Changes in gene expression during hexamethylene bisacetamide induced erythroleukemia differentiation.
HMBA induces MELC to terminal erythroid differentiation. The mechanism of HMBA action is not known. Culture with HMBA causes changes in gene expression which occur during the early "latent period", that is, prior to commitment to terminal differentiation. The inducer causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and a decrease in phospholipid-dependent protein kinase C activity (within 2 hr) (Figure 2). There is an early suppression (within 1-2 hrs) of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48 to 60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA whereas the level of c-myc mRNA returns to that of uninduced cells. By 36 to 48 hrs, transcription of alpha 1 and beta maj globin genes is increased 10 to 30 fold, while that of rRNA genes is suppressed. It is not yet clear how the protein products of proto-oncogenes elicit or modify cellular responses. Changes in expression of c-myb, c-myc, c-fos and p53 genes which occur during HMBA-induced differentiation, as well as in several other systems, suggest that products of these genes may have a role in regulating expression of multiple genes. One possible application of the established pattern of HMBA-induced modulation of gene expression during MELC differentiation may be in following the effects of cyto-differentiation agents during treatment of cancers. Phase I and Phase II chemical trials have been initiated to evaluate HMBA as a cytodifferentiation agent in human neoplasms (65). For most human tumors, assay for cytologic evidence of induced differentiation is difficult at best. Following the effects of a differentiation inducing agent by determining c-myc, or c-myb, mRNA levels may provide useful indicators of biological activity of HMBA and be a basis for evaluating whether continued administration of the agent is of interest in terms of potential clinical efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)


Lead Fractures in Deep Brain Stimulation during Long-Term Follow-Up.
The purpose was to determine the incidence of lead fracture in patients with DBS over a long period of time. We present a retrospective study of 208 patients who received 387 DBS electrodes. Fourteen patients had sixteen lead fractures (4% of the implanted leads) and two patients suffered from 2 lead fractures. Of all lead fractures, five patients had the connection between the leads and the extension cables located in mastoids region, ten in cervical area and one in thoracic region. The mean distance from the connection between the electrode and the extension cable and the lead fracture was 10.7 mm. The lead fracture is a common, although long-term complication in DBS surgery. In our experience, the most common site of electrode cable breakage is approximately between 9 and 13 mm from the junction between the lead and the extension cable. The most important cause of lead fracture is the rotational movement of the lead-extension cable system. If we suspect lead fracture, we must check the impedance of the electrode and to evaluate the side effects of voltage. Finally, we must conduct a radiological screening.


Assessment of regrowth of flight feathers after manual removal in American kestrels (Falco sparverius).
The objective of this study was to evaluate if extraction of broken feathers outside the molting period was an efficient method to induce growth of new flight feathers as part of the rehabilitation process of raptors with damaged plumage. Primaries, secondaries, and rectrices (four of each) were removed under general anesthesia from 10 American kestrels (Falco sparverius) using two different protocols: with and without filling the follicle with bismuth subnitrate (Orbeseal) to prevent it from sealing. Birds were kept in large aviaries under natural daylight and outdoor temperatures. Rate and quality of growth of new feathers were assessed regularly for 4 mo. Results were significantly different between the types of feathers: 100% of rectrices, 58% of secondaries, and 8% of primaries started to grow within the 4 winter months, and 95% of rectrices, 30% of secondaries, and 0% of primaries completed their growth normally within this period. The use of Orbeseal did not improve the outcome. The tail feathers began to grow between the second and third weeks at about 2.7 mm/day, and growth was completed within 7 wk. Rate, starting time, and duration of remigial growth were less predictable and varied widely among individuals. Although the exact impact of these extractions on the natural molt is still unclear, most of the primaries that were plucked during this study failed to regrow normally during the following molt. In conclusion, plucking damaged tail feathers in kestrels can successfully decrease the duration of rehabilitation. However, this procedure would not be recommended for wing feathers.


Lower Body Strength of Children and Adolescents with and Without Mild Mental Retardation: A Comparison.
The purpose of this study was to compare children and adolescents (ages 8-18 yr) with and without mental retardation (MR) on isometric strength of knee flexion, knee extension, and combined leg and back strength. Sample size of participants with mild MR, but without Down syndrome, was 158 males and 111 females. Sample size of peers without MR was 223 males and 226 females. Analysis was made by gender and age: children (8-10 yr), early adolescents (11-14 yr), and late adolescents (15-18 yr). For all age groups, males and females without MR were significantly stronger than their same-gender peers with MR for all isometric strength measurements. For individuals with MR, the trend toward leveling off or decreasing in leg and back strength is a serious health and social concern.


The association between moral distress and mental health among nurses working at selected hospitals in Iran during the COVID-19 pandemic.
In the event of an epidemic outbreak, the mental health of medical staff, including nurses who serve on the frontlines of hospitals, can be affected; thus, the identification of factors affecting nurses' mental health is of importance. This study aimed to examine the association between moral distress and the mental health of nurses working at four selected hospitals in Iran during the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional questionnaire survey was conducted on 296 nurses working at the selected hospitals in Bushehr and Shiraz (south of Iran) at the time of the COVID-19 outbreak. The collected data were analyzed via logistic regression analysis. The mean scores for nurses' moral distress were low (54.31±24.84). The results of this study indicated more symptoms of mental issues among nurses (73.60%). Moreover, a significant association was observed between mental health and moral distress. Among the examined demographic variables, only gender had a significant association with mental health (p-value = 0.014). The results of this study indicated that an increase in moral distress would lead to a significant increase in mental health issues of the examined nurses. Nurse managers and hospital policymakers should develop strategies to enhance nurses' level of mental health, as well as providing adequate emotional and family support for nurses. Considering the intensifying role of gender in this association, timely interventions are necessary to reduce the negative effects of workplace pressure/stress on female nurses.


Hospital-physician alignment: no decision is a decision.
Deliberate discussions on hospital-physician alignment or relationships are critical as a strategy to manage the effect of healthcare reform. There are many competitive threats to be considered in hospital-physician alignment. Hospitals and physicians should take careful steps to determine the structure and needs of each group in development of a high-quality healthcare system.


Preventable death evaluation of the appropriateness of the on-site trauma care provided by Urgences-Santé physicians.
The study is based on 44 preventable deaths occurring in a cohort of 360 patients with major trauma. These cases were reviewed by a committee of nine experts. The mean Injury Severity Score (ISS) was 28, and most cases had injuries to the head/neck (68%) and chest (64%). The mean (+/- SD) observed prehospital times, and those considered the maximum allowable by the committee, were 40.6 +/- 12.0 minutes for head/neck injuries and 23.9 +/- 12.2 minutes for chest injuries (p < 0.05). Intravenous (i.v.) lines were started in 38 (86%) of the patients. The committee classified this procedure as harmful for 16 (42%) and neutral for 19 (50%). Among the 18 (46%) that were intubated, this intervention was considered harmful for 17% and neutral for 39%. In two of the three patients for whom a pneumatic antishock garment was applied, this procedure was considered harmful. Of the 34 patients that required direct transport at a level I trauma center, 50% were transferred to such a hospital. These results show significant prehospital delays and high rates of inappropriate IV line initiation and intubation in trauma patients receiving on-site care by physicians. We conclude that prehospital care protocols for trauma patients should emphasize prompt transport and specific on-site care algorithms.


Characterization of the 5'-flanking region of the gene for the alpha chain of human fibrinogen.
The 5'-flanking region of the gene coding for the alpha chain of human fibrinogen was isolated, sequenced, and characterized. The principal site of transcription initiation was determined by primer extension analysis and the RNase protection assay and shown to be at an adenine residue located 55 nucleotides upstream from the initiator methionine codon, or 13,399 nucleotides down-stream from the polyadenylation site of the gene coding for the gamma chain. Transient expression of constructs containing sequentially deleted 5'-flanking sequences of the alpha chain gene fused to the chloramphenicol acetyltransferase reporter gene showed that the promoter was liver-specific and inducible by interleukin 6 (IL-6). The shortest DNA fragment with significant promoter activity and full response to IL-6 stimulation encompassed the region from -217 to +1 base pairs (bp). Although six potential IL-6 responsive sequences homologous to the type II IL-6 responsive element were present, a single sequence of CTGGGA localized from -122 to -127 bp was shown to be a functional element in IL-6 induction. A hepatocyte nuclear factor 1 (HNF-1) binding site, present from -47 to -59 bp, in combination with other upstream elements, was essential for liver-specific expression of the gene. A functional CCAAT/enhancer binding protein site (C/EBP, -134 to -142 bp) was also identified within 217 bp from the transcription initiation site. An additional positive element (-1393 to -1133 bp) and a negative element (-1133 to -749 bp) were also found in the upstream region of the alpha-fibrinogen gene.


Inhibin, activin and follistatin bind preferentially to the transformed species of alpha 2-macroglobulin.
alpha 2-Macroglobulin (alpha 2-M), a major serum glycoprotein, has been implicated as a low-affinity binding protein for inhibin and activin. In serum, alpha 2-M exists as two major species, a native form that is abundant and stable, and a transformed ('fast') species that is rapidly cleared from the circulation via alpha 2-M receptors. In this study inhibin, activin and their major binding protein follistatin were investigated for their ability to bind to the native or transformed species of purified human alpha 2-M. Using native PAGE and size exclusion chromatography, radiolabelled inhibin, activin and follistatin bound to the transformed alpha 2-M. Inhibin and follistatin did not bind significantly to native alpha 2-M, whereas activin was able to bind to the native species but with a lower capacity compared with that to transformed alpha 2-M. Under reducing conditions, binding of these hormones to alpha 2-M was abolished. These findings implicate alpha 2-M as a mechanism whereby inhibin, activin and follistatin may be removed from the circulation through alpha 2-M receptors, but also whereby activin can be maintained in the circulation through its ability to bind to native alpha 2-M.


Characterization of the ovine interleukin-2 receptor-alpha chain: differential induction on precultured alpha beta and gamma delta T cells.
A combination of concanavalin A (Con A)-stimulated ovine lymph node (LN) cells and Chinese hamster ovarian (CHO) cells stably transfected with the ovine interleukin-2 receptor-alpha (IL-2R alpha) chain cDNA (CHO IL-2R cells) were used in a differential immunization strategy to generate several monoclonal antibodies (mAb) against the ovine IL-2R alpha chain. The specificity of one of the mAb, designated mAb 9-14, for the ovine IL-2R alpha chain was demonstrated by its reactivity with Con A-stimulated LN cells and CHO IL-2R cells, immunoprecipitation of a 47,000 MW protein from CHO IL-2R cells and inhibition of IL-2-dependent proliferation of Con A-stimulated ovine LN cells. Examination of IL-2R alpha chain expression on resting lamb peripheral blood lymphocyte populations showed a high frequency of IL-2R alpha chain expression on CD4 T cells but not on CD8 T cells, CD45RA+ cells or gamma delta T cells, which comprise up to 60% of lamb peripheral blood T cells. The kinetics of IL-2R alpha chain induction on Con A-stimulated peripheral blood alpha beta and gamma delta T cells was compared. A rapid induction of IL-2R alpha chain expression on precultured gamma delta T cells but not alpha beta T cells was observed within 6 hr of Con A stimulation. A preculturing period was required to 'prime' gamma delta T cells for rapid responsiveness to Con A. Using appropriate inhibitors, we demonstrated that both transcription and translation events were required for rapid IL-2R expression on precultured gamma delta T cells and therefore the 'priming' of gamma delta T cells by in vitro culture did not involve an accumulation of IL-2R alpha chain mRNA or preformed receptors within these cells.


Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus.
Induction of telomerase, the enzyme that extends telomeres, accompanies human T lymphocyte activation. Nevertheless, high proportions of memory T cells with shortened telomeres are present in vivo during HIV infection and aging. To elucidate the long-term telomerase dynamics in human T cells, longitudinal analyses were performed on T cells subjected to repeated encounters with an allogeneic cell line in long-term culture. Whereas CD4(+) and CD8(+) T cells showed similarly dramatic increases in telomerase activity following primary stimulation, by the fourth stimulation, telomerase activity was nearly undetectable in the CD8(+) subset, but remained high in the CD4(+) subset. In addition, we document the dependence of antigen-specific telomerase inducibility on CD28 and that the decline in telomerase activity parallels the loss of CD28 expression. These findings suggest stringent telomerase regulation in human T cells, a property that may ultimately contribute to telomere shortening, finite replicative potential, and loss of control over certain pathogens.


Silent myocardial ischaemia in patients undergoing transurethral prostatectomy. A study to evaluate risk scoring and anaesthetic technique with outcome.
Ninety four patients undergoing transurethral resection of the prostate underwent Holter electrocardiographic monitoring pre- and postoperatively. There was no difference in silent myocardial ischaemia incidence or load between the spinal (n = 60) and the general anaesthesia (n = 34) groups. Ischaemic heart disease and a higher Detsky score both significantly increased the incidence of silent myocardial ischaemia but not the ischaemic load of those patients that actually demonstrated ischaemia. In this specific surgical population, not undergoing cardiac or vascular surgery, both ischaemic heart disease and cardiac risk scores are poor predictors of ischaemic load. Merely the presence of short duration silent myocardial ischaemia probably has little predictive value for postoperative adverse outcome.


Effects of deployment on depression screening scores in pregnancy at an army military treatment facility.
To estimate the relationship of positive screening for depression during and after pregnancy with deployment status of the spouse. We conducted a retrospective cohort study by reviewing a departmental database of women who completed the Edinburgh Postpartum Depression Scale during pregnancy from 2007 to 2009. Per departmental protocol, screening is offered at the initial obstetric visit, at 28 weeks of gestation, and at 6 weeks postpartum. A score of 14 or higher was considered high risk for having depression, and referral for additional evaluation was recommended. Included in our survey was an additional question that asked if the patient's spouse was currently deployed, returning from deployment, preparing to deploy, or if no deployment was planned. All data were entered into an electronic database and statistical analysis performed comparing Edinburgh Postpartum Depression Scale scores at each time period and deployment status. A total of 3,956 surveys were complete and available for analysis. The risk of a positive screen was more than doubled compared with the control group (no deployment planned) if the spouse was deployed during the 28-32 week visit (4.3% compared with 13.1%, P=.012) or the postpartum period (8.1% compared with 16.2%, P=.006). Deployment status has a measurable effect on the prevalence of elevated depression screening scores during pregnancy and in the postpartum period. These findings suggest that more intense monitoring, assessment, and treatment may be warranted for this at-risk population. II.


Transport and fate of methyl iodide and its pest control in soils.
For fumigants, information on transport and fate as well as pest control is needed to develop management practices with the fewest negative environmental effects while offering sufficient pest control efficacy. For this purpose, a 2-D soil chamber with a surface-mounted flux chamber was designed to determine volatilization, real-time soil gas-phase concentration, degradation, and organism survivability after methyl iodide (MeI) fumigation. Three types of pests were used to give a broad spectrum of pest control information. An infected sandy loam soil with a volumetric water content of 10.6% was packed carefully into the 2-D chamber to a bulk density of 1.34 g cm(-3). After MeI fumigation at a rate of 56.4 kg ha(-1) for 24 h, about 28.9% of MeI was emitted into air, 6.8% remained in the soil, and 43.6% degraded in the soil (based on the residual iodide concentration). The uncertainty in the measured MeI degradation using iodide concentration was thought to mainly contribute to the unrecovered MeI (about 20%). The citrus nematodes [Tylenchulus semipenetrans] were effectively eliminated even at low concentration-time (CT) values (<30 microg h mL(-1)), but all Fusarium oxysporum survived. The response of barnyardgrass seeds [Echinochloa crus-galli] spatially varied with the CT values in the chamber. To fully control barnyardgrass seeds, CT of greater than 300 microg h mL(-1) was required. Using this experimental approach, different fumigant emission reduction strategies can be tested, and mathematical models can be verified to determine which strategies produce the least emission to the atmosphere while maintaining sufficient pest control efficacy.


Study on the interaction of polyamine transport (PAT) and 4-Chloro-naphthalimide-homospermidine conjugate (4-ClNAHSPD) by molecular docking and dynamics.
Polyamine transporter (PAT) is a protein that can deliver "drug-polyamine" conjugates to tumor cells. 4-Chloro-naphthalimide- homospermidine (4-ClNAHSPD) displayed good antitumor activity and excellent cell selectivity via PAT pathway. In this paper, 4-ClNAHSPD and spermidine (SPD) were docked against PAT. The results showed that 4-ClNAHSPD could bind to PAT through hydrogen bond, Van der Waals, salt bridge or attractive charge and hydrophobic interaction. The interaction of SPD and PAT, however, was hydrogen bond and Van der Waals interaction. Moreover, their binding sites were also different. The primary binding sites of 4-ClNAHSPD with PAT are the residues of VAL59, HIS222, ASP61, ASP179 and GLU64, while SPD interacts with PAT in the sites of ASP37, ASP244, APS275 and SER36. The docked ligand-protein complexes were simulated for 5000ps. In simulations, various binding sites further resulted in the diverse root-mean-square deviation (RMSD) and root-mean-square deviation fluctuation (RMSF) values. The RMSD and RMSF values of 4-ClNAHSPD-PAT indicated that 4-ClNAHSPD caused a weak conformational change of PAT in a different style from SPD. More importantly, the interaction force numbers of 4-ClNAHSPD-PAT were also changed after the simulation. These results supported that 4-ClNAHSPD harnesses PAT pathway for cellular entrance.Communicated by Ramaswamy H. Sarma.


Prediction of the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients after Sustained Virological Response by Aspartate Aminotransferase to Platelet Ratio Index.
Following sustained virological response (SVR) for chronic hepatitis C (CHC) infection, patients with advanced fibrosis require regular monitoring for hepatocellular carcinoma (HCC). The aspartate aminotransferase to platelet ratio index (APRI) is a simple noninvasive surrogate marker known to reflect fibrosis. We retrospectively analyzed 598 patients who achieved SVR with interferonbased therapy for CHC. Over a median of 5.1 years of follow-up, there were eight patients diagnosed with HCC and a 5-year cumulative incidence rate of 1.3%. The median pretreatment APRI was 0.83, which decreased to 0.29 after achieving SVR (p<0.001). Both the pre- and posttreatment indices were associated with HCC development. The 5-year cumulative HCC incidence rates were 0% and 2.8% for patients with pretreatment APRI <1.0 and ≥1.0, respectively (p=0.001) and 0.8% and 12.8% for patients with posttreatment APRI <1.0 and ≥1.0, respectively (p<0.001). Pretreatment APRI at a cutoff of 1.0 had a 100% negative predictive value until 10 years after SVR. HCC development was observed among CHC patients who achieved SVR. The pre- and post-treatment APRI could stratify HCC risk, indicating that the APRI could be a useful marker to classify HCC risk in CHC patients who achieved SVR. However, given the small number of HCC patients, this finding warrants further validation.


Disentangling the causal inter-relationship between negative life events and depressive symptoms in women: a longitudinal twin study.
Negative life events are strongly associated with the development of depression. However, the etiologic relationship between life events and depression is complex. Evidence suggests that life events can cause depression, and depression increases the risk for life events. Additionally, third factors influencing both phenotypes may be involved. In this work we sought to disentangle these relationships using a genetically informative longitudinal design. Adult female twins (n=536, including 281 twin pairs) were followed up for measurements of negative life event exposure and depressive symptoms. Four follow-ups were completed, each approximately 3 months apart. Model fitting was carried out using the Mx program. The best-fitting model included causal paths from life events to depressive symptoms for genetic and shared environmental risk factors, whereas paths from depressive symptoms to life events were apparent for shared environmental factors. Shared latent influence on both phenotypes was found for individual-specific effects. Life events and depressive symptoms have complex inter-relationships that differ across sources of variance. The results of the model, if replicated, indicate that reducing life event exposure would reduce depressive symptoms and that lowering depressive symptoms would decrease the occurrence of negative life events.


Epidemiology, burden, and policy of chronic obstructive pulmonary disease in South Korea: a narrative review.
Chronic obstructive pulmonary disease (COPD) is a global health problem and a significant cause of mortality and morbidity worldwide. COPD also occupies a significant and considerable economic burden on individuals and society in South Korea. We investigated the epidemiology and burden of COPD in South Korea and reviewed the policy regarding COPD. In South Korea, a national COPD prevalence survey has been conducted for two decades. The prevalence of COPD has increased with increasing age, particularly among males, and those also with a higher smoking history and with lower income. The total societal cost of COPD increased by 1.85 times between 2004 and 2013. As the use of inhaled medications has increased, the total medical cost per person has increased. The trends of increasing numbers of patients diagnosed with COPD and the total societal costs are expected to continue. There is one universal-health-coverage system in South Korea. The costs and reimbursement criteria of COPD drugs are established and controlled by the Health Insurance Review and Assessment Service (HIRA). The HIRA has also implemented quality assessment, including evaluating the appropriateness of a COPD diagnosis and treating all COPD patients to reduce the severity of illness and improve the adequacy of medical-care benefits.


Concentrations of metal elements in mouse organs after intratracheal administration of coal fly ash.
Size-density fractionated coal fly ash particles, 1-5 microns in diameter and 2.4-2.8 g/cm3 in density, were administered to mouse lungs intratracheally. The change in the concentrations of metal elements in the lungs, kidneys, livers and spleens was measured by inductively coupled plasma atomic emission spectroscopy and atomic absorption spectroscopy up to 16 weeks after administration. In the lungs, each elemental concentration increased 1 week after administration and decreased thereafter with time after administration. For example, the concentrations of Al were 1018 +/- 272 micrograms/g tissue at 1 week and decreased thereafter to 556 +/- 177 micrograms/g tissue at 16 weeks after administration. The concentrations of Ca, Mn and Ni decreased more rapidly than the other elements, suggesting that Ca, Mn and Ni were dissociated from the alumino-silicate matrix of the fly ash particles in the lungs. In the kidneys, the concentration of Ni significantly increased at 2, 8 and 16 weeks after administration; the concentration of Ni showed an increase of 0.4 +/- 0.2 micrograms/g over the control mouse at 16 weeks after administration. In the livers, increased concentrations of Ca and Mn were observed at 2, 4 and 16 weeks. On the other hand, no changes in the concentrations of these elements were observed in the spleen.


Optogenetic stimulation effectively enhances intrinsically generated network synchrony.
Synchronized bursting is found in many brain areas and has also been implicated in the pathophysiology of neuropsychiatric disorders such as epilepsy, Parkinson's disease, and schizophrenia. Despite extensive studies of network burst synchronization, it is insufficiently understood how this type of network wide synchronization can be strengthened, reduced, or even abolished. We combined electrical recording using multi-electrode array with optical stimulation of cultured channelrhodopsin-2 transducted hippocampal neurons to study and manipulate network burst synchronization. We found low frequency photo-stimulation protocols that are sufficient to induce potentiation of network bursting, modifying bursting dynamics, and increasing interneuronal synchronization. Surprisingly, slowly fading-in light stimulation, which substantially delayed and reduced light-driven spiking, was at least as effective in reorganizing network dynamics as much stronger pulsed light stimulation. Our study shows that mild stimulation protocols that do not enforce particular activity patterns onto the network can be highly effective inducers of network-level plasticity.


Diagnostic and prognostic utility of C-reactive protein, alpha-1-antitrypsin and alpha-2-macroglobulin in neonatal sepsis: a comparative account.
C-reactive protein (CRP), alpha-1-antitrypsin (alpha-1-AT) and alpha-2-macroglobulin (alpha-2-MG) levels were evaluated serially in 25 healthy and 20 septicemic neonates and then compared as early diagnostic aids and prognostic indicators in this illness. Compared to healthy controls, septicemic neonates had significantly higher mean CRP levels (p less than 0.01). Neonates with septicemia, who recovered, had higher mean CRP levels than the group which died (p less than 0.05). As an early diagnostic aid CRP had a low Youden index, whereas for prognosis its index was higher. Septicemic neonates also had significantly higher mean alpha-1-AT levels (p less than 0.05), 12-24 hours after onset of illness, as compared to healthy neonates. Alpha-1-antitrypsin could not be used as an early diagnostic aid in septicemia, but was useful for predicting outcome. Mean alpha-2-macroglobulin levels did not show significant variation in healthy and septicemic neonates. Lower mean alpha-2-MG levels were observed in neonates recovering from septicemia. As an early diagnostic aid alpha-2-MG had a low Youden index, whereas for prognosis its index was higher. CRP had a higher Youden index than alpha-2-MG for early diagnosis of neonatal septicemia and had a higher index than both alpha-1-AT and alpha-2-MG for predicting outcome in septicemia. Serial use of CRP alone is, therefore, recommended for both purposes.


Phosphorylation of Plk1 at Ser326 regulates its functions during mitotic progression.
Polo-like kinase 1 (Plk1), the best characterized member of the mammalian polo-like kinase family, is well regulated throughout the cell cycle at the protein expression level. Moreover, it is known that Plk1 kinase activity is also regulated at the post-translational level through phosphorylation. However, the upstream kinases of Plk1 have not been identified. Although the involvement of the p38 MAP kinase pathway in cellular responses to stress has been well documented, the role of this pathway in normal cell cycle progression is unclear. Here, we show that phosphorylated p38 and MAP kinase-activated protein kinase 2 (MK2) are colocalized with Plk1 to the spindle poles during prophase and metaphase. Specific depletion of various members of the p38 MAP kinase pathway by the use of RNA interference revealed that the pathway is required for mitotic progression under normal growth conditions. Furthermore, MK2 directly phosphorylates Ser326 of Plk1. Ectopic expression of Plk1-S326A completely blocked cells at mitosis, likely due to the defect of bipolar spindle formation and subsequent activation of the spindle checkpoint. Only Plk1-S326E, but not the Plk1-S326A, efficiently rescued the p38 or MK2-depletion-induced mitotic defects, further solidifying the requirement of S326 phosphorylation during mitotic progression.


Don't look back in anger: the rewarding value of a female face is discounted by an angry expression.
The modulating effect of emotional expression on the rewarding nature of attractive and nonattractive female faces in heterosexual men was explored in a motivated viewing paradigm. This paradigm, which is an indicator of neural reward, requires the viewer to expend effort to maintain or reduce image-viewing times. Males worked to extend the viewing time for happy and neutral attractive faces but to reduce the viewing time for the attractive angry faces. Attractive angry faces were rated as more aesthetically pleasing than the nonattractive faces; however, the males worked to reduce their viewing time to a level comparable with the nonattractive neutral and happy faces. Therefore, the addition of an angry expression onto an otherwise attractive face renders it unrewarding and aversive to potential mates. Mildly happy expressions on the nonattractive faces did little to improve their attractiveness or reward potential, with males working to reduce viewing time for all nonattractive faces.


Ultrasound measurements of the saphenous vein in the pediatric emergency department population with comparison to i.v. catheter size.
Saphenous vein cutdown is a rare venous access procedure. Ultrasound (US) can assist with many vascular access procedures. Our objective was to identify the saphenous veins (SVs) using US in pediatric emergency department (ED) patients, and to determine if the SV size allows for potential cannulation by different standard-size intravenous (i.v.) catheters. This study was a prospective, observational convenience sample of 60 pediatric patients at an urban, regional referral pediatric ED. Inclusion criteria were children ages 1 through 12 years categorized into four age groups: 1-<2, 2-4, 5-7, and 8-12 years, with informed consent and assent. Investigators performed US examination using a 10-MHz multi-frequency transducer to identify the SV on both legs and measure the SV in short-axis view. The US measurements were then used to calculate the SV areas. Diameters of typical pediatric gauge (G) catheters (24G, 22G, 20G, 18G) were used to calculate catheter areas. Sixty patients were enrolled, with five SVs unable to be measured in 4 patients (1 patient with both SVs). For the remaining 115 (96%) SVs available for further analysis, the median age was 4 years (interquartile range [IQR] 2) and median weight was 22.7 kg (IQR 14.5). Mean area (mm(2)) of the right SV was 2.85 ± 1.9 and for the left SV, 2.88 ± 1.8. For our study group, the compatibility rates of different size i.v. catheters to fit the measured SV areas were as follows: 24G = 100%, 22G = 100%, 20G = 97.3%, and 18G =86.1%. US can localize the SV in pediatric ED patients. US size of the SV in various pediatric age ranges suggests that the SV may be a potential US venous access site with multiple-size i.v. catheters up to 18G.


Structural Cutting of Non-fullerene Acceptors by Chlorination: Effects of Substituent Number on Device Performance.
Effects of chlorination on photovoltaic performance of organic solar cells are yet largely unclear though it is emerging as a special yet effective strategy to design highly efficient non-fullerene acceptors (NFAs). Herein, a bi-chlorine-substituted NFA with regioregularity, namely, bichlorinated dithienothiophen[3.2-b]- pyrrolobenzothiadiazole (BTP-2Cl-δ), is synthesized and compared to the non-chlorinated BTP and tetra-chlorine-substituted BTP-4Cl to study the effects of Cl number on the photovoltaic performance. From BTP to BTP-2Cl-δ and BTP-4Cl, the three molecules show gradually red-shifted absorption peaks, narrowed band gaps, and lowered highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs). Polymer solar cells are fabricated using PM6 as the donor and the three small molecules as the acceptors. From BTP to BTP-2Cl-δ, efficiencies (8.8 vs 15.4%) are significantly enhanced due to the better film morphology and strong crystallization of the BTP-2Cl-δ-based device, giving rise to boosted fill factors (FFs) and short-circuit current densities (JSC's). From BTP-2Cl-δ to BTP-4Cl, although JSC's (24.3 vs 25.0 mA cm-2) are slightly elevated due to the higher crystallinity of BTP-4Cl, leading to improved exciton dissociation and collection efficiencies, FFs (71.1 vs 68.0%) are obviously decreased owing to the unfavorable film morphology, unbalanced hole-electron mobilities, and higher charge recombination in BTP-4Cl-based devices. As such, the efficiency of the BTP-2Cl-δ-based device (15.4%) is superior to that of the BTP-4Cl-based device (14.5%). This work elucidates a design strategy by cutting the numbers of substituent chlorine to obtain desired energy levels and crystallization with optimal performance.


B-Raf and C-Raf signaling investigated in a simplified model of the mitogenic kinase cascade.
Signaling pathways based on the reversible phosphorylation of proteins control most aspects of cellular life in higher organisms. Extracellular stimuli can induce growth, differentiation, survival and the stress response through a number of highly conserved signaling pathways. We discuss how the intensity and duration of signals may have dramatic consequences on the way cells respond to stimuli. Picking the central Ras-Raf-MEK-ERK signal cascade, we developed a mathematical model of how stimuli induce different signal patterns and thereby different cellular responses, depending on cell type and the ratio between B-Raf and C-Raf. Based on biochemical data for activation and dephosphorylation, as well as the differential equations of our model, we suggest a different signaling pattern and response result for B-Raf (strong activation, sustained signal) and C-Raf (steep activation, transient signal). We further support the significance of such differential modulatory signaling by showing different Raf isoform expression in various cell lines and experimental testing of the predicted kinase activities in B-Raf, C-Raf and mutated versions.


Palliative care in the emergency department as seen by providers and users: a qualitative study.
Much effort has been made to explore how patients with advanced chronic illness and their families experience care when they attend the Emergency Department, and many studies have investigated how healthcare professionals perceive Palliative Care provision in the Emergency Department. Various models exist, but nonetheless incorporating palliative care into the Emergency Department remains challenging. Considering both healthcare professionals' and users' perspective on problems encountered in delivering and receiving appropriate palliative care within this context may provide important insight into meaningful targets for improvements in quality of care. Accordingly, this study aims at exploring issues in delivering palliative care in the Emergency Department from the perspective of both providers and users, as part of a larger project on the development and implementation of a quality improvement program in Italian Emergency Departments. A qualitative study involving focus group interviews with Emergency Department professionals and semi-structured interviews with patients with palliative care needs in the Emergency Department and their relatives was conducted. Both datasets were analyzed using Thematic Analysis. Twenty-one healthcare professionals, 6 patients and 5 relatives participated in this study. Five themes were identified: 1) shared priorities in Emergency Department among healthcare professionals and patients, 2) the information provided by healthcare professionals and that desired by relatives, 3) perception of environment and time, 4) limitations and barriers to the continuity of care, and 5) the contrasting interpretations of giving and receiving palliative care. This study provides insights into targets for changes in Italian Emergency Departments. Room for improvement relates to training for healthcare professionals on palliative care, the development of a shared care pathway for patients with palliative care needs, and the optimization of Emergency Department environment. These targets will be the basis for the development of a quality improvement program in Italian Emergency Departments.


Modulation of lipopolysaccharide-induced cytotoxic factor and interferon production by moxibustion in mice.
Pretreatment of mice with moxibustion (Mox) modulated lipopolysaccharide (LPS)-induced endogenous cytotoxic factor (CF) and interferon (IFN) production in serum. CF was measured by the L929 cytotoxicity test and IFN by the cytopathic effect microassay on L929 cells with vesicular stomatitis virus. Significant inhibition of CF activity was observed when Mox and LPS were applied simultaneously. Its potentiation was maximal, about 9 times the control level, when treatment intervals between Mox and LPS were 24-72 hours, and declined thereafter. Mox treatment modified LPS-induced IFN production with a similar biphasic pattern but the onset of modification was delayed. This is the first report of modulation of cytokine production by Mox treatment.


Antioxidant activity of different parts of Pistacia khinjuk Stocks fruit and its correlation to phenolic composition.
The fruits of Pistacia khinjuk Stocks were collected from Ilam province, Iran. The aim of this study was to analyse antioxidant capacity and phenolic composition of different parts of P. khinjuk fruit. The antioxidant capacity of extracts was measured using different assays: ferric reducing ability of plasma, 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radical scavenging. The phenolic composition of P. khinjuk fruit is reported for the first time. Amongst different parts of the fruit analysed in this study, hull extract contained the highest total phenolic and flavonoid contents. We observed a high correlation between different antioxidant activity and total phenolic and flavonoid contents. Therefore, antioxidant capacity can be related to total phenolic and flavonoid contents. A correlation analysis revealed that ascorbic acid, gallic acid, rutin, caffeic acid, ferulic acid and sinapic acid were the phenolic compounds mainly responsible for antioxidant power of the fruit extracts.


The Positive Rate of Nucleic Acid Testing and the Epidemiological Characteristics of COVID-19 in Chongqing.
The purpose of this study is to analyze the positive rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid testing (NAT), cases of and deaths due to SARS-CoV-2, and the epidemiological characteristics of SARS-CoV-2 to identify high-risk populations. A retrospective study in Jiulongpo district of Chongqing was conducted by performing continuous observations of the frequency of SARS-CoV-2 NAT, analyzing the data of close contacts of patients and asymptomatic carriers, and collecting epidemiological data. Data were collected from January 20, 2020, when the first case of SARS-CoV-2 infection was reported, to March 26, 2020. Descriptive statistical analysis and Cochrane-Mantel-Haenszel analysis were used to compare the positive detection rates and positive diagnostic rates of different exposure groups. A total of 7,118 people received 10,377 SARS-CoV-2 nucleic acid tests in one district, and the SARS-CoV-2 positive rates were 0.40% (18/4446) and 0.15% (4/2672) in people receiving one and ≥ two nucleic acid tests (p = 0.06), respectively. Those with suspected cases (12.35%) and close contacts (8%) had higher positive rates than people tested at fever clinics (0.39%) (p < 0.001). The median latency (range) of cases was 5 (2, 9) days, and the median time from diagnosis to recovery was 22 (14, 25) days. One recovered patient received a positive test result at 28 days after recovery when she attempted to donate blood. Six clustered cases, including one patient who died, indicated persistent human-to-human transmission. One patient who was diagnosed after death was found to have infected 13 close contacts. People working in catering and other public service departments (36.36%) and people who are unemployed and retirees (45.45%) have an increased risk of infection compared with technical staff (9.09%) and farmers (9.09%). The total positive rate was low in the tested population, and more effective detection ranges should be defined to improve precise and differentiated epidemic control strategies. Moreover, in asymptomatic carriers, SARS-CoV-2 tests were positive after recovery, and patients with suspected SARS-CoV-2 infection who die may pose serious potential transmission threats.


Satisfaction with methadone as a medication: psychometric properties of the Spanish version of the treatment satisfaction questionnaire for medication.
There is a manifest lack of psychometrically sound instruments designed for specific and multidimensional assessment of satisfaction with methadone as a medication within the context of methadone maintenance treatment. Therefore, it may be worthwhile to assess the pertinence and utility of using a generic and multidimensional medication satisfaction instrument that has not been specifically developed for use in methadone maintenance treatment.The aim of this study was thus to explore the psychometric properties of the Spanish version of the Treatment Satisfaction Questionnaire for Medication (TSQM version 1.4 [Health Qual Life Outcomes. 2004;2:12]) in a sample of methadone-maintained heroin-dependent patients.Two hundred three methadone-maintained patients filled out the TSQM and other several measures related to the construct of patient satisfaction (eg, Verona Service Satisfaction Scale for methadone treatment). Dimensionality of the TSQM was assessed by means of a confirmatory factor analysis. Internal consistency was examined using the ordinal coefficient α. Spearman correlations were used to explore the relationship between the TSQM and the measures conceptually related to patient satisfaction.Regarding the dimensionality of the TSQM, its original factor structure adequately fitted the data (Satorra-Bentler χ58, 72.14 [P = 0.100]; root-mean-square error of approximation, 0.045; comparative fit index, 0.978). All but 1 of the 4 TSQM subscales showed acceptable to good internal consistency values (0.78-0.89). The dimensions of the TSQM were differentially and congruently correlated with related measures.The results strongly suggest the TSQM value as a brief, generic, and psychometrically sound instrument to assess satisfaction with methadone as a medication in a multidimensional manner. Notwithstanding, more research is needed not only to assess the generalizability of these findings but also to provide pieces of evidence for other psychometric properties, especially the TSQM predictive validity.


An optimized isolation protocol yields high-quality RNA from cassava tissues (Manihot esculenta Crantz).
We developed and modified a precise, rapid, and reproducible protocol isolating high-quality RNA from tissues of multiple varieties of cassava plants (Manihot esculenta Crantz). The resulting method is suitable for use in mini, midi, and maxi preparations and rapidly achieves high total RNA yields (170-600 μg·g-1) using low-cost chemicals and consumables and with minimal contamination from polysaccharides, polyphenols, proteins, and other secondary metabolites. In particular, A260 : A280 ratios were > 2.0 for RNA from various tissues, and all of the present RNA samples yielded ribosomal integrity number values of greater than six. The resulting high purity and quality of isolated RNA will facilitate downstream applications (quantitative reverse transcriptase-polymerase chain reaction or RNA sequencing) in cassava molecular breeding.


A reproducible and quantifiable model of choroidal neovascularization induced by VEGF A165 after subretinal adenoviral gene transfer in the rabbit.
To determine the effects of the vascular endothelial growth factor (VEGF)-A(165) delivered using a high capacity adenoviral vector (HC Ad.VEGF-A) on vascular growth and pathological changes in the rabbit eye. To combine different detection methods of VEGF-A(165) overexpression-induced neovascularization in the rabbit. HC Ad.VEGF-A(165) was constructed and injected at 5 x 10(6) infectious units (iu) into the subretinal space of rabbit eyes. Two and four weeks postinjection, the development of neovascularization and the expression of HC Ad-transduced VEGF-A(165) protein were followed up in vivo by scanning laser ophthalmoscopy, fluorescein and indocyanine green angiographies and ex vivo by electron microscopy and immunohistochemistry We observed a choroidal neovascularization (CNV) with leakage in 83% of the rabbit eyes. Our findings present clear indications that there is a significant effect on the endothelial cells of the choriocapillaris after subretinal transduction of the retinal pigment epithelium (RPE) with VEGF-A(165) vector. The choroidal endothelial cells were activated, adherent junctions opened, and the fenestration was minimized, while the extracellular matrix localized between the RPE and the endothelium of the choriocapillaris was enlarged toward the lumen of the vessels, inducing a deep invagination of the endothelial cells into the vessel lumen. They also proliferated and formed pathological vessels in the subretinal space. Moreover,there was an increased expression of basic fibroblast growth factor and VEGF-A accompanied by macrophage stimulation, retinal edema, and photoreceptor loss. This is the first model of VEGF-induced CNV in the rabbit in which the pathological events following overexpression of VEGF by RPE cells have been described in detail. Many of the features of our experimental CNV resemble those observed clinically in patients having wet age-related macular degeneration.


Multi-victim sexual assault: a case study in rural Australia.
There is a paucity of information regarding cases of multi-victim sexual assault of children. The reported incidence suggests that these cases are rare. The aim of this paper is to provide practitioners with information about effective intervention strategies arising out of the direct experience of managing a case of multi-victim sexual assault in an Australian rural community. A descriptive, case-report methodology summarizing the investigation and intervention in a case of multi-victim sexual assault is reported. A community based intervention arising out of the disclosures of 21 male children is described. The intervention occurred at an individual, group, and community level using a coordinated multi-disciplinary team and natural helping networks. The coordination of police and welfare services increased the communication flow to victims, their families, and the community. The case also demonstrated the utility in regularly briefing political and bureaucratic authorities as well as local officials about emergent issues. Coordinating political and bureaucratic responses was essential in obtaining ongoing support and sufficient researching to enable the effective delivery of services. Interventions were focussed at an individual, group, and community level using a coordinated multi-disciplinary team and natural helping networks. This provided a choice of services which were sensitive to the case setting. Recommendations are offered for practitioners who are confronted with similar events. While this paper describes an approach for intervening in a case of multi-victim sexual assault, further empirical research is needed to enable service deliverers to efficaciously target interventions which offer choice to victims and their families.


Biosimilars in Inflammatory Bowel Disease.
Over the past 2 decades, biological therapy with monoclonal antibodies targeting tumor necrosis factor-α has become a cornerstone of treatment of patients with inflammatory bowel disease. Although clinically effective, the biological therapies remain expensive, and their availability and utilization have been at times limited due to their high costs. Biosimilars are biological products similar to but not identical to the original biological agent or "reference biologic," also called "originator biologic." It is hoped that the use of biosimilars might enable these agents to become more available and, thus, decrease further expenditures related to the use of the original reference agents such as infliximab and adalimumab. In this study, we review the currently available evidence and shortcomings of these data supporting the use of biosimilars for the treatment of patients with inflammatory bowel disease, including their efficacy and safety as related to initiating therapy with biosimilar agents or switching between reference and biosimilar biologic agents.


ORAI1-dependent synaptic plasticity in rat hippocampal neurons.
It is well established that neurons are plastic and can change the strength of their connections with other neurons depending on their recent history. While many molecular entities involved in plastic processes were already described, the role of a store-operated calcium channel ORAI1 in neuronal plasticity is not known as yet. Using dominant negative form of ORAI1, we were able to show that ORAI1 is needed for formation of new dendritic spines following chemical induction of long term potentiation (cLTP), and that this is due to the release of Ca+2 from ryanodine receptor-associated endoplasmic reticulum stores. We propose that when ORAI1 is deficient, there is less Ca+2 in the stores, less releasable Ca+2 and consequently less LTP and spine formation.


Interest of punch skin grafting for the treatment of painful ulcers.
Skin leg ulcers are chronic painful wounds. The treatment of these ulcers is crucial for patients because pain has a significant impact on their daily lives. The analgesic effect of punch skin grafting (PSG) for the treatment of painful ulcers is not well described. The objective of the study is to assess the level of pain in patients with an ulcerated wound and to see if there is an analgesic effect of PSG. A single-center, non-interventional study conducted in hospitalized patients with one or several ulcer(s) of any type and which has been painful for more than six weeks. Pain was assessed before, the day after a PSG and then on the way out of hospital by a questionnaire and a numeric pain rating scale. Permanent pain and pain peaks were identified. Forty-one patients were included (23 men and 18 women) with a mean age of 73±21 years, 36% (n=15) with arterial ulcers, 36% (n=15) with venous ulcers, 12% (n=5) with necrotic angiodermatitis, 12% (n=5) with mixed ulcers and 4% (n=2) with "other ulcers" (due to infection and use of hydroxycarbamide). On day 1 of PSG, patients showed an improvement in terms of permanent pain (77%, n=24/31) and pain peaks (90%, n=37/41) respectively and 90% (n=28/31) and 95% (n=39/41) on the last day at hospital. Reduction in the use of strong opioids was found in 13 patients (81%). Punch skin grafting is a simple and validated treatment, which can reduce or eliminate pain related to ulcers. It has an effect on permanent pain and pain peaks. Its efficiency is particularly demonstrated on venous ulcers and mixed ulcers but also initially painful ulcers such as necrotic angiodermatitis or arterial ulcers.


Evaluation of involvement of testicular metallothionein gene expression in the protective effect of zinc against cadmium-induced testicular pathophysiology in rat.
To investigate the effects of exposure to Cd and Zn on testicular MT-1 and MT-2 gene expression and evaluate their involvement in Zn protection against Cd-induced testicular pathophysiology, male rats received either tap water, Cd or Cd+Zn in their drinking water for 35 days. Cd induced histopathological changes in testicular tissues were accompanied by decreased plasma testosterone level, plasma and testicular Zn concentrations, oxidative stress, and by increased MT-1 and MT-2 gene expression. Co-treatment with Cd and Zn reversed the Cd-induced decrease testosterone level and SOD activity, decreased testicular Cd accumulation and partially restored Cd-induced histological changes, lipid peroxidation, and Zn depletion. The increase of testicular MT-1 and MT-2 gene expression under Cd influence was significantly reduced in Cd+Zn group. These data suggest that Zn enhances the protection against Cd-induced testicular pathophysiology through non-MT gene expression mechanisms but essentially by preventing Cd accumulation, Zn deprivation and by ameliorating the testicular antioxidant status.


Urinary tract infections in patients with urinary diversion.
Several surgical techniques have been used to provide urinary diversion after radical cystectomy. The noncontinent type of urinary diversion (using an intestinal conduit) and the continent urinary diversion (ureterosigmoidostomy or construction of an intestinal pouch that serves as a deposit of urine) were used commonly in the past, leading to a cumulative considerable number of patients encountered in clinical practice. The orthotopic urinary diversion (neobladder) has been used widely during the last years. The incidence and characteristics of urinary tract infection in patients with different types of urinary diversion are reviewed. Clinicians should be aware that urinary tract infection is a frequent cause of fever in patients with urinary diversion because it occurs in a significant proportion. In addition, symptoms from the lower urinary tract may not be prominent in this population.


Pattern Recognition of Chemical Waves: Finding the Activation Energy of the Autocatalytic Step in the Belousov-Zhabotinsky Reaction.
The Belousov-Zhabotinsky (BZ) reaction is an example of a homogeneous, nonequilibrium reaction used commonly as a model for the study of biological structure and morphogenesis. We report the experimental effects of temperature on spontaneously nucleated trigger waves in a quasi-two-dimensional BZ reaction-diffusion system, conducted isothermally at temperatures between 9.9 and 43.3 °C. Novel application of filter-coupled circle finding and localized pattern analysis is shown to allow the highly accurate extraction of average radial wave velocity and nucleation period. Using this, it is possible to verify a strong Arrhenius dependence of average wave velocity with temperature, which is used to find the effective activation energy of the reaction in accordance with predictions elaborated from the widely used Oregonator model of the BZ reaction. On the basis of our experimental results and existing theoretical models, the value for activation energy of the important self-catalyzed step in the Oregonator model is determined to be 86.58 ± 4.86 kJ mol-1, within range of previous theoretical prediction.


Comparison of the effect and treatment sequence between a 2-week parallel repetitive transcranial magnetic stimulation and rehabilitation and a 2-week rehabilitation-only intervention during a 4-week hospitalization for upper limb paralysis after stroke: An open-label, crossover observational study.
NEURO® is a 2-week program that combines low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) to treat patients with chronic hemiparesis following stroke. The degree to which each element contributes to the improvement of upper limb function remains unclear. It has been suggested that low-frequency rTMS applied to a healthy cerebrum activates neural activity in the contralateral hemispheric area surrounding the lesion. Intensive OT performed in parallel to rTMS promotes the functional remodeling of the cerebrum to help with rehabilitation. However, this has not been demonstrated using NEURO®. Therefore, we aimed to compare the effects of the NEURO® and OT-only protocols in patients with hemiparesis following stroke. Thirty-seven patients with upper limb paralysis following stroke were recruited and hospitalized for treatments and randomly divided into two groups. Group A consisted of 16 patients who underwent NEURO® for the first 2 weeks, and Group B consisted of 21 patients who underwent OT-only for the first 2 weeks. After 2 weeks of hospitalization, the treatments of Groups A and B were reversed for the subsequent 2 weeks of treatment. Improvement in upper limb motor function in Groups A and B at 2 and 4 weeks after the start of treatment was evaluated using the Fugl-Meyer Motor Assessment (FMA) and the Wolf Motor Function Test (WMFT). Group A, who underwent NEURO® first during their initial 2-week hospitalization, showed significantly greater improvement than that in Group B, who underwent OT-only first (P = .041 for FMA and P < .01 for WMFT). At 4 weeks following the reversal of treatments, Group A who underwent NEURO® and then OT-only showed significantly greater improvement than that in Group B, who underwent OT-only followed by NEURO® (P = .011 for FMA and P = .001 for WMFT). Our findings indicate that rTMS facilitates neuromodulation when combined with OT, which leads to more effective rehabilitation than with OT alone (Trial registration: JMACCT (http://www.jmacct.med.or.jp/); trial ID JMA-IIA00215).


Garlic burns: a naturopathic remedy gone awry.
We report the case of a child who sustained partial thickness burns from a garlic-petroleum jelly plaster, which had been applied at the direction of a naturopathic physician. A review of the literature reveals that "garlic burns" have not previously been reported, although medicinal properties of garlic have been investigated by physicians and biochemists. The pediatrician caring for children in an area where naturopathic medicine is routinely practiced should be aware of the potential side effects of plasters, poultices, and other "natural" remedies in children.


Cold injuries among Israeli soldiers operating and training in a semiarid zone: a 10-year review.
Cold weather injuries (CIs) in 242 incidences among Israeli soldiers, who were operating and training in a relatively warm country, were reviewed. Peripheral CIs accounted for 55% of all CIs, whereas hypothermia accounted for 45%. A significant relationship was found between peripheral CIs and continuous operations, characterized by prolonged static exposures to a relatively high environmental cold stress. A significant relationship was also found between hypothermia cases and training activities, characterized by relatively short exposures to a low environmental cold stress in the absence of adequate protective clothing for the cold. Static exposure to a cold environment while wearing wet clothing was found to be the leading cause of both CI types. Peripheral CI prevention requires the improvement of protective clothing for the cold, with special emphasis on protective gear for the extremities. Hypothermia prevention requires increased awareness of military regulations regarding cold weather behavior, especially the importance of changing wet clothing during static periods of the training program.


mRNA differential display reveals Krox-20 as a neural plasticity-regulated gene in the rat hippocampus.
The prolonged maintenance of hippocampal long-term potentiation depends on de novo protein and RNA synthesis, indicating an involvement of altered gene expression in long-lasting plastic changes in synaptic efficacy. We have used an mRNA differential display technique to identify a set of genes that are induced by neural activity in the rat hippocampus. Sixteen independent cDNAs were isolated whose mRNA level was markedly modulated by convulsive seizure. One of these encodes Krox-20, a zinc finger DNA binding protein. High frequency tetanic stimulation of perforant pathway, which elicited a persistent long-term potentiation (>10 h), rapidly induced expression of krox-20 mRNA in the hippocampus of urethane-anesthetized rat. The increase in krox-20 mRNA was transient and NMDA receptor-dependent. These results suggest a role for krox-20 in the maintenance of long-term potentiation.


Waiting times for diagnosis of attention-deficit hyperactivity disorder in children and adolescents referred to Italian ADHD centers must be reduced.
To investigate timely access to and the time needed to complete the diagnostic path of children and adolescents with suspected attention deficit hyperactivity disorder (ADHD) in the 18 Italian Lombardy Region ADHD reference centers. Data of children and adolescents enrolled in the Regional ADHD disease-oriented Registry for suspected ADHD who requested their first visit in 2013-2017 were analyzed. The sample comprised 2262 children and adolescents aged 5-17 years who accessed the ADHD centers for diagnostic classification and management. The median waiting time was of 177 days (range 66-375) from the request for the initial appointment to the completion of the diagnostic path, with a three - fold difference between centers. In addition to the center, the strongest significant predictors of long waiting times were age comorbidities, the severity of the disorder, and having already completed some diagnostic procedures provided by the common standard path. To guarantee an equal standard of care in ADHD centers for all children and adolescents there is a pressing need to reduce the times to complete the diagnostic path. It is the task of both policymakers and each center to optimize the quality of the service and of the care delivered.


SARS-CoV-2 B.1.619 and B.1.620 Lineages, South Korea, 2021.
We report the rapid emergence of severe acute respiratory syndrome coronavirus 2 lineages B.1.619 and B.1.620 in South Korea. The surge in frequency in a relatively short time emphasizes the need for ongoing monitoring for new lineages to track potential increases in transmissibility and disease severity and reductions in vaccine efficacy.


[Intraneural perineurioma: an unusual nerve sheath tumor].
We report a case of intraneural perineurioma, developed in the left cubital nerve, in a five-year old girl. This intraneural tumor is rare and shows a typical histologic appearance: concentric whorls of perineurial cells EMA+, PS100-, around nerve fibers. This tumor must be distinguished from extraneural or soft tissue perineurioma, also composed of perineurial cells, with distinct clinical presentation and histological appearance.


Design and Fabrication by Thermal Imprint Lithography and Mechanical Characterization of a Ring-Based PDMS Soft Probe for Sensing and Actuating Forces in Biological Systems.
In this paper, the design, fabrication and mechanical characterization of a novel polydimethylsiloxane (PDMS) soft probe for delivering and sensing forces in biological systems is proposed. On the basis of preliminary finite element (FEM) analysis, the design takes advantage of a suitable core geometry, characterized by a variable spring-like ring. The compliance of probes can be finely set in a wide range to measure forces in the micronewton to nanonewton range. In particular, this is accomplished by properly resizing the ring geometry and/or exploiting the mixing ratio-based elastic properties of PDMS. Fabrication by the thermal imprint lithography method allows fast and accurate tuning of ring sizes and tailoring of the contact section to their targets. By only varying geometrical parameters, the stiffness ranges from 1080 mNm-1 to 50 mNm-1, but by changing the base-curing agent proportion of the elastomer from 10:1 to 30:1, the stiffness drops to 37 mNm-1. With these compliances, the proposed device will provide a new experimental tool for investigating force-dependent biological functions in sensory systems.


Analytic second derivatives of the energy in the fragment molecular orbital method.
We developed the analytic second derivatives of the energy for the fragment molecular orbital (FMO) method. First we derived the analytic expressions and then introduced some approximations related to the first and second order coupled perturbed Hartree-Fock equations. We developed a parallel program for the FMO Hessian with approximations in GAMESS and used it to calculate infrared (IR) spectra and Gibbs free energies and to locate the transition states in SN2 reactions. The accuracy of the Hessian is demonstrated in comparison to ab initio results for polypeptides and a water cluster. By using the two residues per fragment division, we achieved the accuracy of 3 cm(-1) in the reduced mean square deviation of vibrational frequencies from ab initio for all three polyalanine isomers, while the zero point energy had the error not exceeding 0.3 kcal/mol. The role of the secondary structure on IR spectra, zero point energies, and Gibbs free energies is discussed.


Fibrillary-immunotactoid glomerulopathy with renal deposits of IgAlambda: a rare cause of glomerulonephritis.
We describe a 24-year-old patient who presented with a nephrotic syndrome. His renal biopsy revealed a diffuse mesangioproliferative glomerulonephritis with eosinophilic deposits. Electron microscopy showed organized, Congo-red negative deposits, forming microtubules of about 20 nm width in the capillary walls and in the mesangium, establishing a diagnosis of fibrillary-immunotactoid glomerulopathy. Fibrillary-immunotactoid glomerulopathy is a rare cause of glomerulonephritis, characterized by Congo-red-negative glomerular deposits of fibrils, sometimes organized in microtubules, predominantly containing IgG and C3. Patients clinically present with the nephrotic syndrome, hematuria and hypertension. The pathogenesis of this glomerulopathy has not been elucidated yet. In our patient, the renal deposits contained IgAlambda. This peculiar feature is suggestive of an underlying paraproteinemia. However, in the serum no paraproteins or cryoglobulins were found, and also microscopical examination and immunophenotyping of the bone marrow did not point to the presence of a monoclonal plasma cell dyscrasia. Our patient was not treated with immunosuppressive drugs and he is currently progressing to end-stage renal disease.


Preneoplastic transformation in mouse mammary tissue: identification and validation of intermediate biomarkers for chemoprevention.
Specific and sensitive markers capable of determining the extent of tumorigenesis are important end points not only for evaluating the carcinogenic potency, but also for assessment of chemopreventive efficacy of modulators. Prototypic mammary carcinogens induce a high frequency of mammary adenocarcinomas. The appearance of tumors, however, is a culmination of initiational and promotional events whose modulation may constitute an effective means for chemopreventive interventions. The purpose of this study was i) to identify intermediate biomarkers for mammary cell transformation and ii) to apply these biomarkers and validate the ability of selected fatty acids to modulate chemical carcinogen-induced tumorigenic transformation. An in vitro model derived from mouse mammary explant cultures was utilized to examine the effects of 7,12 dimethylbenz (a) anthracene (DMBA), a prototype chemical carcinogen for rodent mammary gland. The effects of DMBA exposure were quantified at the molecular level by determining induction of oncogene expression, at metabolic level by determining the extent of estradiol metabolism, and at cellular level by determining the emergence of hormone-independent mammary alveolar lesions (MAL) and their tumorigenic potential. DMBA treatment induced binding of ras oncogene product ras p21 to [alpha 32P] GTP, altered estradiol metabolism by increasing the ratio of C16 alpha/C2 hydroxylation in favor of 16 alpha-OHE1 formation, and exhibited high frequency of MAL. Transplantation of cells from these MAL produced rapidly growing tumors. Treatment of DMBA-exposed cultures with polyunsaturated n-6 fatty acids enhanced, and treatment with polyunsaturated n-3 fatty acid suppressed the molecular, metabolic and cellular intermediate biomarkers for tumorigenic transformation. Thus, oncogene expression, estradiol metabolism and formation of MAL may constitute useful molecular, metabolic and cellular intermediate biomarkers. Alteration of these biomarkers by selected fatty acids is suggestive of their utility as end points for the chemopreventive efficacy of dietary agents.


Simulating the action of zeitgebers on a coupled two-oscillator model of the human circadian system.
Our two-oscillator model was originally designed to describe the circadian rhythms of human subjects maintained in temporal isolation. The performance of this model in response to simulated environmental synchronizing cycles (zeitgebers) is examined here. Six distinct types of synchronization are demonstrated between the x oscillator (postulated to regulate the core temperature rhythm), the y oscillator (postulated to regulate the rest-activity rhythm), and z (the zeitgeber). Four types of synchronization are identifiable, if we consider only the periods of the three oscillators. Both x and y may be synchronized by z; either may synchronize with z while the other exhibits a different period; or x, y, and z may each show different periods. Two further classes of synchronization are discernible when phase criteria are taken into account. When either x or y is on the verge of desynchronizing from the other two oscillators, it undergoes periodic phase modulations while retaining the common overall period. The type of synchronization observed depends on the periods of x, y, and z and on the strength of the z drive. The effects of modifying each of these parameters have been systematically investigated by simulation, and model performance is summarized in terms of range of entrainment "maps." These constitute extensive sets of predictions about expected patterns of entrainment of the core temperature and rest-activity rhythms of human subjects exposed to various environmental zeitgebers. Experimental data are available against which model predictions can be tested.


Psychological issues arising from the development of new male contraceptives.
Reading et al. (Bulletin, October 1982) report low correlations between morning erectile frequency and diary card records of sexual behavior, and consider difficulties in accurately assessing the monthly frequency of such erections. It seems that the authors have a problem that may derive from the assumption that erections are always associated with sexual arousal. I would argue that this is not the case. If the authors consider the frequency with which morning erections are maintained following micturation, I suspect they would find a lower incidence of early morning erection than they have hiterto. A full bladder in the morning is frequently associated with erection, with detumescence following micturation (Fielding, R. unpublished observations on a single case study for 16 years). Is it possible, therefore, that to consider the term erection as synonymous with sexual arousal can sometimes confuse the simple minds of men? The authors also considered whether retarded ejaculation is perceived as positive or negative. Obviously, this would depend on the duration of retardation. Total retardation would, I predict, prove to be an effective, though unpopular means of contraception, whilst a contraceptive which trebled or quadrupled the duration of intercourse might be much more popular. Finally, as an effective male contraceptive would function by preventing spermatogenesis only, and as spermatozoa constitute less than 1% of the total volume of ejaculatory fluid, no significant changes in the volume of ejaculate should occur. Perhaps contrary to the author's assumption than basic information on the subject is lacking, it has been there under our noses, so to speak, all the time.


Biological activities of crude extracts and chemical constituents of Bael, Aegle marmelos (L.) Corr.
Bael (Aegle marmelos (L.) Corr.) is an important medicinal plant of India. Leaves, fruits, stem and roots of A. marmelos have been used in ethno medicine to exploit its' medicinal properties including astringent, antidiarrheal antidysenteric, demulcent, antipyretic and anti-inflammatory activities. Compounds purified from bael have been proven to be biologically active against several major diseases including cancer, diabetes and cardiovascular diseases. Preclinical studies indicate the therapeutic potential of crude extracts of A. marmelos in the treatment of many microbial diseases, diabetes and gastric ulcer. This review covers the biological activities of some isolated chemical constituents of A. marmelos and preclinical studies on some crude extracts and pure compounds to explore novel bioactive compounds for therapeutic application.


A thermodynamic molecular switch in biological systems: ribonuclease S' fragment complementation reactions.
It is well known that essentially all biological systems function over a very narrow temperature range. Most typical macromolecular interactions show DeltaH degrees (T) positive (unfavorable) and a positive DeltaS degrees (T) (favorable) at low temperature, because of a positive (DeltaCp degrees /T). Because DeltaG degrees (T) for biological systems shows a complicated behavior, wherein DeltaG degrees (T) changes from positive to negative, then reaches a negative value of maximum magnitude (favorable), and finally becomes positive as temperature increases, it is clear that a deeper-lying thermodynamic explanation is required. This communication demonstrates that the critical factor is a temperature-dependent DeltaCp degrees (T) (heat capacity change) of reaction that is positive at low temperature but switches to a negative value at a temperature well below the ambient range. Thus the thermodynamic molecular switch determines the behavior patterns of the Gibbs free energy change and hence a change in the equilibrium constant, K(eq), and/or spontaneity. The subsequent, mathematically predictable changes in DeltaH degrees (T), DeltaS degrees (T), DeltaW degrees (T), and DeltaG degrees (T) give rise to the classically observed behavior patterns in biological reactivity, as may be seen in ribonuclease S' fragment complementation reactions.


Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion.
The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects (n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) (n = 6). During fasting, no significant difference in weight-specific rate of appearance (R(a)) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma beta-hydroxybutyrate in both groups. The correlation between free fatty acids and beta-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine R(a) in both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione.


Oxidation investigation of nickel nanoparticles.
This work reported an experimental investigation of complete oxidation of nickel nanoparticles using simultaneous thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC). Nickel nanoparticles and their elemental compositions were characterized by Brunauer-Emmett-Teller (BET) analysis, transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). The oxidation experiments were performed under isoconversion conditions for seven heating rates, varying from 2 to 20 K min(-1), with temperatures up to 1000 degrees C. The experiments revealed unique oxidation behaviour of nickel at the nanometre scale, such as early oxidation and melting phenomena, variable activation energies and different oxidation kinetics between low and high conversion ratios. Unlike its bulk counterpart where the activation energy is a constant, the activation energy of nickel nanoparticles depended on the conversion ratio, ranging between 1.4 and 1.8 eV. The oxidation kinetics of nickel nanoparticles changed from the classical diffusion controlled mechanism to a pseudo-homogeneous reaction as conversion ratios were over 50%. The oxidation mechanisms of nickel nanoparticles were further discussed and future studies to enhance understanding were identified.


The design and preliminary evaluation of a home electrocardiography and blood pressure monitoring network.
A home electrocardiography (ECG) and blood pressure (BP) monitoring network was established in Beijing. The network consisted of three parts: (1) the home ECG and BP monitoring devices; (2) the monitoring centre at the hospital; and (3) the data communication network, for which we chose the public telephone network. The system was tested in our university hospital for two months with 30 patients and six normal volunteers. A preliminary evaluation by the users indicated that the system was acceptable in terms of its efficiency and effectiveness. This paper describes the system design, the preliminary testing procedure, and results.


A decision support system for preventing Legionella disease.
Information systems plays an important role in medicine because it helps process more data more efficiently while providing access to more people in different parts of the world. In this research we analyzed the data of legionella pneumophila and other legionella species collected by the public hygiene center (PHC). PHC collected 7,211 water samples from different sources of different locations in different cities in Turkey from year 1995 to 2008. The main goal of this research is to develop a conceptual framework for preventing disease and to design a medical decision support system to help administration assessing the risk of Legionnaires' disease and preventing the outbreaks of the disease. The DSS involves SOM software which was programmed with C# to search for patterns and similarities in data sets by producing SOM risk maps. Thus administrators can decide where to monitor cautiously to prevent the disease.


Metabolic myopathy in heart failure.
Heart failure is a syndrome that also affects the periphery. Exercise intolerance and early fatigue seem to be linked in part to intrinsic alterations of skeletal muscle with decreases in both the production of ATP by mitochondria and the transfer of energy through the phosphotransfer kinases.


Cloning and expression of two novel aldo-keto reductases from Digitalis purpurea leaves.
The aldo-keto reductase (AKR) superfamily comprises proteins that catalyse mainly the reduction of carbonyl groups or carbon-carbon double bonds of a wide variety of substrates including steroids. Such types of reactions have been proposed to occur in the biosynthetic pathway of the cardiac glycosides produced by Digitalis plants. Two cDNAs encoding leaf-specific AKR proteins (DpAR1 and DpAR2) were isolated from a D. purpurea cDNA library using the rat Delta4-3-ketosteroid 5beta-reductase clone. Both cDNAs encode 315 amino acid proteins showing 98.4% identity. DpAR proteins present high identities (68-80%) with four Arabidopsis clones and a 67% identity with the aldose/aldehyde reductase from Medicago sativa. A molecular phylogenetic tree suggests that these seven proteins belong to a new subfamily of the AKR superfamily. Southern analysis indicated that DpARs are encoded by a family of at most five genes. RNA-blot analyses demonstrated that the expression of DpAR genes is developmentally regulated and is restricted to leaves. The expression of DpAR genes has also been induced by wounding, elevated salt concentrations, drought stress and heat-shock treatment. The isolated cDNAs were expressed in Escherichia coli and the recombinant proteins purified. The expressed enzymes present reductase activity not only for various sugars but also for steroids, preferring NADH as a cofactor. These studies indicate the presence of plant AKR proteins with ketosteroid reductase activity. The function of the enzymes in cardenolide biosynthesis is discussed.


[Ultrastructure of afferent synapses on the ventral dendrite of mauthner neurons after goldfish adaptation to optokinetic stimulation].
Using the morphometric techniques, the ultrastructural changes of the afferent synapses on the ventral dendrite of the Mauthner neurons (MNs) were studied after the adaptation of goldfish to long-term fatiguing sensory (visual) stimulation, characterized by the growth of MN resistance. It was shown that after the adaptation, the length of active zones (AZs) in the synapses located on the MN ventral dendrite was significantly reduced by 23%. At the same time, the length the AZs of the excitatory visual synapses was reduced by 29% in comparison with the control, while the length of desmosome-like contacts (DLCs) bordering AZs was increased by 71%. It was also found that the length of AZs in the inhibitory synapses was decreased by 19% after the adaptation, which is consistent with the important role of inhibitory processes in the sensory pathways during the memory formation. Taking into account the actin nature of the DLCs, the basis of the adaptation to the visual stimulation is suggested to be in the presynaptic mechanism of neurotransmitter secretion regulation by actin.


Dexmedetomidine and levobupivacaine co-loaded, transcriptional transactivator peptide modified nanostructured lipid carriers or lipid-polymer hybrid nanoparticles, which performed better for local anesthetic therapy?
Local anesthetics (LAs) have been widely applied in clinic for regional anesthesia, postoperative analgesia, and management of acute and chronic pain. Nanostructured lipid carriers (NLCs) and lipid-polymer hybrid nanoparticles (LPNs) are reported as good choices for LA therapy. Transactivated transcriptional activator (TAT) was reported as a modifier for the topical delivery of drugs. In the present study, TAT modified, levobupivacaine (LEV) and dexmedetomidine (DEX) co-delivered NLCs (TAT-LEV&DEX-NLCs, T-L&D-N) and LPNs (TAT-LEV&DEX-LPNs, T-L&D-L) were designed and compared for the LA therapy. T-L&D-L exhibited better efficiency in improving the skin permeation, analgesic time, and pain control intensity than T-L&D-N both in vitro and in vivo. On the other side, T-L&D-N also improved the therapeutic effect of drugs to a large extent. These two systems both exhibited superiority in some respects. TAT modified LPNs are more promising platform for the long-term local anesthesia.


[Neuroprotective effect of exogenous vascular endothelial growth factor on anoxic rat spinal cord astrocyte and the underlying mechanism].
To observe the effect of hypoxia on primary cultured rat spinal cord astrocyte and investigate the neuroprotective effect of exogenous vascular endothelial growth factor (VEGF) on anoxic astrocyte in vitro. The rat embryonic spinal cord astrocytes were cultured and identified by cellular morphology and glial fibrillary acidic protein (GFAP). The astrocytes were treated with VEGF at different concentrations (10 ng/ml-100 ng/ml) as well as with VEGF receptor (Flk-1) inhibitor SU1498. Then the astrocytes were exposed to hypoxia for different time. The light microscope, MTT assay, TUNEL labeling and SABC immuno-histochemistry were used to measure and observe the changes of the astrocytes in cell morphology, growth, proliferation, GFAP identified that 98% of the purified 1-week cultured cells apoptosis, VEGF and Flk-1 expression. were astrocytes. 8-12 hours hypoxia obviously induced the activity of astrocyte. The cytobody became bigger, the cytoskeleton grew thicker. The activity of proliferation decreased but apoptosis index increased. The GFAP, VEGF and Flk-1 expression increased. The treatment with 50 ng/ml VEGF 20-24 hours before hypoxia apparently enhanced the activity, decreased the apoptosis index of the astrocytes, and hence improved the hypoxia-injuried astrocytes. Howerver, 700 ng/ml SU1498 obviously inhibited the neuroprotective effect of VEGF on anoxic astrocytes. Hypoxia induces reactive activity of astrocyte. The exogenous VEGF exerts neuroprotective effect on astrocytes via VEGF receptor-Flk-1.


Airway endothelial dysfunction in asthma and chronic obstructive pulmonary disease: a challenge for future research.
Endothelial dysfunction in the extrapulmonary circulation has been linked to cardiovascular disease. Recent investigations have revealed that in the airway circulation, cigarette smoking, chronic obstructive pulmonary disease (COPD), and asthma are also accompanied by endothelial dysfunction. Inhaled glucocorticosteroids can partially or fully restore normal endothelium-dependent vasodilation in these conditions, thereby identifying the airway endothelium as a novel therapeutic target in the treatment of airway disease. The role of the defective endothelium-dependent vasodilation in the pathophysiology in asthma and COPD is still subject to speculation. However, there appears to be an association between COPD and extrapulmonary vascular dysfunction, and the possibility exists that the use of inhaled glucocorticosteroids has a beneficial effect on cardiovascular disease in COPD as suggested by database studies showing that inhaled glucocorticosteroids reduce the incidence of nonfatal and fatal cardiovascular events in COPD.


Interface-Engineered Nickel Cobaltite Nanowires through NiO Atomic Layer Deposition and Nitrogen Plasma for High-Energy, Long-Cycle-Life Foldable All-Solid-State Supercapacitors.
The large-scale application of supercapacitors (SCs) for portable electronics is restricted by low energy density and cycling stability. To alleviate the limitations, a unique interface engineering strategy is suggested through atomic layer deposition (ALD) and nitrogen plasma. First, commercial carbon cloth (CC) is treated with nitrogen plasma and later inorganic NiCo2 O4 (NCO)/NiO core-shell nanowire arrays are deposited on nitrogen plasma-treated CC (NCC) to fabricate the ultrahigh stable SC. An ultrathin layer of NiO deposited on the NCO nanowire arrays via conformal ALD plays a vital role in stabilizing the NCO nanowires for thousands of electrochemical cycles. The optimized NCC/NCO/NiO core-shell electrode exhibits a high specific capacitance of 2439 F g-1 with a remarkable cycling stability (94.2% over 20 000 cycles). Benefiting from these integrated merits, the foldable solid-state SCs are fabricated with excellent NCC/NCO/NiO core-shell nanowire array electrodes. The fabricated SC device delivers a high energy density of 72.32 Wh kg-1 at a specific capacitance of 578 F g-1 , with ultrasmall capacitance decline rate of 0.0003% per cycle over 10 000 charge-discharge cycles. Overall, this strategy offers a new avenue for developing a new-generation high-energy, ultrahigh stable supercapacitor for real-life applications.


National survey of general practitioners' experience of delivering the National Human Papillomavirus Vaccination Program.
Between 2007 and 2009, Australian general practitioners (GPs) were involved in implementing a population-based human papillomavirus (HPV) vaccination program. We investigated GPs' experiences of delivering the HPV vaccine to women aged 18-26. We posted a survey to 1000 GPs. The survey was informed by 12 domains incorporating constructs from psychological theories that focus on individual and environmental barriers and facilitators to effective implementation of evidence-based practice by health professionals. The response rate was 32%. The 298 vaccinating GPs were positive about HPV vaccine implementation as part of their professional role as a worthwhile initiative within existing general practice infrastructure. They had more negative views about some aspects of program organisation, such as the timelines and potential adverse impacts on cervical screening rates. Vaccine safety was not a key concern. Actual levels of knowledge about HPV were moderate (mean score 3.41 out of 6 (s.d. 0.99)) and contrasted with self-rated knowledge, which was high (93% perceived their knowledge to be adequate). Notably, there were unrealistic expectations about the likely reduction in Pap abnormalities due to vaccination, which is important to clarify to avoid loss of confidence in the vaccine when this reduction does not eventuate. Australian GPs viewed HPV vaccination of women aged 18-26 years as an integrated part of their routine practice, with positive attitudes regarding its benefits and achievability. GPs are well placed to implement mass immunisation programs as long as they are supported by effective and timely communication strategies and resources.


Abstraction of covariation in category learning: a critical note on K. Richardson's studies.
Several studies directed by K. Richardson (Richardson, 1986, 1987; Richardson & Carthy, 1989, 1990) claimed that people are able to abstract imperfect covariations among feature variables defining artificial categories, and to use that information in various subsequent tasks. We challenge this claim on a twofold basis. First, a large part of the performance variance Richardson attributed to covariation knowledge may be accounted for by a very simple exemplar model, which assumes no abstractive processes. Second, the residual influence of relational information on performance may be attributed to the knowledge subjects have acquired in real-world situations before their training with the study exemplars.


Intertwined Relationship of Mitochondrial Metabolism, Gut Microbiome and Exercise Potential.
The microbiome has emerged as a key player contributing significantly to the human physiology over the past decades. The potential microbial niche is largely unexplored in the context of exercise enhancing capacity and the related mitochondrial functions. Physical exercise can influence the gut microbiota composition and diversity, whereas a sedentary lifestyle in association with dysbiosis can lead to reduced well-being and diseases. Here, we have elucidated the importance of diverse microbiota, which is associated with an individual's fitness, and moreover, its connection with the organelle, the mitochondria, which is the hub of energy production, signaling, and cellular homeostasis. Microbial by-products, such as short-chain fatty acids, are produced during regular exercise that can enhance the mitochondrial capacity. Therefore, exercise can be employed as a therapeutic intervention to circumvent or subside various metabolic and mitochondria-related diseases. Alternatively, the microbiome-mitochondria axis can be targeted to enhance exercise performance. This review furthers our understanding about the influence of microbiome on the functional capacity of the mitochondria and exercise performance, and the interplay between them.


Prognosis of Masked and White Coat Uncontrolled Hypertension Detected by Ambulatory Blood Pressure Monitoring in Elderly Treated Hypertensive Patients.
Prognosis of masked and white coat uncontrolled hypertension (MUCH and WCUCH, respectively) detected by ambulatory blood pressure (BP) monitoring is incompletely clear in elderly treated hypertensive patients. We evaluated prognosis of MUCH and WCUCH identified by ambulatory BP monitoring in this setting. The occurrence of a composite endpoint was evaluated in 1,191 elderly treated hypertensive patients. Controlled hypertension (CH) was defined as clinic BP <140/90 mm Hg and 24-hour BP <130/80 mm Hg, MUCH as clinic BP <140/90 mm Hg and 24-hour BP ≥130 and/or ≥80 mm Hg, WCUCH as clinic BP ≥140 and/or ≥90 mm Hg and 24-hour BP <130/80 mm Hg and sustained uncontrolled hypertension (SUCH) as clinic BP ≥140 and/or ≥90 mm Hg and 24-hour BP ≥130 and/or ≥80 mm Hg. MUCH was identified in 142 patients (12% of all the population, 34% of those with normal clinic BP) and WCUCH in 230 patients (19% of all the population, 30% of those with high clinic BP). During the follow-up (9.1 ± 4.9 years, range 0.4-20 years), 392 events occurred. After adjustment for various covariates, patients with MUCH (hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.12-2.29, P = 0.01) and SUCH (HR 1.81, 95% CI, 1.35-2.42, P < 0.001) had significantly higher cardiovascular risk than those with CH, whereas those with WCUCH (HR 1.09, 95% CI, 0.74-1.60, P = 0.66) had not significantly higher risk. In elderly treated hypertensive patients evaluated by ambulatory BP monitoring, compared to individuals with CH, those with MUCH have significantly higher risk and those with WCUCH have slightly and not significantly higher risk.


Object exploration during the transition to sitting: A study of infants at heightened risk for autism spectrum disorder.
Learning to sit promotes infants' object exploration because it offers increased access to objects and an improved position for exploration (e.g., ). Infants at heightened risk (HR) for autism spectrum disorder (ASD) exhibit delays in sitting and differences in object exploration. However, little is known about the association between sitting and object exploration among HR infants. We examined changes in object exploration as HR infants (N = 19) and comparison infants with no family history of ASD (Low Risk; LR; N = 23) gained experience sitting independently. Infants were observed monthly from 2.5 months until 1 month after the onset of independent sitting. At 12, 18, 24, and 36 months, infants completed standardized developmental assessments, and HR infants were assessed for ASD symptoms at 36 months. Although HR infants began sitting later than LR infants, both groups increased time spent grasping, shaking, banging, and mouthing objects as they gained sitting experience. Groups only differed in time spent actively mouthing objects, with LR infants showing a greater increase in active mouthing than HR infants. Findings suggest that HR infants experience a similar progression of object exploration across sitting development, but on a delayed time scale.