A novel SMARCA2-CREM fusion: expanding the molecular spectrum of intracranial mesenchymal tumors beyond the FET genes.

Abstract: A novel histomolecular tumor of the central nervous system, the "intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive" has recently been identified in the literature and will be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. However, our latest study using DNA-methylation analyses has revealed that intracranial FET-CREB fused tumors do not represent a single molecular tumor entity. Among them, the main subgroup presented classical features of angiomatoid fibrous histiocytoma, having ultrastructural features of arachnoidal cells, for. Another tumor type with clear cell component and histopathological signs of aggressivity clustered in close vicinity with clear cell sarcoma of soft tissue. Herein, we report one case of IMT with a novel SMARCA2-CREM fusion which has until now never been described in soft tissue or the central nervous system. We compare its clinical, histopathological, immunophenotypic, genetic and epigenetic features with those previously described in IMT, FET-CREB fusion-positive. Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient's death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology "IMT, FET-CREB fusion-positive", and that further series of cases are needed to better characterize them.

Tauziède-Espariat|Arnault|A| Pierron|Gaëlle|G| Guillemot|Delphine|D| Sievers|Philipp|P| Cazals-Hatem|Dominique|D| Faillot|Thierry|T| Roux|Alexandre|A| Benzakoun|Joseph|J| Bockel|Sophie|S| Weinbreck|Nicolas|N| Hasty|Lauren|L| Lechapt|Emmanuèle|E| Chrétien|Fabrice|F| Varlet|Pascale|P|

Intracranial mesenchymal tumor
CREM
SMARCA2


Prolonged Positive COVID-19 Test in Recovered Patient.

Abstract: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has affected millions worldwide since its initial outbreak in Wuhan, China in December 2019. Discussion of atypical cases of COVID-19 is essential to gaining insight into the clinical presentations of this infection. The authors report a case in which a 74-year-old female who sought medical evaluation via telemedicine for chief complaints of recurrent low-grade fever, dyspnea, dry cough, and myalgias and subsequently tested positive for the SARS-CoV-2 multiple times in over 7 weeks despite prior resolution of symptoms. The patient's 78-year-old husband who resides in the same household also contracted the SARS-CoV-2.

Pham|Christine X Q|CXQ|
Uttaburanont|Michelle|M|
Witkos|Maciej|M|

COVID-19 SARS-CoV-2 Pandemic Telemedicine Antibody RT-PCR Self-quarantine Transmissibility


The impact of comorbid gastroesophageal reflux disease on endoscopic sinus surgery quality-of-life outcomes.

Abstract:
BACKGROUND
Chronic rhinosinusitis (CRS) and gastroesophageal reflux disease (GERD) are common entities that overlap in patient demographics. The pathophysiologic role of GERD has yet to be elucidated, but it is postulated that extraesophageal reflux may contribute to worsening symptoms of CRS. This study seeks to investigate whether patients with CRS with and without a history of GERD experience comparable quality-of-life (QOL) improvement after endoscopic sinus surgery (ESS).

METHODS
An adult cohort (n = 229) with medically refractory CRS was prospectively assessed following ESS using 3 disease-specific QOL constructs. A patient subset with a history of comorbid GERD was retrospectively identified (n = 72) and preoperative and postoperative QOL were compared to patients without GERD (n = 157).

RESULTS
Patients with comorbid GERD and CRS were comparable across all baseline patient characteristics (p > 0.050) with the exception of patients with a history of GERD; those patients were less likely to have undergone allergy testing (p < 0.002) and were older (53.8 years vs 47.6; p < 0.002). Similarly, baseline objective and subjective measures of disease were comparable between patients with CRS with and without GERD (p > 0.050). Both groups experienced significant QOL improvement across all QOL constructs (p ≤ 0.021), and no difference was detected in the magnitude of that improvement between patients with and without a history of GERD (p > 0.050). Similarly, patients on active medical therapy for GERD (n = 49) had QOL gains comparable to patients not reporting GERD medical therapy (p > 0.050).

CONCLUSION
Patients electing ESS for CRS with and without comorbid GERD have comparable baseline characteristics and QOL outcomes following surgery.

DeConde|Adam S|AS|
Mace|Jess C|JC|
Smith|Timothy L|TL|

gastroesophageal reflux
confounding factors
endoscopy
outcome assessment
quality of life
sinusitis


Ultrastructural characteristics of black marsh turtle spermatozoa obtained by electroejaculation.

Abstract: The black marsh turtle (Geoemydidae: Siebenrockiella crassicollis) is a freshwater turtle that occurs in equatorial tropical climates in South East Asia. The semen of S. crassicollis was investigated by electroejaculation. The spermatozoa of S. crassicollis are filiform in shape with curved heads. The entire length, midpiece to tail length, tail width and tail length of the spermatozoa were 71.33 ± 1.55 μm, 49.92 ± 1.13 μm, 0.43 ± 0.02 μm and 48.53 ± 0.25 μm, respectively. The head length, head width across the middle and head width across the base were 14.00 ± 0.38 μm, 0.79 ± 0.03 μm and 0.91 ±0.0.03 μm, respectively. The acrosomal region of the S. crassicollis spermatozoa was narrower than the head, with an acrosomal length and width at the annulus of 2.90 ± 0.13 μm and 0.43 ± 0.01 μm, respectively. The midpiece of the S. crassicollis spermatozoa was narrower than the head and contained 30-40 mitochondrial balls, each with a ball diameter of 0.16 ± 0.002 μm. The midpiece length, midpiece width and tail length were 4.92 ± 0.16, 0.78 ± 0.03 and 48.53 ± 0.25 μm, respectively. This study presents the characteristic appearance of a freshwater turtle spermatozoa in Southeast Asia, as observed under an electron microscope. The spermatozoa of Siebenrockiella crassicollis are morphologically different from those of other freshwater turtles from other regions described in previous studies.

Siebenrockiella crassicollis
freshwater turtle
sperm morphology


Metal injection molding as enabling technology for the production of metal prosthesis components: electrochemical and in vitro characterization.

Abstract: Industrial manufacturing of prosthesis components could take significant advantage by the introduction of new, cost-effective manufacturing technologies with near net-shape capabilities, which have been developed during the last years to fulfill the needs of different technological sectors. Among them, metal injection molding (MIM) appears particularly promising for the production of orthopedic arthroplasty components with significant cost saving. These new manufacturing technologies, which have been developed, however, strongly affect the chemicophysical structure of processed materials and their resulting properties. In order to investigate this relationship, here we evaluated the effects on electrochemical properties, ion release, and in vitro response of medical grade CoCrMo alloy processed via MIM compared to conventional processes. MIM of the CoCrMo alloy resulted in coarser polygonal grains, with largely varying sizes; however, these microstructural differences between MIM and forged/cast CoCrMo alloys showed a negligible effect on electrochemical properties. Passive current densities values observed were 0.49 µA cm(-2) for MIM specimens and 0.51 µA cm(-2) for forged CoCrMo specimens, with slightly lower transpassive potential in the MIM case; open circuit potential and Rp stationary values showed no significant differences. Moreover, in vitro biocompatibility tests resulted in cell viability levels not significantly different for MIM and conventionally processed alloys. Although preliminary, these results support the potential of MIM technology for the production of CoCrMo components of implantable devices.

Melli|Virginia|V|
Rondelli|Gianni|G|
Sandrini|Enrico|E|
Altomare|Lina|L|
Bolelli|Giovanni|G|
Bonferroni|Benedetta|B|
Lusvarghi|Luca|L|
Cigada|Alberto|A|
De Nardo|Luigi|L|

D055664:Electrochemical Techniques
D008422:Materials Testing
D019736:Prostheses and Implants
D014800:Vitallium

in vitro
orthopedic
cobalt-chromium (alloys)
corrosion
implant design


Tissue accumulation and urinary excretion of Cr in chromium picolinate (CrPic)-supplemented lambs.

Abstract: Chromium (Cr) concentrations in liver, kidney, spleen, heart, lymph node, skeletal muscle, bone, testis and urine of lambs were measured to trace the biodistribution and bioaccumulation of Cr after oral supplementation with chromium picolinate (CrPic). Twenty-four Santa Inês lambs were treated with four different concentrations of CrPic: placebo, 0.250, 0.375 and 0.500 mg of CrPic/animal/day for 84 days. The basal diet consisted of Panicum maximum cv Massai hay and concentrate. Cr concentrations were measured by ICP-MS measuring (52)Cr as collected mass. There was a positive linear relationship between dose administered and the accumulation of Cr in the heart, lungs and testis. Urinary excretion of Cr occurred in a time and dose-dependent manner, so the longer or more dietary Cr provided, the greater excretion of the element. As some non-carcass components (such as lungs or heart) are added to bone and visceral meal to feed animals, there is a risk of bioaccumulation and biomagnification due to Cr offered as CrPic in the diet.

Dallago|Bruno Stéfano Lima|BS|
Lima|Bárbara Alcântara Ferreira|BA|
Braz|Shélida Vasconcelos|SV|
Mustafa|Vanessa da Silva|Vda S|
McManus|Concepta|C|
Paim|Tiago do Prado|Tdo P|
Campeche|Aline|A|
Gomes|Edgard Franco|EF|
Louvandini|Helder|H|

Biodistribution
Bioaccumulation
Santa Inês
ICP–MS
Mineral supplement


Epidemiology of the zoonotic malaria Plasmodium knowlesi in changing landscapes.

Abstract: Within the past two decades, incidence of human cases of the zoonotic malaria Plasmodium knowlesi has increased markedly. P. knowlesi is now the most common cause of human malaria in Malaysia and threatens to undermine malaria control programmes across Southeast Asia. The emergence of zoonotic malaria corresponds to a period of rapid deforestation within this region. These environmental changes impact the distribution and behaviour of the simian hosts, mosquito vector species and human populations, creating new opportunities for P. knowlesi transmission. Here, we review how landscape changes can drive zoonotic disease emergence, examine the extent and causes of these changes across Southeast and identify how these mechanisms may be impacting P. knowlesi dynamics. We review the current spatial epidemiology of reported P. knowlesi infections in people and assess how these demographic and environmental changes may lead to changes in transmission patterns. Finally, we identify opportunities to improve P. knowlesi surveillance and develop targeted ecological interventions within these landscapes.

Cuenca|Pablo Ruiz|PR|
Key|Stephanie|S|
Jumail|Amaziasizamoria|A|
Surendra|Henry|H|
Ferguson|Heather M|HM|
Drakeley|Chris J|CJ|
Fornace|Kimberly|K|

Plasmodium knowlesi
Deforestation
Spatial epidemiology
Emerging diseases
Land use change


Evaluation of performance of bacterial culture of feces and serum ELISA across stages of Johne's disease in cattle using a Bayesian latent class model.

Abstract: The objective of this study was to evaluate the performance of bacterial culture of feces and serum ELISA to correctly identify cows with Mycobacterium avium ssp. paratuberculosis (MAP) at heavy, light, and non-fecal-shedding levels. A total of 29,785 parallel test results from bacterial culture of feces and serum ELISA were collected from 17 dairy herds in Minnesota, Pennsylvania, and Colorado. Samples were obtained from adult cows from dairy herds enrolled for up to 10 yr in the National Johne's Disease Demonstration Herd Project. A Bayesian latent class model was fitted to estimate the probabilities that bacterial culture of feces (using 72-h sedimentation or 30-min centrifugation methods) and serum ELISA results correctly identified cows as high positive, low positive, or negative given that cows were heavy, light, and non-shedders, respectively. The model assumed that no gold standard test was available and conditional independency existed between diagnostic tests. The estimated conditional probabilities that bacterial culture of feces correctly identified heavy shedders, light shedders, and non-shedders were 70.9, 32.0, and 98.5%, respectively. The same values for the serum ELISA were 60.6, 18.7, and 99.5%, respectively. Differences in diagnostic test performance were observed among states. These results improve the interpretation of results from bacterial culture of feces and serum ELISA for detection of MAP and MAP antibody (respectively), which can support on-farm infection control decisions and can be used to evaluate disease-testing strategies, taking into account the accuracy of these tests.

Espejo|L A|LA|
Zagmutt|F J|FJ|
Groenendaal|H|H|
Muñoz-Zanzi|C|C|
Wells|S J|SJ|

D016927:Mycobacterium avium subsp. paratuberculosis

paratuberculosis
diagnostic test
dairy cow
fecal shedding


Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens.

Abstract: The fungal cytochrome P450 enzyme sterol 14α-demethylase (SDM) is a key enzyme in the ergosterol biosynthesis pathway. The binding of azoles to the active site of SDM results in a depletion of ergosterol, the accumulation of toxic intermediates and growth inhibition. The prevalence of azole-resistant strains and fungi is increasing in both agriculture and medicine. This can lead to major yield loss during food production and therapeutic failure in medical settings. Diverse mechanisms are responsible for azole resistance. They include amino acid (AA) substitutions in SDM and overexpression of SDM and/or efflux pumps. This review considers AA affecting the ligand-binding pocket of SDMs with a primary focus on substitutions that affect interactions between the active site and the substrate and inhibitory ligands. Some of these interactions are particularly important for the binding of short-tailed azoles (e.g., voriconazole). We highlight the occurrence throughout the fungal kingdom of some key AA substitutions. Elucidation of the role of these AAs and their substitutions may assist drug design in overcoming some common forms of innate and acquired azole resistance.

sterol 14α-demethylase
cytochrome P450
ergosterol biosynthesis
amino acid substitution
antifungal resistance
azole agrochemicals
azole drugs
cross-kingdom pathogens
heme-containing active site
imidazole
lanosterol 14α-demethylase
pan-fungal kingdom mutation
point mutations
promotor region
prophylaxis
substrate entry channel
tandem repeat
therapy
treatment
triazole
water-mediated hydrogen bond network

P P P R M M R M M U M M U U U M U U U U U


Brunner's gland hamartoma: a cause of the double-duct sign.

Abstract: Introduction Brunner's glands are submucosal glands found in the duodenum. Proliferation of these glands can lead to the formation of Brunner's gland hamartomas (BGHs), which are uncommon, asymptomatic and usually found incidentally. They are predominantly benign lesions, but instances of malignant transformation have been reported. Case History We describe a rare case in which a periampullary lesion was causing biliary obstruction on a background of weight loss, and was associated with dilatation of the common bile duct and pancreatic duct on computed tomography and magnetic resonance imaging. Further investigation with endoscopic ultrasound and biopsy did not provide a definitive diagnosis. Given the symptoms and findings upon investigations, we proceeded to pylorus-preserving pancreatoduodenectomy. Conclusions This was a rare case in which BGH gave rise to biliary obstruction against a background of weight loss. Due to a high index of suspicion (weight loss and evidence of dilatation of the common bile duct and pancreatic duct), this procedure was justified because the consequences of a missed periampullary cancer far outweighed surgical risks.

Periampullary lesion
Pancreatoduodenectomy
Brunner’s glands


Pathologic nodal staging for clinically node negative soft tissue sarcoma of the extremities.

Abstract:
BACKGROUND AND OBJECTIVES
Synovial, clear cell, angiosarcoma, rhabdomyosarcoma, and epithelioid (SCARE) soft tissue sarcoma are at risk for nodal involvement, although the nodal positivity rates and impact on prognostication in clinically node negative patients are not well described.

METHODS
Patients with extremity SCARE sarcoma without clinical nodal involvement undergoing surgical resection in the National Cancer Database (2004-2017) were included. Logistic regression was used to evaluate the likelihood of nodal surgery and nodal positivity. Kaplan-Meier method and Cox regression were used to assess associations of nodal status to overall survival.

RESULTS
We included 4158 patients, and 669 patients (16%) underwent regional lymph node surgery (RLNS). On multivariable logistic analysis, patients with epithelioid (odds ratio [OR]: 3.77; p < .001) and clear cell (OR: 6.38; p < .001) were most likely to undergo RLNS. Forty-five patients (7%) had positive nodes. Clear cell sarcoma (14%) and angiosarcoma (13%) had the highest rates of nodal positivity. Patients with positive nodes had reduced 5-year overall survival, and the stratification was largest in clear cell and angiosarcoma.

CONCLUSION
Discordance exists between selection for pathologic nodal evaluation and factors associated with nodal positivity. Clinically node negative patients with clear cell and angiosarcoma should be considered for pathologic nodal evaluation.

angiosarcoma
rhabdomyosarcoma
clear cell sarcoma
SLNB
epithelioid sarcoma
synovial sarcoma


Deduced probable human leukocyte antigen haplotypes associated with HLA-A*11:256Q and HLA-A*02:621 identified by case analyses of Taiwanese individuals.

Abstract:
Objective
HLA-A*11:256Q and HLA-A*02:621 are two low-frequency HLA-A alleles. The aim here is to report the ethnicity of A*11:256Q and A*02:621 and associated human leukocyte antigen (HLA) haplotypes among Taiwanese individuals.

Materials and Methods
HLA data from randomized Taiwanese registered in the Tzu Chi Stem Cells Centre and China Shanghai Tissuebank Diagnostics were analyzed. HLA typing of the donors was carried out using a sequence-based typing method to confirm the two low-incidence alleles. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. Exon 1 and exons 4-8 of the A*11:256Q allele were also sequenced and analyzed.

Results
The Taiwanese ethnicity for both A*11:256Q and A*02:621 alleles was confirmed in this study. Further, the DNA sequence of A* 11:256Q was confirmed to be identical to A*11:02:01from exon 1 to exon 8 except for the residues from 409 to 417 where a segment of nine nucleotides (TACCGGCAG) is deleted in A*11:256Q. The HLA haplotype associated with A*11:256Q was deduced as A*11:256Q-B*27-DRB1*12. In exons 2 and 3, the DNA sequence of A*02:621 is identical to A*02:01:01:01 except at residue 169 where T of A*02:01:01:01 is replaced by C in A*02:621 (at codon 33; TTC->CTC). The HLA haplotype in association with A*02:621 was deduced as A*02:621-B*15:18-DRB1*12:02.

Conclusion
The information on the ethnicity of the A*11:256Q and A*02:621 alleles and the deduced probable HLA haplotypes associated with the two low-incidence alleles reported here are valuable to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid in finding compatible donors in unrelated bone marrow donor registries when a patient carries these uncommon HLA alleles.


Crystal Structure of Escherichia coli Agmatinase: Catalytic Mechanism and Residues Relevant for Substrate Specificity.

Abstract: Agmatine is the product of the decarboxylation of L-arginine by the enzyme arginine decarboxylase. This amine has been attributed to neurotransmitter functions, anticonvulsant, anti-neurotoxic, and antidepressant in mammals and is a potential therapeutic agent for diseases such as Alzheimer's, Parkinson's, and cancer. Agmatinase enzyme hydrolyze agmatine into urea and putrescine, which belong to one of the pathways producing polyamines, essential for cell proliferation. Agmatinase from Escherichia coli (EcAGM) has been widely studied and kinetically characterized, described as highly specific for agmatine. In this study, we analyze the amino acids involved in the high specificity of EcAGM, performing a series of mutations in two loops critical to the active-site entrance. Two structures in different space groups were solved by X-ray crystallography, one at low resolution (3.2 Å), including a guanidine group; and other at high resolution (1.8 Å) which presents urea and agmatine in the active site. These structures made it possible to understand the interface interactions between subunits that allow the hexameric state and postulate a catalytic mechanism according to the Mn2+ and urea/guanidine binding site. Molecular dynamics simulations evaluated the conformational dynamics of EcAGM and residues participating in non-binding interactions. Simulations showed the high dynamics of loops of the active site entrance and evidenced the relevance of Trp68, located in the adjacent subunit, to stabilize the amino group of agmatine by cation-pi interaction. These results allow to have a structural view of the best-kinetic characterized agmatinase in literature up to now.

D000376:Agmatine
D020134:Catalytic Domain
D018360:Crystallography, X-Ray
D004926:Escherichia coli
D029968:Escherichia coli Proteins
D008958:Models, Molecular
D011487:Protein Conformation
D055503:Protein Multimerization
D013379:Substrate Specificity
D014512:Ureohydrolases

agmatinase
agmatine
arginase
enzyme specificity
ureohydrolase


Psychiatric Patients Tracking Through a Private Social Network for Relatives: Development and Pilot Study.

Abstract: The treatment of psychiatric patients requires different health care from that of patients from other medical specialties. In particular, in the case of Department of Psychiatry from the Zamora Hospital (Spain), the period of time which patients require institutionalized care is a tiny part of their treatment. A large part of health care provided to the patient is aimed at his/her rehabilitation and social integration through day-care centres, supervised flats or activities. Conversely, several reports reveal that approximately 50 % of Internet users use the network as a source of health information, which has led to the emergence of virtual communities where patients, relatives or health professionals share their knowledge concerning an illness, health problem or specific health condition. In this context, we have identified that the relatives have a lack of information regarding the daily activities of patients under psychiatric treatment. The social networks or the virtual communities regarding health problems do not provide a private space where relatives can follow the patient's progress, despite being in different places. The goal of the study was to use technologies to develop a private social network for being used by severe mental patients (mainly schizophrenic patients). SocialNet is a pioneer social network in the health sector because it provides a social interaction context restricted to persons authorized by the patient or his/her legal guardian in such a way that they can track his/her daily activity. Each patient has a private area only accessible to authorized persons and their caregivers, where they can share pictures, videos or texts regarding his/her progress. A preliminary study of usability of the system has been made for increasing the usefulness and usability of SocialNet. SocialNet is the first system for promoting personal interactions among formal caregivers, family, close friends and patient, promoting the recovery of schizophrenic patients. Future studies should study the network's potential usefulness for improving the prognosis and recovery of schizophrenia.

García-Peñalvo|Francisco J|FJ|
Martín|Manuel Franco|MF|
García-Holgado|Alicia|A|
Guzmán|José Miguel Toribio|JM|
Antón|Jesús Largo|JL|
Sánchez-Gómez|Ma Cruz|MC|

Social network
Usability
Information system
Mental health
Patient care system


Primordial odontogenic tumour: clinicopathological analysis of six cases of a previously undescribed entity.

Abstract:
AIM
To describe the clinicopathological and immuno-histochemical features of six tumours that do not fulfil the criteria of any of the currently classified odontogenic tumours.

METHODS AND RESULTS
The patients were three males and three females, whose ages ranged from 3 years to 18 years (mean, 11.05 years). In all cases there were well-defined radiolucencies associated with unerupted teeth apparently showing a pericoronal relationship. Microscopically, all tumours were composed of variably cellular loose fibrous tissue with areas similar to dental papilla, entirely surrounded by cuboidal to columnar epithelium resembling the internal epithelium of the enamel organ. Mesenchymal tissue was positive only for vimentin, and Ki67 expression was very low (<2%). The epithelium was positive for CK AE1/AE3, CK5, CK14, and CK19, but negative for CK18 and CK20. All cases showed clear demarcation from the surrounding bone, and were surgically removed, with no recurrences after follow-up ranging from 6 months to 20 years.

CONCLUSIONS
These findings differ from those observed in other odontogenic lesions, such as ameloblastic fibroma, odontogenic myxoma, odontogenic fibroma, and hyperplastic dental follicles. The term primordial odontogenic tumour is proposed to describe this novel lesion.

Mosqueda-Taylor|Adalberto|A|
Pires|Fabio Ramoa|FR|
Aguirre-Urízar|José Manuel|JM|
Carlos-Bregni|Roman|R|
de la Piedra-Garza|José Mario|JM|
Martínez-Conde|Rafael|R|
Martínez-Mata|Guillermo|G|
Carreño-Álvarez|Sergio J|SJ|
da Silveira|Henrique Martins|HM|
de Barros Dias|Bruno Santos|BS|
de Almeida|Oslei Paes|OP|

odontogenic tumour
dental papilla
dental follicle
jaws
tooth primordium


Correlation of chest computed tomography findings with dyspnea and lung functions in post-tubercular sequelae.

Abstract:
AIMS
To study the correlation between dyspnea, radiological findings, and pulmonary function tests (PFTs) in patients with sequelae of pulmonary tuberculosis (TB).

MATERIALS AND METHODS
Clinical history, chest computed tomography (CT), and PFT of patients with post-TB sequelae were recorded. Dyspnea was graded according to the Modified Medical Research Council (mMRC) scale. CT scans were analyzed for fibrosis, cavitation, bronchiectasis, consolidation, nodules, and aspergilloma. Semi-quantitative analysis was done for these abnormalities. Scores were added to obtain a total morphological score (TMS). The lungs were also divided into three zones and scores added to obtain the total lung score (TLS). Spirometry was done for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC.

RESULTS
Dyspnea was present in 58/101 patients. A total of 22/58 patients had mMRC Grade 1, and 17/58 patients had Grades 2 and 3 dyspnea each. There was a significant difference in median fibrosis, bronchiectasis, nodules (P < 0.01) scores, TMS, and TLS (P < 0.0001) between dyspnea and nondyspnea groups. Significant correlations were obtained between grades of dyspnea and fibrosis (r = 0.34, P = 0.006), bronchiectasis (r = 0.35, P = 0.004), nodule (r = 0.24, P = 0.016) scores, TMS (r = 0.398, P = 0.000), and TLS (r = 0.35, P = 0.0003). PFTs were impaired in 78/101 (77.2%) patients. Restrictive defect was most common in 39.6% followed by mixed in 34.7%. There was a negative but statistically insignificant trend between PFT and fibrosis, bronchiectasis, nodule scores, TMS, and TLS. However, there were significant differences in median fibrosis, cavitation, and bronchiectasis scores in patients with normal, mild to moderate, and severe respiratory defects. No difference was seen in TMS and TLS according to the severity of the respiratory defect.

CONCLUSION
Both fibrosis and bronchiectasis correlated with dyspnea and with PFT. However, this correlation was not linear. The overall extent of radiological abnormalities correlated only with dyspnea but not with PFT.

Panda|Ananya|A|
Bhalla|Ashu Seith|AS|
Sharma|Raju|R|
Mohan|Anant|A|
Sreenivas|Vishnu|V|
Kalaimannan|Umasankar|U|
Upadhyay|Ashish Dutt|AD|

Computed tomography
dyspnea
pulmonary function test
pulmonary tuberculosis
posttubercular sequelae
radiological-functional correlation


Long-term outcomes of transvaginal mesh surgery for pelvic organ prolapse: a retrospective cohort study.

Abstract:
BACKGROUND
The objective of this study was to evaluate the overall outcomes and complications of transvaginal mesh (TVM) placement for the management of pelvic organ prolapse (POP) with different meshes with a greater than 10-years of follow-up.

METHODS
We performed a retrospective review of patients with POP who underwent prolapse repair surgery with placement of transvaginal mesh (Prolift kit or self-cut Gynemesh) between January 2005 and December 2010. Baseline of patient characteristics were collected from the patients' medical records. During follow-up, the anatomical outcomes were evaluated using the POP Quantification system, and the Patient Global Impression of Improvement (PGI-I) was used to assess the response of a condition to therapy. Overall postoperative satisfaction was assessed by the following question: "What is your overall postoperative satisfaction, on a scale from 0 to 10?". Relapse-free survival was analyzed using Kaplan-Meier curves.

RESULTS
In total, 134 patients were included. With a median 12-year (range 10-15) follow-up, 52 patients (38.8%) underwent TVM surgery with Prolift, and Gynemesh was used 82 (61.2%). 91% patients felt that POP symptom improved based on the PGI-I scores, and most satisfied after operation. The recurrence rates of anterior, apical and posterior compartment prolapse were 5.2%, 5.2%, and 2.2%, respectively. No significant differences in POP recurrence, mesh-associated complications and urinary incontinence were noted between TVM surgery with Prolift versus Gynemesh.

CONCLUSIONS
Treatment of POP by TVM surgery exhibited long-term effectiveness with acceptable morbidity. The outcomes of the mesh kit were the same as those for self-cutmesh.

Wang|Xiaojuan|X| Chen|Yisong|Y| Hu|Changdong|C| Hua|Keqin|K|

Transvaginal mesh
Pelvic organ prolapse
Long-term follow-up


Meningovascular syphilis causing recurrent stroke and diagnostic difficulties: a scourge from the past.

Abstract: We describe a case of a 49-year-old man who presented with recurrent strokes in the left middle cerebral artery territory, manifesting with dysphasia, higher cognitive deficits, motor deficits and subsequent infarcts in the right middle cerebral and anterior cerebral artery territories, manifesting with seizures, behavioural and social issues. A key issue of the case was the diagnostic difficulty faced by the physicians. 'Meningovascular syphilis' was subsequently confirmed and appropriate treatment was given but there was subsequent relapse with worsening of the symptoms. Multiple specialists were involved in the management, namely stroke team, neurologists, psychiatrists, infectious disease and multidisciplinary therapy teams. This case highlights the need to be vigilant to the resurgence of syphilis, a scourge from the past, as a cause of stroke, especially in individuals who have had exposure to affected people. It is easy to miss the diagnosis and mistake it for other conditions unless a detailed history is taken and appropriate investigations are conducted, with a low threshold for diagnosis.

Munshi|Sunil|S|
Raghunathan|Senthil K|SK|
Lindeman|Ileana|I|
Shetty|Ashit K|AK|


Semi-outdoor filterless air purifier for smog and microbial protection with water purifier system.

Abstract:
PURPOSE
Air pollution and COVID-19 problems are being increasingly scrutinized. This article discusses the optimum design of an indoor and semi-outdoor air purifier, using a water-based filtration system.

METHODS
An air purifier was fabricated, then comparison of purifying efficacy of the system between untreated air and using an air pump was done. Incense smoke was generated within a room for 10 seconds. The number of particle sizes of PM0.3, PM0.5, PM1.0, PM3.0, PM5.0, and PM10 μm (particle/ m3) as well as the detection of mass concentration of PM1.0, PM2.5, PM5.0, and PM10 (mg/m3) at 0 and 5 min were recorded. Each experiment was repeated 10 times.

RESULTS
Particles in untreated air, except PM10, showed the maximum increase rate of the number of particle sizes greater than the air pump experiment. The highest differentiation between two methods was that PM1.0 and PM0.5 of untreated air increased to 113.647 and 61.539 % whereas the air pump method showed 4.720 and 2.533 %, respectively. The PM mass concentration of untreated air increased from 50.217 to 51.167 % while the increased rate of PM using an air pump was 2.784 to 2.902 %.

CONCLUSION
This study proposed a water-based air filtration technique, which can reduce the level of particulate matter, and also is a low-cost prototype. For the next experiment, the study should extend test length, clarify an optimum ratio of disinfectant technologies, connect with the internet of things, compare the efficiency with a HEPA filter air purifier, and then also measure some particles which are smaller than 0.2 μm.

Filterless air purifier
Smog
COVID-19
Particulate matter


First-line therapy for T cell lymphomas: a retrospective population-based analysis of 906 T cell lymphoma patients.

Abstract: Peripheral T cell lymphomas (PTLs) have a globally poor prognosis. The CHOP regimen shows insufficient efficacy; first-line consolidation with autologous stem cell transplantation (auto-SCT) is a promising strategy but has never been confirmed by randomized data. We analyzed retrospectively 906 patients diagnosed with PTL between 1999 and 2015. Chemotherapy was given to 862 patients, and 412 of them were < 60 years. In this subset, we compared induction with CHOP (n = 113) vs. CHOEP (n = 68) and tested auto-SCT (n = 79) vs. no SCT (n = 73) in the intent-to-treat analysis. The median age of the whole cohort at diagnosis was 60 years (range; 18-91); the median follow-up was 4.3 years (range; 0.1-17.8). A shorter overall survival (OS) was associated with the male gender, age ≥ 60 years, stage III/IV, performance status ≥ 2, bulky tumor ≥ 10 cm, and elevated LDH. CHOEP induction showed a better 5-year PFS (25.0% vs. 32.9%; p.001), and 5-year OS (65.6% vs. 47.6%; p.008) than CHOP. Auto-SCT compared to no SCT brought a 5-year OS of 49.2% vs. 59.5% (p.187). Auto-SCT did not influence the OS in low-risk or low-intermediate risk PTLs. The high-intermediate and high-risk IPIs displayed a worse 5-year OS in auto-SCT arm (17.7% vs.46.2%; p.049); however, 73.9% of the patients never received planned auto-SCT. Our population-based analysis showed the superiority of CHOEP over CHOP in first-line treatment. We confirm the 5-year OS of around 50% in PTLs undergoing auto-SCT. However, the intended auto-SCT could not be given in 73.9% of the high-risk PTLs.

D000971:Antineoplastic Combined Chemotherapy Protocols

D018380:Hematopoietic Stem Cell Transplantation

T cell lymphoma
Prognosis
Auto-SCT
Etoposide


Recharacterizing the Metabolic State of Energy Balance in Thrifty and Spendthrift Phenotypes.

Abstract:
PURPOSE
The human thrifty phenotype hypothesis presupposes that lower 24-hour (24h) energy expenditure (24EE) during famine preserves body mass and promotes survival. The prevailing view defines thrifty individuals as having a lower 24EE during fasting. However, it is also plausible that the greater decline in 24EE during fasting in thrifty individuals is due to higher 24EE during energy balance conditions (ENBAL). Herein, we provide evidence that this is indeed the case.

METHODS
In 108 healthy subjects, 24EE was measured in a whole-room indirect calorimeter both during ENBAL and 24h fasting conditions. Subjects were categorized as thrifty or spendthrift based on the median value (-162 kcal/day) of the difference in 24EE (adjusted for body composition) between fasting and ENBAL conditions. Concomitant 24h urinary catecholamines were assessed by liquid chromatography-mass spectrometry.

RESULTS
Compared to ENBAL, 24EE decreased during 24h fasting by 172 kcal/day (standard deviation = 93; range, -470 to 122). A greater-than-median decrease in 24EE ("thriftier" phenotype) was due to higher 24EE during ENBAL (+124 kcal/day; P < 0.0001) but not to lower 24EE during fasting (P = 0.35). Greater fasting-induced increase in epinephrine was associated with concomitant lower decrease in 24EE (r = 0.27; P = 0.006).

MAIN CONCLUSION
The greater decrease in 24EE during acute fasting (which characterizes the thrifty phenotype) is not due to reduced metabolic rate during fasting but to a relatively higher 24EE during feeding conditions, and this decrease in 24EE during fasting is accompanied by a smaller increase in epinephrine. These results recharacterize the prevailing view of the short-term 24EE responses that define the human metabolic phenotypes. Clinical Trials: NCT00523627, NCT00687115, NCT02939404.

Hollstein|Tim|T|
Basolo|Alessio|A|
Ando|Takafumi|T|
Votruba|Susanne B|SB|
Walter|Mary|M|
Krakoff|Jonathan|J|
Piaggi|Paolo|P|

energy balance
thrifty phenotype
energy expenditure
fasting
epinephrine
FGF21


Total extraperitoneal endoscopic hernioplasty (TEP) versus Lichtenstein hernioplasty: a systematic review by updated traditional and cumulative meta-analysis of randomised-controlled trials.

Abstract:
BACKGROUND-PURPOSE
Totally extraperitoneal (TEP) endoscopic hernioplasty and Lichtenstein hernioplasty are the most commonly used approaches for inguinal hernia repair. However, current evidence on which is the preferred approach is inconclusive. This updated meta-analysis was conducted to track the accumulation of evidence over time.

METHODS
Studies were identified by a systematic literature search of the EMBASE, PubMed, Cochrane Library, and Google Scholar databases. Fixed- and random-effects models were used to cumulatively assess the accumulation of evidence over time.

RESULTS
The TEP cohort showed significantly higher rates of recurrences and vascular injuries compared to the Lichtenstein cohort; [Peto Odds ratio (OR) = 1.58 (1.22, 2.04), p = 0.005], [Peto OR = 2.49 (1.05, 5.88), p = 0.04], respectively. In contrast, haematoma formation rate, time to return to usual activities, and local paraesthesia were significantly lower in the TEP cohort compared to the Lichtenstein cohort; [Peto OR = 0.26 (0.16, 0.41), p ≤ 0.001], [mean difference = - 6.32 (- 8.17, - 4.48), p ≤ 0.001], [Peto OR = 0.26 (0.17, 0.40), p ≤ 0.001], respectively.

CONCLUSIONS
This study, which is based on randomised-controlled trials (RCTs) of high quality, showed significantly higher rates of recurrences and vascular injuries in the TEP cohort than in the Lichtenstein cohort. In contrast, rate of postoperative haematoma formation, local paraesthesia, and time to return to usual activities were significantly lower in the TEP cohort than in the Lichtenstein cohort. Future multicentre RCTs with strict adherence to the standards recommended in the Consolidated Standards of Reporting Trials guidelines will shed further light on the topic.

D016032:Randomized Controlled Trials as Topic

Inguinal hernia repair
Hernia repair
Groin hernia
Lichtenstein technique
Mesh
TEPP
Total extraperitoneal hernioplasty


Effects of Temperature During Package Transportation on Queen Establishment and Survival in Honey Bees (Hymenoptera: Apidae).

Abstract: Honey bee (Apis mellifera) (Linnaeus) (Hymenoptera: Apidae) queens, the reproductive female caste, are crucial for colony success, and many management problems that beekeepers face are related to their diminished reproductive quality and premature failure. Previous research has suggested that temperature extremes may affect the viability of stored sperm in queens' spermathecae, thus the abiotic conditions of queens during transport may be germane to these problems. We recorded the temperatures experienced by queens during 2 yr of package transportation and tracked the newly installed colonies through establishment and buildup. During this critical 6-8 wk period, we observed typically high rates of queen failure (~25%) but found no indication that these postinstallation queen events were driven by temperature-related damage to stored sperm (an essential component of queen quality) incurred during transportation. We also found no indication of significant hot or cold zones across the truckloads of packages that would suggest a problem in how packages are insulated during transportation. However, we did observe significantly higher temperatures (31.2 vs. 29.9°C) and lower temperature variance (8.8 vs. 12.2) in queens that ultimately failed during the observation period, indicating that workers may respond differently to these queens in a way that manifests as more insulating clusters around queen cages. If so, then the collective process by which workers accept or reject a foreign queen may already be detectable even if it does not ultimately conclude until some weeks later. Nevertheless, it remains unclear why large numbers of otherwise high-quality queens are failing in newly installed packages.

Withrow|James M|JM|
Pettis|Jeffery S|JS|
Tarpy|David R|DR|

package
transportation
honey bee
queen failure


Conservation in the mechanism of glucuronoxylan hydrolysis revealed by the structure of glucuronoxylan xylanohydrolase (CtXyn30A) from Clostridium thermocellum.

Abstract: Glucuronoxylan endo-β-1,4-xylanases cleave the xylan chain specifically at sites containing 4-O-methylglucuronic acid substitutions. These enzymes have recently received considerable attention owing to their importance in the cooperative hydrolysis of heteropolysaccharides. However, little is known about the hydrolysis of glucuronoxylans in extreme environments. Here, the structure of a thermostable family 30 glucuronoxylan endo-β-1,4-xylanase (CtXyn30A) from Clostridium thermocellum is reported. CtXyn30A is part of the cellulosome, a highly elaborate multi-enzyme complex secreted by the bacterium to efficiently deconstruct plant cell-wall carbohydrates. CtXyn30A preferably hydrolyses glucuronoxylans and displays maximum activity at pH 6.0 and 70°C. The structure of CtXyn30A displays a (β/α)8 TIM-barrel core with a side-associated β-sheet domain. Structural analysis of the CtXyn30A mutant E225A, solved in the presence of xylotetraose, revealed xylotetraose-cleavage oligosaccharides partially occupying subsites -3 to +2. The sugar ring at the +1 subsite is held in place by hydrophobic stacking interactions between Tyr139 and Tyr200 and hydrogen bonds to the OH group of Tyr227. Although family 30 glycoside hydrolases are retaining enzymes, the xylopyranosyl ring at the -1 subsite of CtXyn30A-E225A appears in the α-anomeric configuration. A set of residues were found to be strictly conserved in glucuronoxylan endo-β-1,4-xylanases and constitute the molecular determinants of the restricted specificity displayed by these enzymes. CtXyn30A is the first thermostable glucuronoxylan endo-β-1,4-xylanase described to date. This work reveals that substrate recognition by both thermophilic and mesophilic glucuronoxylan endo-β-1,4-xylanases is modulated by a conserved set of residues.

Freire|Filipe|F|
Verma|Anil|A|
Bule|Pedro|P|
Alves|Victor D|VD|
Fontes|Carlos M G A|CM|
Goyal|Arun|A|
Najmudin|Shabir|S|

D000595:Amino Acid Sequence
D001426:Bacterial Proteins
D020134:Catalytic Domain
D048013:Clostridium thermocellum
D018360:Crystallography, X-Ray
D043364:Endo-1,4-beta Xylanases
D004795:Enzyme Stability
D006868:Hydrolysis
D008958:Models, Molecular
D011487:Protein Conformation
D016415:Sequence Alignment
D013379:Substrate Specificity
D013696:Temperature
D014990:Xylans
D014995:Xylosidases

glucuronoxylan endo-β-1,4-xylanase
cellulosome
xylotetraose
GH30 subfamily 8
substrate cleavage
thermophilic enzymes


Poly(l-Lactic Acid)/Gelatin Fibrous Scaffold Loaded with Simvastatin/Beta-Cyclodextrin-Modified Hydroxyapatite Inclusion Complex for Bone Tissue Regeneration.

Abstract: Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β-cyclodextrin (βCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering.

Lee|Jung Bok|JB|
Kim|Ji Eun|JE|
Balikov|Daniel A|DA|
Bae|Min Soo|MS|
Heo|Dong Nyoung|DN|
Lee|Donghyun|D|
Rim|Hyun Joon|HJ|
Lee|Deok-Won|DW|
Sung|Hak-Joon|HJ|
Kwon|Il Keun|IK|

simvastatin
adipose derived stem cell
bone tissue engineering
adamantine
beta-cyclodextrin


Management and Anesthetic Considerations for Patients With Anomalous Aortic Origin of a Coronary Artery.

Abstract: The term "coronary artery anomalies" encompasses a large and heterogeneous group of disorders that may affect origin, intrinsic anatomy, course, location, and termination of the coronary arteries. With these different anatomies, presentation, symptoms, and outcomes are heterogeneous as well. While significant efforts are directed toward improving diagnosis and risk-stratification, best evidence-guided practices remain in evolution. Data about anesthetic management of patients with coronary anomalies are lacking as well. This review aims to provide the anesthesiologist with a better understanding of an important subgroup of coronary artery anomalies: anomalous aortic origin of a coronary artery. We will discuss classification, pathophysiology, incidence, evaluation, management, and anesthetic implications of this potentially fatal disease group.

anomalous coronary artery arising from the opposite sinus of Valsalva


A novel programmed cell death protein 4 negatively regulates CgIL17-5 expression in hemocytes of oyster Pacific oyster (Crassostrea gigas).

Abstract: The programmed cell death protein 4 (PDCD4) is a newly defined transcriptional and translational inhibitor, which plays a key role in regulating the synthesis of inflammatory cytokines in vertebrates species. In the present study, the full-length cDNA of PDCD4 from oyster Crassostrea gigas (designed as CgPDCD4) was identified to explore its possible involvement in immune response. The open reading frame of pdcd4 gene was of 1344 bp encoding a polypeptide of 447 amino acids with two conserved MA-3 domains. The deduced amino acid sequence of CgPDCD4 shared 60.18% similarity with PDCD4 from Mizuhopecten yessoensis. The mRNA transcripts of CgPDCD4 could be detected in all the tested tissues with a higher expression level in adductor muscle and hemocytes. The mRNA expression of CgPDCD4 in hemocytes was significantly down-regulated at 3 h and 6 h (0.61-fold and 0.42-fold of that in PBS group, p < 0.01, respectively) after LPS stimulation. In hemocytes, CgPDCD4 protein was found to be mainly located in the cytoplasm. After the mRNA expression of CgPDCD4 in hemocytes was knocked down (0.40-fold of that in EGFP-RNAi group) by CgPDCD4 dsRNA (dsCgPDCD4) injection, the CgIL17-5 transcripts were up-regulated (20.11-fold of that in PBS group, p < 0.01) post LPS stimulation, which was significantly higher than that in dsEGFP-injected oysters (7.06-fold of that in PBS group, p < 0.01). Meanwhile, the nuclear translocation of CgRel (homologue of Rel/NF-κB) was significantly enhanced (about 1.36-fold of that in PBS group, p < 0.01), but it was similar as that in EGFP-RNAi group (about 1.52-fold of that in PBS group, p < 0.01) after LPS stimulation. All the results suggested that CgPDCD4 in oysters played the same role as PDCD4 of vertebrates in negatively regulating the production of interleukin in immune response, but the underpinning signal pathway was not conserved during evolution.

Yan|Yunchen|Y| Wang|Weilin|W| Liu|Zhaoqun|Z| Lv|Xiaojing|X| Li|Meijia|M| Yang|Wen|W| Wang|Lingling|L| Song|Linsheng|L|

Programmed cell death protein 4
Negative regulation
Crassostrea gigas
IL17 production
NF-κB pathway


An approach to preparing decellularized whole liver organ scaffold in rat.

Abstract:
OBJECTIVES
In present study, we plan to produce a decellularization protocol from rat liver to generate a three-dimensional whole organ scaffold.

METHODS
A combination of 1% SDS and 1% tritonX-100 were used orderly to decellularize rat livers. After about 6 h of interactive antegrade/retrograde perfusion, a decellularized whole translucent liver scaffold with integrated blood vessel networks was generated. The decellularized livers are charactered by light microscopy, scanning electron microscopy, and biochemical analysis (DNA quantification) for preservation of the three-dimension of extracellular matrix architecture.

RESULTS
The decellularization protocol was verified by observation of the whole translucent liver organ with intact vascular trees under macroscopy, in conjunction with the hematoxylin-eosin staining that showed no cells or nuclear material remained. Additionally, the Masson's stain indicted that the extracellular proteins were well kept and scanning electron microscopy (SEM) revealed a preserved decellularized matrix architecture. Compared to normal livers, DNA in the decellularized livers was quantified less than 10% at the same mass.

CONCLUSIONS
The current method of decellularization protocol was feasible, simple and quick, and was verified by an absence of residual cells. The decellularized extracellular matrix had preserved integrate vascular network and a three-dimensional architecture.

Ye|Jun-Song|JS|
Stoltz|Jean-François|JF|
de Isla|Natalia|N|
Liu|Yang|Y|
Yin|Yan-Feng|YF|
Zhang|Lei|L|

D000818:Animals
D002474:Cell-Free System
D004867:Equipment Design
D019544:Equipment Failure Analysis
D005109:Extracellular Matrix
D005260:Female
D008099:Liver
D019164:Liver, Artificial
D051381:Rats
D017207:Rats, Sprague-Dawley
D023822:Tissue Engineering
D054457:Tissue Scaffolds

Decellularization
whole liver organ scaffold
perfusion


A Prospective Italian Study on Baseline NS3 and NS5A Resistance to Direct-Acting Antivirals in a Real-World Setting of HIV-1/HCV Coinfected Patients and Association with Treatment Outcome.

Abstract: We prospectively evaluated the frequency of natural resistance-associated substitutions (RASs) in the NS3 and NS5A regions according to different HCV genotypes and their possible effect on treatment outcome in HIV-1/HCV patients treated with direct-acting antivirals (DAAs). Baseline RASs in the NS3 and NS5A domains were investigated in 62 HIV-1/HCV patients treated with DAAs: 23 patients harbored HCV-GT1a, 26 harbored GT3a, and 13 harbored GT4d. A higher occurrence of RASs was found in the NS3 domain within GT1a (13/23) than GT3a (0/26) or GT4d (2/13). With regard to treatment outcome, NS3 RASs were detected in 14/56 patients with sustained virological response (SVR) and in 1/6 non-responder (NR) patients. Occurrence of RASs of NS5A domain was lower in SVR (4/56, had RASs) than in NR (3/6, had RASs). Evaluation of RASs at baseline instead of at virological failure, especially in the NS5A domain, could positively influence the choice of new DAA combinations for the treatment of HIV-1/HCV patients.

Bagaglio|Sabrina|S|
Hasson|Hamid|H|
Peano|Luca|L|
Vercesi|Riccardo|R|
Messina|Emanuela|E|
Galli|Andrea|A|
Foppa|Caterina Uberti|CU|
Morsica|Giulia|G|0000-0003-4891-5376

HIV-1
genotype
HCV resistance
direct acting antivirals


Building age, type of indoor heating and the occurrence of allergic rhinitis and asthma.

Abstract:
Introduction
Structural materials and interior appliances are frequently mentioned as elements of modern buildings which may have an impact on the natural history of allergic diseases.

Aim
We hypothesized that the building age, the type of the heating system and the use of various indoor appliances can influence the occurrence of allergic rhinitis (AR) and asthma.

Material and methods
The study group comprised 18,617 individuals. The tool used in the study was the European Community Respiratory Health Survey (ECRHS) and the International Study of Asthma and Allergies in Childhood (ISAAC) study questionnaire, adapted to European conditions (Middle and Eastern Europe) and used as part of the study called "Implementation of a System for the Prevention and Early Detection of Allergic Diseases in Poland".

Results
Questionnaire results indicated that people living in homes built in the years 1971-1990 had higher rates of allergic rhinitis (OR = 1.15025), which was correlated with clinical findings of increased occurrence of seasonal allergic rhinitis (OR = 1.60543). The leading factor contributing to the intensification of AR symptoms was the central heating (OR = 1.45358). As opposed to AR, people living in buildings with central heating less often declared asthma (OR = 0.8407). A clinical examination confirmed that central heating reduced the symptoms of moderate asthma (OR = 0.3524).

Conclusions
Increasing building age and certain indoor heating methods are important risk factors for the occurrence of allergic rhinitis and asthma.

Piekarska|Barbara|B|
Furmańczyk|Konrad|K|
Jaworski|Stanisław|S|
Stankiewicz-Choroszucha|Bożenna|B|
Krzych-Fałta|Edyta|E|
Białoszewski|Artur Z|AZ|
Kłak|Anna|A|
Samoliński|Bolesław K|BK|

indoor heating
allergic rhinitis
asthma
age of the building
indoor environmental factors


Plastein reaction enhanced bile-acid binding capacity of soybean protein hydrolysates and whey protein hydrolysates.

Abstract: Plastein reaction is a modification reaction that can improve the functional properties of protein hydrolysate. The product of the reaction is a thixotropic aggregation of peptides. This study investigated the formation condition of soybean-whey plastein and bile acid binding capacity of plastein. Soy protein and whey protein were hydrolyzed by pepsin. The mixture (1:1, w/w) of two hydrolysates was modified by pepsin again. After the reaction, the decrease in free amino groups and the turbidity of the modified hydrolysate were measured to obtain appropriate reaction condition. Results showed that the concentration of hydrolysates 40% (w/v), enzyme ratio of 2.0 KU/g protein, pH 5.0, 37 °C, reaction time of 3.0 h respectively, were showed maximum changes in protein hydrolysates. Tricine SDS-PAGE analysis under denaturing conditions revealed that whey protein was more sensitive to pepsin and yielded different polypeptides (PPs) of molecular weight ranged from 3.5-17 kDa. However, a high molecular weight PP was completely hydrolyzed while PPs of 14.2-26 kDa were partially digested after pepsin treatment. Native page analysis further revealed the presence of a high-molecular weight PP in crude and purified plastein product. The bile acid binding capacity was improved by the plastein reaction. The amount of binding sodium deoxycholate, sodium taurocholate, and sodium cholate were 0.75, 2.0 and 1.87 μmol/100 mg respectively.

Qian|Fang|F| Wang|Ying|Y| Wen|Zi-Jian|ZJ| Jiang|Shu-Juan|SJ| Tuo|Yan-Feng|YF| Mu|Guang-Qing|GQ|

Plastein reaction
Soybean protein hydrolysate
Whey protein hydrolysate
Bile acid binding capacity
Pepsin


Differences in unilateral chest press muscle activation and kinematics on a stable versus unstable surface while holding one versus two dumbbells.

Abstract: Training the bench press exercise on a traditional flat bench does not induce a level of instability as seen in sport movements and activities of daily living. Twenty participants were recruited to test two forms of instability: using one dumbbell rather than two and lifting on the COR bench compared to a flat bench. Electromyography (EMG) amplitudes of the pectoralis major, middle trapezius, external oblique, and internal oblique were recorded and compared. Differences in range of motion (ROM) were evaluated by measuring an angular representation of the shoulder complex. Four separate conditions of unilateral bench press were tested while lifting on a: flat bench with one dumbbell, flat bench with two dumbbells, COR Bench with one dumbbell, and COR Bench with two dumbbells. The results imply that there are no differences in EMG amplitude or ROM between the COR bench and traditional bench. However, greater ROM was found to be utilized in the single dumbbell condition, both in the COR bench and the flat bench.

Patterson|Jeffrey M|JM|
Vigotsky|Andrew D|AD|
Oppenheimer|Nicole E|NE|
Feser|Erin H|EH|

Bench press
COR bench
Electromyography
EMG
Range of motion
ROM
Cocontraction
Dumbbell bench
Dumbbell press
Stability


Piezo1 channels mediate trabecular meshwork mechanotransduction and promote aqueous fluid outflow.

Abstract:
KEY POINTS
Trabecular meshwork (TM) is a highly mechanosensitive tissue in the eye that regulates intraocular pressure through the control of aqueous humour drainage. Its dysfunction underlies the progression of glaucoma but neither the mechanisms through which TM cells sense pressure nor their role in aqueous humour outflow are understood at the molecular level. We identified the Piezo1 channel as a key TM transducer of tensile stretch, shear flow and pressure. Its activation resulted in intracellular signals that altered organization of the cytoskeleton and cell-extracellular matrix contacts and modulated the trabecular component of aqueous outflow whereas another channel, TRPV4, mediated a delayed mechanoresponse. This study helps elucidate basic mechanotransduction properties that may contribute to intraocular pressure regulation in the vertebrate eye.

ABSTRACT
Chronic elevations in intraocular pressure (IOP) can cause blindness by compromising the function of trabecular meshwork (TM) cells in the anterior eye, but how these cells sense and transduce pressure stimuli is poorly understood. Here, we demonstrate functional expression of two mechanically activated channels in human TM cells. Pressure-induced cell stretch evoked a rapid increase in transmembrane current that was inhibited by antagonists of the mechanogated channel Piezo1, Ruthenium Red and GsMTx4, and attenuated in Piezo1-deficient cells. The majority of TM cells exhibited a delayed stretch-activated current that was mediated independently of Piezo1 by TRPV4 (transient receptor potential cation channel, subfamily V, member 4) channels. Piezo1 functions as the principal TM transducer of physiological levels of shear stress, with both shear and the Piezo1 agonist Yoda1 increasing the number of focal cell-matrix contacts. Analysis of TM-dependent fluid drainage from the anterior eye showed significant inhibition by GsMTx4. Collectively, these results suggest that TM mechanosensitivity utilizes kinetically, regulatory and functionally distinct pressure transducers to inform the cells about force-sensing contexts. Piezo1-dependent control of shear flow sensing, calcium homeostasis, cytoskeletal dynamics and pressure-dependent outflow suggests potential for a novel therapeutic target in treating glaucoma.

D001082:Aqueous Humor
D003599:Cytoskeleton
D006801:Humans
D007429:Intraocular Pressure
D007473:Ion Channels
D040542:Mechanotransduction, Cellular
D050916:TRPV Cation Channels
D014129:Trabecular Meshwork

Piezo1
trabecular meshwork
TRPV4
shear stress
ion channel
mechanosensation


Management of recalcitrant Trichomonas vaginalis in pregnancy: a case report.

Abstract: A case report of a pregnant woman with recalcitrant Trichomonas vaginalis is described. This case was managed with suppressive treatment with metronidazole during pregnancy and cleared with paromomycin vaginal treatment after delivery.

recalcitrant
Trichomonas vaginalis
pregnancy
treatment
metronidazole
paromomycin
sexually transmitted infections
trichomoniasis


Evolving Perspectives on Innate Immune Mechanisms of IPF.

Abstract: While epithelial-fibroblast interactions are viewed as the primary drivers of Idiopathic Pulmonary Fibrosis (IPF), evidence gleaned from animal modeling and human studies implicates innate immunity as well. To provide perspective on this topic, this review synthesizes the available data regarding the complex role of innate immunity in IPF. The role of substances present in the fibrotic microenvironment including pathogen associated molecular patterns (PAMPs) derived from invading or commensal microbes, and danger associated molecular patterns (DAMPs) derived from injured cells and tissues will be discussed along with the proposed contribution of innate immune populations such as macrophages, neutrophils, fibrocytes, myeloid suppressor cells, and innate lymphoid cells. Each component will be considered in the context of its relationship to environmental and genetic factors, disease outcomes, and potential therapies. We conclude with discussion of unanswered questions and opportunities for future study in this area.

Ishikawa|Genta|G|
Liu|Angela|A|
Herzog|Erica L|EL|

innate immunity
pulmonary fibrosis
microenvironment
macrophage
biomarker


Leadership Amongst Regional and National Surgical Organizations: The Tides Are Changing.

Abstract:
INTRODUCTION
Leadership amongst professional organizations is a key opportunity for scholarly activity which is essential for academic advancement. Our objective was to examine the differences between men and women in leadership within surgical organizations.

METHODS
Credentials were obtained through an internet search. Variables included organization type, leadership role, gender, advanced degree, medical school graduation year, and publications. A bivariate analysis was performed between genders. A p-value <0.05 was considered statistically significant.

RESULTS
Five hundred forty-three leaders were identified in 43 surgical organizations. There was a significant difference in the number of male and female leaders (72.7% vs 27.3%, p=0.016). Women were most likely to hold the role of "Other", which consisted of lower-level leadership roles including committee chair positions and resident and medical student delegates (35.5%). Fewer women had publications (85.8% vs 92.9%, p=0.01), more women had advanced degrees (24.5% vs 17.0%, p=0.049), and women were involved earlier in their careers (5.9 years, 95% CI 4.1-7.7 years, p<0.001) than their male colleagues.

CONCLUSION
Gender disparity in leadership of surgical organizations exists. Women are involved earlier in their careers and hold lower-level leadership positions reflecting potential for increased involvement in high-level leadership roles in the future. Data need to be trended to discern if women in surgical organizations rise within leadership roles as more women continue to enter surgical subspecialties.

Krise|Stephanie M|SM|
Etheart|Ian|I|
Perzynski|Adam|A|
Como|John|J|
Carneval|Mary|M|
Conrad-Schnetz|Kristen|K|

surgical organization
women in leadership
academic leadership
academic promotion
academic surgery
gender equity
gender parity
organization leadership
surgical careers
women in surgery


Development of a Novel Dorsal Incision Only Invagination Type Pancreatogastrostomy (Charité-PG) Following Open Pancreaticoduodenectomy-A Single Centre Experience.

Abstract: The implementation of a pancreatico-enteric anastomosis following open single stage pancreaticoduodenectomy (PD) is still associated with the most threatening complications in modern pancreatic surgery, such as postoperative pancreatic fistula (POPF), postpancreatectomy haemorrhage (PPH), delayed gastric emptying (DGE), intraabdominal abscesses and related mortality. With this study, we introduce Charité-PG, a new dorsal incision only invagination type pancreatogastrostomy (dioPG) for the restoration of the pancreatic remnant following PD, and compare it to a PG requiring ventral gastrotomy (vgPG). A total of 49 consecutive patients, who underwent reconstruction via dioPG, and 92 consecutive patients, who underwent restoration via vgPG, were identified from our prospective database and further reviewed for perioperative parameters, complication rates, mortality and follow-up. The percentage of overall complications (p = 0.301), as well as the 30-day mortality rate (p = 0.725) and survival (p = 0.543), were comparable in both groups. The operation time in the dioPG group was significantly shorter (p = 0.04), and patients in this group developed substantially fewer rates of DGE (p = 0.036). We provide a feasible and safe technique for restoration following PD via our novel dioPG, causing fewer cases of DGE. Nevertheless, pancreatico-enteric anastomoses require expertise and experience.

Timmermann|Lea|L| Bahra|Marcus|M| Pratschke|Johann|J| Malinka|Thomas|T|0000-0002-5860-5710

pancreatogastrostomy
pancreaticoduodenectomy
pancreato-enteric anastomosis


The Impact of Consumption Patterns on the Generation of Municipal Solid Waste in China: Evidences from Provincial Data.

Abstract: Municipal solid waste (MSW) is the derivative of urban development and it is harmful to the environment and residents' health. But with sustainable MSW management, MSW can be applied as an important renewable energy. In order to achieve sustainable MSW management, it is necessary to understand the mechanism of MSW generation. Consumption patterns differ in various regions of China, which make the influencing factors of MSW have unique characteristics. To explore the factors influencing MSW generation in China, this study builds a global model based on the panel data of 30 Chinese provinces. Considering regional heterogeneity, provinces are clustered into three groups according to economic and consumption indicators. Each group has its own local model of MSW generation. The results show that household expenditure on housing and the tertiary industry proportion show opposite impacting directions in high-level and low-level provinces. Finally, with the combination of the grey model (1,1) (GM(1,1)) and multiple linear regression (MLR), we find that developing provinces will generate more MSW than developed regions. According to this, different provinces should control MSW by optimizing consumption pattern and efficient fiscal expenditure, and developing provinces should pay attention to MSW management and learn from the experience of developed provinces.

Liu|Jinhui|J| Li|Qing|Q|0000-0001-9362-926X Gu|Wei|W| Wang|Chen|C|

D002681:China
D003258:Consumer Behavior
D006801:Humans
D015999:Multivariate Analysis
D062611:Solid Waste
D014506:Urban Renewal
D018505:Waste Management

consumption patterns
clustering analysis
municipal solid waste generation
provincial panel data


MDCKpred: a web-tool to calculate MDCK permeability coefficient of small molecule using membrane-interaction chemical features.

Abstract: Structure-based models to understand the transport of small molecules through biological membrane can be developed by enumerating intermolecular interactions of the small molecule with a biological membrane, usually a dimyristoylphosphatidylcholine (DMPC) monolayer. This ADME (absorption, distribution, metabolism, and excretion) property based on Madin-Darby Canine Kidney (MDCK) cell line demonstrates intestinal drug absorption of small molecules and correlated to human intestinal absorption which acts as a determining factor to forecast small-molecule prioritization in drug-discovery projects. We present here the development of MDCKpred web-tool which calculates MDCK permeability coefficient of small molecule based on the regression model, developed using membrane-interaction chemical features. The web-tool allows users to calculate the MDCK permeability coefficient (nm/s) instantly by providing simple descriptor inputs. The chemical-interaction features are derived from different parts of the DMPC molecule viz. head, middle, and tail regions and accounts overall intermolecular contacts of the small molecule when passively diffused through the phospholipid-rich biological membrane. The MDCKpred model is both internally (R2 = .76; [Formula: see text]= .68; Rtrain = .87; Rtest = .69) and externally (Rext = .55) validated. Furthermore, we used natural molecules as application examples to demonstrate its utility in lead exploration and optimization projects. The MDCKpred web-tool can be accessed freely at http://www.mdckpred.in . This web-tool is designed to offer an intuitive way of prioritizing small molecules based on calculated MDCK permeabilities.

Patel|Rikin D|RD|
Prasanth Kumar|Sivakumar|S|
Pandya|Himanshu A|HA|
Solanki|Hitesh A|HA|

web-tool
MDCK
permeability
permeability coefficient
Caco-2
QSAR


Towards engineering heart tissues from bioprinted cardiac spheroids.

Abstract: Currentin vivoandin vitromodels fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advancedin vitromodels of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long termin vitrotesting. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.

Polonchuk|Liudmila|L|
Surija|Lydia|L|
Lee|Min Ho|MH|
Sharma|Poonam|P|
Liu Chung Ming|Clara|C|
Richter|Florian|F|
Ben-Sefer|Eitan|E|
Rad|Maryam Alsadat|MA|
Mahmodi Sheikh Sarmast|Hadi|H|
Shamery|Wafa Al|WA|
Tran|Hien A|HA|
Vettori|Laura|L|
Haeusermann|Fabian|F|
Filipe|Elysse C|EC|
Rnjak-Kovacina|Jelena|J|
Cox|Thomas|T|
Tipper|Joanne|J|
Kabakova|Irina|I|0000-0002-6831-9478
Gentile|Carmine|C|0000-0002-3689-4275

D042461:Vascular Endothelial Growth Factor A

bioprinting
spheroids
vascularization
VEGF
fusion
bioinks
cardiac physiology


Depression and anxiety among left-behind children in China: a systematic review.

Abstract: This study aimed to systematically review evidence of the prevalence and predictors of depression and anxiety among 'left-behind children' in rural China. The electronic databases PubMed/MEDLINE and Chinese National Knowledge Infrastructure/Wanfang (Chinese) were utilized to search for terms including 'depression' or 'depressive disorder', 'anxiety' or 'mental health', combined with 'left behind', 'children' and 'China'. High rates of psychological depression/anxiety have been reported among left-behind children compared with their age-matched peers. Prevalence rates of depression are reported to range from 12.1 to 51.4% and of anxiety are reported to range from 13.2 to 57.6%. Variability between studies is likely attributable to methodological variations relating to measures used and research setting. Potential predictors measured in studies include age and gender, types of being left, age/years of separation, socio-economic status, etc. These high rates of reported psychological problems among this group of young people suggest the need to develop more effective approaches to prevention and management.

depression
anxiety
left-behind children
systematic review


Social networking site usage: A systematic review of its relationship with social isolation, loneliness, and depression among older adults.

Abstract:
OBJECTIVE
Older adults, age ≥ 60 years, are at risk of depression, which is aggravated by loneliness and social isolation. The use of social networking sites (SNS) has been reported to be beneficial to help people stay in touch with their families and communities. The purpose of this study was to examine the relationship between SNS usage and social isolation, loneliness, and depression among older adults.

METHODS
The online electronic search for literature was conducted up to June 2020 using three databases and searching from reference lists to find potential studies. The inclusion criteria were based on three main study characteristics: (i) a study population of adults age ≥ 60 years, (ii) examine SNS usage, and (iii) report depression or loneliness or social isolation as outcomes.

RESULTS
Fifteen articles were included: ten observational and five experimental studies. Five studies focused on depression and five studies on loneliness/social isolation, while five studies reported on both outcomes. Among observational studies, there was some evidence that SNS usage was associated with lower levels of depression and loneliness scores, but a very limited number of experimental studies were able to obtain similar results. For social isolation, no study found significant associations between SNS usage and lower levels of social isolation.

CONCLUSIONS
This review found very limited evidence, especially from experimental studies, to support associations between SNS use with depression, loneliness, and social isolation among older adults. More studies are needed to enhance understanding to make valid conclusions.

The systematic review was registered in the PROSPERO database on 10 April 2019 and updated in July 2020 (CRD42019125267).

Social network
isolation
loneliness
depression
older adult


Instructed and Acquired Contingencies in Response-Inhibition Tasks.

Abstract: Inhibitory control can be triggered directly via the retrieval of previously acquired stimulus-stop associations from memory. However, a recent study suggests that this item-specific stop learning may be mediated via expectancies of the contingencies in play (Best, Lawrence, Logan, McLaren, & Verbruggen, 2016). This could indicate that stimulus-stop learning also induces strategic proactive changes in performance. We further tested this hypothesis in the present study. In addition to measuring expectancies following task completion, we introduced a between-subjects expectancy manipulation in which one group of participants were informed about the stimulus-stop contingencies and another group did not receive any information about the stimulus-stop contingencies. Moreover, we combined this instruction manipulation with a distractor manipulation that was previously used to examine strategic proactive adjustments. We found that the stop-associated items slowed responding in both conditions. Furthermore, participants in both conditions generated expectancies following task completion that were consistent with the stimulus-stop contingencies. The distractor manipulation was ineffective. However, we found differences in the relationship between the expectancy ratings and task performance: in the instructed condition, the expectancies reliably correlated with the response slowing for the stop-associated items, whereas in the uninstructed condition we found no reliable correlation. These differences between the correlations were reliable, and our conclusions were further supported by Bayesian analyses. We conclude that stimulus-stop associations that are acquired either via task instructions or via task practice have similar effects on behaviour but could differ in how they elicit response slowing.

Best|Maisy|M|0000-0002-8064-2999
McLaren|Ian P L|IPL|
Verbruggen|Frederick|F|

Learning
Cognitive control
Executive functions


Tooth loss and its relationship with protein intake by elderly Brazilians-A structural equation modelling approach.

Abstract:
OBJECTIVE
This study aimed at assessing the relationship between self-perceived tooth loss and wearing dentures, on the one hand, and the consumption of protein, on the other hand, among the elderly population of Botucatu, SP. Food consumption tends to decrease with ageing, especially protein intake, and one of the causes could be the precariousness of oral health. Several risk factors associated with deficient dietary protein intake have been identified, namely greater physical dependence, reduced caloric intake and food insecurity, but no studies have analysed whether tooth loss and prostheses interfere with protein intake.

METHODS
An interview was conducted among 365 elderly individuals, in which we examined oral health-related quality of life (OHRQoL) as the only latent variable, in a 24-hour nutritional assessment dietary recall repeated 3 times, conducted in person by a trained nutritionist and also performed an analysis of nutritional needs using the Nutrition Data System Research (NDSR) Program.

RESULTS
The structural equation model, performed using Stata v.14, showed that lack of teeth (standardised coefficient [SC] = 0.21, P < .001), and prosthesis use (SC = -0.21, P < .001) was associated with OHRQoL. Lack of teeth had a direct effect on the consumption of animal protein (SC = 0.08, P = .02), a strong total effect on animal protein intake (SC = 0.51, P = .04) and a medium effect on total protein intake (SC = 0.20, P = .03), adjusted for confounders (depression and medical problems).

CONCLUSION
Tooth loss had a strong and significant total effect on animal protein intake and a medium effect on total protein intake among elderly Brazilians.

elderly
ageing
quality of life
nutrient intake


Guggulsterone induces apoptosis and inhibits lysosomal-dependent migration in human bladder cancer cells.

Abstract:
BACKGROUND
The survival rate and therapeutic options for patients with bladder cancer have improved little in recent decades. Guggulsterone (GS), a phytoestrogen, has been investigated as an anticancer drug in various malignancies.

PURPOSE
The present study aimed to evaluate the anticancer effects of E-isomer and Z-isomer GS in the human bladder cancer cell lines TSGH8301 (low-grade) and T24 (high-grade) and their underlying mechanisms.

METHODS
The cell survival effect of GS was investigated by the MTT and colony formation assays in bladder cancer cell lines. Flow cytometry was used to analyze the cell cycle and cell death. Migration ability was measured by wound healing and transwell assays. Protein expression was determined by Western blot after GS treatment. The potency of GS on subcutaneous TSGH8301 bladder tumors was evaluated using an in vivo imaging system.

RESULTS
E-isomer GS reduced the survival rate of both low- and high-grade human bladder cancer cells. GS caused cell cycle arrest, accompanied by the decrease and increase in cyclin A and p21 levels, respectively. Additionally, caspase-dependent apoptosis was observed following GS treatment. Furthermore, GS treatment downregulated mTOR-Akt signaling and induced autophagy with p62 and LC3β-II expression. Moreover, the farnesoid X receptor was involved in GS-inhibited cell growth. In addition, GS reduced the migration ability with a decrease in integrin-focal adhesion kinase and myosin light chain. Interestingly, the suppression of GS-mediated migration was prevented by the lysosomal inhibitor ammonium chloride (NH4Cl). GS also reduced TSGH8301 bladder cancer cell progression by increasing the level of p21, cleaved caspase 3, cleaved poly (ADP-ribose) polymerase (PARP), and LC3β-II in vivo.

CONCLUSIONS
The current findings suggest that GS treatment may serve as a potential anticancer therapy for different grades of urothelial carcinoma.

Chen|Ying|Y|
Wang|Hisao-Hsien|HH|
Chang|Hsin-Han|HH|
Huang|Yun-Hsuan|YH|
Wang|Jeffrey R|JR|
Changchien|Chih-Ying|CY|
Wu|Sheng-Tang|ST|

D023041:Xenograft Model Antitumor Assays

Guggulsterone
Apoptosis
Migration
Bladder cancer
Autophagy


Impulsivity Dimensions and Risky Sex Behaviors in an At-Risk Young Adult Sample.

Abstract: Impulsivity is a personality-based risk factor that has been well studied in relation to risky sexual behavior. Recent conceptualizations of impulsivity have proposed multidimensional facets comprised of premeditation, perseverance, sensation seeking, negative urgency, and positive urgency (UPPS-P model). Prior studies have found that these facets are associated with risky sexual behavior in adolescent and college student samples, but no prior studies have evaluated them in clinical samples. The current study examined how impulsivity-related traits related to two different risky sexual behaviors in a clinical sample of at-risk young adults who had both conduct disorder and substance use disorder symptoms as adolescents (n = 529). Lack of premeditation was also tested as a moderator of the relationship between facets of impulsivity and both risky sex outcomes. Results demonstrated that sensation seeking, negative urgency, and positive urgency were correlated with risky sex behaviors. Additionally, multiple regression analyses indicated that sensation seeking was uniquely associated with the number of sexual partners in the past 5 years, whereas positive urgency was uniquely associated with unprotected sex while under the influence. Finally, a significant interaction between lack of premeditation and negative urgency suggests that at-risk young adults with both high negative urgency and lack of premeditation were the likeliest to have the most sexual partners in the past 5 years. This study adds to the current understanding of the relationship between reward- and affect-driven facets of impulsivity and risky sexual behaviors and may lend utility to the development of interventions for at-risk populations.

Curry|Inga|I|0000-0001-9275-0316
Luk|Jeremy W|JW|
Trim|Ryan S|RS|
Hopfer|Christian J|CJ|
Hewitt|John K|JK|
Stallings|Michael C|MC|
Brown|Sandra A|SA|
Wall|Tamara L|TL|

Impulsivity
Risky sex
UPPS-P
Clinical sample


The science underlying frugal innovations should not be frugal.

Abstract: In recent years, frugal products of the grassroots and advanced types are being widely used due to their sustainable nature and also affordability. However, despite the origins of frugality at grassroots level, grassroots innovations continue to be fabricated in an ad hoc manner that precludes application of science and are thus susceptible to premature failure. This work advocates the use of scientific principles for developing frugal products in general with emphasis on classical and new design methodologies that are rooted in science to save resources, and hence lower costs, while aiming for robust product functionality. This paper sheds light on the importance of the safety factor in frugal designs and the need, from here onwards, of a factor of frugality for the systematic realization of both grassroots and advanced frugal products. In particular, adoption of the factor of frugality, that was developed recently, has been supported in this effort with a numerical example to display the effectiveness of applying science for designing from scratch frugal products that are both streamlined and robust in their functionality.

factor of frugality
advanced frugal innovation
factor of safety
sustainable development


Pituitary adenylate cyclase-activating polypeptide attenuates tumor necrosis factor-α-induced apoptosis in endothelial colony-forming cells.

Abstract: Endothelial colony-forming cells (ECFCs) are important in angiogenesis and vascular proliferation. Tumor necrosis factor (TNF)-α is a significant risk factor for the development of atherosclerosis and a key proinflammatory cytokine known to induce apoptosis in endothelial cells. Pituitary adenylate cyclase-activating polypeptide (PACAP) is one of the members of the vasoactive intestinal peptide/secretin/growth hormone-releasing hormone/glucagon superfamily and exists in two biological active forms, PACAP 38 and PACAP 27. PACAP has been reported to help prevent endothelial apoptosis via an anti-inflammatory mechanism. However, to the best of our knowledge, the anti-apoptotic potential of PACAP has not been investigated in ECFCs. The aim of the present study was to demonstrate the efficacy of PACAP for decreasing TNF-α-induced apoptosis in ECFCs. The results indicated that PACAP exerts a cytoprotective effect on ECFCs exposed to TNF-α. Furthermore, PACAP partially rescues the proliferation potential of ECFCs inhibited by prolonged TNF-α exposure. These findings support an anti-inflammatory role for PACAP in circulation diseases.

Bian|Ning|N|
Du|Gang|G|
Ip|Man Fai|MF|
Ding|Juan|J|
Chang|Qing|Q|
Li|Zicheng|Z|

pituitary adenylate cyclase-activating polypeptide


Successful Surgical Resection of Spinal Artery Aneurysms: Report of 3 Cases.

Abstract:
BACKGROUND
Spinal artery aneurysms (SAAs) are extremely rare lesions that can occur in isolation or associated with vascular malformations. Herein, we present 3 unusual cases of SAAs and discuss imaging, diagnosis, and surgical management strategies.

CASE DESCRIPTION
The first patient was a 57-year-old woman who presented with sudden onset of severe headache. Spinal angiography demonstrated an isolated anterior spinal artery (ASA) aneurysm at the level of the craniocervical junction. The second patient was a 27-year-old woman who presented with progressive bilateral pain of her lower limbs. The result of spinal angiography was consistent with an aneurysm at the level of L1. The third patient was a 26-year-old man who presented with bilateral weakness and numbness of the lower limbs. Spinal angiography revealed a conus medullaris aneurysm associated with an arteriovenous malformation (AVM). All these lesions were successfully managed with clipping or resection, and good outcomes were achieved.

CONCLUSION
Spinal artery aneurysms are rare lesions. Herein, we report 3 such cases and emphasize the importance of surgical management.

Ren|Yanming|Y| He|Min|M| You|Chao|C| Li|Jin|J|

Spinal artery aneurysm
Arteriovenous malformations
Surgical excision


Preclinical Studies of MSC-Derived Extracellular Vesicles to Treat or Prevent Graft Versus Host Disease: a Systematic Review of the Literature.

Abstract:
INTRODUCTION
Treating and preventing graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT) remains a significant challenge. The use of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) appears promising and a systematic review of preclinical studies is needed to accelerate the design of translational studies.

METHODS
We identified 4 eligible studies from a systematic review performed on December 1, 2018. In brief, eligible studies included the treatment or prevention of GVHD in animal models and the use of MSC-EVs. Study design and outcome data were extracted and reporting was evaluated using the SYRCLE tool to identify potential bias.

RESULTS
Two studies assessed the efficacy of MSC-EVs in treatment of GVHD and 2 studies address prevention. Mice treated with MSC-EVs showed improved median survival, GVHD clinical scores and histology scores as compared to untreated mice with GVHD. Prophylactic treatment with MSC-EVs attenuated GVHD severity and improved median survival as compared to no treatment or saline.

CONCLUSION
Our systematic review provides important insight regarding the potential of MSC-EVs to treat or prevent GVHD. Although few studies were identified, improved survival and attenuated histologic findings of GVHD were observed in mice after MSC-EV administration for the treatment and prevention of GVHD. Dosing of EVs and route of administration remain inconsistent, however, and scalability of EV isolation for clinical studies remains a challenge. Standardized outcome reporting is needed to pool results for metanalysis. Graphical abstract.

Gupta|Manika|M|
Tieu|Alvin|A|
Slobodian|Mitchell|M|
Shorr|Risa|R|
Burger|Dylan|D|
Lalu|Manoj M|MM|
Allan|David S|DS|0000-0003-3261-8289

Preclinical
Extracellular vesicles
Graft versus host disease
Systematic review
Mesenchymal stromal cells


Development of a Very Brief Measure of ADHD: The CHAOS Scale.

Abstract:
OBJECTIVE
We sought to develop a brief, easy to use behavior checklist to address common limitations in the use of ADHD rating scales in busy clinical settings.

METHOD
Items for the CHAOS ( Conduct- Hyperactive- Attention Problem- Oppositional Symptom) scale were developed based on the ratings of Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria provided by experienced clinicians. The scale was administered to mothers of 205 clinically referred children for the purpose of subscale creation based on principal components analysis (PCA). Reliability and validity were analyzed using a separate sample of 139 children referred for psychological testing.

RESULTS
PCA resulted in four subscales (Attention Problems, Hyperactivity-Impulsivity, Oppositional Behavior, and Conduct Problems), which demonstrated moderate to high test-retest and interrater reliability. Subscale scores correlated significantly with subscales from a DSM-referenced behavior checklist, along with tests of executive functioning.

CONCLUSION
These data suggest that the CHAOS scale is a brief, psychometrically sound tool for evaluation and monitoring of ADHD symptoms.

Levy|Jess D|JD|
Kronenberger|William G|WG|
Dunn|David W|DW|

D001289:Attention Deficit Disorder with Hyperactivity

D019958:Attention Deficit and Disruptive Behavior Disorders

D039721:Diagnostic and Statistical Manual of Mental Disorders

ADD/ADHD
ADHD informant ratings
Conduct Disorder
Oppositional Defiant Disorder
assessment


Guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic overactive bladder management: Translation of French recommendations.

Abstract:
OBJECTIVE
Provide guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic overactive bladder management.

PATIENTS AND METHODS
Guidelines using formalized consensus guidelines method. These guidelines have been validated by a group of 13 experts quoting proposals, subsequently reviewed by an independent group of experts.

RESULTS
In the case of patients with urinary tract infection, it must be treated and injection postponed. Before proposing an injection, it is recommended to ensure the feasibility and acceptability of self-catheterisation by patient. The injection can be performed after local anesthesia of the bladder and urethra (lidocaine), supplemented where necessary by nitrous oxide inhalation and sometimes under general anesthesia. Injection is performed in the operating room or endoscopy suite. The bladder should not be too filled (increased risk of perforation). Treatment should be applied in 10 to 20 injections of 0.5 to 1 mL homogeneously distributed in the bladder at a distance from the urethral orifices. It is not recommended to leave a urinary catheter in place except in cases of severe hematuria. The patient should be monitored until resumption of micturition. After the first injection, an appointment must be scheduled within 3 months (micturition diary, uroflowmetry, measurement of residual urine and urine culture). Performance of self-catheterisation should be questioned in the case of a symptomatic post-void residual and/or a residue>200 mL. A new injection may be considered when the clinical benefit of the previous injection diminishes (between 6 and 9 months). A period of three months must elapse between each injection.

CONCLUSIONS
Implementation of these guidelines may promote best practice usage of BoNTA with optimal risk/benefit ratio.

Hermieu|J-F|JF|
Ballanger|P|P|
Amarenco|G|G|
Chartier-Kastler|É|É|
Cosson|M|M|
Costa|P|P|
Fatton|B|B|
Saussine|C|C|
Denys|P|P|
Gamé|X|X|
Haab|F|F|
Karsenty|G|G|
Le Normand|L|L|
Ruffion|A|A|
Deffieux|X|X|

D019274:Botulinum Toxins, Type A
D006801:Humans
D009465:Neuromuscular Agents
D017410:Practice Guidelines as Topic
D053201:Urinary Bladder, Overactive

Refractory idiopathic overactive bladder

Hyperactivité vésicale idiopathique réfractaire


Tauroursodeoxycholic acid attenuates colitis-associated colon cancer by inhibiting nuclear factor kappaB signaling.

Abstract:
BACKGROUND AND AIM
Inflammatory bowel diseases is associated with an increased risk for the development of colorectal cancer. However, the mechanism of immune signaling pathways linked to colitis-associated cancer (CAC) has not been fully elucidated. Tauroursodeoxycholic acid (TUDCA) exhibits anti-inflammatory and anti-cancer activities. The aim of this study is to investigate the role of TUDCA in the pathogenesis of CAC.

METHODS
Colitis-associated cancer was induced in mice using azoxymethane and dextran sodium sulfate administration, and TUDCA's effect on tumor development was evaluated. HCT 116 and COLO 205 were treated with TUDCA or vehicle and then stimulated with tumor necrosis factor-α (TNF-α). Expression of interleukin (IL)-8 was determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, and IκBα phosphorylation and degradation was evaluated by immunoblot assay. The DNA-binding activity of NF-κB was assessed by electrophoretic mobility shift assay. Cell viability assay and real-time reverse transcription-polymerase chain reaction of bcl-xL, MCL1, c-FLIP-L, and VEGF were performed.

RESULTS
Tauroursodeoxycholic acid significantly attenuated the development of CAC in mice. Exposure to TUDCA resulted in extensive epithelial apoptosis and reduced levels of phospho-IκB kinase in the colon. In HCT 116 cells stimulated with TNF-α, TUDCA significantly inhibited IL-8 and IL-1α expression and suppressed TNF-α-induced IκBα phosphorylation/degradation and DNA-binding activity of NF-κB. Furthermore, in both HCT 116 and COLO 205 cells, TUDCA reduced cell viability and downregulated the expression of bcl-xL, MCL1, c-FLIP-L, and VEGF.

CONCLUSION
These results demonstrated that TUDCA suppresses NF-κB signaling and ameliorates colitis-associated tumorigenesis, suggesting that TUDCA could be a potential treatment for CAC.

tauroursodeoxycholic acid
inflammatory bowel disease
mice
NF-kappaB
colonic neoplasms


Development and validation of an LC-MS/MS method for simultaneous quantification of co-administered trastuzumab and pertuzumab.

Abstract: Given the increasing use of combination therapy with multiple monoclonal antibodies (mAbs), there is a clinical need for multiplexing assays. For the frequently co-administered anti-human epidermal growth factor receptor 2 (HER2) mAbs trastuzumab and pertuzumab, we developed a high-throughput and robust hybrid ligand-binding liquid chromatography-mass spectrometry (LC-MS)/MS quantitative assay. Nanomolar concentrations of trastuzumab and pertuzumab were determined in 10 µL serum samples after extraction by affinity purification through protein A beads, followed by on-bead reduction, alkylation, and trypsin digestion. After electrospray ionization, quantification was obtained by multiple reaction monitoring LC-MS/MS using SILuMab as an internal standard. The method was validated according to the current guidelines from the US Food and Drug Administration and the European Medicines Agency. Assay linearity was established in the ranges 0.250-250 μg/mL for trastuzumab and 0.500-500 μg/mL for pertuzumab. The method was accurate and selective for the simultaneous determination of trastuzumab and pertuzumab in clinical samples, thereby overcoming the limitation of ligand binding assays that cannot quantify mAbs targeting the same receptor. Furthermore, this method requires a small blood volume, which reduces blood collection time and stress for patients. The assay robustness was verified in a clinical trial where trastuzumab and pertuzumab concentrations were determined in 670 serum samples. As we used commercially available reagents and standards, the described generic bioanalytical strategy can easily be adapted to multiplex quantifications of other mAb combinations in non-clinical and clinical samples.

van Laarhoven|Hanneke W M|HWM|0000-0003-3546-9709

validation
lc-MS
Trastuzumab
pertuzumab
monoclonal antibodies
mAbs
multiplex
pharmacokinetics