Laparoscopic Management of Huge Cervical Myoma.

Abstract:
STUDY OBJECTIVE
To demonstrate the feasibility of laparoscopic management of a huge cervical myoma.

DESIGN
Step-by-step video demonstration of the surgical procedure (Canadian Task Force classification III-C).

SETTING
Uterine myoma is the most common benign neoplasm of the female reproductive tract, with an estimated incidence of 25% to 30% at reproductive age [1,2]. Patients generally have no symptoms; however, those with such symptoms as severe pelvic pain, heavy uterine bleeding, or infertility may be candidates for surgery. The traditional management is surgery; however, uterine artery embolization or hormonal therapy using a gonadotropin-releasing hormone agonist or a selective estrogen receptor modulator should be preferred as the medical approach. Surgical management should be performed via laparoscopy or laparotomy; however, the use of laparoscopic myomectomy is being debated for patients with huge myomas. Difficulties in the excision, removal, and repair of myometrial defects, increased operative time, and blood loss are factors keeping physicians away from laparoscopic myomectomy [1,2].

INTERVENTIONS
A 40-year-old gravida 0, para 0 woman was admitted to our clinic with complaints of chronic pelvic pain, dyspareunia, and infertility. Her health history was unremarkable. Ultrasonographic examination revealed a 14 × 10-cm myoma in the cervical region. On bimanual examination, an immobile solid mass originating from the uterine cervix and filling the pouch of Douglas was palpated. The patient was informed of the findings, and laparoscopic myomectomy was recommended because of her desire to preserve her fertility. Abdominopelvic examination revealed a huge myoma filling and enlarging the cervix. Myomectomy was performed using standard technique as described elsewhere. A transverse incision was made using a harmonic scalpel. The myoma was fixed with a corkscrew manipulator and enucleated. Once bleeding was controlled, the myoma bed was filled with Spongostan to prevent possible bleeding from leakage. Owing to the anatomic structure of the cervical region, the incision was closed in a monolayer with 0 Vicryl. Total intraoperative blood loss was 300 mL, the total weight of the myoma was 670 g, and the operation lasted approximately 140 minutes. The patient experienced no intraoperative complications. She was discharged on postoperative day 1 and did not exhibit any problems at follow-up. The final histopathological examination confirmed the diagnosis of uterine leiomyoma.

CONCLUSION
Laparoscopic management of huge myomas in difficult locations such as the cervical region seems to be a feasible and safe surgical option, especially in experienced hands.

D019060:Minimally Invasive Surgical Procedures


TEAD2 as a novel prognostic factor for hepatocellular carcinoma.

Abstract: TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial‑mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target.

Joo|Jong Seok|JS|
Cho|Sang Yeon|SY|
Rou|Woo Sun|WS|
Kim|Ju Seok|JS|
Kang|Sun Hyung|SH|
Lee|Eaum Seok|ES|
Moon|Hee Seok|HS|
Kim|Seok Hyun|SH|
Sung|Jae Kyu|JK|
Kwon|In Sun|IS|
Eun|Hyuk Soo|HS|
Lee|Byung Seok|BS|

D000091262:TEA Domain Transcription Factors

TEAD2
hepatocellular carcinoma
prognosis
The Cancer Genome Atlas data
survival analysis


Label-free high-resolution imaging of prostate glands and cavernous nerves using coherent anti-Stokes Raman scattering microscopy.

Abstract: A custom built coherent anti-Stokes Raman scattering (CARS) microscope was used to image prostatic glands and nerve structures from 17 patients undergoing radical prostatectomy. Imaging of glandular and nerve structures showed distinctive cellular features that correlated to histological stains. Segmentation of cell nucleus was performed to establish a cell feature-based model to separate normal glands from cancer glands. In this study, we use a single parameter, average cell neighbor distance based on CARS imaging, to characterize normal and cancerous glandular structures. By combining CARS with our novel classification model, we are able to characterize prostate glandular and nerve structures in a manner that potentially enables real-time, intra-operative assessment of surgical margins and neurovascular bundles. As such, this method could potentially improve outcomes following radical prostatectomy.

Gao|Liang|L|
Zhou|Haijun|H|
Thrall|Michael J|MJ|
Li|Fuhai|F|
Yang|Yaliang|Y|
Wang|Zhiyong|Z|
Luo|Pengfei|P|
Wong|Kelvin K|KK|
Palapattu|Ganesh S|GS|
Wong|Stephen T C|ST|

(170.3880) Medical and biological imaging

(170.4580) Optical diagnostics for medicine


Wound Healing in Diabetic Foot Ulcer Patients Using Combined Use of Platelet Rich Fibrin and Hyaluronic Acid, Platelet Rich Fibrin and Placebo: An Open Label, Randomized Controlled Trial.

Abstract:
BACKGROUND
Autologous platelet-rich fibrin (A-PRF) is an adjunctive method for diabetic foot ulcer (DFU) in addition to glycaemic control and debridement. This study aimed to evaluate the role of A-PRF + hyaluronic acid (HA), A-PRF and sodium chloride 0.9% (control) in DFU wound healing. Nowaday, the use of  PRF autologous consider as adjuvant therapy in DFU treatment.

METHODS
This open-label randomized controlled trial was conducted at Koja District Hospital and Gatot Soebroto Hospital from July 2019 to April 2020. DFU patients with wound duration of three months, Wagner-2, and ulcer size < 40 cm2 were recruited and randomly assigned into A-PRF + AH, A-PRF and control group. On day-0, day-3 and day -7, samples and photographs were taken. Samples were analysed with ELISA and photographs were analysed with ImageJ to calculate granulation index (GI). Statistical analysis was performed using SPSS version 20.

RESULTS
Topical therapy with A-PRF + AH was associated with a significant increase in VEGF from day 0 (232.8 pg/mg) vs day 7 (544.5 pg/mg) compared to A-PRF on day 0 (185.7 pg/mg) vs day 7 (272.8 pg/mg), and the controls on day 0 (183.7 pg/mg) vs day 7 (167.4 pg/mg). On evaluation  of VEGF swab, there is increasing significantly in A-PRF+HA group compare others group in day -3 ( p=0.022) and day -7 (p= 0.001).In the A-PRF + AH group, there was a significant decrease in IL-6 from day 0 (106.4 pg/mg) vs day 7 (88.7 pg/mg) compared with PRF on day 0 (91.9 pg/mg) vs day 7 (48,8 pg/mg). IL-6 was increased in the control group from day 0 (125.3 pg/mg) vs day 7 (167.9 pg/mg). On evaluation  of IL-6 swab, there is decreasing significantly in A-PRF+HA group compare others group in day -7 (p= 0.041).

CONCLUSION
The PRF + HA combination increased angiogenesis and reduced inflammation in DFUs and may represent a new DFU therapy.

Kartika|Ronald Winardi|RW|
Alwi|Idrus|I|
Suyatna|Franciscus D|FD|
Yunir|Em|E|
Waspadji|Sarwono|S|
Immanuel|Suzana|S|
Bardosono|Saptawati|S|
Sungkar|Saleha|S|
Rachmat|Jusuf|J|
Hediyati|Mirta|M|
Silalahi|Todung|T|

diabetic foot ulcer
hyaluronic acid
platelet-rich fibrin


Hemifacial spasm as a manifestation of pilocytic astrocytoma in a pediatric patient.

Abstract: Hemifacial spasm is a disorder of the seventh cranial nerve, which is characterized by irregular, involuntary and recurrent tonic and clonic contractions of the ipsilateral facial expression muscles. This disorder affects mainly adults, and there are few cases reported in childhood. The main etiologies are vascular problems, although tumors are an important cause of hemifacial spasm via a direct or an indirect mass effect. We report a 6-year-old girl who presented with right hemifacial spasm. Magnetic resonance imaging showed a lesion in the cerebellopontine angle, extending from the midbrain to the pons with a slight mass effect on the fourth ventricle. The histological examination revealed a pilocytic astrocytoma.

Masruha|Marcelo R|MR|
Fialho|Libânia M N|LM|
da Nóbrega|Marcel V|MV|
Lin|Jaime|J|
Pinho|Ricardo S|RS|
Cavalheiro|Sérgio|S|
Vilanova|Luiz Celso P|LC|

hemifacial spasm
Astrocytoma
cerebellopontine angle


Increased risk and severity of unprovoked venous thromboembolism with clustering cardiovascular risk factors for atherosclerosis: Results of the REMOTEV registry.

Abstract:
BACKGROUND
The role of cardiovascular risk factors (CVRF) for atherosclerosis in venous thromboembolic disease (VTE) is controversial. The aim of this study was to evaluate the impact of CVRF and their cumulative effects on the occurrence of unprovoked VTE, severity, recurrence and survival.

METHODS AND RESULTS
This is a prospective cohort from the REMOTEV registry including all consecutively hospitalized patients for acute symptomatic VTE. From November 2013 to December 2016, 515 patients with 6months follow-up (FU) were selected for the analysis. Events were classified as unprovoked or provoked VTE. In univariate analysis, hypertension (OR 1.44, [95% CI 1.01-2.06]), diabetes (OR 2.07, [95% CI: 1.25-3.55]) and age (OR 1.94, [95% CI: 1.31-2.88]) were significantly associated with the risk of unprovoked VTE. After adjustment, diabetes (OR 1.82, [95% CI: 1.07-3.18]) and age (OR 1.79, [95% CI: 1.15-2.8]) remained associated with the risk of unprovoked VTE. The proportion of unprovoked VTE increased significantly with the number of CVRF adjusted for thrombophilia (1 CVRF: OR 3 [95% CI: 1.44-6.52]) 2 CVRF: OR 4.33 [95% CI: 2.07-9.49] and ≥3 CVRF: OR 4.58 [95% CI: 2.27-9.7]). The severity of pulmonary embolism was significantly associated with CVRF clustering. There were more VTE recurrences and deaths during the 6months of FU with cumulative CVRF.

CONCLUSION
The risks of unprovoked VTE and PE severity are associated with clustering CVRF. The role of cumulative CVRF predominates rather than the specific burden of each of the CVRF in the risk of VTE occurrence.

Gaertner|S|S| Cordeanu|E-M|EM| Mirea|C|C| Frantz|A-S|AS| Auger|C|C| Bilbault|P|P| Ohlmann|P|P| Schini-Kerth|V|V| Stephan|D|D|

Unprovoked
Venous thromboembolism
Cardiovascular risk factors
Atherosclerosis


An objective structured clinical exam to measure intrinsic CanMEDS roles.

Abstract:
BACKGROUND
The CanMEDS roles provide a comprehensive framework to organize competency-based curricula; however, there is a challenge in finding feasible, valid, and reliable assessment methods to measure intrinsic roles such as Communicator and Collaborator. The objective structured clinical exam (OSCE) is more commonly used in postgraduate medical education for the assessment of clinical skills beyond medical expertise.

METHOD
We developed the CanMEDS In-Training Exam (CITE), a six-station OSCE designed to assess two different CanMEDS roles (one primary and one secondary) and general communication skills at each station. Correlation coefficients were computed for CanMEDS roles within and between stations, and for general communication, global rating, and total scores. One-way analysis of variance (ANOVA) was used to investigate differences between year of residency, sex, and the type of residency program.

RESULTS
In total, 63 residents participated in the CITE; 40 residents (63%) were from internal medicine programs, whereas the remaining 23 (37%) were pursuing other specialties. There was satisfactory internal consistency for all stations, and the total scores of the stations were strongly correlated with the global scores r=0.86, p<0.05. Noninternal medicine residents scored higher in terms of the Professional competency overall, whereas internal medicine residents scored significantly higher in the Collaborator competency overall.

DISCUSSION
The OSCE checklists developed for the assessment of intrinsic CanMEDS roles were functional, but the specific items within stations required more uniformity to be used between stations. More generic types of checklists may also improve correlations across stations.

CONCLUSION
An OSCE measuring intrinsic competence is feasible; however, further development of our cases and checklists is needed. We provide a model of how to develop an OSCE to measure intrinsic CanMEDS roles that educators may adopt as residency programs move into competency-based medical education.

D057189:Checklist
D002983:Clinical Competence
D003142:Communication
D003162:Competency-Based Education
D003299:Cooperative Behavior
D004503:Education, Medical, Graduate
D004521:Educational Measurement
D006801:Humans
D010817:Physician-Patient Relations
D058996:Quality Improvement
D015203:Reproducibility of Results

objective structured clinical exam
intrinsic roles
postgraduate medical education
competency-based medical education


Anxiety level of early- and late-stage prostate cancer patients.

Abstract:
PURPOSE
Anxiety can worsen prostate cancer patients' decision making and quality of life. Early identification of anxiety disorders is thus very important for excellent prostate cancer treatment. This study aimed to determine the levels of anxiety in patients with early-stage prostate cancer compared with advanced-stage disease.

METHODS
This cross-sectional study was performed at the Department of Urology, 'Cipto Mangunkusumo' Hospital, Faculty of Medicine, University of Indonesia. The subjects were early-stage prostate cancer patients and advanced-stage prostate cancer patients with bone metastatic lesions proved by bone scan. Comparative analysis was done to analyze anxiety scores assessed by use of an 11-item modified Memorial Anxiety Scale for Prostate Cancer (MAX-PC) questionnaire. We also assessed the relationship of the MAX-PC score with age, prostate-specific antigen (PSA) value, number of bone metastases, and pain. Data were analyzed by using SPSS ver. 17 (SPSS Inc.).

RESULTS
There were 34 subjects with early-stage prostate cancer and 34 subjects with advanced-stage prostate cancer. We found that the mean anxiety score was significantly lower (P=0.0001) in the early-stage prostate cancer group (8.32±3.65) than in the advanced-stage prostate cancer group (12.61±4.56). Nine subjects had a pathological MAX-PC score (≥16), of whom 1 subject had early-stage disease and 8 subjects had advanced-stage disease. Furthermore, there were significant positive correlations (P<0.001) between MAX-PC score and visual analogue scale pain score (r=0.633), PSA value (r=0.263), and number of bone metastatic lesions (r=0.464). However, the correlation between age and anxiety score was not significant (P=0.170).

CONCLUSIONS
The MAX-PC anxiety score was significantly associated with the stage of prostate cancer. Furthermore, visual analogue scale pain score, PSA value, and number of bone metastatic lesions can also affect the MAX-PC anxiety score.

Johanes|Charles|C|
Monoarfa|Richard Arie|RA|
Ismail|Raden Irawati|RI|
Umbas|Rainy|R|

Anxiety disorders
Neoplasm staging
Pain measurement
Prostatic neoplasms


Metal-backed glenoid implant with polyethylene insert is not a viable long-term therapeutic option.

Abstract:
BACKGROUND
The aims of this study were to determine the survival of anatomic total shoulder arthroplasty with uncemented metal-backed (MB) glenoid components with a polyethylene (PE) insert in primary osteoarthritis, to assess the reasons for revision surgery, and to identify patients and diagnostic factors that influence failure rates.

METHODS
Between 1994 and 1999, 165 patients (mean age, 68 years) with primary osteoarthritis were treated with anatomic total shoulder arthroplasty using an uncemented MB/PE glenoid component. Outcomes were assessed both clinically and radiologically with a minimum of 2 years of follow-up. A prosthetic survival curve was constructed with the end point defined as either partial or complete revision, using 100% confidence intervals.

RESULTS
Survival rate free of revision was 46% (100% confidence interval, 32%-54%) at 12 years. At a mean follow-up of 8.5 years (range, 2-16 years), revision was required in 61 patients (37%); 80% of shoulders undergoing revision (49 of 61) had evidence of PE wear. Glenoid loosening (because of osteolysis secondary to wear debris), soft tissue deficiency, and prosthetic instability were the most common modes of failure. Younger patients and biconcave glenoids (with posterior humeral subluxation) have a negative effect on implant survival. Proximal humerus osteolysis was significantly more frequent in shoulders with PE wear. Exchange of the PE insert (with conservation of the MB tray) was possible in only 3% of the revised shoulders.

CONCLUSION
Uncemented MB glenoid resurfacing is not a viable long-term therapeutic option because of accelerated PE wear leading to early revision surgery. Conservation of the MB tray with reinsertion of a new PE insert is rarely possible because of glenoid bone loss, implant loosening, soft tissue deficiency, and prosthetic instability. Younger patients and biconcave glenoids have a negative effect on implant survival.

Boileau|Pascal|P| Moineau|Grégory|G| Morin-Salvo|Nicolas|N| Avidor|Cyrille|C| Godenèche|Arnaud|A| Lévigne|Christophe|C| Baba|Mohamed|M| Walch|Gilles|G|

Total shoulder arthroplasty
revision
glenoid survival
uncemented glenoid


Gender differences in nutritional status, diet and physical activity among adolescents in eight countries in sub-Saharan Africa.

Abstract:
OBJECTIVE
The objective of this study was to evaluate gender differences in nutritional status, dietary intake, physical activity and hand hygiene among adolescents from diverse geographical settings in sub-Saharan Africa.

METHODS
This study utilised cross-sectional data from six countries (Burkina Faso, Ethiopia, Ghana, Nigeria, Tanzania and Uganda) within the ARISE Adolescent Health Survey (n = 7625). Body mass index (BMI) was calculated using measured heights and weights, and z-scores were calculated based on the 2007 WHO growth standards for age and sex. Information on demographics, diet and health behaviours was collected through face-to-face interviews using a standardised questionnaire. Site-specific and pooled prevalence ratios were determined.

RESULTS
The prevalence of underweight, overweight and stunting pooled across sites was 14.3%, 6.8% and 18.1%, respectively. Female sex was associated with a lower risk of being underweight (pooled prevalence ratio 0.66, 95% 0.57, 0.77) and stunted (pooled PR 0.63, 95% CI 0.55, 0.71), but a higher risk of being overweight (pooled PR 1.60, 95% CI 1.26, 2.06). Females were also less likely to exercise for 1 h or more per day (pooled PR 0.77, 95% CI 0.67, 0.88), and more likely to wash hands after using toilets or latrines and to wash hands with soap (pooled PRs 1.13, 95% CI 1.05, 1.21 and 1.35, 95% CI 1.23, 1.45, respectively).

CONCLUSION
Our results emphasise that sex is a key predictor of nutritional status among sub-Saharan African adolescents and suggest that gender-specific interventions may be required to reduce the double burden of under- and overnutrition.

Darling|Anne Marie|AM|
Sunguya|Bruno|B|
Ismail|Abbas|A|
Manu|Abubakar|A|
Canavan|Chelsey|C|
Assefa|Nega|N|
Sie|Ali|A|
Fawzi|Wafaie|W|
Sudfeld|Chris|C|
Guwattude|David|D|

gender
nutritional status
physical activity
sub-Saharan Africa
dietary intake
hand hygiene
sexe
Afrique subsaharienne
activité physique
apport alimentaire
hygiène des mains
état nutritionnel


Alternative splicing of VEGFA, APP and NUMB genes in colorectal cancer.

Abstract:
AIM
To investigate alternative splicing in vascular endothelial growth factor A (VEGFA), amyloid beta precursor protein (APP), and Numb homolog (NUMB) in colorectal cancer (CRC).

METHODS
Real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and PCR-restriction fragment length polymorphism analyses were performed to detect the expression of VEGFA, APP, and NUMB mRNA in 20 CRC tissues and matched adjacent normal tissues, as well as their alternative splicing variants.

RESULTS
qRT-PCR analysis revealed that the expression of APP, NUMB, and VEGFA165b mRNA were significantly downregulated, while VEGFA mRNA was upregulated, in CRC tissues (all P < 0.05). PCR-restriction fragment length polymorphism analysis revealed that the expression of VEGFA165a/b in CRC tissues was significantly higher than in adjacent normal tissues (P < 0.05). Compared with adjacent normal tissues, the expression of NUMB-PRR(S) in CRC tissues was significantly decreased (P < 0.05), and the expression of NUMB-PRR(L) was increased (P < 0.05).

CONCLUSION
Alternative splicing of VEGFA, APP, and NUMB may regulate the development of CRC, and represent new targets for its diagnosis, prognosis, and treatment.

Zhao|Yi-Jun|YJ| Han|Hua-Zhong|HZ| Liang|Yong|Y| Shi|Chen-Zhang|CZ| Zhu|Qing-Chao|QC| Yang|Jun|J|

D054458:Amplified Fragment Length Polymorphism Analysis

D015972:Gene Expression Regulation, Neoplastic

D012150:Polymorphism, Restriction Fragment Length

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction

D042461:Vascular Endothelial Growth Factor A

Alternative splicing
Colorectal cancer
Vascular endothelial growth factor A
Amyloid beta precursor protein
Numb homolog


Improving seed germination and oil contents by regulating the GDSL transcriptional level in Brassica napus.

Abstract: Seed germination rate and oil content can be regulated at theGDSL transcriptional level by eitherAtGDSL1 orBnGDSL1 inB. napus. Gly-Asp-Ser-Leu (GDSL)-motif lipases represent an important subfamily of lipolytic enzymes, which play important roles in lipid metabolism, seed development, abiotic stress, and pathogen defense. In the present study, two closely related GDSL-motif lipases, Brassica napus GDSL1 and Arabidopsis thaliana GDSL1, were characterized as functioning in regulating germination rate and seed oil content in B. napus. AtGDSL1 and BnGDSL1 overexpression lines showed an increased seed germination rate and improved seedling establishment compared with wild type. Meanwhile, the constitutive overexpression of AtGDSL1 and BnGDSL1 promoted lipid catabolism and decreased the seed oil content. While RNAi-mediated suppression of BnGDSL1 (Bngdsl1) in B. napus improved the seed oil content and decreased seed germination rate. Moreover, the Bngdsl1 transgenic seeds showed changes in the fatty acid (FA) composition, featuring an increase in C18:1 and a decrease in C18:2 and C18:3. The transcriptional levels of six related core enzymes involved in FA mobilization were all elevated in the AtGDSL1 and BnGDSL1 overexpression lines, but strongly suppressed in the Bngdsl1 transgenic line. These results suggest that improving the seed germination and seed oil content in B. napus could be achieved by regulating the GDSL transcriptional level.

Ding|Li-Na|LN| Guo|Xiao-Juan|XJ| Li|Ming|M| Fu|Zheng-Li|ZL| Yan|Su-Zhen|SZ| Zhu|Ke-Ming|KM| Wang|Zheng|Z| Tan|Xiao-Li|XL|

D018507:Gene Expression Regulation, Developmental

D018506:Gene Expression Regulation, Plant

Seed germination
Oil contents
Brassica napus
Fatty acid
GDSL lipase


BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.

Abstract: In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8+ T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) and clinical response. Here, we further characterized this CD8+BTLA+ TIL subset and their CD8+BTLA- counterparts. We found that the CD8+ BTLA+ TILs had an increased response to IL-2, were less-differentiated effector-memory (TEM) cells, and persisted longer in vivo after infusion. In contrast, CD8+BTLA- TILs failed to proliferate and expressed genes associated with T-cell deletion/tolerance. Paradoxically, activation of BTLA signaling by its ligand, herpes virus entry mediator (HVEM), inhibited T-cell division and cytokine production, but also activated the Akt/PKB pathway thus protecting CD8+BTLA+ TILs from apoptosis. Our results point to a new role of BTLA as a useful T-cell differentiation marker in ACT and a dual signaling molecule that curtails T-cell activation while also conferring a survival advantage for CD8+ T cells. These attributes may explain our previous observation that BTLA expression on CD8+ TILs correlates with clinical response to adoptive T-cell therapy in metastatic melanoma.

Haymaker|Cara L|CL|
Wu|Richard C|RC|
Ritthipichai|Krit|K|
Bernatchez|Chantale|C|
Forget|Marie-Andrée|MA|
Chen|Jie Qing|JQ|
Liu|Hui|H|
Wang|Ena|E|
Marincola|Francesco|F|
Hwu|Patrick|P|
Radvanyi|Laszlo G|LG|

tumor-infiltrating lymphocytes
melanoma
B- and T-lymphocyte attenuator
CD8+ effector-memory
T cell survival/persistence


Quality of life of nasopharyngeal cancer survivors in China.

Abstract:
PURPOSE
We assessed the quality of life (qol) of nasopharyngeal carcinoma (npc) survivors with a survival time of more than 2 years in Fujian, China, and we analyzed factors influencing qol.

METHODS
We calculated the prevalence of psychological distress and radiotherapy (rt)-induced symptoms in 216 npc survivors who participated in a cross-sectional survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (version 3.0) was used to assess the qol of npc survivors. Multiple linear regression was applied to analyze the factors influencing qol.

RESULTS
The prevalence rates of rt-induced symptoms and psychological problems were 11.58% (95% ci: 7.21% to 15.58%) for difficulty in swallowing, 17.59% (95% ci: 12.51% to 22.67%) for mouth dryness or sores, 13.89% (95% ci: 9.28% to 18.50%) for nasal dryness or congestion, 18.52% (95% ci: 13.34% to 23.70%) for fatigue, 11.11% (95% ci: 6.92% to 15.30%) for frequent dizziness, 18.06% (95% ci: 12.93% to 23.19%) for decline in hearing, 14.81% (95% ci: 10.07% to 19.55%) for poor sleep quality, 18.52% (95% ci: 13.34% to 23.70%) for worry about disease recurrence, 18.98% (95% ci: 13.75% to 24.21%) for anxiety, and 25.00% (95% ci: 19.23% to 30.77%) for depression. Mean survival times were 4.32 ± 2.63 years in patients with mouth dryness or sores, 4.26 ± 2.90 years in patients with fatigue, and 5.60 ± 2.94 years in patients with a decline in hearing. The mean global qol score was 74.21 (95% ci: 72.22 to 76.20). At a significance level of α = 0.05, the factors influencing qol were age (p = 0.032), education level (p = 0.001), anxiety score (p < 0.001), depression score (p < 0.001), mouth dryness or sores (p < 0.001), fatigue (p = 0.027), and disease stage (p = 0.044).

CONCLUSIONS
The prevalence rates of mouth dryness or sores, fatigue, decline in hearing, depression, and anxiety were high in npc survivors with a survival time of more than 2 years. These rt-induced symptoms and psychological problems can last for many years after rt. The qol of the npc survivors was good. Factors influencing qol were age, education level, anxiety, depression, mouth dryness or sores, fatigue, and disease stage. Our results suggest that during clinical treatment, doctors should minimize the radiation dose to the ears of patients. In addition, our results emphasize the importance of providing oral and ear nursing and psychological care to npc survivors.

Hong|J S|JS|
Tian|J|J|
Han|Q F|QF|
Ni|Q Y|QY|

quality of life
Nasopharyngeal cancer
anxiety
depression
side effects


Exercise and inflammation in coronary artery disease: A systematic review and meta-analysis of randomised trials.

Abstract: Current evidence suggests that chronic inflammation contributes to the development of coronary artery disease (CAD). Interestingly, exercise may constitute a method of reducing inflammation in this patient population. As such, this systematic review and meta-analysis examined the evidence generated by randomised studies that investigated the effect of exercise on inflammatory biomarkers in CAD. Literature was sought from various sources. Outcomes were pooled in a random-effects model to calculate standardised mean differences (SMD) with 95% confidence intervals (CI). Twenty-five studies were reviewed; post-intervention C-reactive protein (SMD: -0.55 (95% CI: -0.93, -0.16), P = 0.005), fibrinogen (SMD: -0.52 (95% CI: -0.74, -0.29, P = <0.00001)), and von Willebrand factor (SMD: -1.57 (95% CI: -2.23, -0.92), P = <0.00001) values were significantly lower in exercise groups compared to controls. In addition, qualitative analyses identified evidence that supports a beneficial effect of exercise on these acute-phase reactants. However, the impact of exercise on anti-inflammatory cytokines, adhesion molecules, and chemokines is equivocal, which may be attributed to a paucity of research. Nevertheless, the findings of this review suggest that exercise induces an anti-inflammatory effect in CAD patients. Although, the quality of evidence needs to be improved by further randomised studies with high methodological qualities and large sample sizes.

Exercise
inflammation
coronary artery disease
systematic review
meta-analysis


Depression-like behavior associated with E/I imbalance of mPFC and amygdala without TRPC channels in mice of knockout IL-10 from microglia.

Abstract: Depression has a growing impact on public health. Accumulating evidence supports an association between depression and increased immune system activity. IL-10 is a key cytokine that inhibits excessive inflammatory responses and is related to the anti-inflammatory and protective functions of the central nervous system (CNS). Cx3cr1CreERIL-10-/- mice were used in our study. We aimed to identify the role of IL-10 in microglia in depression and anxiety-like behavior. We performed a series of behavioral tests on the mice; the Cx3cr1CreERIL-10-/- male mice showed depression- and anxiety-like behavior compared with the littermates. The expression of transient receptor potential canonical 5 (TRPC5) decreased in both the medial prefrontal cortex (mPFC) and amygdala regions. The cytokines IL-1β and IL-6 increased, and IL-10 was decreased by western blotting. The knockout mice showed different trends in the effects of synaptic proteins. In the mPFC, IL-10 knockout induced a decrease in NR2B and synaptophysin; in the amygdala region, there was a significant increase in NR2B and PSD95. IL-10 knockout from microglia induced a decrease in GAD67 and parvalbumin (Pv) in the mPFC, but not in the amygdala. Our results showed enhanced depression and anxiety-like behavior in the Cx3cr1CreER IL-10-/- mice, which could be related to an imbalance in local excitatory and inhibitory transmission, as well as neuroinflammation in the mPFC and amygdala. This imbalance was associated with increased local inflammation. Although many studies have demonstrated the role of TRPC channels in emotional responses, our study showed that TRPC was not involved in this process in Cx3cr1CreERIL-10-/- mice.

Yang|Liang|L| Liu|Chang|C| Li|Weiya|W| Ma|Yunqing|Y| Huo|Shiji|S| Ozathaley|Ahsawle|A| Ren|Jiling|J| Yuan|Wenjian|W| Ni|Hong|H| Li|Dong|D| Zhang|Jing|J| Liu|Zhaowei|Z|

E/I imbalance
TRPC
IL-10
Microglia
Depression


Metastatic castration-resistant prostate cancer: time for innovation.

Abstract: Androgen deprivation is the mainstay of advanced prostate cancer treatment. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). The understanding of the biology of CRPC and the evidence that CRPC still remains driven by androgen receptor signaling led to the discovery of new therapeutic targets. In the last few years, large Phase III trials showed improvements in survival and outcomes and led to the approval of a CYP17 inhibitor (abiraterone), an androgen receptor antagonist (enzalutamide), the taxane cabazitaxel, an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T). This article describes the molecular mechanisms underlying castration resistance, discusses recent and ongoing trials and offers some insights into identifying the best sequence of new drugs.

Tucci|Marcello|M|
Scagliotti|Giorgio Vittorio|GV|
Vignani|Francesca|F|

D017326:Clinical Trials, Phase III as Topic

castration-resistant prostate cancer
immunotherapy
bone-targeting agents
chemotherapy
endocrine therapy


Sleep disorders in Prader-Willi syndrome, evidence from animal models and humans.

Abstract: Prader-Willi Syndrome (PWS) is a complex genetic disorder with multiple cognitive, behavioral and endocrine dysfunctions. Sleep alterations and sleep disorders such as Sleep-disordered breathing and Central disorders of hypersomnolence are frequently recognized (either isolated or in comorbidity). The aim of the review is to highlight the pathophysiology and the clinical features of sleep disorders in PWS, providing the basis for early diagnosis and management. We reviewed the genetic features of the syndrome and the possible relationship with sleep alterations in animal models, and we described sleep phenotypes, diagnostic tools and therapeutic approaches in humans. Moreover, we performed a meta-analysis of cerebrospinal fluid orexin levels in patients with PWS; significantly lower levels of orexin were detected in PWS with respect to control subjects (although significantly higher than the ones of narcoleptic patients). Sleep disorders in humans with PWS are multifaceted and are often the result of different mechanisms. Since hypothalamic dysfunction seems to partially influence metabolic, respiratory and sleep/wake characteristics of this syndrome, additional studies are required in this framework.

Cataldi|Matteo|M|
Arnaldi|Dario|D|
Tucci|Valter|V|
De Carli|Fabrizio|F|
Patti|Giuseppa|G|
Napoli|Flavia|F|
Pace|Marta|M|
Maghnie|Mohamad|M|
Nobili|Lino|L|

D006970:Disorders of Excessive Somnolence

Hypersomnolence
Orexin
CSA
Excessive daytime sleepiness
Hypothalamus
Narcolepsy
OSA
Prader Willi Syndrome
SDB


The Bioactive Compound Contents and Potential Protective Effects of Royal Jelly Protein Hydrolysates against DNA Oxidative Damage and LDL Oxidation.

Abstract: In this study, the inhibition of DNA oxidative damage and low-density lipoprotein (LDL) oxidation of royal jelly protein (RJP) hydrolysates obtained from two commercial proteases were investigated. The results showed that the inhibition of DNA oxidative damage induced by the Fenton reaction, RJP, RJPs hydrolyzed by alcalase (RJP-A), RJPs hydrolyzed by flavourzyme (RPJ-F) and RJP two-stage hydrolysates (RPJ-AF) all had the effect of inhibiting deoxyribose oxidative damage. The inhibition effect of RJP, RJP-A, RJP-F and RJP-AF (1.0 mg/mL) were 47.06%, 33.70%, 24.19% and 43.09%, respectively. In addition, studies have also found that both RJP and RJP hydrolysates can reduce the production of 8-OH-2'-dG and the order of its inhibitory ability is RJP-AF ≒ RJP-A > RJP-F > RJP. The inhibition of DNA damage induced by bleomycin-Fe3+/ascorbic acid (Asc) with the addition of RJP, RJP-A, RPJ-F and RPJ-AF were 17.16%, 30.88%, 25.00% and 37.25%, respectively. The results of LDL oxidation inhibition showed that RJP-AF (1 mg/mL) not only had the most effective inhibitory Cu2+-induced LDL oxidation to produce a thiobarbituric acid reactive substance (TBARS) but also extended the lag time of conjugated diene formation to 300 min, which was 3.3 times that of the control group.

Chiang|Shu-Hua|SH| Yang|Kia-Min|KM|0000-0003-0270-3511 Sheu|Shiann-Cherng|SC| Chen|Chih-Wei|CW|

royal jelly
protein hydrolysate
DNA oxidative damage
LDL oxidation
Fenton reaction
conjugated diene


How frequent is the fifth arch artery?

Abstract: Although usually shown in embryology textbooks, the presence of the fifth pair of pharyngeal arch arteries has long been controversial. To the best of our knowledge, six pairs of bilaterally symmetrical arteries developing within the pharyngeal arches are yet to be found in any mammalian or avian species. Collateral channels between the distal ends of the fourth and sixth arch arteries, in contrast, have been found in up to half of all developing mouse embryos. In only one human embryo, again to the best of our knowledge, has a channel been found that extends from the aortic sac to the dorsal aorta, and hence qualifies as an arch artery. Despite these confounding factors in terms of the developmental heritage of the fifth arch arteries, the purported channels are invoked with increasing frequency to describe various lesions discovered in the setting of the congenitally malformed heart. Persistence of the artery of the fifth arch was initially proposed to explain double-barrelled aorta. It was subsequently proposed to account for various systemic-to-pulmonary channels feeding the pulmonary circulation in the setting of pulmonary atresia. It has also been claimed to persist so as to explain abnormal branching of the brachiocephalic arteries from the aortic arch. In the light of the ongoing doubts concerning the existence of the arteries of the fifth arch themselves, we have reviewed the various descriptions of purported fifth arch arteries within the world literature. We have then sought to validate the descriptions on the basis of our own understanding of development, for this purpose providing images of the remoulding arch arteries in the mouse so as to substantiate our conclusions. While accepting that our own interpretations are speculative, we suggest that more convincing alternative explanations can be advanced to account for the majority of lesions currently interpreted on the basis of persistence of the arteries of the fifth arches. Although the interpretations do not necessarily change the therapeutic approaches to the channels, appropriate description is important in terms of their classification.

Gupta|Saurabh K|SK|
Bamforth|Simon D|SD|
Anderson|Robert H|RH|


HIV infection, hunger, breastfeeding self-efficacy, and depressive symptoms are associated with exclusive breastfeeding to six months among women in western Kenya: a longitudinal observational study.

Abstract:
BACKGROUND
Exclusive breastfeeding for the first six months of life is recommended for all infants. However, breastfeeding rates remain suboptimal; around 37% of infants are exclusively breastfed for the first six months globally. In Nyanza region, western Kenya, numerous challenges to breastfeeding have been identified, including food insecurity, hunger, depressive symptoms, and HIV infection. Yet, evidence to inform our understanding of how these problems influence women's breastfeeding behaviors across time is lacking. We therefore sought to examine these factors and how they interact to affect the initiation and duration of exclusive breastfeeding in this region. We hypothesized that women experiencing greater food insecurity, hunger, and/or depressive symptoms would be less likely to maintain exclusive breastfeeding for six months than women who were food secure or not depressed. We also hypothesized that women living with HIV would be more likely to maintain exclusive breastfeeding to six months compared to HIV-uninfected women.

METHODS
Women in Pith Moromo, a longitudinal cohort study in western Kenya, were surveyed at two antenatal and three postpartum timepoints (n = 275). Data were collected on breastfeeding behavior and self-efficacy, maternal food insecurity and hunger, maternal psychosocial health, and HIV status. Cox proportional hazards models were used to identify predictors of early exclusive breastfeeding cessation.

RESULTS
The majority of women (52.3%) exclusively breastfed for the first six months. In the final multivariable Cox proportional hazards model, living with HIV was associated with a 64% decrease in the rate of early exclusive breastfeeding cessation. Additionally, the rate of early exclusive breastfeeding cessation increased by 100 and 98% for those experiencing probable depression or hunger, respectively. Although there was no main effect of breastfeeding self-efficacy, the interaction between breastfeeding self-efficacy and hunger was significant, such that the rate of early exclusive breastfeeding cessation was predicted to decrease by 2% for every point increase in breastfeeding self-efficacy score (range: 0-56).

CONCLUSIONS
This study contributes to previous work demonstrating that women living with HIV more consistently exclusively breastfeed and suggests that rates of exclusive breastfeeding could be increased through targeted support that promotes maternal mental health and breastfeeding self-efficacy, while reducing maternal hunger.

TRIAL REGISTRATION
Study registration NCT02974972.

Tuthill|Emily L|EL|
Miller|Joshua D|JD|
Collins|Shalean M|SM|
Widen|Elizabeth M|EM|
Onono|Maricianah|M|
Young|Sera L|SL|0000-0002-1763-1218

HIV
Hunger
Breastfeeding self-efficacy
Exclusive breastfeeding
Food insecurity
Breastfeeding determinants
Perinatal depression
Sub-Saharan Africa


Saccharomyces cerevisiae containing 28% polyphosphate and production of a polyphosphate-rich yeast extract thereof.

Abstract: Currently, inorganic polyphosphate is chemically synthesized from phosphate rock and added directly to food products. Yeast extract is a concentrate of soluble fractions of Saccharomyces cerevisiae and is, as a food additive, generally regarded as safe. The aim of this study was to biotechnologically produce a naturally polyphosphate-rich yeast extract. Polyphosphate-rich cells were produced with a wild type (non-genetically modified) S. cerevisiae by orthophosphate-starvation and subsequent orthophosphate-feeding, and contained 28% (w/w) polyphosphate (as KPO3) in cell dry weight, which is the highest content reported so far. Four yeast extract production protocols (autolysis, plasmolysis, enzymatic hydrolysis without and with prior heat inactivation) were tested, whereas the latter was the most promising. From the polyphosphate-rich cells, yeast extract paste and powder were produced containing 20% and 14% (w/w, as KPO3) polyphosphate with an average chain length of 31 and 3 P-subunits, 7% and 14% (w/w, as K1.5H1.5PO4) orthophosphate, 22% and 0% (w/w) water, respectively. For the first time, naturally polyphosphate-rich yeast extracts were produced, which possibly can be used as a clean-label food additive and biological alternative to chemically synthesized polyphosphate in food products.

Christ|Jonas Johannes|JJ|
Blank|Lars Mathias|LM|

Saccharomyces cerevisiae
polyphosphate
yeast extract


Lifestyle in Undergraduate Students and Demographically Matched Controls during the COVID-19 Pandemic in Spain.

Abstract: Few studies have used a multidimensional approach to describe lifestyle changes among undergraduate students during the COVID-19 pandemic or have included controls. This study aimed to evaluate lifestyle behaviors and mental health of undergraduate students and compare them with an age and sex-matched control group. A cross-sectional web survey using snowball sampling was conducted several months after the beginning of COVID-19 pandemic in Spain. A sample of 221 students was recruited. The main outcome was the total SMILE-C score. Students showed a better SMILE-C score than controls (79.8 + 8.1 vs. 77.2 + 8.3; p < 0.001), although these differences disappeared after controlling for covariates. While groups did not differ in the screenings of depression and alcohol abuse, students reported lower rates of anxiety (28.5% vs. 37.1%; p = 0.042). A lower number of cohabitants, poorer self-perceived health and positive screening for depression and anxiety, or for depression only were independently associated (p < 0.05) with unhealthier lifestyles in both groups. History of mental illness and financial difficulties were predictors of unhealthier lifestyles for students, whereas totally/moderate changes in substance abuse and stress management (p < 0.05) were predictors for the members of the control group. Several months after the pandemic, undergraduate students and other young adults had similar lifestyles.

lifestyle
undergraduate students
COVID-19
pandemic
mental health


Flood resilience.

Abstract: Three different conceptual frameworks of resilience, including engineering, ecological and social-ecological have been presented and framed within the context of flood risk management. Engineering resilience has demonstrated its value in the design and operation of technological systems in general and in flood resilient technologies in particular. Although limited to the technical domain, it has broadened the objectives of flood resilient technologies and provided guidance in improving their effectiveness. Socio-ecological resilience is conceived as a broader system characteristic that involves the interaction between human and natural systems. It acknowledges that these systems change over time and that these interactions are of complex nature and associated with uncertainties. Building (socio-ecological) resilience in flood risk management strategies calls for an adaptive approach with short-term measures and a set of monitoring criteria for keeping track of developments that might require adaptation in the long-term (adaptation pathways) and thus built-in adaptive capacity as opposed to building engineering resilience which involves a static approach with a fixed time horizon a set of robust measures designed for specific future conditions or scenarios. The two case studies, from a developing and a developed country, indicate that the concepts of ecological and socio-ecological resilience provide guidance for building more resilient flood risk management systems resulting in an approach that embraces flood protection, prevention and preparedness. The case studies also reveal that the translation of resilience concepts into practice remains a challenge. One plausible explanation for this is our inability to arrive at a quantification of socio-ecological resilience taking into account the various attributes of the concept. This article is part of the theme issue 'Urban flood resilience'.

flood resilience
adaptation
adaptive planning
climate change


In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica.

Abstract: Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development.

Malami|Ibrahim|I|
Abdul|Ahmad Bustamam|AB|
Abdullah|Rasedee|R|
Bt Kassim|Nur Kartinee|NK|
Waziri|Peter|P|
Christopher Etti|Imaobong|I|

in silico
Alpinia mutica
UCK2
flavokawain B
alpinetin
amino acid active site residues
nucleoside analogues


Visual asymmetries for relative depth judgments in a three-dimensional space.

Abstract: Our ability to process information about an object's location in depth varies along the horizontal and vertical axes. These variations reflect functional specialisation of the cerebral hemispheres as well as the ventral/dorsal visual streams for processing stimuli located in near and far space. Prior research has demonstrated visual field superiorities for processing near space in the lower and right hemispaces and for far space in the upper and left hemispaces. No research, however, has directly tested whether the functional specialisation of the visual fields actually makes objects look closer when presented in the lower or right visual fields. To measure biases in the perception of depth, we employed anaglyph stimuli where participants made closer/further judgments about the relative location of two spheres in a three-dimensional virtual space. We observed clear processing differences in this task where participants perceived the right and lower spheres to be closer and the left and upper spheres to be further away. Furthermore, no relationship between the horizontal and vertical dimensions was observed suggesting separate cognitive/neural mechanisms. Not only does this methodology clearly demonstrate differences in perceived depth across the visual field, it also opens up many possibilities for studying functional asymmetries in three-dimensional space.

Szpak|Ancrêt|A|
Loetscher|Tobias|T|
Bastian|John|J|
Thomas|Nicole A|NA|
Nicholls|Michael E R|ME|

Visual asymmetries
Relative depth
Anaglyphs
Depth perception
Three-dimensions


Genetic variation in NOD1/CARD4 and NOD2/CARD15 immune sensors and risk of osteoporosis.

Abstract: The present study was aimed to investigate the relationship between NOD1/CARD4 and NOD2/CARD15 gene polymorphisms and osteoporosis in the Turkish population. The first time we thought that the functional polymorphisms in NOD1/CARD4 and NOD2/CARD15 genes might have triggered the development of osteoporosis. The objective of our study was to determine the relationship between NOD1/CARD4 and NOD2/CARD15 SNPs and osteoporosis. The NOD1/CARD4 (rs5743336) and NOD2/CARD15 (rs2066847) SNPs were analyzed by PCR restriction fragment length polymorphism (PCR-RFLP) in 94 healthy controls and 164 subjects with osteoporosis. PCR products were digested with restriction enzymes AvaI for NOD1/CARD4 and ApaI for NOD2/CARD15. We found that NOD1/CARD4 genotype distribution of AA, GA and GG were 15, 44 and 41% for patients and 17, 46 and 37% for controls, respectively. NOD2/CARD15 mutation was found only in three patients (1.8%) as heterozygote. The results did not show any statistical difference between NOD1/CARD4 and NOD2/CARD15 genotype distribution of patients and healthy groups (χ2 = 1.740, P=0.187; χ2 = 1.311, P=0.519). However, the most frequent AG genotype (46%) of NOD1/CARD4 was observed in healthy controls, GG genotype (44%) of NOD1/CARD4 was observed as the most frequent in osteoporotic patients. NOD2/CARD15 WT/WT genotype, the most frequent genotype, was observed in both groups. Statistical analysis revealed that NOD1/CARD4 and NOD2/CARD15 polymorphisms are not associated with osteoporosis. However, a definite judgement is difficult to be made due to restricted number of patients and small size of control group. Further research is sorely warranted in this direction.

Soyocak|Ahu|A|
Özgen|Merih|M|
Turgut Coşan|Didem|D|
Kurt|Hülyam|H|
Doğaner|Fulya|F|
Armağan|Onur|O|
Değirmenci|İrfan|İ|
Şahin Mutlu|Fezan|F|

D020022:Genetic Predisposition to Disease


Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR).

Abstract: The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.

Ramachandran|Sreekanth A|SA|
Jadhavar|Pradeep S|PS|
Singh|Manvendra P|MP|
Sharma|Ankesh|A|
Bagle|Gaurav N|GN|
Quinn|Kevin P|KP|
Wong|Po-Yin|PY|
Protter|Andrew A|AA|
Rai|Roopa|R|
Pham|Son M|SM|
Lindquist|Jeffrey N|JN|

D064007:Ataxia Telangiectasia Mutated Proteins

Pyrazolopyrimidine
ATR
DNA damage
HTS
PI3K


Comparison of Two Methods of Estradiol Replacement: their Physiological and Behavioral Outcomes.

Abstract: Fluctuating sex steroids during the estrous or menstrual cycle of mammalian females make it difficult to determine their role on behaviors and physiology. To avoid this, many investigators ovariectomize their animals and administer progesterone, estradiol or a combination of both. Several different strategies are used to administer estradiol, which confounds interpretation of results. This study compared two methods of estradiol replacement implants: Silastic tubes filled with crystalline estradiol benzoate (E2) and commercially available estradiol benzoate pellets. Implants were placed subcutaneously in adult ovariectomized (OVX) rats and blood samples obtained weekly. Control OVX rats received empty Silastic tubes or placebo pellets. Our data shows that E2 plasma levels from rats with Silastic implants peaked after one week and decreased slowly thereafter. In contrast, plasma E2 from commercial pellets peaked after two weeks, increasing and decreasing over time. To validate hormone release, body weight was monitored. All E2 treated animals maintained a similar body weight over the four weeks period whereas an increase in body weight over time was observed in the OVX group that received empty implants, confirming E2 release and supporting the role of E2 in the regulation of body weight. Furthermore, the effects of E2 on basal locomotor activity were assessed using animal activity cages. Results showed no difference between E2 and control group in several locomotor activities. These results indicate that Silastic implants achieve more stable plasma estradiol levels than pellets and thus are a better alternative for studies of estradiol on brain function and behavior.

Mosquera|Laurivette|L|
Shepherd|Luz|L|
Torrado|Aranza I|AI|
Torres-Diaz|Yvonne M|YM|
Miranda|Jorge D|JD|
Segarra|Annabell C|AC|

Estradiol
Silastic implants
Body weight
Locomotor activity
Estradiol pellets


Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?

Abstract: Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments.

D000818:Animals
D005786:Gene Expression Regulation
D015316:Genetic Therapy
D006801:Humans
D008103:Liver Cirrhosis
D035683:MicroRNAs
D016376:Oligonucleotides, Antisense
D034622:RNA Interference
D034741:RNA, Small Interfering
D016896:Treatment Outcome

Gene therapy
Liver cirrhosis
Antisense
Oligodeoxynucleotides
Decoy
Micro RNA
Small interfering RNA


Morpho-Physiological Testing of NaCl Sensitivity of Tobacco Plants Overexpressing Choline Oxidase Gene.

Abstract: In this study the transgenic lines (TLs) of tobacco (Nicotianatabacum L.), which overexpress the heterologous gene encoding the bacterial enzyme choline oxidase were evaluated. The goal of our work is to study the effect of choline oxidase gene expression on the sensitivity of plant tissues to the action of NaCl. The regenerative capacity, rhizogenesis, the amount of photosynthetic pigments and osmotically active compounds (proline and glycine betaine) were assessed by in vitro cell culture methods using biochemical and morphological parameters. Transgenic lines with confirmed expression were characterized by high regeneration capacity from callus in the presence of 200 mmol NaCl, partial retention of viability at 400 mmol NaCl. These data correlated with the implicit response of regenerants and whole plants to the harmful effects of salinity. They turned out to be less sensitive to the presence of 200 mmol NaCl in the cultivation medium, in contrast to the WT plants.

proline
glycine betaine
salinity
Nicotiana tabacum L.
codA gene
osmolytes
salt tolerance
transgenic plants


Overexpression of the Heterochromatinization Factor BAHD1 in HEK293 Cells Differentially Reshapes the DNA Methylome on Autosomes and X Chromosome.

Abstract: BAH domain-containing protein 1 (BAHD1) is involved in heterochromatin formation and gene repression in human cells. BAHD1 also localizes to the inactive X chromosome (Xi), but the functional significance of this targeting is unknown. So far, research on this protein has been hampered by its low endogenous abundance and its role in epigenetic regulation remains poorly explored. In this work, we used whole-genome bisulfite sequencing (BS-seq) to compare the DNA methylation profile of HEK293 cells expressing low levels of BAHD1 (HEK-CT) to that of isogenic cells stably overexpressing BAHD1 (HEK-BAHD1). We show that increasing BAHD1 levels induces de novo DNA methylation on autosomes and a marked hypomethylation on the X chromosome (chrX). We identified 91,358 regions that have different methylation patterns in HEK-BAHD1 compared to HEK-CT cells (termed "BAHD1-DMRs"), of which 83,850 mapped on autosomes and 7508 on the X chromosome (chrX). Autosomal BAHD1-DMRs were predominantly hypermethylated and located to satellites, interspersed repeats, and intergenic regions. In contrast, BAHD1-DMRs on chrX were mainly hypomethylated and located to gene bodies and enhancers. We further found that BAHD1-DMRs display a higher-order organization by being clustered within large chromosomal domains. Half of these "BAHD1-Associated differentially methylated Domains" (BADs) overlapped with lamina-associated domains (LADs). Based on these results, we propose that BAHD1-mediated heterochromatin formation is linked to DNA methylation and may play a role in the spatial architecture of the genome.

Libertini|Emanuele|E| Lebreton|Alice|A| Lakisic|Goran|G| Dillies|Marie-Agnès|MA| Beck|Stephan|S| Coppée|Jean-Yves|JY| Cossart|Pascale|P| Bierne|Hélène|H|

heterochromatin
Xi
epigenetics
DNA methylation
LAD
cytosine methylation
whole genome bisulfite sequencing


Healthcare professionals' perspectives on rehabilitating persons with cognitive impairment.

Abstract:
BACKGROUND AND OBJECTIVES
Despite emerging evidence that persons with cognitive impairment (CI) (including dementia and/or delirium) can be rehabilitated post-hip fracture surgery, there still remains a paucity of research on best practice rehabilitation strategies that help healthcare providers effectively rehabilitate persons with CI. Therefore, this qualitative study explores healthcare professionals' (HCPs) perspectives who have been successfully providing rehabilitation for people with CI.

RESEARCH DESIGN AND METHODS
Sixteen HCPs with a specialty in rehabilitating persons with CI from one inpatient rehabilitation facility with various professional backgrounds were purposively sampled using a maximum diversity sampling strategy. Three focus group discussions were conducted to explore their experiences of providing rehabilitation to persons with CI. A hybrid inductive-deductive approach was used to analyze the data.

FINDINGS
HCPs acknowledged that older adults with CI deserved the opportunity for inpatient rehabilitation and that good outcomes were achievable; however, their knowledge, skills, and attitudes required reframing. The analysis identified three essential components to rehabilitation: (1) staff education and support, (2) tailored rehabilitation approaches, and (3) care partner involvement and support.

DISCUSSION AND IMPLICATIONS
Rehabilitation of persons with CI post-hip fracture surgery is achievable, and HCPs can learn to modify their practices to achieve positive patient outcomes. The attitudes of the healthcare team members had to be shifted to embrace the belief that persons with CI can be rehabilitated. However, it takes a steep learning curve, creativity, ingenuity, and tailored approaches to rehabilitate persons with CI successfully. This involves knowing the individual, maintaining routines, and learning the best ways to engage and motivate the person. As well, care partners' knowledge and understanding of the individual improved the chances of a successful rehabilitation stay and discharge. Essential to the success of rehabilitation of persons with CI includes a supportive management team to help create the processes to enable their staff to succeed.

rehabilitation
cognitive impairment
dementia
aged
hip fracture
patient-centered care


Smad signaling coincides with epithelial-mesenchymal transition in a rat model of intrauterine adhesion.

Abstract:
PURPOSE
Intrauterine adhesion (IUA) is a fibrotic disease mainly caused by tissue injury, yet the mechanism is poorly understood. The aim of this study was to investigate the roles of TGF-β1/BMP7/Smad signaling coincident with epithelial-mesenchymal transition (EMT) in IUA.

METHODS
Twenty-four female SD rats were divided into IUA and sham groups. For each animal, a mechanical injury or sham operation was performed on the left uterus (IUA-L, Sham-L), and the right uterus (IUA-R, Sham-R) was used as the control. Animals were sacrificed in batches on days 7 and 28. The endometrial morphology, number of endometrial glands, microvascular density (MVD), area of endometrial fibrosis and immunohistochemistry (IHC) analysis of biomarkers of EMT, as well as levels of TGF-β1, phosphorylated Smad3 (pSmad3), BMP7, phosphorylated Smad1/5 (pSmad1/5) and estrogen receptor (ER) were evaluated. Besides, the correlation between these IHC markers was also analyzed. RT-PCR and western blot were used to test relevant genes.

RESULTS
Compared with other groups, the IUA-L group showed a significant decrease in the number of glands and MVD. And it also showed a significant increase in the stromal fibrosis rate and a-SMA level. Moreover, in the IUA-L group, TGF-β1 and pSmad3 levels were consistently high, and levels of BMP7, pSmad1/5 and ER were low. EMT markers E-cadherin was decreased, while N-cadherin was increased. Sham and control groups showed no significant difference in these markers. In addition, E-cadherin with a-SMA, fibrosis rate with BMP7, TGF-β1 with pSmad3 and BMP7 with pSmad1/5 showed correlation in IUA-L group, which had statistical significance. The mRNA expression of TGF-β1, a-SMA and ccn2 in 7 d IUA-L was higher than 7 d IUA-R while BMP7 was lower, which had significant difference. The protein expression of BMP7 in 7 d IUA-L was lower than 7 d IUA-R, which had significant difference.

CONCLUSIONS
These results suggest a potential role of Smad signaling together with EMT in endometrial fibrosis development.

Guo|Luo-Pei|LP| Chen|Li-Mei|LM| Chen|Fang|F| Jiang|Ning-Hong|NH| Sui|Long|L|


Comparison of 4 tests' utility for predicting need for emergency department care in patients with alcohol-related complaints.

Abstract:
INTRODUCTION
Intoxication is a common presenting complaint in emergency departments (ED), but many patients with intoxication do not need emergency care. Three screens (BLINDED, Brown, and San Francisco) attempt to determine which intoxicated patients can be triaged to a lower level of care.

METHODS
Observational multi-center cohort study of patients presenting to one of three ED with complaints consistent with acute intoxication. When a qualifying patient was brought to the emergency department, a team member interviewed the triaging provider. Interviews covered all three screens and the provider's gestalt. Receiver operating curve (ROC) analysis was used to determine which screen performed best. Cases were reviewed to determine need for emergency care.

RESULTS
Of the 199 subjects studied, 91% (181/199) were male and were 50 years old on average (SD = 12 years). Of the 55 subjects tested (28%), their average alcohol level was 251 mg/dL (SD = 146 mg/dL). Only 117 subjects (59%) had complete information for inclusion in the final comparison of screens. Provider gestalt performed best (AUC = 0.69), but there were no meaningful differences between any of the screens (AUC = 0.62-0.66, p > 0.05 for all comparisons). Inability to sit up was sensitive for needing emergent care (88%), but it was non-specific (17%). Similarly, signs of trauma were specific (99%) for ED care, but insensitive (18%).

CONCLUSIONS
The three formal screens and provider gestalt performed similarly.

Leslom|Salman|S|
Patel|Sumit|S|
Sommerkamp|Sarah|S|
Dezman|Zachary D W|ZDW|

Screening
Stabilization center
Substance use disorders


The Efficiency of Color Space Channels to Quantify Color and Color Intensity Change in Liquids, pH Strips, and Lateral Flow Assays with Smartphones.

Abstract: Bottom-up, end-user based feed, and food analysis through smartphone quantification of lateral flow assays (LFA) has the potential to cause a paradigm shift in testing capabilities. However, most developed devices do not test the presence of and implications of inter-phone variation. Much discussion remains regarding optimum color space for smartphone colorimetric analyses and, an in-depth comparison of color space performance is missing. Moreover, a light-shielding box is often used to avoid variations caused by background illumination while the use of such a bulky add-on may be avoidable through image background correction. Here, quantification performance of individual channels of RGB, HSV, and LAB color space and ΔRGB was determined for color and color intensity variation using pH strips, filter paper with dropped nanoparticles, and colored solutions. LAB and HSV color space channels never outperformed the best RGB channels in any test. Background correction avoided measurement variation if no direct sunlight was used and functioned more efficiently outside a light-shielding box (prediction errors < 5%/35% for color/color intensity change). The system was validated using various phones for quantification of major allergens (i.e., gluten in buffer, bovine milk in goat milk and goat cheese), and, pH in soil extracts with commercial pH strips and LFA. Inter-phone variation was significant for LFA quantification but low using pH strips (prediction errors < 10% for all six phones compared). Thus, assays based on color change hold the strongest promise for end-user adapted smartphone diagnostics.

Nelis|Joost Laurus Dinant|JLD|
Bura|Laszlo|L|
Zhao|Yunfeng|Y|
Burkin|Konstantin M|KM|
Rafferty|Karen|K|
Elliott|Christopher T|CT|
Campbell|Katrina|K|

color space
smartphone colorimetrics
background correction
allergens
food contaminant screening
image correction
lateral flow assay quantification
point of site analyses


Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions.

Abstract: Definitive molecular diagnoses in disorders apparently due to genetic or genomic defects are still lacking in a significant number of investigated cases, despite use of studies designed to discover defects in the protein coding regions of the genome. Increasingly studies are being designed to search for defects in the non-protein coding genome, and for alterations in gene expression. Here we review new insights into genomic elements involved in control of gene expression, including methods to analyze chromatin that is accessible for transcription factor binding, enhancers, chromatin looping, transcription, RNA binding proteins, and alternative splicing. We review new studies on levels of genome organization, including the occurrence of transcriptional domains and their boundary elements. Information is presented on specific malformation syndromes that arise due to structural genomic changes that impact the non-protein coding genome and sometimes impact specific transcriptional domains. We also review convergence of genome-wide association with studies of gene expression, discoveries related to expression quantitative trait loci and splicing quantitative trait loci and the relevance of these to specific complex common diseases. Aspects of epigenetic mechanisms and clinical applications of analyses of methylation signatures are also discussed.

transcription
enhancer
enhancer
domains
malformation
epigenetic
enhancers
modifications malformations
structural damage


Extracellular Zn2+ Influx into Nigral Dopaminergic Neurons Plays a Key Role for Pathogenesis of 6-Hydroxydopamine-Induced Parkinson's Disease in Rats.

Abstract: Parkinson's disease (PD) is a progressive neurological disease characterized by a selective loss of nigrostriatal dopaminergic neurons. The exact cause of the neuronal loss remains unclear. Here, we report a unique mechanism of nigrostriatal dopaminergic neurodegeneration, in which extracellular Zn2+ influx plays a key role for PD pathogenesis induced with 6-hydroxydopamine (6-OHDA) in rats. 6-OHDA rapidly increased intracellular Zn2+ only in the substantia nigra pars compacta (SNpc) of brain slices and this increase was blocked in the presence of CaEDTA, an extracellular Zn2+ chelator, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, indicating that 6-OHDA rapidly increases extracellular Zn2+ influx via AMPA receptor activation in the SNpc. Extracellular Zn2+ concentration was decreased under in vivo SNpc perfusion with 6-OHDA and this decrease was blocked by co-perfusion with CNQX, supporting 6-OHDA-induced Zn2+ influx via AMPA receptor activation in the SNpc. Interestingly, both 6-OHDA-induced loss of nigrostriatal dopaminergic neurons and turning behavior to apomorphine were ameliorated by co-injection of intracellular Zn2+ chelators, i.e., ZnAF-2DA and N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Co-injection of TPEN into the SNpc blocked 6-OHDA-induced increase in intracellular Zn2+ but not in intracellular Ca2+. These results suggest that the rapid influx of extracellular Zn2+ into dopaminergic neurons via AMPA receptor activation in the SNpc induces nigrostriatal dopaminergic neurodegeneration, resulting in 6-OHDA-induced PD in rats.

Dopaminergic neuron
6-hydroxydopamine
Substantia nigra
Parkinson’s disease
Zinc


Simultaneous determination of amantadine, rimantadine, and memantine in processed products, chicken tissues, and eggs by liquid chromatography with tandem mass spectrometry.

Abstract: A simultaneous determination of amantadine, rimantadine, and memantine in processed products (deep-fried chicken, fried chicken, fried quail egg, and grilled chicken) with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. This new method was also applicable for chicken tissue (muscle, liver, and gizzard) and eggs. The chromatographic separation was performed on a Kinetex® XB-C18 core-shell technology column using a mobile phase of acetonitrile and 0.1% formic acid in a 10mmol/L ammonium formate solution, resulting in the complete separation of isomers (rimantadine and memantine) and any other obstructive peaks from the sample matrices. Sample preparation was performed by a modified QuEChERS method using acetonitrile and a 0.1% acetic acid extraction solution and cleaned using an Oasis® MCX cartridge. The sample matrix had no effect on the identification of the compounds. For quantification, an external solvent calibration curve was used. This new method exhibited good accuracy ranging from 79.9% to 91.5%. The relative standard deviation of repeatability (RSDr) ranged from 1.2% to 3.6% and the relative standard deviation of within-laboratory reproducibility (RSDWR) ranged from 1.3% to 6.0%. These standard deviations satisfied the criteria for Japanese validation guidelines. The limit of quantification (LOQ) was 1.0μg/kg for all samples. Analyte residues were not detected in 55 samples using the validated method.

Tsuruoka|Yumi|Y| Nakajima|Takayuki|T| Kanda|Maki|M| Hayashi|Hiroshi|H| Matsushima|Yoko|Y| Yoshikawa|Souichi|S| Nagata|Marie|M| Koike|Hiroshi|H| Nagano|Chieko|C| Sekimura|Kotaro|K| Hashimoto|Tsuneo|T| Takano|Ichiro|I| Shindo|Tetsuya|T|

Amantadine
Rimantadine
Memantine
Processed products
External solvent calibration curve
LC–MS/MS


Comparison of topical ropivacaine with and without ketamine on post-surgical pain in children undergoing tonsillectomy: a randomized controlled double-blind study.

Abstract:
PURPOSE
Tonsillectomy in pediatric patients may cause severe postoperative pain. Topical local anesthetics are an easy and safe way to control post-tonsillectomy pain, but there is no benefit during the early postoperative stage. Topical ketamine shows a good effect on early stage postoperative pain. We compared the effect of topical ropivacaine with and without ketamine on post-tonsillectomy pain.

METHODS
Patients aged 3-7 years undergoing tonsillectomy were selected to participate in the study. Our study was performed in a randomized, placebo-controlled, double-blind manner. Patients were randomly assigned to one of two groups using computer-generated random numbers. The researchers who assessed the pain score, the caregivers, and the patient were blinded to group assignment. One group received topical ropivacaine with saline (RS group) and the other group received topical ropivacaine with 20 mg ketamine (RK group) on the tonsillar bed. Pain scores using the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS) at 15 min and 30 min, and at 1, 2, 4, 8, 16 and 24 h were recorded. Rescue analgesic requirement and complications were also recorded.

RESULTS
A total of 66 patients were randomly assigned to the RS group (n = 33) and the RK group (n = 33). The mCHEOPS scores were significantly lower in the RK group at 15 min (P = 0.046). The mCHEOPS scores of the two groups decreased with time, but there was no intergroup interaction. The RS group received more analgesics until 1 h after surgery and the RK group received more analgesics during 1-24 h after surgery. There were no differences in adverse outcomes.

CONCLUSIONS
Topical ropivacaine with ketamine can reduce immediate postoperative pain and analgesic requirement better than ropivacaine alone.

Hong|Boohwi|B|
Lim|Chae Seong|CS|
Kim|Yoon-Hee|YH|
Lee|Jung Un|JU|
Kim|Yong Min|YM|
Jung|Choonho|C|
Jo|Yumin|Y|


Anthrax lethal toxin (LeTx) neutralization by PA domain specific antisera.

Abstract: Anthrax associated causalities in humans and animals are implicated mainly due to the action of two exotoxins that are secreted by the bacterium Bacillus antharcis during the infection. These exotoxins comprise of three protein components namely protective antigen (PA), lethal factor (LF) and edema factor (EF). The protective antigen is the common toxin component required to form both lethal toxin (LeTx) and edema toxin (EdTx). The LeTx is formed, when PA combines with LF and EdTx is formed when PA combines with EF. Therapeutic interventions aiming to neutralize these key effectors of anthrax pathology would therefore, provide an effective means to counter the toxicity imposed by the anthrax toxins on the host. The present work describes the lethal toxin neutralization potential of polyclonal antisera developed against the individual domains of the protective antigen component of the anthrax toxin. The individual domains were produced as recombinant proteins in E. coli and validated with peptide mass fingerprinting by MALDI-TOF analysis and corresponding mice polyclonal antisera by western blotting. Each domain specific antibody titre and isotype was ascertained by ELISA. The isotyping revealed the predominance of IgG1 isotype. The toxin neutralizing potential of these domain specific antisera were evaluated by in-vitro cell viability MTT assay, employing J774.1 mouse macrophage cell line against LeTx (0.25 μg ml-1 PA and 0.125 μg ml-1 LF concentrations). Among the four domain specific antisera, the antiserum against PA domain IV could neutralize LeTx with high efficiency. No significant neutralization of LeTx was observed with other domain specific antibodies. Results indicate that antibodies to r-PA domain IV could be explored further as therapeutic anti toxin molecule along with appropriate antibiotic regimens against anthrax.

Verma|Monika|M|
Suryanarayana|Nagendra|N|
Tuteja|Urmil|U|
Thavachelvam|Kulanthaivel|K|
Rao|M K|MK|
Bhargava|Rakesh|R|
Shukla|Sangeeta|S|

D000818:Animals
D000881:Anthrax
D000942:Antigens, Bacterial
D001426:Bacterial Proteins
D001427:Bacterial Toxins
D002460:Cell Line
D004926:Escherichia coli
D005098:Exotoxins
D007106:Immune Sera
D051379:Mice
D009500:Neutralization Tests
D000072417:Protein Domains
D011994:Recombinant Proteins

Anthrax lethal toxin
PA domain specific antisera
Lethal toxin neutralization
MALDI –TOF


Association between maternity harassment and depression during pregnancy amid the COVID-19 state of emergency.

Abstract:
OBJECTIVES
Maternity harassment, known in English as pregnancy discrimination, remains prevalent in developed countries. However, research examining the mental health effects of maternity harassment is lacking. We aimed to examine the association between maternity harassment and depression during pregnancy in Japan.

METHODS
A cross-sectional Internet survey was conducted on 359 pregnant employees (including women who were working at the time their pregnancy was confirmed) from May 22 to May 31, 2020, during which time a COVID-19 state of emergency was declared. Maternity harassment was defined as being subjected to any of the 16 adverse treatments prohibited by national guidelines. Depression was defined as a score of ≥9 on the Edinburgh Postnatal Depression Scale (Japanese version). Logistic regression analysis was performed.

RESULTS
Overall, 24.8% of the pregnant employees had experienced maternity harassment by supervisors and/or colleagues. After adjusting for demographics, pregnancy status, work status, and fear of COVID-19, pregnant employees who experienced maternity harassment were more likely to have depression than those who did not (odds ratio 2.48, 95% confidential interval 1.34-4.60). This association was not influenced by whether they were teleworking or not as a COVID-19 measure.

CONCLUSIONS
One quarter of pregnant employees experienced maternity harassment and had a higher prevalence of depression than those who did not. Being physically away from the office through teleworking may not reduce the effect of maternal harassment on depression. To protect the mental health and employment of pregnant women, employers should comply with the laws and take measures to prevent maternity harassment.

D011569:Psychiatric Status Rating Scales

maternity harassment
pregnancy discrimination
mental health
pregnant employees


Growth Behavior of Listeria monocytogenes in a Traditional Norwegian Fermented Fish Product (Rakfisk), and Its Inhibition through Bacteriophage Addition.

Abstract: Listeria monocytogenes may persist in food production environments and cause listeriosis. In Norway, a product of concern is the traditional and popular fermented fish product "rakfisk", which is made from freshwater salmonid fish by mild-salting and brine maturation at low temperatures for several months. It is eaten without any heat treatment, and L. monocytogenes, therefore, poses a potential hazard. We investigated the effect of salt and temperature on the growth of L. monocytogenes in rakfisk during the 91 days of maturation. The amounts of organic acids produced during fermentation were too low to inhibit growth of L. monocytogenes. Temperature was clearly the most important parameter for controlling L. monocytogenes. At 7 °C, approximately 2 log growth was observed during the first 14 days of fermentation, and the level of L. monocytogenes thereafter remained constant. At 4 °C, only a little growth potential of the pathogen was recorded. We also investigated the effect of the anti-Listeria bacteriophage P100 on rakfisk with added L. monocytogenes. The phage was introduced to the L. monocytogenes-inoculated fish before fermentation, and an average of 0.9 log reduction was observed throughout the fermentation period. This is the first study of L. monocytogenes behavior in rakfisk and points to possible measures for increasing the product safety.

Axelsson|Lars|L|
Bjerke|Guro Alette|GA|
McLeod|Anette|A|
Berget|Ingunn|I|
Holck|Askild L|AL|

Listeria monocytogenes
fermented fish
anti-Listeria bacteriophage
food safety
ripening conditions


Bacterial phototoxicity of biomimetic CdTe-GSH quantum dots.

Abstract:
AIM
Fluorescent semiconductor nanoparticles or quantum dots (QDs) have excellent properties as photosensitizers in photodynamic therapy. This is mainly a consequence of their nanometric size and the generation of light-activated redox species. In previous works, we have reported the low-cost biomimetic synthesis of glutathione (GSH) capped QDs (CdTe-GSH QDs) with high biocompatibility. However, no studies have been performed to determine their phototoxic effect. The aim of this work was to characterize the light-induced toxicity of green (QDs500 ) and red (QDs600 ) QDs in Escherichia coli, and to study the molecular mechanism involved.

METHODS AND RESULTS
Photodegradation and reduction power of biomimetic QDs was determined to analyse their potential for radical generation. Escherichia coli cells were exposed to photoactivated QDs and viability was evaluated at different times. High toxicity was determined in E. coli cells exposed to photoactivated QDs, particularly QDs500 . The molecular mechanism involved in QDs phototoxicity was studied by determining Cd2+ -release and intracellular reactive oxygen species (ROS). Cells exposed to photoactivated QDs500 presented high levels of ROS. Cells exposed to photoactivated QDs500 presented high levels of ROS. Finally, to understand this phenomenon and the importance of oxidative and cadmium-stress in QDs-mediated phototoxicity, experiments were performed in E. coli mutants in ROS and Cd2+ response genes. As expected, E. coli mutants in ROS response genes were more sensitive than the wt strain to photoactivated QDs, with a higher effect in green-QDs500 . No increase in phototoxicity was observed in cadmium-related mutants.

CONCLUSION
Obtained results indicate that light exposure increases the toxicity of biomimetic QDs on E. coli cells. The mechanism of bacterial phototoxicity of biomimetic CdTe-GSH QDs is mostly associated with ROS generation.

SIGNIFICANCE AND IMPACT OF THE STUDY
The results presented establish biomimetic CdTe-GSH QDs as a promising cost-effective alternative against microbial infections, particularly QDs500 .

phototoxicity
CdTe-GSH
photodynamic therapy
biomimetic quantum dots


Differential embryotoxicity of the organic pollutants in rural and urban air particles.

Abstract: Airborne particulate matter (PM) is a recognized risk factor for human populations. Here we assessed the toxic potential of the organic constituents from PM collected in urban and rural sites during warm and cold periods of 2012/2013, and fractionated into 6 size fractions. The finest PM fraction (<0.5 μm) showed the highest biological activity (dioxin-like activity and fish embryotoxicity) in all samples, and the maximal activity was observed in rural samples from the cold period. Zebrafish embryo transcriptome analysis showed a strong induction of the AhR signaling pathway correlated to PAH concentrations. Oxidative stress-related genes and pancreatic and eye-lens gene markers appeared de-regulated in embryos exposed to urban extracts, whereas exposure to rural extracts affected genes implicated in basic cellular functions. The observed effects can be directly related to air pollution-related human disorders, suggesting different potential adverse outcomes for human populations exposed to air pollution from specific sources.

Mesquita|Sofia R|SR|
van Drooge|Barend L|BL|
Oliveira|Eva|E|
Grimalt|Joan O|JO|
Barata|Carlos|C|
Vieira|Natividade|N|
Guimarães|Laura|L|
Piña|Benjamin|B|

Air pollution
Air quality
Danio rerio
Embryo toxicity
GC–MS
PM10
Toxicogenomics


3D modelling of solute transport and mixing during managed aquifer recharge with an infiltration basin.

Abstract: Artificial basins are used to recharge groundwater by many municipalities to improve the sustainability of storm water management. Despite its increasing operational implementation, artificial recharge still raises numerous questions related to its impact on groundwater quality. In this paper, a 3D numerical model of MAR basin/aquifer system was implemented in order to simulate the fate of water and pollutants. It was used to illustrate the complex distribution in time and space of a tracer contaminant injected in the basin. The model was based on a well instrumented storm water infiltration basin located in Chassieu (Lyon area, France). The well-known Richards model was used to simulate the water flow in the saturated and unsaturated zone of the study site. The transfer of solutes in the basin/aquifer system was modelled by the advection-dispersion-equation (ADE). The model was calibrated during a rain event using hydraulic head and electric conductivity data from a set of piezometers located around the basin. The flow model was validated on a one month period of basin operation presenting several rain events. The model was then used to simulate the fate of a solute pollutant considered as a tracer during a high intensity rain event. This simplified test case illustrated the mechanism of capillary trapping in the vadose zone and the effect of sampling point location on concentration measurements. Three main results were obtained: (1) capillary trapping promoted a retention of up to 20% of the injected tracer in the vadose zone, (2) 0 to 24% of the injected solute concentration could be recovered depending on the piezometer location, (3) the averaged concentration decreased by 50% if the measuring device is lowered by 5 m under the water table. These results were strongly site and event dependant but observed trends should be considered while discussing punctual water quality measurements used to monitor MAR systems. It also allowed to suggest some guidelines for sampling point positioning.

Bahar|Tidjani|T| Oxarango|Laurent|L| Castebrunet|Hélène|H| Rossier|Yvan|Y| Mermillod-Blondin|Florian|F|

3D modelling
MAR system
Contaminant transport


Morphology and Ultrastructure of Group A Streptococcus Biofilms.

Abstract: Light and electron microscopy enables researchers to study the ultrastructure of GAS biofilms formed on abiotic surfaces. Chains of streptococci surrounded by a bluish film are seen under a light microscope after alcian blue staining of preparations grown on coverslips. The extracellular matrix (indicator of biofilm maturity) becomes visible on ultrathin sections in transmission electron microscopy after additional staining with alcian blue; filamentous structures, characteristic of biofilm, are observed in intercellular spaces. The data obtained by scanning electron microscopy also demonstrate the presence of biofilm.

Danilova|Tatyana A|TA|
Smirnova|T A|TA|
Danilina|G A|GA|
Adzhieva|A A|AA|
Shevlyagina|N V|NV|
Zhukhovitsky|V G|VG|

Biofilm
Electron microscopy
Matrix
Light microscopy


Acute cholecystitis and residual choledocholithiasis in a situs inversus patient, successful laparoscopic approach and ERCP a case report from Ecuador.

Abstract:
Background
Situs inversus totalis is a rare genetic condition characterized by the transposition of organs to the opposite side of the body, consequently, clinical syndromes show an atypical clinical picture creating a challenge for the surgery team and predisposing to delays in treatment and diagnosis. Laparoscopic cholecystectomy is the gold standard for acute cholecystitis, and in patients with situs inversus, the laparoscopic technique must be modified to accommodate the patient's anatomy.

Case presentation
We present the case of a 55-year-old male patient without any past medical history, he presented to the emergency room with abdominal pain in his upper left quadrant. After a thorough examination, acute cholecystitis and situs inversus was diagnosed. He underwent a modified laparoscopic cholecystectomy without complications. In his postoperative period, residual choledocholithiasis was identified and ERCP was done. On follow-ups, the patient is doing well.

Conclusions
Although rare and technically demanding, laparoscopic cholecystectomy and ERCP in a patient with situs inversus is feasible. The altered anatomy could lead to complex procedures, therefore proper planning and careful execution of intraoperative techniques are required to treat these patients safely and effectively.

Moyon C|Miguel A|MA|
Rojas|Christian L|CL|
Moyon C|Fernando X|FX|
Aguayo|William G|WG|
Molina|Gabriel A|GA|
Ochoa|Carlos|C|
Neira|Andres|A|
Vinueza|Maria Elena|ME|

Acute cholecystitis
Situs inversus
Laparoscopic cholecystectomy


Clopidogrel Hypersensitivity: Pathogenesis, Presentation and Diagnosis.

Abstract: This paper provides an overview of the pathogenesis, presentation and diagnosis of clopidogrel hypersensitivity. The majority of clopidogrel hypersensitivity cases are due to a T cell mediated Gell and Coombs Type IV reaction. History, histology, and patch testing have shown consistency with a T cell mediated mechanism. Clopidogrel reactions most commonly present as a mild delayed maculopapular erythematous rash 5 to 10 days after introduction of the drug, and do not always require discontinuation of the drug. Severe cutaneous, systemic, and immediate adverse reactions to clopidogrel are rare. For the diagnosis of clopidogrel hypersensitivity, drug causality can be determined using patch testing, or for mild reactions, recurrence of symptoms after drug reintroduction, although neither are required for diagnosis.

D058921:Purinergic P2Y Receptor Antagonists

Clopidogrel
hypersensitivity
diagnosis
clopidogrel allergy
drug allergy
pathogenesis.


Transcriptomic Analysis Provides Novel Insights into Heat Stress Responses in Sheep.

Abstract: With the intensified and large-scale development of sheep husbandry and global warming, sheep heat stress has become an increasingly important issue. However, little is known about the molecular mechanisms related to sheep responses to heat stress. In this study, transcriptomic analysis of liver tissues of sheep in the presence and absence of heat stress was conducted, with the goal of identifying genes and pathways related to regulation when under such stress. After a comparison with the sheep reference genome, 440,226,436 clean reads were obtained from eight libraries. A p-value ≤ 0.05 and fold change ≥ 2 were taken as thresholds for categorizing differentially expressed genes, of which 1137 were identified. The accuracy and reliability of the RNA-Seq results were confirmed by qRT-PCR. The identified differentially expressed genes were significantly associated with 419 GO terms and 51 KEGG pathways, which suggested their participation in biological processes such as response to stress, immunoreaction, and fat metabolism. This study's results provide a comprehensive overview of sheep heat stress-induced transcriptional expression patterns, laying a foundation for further analysis of the molecular mechanisms of sheep heat stress.


Coloproctology procedure clinic: a novel service developed to reduce suffering of patients with bleeding per rectum.

Abstract:
AIMS
Evaluation of the role and impact of introducing a dedicated coloproctology procedure clinic in tertiary referral colorectal unit.

METHODS
A retrospective analysis of 126 consecutive patients managed in the coloproctology clinic between March2015 and September 2016 was carried out. All patients were preselected for attendance based on symptom-based protocol.

RESULTS
Based on the information available in GP referrals, 126 patients with bleeding per rectum with low risk of cancer were re-triaged from the general outpatient to dedicated coloproctology procedure clinic. Those patients accounted for 14% of waiting list. The average waiting time to attend clinic was 27 months from referral to undergoing definitive procedure. A proctoscopy or/and rigid sigmoidoscopy was performed in patients. Seventy-nine (89.7%) patients were completely managed and discharged after attending their first visit. Sixty-seven (76%) patients had 2nd- or 3rd-degree haemorrhoids and were treated with rubber band ligation (RBL) or phenol injection in outpatient setting. Two patients had an anal fissure and were managed conservatively with medication. After clinic, follow-up was through telephone clinic. This avoids attendance physically in the hospital. Symptoms persisted in nine patients and were subsequently scheduled for colonoscopy, three had benign polyps. With the introduction of the procedure clinic, the waiting time from referral to treatment was reduced from 27 to 6 months (p < 0.05).

CONCLUSIONS
Establishing a dedicated "Coloproctology procedure clinic" is an effective strategy in reducing number of hospital visits per patient and hospital waiting list. This innovative clinic reduces utilisation of precious endoscopy unit resources. This ultimately will improve endoscopy efficiency.

Bleeding per rectum
Haemorrhoids
Rubber band ligation
Colonoscopy
Benign colorectal disease
Colorectal cancer


Repeating firing fields of CA1 neurons shift forward in response to increasing angular velocity.

Abstract: Self-motion information influences spatially-specific firing patterns exhibited by hippocampal neurons. Moreover, these firing patterns can repeat across similar subsegments of an environment, provided that there is similarity of path shape and head orientations across subsegments. The influence of self-motion variables on repeating fields remains to be determined. To investigate the role of path shape and angular rotation on hippocampal activity, we recorded the activity of CA1 neurons from rats trained to run on spiral-shaped tracks. During inbound traversals of circular-spiral tracks, angular velocity increases continuously. Under this condition, most neurons (74%) exhibited repeating fields across at least three adjacent loops. Of these neurons, 86% exhibited forward shifts in the angles of field centers relative to centers on preceding loops. Shifts were absent on squared-spiral tracks, minimal and less reliable on concentric-circle tracks, and absent on outward-bound runs on circular-spiral tracks. However, outward-bound runs on the circular-spiral track in the dark were associated with backward shifts. Together, the most parsimonious interpretation of the results is that continuous increases or decreases in angular velocity are particularly effective at shifting the center of mass of repeating fields, although it is also possible that a nonlinear integration of step counts contributes to the shift. Furthermore, the unexpected absence of field shifts during outward journeys in light (but not darkness) suggests visual cues around the goal location anchored the map of space to an allocentric reference frame.

angular acceleration
hippocampus
memory
navigation
place fields


Microbiomes in supragingival biofilms and saliva of adolescents with gingivitis and gingival health.

Abstract:
BACKGROUND
Important alterations exist in the microbiomes of supragingival biofilm and saliva samples from adolescent patients developing induced or spontaneous gingivitis relative to healthy controls. These and the relationships to dental health are not fully understood yet.

SUBJECTS AND METHODS
Supragingival biofilm samples (n = 36) were collected from the teeth of 9 adolescents with gingivitis induced by orthodontic appliances, as well as dental plaques (n = 40) from 10 adolescents with spontaneous gingivitis, in addition to similar samples (n = 36) from 9 healthy controls. The bacterial metagenomes were analyzed by 16S rRNA gene amplicon sequencing. Salivary microbiomes of the same persons were characterized by shotgun metagenome sequencing. The data sets were examined using advanced bioinformatics workflows and two reference databases.

RESULTS
The composition and diversity of bacterial communities did not differ extensively among the three study groups. Nevertheless, the relative abundances of the genera Fusobacterium, Akkermansia, Treponema, and Campylobacter were prominently higher in gingivitis patients versus controls. In contrast, the genera Lautropia, Kingella, Neisseria, Actinomyces, and Rothia were significantly more abundant in controls than in either of the two gingivitis groups.

CONCLUSIONS
The abundance pattern of certain taxa rather than individual strains shows characteristic features of potential diagnostic value. Stringent bioinformatics treatment of the sequencing data is mandatory to avoid unintentional misinterpretations.

microbiome
supragingival biofilm
saliva
amplicon sequencing
gingivitis in adolescents
shotgun sequencing