MORC2 and MAX contributes to the expression of glycolytic enzymes, breast cancer cell proliferation and migration.
Cancer cell proliferation is a high energy demanding process, where the cancer cells acquire energy by high rates of glycolysis, and this phenomenon is known as the "Warburg effect". Microrchidia 2 (MORC2), an emerging chromatin remodeler, is over expressed in several cancers including breast cancer and found to promote cancer cell proliferation. However, the role of MORC2 in glucose metabolism in cancer cells remains unexplored. In this study, we report that MORC2 interacts indirectly with the genes involved in glucose metabolism via transcription factors MAX (MYC-associated factor X) and MYC. We also found that MORC2 co-localizes and interacts with MAX. Further, we observed a positive correlation of expression of MORC2 with glycolytic enzymes Hexokinase 1 (HK1), Lactate dehydrogenase A (LDHA) and Phosphofructokinase platelet (PFKP) type in multiple cancers. Surprisingly, the knockdown of either MORC2 or MAX not only decreased the expression of glycolytic enzymes but also inhibited breast cancer cell proliferation and migration. Together, these results demonstrate the involvement of the MORC2/MAX signaling axis in the expression of glycolytic enzymes and breast cancer cell proliferation and migration.


The 2011 Tohoku-oki tsunami-induced sediment remobilization on the Sendai shelf, Japan, from a comparison of pre- and post-tsunami surface sediments.
Tsunamis are generally considered to disturb the seafloor, rework surface sediments, and change seafloor environments. However, the response of the seafloor to such extreme wave events has not been fully elucidated. Herein, we compare the surface sediments before and after the 2011 Tohoku-oki tsunami on the Sendai shelf and demonstrate that both sandy and muddy sediments were significantly reworked on the shelf. Muddy sediments (> 10 cm thick) were redeposited as graded mud with no or little bioturbation, characterizing the offshore muddy tsunami deposit, while well-sorted sand was found as the sandy tsunami deposit. This redeposited layer could also be retained in the shelf mud sequence. The results imply that the high friction velocity of the tsunami wave and its long-term effect on Sendai Bay might contribute to the large sediment reworking. Part of the resuspended mud moved offshore to the slope area as turbidity currents. Thus, the tsunami is an important mechanism not only for shelf sedimentation but also for deep-sea sedimentation along active plate margins. The detection of 134Cs derived from the Fukushima Daiichi Nuclear Power Plant accident in the redeposited mud indicates that the suspended shelf water state was maintained for some days after the tsunami.


How Influential are Adverse Childhood Experiences (ACEs) on Youths?: Analyzing the Immediate and Lagged Effect of ACEs on Deviant Behaviors.
Although the effect of adverse childhood experiences (ACEs) on antisocial behaviors is well established in the literature, limited research, if any, has analyzed the effect that ACEs have on behaviors at two different times. Limited research also has analyzed the effect that specific ACEs have on deviant behaviors after statistically controlling for respondents' protective factors. This study expands the literature in this area by analyzing in a sample of 555 adolescents the immediate and lagged effect that individual ACEs, and exposure to a number of ACEs, have on three deviant behaviors after controlling for respondents' protective factors not previously examined in ACEs studies. Results obtained from multivariate logistic regression models revealed that stealing things was predicted by being hit hard, being sexually molested, and having lived with a depressed or suicidal individual; and receiving threats over the internet predicted physical fights. Only being hit hard and living with an alcoholic had a lagged effect on smoking marijuana. Results also showed that the protective factors of school connection, anger management skills, and parental supervision reduced the effect of ACEs on the behaviors analyzed. Research, theory, and policy implications are discussed.


Can Radiotherapy After Breast-Conserving Surgery be Omitted in Elderly Patients with Early-Stage, Hormone-Receptor Negative Breast Cancer? A Population-Based Study and Proposed Nomogram.
We aimed to evaluate whether radiotherapy (RT) after breast-conserving surgery (BCS) can be omitted in elderly patients with early-stage, hormone receptor-negative breast cancer. Patients aged 65 years and older with T1-2N0-1, hormone receptor-negative breast cancer in 2010-2015 were extracted from the Surveillance, Epidemiology, and End Results program. Propensity score matching was used to balance the baseline of different groups. Survival analysis was performed using Kaplan-Meier plot and log-rank test. Independent risk factors were identified by multivariate Cox analysis. A nomogram predicting breast cancer-specific survival (BCSS) and a risk stratification model were constructed and validated. A total of 4465 patients were included and 27.7% (1237/4465) patients did not receive postoperative RT. RT was significantly associated with improved overall survival (OS) (HR = 0.552 P < 0.001) and BCSS (HR = 0.559, P < 0.001) in the matched cohort. The same results were found after adjusting independent risk factors by multivariate analysis. On the basis of the nomogram predicting BCSS of patients without RT by incorporating independent risk factors (age, race, HER2 status, T stage, and N stage), we built a risk stratification model which indicated that RT improved OS (HR = 0.511, P < 0.001) and BCSS (HR = 0.517, P < 0.001) in the high-risk group (total score > 150), but not in the low-risk group (total score ≤ 120). The C-index and all calibration curves demonstrated sufficient accuracies and good predictive capabilities. RT is indeed beneficial for the whole cohort in this study. However, it may be omitted in the low-risk subgroup without significantly sacrificing survival. For patients in the high-risk group, RT following BCS remained beneficial. This study highlights the need for prospective randomized trials to study RT de-escalation strategies.


Under the shadow of Tuskegee: African Americans and health care.
The Tuskegee Syphilis Study continues to cast its long shadow on the contemporary relationship between African Americans and the biomedical community. Numerous reports have argued that the Tuskegee Syphilis Study is the most important reason why many African Americans distrust the institutions of medicine and public health. Such an interpretation neglects a critical historical point: the mistrust predated public revelations about the Tuskegee study. This paper places the syphilis study within a broader historical and social context to demonstrate that several factors have influenced--and continue to influence--African American's attitudes toward the biomedical community.


Study of the impact of metal and organic pollution on benthic macrofauna using multivariate analyses in coastal wetland of Reghaïa, Algeria.
In this study, we studied the impact of pollution, metallic, organic, and environmental parameters, on benthic macroinvertebrates of the Reghaïa wetland and coastal zone, which is a nature reserve located in northern Algeria and is one of the last heritage sites on the central coast of the country. To do this, multivariate methods are used. The results of the multivariate analyses clearly show the impact of metal and organic pollution on the macroinvertebrates of this wetland which is really striking; this pollution has destroyed and upset the biodiversity of the benthic macrofauna and it has led to the disappearance of several taxa. This pollution has drained this wetland of the taxonomic richness of benthic macroinvertebrates, the only taxa that have resisted are the Diptera such as Psychodidae, Ceratopogonidae, and Syrphidae.


The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression.
Class I selective histone deacetylase inhibitors (HDACi) have been previously demonstrated to not only increase major histocompatibility complex class I surface expression in Merkel cell carcinoma (MCC) cells by restoring the antigen processing and presentation machinery, but also exert anti-tumoral effect by inducing apoptosis. Both phenomena could be due to induction of type I interferons (IFN), as has been described for HDACi. However, the mechanism of IFN induction under HDACi is not fully understood because the expression of IFNs is regulated by both activating and inhibitory signaling pathways. Our own preliminary observations suggest that this may be caused by suppression of HES1. The effect of the class I selective HDACi domatinostat and IFNα on cell viability and the apoptosis of MCPyV-positive (WaGa, MKL-1) and -negative (UM-MCC 34) MCC cell lines, as well as, primary fibroblasts were assessed by colorimetric methods or measuring mitochondrial membrane potential and intracellular caspase-3/7, respectively. Next, the impact of domatinostat on IFNA and HES1 mRNA expression was measured by RT-qPCR; intracellular IFNα production was detected by flow cytometry. To confirm that the expression of IFNα induced by HDACi was due to the suppression of HES1, it was silenced by RNA interference and then mRNA expression of IFNA and IFN-stimulated genes was assessed. Our studies show that the previously reported reduction in viability of MCC cell lines after inhibition of HDAC by domatinostat is accompanied by an increase in IFNα expression, both of mRNA and at the protein level. We confirmed that treatment of MCC cells with external IFNα inhibited their proliferation and induced apoptosis. Re-analysis of existing single-cell RNA sequencing data indicated that induction of IFNα by domatinostat occurs through repression of HES1, a transcriptional inhibitor of IFNA; this was confirmed by RT-qPCR. Finally, siRNA-mediated silencing of HES1 in the MCC cell line WaGa not only increased mRNA expression of IFNA and IFN-stimulated genes but also decreased cell viability. Our results demonstrate that the direct anti-tumor effect of HDACi domatinostat on MCC cells is at least in part mediated via decreased HES1 expression allowing the induction of IFNα, which in turn causes apoptosis.


Kissing Bug Intrusions into Homes in the Southwest United States.
Kissing bugs readily enter homes in the Sonoran Desert and bite the residents. Their saliva is highly antigenic, causing local and systemic skin reactions and life-threatening anaphylaxis. We attempted to determine what characteristics of homesites may have contributed to home intrusion by kissing bugs. Extensive and detailed information about the homes and the home environment was collected from 78 homeowners in Tucson who suffered kissing bug intrusions. Homeowners collected 298 Triatoma rubida in and around their homes. Of the homes entered by kissing bugs, 29 of 46 (63%) contained bugs harboring Trypanosoma cruzi. Although in the aggregate, homeowners were bitten > 2200 times, no individual tested positive for Chagas disease (N = 116). Although yearly intrusion likely occurs in some homes, T. rubida does not domiciliate within homesites in the Desert Southwest. We conclude there is little risk to homeowners for Chagas disease given the current behavior of resident kissing bugs and absent ingesting kissing bug fecal matter.


Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography.
Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using 18F-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of 18F. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced (especially in gray matter) and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. These changes in the peri-tumoral region may be secondary to edema. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. On a narrow margin of tumor and brain, corresponding to a zone of increased vascularity, CBF was moderately high. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.


Genome wide association study of the whiteness and colour related traits of flour and dough sheets in common wheat.
Flour whiteness and colour are important factors that influence the quality of wheat flour and end-use products. In this study, a genome wide association study focusing on flour and dough sheet colour using a high density genetic map constructed with 90K single nucleotide polymorphism arrays in a panel of 205 elite winter wheat accessions was conducted in two different locations in 2 years. Eighty-six significant marker-trait associations (MTAs) were detected for flour whiteness and the brightness index (L* value), the redness index (a* value), and the yellowness index (b* value) of flour and dough sheets (P < 10-4) on homologous group 1, 2, 5 and 7, and chromosomes 3A, 3B, 4A, 6A and 6B. Four, three, eleven, eleven MTAs for the flour whiteness, L* value, a* value, b* value, and one MTA for the dough sheet L* value were identified in more than one environment. Based on MATs, some important new candidate genes were identified. Of these, two candidate genes, TraesCS5D01G004300 and Gsp-1D, for BS00000020_51 were found in wheat, relating to grain hardness. Other candidate genes were associated with proteins, the fatty acid biosynthetic process, the ketone body biosynthetic process, etc.


Does systemic lupus erythematosus increase the risk of complications from total hip arthroplasty?
Patients with systemic lupus erythematosus are more likely to receive THA than the general population. However, it is controversial whether SLE increases the risk of complications from THA. The purpose of this retrospective study was to reassess the risks from THA in patients with SLE under the management model of enhanced recovery after surgery. Patients with systemic lupus erythematosus diagnosed from December 2011 to December 2017 and treated with THA were compared with THA patients with osteoarthritis. The data were extracted from the medical record system of our department. The chi-square test and t-test were used for comparison. The postoperative blood loss in patients with SLE was significantly higher than that in the control group, and the postoperative hemoglobin (Hb) and hematocrit (Hct) in the control group were lower than those in the control group (P < 0.05). There was no significant difference in the rate of blood transfusion (9.733 vs 8.133 P = 0.3148) or other complications between the two groups (P > 0.05). Well-controlled and well-managed SLE will not increase the risk of complications in THA, but can increase the amount of perioperative blood loss. Therefore, perioperative blood management is still essential in SLE patients.


Randomised clinical trial: adjunctive induction therapy with oral effervescent budesonide in newly diagnosed coeliac disease.
The healing of the mucosal lesion in patients with coeliac disease is slow. To determine whether concurrent budesonide and gluten-free diet hasten small bowel healing and symptomatic improvement in patients with newly diagnosed coeliac disease. In a pilot, randomised, double-blind trial, effects on Marsh grading and quantitative duodenal morphometry of 10 weeks' effervescent budesonide (initially 9 mg/day) or placebo were assessed after 8 and 52 weeks. Multiple clinical measures and adverse events were assessed. Nineteen patients were randomised to budesonide and 18 to placebo. No differences (all P > 0.32) were observed for the week-8 mucosal response (Marsh 0 or 1) (budesonide: 37% vs placebo: 28%), week-8 remission (Marsh 0) (32% vs 17%), week-52 response (63% vs 44%) and week-52 remission (42% vs 33%). Likewise, the improvement from baseline in villous-height : crypt-depth ratio was not different for the treatment groups. There were no statistically significant differences in clinical measures or adverse events between the treatment groups. No corticosteroid adverse effects were observed. In a post hoc analysis of all patients, Marsh 3C was present at the diagnostic biopsy in 1/9 achieving mucosal remission at 8 weeks versus 18/23 not (P < 0.001) and mean villous-height : crypt-depth ratio was 1.06 (SD: 0.73) versus 0.46 (0.38) (P = 0.005). In this pilot trial, induction therapy with budesonide had no significant effect on mucosal healing in patients with coeliac disease concurrently initiated on a gluten-free diet. Mucosal remission at 8 weeks occurred in approximately one in four patients and was associated with less severe histological lesions at diagnosis.


Quantitative analysis of masticatory muscle changes by Eichner index using diffusion-weighted imaging.
Diffusion-weighted imaging (DWI) provides quantitative functional information about the microscopic movement of water at the cellular level. However, few reports have quantitatively evaluated histological changes in masticatory muscles due to changes in occlusal relationships using DWI. This study aimed to assess the changes in masticatory muscles by Eichner index using DWI. We analyzed magnetic resonance imaging (MRI) studies of 201 patients from November 2017 to April 2018. Each Eichner index group, age, and sex were used as criterion variables, and the average apparent diffusion coefficient (ADC) values of the masticatory muscles were the explanatory variable. The mean ADC value differences were analyzed in each Eichner index group. We analyzed the data using the Kruskal-Wallis test and post hoc Mann-Whitney test with Bonferroni adjustment multiple regression analysis with Shapiro-Wilk test and Spearman's correlation coefficients. P < 0.05 was considered statistically significant. The mean ADC values of each Eichner classification group were significantly different, with the lowest value in group C (P < 0.001). There was a negative correlation between the ADC value of the masseter, lateral pterygoid muscle, and age (P < 0.001). There were significant differences between the sex groups (P < 0.001). ADC values of masticatory muscles were significantly different in the Eichner index groups. The ADC values of masticatory muscles may be useful for the quantitative evaluation of the masticatory muscles affected by the occlusal state.


Identification of differentially expressed microRNA in parathyroid tumors.
The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR). One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776. Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma.


Association of Tenebrio molitor L. alpha-amylase with two protein inhibitors--one monomeric, one dimeric--from wheat flour. Differential scanning calorimetric comparison of heat stabilities.
Thermal stabilization resulting from protein . protein association between two protein inhibitors (coded as 0.19, a dimer, and 0.28, a monomer) from wheat flour and the alpha-amylase from Tenebrio molitor L. (yellow mealworm) larvae was investigated by differential scanning calorimetry (heating rate 10 degrees C/min). Thermograms (plots of heat flow vs. temperature) for the two inhibitors showed broad endothermic peaks with the same extrema (denaturation temperatures) at 93 degrees C, and equal, small enthalpies of denaturation (2 cal/g). The amylase produced a sharp endotherm at 70.5 degrees C, but a larger enthalpy change on denaturation (6 cal/g). The amylase . inhibitor complexes differed in thermal stability, but both showed significant stabilization relative to free enzyme. The complex formed with monomeric inhibitor 0.28 showed a higher denaturation temperature (85.0 degrees C) than that formed with dimeric inhibitor 0.19 (80.5 degrees C). This order of stabilization agrees with the relative affinities of the inhibitors for the amylase. These thermograms are consistent with previous results which indicated that 1 mol of amylase binds 1 mol of inhibitor 0.19.


Spatio-temporal distribution of cell-bound and dissolved geosmin in Wahnbach Reservoir: Causes and potential odour nuisances in raw water.
In many lakes and reservoirs, problems caused by off-flavours are known to be particularly associated with the occurrence of planktonic and benthic cyanobacteria. Frequently observed objectionable taste and odorous products of cyanobacteria are geosmin and 2-methylisoborneol. Investigations focused on the littoral zone of Wahnbach Reservoir (Germany) revealed that benthic cyanobacteria were present in this oligotrophic drinking water reservoir. Benthic cyanobacteria were found in the depth horizon between 1.75 m and 11 m, particularly on south-exposed slopes. This spatial distribution indicates a possible key role of the underwater light climate. Moreover, cell-bound and dissolved geosmin were detected in corresponding littoral samples. Both fractions were subjected to spatial and primarily temporal variations with maximum concentrations at the end of summer. However, a substantial lowering of the water level caused a diminution of cyanobacterial growth. Due to the drawdown of the water level concentrations of cell-bound geosmin and pigments (as a proxy of cyanobacterial biomass) were remarkably reduced, and dissolved geosmin was never detected during this phase. Except for the influence of water level fluctuation no other abiotic variables had a significant influence on pigment and geosmin concentrations. From geosmin concentrations detected in the littoral zone, the probability of serious episodes of odour events in the raw water of the Wahnbach Reservoir was estimated. Hence, the probability that the raw water was affected by geosmin was minor, which was supported by routine flavour profiles. Nevertheless, the study shows that odorous episodes caused by benthic cyanobacteria are likely to develop even in an oligotrophic lake or reservoir when these cyanobacteria, and consequently odorous production, proliferate. In principle, such a proliferation cannot be excluded as nutrients are available from the sediment pore water, and underwater light at the sediment surface in the sub-littoral is sufficiently high due to very low phytoplankton-induced turbidity under oligotrophic conditions. Thus, management-induced fluctuations of the water level seem to be the main control variable to generate light conditions at the sediment surface fluctuating in a given depth horizon faster than cyanobacteria can develop there.


[Current indications of azathioprine in nephrology].
Azathioprine is an immunosuppressive agent belonging to the antimetabolite family whose action blocks purine synthesis. It inhibits lymphocyte proliferation. In recent years, several trials have clarified the role of this compound used for three main indications: lupus glomerulonephritis, necrotizing vasculitis associated with antineutrophil cytoplasmic antibodies and renal involvement, and kidney transplantation. This review of the literature details practical conditions for the use of azathioprine in these three situations.


Age distribution of HPV genotypes in cervical intraepithelial neoplasia.
Recent data showed that HPV16 infections in young women can lead to CIN3 formation very quickly and questioned the common assumption that invasive cervical cancer develops through slowly progressing pre-cancer lesions, CIN1, CIN2 and CIN3. The aim of the study is to compare the age distribution of HPV 16/18 related and HPV16/18 not related CIN. We used the data generated from the clinical use of HPV genotyping (LINEAR ARRAY, Roche Diagnostics). Patients were grouped on the basis of histology, CIN1 vs. CIN2+ and on HR-HPV genotype status. The probability to develop a CIN2+ seemed to decrease with age in patients infected with HR-HPV genotype 16/18 while the inverse effect was observed in CIN2+ patients who were HR-HPV positive but HPV16/18 negative (Chi-square test, p(trend)=0.01). Only in HR-HPV positive but HPV 16/18 negative patients, a relative reduction of CIN1 vs. CIN2+ was observed with increasing age (Cochran-Armitage test, p(trend)=0.01); finally, in HR-HPV non-16/18 infected patients only a statistically significant difference in mean age between CIN1 and CIN2+ patients below age 35 was observed. Besides the limitations of the present cross-sectional analysis, these data suggest a genotype specific natural history of cervical cancer precursors development: one type, more frequent, HPV16/18 related, which develops quick and early in life; another one, non-16/18 HR-HPV related, which develops later, slowly, through low- to high-grade lesions. If confirmed, this hypothesis could influence screening policies, especially in the vaccinated population.


Improvement of L-arginine production by overexpression of a bifunctional ornithine acetyltransferase in Corynebacterium crenatum.
Ornithine acetyltransferase (EC 22.214.171.124; OATase) gene (argJ) from the L-arginine-producing mutant Corynebacterium crenatum SYPA5-5 was cloned, sequenced, and expressed in Escherichia coli BL21 (DE3). Analysis of the argJ sequence revealed that the argJ coded a polypeptide of 388 amino acids with a calculated molecular weight of 39.7 kDa. In this study, the function of the OATase (argJ) of C. crenatum SYPA5-5 has been identified as a conserved ATML sequence for the autolysis of the protein to α- and β-subunits. When the argJ regions corresponding to the α- and β-subunits were cloned and expressed separately in E. coli BL21, OATase activities were abolished. At the same time, a functional study revealed that OATase from C. crenatum SYPA5-5 was a bifunctional enzyme with the functions of acetylglutamate synthase (EC 18.104.22.168, NAGS) and acetylornithine deacetylase (EC 22.214.171.124, AOase) activities. In order to investigate the effects of the overexpression of the argJ gene on L: -arginine production, the argJ gene was inserted into pJCtac to yield the recombinant shuttle plasmid pJCtac-argJ and then transformed into C. crenatum SYPA5-5. The results showed that the engineered strains could not only express more OATase (90.9%) but also increase the production of L: -arginine significantly (16.8%).


Adaptation of Mycoplasma hominis to an obligate parasitic existence in monkey kidney cell culture (BSC-1).
During attempts to eliminate Mycoplasma hominis from a monkey kidney BSC-1 cell line with antibiotics, the mycoplasmas were isolated repeatedly. However, the organisms ultimately failed to grow on medium although electron microscopy confirmed that the cell culture still contained mycoplasmas. Thus, the mycoplasma had adapted to an environment in which viable cells were required for growth. Budding mycoplasmas which are indicative of replication were seen associated with viable cells extracellularly. Moreover, structures resembling cycoplasmas were observed budding from the cells which suggests that the mycoplasmas replicate within the cells and are similar to many viruses in their manner of release from the cells.


Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: evidence for malignant transformation of liver with a sustained increase in cyclic AMP.
There is evidence than adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) may have antagonistic actions on cell growth, with cAMP inhibiting and cGMP stimulating this process. However, reductions in cAMP and increases in cGMP are not charactersitic of all neoplastic tissues. Thus, benign and malignant tissues from hepatoma-bearing rats exposed to the hepatic carcinogen DL-ethionine have elevated rather than depressed cAMP, compared to control liver, and parenteral administration of this drug increases hepatic cAMP within hours. In the present study, the effects of ethionine ingestion on the hepatic content and metabolism of both cAMP and cGMP were examined sequentially in rats at 2 and then 6 wk intervals, from the initiation of drug administration until the development of hepatomas. After 2 wk, cAMP content of quick-frozen liver from rats receiving ethionine (E) was significantly increased (826 +/- 91 pmole/g wet weight) above that of liver from pair-fed controls (C, 415 +/- 44), whether calculated by tissue wet weight, protein, or DNA content. In benign tissue from E, higher cAMP was still evident after in vitro incubations of slices with 2 mM 1-methyl-3-iso-butylxanthine (MIX) and was associated with enhanced adenylate cyclase and unchanged high or low Km cAMP-phosphodiesterase activities. These findings are compatible with accelerated cAMP generation in liver from E. Protein kinase activity ratios were significantly increased in frozen liver from E (0.52 +/- 0.04 versus 0.36 +/- 0.03 in C), and the percent glycogen synthetase in the I form was clearly reduced (19% +/- 2% in E versus 47% +/- 5% in c). incubation of hepatic slices from E or C with MIX and/or 10 muM glucagon further increased cAMP and protein kinase activity ratios, data which imply higher effective, as well as total, cellular cAMP in E. Changes in cAMP metabolism and action observed at 2 wk persisted throughout the 38-wk period of drug ingestion. Adenylate cyclase activity, cAMP content, and protein kinase activity ratios of ethionine-induced hepatomas exceeded those of both the surrounding liver from tumor-bearing rats and that of control liver, but alterations in these parameters were qualitatively similar in both tissues from E. By contrast, while cGMP in quick-frozen surrounding liver from tumor-bearing rats (36 +/- 4 pmole/g wet weight) did not differ from that of control liver (30 +/- 3), cGMP in the hepatomas was increased. This change was evident in both frozen tumor (89 +/- 10) and in tumor slices incubated in vitro with MIX (C, 90 +/- 11; surrounding liver, 85 +/- 10; hepatoma 231 +/- 29). These results indicate that malignant conversion can occur in liver with a sustained elevation of both total and effective cAMP during the premalignant phase. The increase in cGMP detected in ethionine-induced hepatomas could also be a key determinant of malignant transformation in the model, although premalignant changes in cGMP were not apparent.


Effect of Salicylic AcidFormulations on Induced Plant Defense against Cassava Anthracnose Disease.
This study was to investigate defense mechanisms on cassava induced by salicylic acid formulation (SA) against anthracnose disease. Our results indicated that the SA could reduce anthracnose severity in cassava plants up to 33.3% under the greenhouse condition. The β-1,3-glucanase and chitinase enzyme activities were significantly increased at 24 hours after inoculation (HAI) and decrease at 48 HAI after Colletotrichum gloeosporioides challenge inoculation, respectively, for cassava treated with SA formulation. Synchrotron radiation-based Fourier-transform infrared microspectroscopy spectra revealed changes of the C=H stretching vibration (3,000-2,800 cm-1), pectin (1,740-1,700 cm-1), amide I protein (1,700-1,600 cm-1), amide II protein (1,600-1,500 cm-1), lignin (1,515 cm-1) as well as mainly C-O-C of polysaccharides (1,300-1,100 cm-1) in the leaf epidermal and mesophyll tissues treated with SA formulations, compared to those treated with fungicide carbendazim and distilled water after the challenged inoculation with C. gloeosporioides. The results indicate that biochemical changes in cassava leaf treated with SA played an important role in the enhancement of structural and chemical defense mechanisms leading to reduced anthracnose severity.


Hydrocortisone and airflow impairment in aspirin-induced asthma.
We studied the effects of intravenous injection of hydrocortisone, as compared to its solvent, in 31 patients with aspirin-induced asthma. Mean FEV1 fell significantly 5 minutes after an intravenous bolus of 300 mg of hydrocortisone, but not after the solvent, and returned to the initial values 1 hour later. Only three of 31 patients displayed at this time clinical signs of increased impairment of airflow that resolved spontaneously. Neither in these three patients nor in another patient known already to respond with bronchoconstriction to 30 to 50 mg of hydrocortisone did intravenous injections of 20 mg of methylprednisolone, 4 mg of dexamethasone, or 4 mg of betamethasone produce any signs of bronchial obstruction. In the whole group of patients, mean FEV1 increased significantly 3 to 5 hours after hydrocortisone injection. It is hypothesized that hydrocortisone might induce early bronchoconstriction in patients with aspirin-induced asthma through its inhibitory effects on prostanoid biosynthesis. Use of intravenous steroids other than hydrocortisone is advisable in patients with aspirin-induced asthma.


Biocatalytic versatility of engineered and wild-type tyrosinase from R. solanacearum for the synthesis of 4-halocatechols.
We evaluated the kinetic characteristics of wild type (WT) and three engineered variants (RVC10, RV145, and C10_N322S) of tyrosinase from Ralstonia solanacearum and their potential as biocatalysts to produce halogenated catechols. RV145 exhibited a 3.6- to 14.5-fold improvement in catalytic efficiency (kcat/Km) with both reductions in Km and increases in kcat compared to WT, making it the best R. solanacearum tyrosinase variant towards halogenated phenols. RVC10 also exhibited increases in catalytic efficiency with all the tested phenols. A single-mutation variant (C10_N322S) exhibited the greatest improvement in kcat but lowest improvement in catalytic efficiency due to an increase in Km compared to WT. Consistent with kinetic characteristics, biotransformation experiments showed that RV145 was a superior biocatalyst in comparison to WT. To prevent through conversion of the catechol to quinone, ascorbic acid (AA) was added to the biotransformation medium in 1:2 (substrate:AA) ratio resulting in a catechol yield of > 90%. Flask experiments with 10 mM 4-iodophenol and 10 μg/mL of the RV145 enzyme yielded 9.5 mM 4-iodocatechol in the presence of 20 mM AA in 30 min. Similarly, 10 mM 4-fluorophenol was completely consumed by 20 μg/mL of RV145 enzyme and yielded 9.2 mM 4-fluorocatechol in the presence of 20 mM AA in 80 min. The biotransformation of 20 mM 4-fluorphenol was incomplete (93%) and the yield of 4-flurocatechol was 87.5%. The 4-halophenol conversion rates and product yields obtained in this study are the highest reported using tyrosinase or any other enzyme.


Altered functional connectivity networks in acallosal and socially impaired BTBR mice.
Agenesis of the corpus callosum (AgCC) is a congenital condition associated with wide-ranging emotional and social impairments often overlapping with the diagnostic criteria for autism. Mapping functional connectivity in the acallosal brain can help identify neural correlates of the deficits associated with this condition, and elucidate how congenital white matter alterations shape the topology of large-scale functional networks. By using resting-state BOLD functional magnetic resonance imaging (rsfMRI), here we show that acallosal BTBR T+tpr3tf/J (BTBR) mice, an idiopathic model of autism, exhibit impaired intra-hemispheric connectivity in fronto-cortical, but not in posterior sensory cortical areas. We also document profoundly altered subcortical and intra-hemispheric connectivity networks, with evidence of marked fronto-thalamic and striatal disconnectivity, along with aberrant spatial extension and strength of ipsilateral and local connectivity. Importantly, inter-hemispheric tracing of monosynaptic connections in the primary visual cortex using recombinant rabies virus confirmed the absence of direct homotopic pathways between posterior cortical areas of BTBR mice, suggesting a polysynaptic origin for the synchronous rsfMRI signal observed in these regions. Collectively, the observed long-range connectivity impairments recapitulate hallmark neuroimaging findings in autism, and are consistent with the behavioral phenotype of BTBR mice. In contrast to recent rsfMRI studies in high functioning AgCC individuals, the profound fronto-cortical and subcortical disconnectivity mapped suggest that compensatory mechanism may not necessarily restore the full connectional topology of the brain, resulting in residual connectivity alterations that serve as plausible substrates for the cognitive and emotional deficits often associated with AgCC.


Proteoglycans synthesized by human polymorphonuclear leucocytes in vitro.
Polymorphonuclear leucocytes (PMN) were assessed in vitro for their ability to synthesize and secrete proteoglycans. The PMN were isolated from human peripheral blood and were found to contain less than 5% mononuclear cells. Following 24 h incubation in the presence of (35S)-sulfate, significant quantities of 35S-labelled macromolecules were detected both within the culture medium and cells. Although the PMN preparations contained some platelets (approximately five platelets:one PMN), culture of platelets alone did not result in the detection of any 35S-labelled macromolecules in either the medium or platelets. 35S/3H-labelled macromolecules from the PMN cultures were identified as proteoglycans on the basis of their degradation by papain, alkaline sodium borohydride, chondroitinase ACII, chondroitinase ABC and nitrous acid. The labelled proteoglycans isolated from the medium and cells eluted from Sepharose CL-4B with a Kav of 0.63; this indicated a small size compared with many other proteoglycans. The glycosaminoglycans associated with the proteoglycans were identified as heparan sulfate, chondroitin sulfate and dermatan sulfate, with chondroitin sulfate being the principal component. The average molecular weight of the glycosaminoglycans was determined to be 16,000. Therefore, the data from this study demonstrate the ability of human PMN to synthesize and secrete proteoglycans in vitro which appear to differ from those synthesized by mesenchymal cells with respect to molecular size and glycosaminoglycan composition.


Identification of failure type in corroded pipelines: a bayesian probabilistic approach.
Spillover of hazardous materials from transport pipelines can lead to catastrophic events with serious and dangerous environmental impact, potential fire events and human fatalities. The problem is more serious for large pipelines when the construction material is under environmental corrosion conditions, as in the petroleum and gas industries. In this way, predictive models can provide a suitable framework for risk evaluation, maintenance policies and substitution procedure design that should be oriented to reduce increased hazards. This work proposes a bayesian probabilistic approach to identify and predict the type of failure (leakage or rupture) for steel pipelines under realistic corroding conditions. In the first step of the modeling process, the mechanical performance of the pipe is considered for establishing conditions under which either leakage or rupture failure can occur. In the second step, experimental burst tests are used to introduce a mean probabilistic boundary defining a region where the type of failure is uncertain. In the boundary vicinity, the failure discrimination is carried out with a probabilistic model where the events are considered as random variables. In turn, the model parameters are estimated with available experimental data and contrasted with a real catastrophic event, showing good discrimination capacity. The results are discussed in terms of policies oriented to inspection and maintenance of large-size pipelines in the oil and gas industry.


Clocinnamox dose-dependently antagonizes morphine-analgesia and [3H]DAMGO binding in rats.
Clocinnamox is a long-lasting, nonequilibrium, mu-opioid receptor antagonist in mice and monkeys. The present studies examined the in vivo and ex vivo effects of clocinnamox in rats. Under control conditions, morphine dose-dependently increased tail-withdrawal latencies from 50 degrees C water, with a mean ED50 of 7.3 +/- 1.1 mg/kg. Clocinnamox antagonized the antinociceptive effects of morphine. 1.0 mg/kg clocinnamox displaced the morphine dose-response curve 4-fold to the right of the control curve and 10 mg/kg clocinnamox eliminated morphine's antinociceptive effects at doses up to 1000 mg/kg for at least seven days. There was a gradual recovery of the antinociceptive response to morphine; however, the morphine dose-response curve did not return to its original position by five weeks after 10 mg/kg clocinnamox. Whole brain membranes were prepared from separate groups of rats for determination of binding parameters of [3H][D-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO). Clocinnamox dose-dependently decreased [3H]DAMGO binding ex vivo and the decreased binding was a result of changes in Bmax. The control Bmax for [3H]DAMGO was 234 +/- 8 fmol/mg protein; in membranes prepared from rats pretreated with 10 mg/kg clocinnamox, the Bmax value for [3H]DAMGO was 54 +/- 2 fmol/mg protein. The Bmax values for [3H]DAMGO binding after an injection of 10 mg/kg clocinnamox returned towards control values gradually, four weeks after clocinnamox the Bmax was 178 +/- 10 fmol/mg protein. These results suggest that clocinnamox is a long-lasting, nonequilibrium mu-opioid receptor antagonist in rats.


Effects of platelet rich plasma (PRP) on human gingival fibroblast, osteoblast and periodontal ligament cell behaviour.
The use of platelet rich plasma (PRP, GLO) has been used as an adjunct to various regenerative dental procedures. The aim of the present study was to characterize the influence of PRP on human gingival fibroblasts, periodontal ligament (PDL) cells and osteoblast cell behavior in vitro. Human gingival fibroblasts, PDL cells and osteoblasts were cultured with conditioned media from PRP and investigated for cell migration, proliferation and collagen1 (COL1) immunostaining. Furthermore, gingival fibroblasts were tested for genes encoding TGF-β, PDGF and COL1a whereas PDL cells and osteoblasts were additionally tested for alkaline phosphatase (ALP) activity, alizarin red staining and mRNA levels of osteoblast differentiation markers including Runx2, COL1a2, ALP and osteocalcin (OCN). It was first found that PRP significantly increased cell migration of all cells up to 4 fold. Furthermore, PRP increased cell proliferation at 3 and 5 days of gingival fibroblasts, and at 3 days for PDL cells, whereas no effect was observed on osteoblasts. Gingival fibroblasts cultured with PRP increased TGF-β, PDGF-B and COL1 mRNA levels at 7 days and further increased over 3-fold COL1 staining at 14 days. PDL cells cultured with PRP increased Runx2 mRNA levels but significantly down-regulated OCN mRNA levels at 3 days. No differences in COL1 staining or ALP staining were observed in PDL cells. Furthermore, PRP decreased mineralization of PDL cells at 14 days post seeding as assessed by alizarin red staining. In osteoblasts, PRP increased COL1 staining at 14 days, increased COL1 and ALP at 3 days, as well as increased ALP staining at 14 days. No significant differences were observed for alizarin red staining of osteoblasts following culture with PRP. The results demonstrate that PRP promoted gingival fibroblast migration, proliferation and mRNA expression of pro-wound healing molecules. While PRP induced PDL cells and osteoblast migration and proliferation, it tended to have little to no effect on osteoblast differentiation. Therefore, while the effects seem to favor soft tissue regeneration, the additional effects of PRP on hard tissue formation of PDL cells and osteoblasts could not be fully confirmed in the present in vitro culture system.


New synthesis of PNA-3'DNA linker monomers, useful building blocks to obtain PNA/DNA chimeras.
A new synthetic strategy to get the PNA-3'DNA linker with the monomethoxytrityl (Mmt) group as temporary protection of the backbone to be used for the synthesis of PNA/DNA chimeras was employed and a convenient strategy to obtain Mmt PNA monomers was developed. The synthetic strategies take advantage of the introduction of the acid-labile Mmt-protecting group in the first step.


Preparing nurses and midwives to provide perinatal bereavement care: A systematic scoping review.
To provide a comprehensive cross-sectional overview of published studies on perinatal bereavement care education programmes developed and tested with nurses and midwives. A scoping review following the Arksey and Malley's framework. Eight electronic databases were searched in December 2020 without restriction on language and publication date: PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO, Web of Science, Scopus and ProQuest. All identified studies were reviewed by two reviewers based on the article title and abstract screening. Full-text articles were assessed according to the inclusion criteria. Original studies that reported on perinatal bereavement care education for nursing and midwifery students or clinical nurses and midwives were included. Eighteen studies out of 817 articles were included. Perinatal bereavement care knowledge and skills, improvement in clinical skills in abortion care and psychological support for nurses and midwives are three core elements of the education content. Workshops and debriefing are the most frequently used formats. The duration mostly ranges from a half day to 3 days. Knowledge, confidence, satisfaction and relevant psychological variables such as posttraumatic stress symptoms are frequently used to evaluate the education programme's effectiveness. Most studies chose to use self-designed questionnaires as measurement tools. Nurses and midwives reported both positive experiences and improvement suggestions for perinatal bereavement care education programmes. This scoping review highlights the benefits of implementing education programmes for preparing nurses and midwives for perinatal bereavement care in the context of universities and hospitals. Longitudinal randomized controlled trials or quasi-experiments could further investigate the effectiveness of a more enhanced perinatal bereavement care education programme with a longer intervention time using valid and reliable evaluation tools.


Study on the antigens and antibodies of Mur and Mia blood groups in southern China.
The frequency of Mur and Mia blood group antigens in Asian population is much higher than that in Caucasian population. However, due to the scarcity and high price of commercial detection reagents, there are few studies on antigen and antibody detection and comparative analysis in large samples. To study the occurrence frequency, antigen correlation and antibody properties of Mur and Mia antigens and their corresponding antibodies in southern China. Mur and Mia antigens and antibodies in local blood donors and patients were detected by routine serological microplate method. Statistical methods were used to calculate the incidence of two antigens and antibodies and analyze their correlation. Among blood donors, the positive rates of Mur and Mia antigens were 6.4 % and 6.5 % respectively, with no significant difference (P > 0.05). In this region, the incidence of anti-"Mur" and anti-"Mia" was 0.65 % and 0.45 % respectively. But significant difference existed between blood donors and patients (P < 0.05). Among the anti-"Mur" and anti-"Mia" positive patients, most of the antibodies were IgM or IgM + IgG mixed type and had saline activity. Mur and Mia antigens and their corresponding antibodies have a high frequency in the population of southern China. In the routine clinical detection of irregular antibodies, Mur or Mia positive (GP.Mur) should be added to screen erythrocytes. Moreover, given the high correlation between Mur and Mia antigens expression on red blood cells, using monoclonal antibodies against Mia could predict the presence of Mur antigen.


[Effect of benz(a)pyrene on a monolayer culture of normal and malignant mouse liver cells].
Both the cells of monolayer culture of mouse embryonic liver and that of highly malignant hepatoma 22A transplanted for 20 years actively metabolized the carcinogenic hydrocarbon benz(a)pyrene and were highly sensitive to iits toxic action. Since hepatic tissue was resistant in vivo to carcinogenic carbohydrates it is suggested that the resistance depended on factors acting at the organ or the organism but not as the cellular level. The mechanism of retention of hepatoma 22A sensitivity to the toxic action of benz(a)pyrene is also discussed.


Effect of strut thickness on neointimal atherosclerotic change over an extended follow-up period (≥ 4 years) after bare-metal stent implantation: intracoronary optical coherence tomography examination.
Neointima inside the bare-metal stents (BMSs) can transform into atherosclerotic tissue during an extended follow-up because of a persistent inflammatory reaction to the metal. We sought to investigate whether strut thickness may impact on the atherosclerotic change in neointima 4 years or more after BMS implantation using optical coherence tomography. Forty-six stented lesions of 41 patients with BMS ≥ 4 years after implantation who underwent optical coherence tomography were enrolled in the study. The strut was defined as thin when less than 100 μm and thick when ≥ 100 μm. According to these criteria, stents were divided into 2 groups (thin strut n = 19, thick strut n = 27). Neointimal tissue was categorized into normal neointima, characterized by a signal-rich band without signal attenuation, or lipid-laden intima, with marked signal attenuation and a diffuse border. Intimal disruption, thrombus, and neovascularization were also evaluated. The mean period after implantation was 98.2 ± 25.8 months in the thin-strut group and 91.1 ± 22.8 months in the thick-strut group (P = .330). Lipid-laden intima (70% vs 32%, P = .016), thin-cap fibroatheroma-like intima (59% vs 16%, P = .0056), and intimal disruption (48% vs 16%, P = .031) were observed more frequently in the thick-strut group than in the thin-strut group, but no significant difference was observed in the frequency of thrombus. Although peristrut neovascularization was a common finding in both groups (thick vs thin 81% vs 79%, P = 1.000), the frequency of intraintima neovascularization tended to be higher in the thick-strut group (67% vs 42%, P = .135). A thinner strut thickness may have favorable effects on neointimal atherosclerotic changes after BMS implantation.


Spatiotemporal variations in the composition of algal mats in wastewater treatment ponds of tannery industry.
Wastewater Treatment Pond (WTP) is an effective remediation technology for economically developing nations. Although it's excessive organic and nutrient loads with higher water logging time triggers mixed and unprofitable microalgal mats. This may serve as a seeding source for Cyanobacterial bloom in receiving waterbodies. Since, to maintain the growth of desirable algal species in WTPs, understanding towards environmental regulation and algal mat composition is important, especially for tropical countries, like India. In this study, biological treatment pond (BTP) and outlet pond (OP), of a tannery effluent treatment plant in eastern coast of India, were chosen for surveying the algal community composition concerning ecological parameters. Nearly, both the ponds were polluted, but the diversity was lower in BTP due to its elevated nutrient content (Ammonia 173 mg L-1) and higher persistent organic matters (COD 301.7 mg L-1) than OP. Using canonical correspondence analysis, seasonal variations showed higher species abundance during early summer compared to other seasons. A total of 37 taxa forming thick algal mats were recorded. The matrix of mats was mainly composed of Cyanobacterial members such as Phormidium, Leptolyngbya, Spirulina, and Pseudanabaena, followed by diatoms, especially Amphora and Nitzschia. Diatoms commonly occurred as embedded component in the entangled matrix of blue-green algal filaments. Hierarchical cluster analysis was employed to group all these taxa based on their seasonal appearance and abundance. This year-long intensive study revealing seasonal algal mat composition patterns in these WTPs will ultimately safeguard the livelihood and security of adjoining localities through proper site-specific pollution control.


Study on the Treatment of ITP Mice with IVIG Sourced from Distinct Sex-Special Plasma (DSP-IVIG).
Intravenous immunoglobulin (IVIG) is a first-line drug prepared from human plasma for the treatment of autoimmune diseases (AIDs), especially immune thrombocytopenia (ITP). Significant differences exist in protein types and expression levels between male and female plasma, and the prevalence of autoimmune diseases varies between sexes. The present study seeks to explore potential variations in IVIG sourced from distinct sex-specific plasma (DSP-IVIG), including IVIG sourced from female plasma (F-IVIG), IVIG sourced from male plasma (M-IVIG), and IVIG sourced from a blend of male and female plasma (Mix-IVIG). To address this question, we used an ITP mouse model and a monocyte-macrophage inflammation model treated with DSP IVIG. The analysis of proteomics in mice suggested that the pathogenesis and treatment of ITP may involve FcγRs mediated phagocytosis, apoptosis, Th17, cytokines, chemokines, and more. Key indicators, including the mouse spleen index, CD16+ macrophages, M1, M2, IL-6, IL-27, and IL-13, all indicated that the efficacy in improving ITP was highest for M-IVIG. Subsequent cell experiments revealed that M-IVIG exhibited a more potent ability to inhibit monocyte phagocytosis. It induced more necrotic M2 cells and fewer viable M2, resulting in weaker M2 phagocytosis. M-IVIG also demonstrated superiority in the downregulation of surface makers CD36, CD68, and CD16 on M1 macrophages, a weaker capacity to activate complement, and a stronger binding ability to FcγRs on the THP-1 surface. In summary, DSP-IVIG effectively mitigated inflammation in ITP mice and monocytes and macrophages. However, M-IVIG exhibited advantages in improving the spleen index, regulating the number and typing of M1 and M2 macrophages, and inhibiting macrophage-mediated inflammation compared to F-IVIG and Mix-IVIG.


Scores for preoperative risk evaluation of postoperative mortality.
Preoperative risk evaluation scores are used prior to surgery to predict perioperative risks. They are also a useful tool to help clinicians communicate the risk-benefit balance of the procedure to patients. This review identifies and assesses the existing preoperative risk evaluation scores (also called prediction scores) of postoperative mortality in all types of surgery (emergency or scheduled) in an adult population. We systematically identified studies using the MEDLINE, Ovid EMBASE and Cochrane databases and published studies reporting the development and validation of preoperative predictive scores of postoperative mortality. We assessed usability, the level of evidence of the studies performed for external validation, and the predictive accuracy of the scores identified. We found 26 scores described within 60 different reports. The most suitable scores with the highest validity identified for anaesthesia practice were the Preoperative Score to Predict Postoperative Mortality (POSPOM), the Universal ACS NSQIP surgical risk calculator (ACS-NSQUIP), the Clinical Frailty Scale (CFS) and the American Society of Anesthesiologists Physical Status (ASA-PS) classification system. While other scores identified in this review could also be endorsed, their level of validity and generalizability to the general surgical population should be carefully considered.


Functional foods.
The concept of functional foods containing specific physiologically active components originated in Japan as a means of improving the health of the nation and thus, reducing the drain on the economy caused by escalating health costs. Some aspects of the Japanese physiologically functional foods programme will be discussed. There is a growing interest in this area from food manufacturers both in Europe and the USA, and a few functional food products are appearing on the market. It is likely that there will be competition between the food industry and the pharmaceutical industry in the grey area of overlapping interest. The regulatory aspects concerning functional foods have yet to be satisfactorily resolved, both in Europe and the USA, but consumer pressure promises to accelerate the incorporation of the concept of functional foods into western food regulations. There are early indications that in Europe, consumer perception of the benefits of functional foods compared to normal foods will not be the same as in Japan, nor will the consumer be as receptive. Some consumer groups question the necessity of such foods from a health point of view and see the concept rather as a marketing tool. We are likely to see a number of foods for which anti-carcinogenic and other well defined properties are likely to be claimed. The active components will be present in the raw materials or produced or enhanced by the manufacturing process.


Hyaluronic acid coated spinel ferrite for combination of chemo and photodynamic therapy: Green synthesis, characterization, and in vitro and in vivo biocompatibility study.
In this project, different photosensitizers were prepared using different ratios of nickel, manganese, and iron. Then, multiple analysis were performed to evaluate their efficiency, and the most suitable one was used to be coated by hyaluronic acid to improve the nano-platform's biocompatibility and target ability. Moreover, another chemical targeting agent (riboflavin) was used to further improve the target ability of the prepared nano-platform. Different spectroscopies and thermal analysis were used to determine the physical and chemical characteristics of the prepared nano-platform. Also, in order to determine the biocompatibility of the nano-platform, in vitro and in vivo tests such as blood hemolysis, blood aggregation and lethal dose were performed. Then, an anti-cancer agent (curcumin) was loaded on the selected nano-platform to makes us able utilizing the synergistic effect of chemotherapy and photodynamic therapy simultaneously. Finally, the cell cytotoxicity results showed that the prepared nano-platform had a great anti-cancer potential which can make it a great candidate as a dual photo and chemo therapy agent for treatment of breast cancers.


High-density lipoprotein cholesterol is positively associated with hypertension in apparently healthy Japanese men and women.
Among five components of metabolic syndrome, high-density lipoprotein (HDL) cholesterol is unique because it is not significantly associated with blood pressure. This study looks at cross-sectional relationships between HDL cholesterol and hypertension using medical check-up data from 1803 apparently healthy Japanese men aged 49.9 +/- 9.0 years, and 1150 Japanese women aged 49.5 +/- 9.0 years. Pearson's correlation coefficients between systolic blood pressure (SBP)/diastolic blood pressure (DBP) and HDL cholesterol were -0.01 (ns)/-0.01 (ns) in men and -0.04 (ns)/-0.01 (ns) in women. The standardised partial regression coefficient of HDL cholesterol for SBP/DBP (mmHg) controlling for age, body mass index (BMI), fasting plasma glucose (FPG), triglycerides, high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein (LDL) cholesterol were 0.15 (P < 0.0001)/0.15 (P < 0.0001) in men and 0.10 (P < 0.0001)/0.12 (P < 0.0001) in women. The odds ratio (OR; 95% confidence interval [CI]) of a 1 mg/dL increment of HDL cholesterol for hypertension controlling for age, BMI, FPG, triglycerides, hs-CRP, LDL cholesterol, metabolic syndrome, diabetes, exercise status, drinking status, and smoking status was 1.03 (1.02-1.04; P < 0.001) in men and 1.03 (1.01-1.05; P = 0.002) in women. Thus, HDL cholesterol was independently positively associated with hypertension in apparently healthy Japanese men and women.


Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics.
The advent of the 5HT(3) receptor antagonists (5HT(3) antagonists) in the 1990 s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase. 5HT(3) antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK(1) antagonists) belong to a new class of antiemetic agents that specifically target the NK(1) receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK(1) antagonists to dual therapy with a 5HT(3) antagonist plus dexamethasone improves the acute emesis protection by a further 10-15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20-30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled.


Genetic risk factors for venous thromboembolism.
Venous thromboembolism (VTE) is a complex disease that aggregates in families. Both acquired and genetic risk factors are important. Proper recognition and management of high-risk individuals are important. The genetic risk factors for VTE, the clinical consequences, and future perspectives are summarized. Classical thrombophilia i.e., factor V Leiden (rs6025), the prothrombin G20210A mutation (rs1799963), deficiencies of antithrombin, protein C, and protein S and the recent findings from genome wide association studies (GWAS), transcriptome-wide association studies (TWAS), genetic risk score (GRS), VTE candidate genes, expression studies, animal studies, studies using next generation sequencing, pathway analysis, and clinical implications are discussed. Screening of inherited thrombophilia should be performed in special cases. Identification of strong risk variants might affect the management. The increasing number of genetic risk variants is likely to change management of VTE.


Maternal ABO groups and the sex ratio of live births.
The sex ratio of 67,205 single, live births was significantly associated with maternal ABO, but not Rh, types. The proportion of males was highest among children of AB mothers in both the Rh+ and Rh- subpopulations, corroborating previous data. The findings are discussed with relation to earlier reports and possible mechanisms.


Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study.
The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis-α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. We included 5468 biologic-naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25-p75) follow-up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16-3.21), 1.93 (1.05-3.34), 1.94 (1.09-3.32), 1.92 (0.93-3.45) and 1.43 (0.84-2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41-2.22); ustekinumab vs. adalimumab: 0.81 (0.30-2.17); etanercept vs. adalimumab: 0.81 (0.28-2.30)] and methotrexate against adalimumab [1.05 (0.34-3.28)]. In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow-up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.


Early-onset bipolar disorder: how about visual-spatial skills and executive functions?
Early-onset bipolar disorder is an impairing condition that is strongly associated with genetic inheritance. Neurocognitive deficits are core traits of this disorder which seem to be present in both young and adult forms. Deficits in verbal memory and attention are persistent within euthymic phases in bipolar adults, adolescents, and children. In younger samples, including type I or II and not otherwise specified patients, executive functions are not widely impaired and the existence of visual-spatial deficits remains unclear. The main aim of this study was to compare the neurocognitive performance in young stabilized type I or II bipolar patients and healthy controls. Fifteen medicated adolescents with bipolar disorder and 15 healthy adolescents, matched in age and gender, were compared on visual-spatial skills (reasoning, memory, visual-motor accuracy) and executive functioning (attention and working memory, set-shifting, inhibition) using t-tests and MANCOVA. Correcting for verbal competence, MANCOVA showed that patients performed significantly worse than controls in letters and numbers sequencing (P = 0.003), copy (P < 0.001) and immediate recall (P = 0.007) of the Rey Complex Figure Test, interference of the Stroop Color-Word Test (P = 0.007) and non-perseverative errors on the Wisconsin Card Sorting Test (P = 0.038). Impaired cognitive performance was found in young bipolar patients in working memory, visual-motor skills, and inhibitory control.


Performance standards improve American Board of Surgery In-Training Examination scores.
Although several studies have evaluated factors affecting American Board of Surgery In-Training Examination (ABSITE) performance, none has examined the impact of setting a minimally acceptable standard. It was hypothesized that establishing such a criterion would improve ABSITE scores. An expectation for residents to score at the 35th percentile or higher was established in 1996. The proportion of test scores above or below the 35th and 50th percentiles for the time periods before and after institution of the standard were compared using Fisher's exact test. The subsequent performance of residents scoring below the 35th percentile was analyzed for the 2 time periods. After the institution of the standard, the proportion of scores below the 35th percentile decreased from 46.7% to 21.9% (p = 0.0005). Similarly, the proportion of scores at or above the national average increased from 42.1% to 65.6% (p = 0.0005). After establishing the standard, fewer residents continued to have scores below the criterion in subsequent years. Establishing a performance criterion improved ABSITE scores. The decision to institute a standard must be individualized for each program. The rationale for the standard and a plan to assist residents failing to achieve the benchmark must be communicated.


Topological characterization of the simian virus 40 transcription complex.
We have used sedimentation analysis as well as agarose gel electrophoresis to characterize the topological state of the DNA of the Simian Virus 40 (SV40) transcription complex. We found that the complex DNA contained constrained topological tension, presumably resulting from nucleosome-like structures, but no detectable unconstrained (i.e., relaxable) topological tension. These results contradict previous conclusions that the SV40 transcription complex contains only unconstrained topological tension. Our findings are also the opposite of what has been proposed to be the case for the 5S gene analyzed in Xenopus oocytes. Thus the proposal that expression from the 5S gene is associated with substantial topological tension is not valid for expression from the SV40 late gene.


Strain-dependent effects of transforming growth factor-β1 and 2 during mouse secondary palate development.
Cleft palate is a common birth defect affecting 1 in 700 births. Transforming growth factor-βs (TGF-βs) are important signaling molecules, and their functions in murine palate development have received great attention. TGF-β3 is expressed exclusively in palatal epithelial cells and mediates epithelial fusion, whereas the importance of TGF-β1 and 2 in palate have not yet been demonstrated in vivo, since inactivation of Tgf-β1 or Tgf-β2 genes in mice did not reveal significant palate defects. We hypothesized that TGF-β1 and TGF-β2 can compensate each other during palate formation. To test this, we generated Tgf-β1 and Tgf-β2 compound mutant mice and found that approximately 40% of [Tgf-β1(+/-); Tgf-β2(-/-)] compound mutant embryos display cleft palate on C57 background. In addition, 26% of Tgf-β2(-/-) embryos on 129 background, but not in C57 or Black Swiss, displayed cleft palate. TGF-β1 and 2 functions are required for murine palate development in strain-dependent manner.


Narrative Review: Peripheral Arterial Disease in Patients with Hyperuricemia and Gout.
To discuss what is currently known about the association and potential mechanistic interactions of hyperuricemia and gout with peripheral arterial disease (PAD). Gout patients are at increased risk for coronary artery disease, but less is known about their risk for PAD. Studies suggest that the presence of gout and hyperuricemia are associated with PAD independent of known established risk factors. Moreover, higher SU was found to be associated with greater odds of having PAD and was independently associated with decreased absolute claudication distance. Urate's role in free radical formation, platelet aggregation, vascular smooth muscle proliferation, and impaired endothelial vasodilation may promote atherosclerotic progression. Studies suggest that patients with hyperuricemia or gout are at higher risk for developing PAD. Evidence is stronger for the relationship between elevated SU and PAD than for gout and PAD, but more data is needed. Whether elevated SU serves as a marker or cause of PAD remains to be investigated.


Subintimal angioplasty in the treatment of patients with intermittent claudication: long term results.
Reporting the long-term results of subintimal angioplasty (SA) in patients with intermittent claudication (IC). A prospective study. One hundred and sixteen SA procedures were performed in 104 patients, from February 1997 to January 2000. This is a prospective study of patients treated for IC with infrainguinal SA. Primary assisted patency rates were calculated, also on intention to treat basis. Univariate and multivariate Cox regression tests were used to assess whether patency was correlated with co-morbidities, run-off or occlusion length. There was no early mortality. Technical success was achieved in 101 cases (87%). Primary assisted patency rates on intention to treat basis (116 cases) at 6, 12, 36 and 60 months were 69, 62, 57 and 54%, respectively. For successfully recanalized patients (101 cases) these respective numbers are 79, 70, 66 and 64%. Length of occlusion, age and male gender were independent risk factors for reocclusion. The satisfactory results obtained in the present study are probably due to two main factors. First, the three participating radiologist are highly skilled and experienced. Secondly, a conscientious surveillance was adhered to, so that restenoses could be diagnosed and treated early. SA is a relevant alternative to bypass surgery in patients with disabling IC due to long femoro-popliteal occlusions. It is far less traumatic than conventional vascular reconstructions, complications are few and not serious. Very importantly, SA never interfered with later successful vascular surgery. Therefore, we have adopted SA as the primary treatment for patients with IC when medical treatment alone has not been satisfactory.


CD24 regulates stemness and the epithelial to mesenchymal transition through modulation of Notch1 mRNA stability by p38MAPK.
We report here that CD24 knockdown resulted in decreased expression of Notch1 in MCF-7 cells. CD24-downstream p38MAPK was shown to regulate Notch1 at the level of mRNA stability. We also found that CD24-mediated cell migration, invasion, mammosphere formation, and drug resistance was regulated by its downstream target Notch1. Together, our results indicate that CD24 may regulate the epithelial to mesenchymal transition and stemness through Notch1 signaling in breast cancer cells.


Preference for and understanding of graphs presenting health risk information. The role of age, health literacy, numeracy and graph literacy.
To investigate 1) younger (< 65) and older (> 65) adults' preference for and understanding of graph formats presenting risk information, and 2) the contribution of age, health literacy, numeracy and graph literacy in understanding information. To assess preferences, participants (n = 219 < 65 and n = 227>65) were exposed to a storyboard presenting six types of graphs. Understanding (verbatim and gist knowledge) was assessed in an experiment using a 6 (graphs: clock, bar, sparkplug, table, pie vs pictograph) by 2 (age: younger [<65] vs older [>65]) between-subjects design. Most participants preferred clock, pie or bar chart. Pie was not well understood by both younger and older people, and clock not by older people. Bar was fairly well understood in both groups. Table yielded high knowledge scores, particularly in the older group. Lower age, higher numeracy and higher graph literacy contributed to higher verbatim knowledge scores. Higher health literacy and graph literacy were associated with higher gist knowledge. Although not the preferred format, tables are best understood by older adults. Graph literacy skills are essential for both verbatim and gist understanding, and are important to take into account when developing risk information.


Mouse model of the adipose organ: the heterogeneous anatomical characteristics.
Adipose tissue plays a pivotal role in energy storage, hormone secretion, and temperature control. Mammalian adipose tissue is largely divided into white adipose tissue and brown adipose tissue, although recent studies have discovered the existence of beige adipocytes. Adipose tissues are widespread over the whole body and each location shows distinctive metabolic features. Mice are used as a representative experimental model system in metabolic studies due to their numerous advantages. Importantly, the adipose tissues of experimental animals and humans are not perfectly matched, and each adipose tissue exhibits both similar and specific characteristics. Nevertheless, the diversity and characteristics of mouse adipose tissue have not yet been comprehensively summarized. This review summarizes diverse information about the different types of adipose tissue being studied in mouse models. The types and characteristics of adipocytes were described, and each adipose tissue was classified by type, and features such as its distribution, origin, differences from humans, and metabolic characteristics were described. In particular, the distribution of widely studied adipose tissues was illustrated so that researchers can comprehensively grasp its location. Also, the adipose tissues misused or confusingly used among researchers were described. This review will provide researchers with comprehensive information and cautions needed to study adipose tissues in mouse models.


Preliminary studies on cholinergic control of pituitary gonadotrophin secretion in the ewe.
Administration of neostigmine, a cholinomimetic, to anoestrous ewes diminished the increase in jugular plasma luteinising hormone and follicle-stimulating hormone induced by oestradiol. Intravenous injection of atropine had no effect on the gonadotrophin surge.


Distinct PGE2-responder and non-responder phenotypes in human mast cell populations: "all or nothing" enhancement of antigen-dependent mediator release.
Reports indicate that prostaglandin (PG)E(2) markedly enhances antigen-mediated degranulation in mouse bone marrow-derived mast cells (BMMCs) but not in human mast cells (HuMCs). We have examined the underlying mechanism(s) for this disparity in HuMCs derived from the peripheral blood of multiple donors in addition to mouse BMMCs. HuMCs from half of these donors failed to respond to PGE(2) and the PGE(2) EP3 receptor agonist, sulprostone. However, HuMCs from the remaining donors and the LAD2 human MC line responded to PGE(2) and sulprostone with marked enhancement of antigen-mediated degranulation and IL-8 production in a similar manner to that observed in mouse BMMCs. The EP2 agonist, butaprost, failed to modulate antigen-mediated responses in any type of MCs. These distinct phenotypes could not be explained by differences in EP2 or EP3 expression nor by differences in the ability of PGE(2) to elevate levels of cAMP, a signal recognized to down-regulate mast cell activation. Moreover, both responder and non-responder HuMC populations exhibited similar activation of phosphatidylinositol 3-kinase, and MAP kinases. However, translocation of PLCγ(1) to the cell membrane and the associated calcium signal were enhanced only in the responder HuMC population indicating that the link between EP3 and PLCγ is impaired in the non-responder HuMCs. These data provide a cautionary note for the translating of observations in the mouse to human mast cell-dependent disorders, but may also provide a basis for examining the effects of co-activating receptors in patients susceptible to allergic conditions.


Survey data on joint cropland management among agri-food cooperatives in Mediterranean Spanish Regions.
This dataset presents data collected from joint cropland management practices survey in agri-food cooperatives of Mediterranean Spanish Regions. The objective was to examine to what extent cooperatives offer joint services, including joint management or integral exploitation of smallholdings, for the incorporation of new professionals. Data collection was conducted to five agri-food organizations: three agri-food cooperatives federations -Castilla-La Mancha, Comunitat Valenciana, and Murcia-, two second-degree agri-food cooperatives -Anecoop and Unió Nuts-, all of them located in Mediterranean Spanish Regions. A total of 1.168 survey questionnaires were distributed between July 2020 and February 2021 across five organizations through the snowball sampling method. Data from 112 collected questionnaires were correctly answered, but 106 were selected for analysis. The dataset includes socioeconomic data, productive information, and innovative characteristics from agri-food cooperatives surveyed, all in order to be able to examine the relationship between those factors and joint cropland management practices they carry on.


Stigmas and childhood traumas associated with psychological help-seeking in suicide attempted individuals.
The aim was to investigate the possible associations of suicide attempt with childhood trauma, social support, psychological support seeking, stigmatizations. The study was case-control study and included 100 participants (50 suicide, 50 controls). BDI, BAI scores were higher in the patient (p < 0.001). While scores of all-subscales of Childhood-Trauma-Questionnaire were higher (p < 0.05) in the patients, scores of Perceived-Social-Support were lower (p < 0.001). Repeating suicide attempts has higher Stigma-Scale-for-Receiving-Psychological-Help scores than the patients who attempted to the first time (p = 0.045). Suicide is relationship with more childhood traumas, less social support. Repeating suicide attempts, individuals felt public stigma for receiving psychological help.


Assessing Older Adults' Decision-Making Capacity for Independent Living: Practice Tensions and Complexities.
Decision-making capacity (DMC) is a salient issue due to increasing ageing populations and associated dementia-related diseases. Legislative and policy developments emphasise older adults' rights to participate in decision-making. Fifty-two occupational therapists working with older adults from a range of practice settings in Ireland participated in focus groups to discuss their contribution to multidisciplinary assessments of older adult's DMC for independent living. Findings indicate lack of shared understanding of DMC and conflicting philosophies of practice and highlight the need for a comprehensive and multidisciplinary approach. Findings also highlight that older people are often excluded from care-planning, and independent living options are determined by availability of community services rather than their preferences. Future research will attempt to inform practice in assessing and supporting older adults' DMC for independent living.


Computerized Cognitive and Skills Training in Older People With Mild Cognitive Impairment: Using Ecological Momentary Assessment to Index Treatment-Related Changes in Real-World Performance of Technology-Dependent Functional Tasks.
Cognitive and functional skills training improves skills and cognitive test performance, but the true test of efficacy is real-world transfer. We trained participants with mild cognitive impairment (MCI) or normal cognition (NC) for up to 12 weeks on six technology-related skills using remote computerized functional skills assessment and training (FUNSAT) software. Using ecological momentary assessment (EMA), we measured real-world performance of the technology-related skills over 6 months and related EMA-identified changes in performance to training gains. Randomized clinical trial with post-training follow-up. A total of 14 Community centers in New York City and Miami. Older adults with normal cognition (n = 72) or well-defined MCI (n = 92), ranging in age from 60 to 90, primarily female, and racially and ethnically diverse. Computerized cognitive and skills training. EMA surveys measuring trained and untrained functional skills 3 or more days per week for 6 months and training gains from baseline to end of training. Training gains in completion times across all 6 tasks were significant (p <0.001) for both samples, with effect sizes more than 1.0 SD for all tasks. EMA surveys detected increases in performance for both trained (p <0.03) and untrained (p <0.001) technology-related skills for both samples. Training gains in completion times predicted increases in performance of both trained and untrained technology-related skills (all p <0.001). Computerized training produces increases in real-world performance of important technology-related skills. These gains continued after the end of training, with greater gains in MCI participants.


Analysis of SOD1 mutations in a Chinese population with amyotrophic lateral sclerosis: a case-control study and literature review.
Although the copper/zinc superoxide dismutase-1 (SOD1) gene has been identified in both familial ALS (FALS) and sporadic ALS (SALS), it has rarely been studied in Chinese patients with ALS, and there are few studies with large samples. This study sought to assess the prevalence of SOD1 mutations in Chinese ALS patients. We screened a cohort of 499 ALS patients (487 SALS and 12 FALS) from the Department of Neurology at the West China Hospital of Sichuan University and analyzed all coding exons of SOD1 by Sanger sequencing. In addition, we reviewed the mutation frequencies of common ALS causative genes in Chinese populations. Eight missense mutations in SOD1 were found in 8 ALS individuals: two novel mutations (p.G73D and p.V120F) and six previously reported mutations. The frequencies of SOD1 mutations were 1.03% (5/487) in SALS and 25% (3/12) in FALS from Southwest China. A literature review indicated that the mutation rates of major ALS causative genes were 53.55% in FALS and 6.29% in SALS. In Chinese SALS and FALS, the highest mutation frequency was in the SOD1 gene. Our results suggest that SOD1 mutation is the most common cause of ALS in Chinese populations and that the mutation spectrum of ALS varies among different ethnic populations.


Fibroblast and Myofibroblast Subtypes: Single Cell Sequencing.
The stroma constitutes the structural framework of an organ and plays crucial roles in health and following organ damage. The major player of the stroma with respect to extracellular matrix deposition, maintenance, and remodeling is the fibroblast and its activated derivative, the myofibroblast. It has long been recognized that there is considerable variability to the fibroblast phenotype. The recent advent of new single cell "omics" technologies has revolutionized our understanding and appreciation of cellular heterogeneity of fibroblasts been revolutionized. With these tools, the nature and defining characteristics of the cells comprising the stroma is finally being defined not just through a few markers, but by taking a wholistic look at transcriptional programs. It is now apparent that stromal cells are not only transcriptionally diverse, but also functionally, epigenetically, and spatially heterogeneous. Studying populations at single cell resolution has enabled identification of new clusters of cells with unique transcriptional signatures. Whether these clusters truly represent distinct subpopulations or different states of the same population remains to be clarified. In this chapter, we first describe a procedure for purification and preparation of a single cell suspension from tissue samples (in this case the heart) for single cell RNA sequencing. We also describe preparation of high-quality tissue sections for spatial transcriptomics. Secondly, we outline a workflow for computational analysis of single cell RNA sequencing and spatial transcriptomics data, as well as integrating them together, to explore the heterogeneity within fibroblasts/myofibroblasts and identify different subtypes and their locations in the heart.


Adrenocortical-related maturational events in the fetus.
In various organs in fetal animals, maturation is inducible by corticosteroids and delayed by hypophysectomy. A surge of corticosteroid in the fetal circulation preceding parturition may cause rapid organ maturation and enhanced viability. Since this phase of accelerated maturation is linked to the parturitional mechanisms, the changes can be termed collectively "preparation for birth." Support for similar adrenocortical-related maturation of organs in the human fetus is less clear-cut. Nevertheless, evidence is accumulating to suggest that a similar concept can be usefully applied in man.


Spatial prediction of malaria prevalence in Papua New Guinea: a comparison of Bayesian decision network and multivariate regression modelling approaches for improved accuracy in prevalence prediction.
Considerable progress towards controlling malaria has been made in Papua New Guinea through the national malaria control programme's free distribution of long-lasting insecticidal nets, improved diagnosis with rapid diagnostic tests and improved access to artemisinin combination therapy. Predictive prevalence maps can help to inform targeted interventions and monitor changes in malaria epidemiology over time as control efforts continue. This study aims to compare the predictive performance of prevalence maps generated using Bayesian decision network (BDN) models and multilevel logistic regression models (a type of generalized linear model, GLM) in terms of malaria spatial risk prediction accuracy. Multilevel logistic regression models and BDN models were developed using 2010/2011 malaria prevalence survey data collected from 77 randomly selected villages to determine associations of Plasmodium falciparum and Plasmodium vivax prevalence with precipitation, temperature, elevation, slope (terrain aspect), enhanced vegetation index and distance to the coast. Predictive performance of multilevel logistic regression and BDN models were compared by cross-validation methods. Prevalence of P. falciparum, based on results obtained from GLMs was significantly associated with precipitation during the 3 driest months of the year, June to August (β = 0.015; 95% CI = 0.01-0.03), whereas P. vivax infection was associated with elevation (β = - 0.26; 95% CI = - 0.38 to - 3.04), precipitation during the 3 driest months of the year (β = 0.01; 95% CI = - 0.01-0.02) and slope (β = 0.12; 95% CI = 0.05-0.19). Compared with GLM model performance, BDNs showed improved accuracy in prediction of the prevalence of P. falciparum (AUC = 0.49 versus 0.75, respectively) and P. vivax (AUC = 0.56 versus 0.74, respectively) on cross-validation. BDNs provide a more flexible modelling framework than GLMs and may have a better predictive performance when developing malaria prevalence maps due to the multiple interacting factors that drive malaria prevalence in different geographical areas. When developing malaria prevalence maps, BDNs may be particularly useful in predicting prevalence where spatial variation in climate and environmental drivers of malaria transmission exists, as is the case in Papua New Guinea.


Ameliorating end-product inhibition to improve cadaverine production in engineered Escherichia coli and its application in the synthesis of bio-based diisocyanates.
Cadaverine is an important C5 platform chemical with a wide range of industrial applications. However, the cadaverine inhibition on the fermenting strain limited its industrial efficiency of the strain. In this study, we report an engineered Escherichia coli strain with high cadaverine productivity that was generated by developing a robust host coupled with metabolic engineering to mitigate cadaverine inhibition. First, a lysine producing E. coli was treated with a combination of radiation (ultraviolet and visible spectrum) and ARTP (atmospheric and room temperature plasma) mutagenesis to obtain a robust host with high cadaverine tolerance. Three mutant targets including HokD, PhnI and PuuR are identified for improved cadaverine tolerance. Further transcriptome analysis suggested that cadaverine suppressed the synthesis of ATP and lysine precursor. Accordingly, the related genes involved in glycolysis and lysine precursor, as well as cadaverine exporter was engineered to release the cadaverine inhibition. The final engineered strain was fed-batch cultured and a titer of 58.7 g/L cadaverine was achieved with a yield of 0.396 g/g, both of which were the highest level reported to date in E. coli. The bio-based cadaverine was purified to >99.6% purity, and successfully used for the synthesis of polyurethane precursor 1,5-pentamethylene diisocyanate (PDI) through the approach of carbamate decomposition.


Reading acuity in albinism: evaluation with MNREAD charts.
The MNREAD reading acuity (RA) charts use continuous-text reading to measure (1) RA, ie, the smallest size of print that the patient can resolve; (2) maximum reading speed (MRS); and (3) critical print size (CPS), ie, the smallest print that the patient can read with maximum speed. This project used the MNREAD charts to evaluate reading performance in children and adults with albinism to determine the smallest print size recommended to facilitate effortless reading. A total of 63 subjects with albinism were administered the MNREAD test to determine the critical print size for effortless reading. The subjects read continuous, high-contrast text print until they could no longer discern the words. The MRS and CPS were determined with the MNREAD protocol. Presence or absence of nystagmus and strabismus was recorded. Distance visual acuity was measured with ETDRS charts. The sample included 25 male and 38 female subjects with a median age of 16 years. Median MRS was 150 words per minute. The mean CPS was 0.84 logMAR, notably larger than the mean RA of 0.53 logMAR. The MNREAD acuity charts can be used to determine functional reading ability and critical print size for effortless reading in individuals with albinism. The amount of enlargement in print size can be used in educational and vocational recommendations to facilitate reading.


Trajectory and predictors of depression in a 12-month prospective study after the Madrid March 11 terrorist attacks.
Few longitudinal studies have examined the trajectory of and the risk factors for depression in a representative sample of the population exposed to terrorism. A 12 month prospective study was conducted among a sample of Madrid city residents after the March 11, 2004 terrorist attacks. We aimed to document the trajectories of depressive symptoms and determine the risk factors associated with these trajectories. We conducted telephone surveys among a representative sample of Madrid citizens (N = 1589) to recruit baseline respondents approximately 1 month after the March 11 terrorist attacks. Participants were re-contacted at 6 and 12 months after baseline for further telephone interviews. Findings reveal heterogeneity in the longitudinal trajectories of depression ranging from the absence of depressive symptoms over time, to transient or chronic depression. Life and recent stressors, experiencing direct exposure to the attacks, personality traits, poor physical health and other psychological disorders were principally associated with a worse trajectory of depression after this event. Consistent with a stress diathesis model, ongoing stressors and intense event exposure are key drivers of a chronic depression trajectory after a mass traumatic event.


Preconsultation compassion intervention to reduce anxiety among patients referred to a cancer center: protocol for a randomised control trial.
Patients diagnosed with cancer commonly have a high degree of anxiety during an initial oncology consultation, which may interfere with a patient's ability to retain information required to make informed treatment decisions. A previous study randomised breast cancer survivors (volunteers) to view either (a) a brief video depicting a standard initial consultation from an oncologist or (b) an identical consultation with the addition of compassionate statements from the oncologist, and found the compassionate statements reduced anxiety among the volunteers. However, while compassionate statements reduced anxiety during simulation, it is currently unknown whether watching a video containing compassionate statements from an oncologist prior to an initial oncology consultation will reduce anxiety among patients referred to a cancer centre. The aim of this randomised control trial is to test whether watching a brief video containing compassionate statements from an oncologist, compared with watching a standard introduction video, prior to an initial oncology consultation will reduce the degree of anxiety among patients referred to a cancer centre. This is a prospective, randomised controlled clinical trial at an academic cancer centre. We will enrol adult patients scheduled for an initial oncology consultation. Subjects will be randomly assigned to receive a standard introduction video or enhanced compassion video for viewing prior to the initial oncology consultation. On arrival to the cancer centre, we will measure anxiety severity using the Hospital Anxiety and Depression Scale (HADS). The HADS has two 7-item subscales (HADS anxiety and HADS depression) and is well-validated among oncology patients. We will use Wilcoxon rank-sum test to test for a difference in the HADS subscales between the two video groups. The Cooper University Hospital Institutional Review Board approved this study. The results from this randomised control trial will be submitted for publication to a peer-reviewed journal. NCT04503681.