Notes

Serialized 6-month change in compelled important ability predicts subsequent drop and death throughout Japoneses people along with fresh identified idiopathic lung fibrosis.
Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited.

To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action.

Animal study of a rat model of degenerated discs.

A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.
Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.Coronavirus disease 2019 (COVID-19) rapidly spread worldwide in the first quarter of 2020 and resulted in a global crisis. Investigation of the potential association of the spread of the COVID-19 infection with climate or ambient air pollution could lead to the development of preventive strategies for disease control. To examine this association, we conducted a longitudinal cohort study of 28 geographical areas of Japan with documented outbreaks of COVID-19. We analyzed data obtained from March 13 to April 6, 2020, before the Japanese government declared a state of emergency. The results revealed that the epidemic growth of COVID-19 was significantly associated with increase in daily temperature or sunshine hours. This suggests that an increase in person-to-person contact due to increased outing activities on a warm and/or sunny day might promote the transmission of COVID-19. Our results also suggested that short-term exposure to suspended particles might influence respiratory infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Further research by well-designed or well-controlled study models is required to ascertain this effect. Our findings suggest that weather has an indirect role in the transmission of COVID-19 and that daily adequate preventive behavior decreases the transmission.This study aimed to investigate the detoxification metabolism responses in scallop Chlamys farreri exposed to phenanthrene (PHE), chrysene (CHR), benzo[a]pyrene (B[a]P) and PHE + CHR + B[a]P for 15 days under laboratory conditions. The mRNA expression levels of AhR signaling pathway (AhR, HSP90, XAP2 and ARNT), detoxification system (phase I CYP1A1 and CYP1B1; phase II SULTs, UGT and GSTs) and ATP-binding cassette transporters (phase 0 ABCB1 and phase III ABCC1, ABCG2) in digestive glands of scallops exposed to PHE (0.7, 2.1 μg/L), CHR (0.7, 2.1 μg/L), B[a]P (0.7, 2.1 μg/L), and PHE + CHR + B[a]P (0.7 + 0.7 +0.7, 2.1 + 2.1 + 2.1 μg/L) were detected. In present study, key genes (AhR, HSP90, XAP2 and ARNT) of the AhR signaling pathway can be significantly induced by pollutants, suggesting that the AhR/ARNT signaling pathway plays a role directly or indirectly. AhR, HSP90 and ARNT reached the maximum value on day 6, which can be preliminarily understood as the synchronization of their functions. Besides, the results also indicated that different genes had specific response to different pollution exposure. CYP1B1, GST-2, GST-omega and GST-microsomal could be potional indexes to PHE, ARNT, GST-sigma 2 and GST-3 were sensitive to CHR exposure, HSP90, GST-theta and ABCG2 were considered as potional indexes to BaP while CYP1A1 and UGT were possible to be indexes for monitoring the mix exposure of these three PAHs. These findings in C. farreri suggested that phase II detoxification metabolic enzymes isoforms played an essential role in detoxification mechanisms and mRNA expression levels of specific SULTs, UGTs and GSTs were potentially to be ideal indexes in PAHs pollution research. In summary, this study provides more valuable information for the risk assessments of different rings of PAHs.Some environmental aspects are being increasingly studied in relation to the COVID-19 pandemic. Specifically, studies focusing on wastewater could be used for early warning, based on wastewater based epidemiology precepts. However, sewage sludge has been poorly studied in this regard up to now. In addition, soils have not been considered in publications related to SARS-CoV-2. In this piece, some comments are included to suggest a discussion regarding the eventual convenience of considering future studies focusing on soils receiving the spreading of wastewater and sewage sludge, as well as on plants growing on them.
To describe a novel technique developed for the treatment of patients with thoracoabdominal aortic aneurysms having narrow aortic lumens using branched endografts.

When treating patients with a narrow aortic inner diameter with branched endografts, we propose a partial graft deployment leaving the distal portion of the device inside the delivery system with the aim of spare space and facilitate target vessel cannulation.

Partial endograft deployment could be considered in the case of expected difficulty associated with encumbrance deriving from the distal straight graft portion. This technique could be useful to avoid target vessel loss and therein save procedural and fluoroscopy time.
Partial endograft deployment could be considered in the case of expected difficulty associated with encumbrance deriving from the distal straight graft portion. This technique could be useful to avoid target vessel loss and therein save procedural and fluoroscopy time.
Walking is recommended for patients with peripheral arterial disease (PAD). It has been shown that patients with PAD present sharper increases in blood pressure (BP) and heart rate (HR) during maximal walking when compared with healthy subjects. Additionally, women with PAD present a worse physiological profile, and it is possible that they may present higher cardiovascular load during and after a bout of maximal walking than men. Thus, the objective of this study was to compare cardiovascular and autonomic responses during and after maximal walking between men and women with PAD and intermittent claudication (IC).

Forty patients with PAD and IC (20 men and 20 women) underwent, in random order, 2 sessions control (standing on treadmill) and exercise (maximal treadmill walking test with Gardner's protocol). During the exercise, HR and BP were measured. Before and after the sessions, cardiovascular variables (BP HR, cardiac output, peripheral vascular resistance, and stroke volume) and autonomic modulation (HR and BP variabilities and baroreflex sensitivity) were assessed. In addition, an ambulatory BP monitoring was recorded after each session.

Men and women presented similar maximal walking capacity. During the walking test, HR and systolic BP increased similarly in men and women. After the maximal walking, cardiovascular and autonomic responses did not differ between the genders. In addition, postintervention ambulatory BP parameters were also similar in men and women. Therefore, in men and women, maximal walking similarly reduced clinic systolic BP and stroke volume, and increased HR and total power of HR variability during the recovery period.

Men and women with PAD and IC present similar cardiovascular and autonomic responses during and after maximal walking.
Men and women with PAD and IC present similar cardiovascular and autonomic responses during and after maximal walking.
The ability to salvage the mangled lower extremity is both technically challenging and time consuming. It requires the collaborative efforts among multiple surgical specialties in addition to comprehensive post-traumatic wound follow-up. Our institution has integrated a dynamic effort among these specialists in the planning and facilitating a successful limb salvage program with creation of a mangled extremity algorithm. An integral part in this process is the vascular inflow to prepare coverage for large tissue defects lacking adequate recipient targets. Utilization of long saphenous arteriovenous (AV) loop has been cited with minimal data available using larger inflow vessels in the acute trauma setting. We performed a retrospective review and describe our early experience using our protocol with AV loop creation with free flap reconstruction to salvage traumatic leg injuries. Using the data, we sought to develop a mangled extremity protocol for trauma centers to guide mangled limb salvage.

Since June 2ol to guide limb salvage has proven successful in our early experience. Long-term data need to be complied to assess patency of the free flap transfer and quality of life outcomes.
Although a small patient cohort, utilization of long saphenous vein AV loop is successful as a bridge to free flap transfer for isolated mangled lower extremities. Development and incorporation of our mangled extremity protocol to guide limb salvage has proven successful in our early experience. Long-term data need to be complied to assess patency of the free flap transfer and quality of life outcomes.
Shaggy aorta (SA) depicts the severe aortic surface degeneration, extremely friable, and likely to cause spontaneous peripheral and visceral embolization or during catheterization, aortic manipulation, surgery, or minimally invasive procedures. This study aims to provide the most accurate and up-to-date information on this disease.

Potentially eligible studies to be included were identified by searching the following databases CENTRAL Library, ClinicalTrials.gov, MEDLINE, and CINAHL, using a combination of subject headings and text words to identify relevant studies (Shaggy aorta) OR (aortic embolization) OR (aortic embolism) OR (aortic thrombus) OR (aortic plaque). From a total of 29,111 abstracts, and after applying inclusion and exclusion criteria, we considered 60 studies for inclusion in this review.

Appropriate measurement and assessment of the aortic wall are pivotal in the modern era, in particular when percutaneous procedures are performed, as SA has been identified as an independent risk factor for spinal cord injury, mesenteric embolization, and cerebral infarction after endovascular aortic repair. Furthermore, SA increases the rate of cerebral complications during transcatheter aortic valve implantation.

In conclusion, prompt diagnosis of SA syndrome and appropriate guidelines on the management of these conditions may help physicians to better assess the patient risk and to minimize the dreadful-related complications.
In conclusion, prompt diagnosis of SA syndrome and appropriate guidelines on the management of these conditions may help physicians to better assess the patient risk and to minimize the dreadful-related complications.
The aim of this study is to compare early and late results of an expanded polytetrafluoroethylene (ePTFE-Gore TAG®, group A) mesh structured endograft versus a Dacron one (Relay Plus® Bolton, group B) in thoracic endovascular aneurysm repair (TEVAR).

A prospective database was used to extract information from anonymous patients who underwent TEVAR for descending thoracic aortic aneurysms (DTAAs) between February 2005 and February 2019 at 3 referral university hospitals. Cases treated by means of ePTFE endograft (Gore TAG, group A) and Dacron graft (Relay Plus Bolton, group B) in elective and urgent settings were included. Early and late outcomes were compared.

A total of 129 consecutive patients were included (115 men and 14 women). ePTFE-Gore TAG® and Dacron-Relay Plus® Bolton were used in 56 (43.4%) and 73 (56.5%) patients, respectively. Preoperative characteristics of patients were similar. Technical success was 100%. Urgent procedures were 22.4%. Mean aortic coverage and partial debranching were 217similar early and late results in terms of mortality, SCI, EL, and TEVAR-related reinterventions. Effectiveness of TEVAR procedure was confirmed by the high rate of sac shrinkage and it was not influenced by endograft fabric.
ePTFE-Gore TAG and Dacron-Relay Plus Bolton in DTAA presented similar early and late results in terms of mortality, SCI, EL, and TEVAR-related reinterventions. Effectiveness of TEVAR procedure was confirmed by the high rate of sac shrinkage and it was not influenced by endograft fabric.
Free-floating thrombus in the internal carotid artery (ICA) has traditionally been treated via an open surgical approach through a longitudinal incision and exposure similar to that for carotid endarterectomy (CEA). In this case report, we present a novel use of transcarotid artery revascularization (TCAR) for the treatment of recurrent carotid stenosis associated with free-floating ICA thrombus.

We describe a 67-year-old female who presented with a diagnosis of right hemispheric stroke in evolution and prior history of right CEA and a mechanical mitral valve. Imaging confirmed high-grade recurrent stenosis of the right ICA with free-floating thrombus. TCAR was utilized to repair both the recurrent stenosis and the thrombus.

Redo CEA in the face of recurrent stenosis is a challenging clinical scenario, which in this instance, was further complicated by the presence of free-floating thrombus and active anticoagulation due to a mechanical mitral valve. This case report describes the successful management of ICA thrombus and restenosis with the novel use of TCAR.
Redo CEA in the face of recurrent stenosis is a challenging clinical scenario, which in this instance, was further complicated by the presence of free-floating thrombus and active anticoagulation due to a mechanical mitral valve. This case report describes the successful management of ICA thrombus and restenosis with the novel use of TCAR.One of the difficulties of the subintimal arterial flossing with antegrade-retrograde intervention technique (SAFARI) technique is to properly achieve a rendezvous between both antegrade and retrograde accesses. We propose a new technique to overcome this difficulty. It consists of directly percutaneously puncturing 2 loop snares, placed via each access, which are then both used to snare an externally introduced guidewire introduced through the needle. The snares are then moved en bloc, bringing both snares and the wire into the same channel.
Data from multiple surgical studies and settings have reported an increase in adverse events in patients admitted or treated on weekends. The aim of this study was to investigate short-term outcomes for patients undergoing carotid endarterectomy (CEA) in Australia and New Zealand based on the day of surgery.

This is a retrospective observational cohort study. Analysis of 7,857 CEAs recorded for more than 4 years in the Australasian Vascular Audit database was performed. Multivariate logistic regression was used to compare the following outcomes between CEAs performed during the week and on the weekend (1) in-hospital stroke and/or death; (2) other postoperative complications; and (3) shorter (2 days or less) length of stay (LOS).

A total of 7,857 CEAs were recorded, with significantly more procedures performed during the week (n=7,333, P<0.001). There was no statistically significant difference in the frequency of stroke and/or death or other complications between CEAs performed during the week or onhorter hospital LOS.
In Australia and New Zealand, there appears to be no disadvantage to performing CEA on the weekend, in terms of stroke and/or death. Level of experience of the primary operator does not affect rates of stroke and/or death after CEA. Weekend CEA is associated with a shorter hospital LOS.Traumatism of head arteries is rare, but among them, the superficial temporal artery is the most exposed and less protected vessel. A pseudoaneurysm of the superficial temporal artery may occur after blunt head trauma in old patients or during vigorous activity in younger people. Diagnosis should be made primarily upon history and physical examination, while duplex ultrasound is appropriate to confirm the diagnosis and CT scan to exclude other possible concomitant pathologies. Direct surgical treatment is the first and main option to solve bleeding and prevent future complications. Here reported the case of an old woman treated for a post-traumatic STA pseudoaneurysm.
The objective of this study was to determine whether the angiosome concept and WIfI classification in patients undergoing endovascular treatment is associated with the limb salvage rate and wound healing rate in patients with critical limb ischemia(CLI).

This was a retrospective, consecutive cohort study of CLI patients who underwent infrapopliteal angioplasty at the Vascular and Endovascular Surgery Service of the Hospital do Servidor Público Estadual, São Paulo, between January 2013 and January 2019. The primary outcome variable was the limb salvage rate and wound healing rate. The secondary outcome variables were patency, survival, time free from reintervention, and operative mortality rate.

Overall, 95 infrapopliteal endovascular procedures were performed in 95 patients. The initial technical success rate was 100%. The mean±standard deviation outpatient follow-up time was 775±107.5days. The analyses were performed at 360days for wound healing rate and 720days for limb salvage rates, overall survival to limb salvage rates, nor ulcer/wound healing rates. Moreover, the WIfI classification 0-1 is associated with faster and higher wound/ulcer healing rates than WIfI classification 2-3.
Six-min walking test (6MWT) has been widely in patients with symptomatic peripheral artery disease (PAD) to quantify the walking impairment and the efficacy of different therapeutic interventions. Despite the aforementioned usefulness of 6MWT for PAD, the information provided by this test goes beyond the meters walked. The aim of this study was to describe the relative values of 6MWT and body weight-walking distance product (DW) in patients with symptomatic PAD.

Two hundred twenty-seven patients with symptomatic PAD participated in the study. The 6MWT was performed and absolute and claudication distances were obtained. The results of 6MWT were then relativized and expressed as a percentage of a healthy subject. DW was obtained by the product of 6MWT distance by weight. In both sexes, the relative 6MWT ranged from 57% to 64%.

Absolute 6MWT total distance (P<0.001) was lower in women than in men, whereas the relative 6MWT total distance was similar between sexes (P=0.398). The absolute and relative 6MWT total distance were similar among age categories (P>0.072). The DW was higher in men than in women (P<0.05). In addition, in women, DW was higher in younger group than in other age groups (P<0.05).

Patients with symptomatic PAD achieve less than 70% of the distance achieved by an age-matched healthy subject. In patients with symptomatic PAD, the relative values of 6MWT total distance are similar between sexes and among different age groups, whereas DW are influenced by age and sex.
Patients with symptomatic PAD achieve less than 70% of the distance achieved by an age-matched healthy subject. In patients with symptomatic PAD, the relative values of 6MWT total distance are similar between sexes and among different age groups, whereas DW are influenced by age and sex.Caprine parainfluenza virus type3 (CPIV3) is a newly identified member of Paramyxoviridae family. CPIV3 is highly prevalence in China and showed pathogenicity to goats; in addition, CPIV3 infection causes severe clinical disease under stress and/or co-infection conditions. Viperin is one of the hundreds of interferon-stimulated genes (ISGs), and possesses a wide range of antiviral activities. The aim of this study was to systemically explore the anti-CPIV3 activity of ruminants' Viperin. CPIV3 infection up-regulated Viperin transcription but not protein expression in MDBK cells. Bovine and caprine Viperin genes (bVi and gVi) were amplified and analyzed by BLAST and multiple alignment. The obtained bVi/gVi amino acid sequences showed 99.5%-100% identity with previously submitted sequences and has variants at N-terminal domain (1-70aa) between each other. The pcDNA3.1 plasmids containing bVi and gVi genes were constructed to over-express the target proteins. CPIV3 was inoculated in MDBK cells over-expressing bVs transfected or CPIV3 infected cell samples. In conclusion, the bVi and gVi Viperin effectively inhibited CPIV3 replication potentially via the interaction of Viperin with viral N protein. The present results gave more information about antiviral activity of ruminants Viperin and provided foundation for further studies of the interaction of Viperin with CPIV3 and other related viruses.There is a pressing need for new vaccines against alphaviruses, which can cause fatal encephalitis (Venezuelan equine encephalitis virus (VEEV) and others) and severe arthralgia (e.g. Chikungunya virus, CHIKV). These positive-strand RNA viruses are diverse and evolve rapidly, meaning that the sequence of any vaccine should cover multiple strains that may be quite different from any previous isolate. Here, consensus proteins were produced to represent the common physicochemical properties (PCPs) of the epitope rich, B domain of the E2 envelope protein. PCP-consensus proteins were based on multiple strains of VEEV (VEEVcon) and CHIKV (CHIKVcon) or the conserved PCPs of 24 different alphaviruses (AllAVcon). The AllAVcon was altered to include binding sites for neutralizing antibodies of both VEEV and CHIKV strains (Mosaikcon). All four designed proteins were produced solubly in E. coli and purified. They formed the β-strand core expected from experimental structures of this region of the wild type E2 proteins as indicated by circular dichroism (CD) spectra. Furthermore, the CHIKVcon protein bound to a structure dependent, CHIKV neutralizing monoclonal antibody. The AllAVcon and Mosaikcon proteins bound to polyclonal antibodies generated during natural infection with either VEEV or CHIKV, indicating they contained epitopes of both serotypes. The Mosaikcon antigen induced antibodies in rabbit sera that recognized both the VEEVcon and CHIKVcon spike proteins. These PCP-consensus antigens are promising starting points for novel, broad-spectrum alphavirus vaccines.Nanoparticles (NPs) that permit active targeting promise to play a key role in cancer therapy moving forward. However, in order to successfully advance into clinic, these delivery platforms not only must target individual tumoural cellular components but also require safe, efficient and scalable production. Herein, we review recent and innovative targeted nanoparticle delivery strategies to individual TME components, including cancer-associated blood and lymphatic vessels, pericytes, cancer associated fibroblasts, and cancer stem cells. In contrast to traditional therapies that promote widespread ablation, emerging nano-strategies that specifically modulate different cell populations of the TME, such as targeting pericytes and endothelial cells for vascular normalization, are proving to effectively deliver therapeutics to tumours. Additionally, new smart targeted NPs with transformable characteristics responsive to specific tumour microenvironmental cues demonstrate enhanced spatiotemporal control over cell targeting and therapeutic release. However, translating these therapies to the clinic requires overcoming several significant barriers such as failure to recapitulate the human TME in animal models and issues with NP targeting efficacy, safety and scalable production. We discuss recent efforts to overcome these challenges and innovative means to reduce off-target toxicities. We also highlight important deficiencies in current NP development and offer new perspectives on the design of pre-clinical and clinical trials to accelerate clinical translation of targeted NP platforms.Advances in nanomedicine, including early cancer detection, targeted drug delivery, and personalized approaches to cancer treatment are on the rise. For example, targeted drug delivery systems can improve intracellular delivery because of their multifunctionality. Novel endogenous-based and exogenous-based stimulus-responsive drug delivery systems have been proposed to prevent the cancer progression with proper drug delivery. To control effective dose loading and sustained release, targeted permeability and individual variability can now be described in more-complex ways, such as by combining internal and external stimuli. Despite these advances in release control, certain challenges remain and are identified in this research, which emphasizes the control of drug release and applications of nanoparticle-based drug delivery systems. Using a multiscale and multidisciplinary approach, this study investigates and analyzes drug delivery and release strategies in the nanoparticle-based treatment of cancer, both mathematically and clinically.In repigmentation of human vitiligo, the melanocyte (MC) precursors in the hair follicle bulge proliferate, migrate, and differentiate to repopulate the depigmented epidermis. Here, we present a comprehensive characterization of pathways and signals in the bulge that control the repigmentation process. Using biopsies from patients with vitiligo, we have selectively harvested, by laser capture microdissection, MC and keratinocyte precursors from the hair follicle bulge of untreated vitiligo skin and vitiligo skin treated with narrow-band UVB. The captured material was subjected to whole transcriptome RNA-sequencing. With this strategy, we found that repigmentation in the bulge MC precursors is driven by KCTD10, a signal with unknown roles in the skin, and CTNNB1 (encoding β-catenin) and RHO guanosine triphosphatase [RHO GTPase, RHO], two signaling pathways previously shown to be involved in pigmentation biology. Knockdown studies in cultured human MCs of RHOJ, the upmost differentially expressed RHO family component, corroborated with our findings in patients with vitiligo, identified RHOJ involvement in UV response and melanization, and confirmed previously identified roles in melanocytic cell migration and apoptosis. A better understanding of mechanisms that govern repigmentation in MC precursors will enable the discovery of molecules that induce robust repigmentation phenotypes in vitiligo.Ciguatera fish poisoning is caused by the consumption of fish contaminated with ciguatoxins (CTXs). The most distressing symptoms are cutaneous sensory disturbances, including cold dysesthesia and itch. CTXs are neurotoxins known to activate voltage-gated sodium channels, but no specific treatment exists. Peptidergic neurons have been critically involved in ciguatera fish poisoning sensory disturbances. Protease-activated receptor-2 (PAR2) is an itch- and pain-related G protein‒coupled receptor whose activation leads to a calcium-dependent neuropeptide release. In this study, we studied the role of voltage-gated sodium channels, PAR2, and the PAR2 agonist cathepsin S in the cytosolic calcium increase and subsequent release of the neuropeptide substance P elicited by Pacific CTX-2 (P-CTX-2) in rat sensory neurons and human epidermal keratinocytes. In sensory neurons, the P-CTX-2‒evoked calcium response was driven by voltage-gated sodium channels and PAR2-dependent mechanisms. In keratinocytes, P-CTX-2 also induced voltage-gated sodium channels and PAR2-dependent marked calcium response. In the cocultured cells, P-CTX-2 significantly increased cathepsin S activity, and cathepsin S and PAR2 antagonists almost abolished P-CTX-2‒elicited substance P release. Keratinocytes synergistically favored the induced substance P release. Our results demonstrate that the sensory effects of CTXs involve the cathepsin S-PAR2 pathway and are potentiated by their direct action on nonexcitable keratinocytes through the same pathway.The aging process deleteriously alters the structure and function of dermal collagen. These alterations result in thinning, fragility, wrinkles, laxity, impaired wound healing, and a microenvironment conducive to cancer. However, the key factors responsible for these changes have not been fully elucidated, and relevant models for the study of skin aging progression are lacking. CCN1, a secreted extracellular matrix‒associated matricellular protein, is elevated in dermal fibroblasts in aged human skin. Toward constructing a mouse model to study the key factors involved in skin-aging progression, we demonstrate that transgenic mice, with selective expression of CCN1 in dermal fibroblasts (COL1A2-CCN1), display accelerated skin dermal aging. The aged phenotype in COL1A2-CCN1 mice resembles aged human dermis the skin is wrinkled and the dermis is thin and composed of loose, disorganized, and fragmented collagen fibrils. These dermal alterations reflect reduced production of collagen due to impaired TGFβ signaling and increased expression of matrix metalloproteinases driving the induction of c-Jun/activator protein-1. Importantly, similar mechanisms drive human dermal aging. Taken together, the data demonstrate that elevated expression of CCN1 by dermal fibroblasts functions as a key mediator of dermal aging. The COL1A2-CCN1 mouse model provides a novel tool for understanding and studying the mechanisms of skin aging and age-related skin disorders.Palliative care has been shown to improve quality of life, symptom, and caregiver burden for a range of life-limiting diseases. Palliative care use among patients with severe dermatologic disease remain relatively unexplored, but the limited available data suggest significant unmet care needs and low rates of palliative care utilization. This review summarizes current palliative care patterns in dermatology, identifying areas for improvement and future investigation.
In the context of the COVID-19 worldwide pandemic, an up-to-date review of current challenges in addictions is necessary. While large scale disasters may have an impact on substance use and addictions, the use of some substances is also likely to modify the risk of COVID-19 infection or course. Many countries have imposed lockdowns. Whether this quarantine or the end of lockdown measures will have an impact on substance use is discussed. The aim of this review is to gather knowledge for clinicians and to guide public health policies during/after lockdown.

PubMed was reviewed in August 6th (2020), to determine the current evidences and observations concerning the addictions and SARS-CoV2. We used all the names of the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV2 previously 2019 nCoV), the name of the coronavirus disease 2019 (COVID-19), and common substances of abuse. For the physiopathological parts, searches were conducted using key words such as "infection" or "pneumonia". For the lockdomportant areas for future research.Rats display a rich social behavioral repertoire. An important component of this repertoire is the emission of whistle-like calls in the ultrasonic range, so-called ultrasonic vocalizations (USV). Long low-frequency 22-kHz USV occur in aversive situations, including aggressive interactions, predator exposure, and electric shocks during fear conditioning. They are believed to reflect a negative affective state akin to anxiety and fear. A prominent theory suggests that 22-kHz USV function as alarm calls to warn conspecifics. Serotonin (5-hydroxytryptamine, 5-HT) is strongly implicated in the regulation of affective states, particularly anxiety and fear. A key component of the system is the 5-HT transporter (5-HTT, also known as SERT), regulating 5-HT availability in the synaptic cleft. In the present experiment, we studied the effects of SERT deficiency on overt fear-related behavior and alarm 22-kHz USV during fear conditioning in male and female rats. While overt fear-related behavior was not affected by SERT deficiency and sex, the emission of alarm 22-kHz USV was clearly reduced in homozygous SERT-/- but not heterozygous SERT+/- mutants, as compared to their wildtype SERT+/+ littermate controls. Genotype effects were particularly prominent in females. Females in general emitted fewer alarm 22-kHz USV than males. This supports the view that 22-kHz USV are, at least partly, independently regulated from anxiety or fear and as socially mediated alarm calls do not simply express a negative affective state. Reduced 22-kHz USV emission in rats lacking SERT might be due to social deficits in the use of 22-kHz USV as a socio-affective signal to warn conspecifics about threats.Methylphenidate (MPH) is a psychostimulant widely misused to increase wakefulness by drivers and students. Also, MPH can be found in dietary supplements in a clandestine manner aiming to burst performance of physical exercise practitioners. The abusive use of high doses of caffeine (CAF) in these contexts is equally already known. Here, we demonstrate the behavioral, oxidative and mitochondrial effects after acute exposure to high doses of MPH (80 mg/L) and CAF (150 mg/L), alone or associated (80 mg/L + 150 mg/L, respectively). We used zebrafish as animal model due to its high translational relevance. We evaluated the behavioral effects using the Novel Tank Test (NTT), Social Preference Test (SPT) and Y-maze Task and analyzed biomarkers of oxidative stress and activity of mitochondrial respiratory chain complexes. MPH alone induced antisocial behavior. MPH inhibited lipid peroxidation. The association of MPH + CAF presented memory impairment and anxiogenic behavior. In oxidative status, it inhibited lipid peroxidation, increased protein carbonylation and mitochondrial complex II, III and IV activity. Our results demonstrate that MPH and CAF alone negatively impact the typical behavioral of zebrafish. When associated, changes in cognition, memory, oxidative and mitochondrial status are more relevant.
Investigate the effects of CACNA1C rs1006737 on cortical and subcortical neurostructural phenotypes in Caucasian bipolar disorder (BD) and healthy control (HC) adolescents.

Seventy-one adolescents (14-20years; 38BD, 33HC) underwent 3-Tesla Magnetic Resonance Imaging (MRI). Region of interest (ROI) and vertex-wise analyses examined cortical volume, surface area (SA), and thickness, as well as subcortical volume. ROIs included the ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC), anterior cingulate cortex (ACC), putamen, and amygdala. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and total intracranial volume.

Vertex-wise analysis found significant BD-by-rs1006737 interactions for prefrontal and occipital regions such that BD A-carriers were found to have greater SA relative to BD non-carriers, while HC A-carriers had reduced SA relative to HC non-carriers. ROI analysis found an interaction in the ACC such that BD A-carriers were found to have greater SA relative to BD non-carriers, while no significant difference was found in HCs. Main effects of rs1006737 were also found on ACC SA from ROI analysis, and occipital SA from vertex-wise analysis, such that A-carriers had larger SA relative to non-carriers in both of these regions.

The current study identified neurostructural intermediate phenotypes relevant to the impact of CACNA1C rs1006737 on adolescent BD. Further investigation is warranted into the neurofunctional and neurocognitive relevance of rs1006737 associations with BD-specific elevations in regional SA.
The current study identified neurostructural intermediate phenotypes relevant to the impact of CACNA1C rs1006737 on adolescent BD. Further investigation is warranted into the neurofunctional and neurocognitive relevance of rs1006737 associations with BD-specific elevations in regional SA.
Acute aortic dissection (AAD) has been considered a contraindication for extracorporeal cardiopulmonary resuscitation (ECPR). However, studies are lacking regarding the epidemiology and effectiveness of ECPR for AAD. We aimed to examine whether ECPR for AAD during refractory cardiac arrest is effective.

Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified all emergently hospitalized adults who received ECPR on the day of admission and all AAD patients who received cardiopulmonary resuscitation on the day of admission. ECPR was defined as receiving both cardiopulmonary resuscitation and percutaneous extracorporeal membrane oxygenation. Outcomes were in-hospital mortality and neurological outcomes. We calculated the incremental cost-effectiveness ratio of ECPR for AAD.

We identified 398 AAD patients with ECPR, 9840 non-AAD patients with ECPR, and 9709 AAD patients with cardiopulmonary resuscitation but not ECPR. The incidence of AAD among the patients with ECPR on the day of admission was 3.9%. In-hospital mortality was 98% in AAD patients with ECPR, 79% in non-AAD patients with ECPR, and 98% in AAD patients with cardiopulmonary resuscitation but not ECPR. Seven AAD patients survived to discharge after ECPR; of these, six patients had good neurological outcomes at discharge. The incremental cost-effectiveness ratio of ECPR for AAD was estimated at 161,504 US dollars per quality-adjusted life year gained.

ECPR successfully improved outcomes and/or facilitated surgery for a small number of AAD patients with refractory cardiac arrest; however, the cost burden of ECPR for AAD patients may be unacceptably high.
ECPR successfully improved outcomes and/or facilitated surgery for a small number of AAD patients with refractory cardiac arrest; however, the cost burden of ECPR for AAD patients may be unacceptably high.
To compare the performance of two syndromic panels Luminex xTAG Gastrointestinal Pathogen Panel (GPP) and FilmArray Gastrointestinal (GI) panel.

A total of 243 diarrhea specimens were detected by two panels in parallel, and the inconsistent results were analyzed by real-time PCR or reverse transcription PCR (RT-PCR). The target concentration in specimens was examined by comparing the crossing point values of FilmArray, the median fluorescence intensity of xTAG and the cycle threshold values in any discrepancies.

For pathogens detected by both panels, the positive rates of FilmArray GI and xTAG GPP were 65.0% and 48.6%, respectively. The two panels showed high consistency (kappa ≥0.74) in detecting norovirus, rotavirus and Campylobacter, while there was low consistency (kappa ≤0.40) in detecting Cryptosporidium, Salmonella, Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic Escherichia coli (ETEC). Samples with low concentration targets were more often detected by FilmArray than with xTAG GPP. The xTAG GPP was more likely to be affected by amplification inhibitors. Several defects of xTAG GPP were found in detecting ETEC.

FilmArray was more sensitive. For specimens with low target concentrations or containing ETEC heat stable enterotoxin, the false negatives of xTAG GPP need to be considered.
FilmArray was more sensitive. For specimens with low target concentrations or containing ETEC heat stable enterotoxin, the false negatives of xTAG GPP need to be considered.
Deadly emerging infectious pathogens pose an unprecedented challenge to health systems and economies, especially across Africa, where health care infrastructure is weak, and poverty rates remain high. Genomic technologies are vital for enhancing the understanding and development of intervention approaches against these pathogens, including Ebola and the novel coronavirus disease 2019 (COVID-19).

Africa has contributed few genomes of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) to the global pool in growing open access repositories. To bridge this gap, the Africa Centre for Disease Control and Prevention (ACDC) is coordinating continent-wide initiatives to establish genomic hubs in selected well-resourced African centres of excellence. This will allow for standardisation and efficient and rapid data generation and curation. However, the strategy to ensure capacity for high-throughput genomics at selected hubs should not overshadow the deployment of portable, field-friendly and technically less demanding genomics technologies in all affected countries. This will enhance small-scale local genomic surveillance in outbreaks, leaving validation and large-scale approaches to be taken at central genomic hubs.

The ACDC needs to scale-up its campaign for government support across African Union countries to ensure the sustainable financing of its strategy for increased pathogen genomic intelligence and other interventions in current and inevitable future epidemics in Africa.
The ACDC needs to scale-up its campaign for government support across African Union countries to ensure the sustainable financing of its strategy for increased pathogen genomic intelligence and other interventions in current and inevitable future epidemics in Africa.
The World Health Organization has identified the need for a non-sputum-based test capable of detecting active tuberculosis (TB) as a priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a suitable biomarker for active TB.

We evaluated a commercial enzyme-linked immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients with active TB compared to latently infected controls, with and without HIV.

The two methods showed good agreement, with a mean bias of 0.01 (limit of agreement from -0.06 to 0.10). Using ELISA, it was found that HIV-infected patients with active TB disease had higher K/T ratios than those without TB (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 0.034-0.077], P<0.0001). At a cutoff of 0.080, the K/T ratio produced a sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 82%, and a negative predictive value (NPV) of 90%. In a receiver operating characteristics analysis, the K/T ratio had an area under the curve of 0.93. HIV-uninfected patients with active TB also had higher K/T ratios than those with latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 0.016-0.027], P<0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a specificity of 92%, a PPV of 91%, and an NPV of 84%.

The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.
The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.
Epidemic modelling studies predict that physical distancing is critical in containing COVID-19. However, few empirical studies have validated this finding. Our study evaluates the effectiveness of different physical distancing measures in controlling viral transmission.

We identified three distinct physical distancing measures with varying intensity and implemented at different times-international travel controls, restrictions on mass gatherings, and lockdown-type measures-based on the Oxford COVID-19 Government Response Tracker. We also estimated the time-varying reproduction number (R
) for 142 countries and tracked R
temporally for two weeks following the 100th reported case in each country. We regressed R
on the physical distancing measures and other control variables (income, population density, age structure, and temperature) and performed several robustness checks to validate our findings.

Complete travel bans and all forms of lockdown-type measures have been effective in reducing average R
g from home, and a full lockdown in the case of a probable uncontrolled outbreak.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) was characterized at the end of 2019, and soon spread around the world, generating a pandemic. It has been suggested that men are more severely affected by the viral disease (COVID-19) than women.

The aim of this systematic literature review (SRL) and meta-analysis was to analyse the influence of gender on COVID-19 mortality, severity, and disease outcomes. A SRL was performed in PubMed and Embase, searching terms corresponding to the 'PEO' format population = adult patients affected with COVID-19; exposure = gender; outcome = any available clinical outcomes by gender, including mortality and disease severity. The search covered the period from January 1 to April 30, 2020. Exclusion criteria were case reports/series, reviews, commentaries, languages other than English. Full-text, original articles were included. Data on study type, country, and patients' characteristics were extracted. Study quality was evaluated using the Newcastle-Ottawa scale ions.
Nosocomial infection is an ongoing concern in the COVID-19 outbreak. The effective screening of suspected cases in the healthcare setting is therefore necessary, enabling the early identification and prompt isolation of cases for epidemic containment. We aimed to assess the cost and health outcomes of an extended screening strategy, implemented in Singapore on 07 February 2020, which maximizes case identification in the public healthcare system.

We explored the effects of the expanded screening criteria which allow clinicians to isolate and investigate patients presenting with undifferentiated fever or respiratory symptoms or chest x-ray abnormalities. We formulated a cost appraisal framework which evaluated the treatment costs averted from the prevention of secondary transmission in the hospital setting, as determined by a branching process infection model, and compared these to the costs of the additional testing required to meet the criteria.

In the base case analysis, an R
of 2.5 and incubation peurred from the testing of negative patients could be negated by the averted costs. Outbreak control must be sustainable and effective; the proposed screening criteria should be considered to mitigate nosocomial transmission risk within healthcare facilities.In routine clinical practice, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is determined by reverse-transcription PCR (RT-PCR). In the current pandemic, a more rapid and high-throughput method is in growing demand. Here, we validated the performance of a new antigen test (LUMIPULSE) based on chemiluminescence enzyme immunoassay. A total of 313 nasopharyngeal swabs (82 serial samples from 7 infected patients and 231 individual samples from 4 infected patients and 215 uninfected individuals) were analyzed for SARS-CoV-2 with quantitative RT-PCR (RT-qPCR) and then subjected to LUMIPULSE. We determined the cutoff value for antigen detection using receiver operating characteristic curve analysis and compared the performance of the antigen test with that of RT-qPCR. We also compared the viral loads and antigen levels in serial samples from seven infected patients. Using RT-qPCR as the reference, the antigen test exhibited 55.2% sensitivity and 99.6% specificity, with a 91.4% overall agreement rate (286/313). In specimens with > 100 viral copies and between 10 and 100 copies, the antigen test showed 100% and 85% concordance with RT-qPCR, respectively. This concordance declined with lower viral loads. In the serially followed patients, the antigen levels showed a steady decline, along with viral clearance. This gradual decline was in contrast with the abrupt positive-to-negative and negative-to-positive status changes observed with RT-qPCR, particularly in the late phase of infection. In summary, the LUMIPULSE antigen test can rapidly identify SARS-CoV-2-infected individuals with moderate to high viral loads and may be helpful for monitoring viral clearance in hospitalized patients.
To investigate the potential of host urinary biomarkers as diagnostic candidates for tuberculosis (TB).

Adults self-presenting with symptoms requiring further investigation for TB were enrolled in Cape Town, South Africa. Participants were later classified as having TB or other respiratory diseases (ORD) using results from TB confirmatory tests. The concentrations of 29 analytes were evaluated in urine samples from participants using the Luminex platform, and their diagnostic potential was assessed using standard statistical approaches.

Of the 151 study participants, 34 (22.5%) were diagnosed with TB and 26 (17.2%) were HIV-positive. Seven biomarkers showed potential as TB diagnostic candidates, with accuracy improving (in HIV-positives) when stratified according to HIV status (area under the receiver operating characteristics curve; AUC ≥0.80). In HIV-positive participants, a four-marker biosignature (sIL6R, MMP-9, IL-2Ra, IFN-γ) diagnosed TB with AUC of 0.96, sensitivity of 85.7% (95% confidence interval (CI) 42.1-99.6%), and specificity of 94.7% (95% CI 74.0-99.9%). In HIV-negatives, the most promising was a two-marker biosignature (sIL6R and sIL-2Ra), which diagnosed TB with AUC of 0.76, sensitivity of 53.9% (95% CI 33.4-73.4%), and specificity of 79.6% (95% CI 70.3-87.1%).

Urinary host inflammatory biomarkers possess TB diagnostic potential but may be influenced by HIV infection. The results of this study require validation in larger studies.
Urinary host inflammatory biomarkers possess TB diagnostic potential but may be influenced by HIV infection. The results of this study require validation in larger studies.Parkinson's disease (PD) is the second most common neurodegenerative disease, which is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to a decrease in striatal dopamine. There is no antiparkinsonian therapy that offers a true disease-modifying treatment till date and there is an urgent need for a safe and effective neuroprotective or neurorestorative therapy. Our previous study demonstrated that metformin upregulated dopamine in the mouse brain and provided significant neuroprotection in animal model of PD. Therefore, we designed this study to investigate the molecular mechanism underlying such pharmacological effect of metformin. Herein, we found that metformin enhanced the phosphorylation of tyrosine hydroxylase (TH) which was accompanied by increase in brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and activation of their downstream signaling pathways in the mouse brain and SH-SY5Y cells. We further investigated the role of the neurotrophic factors in the activation of TH and observed that both BDNF and GDNF-induction were essential for metformin-induced TH activation.
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