The Frequency and Predictors of Unsuppressed HIV Viral Load Among People with HIV in Nyaruguru District, Rwanda.
By the end of 2015, epidemiological studies approximated 37 million people living with HIV (PLHIV) and 46.3% of them were initiated to antiretroviral therapies. From the 90-90-90 strategy, by 2020 at global level, 90% of all people living with HIV were expected to suppress viral load (VL). Although VL suppression is an important indicator of treatment success in PLHIV, studies on this indicator remain scarce in Rwanda where the prevalence of HIV is 3% with 9% for non-suppression. This work, thus, determined the prevalence of VL non-suppression and its associated predictors among PLHIV. A cross-sectional study was conducted among 637 PLHIV enrolled in healthcare services between 2016 and 2017 in Nyaruguru district. Socio-demographic, treatment, clinical, immunological and VL data were extracted from medical records. Bivariate and multivariate logistic regression analyses were performed to determine associated factors with VL suppression considering 95% confidence intervals and statistical significance of p<0.005. More than half of participants were female (57.77%). The prevalence of unsuppressed HIV VL was 8.9% and 88.7% of respondents were satisfied with the service provided. Males were more likely to be unsuppressed HIV VL [aOR = 3.02; 95% CI (1.19-7.64), p = 0.02] than females. Higher likelihoods of VL non-suppression were among those with history of clinical failure [aOR = 3.14; 95% CI (1.70-14.03), p = 0.034] or history of treatment interruption [aOR = 8.29; 95% CI (2.60-26.42) p = 0.002]. Those with a bad perception toward the whole life treatment were more likely to be unsuppressed [aOR = 4.32; 95% CI (1.98-18.99), p = 0.049] than their counterparts. Sex, treatment interruption, bad perception toward the whole life treatment, clinical failure and lack of confidentiality were the major predictors of being unsuppressed. More efforts on counseling HIV patients to improve their knowledge would drop levels of VL non-suppression, so improving the quality of service should be prioritized to increase suppression.


Comparison of the peak exercise response measured by the ramp and 1-min step cycle exercise protocols in patients with exertional dyspnea.
To compare the peak exercise response and determine the limits of agreement between the ramp and the 1-min step cycle protocols in a representative population of patients with exertional breathlessness attending a respiratory outpatient clinic. Crossover with the test order double blinded and randomized. Outpatient exercise physiology laboratory. Twenty-two patients (12 men; mean [SD] age, 59 [8] years; FEV(1), 71% [21%]) with lung disease and/or exertional breathlessness. Symptom-limited, maximum cycle exercise tests using a ramp and a 1-min step work rate (WR) protocols. The two protocols were assigned to subjects in a randomized manner. Oxygen uptake (O(2)), minute ventilation (E), heart rate (HR), WR, exercise time, and Borg scores were compared at symptom-limited peak exercise. The mean (SD) peak values for the ramp and the step protocols, respectively, were as follows: peak O(2), 1.51 (0.44) L/min and 1.49 (0.43) L/min; peak E, 50.8 (12.9) L/min and 49.9 (14.5) L/min; and peak HR, 133 (24) beats/min and 131 (22) beats/min (p > 0.05). There were no significant differences between breathlessness and perceived exertion at peak exercise. Peak WR (WRpeak) and exercise time were significantly higher using the ramp protocol: 110.5 (37.1) W vs 105.6 (35.6) W, and 8.2 (2.0) min vs. 7.6 (1.9) min, respectively. The ramp protocol leads to a higher WRpeak, and this may have implications for exercise prescription. However, there were no significant differences between the two protocols for the peak physiologic responses. The choice of protocol for the measurement of maximal exercise capacity remains one of laboratory preference.


Judicious use of kinetin to improve growth and yield of rice in nickel contaminated soil.
The present study was conducted to evaluate the effect of kinetin on growth and yield of rice in the presence and absence of nickel contamination. Rice seedlings were dipped in kinetin solution (10(-3), 10(-4) and 10 M(-5)) for 2 hours and transplanted in pots having soil contaminated with nickel sulfate @ 130 mg kg(-1). Experiment was laid out according to completely randomized design with four replications. Results revealed that kinetin significantly improved growth and yield of rice grown in nickel contamination. Kinetin @ 10(-4) M showed maximum improvement in plant height, paddy yield, 1000 grain weight, number of tillers and panicles up to 9.76, 15.72, 11.77, 11.87, and 10.90%, respectively, as compared to plants grown in contaminated soil without kinetin. Kinetin also improved the uptake of nutrients (NPK) in straw and grain of plants grown in Ni contaminated soil. Plants treated with kinetin had more concentration of Ni in shoot but less in grain compared to plants grown in Ni contaminated soil without application of kinetin. The application of kinetin can reduce stress effect on plants through improvement in the biomass of plant. This strategy could be used to increase the phytoextraction of Ni from the contaminated soil.


Breast cancer screening and the changing population pyramid of Japan.
Breast cancer has been the most prevalent cancer in Japan since the 1990s. The mortality from breast cancer is increasing in Japan, whereas in other industrialized countries it has been decreasing since 1990. On the other hand, Japan faces unparalleled growth in its aging population. The aim of this study was to report the mammography screening among Japanese women and the related upcoming changes in the population pyramid of Japan. The reference data for our study were obtained from the Center for Cancer Control and Information Services, Japan Ministry of Internal Affairs and Communications, Ministry of Health, Labour and Welfare, the Japanese Cancer Society, and the National Institute of Population and Social Security. The survey data were obtained from breast cancer and mammography screenings in the Tokyo Prefecture in 2008. The following parameters were analyzed: annual breast cancer incidence, current screening rates, average life-span, and predicted demographic statistics. Our results showed that breast cancer incidence and mortality have been increasing annually in Japan. The average age of breast cancer patients increased to 58.40 years in 2010. The incidence of breast cancer in women aged 65 years and older increased from 25.3 to 32.9 % in the last 10 years and is expected to continue to increase in the future. The check-up rate was 16.0-20.0 % for women aged 65-74 years and 43.0-46.0 % for women aged 40-54 years. According to our questionnaire survey, concerns about breast cancer and mammography screening were high in the young and low in the elderly women. The Japanese population aged 65 years and older was 30,740 (24.1 %) in 2012 and is estimated to increase by 40 % over the next 20 years despite Japan's declining population size. Breast cancer incidence has increased in Japan, even among patients aged 65 years and older. Breast cancer has become increasingly prevalent in older Japanese women. As the population pyramid of Japan changes, women aged 65 years and older, who think that there is no longer need to receive mammography screening and are not educated regarding self-examinations, should be encouraged to receive regular check-ups for breast cancer.


Magnetoelectric relaxor and reentrant behaviours in multiferroic Pb(Fe2/3W1/3)O3 crystal.
Significant quenched disorder in crystal structure can break ferroic (magnetic or electric) long-range order, resulting in the development of ferroic glassy states at low temperatures such as magnetic spin glasses, electric dipolar glasses, relaxor ferroelectrics, etc. These states have been widely studied due to novel physical phenomena they reveal. Much less known are the effects of quenched disorder in multiferroics, i.e. the materials where magnetic and electric correlations coexist. Here we report an unusual behaviour in complex perovskite Pb(Fe2/3W1/3)O3 (PFW) crystals: the coexistence of electric relaxor, magnetic relaxor and antiferromagnetic (AFM) states. The most striking finding is the transformation of the AFM phase into a new reentrant-type magnetic glassy phase below Tg ≅ 10 K. We show that the behaviour at this transformation contrasts the typical behaviour of canonical spin glasses and is similar to the behaviour of relaxor ferroelectrics. Magnetoelectric effect is also observed in the AFM phase in the temperature range of the transition into electric relaxor phase at Tf ≅ 200. The mechanism of magnetic relaxor behaviour is supposed to arise from the frustrated interactions among the spins located at the AFM domain walls. Our results should inspire further studies of multirelaxor behaviour in other multiferroic systems.


New mutation, P575L, in the GUCY2D gene in a family with autosomal dominant progressive cone degeneration.
To clinically characterize the retinal abnormalities and identify the mutation causing an autosomal dominant cone degeneration in an African American family. Clinical characterization of family members using fundus photography, fluorescein angiography, and electrophysiological testing. Standard molecular genetic methods were used, including segregation analysis and DNA sequencing of candidate genes. Genetic mutation screening was performed in 20 individuals: 10 clinically unaffected and 10 affected. The affected family members had findings consistent with a primary cone degeneration. A novel mutation, P575L, was found in exon 8 of the GUCY2D gene in 12 members of this family. In addition to finding a previously undescribed mutation in GUCY2D, 2 of the family members who were thought to be unaffected through routine clinical examinations also had this mutation. These findings suggest that autosomal dominant cone degeneration in this family demonstrated age-dependent penetrance, which appears incomplete. This is the first African American family reported with a mutation in GUCY2D. Because the disease in this family and the one we previously described is primarily a cone degeneration, this disease should be more properly classified as cone degeneration and be called cone degeneration 2. This study helps to expand the phenotype of the disease and help clinicians identify patients with cone degenerations.


Application of high-performance liquid chromatography to the assessment of subunit heterogeneity in plant 11S storage globulins.
Plant 11S storage proteins from a wide range of species have been resolved into their component subunits by ion-exchange fast protein liquid chromatography under denaturing conditions. The complex profiles obtained were reproducible and characteristic for each plant species analysed. The technique is shown to have distinct advantages over the more conventional electrophoretic approaches used to assess 11S subunit heterogeneity. The potential for the fast protein liquid chromatographic method as a simple screening system is discussed.


A Longitudinal Study Examining Self-Regulation Practices in Older Drivers with and without Suspected Mild Cognitive Impairment.
Mild cognitive impairment can impact driving performance and self-regulation practices. However, there is little evidence on how cognitive impairment may impact these self-regulation practices over a period of time. Therefore, the aim of this study was to examine changes in the number and type of situations in which older drivers with and without suspected mild cognitive impairment (MCI) self-regulate their driving over a one-year period, after accounting for relevant confounders. A longitudinal cohort study involving older drivers (65+ years) from metropolitan Western Australia was interviewed by a telephone interview at baseline and one-year follow-up. The Telephone Cognitive Screen (T-CogS) was also administered to determine changes in their cognitive status. The outcome of interest was the number and type of situations older drivers self-regulated their driving. A total of 670 drivers were interviewed at baseline (suspected MCI: n = 227; no cognitive impairment: n = 443) and one-year follow-up (suspected MCI: n = 251; no cognitive impairment: n = 419), which provided 1340 observations. Drivers with suspected MCI increased the number of driving situations in which they self-regulated by 13% over a period of one-year compared with drivers without cognitive impairment (IRR = 1.13, 95% CI = 1.02-1.27, p = 0.025). Specifically, drivers with suspected MCI had 60% increased odds of self-regulating when "making turns across oncoming traffic" compared with drivers without cognitive impairment (unadjusted OR = 1.60, 95% CI = 1.02-2.53, p = 0.041). Other significant factors included being female (IRR = 1.87, 95% = 1.52-2.32, p = 0.001), aged 75+ years (IRR = 1.33, 95% CI = 1.10-1.60, p = 0.003), higher number of comorbidities (1-3 comorbidities: IRR = 1.26, 95% CI = 1.01-1.58, p = 0.040; 4+ comorbidities: IRR = 1.39, 95% CI = 1.08-1.78, p = 0.011), "decreased driving confidence" (IRR = 1.32, 95% CI = 1.10-1.58, p-value = 0.003) and "preference of having someone else drive" (IRR = 1.38, 95% CI = 1.12-1.70, p = 0.003). Having one or more traffic infringements was also associated with a decrease in the number of self-regulated driving situations (IRR = 0.80, 95% CI = 0.67-0.95, p = 0.011). Over a one-year period, drivers with suspected MCI increased the number of situations in which they self-regulated their driving compared with drivers without cognitive impairment, particularly when "making turns across oncoming traffic". Future studies should examine whether this increase in the types and number of self-regulated driving situations is enough to compensate for declines in cognition.


Changes in coagulation-fibrinolysis balance in blood mononuclear cells and in gastric mucosa from patients with Helicobacter pylori infection.
Helicobacter pylori and some of its virulence factors stimulate human blood mononuclear cells (MNC) in vitro to produce tissue factor (TF) and plasminogen activator inhibitor-2 (PAI-2). In this study we investigated the procoagulant-fibrinolytic potential of blood MNC in patients with H. pylori infection. In the same patients we also evaluated the coagulation-fibrinolysis profile in gastric tissue and in plasma. The production of TF and PAI-2 was evaluated in 61 patients with dyspepsia, 31 positive and 30 negative for H. pylori infection. TF expressed by MNC and PAI-2 accumulation in cell culture medium after incubation for 20 h at 37 degrees C were significantly higher in H. pylori(+) than in H. pylori(-) patients and were significantly correlated. TF and PAI-2 content in extracts of gastric mucosa was similar in the two groups whereas lower levels of tissue plasminogen activator (t-PA) and thrombomodulin (TM) antigens were found in the antrum of H. pylori(+) patients. No difference between the groups was observed in plasma thrombus precursor protein, prothrombin fragment 1+2, D-dimer, t-PA, PAI-1, TM and thrombin activatable fibrinolysis inhibitor. H. pylori infection is associated with functional abnormalities of blood MNC resulting in the coordinate expression of TF and antifibrinolytic activity. Changes in cell coagulation-fibrinolysis balance may represent a link between H. pylori infection and ischemic heart disease.


Age and long-term outcomes of patients with venous thromboembolism: From the COMMAND VTE Registry.
There is still a scarcity of data on the relation between age and long-term clinical outcomes of patients with venous thromboembolism (VTE). The COMMAND VTE Registry was a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We divided the entire cohort into 3 groups: patients aged <65 years (N = 1100, 36.7%), patients aged 65 ≤ and ≤ 80 years (N = 1314, 43.4%), and patients aged >80 years (N = 603, 19.9%). Discontinuation of anticoagulation therapy during the follow-up period was most frequent in patients aged <65 years (44%, 38% and 33%, P < 0.001). The cumulative 5-year incidences were 12.7%, 9.8% and 7.4% for recurrent VTE, 10.8%, 12.2% and 14.9% for major bleeding, and 23.0%, 31.4%, and 38.6% for all-cause death. Adjusting for cofounders and taking into account the competing risk of all-cause death, the lower risk of patients aged >80 years, and those aged 65 ≤ and ≤ 80 years relative to those aged <65 years remained significant for recurrent VTE (65 ≤ age ≤ 80 years, HR: 0.71, 95%CI: 0.53-0.94, P = 0.02; age > 80 years, HR: 0.59, 95%CI: 0.39-0.89, P = 0.01), and the risk remained insignificant for major bleeding (65 ≤ age ≤ 80 years, HR: 1.00, 95%CI: 0.76-1.31, P = 0.98; age > 80 years, HR: 1.17, 95%CI: 0.83-1.65, P = 0.37). In the current real-world VTE registry, there was no significant difference in the risk of major bleeding depending on different age groups, while younger patients showed an excess risk for recurrent VTE compared with older patients.


Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver.
Arginine is a precursor for the synthesis of urea, polyamines, creatine phosphate, nitric oxide and proteins. It is synthesized from ornithine by argininosuccinate synthetase and argininosuccinate lyase and is degraded by arginase, which consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Recently, cDNAs for human and rat arginase II have been isolated. In this study, immunocytochemical analysis showed that human arginase II expressed in COS-7 cells was localized in the mitochondria. Arginase II mRNA was abundant in the rat small intestine and kidney. In the kidney, argininosuccinate synthetase and lyase were immunostained in the cortex, intensely in proximal tubules and much less intensely in distal tubules. In contrast, arginase II was stained intensely in the outer stripes of the outer medulla, presumably in the proximal straight tubules, and in a subpopulation of the proximal tubules in the cortex. Immunostaining of serial sections of the kidney showed that argininosuccinate synthetase and arginase II were colocalized in a subpopulation of proximal tubules in the cortex, whereas only the synthetase, but not arginase II, was present in another subpopulation of proximal tubules. In the liver, all the enzymes of the urea cycle, i.e. carbamylphosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase and lyase and arginase I, showed similar zonation patterns with staining more intense in periportal hepatocytes than in pericentral hepatocytes, although zonation of ornithine transcarbamylase was much less prominent. The implications of these results are discussed.


Nonpharmacologic means of preventing asthma.
Cessation of smoking in the home is one of the most important nonpharmacologic actions to be recommended. There is a highly significant increase in wheezing, coughing, and respiratory infections in children with smoking mothers, and this increase is directly proportional to the number of cigarettes smoked. Cord blood IgE levels are increased in babies whose mothers smoke during pregnancy. Other agents, such as sulpur dioxide and chemical pollutants from industrial processes may play a role in the development or exacerbation, of asthma symptoms and should be avoided. One of the most interesting areas in food allergy is whether breast feeding causes sensitization or induces tolerance in infants to foods ingested by the mother. There is an increase in asthma in second-generation immigrant populations who are exposed, from birth, to the Western style of living which increases their exposure to house dust mite. Several studies have shown that month of birth is important in the development of specific allergies, for example, in the incidence of birch pollen allergy in Scandinavia. The presence of a pet in the home at birth is associated with a greater incidence of allergy to that animal. Our study in asthmatic children has shown a strong association (p less than 0.001) between the presence of allergens in the air in their homes (sampled retrospectively in the month of birth) with a positive skin test to those allergens.(ABSTRACT TRUNCATED AT 250 WORDS)


Diffuse dermal mucinosis secondary to colony-stimulating factor 1 receptor monoclonal antibody treatment: A novel and peculiar drug-induced diffuse cutaneous mucinosis.
Colony-stimulating factor 1 receptor (CSF1R) inhibitors represent a new class of immune-modulatory drugs, mostly investigated in clinical trials in different malignant neoplasms. Four patients, diagnosed with recurrent or advanced malignant neoplasm and treated with a combination of anti-programmed death ligand 1 and anti-CSF1R monoclonal antibodies, developed an asymptomatic cutaneous eruption characterized by an ill-defined pseudoedematous to waxy diffuse infiltration with a reticular cobblestone-like pattern. Histopathological examination revealed diffuse mucin deposition involving the superficial and mid-dermis with fragmented and scattered elastic fibers. The exact pathogenic mechanisms implicated in the development of mucin deposits in patients treated with CSF1R inhibitors remain to be elucidated. A reduced degradation and clearance of components of the extracellular matrix by macrophages secondary to CSF1 pathway inhibition may be hypothesized. Shredding and fragmentation of elastic fibers may be a result of the increased accumulation of mucopolysaccharides. This observation illustrates the new spectrum of skin-related toxicities secondary to new targeting therapies. This may contribute to a better understanding of the underlying pathogenic mechanisms in skin diseases characterized by a persistent dermal glycosaminoglycan deposition.


Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality.
We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00, P = .05). Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.


Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer.
Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL- 1, 0.01-10 ng mL- 1, 10-50 ng mL- 1, and 50-500 ng mL- 1). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL- 1 concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20-30 s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.


The gut microbiota of Cystidicola farionis parasitizing the swim bladder of the nosed charr morph Salvelinus malma complex in Lake Kronotskoe (Kamchatka, Russia).
Using the approach of sequencing the V3-V4 region of the 16S rRNA gene, we have analyzed the bacterial diversity associated with the gut and "body" (other parts of nematode after dissection: cuticle, epidermis and longitudinal muscles, etc) of Cystidicola farionis parasitizing the swim bladder of different morphotypes of the nosed charr. Comparisons of the gut microbiota of nematodes with their "body" has revealed that the associated microbiota are closely related to each other. Taxonomic analysis indicated that the relative abundances of the dominant nematode-associated bacteria varied with individual fish. The common dominant microbiota of the gut and "body" of nematodes were represented by Aeromonas, Pseudomonas, Shewanella, and Yersinia, while the associated microbiota of the swim bladder of the nosed charr was dominated by Acinetobacter, Cetobacterium, Pajaroellobacter, Paracoccus, Pseudomonas, Shewanella. By comparing the associated microbiota of nematode parasitizing the different morphotypes of the nosed charr the difference in richness estimates (number of OTU's and Chao1) were revealed between the N1g and N2 morphs.


Does multiorgan versus kidney-only cadaveric organ procurement affect graft outcomes?
The majority of kidney grafts in most European countries still come from deceased donors who provide other organs. We analyzed whether multiorgan procurement portends a worse functional outcome compared with kidney-only harvesting. We performed a retrospective analysis of 1043 consecutive brain-dead donor kidney transplantations performed at a single academic institution from September 2002 to June 2011. The graft outcomes using kidney-only donors (n = 243) were compared with multiorgan donor grafts (n = 800) analyzing donor age, gender, cause of death, duration of mechanical ventilation, renal function, and cold ischemic interval. We compared delayed graft function and serum creatinine values at 1, 3, 6, and 12 months posttransplantation as well as graft survivals. This methodology was also applied to the subset of expanded criteria donors: 179 kidney-only versus 474 multiorgan. The influence of donor variables on graft survival was also analyzed in a Cox regression model. Immunosuppressive regimens and preservation solutions were similar in both groups. Kidney-only donors were older than their multiorgan counterparts (53.1 versus 44.8, P < .0005) and predominantly male (76.5% versus 62.6% male donors, P < .0005). Other donor variables were comparable. Kidney-only donor grafts showed a slightly higher incidence of delayed function (27.2 versus 21.1%, P = .049), but the mean serum creatinine values were similar at all intervals. No differences were observed in 7-year graft survival: 80.7% versus 79.9%. Expanded criteria donor grafts showed overlapping results, except for a higher rate of donor oligoanuria and a lower 1-month mean creatinine among kidney-only donors. Multivariate analysis revealed that the number of harvested organs did not influence graft survival. Immediate and long-term outcomes of kidney grafts did not correlate with the number of organs harvested from the donor. The longer explantation time associated with multiorgan procurement did not seem to affect graft function.


Efficacy and safety of sucroferric oxyhydroxide in the treatment of hyperphosphataemia in chronic kidney disease. FOSFASTUR study.
Alterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is sucroferric oxyhydroxide (SFO). To analyse the efficacy and safety of SFO in 3 cohorts of patients, one with advanced CKD not on dialysis, another on peritoneal dialysis and the last on haemodialysis, followed for 6 months. A prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed. Eighty-five patients were included in the study (62±12 years, 64% male, 34% diabetic), 25 with advanced CKD not on dialysis, 25 on peritoneal dialysis and lastly, 35 on haemodialysis. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964±323mg/day. Overall, serum phosphate levels saw a significant reduction at 3 months of treatment (19.6%; P<.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, transferrin saturation index or haemoglobin, although there was a tendency for the last 2 to increase. Twelve patients (14%) withdrew from follow-up, 10 due to gastrointestinal adverse effects (primarily diarrhoea) and 2 were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1,147±371mg/day. SFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the 3 groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1,000mg/day. Diarrhoea was the most common side effect, although it generally was not significant.


Deficiency of Pink1 promotes the differentiation of Th1 cells.
Previous studies have found that Pink1 is crucial for T cell activation and the function of Treg cells. However, the effect of Pink1 on inflammatory Th1 cells is largely unknown. In the process of Th1 differentiation from human naïve T cells, we found a reduction of Pink1 and Parkin. We then focused our attention on the Pink1 KO mice. Although there was no difference in the baseline of the T cell subset of Pink1 KO mice, Th1 differentiation from Pink1 KO naïve T cells in vitro showed a significant increase. Subsequently, we transferred naïve CD4+ T cells into Rag2 KO mice to establish a T-cell colitis mouse model and found that CD4+ T cells in mesentery lymph nodes of mice receiving Pink1 KO cells increased significantly, especially Th1 cells. Intestinal IHC staining also showed that the transcription factor T-bet of Th1 increased. Treatment of CD4+ T cells from lupus-like mice with mitophagy agonist urolithin A, a reduction of Th1 cells was observed, suggesting the clinical value of using mitophagy agonists to suppress Th1-dominated disease in the future.


Upper trapezius muscle activation patterns in neck-shoulder pain patients and healthy controls.
This study aimed at investigating whether patients with neck-shoulder complaints from different aetiologies (work-related musculo-skeletal disorders, WMSD; whiplash associated disorders, WAD) show comparable muscle activation patterns, characterised by higher activation and lower relaxation levels of the trapezius muscles compared to healthy controls. Twenty healthy controls, 21 WMSD and 20 WAD patients with non-acute neck-shoulder pain were recruited for this cross-sectional study. Surface electromyography (sEMG) recordings were performed at the upper trapezius muscles during reference contractions, standardised computer tasks (typing and unilateral stress task), and rest measurements. sEMG was continuously recorded during these measurements. Outcome measures were root mean square (RMS) to study muscle activity, and relative rest time (RRT) to study muscle relaxation. Statistical analysis comprised the bootstrap technique and Kruskall-Wallis tests. Results showed no clear evidence for abnormal muscle activation patterns in WMSD and WAD patients compared to healthy controls. However, a tendency was observed for higher RMS levels during the reference contractions and computer tasks in both patient groups compared to healthy controls, and lower RRT levels at the non-dominant side during stress. Both patient groups also showed larger variability in RMS and RRT values. This variability has more often been reported in literature and may suggest the existence of subgroups of pain patients with corresponding different muscle activation patterns not related to aetiology. Future research may focus on identifying these subgroups of patients with neck-shoulder pain.


Cytoplasmic free calcium concentration in porcine platelets. Regulation by an intracellular nonmitochondrial calcium pump and increase after thrombin stimulation.
Mechanisms are assumed to exist in the resting platelet which maintain the concentration of cytoplasmic free calcium below that level required to activate cellular responses. To assess such processes the porcine platelet plasma membrane was selectively lysed with digitonin and the uptake (or flux) of free calcium monitored by an extracellular calcium electrode. Lysis resulted in an immediate lowering of the extracellular free calcium, due to the action of intracellular organelle(s) acting on the extracellular space through the permeabilized plasma membrane. In resting platelets, the rate of calcium uptake was first order with respect to the extracellular prelytic calcium concentration, and hence the cytoplasmic free concentration was found to be 1 X 10(-7) M by extrapolation to a point of zero flux (i.e., the null point). This approach could not be used with thrombin-stimulated platelets, as external calcium was required for both secretion of ATP + ADP and aggregation. Nevertheless, evidence for an increase in cytoplasmic free calcium after thrombin stimulation was obtained. Metabolic inhibitors and agents known to inhibit calcium uptake by mitochondria had no effect on the calcium flux following lysis, indicating different mechanisms for calcium homeostasis in the platelet when compared with other cell types (e.g., liver). Levels of ionophore A23187, which caused platelet aggregation, gave a massive release of the nonmitochondrial pool of calcium into the cytoplasmic space. Thus, in porcine platelets an intracellular energy-requiring calcium pump, which sequesters calcium in a nonmitochondrial membranous compartment, is crucial for intracellular calcium homeostasis.


Ventricular septal summit stimulation in atrioventricular nodal reentrant tachycardia.
In all, 18 consecutive patients with atrioventricular nodal reentry tachycardia (AVNRT) underwent right ventricular (RV) stimulation during AVNRT from either the RV apex or summit. Stimulation from the RV apex advanced the tachycardia with the same atrial sequence in 6 of 18 patients (33%), but never conclusively excluded the presence of a low atrial tachycardia. RV summit stimulation resulted in direct stimulation of the low septal right atrium in 6 patients. RV summit stimulation advanced the tachycardia in 4 patients, delayed it in 2 and terminated it in 3 without an atrial electrogram. The latter 2 findings exclude the presence of a low atrial tachycardia. Thus, in patients with AVNRT, application of extrastimuli closer to the putative reentrant site enables greater efficacy in tachycardia resetting and in excluding a low septal atrial tachycardia.


Proapoptotic activity of aflatoxin B1 and sterigmatocystin in HepG2 cells.
Aflatoxin B1 (AFB1) and sterigmatocystin (ST) are two hepatocarcinogenic mycotoxins that are commonly coexisted in cereal grains, and their co-proapoptotic activity in HepG2 cells was studied. The values of IC50, which is the dosage of mycotoxin resulting in a 50% cell growth inhibition measured by a sulforhodamine B (SRB) colorimetric assay, were 16.9 μM and 7.3 μM for AFB1 and ST, respectively. Additively and dose-dependently, cell apoptosis-related toxicity endpoints of double strand DNA and ATP content were decreased while the intracellular ROS and mitochondria membrane permeability (MMP) were increased. Consistently, when cell cycle is arrest at G0/G1 or S phase by AFB1 and/or ST, the experimental results from flow cytometry assay demonstrated that the rate of cell apoptosis and mitochondrial membrane potential were also additively increased and decreased, respectively, in a dose-dependent manner. Thus, the integrity of mitochondria (MMP and membrane potential) that is the central component of cell apoptosis is disrupted by AFB1 and ST in an additive manner. With the immunocytochemistry analysis showing increased expression of apoptosis-related proteins of Bax, Caspase-3 and p53 and decreased expression of Bcl-2 protein, an additive nature of the co-proapoptotic activity of AFB1 and ST was revealed.


COVID-19 underreporting and its impact on vaccination strategies.
Underreporting cases of infectious diseases poses a major challenge in the analysis of their epidemiological characteristics and dynamical aspects. Without accurate numerical estimates it is difficult to precisely quantify the proportions of severe and critical cases, as well as the mortality rate. Such estimates can be provided for instance by testing the presence of the virus. However, during an ongoing epidemic, such tests' implementation is a daunting task. This work addresses this issue by presenting a methodology to estimate underreported infections based on approximations of the stable rates of hospitalization and death. We present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease 2019 (COVID-19) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease-transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model. For the considered locations, during the period of study, the estimations suggest that the number of infected individuals could reach 30% of the population of these places, representing, in some cases, more than six times the observed numbers. These results are in close agreement with estimates from independent seroprevalence studies, thus providing a strong validation of the proposed methodology. Moreover, the presence of large numbers of underreported infections can reduce the perceived impact of vaccination strategies in reducing rates of mortality and hospitalization. pBy using the proposed methodology and employing a judiciously chosen data analysis implementation, we estimate COVID-19 underreporting from publicly available data. This leads to a powerful way of quantifying underreporting impact on the efficacy of vaccination strategies. As a byproduct, we evaluate the impact of underreporting in the designing of vaccination strategies.


A comparison by ultracentrifugation of the effects on DNA of ethidium bromide and of acridine orange at low ionic strength.
The application of scaled particle theory to the gels formed by DNA in the ultracentrifuge has provided values for the effective length and the effective radius of the DNA particle. Ethidium bromide has been shown to cause extensive lengthening of the DNA in dilute salt. Acridine orange interaction with DNA resulted in modest changes in DNA dimensions. These results are explained in terms of binding for acridine orange and of denaturation of DNA by ethidium bromide.


Clinicopathological pattern of malignant parotid gland tumors in Saudi Arabia.
To report our experience of varied presentations and diverse histopathological spectrum of parotid gland malignancies. This retrospective analysis incorporated patients with histological evidence of malignant parotid tumors at King Khalid University Hospital, Riyadh, Saudi Arabia over a 20-year period from 1984 through 2004. The medical records of these patients were analyzed for their demographic characteristics, clinical features, operations performed, and pathological diversity. Thirty-two patients comprised this study group. There is a male preponderance over females with a ratio of 2.2:1 (22 men and 10 women) and mean age of 51.8 (range 28-81 years). A painless lump was the most frequent clinical manifestation observed in 23 (71.8%) patients followed by facial nerve dysfunction in 14 (43.7%) patients. Parotidectomy was performed in 22 (68.7%) patients: 16 superficial and 6 total. A partial facial nerve sacrifice was undertaken in 14 (43.7%), and total nerve sacrifice in 9 (28.1%) patients. Four (12.5%) patients presented with cervical lymph node metastases necessitating radical neck dissection. Nine (28.1%) patients had mucoepidermoid carcinoma, 8 (25%) adenoid cystic carcinoma, 6 (18.7%) adenocarcinoma, not otherwise specified, and 2 (6.2%) were reported to have carcinoma in pleomorphic adenoma. Twenty (62.5%) specimens revealed high-grade aggressive lesions, and out of these, 19 (59.3%) patients presented with stage III/IV disease. Malignant parotid tumors are exceedingly rare, occurring at a relatively earlier age group with male preponderance, and invariably declare at a late clinical stage in our community. Histopathological features hallmark a locally advanced disease with an aggressive behavior.


High HbA1c level was the most important factor associated with prevalence of diabetic retinopathy in Taiwanese type II diabetic patients with a fixed duration.
To identify the prevalence and related risk factors for diabetic retinopathy (DR) in non-insulin dependent diabetes in Taiwan. A retrospective review of type II diabetic patients in the Diabetes Shared Care System database of our Hospital enrolled from 2002 to 2009. A retinopathy severity score was assigned according to fundus examination by indirect ophthalmoscopy or binocular biomicroscopy. Data was collected on 901 subjects, 497 males and 404 females. Of these, 230 (25.53 %) had DR at enrolment. Compared with patients without DR, those with DR were more likely to be female (p = 0.03) or have higher HbA1c (p < 0.001), longer duration of diabetes (p < 0.001), hypertension (p < 0.001), higher systolic blood pressure (p < 0.001), higher diastolic blood pressure (p = 0.05), as well as impaired renal function (p = 0.001). In subgroup analysis stratified by diabetes duration, HbA1c was the most consistent independent risk factor associated to the prevalence of DR. Higher systolic blood pressure and female sex were significantly independent risk factors only in patients with a duration of diabetes < 4 years. On the contrary, old onset age showed a protective effect against DR only in those with a disease duration > 8 years. High HbA1c level was the most important factor associated with prevalence of DR in Taiwanese type II DM patients with a fixed duration.


Gaucher's disease: a paradigm for interventional genetics.
Gaucher's disease (GD) is one of the most prevalent lysosomal storage disorders (LSDs) and a rare genetic disease for which specific therapy is now available. GD is an autosomal, recessive, inborn error of glycosphingolipid metabolism, due to a deficiency in the enzyme acid beta-glucosidase. Partial deficiency of acid beta-glucosidase is associated with parenchymal disease of the liver, spleen, and bone marrow with concomitant anemia and thrombocytopenia in non-neuronopathic, type 1 GD. Severe deficiency of glucocerebrosidase caused by severe mutations is additionally associated with neurological manifestations in the less common type 2 and type 3 GD subtypes. Outside of the Ashkenazi Jewish community, a high molecular diversity is observed. Clarification of genotype/phenotype relationship and the identification of modifier loci that impact on GD phenotypes remains a critical area for research. Enzyme replacement therapy (ERT) is proven to be safe and effective in the treatment of type 1 GD, establishing imiglucerase as the current standard of care. Amelioration of hepatosplenomegaly and of hematological manifestations is usually apparent within 6-12 months, whereas the bone disease responds more slowly. ERT cannot reverse the neurological deficits in type 2 or type 3 GD. Small molecule inhibitors of glucosylceramide synthase are being developed for substrate reduction therapy. Other potential therapeutic options such as chaperon-mediated enzyme enhancement therapy and gene therapy are being explored.


[Isolation of the antibiotic hordecin by sorption on anionite AN-15].
It has been shown that Na-salt of hordecine can be selectively adsorbed on anion exchange resin AN-15 and the antibiotic can be then eluated with 96% ethanol acidified with HCl to bring pH to 3.0--3.5. Spectral analysis and testing of the antibiotic activity have demonstrated that hordecine prepared by the above method and that obtained by paper chromatography are identical.


Health care professional perceptions of online information and support for young people with cancer in the United Kingdom.
The internet is integral to young people, providing round-the-clock access to information and support. Young people with cancer report searching for online information and support. What they search for and why varies across their timeline and is mainly driven by negative emotion. We sought to understand how health care professionals (HCPs) perceived online information and support for young people with cancer. Semi-structured interviews with eight HCPs across the UK informed the development of a survey, completed by 38 HCPs. Framework analysis was used to identify key themes and the survey was analyzed descriptively. Seven themes emerged as integral to HCP's perceptions of online information and support, these included: views about young people's use of online resources; how needs change along the cancer timeline; different platforms where HCPs refer young people to online; whether young people's online needs are currently met; recognition of the emotional relationship between young people and the internet; barriers and concerns when referring young people to online resources; and strategies used in practice. Professionals play an important role in signposting young people to online resources, where they are confident about the accuracy and delivery of information. The biggest perceived barrier to facilitating online access was the cost to the NHS, and most concerning factor for HCPs was keeping young people safe online. There is a need to develop online resources specific for young people on psychosocial topics beyond treatment to support young people and HCPs through this period.


Early developmental subdivisions of the wing disk in Drosophila.
The properties of the mutation wingless discovered by Sharma are discussed. It appears that this mutation interferes with a step leading to normal wing-notum compartmentation of the wing disk. From the study of mutational mosaics in the wingless locus we conclude that mutations in this gene can be autonomous in mosaics.


Xenotransplantation: an update.
Over the past 20 years, the mortality and morbidity associated with cardiac allotransplantation has fallen significantly, providing a viable treatment for patients with terminal cardiac failure. Unfortunately, the increase in the number of patients who could benefit from cardiac transplantation has not been matched with an increase in the number of organs available for transplantation. Thus, many patients with cardiac failure die waiting for a suitable organ, unlike patients with renal failure, who can be maintained on dialysis while waiting for a kidney. Although the development of artificial hearts may provide a life-sustaining bridging therapy until a donor organ becomes available, the quality of life associated with cardiac prostheses is currently less than that following successful cardiac allotransplantation.


Proteomics in the Diagnosis of Inborn Encephalopathies of Unknown Origin: A Myth or Reality.
Synaptopathy underlies a great variety of neurological or neurodevelopmental disorders, including neurodegenerative diseases and the highly complex neuropsychiatric syndromes. Standard diagnostic assays in the majority of synaptopathies are insufficient to make an appropriate and fast diagnosis, which has spurred a search for more accurate diagnostic methods using recent technological advances. As synaptopathy phenotypes strictly depend on genetics and environmental factors, the best way to approach these diseases is the investigation of entire sets of protein characteristics. Thus, proteomics has emerged as a mainstay in the studies on synaptopathies, with mass spectrometry as a technology of choice. This review is an update on the proteomic methods and achievements in the understanding, diagnostics, and novel biomarkers of synaptopathies. The article also provides a critical point of view and future perspectives on the application of neuroproteomics in clinical practice.


Management of choroidal neovascularization within the foveal avascular zone in senile macular degeneration.
After fluorescein angiography, central visual field testing, and photofield mapping, 94 eyes with senile macular degeneration and foveal choroidal new vessels (distance of 200 micron or less from the center of the foveal avascular zone) were treated with the monochromatic green argon laser. By the end of the follow-up period (average follow-up, 15 months), the new vessels were closed in 88 eyes and visual acuity was stabilized or improved in 70 eyes. These 70 eyes included 68 of 80 eyes with preoperative visual acuities of 20/70 or worse and only two of 14 eyes with preoperative visual acuities of 20/60 or better. Visual acuity was stabilized or improved in 55 of 62 eyes in which the foveal edge of the choroidal new vessels was within the margins of the pretreatment scotoma and in only 15 of 32 eyes with foveal edges extending beyond the scotoma margins.


[Early arthroscopic reconstruction in treatment of acute complete rupture of anterior cruciate ligament].
To early reconstruct acute and complete rupture of anterior cruciate ligament (ACL) and treat combined injuries for the recovery of knee joint stability. Ten cases of acute complete rupture of anterior cruciate ligament and medial collateral ligament were treated arthroscopically by anterior cruciate ligament reconstruction using patellar tendon autograft fixed with interference screw from February 1998 to March 1999. Follow-up ranged from 5 months to 1 year and 3 months (average 10 months). Clinical results showed that the stability of knee joint was satisfactory in the early stage. Acute the ACL rupture can be reconstructed arthroscopically in the early stage and the injuries were moderate, combined injuries could be treated at the same time, and the stability of knee joint could recover in the early stage after operation.


Cycloheximide inhibits follicle-stimulating hormone β subunit transcription by blocking de novo synthesis of the labile activin type II receptor in gonadotrope cells.
The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), play essential roles in the regulation of vertebrate reproduction. Activins and inhibins have opposing actions on FSH (but not LH) synthesis, either inducing or inhibiting transcription of the FSHβ subunit gene (Fshb). The translational inhibitor cycloheximide (CHX) produces inhibin-like effects in cultured pituitary cells, selectively suppressing FSH production. Using the murine gonadotrope-like cell line, LβT2, as a model, we tested the hypothesis that a component of the activin pathway is highly labile in gonadotrope cells and that its rapid loss following CHX treatment impairs activin-stimulated Fshb transcription. Treatment of cells with CHX for 6h, but not 1h, blocked activin A-stimulated Fshb transcription. Pre-treatment of LβT2 cells with CHX for as few as 2-3h inhibited activin A-stimulated SMAD2/3 phosphorylation without altering total SMAD2/3 protein levels. These data indicated that CHX affects activin signalling upstream of SMAD proteins, most likely at the receptor level. Indeed, CHX rapidly reduced activin A binding to LβT2 cells. We went on to show that activin A signals via the type II receptor ACVR2, rather than ACVR2B, to regulate Fshb transcription and that the receptor has a half life of ~2h in LβT2 cells. The mechanism of ACVR2 turnover remains undefined, but appears to be ligand-, proteasome-, and lysosome-independent. Collectively, these data indicate that CHX produces inhibin-like effects in gonadotropes by preventing de novo synthesis of the highly labile ACVR2, thereby blocking activin signaling to the Fshb promoter.


Exploring links between resilience and the macro-level development of healthcare regulation- a Norwegian case study.
The relationship between quality and safety regulation and resilience in healthcare has received little systematic scrutiny. Accordingly, this study examines the introduction of a new regulatory framework (the Quality Improvement Regulation) in Norway that aimed to focus on developing the capacity of hospitals to continually improve quality and safety. The overall aim of the study was to explore the governmental rationale and expectations in relation to the Quality Improvement Regulation, and how it could potentially influence the management of resilience in hospitals. The study applies resilience in healthcare and risk regulation as theoretical perspectives. The design is a single embedded case study, investigating the Norwegian regulatory healthcare regime. Data was collected by approaching three regulatory bodies through formal letters, asking them to provide internal and public documents, and by searching through open Internet-sources. Based on this, we conducted a document analysis, supplemented by interviews with seven strategic informants in the regulatory bodies. The rationale for introducing the Quality Improvement Regulation focused on challenges associated with implementation, lack of management competencies; need to promote quality improvement as a managerial responsibility. Some informants worried that the generic regulatory design made it less helpful for managers and clinicians, others claimed a non-detailed regulation was key to make it fit all hospital-contexts. The Government expected hospital managers to obtain an overview of risks and to adapt risk management and quality improvement measures to their specific context and activities. Based on the rationale of making the Quality Improvement Regulation flexible to hospital context, encouraging the ability to anticipate local risks, along with expectations about the generic design as challenging for managers and clinicians, we found that the regulators did consider work as done as important when designing the Quality Improvement Regulation. These perspectives are in line with ideas of resilience. However, the Quality Improvement Regulation might be open for adaptation by the regulatees, but this may not necessarily mean that it promotes or encourages adaptive behavior in actual practice. Limited involvement of clinicians in the regulatory development process and a lack of reflexive spaces might hamper quality improvement efforts.


[The anteroposterior (a--p) X-ray-picture in lateral radiographic position in patients after thoracic surgery (author's transl)].
A new approach to the X-ray checking after chest operations is described. Instead of sitting upright the patient is lying on his nonoperated side, the operated side of the chest upward. By this way it is easy to differentiate pleural effusions from basal infiltrations of the remaining lung segments. Furthermore it is possible to check the diaphragm and the lateral portions of the lung much easier than with the conventional X-ray pictures taken in sitting position.


Integrated continuous melt granulation-based powder-to-tablet line: Process investigation and scale-up on the same equipment.
In the last decades, continuous manufacturing (CM) has become a research priority in the pharmaceutical industry. However, significantly fewer scientific researches address the investigation of integrated, continuous systems, a field that needs further exploration to facilitate the implementation of CM lines. This research outlines the development and optimization of an integrated, polyethylene glycol aided melt granulation-based powder-to-tablet line that operates fully continuously. The flowability and tabletability of a caffeine-containing powder mixture were improved through twin-screw melt granulation resulting in the production of tablets with improved breaking force (from 15 N to over 80 N), excellent friability, and immediate release dissolution. The system was also conveniently scaleable: the production speed could be increased from 0.5 kg/h to 8 kg/h with only minimal changes in the process parameters and using the same equipment. Thereby the frequent challenges of scale-up can be avoided, such as the need for new equipment and separate optimization.


National cohort and meteorological data based nested case-control study on the association between air pollution exposure and thyroid cancer.
The objective of this study was to evaluate the influence of exposure to meteorological conditions, including air pollution, on thyroid cancer. A nested case-control study was conducted utilizing 4632 patients with thyroid cancer and 18,528 control subjects who were matched at a 1:4 ratio by age group, sex, income, and region of residence. Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 were used. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for thyroid cancer correlated with meteorological and air pollution exposure over a moving average of 3 years before the index dates. For all participants, the adjusted ORs associated with relative humidity (1.01, 95% CI 1.00-1.03, P value = 0.023), ambient atmospheric pressure (1.02, 95% CI 1.01-1.03, P value < 0.001), and sunshine duration (1.17, 95% CI 1.04-1.31, P value = 0.007) indicated correlations with the occurrence of thyroid cancer; however, these results were inconsistent in the subgroup analyses. Overall, exposure to nitrogen dioxide (NO2) (1.33, 95% CI 1.24-1.43, P value < 0.001) and particulate matter (PM10) (0.64, 95% CI 0.60-0.69, P value < 0.001) were related to thyroid cancer. These relationships persisted in the subgroup analyses. In conclusion, thyroid cancer occurrence was positively associated with NO2 exposure and negatively associated with PM10 exposure.


Quantitative expression analysis of the apoptosis-related genes BCL2, BAX and BCL2L12 in gastric adenocarcinoma cells following treatment with the anticancer drugs cisplatin, etoposide and taxol.
The BCL2 family of proteins includes apoptosis-related molecules involved in normal physiology, as well as cancer pathology. Members of our team have discovered and cloned the novel gene BCL2L12, which codes for a protein member of the BCL2 family. The BCL2L12 expression has been studied extensively in various types of cancer and its important clinical value has been underlined. The main objective of this study is the relative quantification of the mRNA expression of the apoptosis-related genes BCL2, BAX and BCL2L12 in gastric cancer cells, following treatment with anticancer drugs. Gastric adenocarcinoma cells AGS were treated with various concentrations of the chemical substances cisplatin, etoposide and taxol for three time periods. Cell viability was examined by using the MTT assay. Total RNA was extracted and reverse transcribed into cDNA. A highly sensitive, quantitative real-time PCR method was developed based on the SYBR Green chemistry, for the proper mRNA quantification. GAPDH was used as a housekeeping gene. Relative quantification analysis was performed by using the comparative C(T) method ([Formula: see text]). Treatment of AGS cells with 10 μM cisplatin, 0.5 μM etoposide and 10 nM taxol affected the BCL2, BAX and BCL2L12 mRNA levels, compared to the untreated cells. Cisplatin and etoposide induced a major down-regulation in the BCL2 mRNA levels after 72 h of treatment, while the BAX mRNA levels were slightly up-regulated. Moreover, taxol had an up-regulating effect on both BCL2 and BAX transcript levels after 48 h of incubation. Chemotherapy had a much smaller effect on the BCL2L12 expression levels, eventually characterised by a small down-regulation.


Intact global cognitive and olfactory ability predicts lack of transition to dementia.
Odor identification deficits characterize Alzheimer's disease and other dementias. We examined if intact performance on brief cognitive and odor identification tests predicts lack of transition to dementia. In an urban community, 1037 older adults without dementia completed the 40-item University of Pennsylvania Smell Identification Test, which includes the 12-item Brief Smell Identification Test (B-SIT). Data from 749 participants followed up for 4 years were analyzed. In covariate-adjusted survival analyses, impairment on the Blessed Orientation Memory Concentration Test and B-SIT each predicted dementia (n = 109), primarily Alzheimer's disease (n = 101). Among participants with intact olfactory (B-SIT ≥ 11/12 correct) and cognitive (Blessed Orientation Memory Concentration Test ≤ 5/28 incorrect) ability, 3.4% (4/117) transitioned to dementia during follow-up with no transitions in the 70-75 and 81-83 years age group quartiles. Odor identification testing adds value to global cognitive testing, and together can identify individuals who rarely transition to dementia, thereby avoiding unnecessary diagnostic investigation.


Quantitation of anticephalin antibodies in a computer-assisted enzyme-linked immunosorbent assay (ELISA): relation to lupus anticoagulant.
Lupus anticoagulants (LA) are IgG or IgM antibodies which prolong phospholipid-dependent coagulation tests. For the detection and quantitation of such antibodies, we have developed an ELISA with cephalin as the coating antigen. The sensitivity of this assay was compared to the activated partial thromboplastin time (APTT). LA was defined as greater than or equal to 5 sec prolongation of the APTT with standard cephalin dilution, or greater than or equal to 10 sec prolongation with a high cephalin dilution, on a 1:1 mixture of patient and control plasma. Plasma samples from 158 healthy individuals were tested for anticephalin antibodies. The 97.5 percentile was chosen as the upper reference limit and allocated a value of 1 ELISA unit. A "four-parameter logistic" model was used for transformation of the absorbances to ELISA units. Of 314 plasma samples referred for LA screening, positive results were found in 62 by both APTT and ELISA. Twenty-three samples were ELISA positive and APTT negative; this finding may be explained by greater sensitivity of the ELISA, which gave positive results in a four-fold greater dilution than the APTT. Prolongation of the APTT without antibody activity was found in 8 samples of which 2 had an inhibitor of factor VIII:C, the remaining 6 probably had true LA. In conclusion, our computer-assisted ELISA is a sensitive and reliable test method for quantitation of anticephalin antibodies. This assay has a high concordance with LA as detected with the APTT.


Abnormal colonic cholinergic and nitrergic activities in relation to elastosis in uncomplicated diverticular disease.
I read with interest the review on the pathogenesis of diverticular disease by Commane et al in World J Gastroenterol 2009; 15(20): 2479-2488. However, I would like to discuss several important errors that the authors made whilst citing information from previously published work on the neuromuscular dysfunction in the disease.


Clinically relevant increases in serum neurofilament light chain and glial fibrillary acidic protein in patients with Susac syndrome.
Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age- and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS.


Individual differences in behavioural responses to the financial threat posed by the COVID-19 pandemic.
Using a representative sample of 400 Slovaks, the present study investigated the mediating role of subjective perception of financial threat to the relation between psychological resources and behavioural responses in the adaptation to financial stress posed by the COVID-19 pandemic. The results of structural equation modelling analyses showed that greater neuroticism and uncertainty intolerance were positively related to aggravated perception of financial threat. This, in turn, led to greater willingness to change consumption patterns and use of mostly problem-focused coping strategies. The model remained robust after controlling for chronic financial hardship moderators, including the absence of savings and indebtedness. In contrast, the acute financial hardship caused by the deterioration of one's financial situation during the COVID-19 pandemic showed to significantly moderate the relation between one's psychological resources and perceived financial threat.


Emerging trends in nanomaterial design for the development of point-of-care platforms and practical applications.
Nanomaterials and nanotechnology offer promising opportunities in point-of-care (POC) diagnostics and therapeutics due to their unique physical and chemical properties. POC platforms aim to provide rapid and portable diagnostic and therapeutic capabilities at the site of patient care, offering cost-effective solutions. Incorporating nanomaterials with distinct optical, electrical, and magnetic properties can revolutionize the POC industry, significantly enhancing the effectiveness and efficiency of diagnostic and theragnostic devices. By leveraging nanoparticles and nanofibers in POC devices, nanomaterials have the potential to improve the accuracy and speed of diagnostic tests, making them more practical for POC settings. Technological advancements, such as smartphone integration, imagery instruments, and attachments, complement and expand the application scope of POCs, reducing invasiveness by enabling analysis of various matrices like saliva and breath. These integrated testing platforms facilitate procedures without compromising diagnosis quality. This review provides a summary of recent trends in POC technologies utilizing nanomaterials and nanotechnologies for analyzing disease biomarkers. It highlights advances in device development, nanomaterial design, and their applications in POC. Additionally, complementary tools used in POC and nanomaterials are discussed, followed by critical analysis of challenges and future directions for these technologies.


Is esophagoscopy alone sufficient for patients with reflux symptoms?
Unsedated esophagoscopy with ultrathin endoscopes is a valuable screening modality for Barrett's esophagus, but the stomach and the duodenum cannot be examined completely with the smallest and best tolerated of these endoscopes. There are no data as to how often disease in the stomach and the duodenum would be missed when using this screening strategy. Our hypothesis is that patients with reflux symptoms, in the absence of daily abdominal pain, nausea, or history of ulcer, were unlikely to have clinically significant gastroduodenal disease. Patients scheduled for upper endoscopy at a single outpatient endoscopy unit in a tertiary referral center were screened. The inclusion criterion was reflux symptoms as the primary indication for upper endoscopy. Patients with another valid indication were excluded. A detailed history was recorded and symptom questionnaire completed for each patient before endoscopy; these data were compared with the endoscopy findings. A total of 175 patients were included. Indications for upper endoscopy were the following: worsening symptoms (n=74), ongoing reflux despite therapy (n=27), and long-standing reflux (n=74). Major esophageal findings were discovered in 95 patients. In 10 patients, major gastric or duodenal findings were detected as follows: erosive gastritis (n=8), gastric ulcer (n=2), duodenal ulcer (n=2), erosive duodenitis (n=2), and duodenal polyp (n=1). Daily abdominal pain (p=0.014) or possibly daily nausea (p=0.028 unadjusted, 0.197 adjusted) was associated with major gastric/duodenal disease. Patients without daily abdominal pain, nausea, or a history of gastric/duodenal ulcer were much less likely to have major disease (0.9%) than patients with one of these predictors (13.2%, p=0.00097). Daily abdominal pain and nausea, in combination with a history of ulcer disease, are strong predictors of major gastric or duodenal disease. Patients with reflux without these predictors are highly unlikely to have a major disease involving the stomach or duodenum, and are suitable candidates for esophagoscopy alone.


Measurement of lactate-induced panic and anxiety.
Acute Panic Inventory (API) scores were obtained from 26 normal controls and 89 patients with either panic disorder or agoraphobia with panic attacks before and during lactate infusions. Retrospective ratings of the patients' usual spontaneous attacks were much higher, by API, than ratings of moments of severe stress by the controls. Point of panic API scores, as well as increments of panic scores over prelactate scores, were higher for patients who experienced lactate panics than for both controls and patients who did not panic.


Meta-analysis of studies analyzing the role of human papillomavirus in the development of bladder carcinoma.
We aimed to ascertain the degree of association between bladder cancer and human papillomavirus (HPV) infection. We performed a meta-analysis of observational studies with cases and controls with publication dates up to January 2011. The PubMed electronic database was searched by using the key words "bladder cancer and virus." Twenty-one articles were selected that met the required methodological criteria. We implemented an internal quality control system to verify the selected search method. We analyzed the pooled effect of all the studies and also analyzed the techniques used as follows: 1) studies with DNA-based techniques, among which we found studies with polymerase chain reaction (PCR)-based techniques and 2) studies with non-PCR-based techniques, and studies with non-DNA-based techniques. Taking into account the 21 studies that were included in the meta-analysis, we obtained a heterogeneity chi-squared value of Q(exp)=26.45 (p=0.383). The pooled odds ratio (OR) was 2.13 (95% confidence interval [CI], 1.54 to 2.95), which points to a significant effect between HPV and bladder cancer. Twenty studies assessed the presence of DNA. The overall effect showed a significant relationship between virus presence and bladder cancer, with a pooled OR of 2.19 (95% CI, 1.40 to 3.43). Of the other six studies, four examined the virus's capsid antigen and two detected antibodies in serum by Western blot. The estimated pooled OR in this group was 2.11 (95% CI, 1.27 to 3.51), which confirmed the relationship between the presence of virus and cancer. The pooled OR value showed a moderate relationship between viral infection and bladder tumors.


Expression of CD163 in the liver of patients with viral hepatitis.
CD163 is a marker of activated macrophages, and increased levels of soluble CD163 have been detected in sera obtained from patients with hepatitis. The aim of this study was to detect the expression of CD163 in the liver from patients with viral hepatitis. Frozen sections of liver specimens were obtained from 5 patients with acute viral hepatitis (AH) and from 23 patients with chronic viral hepatitis (CH). The expression of CD163 in the liver was determined immunohistochemically using monoclonal antibody to human CD163. Double immunostaining was done to assess those cell types that express CD163 in the liver. The frequencies of CD163-positive cells were significantly higher both in the portal areas and in the hepatic lobules in the liver of patients with AH compared to those with CH (p < 0.05). Double immunostaining revealed that most of the CD163-positive cells were macrophages and Kupffer cells, because they expressed CD68. The expression of CD163 was very low in endothelial cells and liver stellate cells. This study shows that macrophages are activated in hepatitis liver.


Psychological factors and recovery from trauma.
Recent research has identified a high prevalence of psychological illnesses in patients who have sustained orthopaedic trauma. Depressive symptoms in this patient population have been reported to range from 13% to as high as 56%. Moreover, symptoms of depression, catastrophic thinking, and post-traumatic stress disorder (PTSD), have been consistently shown to negatively impact patient outcomes following treatment for their traumatic injuries. Specifically, patients with higher levels of psychosocial dysfunction have shown increased levels of pain, disability, and complications throughout their recovery. However, current research in orthopaedic trauma continues to be substantially focused on the physical and technical factors involved in the treatment of orthopaedic injuries. More research which applies the "biopsychosocial model" of health and evaluates the significant impact of psychological and social factors on recovery from trauma is needed. In particular, investigation which evaluates effective screening strategies and interventions to treat psychosocial dysfunction during recovery from trauma is highly desirable. This article reviews the current state of knowledge in this area and suggests future directions for research.


Serum miR-503 is a Candidate Biomarker for Differentiating Metabolic Healthy Obesity from Metabolic Unhealthy Obesity.
Overweight and obesity are associated with metabolic diseases. However, a subgroup of the overweight/obese population does not present metabolic abnormalities. Hence, there is an urgent need to identify biomarkers that can distinguish different obesity phenotypes and metabolic status. A total of 98 individuals were divided into three groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Participants were evaluated for anthropometric and biochemical parameters and serum BMPR1A concentration and miR-503 level. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were performed. The level of miR-503 was significantly higher in the MHO group compared with that in the MUO group, but no difference was observed between the MHNW and MHO groups. Meanwhile, no significant differences in serum BMPR1A concentration were observed between the three groups. ROC curve analysis showed that miR-503 could be used as a marker to distinguish the MUO from the MHO. Logistic regression analysis suggested that miR-503 was an important related factor associated with an unhealthy metabolic state in overweight/obese subjects. miR-503 can be considered as a suitable biomarker to distinguish between the MUO and MHO, which may be a related factor for the incidence of metabolic disorders in overweight/obese subjects.


Small-scale preparation of perfluorocarbon-nanoemulsions utilizing dual centrifugation.
Perfluorocarbon-nanoemulsions (PFC-NE) made of PFC and phospholipids (PL) by homogenization are optimal for in vivo-19F labelling of monocytes and subsequently of inflamed tissues in magnetic resonance imaging (MRI). Necessary requirements for in vivo use of PFC-NE are sterility, suitable droplet sizes and the absence of immune activating liposomes, which are a typical byproduct of the homogenization process. To meet these requirements, we developed an aseptic in-vial preparation technique for PFC-NE based on dual centrifugation (DC) by testing different PFC/phospholipid ratios as well as the application of additives. Two different PFC, perfluorooctylbromide (PFOB) and perfluoro-15-crown-5-ether (PFCE), were investigated. Particle sizes were assessed by dynamic light scattering and NE morphology by cryoTEM. DC homogenization was optimal when using an excess of PL (8.7 % (m/m) of utilized PFC, z-ave: 180 nm, pdi: 0.2). A purification approach by centrifugation was implemented to remove liposomes formed from the excess of PL during homogenization. The purification success was proven by phospholipid assay and PFC quantification via density and sound velocity measurements. DC in combination with a short centrifugation is a fast and reliable way of small-scale aseptic PFC-NE production for 19F MRI passive-targeting experiments of monocytes and inflamed tissues.


Single Stapler Technique for Vascular Control in Laparoscopic Donor Nephrectomy.
Recent advancements in surgical instruments, energy sources, vascular staplers, and increased experience altogether led to several modifications in the laparoscopic donor nephrectomy (LDN) technique. In the conventional approach, the renal artery and vein are divided separately by vascular stapling. This study aimed to evaluate the safety and feasibility of using single vascular stapling technique for dividing the renal artery and vein simultaneously. Patients who underwent LDN performed by the same surgeon between January 2018 and January 2020 were included. Demographic data, body mass index, number of arteries and veins, vascular division technique, estimated blood loss, surgical time, warm ischemia time, surgical complications, and length of hospital stay were recorded. Descriptive statistics were used to describe the characteristics of the dataset. A total of 196 donors were included in the cohort. The mean age was 44.5 years (19-80 years, standard deviation: 13.2). A total of 132 donors (82.65%) underwent left-sided LDN, and 34 (17.35%) underwent right-sided LDN. The mean surgical time and warm ischemia time were 68.4 ± 24.7 (32-116) and 2.8 ± 1.2 (1.6-4.0) minutes, respectively. Two cases were converted to open donor nephrectomy (1.02%). The single stapling technique was successfully performed in 168 (85.7%) donors with a single renal artery and vein. Single stapling for the concurrent division of the renal artery and vein in the setting of LDN seems to be a safe and feasible approach. It also has the potential to shorten warm ischemia time and reduce the cost of LDN.


Comparing the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score with transient elastography scores of people with non-alcoholic fatty liver disease.
With the rate of non-alcoholic fatty liver disease (NAFLD) on the rise, the necessity of identifying patients at risk of cirrhosis and its complications is becoming ever more important. Liver biopsy remains the gold standard for assessing fibrosis, although costs, risks, and availability prohibit its widespread use with at-risk patients. Transient elastography has proven to be a non-invasive and accurate way of assessing fibrosis, although the availability of this modality is often limited in primary care settings. The Fibrosis-4 (FIB-4) and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) are scoring systems that incorporate commonly measured lab parameters and BMI to predict fibrosis. In this study, we compared FIB-4 and NFS scores with transient elastography scores to assess the accuracy of these inexpensive and readily available scoring systems in detecting fibrosis. Using an NFS score cut-off of -1.455 and a FibroScan score cut-off of ≥8.7 kPa, the NFS score had a negative predictive value of 94.1%. Using a FibroScan score cut-off of ≥8.7 kPa, the FIB-4 score had a negative predictive value of 91.6%. The NFS and FIB-4 are non-invasive, inexpensive scoring systems that have high negative predictive value for fibrosis compared with transient elastography scores. These findings suggest that the NFS and FIB-4 can provide adequate reassurance to rule out fibrosis in patients with NAFLD and can be used with select patients to circumvent the need for transient elastography or liver biopsy.


In vitro susceptibility to antibiotics of staphylococci in biofilms isolated from orthopaedic infections.
Prosthetic joint infections (PJIs) are related to the formation of biofilms, mainly by Staphylococcus aureus and Staphylococcus epidermidis. Therapy is usually selected according conventional susceptibility testing, but these data may be insufficient to detect the true antibiotic susceptibility in the biofilm. In total, 32 clinical strains (17 S. aureus and 15 S. epidermidis) isolated from patients with PJIs as well as 2 collection strains (S. aureus 15981 and S. epidermidis ATCC 35984) were tested against nine antibiotics commonly used in the treatment of PJIs (rifampicin, vancomycin, tigecycline, clindamycin, trimethoprim/sulfamethoxazole, ciprofloxacin, cloxacillin, daptomycin and fosfomycin) using the Calgary Biofilm Device. None of the antibiotics proved to be totally effective against biofilms in both species, with minimum biofilm eradication concentrations (MBECs) highly above the minimum inhibitory concentrations for most of the antibiotics (>1024 mg/L). Rifampicin and tigecycline showed MBECs slightly lower, mainly against S. epidermidis biofilms, and only two strains of this staphylococcal species were susceptible to almost all of the antibiotics tested. These results show that the search for new compounds with antimicrobial and antibiofilm properties is mandatory as well as the development of other strategies that could lead to the prevention and treatment of PJIs. In addition, more studies are necessary to obtain a better understanding of the mechanisms involved in antimicrobial resistance of biofilms.


Improved Expression and Purification of the Carotenoid Biosynthetic Enzyme Z-ISO.
Carotenoids are a large class of pigments that are essential for survival of plants and other species that consume these plant-derived compounds and their bioactive derivatives. The plant biosynthetic pathway is nuclear-encoded and localized in plastids. The pathway enzymes had been known for many years, except for a recently discovered isomerase, 15-cis-ζ-carotene isomerase (Z-ISO) which utilizes a novel mechanism to mediate isomerization in response to the redox state of its heme b cofactor. To further study this enzyme, a protocol is described which maximizes purification of a fusion between Maltose Binding Protein and Zea mays (maize) Z-ISO (MBP::Z-ISO) expressed in E. coli treated with heme biosynthesis precursors which were used to increase heme available for loading into the expressed protein. Further enrichment of the protein was accomplished by improved sonication to release membranes containing Z-ISO, an integral membrane protein, and collection of the membrane fraction which was subjected to Nickel affinity chromatography. The fusion protein bound to the column through a His-tag. The MBP::Z-ISO protein was released using histidine, and not imidazole which binds heme and would interfere with enzyme recovery. Purification of the 75.46 kD MBP::Z-ISO expressed in E. coli was accomplished with fivefold improvement of yield and doubled heme content compared to the previously published method Beltrán et al. (Nat Chem Biol 11(8):598-605, 2015). The newer protocol will yield, per liter of culture, 5-6 mg MBP::Z-ISO protein with ~1:1 heme to Z-ISO ratio.


Short-term outcomes after sodium-glucose cotransporter-2 inhibitor initiation in a cohort of heart failure patients.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease mortality and risk of hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate rates of acute kidney injury (AKI) and therapy discontinuation with SGLT2i initiation in a real-world cohort of HFrEF patients. We abstracted data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting at the University of Michigan (between 1 July 2016 and 2 July 2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. A total of 200 patients were included. The majority of patients were male (64%) with a mean left ventricular ejection fraction (LVEF) of 27%. One hundred and four (52%) patients had diabetes mellitus. Most patients exhibited New York Heart Association class II (51.5%) or III (33.5%) symptoms. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. AKI occurred in 22 patients and 18 patients discontinued their SGLT2i. Yeast infection (n = 6), hypotension (n = 5), and AKI (n = 4) were the most common reasons for discontinuation. Using receiver operating characteristic curve analysis, the strongest models for AKI were A1C [area underneath its curve (AUC) = 75.8, empirical confidence interval (ECI) 66.5-83.5]; baseline serum creatinine (SCr) (AUC = 72.0, ECI 65.7-78.7); LVEF (AUC = 67.6, ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0, ECI 57.5-74.6). Similarly, the strongest positive models for SGLT2i discontinuation were A1C (AUC = 81.1, ECI 74.8-87.2); baseline SCr (AUC = 67.4, ECI 58.7-75.5); LVEF (AUC = 68.7, ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2, ECI 58.2-76.0). A1C was the strongest model of AKI, and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. Patients with higher baseline SCr on higher doses of loop diuretics may be at greater risk of these outcomes. Future prospective studies will be needed to further evaluate these findings and other models of AKI and SGLT2i discontinuation to guide clinical use of SGLT2 inhibitors.


Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system.
In this randomized, double-blind, crossover study, the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) was compared following missed doses. Design and methods In a randomized crossover design, 42 patients were randomized to receive amlodipine (5-10 mg) or the GITS formulation of nifedipine (nifedipine GITS) (30-60 mg) once daily for 12 weeks, then vice versa. During weeks 8, 10 and 12 of each treatment period, compliance failures were simulated by patients missing 0, 1 or 2 doses of their medication, and ambulatory systolic (SBP) and diastolic (DBP) blood pressure measurements were obtained. Following steady-state treatment (i.e. 'perfect compliance'), there was no difference between amlodipine and nifedipine GITS in SBP (140.1 versus 134.2 mmHg) or DBP (84.0 versus 85.8 mmHg) at 0-24 h post-dose. When compliance was not perfect, i.e. when one or two doses were missed, DBP was maintained at a significantly lower level with amlodipine compared with nifedipine GITS at 24-48 h post-dose (83.1 versus 86.4 mmHg, P = 0.005) and at 48-72 h post-dose (84.2 versus 89.7 mmHg, P < 0.001). Plasma concentrations of amlodipine were better maintained than those of nifedipine GITS. At 72 h post-dose, the plasma concentration of amlodipine was 61% (17.0 +/- 11.2 ng/ml) compared with < 25% (28.3 +/- 49.9 ng/ml) for nifedipine GITS. During short periods of non-compliance, antihypertensive efficacy remains more predictable with amlodipine than with nifedipine GITS.


Relationship Not Found Between Blood and Urine Concentrations and Body Mass Index in Humans With Apparently Adequate Boron Status.
The impact of boron on the development of obesity remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the relationship between blood and urine boron concentrations and obesity in normal, overweight, obese, and morbidly obese subjects in different age groups. A total of 105 subjects were categorized into 12 groups based on body mass index and three different age levels: as young adult (18 to 34 years old), adult (35 to 54 years old), and older adult (greater than 55 years old). Age, gender, body mass index, and blood and urine boron concentrations were recorded for each subject. There were 50 women and 55 men, with a mean age of 44.63 ± 17.9 years. Blood and urine boron concentrations were similar among the groups (p = 0.510 and p = 0.228, respectively). However, a positive correlation between age and blood boron concentration (p = 0.001) was detected in contrast to the presence of a negative correlation between age and urine boron concentration (p = 0.027). Multiple linear regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron concentrations. Although the relationship between boron and obesity has not been confirmed, changes of blood and urine boron concentrations with age may have some physiologic sequences to cause obesity.


Extraction of intrinsic fluorescence from single fiber fluorescence measurements on a turbid medium.
This study utilizes Monte Carlo simulations of single fiber fluorescence to develop an empirical model that corrects for the influence of scattering and absorption on fluorescence intensity (F(SF)). The model expresses F(SF) in terms of the reduced scattering coefficient (μs') and absorption coefficient (μ(a)), each determined independently at excitation and emission wavelengths (λ(x) and λ(m)), and the fiber diameter (d(f)). This model returns accurate descriptions (mean residual <6%) of F(SF) across a biologically relevant range of μs' and μ(a) values and is insensitive to the form of the scattering phase function.


How calcium helps α7 nicotinic acetylcholine receptors fulfill their potential.
Study reveals that, at low acetylcholine concentrations, calcium enhances channel opening by binding to a novel motif near the ligand binding site.


Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.
Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.


Pretreatment with topical all-trans-retinoic acid is beneficial for wound healing in genetically diabetic mice.
Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to improve healing of cutaneous wounds. We tested the effect of atRA on wound healing of genetically diabetic db/db mice. It is known that cutaneous wounds of db/db mice show delayed wound healing due to impaired wound contraction, delayed granulation tissue formation and underexpression of keratinocyte growth factor (KGF). 0.1% atRA in 100 mg aqueous gel was applied to the back skin of db/db mice as well as to their normal heterozygous littermates, db/+ mice, for five consecutive days, and 2 days after completion of the atRA treatment, two round excisional wounds were created down the panniculus carnosus with a 6-mm punch biopsy on the back skin of each mouse. After 5 days treatment with 0.1% atRA, significant hypertrophy of the epidermis and dermis, neovascularization, and inflammatory cell invasion were seen in the skin of the db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA-treated db/db mice closed more rapidly than those in vehicle-treated db/db mice. KGF mRNA expression, which is usually significantly lower in db/db mice than in normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as strong as in db/+ mice. Pretreatment with atRA reversed the impaired wound healing in db/db mice.


Correlation Between Coronary and Retinal Microangiopathy in Patients With STEMI.
To investigate the morphological and functional correlation between microvascular retinal changes in optical coherence tomography angiography (OCTA) and the microvascular coronary circulation in patients with ST elevation myocardial infarction (STEMI) coronary heart disease (CHD). A total of 330 eyes from 165 participants (88 cases and 77 controls) were enrolled and imaged. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vascular density was measured in the central (1 mm) and perifoveal (1-3 mm) areas and in the superficial foveal avascular zone (FAZ) and choriocapillaris (3 mm). These parameters were then correlated to the left ventricular ejection fraction (LVEF), and the number of affected coronary arteries. Decreased vessel densities in the SCP and DCP and choriocapillaris were positively correlated to the LVEF values (P = 0.006, P = 0.026, and P = 0.002, respectively). No statistically significant correlation between the SCP and DCP central area or FAZ area was found. Regarding the number of affected vessels, significant negative correlations were revealed for the SCP and DCP central vessel densities (P < 0.001 and P < 0.001, respectively) and the SCP perifoveal vascular density (P = 0.009). OCTA vascular indices are significantly correlated with morphological and functional parameters in patients with STEMI CHD. SCP vascular density especially seems to be a promising biomarker for the extent of both macrovascular damage (number of affected coronary arteries) and microvascular damage, as mirrored in the decreased LVEF at admission. OCTA vascular indices offer a valuable insight into the microvascular status of coronary circulation.


Assessment of global habitat suitability and risk of ocean green tides.
Green tides, which are widespread problems, are harmful issues that affect the protection of ocean ecosystems and natural resources. Scientific assessment and prevention of the green tides are essential for sustainable planning and the utilization of maritime traffic, tourism, and industry. However, the suitable or risk habitats and their dominant factors of green tides from global perspective are unknown. Here, this study proposed a novel framework to show the habitat suitability and risk of ocean green tides by considering marine environmental factors (i.e., sea surface temperature, sea surface salinity, solar irradiance, chlorophyll-a concentration, and sea surface wind). Through global remote sensing images and marine environmental factor data, this study found that (1) suitable and at-risk green tides areas are located in the north and south temperate zones; (2) marine physical factors are expected to weaken the green tide risk globally and enhance the green tide risk in coastal areas; (3) the green tides in the North Atlantic Ocean and the West Pacific Ocean are dominated by environmental factors and physical factors, respectively; and (4) when reducing carbon to promote sustainability, more potentially suitable green tide areas may appear at high latitudes. The results demonstrate the at-risk location and future trend of green tides, which are helpful for sustainable planning of ocean ecosystems.