bluuebunny/crossref_metadata_2025 huggingface dataset:
The renoprotective effects of sodium‐glucose cotransporter 2 inhibitors versus placebo in patients with type 2 diabetes with or without prevalent kidney disease: A systematic review and meta‐analysis
Authors: Wang Chen , Zhou Yue , Kong Zili , Wang Xiang , Lv Wenshan , Geng Zhuang , Wang Yangang
Published: December 2018

Aims

We undertook a systematic review and meta‐analysis to assess the efficacy and safety of sodium‐glucose cotransporter 2 inhibitors (SGLT2is) concerning kidney outcomes in patients with type 2 diabetes mellitus (T2DM), with or without prevalent kidney disease.

Materials and Methods

PubMed, Web of science, Embase and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) to assess the efficacy and safety of treatment with SGLT2is versus placebo in patients with T2DM. The weighted mean difference (WMD) and its 95% confidence interval (CI) were applied for continuous variables, and the risk ratio (RR) and corresponding 95% CI were used for dichotomous outcomes. Patients were categorized according to whether the baseline mean estimated glomerular filtration rate (eGFR) was less or was more than 60 mL/min/1.73 m2.

Results

A total of 25 eligible studies with 43 721 participants were included. There was an initial and small decrease in eGFR during the early treatment period (WMD, −4.63; 95% CI, −6.08 to −3.19 mL/min/1.73 m2), which was noted at 1‐6 weeks and gradually narrowed over time, with a decline in protection from eGFR in the long term (WMD, 3.82; 95% CI, 2.80‐4.85 mL/min/1.73 m2). SGLT2is significantly delayed albuminuria progression (RR, 0.71; 95% CI, 0.66‐0.76), promoted albuminuria regression (RR,1.71; 95% CI, 1.54‐1.90), improved the composite of ≥40% decrease in eGFR, in the need for renal‐replacement and in death from renal causes (RR, 0.57; 95% CI, 0.49‐0.66), and reduced all‐cause mortality (RR, 0.84; 95% CI, 0.75‐0.94). At the same time, they significantly increased the risk of genital infection (RR, 3.43; 95% CI, 2.87‐4.10) vs placebo in patients with T2DM. Meta‐regression analyses showed that eGFR‐preservation effects were not significantly associated with basic patient characteristics (age, BMI, HbA1c, eGFR level), but were influenced by drug administration (treatment duration, type, dosage of SGLT2is). Subgroup analyses showed that the relative effects on renal outcomes of SGLT2is vs placebo were similar across eGFR subgroups (P heterogeneity >0.05).

Conclusions

SGLT2is slowed eGFR decline, lowered albuminuria progression, improved adverse renal endpoints and reduced all‐cause mortality, but increased risk of genital infections vs placebo in patients with T2DM. The indication of consistent renal benefits across categories of baseline eGFR levels may allow additional individuals to benefit from SGLT2is therapy.
BioChaperone Lispro versus faster aspart and insulin aspart in patients with type 1 diabetes using continuous subcutaneous insulin infusion: A randomized euglycemic clamp study
Authors: Heise Tim , Meiffren Grégory , Alluis Bertrand , Seroussi Cyril , Ranson Aymeric , Arrubla Jorge , Correia José , Gaudier Martin , Soula Olivier , Soula Rémi , DeVries J. Hans , Klein Oliver , Bode Bruce
Published: December 2018

We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double‐blind, three‐way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC‐GIR,0–60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44–1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94–1.18; P = 0.4609). BCLIS showed faster‐on PD (tearly0.5GIRmax) than ASP and faster‐off PD (tlate0.5GIRmax) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0–60 minutes) and lower late exposure (AUCins,120–600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off‐PD than FIA.
Use of ultrasound enhancing agents in transesophageal echocardiography to improve interpretive confidence of left atrial appendage thrombus
Authors: Doukky Rami , Donenberg Merrick J. , Parker Jeremy , Kaplan Jonathan , Travers Chad , Soble Jeffrey S. , Sattar Payman , Krishnan Kousik , Madias Christopher , Tracy Melissa , Feinstein Steven B.
Published: December 2018

Background

The value of ultrasound enhancing agents (UEA) in patients undergoing transesophageal echocardiography (TEE) for the exclusion of left atrial appendage (LAA) thrombi prior to direct current cardioversion (DCCV) is evolving.

Methods

We retrospectively identified 88 consecutive TEEs, where a commercial UEA was used during LAA interrogation. De‐identified non‐enhanced (pre‐UEA) and enhanced cine loop images (post‐UEA) from the same subjects were randomly reviewed by four expert readers in a blinded fashion.

Results

In 33% of the cases, UEA use was associated with a statistically insignificant improvement in physician confidence (scale, 0‐3) in determining the presence or absence of a LAA thrombus (P = 0.071). In instances where non‐enhanced images yielded an uncertain interpretation or when the left atrium contained spontaneous echo contrast (SEC), UEA use was associated with an improvement in interpretive confidence in 49% (P < 0.001) and 41% of the cases (P = 0.001), respectively. Overall, the absolute rate of hypothetical decision to proceed with DCCV rose by 9% with the application of UEA (P = 0.004). In instances where non‐enhanced images were interpreted with limited confidence or when SEC was present, there were absolute increases of 16% (P < 0.001) and 21% (P < 0.001) in hypothetical procession to DCCV, respectively. In cases of a combination of limited interpretive confidence and SEC, UEA use was associated with a 29% absolute increase in the rate of procession to DCCV (P < 0.001).

Conclusions

In patients undergoing TEE interrogation of the LAA, the use of UEA is associated with an increase in the level of interpretive confidence and higher rates of theoretical procession to DCCV.
A comparative study of three different methods for assessing fish communities in a small eutrophic lake
Authors: Ravn Henrik Dalby , Lauridsen Torben Linding , Jepsen Niels , Jeppesen Erik , Hansen Peter Gruth , Hansen Johan Gruth , Berg Søren
Published: December 2018

Sound decisions on the management of fish stocks depend on knowledge about the species composition, number, biomass and size structure of existing populations. Accordingly, the ability to make solid population estimates is essential. In this study, a 2.15 ha lake was completely drained and the total number of fish was recorded and amounted to 180,915 individuals divided into seven species having a total weight of 1,395 kg. Before the draining, three commonly used methods in fish surveys were applied: multi‐mesh gillnets, point abundance sampling by electrofishing (PASE) and mark–recapture. Following the determination of the actual number and size distribution of each species, we evaluated the efficiency of the methods and found that gillnets caught a relatively high number of species (five out of seven) and thus proved to be the best tool for mapping species richness. However, gillnets were size selective towards larger individuals of perch (Perca fluviatilis) and did not catch roach (Rutilus rutilus) <5 cm. In contrast to gillnets, PASE was very effective at catching YOY fish in the shore zone but selected for larger‐sized roach. In sum, gillnetting proved to be the most accurate method for estimating species composition, PASE also being useful. Overall, mark–recapture provided relatively good estimates of population size but small‐sized (<11 cm) roach proved not to be well suited for mark–recapture surveys. We conclude that the best method(s) surveying fish stocks depends on various factors such as target species, size distribution and the purpose of the survey.
Alcoholic beverages as trigger factor and the effect on alcohol consumption behavior in patients with migraine
Authors: Onderwater G. L. J. , van Oosterhout W. P. J. , Schoonman G. G. , Ferrari M. D. , Terwindt G. M.
Published: December 2018

Background and purpose

Alcoholic beverages are frequently reported migraine triggers. We aimed to assess self‐reported alcohol consumption as a migraine attack trigger and to investigate the effect on alcohol consumption behavior in a large migraine cohort.

Methods

We conducted a cross‐sectional, web‐based, questionnaire study among 2197 patients with migraine from the well‐defined Leiden University MIgraine Neuro‐Analysis (LUMINA) study population. We assessed alcoholic beverage consumption and self‐reported trigger potential, reasons behind alcohol abstinence and time between alcohol consumption and migraine attack onset.

Results

Alcoholic beverages were reported as a trigger by 35.6% of participants with migraine. In addition, over 25% of patients with migraine who had stopped consuming or never consumed alcoholic beverages did so because of presumed trigger effects. Wine, especially red wine (77.8% of participants), was recognized as the most common trigger among the alcoholic beverages. However, red wine consistently led to an attack in only 8.8% of participants. Time of onset was rapid (<3 h) in one‐third of patients and almost 90% had an onset <10 h independent of beverage type.

Conclusions

Alcoholic beverages, especially red wine, are recognized as a migraine trigger factor by patients with migraine and have a substantial effect on alcohol consumption behavior. Rapid onset of provoked migraine attacks in contrast to what is known about hangover headache might point to a different mechanism. The low consistency of provocation suggests that alcoholic beverages acting as a singular trigger is insufficient and may depend on a fluctuating trigger threshold.
Left ventricular ejection fraction is associated with small vessel disease in ischaemic stroke patients
Authors: Nam K.‐W. , Kwon H.‐M. , Kim H.‐L. , Lee Y.‐S.
Published: December 2018

Background and purpose

The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients.

Methods

Consecutive first‐ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid‐attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose–response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated.

Results

A total of 841 patients were included [median WMH volume 2.98 (1.22–10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B = −0.052, P < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978, P = 0.012], CMBs (aOR = 0.96, P < 0.001) and moderate to severe EPVSs (aOR = 0.94, P < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P = 0.026), CMBs (P < 0.001) and EPVSs (P = 0.002). The total cSVD score also showed a negative association with LVEF in a dose–response manner (P < 0.001).

Conclusions

The burden of cSVD is negatively correlated with the LVEF in a dose–response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.
Clinical relevance of amnestic versus non‐amnestic mild cognitive impairment subtyping in Parkinson's disease
Authors: Chung S. J. , Park Y.‐H. , Yun H. J. , Kwon H. , Yoo H. S. , Sohn Y. H. , Lee J.‐M. , Lee P. H.
Published: December 2018

Background and purpose

To clarify whether subtyping of amnestic and non‐amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes.

Methods

We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting‐state functional connectivity between the patients with de‐novo PD with amnestic MCI (PD‐aMCI) (n = 50) and non‐amnestic MCI (PD‐naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de‐novo PD‐aMCI (n = 125) and PD‐naMCI (n = 61).

Results

The demographic data showed that scores in memory domains were lower in the PD‐aMCI group compared with the PD‐naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD‐aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD‐aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD‐naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD‐aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD‐naMCI (P = 0.022). In addition, the PD‐aMCI group had a higher risk of dementia conversion than the PD‐naMCI group.

Conclusions

This study suggests that the designation of PD‐MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.
Evolutionary epidemiology models to predict the dynamics of antibiotic resistance
Authors: Blanquart François
Published: December 2018

The evolution of resistance to antibiotics is a major public health problem and an example of rapid adaptation under natural selection by antibiotics. The dynamics of antibiotic resistance within and between hosts can be understood in the light of mathematical models that describe the epidemiology and evolution of the bacterial population. “Between‐host” models describe the spread of resistance in the host community, and in more specific settings such as hospitalized hosts (treated by antibiotics at a high rate), or farm animals. These models make predictions on the best strategies to limit the spread of resistance, such as reducing transmission or adapting the prescription of several antibiotics. Models can be fitted to epidemiological data in the context of intensive care units or hospitals to predict the impact of interventions on resistance. It has proven harder to explain the dynamics of resistance in the community at large, in particular because models often do not reproduce the observed coexistence of drug‐sensitive and drug‐resistant strains. “Within‐host” models describe the evolution of resistance within the treated host. They show that the risk of resistance emergence is maximal at an intermediate antibiotic dose, and some models successfully explain experimental data. New models that include the complex host population structure, the interaction between resistance‐determining loci and other loci, or integrating the within‐ and between‐host levels will allow better interpretation of epidemiological and genomic data from common pathogens and better prediction of the evolution of resistance.
Population genomic analyses reveal a highly differentiated and endangered genetic cluster of northern goshawks (Accipiter gentilis laingi) in Haida Gwaii
Authors: Geraldes Armando , Askelson Kenneth K. , Nikelski Ellen , Doyle Frank I. , Harrower William L. , Winker Kevin , Irwin Darren E.
Published: December 2018

Accurate knowledge of geographic ranges and genetic relationships among populations is important when managing a species or population of conservation concern. Along the western coast of Canada, a subspecies of the northern goshawk (Accipiter gentilis laingi) is legally designated as Threatened. The range and distinctness of this form, in comparison with the broadly distributed North American subspecies (Accipiter gentilis atricapillus), is unclear. Given this morphological uncertainty, we analyzed genomic relationships in thousands of single nucleotide polymorphisms identified using genotyping‐by‐sequencing of high‐quality genetic samples. Results revealed a genetically distinct population of northern goshawks on the archipelago of Haida Gwaii and subtle structuring among other North American sampling regions. We then developed genotyping assays for ten loci that are highly differentiated between the two main genetic clusters, allowing inclusion of hundreds of low‐quality samples and confirming that the distinct genetic cluster is restricted to Haida Gwaii. As the laingi form was originally described as being based on Haida Gwaii (where the type specimen is from), further morphological analysis may result in this name being restricted to the Haida Gwaii genetic cluster. Regardless of taxonomic treatment, the distinct Haida Gwaii genetic cluster along with the small and declining population size of the Haida Gwaii population suggests a high risk of extinction of an ecologically and genetically distinct form of northern goshawk. Outside of Haida Gwaii, sampling regions along the coast of BC and southeast Alaska (often considered regions inhabited by laingi) show some subtle differentiation from other North American regions. These results will increase the effectiveness of conservation management of northern goshawks in northwestern North America. More broadly, other conservation‐related studies of genetic variation may benefit from the two‐step approach we employed that first surveys genomic variation using high‐quality samples and then genotypes low‐quality samples at particularly informative loci.
Development and validation of a novel 13‐plex PCR system for commonly used short tandem repeats in horses (Equus caballus)
Authors: Shang S. , Zhang M. , Zhao Y. , Dang W. , Hua P. , Zhang S. , Wang Z.
Published: December 2018

Background

Due to the thriving development of the modern horse industry and the occurrence of horse related crimes, the demand for methods of individual horse identification, parentage tests and other genetic analyses is increasing. Previous methods had disadvantages that decreased the accuracy of the results, lacked the inclusion of all commonly used short tandem repeats (STR) or increased the experimental cost and time.

Objectives

We aimed to develop a novel 13‐plex STR typing system to resolve the above issues.

Study design

Experimental study.

Methods

Twelve autosomal and most commonly used di‐nucleotide STRs (AHT4, AHT5, ASB2, ASB17, ASB23, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10 and VHL20), and a Y‐chromosomal STR (YJ10) were included. We redesigned the primers of eight STRs to establish a novel multiplex PCR system and tested this system for species specificity, sensitivity and repeatability.

Results

Full profiles were easily generated in one fast PCR reaction using a low‐cost polymerase, as little as 1 ng of horse DNA template and 13 pairs of primers labelled with fluorescent dyes. No full profile was generated from DNA templates of humans or other commonly encountered animals. We also established an allelic ladder that contained 110 alleles based on 200 horses from 12 breeds and calculated standard population genetic parameters based on 150 Thoroughbreds. Stutter analysis showed that the averages of the stutter ratios were distinctly lower than those of lower allele ratios and the combined probability of paternity exclusion for this system were 0.994659935 (CPEduo) and 0.999854032 (CPEtrio).

Main limitations

A nonspecific and relatively low peak at 316 bp was frequently observed in locus HMS2, which is a nonexistent allele in all horses and should be ignored.

Conclusions

Our results indicate that this 13‐plex STR genotyping system is sensitive, species‐specific, cost‐effective and robust for applications in the horse industry and forensic investigation.
Therapeutic potential of topically administered γ‐AlOOH on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis‐like lesions in Balb/c mice
Authors: Bak Dong‐Ho , Lee Esther , Lee Byung Chul , Choi Mi Ji , Kwon Tae‐Rin , Hong Jiyeon , Mun Seog‐kyun , Lee Keugrae , Kim Sungyup , Na Jungtae , Kim Beom Joon
Published: December 2018

Boehmite (γ‐AlOOH) has a wide range of applications in a variety of industrial and biological fields. However, little is known about its potential roles in skin diseases. The current study investigated its effect on atopic dermatitis (AD). Following characterization, cytotoxicity, pro‐inflammatory response and oxidative stress associated with boehmite were assessed, using TNF‐α‐induced keratinocytes and mast cells. In addition, therapeutic effects of boehmite, topically administered to Balb/c mice induced by 2,4‐dinitrochlorobenzene (DNCB), were evaluated. Expression of cytokines (TLSP, IL‐25 and IL‐33) and the generation of ROS from keratinocytes induced by TNF‐α were significantly inhibited by boehmite without affecting cell viability. MAPKs (ERK, JNK and p38) required for cytokine expression were suppressed by boehmite treatment. Up‐regulation of cytokines (TSLP, IL‐4, IL‐5, IL‐13, RANTES) in human mast cells treated with phorbol 12‐myristate 13‐acetate and calcium ionophore was also suppressed by boehmite. Boehmite improved the AD severity score, epidermal hyperplasia and transepidermal water loss in DNCB‐induced AD‐like lesions. Moreover, Th2‐mediated cytokine expression, mast cell hyperplasia and destruction of the skin barrier were improved by boehmite treatment. Overall, we demonstrated that boehmite may potentially protect against AD.
Association of dynapenia, obesity and chronic diseases with all‐cause mortality of community‐dwelling older adults: A path analysis
Authors: Komatsu Tiemy R , Borim Flávia SA , Neri Anita L , Corona Ligiana P
Published: December 2018

Aim

The objective of the present study was to evaluate the effect of dynapenia, central obesity and the presence of chronic diseases in 8‐year mortality of community‐dwelling older adults.

Methods

Participants comprised 610 older adults, aged ≥65 years at baseline, who participated in the “Frailty in Brazilian Older People” study carried out in 2008. Baseline data, such as weight, height, waist circumference, muscle strength, sex, self‐reported diseases and physical activity, were assessed. Vital status in 2016 was assessed by Mortality Information System database of Campinas. The χ2‐test and Mann–Whitney U‐test were used to compare categorical and continuous variables, respectively. Path analysis was carried out to study the factors associated with mortality.

Results

There was a statistical difference between alive and deceased groups for the variables sex, age group, physical activity, waist circumference and dynapenia. Path analysis explored the relationship among the studied variables. Direct paths showed a positive association to mortality for those who presented the combination of more diseases (β = 0.105), male sex (β = 0.108), low physical activity (β = 0.121), low handgrip strength (β = 0.090) and no central obesity (β = −0.143). When indirect paths were concerned, variables “central obesity”, the presence of “more diseases” and dynapenia had a mediator role.

Conclusions

Central obesity was not positively associated with higher mortality, unless it was associated with the presence of chronic diseases. Dynapenia showed a direct effect on mortality, but not combined with central obesity. The findings of this study shed light on complex relationships between nutritional status and elderly mortality through the use of simple measurements. Geriatr Gerontol Int 2019; 19: 108–112.
Relationship between the occurrence of falls by season and physical functions of community‐dwelling old‐old people living in cold, snowy areas
Authors: Kihara Yuriko , Yamaguchi Ryo , Makino Keitaro , Shimizu Kotaro , Ito Kazunari , Furuna Taketo
Published: December 2018

Aim

To investigate the functional characteristics of older adults who experienced a fall in the winter season and other seasons.

Methods

Participants were 403 older adults enrolled in the project “Population‐Based and Inspiring Potential Activity for Old‐old Inhabitants,” and were living in cold, snowy regions in Japan. They were aged ≥75 years, and 41.9% (n = 169) were men. Sociodemographic characteristics, and physical, psycho‐cognitive and social factors were surveyed. By experiences of falls, they were divided into three groups: the non‐fall group, the fall in non‐winter group and the fall in winter group. Each factor was compared with a χ2‐test, Student's t‐test and Mann–Whitney U‐test. Logistic regression analysis was carried out. spss version 25 was used for the statistical analysis. The level of significance was set at 5%.

Results

No differences were confirmed between the non‐fall and fall in winter groups. In contrast, the maximum walking speed in the fall in non‐winter group was significantly slower than the non‐fall group, even with adjustment by variables, such as age, sex and self‐efficacy.

Conclusions

When considering intervention methods for health promotion, it is necessary to consider not only the presence or absence of falls, but also the seasons of falls. Geriatr Gerontol Int 2019; 19: 124–129.
Completed suicide rates of older adults in 5‐year age bands in Turkey between 2002 and 2013: A retrospective study
Authors: Altınöz Ali E , Yenilmez Çınar , Öner Setenay KD , Yıldız Pınar
Published: December 2018

Aim

Studies have shown that the causes and methods of suicides differ among young and old individuals; consequently, it is important to identify the subgroups that are at high risk for suicide to aid in suicide prevention. The present study compared the causes and methods of suicides between 2002 and 2013 among older adults aged 65–69 years, 70–74 years and ≥75 years by completed crude suicide rate and sex.

Methods

Data detailing sex, the causes and methods of completed suicides in older adults aged 65–69 years, 70–74 years and ≥75 years that occurred between 2002 and 2013 were drawn from the Turkish Statistical Institute.

Results

In all age groups, crude suicide rates were threefold more frequent among men than among women. In both sexes, the most frequent suicide cause was mental illness. In the group aged 65–69 years, the most common cause of suicide was financial difficulty for men and marital conflict for women. The most frequent suicide method among older adults of both sexes was hanging. In all age groups, firearms use was more common among men and jumping from a high place was more common among women.

Conclusion

The present findings suggest that the most common suicide cause in both sexes and in all age groups was mental illness in Turkey. To prevent suicidal behavior in older adults,; it is important to diagnose mental disorders, such as mood disorders and substance abuse, and to treat them quickly. Geriatr Gerontol Int 2019; 19: 66–69.
Optimisation of Lithium Chromatography for Isotopic Analysis in Geological Reference Materials by MC‐ICP‐MS
Authors: Li Wenshuai , Liu Xiao‐Ming , Godfrey Linda V.
Published: December 2018

The lithium isotope system can be an important tracer for various geological processes, especially tracing continental weathering. The key to this application is the accurate and precise determination of lithium isotopic composition. However, some of the previously established column separation methods are not well behaved when applied to chemically diverse materials, due to the significant variations in matrix/lithium ratios in some materials. Here, we report a new dual‐column system for lithium purification to achieve accurate and precise analysis of lithium isotopic compositions using a multi‐collector inductively coupled plasma‐mass spectrometer (MC‐ICP‐MS). Compared with single‐column systems, our dual‐column system yielded a consistent elution range of the lithium‐bearing fraction (7–16 ml) for samples with a large range of lithium loads and matrix compositions, so that column re‐calibration is not required. In addition, this method achieved complete lithium recovery and low matrix interference (e.g., Na/Li ≤ 1) with a short elution time (~ 6 h, excluding evaporation), with the entire procedure completed in 1.5 days. We report high precision Li isotopic compositions in twelve chemically diverse materials including seawater, silicates, carbonates, manganese nodules and clays. New recommended Li isotopic values and associated uncertainties are presented as reference values for quality control and inter‐laboratory calibration for future research and were consistent with previously published data. However, significant lithium isotopic variances (~ 1‰) in BHVO‐2 from different batches suggest Li isotopic heterogeneity in this reference material and that Li isotopic studies using this reference material should be treated with caution.
Defining clinically significant prostate cancer on the basis of pathological findings
Authors: Matoso Andres , Epstein Jonathan I
Published: December 2018

The definition of clinically significant prostate cancer is a dynamic process that was initiated many decades ago, when there was already evidence that a great proportion of patients with prostate cancer diagnosed at autopsy never had any clinical symptoms. Autopsy studies led to examinations of radical prostatectomy (RP) specimens and the establishment of the definition of significant cancer at RP: tumour volume of 0.5 cm3, Gleason grade 6 [Grade Group (GrG) 1], and organ‐confined disease. RP studies were then used to develop prediction models for significant cancer by the use of needle biopsies. The first such model was used to delineate the first active surveillance (AS) criteria, known as the ‘Epstein’ criteria, in which patients with a cancer Gleason score of 3 + 3 = 6 (GrG1) involving fewer than two cores, and <50% of any given core, and a prostate‐specific antigen density of <0.15 ng/ml per cm3 had a minimal risk of significant cancer at RP. These were adopted as components of the ‘very‐low‐risk category’ of the National Comprehensive Cancer Network guidelines, in which AS is supported as a management option. With the increase in the popularity of AS, much research has been carried out to better define significant/insignificant cancer, in order to be able to safely offer AS to a larger proportion of patients without the risk of undertreatment. Research has focused on allowing higher volume tumours, focal extraprostatic extension, and a limited amount of Gleason pattern 4, and the significance of different morphological patterns of Gleason 4. Other areas of research that will probably impact on the field but that are not covered in this review include the molecular classification of tumours and imaging techniques.
Variants and new entities of bladder cancer
Authors: Lopez‐Beltran Antonio , Henriques Vanessa , Montironi Rodolfo , Cimadamore Alessia , Raspollini Maria R , Cheng Liang
Published: December 2018

Pathological evaluation of bladder cancer typically reveals great tumour heterogeneity, and therefore the common observation of urothelial carcinoma exhibiting a wide variety of histopathological patterns is not surprising. Some of these patterns are so distinctive that they have been recognised as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organisation (WHO) classification of tumours of the urinary system and male genital organs. The current WHO classifications clarify terminological issues and provide better definition criteria, but also incorporate some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily pathology practice. This review will discuss the features of variants of urothelial carcinoma in the context of our current clinical practice. Histological variations and new entities of bladder cancer not included in the current WHO classification of urothelial tumours will be briefly discussed.
Precursor lesions of the urinary bladder
Authors: McKenney Jesse K
Published: December 2018

The classification of neoplastic precursor lesions in the urinary tract has evolved slowly with the gradual accumulation of clinicopathological data. Current nomenclature was codified most recently by the 2016 WHO classification, which is based on primary data with clinical outcome, consensus group statements and considerations of practical utility in routine diagnosis. This review discusses precursor lesions of urothelial, squamous and glandular lineage. For urothelial neoplasia, both flat lesions with atypia and early ‘difficult‐to‐classify’ proliferations are considered. Subtypes of squamous metaplasia, florid non‐invasive squamous proliferations and frank squamous dysplasia are also addressed. Finally, rare glandular precursors of adenocarcinoma are reviewed, to include intestinal metaplasia, glandular dysplasia and villous adenoma. For each category, morphology (including differential diagnostic considerations), immunohistochemistry and any known molecular correlates are detailed. The goal is to provide a concise, practical up‐to‐date overview of this complex topic.
Grading of prostate cancer: a work in progress
Authors: Kweldam C F , van Leenders G J , van der Kwast T
Published: December 2018

Grading of prostate cancer has evolved substantially over time, not least because of major changes in diagnostic approach and concomitant shifts from late‐ to early‐stage detection since the adoption of PSA testing from the late 1980s. After the conception of the architecture‐based nine‐tier Gleason grading system more than 50 years ago, several changes were made in order to increase its prognostic impact, to reduce interobserver variation and to improve concordance between prostate needle biopsy and radical prostatectomy grading. This eventually resulted in the current five‐tier grading system, with a much more detailed description of the individual architectural patterns constituting the remaining three Gleason patterns (i.e. grades 3–5). Nevertheless, there is room for improvement. For instance, distinction of common grade 4 subpatterns such as ill‐formed and fused glands from the grade 3 pattern is challenging, blurring the division between low‐risk patients who could be eligible for deferred therapy and those who need curative therapy. The last few years have witnessed the publication of several studies on the prognostic impact of individual architectural subpatterns showing that, in particular, the cribriform pattern exceeded the prognostic impact of other grade 4 subpatterns. This review provides an overview of the changes in prostate cancer grading over time and provides a thorough description of the various Gleason subpatterns, the current evidence of their prognostic impact and areas of contention. Potential practical ways for improvements of the current grading system are also put forward.
A facile route for the preparation of silica foams using rice husk ash
Authors: Hossain SK Saddam , Mathur Lakshya , Bhardwaj Aman , Roy Pradip Kumar
Published: December 2018

This work aims to synthesize silica foam with around 75 vol. % open porosity without using any additive or pore forming agents, in order to prevent the generation of greenhouse gases during pore formation in the silica matrix. Waste rice husk ash (RHA) derived silica is used as a silica source, which is extracted through the alkali extraction synthesis route. Several physical characterizations such as X‐ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), differential thermal‐thermogravimetric (DTA‐TGA) and FTIR analysis have been done for RHA extracted silica. Silica foam specimens are fabricated through control compaction pressure and at low foaming temperature. Samples which are fired at 550°C for 30 minutes exhibit both a adequate apparent porosity (AP; ~75.82%) and significant compressive strength (~1.54 MPa). It can also be observed that the porosity and strength values are changed with the variation in compaction pressure and foaming temperature.
Skin lesions in organ transplant recipients: a study of 177 consecutive Brazilian patients
Authors: Oliveira Walmar R. P. , Tirico Maria C. C. P. , Souza Anaisa A. V. , Codarin Felipe R. , Silva Lana L. C. , Festa Neto Cyro
Published: December 2018

Background

Skin lesions are very common among organ transplant recipients (OTR), particularly infections and tumors, because of the immunosuppressive state these patients are put in.

Methods

177 OTR were examined. Skin lesions were categorized into neoplastic, infectious, and inflammatory diseases.

Results

The mean age of OTR was 52 years, the mean age at transplantation was 42.7 years, and kidney was the most common organ transplanted (72%). Skin lesions were found in 147 patients (83%). Cutaneous infections were seen in 106 patients (60%). Warts (30%) had the larger incidence and were associated with azathioprine (P = 0.026), cyclosporine (P = 0.006), and tacrolimus (P = 0.009). Superficial mycoses occurred in 16% of OTR, mostly onychomycosis, which was associated with tacrolimus (P = 0.040). Actinic keratosis (AK) occurred in 31% of patients and cutaneous tumors in 56%. Squamous cell carcinoma (SCC) was the most common tumor type affecting 36% of OTR (n = 64), with invasive SCC predominating over in situ SCC, whereas basal cell carcinoma (BCC) accounted for 17%. Both SCC and BCC were more numerous in patients’ skin type I (P < 0.05). SCC was more frequent (36%) in combined kidney and liver recipients (P = 0.004), and BCC was associated with cyclosporine (P = 0.047). Inflammatory complications (acne, alopecia, hypertrichosis, and gingival overgrowth) were observed in 17.5% of patients.

Conclusions

Organ transplant recipients must be regularly evaluated by dermatologists, who should be alert to the onset of infections and skin (pre)malignant diseases in these patients.
High burden of the metabolic syndrome and its component disorders in South Africans with psoriasis
Authors: Goolam Mahyoodeen Nasrin , Crowther Nigel J. , Snyman Tracy , Pillay Lushen , Tikly Mohammed
Published: December 2018

Background

Psoriasis is associated with cardiometabolic diseases (CMDs) in Caucasians, but no data is available from sub‐Saharan populations on either CMD prevalence or psoriasis risk factors. Our aim was to investigate the prevalence of CMDs in a predominantly non‐Caucasian cohort of South Africans with psoriasis and to determine the principal risk factors associated with psoriasis.

Methods

This was a cross‐sectional case‐control study of adult psoriasis patients (n = 103) and controls (n = 98), comparing sociodemographic, anthropometric, clinical, and biochemical characteristics. The groups were matched for gender, ethnicity, and body mass index (BMI).

Results

The prevalence of metabolic syndrome (MetS) (52.4% vs. 33.7%; P = 0.007), type 2 diabetes (T2D) (25.2% vs. 4.1%; P < 0.0001), and hypertension (70.9% vs. 46.6%; P = 0.001) were all higher in the psoriasis group. High‐sensitivity CRP was higher in psoriasis patients than controls (4.70 (2.00, 10.9) vs. 2.00 (1.10, 4.80) ng/ml; P < 0.0005). Multivariable logistic regression analysis showed that severe psoriasis was independently associated with MetS (odds ratio [95% CIs]: 4.42 [1.72, 11.4]; P = 0.002), T2D (11.3 [3.07, 41.3]; P = 0.0002), and hypertension (2.48 [0.97, 6.32]; P = 0.05), whilst for psoriasis the principal risk factors were smoking (3.87 [1.97, 7.63]; P < 0.0001) and hsCRP (1.05 [1.00, 1.10]; P = 0.029), with completion of high school (0.23 [0.11, 0.48]; P < 0.0001) being protective.

Conclusions

In this population, psoriasis is characterized by a high burden of CMDs, particularly in those subjects with severe psoriasis. Inflammation plays a role in the etiology of psoriasis, whilst smoking and poor education further increase disease risk.
Lichen planus‐like keratosis: clinicopathological evaluation of 1366 cases
Authors: Vincek Vladimir
Published: December 2018

Background

Lichen planus‐like keratosis (LPLK) is a frequent skin lesion usually biopsied to rule out basal cell carcinoma (BCC). Because of overlapping histopathological characteristics, LPLK is frequently muddled with lichen planus (LP), lichenoid actinic keratosis (LAK), and lupus erythematosus (LE).

Objective

To investigate the clinical and histopathological characteristics of LPLK.

Methods

A clinicopathologic review was performed of all LPLK cases (1366) signed in one calendar year in a busy academic practice.

Results

LPLK occurs mostly as a single lesion (97%) with the chest (41.4%) being the most common site. It is almost equally present in women and men (51.5%–48.5%). The most common clinical concern (65%) is basal cell carcinoma. Parakeratosis, red blood extravasation, and presence of dermal eosinophils and plasma cells, usually not seen in lichen planus, are helpful signs to suggest LPLK but are seen only in a minority of cases.

Conclusion

Clinicopathologic correlation is necessary to diagnose lichen planus‐like keratosis, as the most consistent feature is a clinical history of a lesion/neoplastic process rather than an inflammatory process. There are histopathologic features that can help distinguish lichen planus‐like keratosis from lichen planus; however, these features are nonspecific and lacking in almost half of the cases.
The distribution of 4‐hydroxy‐hexenal and 4‐hydroxy‐nonenal in different vegetable oils and their formation from fatty acid methyl esters
Authors: Ma Lukai , Liu Guoqin , Cheng Weiwei , Liu Xinqi
Published: December 2018

The formation of 4‐hydroxy‐hexenal (HHE) and 4‐hydroxy‐nonenal (HNE) in eight vegetable oils was investigated at 180 °C. HHE was only detectable in soybean (SBO), rapeseed (RO) and linseed oils (LO). HNE was measured in all tested oils, but was found mainly in corn (CO), sunflower (SO) and soybean oil (SBO). Oil‐dependent formation of HHE/HNE was remarkably observed. Furthermore, different fatty acid methyl esters in tricaprylin, as model oil systems, were constructed to demonstrate their characteristic contribution to HHE/HNE formation. As expected, HHE and HNE originated from the oxidative degradation of methyl linolenate (MLN) and methyl linoleate (ML) respectively. Whereas low concentrations of MLN (<5.0%) and ML (<1.0%) produced no detectable HHE/HNE. The results suggested MLN/ML could induce both HHE/HNE formation and pro‐oxidation at higher concentrations. Unexpectedly, methyl stearate and methyl oleate slightly promoted HHE/HNE formation, which might be attributed to free radical transfer mechanisms during thermal oxidation.
How the thymus shaped immunology and beyond
Authors: Miller Jacques
Published: December 2018

Barely 60 years ago, the thymus was considered to be a vestigial organ with no known function or just a graveyard for dying lymphocytes. Now, the thymus and its cells cover a vast area of immunology, genetics and epigenetics relating to medicine, including inflammation, infection, vaccination, dysbiosis, immunodeficiency, allergy, autoimmunity, transplantation, tissue repair, pregnancy and cancer. New technology and approaches, now becoming available, will lead to a much deeper understanding of many of these conditions. Hence, the thymus and its cells will be occupying researchers and clinicians for decades to come.
Primary immunodeficiencies caused by mutations in actin regulatory proteins
Authors: Janssen Erin , Geha Raif S.
Published: December 2018

The identification of patients with monogenic gene defects have illuminated the function of different proteins in the immune system, including proteins that regulate the actin cytoskeleton. Many of these actin regulatory proteins are exclusively expressed in leukocytes and regulate the formation and branching of actin filaments. Their absence or abnormal function leads to defects in immune cell shape, cellular projections, migration, and signaling. Through the study of patients’ mutations and generation of mouse models that recapitulate the patients’ phenotypes, our laboratory and others have gained a better understanding of the role these proteins play in cell biology and the underlying pathogenesis of immunodeficiencies and immune dysregulatory syndromes.
Zero tolerance! A perspective on monogenic disorders with defective regulatory T cells and IBD‐like disease
Authors: Abdel‐Motal Ussama M. , Al‐Shaibi Ahmad , Elawad Mamoun , Lo Bernice
Published: December 2018

Recently, several studies have investigated a number of rare monogenic autoimmune disorders, in which the causative genetic defects were identified and found to affect the development or function of regulatory T cells (Tregs). The studies of these disorders have facilitated a deeper understanding of the mechanisms involved in immune regulation and tolerance. Furthermore, these studies have highlighted the importance of Tregs in maintaining homeostasis at the mucosal interface between the host and microbiome. Here, we offer our perspective on these monogenic autoimmune disorders, highlighting their overlapping clinical features with inflammatory bowel disease.
FAS and RAS related Apoptosis defects: From autoimmunity to leukemia
Authors: Meynier Sonia , Rieux‐Laucat Frédéric
Published: December 2018

The human adaptive immune system recognizes almost all the pathogens that we encounter and all the tumor antigens that may arise during our lifetime. Primary immunodeficiencies affecting lymphocyte development or function therefore lead to severe infections and tumor susceptibility. Furthermore, the fact that autoimmunity is a frequent feature of primary immunodeficiencies reveals a third function of the adaptive immune system: its self‐regulation. Indeed, the generation of a broad repertoire of antigen receptors (via a unique strategy of random somatic rearrangements of gene segments in T cell and B cell receptor loci) inevitably creates receptors with specificity for self‐antigens and thus leads to the presence of autoreactive lymphocytes. There are many different mechanisms for controlling the emergence or action of autoreactive lymphocytes, including clonal deletion in the primary lymphoid organs, receptor editing, anergy, suppression of effector lymphocytes by regulatory lymphocytes, and programmed cell death. Here, we review the genetic defects affecting lymphocyte apoptosis and that are associated with lymphoproliferation and autoimmunity, together with the role of somatic mutations and their potential involvement in more common autoimmune diseases.