Advances in Management of Psychosis in Neurodegenerative Diseases.

Abstract:
PURPOSE OF THE REVIEW
Psychosis is broadly defined as a disengagement from reality. It describes syndromes that impair both thought content and thought process. Psychosis negatively impacts an individual's quality of life, in addition to the families caring for them. Psychosis with different types of hallucinations and delusions occurs in the context of delirium. Neuropsychiatric symptoms (NPS) are almost universal in the course of common neurodegenerative disorders (NDD) like Alzheimer's disease (AD) or Parkinson's disease (PD). In this paper, the authors took an effort to characterize AD and PD psychosis with a special focus on the most diagnostically reliable features. Effectiveness and limitations of pharmacological interventions are discussed.

RECENT FINDINGS
Consensus diagnostic criteria have evolved for psychosis secondary to AD as well as psychosis in PD. Psychotropic medications can be effective in the treatment of NPS in NDD; however, clinicians must be mindful of the side effects. There is a consensus on benefit of initiating any acetylcholinesterase inhibitor (ACHI: donepezil, rivastigmine, and galantamine) as a first line of treatment for psychosis in AD, as it may reduce and/or avoid the need for the use antipsychotics. Pimavanserin, a selective-serotonin inverse agonist that preferentially targets 5-HT2A receptors, while avoiding activity at dopamine and other receptors commonly targeted by antipsychotics had recently been approved by FDA to treat hallucinations and delusions in PD. Quetiapine is widely prescribed for the treatment of psychosis in different NDD, but the data remains equivocal. Psychosis with different types of hallucinations and delusions may occur in the context of delirium and is almost universal as a neuropsychiatric symptom in the course of PD and AD. Currently, pimavanserin remains the only pharmacologic agent approved for treatment of psychosis in PD. In cases of other NPS in other than Parkinson's diseases, atypical antipsychotics are commonly used off-label. More research is greatly needed to advance this field and address NPS especially psychosis in geriatric population.

Neuropsychiatric symptoms (NPS)
Neurodegenerative disorders (NDD)
Alzheimer’s disease psychosis
Parkinson’s disease psychosis


Beyond type 2 diabetes: sodium glucose co-transporter-inhibition in type 1 diabetes.

Abstract: Use of sodium glucose cotransporter (SGLT) inhibitors are a well-established therapeutic option in type 2 diabetes (T2D) with a variety of proven therapeutic benefits. They have become a pillar of current treatment guidelines. In type 1 diabetes (T1D), initial exploratory studies have shown benefits in glycemic control, weight control, and cardiovascular risk parameters, leading to trials aiming for regulatory submission with several agents. Results from four 1-year trials, which included a total of 3052 patients, are now available, demonstrating promising findings that target the unmet needs of patients with T1D with a novel insulin-independent adjunct therapy. However, these positive effects must be balanced against the risks associated with this class of drugs. Specifically, current T1D studies have shown an increased risk of diabetic ketoacidosis (DKA), which, in some cases, presented with only slightly elevated glucose levels. While this complication may be clinically manageable once detected, the metabolic shift towards ketogenesis associated with this class of agents mandates appropriate patient selection. Currently, there are no validated tools for DKA risk assessment. Although the experience gained in studies and off-label use provides some indication for appropriate patient selection, this would have to be evaluated closely in the event that these drugs would receive regulatory approval. Risk mitigation includes training in ketone measurement (preferably as blood β-hydroxybutyrate testing), teaching the concept of euglycemic DKA, and providing a clear treatment algorithm to avoid progression of ketosis to full-blown DKA. Because similar unmet needs also exist in pediatric population studies, risk mitigation in youth should be initiated as well to allow an evidence-based, risk-benefit assessment in this vulnerable population.

D000077203:Sodium-Glucose Transporter 2 Inhibitors

SGLT
diabetic ketoacidosis
DKA
ketone
β-hydroxybutyrate
insulin
type-1 diabetes


Solitary neurofibroma of the adrenal gland not associated with type-1 neurofibromatosis.

Abstract: Neurofibromas are tumors of neural origin. They can be solitary or may be associated with neurofibromatosis type-1 (NF-1). These are mostly seen in the head and neck region, upper extremities or along the nerves. Visceral neurofibromas are extremely rare. In this paper, we present an unusual case of solitary neurofibroma of the adrenal gland not associated with NF-1.


Radio electric tissue optimization in the treatment of surgical wounds.

Abstract:
PURPOSE
To report preliminary results with the tissue optimization (TO) treatment with a radio electric asymmetric conveyer (REAC) in promoting the repair of surgical wounds.

PATIENTS AND METHODS
Two subjects, a 54-year-old male with a tear bruise on the upper third of the leg and a 19-year-old female with a stab wound to the hand, were treated with 12 REAC-TO treatment sessions.

RESULTS
In both patients, the wounds showed shorter healing time compared with the time usually required for similar wounds, and good repair quality.

CONCLUSION
REAC device with its specific treatment protocols may be an alternative therapy for wound healing.

Castagna|Alessandro|A| Fontani|Vania|V| Rinaldi|Salvatore|S| Mannu|Piero|P|

healing time
quality of repair
tissue regeneration
tissue repair


Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum.

Abstract: Granule cells (GCs) are the most numerous cell type in the cerebellum and indeed, in the brain: at least 99% of all cerebellar neurons are granule cells. In this review article, we first consider the formation of the upper rhombic lip, from which all granule cell precursors arise, and the way by which the upper rhombic lip generates the external granular layer, a secondary germinal epithelium that serves to amplify the upper rhombic lip precursors. Next, we review the mechanisms by which postmitotic granule cells are generated in the external granular layer and migrate radially to settle in the granular layer. In addition, we review the evidence that far from being a homogeneous population, granule cells come in multiple phenotypes with distinct topographical distributions and consider ways in which the heterogeneity of granule cells might arise during development.

Consalez|G Giacomo|GG|
Goldowitz|Daniel|D|
Casoni|Filippo|F|
Hawkes|Richard|R|

compartmentation
granule cell
cerebellum
upper rhombic lip
external granular layer
Bergmann glial fibers
radial migration


Sorting out cirrhosis: mechanisms of non-response to hepatitis C therapy.

Abstract: Although cirrhosis has long been recognized as an important negative predictor of treatment response for hepatitis C virus (HCV) therapy, the mechanisms underlying this association remain relatively poorly understood. Treatment has progressed rapidly with the introduction of highly effective all-oral therapies, with promising outcomes even in patients with advanced cirrhosis. However, even with the new therapies, it is clear that patients with cirrhosis require special attention. Efficacy continues to be somewhat reduced compared to non-cirrhotic patients and safety is an important concern. In this review, we explore the reasons for treatment non-response in patients with cirrhosis. We focus on how cirrhosis impacts on four important areas including drug delivery, drug uptake and metabolism, immune responses and drug toxicity with examples from the clinical and basic literature. Fortunately, as treatment continues to progress, many of the challenges of treating patients with cirrhosis will become less and less problematic.

cirrhosis
mechanisms of non-response
therapy
hepatitis C virus
direct-acting antivirals
interferon


Genomic insights into waste valorized extracellular polymeric substances (EPS) produced by Bacillus sp. ISTL8.

Abstract: The present study discusses the genomic analysis of Bacillus sp. ISTL8 along with the production of EPS (Extracellular polymeric substances) using carbofuran, a toxic carbamate pesticide. Bacillus strain was isolated from landfill soil and evaluated for high growth rates and EPS production. One strain, renamed ISTL8 grew on a broad range of carbon sources, including toxic carbofuran, while producing copious EPS. Growth assays verified the strain to be thermophilic, low salt tolerant, and with a preference for neutral pH. SEM (Scanning Electron Microscopy) was used for morphological characterization of the EPS while the monomeric composition, bonding patterns and functional groups were deduced by GC-MS (Gas Chromatography-Mass Spectrometry), 1H and 13C NMR (Nuclear Magnetic Resonance) and FTIR (Fourier Transform Infrared Spectroscopy). The production of EPS using carbofuran (carbamate pesticide) as a carbon source was found to be 6.20 ± 0.29 g L-1 containing 61.17% w/w carbohydrates, 29.72% w/w proteins and 6.11% w/w lipids (of dry EPS). The potential cytotoxicity of EPS was evaluated with 3- (4,5-dimethyl thiazol-2-Yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and found non-toxic (2.25%). WGS (Whole genome sequencing) was performed for the strain Bacillus sp. ISTL8 producing EPS; an array of genes putatively involved in the EPS production were identified in several different genomic locations, guiding potential genetic manipulation studies in the future. The results highlight the potency of a bacterial isolate Bacillus sp. ISTL8 to produce non-cytotoxic EPS using carbofuran that can be further harnessed for environmental and commercial applications. Additionally, WGS revealed an array of EPS specific genes which can be effectively engineered for much enhanced production.

Gupta|Juhi|J|
Rathour|Rashmi|R|
Dupont|Christopher L|CL|
Kaul|Drishti|D|
Thakur|Indu Shekhar|IS|

D000077317:Extracellular Polymeric Substance Matrix

D017550:Spectroscopy, Fourier Transform Infrared

Extracellular polymeric substance
Carbofuran
Whole genome sequencing
Bacillus ISTL8
HepG2 cell line


Strain behavior of native and reconstructed medial patellofemoral ligaments during dynamic knee flexion - a cadaveric study.

Abstract:
BACKGROUND
Surgical reconstruction of the Medial Patello-Femoral Ligament (MPFL) has been recognized as an effective treatment for patients with instability despite conservative treatment. The purpose of this cadaveric study is to compare the strain patterns within the native and reconstructed single and double-bundle MPFL. This will help ascertain if the native biomechanics are restored with the reconstructions.

METHODS
Twelve cadaveric knees were dissected and the native MPFL of each specimen was identified. The knees were subjected to dynamic flexion using a customized jig. Continuous strain measurements were taken for each knee from 0 to 120 degrees flexion and then back to full extension using differential variable reluctance transducers (DVRTs). The MPFL was then cut. Six single bundle and six double bundle MPFL reconstructions were performed using hamstring tendon grafts. The DVRTs were reattached to the grafts and strain measurements were retaken. Statistical analysis was performed using a paired t-test.

RESULTS
Strain patterns of the native and reconstructed MPFL showed an increase in strain from 0 to 120 degrees of flexion except for the inferior bundle of the double bundle reconstruction. The strain patterns in the intact specimens were higher than the reconstructed MPFL through different degrees of knee flexion. In the double-bundle group, the superior graft had statistically significantly lower strains compared to the native MPFL with p-value <.05 at all flexion angles. The reconstructed inferior band showed loss of tension as the knee flexed. Higher strain with statistical significance (p-value <.05) was found in the single-bundle compared to the superior band of the double-bundle reconstruction at flexion angles less than 90 degrees.

CONCLUSION
The strain variation at progressive angles of knee flexion is dissimilar between the native and reconstructed MPFL. The reconstructed MPFL exhibited non-physiological biomechanics with the inferior band losing tension. Although the single-bundle reconstruction shows a better strain profile compared to double-bundle reconstruction, the grafts are significantly stiffer than the native MPFL.

Kizher Shajahan|Mohamed Buhary|MB|
Choh|Chaw Tat Alex|CTA|
Yew|Khye Soon Andy|KSA|
Chan|Hiok Yang|HY|
Howe|Tet Sen|TS|
Lie|Tjiauw Tjoen Denny|TTD|
Koh|Suang Bee Joyce|SBJ|
Chang|Chee Cheng Paul|CCP|


Improved Diagnosis of Pulmonary Tuberculosis using bleach Microscopy Method.

Abstract:
BACKGROUND
The bacteriological diagnosis of tuberculosis (TB) is largely dependent on the Ziehl-Neelsen (ZN) microscopy. This method has a low sensitivity, which can be improved by the concentration of the specimen with sodium hypochlorite (NaoCl), followed by centrifugation before doing acid fast staining (AFB).

AIM
To study the improvement in the sensitivity of the sputum smear by the bleach method. Setting and Study Design: This study was conducted in BLDEU's Shri B.M. Patil Medical College, Hospital and Research Centre, Bijapur, Karnataka, India. Eighty five patients who visited Shri B.M. Patil Medical College, Hospital and Research Centre between January 2012 to December 2012 were investigated. On spot, morning and second on spot samples were collected from each patient. Direct smears were prepared and they were stained with the hot ZN technique and the remaining samples were concentrated by using 5% NaoCl, followed by centrifugation and staining with ZN stain. The improvement in the sensitivity following the bleach method was studied.

STATISTICAL ANALYSIS
The Fisher's exact test was used.

RESULTS
A total of two hundred and fifty five specimens from eighty five patients were included in this study; each patient produced three specimens. AFB was detected in twenty five direct smears and in eighty four bleach smears. A statistically significant (p < 0.001) increase in the positivity with the use of the bleach method was detected as compared to that with the use of the direct method. The ZN sensitivity, specificity, positive predictive value (PPV), and the negative predictive value (NPV) were 29%, 99%, 96% and 74% respectively with a 95% confidence interval, with the use of the 5% NaoCl method.

CONCLUSION
The bleach method has advantages over the direct ZN method, as it is simple and as it does not require any additional expertise beyond that which is required for the conventional direct smear microscopy. The materials and the reagents are also affordable and they are available locally.

Mindolli|Preeti B|PB|
Salmani|Manjunath P|MP|
Parandekar|Prashant K|PK|

Tuberculosis
Sodium hypochlorite
Acid fast bacilli
Ziehl-Neelsen method


Association of Higher Daptomycin Dose (7 mg/kg or Greater) with Improved Survival in Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

Abstract:
STUDY OBJECTIVE
Current guidelines recommend higher daptomycin doses than the daptomycin label dose of 6 mg/kg for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, the evidence supporting this recommendation is from in vitro and case series studies. This study evaluated the comparative effectiveness of the daptomycin label dose versus higher daptomycin doses in patients with MRSA bacteremia.

DESIGN
Retrospective national cohort study.

SETTING
Veterans Affairs medical centers.

PATIENTS
A total of 371 adults with MRSA bacteremia who were admitted between 2002 and 2015 and treated initially with vancomycin within 24 hours of initial culture collection and then switched to daptomycin therapy within 7 days; 138 patients (37.2%) received daptomycin doses higher than the daptomycin label dose (7 mg/kg or greater), and 233 (62.8%) received the daptomycin label dose (6 mg/kg).

MEASUREMENTS AND MAIN RESULTS
Clinical outcomes were compared among those who received the daptomycin label dose and those who received the higher dose using propensity score-matched Cox proportional hazards regression models. To identify dose partitioning associated with optimal survival, classification and regression tree (CART) analysis was used among patients, controlling for confounding with a 30-day mortality disease risk score. Propensity score-matched 30-day mortality was 8.6% (6/70 patients) among the higher dose group versus 18.6% (13/70 patients) among the label dose group (hazard ratio 0.31, 95% confidence interval 0.10-0.94). No significant differences were observed in inpatient mortality, length of stay, 30-day readmission, or 30-day S. aureus reinfection between groups. CART analysis resulted in doses of 7 mg/kg or greater providing benefit only among patients with higher (more than 51%) predicted probabilities of 30-day mortality (p<0.001).

CONCLUSION
To our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (7 mg/kg or greater) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia.

Timbrook|Tristan T|TT|
Caffrey|Aisling R|AR|
Luther|Megan K|MK|
Lopes|Vrishali|V|
LaPlante|Kerry L|KL|0000-0002-9650-4275

daptomycin
dosing
Staphylococcus aureus
bacteremia
mortality


Molecular Characterization of Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar.

Abstract:
Introduction
Although extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are a public health problem in the Arabian Peninsula, data on the molecular characteristic of their antimicrobial resistance determinants in children is limited.

Aim
To determine the molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae in the pediatric population of Qatar.

Methods
Whole-genome sequencing was performed on ESBL-producing E. coli and K. pneumoniae isolates recovered from screening and clinical specimens from pediatric patients at Sidra Medicine in Doha from January to December 2018.

Results
A total of 327 ESBL producers were sequenced: 254 E. coli and 73 K. pneumoniae. Non-susceptibility rates to non-β-lactam antibiotics for both species were 18.1 and 30.1% for gentamicin, 0.8 and 4.1% for amikacin, 41.3 and 41.1% for ciprofloxacin, and 65.8 and 76.1% for cotrimoxazole. The most common sequence types (STs) were ST131 (16.9%), ST38 and ST10 (8.2% each) in E. coli and ST307 (9.7%), and ST45 and ST268 (6.9% each) in K. pneumoniae. CTX-M type ESBLs were found in all but one isolate, with CTX-M-15 accounting for 87.8%. Among other β-lactamases, TEM-1B and OXA-1 were coproduced in 41 and 19.6% of isolates. The most common plasmid-mediated quinolone resistance genes cocarried were qnr A/B/E/S (45.3%). Ninety percent of gentamicin non-susceptible isolates harbored genes encoding AAC(3) enzymes, mainly aac(3)-IIa. Only two of 57 isolates harboring aac(6')-Ib-cr were non-susceptible to amikacin. Chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV enzymes were detected in 96.2% fluoroquinolone-non-susceptible E. coli and 26.7% fluoroquinolone-non-susceptible K. pneumoniae.

Conclusion
Our data show that CTX-M enzymes are largely the most prevalent ESBLs in children in Qatar with a predominance of CTX-M-15. Carbapenem-sparing options to treat ESBL infections are limited, given the frequent coproduction of OXA-1 and TEM-1B enzymes and coresistance to antibiotic classes other than β-lactams.

Perez-Lopez|Andres|A|
Sundararaju|Sathyavathi|S|
Al-Mana|Hassan|H|
Tsui|Kin Ming|KM|
Hasan|Mohammad Rubayet|MR|
Suleiman|Mohammed|M|
Janahi|Mohammed|M|
Al Maslamani|Eman|E|
Tang|Patrick|P|

extended-spectrum β-lactamases
children
whole-genome sequencing
E. coli
K. pneumoniae
CTX-M-15
fluoroquinolones


Risk of work-related violence in England and Wales.

Abstract:
BACKGROUND
There is an urgent need to address high levels of work-related violence (WRV) in Britain to improve the workplace experience of both employers and employees.

AIMS
This study specifically explores prevalence rates of work-related violence assaults (WRVAs) for staff at high risk that have supervisor responsibilities and work full-time.

METHODS
Five years of data were used for analysis from the Crime Survey of England and Wales (CSEW). Data were filtered for victims of crime from a working population in Britain.

RESULTS
Forty-four per cent of respondents who are supervisors and have full-time jobs report that they had been victims of WRVAs. This figure is higher than other previous studies of WRV.

CONCLUSIONS
The current study provides further alternative evidence to support high prevalence rates of WRV by selecting for analysis specific work characteristics data that are strongly associated with WRV (supervisor responsibilities and full-time work). It is therefore recommended that future work explores different means of intervention for organizations to implement within the workplace to reduce WRV and protect workers from harm.


Hyrtl's fissures in cochlear implant surgery.

Abstract: This case study presents a rare anatomical anomaly complicating cochlear implantation in the form of patent periotic ducts and Hyrtl's (tympanomeningeal) fissures. Hyrtl's fissures are transient anatomical conduits which normally ossify by the 24th week of gestation. Their persistence may cause inadvertent insertion of the cochlear implant electrode into this channel and prevent a successful outcome. This case study and a review of the relevant literature highlights the importance of recognizing this rare anomaly which is easily missed on preoperative imaging.

D003051:Cochlea
D019929:Cochlear Implantation
D003054:Cochlear Implants
D004567:Electrodes, Implanted
D006801:Humans
D013701:Temporal Bone

Cochlear implant
Periotic duct
Cochlear aqueduct
Hyrtl’s fissure
Temporal bone anatomy
Temporal bone embryology
Tympanomeningeal fissure


The Afro-Cardiac Study: Cardiovascular Disease Risk and Acculturation in West African Immigrants in the United States: Rationale and Study Design.

Abstract: Cardiovascular disease (CVD) remains the leading cause of death in the United States (US). African-descent populations bear a disproportionate burden of CVD risk factors. With the increase in the number of West African immigrants (WAIs) to the US over the past decades, it is imperative to specifically study this new and substantial subset of the African-descent population and how acculturation impacts their CVD risk. The Afro-Cardiac study, a community-based cross-sectional study of adult WAIs in the Baltimore-Washington metropolis. Guided by the PRECEDE-PROCEED model, we used a modification of the World Health Organization Steps survey to collect data on demographics, socioeconomic status, migration-related factors and behaviors. We obtained physical, biochemical, acculturation measurements as well as a socio-demographic and health history. Our study provides critical data on the CVD risk of WAIs. The framework used is valuable for future epidemiological studies addressing CVD risk and acculturation among immigrants.

Commodore-Mensah|Yvonne|Y|
Sampah|Maame|M|
Berko|Charles|C|
Cudjoe|Joycelyn|J|
Abu-Bonsrah|Nancy|N|
Obisesan|Olawunmi|O|
Agyemang|Charles|C|
Adeyemo|Adebowale|A|
Himmelfarb|Cheryl Dennison|CD|

Cardiovascular disease
Acculturation
African immigrants
Immigrants


High Grade Glioma Surgery - Clinical Aspects and Prognosis.

Abstract:
INTRODUCTION
High grade gliomas (HGG) are a group of tumors with infiltrative nature in general. Surgery is the first step in their treatment. It can be beneficial in two aspects: firstly, in establishing normal intracranial pressure and, secondly, in reducing the tumour volume. The choice of method depends on the location of the lesion, the expected grade of malignancy, and the general condition of the patient. Despite constant development of neuro-oncology and microsurgical techniques, the 5-year survival rate in patients with HGG remains less than 10% and the median survival is still less than 2 years. Aim: At present, there is no final therapeutic "segment" to provide a better outcome than the complex treatment of HGG. Moreover, the treatment's relative efficacy and recurrence of these tumours carry an additional problem. The aim of this study was to estimate the overall survival of patients with HGG operated in our clinic and compare it with literature data. Materials and methods: One hundred twenty-one cranial operations for HGG were reviewed (conducted between 2014 and 2019). Summary characteristics of the various parameters were presented in respect to the radical nature of the operative intervention using Kaplan-Meier analysis and chi square tests. All patients were followed up at regular check-ups.

RESULTS
HGGs were 103 or 85.12% of all gliomas operated for the 2014-2019 period. The most common cases were in the 51 to 60 age group. The cases in men were twice as common. The most common localization of the neoplasm is in the temporal region (36.36%) and the rarest was found in the occipital region (3.30%). It was estimated that our operated patients with HGG had 12.23 months over-all survival. Gross total resected patients had a median survival (OS) of 14.53 months, while subtotal resected patients had a median survival (OS) of 10.44 months. It is estimated 7.97 months free tumor survival period (time to relapse - FTS) for our operated patients with HGG. Gross total resected patients had a median FTS of 10.88 months, while subtotal resected patients had median FTS of 5.70 months. We noticed permanent new neurological deficit (NND) in 20 patients (19.45%) operated with GTR, and in 5 patients (4.85%) operated with STR. Conclusions: Median survival - OS, free tumor survival period - FTS and new neurological deficit - NND were statistically significant (p.

Mladenovsk|Milan|M|0000-0003-3675-5475 Valkov|Iliya|I| Ovcharov|Mladen|M| Vasilev|Nikolay|N| Duhlenski|Iliya|I|

high grade glioma
prognosis
gross total
subtotal resection
extent of resection


Muscle mass evaluation using psoas muscle mass index by computed tomography imaging in hemodialysis patients.

Abstract:
BACKGROUND AND AIMS
The use of the psoas muscle mass index (PMI) using computed tomography (CT) has become a marker of interest to evaluate whole body muscle mass. However, in hemodialysis (HD) patients, reports about the clinical significance of psoas muscle evaluation are limited. We aimed to clarify the association between PMI and skeletal muscle mass index (SMI) using bioelectrical impedance analysis (BIA), and to investigate factors affecting PMI in HD patients.

METHODS
In this prospective observational study, to evaluate muscle mass, SMI was measured using BIA after HD, and PMI was measured by the manual trace method on routinely available CT scans. PMI measurement was assessed twice by two physicians to compute intra-rater and inter-rater reliability. The correlations between PMI and the clinical factors were evaluated using Pearson's correlation coefficient and a linear regression analysis. Variables with a p-value < 0.05 in the simple linear regression analysis were included in the multivariable linear regression analysis to identify the factors that affected PMI of the HD patients.

RESULTS
Fifty HD patients were recruited (31 males and 19 females; HD duration, 9.0 ± 8.8 years). The SMI was 6.10 ± 1.20 kg/m2, and the PMI was 4.79 ± 1.61 cm2/m2. Regarding the reliability of PMI measurements, intra-rater reliability [intra-class correlation (ICC) = 0.999] and inter-rater reliability (ICC = 0.998) were high in this study. The mean PMI of male patients was 5.40 ± 1.62 cm2/m2, while that of female patients was significantly lower (3.78 ± 0.98 cm2/m2; p < 0.001). The PMI was significantly and positively correlated with SMI (r = 0.630, p < 0.001), in addition to HD duration, body mass index (BMI), serum phosphate and serum creatinine (Cr). In the multivariate linear regression analysis by two models using SMI or BMI, they were respectively extracted as an independent factor associating with PMI, in addition to serum Cr and the difference of sex.

CONCLUSIONS
PMI assessed with CT positively correlated with SMI measured using BIA. PMI might be one of the methods for evaluating the muscle mass in HD patients, when CT scans are taken as part of routine care.

Ito|Kiyonori|K| Ookawara|Susumu|S| Imai|Sojiro|S| Kakuda|Hideo|H| Bandai|Yusaku|Y| Fueki|Mariko|M| Yasuda|Masatoshi|M| Kamimura|Tatsuya|T| Kiryu|Satoshi|S| Wada|Noriko|N| Hamashima|Yuri|Y| Shindo|Mitsutoshi|M| Kobayashi|Tadanao|T| Sanayama|Hidenori|H| Kaku|Yoshio|Y| Tanno|Keisuke|K| Ohnishi|Yasushi|Y| Iino|Noriaki|N| Dezaki|Katsuya|K| Kakei|Masafumi|M| Tabei|Kaoru|K| Morishita|Yoshiyuki|Y|

Psoas muscle mass index
Computed tomography
Hemodialysis
Skeletal muscle mass index
Sarcopenia


Postpneumonectomy syndrome related to the thickness of the fat tissue in the anterior mediastinum: a retrospective observational study.

Abstract:
Background
Postpneumonectomy syndrome (PPS) is a life-threatening condition characterized by the extrinsic compression of the mainstem bronchus after pneumonectomy, causing rapidly progressive dyspnea. Information regarding the predictive factors of this condition is limited. Thus, the current study aimed to identify the predictive findings that can help prepare the treatment of PPS in advance.

Methods
The present study is a retrospective observational study. We reviewed the medical records of 12 consecutive patients who underwent pneumonectomy for lung cancer or tuberculosis between 2009 and 2020. The anatomical findings evaluated via computed tomography scan, nutritional status assessed using laboratory data, respiratory function, intraoperative variables between PPS and non-postpneumonectomy-syndrome patients were compared.

Results
There were two female patients who presented with left PPS (PPS 1 and PPS 2 aged 73 and 55 years, respectively). The median age of 10 non-postpneumonectomy-syndrome patients (n=6, men and n=4 women) was 66 (range, 54-76 years). Four and six patients underwent right and left pneumonectomy, respectively. The fat tissue thickness in the anterior mediastinum was significantly thinner in PPS than in non-postpneumonectomy-syndrome patients. However, the body mass index (BMI) and other nutritional parameters did not differ between PPS and non-postpneumonectomy-syndrome patients. The median vital capacity was higher in PPS than in non-postpneumonectomy-syndrome patients. The decrement of respiratory function and body weight after pneumonectomy did not differ between two groups. The intraoperative variables did not also differ between two groups.

Conclusions
The fat tissue in the anterior mediastinum between the bilateral lungs is an anchor that can help maintain the normal position of the mediastinum after pneumonectomy. Thus, the fat tissue thickness between the bilateral lungs can be a predictive factor for the occurrence of PPS before surgery.

mediastinum
postpneumonectomy syndrome (PPS)
Pneumonectomy
lung cancer


Effect of light conditions on mixotrophic cultivation of green microalgae.

Abstract: Current research aimed to increase mixotrophic biomass from various organic carbon sources by exploring best light conditions. Three substrates glucose, acetic acid and glycerol were studied for their effects on mixotrophic microalgae cultivation under four light conditions. Light irradiance exhibited variability in growth response and photosynthetic efficiency based on type of substrates used in mixotrophic growth. Each substrate showed variability in light requirements for their effective assimilations. From growth responses, glucose and acetic acid respectively exhibited heterotrophic and mixotrophic (better growth in light) natures. Continuous light-deficient condition was adequate for effective mixotrophic growth as well as energy saving for glucose. However, light-sufficient condition required for effective acetic acid supported mixotrophic growth. Mixotrophic benefits from glycerol and its uptake by Chlorella protothecoides was negligible in all light conditions. Investigation of heterotrophic biomass contribution by various substrates in overall mixotrophic yield, glucose offered maximum approx. 43% contribution.

Patel|Anil Kumar|AK|
Joun|Jae Min|JM|
Hong|Min Eui|ME|
Sim|Sang Jun|SJ|

Mixotrophic
Microalgae
Glucose
Acetic acid
Glycerol
Chlorella
Autotrophic


Association with the Plasma Membrane Is Sufficient for Potentiating Catalytic Activity of Regulators of G Protein Signaling (RGS) Proteins of the R7 Subfamily.

Abstract: Regulators of G protein Signaling (RGS) promote deactivation of heterotrimeric G proteins thus controlling the magnitude and kinetics of responses mediated by G protein-coupled receptors (GPCR). In the nervous system, RGS7 and RGS9-2 play essential role in vision, reward processing, and movement control. Both RGS7 and RGS9-2 belong to the R7 subfamily of RGS proteins that form macromolecular complexes with R7-binding protein (R7BP). R7BP targets RGS proteins to the plasma membrane and augments their GTPase-accelerating protein (GAP) activity, ultimately accelerating deactivation of G protein signaling. However, it remains unclear if R7BP serves exclusively as a membrane anchoring subunit or further modulates RGS proteins to increase their GAP activity. To directly answer this question, we utilized a rapidly reversible chemically induced protein dimerization system that enabled us to control RGS localization independent from R7BP in living cells. To monitor kinetics of Gα deactivation, we coupled this strategy with measuring changes in the GAP activity by bioluminescence resonance energy transfer-based assay in a cellular system containing μ-opioid receptor. This approach was used to correlate changes in RGS localization and activity in the presence or absence of R7BP. Strikingly, we observed that RGS activity is augmented by membrane recruitment, in an orientation independent manner with no additional contributions provided by R7BP. These findings argue that the association of R7 RGS proteins with the membrane environment provides a major direct contribution to modulation of their GAP activity.

Muntean|Brian S|BS|
Martemyanov|Kirill A|KA|

D060807:Bioluminescence Resonance Energy Transfer Techniques

regulator of G protein signaling (RGS)
G protein
G protein-coupled receptor (GPCR)
GTPase-activating protein (GAP)
allosteric regulation
signal transduction


Metabolic Profiling and Cold-Starvation Stress Response of Oxygen-Tolerant Lactobacillus gasseri Strains Cultured in Batch Bioreactor.

Abstract: Phenotypic and genotypic evidence indicates that many LAB strains can grow in presence of oxygen and can shift from fermentative to aerobic and/or respiratory metabolism. The aerobic and respiratory growth of several LAB species have been studied, allowing the selection of strains showing improved biomass production, long-term survival, and resistance under oxygen and stress conditions. The aim of this work was to observe the adaptation of two Lactobacillus gasseri strains, described in a previous work, to aerobic (air injection) and respiratory (air injection plus hemin and menaquionone) conditions obtained in a batch bioreactor. One strain showed the higher biomass production and oxygen consumption as well as the lower acidification in respiratory condition. Instead, the other one grew better in aerobic condition, even though the higher resistance to cold-starvation stress was registered in respiratory condition. In silico analysis revealed notable differences between AL3 and AL5 genomes and that of the type strain. This work contributes to understanding the adaptation response of lactobacilli to aerobic and respiratory metabolism. We demonstrated that the supposed activation of respiratory metabolism may provide several modifications to cell physiology. These features may be relevant in some technological and health-promoting applications, including starter and probiotic formulations.

cold-starvation stress
in silico analysis
aerobic and respiratory metabolism
lactic acid bacteria
tricarboxylic acid cycle


Plasticity of Persistent Activity and Its Constraints.

Abstract: Stimulus information is maintained in working memory by action potentials that persist after the stimulus is no longer physically present. The prefrontal cortex is a critical brain area that maintains such persistent activity due to an intrinsic network with unique synaptic connectivity, NMDA receptors, and interneuron types. Persistent activity can be highly plastic depending on task demands but it also appears in naïve subjects, not trained or required to perform a task at all. Here, we review what aspects of persistent activity remain constant and what factors can modify it, focusing primarily on neurophysiological results from non-human primate studies. Changes in persistent activity are constrained by anatomical location, with more ventral and more anterior prefrontal areas exhibiting the greatest capacity for plasticity, as opposed to posterior and dorsal areas, which change relatively little with training. Learning to perform a cognitive task for the first time, further practicing the task, and switching between learned tasks can modify persistent activity. The ability of the prefrontal cortex to generate persistent activity also depends on age, with changes noted between adolescence, adulthood, and old age. Mean firing rates, variability and correlation of persistent discharges, but also time-varying firing rate dynamics are altered by these factors. Plastic changes in the strength of intrinsic network connections can be revealed by the analysis of synchronous spiking between neurons. These results are essential for understanding how the prefrontal cortex mediates working memory and intelligent behavior.

Li|Sihai|S| Zhou|Xin|X| Constantinidis|Christos|C| Qi|Xue-Lian|XL|

working memory
prefrontal cortex
training
neurophysiology
monkey


Diet and root surface caries in a cohort of older Japanese.

Abstract:
OBJECTIVES
Root surface caries experience tends to increase with age. The purpose of this longitudinal study was to evaluate the relationship between aspects of dietary intake, including milk and sucrose in coffee or tea (SCT), and root surface caries in older Japanese individuals.

METHODS
303 community-dwelling older individuals (age 75 years) were enrolled for analysis. All participants underwent a dental examination at baseline and then annually from 2003 to 2008 (ie six times over a 5-year period). A disease event was considered to have occurred when root surface caries was detected on a previously sound or nonexposed root surface. Over the observation period, disease events in each year were counted. Dietary habits during the preceding month were evaluated using a brief self-administered diet history questionnaire (BDHQ) in 2003 and 2008. Poisson regression analysis performed crude and adjusted increment-rate ratios (IRRs) for root surface caries and the intake of milk and SCT.

RESULTS
The adjusted increment-rate ratio (IRR) of the increment of root surface caries for participants in the highest SCT tertile was 1.72 (95%CI: 1.40-2.14) compared with the referent group. In addition, for the amount of milk intake, the adjusted IRR in the highest tertile was 0.63 (95% CI: 0.51-0.78) compared with the referent group.

CONCLUSIONS
Much SCT and low milk intake were associated with the increment of root surface caries in community-dwelling older people in Japan. These findings suggest that to help prevent root surface caries, community-dwelling older people in Japan should consume adequate amounts of milk daily and limit their intake of SCT.

Yoshihara|Akihiro|A|0000-0002-0424-8228 Suwama|Kana|K| Miyamoto|Akane|A| Watanabe|Reiko|R| Ogawa|Hiroshi|H|

root surface caries
milk intake
older people
sucrose intake in coffee or tea


An Investigation of Rotary Drone HERM Line Spectrum under Manoeuvering Conditions.

Abstract: Detecting and identifying drones is of great interest due to the proliferation of highly manoeuverable drones with on-board sensors of increasing sensing capabilities. In this paper, we investigate the use of radars for tackling this problem. In particular, we focus on the problem of detecting rotary drones and distinguishing between single-propeller and multi-propeller drones using a micro-Doppler analysis. Two different radars were used, an ultra wideband (UWB) continuous wave (CW) C-band radar and an automotive frequency modulated continuous wave (FMCW) W-band radar, to collect micro-Doppler signatures of the drones. By taking a closer look at HElicopter Rotor Modulation (HERM) lines, the spool and chopping lines are identified for the first time in the context of drones to determine the number of propeller blades. Furthermore, a new multi-frequency analysis method using HERM lines is developed, which allows the detection of propeller rotation rates (spool and chopping frequencies) of single and multi-propeller drones. Therefore, the presented method is a promising technique to aid in the classification of drones.

drone
HERM lines
radar
micro-Doppler
chopping lines
multi-frequency analysis
UAV
log harmonic summation
spool lines


The effect of knee orthoses on gait parameters in medial knee compartment osteoarthritis: A literature review.

Abstract:
BACKGROUND
Knee osteoarthritis is a musculoskeletal condition which is most prevalent in the medial compartment. This injury causes considerable pain, disability, and negative changes in kinetic and kinematic parameters. The efficiency of unloader valgus brace as a conservative treatment for medial knee osteoarthritis is not well documented.

OBJECTIVES
The aim of this study was to review the previous research regarding the biomechanical effects of knee valgus braces on walking in medial compartment knee osteoarthritis patients.

STUDY DESIGN
Literature review

METHODS
According to the population intervention comparison outcome measure methods and based on selected keywords, 12 studies were chosen according to (met) the inclusion criteria.

RESULTS
The results indicated that treatment with knee braces was effective in decreasing pain, improving function, ameliorating improvement in range of motion, and increasing speed of walking and step length in conjunction with a reduction in the adduction moment applied to the knee.

CONCLUSION
Osteoarthritis knee braces may be considered for improvement of walking and treatment of medial compartment knee osteoarthritis.

CLINICAL RELEVANCE
Knee braces are an orthotic intervention that could potentially be significant in assisting in improving the walking parameters and treatment of medial compartment knee osteoarthritis.

Maleki|Maryam|M|
Arazpour|Mokhtar|M|
Joghtaei|Mahmoud|M|
Hutchins|Stephen W|SW|
Aboutorabi|Atefeh|A|
Pouyan|Ali|A|

pain
kinetic and kinematic parameter
Medial knee osteoarthritis
knee valgus braces


Alu RNA and their roles in human disease states.

Abstract: Alu RNA are implicated in the poor prognosis of several human disease states. These RNA are transcription products of primate specific transposable elements called Alu elements. These elements are extremely abundant, comprising over 10% of the human genome, and 100 to 1000 cytoplasmic copies of Alu RNA per cell. Alu RNA do not have a single universal functional role aside from selfish self-propagation. Despite this, Alu RNA have been found to operate in a diverse set of translational and transcriptional mechanisms. This review will focus on the current knowledge of Alu RNA involved in human disease states and known mechanisms of action. Examples of Alu RNA that are transcribed in a variety of contexts such as introns, mature mRNA, and non-coding transcripts will be discussed. Past and present challenges in studying Alu RNA, and the future directions of Alu RNA in basic and clinical research will also be examined.

translation
intron
Mature mRNA
non-coding
A-to-I editing
circular rna
cryptic
inverted repeat alu rna
miRNA sponge
splicing


Consensus statements on the clinical understanding and use of milnacipran in Hong Kong.

Abstract:
OBJECTIVE
Our aim is to develop a local consensus to guide medical practitioners and psychiatrists on the use of milnacipran in different psychiatric conditions.

METHODS
By utilizing the modified Delphi technique, 12 statements were electronically voted on anonymously for their practicability of recommendation.

RESULTS
There was a very high degree of agreement among the consensus group on 10 finalized consensus statements, but 2 statements were voted down due to a poor degree of agreement.

CONCLUSIONS
The present consensus statements were developed as general recommendations for medical practitioners and psychiatrists to be practically referred to in clinical settings.

Lee|Wing King|WK|
Au Yeung|Kwok Leung|KL|
Lam|Ho Bun|HB|
Wong|Chi Keung|CK|
Au|Ming Kai|MK|
Chan|Hoi Yee Karina|HYK|
Cheung|Yat Wo Eric|YWE|
Chui|Wing Ho|WH|
Wong|Ting Chi Vanessa|TCV|
Fu|Chi Kin|CK|
Sham|Shiu Kow|SK|
Mak|Ki Yan|KY|

consensus statements
milnacipran
Hong Kong


Antioxidative and aldose reductase-inhibitory effects of a fermentation filtrate of Rubus coreanus.

Abstract: Antioxidative and aldose reductase (AR)-inhibitory effects of a fermentation filtrate of Rubus coreanus (FRC) were investigated using corneal/retinal homogenate and lens cytosol, respectively. Rat corneal/retinal homogenate was treated with 50 µM FeCl(3) in the presence of FRC (3.2-100 µg/mL) for 30 min at 37℃, and thiobarbituric acid-reactive substances (TBARS) was quantified as a lipid peroxidation parameter. FRC markedly suppressed the TBARS production in a concentration-dependent manner, leading to 50% (IC(50)) and 100% (IC(100)) inhibitory concentrations of 20 and 95 µg/mL, respectively, which was similar to the effect of butylated hydroxyanisole. Activity of AR from rat lens was assayed in the presence of FRC (1-31.6 µg/mL) at 25℃ using glyceraldehyde as a substrate. FRC inhibited lens AR by 50% (IC(50)) and 90% (IC(90)) at approximately 2 and 31.6 µg/mL, respectively, comparable to the effect of quercetin. The results indicate that ERC could be a promising candidate for the improvement of eye injury and visual dysfunction of dry eye and diabetic patients.

Rubus coreanus
aldose reductase inhibition
antioxidative activity


Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: A prospective population-based cohort study.

Abstract:
OBJECTIVE
Thyroid dysfunction, a common complication of pregnancy, is associated with adverse obstetric and neonatal consequences. This study aimed to determine the effect of TSH levels on early pregnancy outcome in a prospective population-based cohort study.

DESIGN AND METHODS
The serum TSH, free thyroxine, free triiodothyronine, thyroid peroxidase antibody levels and urinary iodine concentration of 418 pregnant women in their first trimester of pregnancy were measured. According to the American Thyroid Association (ATA) and the local reference ranges for TSH, women were divided into two groups of 0.1-2.5, >2.5 mIU/L and 0.2-4.6, >4.6 mIU/L. The risk of spontaneous abortion (SA) was calculated for each group.

RESULTS
Spontaneous abortion was detected in 7.2% (n = 30) of total 418 pregnancies. Women with TSH levels > 2.5 mIU/L had an increased risk of SA, compared to women with TSH levels of 0.1-2.5 mIU/L (relative risk [RR] 3.719, 95% confidence interval [CI]:1.713-8.074). The risk of SA was increased in women with TSH levels > 4.6 mIU/L (RR 5.939, 95% CI: 1.711-20.620). The rate of SA was increased by 78% for every unit increase in standard deviation of TSH concentration (RR 1.35, 95% CI: 1.09-1.70). The rate of miscarriages in the treated group by levothyroxine was 9.8% (n = 6) compared to 28.6% (n = 8) in the untreated group (P = 0.024).

CONCLUSIONS
Our finding suggests that the upper limit for the TSH normal range should be redefined to <2.5 mIU/L during the first trimester of gestation. The local upper limit was 4.6 mIU/L, consistent with 4.0 mIU/L cut-off value recommended by the ATA.

spontaneous abortion
pregnancy
pregnancy outcome
first trimester
hypothyroidism
pregnancy loss
thyroid-stimulating hormone levels


Chinese perspectives on primary care for common mental disorders: Barriers and policy implications.

Abstract:
BACKGROUND
The World Health Organization (WHO) has called for integration of mental health into primary care for a decade. In Western countries, around 15% to 25% of patients with common mental disorders including mood and anxiety disorders seek help from primary care physicians (PCPs). The rate is only about 5% in China.

AIMS
This article reviews the Chinese findings on the barriers to primary care for common mental disorders and how they compared with Western findings.

METHODS
A narrative literature review was conducted, focusing on literature published from mid-1990s in English or Chinese. Patient, PCP and health system factors were reviewed.

RESULTS
Although Chinese and Western findings show similar themes of barriers, the Chinese have stronger barriers in most aspects, including under-recognition of the need for treatment, stigma on mental illness, somatization, worries about taking psychiatric drugs, uncertainties in the role, competency and legitimacy of PCPs in mental health care and short consultation time.

CONCLUSION
Current policies in China emphasize enhancement of mental health facilities and workforce in the community. Our review suggests that patients' intention to seek help and PCPs' competency in mental health care are other fundamental factors to be addressed.

Sun|Kai Sing|KS|0000-0003-0631-9699
Lam|Tai Pong|TP|
Wu|Dan|D|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

Chinese
primary care
common mental disorder
Barriers
Western
help-seeking


Quantitative determination of saroglitazar, a predominantly PPAR alpha agonist, in human plasma by a LC-MS/MS method utilizing electrospray ionization in a positive mode.

Abstract: A sensitive LC-MS/MS method was developed and validated for quantitation of saroglitazar using turboion spray interface with positive ion mode. A liquid-liquid extraction, with a mixture of dichloromethane and diethyl ether, was employed for the extraction of saroglitazar and glimepiride (IS) from human plasma. The chromatographic separation was achieved using an ACE-5, C18 (4.6 × 100 mm) column with a gradient mobile phase comprising acetonitrile and ammonium acetate buffer with trifluoracetic acid in purified water. Both analytes were separated within 10 min with retention times of 4.52 and 2.57 min for saroglitazar and IS, respectively. Saroglitazar quantitation was achieved by the summation of two MRM transition pairs (m/z 440.2 to m/z 366.0 and m/z 440.2 to m/z 183.1), while that of IS was achieved using transition pair m/z 491.3 to m/z 352.0. The calibration standards of saroglitazar showed linearity from 0.2 to 500 ng/mL, with a lower limit of quantitation of 0.2 ng/mL. The biases for inter- and intra-batch assays were -7.51-1.15% and -11.21 to -3.25%, respectively, while the corresponding precisions were 5.04-8.06% and 1.53-7.68%, respectively. The developed method was used to monitor the plasma concentrations of saroglitazar in clinical samples.

Ghoghari|Ashok|A|
Dash|Ranjeet|R|
Bhatt|Chandrakant|C|
Singh|Kanchan|K|
Jha|Anil|A|
Patel|Harilal|H|
Gupta|Rahul|R|
Kansagra|Kevinkumar|K|
Srinivas|Nuggehally R|NR|

D021241:Spectrometry, Mass, Electrospray Ionization

saroglitazar
plasma
LC-MS/MS
Lipaglyn™
PPAR-α
method validation
pharmacokinetics


Drought-Mediated Changes in Tree Physiological Processes Weaken Tree Defenses to Bark Beetle Attack.

Abstract: Interactions between water stress and induced defenses and their role in tree mortality due to bark beetles are poorly understood. We performed a factorial experiment on 48 mature ponderosa pines (Pinus ponderosa) in northern Arizona over three years that manipulated a) tree water stress by cutting roots and removing snow; b) bark beetle attacks by using pheromone lures; and c) phloem exposure to biota vectored by bark beetles by inoculating with dead beetles. Tree responses included resin flow from stem wounds, phloem composition of mono- and sesqui-terpenes, xylem water potential, leaf gas exchange, and survival. Phloem contained 21 mono- and sesqui-terpenes, which were dominated by (+)-α-pinene, (-)-limonene, and δ-3-carene. Bark beetle attacks (mostly Dendroctonus brevicomis) and biota carried by beetles induced a general increase in concentration of phloem mono- and sesqui-terpenes, whereas water stress did not. Bark beetle attacks induced an increase in resin flow for unstressed trees but not water-stressed trees. Mortality was highest for beetle-attacked water-stressed trees. Death of beetle-attacked trees was preceded by low resin flow, symptoms of water stress (low xylem water potential, leaf gas exchange), and an ephemeral increase in concentrations of mono- and sesqui-terpenes compared to surviving trees. These results show a) that ponderosa pine can undergo induction of both resin flow and phloem terpenes in response to bark beetle attack, and that the former is more constrained by water stress; b) experimental evidence that water stress predisposes ponderosa pines to mortality from bark beetles.

Induced defenses
Tree mortality
Pinus ponderosa
Dendroctonus
Terpenes
Drought
Tree chemical defense


Deep vein thrombosis of upper extremities due to reactive thrombocytosis in septic patients.

Abstract: Deep venous thrombosis (DVT) is not an uncommon condition in the intensive care unit (ICU), and having high morbidity and mortality. Upper limb DVT also is increasingly being recognized as a clinical entity. The presence of the indwelling catheter in neck veins is a risk for developing venous thrombus, which may be further aggravated by presence of thrombocytosis. In ICU patients with sepsis, reactive thrombocytosis has been found during the recovery phase. Here, we are presenting two cases, having thrombocytosis and central venous catheter who developed upper limb DVT.

Mishra|Shakti Bedanta|SB|
Bhoyer|Jashwini|J|
Gurjar|Mohan|M|
Muzaffar|Nabeel|N|
Verma|Anupam|A|

thrombocytosis
deep venous thrombosis
Central venous catheter


Pilot One-Hour Multidisciplinary Team Training Simulation Intervention in the Operating Room Improves Team Nontechnical Skills.

Abstract:
Background
The primary objective of this study was to determine if a 1-hour simulation-based training with interdisciplinary operating room (OR) teams could improve nontechnical skills of the providers as assessed by the nontechnical skills tool (NOTECHS II).

Methods
Interprofessional otolaryngology OR teams consisting of surgery faculty and resident, anesthesiology faculty and resident, and OR nurses, scrub technician, and perioperative technician underwent a 1-hour simulation-based intervention in the OR. The teams were rated on their nontechnical skills during the intervention and throughout the clinical day following. They also completed self-reflection surveys (SRS) before the intervention and in 3 intervals after the intervention (immediately following the intervention, at the end of their shift on the day of the intervention, and again 2 weeks later).

Results
Four interprofessional teams with a total of 26 unique participants participated in this pilot program. Team nontechnical skills, assessed using NOTECHS II, improved from the first simulation to the second simulation during the intervention. Team NOTECHS II scores remained higher throughout the clinical day. Individual self-reflection scores (SRS) followed the same trend.

Conclusions
On-site interprofessional OR team training simulation can take place in a brief time period that is dedicated for education. A brief intervention resulted in improved team nontechnical scores when assessed following intervention. In addition, participants found the intervention to be effective and beneficial to their learning.

Rochlen|Lauryn R|LR|
Malloy|Kelly M|KM|
Chang|Hele|H|
Kim|Sherr|S|
Guichard|Laurian|L|
Cassidy|Rut|R|
Zisblatt|Lar|L|

intervention
Teamwork
interprofessional education
simulation-based medical education


Lichen Amyloidosis: Novel Treatment with Fractional Ablative 2,940 nm Erbium: YAG Laser Treatment.

Abstract: Lichen amyloidosis (LA) is a type of primary localized cutaneous amyloidosis clinically characterized by persistent pruritic, hyperkeratotic papules commonly distributed on the shins and histopathologically characterized by amyloid deposits in the papillary dermis. The condition is difficult to treat though various treatment modalities have been tried. We report a case of LA treated successfully with Fractional ablative 2,940 nm Erbium: YAG Laser treatment. To the best of our knowledge, this is the first documented report of the successful use of fractional ablative laser in the treatment of LA.

lichen amyloidosis
Erbium: YAG laser
fractional photothermolysis


The potential for technology to enhance independence for those aging with a disability.

Abstract: Technologies of all kinds can sustain and accelerate improvements in health and quality of life for an aging population, and enhance the independence of persons with disabilities. Assistive technologies are widely used to promote independent functioning, but the aging of users and their devices produces unique challenges to individuals, their families, and the health care system. The emergence of new "smart" technologies that integrate information technology with assistive technologies has opened a portal to the development of increasingly powerful, individualized tools to assist individuals with disabilities to meet their needs. Yet, issues of access and usability remain to be solved for their usefulness to be fully realized. New cohorts aging with disabilities will have more resources and more experience with integrated technologies than current elders. Attention to technological solutions that help them adapt to the challenges of later life is needed to improve quality of life for those living long lives with disabilities.

D006301:Health Services Needs and Demand


Network pharmacology-based analysis in determining the mechanisms of Huoxin pill in protecting against myocardial infarction.

Abstract:
CONTEXT
Huoxin pill (HXP) is a commonly used TCM prescription for treatment of cardiovascular diseases. However, its mechanism in protecting against myocardial infarction (MI) remains unknown.

OBJECTIVE
We performed a network pharmacology analysis to explore the bioactive ingredients, therapeutic effects, and mechanisms of HXP in protecting against MI.

MATERIALS AND METHODS
HPLC was used to identify major bioactive compounds, and overlap with MI target genes were visualised. 10-Week old C57BL/6 mice were randomly assigned as: Sham-operated control, MI + Phosphate buffered saline (PBS), and MI + HXP (3 mg/mL and 9 mg/mL) treatment groups, received oral gavage administration once every two-days starting from 1-week prior to MI, and subsequently MI models were established for one-week before sacrifice.

RESULTS
AKT1, VEGFA, TNF and RELA were identified as core target proteins among eighty-five candidate bioactive compounds identified in HXP with overlapping MI-related genes. HXP protection against MI was mainly via regulation of inflammatory pathways, notably TNF signalling pathway. Mouse models of MI and cardiac myoblasts demonstrated that HXP improved MI-induced injury via improving regulation of inflammatory response.

DISCUSSION AND CONCLUSION
Stellasterol, deoxycholic acid, kaempferol, and quercetin are important active compounds contained in HXP with anti-inflammatory properties in the therapeutic treatment of MI. Due to the straightforward nature and effectiveness of taking oral HXP medications, our findings provide a theoretical basis for the clinical application of HXP in treating patients with angina or myocardial ischaemia. Future research into the combination of surgical procedures or medications that restore blood flow together with HXP as supportive medication would be worthwhile.

He|Jia|J| Wo|Da|D| Ma|En|E| Wang|Qing|Q| Chen|Jinxiao|J| Peng|Jun|J| Zhu|Weidong|W| Ren|Dan-Ni|DN|

cardiovascular disease
pharmacological analysis
bioactive compounds
inflammatory response
Myocardial ischaemia


Correlation of Orthodontic Treatment by Fixed or Myofunctional Appliances and Periodontitis: A Retrospective Study.

Abstract:
INTRODUCTION
Malocclusion plays an important role in the development of periodontitis. Thus, by treating malocclusion, a good gingival health can be achieved. This study was conducted to establish the correlation between orthodontic tooth movement and periodontitis.

MATERIALS AND METHODS
This is a retrospective study conducted on 220 patients who underwent orthodontic treatment for malocclusion. They were divided into two groups: Group I patients were treated with fixed orthodontics, while group II patients received myofunctional appliances.

RESULTS
The value for plaque, gingival recession, and tooth mobility significantly increased in group I patients. However, the difference was statistically nonsignificant in group II patients.

CONCLUSION
The authors concluded that there is correlation between malocclusion and periodontitis. Malocclusion leads to periodontitis.

CLINICAL SIGNIFICANCE
Malocclusion is the main reason for the development of poor periodontal health. Combined effort has to be played by both periodontist and orthodontist for the treatment of various orthodontic-periodontal problems.

Sharma|Kanchan|K|
Mangat|Sukhpreet|S|
Kichorchandra|Modi S|MS|
Handa|Akash|A|
Bindhumadhav|Suresh|S|
Meena|Meenakshi|M|

Malocclusion
Myofunctional appliances Periodontitis.


The effect of ghrelin O-acyltransferase inhibitor on gastric H+-K+-ATPase activity and GOAT/ghrelin system in gastric mucosal cells in vitro.

Abstract: Ghrelin is implicated in the regulation of gastric functional development. The octanoylation of ghrelin is critical for its physiological functions which dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. To investigate the effect of GOAT on gastric acid secretion and expression of ghrelin in vitro. Primary cultures of gastric mucosal cells were challenged with 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (The GOAT inhibitor), respectively, for 24 h in order to further clarify the effect of GOAT on H+-K+-ATPase activity. In vitro, GO-CoA-Tat significantly increased ghrelin and GOAT mRNA expression at 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL, and augmented cell total ghrelin secretion at 1.5 × 10-3 mol/mL. But cell acylated ghrelin secretion was reduced at 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). And cell acylated ghrelin synthesis was reduced at 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). In accordance with acylated ghrelin level, H+-K+-ATPase activity were decreased with 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). These results indicated that GOAT inhibitor decreases the acylated ghrelin level and H+-K+-ATPase activity in vitro.

Du|Gai Mei|GM|
Luo|Bi Ping|BP|
Hu|Zhi Hua|ZH|
Wu|Jie Ge|JG|
Yan|Wen Mei|WM|
Han|Zheng Qiang|ZQ|
Zhang|Yu Hong|YH|
Liu|Mao Jun|MJ|

GOAT
Total ghrelin
Acylated ghrelin
H(+)–K(+)-ATPase activity


Crystal structure of 4-sulfamoylanilinium di-hydrogen phosphate.

Abstract: In the crystal structure of the title mol-ecular salt, C6H9N2O2S(+)·H2PO4 (-), the sulfomylalinium cations and the di-hydrogen phosphate anions form independent [100] chains through Ns-H⋯O (s = sulfamo-yl) and O-H⋯O hydrogen bonds, respectively. The chains are cross-linked by Na-H⋯O (a = amine) hydrogen bonds, generating (010) sheets. Two C-H⋯O hydrogen bonds involving diametrically opposite C atoms in the benzene ring of the cation as donors form chains parallel to [202] in which P=O and P-OH groups are acceptors. Together, these inter-actions lead to a three-dimensional network.

Muthuselvi|C|C|
Mala|N|N|
Srinivasan|N|N|
Pandiarajan|S|S|
Krishnakumar|R V|RV|

crystal structure
4-sulfamoylanilinium
hydrogen bonding
dihydrogen phosphate
sulfa drugs
sulfanilamide derivatives


The regenerating family member 3 β instigates IL-17A-mediated neutrophil recruitment downstream of NOD1/2 signalling for controlling colonisation resistance independently of microbiota community structure.

Abstract:
OBJECTIVE
Loss of the Crohn's disease predisposing NOD2 gene results in an intestinal microenvironment conducive for colonisation by attaching-and-effacing enteropathogens. However, it remains elusive whether it relies on the intracellular recruitment of the serine-threonine kinase RIPK2 by NOD2, a step that is required for its activation of the transcription factor NF-κB.

DESIGN
Colonisation resistance was evaluated in wild type and mutant mice, as well as in ex-germ-free (ex-GF) mice which were colonised either with faeces from Ripk2-deficient mice or with bacteria with similar preferences for carbohydrates to those acquired by the pathogen. The severity of the mucosal pathology was quantified at several time points postinfection by using a previously established scoring. The community resilience in response to infection was evaluated by 16S ribosomal RNA gene sequence analysis. The control of pathogen virulence was evaluated by monitoring the secretion of Citrobacter-specific antibody response in the faeces.

RESULTS
Primary infection was similarly outcompeted in ex-GF Ripk2-deficient and control mice, demonstrating that the susceptibility to infection resulting from RIPK2 deficiency cannot be solely attributed to specific microbiota community structures. In contrast, delayed clearance of Citrobacter rodentium and exacerbated histopathology were preceded by a weakened propensity of intestinal macrophages to afford innate lymphoid cell activation. This tissue protection unexpectedly required the regenerating family member 3β by instigating interleukin (IL) 17A-mediated neutrophil recruitment to the intestine and subsequent phosphorylation of signal transducer and activator of transcription 3.

CONCLUSIONS
These results unveil a previously unrecognised mechanism that efficiently protects from colonisation by diarrhoeagenic bacteria early in infection.

Waldschmitt|Nadine|N|
Kitamoto|Sho|S|
Secher|Thomas|T|
Zacharioudaki|Vassiliki|V|
Boulard|Olivier|O|
Floquet|Emilie|E|
Delacre|Myriam|M|
Lamas|Bruno|B|
Pham|Hang-Phuong|HP|
Six|Adrien|A|
Richard|Mathias L|ML|
Dagorn|Jean-Charles|JC|
Eberl|Gérard|G|
Langella|Philippe|P|
Chatel|Jean-Marc|JM|
Ryffel|Bernhard|B|
Iovanna|Juan Lucio|JL|
Poulin|Lionel F|LF|
Sokol|Harry|H|
Kamada|Nobuhiko|N|
Chamaillard|Mathias|M|

D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2

D053422:Receptor-Interacting Protein Serine-Threonine Kinases

Macrophages
Interleukins
Antibacterial Peptide
Barrier Function
Colonic Microflora


Reciprocal space tomography of 3D skyrmion lattice order in a chiral magnet.

Abstract: It is commonly assumed that surfaces modify the properties of stable materials within the top few atomic layers of a bulk specimen only. Exploiting the polarization dependence of resonant elastic X-ray scattering to go beyond conventional diffraction and imaging techniques, we have determined the depth dependence of the full 3D spin structure of skyrmions-that is, topologically nontrivial whirls of the magnetization-below the surface of a bulk sample of Cu2OSeO3 We found that the skyrmions change exponentially from pure Néel- to pure Bloch-twisting over a distance of several hundred nanometers between the surface and the bulk, respectively. Though qualitatively consistent with theory, the strength of the Néel-twisting at the surface and the length scale of the variation observed experimentally exceed material-specific modeling substantially. In view of the exceptionally complete quantitative theoretical account of the magnetic rigidities and associated static and dynamic properties of skyrmions in Cu2OSeO3 and related materials, we conclude that subtle changes of the materials properties must exist at distances up to several hundred atomic layers into the bulk, which originate in the presence of the surface. This has far-reaching implications for the creation of skyrmions in surface-dominated systems and identifies, more generally, surface-induced gradual variations deep within a bulk material and their impact on tailored functionalities as an unchartered scientific territory.

Zhang|Shilei|S|
van der Laan|Gerrit|G|
Müller|Jan|J|
Heinen|Lukas|L|
Garst|Markus|M|
Bauer|Andreas|A|
Berger|Helmuth|H|
Pfleiderer|Christian|C|
Hesjedal|Thorsten|T|0000-0001-7947-3692

skyrmions
resonant elastic X-ray scattering
3D magnetic imaging
magnetic surface effects
spintronics


Numerical Simulation of Flow Field and Ion Transport for Different Ion Source Sampling Interfaces of a Mass Spectrometer.

Abstract: Understanding ion transport mechanisms in the flow expansion section of the first vacuum region of a mass spectrometer (MS) with an atmospheric pressure ionization source is essential for optimizing the MS sampling interface design. In this study, numerical simulations of three types of ions in two different MS interface designs have been carried out. In contrast to previously reported numerical studies, nonequilibrium gas dynamics due to rarefied gas effects has been considered in modeling the flow expansion and a realistic space charge effect has been considered in a continuous ion injection mode. Numerical simulations reveal that a flat plate interface has a higher peak buffer gas velocity but a narrower zone of silence compared to the conical interface. Shock wave structures are clearly captured, and the Knudsen number distribution is displayed. Simulation results show that in the axial direction the buffer gas effect is much stronger than the electric force effect in the current configuration. The conical interface leads to both a strong ion acceleration in the zone of silence and a strong ion deceleration downstream. In the radial direction, both the electric force and buffer gas drag force play an important role. The conical interface introduces a relatively stronger ion focusing effect from the radial buffer gas effect and a stronger ion dispersion from the radial electric force than the flat plate interface. The net effect for the current configuration is an increase in ion losses for the conical interface. Nanoelectrospray ionization experiments were carried out to validate the ion transmission efficiency.

ion transport
flow expansion
nano-ESI
numerical gas dynamic simulation
space-charge effect


Stability and transition of depression subtypes in late life.

Abstract:
BACKGROUND
The heterogeneity of late-life depression hampers diagnosis and treatment. Data-driven methods have identified several subtypes of depression in older persons, but the longitudinal stability of these subtypes remains unknown.

METHODS
In total 111 older persons with a major depressive disorder both at baseline and 2-year follow-up from the Netherlands Study of Depression in Older persons (NESDO) were included. Latent class analysis was performed to identify subtypes of depression at baseline and at 2-year follow-up, and latent transition analysis was used to examine the stability of these subtypes over time. Transition rates between subtypes and characteristics of groups were examined.

RESULTS
Two subtypes were identified in both baseline (T0) and follow-up data (T1), including a 'melancholic' subtype (prevalence 80.2% (T0) and 62.2% (T1)), and an 'atypical' subtype (prevalence 19.8% (T0) and 37.8% (T1)). The melancholic subtype was characterized by decreased appetite and weight and had a stability of 0.86. The atypical subtype was characterized by increased appetite and weight and had a stability of 0.93, although the discriminating power of different symptoms had decreased at T1. Mean age and education differed significantly between stable and transitioning subgroups, other characteristics did not differ between subgroups.

LIMITATIONS
Limited sample size might have hampered the analyses.

CONCLUSIONS
Subtypes of late-life depression are relatively stable, but symptoms of depression (like weight loss) seem to blur with symptoms of (patho)physiological aging. This underlines the clinical relevance of depression subtyping, but also the importance of further research into subtypes and the influence of aging.

Veltman|Eveline|E|
Kok|Almar|A|
Lamers|Femke|F|
Stek|Max|M|
van der Mast|Roos|R|
Rhebergen|Didi|D|

Depression subtypes
Late-life depression
Latent transition analysis
Atypical depression
Melancholic depression
Stability of depressive subtypes


Primary intracranial intraventricular leiomyoma: a literature review.

Abstract: Leiomyomas, benign tumors of well-differentiated smooth muscle and vascular collagenous tissue, usually occur in the uterus but can develop wherever smooth muscle is present. Primary intracranial leiomyomas are rare tumors. We present the case of a 40-year-old woman with a primary intraventricular leiomyoma. She consulted us for headache, dizziness, and black spots in her vision. Magnetic resonance images (MRI) disclosed a mass rooted in the posterior septum pellucidum. The tumor was totally excised by the senior author with no residual seen on intraoperative MRI. Pathological examination showed it to be a benign spindle-cell neoplasm. On the 6th month control MRI, there was no recurrence. We also reviewed articles relevant to primary intracranial leiomyomas.

Yaltırık|Cumhur Kaan|CK|
Yamaner|Emin Oğuzcan|EO|
Harput|Mehmet Volkan|MV|
Sav|Murat Aydın|MA|
Türe|Uğur|U|

Intracranial
Leiomyoma
Magnetic resonance imaging
Intraventriculer


Vitamin D deficiency is associated with an oxidized plasma cysteine redox potential in critically Ill children.

Abstract: Critically ill populations incur high levels of oxidative stress and commonly present with vitamin D deficiency. This study aimed to investigate the relationship between vitamin D status and plasma markers of glutathione (GSH) and cysteine (Cys) redox and immunity in critically ill children. This was a cross-sectional study of n=50 PICU patients. Subjects were categorized according to their plasma 25-hydroxyvitamin D [25(OH)D] concentrations: (<20, 20-30, and ≥30ng/dL). Plasma GSH, glutathione disulfide (GSSG), Cys, and cystine (CySS) were measured with high-performance liquid chromatography, and their associated redox potentials determined (EhGSSG and EhCySS, respectively). Plasma LL-37, an indicator of innate immune function, was assayed with ELISA. Data were analyzed using general linear regression before and after adjustment for age, sex, and race. Results showed that EhCySS was more reduced in subjects with plasma 25(OH)D concentrations ≥30ng/mL compared to those with 25(OH)D concentrations <20ng/mL (P=0.009). Plasma GSH, GSSG, and total GSH decreased with increasing 25(OH)D category (P=0.06, 0.03, and 0.01, respectively), and plasma glutamine levels were lowest in subjects with plasma 25(OH)D concentrations ≥30ng/mL (P=0.004). Plasma LL-37 concentrations did not significantly differ by vitamin D status (P=0.08). In conclusion, vitamin D sufficiency was associated with more reduced plasma EhCySS, indicative of lower oxidative stress in critically ill children. Plasma GSH, GSSG, and glutamine, however, were lower in the vitamin D sufficient group. The role of vitamin D in maintaining redox status during pediatric critical illness requires further study.

Alvarez|Jessica A|JA|
Grunwell|Jocelyn R|JR|
Gillespie|Scott E|SE|
Tangpricha|Vin|V|
Hebbar|Kiran B|KB|

Oxidative stress
LL-37
Pediatrics
Calcidiol
Cathelicidin
Critical care


Caring: An Undiscovered "Super Ility" of Smart Healthcare.

Abstract: As new and exciting applications emerge using smart technologies, the Internet of Things, data analytics, and others for healthcare, a critical problem is emerging: the potential loss of caring. While these exciting technologies have improved patient care by allowing for better assessment, surveillance, and treatment, the use of technology can disassociate the caregiver from the patient, essentially removing the "care" from healthcare. Here we introduce the notion of caring as an undiscovered ility that ranks at least as important as other well-known ilities in healthcare systems.

ilities
internet of things
requirements
smart healthcare system


Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats.

Abstract:
PURPOSE
Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3).

METHODS
Experiment 1 examined the effects of increasing concentrations (2.5-20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals.

RESULTS
Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals.

CONCLUSION
Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

Chukwuma|Chika Ifeanyi|CI|
Mopuri|Ramgopal|R|
Nagiah|Savania|S|
Chuturgoon|Anil Amichund|AA|
Islam|Md Shahidul|MS|

Erythritol
Glucose absorption
Glucose uptake
Glut-4
IRS-1
Type 2 diabetes (T2D)


Frailty In Patients Undergoing Vascular Surgery: A Narrative Review Of Current Evidence.

Abstract: Frailty is presumably associated with an elevated risk of postoperative mortality and adverse outcome in vascular surgery patients. The aim of our review was to identify possible methods for risk assessment and prehabilitation in order to improve recovery and postoperative outcome. The literature search was performed via PubMed, Embase, OvidSP, and the Cochrane Library. We collected papers published in peer-reviewed journals between 2001 and 2018. The selection criterion was the relationship between vascular surgery, frailty and postoperative outcome or mortality. A total number of 52 publications were included. Frailty increases the risk of non-home discharge independently of presence or absence of postoperative complications and it is related to a higher 30-day mortality and major morbidity. The modified Frailty Index showed significant association with elevated risk for post-interventional stroke, myocardial infarction, prolonged in-hospital stays and higher readmission rates. When adjusted for comorbidity and surgery type, frailty seems to impact medium-term survival (within 2 years). Preoperative physical exercising, avoidance of hypalbuminemia, psychological and cognitive training, maintenance of muscle strength, adequate perioperative nutrition, and management of smoking behaviours are leading to a reduced length of stay and a decreased incidence of readmission rate, thus improving the effectiveness of early rehabilitation. Pre-frailty is a dynamically changing state of the patient, capable of deteriorating or improving over time. With goal-directed preoperative interventions, the decline can be prevented.

prehabilitation
postoperative outcome
patient management
preoperative risk assessment


Altered Spontaneous Neural Activity in Peripartum Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

Abstract: Abnormalities related to peripartum depression (PPD) have been detected in several brain regions through tasking-state functional magnetic resonance imaging (fMRI). In this study, we used the two markers of resting-state fMRI (rs-fMRI) to investigate changes in spontaneous neural activity of PPD and their correlation with depression severity. A total of 16 individuals with PPD were compared with 16 age- and education-matched healthy controls (HCs) by using rs-fMRI. Two-sample t-test was used to compare the fractional amplitudes of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the fALFF and ReHo of the abnormal brain region and the Hamilton Depression Scale (HAMD) and Edinburgh Postnatal Depression Scale scores. The spontaneous neural activity of the PPD group significantly increased mainly in the left middle frontal gyrus, left precuneus, left inferior parietal lobule, and left dorsolateral prefrontal cortex (DLPFC) and decreased mainly in the bilateral precentral gyrus and right inferior occipital gyrus compared with those of the HCs. The fALFF value of the left DLPFC was negatively correlated with the HAMD score in PPD. This rs-fMRI study suggests that changes in the spontaneous neural activity of these regions are related to emotional responses. PPD cases with low fALFF values in the left DLPFC have severe depression.

Che|Kaili|K| Mao|Ning|N| Li|Yuna|Y| Liu|Meijie|M| Ma|Heng|H| Bai|Wei|W| Xu|Xiao|X| Dong|Jianjun|J| Li|Ying|Y| Shi|Yinghong|Y| Xie|Haizhu|H|

fractional amplitude of low-frequency fluctuation


Role of Complement and Histones in Sepsis.

Abstract: The wide use of the mouse model of polymicrobial sepsis has provided important evidence for events occurring in infectious sepsis involving septic mice and septic humans. Nearly 100 clinical trials in humans with sepsis have been completed, yet there is no FDA-approved drug. Our studies of polymicrobial sepsis have highlighted the role of complement activation products (especially C5a anaphylatoxin and its receptors C5aR1 and C5aR2) in adverse effects of sepsis. During sepsis, the appearance of these complement products is followed by appearance of extracellular histones in plasma, which have powerful proinflammatory and prothrombotic activities that cause cell injury and multiorgan dysfunction in septic mice. Similar responses occur in septic humans. Histone appearance in plasma is related to complement activation and appearance of C5a and its interaction with its receptors. Development of the cardiomyopathy of sepsis also depends on C5a, C5a receptors and histones. Neutralization of C5a with antibody or absence of C5aR1 blocks appearance of extracellular histones and cell and organ failure in sepsis. Survival rates in septic mice are greatly improved after blockade of C5a with antibody. We also review the various strategies in sepsis that greatly reduce the development of life-threatening events of sepsis.

histones
C5a
anaphylatoxins
C5b-9
METs
NETs
NLRP3 inflammasome
ROS


The cross-talk between enterocytes and intraepithelial lymphocytes.

Abstract: The gut mucosa is continuously exposed to food and microbial antigens. Both enterocytes and intraepithelial lymphocytes have a pivotal role in maintaining the integrity of intestinal mucosa, as these cells guarantee a first line of defense against pathogens and toxic molecules. Enterocytes maintain a physical barrier against microbes and directly contribute to the gut homeostasis by sampling the luminal agents through several pattern recognition receptors or presenting antigen to mucosa T cells. Similarly, due to a close physical contact with the intestinal epithelial cells, the intraepithelial lymphocytes represent an important part of the gut lymphoid tissue, contrasting the entry and spread of pathogens. An alteration of the cross-talk between intestinal epithelial cells and intraepithelial lymphocytes might actively contribute to the development of intestinal immune disorders, as occurring in patients with celiac disease. In genetically predisposed individuals, the gluten exposure results in a massive production of interleukin-15, activation of intraepithelial lymphocytes, and modification of small intestinal mucosa architecture and function. We will review the recent studies on the pathophysiology of cross-talk between enterocytes and intraepithelial T cells, and how this interaction is crucial for intestinal integrity and homeostasis.

Enterocytes
Celiac disease
Intestinal intraepithelial lymphocytes


Use of circulating tumor cells in prospective clinical trials for NSCLC patients - standardization of the pre-analytical conditions.

Abstract:
BACKGROUND
Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage.

METHODS
Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs.

RESULTS
Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement.

CONCLUSIONS
The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.

D017404:In Situ Hybridization, Fluorescence

Isolation by SizE of Tumor/Trophoblastic Cells (ISET)


Lipid-Polyglutamate Nanoparticle Vaccine Platform.

Abstract: Peptide-based subunit vaccines are attractive in view of personalized cancer vaccination with neo-antigens, as well as for the design of the newest generation of vaccines against infectious diseases. Key to mounting robust antigen-specific immunity is delivery of antigen to antigen-presenting (innate immune) cells in lymphoid tissue with concomitant innate immune activation to promote antigen presentation to T cells and to shape the amplitude and nature of the immune response. Nanoparticles that co-deliver both peptide antigen and molecular adjuvants are well suited for this task. However, in the context of peptide-based antigen, an unmet need exists for a generic strategy that allows for co-encapsulation of peptide and molecular adjuvants due to the stark variation in physicochemical properties based on the amino acid sequence of the peptide. These properties also strongly differ from those of many molecular adjuvants. Here, we devise a lipid nanoparticle (LNP) platform that addresses these issues. Key in our concept is poly(l-glutamic acid) (PGA), which serves as a hydrophilic backbone for conjugation of, respectively, peptide antigen (Ag) and an imidazoquinoline (IMDQ) TLR7/8 agonist as a molecular adjuvant. Making use of the PGA's polyanionic nature, we condensate PGA-Ag and PGA-IMDQ into LNP by electrostatic interaction with an ionizable lipid. We show in vitro and in vivo in mouse models that LNP encapsulation favors uptake by innate immune cells in lymphoid tissue and promotes the induction of Ag-specific T cells responses both after subcutaneous and intravenous administration.

vaccine
peptides
lipid nanoparticles
TLR agonists


The challenge of maintaining necessary vascular and endovascular services at a referral center in Northern Italy during the COVID-19 outbreak.

Abstract:
OBJECTIVES
The Padova Hospital Vascular Surgery Division is located in Veneto, one of the area of the Northern Italy most hit by the Coronavirus disease 2019 outbreak. The aim of this paper is to describe the protocols adopted and to evaluate their impact during the acute phase of Coronavirus spread, focusing on the management of elective and urgent/emergent surgery, outpatients activity, and also health staff preservation from intra-hospital Coronavirus disease 2019 infection.

METHODS
Several measures were progressively adopted in the Padova University Hospital to front the Coronavirus disease 2019 outbreak, with a clear strong asset established by 9 March 2020, after the Northern Italy lockdown. Since this date, the Vascular Surgery Unit started a "scaled-down" activity, both for elective surgical procedures and for the outpatient Clinical activities; different protocols were developed for health preservation of staff and patients. We compared a two months period, 30 days before and 30 days after this time point. In particular, emergent vascular surgery was regularly guaranteed as well as urgent surgery (to be performed within 24 h). Elective cases were scheduled for "non-deferrable" pathology. A swab test protocol for COVID-19 was applied to health-care professionals and hospitalized patients.

RESULTS
The number of urgent or emergent aortic cases remained stable during the two months period, while the number of Hospital admissions via Emergency Room related to critical limb ischemia decreased after national lockdown by about 20%. Elective vascular surgery was scaled down by 50% starting from 9 March; 35% of scheduled elective cases refused hospitalization during the lockdown period and 20% of those contacted for hospitalization where postponed due to fever, respiratory symptoms, or close contacts with Coronavirus disease 2019 suspected cases. Elective surgery reduction did not negatively influence overall carotid or aortic outcomes, while we reported a higher major limb amputation rate for critical limb ischemia (about 10%, compared to 4% for the standard practice period). We found that 4 out of 98 (4%) health-care providers on the floor had an asymptomatic positive swab test. Among 22 vascular doctors, 3 had a confirmed Coronavirus disease 2019 infection (asymptomatic); a total of 72 swab were performed (mean = 3.4 swab/person/month) during this period; no cases of severe Coronavirus disease 2019 (deaths or requiring intensive care treatment) infection were reported within this period for the staff or hospitalized patients.

CONCLUSIONS
Elective vascular surgery needs to be guaranteed as possible during Coronavirus disease 2019 outbreak. The number of truly emergent cases did not reduce, on the other side, Emergency Room accesses for non-emergent cases decreased. Our preliminary results seem to describe a scenario where, if the curve of the outbreak in the regional population is flattened, in association with appropriate hospitals containment rules, it may be possible to continue the activity of the Vascular Surgery Units and guarantee the minimal standard of care.

D019033:Delivery of Health Care, Integrated


The effects of 7-week cognitive training in patients with vascular cognitive impairment, no dementia (the Cog-VACCINE study): A randomized controlled trial.

Abstract:
INTRODUCTION
Evidence for the efficacy of cognitive training in patients with subcortical vascular cognitive impairment no dementia is still lacking.

METHODS
A randomized, active controlled design using multidomain, adaptive, computerized cognitive training for 30 minutes, 5 days/week for 7 weeks. Assessments included global cognitive function and executive function (primary outcomes) and brain functional connectivity and structural changes (secondary outcomes).

RESULTS
Sixty patients were randomized across three medical centers in Beijing. At the end of the intervention, the cognitive training group showed significant improvement in Montreal Cognitive Assessment relative to the active control group (P = .013) and significantly increased functional connectivity between the left dorsolateral prefrontal cortex and medial prefrontal cortex, which was significantly correlated with Montreal Cognitive Assessment change (P = .017).

DISCUSSION
Computerized cognitive training significantly improved global cognitive function, which was supported by the improved brain plasticity. Incorporation of biomarkers should be implemented in cognitive training trials.

Tang|Yi|Y|
Xing|Yi|Y|
Zhu|Zude|Z|
He|Yong|Y|
Li|Fang|F|
Yang|Jianwei|J|
Liu|Qing|Q|
Li|Fangyu|F|
Teipel|Stefan J|SJ|
Zhao|Guoguang|G|
Jia|Jianping|J|

D000073216:Mental Status and Dementia Tests

Vascular cognitive impairment no dementia


Anti-HER2 Therapy Beyond Second-Line for HER2-Positive Metastatic Breast Cancer: A Short Review and Recommendations for Several Clinical Scenarios from a Spanish Expert Panel.

Abstract:
BACKGROUND
The aim of this project was to provide an expert opinion regarding anti-human epidermal growth factor receptor 2 (HER2) therapy beyond second-line treatment of metastatic breast cancer (mBC).

METHODS
A group of experts discussed specific issues concerning anti-HER2 therapy in late-line settings in mBC.

RESULTS
Trastuzumab emtansine (T-DM1) or dual HER2 blockade appeared to be good options for HER2-positive mBC after ≥ 2 HER2-targeted therapies. Once an objective response has been achieved with anti-HER2-containing therapy, the anti-HER2 agent can be continued until progression of the disease, unacceptable toxicity or patient decision. mBC treated with ≥ 3 consecutive lines of anti-HER therapy, ≥ 1 being a dual HER2 blockade and with early progression of disease during a fourth or later-line treatment, are clinically resistant to anti-HER therapy. For progression of metastasis in the brain after anti-HER2 therapy, lapatinib and chemotherapy appear to be a good alternative after best local treatment.

CONCLUSIONS
Further clinical trials are needed to provide valuable knowledge about the best treatment options in the later settings of mBC.

Martínez-Jañez|Noelia|N|
Chacón|Ignacio|I|
de Juan|Ana|A|
Cruz-Merino|Luis|L|
Del Barco|Sònia|S|
Fernández|Isaura|I|
García-Teijido|Paula|P|
Gómez-Bernal|Amalia|A|
Plazaola|Arrate|A|
Ponce|José|J|
Servitja|Sonia|S|
Zamora|Pilar|P|

Anti-HER2
Metastatic breast cancer
Clinical practice


Evaluation of five different questionnaires for assessing sleep apnea syndrome in a sleep clinic.

Abstract:
BACKGROUND
Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a major cause of morbidity and mortality. Different clinical models and questionnaires have been used to evaluate patients with the highest OSAHS probability.

OBJECTIVES
To evaluate the clinical utility of five different questionnaires--STOP, STOPBang (SB), Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS), and 4-Variable Screening Tool (4-V) - in a sleep clinic in order to identify patients at risk for OSAHS and to assess the best possible combination of these tools.

METHODS
1853 (74.4% males) patients (mean age 52±14 years; mean body mass index 32.8±7 kg/m2) visiting a sleep clinic were studied retrospectively.

RESULTS
SB had the highest sensitivity (97.6%), the largest area under the receiver operating characteristics curve (AUC) (0.73; 95% CI, 0.7-0.76) and best OR (5.9; 95% CI, 3.6-9.5), but the lowest specificity (12.7%) for AHI > or =15. The 4-V > or = 14 had the highest specificity (74.4%) followed by ESS (67%). BQ had good sensitivity (87%), worse specificity (33%) than 4-V and ESS but better than STOP (13%) and SB (12.7%). The combination of questionnaires did not improve their predictive value.

CONCLUSIONS
SB had the highest sensitivity, OR, and AUC, but rather low specificity, and 4-V the highest specificity. The combination of different questionnaires did not improve their predictive value.

Pataka|Athanasia|A|
Daskalopoulou|Euphemia|E|
Kalamaras|George|G|
Fekete Passa|Katalin|K|
Argyropoulou|Parakevi|P|

Evaluation
STOPBang
Berlin Questionnaire
ESS
4-Variable Screening Tool
STOP