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Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, nondestructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here, we report a completely different mechanism by which neutrophils act nondestructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of Serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy individuals. This nondestructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms., Introduction Neutrophils are the most abundant type of polymorphonucleated leukocytes in circulation, typically accounting for around 60% of the total in humans. When organs such as the liver, lungs, and [...]

Byline: Rajashree. Sriram, V. Gopal The skin aging which entails modifications in the entire skin and skin support system is caused as a result of complex blend of intrinsic and [...]

* Context.--Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management. Objective.--To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management. Design.--We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not. Results.--A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients. Conclusions.--Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified, thus, resulting in critical changes in recommendations for clinical management., The diagnosis of pigmented lesions has historically been based on a systematic appraisal of the light microscopic features of the lesion. However, particularly in the case of borderline lesions, interobserver [...]

Knowledge of juvenile recruitment (defined here as the quantitative addition of early benthic life stages to a local population) is important for conserving heavily harvested species and their critical habitats. Stone crabs (genus Menippe) are commercially and ecologically important throughout the Gulf of Mexico nearshore waters off Florida, but very little is known about their recruitment. Using standard commercial stone crab traps, megalopal and postsettlement juvenile (collectively, youngof-the-year. 'YOY') stone crabs were sampled at multiple spatial scales and for multiple stone crab generations to characterize geographical, seasonal, and interannual variation in their distribution and relative abundance (numbers collected on traps) in the Gulf of Mexico off peninsular Florida and north of the Florida Keys (the 'Florida Gulf'). The influences of potentially relevant oceanographic and biological variables [temperature, salinity, benthic community on the traps (trap fouling community). depth, distance from shore] on YOY stone crabs were investigated at locations distributed throughout the study area. Trap fouling communities had never been analyzed in detail prior to this study; an importance index was developed to quantify the seasonality, commonality, and density of the fouling communities and organisms composing the communities. Continuous, long-term data from the Tampa Bay location allowed investigation of the effects of biological relationships [relative abundance of female Menippe carrying eggs (ovigerous). occurrences of red tide (Karenia brevis, a toxic dinoflagellate) blooms] and meteorological events [tropical cyclones. El Nino Southern Oscillation (ENSO) occurrences] on temporal patterns of variation in recruitment. High relative abundances of YOY stone crabs were collected off peninsular Florida from dense, complex benthic biota that grew on crab traps located off large, pristine estuaries in relatively turbid water less than 5 m deep, where salinity ranged 24-36 and water temperature averaged 29[degrees]C-32[degrees]C. Two major recruitment locations, stable through decades, consistently accounted for approximately 50% of the YOY stone crabs collected: two secondary recruitment locations similarly accounted for another 25%. Relative abundance of YOY stone crabs was highest nearshore at the major recruitment locations, particularly during years of high relative abundance. Approximately 65%-75% of the recruits were collected August to October; however, the timing of both peak relative abundance and lowest relative abundance shifted to later in the year as latitude decreased. Patterns of change among months in relative abundance differed among locations within years and among years within locations. Water temperature, salinity, and trap fouling community were the important determinants of temporal and spatial variation in YOY stone crab relative abundance: depth and distance from shore were also important in areas where they varied notably among stations within locations and across broader expanses of the study area. At Tampa Bay, a sharp increase in relative abundance of ovigerous females in spring was followed by a similarly sharp increase in YOY stone crab relative abundance (principally stage 3-5 crabs) 3 mo later; whereas a sharp decrease in ovigerous female relative abundance in autumn was followed by a similarly sharp decrease in YOY stone crab relative abundance 1 mo later. Coincidence of the normal autumnal decrease in YOY stone crab relative abundance with red tides and tropical cyclones prevented assigning clear relationships between seasonal change in relative abundance and these potential external influences. Annual decreases in relative abundance were significantly related to the occurrence of tropical cyclones that came near Tampa Bay during the previous year. Twice, confluences of multiple hurricanes. timely red tides, and ENSO events were followed by nearly complete. 1- to 2-y recruitment collapses. In contrast, a single meteorologically and oceanographically highly anomalous year coincided with exceptionally high abundances of both YOY and ovigerous female stone crabs. A relationship between YOY stone crabs and subsequent fishery harvest was not evident, possibly due to a variety of fishery practices. Because stone crabs are subjected to intense fishing pressure throughout the Florida Gulf, the YOY stone crab recruitment grounds and their associated estuaries should be protected from the effects of development. agriculture, aquaculture. and commercial and recreational crabbing. KEY WORDS: abundance, depth, distance from shore, distribution. ENSO events, fishery, Florida, geographic variation. Gulf of Mexico, juveniles, megalopae, Menippe, ovigerous female crab, recruitment, red tide, salinity, seasonality, stone crab. Tampa Bay. temperature, trap fouling, INTRODUCTION Understanding the recruitment patterns of mobile marine benthic invertebrates with pelagic larval dispersal is important because the distribution and abundance of early benthic life stages can greatly influence a [...]

Using the Nephrotic Syndrome Study Network Consortium data set and other publicly available transcriptomic data sets, we identified retinoic acid receptor responder protein 1 (RARRES1) as a gene whose expression positively correlated with renal function decline in human glomerular disease. The glomerular expression of RARRES1, which is largely restricted to podocytes, increased in focal segmental glomerulosclerosis (FSGS) and diabetic kidney disease (DKD). TNF-[alpha] was a potent inducer of RARRES1 expression in cultured podocytes, and transcriptomic analysis showed the enrichment of cell death pathway genes with RARRES1 overexpression. The overexpression of RARRES1 indeed induced podocyte apoptosis in vitro. Notably, this effect was dependent on its cleavage in the extracellular domain, as the mutation of its cleavage site abolished the apoptotic effect. Mechanistically, the soluble RARRES1 was endocytosed and interacted with and inhibited RIO kinase 1 (RIOK1), resulting in p53 activation and podocyte apoptosis. In mice, podocyte-specific overexpression of RARRES1 resulted in marked glomerular injury and albuminuria, while the overexpression of RARRES1 cleavage mutant had no effect. Conversely, podocyte-specific knockdown of Rarresl in mice ameliorated glomerular injury in the setting of adriamycin-induced nephropathy. Our study demonstrates an important role and the mechanism of RARRES1 in podocyte injury in glomerular disease., Introduction Podocytes are an integral component of the glomerular filtration unit, and its injury leads to proteinuria and glomerulosclerosis in multiple glomerular diseases, such as diabetic kidney disease (DKD) and [...]

A series of methacrylate-acrylonitrile-butadiene-styrene (MABS) resins was prepared using bulk polymerization. The polarity of the continuous phase and the compatibility of two phases were changed by adjusting the methyl methacrylate (MMA) content, choosing values that were close to styrene-butadiene rubber solubility value. The possibility of controlling the microstructure of the MABS resin by changing the polarity of the components and the compatibility of two phases was assessed. The dynamic mechanical analysis shows that the compatibility of two phases varies with the MMA content. The morphological analysis shows that increasing MMA contents results in a gradual decrease in the sub-inclusion structure with a network skeleton of rubber particles, and that all the particles become solid rubber when the MMA content reaches 75%. The sub-inclusion structure reappears but does not have a network skeleton when the MMA content is 90%. The impact strength and morphological analysis indicate that the solid rubber particles and the sub-inclusion structure with a network skeleton provide excellent toughness, while the sub-inclusion structure without a network skeleton does not. In contrast, the transmittance of the ABS resin first increased and then decreased with increasing MMA content. KEYWORDS bulk polymerization, microstructure, sub-inclusion, the compatibility of two phases, transparent MABS resin, 1 | INTRODUCTION Recent developments in industrial design have introduced a natural style and a culture of soft colors. This style requires the use of transparent materials so that the [...]

* Context.--There have been major advances in the understanding of melanoma since the last revision of the World Health Organization (WHO) classification in 2006. Objective.--To discuss development of the 9 distinct types of melanoma and distinguishing them by their epidemiology, clinical and histologic morphology, and genomic characteristics. Each melanoma subtype is placed at the end of an evolutionary pathway that is rooted in its respective precursor, wherever appropriate and feasible, based on currently known data. Each precursor has a variable risk of progression culminating in its fully evolved, invasive melanoma. Data Sources.--This review is based on the 'Melanocytic Tumours' section of the 4th edition of the WHO Classification of Skin Tumours, published in 2018. Conclusions.--Melanomas were divided into those etiologically related to sun exposure and those that are not, as determined by their mutational signatures, anatomic site, and epidemiology. Melanomas on the sun-exposed skin were further divided by the histopathologic degree of cumulative solar damage (CSD) of the surrounding skin, into low and high CSD, on the basis of degree of associated solar elastosis. Low-CSD melanomas include superficial spreading melanomas and high-CSD melanomas incorporate lentigo maligna and desmoplastic melanomas. The 'nonsolar' category includes acral melanomas, some melanomas in congenital nevi, melanomas in blue nevi, Spitz melanomas, mucosal melanomas, and uveal melanomas. The general term melanocytoma is proposed to encompass 'intermediate' tumors that have an increased (though still low) probability of disease progression to melanoma. (Arch Pathol Lab Med. 2020;144:500-522; doi: 10.5858/arpa.2019-0561-RA), This monograph represents a summary and discussion of a classification of melanoma that was developed for the WHO Classification of Skin Tumours, 4th edition, published in 2018. (1) As in [...]

* Context.--Melanocytic lesions are common in routine surgical pathology. Although the majority of these lesions can be confidently diagnosed using well-established morphologic criteria, there is a significant subset of lesions that can be diagnostically difficult. These can be a source of anxiety for patients, clinicians, and pathologists, and the potential consequences of a missed diagnosis of melanoma are serious. Objective.--To provide a practical approach to the diagnosis of melanocytic lesions, including classic problem areas as well as suggestions for common challenges and appropriate incorporation of ancillary molecular techniques. Data Sources.--Literature search using PubMed and Google Scholar, incorporating numerous search terms relevant to the particular section, combined with contemporaneous texts and lessons from personal experience. Conclusions.--Although a subset of melanocytic lesions can be diagnostically challenging, the combination of a methodical approach to histologic assessment, knowledge of potential diagnostic pitfalls, opinions from trusted colleagues, and judicious use of ancillary techniques can help the pathologist navigate this difficult area. (Arch Pathol Lab Med. 2019;143:789-810; doi: 10.5858/arpa.2017-0547-RA), Melanocytic lesions are a common component of the everyday workload for a surgical pathologist. Although distinction between nevi and melanoma can usually be easily achieved using well-established morphologic criteria, (1) [...]

A persistent feature in Jesuit reports about the late Ming and early Qing was the notion that an enduring peace and concord pervaded the Chinese political system. Although the Jesuits did not invent this association, which was rooted in Greco-Roman historiography, the Jesuit encyclopaedist Antonio Possevino (1533-1611) was the first to link the 'perpetual peace' (perpetua pax) and 'supreme concord' (summa concordia) of the Chinese state to the Confucian intellectual tradition. As the Jesuits' missionary strategy developed under the tutelage of Matteo Ricci (1552-1610), 'public peace' (pax publica) and 'the calm of the Republic' (Republica quies) came to be perceived as the ultimate purpose of the Confucian precepts and one of the hinges on which the aims of Christianity, Confucianism and natural law can be reconciled. The supreme expression of the link between Confucianism and peace can be found in the Confucius Sinarum philosophus (1687), which presented for the first time an accessible translation of three of the four Confucian classics. Yet while retaining the view that pre-Qin Confucianism espoused peace as a central political aim, the Confucius Sinarum philosophus challenged the view that contemporary China could be regarded as a utopic actualization of Confucian peace. This paper will discuss this shift as an attempt to coopt the Chinese political experience as an argument against the pragmatic political philosophy known as 'reason of state', which was perceived by Jesuit thinkers as atheistic and immoral. Keywords: atheism, Confucianism, Confucius Sinarum philosophus, Philippe Couplet, heresy, Jesuit China mission, Machiavelli, Reason of State, A recurrent perception in Jesuit writings about the late Ming and early Qing was that the Chinese state was characterised by peace. While the Jesuits may have promoted this idea [...]

Objectives In many sub-Saharan African countries, the use of long-acting reversible contraceptives (LARCs) is low while unmet need for family planning (FP) remains high. We evaluated the effectiveness of a LARC access expansion initiative in reaching young, less educated, poor, and rural women. Methods Starting in 2008, Marie Stopes International (MSI) has implemented a cross-country expansion intervention to increase access to LARCs through static clinics, mobile outreach units, and social franchising of private sector providers. We analyzed routine service statistics for 2008-2014 and 2014 client exit interview data. Indicators of effectiveness were the number of LARCs provided and the percentages of LARC clients who had not used a modern contraceptive in the last 3 months ('adopters'); switched from a short-term contraceptive to a LARC ('switchers'); were aged, Author(s): Thoai D. Ngo [sup.1] , Olivia Nuccio [sup.2] , Shreya K. Pereira [sup.3] , Katharine Footman [sup.2] , Kate Reiss [sup.2] Author Affiliations: (1) Research and Knowledge Management, Innovations [...]

Byline: Pradeep. Dongare, S. Bhaskar, S. Harsoor, Rakesh. Garg, Sudheesh. Kannan, Umesh. Goneppanavar, Zulfiqar. Ali, Ramachandran. Gopinath, Jayashree. Sood, Kalaivani. Mani, Pradeep. Bhatia, Priyanka. Rohatgi, Rekha. Das, Santu. Ghosh, Subramanyam. [...]

Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration., Transected axons fail to regrow spontaneously across severe tissue lesions in the mature mammalian central nervous system (CNS). Potential mechanisms include: (i) reduced intrinsic growth capacity of mature CNS neurons [...]

Foraminifera are commonly defined as marine testate protists, and their diversity is mainly assessed on the basis of the morphology of their agglutinated or mineralized tests. Diversity surveys based on environmental DNA (eDNA) have dramatically changed this view by revealing an unexpected diversity of naked and organic-walled lineages as well as detecting foraminiferal lineages in soil and freshwater environments. Moreover, single-cell analyses have allowed discrimination among genetically distinctive types within almost every described morphospecies. In view of these studies, the foraminiferal diversity appeared to be largely underestimated, but its accurate estimation was impeded by the low speed and coverage of a cloning-based eDNA approach. With the advent of high-throughput sequencing (HTS) technologies, these limitations disappeared in favor of exhaustive descriptions of foraminiferal diversity in numerous samples. Yet, the biases and errors identified in early HTS studies raised some questions about the accuracy of HTS data and their biological interpretation. Among the most controversial issues affecting the reliability of HTS diversity estimates are (1) the impact of technical and biological biases, (2) the sensitivity and specificity of taxonomic sequence assignment, (3) the ability to distinguish rare species, and (4) the quantitative interpretation of HTS data. Here, we document the lessons learned from previous HTS surveys and present the current advances and applications focusing on foraminiferal eDNA. We discuss the problems associated with HTS approaches and predict the future trends and avenues that hold promises for surveying foraminiferal diversity accurately and efficiently., Introduction During the last two decades there have been tremendous changes in our understanding of the diversity and evolutionary history of microbial eukaryotes. In the early stage, the development of [...]

Byline: Sunil. Pandya, Kiran. Mangalampally Pregnancy is a normal physiologic process with the potential for pathologic states. Pregnancy has several unique characteristics including an utero-placental interface, a physiologic stress that [...]

The fastest and most manoeuvrable terrestrial animals are found in savannah habitats, where predators chase and capture running prey. Hunt outcome and success rate are critical to survival, so both predator and prey should evolve to be faster and/or more manoeuvrable. Here we compare locomotor characteristics in two pursuit predatorprey pairs, lionzebra and cheetahimpala, in their natural savannah habitat in Botswana. We show that although cheetahs and impalas were universally more athletic than lions and zebras in terms of speed, acceleration and turning, within each predatorprey pair, the predators had 20% higher muscle fibre power than prey, 37% greater acceleration and 72% greater deceleration capacity than their prey. We simulated hunt dynamics with these data and showed that hunts at lower speeds enable prey to use their maximum manoeuvring capacity and favour prey survival, and that the predator needs to be more athletic than its prey to sustain a viable success rate., Author(s): Alan M. Wilson (corresponding author) [1]; Tatjana Y. Hubel [1]; Simon D. Wilshin [1]; John C. Lowe [1]; Maja Lorenc [1]; Oliver P. Dewhirst [1]; Hattie L. A. Bartlam-Brooks [...]

Background Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia that is caused by mutations in the sodium-glucose cotransporter SGLT2 coding gene, SLC5A2. Objective We conducted molecular and phenotype analyses of a cohort of 23 unrelated Korean children with FRG. Methods Mutational analysis of the SLC5A2 gene was conducted in this multicenter study organized by the Korean Society of Pediatric Nephrology. Results A total of 21 different SLC5A2 mutations were detected, including 19 novel mutations. All patients had at least one mutated allele; ten patients had homozygous or compound heterozygous mutations and 13 patients had a single heterozygous mutation. Most mutations were private. Patients with two mutations were diagnosed earlier with larger amounts of urinary glucose excretion than patients with single mutations. Pedigree analysis data were consistent with the inheritance of a codominant trait with incomplete penetrance. Conclusions These findings extend the allelic heterogeneity in FRG and confirm previous observations of inheritance and genotype-phenotype correlation in patients with this disease. Keywords Familial renal glucosuria * Sodium-glucose cotransporter * SGLT2 * SLC5A2 gene * Mutation, Introduction Familial renal glucosuria (FRG, OMIM #233100) is characterized by persistent glucosuria owing to decreased renal tubular reabsorption of glucose in the presence of a normal serum glucose concentration and [...]

Clinical trials exploring the effectiveness of counseling and psychotherapy in treatment of depression in school-age youth composed this meta-analysis. Results were synthesized using a random effects model for mean difference and mean gain effect size estimates. No effects of moderating variables were evident. Counseling and psychotherapy are effective for treatment of depression in school-age youth both at termination and follow- up, and in school and nonschool settings., Depression is a mood state that involves frequent and intense feelings of sadness that cause an individual to lose interest in normal daily activities, such as work or school performance, [...]

Internationally, cognitive behavioral theories form the foundation of work with offenders, because they have proved to be the most effective in bringing about changes and reducing levels of reoffending. As [...]

Summary Until recently there has been little attention paid in health policy and practice to older people who smoke. But this is changing because of the increasing numbers of current [...]

Research has suggested that engagement in patterns of risk-taking behaviour might have a negative influence on the processing of risk information. However, risk-takers display higher risk perceptions than non-risk takers. This paradox might be resolved by removing the confounding effect of risk takers' increased exposure to risk. A longitudinal survey was administered to 255 motorists to examine the extent to which Time I (T1) self-reported speeding behaviour predicted exposure-free measures of Time 2 (T2) risk perceptions. Hierarchical regression analyses, controlling for demographics and T1 risk perceptions, showed that T1 speeding, and T1 to T2 speeding changes, both inversely predicted T2 risk perceptions. This suggests that successive increments in risk-taking behaviour will lead to progressively lower increases in personal risk perception. Possible foundations and implications of this effect are discussed., Risk perception theories of health and safety behaviour propose that people make a first step toward the initiation of healthier behaviour when they perceive current behaviours to be risky (Weinstein, [...]