Diastolic function and its association with diabetes, hypertension and age in an outpatient population with normal stress echocardiography findings.
Diastolic dysfunction can be caused by hypertension or diabetes mellitus, and it is also often found with increasing age. In a given patient, the cause of diastolic dysfunction is therefore not always obvious. We sought to study the interplay of these risk factors for diastolic dysfunction in an outpatient population with a low likelihood of ischemic heart disease. Consecutive patients referred for stress echocardiography were included retrospectively. Exclusion criteria included pathological stress response, atrial arrhythmia, left ventricular ejection fraction < 55%, and more than mild valvular disease. Standard diastolic parameters were recorded in all patients. In a subset of patients, mechanistic analysis of early filling was performed using the parameterized diastolic filling (PDF) method. We included 726 patients (median [interquartile range] age 56 (44-65) years, 57% male). The prevalence of diabetes and hypertension was 43 and 49%, respectively. In multiple linear regression modeling, the presence of diabetes, hypertension, sex and increasing age explained a moderate amount of the variance in e' velocities, E/A ratio and E/e' (R2 = 0.31-0.48, p < 0.001), and a low amount of the variance in left atrial volume index (LAVI) and the PDF parameters (n = 446, R2 = 0.05-0.17, p < 0.001). Sex was only related to LAVI and E/e' for the conventional parameters (beta - 0.94, p = 0.04, and beta - 0.91, p < 0.001, respectively). Diabetes, hypertension, increasing age, and to a lesser extent sex, explain a moderate amount of the variance in conventional diastolic parameters related to myocardial tissue velocities and E/A ratio in a healthy outpatient population. The effect of these risk factors was substantially less pronounced on left atrial volume index and the PDF parameters.


Clinical features and surgical selection in colitis-associated colorectal cancer with ulcerative colitis.
The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA. Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively. The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2-590) in the cancer/dysplasia group and 48 (1-580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7-99.6) kg: 49.9 (20.3-85.2) kg), body mass index (21.0 (13.9-32.5) kg/m2: 18.3 (11.4-34.1)kg/m2), serum albumin level (4.3 (2.7-5.0)g/dl: 3.4 (1.4-5.2)g/dl) and prognostic nutrition index (49.2 (33.2-61.2): 40.9 (17.4-61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01). UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status.


Subgingival microbial profiles of generalized aggressive and chronic periodontal diseases.
The aim of this study was to distinguish between generalized aggressive (GAgP) and chronic periodontitis (CP) based on the subgingival microbial profiles predominant in these diseases. Two-hundred and sixty subjects, 75 with GAgP and 185 with CP were recruited. Full-mouth clinical measurements were recorded. Individual subgingival plaque samples were taken from 7 sites per subject and analyzed for the prevalence and levels of 51 species by chequerboard. Differences between groups were examined by the Mann-Whitney test. Associations between bacterial species and GAgP were examined by logistic regression analysis. Actinomyces gerensceriae, Actinomyces israelli, Eubacterium nodatum and Propionibacterium acnes were detected in significantly greater counts in GAgP, whereas Capnocytophaga ochracea, Fusobacterium periodonticum, Staphylococcus aureus and Veillonella parvula were more predominant in CP patients (adjusted p < 0.001). E. nodatum (at mean levels ≥4 × 10(5)) increased significantly the probability of a subject being diagnosed with GAgP than CP (OR 2.44 [0.96-6.20]), whereas P. gingivalis (OR 0.34 [0.11-0.93]) and T. denticola (OR 0.35 [0.11-0.94]) were associated with CP. Very few subgingival species differed in prevalence and/or levels between GAgP and CP in this sample population. In particular, E. nodatum was strongly related to GAgP, whereas P. gingivalis and T. denticola were associated with CP.


Malignant external otitis complicated by spinal cord compression: Case report.
Malignant otitis externa is a life-threatening infectious pathology that occurs mainly in diabetic patients; in a picture of otorrhea, with facial paralysis. We report the case of a necrotizing otitis externa, treated with antibiotics, which was complicated a few months later by spinal compression. This is the case of a 60-year-old patient, diabetic, who presented a painful otorrhea associated to left facial palsy.The diagnosis of necrotizing otitis externa was retained after performing a CT scan of the temporal bone.6 months after medical treatment, the patient became has been complicated by tetraparesis with respiratory distress. Necrotizing otitis externa is an osteitis of the base of the skull, which occurs in the diabetic patient and which starts in the external ear and spreads by contiguity after infection of the temporal bone.It represented clinically by otalgia and purulent otorrhea.The role of imaging is to confirm the involvement and to specify the extension of the lesions. CT scan is useful to evaluate the bone involvement. MRI is the examination of choice for the study of soft tissues and is essential in advanced forms.Its treatment is based on antibiotic therapy for a minimum of 6 weeks. OEM is an infection occurring in elderly and diabetic patients. Imaging allows to confirm the diagnosis and to carry out the assessment of extension; but also has a great interest in the follow-up of these immunocompromised patients who are subject to complications with insidious evolution.


Spontaneous mutations in the single TTN gene represent high tumor mutation burden.
Tumor mutation burden (TMB) is an emerging biomarker, whose calculation requires targeted sequencing of many genes. We investigated if the measurement of mutation counts within a single gene is representative of TMB. Whole-exome sequencing (WES) data from the pan-cancer cohort (n = 10,224) of TCGA, and targeted sequencing (tNGS) and TTN gene sequencing from 24 colorectal cancer samples (AMC cohort) were analyzed. TTN was identified as the most frequently mutated gene within the pan-cancer cohort, and its mutation number best correlated with TMB assessed by WES (rho = 0.917, p < 2.2e-16). Colorectal cancer was one of good candidates for the application of this diagnostic model of TTN-TMB, and the correlation coefficients were 0.936 and 0.92 for TMB by WES and TMB by tNGS, respectively. Higher than expected TTN mutation frequencies observed in other FLAGS (FrequentLy mutAted GeneS) are associated with late replication time. Diagnostic accuracy for high TMB group did not differ between TTN-TMB and TMB assessed by tNGS. Classification modeling by machine learning using TTN-TMB for MSI-H diagnosis was constructed, and the diagnostic accuracy was 0.873 by area under the curve in external validation. TTN mutation was enriched in samples possessing high immunostimulatory signatures. We suggest that the mutation load within TTN represents high TMB status.


Electrolytic lesions to the ventromedial hypothalamus abolish receptivity in female whiptail lizards, Cnemidophorus uniparens.
Lesions to the ventromedial hypothalamus (VMH) inhibit receptive sexual behavior in the whiptail lizard, Cnemidophorus uniparens, an all-female species. All lesions to the VMH that effectively abolished receptivity specifically damaged the dorsal lateral VMH, an area containing high concentrations of estrogen receptor in this species. These data further emphasize conservation of the VMH as a brain area critical to the expression of female sexual behavior in vertebrates.


Ulcerative colitis progression: a retrospective analysis of disease burden using electronic medical records.
Ulcerative colitis (UC) is a debilitating inflammatory bowel disease. Present knowledge regarding UC disease progression over time is limited. To assess UC progression to severe disease along with disease burden and associated factors. Electronic medical records linked with Swedish national health registries (2005-2015) were used to identify disease progression of UC. Odds of all-cause and disease-related hospitalization within 1 year were compared between patients with disease progression and those without. Annual indirect costs were calculated based on sick leave, and factors related to UC progression were examined. Of the 1,361 patients with moderate UC, 24% progressed to severe disease during a median of 5.2 years. Severe UC had significantly higher odds for all-cause (OR [odds ratio] 1.47, 95% CI [confidence interval]: 1.12-1.94, P < 0.01) and UC-related hospitalization (OR 2.47, 95% CI: 1.76-3.47, P < 0.0001) compared to moderate disease. Average sick leave was higher in patients who progressed compared to those who did not (64.4 vs 38.6 days, P < 0.001), with higher indirect costs of 151,800 SEK (16,415 €) compared with 92,839 SEK (10,039 €) (P < 0.001), respectively. UC progression was related to young age (OR 1.62, 95% CI: 1.17-2.25, P < 0.01), long disease duration (OR 1.09, 95% CI: 1.03-1.15, P < 0.001), and use of corticosteroids (OR 2.49, 95% CI: 1.67-3.72, P < 0.001). Disease progression from moderate to severe UC is associated with more frequent and longer hospitalizations and sick leave. Patients at young age with long disease duration and more frequent glucocorticosteroid medication are associated with progression to severe UC.


Changes on bone mineral density after adjuvant treatment in women with non-metastatic breast cancer.
. Adjuvant therapies have prolonged survival of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). We have analyzed the effects of chemotherapy, hormone therapy with tamoxifen or both, on BMD of women with NMBC. We prospectively included 168 women with NMBC (stage I-III) referred to the Medical Oncology Service of University Hospital of Canary Islands between 1997 and 2001 (55 +/- 12 years; 37% premenopausal; 43 +/- 13 months of follow-up). We measured lumbar and hip BMD (g/cm2) at diagnosis, after chemotherapy and after 12 months of tamoxifen. If a low BMD was detected, women were treated with bisphosphonates. BMD after chemotherapy (n = 83) significantly decreased at lumbar (1.014 +/- 0; 0.995 +/- 0, p = 0.0001), trochanter (0.701 +/- 0; 0.690 +/- 0, p = 0.001), intertrochanter (1.095 +/- 0; 1.078 +/- 0, p = 0.0001) and total hip (0.924 +/- 0; 0.915 +/- 0, p = 0.046) areas. Although 60% of the premenopausal women suffered amenorrhea after chemotherapy, there were not significant differences in BMD between them and women who retained menses. BMD of women who received 12 months of tamoxifen after chemotherapy increased--total hip (0.907 +/- 0; 0.922 +/- 0, p = 0.005) and intertrochanter (1.071 +/- 0; 1.091 +/- 0, p = 0.003)--or remained stable--lumbar, femoral neck, trochanter, and Ward's triangle (n = 39). When tamoxifen was the only adjuvant treatment, BMD after 12 months (n = 22) increased in trochanter area (0.644 +/- 0; 0.663 +/- 0, p = 0.011), and remained stable in all other sites. 50 (30%) patients were treated with bisphosphonates because of osteopenia. Women with NMBC are affected by early bone loss after adjuvant chemotherapy. This bone loss is attenuated by one year of tamoxifen treatment.


DNA supercoiling and transcription in Escherichia coli: influence of RNA polymerase mutations.
Coumermycin A1, a specific inhibitor of DNA gyrase, differentially changes the spectrum of proteins synthesized in wild type E. coli cells but has no effect on the protein spectrum in mutant cells with coumermycin-resistant DNA gyrase. The rpoB265 mutation affecting RNA polymerase decreases the coumermycin A1-sensitivity of bacteria while the rpoC3 mutation increases it. The interaction of wild type and mutant RpoB265 RNA polymerases with ColEl plasmid DNA in vitro is differently affected by DNA supercoiling. No such differences are observed in the case of RpoC3 RNA polymerase. The results suggest that template supercoiling may have a substantial effect on transcription in vivo, an effect which, in some cases, depends on the properties of RNA polymerase.


Is transureteroureterostomy performed during multi-organ resection for non-urothelial malignancy safe and effective?
Multi-organ resection in patients with non-urothelial cancer may include segmental ureteral resection. The resulting ureteral defect can be reconstructed with a transureteroureterostomy (TUU); however, whether TUU is safe and effective in this patient group remains unclear. In the current retrospective analysis, we evaluated renal function before and after complex multi-organ resection that included TUU to determine whether TUU is safe and effective. We retrospectively reviewed the charts of patients who underwent TUU between 1995 and 2011. Renal imaging studies performed before and after TUU were used to determine whether hydronephrosis was present in either kidney. Kidney function was assessed by measuring serum creatinine levels and calculating the estimated glomerular filtration rate (eGFR) before and after TUU. Twelve patients underwent TUU during multiorgan resection. Median follow-up time was 15 months. Three patients with cancer recurrence involving the TUU developed progressive hydronephrosis. Serum creatinine levels did not increase more than 0.5 mg/dl in any patient. Kidney function as assessed by eGFR was maintained in all patients (until the time of recurrence in the three patients with recurrence affecting the TUU). TUU during multi-organ resection for non-urothelial malignancy is safe and effective. Long-term renal function is maintained in the majority of patients.


How healthcare workers respond to COVID-19: The role of vulnerability and social support in a close relationships defense mechanism.
Healthcare workers play a vital role in the fight against COVID-19. Based on Terror Management Theory (TMT), the present research examined whether a close relationships defense mechanism reduces anxiety among healthcare workers (N = 729) in China. Our results suggest that this defense mechanism, as indexed by relationship satisfaction, serves as an effective terror management source after exposure to reminders of death (MS; mortality salience). These findings extend TMT by identifying two moderating variables: vulnerability and social support. In a low objective vulnerability group, healthcare workers who subjectively believed themselves as less vulnerable to COVID-19 showed a stronger defense mechanism after a MS manipulation as compared to those who felt more vulnerable. Further, healthcare workers with higher levels of social support reported more relationship satisfaction. These findings have practical implications for guiding healthcare workers on how to buffer death-related anxiety and maintain their mental health in the fight against COVID-19.


Pyrene dodecanoic acid coenzyme A ester: peroxisomal oxidation and chain shortening.
Pyrenedodecanoyl-CoA was beta-oxidized by isolated rat liver peroxisomes at a rate which was about 50% of that observed with palmitoyl-CoA. Measurement of the quantity of NADH formed from a limiting amount of pyrenedodecanoyl-CoA suggested that it was subjected to two to three cycles of beta-oxidation. Pyrenedodecanoyl-CoA was a very poor substrate for carnitine palmitoyltransferase, exhibiting less than 1% of the rate obtained with palmitoyl-CoA; it also was a strong inhibitor of this enzyme. With rat liver microsomal alpha-glycerophosphate acyltransferase the rate of reaction with pyrenedodecanoyl-CoA was only 3-4% of that observed with palmitoyl-CoA.


An intronic AP-1 sequence mediates the transcriptional activation of the F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase by serum.
The expression of F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is rapidly induced by growth factors. We report here that an AP-1 intragenic sequence located at position +612 of the F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transcription initiation site is involved in the transcriptional activation of this gene by serum. We have demonstrated in vitro DNA-protein interaction on this AP-1 site of the F-promoter. Indeed, this element was recognized by c-Fos and JunD in vitro, and mutation or deletion of this element reduced the early response to serum stimulation by 60%. We conclude that the serum response of the F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene requires the co-ordinated function of ets, E2F and AP-1 binding sites.


Monitoring anti-PLA2R antibody titres to predict the likelihood of spontaneous remission of membranous nephropathy.
In anti-phospholipase A2 receptor (PLA2R) membranous nephropathy (MN) there is controversy whether spontaneous remission (SR) can be predicted using a single titre or by assessing the dynamic changes in anti-PLA2R antibody (ab) titres. The study objective was to identify the optimal dynamics of anti-PLA2Rab titres to predict SR in MN. A total of 127 nephrotic patients with anti-PLA2R-MN were prospectively followed up for 6 months under conservative treatment. Anti-PLA2Rabs and proteinuria were assessed at diagnosis and monthly thereafter. The primary endpoint (PEP) was a reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive anti-PLA2Rab titres were developed to predict the PEP. A total of 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titres. An anti-PLA2R titre ≤97.5 RU/mL at diagnosis had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rabs and a reduction ≥15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an area under the curve that was significantly greater than that obtained with relative changes of proteinuria in the same period of time {odds ratio [OR] 0.95 [95% confidence interval (CI) 0.91-0.98 versus OR 0.79 [95% CI 0.70-0.88], respectively; P = 0.0013}. Combining the baseline anti-PLA2Rab titres with their relative changes at 3 months after diagnosis gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy.


A role for Rab30 in retrograde trafficking and maintenance of endosome-TGN organization.
Rab30 is a poorly characterized small GTPase. Here we show that Rab30 is localised primarily to the TGN and recycling endosomes in a range of cell types, including primary neurons; minor levels of Rab30 were also detected throughout the Golgi stack and early endosomes. Silencing of Rab30 resulted in the dispersal of both early and recycling endosomes and TGN compartments in HeLa cells. By analyzing cargo trafficking in Rab30-silenced and Rab30-overexpressing HeLa cells, we demonstrate that Rab30 plays a role in retrograde trafficking of TGN38 from endosomes to the Golgi, but has no apparent role in the endocytic recycling of the transferrin receptor to the plasma membrane. Five interactive partners with Rab30 were identified by pull-down and MS analysis using GFP-tagged Rab30 mutant, Rab30(Q68L). Two of the interactive partners identified were Arf1 and Arf4, known regulators of endosome to TGN retrograde transport. Knockdown of Arf1 and Arf4 results in GFP-Rab30 decorated tubules arising from the recycling endosomes, suggesting association of Rab30 with tubular carriers. Overall our data demonstrates a role for Rab30 in regulating retrograde transport to the TGN and maintenance of endosomal-TGN organization.


Ultrastructural changes in cristae of lymphoblasts in acute lymphoblastic leukemia parallel alterations in biogenesis markers.
We explored the link between mitochondrial biogenesis and mitochondrial morphology using transmission electron microscopy (TEM) in lymphoblasts of pediatric acute lymphoblastic leukemia (ALL) patients and compared these characteristics between tumors and control samples. Gene expression of mitochondrial biogenesis markers was analysed in 23 ALL patients and 18 controls and TEM for morphology analysis was done in 15 ALL patients and 9 healthy controls. The area occupied by mitochondria per cell and the cristae cross-sectional area was observed to be significantly higher in patients than in controls (p-value = 0.0468 and p-value< 0.0001, respectively). The mtDNA copy numbers, TFAM, POLG, and c-myc gene expression were significantly higher in ALL patients than controls (all p-values< 0.01). Gene Expression of PGC-1α was higher in tumor samples. The analysis of the correlation between PGC-1α expression and morphology parameters i.e., both M/C ratio and cristae cross-sectional area revealed a positive trend (r = 0.3, p = 0.1). The increased area occupied by mitochondria and increased cristae area support the occurrence of cristae remodelling in ALL. These changes might reflect alterations in cristae dynamics to support the metabolic state of the cells by forming a more condensed network. Ultrastructural imaging can be useful for affirming changes occurring at a subcellular organellar level.


Human granulocyte 6 phosphogluconate dehydrogenase. Purification by elective elution with NADP+, immunological and kinetic properties.
Human granulocyte 6 phosphogluconate dehydrogenase has been totally purified from a single patient with chronic granulocytic leukaemia. 48 mg of protein, of specific activity 20 IU per mg of protein, have been obtained in the course of three different steps only. The overall yield was 30 p. cent and the purification was 100 folds. Purified 6 phosphogluconate dehydrogenase was homogeneous when tested in acrylamide and acrylamide SDS gel electrophoresis or in immunodiffusion. The enzyme was immunologically identical in red blood cells, blood platelets and normal leukocytes. The fixation of both substrates, NADP-+ and 6 phosphogluconate, seemed to proceed through a non ordered mechanism. NADPH was an inhibitor strictly competitive with respect to NADP-+ and non competitive with respect to 6 phosphogluconate. 2-3 Diphosphoglycerate seemed to be able to bind on both the fixation sites of NADP-+ and 6 phosphogluconate. The inhibition by ATP was competitive with 6 phosphogluconate and non competitive with NADP-+. 6 phosphogluconate dehydrogenase was inactivated by SH reagents and was partially protected against this inactivation by both substrates. Both substrates protected the enzyme against thermal inactivation. The influence of ionic strength, pH and ions have been studied, and the results have been compared to those reported by other authors for erythrocyte enzyme.


Publicly available information about fertility benefits for trainees at medical schools in the US.
Infertility affects one in four female physicians, yet current availability of fertility benefits within Accreditation Council for Graduate Medical Education (ACGME) accredited residency programs in the United States (US) is unknown. Our objective was to examine publicly available fertility benefits information for residents and fellows. The top 50 medical schools in the US for research were identified using US News & World Report 2022. In April 2022, we reviewed fertility benefits available to residents and fellows at these medical schools. Websites of their associated graduate medical education (GME) websites were queried for details surrounding fertility benefits. Two investigators collected data from GME and publicly available institutional websites. The primary outcome was fertility coverage and rates are reported as percentages. Within the top 50 medical schools, 66% of institutional websites included publicly available medical benefits, 40% included any mention of fertility benefits, and 32% had no explicit information on fertility or medical benefits. Fertility benefit coverage included infertility diagnostic workup (40%), intrauterine insemination (32%), prescription coverage (12%), and in vitro fertilization (IVF, 30%). No information on coverage for third party reproduction or LGBT family building was available on public websites. Most programs with fertility benefits were in the South (40%) or Midwest (30%). To support the reproductive autonomy of physicians in training, it is critical to ensure access to information on fertility care coverage. Given the prevalence of infertility among physicians and the impact of medical training on family planning goals, more programs should offer and publicize coverage for fertility care.


Patient chosen gap payments in primary care: Predictions of patient acceptability, uptake and willingness to pay from a discrete choice experiment.
Compulsory co-payments limit access and may compromise quality in primary care. Patient Chosen Gap Payments (PCGPs) allow patients to specify a (voluntary) out-of-pocket contribution, creating an incentive for patient-centred care without the need for complex outcomes-based funding formulae. It is not yet known if widespread use of PCGP services is consistent with consumer preferences. We conducted a discrete choice experiment (DCE) in a sample of the adult Australian general population (n = 1457) during April 2019 to simulate patient choice between alternative primary care services and describe preferences for PCGP services. Participants also completed a supplementary valuation task in which participants reported their intended PCGP contribution for PCGP services. Finally, we conducted policy-simulations to predict market shares when PCGP clinics operate alongside the two existing models of primary care funding in Australia. Results suggest that patients prefer shorter wait time, longer consults, lower compulsory copayments, services with higher patient satisfaction ratings, choice of doctor and $0 suggested voluntary contribution for PCGP services. Policy-simulations suggest that high-quality PCGP services could obtain market share of up to 39% and voluntary contributions of up to $25.36 per service (95%CI: $10.24, $40.47), potentially adding $1.48 billion AUD in revenues and funding for primary care at no cost to government. Low-quality PCGP services are unlikely to capture significant market share and PCGP contributions were lowest for low-quality PCGP services ($12.12, 95%CI: $2.09, $26.34). Further field testing is recommended where (i) patients make consequential choices (e.g. real payments for simulated services), and (ii) dynamic effects on quality of care and utilisation can be observed; particularly in vulnerable populations. We conclude that PCGP services aligned with patient preferences could capture significant market share and substantially increase revenue to general practice.


Myelin and macrophages in the PNS: An intimate relationship in trauma and disease.
Macrophages of the peripheral nervous system belong to the so-called tissue macrophages, with multiple functions during injury and disease. Their origin during ontogeny has not yet been completely resolved, but it is clear that upon injury and disease conditions, they are supplemented by hematopoietic derivatives. In the peripheral nervous system, the most abundantly investigated scenario in which resident and infiltrating macrophages are involved is the so-called "Wallerian degeneration", a complex degenerative process where macrophages exhibit mostly beneficial functions by phagocytosing myelin and axonal remnants. Of special interest is the implication of macrophages in inflammatory nerve diseases, like acute Guillain-Barré syndromes and its permanent variant, chronic inflammatory demyelinating polyneuropathy, where macrophages are supposed to be substantial (co-)mediators of the diseases. In inherited peripheral neuropathies nerve macrophages possess a clear disease-amplifying function. In the corresponding animal models, a coordinated interplay between mutant Schwann cells, macrophages, endoneurial fibroblasts and the target structure, myelin, emerged. Along this process, a newly discovered disease mechanism mediated by macrophages is the dedifferentiation of myelinating Schwann cells. As macrophages are amplifiers of the genetically-mediated, non-curable diseases, targeting the mechanisms of their activation might be a promising strategy to treat these disorders. This article is part of a Special Issue entitled SI: Myelin Evolution.


Uric acid: a cardiovascular risk factor in patients with recent myocardial infarction.
To date uric acid (UA) is not considered a cardiovascular risk factor, although evidence about a relationship between UA and cardiovascular diseases has been reported. Information from 10,840 patients enrolled in the GISSI-Prevenzione trial was used to evaluate the relationship between UA and risk for total mortality and cardiovascular events (CVE). UA levels were categorized in quintiles, as ≤ 4.5 (Q1), 4.6 to 5.3 (Q2), 5.4 to 6.0 (Q3), 6.1 to 6.8 (Q4) and >6.8 (Q5) mg/dL. Multivariable analysis was used to estimate the relative risks (HR) of outcome measures across categories of UA. The analysis of the area under the receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) tests were used to evaluate the incremental prognostic information of UA. During 36,802 person-years of follow-up, 974 deaths and 1120 cardiovascular events occurred. We found a statistically significant association between high UA and total mortality [HR, P value]: Q1 [reference category, 1.00]; Q2 [1.13, 0.267]; Q3 [1.06, 0.619]; Q4 [1.23, 0.063]; Q5 [1.63, <0.0001], test for trend P<0.0001. Similar results were obtained for cardiovascular events [HR, P value]: Q1 [reference category, 1.00]; Q2 [1.12, 0.271]; Q3 [1.19, 0.094]; Q4 [1.25, 0.031]; Q5 [1.38, 0.002], test for trend P=0.0009. The prognostic accuracy of prediction models for CVE was significantly increased by adding UA to classical cardiovascular risk factors (AUC P=0.0041; NRI P=0.0004; IDI P<0.0001). High UA may be considered a risk factor for death and CVE.


Thyroid cancer neck lymph nodes metastasis: Meta-analysis of US and CT diagnosis.
Ultrasound (US) is the first imaging technique in the assessment of cervical lymph nodes metastasis (LNM) of papillary thyroid cancer (PTC) patients preoperatively. Computed tomography (CT) exerts an influence on surgical strategy especially for patients with lateral cervical LNM. This meta-analysis aimed at assessing the diagnostic values of US and CT in detecting the cervical LNM in thyroid cancer patients. Medline, Embase and Cochrane Library (CENTRAL) were retrieved up to 16th Sep, 2019 for studies about comparison of the diagnostic performance between US and CT. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio (DOR), with each's 95 % CI were calculated. A total of 5656 thyroid cancer patients in 10 studies were included. CT had a higher sensitivity in central (0.400 [0.385, 0.416] vs 0.284 [0.270, 0.298], P < 0.001), lateral (0.811 [0.778, 0.416] vs 0.758 [0.722, 0.792], P = 0.029) and the whole (0.664 [0.633, 0.694] vs 0.593 [0.561, 0.625], P = 0.002) compartments regions. US had a higher specificity in central (0.895 [0.885,0.903] vs 0.950 [0.944, 0.956], P < 0.001), lateral (0.84 [0.813,0.864] vs 0.88 [0.856, 0.901], P = 0.012) and the whole (0.834 [0.804,0.862] vs 0.911 [0.887, 0.932], P < 0.001) compartments regions. US and CT performed poorly when trying to identify the presence of central LNM. CT has a higher sensitivity while US has a higher specificity for the assessment of central, lateral and the whole cervical LNM. Performing CT to detect the lateral cervical LNM will effectively reduce the rate of missed diagnosis and improve surgical planning. Both US and CT are needed for neck lymph nodes staging preoperatively owning to low sensitivities.


Renal filtration, absorption and catabolism of human alpha interferon.
The renal handling of human interferon-alpha has been evaluated by using an isolated and perfused rabbit kidney. IFN-alpha disappears from plasma with a t1/2 of 81 min and the fractional turnover rate is 0.84%/min. About 47 molecules of IFN-alpha are filtrated with 100 molecules of creatinine but most of the IFN is absorbed by tubular cells. This is the first report showing that human IFN-alpha is filtrated by the kidney, largely absorbed, most probably catabolized within tubular epithelium and excreted in negligible amounts with the urine.


Management status and its predictive factors in patients with type 2 diabetes in China: A Nationwide Multicenter Study: A Nationwide Multicenter Study.
The prevalence of type 2 diabetes in China is increasing rapidly. Appropriate management of glycemia, blood pressure and dyslipidemia in this population is a major public health concern. The aim of this study was to assess metabolic control including glycated hemoglobin A1c (HbA1c ), blood pressure (BP) and low density lipoprotein cholesterol (LDL-c), in a large sample of patients with type 2 diabetes in China and to identify factors that correlated with the achievement of HbA1c, BP and LDL-c goals (ABCs). A nationwide survey was conducted in 50 medical centres across China from April to July of 2010. Baseline information on demographics, medical history, HbA1c , BP and LDL-c levels were measured in 5961 patients with type 2 diabetes. Mean age, body mass index (BMI) and HbA1c were 59.5 ± 1.3 years, 24.5 ± 4.1 kg/m(2) and 8.3 ± 2.2%, respectively. With respect to generally accepted ABC treatment goals, 35.2% of participants had HbA1c <7%; 35.5% had BP < 140/80 mmHg, and 45.1% had LDL-c < 100 mg/dl. The proportion of patients who met all three targets was only 5.4%. Logistic regression revealed that smoking (P=0.000), higher BMI (P=0.001) and insulin use (P=0.000) were statistically significant predictors of failing to meet ABC targets. The percentage of Chinese patients with type 2 diabetes who met recommended targets for HbA1c , BP and LDL-c in 2010 was low. Smoking, higher BMI and insulin use were the strongest determinants of failing to meet ABC targets.


Nuclear topology, epigenetics, and keratinocyte differentiation.
Recent progress in epigenetics reveals dynamic chromatin interactions in the nucleus during development, regeneration, reprogramming, and in disease. Higher-order chromatin organization is manifested as changes in the topological distribution of eu-/heterochromatin and in nuclear morphology. We are now able to gain new knowledge about these changes at the genomic level.


Intrafamilial spread of pertussis.
Intrafamilial spread of pertussis was evaluated in 21 families (97 individuals) of patients with whooping cough diagnosed by culture or by ELISA serology. During follow-up (average six months), an infectivity rate of 83% was established by an ELISA within these families. However, 46% of the secondary cases were asymptomatic. Most of the asymptomatic cases were in adults or vaccinated children. Unvaccinated infants had classic whooping cough and were exposed to pertussis by their vaccinated siblings or parents. The incidence of classic symptoms of pertussis decreased with age, and atypical pertussis was usually culture negative but rapidly diagnosed by measurement of the IgM- and IgA-class antibodies by ELISA.


Amygdala connectivity and aggression.
Neurobiological models propose that reactive aggression is predicated on impairments in amygdala-prefrontal connectivity that subserves moral decision-making and emotion regulation. The amygdala is a key component within this neural network that modulates reactive aggression. We provide a review of amygdala dysfunctional brain networks leading to reactive aggressive behavior. We elaborate on key concepts, focusing on moral decision-making and emotion regulation in a developmental context, and brain network connectivity factors relating to amygdala (dys)function-factors which we suggest predispose to reactive aggression. We additionally discuss insights into the latest treatment interventions, providing the utilization of the scientific findings for practice.


[General medicine management of superficial venous thrombosis of the lower limbs: A survey in Saône-et-Loire].
For a long time, superficial venous thrombosis (SVT) of the lower limbs was considered as benign. Due to lack of clear scientific evidence, its treatment was heterogeneous and even potentially deleterious. Since 2010, several major studies have highlighted the seriousness of SVT, and prophylactic doses of fondaparinux have proven their efficacy for this indication. While the French recommendations have not yet taken on board all this data, has practice already changed? To describe in general practice the usual management of suspected SVT. A descriptive cross-sectional study of general practitioners in Saône-et-Loire. Each doctor taking part was asked to note on a paper questionnaire the details of the last patient in whom they suspected SVT. Data collected included: clinical presentation, diagnostic and therapeutic management and follow-up of the patients. Between 01/01/2014 and 31/03/2014, 88 doctors out of 443 contacted (20%) completed the questionnaire. According to the information they provided, 36 physicians (40.9% [95% CI: 30.6-50.2]) searched for an associated pulmonary embolism. Eighty-two physicians (93.2% [95% CI: 87.9-98.4]) prescribed a venous compression ultrasound (CUS) exploration. Twelve etiological assessments were carried out (13.6% [95% CI: 6.5-20.8]) of which 6 (6.8%) appeared to be justified. 64 (72.7%) of the patients were given an anticoagulant therapy (heparin or fondaparinux), including 15 (17%) at a prophylactic dose and 49 (55.7%) at a curative dose. Forty-nine doctors (55.7% [95% CI: 45.3-66.1]) prescribed a CUS follow-up. General practitioners seem to have adapted their diagnostic practices to the data highlighting the potential seriousness of SVT. The treatment they give, however, remains very variable and potentially deleterious, in particular due to a high rate of treatments given at curative doses.


Abdominal mucosectomy reduces the incidence of soiling and sphincter damage after restorative proctocolectomy and J-pouch.
Thirty-two ileoanal J-pouch procedures have been performed by the author between 1983 and 1986. Two pouches have been excised, one has been defunctioned for diarrhea, and seven patients either have not had their ileostomy closed or have not been followed for more than four months after restoration of intestinal continuity. Of the remaining 22 patients, 12 early operations involved endoanal mucosectomy while in the ten most recent procedures, the rectum and anal mucosa have been excised from the abdomen. Incidence of complications between the methods of mucosal excision were comparable apart from cuff abscess (n = 5) which only occur after endoanal muscosectomy. Functional results were identical apart from the incidence of soiling which occurred in six of 12 patients after endoanal mucosectomy but in only one of ten patients after abdominal mucosectomy. Resting anal canal pressures fell significantly after endoanal mucosectomy (87 to 60cm H20, P less than 0.05) but not after abdominal mucosectomy (82 to 81 cm H20). These differences may be due to the duration and extent of anal retraction, which was 72 minutes after endoanal mucosectomy but only 18 minutes after abdominal mucosectomy. Abdominal mucosectomy appears to cause less sphincter damage and soiling than conventional endoanal excision.


Complementary evidence for small-scale spatial assemblages of the exploited grass emperor (Lethrinus laticaudis) in the Shark Bay World Heritage Area, Western Australia.
Understanding the connectivity of exploited fish populations is critical to their management under both rapid and long-term environmental change. Patterns of connectivity are unknown for most fishes in the Shark Bay World Heritage Area (Western Australia), a large, shallow embayment in the eastern Indian Ocean, vulnerable to marine heatwaves. The composition of oxygen (δ18O) and carbon (δ13C) stable isotopes in whole otoliths of the recreationally-important reef fish Lethrinus laticaudis did not differ between Shark Bay's two large inner gulfs, separated by the Peron Peninsula. However, significant differences were found between pairs of locations with different salinities over a spatial scale of ∼60 km within each gulf. Misclassification of samples was greatest between locations mostly in different gulfs, but with similar salinities (15-41%), and rare between adjacent locations in the same gulf with different salinities (0-5%). This is influenced by the strong correlation (ρ = 0.93) between δ18O in otoliths and the salinity gradient of the two gulfs, and further supported by a lack of correlation in the similarities of isotope compositions and distances between locations (ρ = 0.16). Fish samples from each of the different locations were composed of multiple year-classes, yet the otolith chemistry distinguished them at a minimum distance of 16 km apart, indicating that small-scale connectivity of L. laticaudis is likely during the majority of their life cycle. Physical barriers to movement of post-settlement individuals (land masses, expansive seagrass and sand) between the small, isolated reefs of Shark Bay may reduce large scale connectivity, which instead would occur mostly by egg and larval dispersal. The probable scale of connectivity of post-settlement L. laticaudis indicates that this major recreational fishing target species may be vulnerable to localised over-exploitation and negative environmental effects on population sources and sinks within this shallow embayment. Maintaining sustainable spawning biomass at scales relevant to the extent of connectivity for such a species in a World Heritage Area is an important management consideration.


Associations between LGBTQ-affirmative school climate and adolescent drinking behaviors.
We investigated whether adolescents drank alcohol less frequently if they lived in jurisdictions with school climates that were more affirmative of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) individuals. Data from the 2010 School Health Profile survey, which measured LGBTQ school climate (e.g., percentage of schools with safe spaces and gay-straight alliances), were linked with pooled data from the 2005 and 2007 Youth Risk Behavior Survey, which measured sexual orientation identity, demographics, and alcohol use (number of drinking days, drinking days at school, and heavy episodic drinking days) in 8 jurisdictions. Two-level Poisson models tested the associations between school climate and alcohol use for each sexual-orientation subgroup. Living in jurisdictions with more (versus less) affirmative LGBTQ school climates was significantly associated with: fewer heavy episodic drinking days for gay/lesbian (incidence-rate ratio [IRR]=0.70; 95% confidence interval [CI]: 0.56, 0.87; p=0.001) and heterosexual (IRR=0.80; 95% CI: 0.76, 0.83; p<0.001) adolescents; and fewer drinking days at school for adolescents unsure of their sexual orientation (IRR=0.57; 95% CI: 0.35, 0.93; p=0.024). Fostering LGBTQ-affirmative school climates may reduce certain drinking behaviors for gay/lesbian adolescents, heterosexual adolescents, and adolescents unsure of their sexual orientation.


T-tubule recovery after detubulation in isolated mouse cardiomyocytes.
Remodeling of cardiac t-tubules in normal and pathophysiological conditions is an important process contributing to the functional performance of the heart. While it is well documented that deterioration of t-tubule network associated with various pathological conditions can be reversed under certain conditions, the mechanistic understanding of the recovery process is essentially lacking. Accordingly, in this study we investigated some aspects of the recovery of t-tubules after experimentally-induced detubulation. T-tubules of isolated mouse ventricular myocytes were first sealed using osmotic shock approach, and their recovery under various experimental conditions was then characterized using electrophysiologic and imaging techniques. The data show that t-tubule recovery is a strongly temperature-dependent process involving reopening of previously collapsed t-tubular segments. T-tubule recovery is slowed by (1) metabolic inhibition of cells, (2) reducing influx of extracellular Ca2+ as well as by (3) both stabilization and disruption of microtubules. Overall, the data show that t-tubule recovery is a highly dynamic process involving several central intracellular structures and processes and lay the basis for more detailed investigations in this area.


Sialidase substrates for Sialdiase assays - activity, specificity, quantification and inhibition.
Sialidases are glycosidases responsible for the removal of sialic acid (Sia) residues (desialylation) from glycan portions of either glycoproteins or glycolipids. By desialylation, sialidases are able to modulate the functionality and stability of the Sia-containing molecules and are involved in both physiological and pathological pathways. Therefore, evaluation of sialidase activity and specificity is important for understanding the biological significance of desialylation by sialidases and its function and the related molecular mechanisms of the physiological and pathological pathways. In addition, it is essential for developing novel mechanisms and approaches for disease treatment and diagnosis and pathogen detection as well. This review summarizes the most recent sialidase substrates for evaluating sialidase activity and specificity and screening sialidase inhibitors, including (i) general sialidase substrates, (ii) specific sialidase substrates, (iii) native sialidase substrates and (iv) cellular sialidase substrates. This review also provides a brief introduction of recent instrumental methods for quantifying the sialidase activity, such as UV, fluorescence, HPLC and LC-MS methods.


Efficacy of ivermectin for chronic strongyloidiasis: two single doses given 2 weeks apart.
We assessed the efficacy and adverse effects of ivermectin for the treatment of chronic strongyloidiasis. Fifty patients were treated with a single dose of ivermectin at approximately 200 microg/kg, and the dose was repeated 2 weeks later. The eradication rate was 96% (48 of 50 patients) at 2 weeks after the first dose and 98% at 2 weeks after the second dose (49 of 50 patients). In the latter cases, no recurrence was noted at the end of the 4-month post-treatment follow-up period. The gastrointestinal symptoms observed most frequently before the treatment were borborygmus, constipation, and diarrhea. These symptoms improved in the majority of patients after the treatment. Side effects, including nausea and vomiting, occurred in 1 patient (2%), but these were mild and transient. Although abnormal values in laboratory tests were observed in 4 patients (8%), they were mild, and no particular clinical care was required. Thus, ivermectin showed an excellent antihelminthic effect, with little toxicity. Our results indicate that a regimen of two single doses of 200 microg/kg ivermectin, given 2 weeks apart, is clinically suitable for the treatment of chronic strongyloidiasis.


Abnormalities in the metabolism of postprandial and fasting triglyceride-rich lipoprotein subfractions in normal and insulin-dependent diabetic subjects: effects of sex.
To investigate the effect of sex and diabetes on postprandial lipoprotein metabolism, 15 normal and 12 normolipidemic subjects with insulin-dependent diabetes mellitus (IDDM) were studied. Plasma triglyceride (TG) levels were measured and three TG-rich lipoprotein subfractions (Sf greater than 400, 100 to 400, and 20 to 100) were isolated and their composition analyzed before and every 1.5 hours for a total of 7.5 hours following ingestion of corn oil. Normal women compared with men had lower postprandial plasma TG levels (P less than .05) mostly due to lower TG in Sf 100 to 400. The composition of Sf 100 to 400 and Sf 20 to 100 lipoproteins differed in the two sexes (P less than .01), with normal women having particles poorer in TG in both the fasting and postprandial states. Diabetic men compared with normal men had smaller Sf greater than 400 particles following fat ingestion, as shown by a lower TG protein (PR) ratio (7.6 v 12.8, respectively, P less than .05). The composition of Sf 100 to 400 and 20 to 100 lipoproteins was abnormal in IDDM men due to enrichment in total cholesterol (TC) as shown by higher TC/TG, TC/PR, and TG/phospholipid (PL) ratios in both the fasting (P less than .03 to P less than .003) and the postprandial state (P less than .03 to P less than .0001). A lower PL and TG content was also consistently present. A similar enrichment in TC was observed in diabetic v normal women following fat ingestion in Sf greater than 400 only (P less than .003).(ABSTRACT TRUNCATED AT 250 WORDS)


Sleep Deficiency, Sleep Apnea, and Chronic Lung Disease.
With sleep occupying up to one-third of every adult's life, addressing sleep is essential to overall health. Sleep disturbance and deficiency are common in patients with chronic lung diseases and associated with worse clinical outcomes and poor quality of life. A detailed history incorporating nocturnal respiratory symptoms, symptoms of obstructive sleep apnea (OSA) and restless legs syndrome, symptoms of anxiety and depression, and medications is the first step in identifying and addressing the multiple factors often contributing to sleep deficiency in chronic lung disease. Additional research is needed to better understand the relationship between sleep deficiency and the spectrum of chronic lung diseases.


Cervical dermal sinus and intramedullary spinal cord abscess: case report.
Congenital dermal sinuses in the cervical region are rare. A case report is presented in which the persistent anomaly led to formation of an intramedullary spinal cord abscess. The clinical presentation, radiological diagnosis, and surgical management are discussed.


A 5-micron-bright spot on Titan: evidence for surface diversity.
Observations from the Cassini Visual and Infrared Mapping Spectrometer show an anomalously bright spot on Titan located at 80 degrees W and 20 degrees S. This area is bright in reflected light at all observed wavelengths, but is most noticeable at 5 microns. The spot is associated with a surface albedo feature identified in images taken by the Cassini Imaging Science Subsystem. We discuss various hypotheses about the source of the spot, reaching the conclusion that the spot is probably due to variation in surface composition, perhaps associated with recent geophysical phenomena.


The role for liposomal drug delivery in molecular and pharmacological strategies to overcome multidrug resistance.
When P-glycoprotein (PGP) was first identified as a direct mediator of multidrug resistance (MDR) a great deal of excitement was generated as scientists and clinicians anticipated the ability to successfully treat previously refractory cancers by blocking this drug efflux pump. More than twenty years later there is still minimal evidence that inhibiting PGP will have widespread impact on the chemosensitivity of human tumors. Yet, we know that PGP is over-expressed in many cancers, is associated with poor prognosis in certain tumor types and, if functional, will certainly reduce the accumulation of many common anticancer drugs inside tumor cells exhibiting elevated PGP levels. Similar situations have arisen more recently for other potential mediators of chemosensitivity such as the apoptosis antagonist protein Bcl-2. Bcl-2 has been linked to drug resistance and poor patient prognosis in numerous studies. There has been a great deal of interest in blocking expression or function of this protein to increase the susceptibility of tumor cells to apoptotic stimuli such as chemotherapy. However, preclinical and clinical evidence supporting this approach as a unilateral means of significantly enhancing the response of tumors to chemotherapy is limited. In view of these examples, it would appear likely that similar caveats will be experienced in the future as new molecular targets are identified for potential MDR reversal. Given the ever increasing evidence of genetic diversity in cancer development and progression, it should not be surprising that the development of MDR is also complex and heterogeneous. Consequently, it should also not be surprising that solutions to this problem are unlikely to arise from interventions aimed at any single resistance mechanism. These concepts suggest that new approaches to addressing the various molecular and pharmacological features associated with MDR will be necessary in order to make significant in-roads into improving the clinical activity of current and future anticancer agents. This review summarizes many of the current directions being taken to overcome MDR and how liposomal drug delivery systems may play an important role in achieving this aim.


A factor found in aged tungstate solution enhanced the antibacterial effect of beta-lactams on methicillin-resistant Staphylococcus aureus.
We have found a factor (Factor T) in aged mixtures of tungstate and phosphate which greatly enhances the antibacterial effects of beta-lactams on both inducible and constitutive methicillin-resistant Staphylococcus aureus, but not on methicillin-susceptible S. aureus. Factor T alone did not strongly inhibit bacterial growth. There was no synergism of Factor T with other classes of antibiotics, nor with other groups of bacteria, and it reduced the efficacy of amino-glycosides and tetracycline. Upon preparation of Factor T, acidifying and heating the mixture of tungstate and phosphate resulted in a high yield and reproducibility, and no enhancing effect was observed when other anions such as sulfate or molybdate were used instead. Factor T is heat- and acid-stable but labile to alkalization, and is probably a complex of phosphate and tungstate.


A slow EPSP in mammalian inferior mesenteric ganglion persists after in vivo capsaicin.
The non-cholinergic slow excitatory postsynaptic potential (EPSP) in the guinea pig inferior mesenteric ganglion (IMG) is believed to be mediated by substance P (SP). Yet, in ganglia of guinea pigs treated with capsaicin (50, 100, or 350 mg/kg, s.c.), a compound that depletes SP from sensory neurons, slow EPSPs were only 50% smaller in amplitude than those in vehicle-treated controls; this was true at all dosages. When ganglia from capsaicin-treated animals were desensitized to SP, slow EPSP amplitude was decreased by 50% from predesensitization values. These data indicate that capsaicin does not eliminate the slow EPSP in the IMG and suggest that both SP and another transmitter are involved in co-mediating this response.


Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study.
Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as "BA.2" (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as "BA.4/BA.5", and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as "BQ.1.1". The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.


Surgical treatment of double aortic arch malformation combined with descending aortic arch dissection in adults: a case series.
Double aortic arch (DAA) combined with descending aortic arch dissection (DAAD) in adults is a rare aorta vascular disease. Due to the abnormal anatomy of the double arch and arch vessels, the clinical symptoms and surgical methods differ from those of typical aortic dissection. This study was retrospective analysis of a case series involving three patients (mean age, 47.3 years) with DAA combined DAAD underwent total arch replacement or hybrid aortic repair from September 2010 to June 2019. The patients' demographics, initial symptoms, comorbidities, surgical procedures, and outcomes are summarized. Total arch replacement plus frozen stent implantation under deep hypothermic circulatory arrest was performed for 2 patients, one of them developed disseminated intravascular coagulation and multiple organ failure postoperatively. Case 3 underwent a hybrid procedure with left subclavian artery revascularization and thoracic endovascular aortic repair. The symptoms of hoarseness and dysphagia were obviously improved during the follow up. In addition to typical sudden chest and back pain, patients with DAA and DAAD may have hoarseness and dysphagia. Based on the development of DAA, total arch replacement or hybrid surgery may be is an optional treatment.


Safety factors in bone strength.
Functional in vivo strain data are examined in relation to bone material properties in an attempt to evaluate the relative importance of osteoporotic bone loss versus fatigue damage accumulation as factors underlying clinical bone fragility. Specifically, does the skeleton have a sufficiently large safety factor (ratio of bone failure strain to maximum functional strain) to require that fatigue damage accumulation is the main factor contributing to increased risk of fracture in the elderly? Existing methods limit in vivo strain measurements to the surfaces of cortical bone. Peak principal compressive strains measured at cortical sites during strenuous activity in various mammalian and avian species range from -1700 to -5200 mu epsilon, averaging -2500 mu epsilon (-0.0025 strain). Much of this threefold variation reflects differences in the intensity of physical activity, as well as differences among species and bones that have been studied. Peak strains can also vary as much as tenfold at different cortical sites within the same bone. No data exist for cortical bone strain during strenuous activity in humans, but it is likely that human bones experience a similar range of peak strain levels. Compact bone fails in longitudinal compression at strains as high as -14,000 to -21,000 mu epsilon, but begins to yield at strains between -6000 and -8000 mu epsilon. Given that yielding involves rapid accumulation of microdamage within the bone, it seems prudent to base skeletal safety factors on the yield strain, rather than the ultimate failure strain of bone tissue. Safety factors to yield failure therefore range from 1.4 to 4.1.(ABSTRACT TRUNCATED AT 250 WORDS)


Intermediate catheter injections in closed segments during acute stroke intervention: a cautionary note.
In the setting of stroke intervention, there is typically an occlusion that limits angiographic visualization of patent vasculature distal to the embolus. Certain mechanical thrombectomy paradigms include angiography of the vasculature distal to the point of occlusion in preparation for thrombectomy, typically using a microcatheter. Injections using an intermediate catheter allows for higher volume of injection at a faster rate, resulting in radically different pressure gradients. Two patients presenting with acute ischemic stroke were treated via mechanical thrombectomy using the Penumbra 054 system. The first was a tandem occlusion with a high grade narrowing and occlusion of the internal carotid artery (ICA) origin and an ICA terminus thrombus. The second was a long segment, high volume thrombus extending from the cavernous segment to the ICA terminus. Conventional access techniques were utilized to position the Penumbra 054 catheter in the ICA in both cases. Intraprocedurally, angiography through the 054 catheter within the closed segment resulted in contrast extravasation adjacent to the tentorium, originating from the communicating segment of the ICA, both of which cleared within 48 h. Due to the extravasation, the interventions were both terminated, and the infarcts went on to complete. During an acute stroke, flow within large vessels is abnormal, and rapid changes in volume may result in drastic changes in pressure which may lead to extravasation. The authors recommend never performing a contrast injection through a large lumen catheter when flow may be impeded proximally and distally. Closed segment injections of large volumes at a high rate are probably at high risk for vessel injury.


Lean meats make the grade--a collaborative nutrition intervention program.
Lean Meats Make the Grade is a collaborative nutrition intervention program involving the Minnesota Heart Health Program (MHHP), the Minnesota Beef Council, and the Pork Producers Council. The purposes of this program were to educate consumers about identification of leaner cuts of meat, low-fat preparation methods, and selection of appropriate meat portion size. Program components included training for meat managers, taste testing for consumers, recipes and customer information brochures, and labels on individual meat packages to assist in the identification of leaner cuts of meat. The program was implemented through grocery stores in two of the towns selected for MHHP intervention. Population-based telephone surveys indicated that respondents in the intervention towns were more aware of the lean meats program than those in the comparison communities. Knowledge of lean cuts of meat and low-fat preparation methods also increased as a result of the program. Independently collected sales data from five participating and two control stores provided some indications of a greater interest in lean cuts and 80% lean ground beef as a result of the intervention program. Programs such as this have potential for community-wide nutrition education.


Clinical application of mTORi based immunosuppression for renal transplantation in India.
Long-term renal graft survival is hampered by allograft dysfunction and cardiovascular disease resulting from calcineurin inhibitors (CNIs). This has led to the development of immunosuppressive regimens involving mammalian target of rapamaycin (mTOR) inhibitors, sirolimus and everolimus. They seem to provide long-term benefits for kidney function in transplant patients because of their anti-proliferation and anti-tumor properties and absence of nephrotoxicity. Their use has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity associated with CNIs. Both proactive and reactive strategies have been used. Whether existing strategies of using mTORi in renal transplantation is applicable for Indian patient's remains to be seen. Data on side effect profile, economic viability and the impact of these drugs on infections, particularly in India, are worth documenting. After briefly reviewing available data from India, this article explores the indications, patient populations; timing and practical aspects as well as the safety and efficacy of mTORi-based regimens for renal transplantation and suggests a framework which could allow transplant physicians to tailor its use to their own practice with particular reference to the Indian subcontinent.


Dichlorido[2-(3,5-dimethyl-1H-pyrazol-1-yl-κN)ethanamine-κN]zinc(II).
The amine title complex, [ZnCl(2)(C(7)H(13)N(3))], resulted from imine hydrolysis in a Schiff base compound. The Zn metal atom has a distorted tetra-hedral geometry with the most significant deviation identified in the magnitude of the N-Zn-N angle. This deviation stems from the participation of the Zn and N atoms in a six-membered metallocyclic ring. The latter is in an approximate screw-boat conformation. Two strong N-H⋯Cl hydrogen bonds link the mol-ecules into ribbons propagating along the b-axis direction. The ribbons contain two second-order hydrogen-bonded motifs: a chain and a ring. The chain described by the graph set notation C(2) (2)(6) is formed by one hydrogen bond going in the forward direction (donor to acceptor) and the other in the backward direction (acceptor to donor). In the ring motif R(2) (2)(8), both hydrogen bonds propagate in the forward direction.


Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice.
The pineal product melatonin that acts on specific melatonin receptors has been implicated in pathobiological mechanisms of neuropsychiatric disorders including Alzheimer's disease. We used mice lacking melatonin MT(2) receptors (MT(2) knockouts) to investigate the role of these receptors in synaptic plasticity and learning-dependent behavior. In field CA1 of hippocampal slices from wild-type mice, theta burst stimulation induced robust and stable long-term potentiation that was smaller and decremental in slices from MT(2) knockouts. Tested in an elevated plus-maze on two consecutive days, wild-type mice showed shorter transfer latencies to enter a closed arm on the second day; this experience-dependent behavior did not occur in MT(2) knockouts. These results suggest that MT(2) receptors participate in hippocampal synaptic plasticity and in memory processes.


Force depression following skeletal muscle shortening is long lasting.
In a recent manuscript, Edman (1996) reported that force depression following shortening was a transient phenomenon. A transient response would not fit into the mechanism of force depression suggested by Herzog and Leonard (1997) who argued that force depression following shortening was associated with a stress-related inhibition of cross-bridge attachments in the actomyosin overlap zone formed during the shortening phase. The purpose of this study was to test whether force depressions were long lasting or transient, and in the process, to quantify the relationship between force depression and the amount of shortening and the shortening force. It was found that force depression in cat soleus (35-37 degrees C) was long lasting and was linearly related to the amount of shortening and the shortening force. This latter result suggested that force depression might possibly be related to a single scalar variable; the mechanical work performed by the muscle during the shortening phase. Although the present study was not designed to test this hypothesis, pilot results support the idea that force depression following shortening contractions might be explained exclusively by the muscular work during the shortening phase.


The Effect of Exercise Training on the Energetic Cost of Cycling.
The energetic cost of cycling (CE) is a major contributor to cycling performance but whether CE can be improved by exercise intervention remains uncertain. Here, we sought to systematically review and determine the effect of exercise training on CE in healthy humans. MEDLINE, Scopus, and Web of Science were searched since their inceptions up until December 2014 for articles assessing the effect of exercise training in healthy subjects on CE, as determined by cycling economy or efficiency. Meta-analyses were performed to determine the standardized mean difference (SMD) in CE between post- and pre-training measurements. Subgroup and meta-regression analyses were used to evaluate potential moderating/confounding factors. Fifty-one studies were included after systematic review, comprising a total of 531 healthy subjects (mean age = 20-66 years). Exercise interventions primarily consisted of endurance and/or strength training ranging from 4 to 34 weeks of duration. After data pooling, the meta-analysis revealed that CE was improved with strength training alone or along with endurance training (n = 16, SMD = -0.50, P < 0.0001) but not with endurance training alone (n = 33, SMD = -0.18, P = 0.08). In further subgroup analyses, endurance training alone was effective in improving CE in previously untrained (n = 20, SMD = -0.21, P = 0.04) but not in trained (n = 6, SMD = 0.09, P = 0.75) subjects. The SMD in CE was associated with the duration of training (n = 51, B = -0.03, P = 0.0002). The current meta-analysis provides evidence that CE is improved by exercise training, particularly when strength training or untrained subjects are included.


Pyridone methylsulfone hydroxamate LpxC inhibitors for the treatment of serious gram-negative infections.
The synthesis and biological activity of a new series of LpxC inhibitors represented by pyridone methylsulfone hydroxamate 2a is presented. Members of this series have improved solubility and free fraction when compared to compounds in the previously described biphenyl methylsulfone hydroxamate series, and they maintain superior Gram-negative antibacterial activity to comparator agents.


Anti-IgG antibodies during immunotherapy with purified grass pollen extracts.
In a double blind study 40 patients were allocated specific immunotherapy (hyposensitization) with partially purified timothy extract or two timothy major allergens 19, 25. All patients had typical grass pollen hay fever, in 27% associated with grass pollen asthma and in 13% with birch pollen allergy. Serum IgG anti-IgG antibodies were determined after dithiothreitol treatment. Before hyposensitization, IgG anti-IgG titres greater than or equal to 9 were demonstrated in 45% of the patients. During hyposensitization IgG anti-IgG titres showed a slight initial increase followed by a decrease below pretreatment level. Neither increase nor decrease was statistically significant. Reactions to rabbit IgG F(ab')2 fractions were only obtained during hyposensitization. The occurrence of anti-IgG antibodies did no correlate with symptoms, side effects, or the level of allergen-specific IgG. In a previous study it was demonstrated that patients with multiallergy hyposensitized with combined allergen extracts showed a statistically significant increase in IgG anti-IgG titres during treatment. The increase failed to appear in the present patients allergic only to pollen and treated with purified allergen extracts. It is therefore suggested that a multiallergic condition and the combination and/or purification of allergen extracts administered during hyposensitization may influence the production of IgG anti- IgG antibodies.


Exploring the binding profiles of ConA, boronic acid and WGA by MALDI-TOF/TOF MS and magnetic particles.
Concanavalin A, boronic acid and Wheat germ agglutinin functionalized magnetic micro-particles were developed to enrich glycosylated peptides and proteins. The bead functionalities were validated according to their specificity by analyses of model proteins. Validated beads were employed for the enrichment of glycosylated human serum proteins. Eluted glycoproteins were digested by trypsin and the resulting peptides were purified by magnetic MB-HIC C8 beads. Each fraction was analyzed by MALDI-TOF MS and single peaks were subjected to MALDI-TOF/TOF MS with the objective to identify the respective proteins by database search. Search results revealed overlapping profiles of known serum glycoproteins.


Pathological fracture, bone metastases and primary hepatocellular carcinoma.
Pathological fracture and metastatic bone disease without pulmonary metastases were the presenting features in three patients ultimately found to have primary hepatocellular carcinoma. In one case immunoperoxidase staining of bone scrapings for alpha-fetoprotein secreting cells contributed directly to the diagnosis.


CASMI 2016: A manual approach for dereplication of natural products using tandem mass spectrometry.
The Critical Assessment of Small Molecule Identification (CASMI) contest is an initiative designed as an unbiased test of manual and automated strategies for the identification of small molecules from raw mass spectrometric data. In this contest, the participants are provided a set of high resolution MS and MS/MS data and asked to identify the unknown structure. CASMI 2016 is the fourth round of this contest in which the author participated in Category 1: Best Identification of Natural Products using a manual approach. The provided high resolution mass spectrometric data were interpreted manually using a combination of fragment and neutral loss analysis, literature consultation, manual database searches, deductive logic and experience. Out of 18 challenges, the author submitted correct structures as lead candidates for 14 challenges and 2nd ranked candidate for four challenges and was declared the winner of this category Pitfalls and challenges encountered during data interpretation are discussed.


Isolation and characterization of a pure mannan from Oncidium (cv. Gower Ramsey) current pseudobulb during initial inflorescence development.
A water-soluble and neutral polysaccharide was extracted from the current pseudobulbs of Oncidium "Gower Ramsey" during the early inflorescence stage (flower stalk less than 4 cm) by hot water, precipitated with ethanol, and purified with an anion exchanger. From the data of monosaccharide composition and linkage and anomeric configuration analyses, the polysaccharide was identified as a linear beta-1-->4 linked mannan.


[Changes in the spectrum of low-molecular physiologically active substances in patients with acute pneumonia who abuse alcohol].
A study of low-molecular substances in the blood serum of patients with acute pneumonia showing different risk factors as evidenced by fluid chromatography and gel chromatography showed its high value in prognosis of immunosuppression, in assessing the activity of the inflammatory process, an indicator for detoxicating and immunostimulating therapy and determination of treatment efficacy.


Understanding the functional late effects and informational needs of adult survivors of childhood cancer.
To report functional (physical and cognitive) late effects, experiences, and information needs of adult survivors of childhood cancer. Descriptive, mixed methods survey. Two pediatric oncology programs in the Midwest. Convenience sample of 272 young adult survivors. Voluntary survey completion by young adult survivors regarding late effects, experiences, and educational needs to develop appropriate comprehensive care programs for care provision before, during, and after transition to adult care. Survey domains were identified from existing survivorship literature and focused on all aspects of survivorship; however, this article focuses on results specific to the functional domain. Functional late effects, experiences, information needs, age, gender, and treatment intensity of young adult survivors of childhood cancer. Response rate was 48%. Functional late effects, perceptions, and information needs all correlated with intensity of treatment (those survivors most heavily treated experienced the most symptoms). Survivors wanted more information about late effects and how to deal with them. Women wanted more information about fertility-related topics, and participants who received more intense treatment generally wanted more information. Brain tumor survivors perceived greater cognitive difficulties, cognitive late effects, fatigue, and financial difficulties. Survivors experience myriad physical late effects and require ongoing access to information as needs change over time. Identifying new and innovative ways to reach survivors and better meet needs is important for care, research, and program development. The findings of the research underscore the importance of continuous learning opportunities for adult survivors of childhood cancer. The findings also highlight the need for healthcare teams to better understand the current and long-term needs of this population. In addition to traditional communication approaches, technologies such as social media and telemedicine can provide innovative ways to deliver patient-centered care.


Touch-free measurement of body temperature using close-up thermography of the ocular surface.
In experimental animal research body temperature (BT) is measured for the objective determination of an animals' physiological condition. Invasive, probe-based measurements are stressful and can influence experimental outcome. Alternatively BT can be determined touch-free from the emitted heat of the organism at a single spot using infrared thermometers [1]. To get visual confirmation and find more appropriate surfaces for measurement a hand-held thermal imager was equipped with a self-made, cheap, 3D-printable close-up lens system that reproducibly creates eight-time magnified thermal images and improves sensitivity. This setup was used to establish ocular surface temperature (OST), representing the temperature of the brain-heart axis, as a touch-free alternative for measurement of BT in mice, rats, rabbits and humans.OST measurement after isoflurane exposure and myocardial infarction (MI) experiments in mice revealed high physiological relevance and sensitivity, the possibility to discriminate between MI and sham operations in one hour and even long-term outcome-predictive capabilities of OST after MI. Summarized here we present: •Self-made close-up lens for thermal imaging cameras for eight-time magnification•Establishment of OST for touch-free determination of BT in rodents and humans•Short- and long-term predictive capabilities of OST in experimental MI in mice.


Pain neuroscience education and physical exercise for patients with chronic spinal pain in primary healthcare: a randomised trial protocol.
Chronic musculoskeletal pain affects more than 20% of the population, and the prevalence is increasing, causing suffering, loss of quality of life, disability, and an enormous expenditure on healthcare resources. The most common location for chronic pain is the spine. Many of the treatments used are mainly passive (pharmacological and invasive) and poor outcomes. The treatments currently applied in the public health system do not comply with the recommendations of the main clinical practice guidelines, which suggest the use of educational measures and physical exercise as the first-line treatment. A protocol based on active coping strategies is described, which will be evaluated through a clinical trial and which could facilitate the transfer of the recommendations of the clinical practice guidelines to a primary care setting. Randomised and multicentre clinical trials, which will be carried out in 10 Primary Care centres. The trial will compare the effect of a Pain Neuroscience Education program (six sessions, 10 h) and group physical exercise (18 sessions program carried out in six weeks, 18 h), with usual care physiotherapy treatment. Group physical exercise incorporates dual tasks, gaming, and reinforcement of contents of the educational program. The aim is to assess the effect of the intervention on quality of life, as well as on pain, disability, catastrophism, kinesiophobia, central sensitisation, and drug use. The outcome variables will be measured at the beginning of the intervention, after the intervention (week 11), at six months, and a year. Therapeutic interventions based on active coping strategies are essential for the treatment of chronic pain and the sustainability of the Public Health System. Demonstrating whether group interventions have an effect size is essential for optimising resources in such a prevalent problem. NCT03654235 "Retrospectively registered" 31 August 2018.


Myasthenia gravis: further electrophysiological and ultrastructural analysis of transmission failure in the mouse passive transfer model.
Using the mouse passive transfer model the mean amplitude of miniature endplate potentials and endplate potentials of mice treated with myasthenic immunoglobulins was markedly decreased. Miniature endplate potential frequency and quantum content of endplate potentials were normal, arguing against a major presynaptic disarrangement. Under electron-microscopy no gross structural alterations of endplates were demonstrated. It is concluded that the mouse passive transfer model closely resembles human myasthenia gravis of recent onset.


Combining Radiotherapy with Immunotherapy in Cervical Cancer: Where Do We Stand and Where Are We Going?
Combining immunotherapy and radiotherapy as a treatment strategy for cervical cancer has attracted increasing attention. The primary objective of this review is to provide an up-to-date summary of the knowledge regarding the combined use of radiotherapy and immunotherapy for treating cervical cancer. This review discusses the biological rationale combining immunotherapy with radiotherapy in a clinical setting and presents supporting evidence for the combination strategy based on both safety and effectiveness data. Additionally, we discuss the potential and challenges of combining radiotherapy and immunotherapy in clinical practice.


The effectiveness of educational program based on health belief model on promotion of puberty health concepts among teen girls: a cross-sectional study in north of Iran.
Puberty is a sensitive critical stage of human life. As numerous healthy habits and behaviors are created during adolescence, correct health education during puberty is essential to maintain and improve an individual's physical, emotional, and mental health. The present study aimed to determine the impact of educational intervention based on the predictors of the Health Belief Model (HBM) on female nine-grade students' health behaviors in Rasht, Iran. The present randomized controlled trial study examined 110 female nine-grade students. Multi-stage sampling was performed, and the students were randomly divided into two groups of 55 as intervention and control. The data collection tool included a valid and reliable questionnaire with four sections, namely demographic variables, knowledge, HBM constructs, and health behaviors during puberty. The educational program comprised four 45-60-min sessions per group (4 groups of 13) based on HBM. The data were collected two times, before and 1 month after the educational intervention, and were analyzed using the independent t-test, paired t-test, chi-square test, and SPSS 23. The mean age of menarche was 12.26 ± 1.133 in the intervention group and 12.12 ± 1.263 in the control group. The family was a source of information for students and the main cue to action before the intervention. Before the educational intervention, there was no significant difference between the experimental and control groups in terms of knowledge, HBM constructs, and puberty health behaviors; however, the variables increased significantly in the intervention group after educational intervention (P<0.001). Given the effectiveness of the HBM in improving the health behavior of adolescent girls, it is recommended that health policymakers should plan and implement educational interventions in this field.


Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: study protocol for a randomized controlled trial.
Spine metastasis is a common occurrence in cancer patients and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. This is a single-center, prospective, randomized, controlled trial in patients with spine metastasis from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum will be randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients will be treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters will be measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. The primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastasis, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. ClinicalTrials.gov NCT04375891 . Registered on 5 May 2020.


A critical review of various adsorbents for selective removal of nitrate from water: Structure, performance and mechanism.
Nitrate is ubiquitous pollutant due to its high water solubility, usually contributing to eutrophication, and posing a threat to aquatic ecosystem and human health. Adsorption approach has been widely used for nitrate removal because of the simplicity, easy operation, and low cost. Adsorbent plays a key role in the adsorptive removal of nitrate. The adsorption performance and adsorption mechanism are determined by the structural feature of adsorbent that is dependent on the preparation method. In this review, various types of adsorbents for nitrate removal were systematically summarized, their preparation, characterization, and adsorption performance were evaluated; the factors influencing the nitrate adsorption performance were discussed; the adsorption isotherm models, kinetic models and thermodynamic parameters were examined; and the possible adsorption mechanisms responsible for nitrate adsorption were categorized; the possible correlation of adsorbent structure to adsorption performance and adsorption mechanism were explained; the potential applications of adsorbents were discussed; finally, the strategies for improving adsorption capacity and selectivity towards nitrate, the challenges and future perspectives for developing novel adsorbent were also proposed. This review will deepen the understanding of nitrate removal by adsorption process and help the development of high-performance adsorbents for selective nitrate removal from water and wastewater.


Occurrence, source, and ecological risk assessment of organochlorine pesticides and polychlorinated biphenyls in the water-sediment system of Hangzhou Bay and East China Sea.
The pollution characteristics, potential sources, and potential ecological risk of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were investigated in the Hangzhou Bay (HZB) and East China Sea (ECS). Total OCPs concentration ranged from 2.62 to 102.07 ng/L and 4.41 to 75.79 μg/kg in the seawater and sediment samples, with PCBs concentration in the range of 0.40-51.75 ng/L and 0.80-45.54 μg/kg, respectively. The OCPs were positively correlated with nutrients, whereas PCBs presented a negative correlation. The newly imported dichlorodiphenyltrichloroethane (DDT) in HZB is mainly the mixing of technical DDT and dicofol sources. The PCB source composition is more likely related to the mixture of Kanechlor 300, 400, Aroclor 1016, 1242, and Aroclor 1248. Risk assessment results indicate that OCPs posed low risk in seawater. The potential risk of DDTs in the sediments is a cause of concern.


Estrogen modulates metabolic risk profile after resistance training in early postmenopausal women: a randomized controlled trial.
Women experience an unhealthy change in metabolic risk profile at menopause. The purpose of the present study was to determine effects of resistance training with or without transdermal estrogen therapy (ET) on adipose tissue mass and metabolic risk profile in early postmenopausal women. A double-blinded randomized controlled trial, where healthy, untrained postmenopausal women were allocated to supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks. Endpoints with prespecified hypotheses were the change in total fat mass (FM) (main endpoint) and the change in visceral FM (secondary endpoint) from before to after the intervention. Additionally, prespecified endpoints of body composition, metabolic health-related blood markers, fat%, fat cell size, and lipogenic markers in subcutaneous adipose tissue (SAT) from abdominal and femoral region were explored. Compared with the ET group, the PLC group experienced a greater reduction (time × treatment interaction P < 0.05) in total FM (PLC vs ET: -5.6% vs -1.1%) and visceral FM (-18.6% vs -6.8%), and femoral SAT (-5.6% vs 1.0%), but not abdominal SAT mass (-8.5% vs -2.8%, P = 0.15).The ET group improved their metabolic blood profile by reduced low-density lipoprotein, glucose and hemoglobin A1c compared with PLC (time × treatment interaction P < 0.05). The intervention induced changes in lipolytic markers of abdominal SAT, whereas no changes were detected in femoral SAT. Use of transdermal ET reduced adipose tissue loss, but improved metabolic blood markers when combined with 12 weeks of progressive resistance training in early postmenopausal women.


Nine known and five novel mutations in the erythroid transcription factor KLF1 gene and phenotypic expression of fetal hemoglobin in hemoglobin E disorder.
Hemoglobin E is the most common Hb variant found in South East Asia. Variation of Hb F expression in Hb E syndrome is associated with several genetic modifiers. We report several single nucleotide polymorphisms (SNPs), including nine known and five novel mutations of the Krüppel-like factor 1 (KLF1; an erythroid specific transcription factor) gene and determine their associations with phenotypic expression of Hb F in Hb E disorders. KLF1 mutations were examined using high resolution melting (HRM) assay and DNA sequencing in 575 homozygous Hb E, 278 heterozygous Hb E and 100 normal subjects. Fourteen mutations were mostly observed in subjects with elevated Hb F, including nine known mutations (G176AfsX179, T334R, R238H, -154 (C>T), A298P, S270W, R301H, -148 (G>A) and G335R and five novel mutations (Q217X, Q223X, Y290_S293del, K307N, and M358I). None of them, but the -148 (G>A), were observed in normal controls to have Hb F <1%. Combined KLF1 mutations with other SNPs including (G)γ-XmnI, BCL11A and HBS1L-MYB were associated with higher Hb F levels. KLF1 is therefore an important genetic factor associated with increased Hb F and in combination with other modifying factors could explain the phenotypic variation of Hb F expression in this common hemoglobinopathy.


Enhanced Cycling Performance of All-Solid-State Li-S Battery Enabled by PVP-Blended PEO-Based Double-Layer Electrolyte.
Despite the high specific capacity of Li-S battery, shuttle effect of lithium polysulfides (LiPSs) and safety issue pose a great challenge to realize its commercial application. Replacing liquid electrolyte with poly (ethylene oxide) (PEO) -based solid-state electrolyte is considered as a promising method to boost the safety, but the shuttle effect of LiPSs cannot be completely eliminated. In this work, a new kind of double-layer PEO-based polymer electrolyte is designed to restrict the LiPSs. The layer next to cathode consists of PEO and poly(vinylpyrrolidone) (PVP). The other layer consists of PEO. PVP with abundant of amide groups has been proved to have strong affinity to LiPSs. The strong interaction between LiPSs and carbonyl groups in amide is verified by Attenuated Total Reflection-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy tests. As a result, the assembled Li-S battery exhibits a specific capacity of 1100 mAh g-1 and capacity retention of 347 mAh g-1 after 200 cycles at 60 °C and 0.05 C, while the capacity retention of the battery without PVP-blended PEO electrolyte remains only 27 % at the same conditions.


Prediction of SMEs' R&D performances by machine learning for project selection.
To improve the efficiency of government-funded research and development (R&D) programs for small and medium enterprises, it is necessary to make the process of selecting beneficiary firm objective. We aimed to develop machine learning models to predict the performances of individual R&D projects in advance, and to present an objective method that can be utilized in the project selection. We trained our models on data from 1771 R&D projects conducted in South Korea between 2011 and 2015. The models predict the likelihood of R&D success, commercialization, and patent applications within 5 years of project completion. Key factors for predicting the performances include the research period and area, the ratio of subsidy to research budget, the firm's region and venture certification, and the average debt ratio of the industry. Our models' precisions were superior to qualitative expert evaluation, and the machine learning rules could be explained theoretically. We presented a methodology for objectively scoring new R&D projects based on their propensity scores of achieving the performances and balancing them with expert evaluation scores. Our methodology is expected to contribute to improving the efficiency of R&D investment by supplementing qualitative expert evaluation and selecting projects with a high probability of success.


System analysis of Huang-Lian-Jie-Du-Tang and their key active ingredients for overcoming CML resistance by suppression of leukemia stem cells.
BCR-ABL1-based resistance to imatinib, mainly resulting from BCR-ABL1 mutations, is largely solved after second- and third-generation tyrosine kinase inhibitors (TKIs) are discovered. Nonetheless, imatinib resistance without BCR-ABL1 mutations, including intrinsic resistance induced by stem cells within chronic myeloid leukemia (CML), remains the major clinical challenge for many patients. To study the key active ingredients and corresponding target proteins in Huang-Lian-Jie-Du-Tang (HLJDT) against BCR-ABL1-independent CML resistance to therapeutics, and then explore its mechanism of against CML drug resistance. Cytotoxicity of HLJDT and its active ingredients in BCR-ABL1-independent imatinib resistance cells was analyzed through MTT assay. The cloning ability was measured through soft agar assay. Monitoring therapeutic effect on Xenografted mice CML model by in vivo imaging technology and mice survival time. Predicting the potential target protein binding sites by the technology of photocrosslinking sensor chip, molecular space simulation docking, and use Surface Plasmon Resonance (SPR) technology . Flow cytometry to detect the ratio of stem progenitor cells (CD34+). Constructing bone marrow transplantation mice CML leukemia model, detect the effects on leukemia stem cells LSK (Lin-\ Sca-1+ \C-kit+) self-renewal. Treatment with HLJDT, berberine and baicalein inhibited cell viability and colony formation of BCR-ABL1-independent imatinib-resistant cells in vitro while prolonging survival in mouse with CML xenografts and transplatation CML-like mouse models in vivo. JAK2 and MCL1were identified as targets of berberine and baicalein. JAK2 and MCL1 are involved in multi-leukemia stem cell-related pathways. Moreover, the ratio of CD34+ cells in resistant CML cells is higher than in treatment-sensitive CML cells. Treatment with BBR or baicalein partially suppressed CML leukemic stem cells (LSCs) self-renewal in vitro and in vivo. From the above, we concluded that HLJDT and its key active ingredients (BBR and baicalein) allowed to overcome imatinib resistance with BCR-ABL1 independent by eradication of LSCs by targeting the JAK2 and MCL1 protein levels. Our results lay the foundation for applying HLJDT in patients with TKI-resistant CML.