Altered Inferior Parietal Functional Connectivity is Correlated with Praxis and Social Skill Performance in Children with Autism Spectrum Disorder.

Abstract: Children with autism spectrum disorder (ASD) have difficulties perceiving and producing skilled gestures, or praxis. The inferior parietal lobule (IPL) is crucial to praxis acquisition and expression, yet how IPL connectivity contributes to autism-associated impairments in praxis as well as social-communicative skill remains unclear. Using resting-state functional magnetic resonance imaging, we applied independent component analysis to test how IPL connectivity relates to praxis and social-communicative skills in children with and without ASD. Across all children (with/without ASD), praxis positively correlated with connectivity of left posterior-IPL with the left dorsal premotor cortex and with the bilateral posterior/medial parietal cortex. Praxis also correlated with connectivity of right central-IPL connectivity with the left intraparietal sulcus and medial parietal lobe. Further, in children with ASD, poorer praxis and social-communicative skills both correlated with weaker right central-IPL connectivity with the left cerebellum, posterior cingulate, and right dorsal premotor cortex. Our findings suggest that IPL connectivity is linked to praxis development, that contributions arise bilaterally, and that right IPL connectivity is associated with impaired praxis and social-communicative skills in autism. The findings underscore the potential impact of IPL connectivity and impaired skill acquisition on the development of a range of social-communicative and motor functions during childhood, including autism-associated impairments.

Wymbs|Nicholas F|NF|
Nebel|Mary Beth|MB|
Ewen|Joshua B|JB|
Mostofsky|Stewart H|SH|

connectivity
gesture
ICA
dyspraxia
motor skill


Baicalein attenuates caspase-independent cells death via inhibiting PARP-1 activation and AIF nuclear translocation in cerebral ischemia/reperfusion rats.

Abstract: It is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baicalein treatment at dose of 100 mg/kg for 7 days significantly inhibited the release of cytokines, activation of PARP-1, nuclear translocation of apoptosis-inducing factor (AIF) and macrophage migration inhibitory factor (MIF) in cerebral I/R rats, therefore decreased cerebral infarct volume and neurological scores. Then, we further investigated the signal transduction mechanisms of ischemic tissue protection by baicalein in vitro. Following oxygen and glucose deprivation (OGD) in SH-SY5Y cells, the mitochondrial AIF was translocated into nucleus after 12 h. The co-immunoprecipitation analysis showed that the interaction between AIF and MIF was activated by OGD and subsequently resulted in MIF nuclear translocation. Also, the baicalein inhibited apoptosis, reduced oxidative stress, protected mitochondrial function and restored mitochondrial membrane potential in OGD cells. The results obtained from both in vivo and in vitro study demonstrated the PARP-1/AIF pathway involved in mechanisms of baicalein to protect the cerebral tissues from ischemic injury.

PARP-1 activation
AIF nuclear translocation
Parthanatos
Programed cells death


Multiple genetic variations in sodium channel subunits in a case of sudden infant death syndrome.

Abstract:
BACKGROUND
Dysfunction of NaV 1.5 encoded by SCN5A accounts for approximately half of the channelopathic SIDS cases. We investigated the functional effect of two gene variants identified in the same patient, one in SCN5A and one in SCN1Bb. The aim of the study was to risk stratify the proband's family.

METHODS
The family was referred for cardiovascular genetic evaluation to assess familial risk of cardiac disease. Functional analysis of the identified variants was performed with patch-clamp electrophysiology in HEK293 cells.

RESULTS
A 16-month-old healthy boy died suddenly in the context of nonspecific illness and possible fever. Postmortem genetic testing revealed variants in the SCN5A and SCN1Bb genes. The proband's father carries the same variants but is asymptomatic. Electrophysiological analysis of the NaV 1.5_1281X truncation revealed complete loss-of-function of the channel. Coexpression of NaV 1.5 with NaV β1b significantly increased INa density when compared to NaV 1.5 alone. The NaV β1b _V268I variant abolished this INa density increase. Moreover, it shifted the activation curve toward more depolarized potentials.

CONCLUSIONS
Genetic variation of both sodium channel and its modifiers may contribute to sudden unexplained death in childhood. However, the asymptomatic father suggests that genetic variation of these genes is not sufficient to cause sudden death or clinically detectable SCN5A phenotypes.

Denti|Federico|F|
Bentzen|Bo Hjorth|BH|
Wojciak|Julianne|J|
Thomsen|Nancy Mutsaers|NM|
Scheinman|Melvin|M|0000-0002-3793-1867
Schmitt|Nicole|N|0000-0001-9482-9749

D062554:NAV1.5 Voltage-Gated Sodium Channel

D062547:Voltage-Gated Sodium Channel beta-1 Subunit


Risk of chronic kidney disease defined by decreased estimated glomerular filtration rate in individuals with different prediabetic phenotypes: results from a prospective cohort study in China.

Abstract:
OBJECTIVE
We aimed to investigate the effects of prediabetes and its phenotypes of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycated hemoglobin A1c (EHbA1c) on chronic kidney disease (CKD) occurrence, and define the cut-off point of each glycemic index that significantly increases the risk of CKD.

RESEARCH DESIGN AND METHODS
In this prospective cohort study, 6446 non-diabetic subjects aged 40 years and over were followed over a period of 3 years to track the new onset of CKD. Cox regression was used to assess the association of prediabetes and its phenotypes with CKD. Receiver operating characteristic curves were used to define the cut-off point of each glycemic index that significantly increases the occurrence of CKD. Population attributable risk percent was calculated to estimate the contribution of prediabetes to CKD.

RESULTS
Compared to subjects with normal glucose tolerance, patients with prediabetes significantly increased the risk of development of CKD (HR=2.33 (1.19-4.55)). Specifically, this increased risk of CKD development was observed in patients with IFG, IGT and EHbA1c. The cut-off points shown to significantly increase the risk of CKD are fasting plasma glucose of 5.63 mmol/L, 2-hour plasma glucose of 6.80 mmol/L and HbA1c of 5.6%. The contribution of prediabetes to CKD occurrence in the study population was 60.6%.

CONCLUSIONS
This result suggests that the stricter criteria might be needed to define normal plasma glucose level in China that would not be predisposed to diabetic complications, particularly CKD.

Li|Wei|W| Wang|Anping|A| Jiang|Jiajia|J| Liu|Guangxu|G| Wang|Meiping|M| Li|Dongxue|D| Wen|Jing|J| Mu|Yiming|Y| Du|Xiaoyan|X| Gaisano|Herbert|H| Dou|Jingtao|J| He|Yan|Y|0000-0002-8586-075X

chronic kidney disease
prediabetes
HbA1c
population-based studies


Ditopic binuclear copper(II) complexes for DNA cleavage.

Abstract: Herein we present the synthesis of two ligands containing two di(2-picolyl)amine (DPA) units linked by either a 1,1'-(pyridine-2,6-diyl)bis(3-ethylurea) (L1) or a 1,1'-(1,3-phenylene)bis(3-ethylurea) (L2) spacer. The corresponding binuclear CuII and ZnII complexes were prepared and isolated. The X-ray structures of the L1 ligand and the [Cu2L1Cl2]2+ complex evidence an unusual cis/trans conformation of one of the urea groups stabilized by an intramolecular hydrogen bond with the nitrogen atom of the pyridyl spacer. The CuII complexes form rather strong ternary complexes with phosphorylated anions. The [Cu2L1]4+ complex presents a rather high affinity for pyrophosphate (logK11 = 8.19 at pH 7, 25 °C), while [Cu2L2]4+ stands out because of its strong binding to AMP2- (logK11 = 9.3 at pH 7, 25 °C). The interaction of the CuII complexes with deoxyribonucleic acid from calf thymus (ct-DNA) was monitored using circular dichroism (CD) and luminescence spectroscopies. These studies revealed a quite strong interaction of the complexes with ct-DNA (Kb = (6.4 ± 0.7) × 103 for [Cu2L1]4+ and Kb = (6.3 ± 1.0) × 103 for [Cu2L2]4+). Competition experiments carried out in the presence of methyl green and BAPPA (N1,N3-Bis(4-amidinophenyl)propane-1,3-diamine) as major and minor groove competitors, respectively, confirm that the interaction of both complexes with DNA takes place through the minor groove, in agreement with docking studies. The [Cu2L2]4+ complex is quite efficient in promoting the cleavage of the double-stranded pUC19 plasmid DNA, by favoring the conversion of the supercoiled form to the nicked form following a hydrolytic mechanism.

Carreira-Barral|Israel|I|
Riopedre-Fernández|Miguel|M|
de Blas|Andrés|A|
Mosquera|Jesús|J|
Vázquez|M Eugenio|ME|
Platas-Iglesias|Carlos|C|
Esteban-Gómez|David|D|

DNA cleavage
Anion recognition
Binuclear copper complexes
DFT calculations
Ditopic receptors


Adding sweet potato vines improve the quality of rice straw silage.

Abstract: Rice straw and sweet potato vines are the main by-products of agricultural crops, and their disposal creates problems for the environment in the south of China. In order to establish an easy method for making rice straw silage successfully, experiments were conduct to evaluate fermentation quality and nutritive value of rice straw silages ensiled with or without sweet potato vine. Paddy rice straw (PR) and upland rice straw (UP) were ensiled alone or with sweet potato vines (SP) by a ratio of 1:1 (fresh matter basis), over 3 years. Compared with rice straw silages ensiled alone, the mixed-material silages (PR + SP, UR + SP) showed higher fermentation quality with lower propionic acid content and NH3 -N ratio of total N, and higher (P < 0.05) concentrations of lactic acid and acetic acid, resulting in decrease (P < 0.05) of dry matter loss and higher (P < 0.05) in vitro ruminal dry matter digestion. When the fermentation quality, chemical composition and in vitro rumen fermentation characteristics were considered, ensiling would be an effective way of utilization of rice straw and sweet potato vines in the regions where rice and sweet potato are harvested at same season, and the sweet potato vines have the potential to improve rice straw fermentation quality with low water soluble carbohydrate content in south of China.

Li|Ping|P| Ji|Shuren|S| Wang|Qian|Q| Qin|Mengzhen|M| Hou|Chen|C| Shen|Yixin|Y|

sweet potato vine
rice straw
silage
fermentation quality
in vitro ruminal dry matter digestion


Fast detection of Southern tomato virus by one-step transcription loop-mediated isothermal amplification (RT-LAMP).

Abstract: Southern tomato virus (STV) is a double stranded RNA (dsRNA) virus belonging to genus Amalgavirus (family Amalgamaviridae) which has been detected in tomato plants showing stunting, fruit discoloration and size reduction. A one-step reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of STV in total RNA or sap extracts (obtained just by grinding in buffer) from STV-infected tomato plants by using a set of three primers pairs which were designed to the sequence of the STV putative coat protein. Amplification products were visualized by gel electrophoresis or direct staining of DNA. The sensitivity of RT-LAMP was identical to that of the conventional RT-PCR and less affected by the presence of polymerase inhibitors. STV was detected by RT-LAMP in different tomato tissues, i.e. leaves, roots, fruits and seeds. Also the virus was successfully detected by RT-LAMP from sap extracts obtained from field tomato plants whereas conventional RT-PCR did not. Results of this work show that RT-LAMP is a specific, rapid and cheap procedure to detect STV and it could be implemented on field surveys and sanitation programs.

Elvira-González|L|L|
Puchades|A V|AV|
Carpino|C|C|
Alfaro-Fernandez|A|A|
Font-San-Ambrosio|M I|MI|
Rubio|L|L|
Galipienso|L|L|

D021141:Nucleic Acid Amplification Techniques

STV
Amalgamaviru
Plant virus
Seed-borne virus
Solanum lycopersicum


Frequency and Predictors of Pacifier Use in the Low Socioeconomic Group of Karachi, Pakistan: A Cross-Sectional Study.

Abstract: Background Pacifier use has been popular for ages. They are prevalent all over the world because of their various perceived benefits. On the other hand, there is a common belief that they do carry health risks as well. Due to these contradicting belief systems, the frequency of their use, and the factors that determine them, need to be thoroughly evaluated. Since Pakistan is a developing country with a low literacy rate, it can be implied that a vast majority of the country's population may lack awareness regarding the advantages and disadvantages of pacifier use, making them incapable of weighing associated risks versus benefits. The data evaluating these factors in this region are however scarce in the published literature. We, therefore, aimed to highlight the frequency and predictors of pacifier use in the low socioeconomic group of Karachi, Pakistan. Materials and methods A descriptive, cross-sectional study was conducted on a sample of 300 mothers visiting a tertiary care hospital in Karachi, Pakistan. We included mothers who had at least one child under the age of two years, and whose child did not have any oro-nasal anomaly that could prevent them from sucking a pacifier. Data were collected using pre-tested questionnaires and analyzed using the Statistical Package for Social Sciences (SPSS version 23.0, IBM Corp., Armonk, NY, US). Frequencies were calculated and presented in the form of tables. The chi-square test was used to determine the significance of all categorical variables. A P-value of <0.05 was considered to be statistically significant. Results Almost half of our respondents (49%) gave pacifiers to their children. A significant number (59%) of these mothers were uneducated. Almost all (97%) of the users had annual household income less than 15,000 Pakistani rupees (PKR); 34% were primiparous and more than two-thirds (71%) had a normal vaginal delivery. Out of all the factors, maternal age less than 20, annual household income less than 15,000 PKR, and primiparity were significantly associated with pacifier use in mothers (P<0.05). Only a half of the users (51%) cleaned the pacifiers by boiling; one-fourth (25%) washed it with water only; while 18% washed it with soap and water. The majority (84%) of the mothers used the pacifier to soothe the baby when upset. Among mothers who did not use a pacifier, about a third (30%) did not do so as they believed it's a bad practice. About one-fourth (27%) believed it was unhygienic. Conclusions Our study highlights the gap in the awareness of mothers regarding pacifier use. Using this data, we can target to disseminate specific information to this population to integrate safe and healthy child care habits in society.

Riaz|Ramsha|R|
Ahmed|Madiha|M|
Baloch|Mariam|M|
Rizvi|Syed Asad Hasan|SAH|
Shahid|Naureen|N|
Siddiqui|Fatima Qadir|FQ|
Haq|Muhammad S|MS|
Saleem|Sania|S|

pacifiers
pakistan
developing countries
breast feeding
feeding infants and young children
paediatrics


Association between case volume and mortality in pre-hospital anaesthesia management: a retrospective observational cohort.

Abstract:
BACKGROUND
Pre-hospital anaesthesia is a core competency of helicopter emergency medical services (HEMS). Whether physician pre-hospital anaesthesia case volume affects outcomes is unknown in this setting. We aimed to investigate whether physician case volume was associated with differences in mortality or medical management.

METHODS
We conducted a registry-based cohort study of patients undergoing drug-facilitated intubation by HEMS physician from January 1, 2013 to August 31, 2019. The primary outcome was 30-day mortality, analysed using multivariate logistic regression controlling for patient-dependent variables. Case volume for each patient was determined by the number of pre-hospital anaesthetics the attending physician had managed in the previous 12 months. The explanatory variable was physician case volume grouped by low (0-12), intermediate (13-36), and high (≥37) case volume. Secondary outcomes were characteristics of medical management, including the incidence of hypoxaemia and hypotension.

RESULTS
In 4818 patients, the physician case volume was 511, 2033, and 2274 patients in low-, intermediate-, and high-case-volume groups, respectively. Higher physician case volume was associated with lower 30-day mortality (odds ratio 0.79 per logarithmic number of cases [95% confidence interval: 0.64-0.98]). High-volume physician providers had shorter on-scene times (median 28 [25th-75th percentile: 22-38], compared with intermediate 32 [23-42] and lowest 32 [23-43] case-volume groups; P<0.001) and a higher first-pass success rate for tracheal intubation (98%, compared with 93% and 90%, respectively; P<0.001). The incidence of hypoxaemia and hypotension was similar between groups.

CONCLUSIONS
Mortality appears to be lower after pre-hospital anaesthesia when delivered by physician providers with higher case volumes.

Saviluoto|Anssi|A|
Jäntti|Helena|H|
Kirves|Hetti|H|
Setälä|Piritta|P|
Nurmi|Jouni O|JO|

pre-hospital
emergency medical services
intubation
tracheal
air ambulance
airway management
clinical competence
critical care
rapid sequence induction and intubation


High Salinity Relaying to Reduce Vibrio parahaemolyticus and Vibrio vulnificus in Chesapeake Bay Oysters (Crassostrea virginica).

Abstract: Cases of Vibrio infections in the United States have tripled from 1996 to 2009 and these infections are most often associated with the consumption of seafood, particularly oysters (Crassostrea virginica). Information is needed on how to reduce numbers of Vibrio parahaemolyticus and Vibrio vulnificus in bi-valve molluscan shellfish (for example, oysters). The purpose of this study was to evaluate the effectiveness of high salinity relaying or treatment in recirculating aquaculture systems (RASs) as methods to reduce the abundance of V. parahaemolyticus and V. vulnificus in oysters. For relaying field trials, oysters were collected from approved harvest waters, temperature abused outside under a tarp for 4 h, and then transferred to high (29 to 33 ppt.) and moderate (12 to 19 ppt.) salinities. For RAS treatment trial, oysters were transferred to 32 to 34 ppt. salinity at 15 °C. After 7, 14, 21, and in some instances 28 d, oysters were collected and analyzed for V. parahaemolyticus and V. vulnificus levels using multiplex real-time PCR. Initial levels of V. parahaemolyticus and V. vulnificus ranged from 3.70 to 5.64 log10 MPN/g, and were reduced by 2 to 5 logs after 21 to 28 d in high salinity water (29 to 34 ppt.). Oyster mortalities averaged 4% or less, and did not exceed 7%. Relaying of oysters to high salinity field sites or transfer to high salinity RAS tanks was more effective in reducing V. vulnificus compared with V. parahaemolyticus. These results suggest that high salinity relaying of oysters is more effective in reducing V. vulnificus than V. parahaemolyticus in the oyster species used in this study.

Parveen|Salina|S|
Jahncke|Michael|M|
Elmahdi|Sara|S|
Crocker|Helen|H|
Bowers|John|J|
White|Chanelle|C|
Gray|Stephanie|S|
Morris|Amanda C|AC|
Brohawn|Kathy|K|

high salinity
relaying
Vibrio
Oyster
seafood safety


Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme.

Abstract: Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%-3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients' bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.

D015972:Gene Expression Regulation, Neoplastic

micro RNA
immune checkpoints
glioblastoma multiforme
glioma
tumor


Pancreas-preserving management of grade-C pancreatic fistula and a novel bridging technique for repeat pancreaticojejunostomy: An observational study.

Abstract:
PURPOSE
Optimal surgical strategy for grade-C postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is not justified. External wirsungostomy is feasible. However, the subsequent repeat pancreaticojejunostomy (PJ) is challenging. This study aims to introduce our experience of external wirsungostomy for grade-C POPF and a novel technique to do the repeat PJ (re-PJ).

MATERIALS AND METHODS
From January 1, 2012 to December 31, 2016, all consecutive patients who underwent pancreaticoduodenectomy (PD) with PJ were identified. The clinical data were retrospectively collected and analyzed.

RESULTS
Out of 325 patients, 11 patients (3.38%) underwent salvage re-laparotomy for grade-C POPF. External wirsungostomy was performed in 10 patients (3.08%). Four patients died of severe complications within 90 days postoperatively or tumor progression before the scheduled re-PJ was performed. Three patients got their external pancreatic drainage tube pulled out accidentally without causing severe consequences. Three patients underwent planned re-PJ after external wirsungostomy, including one with duct-to-mucosa PJ and two with the novel bridging technique. The operative times of the two patients undergoing the novel bridging technique were 120 min, 135 min, respectively, and the length of post-operative hospital stay (LPHS) were 7 d, 5 d, respectively. The operative time and the LPHS of whom underwent duct-to-mucosa PJ were 315 min, 24 d, respectively. There was no major post-operative complication.

CONCLUSION
External wirsungostomy may be a safe way to preserve the pancreas remnant in grade-C POPF patients. The novel bridging technique may be a simpler alternative to traditional PJ.

Ma|Tao|T| Bai|Xueli|X| Chen|Wen|W| Li|Guogang|G| Lao|Mengyi|M| Liang|Tingbo|T|

Pancreatic fistula
Pancreaticojejunostomy
Pancreaticoduodenectomy
External wirsungostomy
Reoperation


Statistical considerations regarding correlated lots in analytical biosimilar equivalence test.

Abstract: In the evaluation of the analytical similarity data, an equivalence testing approach for most critical and quantitative quality attributes, which are assigned to Tier 1 in their proposed three-tier approach, was proposed. The Food and Drug Administration (FDA) has recommended the proposed equivalence testing approach to sponsors through meeting comments for Pre-Investigational New Drug Applications (PINDs) and Investigational New Drug Applications (INDs) since 2014. The FDA has received some feedback on the statistical issues of potentially correlated reference lot values subjected to equivalence testing since independent and identical observations (lot values) from the proposed biosimilar product and the reference product are assumed. In this article, we describe one method for correcting the estimation bias of the reference variability so as to increase the equivalence margin and its modified versions for increasing the equivalence margin and correcting the standard errors in the confidence intervals, assuming that the lot values are correlated under a few known correlation matrices. Our comparisons between these correcting methods and no correction for bias in the reference variability under several assumed correlation structures indicate that all correcting methods would increase the type I error rate dramatically but only improve the power slightly for most of the simulated scenarios. For some particular simulated cases, the type I error rate can be extremely large (e.g., 59%) if the guessed correlation is larger than the assumed correlation. Since the source of a reference drug product lot is unknown in nature, correlation between lots is a design issue. Hence, to obtain independent reference lot values by purchasing the reference lots at a wide time window often is a design remedy for correlated reference lot values.

D014486:United States Food and Drug Administration

correlated lots
correlation
biosimilarity
equivalence testing
Analytical similarity


European consensus on the standardization of robotic total mesorectal excision for rectal cancer.

Abstract:
AIM
Surgery for rectal cancer is challenging for both technical and anatomical reasons. The European Academy of Robotic Colorectal Surgery (EARCS) provides a competency-based training programme through a standardized approach. However, there is no consensus on technical standards for robotic surgery when used during surgery for rectal cancer. The aim of this consensus study was to establish operative standards for anterior resection incorporating total mesorectal excision (TME) using robotic techniques, based on recommendations of expert European colorectal surgeons.

METHOD
A Delphi questionnaire with a 72-item statement was sent through an electronic survey tool to 24 EARCS faculty members from 10 different countries who were selected based on expertise in robotic colorectal surgery. The task was divided into theatre setup, colonic mobilization and rectal dissection, and each task area was further divided into several subtasks. The levels of agreement (A* > 95% agreement, A > 90%, B > 80% and C > 70%) were considered adequate while agreement of < 70% was considered inadequate. Once consensus was reached, a draft document was compiled and sent out for final approval.

RESULTS
The average length of experience of robotic colorectal surgery for participants in this study was 6 years. Initial agreement was 87%; in nine items, it was < 70%. After suggested modifications, the average level of agreement for all items reached 94% in the second round (range 0.75-1).

CONCLUSION
This is the first European consensus on the standardization of robotic TME. It provides a baseline for technical standards and structured training in robotic rectal surgery.

Consensus
rectal cancer
technical standard
robotic surgery


Bilateral angle-closure during hospitalization for coronavirus disease-19 (COVID-19): A case report.

Abstract:
PURPOSE
This report describes a case of bilateral primary angle closure (PAC) progressing to unilateral end-stage primary angle closure glaucoma (PACG) associated with treatment for coronavirus disease-19 (COVID-19) infection.

METHODS
A 64-year-old man came to our attention because of blurred vision after a 2-month hospital stay for treatment of COVID-19 infection. Examination findings revealed PACG, with severe visual impairment in the right eye and PAC in the left eye due to plateau iris syndrome. The patient's severe clinical condition and prolonged systemic therapy masked the symptoms and delayed the diagnosis. Medical chart review disclosed the multifactorial causes of the visual impairment. Ultrasound biomicroscopy (UBM) aided in diagnosis and subsequent therapy.

RESULTS
The cause behind the primary angle closure and the iridotrabecular contact was eliminated by bilateral cataract extraction, goniosynechialysis, and myotic therapy.

CONCLUSIONS
COVID-19 treatment may pose an increased risk for PAC. Accurate recording of patient and family ophthalmic history is essential to prevent its onset. Recognition of early signs of PAC is key to averting its progression to PACG.

Angle closure
GLAUCOMA
anesthesia/sedation
diagnostic techniques
glaucoma medical therapies


Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

Abstract: Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

Non-motor symptoms
Parkinson's Disease
Age
Axial symptoms
Dementia


Rumen-Protected Glucose Stimulates the Insulin-Like Growth Factor System and mTOR/AKT Pathway in the Endometrium of Early Postpartum Dairy Cows.

Abstract: This study aimed to elucidate the effects of a dietary rumen-protected glucose (RPG) addition on uterine involution through the analysis of an insulin-like growth factor (IGF) system and associated pathways in the post-natal endometrium. Twelve Holstein cows were assigned equally to two groups: a control group (CT) and an RPG group (200 g of RPG per cow per day). The plasma content of insulin-like growth factor 1 (IGF1) was determined by using the ELISA method. Expressions of IGF members, the matrix metalloproteinase, protein kinase B (AKT)/mechanistic target of rapamycin complex1 (mTOR) signaling pathway, and cell proliferation factors (proliferating cell nuclear antigen (PCNA) and Ki67) were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence, respectively. The results showed that the positive cells of PCNA and Ki67 were increased in the endometrium of RPG versus CT cows. The RPG addition significantly increased the plasma IGF1 level 14 d after delivery. The mRNA expressions of the IGF family members (IGF1, IGF2, type 1 IGF receptor (IGF1R) and IGF-binding proteins (IGFBP1, IGFBP2, IGFBP4 and IGFBP5)) were upregulated, and mRNA expressions of matrix metalloproteinase MMP3 and MMP9 were downregulated in cows from the RPG group compared with the CT group. Meanwhile, the protein expressions of IGF1, IGF2, IGF1R, IGFBP1 and IGFBP4 were upregulated in cows from the RPG group compared with the CT group. Immunohistochemical analysis identified a positive response for IGF1R and IGF2R in the endometrium of RPG versus CT cows. Furthermore, the RPG supplementation increased the protein expressions of phosphorylated (p)-AKT to total AKT and p-mTOR to total mTOR ratio in the endometrium. The current results indicated that the RPG supplementation promoted the proliferation of endometrial cells by stimulating the IGFs and mTOR/AKT pathway in the early post-natal endometrium of dairy cows.

rumen-protected glucose
endometrium
cow
involution


Cyclic Nucleotide (cNMP) Analogues: Past, Present and Future.

Abstract: Cyclic nucleotides are important second messengers involved in cellular events, and analogues of this type of molecules are promising drug candidates. Some cyclic nucleotide analogues have become standard tools for the investigation of biochemical and physiological signal transduction pathways, such as the Rp-diastereomers of adenosine and guanosine 3',5'-cyclic monophosphorothioate, which are competitive inhibitors of cAMP- and cGMP-dependent protein kinases. Next generation analogues exhibit a higher membrane permeability, increased resistance against degradation, and improved target specificity, or are caged or photoactivatable for fast and/or targeted cellular imaging. Novel specific nucleotide analogues activating or inhibiting cyclic nucleotide-dependent ion channels, EPAC/GEF proteins, and bacterial target molecules have been developed, opening new avenues for basic and applied research. This review provides an overview of the current state of the field, what can be expected in the future and some practical considerations for the use of cyclic nucleotide analogues in biological systems.

cyclic nucleotide analogues
2′,3′-cGAMP
cAMP
cGMP
cyclic nucleotide binding proteins


The Application of Mucoadhesive Chitosan Nanoparticles in Nasal Drug Delivery.

Abstract: Mucosal delivery of antigens can induce both humoral and cellular immune responses. Particularly, the nasal cavity is a strongly inductive site for mucosal immunity among several administration routes, as it is generally the first point of contact for inhaled antigens. However, the delivery of antigens to the nasal cavity has some disadvantages such as rapid clearance and disposition of inhaled materials. For these reasons, remarkable efforts have been made to develop antigen delivery systems which suit the nasal route. The use of nanoparticles as delivery vehicles enables protection of the antigen from degradation and sustains the release of the loaded antigen, eventually resulting in improved vaccine and/or drug efficacy. Chitosan, which exhibits low toxicity, biodegradability, good cost performance, and strong mucoadhesive properties, is a useful material for nanoparticles. The present review provides an overview of the mucosal immune response induced by nanoparticles, recent advances in the use of nanoparticles, and nasal delivery systems with chitosan nanoparticles.

chitosan nanoparticles
mucosal delivery system
nasal vaccines


A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma.

Abstract: Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT). Advances in radiopharmaceutical development have unlocked the possibility to assess disease at the molecular level allowing individual diagnosis. This leads to the possibility of choosing a tailored, targeted approach for therapeutic modalities. Therapeutic modalities based on radiopharmaceuticals are an exciting development with great potential to promote a personalised approach to medicine. However, an effective targeted radionuclide therapy (TRT) for the treatment of GB entails caveats and requisites. This review provides an overview of existing nuclear imaging and TRT strategies for GB. A critical discussion of the optimal characteristics for new GB targeting therapeutic radiopharmaceuticals and clinical indications are provided. Considerations for target selection are discussed, i.e. specific presence of the target, expression level and pharmacological access to the target, with particular attention to blood-brain barrier crossing. An overview of the most promising radionuclides is given along with a validation of the relevant radiopharmaceuticals and theranostic agents (based on small molecules, peptides and monoclonal antibodies). Moreover, toxicity issues and safety pharmacology aspects will be presented, both in general and for the brain in particular.

Bolcaen|Julie|J| Kleynhans|Janke|J| Nair|Shankari|S| Verhoeven|Jeroen|J| Goethals|Ingeborg|I| Sathekge|Mike|M| Vandevoorde|Charlot|C| Ebenhan|Thomas|T|

glioblastoma
targeted radionuclide therapy
theranostics
PET SPECT imaging
radiochemistry


Accuracy of a modified World Health Organization Disability Assessment Schedule 2.0 as an assessment tool for predicting return-to-work among patients with traumatic brain injury.

Abstract: Purpose: Patients with traumatic brain injury often experience cognition-related problems and difficulty in returning to work. This study analyzed the accuracy of a modified version of World Health Organization Disability Assessment Schedule 2.0 for predicting the return-to-work status of working-age patients diagnosed with traumatic brain injury more than 6 months ago.Materials and methods: We conducted a cross-sectional survey from a nationwide disability database. This study analyzed the data of 1312 patients diagnosed with traumatic brain injury (aged 20-60 years) more than 6 months ago from the Taiwan Data Bank of Persons with Disability for the period from July 2012 to January 2014. The demographic data and modified World Health Organization Disability Assessment Schedule 2.0 standardized scores of patients with traumatic brain injury who could and could not return to work (return-to-work and nonreturn-to-work groups, respectively) were analyzed. Receiver operating characteristic curve analysis was performed to investigate the prediction accuracy of the modified World Health Organization Disability Assessment Schedule 2.0 for predicting the return-to-work status, and the optimal cutoff point was determined using the Youden index. Binary logistic regression was used to determine the predictors of the return-to-work status of the participants.Results: The modified World Health Organization Disability Assessment Schedule 2.0 scores in all domains were lower in the return-to-work group than in the nonreturn-to-work group. Receiver operating characteristic analysis revealed the high accuracy of the summary scores of the modified World Health Organization Disability Assessment Schedule 2.0 (area under the curve >0.8). Binary logistic regression revealed that patients with standardized modified World Health Organization Disability Assessment Schedule 2.0 summary scores less than 39.50 were 11.20 (95% confidence interval, 4.80-26.14; p < 0.001) times more likely to return to work than patients with scores more than 39.50.Conclusions: The modified World Health Organization Disability Assessment Schedule 2.0 can be used as an objective and reliable assessment tool for predicting the return-to-work status of working-age patients with traumatic brain injury. This tool can facilitate goal setting and rehabilitation strategy design to enable patients with traumatic brain injury to return to work.Implications for rehabilitationSummary scores of six domains of a modified World Health Organization Disability Assessment Schedule 2.0 had better accuracy of predicting the opportunity to return to work among traumatic brain injury patients than each domain.Sex, education level and severity of impairment were related to the opportunity to return to work in traumatic brain injury patients.Higher disability scores from a modified version of the World Health Organization Disability Assessment Schedule 2.0 were associated with less opportunity to return to work and can be referenced for establishing effective rehabilitation strategies for facilitating return to work among persons with traumatic brain injury.

Huang|Shih-Wei|SW| Chang|Kwang-Hwa|KH| Escorpizo|Reuben|R| Liou|Tsan-Hon|TH|0000-0002-0959-4023

International Classification of Functioning


How does the activity level of the parents influence their children's activity? The contemporary life in a world ruled by electronic devices.

Abstract:
Introduction
Apart from many positive changes associated with technical civilization, there are also - from the health point of view - some threats. The reduction in the level of physical activity is one of them. The aim of the study was to investigate whether there are any relationships between children's physical activity and behaviors, and to assess the impact of the adults' activity on their children's habits.

Material and methods
The study involved a group of 340 children aged 7-12 years (mean age: 9.81 ±1.7) and their parents. In order to evaluate children's physical activity and the amount of time that they spend with electronic devices, an original questionnaire and the IPAQ questionnaire were used.

Results
Children usually use electronic devices between 2 and 7 days per week (mean: 4.74 ±0.86), regardless of sex (p > 0.09) and spend between 5 and 1620 min per week (mean: 459.46 ±308.1) with their mobile phone, tablet, PCs and TVs. 67.92% of boys and 69.61% of girls lead an active lifestyle. The children's activity level depends on their parents' level of activity (p < 0.000001). Parents of semi-active children lead a lifestyle with a moderate level of physical activity.

Conclusions
The level of physical activity in younger children depends on the children's relationship with their parents and their level of activity. Children spend a lot of free time with their electronic devices. It is necessary to develop and implement activities intended to raise awareness of children and their families about the effects of hypokinesis.

Brzęk|Anna|A| Strauss|Markus|M| Przybylek|Bianca|B| Dworrak|Tarja|T| Dworrak|Birgit|B| Leischik|Roman|R|

activity
electronic device time
inactivity
obesity
sedentary life


Ultrasound versus MRI: is there a difference in measurements of the fetal lateral ventricles?

Abstract:
OBJECTIVE
To evaluate whether fetal brain lateral ventricle measurements differ between ultrasound (US) and MRI.

METHODS
We evaluated 115 fetuses with US and MRI performed within 24 h of each other. Ventricular measurements were performed in the axial plane at the level of the atria for both modalities and the right and left ventricles were evaluated separately. We compared mean measurements; mean differences, association with gestational age (GA), association with the presence of a brain anomaly, and agreement between MRI and US.

RESULTS
The LV and RV were measured in 65 and 64 cases, respectively. LV and RV size estimates were significantly greater when measured by MRI compared with US (p < 0.001). Therefore, LV and RV were 0.87 mm and 0.89 mm larger in MRI versus US, respectively. Neither GA at measurement or presence/absence of a brain anomaly was significantly associated with differences in measurements. When comparing the agreement between the US and MRI measurements for ventriculomegaly; the kappa level of agreement for the LV and RV was 0.74 for each.

CONCLUSION
MRI measurements of ventricles are significantly larger than the measurements by US by ∼1 mm. There is a good level of agreement when categorizing by normal, mild and severe ventriculomegaly.

Behrendt|Nicholas|N|
Zaretsky|Michael V|MV|
West|Nancy A|NA|
Galan|Henry L|HL|
Crombleholme|Timothy M|TM|
Meyers|Mariana L|ML|

Fetal brain
ventricular measurement
fetal MRI
prenatal ultrasound


Soil Bacterial and Archaeal Communities and Their Potential to Perform N-Cycling Processes in Soils of Boreal Forests Growing on Well-Drained Peat.

Abstract: Peatlands are unique wetland ecosystems that cover approximately 3% of the world's land area and are mostly located in boreal and temperate regions. Around 15 Mha of these peatlands have been drained for forestry during the last century. This study investigated soil archaeal and bacterial community structure and abundance, as well as the abundance of marker genes of nitrogen transformation processes (nitrogen fixation, nitrification, denitrification, and dissimilatory nitrate reduction to ammonia) across distance gradients from drainage ditches in nine full-drained, middle-aged peatland forests dominated by Scots pine, Norway spruce, or Downy birch. The dominating tree species had a strong effect on the chemical properties (pH, N and C/N status) of initially similar Histosols and affected the bacterial and archaeal community structure and abundance of microbial groups involved in the soil nitrogen cycle. The pine forests were distinguished by having the lowest fine root biomass of trees, pH, and N content and the highest potential for N fixation. The distance from drainage ditches affected the spatial distribution of bacterial and archaeal communities (especially N-fixers, nitrifiers, and denitrifiers possessing nosZ clade II), but this effect was often dependent on the conditions created by the dominance of certain tree species. The composition of the nitrifying microbial community was dependent on the soil pH, and comammox bacteria contributed significantly to nitrate formation in the birch and spruce soils where the pH was higher than 4.6. The highest N2O emission was recorded from soils with higher bacterial and archaeal phylogenetic diversity such as birch forest soils. This study demonstrates that the long-term growth of forests dominated by birch, pine, and spruce on initially similar organic soil has resulted in tree-species-specific changes in the soil properties and the development of forest-type-specific soil prokaryotic communities with characteristic functional properties and relationships within microbial communities.

Truu|Marika|M| Nõlvak|Hiie|H| Ostonen|Ivika|I| Oopkaup|Kristjan|K| Maddison|Martin|M| Ligi|Teele|T| Espenberg|Mikk|M| Uri|Veiko|V| Mander|Ülo|Ü| Truu|Jaak|J|

soil prokaryotic community
N-cycling genes
drained peatland forests
nitrogen gas emission
plant root biomass


Open surgical secondary procedures after thoracic endovascular aortic repair.

Abstract:
OBJECTIVES
Improved outcomes of thoracic endovascular aortic repair (TEVAR) compared with open repair have changed the therapeutic paradigm of thoracic aortic lesions. As the number of TEVAR survivors has grown, reports of complications have similarly increased. Although secondary endovascular rescue measures are often undertaken, patients with serious complications are often converted, ultimately, to open repair. The aim of this study was to assess causes and midterm results of open surgical secondary procedures after thoracic endovascular aortic repair.

METHODS
A total of 236 patients underwent TEVAR. Fourteen of these patients required open repair because of six aortobronchial fistulas, four retrograde type A dissections, two aneurysm enlargement without endoleak, one thoracic stent-graft collapse, and one aortoesophageal fistula. Eight (57.1%) patients underwent surgical repair using cardiopulmonary bypass. Six stent-grafts were totally removed, and eight stent-grafts were left in situ. Four patients underwent supracoronary ascending aorta replacement, and one an extensive replacement of the aortic arch through sternotomy. Three patients had descending aortic replacement through left thoracotomy combined with a total esophagectomy in one case. One patient was treated by ligation of the aortic arch, ascending to supraceliac abdominal aorta bypass and stent-graft explantation. One patient was treated by exclusion bypass of the descending thoracic aorta. Pulmonary resection and large pleural or intercostal muscle flap interposition to wrap the stent-graft left in situ was done in four cases of aortobronchial fistula.

RESULTS
All patients survived the surgical procedure. Ten patients (71%) had an uneventful postoperative course. There were two in-hospital deaths (14.3%). Both died from multi-organ failure in the early postoperative course after surgical repair of a stent-graft infection and an aortoesophageal fistula. One patient suffered a definitive paraplegia and a secondary aortoesophageal fistula requiring reoperation for esophageal repair. One patient, treated by pulmonary resection and flap interposition to wrap the stent-graft, underwent stent-graft explantation and in situ descending aortic replacement because of stent-graft reinfection. Actuarial survival was 87.7% after a mean follow-up of 26.3 months (range 9-72 months).

CONCLUSIONS
Complications or prevention of complications after TEVAR either due to device failure or adverse events may require conversion to open repair or additional open surgical procedure. Open repair can be performed by a team experienced in management of diseases of the thoracic aorta and a low mortality rate achieved despite the precarious preoperative conditions and complex aortic pathologies of patients.

Canaud|L|L|
Alric|P|P|
Gandet|T|T|
Ozdemir|B A|BA|
Albat|B|B|
Marty-Ane|C|C|

Thoracic endovascular aortic repair
Stent-graft
Thoracic aorta
Surgical conversion


Social determinants of health in teenage girls involved with sexual exploitation on downtown streets late at night.

Abstract: The purpose of this study was to chronicle the experiences of teenage girls who stay downtown late at night and are involved in sexual exploitation, and to clarify characteristics of their social circumstances and social determinants of health: socioeconomic status and educational opportunities. Between November 2009 and June 2013, we spoke with 89 adolescents who were loitering late at night in downtown Nagoya, Japan. We focused our research efforts on a case series of 22 girls who were 14-19 years of age and were involved in sexual exploitation. Semi-structured interviews were performed with the use of a questionnaire on the girls' sexual and mental health, families, school life, living conditions, and future aspirations. Along with the questionnaires, we analyzed case series interviews with a qualitative approach (narratives-under-analysis by in-depth understanding in context). Nine girls worked in the sex industry, while thirteen were independent sex workers. Our observations included child maltreatment, unstable families, distressing school life, insufficient education, and inappropriate relationships with gangs and similar organizations. Moreover, an illegal sex market was linked with these gang associations. Despite their severe living conditions, most of them hoped to have happy families someday. To provide support to this vulnerable population and support their life aspirations, improvement of public health, social welfare, education, and school health systems should be considered carefully.

Tanaka|Tsutomu|T| Furuhashi|Tadaaki|T| Ogawa|Toyoaki|T| Yabushita|Momoko|M|

social determinants of health
teenage girls
sexual exploitation
socioeconomic status and education
social risk


Parametrically Guided Generalized Additive Models with Application to Mergers and Acquisitions Data.

Abstract: Generalized nonparametric additive models present a flexible way to evaluate the effects of several covariates on a general outcome of interest via a link function. In this modeling framework, one assumes that the effect of each of the covariates is nonparametric and additive. However, in practice, often there is prior information available about the shape of the regression functions, possibly from pilot studies or exploratory analysis. In this paper, we consider such situations and propose an estimation procedure where the prior information is used as a parametric guide to fit the additive model. Specifically, we first posit a parametric family for each of the regression functions using the prior information (parametric guides). After removing these parametric trends, we then estimate the remainder of the nonparametric functions using a nonparametric generalized additive model, and form the final estimates by adding back the parametric trend. We investigate the asymptotic properties of the estimates and show that when a good guide is chosen, the asymptotic variance of the estimates can be reduced significantly while keeping the asymptotic variance same as the unguided estimator. We observe the performance of our method via a simulation study and demonstrate our method by applying to a real data set on mergers and acquisitions.

Fan|Jianqing|J| Maity|Arnab|A| Wang|Yihui|Y| Wu|Yichao|Y|

parametric guide
generalized additive model
mergers and acquisitions
leveraged buyout
local polynomial


Does crystallography need a new name?

Abstract: Our notion of crystallography and how we communicate it needs to adapt to the major emerging frontiers of science in order to ensure that our community continues to thrive.


iCAGES: integrated CAncer GEnome Score for comprehensively prioritizing driver genes in personal cancer genomes.

Abstract: Cancer results from the acquisition of somatic driver mutations. Several computational tools can predict driver genes from population-scale genomic data, but tools for analyzing personal cancer genomes are underdeveloped. Here we developed iCAGES, a novel statistical framework that infers driver variants by integrating contributions from coding, non-coding, and structural variants, identifies driver genes by combining genomic information and prior biological knowledge, then generates prioritized drug treatment. Analysis on The Cancer Genome Atlas (TCGA) data showed that iCAGES predicts whether patients respond to drug treatment (P = 0.006 by Fisher's exact test) and long-term survival (P = 0.003 from Cox regression). iCAGES is available at http://icages.wglab.org .

Dong|Chengliang|C| Guo|Yunfei|Y| Yang|Hui|H| He|Zeyu|Z| Liu|Xiaoming|X| Wang|Kai|K|

Cancer genomics
TCGA
Machine learning
Precision medicine
Precision oncology


The relationship between living in urban and rural areas of Scotland and children's physical activity and sedentary levels: a country-wide cross-sectional analysis.

Abstract:
BACKGROUND
Living in urban or rural environments may influence children's levels of physical activity and sedentary behaviours. We know little about variations in device-measured physical activity and sedentary levels of urban and rural children using nationally representative samples, or if these differences are moderated by socioeconomic factors or seasonal variation. Moreover, little is known about the influence of 'walkability' in the UK context. A greater understanding of these can better inform intervention strategies or policy initiatives at the population level.

METHODS
Country-wide cross-sectional study in Scotland in which 774 children (427 girls, 357 boys), aged 10/11 years, wore an accelerometer on one occasion for at least four weekdays and one weekend day. Mean total physical activity, time spent in sedentary, light, and moderate-to-vigorous physical activity (MVPA), per day were extracted for weekdays, weekend days, and all days combined. Regression analyses explored associations between physical activity outcomes, urban/rural residence, and a modified walkability index (dwelling density and intersection density); with interactions fitted for household equivalised income and season of data collection. Sensitivity analyses assessed variation in findings by socioeconomic factors and urbanicity.

RESULTS
Rural children spent an average of 14 min less sedentary (95% CI of difference: 2.23, 26.32) and 13 min more in light intensity activity (95% CI of difference, 2.81, 24.09) per day than those from urban settlements. No urban-rural differences were found for time spent in MVPA or in total levels of activity. Our walkability index was not associated with any outcome measure. We found no interactions with household equivalised income, but there were urban/rural differences in seasonal variation; urban children engaged in higher levels of MVPA in the spring months (difference: 10 mins, p = 0.06, n.s) and significantly lower levels in winter (difference: 8.7 mins, p = 0.036).

CONCLUSIONS
Extrapolated across one-year, rural children would accumulate approximately 79 h (or just over 3 days) less sedentary time than urban children, replacing this for light intensity activity. With both outcomes having known implications for health, this finding is particularly important. Future work should prioritise exploring the patterns and context in which these differences occur to allow for more targeted intervention/policy strategies.

Urban and rural
Physical activity
Season
Income
Children and young people


Optic nerve head morphology in young patients after antiglaucomatous filtering surgery.

Abstract:
PURPOSE
To compare the optic nerve head appearance in glaucomatous eyes before and after marked reduction of intraocular pressure (IOP).

METHODS
The hospital-based observational case-series study included selected glaucoma patients for whom optic disc photographs taken before and 1 week to 5 months after surgical reduction of IOP were morphometrically examined.

RESULTS
The study included 23 eyes of 16 patients (mean age: 28.7 ± 6.0 years). Mean preoperative IOP was 31.6 ± 7.7 mmHg (22-52 mmHg), and mean IOP drop was 21.5 ± 8.4 mmHg (11-45 mmHg). The horizontal disc diameter decreased significantly (p < 0.001) after surgery, while the vertical disc diameter did not change markedly (p = 0.54). The width of the neuroretinal rim increased significantly in all disc quadrants (all p-values ≤ 0.01), optic cup depth decreased (p < 0.001), and reflectivity of the inner retinal surface increased significantly (p < 0.001). Some eyes showed a pronounced reduction in beta zone of parapapillary atrophy parallel to an increase in horizontal disc diameter, and some eyes showed an enlargement of beta zone parallel to a reduction in horizontal disc diameter.

CONCLUSIONS
After marked reduction of high IOP, some eyes of young adult patients with glaucoma can show a horizontal shrinkage of the optic nerve head, in addition to a partial restoration of the neuroretinal rim and a flattening of the optic cup. In addition, beta zone of parapapillary atrophy can decrease or increase, complementarily to changes in the horizontal disc diameter. These findings may be of interest for the biomechanics of the optic nerve head and the precision of imaging techniques.

Panda-Jonas|Songhomitra|S|
Xu|Liang|L|
Yang|Hua|H|
Wang|Ya X|YX|
Jonas|Shefali B|SB|
Jonas|Jost B|JB|

optic nerve head
intraocular pressure
glaucoma
optic disc
parapapillary atrophy


Studies towards the synthesis of medermycin via Dötz benzannulation.

Abstract: The C-arylglycosides are available in enantiomerically pure form via the Dötz benzannulation reaction between Fischer alkenyl chromium carbene complexes and alkynes; it also could be converted to a precursor of medermycin by O-carbamate directed ipso bromination and nitrile substitution in good overall yields.

Qu|Chunrong|C|
Tang|Erqing|E|
Loeppky|Richard|R|
Deng|Zixin|Z|
Pulley|Shon R|SR|
Hong|Xuechuan|X|

Dötz benzannulation
C-arylglycoside
ipso bromination
Fischer carbene complex
Streptomyces sp


Location and direction dependence in the 3D MTF for a high-resolution CT system.

Abstract:
PURPOSE
The purpose of this study was to quantify location and direction-dependent variations in the 3D modulation transfer function (MTF) of a high-resolution CT scanner with selectable focal spot sizes and resolution modes.

METHODS
The Aquilion Precision CT scanner (Canon Medical Systems) has selectable 0.25 mm or 0.5 mm detectors (by binning) in both the axial (x-y) and detector array width (z) directions. For the x-y and z orientations, detectors are configured (x-y) = 0.5 mm/(z) = 0.5 mm for normal resolution (NR), 0.25/0.5 mm for high resolution (HR), and 0.25/0.25 mm for super high resolution (SHR). Six focal spots (FS1-FS6) range in size from 0.4 (x-y) × 0.5 mm (z) for FS1 to 1.6 × 1.4 mm for FS6. Phantoms fabricated from spherical objects were positioned at radial distances of 0, 4.0, 7.5, 11.0, 14.5, and 18.5 cm. Axial and helical acquisitions were utilized and reconstructed using filtered back projection with the FC18 "Body," FC30 "Bone," and FC81 "Bone Sharp" kernels. The reconstructions were used to measure a 1D slice of the 3D MTF by oversampling the 3D ESF in the axial plane [MTF(fr ); φ = 0°)], 45° out of the axial plane [MTF(fr ); φ = 45°)], in the longitudinal direction [MTF(fr ); φ = 80°)], and along the radial and azimuthal directions within the axial plane.

RESULTS
The MTF(fr ); φ = 45°) drops to 10% (f10 ) at 1.20, 1.45, and 2.06 mm-1 for NR, HR, and SHR, respectively, for a helical acquisition with FS1, FC30, and r = 4 cm from the isocenter. The MTF(fr ); φ = 45°) includes contributions of both the axial-plane MTF (f10  = 1.10, 2.04, and 2.01 mm-1 ) and the longitudinal MTF (f10  = 1.17, 1.18, and 1.82 mm-1 ) for the NR, HR, and SHR modes, respectively. For SHR, the axial scan mode showed a 15-25% improvement over helical mode in the longitudinal resolution. Helical pitch, ranging from 0.569 to 1.381, did not appreciably affect the 3D resolution (<2%). The radial MTFs across the axial field of view (FOV) showed dependencies on the focal spot length in z; for example, for SHR with FS2 (0.6 × 0.6 mm), f10 at  r = 11 cm was within 17% of the value at r = 4 cm, but for SHR with FS3 (0.6 × 1.3), the reduction in f10 was 46% from 4 to 11 cm from the isocenter. The azimuthal MTF also decreased as r increased but less so for longer gantry rotation times and smaller focal spot dimensions in the axial plane. The longitudinal MTF was minimally affected (<11%) by position in the FOV and was principally affected by the focal spot length in the z-dimension.

CONCLUSIONS
The 3D MTF was measured throughout the FOV of a high-resolution CT scanner, quantifying the advantages of different resolution modes and focal spot sizes on the axial-plane and longitudinal MTF. Reconstruction kernels were shown to impact axial-plane resolution, imparting non-isotropic 3D resolution characteristics. Focal spot size (both in x-y and in z) and gantry rotation time play important roles in preserving the high-resolution characteristics throughout the field of view for this new high-resolution CT scanner technology.

Hernandez|Andrew M|AM|
Wu|Pengwei|P|
Mahesh|Mahadevappa|M|
Siewerdsen|Jeffrey H|JH|
Boone|John M|JM|

D015898:Tomography Scanners, X-Ray Computed

high-resolution CT
modulation transfer function
image quality
multi-detector CT
spatial resolution


Meeting the orphan: early relational trauma, synchronicity and the psychoid.

Abstract: In this paper I attempt to show how deep engagement, which is gradually developed within the relational container, can facilitate access to the psychoid dimension of the unconscious characterized by a quality of interconnectedness. The resulting synchronistic experiences can support and strengthen this container as well as having profound re-connecting impact on the people involved. With this in mind, I suggest that openness to this dimension can be very important in working with the issues of loss, abandonment, aloneness and mistrust in human connections - the symbolic domain of the orphan. Although none of the patients I describe in this paper were actual orphans, symbolically the orphan theme featured significantly in their processes, in that early relational trauma left them feeling profoundly alone and unable to trust human contact. For this reason, the most important yet difficult challenge of the work was to help them restore their sense of connectedness to themselves and to others. I consider the role of attunement and reverie as the basis for facilitating this openness and propose that such openness can be seen as a feature of the analytic attitude in its own right and that it constitutes a unique contribution of the Jungian approach to working with early trauma.

intergenerational/transgenerational transmission of trauma

intergenerationale/transgenerationale Weitergabe von Trauma

transmisión intergeneracional/transgeneracional del trauma

transmission intergénérationnelle/transgénérationnelle du traumatisme

trasmissione intergenerazionale/transgenerazionale del trauma

грезоподобное состояние

межпоколенческая передача травмы

ранняя травма отношений

孤儿, 梦, 做梦, 共时性, 精神力量, 早期关系创伤, 代际间/跨代际创伤传递, 退行

P P P P U U U U U M U U U M M U U U U U U U U U U U U U U U U U U M U M M M U U U U U U U U U M


One thousand cases of cobalt-based high dose rate brachytherapy treated at a tertiary care center: A retrospective study.

Abstract:
PURPOSE
This is a study of our experience with Co-60 high dose rate brachytherapy (HDR BT) from a tertiary care center.

MATERIALS AND METHODS
One thousand patients were treated with Cobalt-based HDR BT for more than 6 years. The practice of BT was analyzed for clinical outcome, physical, radiobiological, and technical aspects.

RESULTS
Among those 1000 patients, 906 (90.6%) patients had gynecologic cancer, 29 (2.9%) patients had intraluminal BT, 63 (6.3%) hadhead &neck (2.1%), keloid (2.1%) and mold BT (2.1%), and 2 (0.2%) had sarcoma. Dose rate decreased by 48.9%, and treatment time increased from 9.33 to 18.27 min over 5 years. No patients treatment was abandoned because of machine-related problems.

CONCLUSION
Cobalt-based HDR BT is preferable in terms of lesser source exchanges, relatively uniform treatment time, quality assurance requirement, and cost.

Manur Gururajachar|Janaki|J|
Thangaraj|Revathy|R|
Thiruraju|Arul Ponni|AP|
Agrahara Srinivasa|Kirthi Koushik|KK|
Charith Alva|Ram|R|
Somashekhar Kumar|Mohan|M|


Recent progress on fingerprint visualization and analysis by imaging ridge residue components.

Abstract: Fingerprints have long been and are still considered to be the gold standard for personal identification in forensic investigations. Developing or enhancing the visualization of invisible fingerprints, so-called latent fingerprints (LFPs), remains to be the core subject in forensic science. Moreover, the past few years have witnessed a renewal of research interest in the possibility that a fingerprint can provide additional information than just identification of individuals, such as personal traits, the presence of human metabolites with diagnostic values, and the evidence of contact with explosives or illicit drugs. Fingerprint analysis has manifested itself as a research area far beyond the scope of forensics, to which not only conventional fingerprint examiners but also researchers from chemistry, biochemistry, medical science, material science, and nanotechnology fields have made significant contributions in recent years. Beginning with a brief overview of the components present in LFP residue that essentially determines which method or reagent will give the best visualization result, this paper reviews the progress since 2007 on new reagents and methods developed for LFP visualization and simultaneous detection of specific chemicals present in the LFP residue, with an emphasis on the utilization of mass spectrometry, infrared spectroscopy, nanoparticles, and immunogenic and nucleic acid reagents.

Visualization
Latent fingerprints
Forensic science
Analytical chemistry
Component recognition


3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances.

Abstract: 3D printing, an additive manufacturing based technology for precise 3D construction, is currently widely employed to enhance applicability and function of cell laden scaffolds. Research on novel compatible biomaterials for bioprinting exhibiting fast crosslinking properties is an essential prerequisite toward advancing 3D printing applications in tissue engineering. Printability to improve fabrication process and cell encapsulation are two of the main factors to be considered in development of 3D bioprinting. Other important factors include but are not limited to printing fidelity, stability, crosslinking time, biocompatibility, cell encapsulation and proliferation, shear-thinning properties, and mechanical properties such as mechanical strength and elasticity. In this review, we recite recent promising advances in bioink development as well as bioprinting methods. Also, an effort has been made to include studies with diverse types of crosslinking methods such as photo, chemical and ultraviolet (UV). We also propose the challenges and future outlook of 3D bioprinting application in medical sciences and discuss the high performance bioinks.

Derakhshanfar|Soroosh|S| Mbeleck|Rene|R| Xu|Kaige|K| Zhang|Xingying|X| Zhong|Wen|W| Xing|Malcolm|M|

Bioprinting
Review
3D printing
Extrusion
Hydrogel
Inkjet
Laser-assisted
Stereolithography


Characterization and Application of Gelatin Films with Pecan Walnut and Shell Extract (Carya illinoiensis).

Abstract: Phenolic compounds that come from natural products are a good option for minimizing lipid oxidation. It should be noted that these are not only introduced directly into the food, but also incorporated into edible biofilms. In contact with food, they extend its useful life by avoiding contact with other surface and preventing deterioration air, one of the main objectives. In particular, gelatin is a biopolymer that has a great potential due to its abundance, low cost and good film-forming capacity. The aim of this study has been to design and analyse gelatin films that incorporate bioactive compounds that come from the walnut and a by-product, the walnut shell. The results showed that mechanical and water vapor barrier properties of the developed films varied depending on the concentration of the walnut, shell and synthetic antioxidant. With increasing walnut concentration (15%) the permeability to water vapor (0.414 g·mm/m2·day·Pascal, g·mm/m2·day·Pa) was significantly lower than the control (5.0368 g·mm/m2·day·Pa). Furthermore, in the new films the elongation at the break and Young's modulus decrease by six times with respect to the control. Films with pure gelatin cannot act as an antioxidant shield to prevent food oxidation, but adding pecan walnut (15% concentration) presents 30% inhibition of the DPPH stable radical. Furthermore, in the DSC, the addition of walnut (15 and 9% concentrations), showed the formation of big crystals; which could improve the thermal stability of gelatin films. The use of new gelatin films has shown good protection against the oxidation of beef patties, increasing the useful lifetime up to nine days, compared to the control (3-4 days), which opens up a big field to the commercialization of meat products with lower quantities of synthetic products.

pecan walnut
shell
antioxidants
meat
gelatin based films
physicochemical


Lipopeptide-Coated Iron Oxide Nanoparticles as Potential Glycoconjugate-Based Synthetic Anticancer Vaccines.

Abstract: Although iron oxide magnetic nanoparticles (NPs) have been widely utilized in molecular imaging and drug delivery studies, they have not been evaluated as carriers for glycoconjugate-based anticancer vaccines. Tumor-associated carbohydrate antigens (TACAs) are attractive targets for the development of anticancer vaccines. Due to the weak immunogenicity of these antigens, it is highly challenging to elicit strong anti-TACA immune responses. With their high biocompatibilities and large surface areas, magnetic NPs were synthesized for TACA delivery. The magnetic NPs were coated with phospholipid-functionalized TACA glycopeptides through hydrophobic-hydrophobic interactions without the need for any covalent linkages. Multiple copies of glycopeptides were presented on NPs, potentially leading to enhanced interactions with antibody-secreting B cells through multivalent binding. Mice immunized with the NPs generated strong antibody responses, and the glycopeptide structures important for high antibody titers were identified. The antibodies produced were capable of recognizing both mouse and human tumor cells expressing the glycopeptide, resulting in tumor cell death through complement-mediated cytotoxicities. These results demonstrate that magnetic NPs can be a new and simple platform for multivalently displaying TACA and boosting anti-TACA immune responses without the need for a typical protein carrier.

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

magnetic nanoparticles
glycopeptide
MUC1
cancer vaccine
immunology


The DEN and CCl4 -Induced Mouse Model of Fibrosis and Inflammation-Associated Hepatocellular Carcinoma.

Abstract: Human hepatocellular carcinoma (HCC) develops most often as a complication of fibrosis or cirrhosis. Although most human studies of HCC provide crucial insights into the molecular signatures of HCC, they seldom address its etiology. Mouse models provide essential tools for investigating the pathogenesis of HCC, but the majority of rodent cancer models do not feature liver fibrosis. Detailed here is a protocol for an experimental mouse model of HCC that arises in association with advanced liver fibrosis. The disease model is induced by a single injection of N-nitrosodiethylamine (DEN) at 2 weeks of age followed by repeated administration of carbon tetrachloride (CCl4 ) from 8 weeks of age for up to 14 consecutive weeks. A dramatic potentiation of liver tumor incidence is observed following administration of DEN and CCl4 , with 100% of mice developing liver tumors at 5 months of age. This model has been employed for studying the molecular mechanisms of fibrogenesis and HCC development, as well as for cancer hazard/chemotherapy testing of drug candidates. © 2021 Wiley Periodicals LLC. Basic Protocol: The DEN and CCl4 -induced mouse model of fibrosis and inflammation-associated hepatocellular carcinoma.

Uehara|Takeki|T|
Pogribny|Igor P|IP|
Rusyn|Ivan|I|

fibrosis cancer liver mechanisms genotoxic


Structure and characterization of a class 3B proline utilization A: Ligand-induced dimerization and importance of the C-terminal domain for catalysis.

Abstract: The bifunctional flavoenzyme proline utilization A (PutA) catalyzes the two-step oxidation of proline to glutamate using separate proline dehydrogenase (PRODH) and l-glutamate-γ-semialdehyde dehydrogenase active sites. Because PutAs catalyze sequential reactions, they are good systems for studying how metabolic enzymes communicate via substrate channeling. Although mechanistically similar, PutAs vary widely in domain architecture, oligomeric state, and quaternary structure, and these variations represent different structural solutions to the problem of sequestering a reactive metabolite. Here, we studied PutA from Corynebacterium freiburgense (CfPutA), which belongs to the uncharacterized 3B class of PutAs. A 2.7 Å resolution crystal structure showed the canonical arrangement of PRODH, l-glutamate-γ-semialdehyde dehydrogenase, and C-terminal domains, including an extended interdomain tunnel associated with substrate channeling. The structure unexpectedly revealed a novel open conformation of the PRODH active site, which is interpreted to represent the non-activated conformation, an elusive form of PutA that exhibits suboptimal channeling. Nevertheless, CfPutA exhibited normal substrate-channeling activity, indicating that it isomerizes into the active state under assay conditions. Sedimentation-velocity experiments provided insight into the isomerization process, showing that CfPutA dimerizes in the presence of a proline analog and NAD+ These results are consistent with the morpheein model of enzyme hysteresis, in which substrate binding induces conformational changes that promote assembly of a high-activity oligomer. Finally, we used domain deletion analysis to investigate the function of the C-terminal domain. Although this domain contains neither catalytic residues nor substrate sites, its removal impaired both catalytic activities, suggesting that it may be essential for active-site integrity.

Korasick|David A|DA|
Gamage|Thameesha T|TT|
Christgen|Shelbi|S|
Stiers|Kyle M|KM|
Beamer|Lesa J|LJ|
Henzl|Michael T|MT|
Becker|Donald F|DF|
Tanner|John J|JJ|

dehydrogenase
substrate channeling
oligomerization
X-ray crystallography
analytical ultracentrifugation
bifunctional enzyme
enzyme kinetics
flavoprotein


Joint crisis plans and psychiatric advance directives in German psychiatric practice.

Abstract: This study explores the attitude of German psychiatrists in leading positions towards joint crisis plans and psychiatric advance directives. This topic was examined by contacting 473 medical directors of German psychiatric hospitals and departments. They were asked to complete a questionnaire developed by us. That form contained questions about the incidence and acceptance of joint crisis plans and psychiatric advance directives and previous experiences with them. 108 medical directors of psychiatric hospitals and departments responded (response rate: 22.8%). Their answers demonstrate that in their hospitals these documents are rarely used. Among the respondents, joint crisis plans are more accepted than psychiatric advance directives. There is a certain uncertainty when dealing with these instruments. Our main conclusion is that German psychiatry needs an intensified discussion on the use of instruments for patients to constitute procedures for future critical psychiatric events. For this purpose it will be helpful to collect more empirical data. Furthermore, the proposal of joint crisis plans in psychiatric hospitals and departments should be discussed as well as the possibility of consulting an expert during the preparation of a psychiatric advance directive.

Radenbach|Katrin|K| Falkai|Peter|P| Weber-Reich|Traudel|T| Simon|Alfred|A|

Psychiatry
Autonomy
Informed Consent
Legal Aspects


Vestibular neuritis in children and adolescents: Clinical features and recovery.

Abstract:
OBJECTIVE
Describe the clinical presentation and recovery of vestibular neuritis in children and adolescents.

STUDY DESIGN
Retrospective case series.

SETTING
Pediatric tertiary care center.

SUBJECTS AND METHODS
Eleven patients diagnosed with vestibular neuritis were identified from a database of 301 patients evaluated at our pediatric vestibular clinic from January 2012 through January 2015. Medical records were reviewed to determine clinical presentation, vestibular testing results, treatment, and recovery. Incomplete recovery was defined as residual dizziness or imbalance at most recent follow-up >30 days from symptom onset.

RESULTS
Patients were 5-19 years old (mean 13.1±5.34) and included 6 boys and 5 girls. All presented with a sudden rotational vertigo, imbalance, and nausea for an average of 10 days without other associated symptoms. Testing included rotary chair (8 of 9 abnormal), caloric (2 of 2 abnormal), video head impulse (5 of 8 abnormal), subjective visual vertical (4 of 8 abnormal), and cervical vestibular evoked myogenic potential (0 of 6 abnormal) tests. All patients with incomplete recovery (n=4; 36%) were ≥15 years old at symptom onset. All patients with incomplete recovery that underwent vestibular rehabilitation (n=2) initiated it ≥90 days from symptom onset, while 3 out of 4 patients with complete recovery that underwent vestibular rehabilitation initiated it ≤14 days from symptom onset. Two patients received oral steroids, neither of whom had incomplete recovery.

CONCLUSION
Vestibular neuritis should be considered in pediatric patients with vertigo and may result in longstanding symptoms, particularly in adolescents. The treatment of pediatric vestibular neuritis with rehabilitation and steroids deserves further study.

Brodsky|Jacob R|JR|
Cusick|Brandon A|BA|
Zhou|Guangwei|G|

Vestibular neuronitis, Pediatric dizziness, Pediatric vestibular testing, Childhood vertigo, Video head impulse test


Later adults' cultural life scripts of middle and later adulthood.

Abstract: The cultural life script (CLS) refers to expected prototypical life events, often including life transitions overwhelmingly occurring at ages 11-30. This study outlined CLS events at ages after the majority of these events typically occur. Participants, age 38-76, nominated events they expected a person of their age to experience in the future. Participants rated each event's valence, importance, prevalence, and expected age of occurrence. Events were coded into three categories: the normative CLS for events listed by previous CLS studies, offspring's CLS for experiencing CLS events of offspring, and later adulthood CLS for other events nominated by at least 4% of participants. Results suggest scripted events highlighting positivity and change. Offspring's CLS was more positive and occurred earlier than others. Correlations emerged between event characteristics and well-being. Results affirm the prominence of transitions in memory, and suggest ways that older adults maintain well-being despite a cultural narrative that emphasizes decline.

Cultural life script
transitions
positivity
well-being
semantic memory


A new method to estimate photosynthetic parameters through net assimilation rate-intercellular space CO2 concentration (A-Ci ) curve and chlorophyll fluorescence measurements.

Abstract: Gas exchange (GE) and chlorophyll fluorescence (CF) measurements are widely used to noninvasively study photosynthetic parameters, for example the rates of maximum Rubisco carboxylation (Vcmax ), electron transport rate (J), daytime respiration (Rd ) and mesophyll conductance (gm ). Existing methods for fitting GE data (net assimilation rate-intercellular space CO2 concentration (A-Ci ) curve) are based on two assumptions: gm is unvaried with CO2 concentration in the intercellular space (Ci ); and light absorption (α) and the proportion of quanta absorbed by photosystem II (β) are constant in the data set. These may result in significant bias in estimating photosynthetic parameters. To avoid the above-mentioned hypotheses, we present a new method for fitting A-Ci curves and CF data simultaneously. This method was applied to a data set obtained from cucumber (Cucumis sativus) leaves of various leaf ages and grown under eight different light conditions. The new method had significantly lower root mean square error and a lower rate of failures compared with previously published methods (6.72% versus 24.1%, respectively) and the effect of light conditions on Vcmax and J was better observed. Furthermore, the new method allows the estimation of a new parameter, the fraction of incoming irradiance harvested by photosystem II, and the dependence of gm on Ci .

Moualeu-Ngangue|Dany P|DP|
Chen|Tsu-Wei|TW|
Stützel|Hartmut|H|

photosynthetic parameters
chlorophyll fluorescence
mesophyll conductance
A-Ci curves
fitting method


N-Substituted Pyrrole Derivative 12m Inhibits HIV-1 Entry by Targeting Gp41 of HIV-1 Envelope Glycoprotein.

Abstract: The combination of three or more antiviral agents that act on different targets is known as highly active antiretroviral therapy (HAART), which is widely used to control HIV infection. However, because drug resistance and adverse effects occur after long-term administration, an increasing number of HIV/AIDS patients do not tolerate HAART. It is necessary to continue developing novel anti-HIV drugs, particularly HIV entry/fusion inhibitors. Our group previously identified a small-molecule compound, NB-64, with weak anti-HIV activity. Here, we found that N-substituted pyrrole derivative 12m (NSPD-12m), which was derived from NB-64, had strong anti-HIV-1 activity, and NSPD-12m-treated cells showed good viability. The mechanism of action of NSPD-12m might be targeting the gp41 transmembrane subunit of the HIV envelope glycoprotein, thus inhibiting HIV entry. Site-directed mutagenesis confirmed that a positively charged lysine residue (K574) located in the gp41 pocket region is pivotal for the binding of NSPD-12m to gp41. These findings suggest that NSPD-12m can serve as a lead compound to develop novel virus entry inhibitors.

Qiu|Jiayin|J| Liang|Taizhen|T| Wu|Junyan|J| Yu|Fei|F| He|Xiaoyang|X| Tian|Yuanxin|Y| Xie|Lan|L| Jiang|Shibo|S| Liu|Shuwen|S| Li|Lin|L|

HIV-1 entry inhibitor
cell–cell fusion
gp41 envelope
six-helix bundle
small molecular compound


The dynamic changes of X chromosome inactivation during early culture of human embryonic stem cells.

Abstract: X chromosome inactivation (XCI) is required for dosage compensation of X-linked genes in human female cells. Several previous reports have described the promiscuous XCI status in long-term cultured female human embryonic stem cells (hESCs), and the majority of them exhibit non-random XCI. However, when and how such female hESCs acquire the aberrant XCI states during culture is unknown. Herein, through comparing the XCI states in 18 paired hES cell lines throughout early culture, we revealed a uniform dynamic change during this culture period under a widely used culture condition. The female initial hESCs (ihESCs, P4-P9) expressed XIST RNA, H3K27me3 punctate enrichment and displayed random XCI pattern. By further culturing, the female early hESCs (ehESCs, P20-P30) lost the expression of XIST RNA, H3K27me3 punctate enrichment and exhibited a completely skewed XCI pattern. Importantly, a subset of X-linked genes was up-regulated in ehESCs, including some cancer-related genes. At last, we found 5% physiological oxygen was beneficial for the expression of XIST and H3K27me3 punctate enrichment, but not for the XCI pattern. We conclude that the XCI dynamic change is a frequent epigenetic instability event during early culture, which is accompanied by the up-regulation of some X-linked genes. Furthermore, we emphasize that physiological oxygen is beneficial for XCI fidelity.

Xie|Pingyuan|P| Ouyang|Qi|Q| Leng|Lizhi|L| Hu|Liang|L| Cheng|Dehua|D| Tan|Yueqiu|Y| Lu|Guangxiu|G| Lin|Ge|G|

D002454:Cell Differentiation
D002478:Cells, Cultured
D019175:DNA Methylation
D005260:Female
D006657:Histones
D000066449:Human Embryonic Stem Cells
D006801:Humans
D008856:Microscopy, Fluorescence
D010100:Oxygen
D011401:Promoter Regions, Genetic
D062085:RNA, Long Noncoding
D049951:X Chromosome Inactivation

X chromosome inactivation
Human embryonic stem cells
Epigenetics
Culture alteration
Gene expression regulation


Process, Outcomes and Possible Elimination of Aggregation with Special Reference to Heme Proteins; Likely Remediations of Proteinopathies.

Abstract: Protein folding is a natural phenomenon through which a linear polypeptide possessing necessary information attains three-dimension functionally active conformation. This is a complex and multistep process and therefore, the presence of several intermediary structures could be speculated as a result of protein folding. In in vivo, this folding process is governed by the assistance of other proteins called molecular chaperones and heat shock proteins. Due to the mechanism of protein folding, these intermediary structures remain major challenge for modern biology. Mutation in gene encoding amino acid can cause adverse environmental conditions which may result in misfolding of the linear polypeptide followed by the formation of aggregates and amyloidosis. Aggregation contributes to the pathophysiology of several maladies including diabetes mellitus, Huntington's and Alzheimer's disease. The propensity of native structure to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. During aggregation of a protein, transition from α helix to β sheet is observed, and mainly β sheeted structure is visualised in a mature fibril. Heme proteins are very crucial for major life activities like transport of oxygen and carbon dioxide, synthesis of ATP, role in electron transport chain, and detoxification of free radicals formed during biochemical reactions. Any structural variation in the heme proteins may lead to a fatal response. Hence characterization of the folding intermediates becomes crucial. The characterization has been deciphered with the help of strong denaturants like acetonitrile and TFE. Moreover, possible role of elimination of these aggregates and prevention of protein denaturation is also discussed. Current review deals with the basic process and mechanism of the protein folding in general and the ultimate outcomes of the protein misfolding. Since Native conformation of heme proteins is essential for some vital activities as listed above, we have discussed possible prevention of denaturation and aggregation of heme proteins such as Hb, cyt c, catalase & peroxidase.

Aggregation
heme proteins
amyloid inhibitors
anthroquinone
neurodegenerative diseases
polyphenols


Head teachers' opinions on the future of school education conditioned by emergency remote teaching.

Abstract: The study explores the school transformation process as evidenced by the opinions of head teachers. The main goal of the research was to present a content analysis study of the Polish educational environment on the basis of primary and secondary head teachers' views on the risks and perspectives brought by the global Covid-2019 lockdown. The conceptual framework was based on the theoretical perspective (the cognitive and affective processes in multimedia learning, the theory of motivation, and goal setting) as well as the model of the school as a learning organization and the assumptions of Emergency Remote Teaching. The categorized interviews with the head teachers were conducted using a categorized interview questionnaire and the respondents considered various categories problems within educational practice related to the functioning of schools during the pandemic. The selection of study participants was deliberate using the snowball sampling method, 18 head teachers participated in this study. The research conducted allowed the specification of the different areas of influence of Emergency Remote Teaching on the transformation of the school as a learning organization (e.g. the functioning of the school in mutual internal and external network cooperation, the dissemination and extending of communication areas using information technologies, the strengthening of the network interaction through information technologies, and other areas). The paper contains numerous recommendations that can improve the school's functioning in the future, based on the experience gained during Emergency Remote Teaching. These experiences can accelerate the organizational and didactic development of the school as a learning organization.

Head teachers
Education
Emergency Remote Teaching
Pandemic
School as learning organization


Display of quintuple glucagon-like peptide 1 (28-36) nonapeptide on Bacillus subtilis spore for oral administration in the treatment of type 2 diabetes.

Abstract:
AIMS
To develop an oral delivery system of glucagon-like peptide 1 (GLP-1) (28-36) for treating type-2 diabetes, B.S-GLP-1(28-36), a recombinant Bacillus subtilis spores transformed with a plasmid vector encoding five consecutive GLP-1 (28-36) nonapeptides with an enterokinase site was constructed.

METHODS AND RESULTS
GLP-1(28-36) nonapeptide was successfully expressed on the surface of B. subtilis spores and validated by Western blot and immunofluorescence. The therapeutic effect of oral administration of B.S-GLP-1(28-36) spores was evaluated in type 2 diabetic model mice. The efficacy of recombinant spores was examined for a period of 13 weeks after oral administration in diabetic mice. At the end of the sixth week, diabetic mice with oral administration of BS-GLP-1(28-36) spores showed decreased blood glucose levels from 2·4 × 10- 2  mol l-1 to 1·7 × 10- 2  mol l-1 . By the ninth week, the mean fasting blood glucose level in the experimental group was significantly lower than that in the control group 30 min after injection of pyruvate. At the end of the 10th week of oral administration, the blood glucose of the experimental group was significantly lower than that of the control group after intraperitoneal injection of glucose. By the 12th week, fasting blood glucose level and fasting insulin level were measured in all mice, the results showed that the recombinant spores increased the insulin sensitivity of mice.

CONCLUSIONS
The results of pathological observation showed that the recombinant spores also had a certain protective effect on the liver and islets of mice, and the content of GLP-1(28-36) in the pancreas of the experimental group was increased.

SIGNIFICANCE AND IMPACT OF THE STUDY
The results of this study revealed that GLP-1(28-36) nonapeptides can reduce blood glucose and play an important role in the treatment of type 2 diabetes.

D000284:Administration, Oral
D000818:Animals
D001412:Bacillus subtilis
D001786:Blood Glucose
D061505:Cell Surface Display Techniques
D003921:Diabetes Mellitus, Experimental
D003924:Diabetes Mellitus, Type 2
D052216:Glucagon-Like Peptide 1
D054795:Incretins
D007328:Insulin
D008297:Male
D051379:Mice
D011994:Recombinant Proteins
D013171:Spores, Bacterial
D016896:Treatment Outcome

Bacillus subtilis
type-2 diabetes
GLP-1(28-36)
oral protein delivery
surface display


How do mobile health applications support behaviour changes? A scoping review of mobile health applications relating to physical activity and eating behaviours.

Abstract:
OBJECTIVE
The objective of this review was to analyse how researchers conducting studies about mobile health applications (MHApps) effectiveness assess the conditions of this effectiveness.

STUDY DESIGN
A scoping review according to PRIMSA-ScR checklist.

METHODS
We conducted a scoping review of efficacy/effectiveness conditions in high internal validity studies assessing the efficacy of MHApps in changing physical activity behaviours and eating habits. We used the PubMed, Web of Science, SPORTDiscus and PsycINFO databases and processed the review according to the O'Malley and PRISMA-ScR recommendations. We selected studies with high internal validity methodologies (randomised controlled trials, quasi-experimental studies, systematic reviews and meta-analyses), dealing with dietary and/or physical activity behaviours; covering primary, secondary or tertiary prevention and dealing with behaviour change (uptake, maintenance). We excluded articles on MHApps relating to high-level sport and telemedicine. The process for selecting studies followed a set protocol with two authors who independently appraised the studies.

RESULTS
Twenty-two articles were finally selected and analysed. We noted that the mechanisms and techniques to support behaviour changes were poorly reported and studied. There was no explanation of how these MHApps work and how they could be transferred or not. Indeed, the main efficacy conditions reported by authors refer to practical aspects of the tools. Moreover, the issue of social inequalities was essentially reduced to access to the technology (the shrinking access divide), and literacy was poorly studied, even though it is an important consideration in digital prevention. All in all, even when they dealt with behaviours, the evaluations were tool-focused rather than intervention-focused and did not allow a comprehensive assessment of MHApps.

CONCLUSION
To understand the added value of MHApps in supporting behaviour changes, it seems important to draw on the paradigms relating to health technology assessment considering the characteristics of the technologies and on the evaluation of complex interventions considering the characteristics of prevention. This combined approach may help to clarify how these patient-focused MHApps work and is a condition for improved assessment of MHApps in terms of effectiveness, transferability and scalability.

Aromatario|O|O|
Van Hoye|A|A|
Vuillemin|A|A|
Foucaut|A-M|AM|
Crozet|C|C|
Pommier|J|J|
Cambon|L|L|

D016032:Randomized Controlled Trials as Topic

Behaviour
Physical activity
Effectiveness
Eating habits
Prevention
e-health


Prescription drug use during pregnancy and risk of childhood cancer - is there an association?

Abstract: In economically developed countries up to 90% of women are prescribed medications, including vitamins and supplements, during pregnancy. Whilst a number of adverse health outcomes in their offspring have been related to prescription drug use, associations with childhood cancer are less clear and most investigations have been reliant on maternal self-report. With a view to providing new insight we investigated maternal prescription drug use and risk of childhood cancer primary care medical records collected as part of the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted between 1991 and 1996. There was evidence that mothers of children with acute lymphoblastic leukaemia (OR 1.36, 95% CI 1.14-1.63), medulloblastoma (OR 1.79, 95% CI 1.00-3.22) and Wilms tumour (OR 1.79; 95% CI 1.05-3.04) were more likely to have been prescribed iron when compared to mothers of controls. In addition, systemic anti-infectives were positively associated with acute myeloid leukaemia (OR 1.58, 95% CI: 1.05-2.38) and rhabdomyosarcoma (OR 1.80, 95% CI 1.03-3.16), and analgesic use (NO2B) was positively associated with Hodgkin lymphoma (OR 5.02, 95% CI 2.16-11.82) and neuroblastoma (OR 1.99, 95% CI 1.07-3.69). Whilst our findings suggest that maternal use of antibiotics, iron, and nervous system drugs during pregnancy may be associated with some childhood cancer subtypes these associations need to be confirmed elsewhere. Unravelling the mechanisms that may underpin these associations is complex and research is needed to determine whether they are directly related to the drugs themselves, or the illnesses for which they were prescribed.

Bonaventure|A|A| Simpson|J|J| Ansell|P|P| Roman|E|E| Lightfoot|T|T|

D011297:Prenatal Exposure Delayed Effects

Prescription drugs
Childhood cancer
Epidemiology
In utero exposure


Mitochondrial Reactive Oxygen Species and Photodynamic Therapy.

Abstract: Worldwide, the number of cancer cases is increasing. Typically, they are treated by either surgery or chemotherapy. However, these treatments may be undesirable in elderly patients or those who are under medication with antiplatelet drugs. Photodynamic therapy (PDT) represents a potentially attractive treatment option for these types of patients, since it does not involve surgery and has considerably reduced side effects compared to chemotherapy. Porphyrin, one of the most commonly used photosensitizers, has the convenient property of cancer-specific accumulation and therefore, is commonly used in PDT. However, the mechanism by which this cancer-specific accumulation occurs remains unclear. We previously reported that a heme-transport protein, HCP1, was capable of transporting porphyrin compounds. HCP1 expression is associated with increased hypoxia, although the detailed mechanism by which this regulation occurs is also unknown. Here, we review available data on the mechanism of regulation of HCP1 expression through mitochondrial reactive oxygen species (mitROS). Specifically, cancer cells show increased expression of HCP1 compared to normal cells and this over-expression is reduced in cancer cells over-expressing the mitROS scavenging enzyme manganese superoxide dismutase (MnSOD). Thus we conclude that mitROS is involved in regulating HCP1 expression.

Reactive oxygen species
photodynamic therapy
mitochondria