at these sites of emergence and its relationship to range expansion is poorly understood. We followed colonization of I. scapularis on a coastal Maine island over a 17-year period. B. burgdorferi's emergence was documented, as was expansion of ospC strain diversity. Ticks collected from rodents and vegetation were examined for the presence of B. burgdorferi. Sequencing and reverse line blot were used to detect B. burgdorferi ospC major groups (oMG). No I. scapularis were found until year four of the study, after which time they increased in abundance. No B. burgdorferi was detected by darkfield microscopy in I. scapularis until 10 years into the study, when 4% of adult ticks were infected. Seven years later, 43% of adult ticks were infected. In 2003, one oMG accounted for 91% of B. burgdorferi strains. This "founder" strain persisted in 2005, but by 2007 was a minority of the 7 oMGs present. Given the island's isolation, gene flow by avian introduction of multiple strains is suggested in the development of B. burgdorferi oMG diversity.


Domain generalization in deep learning for contrast-enhanced imaging.
The domain generalization problem has been widely investigated in deep learning for non-contrast imaging over the last years, but it received limited attention for contrast-enhanced imaging. However, there are marked differences in contrast imaging protocols across clinical centers, in particular in the time between contrast injection and image acquisition, while access to multi-center contrast-enhanced image data is limited compared to available datasets for non-contrast imaging. This calls for new tools for generalizing single-domain, single-center deep learning models across new unseen domains and clinical centers in contrast-enhanced imaging. In this paper, we present an exhaustive evaluation of deep learning techniques to achieve generalizability to unseen clinical centers for contrast-enhanced image segmentation. To this end, several techniques are investigated, optimized and systematically evaluated, including data augmentation, domain mixing, transfer learning and domain adaptation. To demonstrate the potential of domain generalization for contrast-enhanced imaging, the methods are evaluated for ventricular segmentation in contrast-enhanced cardiac magnetic resonance imaging (MRI). The results are obtained based on a multi-center cardiac contrast-enhanced MRI dataset acquired in four hospitals located in three countries (France, Spain and China). They show that the combination of data augmentation and transfer learning can lead to single-center models that generalize well to new clinical centers not included during training. Single-domain neural networks enriched with suitable generalization procedures can reach and even surpass the performance of multi-center, multi-vendor models in contrast-enhanced imaging, hence eliminating the need for comprehensive multi-center datasets to train generalizable models.


Nuclear Medicine in Pediatric Musculoskeletal Imaging.
The pediatric skeleton is a dynamic structure. Bone scintigraphy depends on bone metabolism and therefore is particularly applicable to changes occurring in the physes (growth-plates). A knowledge of the physiologic changes in the growing skeleton as well as the disease processes affecting the different pediatric age brackets are necessary to accurately solve clinical diagnostic problems with bone scintigraphy. Bone scintigraphy is a readily available, low-radiation imaging procedure. In this article, the common pediatric skeletal aberrations (appendicular growth alterations, hip pain, back pain, some aspects of trauma, inflammatory and infectious processes, and some common benign neoplastic occurrences) that can be addressed by nuclear imaging are discussed.


Uptake of complete postnatal care services and its determinants among rural women in Southern Ethiopia: Community-based cross-sectional study based on the current WHO recommendation.
Postnatal care services are a constellation of preventive care, practices, and assessments designed to identify and manage maternal and newborn complications during the first six weeks after birth. Recognizing the role of the appropriate PNC at this critical time, the World Health Organization recommended four visits as a complete PNC for all post-partum mothers and newborns to ensure their survival. Although there have been numerous studies on the factors affecting the general PNC service in Ethiopia, there is a shortage of evidence on the use of complete postnatal care services and its determinants. Therefore, the objective of this study was to assess the uptake of full postnatal care service and its determinants among women who recently gave birth in the Ezha district of southern Ethiopia. A community-based cross-sectional study was conducted in Ezha district. A two-stage sampling technique was applied. A total of 568 mothers who stayed for at least 6 weeks after childbirth from selected Kebeles were included in the study using computer-generated random numbers. Data collected through pre-established, structured, and interviewer-administered questionnaires were entered into EpiData3.1 and exported to SPPS version 23 for analysis. The Principal Components Analysis (PCA) was carried out to assess the wealth status of participants. The Multivariable logistic regression model has been fitted to identify the determinants of complete post-natal care service uptake. The overall uptake of complete postnatal care services in the study area was 23.9% [95% CI: (19.9, 27.5)]. The factors namely; maternal education of secondary and above [AOR: 4.31, 95%CI: 2.15, 8.05], having four and more antenatal visits [AOR: 4.03, 95%CI: 1.83, 8.85], Caesarean delivery [AOR: 3.75, 95%CI: 1.78, 7.92], having good knowledge on PNC [AOR: 4.31, 95%CI: 2.34, 9.04], and being a model household [AOR: 3.61, 95%CI: 1.97, 6.64] were recognized as determinants complete postnatal care uptake. Complete post-natal care services uptake in the study area was low. Thus, a due emphasis should be given to behavioral change communication activities to improve maternal knowledge on PNC and enhancing adequate ANC uptake by health workers in the district. Besides, health extension workers in the district need to work on creating a model household through continuing education, support, and follow-up.


Characterization of a cDNA clone encoding the calmodulin-binding domain of mouse brain calcineurin.
A cDNA clone corresponding to a portion of the catalytic subunit of calmodulin (CaM)-dependent phosphoprotein phosphatase (calcineurin) was isolated from a murine brain library by expression vector immunoscreening. A beta-galactosidase fusion protein that reacted on Western blots with anti-calcineurin antibodies and biotinylated CaM was purified in preparative amounts using CaM-Sepharose affinity chromatography. Partial digestion of the hybrid protein with Staphylococcus aureus V-8 protease produced several immunoreactive peptides that appeared identical to fragments generated from authentic brain calcineurin. The 1111-base-pair (bp) EcoRI insert contained an open reading frame encoding a protein of 35 kDa followed by a 190-bp 3' noncoding region; seven peptides obtained by partial amino acid sequencing of the bovine brain enzyme were found in the deduced sequence. A domain approximately 12 kDa from the carboxyl terminus was deduced to be the CaM-binding site based on consensus structural features and a sequence of seven amino acids highly related to smooth muscle myosin light-chain kinase. Two regions with identity to protein phosphatases 1 and 2A were found in the amino half of the cloned sequence; however, the intervening sequence contained apparent insertions, suggesting splicing of subdomains. Thus, the structure of calcineurin is chimeric, consisting of conserved catalytic elements and a regulatory CaM-binding domain.


Arachidonic acid plays a role in rat vomeronasal signal transduction.
Sensory neurons of the vomeronasal organ (VNO) detect volatile chemicals that are released by conspecific animals and convey information about social and reproductive behavior. The signal transduction pathway in vomeronasal receptor neurons (VRNs) is not known in detail, but is believed to be distinct from that of the sensory neurons of the main olfactory system. Many of the identified olfactory transduction components are not expressed by VRNs. Using Ca2+ imaging and electrophysiological recordings, we investigated the signal transduction pathway of urine perception and the possible role of polyunsaturated fatty acids (PUFAs) as intracellular messengers in freshly dissociated rat VNO neurons. We found that application of urine induced a transient increase in intracellular Ca2+ that was dependent on the activity of phospholipase C and diacylglycerol (DAG) lipase. The Ca2+ transient was not dependent on depletion of intracellular Ca2+ stores but was dependent on the presence of extracellular Ca2+. Furthermore, the urine response was not sensitive to modulators of adenylate cyclase and inhibitors of inositol 1,4,5-trisphosphate receptors. Application of PUFAs (linolenic acid and arachidonic acid, synthesized in living cells from DAG) also elicited Ca2+ transients in fura 2 measurements and inward currents in whole-cell voltage-clamp recordings. Pharmacological inhibition of lipoxygenase and cyclooxygenase induced a transient increase in intracellular Ca2+, possibly by increasing the endogenous level of PUFAs, leading to activation of transduction channels. These data provide evidence for a role of PUFAs in rat vomeronasal signal transduction.


Immunologic effects of ursodeoxycholic acid in primary biliary cirrhosis.
Investigations were undertaken to determine the effect on lymphocyte reactivity of treatment of primary biliary cirrhosis with ursodeoxycholic acid (UDCA). Eight patients with stage 2 and 6 with stage 3 primary biliary cirrhosis were observed. Patients were treated with 300 mg of UDCA three times daily for 1 to 3 years. UDCA reduced jaundice, pruritus, and serum alkaline phosphatase levels. Repeat liver biopsy showed a decrease in inflammation in 3 patients. One patient with stage 3 primary biliary cirrhosis had disease progression despite UDCA treatment. Phytohemagglutinin (PHA) and concanavalin A (con A) were added to mixed lymphocytes from 9 patients receiving UDCA before and after 1 year of treatment. T-cell reactivity was determined by evaluating tritiated thymidine incorporation into DNA. Patients exhibiting an improvement in liver function tests had a significant reduction in lymphocyte reactivity to these mitogens (P < .01). When UDCA was stopped, the response to PHA and con A returned to pretreatment levels, reflecting continued presence of immunologic abnormalities characteristic of primary biliary cirrhosis. UDCA's effect on lymphocyte reactivity appears to be due to a reduction of hydrophobic bile acids, since it does not alter response to mitogens in patients with a normal liver.


Linking niche theory to ecological impacts of successful invaders: insights from resource fluctuation-specialist herbivore interactions.
Theories of species coexistence and invasion ecology are fundamentally connected and provide a common theoretical framework for studying the mechanisms underlying successful invasions and their ecological impacts. Temporal fluctuations in resource availability and differences in life-history traits between invasive and resident species are considered as likely drivers of the dynamics of invaded communities. Current critical issues in invasion ecology thus relate to the extent to which such mechanisms influence coexistence between invasive and resident species and to the ability of resident species to persist in an invasive-dominated ecosystem. We tested how a fluctuating resource, and species trait differences may explain and help predict long-term impacts of biological invasions in forest specialist insect communities. We used a simple invasion system comprising closely related invasive and resident seed-specialized wasps (Hymenoptera: Torymidae) competing for a well-known fluctuating resource and displaying divergent diapause, reproductive and phenological traits. Based on extensive long-term field observations (1977-2010), we developed a combination of mechanistic and statistical models aiming to (i) obtain a realistic description of the population dynamics of these interacting species over time, and (ii) clarify the respective contributions of fluctuation-dependent and fluctuation-independent mechanisms to long-term impact of invasion on the population dynamics of the resident wasp species. We showed that a fluctuation-dependent mechanism was unable to promote coexistence of the resident and invasive species. Earlier phenology of the invasive species was the main driver of invasion success, enabling the invader to exploit an empty niche. Phenology also had the greatest power to explain the long-term negative impact of the invasive on the resident species, through resource pre-emption. This study provides strong support for the critical role of species differences in interspecific competition outcomes within animal communities. Our mechanistic-statistical approach disentangles the critical drivers of novel species assemblages resulting from intentional and non-intentional introductions of non-native species.


Behavioral, morphological, and biochemical changes after in ovo exposure to methylmercury in chicks.
Methylmercury (MeHg) is an environmental pollutant known to induce neurotoxicity in several animal species, including humans. However, studies focusing the effects of MeHg poisoning in chicks were based on phenomenological approaches and did not delve into the molecular mechanisms. The purpose of this study was to evaluate the postnatal consequences of the in ovo exposure to MeHg on behavioral, morphological and biochemical parameters in chicks. At the fifth embryonic day (E5), Gallus domesticus eggs were submitted to a single injection of 0.1 microg MeHg/0.05 ml saline. After treatment, the eggs returned to the incubator until hatching (E21). From first to fifth postnatal days (PN 1-PN 5), the MeHg-treated chicks showed lower frequency of exploratory movements and a significantly higher frequency of wing and anomalous movements. Cerebellar glutathione (GSH) levels and the activities of the GSH-related enzymes GSH reductase and GSH peroxidase were significantly higher (70, 72, and 80%, respectively) in MeHg exposed chicks in comparison to controls. Mercury impregnation was densest in the granular layer, followed by the Purkinje and molecular layers of treated chicks. A significant reduction of the number of Purkinje cells, as well as a greater distance between these cells were observed in chicks of MeHg group. Our results disclose that the prehatching exposure to MeHg induced motor impairments, which were correlated to histological damage and alterations on the cerebellar GSH system's development from PN 1 to PN 5.


3D Printed Template-Assisted Assembly of Additive-Free Ti3C2Tx MXene Microlattices with Customized Structures toward High Areal Capacitance.
Ti3C2Tx MXene is a promising material for electrodes in microsupercapacitors. Recent efforts have been made to fabricate MXene electrodes with designed structures using 3D printing to promote electrolyte permeation and ion diffusion. However, challenges remain in structural design diversity due to the strict ink rheology requirement and limited structure choices caused by existing extrusion-based 3D printing. Herein, additive-free 3D architected MXene aerogels are fabricated via a 3D printed template-assisted method that combines 3D printed hollow template and cation-induced gelation process. This method allows the use of MXene ink with a wide range of concentrations (5 to 150 mg mL-1) to produce MXene aerogels with high structural freedom, fine feature size (>50 μm), and controllable density (3 to 140 mg cm-3). Through structure optimization, the 3D MXene aerogel shows high areal capacitance of 7.5 F cm-2 at 0.5 mA cm-2 with a high mass loading of 54.1 mg cm-2. It also exhibits an ultrahigh areal energy density of 0.38 mWh cm-2 at a power density of 0.66 mW cm-2.


Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).


Novel p.M96T variant of NRL and shRNA-based suppression and replacement of NRL mutants associated with autosomal dominant retinitis pigmentosa.
Mutations in the gene encoding the transcription factor neural retina leucine zipper (NRL) are known to cause autosomal dominant (adRP) or recessive (arRP) retinitis pigmentosa (RP). In an adRP Spanish family, we detected a novel sequence variation (c.287T>C) in the NRL gene that results in the p.M96T protein change. A functional test of the ability of NRL, in conjunction with cone-rod homeobox (CRX), to transactivate a human rhodopsin (RHO) promoter was used to evaluate the pathogenic mechanisms of NRL. We found upregulation of the RHO promoter by p.M96T protein similar to that shown by other missense NRL mutations that cause adRP. Affected RP patients of the family carry the nucleotide change, although two other family members that also carry the c.287T>C variation remain asymptomatic. This result complicates the genetic counselling of the family. The pathogenic mechanisms associated with adRP NRL mutations appear to be caused by a gain of function. To suppress the negative effect of an NRL mutant, the suppression and replacement strategy seems to be the most suitable therapeutic approach capable of overcoming the mutational heterogeneity associated with NRL-linked adRP. Thus, we evaluated this methodology in the NRL gene for the first time.


The influence of the Brentano illusion on eye and hand movements.
When making an eye movement and a hand movement toward a visual target, the movements could be guided by visual judgments of direction and distance (or length) of the required displacement (vector coding), estimates of the final position (position coding), or both. Using the same information for the eyes and the hand is efficient; however, if this information contains an error, this causes both the eye and the hand to be incorrect. In this study, we tried to find out whether saccades and pointing movements use the same source of information when eye and hand movements are performed either concurrently or separately. Four experiments have been performed using the Brentano illusion, which primarily influences judgments of length but not those of position. This illusion only influences movements if the illusory length is relevant for the task, demonstrating that vector coding is involved. Subjects made saccades, pointing movements, or both between vertices of the Brentano illusion. The illusion influenced saccades and pointing movements when these movements were performed concurrently and separately, showing that the eye and the hand use vector coding. However, depending on the task, eye and hand movements were influenced to a different extent. This favors the interpretation that the eyes and the hand use a common motor command but each with a different relative contribution of vector coding.


Novel mutations identification in exon 4 of LDLR gene in patients with moderate hypercholesterolemia in a Venezuelan population.
Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by increase in low-density lipoprotein (LDL) cholesterol levels and premature coronary artery disease. In Venezuela, the molecular basis of FH has not been characterized, thus, the aim of this study was to investigate mutations in the exon 4 of the LDLR (LDL-receptor) gene in 225 Venezuelan mixed race individuals (65 hypercholesterolemic and 160 normolipidemic). The exon 4 of the LDLR gene was screened by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. Additionally, ApoB-100 gene mutations were investigated. Different LDLR gene mutations were identified in 5 hypercholesterolemic patients (7.7%), 3 missense mutations (4.6%), and 2 frameshift mutations (3%). All mutations were heterozygous. The missense mutations included the amino acid substitution p.E180K, p.R194S, and p.C152G. The frameshift mutations are caused by insertions resulting in the creation of stop codons: p.D157fsX158 and p.S173fsX174, which could code for truncated LDLR of 157 and 173 amino acids, respectively. The apoB gene mutations were not detected in any of our patients and to our knowledge 4 mutations identified in this study have not been reported previously, this study being the first comprehensive mutation analysis of the LDLR causing FH in our region. The early identification of individuals at risk allows changes in lifestyle, including dietary intervention, followed by drug treatment.


Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal dysfunction: a paradigm shift.
End-stage renal disease (ESRD) comprises an enormous public health burden, with an increasing incidence and prevalence. Hypertension is a major risk factor for progressive renal disease. This escalating prevalence suggests that newer therapeutic interventions and strategies are needed to complement current antihypertensive approaches. Although much evidence demonstrates that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Several lines of experimental evidence demonstrate that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (i.e. remnant kidney). Whereas pharmacological blockade with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors reduces proteinuria and nephrosclerosis/ glomerulosclerosis, selective reinfusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Aldosterone may promote fibrosis by several mechanisms, including plasminogen activator inhibitor-1 expression and consequent alterations of vascular fibrinolysis, by stimulation of transforming growth factor-beta 1, and by stimulation of reactive oxygen species. Based on this theoretical construct, randomized clinical studies will be initiated to delineate the potential renal-protective effects of antihypertensive therapy utilizing aldosterone receptor blockade.


A facile synthesis of cis-1-methyl-1,2,3,3a,4,8b- hexahydropyrrolo[3,2-f]pyrindine, an annulated nicotine analog.
[reaction: see text] The title compound, 2, has been synthesized in 45% overall yield in six steps from 3-bromopyridine. The hexahydropyrrolo[3,2-f]pyrindine skeleton was constructed from key intermediate 5, via intramolecular azomethine ylide-alkene [3 + 2] cycloaddition. The present work constitutes a general method for rapid assembly of other related tricyclic nicotine analogues.


Brain structural associations with depression in a large early adolescent sample (the ABCD study®).
Depression is the leading cause of disability worldwide with > 50% of cases emerging before the age of 25 years. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However, most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention. Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample (N = 8634) of early adolescents (9 to 11 years old) from the US-based, Adolescent Brain and Cognitive Development (ABCD) Study®. Data was collected from 2016 to 2018. We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen's d = -0⋅018 to -0⋅041, β = -0·019 to -0⋅057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β = 0⋅048 to 0⋅169). Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology. Wellcome Trust (References: 104036/Z/14/Z and 220857/Z/20/Z) and the Medical Research Council (MRC, Reference: MC_PC_17209).


Are the autism and positive schizotypy spectra diametrically opposed in local versus global processing?
Crespi and Badcock (2008) proposed that autism and psychosis represent two extremes on a cognitive spectrum with normality at its center. Their specific claim that autistic and positive schizophrenia traits contrastingly affect preference for local versus global processing was investigated by examining Embedded Figures Test performance in two groups of students separated on autistic-like traits but matched on positive schizotypy traits, and two groups separated on positive schizotypy traits but matched on autistic-like traits (n = 20 per group). Consistent with their theory, higher levels of autistic-like traits were associated with faster identification of hidden figures, whereas higher levels of positive schizotypy traits were associated with slower identification.


How Safe Is Cancer Care?
Cancer Morbidity, Mortality, and Improvement Rounds is a series of articles intended to explore the unique safety risks experienced by oncology patients through the lens of quality improvement, systems and human factors engineering, and cognitive psychology. For purposes of clarity, each case focuses on a single theme, although, as is true for all medical incidents, there are almost always multiple, overlapping, contributing factors. The quality improvement paradigm used here, which focuses on root cause analyses and opportunities to improve care delivery systems, was previously outlined in this journal.


High-order harmonics from elliptically polarized laser for classification of topological states in 2D Chern insulators and 2D topological insulators.
High-order harmonics (HH) have drawn attention in the field of condensed matter physics mainly because of the capability of light to encode structural, dynamical, and topological information. In this paper, we address the fundamental question whether HH can map topological information in two-dimensional (2D) quantum materials by studying the interaction between topological materials and an elliptically polarized laser. We use the Haldane model for topological Chern insulators (CIs) and the Kane-Mele model for topological insulators (TIs). In the case of a circularly polarized or nearly circularly polarized driving field in CIs and TIs, the harmonic intensity of the co-rotating orders is increased. This increase in topologically non-trivial materials implies that HH can be used to detect topological transitions in 2D CIs and TIs. Moreover, interference between two spin bands in TIs does not affect the elliptical dependence of co-rotating harmonic orders in the plateau region.


Studies in vivo on the efficacy of enrofloxacin against Mycoplasma gallisepticum.
After a 5-day medication with drinking water containing 50 ppm enrofloxacin, Mycoplasma gallisepticum (MG) was culturally reisolated in only one of 80 broiler chicks and specific antibodies to MG were detected in none of the 40 birds tested. Medication with 50 ppm for 3 days and 25 ppm for 5 days was only slightly less effective. A significant decline in efficacy was observed, however, when enrofloxacin was added to the drinking water at 50 ppm for 1 day or 12.5 ppm for 5 days. Tiamulin was also significantly effective (250 ppm, 3 days). However, measured by the cultural reisolation of the pathogen and the presence of antibodies to MG. enrofloxacin (50 ppm, 3 days) proved to be more effective. Treatment with tylosin (50 ppm. 5 days) conferred no significant protection.


Some Physiological Changes Occurring during the Senescence of Auxin-Deprived Pear Cells in Culture.
Part of the changes in the hormonal balance involved in plant senescence is due to an auxin limitation. Some of its physiological consequences are studied using pear (Pyrus communis L.) cells cultured in a continuously renewed medium in which 2,4-dichlorophenoxyacetic acid (2,4-D) was absent. In these conditions, an assessment was made of the absence of nutrient deficiency.In the period preceding cell death, the rate of respiration and ethylene production remain low, and no major changes were observed in the total protein and RNA content of the cells. Beginning around day 9, an important efflux of three amino acids (serine, threonine, and aspartic acid) occurs among which serine represents more than 52%. However, exogenous serine supplied to the medium fails to show any senescence promoting effect. At the same time, leucine uptake and incorporation sharply and simultaneously increased. The presence of 2,4-D inhibits both these phenomena and prevents cell death. It is proposed that auxin deprivation is responsible for unmasking a program of synthesis of new proteins involved in cell death.


The outcome of benign thyroid nodules correlates with the findings of fine needle biopsy.
204 patients with a single or dominant 'cold' thyroid nodule were treated with l-thyroxine, 150-250 micrograms/d, for 4 to 12 months. The two clinicians who evaluated the evolution of the nodules knew that fine-needle biopsy (FNB) had excluded malignancy, but ignored any other morphologic data of the FNB smears. Good outcome, i.e. disappearance of the nodule or definite decrease in its size, was observed in 66 cases (32%). This good clinical outcome was correlated with various morphologic characteristics of the FNB aspirate. The nodule was more likely to regress if FNB showed much colloid, many degenerative changes and many phagocytes, whereas the presence of extensive hyperplasia, lymphocytes or fibrosis were associated with an unfavourable prognosis. With logistic regression, controlling for the confounding effects of sex, age, clinical and histological picture and thyroxine dose, significant correlations were shown with the presence of colloid, hyperplasia and fibrosis. It is concluded that the morphologic characteristics of the FNB aspirate may, to some extent, predict the outcome of cold thyroid nodules.


An enzyme-free capacitive glucose sensor based on dual-network glucose-responsive hydrogel and coplanar electrode.
Glucose sensors are vital devices for blood glucose detection in the diabetes care. Different from traditional electrochemical devices based on glucose oxidase, the glucose sensor based on the glucose-responsive hydrogel is more robust owing to its enzyme-free principle. However, integrating the high sensitivity, fast response, wide measuring range and low-cost fabrication into a hydrogel sensor is still challenging. In this study, we present a physical capacitive sensor, which consists of interdigital carbon electrodes (ICEs) fabricated by a direct laser writing technology and glucose-responsive hydrogel (DexG-Con A hydrogel) built by UV curing in situ. The dielectric property of DexG-Con A hydrogel changes accordingly with the change in environmental glucose concentration. Experimental results demonstrate that in a glucose concentration range of 0-30 mM, the proposed hydrogel sensor is capable of measuring the glucose level in a repeatable and reversible manner, showing a short responsive time of less than 2 min and a high sensitivity of 8.81 pF mM-1 at a glucose range of 0-6 mM. Owing to its simple fabrication process, low-cost and high performance, the proposed glucose sensor shows great potential on batch production for continuous glucose monitoring application.