Role of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review.

Abstract: Spontaneous intestinal perforation (SIP) is a devastating complication of prematurity, and extremely low birthweight (ELBW < 1000 g) infants born prior to 28 weeks are at highest risk. The role of nutrition and feeding practices in prevention and complications of SIP is unclear. The purpose of this review is to compile evidence to support early nutrition initiation in infants at risk for and after surgery for SIP. : A search of PubMed, EMBASE and Medline was performed using relevant search terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstracts and full texts were reviewed by co-first authors. Studies with infants diagnosed with SIP that included information on nutrition/feeding practices prior to SIP and post-operatively were included. Primary outcome was time to first feed. Secondary outcomes were incidence of SIP, time to full enteral feeds, duration of parenteral nutrition, length of stay, neurodevelopmental outcomes and mortality. : Nineteen articles met inclusion criteria-nine studies included feeding/nutrition data prior to SIP and ten studies included data on post-operative nutrition. Two case series, one cohort study and sixteen historical control studies were included. Three studies showed reduced incidence of SIP with initiation of enteral nutrition in the first three days of life. Two studies showed reduced mortality and neurodevelopmental impairment in infants with early feeding. : Available data suggest that early enteral nutrition in ELBW infants reduces incidence of SIP without increased mortality.

D052577:Infant, Extremely Low Birth Weight

nutrition
spontaneous intestinal perforation
prematurity
feeding


Metagenomic Shotgun Sequencing Analysis of Canalicular Concretions in Lacrimal Canaliculitis Cases.

Abstract: Lacrimal canaliculitis is a rare infection of the lacrimal canaliculi with canalicular concretions formed by aggregation of organisms. Metagenomic shotgun sequencing analysis using next-generation sequencing has been used to detect pathogens directly from clinical samples. Using this technology, we report cases of successful pathogen detection of canalicular concretions in lacrimal canaliculitis cases. We investigated patients with primary lacrimal canaliculitis examined in the eye clinics of four hospitals from February 2015 to July 2017. Eighteen canalicular concretion specimens collected from 18 eyes of 17 patients were analyzed by shotgun metagenomics sequencing using the MiSeq platform (Illumina). Taxonomic classification was performed using the GenBank NT database. The canalicular concretion diversity was characterized using the Shannon diversity index. This study included 18 eyes (17 patients, 77.1 ± 6.1 years): 82.4% were women with lacrimal canaliculitis; canalicular concretions were obtained from 12 eyes using lacrimal endoscopy and six eyes using canaliculotomy with curettage. Sequencing analysis detected bacteria in all samples (Shannon diversity index, 0.05-1.47). The following genera of anaerobic bacteria (>1% abundance) were identified: Actinomyces spp. in 15 eyes, Propionibacterium spp., Parvimonas spp. in 11 eyes, Prevotella spp. in 9 eyes, Fusobacterium spp. in 6 eyes, Selenomonas spp. in 5 eyes, Aggregatibacter spp. in 3 eyes, facultative and aerobic bacteria such as Streptococcus spp. in 13 eyes, Campylobacter spp. in 6 eyes, and Haemophilus spp. in 3 eyes. The most common combinations were Actinomyces spp. and Streptococcus spp. and Parvinomonas spp. and Streptococcus spp., found in 10 cases. Pathogens were identified successfully using metagenomic shotgun sequencing analysis in patients with canalicular concretions. Canalicular concretions are polymicrobial with anaerobic and facultative, aerobic bacteria.

Okajima|Yukinobu|Y| Suzuki|Takashi|T| Miyazaki|Chika|C| Goto|Satoshi|S| Ishikawa|Sho|S|0000-0002-8729-7286 Suzuki|Yuka|Y| Aoki|Kotaro|K|0000-0002-9237-1217 Ishii|Yoshikazu|Y| Tateda|Kazuhiro|K| Hori|Yuichi|Y|0000-0002-3781-7976

metagenome
canalicular concretions
lacrimal canaliculitis
polymicrobial infection


Septicemia and meningoencephalitis caused by Listeria monocytogenes in two neonatal llamas.

Abstract: Listeriosis is a disease of humans and domestic mammals (mainly ruminants) with variable manifestations, primarily encephalitis, septicemia, and abortion. Although Listeria monocytogenes readily causes illness in ruminants, the prevalence among domestic South American camelids (llamas and alpacas) is low and has not been documented in their wild counterparts, the vicuna and guanaco. We describe herein the clinical signs, autopsy findings, and histopathology of septicemia and suppurative meningoencephalitis caused by L. monocytogenes in 2 neonatal llamas ( Llama glama) from the same herd. L. monocytogenes was isolated in pure culture and identified by real-time PCR on fresh and paraffin-embedded tissue samples of the brain from both crias. This presentation of septicemic listeriosis with meningoencephalitis in 2 animals from the same group is unusual, especially among llamas.

Hawkins|Ian K|IK|
Ilha|Marcia|M|
Anis|Eman|E|
Wilkes|Rebecca P|RP|

septicemia
meningoencephalitis
Listeria monocytogenes
llamas


Occupational Therapists' Interactions With Older Adult Caregivers: Negotiating Priorities and Expertise.

Abstract: Although numerous studies have examined provider-caregiver interactions and their influence on care outcomes, few represent the perspective of the provider or specifically consider occupational therapy practitioners. The aim of this article is to explore the perspectives of occupational therapists regarding interactions with older adult caregivers in geriatric practice settings. The study was conducted using a constructivist grounded theory approach based on data obtained from repeated focus group sessions and subsequent individual reflections. Occupational therapy practitioners interact with older adult caregivers in ways that reflect negotiations about who holds expertise and whose priorities are most relevant in care situations. These interactions are influenced by health care contexts that foreground the needs of the care recipient. A deeper understanding of caregiving as an occupation via a transactional perspective may serve to illuminate complex care situations and optimize therapist-caregiver interactions.

Womack|Jennifer L|JL|
Lilja|Margareta|M|
Dickie|Virginia|V|
Isaksson|Gunilla|G|

older adults
caregivers
occupational therapy
grounded theory


Enhancing longevity of Plasmodium vivax and P. falciparum sporozoites after dissection from mosquito salivary glands.

Abstract: The pre-erythrocytic stages of Plasmodium vivax and Plasmodium falciparum remain challenging for experimental research in part due to limited access to sporozoites. An important factor limiting availability is the laboratory support required for producing infected mosquitoes and the ephemeral nature of isolated extracellular sporozoites. This study was undertaken to investigate methods to improve the availability of this limited resource by extending the longevity of the extracellular sporozoites after mosquito dissection. Our goal in this study was to determine whether buffer conditions more closely mimicking the insect microenvironment could prolong longevity of ex vivo P. vivax and P. falciparum sporozoites. The study compared the current standard dissection buffer RPMI1640 to Hank's Balanced Salt Solution with 1g/L glucose (HBSS-1) or 2g/L glucose (HBSS-2) and Grace's Insect Medium for ability to extend longevity of ex vivo P. vivax and P. falciparum sporozoites. The effect of each buffer on sporozoite viability was evaluated by measuring sporozoite gliding motility at 0, 4, 8, and 24h post-dissection from mosquito salivary glands. Comparisons of mean gliding percentages of ex vivo sporozoites in the different buffers and time points found that RPMI and Grace's both showed strong gliding at 0h. In contrast, by 4h post-dissection sporozoites in RPMI consistently had the lowest gliding activity, whereas sporozoites in Grace's had significantly more gliding compared to all other buffers at almost all time points. Our results indicate that P. vivax and P. falciparum sporozoites maintained in insect media rather than the standard dissection buffer RPMI and HBSS retain viability better over time.

Lupton|Emily J|EJ|
Roth|Alison|A|
Patrapuvich|Rapatbhorn|R|
Maher|Steve P|SP|
Singh|Naresh|N|
Sattabongkot|Jetsumon|J|
Adams|John H|JH|

D000818:Animals
D000852:Anopheles
D018929:Cell Culture Techniques
D019976:Cloning, Organism
D003470:Culture Media
D010963:Plasmodium falciparum
D010966:Plasmodium vivax
D012469:Salivary Glands
D034101:Sporozoites
D013997:Time Factors

Plasmodium Sporozoite Viability Assays Malaria


Impact of the COVID-19 Pandemic on the Utilization of Hospice Care Services: A Cohort Study in Taiwan.

Abstract:
CONTEXT
Hospice care focuses on improving the quality of end-of-life care and respecting patients' preferences regarding end-of-life treatment. The impact of coronavirus disease 2019 (COVID-19) on the utilization of hospice services is unknown.

OBJECTIVES
To investigate the utilization of hospice care services before and during the COVID-19 pandemic.

METHODS
All patients (n = 19,900) cared for at Taipei City Hospital from January 2019 to April 2020 were divided into three time points: January-April 2019 (before COVID-19), May-December 2019 (interim), and January-April 2020 (during COVID-19). This cohort study compared the monthly utilization of hospice services before and during the COVID-19 pandemic.

RESULTS
There was no significant difference in hospice home visits (194 vs. 184; P = 0.686) and new enrollments (15 vs. 14; P = 0.743) to hospice home care before and during the pandemic. However, the bed occupancy rate in hospice units in the hospital was significantly reduced from 66.2% before the pandemic to 37.4% during the pandemic (P = 0.029), whereas that in nonhospice units had a nonsignificant decrease from 81.6% before the pandemic to 71.8% during the pandemic (P = 0.086). During the pandemic, the number of inpatient days was affected more severely in hospice units than in nonhospice units (-42.4% vs. -10.9%; P = 0.029).

CONCLUSIONS
This study suggests that hospice home care services were maintained during the COVID-19 pandemic, while the utilization of hospice inpatient care services reduced. Home care for hospice patients is an essential component of palliative care during a pandemic.

Chou|Yi-Chang|YC|
Yen|Yung-Feng|YF|
Feng|Rung-Chuang|RC|
Wu|Meng-Ping|MP|
Lee|Ya-Ling|YL|
Chu|Dachen|D|
Huang|Sheng-Jean|SJ|
Curtis|J Randall|JR|
Hu|Hsiao-Yun|HY|

D000078336:Facilities and Services Utilization

COVID-19
pandemic
hospice care service
cohort study


Rapidly progressive growth of Renal Clear Cell Carcinoma and Gastrointestinal Stromal Tumor during the 3rd trimester of pregnancy: A clinical and diagnostic dilemma.

Abstract: The incidence of cancer among pregnancy, albeit rare, presents as a significant diagnostic challenge for clinicians especially with considerations for materno-fetal well-being. The double-edged sword of Renal Clear Cell Carcinoma and Gastrointestinal Stromal Tumor in near-term pregnant woman was encountered in our case and skillfully maneuvered via combination of advanced diagnostic techniques involving CT, MRI and endoscopy. A discussion board comprising of experts was set up and after extended consultation involving patient's relatives, elective cesarean was performed at 34 weeks after which surgical excision resulted in successful extraction of both the tumors, ensuring the survival of both mother and child.

Dey|Sumantra|S| Pakrasi|Rupesh|R| Saha|Dipti|D| Datta|Shreya|S|

Renal clear cell carcinoma
Gastrointestinal stromal tumor
Pregnancy
Gestation


Norepinephrine augmented in vitro growth of uropathogenic E. coli in Type 2 diabetes mellitus and its suppression by silodosin (alpha blocker).

Abstract: Norepinephrine is secreted under conditions of stress in humans. The ability of bacteria to sense mammalian hormone may have a role in propagation of infection. The present study investigated the effect of norepinephrine on in vitro growth of uropathogenic E. coli (UPEC) and the effect of silodosin on norepinephrine-induced changes. The spot urine samples were collected from 56 individuals (14 diabetic patients with UTI, 14 diabetic without UTI, 14 non-diabetic UTI and 14 healthy volunteer controls) for the measurement of urinary norepinephrine concentrations. The concentration of norepinephrine, as found in urine of human subjects, was reproduced in artificial urine medium to study the growth of UPEC. The norepinephrine concentration showing maximum growth response was selected to study the effect of silodosin on the growth inhibition of UPEC. Result showed significantly elevated urinary norepinephrine in diabetic patients with and without UTI and also in nondiabetic UTI groups. The norepinephrine concentration equivalent to that in diabetic UTI patients enhanced the growth of UPEC. Furthermore, silodosin (0.32 μM) inhibited the growth of the UPEC.

Gond|Dinesh Prasad|DP|
Singh|Shivendra|S|
Agrawal|N K|NK|

D058668:Adrenergic alpha-1 Receptor Antagonists

Norepinephrine
Uropathogenic E. coli
Type 2 diabetes
Silodosin
Urinary tract infection


New Genome Similarity Measures based on Conserved Gene Adjacencies.

Abstract: Many important questions in molecular biology, evolution, and biomedicine can be addressed by comparative genomic approaches. One of the basic tasks when comparing genomes is the definition of measures of similarity (or dissimilarity) between two genomes, for example, to elucidate the phylogenetic relationships between species. The power of different genome comparison methods varies with the underlying formal model of a genome. The simplest models impose the strong restriction that each genome under study must contain the same genes, each in exactly one copy. More realistic models allow several copies of a gene in a genome. One speaks of gene families, and comparative genomic methods that allow this kind of input are called gene family-based. The most powerful-but also most complex-models avoid this preprocessing of the input data and instead integrate the family assignment within the comparative analysis. Such methods are called gene family-free. In this article, we study an intermediate approach between family-based and family-free genomic similarity measures. Introducing this simpler model, called gene connections, we focus on the combinatorial aspects of gene family-free genome comparison. While in most cases, the computational costs to the general family-free case are the same, we also find an instance where the gene connections model has lower complexity. Within the gene connections model, we define three variants of genomic similarity measures that have different expression powers. We give polynomial-time algorithms for two of them, while we show NP-hardness for the third, most powerful one. We also generalize the measures and algorithms to make them more robust against recent local disruptions in gene order. Our theoretical findings are supported by experimental results, proving the applicability and performance of our newly defined similarity measures.

Doerr|Daniel|D|
Kowada|Luis Antonio B|LAB|
Araujo|Eloi|E|
Deshpande|Shachi|S|
Dantas|Simone|S|
Moret|Bernard M E|BME|
Stoye|Jens|J|

D000465:Algorithms
D019295:Computational Biology
D023061:Gene Order
D017343:Genes, Plant
D018745:Genome, Plant
D023281:Genomics
D008957:Models, Genetic
D005810:Multigene Family
D010802:Phylogeny

genome similarity measure
gene connections
family-free genome comparison
conserved adjacencies
genome rearrangements


Biomimetic chitosan-graft-polypeptides for improved adhesion in tissue and metal.

Abstract: Inspired by the mussel foot protein and chitosan-based macromolecular adhesives, a series of chitosan-graft-polypeptides were synthesized by ring-opening polymerization of three N-carboxyanhydrides (NCAs) - 3,4-dihydroxyphenylalanine-N-carboxyanhydride (DOPA-NCA), cysteine-NCA (Cys-NCA) and arginine-NCA (Arg-NCA) - using partial-NH2-protected chitosan as an initiator. These copolymers demonstrated good biodegradability and low cytotoxicity. The results of lap-shear adhesion test showed that the maximum lap-shear adhesion strength on the porcine skin and aluminum sheet were 195.97 ± 21.1 kPa and 3080 ± 320 kPa, respectively, and the maximum tensile adhesion strength on bone was 642.70 ± 61.1 kPa. The rat experiment in vivo showed that these copolymers exhibited good hemostatic performance and can promote the healing of skin wound and bone fracture. It is expected that thesecopolymeric adhesives will have broad applications in hemostasis and soft tissue adhesions.

Lu|Dedai|D| Wang|Hongsen|H| Wang|Xiangya|X| Li|Yunfei|Y| Guo|Hongyun|H| Sun|Shaobo|S| Zhao|Xiaolong|X| Yang|Zhiwang|Z| Lei|Ziqiang|Z|

Chitosan
Biocompatible
Biomimetic adhesive
Polypeptide
Surgical adhesive


Therapist concerns and process issues in grappling with functional autobiographical amnesia.

Abstract: Dissociative amnesia is relatively rare form of the dissociative disorder. This paper aims at describing the salient features of a case of functional autobiographical amnesia in a young adult and the approach adopted in the psychological management of this case. The case highlights concerns of the therapist at various stages of the therapy process.

Tripathi|Ravikesh|R| Bharath|Srikala|S| Desai|Geetha|G| Mehrotra|Seema|S|

functional autobiographical amnesia
Dissociative amnesia
dissociation


Communicating prognosis and end-of-life care to heart failure patients: a survey of heart failure nurses' perspectives.

Abstract:
BACKGROUND
Many heart failure (HF) patients have palliative care needs, but communication about prognosis and end-of-life care is lacking. HF nurses can play an important role in such communication, but their views on this have rarely been sought.

AIMS
This study aims to describe HF nurses' perspectives on, and daily practice regarding, discussing prognosis and end-of-life care with HF patients in outpatient care. It further aims to explore barriers, facilitators and related factors for discussing these issues.

METHODS
A national survey including nurses from outpatient clinics and primary health care centres was performed. Data was collected using a questionnaire on communication with HF patients about prognosis and end-of-life care.

RESULTS
In total, 111 (82%) of the HF nurses completed the questionnaire. Most of them reported that physicians should have the main responsibility for discussing prognosis (69%) and end-of-life care (67%). Most nurses felt knowledgeable to have these discussions, but 91% reported a need for further training in at least one of the areas. Barriers for communication about prognosis and end-of-life care included the unpredictable trajectory of HF, patients' comorbidities and the opinion that patients in NYHA class II-III are not in the end-of-life.

CONCLUSION
Although HF nurses feel competent discussing prognosis and end-of-life care with the HF patient, they are hesitant to have these conversations. This might be partly explained by the fact that they consider the physician to be responsible for such conversations, and by perceived barriers to communication. This implies a need for clinical policy and education for HF nurses to expand their knowledge and awareness of the patients' possible needs for palliative care.

Hjelmfors|Lisa|L| Strömberg|Anna|A| Friedrichsen|Maria|M| Mårtensson|Jan|J| Jaarsma|Tiny|T|

D007722:Health Knowledge, Attitudes, Practice

D064946:Hospice and Palliative Care Nursing

communication
prognosis
end-of-life care
Heart failure
palliative care
nurse attitudes


Integration of tuberculosis and HIV services: Exploring the perspectives of co-infected patients in Ghana.

Abstract: Scaling up of integrated tuberculosis (TB)-human immunodeficiency virus (HIV) services remains sub-optimal in many resource-limited countries, including Ghana, where the two conditions take a heavy toll on the financial resources of health systems as well as infected persons. Previous studies have documented several implementation challenges towards TB-HIV service integration, but views of patients on integrated service delivery have not received commensurate research attention. This paper explored the experiences of 40 TB-HIV co-infected patients at different stages of treatment in Ghana. Using Normalisation Process Theory as a framework, data were coded using inter-rater coding technique and analysed inductively and deductively with the help of QSR NVivo 10. For several participants, either of the diseases was diagnosed 'accidentally', leading to inconsistencies in co-therapy administration, constraints regarding separate clinic appointment dates for TB and HIV and prolonged TB treatment due to treatment failure. Put differently, there were widespread negative experiences among TB-HIV co-infected patients with regard to treatment and care, especially among patients who were accessing care in separate facilities or separate units in the same facility. Co-infected patients unanimously support full-service integration. However, they felt powerless to request for reforms on a mode of service delivery.

Anku|Prince Justin|PJ|
Amo-Adjei|Joshua|J|
Doku|David Teye|DT|
Kumi-Kyereme|Akwasi|A|

D019033:Delivery of Health Care, Integrated

integration
Tuberculosis
HIV
co-infected patients
Ghana


Photosensitization of Molecular Oxygen on Graphene Oxide for Ultrasensitive Signal Amplification.

Abstract: H2 O2 and horseradish peroxidase (HRP) are commonly used together in bioassays. HRP is required to accelerate the reaction between a chromogenic substrate (e.g., 3,3',5,5'-tetramethylbenzidine, TMB) and H2 O2 , and thus amplifies the signal. Herein, molecular oxygen for enzyme-free and H2 O2 -free oxidation is explored, still using the same colorimetric reaction. Restricted by spin selection rules, the ground-state triplet oxygen needs to be converted to the singlet state to oxidize TMB. Phloxine B (PB) is used as the photosensitizer because of its excellent performance and safety. Under green light irradiation, each PB has a turnover of approximately 51 TMB molecules in 20 min, making PB a "molecular enzyme mimic" for signal amplification. With its small size, multiple PB molecules are loaded on a graphene oxide nanosheet to design a modified enzyme-linked immunosorbance (ELISA) assay (termed photosensitization immunosorbent assay, PISA), improving the 1:1 enzyme/target ratio to n:1. PISA is more sensitive for carcinoembryonic antigen than a commercial ELISA kit, and successfully measures the antigen in the serum of multiple cancer patients. This simple and green method of oxidation coupled with the small size of the photosensitizer and graphene oxide may enable many other applications in biosensor development, smart materials, and energy harvesting.

photosensitization
graphene oxide
biosensors
colorimetry
immunoassays


Developing a patient decision aid for women aged 70 and older with early stage, estrogen receptor positive, HER2 negative, breast cancer.

Abstract:
OBJECTIVES
Since women ≥70 years with early stage, estrogen receptor positive (ER+), HER2 negative breast cancer face several preference-sensitive treatment decisions, the investigative team aimed to develop a pamphlet decision aid (DA) for such women.

MATERIALS AND METHODS
The content of the DA was informed by literature review, international criteria, and expert feedback, and includes information on benefits and risks of lumpectomy versus mastectomy, lymph node surgery, radiotherapy after lumpectomy, and endocrine therapy. It considers women's overall health and was written using low literacy principles. Women from two Boston-based hospitals who were diagnosed in the past 6-24 months were recruited to provide feedback on the DA and its acceptability. The DA was iteratively revised based on their qualitative input.

RESULTS
Of 48 eligible women contacted, 35 (73%) agreed to participate. Their mean age was 74.3 years; 33 (94%) were non-Hispanic white; and 24 (67%) were college graduates. Overall, 26 (74%) thought the length of the DA was just right, 29 (83%) thought all or most of the information was clear, 32 (91%) found the DA helpful, and 33 (94%) would recommend it. In open ended comments, participants noted that the DA was clear, well-organized, and would help women prepare for and participate in treatment decision-making.

CONCLUSIONS
The investigative team developed a novel breast cancer treatment DA that is acceptable to women ≥70 years with a history of ER+, HER2-, early stage breast cancer. Next, the DA's efficacy needs to be tested with diverse older women newly diagnosed with breast cancer.

Schonberg|Mara A|MA|
Freedman|Rachel A|RA|
Recht|Abram R|AR|
Jacobson|Alicia R|AR|
Aliberti|Gianna M|GM|
Karamourtopoulos|Maria|M|
Nakhlis|Faina|F|
McCarthy|Ellen P|EP|
Pories|Susan E|SE|
Sharma|Ranja|R|
Dominici|Laura S|LS|

Decision aids
Older women
Implementation
Mammography screening


Noninvasive temperature monitoring for dual-modal tumor therapy based on lanthanide-doped up-conversion nanocomposites.

Abstract: Accurate treatment of photothermal therapy (PTT) is crucial to avoid the unnecessary injury of normal cells and tissues. Therefore the real-time temperature monitoring in the PTT process has drawn more and more attention in recent years. Herein, we designed and prepared one kind of lanthanide (Ln3+)-doped up-conversion nanocomposites with multi-functions, which can not only provide temperature feedback in PTT process, but also play the photodynamic therapy (PDT) function for the synergistic effect of tumor therapy. Based on NaYF4:Yb, Er up-conversion nanoparticles (UCNPs), mesoporous SiO2 was modified on the surface combined with photosensitizer Chlorin e6 (Ce6) molecules, which could be excited by red emission of Er3+ under the 980 nm laser. Cit-CuS NPs were further linked on the surface of the composite served as photothermal conversion agent, therefore, the temperature of the PTT site can be monitored by recording the ratio of I525/I545 of green emissions, especially within the physiological range. Based on the guidance obtained from spectral experiments, we further investigated the dual-modal therapy effect both in vitro and in vivo, respectively, and acquired decent results.

Sun|Xueke|X| Sun|Jiao|J| Dong|Biao|B| Huang|Gaosheng|G| Zhang|Li|L| Zhou|Wanhui|W| Lv|Jiekai|J| Zhang|Xinran|X| Liu|Min|M| Xu|Lin|L| Bai|Xue|X| Xu|Wen|W| Yang|Yudan|Y| Song|Xiuling|X| Song|Hongwei|H|

PTT
PDT
Dual modal therapy
Temperature sensing
UC imaging


Full Atrioventricular Block Secondary to Acute Poisoning Mercury: A Case Report.

Abstract: Background: The biological behaviour and clinical significance of mercury toxicity vary according to its chemical structure. Mercury differs in its degree of toxicity and in its effects on the nervous, digestive and immune systems as well as on organs such as the lungs, kidneys, skin, eyes and heart. Human exposure occurs mainly through inhalation of elemental mercury vapours during industrial and artisanal processes such as artisanal and small-scale gold mining. Case presentation: A 52-years-old female, housewife, with a body mass index of 25.3 kg/cm², without smoking or alcohol habits or any important clinical or chronic cardiovascular history, was admitted to the emergency room due to probable accidental poisoning by butane gas. Clinical manifestations with a headache, dizziness, cough, and dyspnoea of medium to small efforts. An initial physical exploration with Glasgow scored at 15, with arrhythmic heart sounds, pulmonary fields with bilateral subcrepitant rales and right basal predominance. Electrocardiographic findings were as follows: a cardiac frequency of 50 beats per minute and atrioventricular dissociation. Laboratory parameters were: white blood cells at 15.8 × 10⁸/L; aspartate aminotransferase at 38 U/L; lactate dehydrogenase at 1288 U/L; creatine-kinase at 115 U/L; CK-MB fraction at 28 U/L; and other biochemical parameters were within the reference values. A radiographic evaluation showed flow cephalization, diffuse bilateral infiltrates with right basal predominance. In addition, the patient presented data of low secondary expenditure to third-degree atrioventricular (AV) block for which the placement of a transvenous pacemaker was decided, substantially improving the haemodynamic parameters. Subsequently, after a family interrogation, the diagnosis of mercury inhalation poisoning was established. An initial detection of mercury concentration (Hg(0)) was carried out, reporting 243.5 µg/L. In view of this new evidence, mercury chelation therapy with intravenous calcium disodium ethylenediamine tetraacetic acid (CaNa₂·EDTA) was initiated. After 8-days of hospital stay, she presented a favourable evolution with both clinical and radiological improvements, so that the mechanical ventilation progressed to extubating. Subsequently, she was referred for cardiology because of her persistent 3rd-degree atrioventricular block, deciding to place a definitive bicameral pacemaker. The patient was discharged from the hospital 14 days after admission due to clinical improvements with mercury plasma levels at 5 µmol/L and a heart rhythm from the pacemaker. Conclusions: We show evidence that acute exposure to elemental mercury can affect the heart rhythm, including a complete atrioventricular blockage.

atrioventricular block
gold mining
mercury exposure


Comparative evaluation of two matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems for the identification of clinically significant yeasts.

Abstract:
OBJECTIVES
To prospectively evaluate the performance of two matrix-assisted laser desorption/ionization time-of-flight mass spectrometry systems (MALDI-TOF MS) for the identification of clinically significant yeast isolates compared to the VITEK 2 system.

METHODS
One hundred and eighty-eight consecutive yeast isolates were analyzed by Bruker Biotyper and VITEK MS. The results were compared with the conventional VITEK 2 yeast identification system. Discrepant results were resolved by direct sequencing of rDNA.

RESULTS
Accurate identification by VITEK 2, VITEK MS, and Bruker Biotyper MS was 94.1% (177/188), 93.0% (175/188), and 92.6% (174/188), respectively. Three isolates were not identified by VITEK MS, while nine Candida orthopsilosis were misidentified as Candida parapsilosis, as this species is not present in its database. Eleven isolates were not identified or were wrongly identified by Bruker Biotyper and although another 14 were correctly identified, the score was unreliable at <1.7.

CONCLUSION
The overall accuracy of rapid MALDI-TOF MS systems was essentially comparable to that of the conventional VITEK 2 yeast identification system. However, future expansion of the databases may further improve the outcome and accuracy of identification of yeast species.

Jamal|W Y|WY|
Ahmad|S|S|
Khan|Z U|ZU|
Rotimi|V O|VO|

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

MALDI-TOF MS
Identification
Yeasts
VITEK 2 system


A Review of Regulatory Mechanisms Used by the WHO, EU, and US to Facilitate Access to Quality Medicinal Products in Developing Countries With Constrained Regulatory Capacities.

Abstract: Adequate medicine regulation requires nations to establish robust regulatory agencies that will subject all pharmaceutical products to pre- and postmarketing evaluation. These agencies are essential for any country wishing to ensure that the medicinal products it authorizes for use in its territory meet internationally agreed standards of safety, quality, and efficacy. Many developing nations, however, lack regulatory systems that can guarantee this set of requirements. As a result, almost all of these nations tend to rely on regulatory decisions made by well-resourced institutions, particularly the US Food and Drug Administration, the European Medicines Agency, and the World Health Organization. In this paper, the authors review the objectives, strengths, and weaknesses of some key regulatory initiatives instituted by these bodies to facilitate product registration in developing countries with constrained regulatory capacities.

Saidu|Yauba|Y|
Angelis|Dario De|D|
Aiolli|Silvia|S|
Gonnelli|Stefano|S|
Georges|Anne Marie|AM|

medicine regulation
developing nations
product registration
National Regulatory Authority


Obesity, dyslipidemia and brain age in first-episode psychosis.

Abstract:
INTRODUCTION
Obesity and dyslipidemia may negatively affect brain health and are frequent medical comorbidities of schizophrenia and related disorders. Despite the high burden of metabolic disorders, little is known about their effects on brain structure in psychosis. We investigated, whether obesity or dyslipidemia contributed to brain alterations in first-episode psychosis (FEP).

METHODS
120 participants with FEP, who were undergoing their first psychiatric hospitalization, had <24 months of untreated psychosis and were 18-35 years old and 114 controls within the same age range participated in the study. We acquired 3T brain structural MRI, fasting lipids and body mass index. We used machine learning trained on an independent sample of 504 controls to estimate the individual brain age of study participants and calculated the BrainAGE score by subtracting the chronological from the estimated brain age.

RESULTS
In a multiple regression model, the diagnosis of FEP (B = 1.15, SE B = 0.31, p < 0.001) and obesity/overweight (B = 0.92, SE B = 0.35, p = 0.008) were each additively associated with BrainAGE scores (R2 = 0.22, F(3, 230) = 21.92, p < 0.001). BrainAGE scores were highest in participants with FEP and obesity/overweight (3.83 years, 95%CI = 2.35-5.31) and lowest in normal weight controls (-0.27 years, 95%CI = -1.22-0.69). LDL-cholesterol, HDL-cholesterol or triglycerides were not associated with BrainAGE scores.

CONCLUSIONS
Overweight/obesity may be an independent risk factor for diffuse brain alterations manifesting as advanced brain age already early in the course of psychosis. These findings raise the possibility that targeting metabolic health and intervening already at the level of overweight/obesity could slow brain ageing in FEP.

Kolenic|Marian|M| Franke|Katja|K| Hlinka|Jaroslav|J| Matejka|Martin|M| Capkova|Jana|J| Pausova|Zdenka|Z| Uher|Rudolf|R| Alda|Martin|M| Spaniel|Filip|F| Hajek|Tomas|T|

Obesity
Dyslipidemia
First-episode psychosis
Schizophrenia
BrainAGE score
Overweight


A Longitudinal Study Investigating Synchronization in a Singing Quintet.

Abstract: Research suggests that synchronization between musicians during ensemble performances can be affected by the rhythmic or tonal complexity of the piece being performed and by group roles such as leader-follower relationships. Since previous studies have mostly been conducted within single performance sessions, developmental aspects of interpersonal synchronization in ensembles remain underinvestigated. This longitudinal study followed a newly formed singing ensemble from initial rehearsals to the performance stage in order to investigate the evolution of synchronization between advanced singing students during a university term of study in relation to the musical content of the piece and leader-follower relationships. An advanced postgraduate singing quintet was recorded using head-worn microphones and laryngograph electrodes to allow fundamental frequency evaluation of the individual voices. The quintet, formed to complete a 1-year Master's programme in ensemble singing, rehearsed two pieces composed for the study, during five rehearsals over 3 months. Singers practised the same pieces in a randomized order across rehearsals and performed three repetitions of the same pieces before and after each rehearsal, resulting in six recordings per piece/rehearsal. Audio and laryngograph data of the repeated performances were collected, and synchronization was measured by extracting note times from the fundamental frequency values. The asynchronies of the two pieces before and after rehearsals were calculated and compared both within rehearsals (pre and post) and between rehearsals (rehearsals 1-5). Results demonstrate an increase in the precision of synchronization over the course of study, depending on the piece being rehearsed, and a more variable synchronization for the more rhythmically complex piece. Results also show changes in the distribution of the tendency to precede all co-performers across rehearsals, which became equally distributed among the musicians during the last rehearsal. The results reported here could have important implications for the tailoring of rehearsal strategies that could improve interpersonal synchronization between musicians during ensemble performances.

Interpersonal synchronization—Rehearsal stages—Entrainment—Ensemble Communication--Ensemble Singing


Low Distortion of Noise Filter Realization with 6.34 V/μs Fast Slew Rate and 120 mVp-p Output Noise Signal.

Abstract: In order to reduce Gaussian noise, this paper proposes a method via taking the average of the upper and lower envelopes generated by capturing the high and low peaks of the input signal. The designed fast response filter has no cut-off frequency, so the high order harmonics of the actual signal remain unchanged. Therefore, it can immediately respond to the changes of input signal and retain the integrity of the actual signal. In addition, it has only a small phase delay. The slew rate, phase delay and frequency response can be confirmed from the simulation results of Multisim 13.0. The filter outlined in this article can retain the high order harmonics of the original signal, achieving a slew rate of 6.34 V/μs and an almost zero phase difference. When using our filter to physically test the input signal with a noise level of 3 Vp-p Gaussian noise, a reduced noise signal of 120 mVp-p is obtained. The noise can be suppressed by up to 4% of the raw signal.

Yu|Fang-Ming|FM|0000-0002-6348-0019 Lee|Kun-Cheng|KC| Jwo|Ko-Wen|KW| Chang|Rong-Seng|RS| Lin|Jun-Yi|JY|

Gaussian noise
fast response
high order harmonics
small phase delay
low distortion noise filter


Nitrate and nitrite levels in commonly consumed vegetables in Hong Kong.

Abstract: Levels of nitrate and nitrite in 73 different vegetables, a total of 708 individual samples grouped into leafy, legumes, root and tuber, and fruiting vegetables, which are traded mainly in Hong Kong, were measured. Where available, five samples of each vegetable type were purchased from different commercial outlets during the winter of 2008 and summer of 2009. Levels of nitrate and nitrite were determined by ion chromatography and flow injection analysis, respectively. Nitrate and nitrite levels of all samples ranged <4-6300 and <0.8-9.0 mg kg⁻¹, respectively. Nitrate concentrations for the different groups, in descending order, were leafy > root and tuber > fruiting and legume vegetables. More than 80% of vegetables had mean nitrate concentrations less than 2000 mg kg⁻¹, but mean nitrate concentrations of three types of leafy vegetables, namely Chinese spinach, Shanghai cabbage and Chinese white cabbage, were >3500 mg kg⁻¹. On the other hand, nitrite concentrations were generally low - <1 mg kg⁻¹ on average. Nitrate in vegetables (i.e. Chinese flowering cabbage, Chinese spinach and celery) can be reduced significantly (12-31%) after blanching for 1-3 min, but not after soaking.

Chung|Stephen W C|SW|
Tran|Jeff C H|JC|
Tong|Katherine S K|KS|
Chen|Melva Y Y|MY|
Xiao|Ying|Y|
Ho|Y Y|YY|
Chan|Constance H Y|CH|

nitrate nitrite vegetables mushrooms plants


Implementing a School-Located Vaccination Program in Denver Public Schools.

Abstract:
BACKGROUND
School-located vaccination (SLV) offers an opportunity to deliver vaccines to students, particularly those without a primary care provider.

METHODS
This SLV program offered 2 clinics at each of 20 elementary schools (influenza vaccine) and 3 clinics at each of 7 middle/preschool-eighth-grade schools (adolescent platform plus catch-up vaccines) during the 2009-2010 and 2010-2011 school years. Established programmatic processes for immunization delivery in an outreach setting were used. Billing and vaccine inventory management processes were developed. Vaccines from the federal Vaccines for Children program were used for eligible students. Third-party payers were billed for insured students; parents were not billed for services.

RESULTS
The proportion of enrolled students who received at least 1 dose of vaccine increased from year 1 to year 2 (elementary: 28% to 31%; middle: 12% to 19%). Issues identified and addressed included program planning with partners, development and implementation of billing processes, development of a solution to adhere to the Family Educational Rights and Privacy Act requirements, development and utilization of an easy-to-comprehend consent form, and implementation of standard work procedures.

CONCLUSIONS
This SLV program offered an alternative approach for providing vaccinations to students outside of the primary care setting. To be successful, ongoing partnerships are needed.

Shlay|Judith C|JC|
Rodgers|Sarah|S|
Lyons|Jean|J|
Romero|Scott|S|
Vogt|Tara M|TM|
McCormick|Emily V|EV|

school-located vaccinations
influenza vaccines
adolescent vaccines


Differential effects of tianeptine on the dorsal hippocampal volume of rats submitted to maternal separation followed by chronic unpredictable stress in adulthood.

Abstract: Early maternal separation (MS) may produce lasting effects in the dorsal hippocampus (DH) that can change its response to chronic stress in adulthood. Chronic stress affects DH morphology and function, but tianeptine (an anti-depressant) can reverse the stress-induced morphological impairments. Morphologic alterations of hippocampus can affect contextual memory. Therefore, we evaluated the effect of tianeptine in MS and chronically stressed rats on: 1) volume of the DH and its areas using stereology and 2) hippocampal-dependent memory using a fear conditioning test. Male Wistar rats were subjected to daily MS for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50 and 74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle, providing eight groups: AFR-unstressed/vehicle (n = 5 for stereology, n = 18 for fear conditioning test); AFR unstressed/tianeptine (n = 6 and n = 10); AFR-chronic stress/vehicle (n = 6 and n = 14); AFR-chronic stress/tianeptine (n = 6 and n = 10), MS-unstressed/vehicle (n = 5 and n = 19), MS-unstressed/tianeptine (n = 6 and n = 10), MS-chronic stress/vehicle (n = 6 and n = 18), and MS-chronic stress/tianeptine (n = 6 and n = 10). MS-chronic stress/tianeptine rats showed a diminished CA1 area than the corresponding MS-unstressed/tianeptine rats. The combination of stressors produced a freezing response similar to those of the control group during postconditioning. During retrieval, MS led to a diminished freezing response compared to the AFR-unstressed groups. Tianeptine had no effect on freezing behavior. Our results show that tianeptine can affect the CA1 area volume differently depending on the nature and quantity of stressors but cannot alter freezing to context.

Pollano|Antonella|A|
Zalosnik|María I|MI|
Durando|Patricia E|PE|
Suárez|Marta M|MM|

hippocampal volume
stereology
fear conditioning test
freezing behavior
Antidepressant
early stress


Proximate determinants of particulate matter (PM2.5) emission, mortality and life expectancy in Europe, Central Asia, Australia, Canada and the US.

Abstract:
BACKGROUND
The growing concern with environmental related impacts on mortality and morbidity means that the conceptual framework of environment-health-economic policy nexus is salient in the global debate on air pollution.

OBJECTIVES
With time series data spanning 2000-2016, this study explored the proximate determinants of ambient air pollution, mortality, and life expectancy in North America, Europe & Central Asia, and East Asia & Pacific regions.

METHODS
The study applied historical data on urban population, total pollution, energy consumption, GDP per capita, life expectancy, mortality rate and industrial PM2.5 emissions to develop six parsimonious models using the generalized least squares (GLS) random-effects model estimation with first-order autoregressive [AR(1)] disturbance across 54 countries.

RESULTS
An increase in income level by 1% declined mortality rate by 0.01% and increased longevity by ~0.02% (95% Confidence Interval [CI]) in the long-run. An increase in industrial PM2.5 emissions per capita by 1% decreased life expectancy by 0.004% and mortality rate by 0.02% (95% CI). Intensification of energy consumption and its related services by 1% were found to increase industrial PM2.5 emissions by 0.42-0.45% (95% CI). An inversed-U shaped curve between PM2.5 emissions per capita and income levels was found at a turning point of US$ 48,061. The validity of an environmental Kuznets curve hypothesis between ambient air pollution and urbanization was confirmed, while a rapid increase in population had a significant positive impact on ambient air pollution.

CONCLUSION
Ambient air pollution contributes significantly in reducing life expectancy and increasing mortality. However, sustained economic development, along with energy efficiency, and sustainable urban settlement planning and management are potential options for reducing ambient air pollution while improving quality of life and environmental sustainability.

Sarkodie|Samuel Asumadu|SA|
Strezov|Vladimir|V|
Jiang|Yijiao|Y|
Evans|Tim|T|

D000393:Air Pollutants
D000397:Air Pollution
D001208:Asia
D001315:Australia
D004781:Environmental Exposure
D005060:Europe
D005202:Far East
D008017:Life Expectancy
D009026:Mortality
D009656:North America
D052638:Particulate Matter
D011788:Quality of Life

Air pollution
Energy consumption
Mortality rate
Environmental sustainability
EKC hypothesis
Panel data


Temporal trend in early sepsis in a very low birth weight infants' cohort: an opportunity for a rational antimicrobial use.

Abstract:
OBJECTIVE
This study aimed to evaluate annual trends of early neonatal sepsis and antimicrobial use in very low birth weight infants for 12 years, as well as to identify microbiological agents, antimicrobial sensitivity profiles, and association with early neonatal death.

METHOD
This was a retrospective cohort study including 1254 very low birth weight infants admitted from 2006 to 2017. Four groups were evaluated: culture-confirmed sepsis; presumed neonatal sepsis; ruled out neonatal sepsis group; and infants not exposed to antibiotics.

RESULTS
The medians of gestational age and birth weight were 29 weeks (27-31) and 1090g (850-1310), respectively. The rates of culture-confirmed sepsis, presumed neonatal sepsis, ruled out neonatal sepsis, and not exposed to antibiotics were 1.3, 9.0, 15.4, and 74.3%, respectively. From the initial group of newborns whose antimicrobial treatment was administered for sepsis' suspicion, it was possible to discontinue antibiotic in 44%. The culture-confirmed sepsis rates remained stable (p=0.906). Significant tendencies of decreasing presumed sepsis rates (p<0.001) and increased ruled out neonatal sepsis/not exposed to antibiotics rates (p<0.001) were observed. Streptococcus agalactiae and enteric Gram-negative rods were the predominant agents and most of them were sensitive to crystalline penicillin/ampicillin (88.2%) and to ampicillin and/or amikacin. Early death occurred in 10.8%, specifically in the culture-confirmed sepsis and presumed neonatal sepsis groups.

CONCLUSION
The confirmed sepsis rate was low and remained stable. There was a significant downward trend in the presumed neonatal sepsis rate and a significant upward trend in the ruled out neonatal sepsis group. The rate of not exposed to antibiotics infants was high, also presenting a significant downward trend. The identified bacteria were those commonly found and showed usual antimicrobial susceptibility patterns. Death predominantly occurred in groups that received antibiotic treatment.

Caldas|Jamil Pedro de Siqueira|JPS|
Montera|Lorenna Cristina|LC|
Calil|Roseli|R|
Marba|Sergio Tadeu Martins|STM|

Very low birth weight
Infant
Neonatal sepsis
Antimicrobial stewardship


A seven-legged tick: Report of a morphological anomaly in Ixodes scapularis (Acari: Ixodidae) biting a human host from the Northeastern United States.

Abstract: Cases of morphological anomalies in the blacklegged tick, Ixodes scapularis (Acari: Ixodidae), have recently been reported from the Northeastern and upper Midwestern United States, potentially complicating identification of this important vector of human disease-causing pathogens. We hereby report a case of a morphological anomaly in I. scapularis, biting a human host residing in Norwich, Connecticut. Using a dichotomous morphological key, high-resolution and scanning electron microscopy images, as well as DNA sequencing, the tick was identified as an adult female I. scapularis with three legs on the left side of the abdomen versus four on the right side, which we believe is the first case of ectromely in an adult I. scapularis. Using diagnostic genes in polymerase chain reaction, the specimen tested positive for Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum, the causative agents for Lyme disease and anaplasmosis, respectively, and also showed evidence of a rickettsial endosymbiont. Here we discuss recent reports of morphological anomalies in I. scapularis, and emphasize the significance of additional studies of teratology in this important tick species and its potential implications.

Molaei|Goudarz|G|
Little|Eliza A H|EAH|
Stafford|Kirby C|KC|
Gaff|Holly|H|

Seven-legged tick
Morphological anomaly
Ixodes scapularis
Blacklegged tick
Northeastern U.S.


Phyllodes Tumor of the Breast: A Clinicopathological Evaluation of 55 Cases.

Abstract:
Objective
Phyllodes tumors are biphasic tumors consisting of epithelial and stromal components that account for less than 1% of all breast tumors. According to the World Health Organization (WHO) phyllodes tumors are classified into three categories as benign, borderline and malignant. It has been reported that these tumors are usually benign and both the stromal component and the epithelial component may progress to malignancy. In this descriptive study, it was aimed to present the cases of phyllodes tumor and to evaluate the clinicopathological features of these tumors in the light of the literature.

Materials and Methods
In our study, 55 cases of phyllodes tumor diagnosed between 2005-2018 in the Department of Medical Pathology were retrospectively studied. A total of 55 cases were included in the study.

Results
All cases were female with a mean age of 39.7+15.2 years. Fifty-seven tumors diagnosed in 55 cases were classed as benign in 20 cases (35.1%), borderline in 14 cases (24.6%) and malignant phyllodes tumors in 23 cases (40.3%). Ductal carcinoma in situ (solid and cribriform type) were detected in one case with malignant phyllodes tumor, whereas invasive ductal carcinoma was detected in one case. Bilateral ductal carcinoma in situ was present in the patient with invasive ductal carcinoma.

Conclusion
These tumors which rapidly grow into large masses can be clinically and pathologically confused with benign lesions, macroscopic and microscopic evaluation of concomitant in situ-invasive carcinomas should be considered. Phyllodes tumors have an important role in breast surgery and pathology.

phyllodes tumor
breast
Fibroepithelial lesion


Design and synthesis of α-conotoxin GID analogues as selective α4β2 nicotinic acetylcholine receptor antagonists.

Abstract: The α4β2 nicotinic acetylcholine receptor (nAChR) is an important target for currently approved smoking cessation therapeutics. However, the development of highly selective α4β2 nAChR antagonists remains a significant challenge. α-Conotoxin GID is an antagonist of α4β2 nAChRs, though it is significantly more potent toward the α3β2 and α7 subtypes. With the goal of obtaining further insights into α-conotoxin GID/nAChR interactions that could lead to the design of GID analogues with improved affinity for α4β2 nAChRs, we built a homology model of the GID/α4β2 complex using an X-ray co-crystal structure of an α-conotoxin/acetylcholine binding protein (AChBP) complex. Several additional interactions that could potentially enhance the affinity of GID for α4β2 nAChRs were observed in our model, which led to the design and synthesis of 22 GID analogues. Seven analogues displayed inhibitory activity toward α4β2 nAChRs that was comparable to GID. Significantly, both GID[A10S] and GID[V13I] demonstrated moderately improved selectivity toward α4β2 over α3β2 when compared with GID, while GID[V18N] exhibited no measurable inhibitory activity for the α3β2 subtype, yet retained inhibitory activity for α4β2. In this regard, GID[V18N] is the most α4β2 nAChR selective α-conotoxin analogue identified to date.

Banerjee|Jayati|J|
Yongye|Austin B|AB|
Chang|Yi-Pin|YP|
Gyanda|Reena|R|
Medina-Franco|José L|JL|
Armishaw|Christopher J|CJ|

α-conotoxin
nicotinic acetylcholine receptors
homology modeling
acetylcholine binding protein


Risk for suicidal behaviors associated with PTSD, depression, and their comorbidity in the U.S. Army.

Abstract:
BACKGROUND
Suicide rates have risen considerably in the United States Army in the past decade. Suicide risk is highest among those with past suicidality (suicidal ideation or attempts). The incidence of posttraumatic stress disorder (PTSD) and depressive illnesses has risen concurrently in the U.S. Army. We examined the relationship of PTSD and depression, independently and in combination, and rates of past-year suicidality in a representative sample of U.S. Army soldiers.

METHODS
This study used the DoD Survey of Health Related Behaviors Among Active Duty Military Personnel (DoD HRB) (N=5927). Probable PTSD and depression were assessed with the PTSD Checklist (PCL) and the 10-item short form of the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Past-year suicidality was assessed via self-report.

RESULTS
Six percent of Army service members reported suicidality within the past year. PTSD and MDD were each independently associated with past-year suicidality. Soldiers with both disorders were almost three times more likely to report suicidality within the past year than those with either diagnosis alone. Population-attributable risk proportions for PTSD, depression, and both disorders together were 24%, 29%, and 45%, respectively.

LIMITATIONS
The current study is subject to the limitations of a cross-sectional survey design and the self-report nature of the instruments used.

CONCLUSIONS
PTSD and depression are each associated with suicidality independently and in combination in the active duty component of the U.S. Army. Soldiers presenting with either but especially both disorders may require additional outreach and screening to decrease suicidal ideation and attempts.

Ramsawh|Holly J|HJ|
Fullerton|Carol S|CS|
Mash|Holly B Herberman|HB|
Ng|Tsz Hin H|TH|
Kessler|Ronald C|RC|
Stein|Murray B|MB|
Ursano|Robert J|RJ|

Depression
Suicidal ideation
Attempted
Stress disorders
Military personnel
Post-traumatic


Changing patterns of tobacco use in a middle-aged population: the role of snus, gender, age, and education.

Abstract:
BACKGROUND
In Sweden, the smoking prevalence has declined. In 2007, it was among the lowest in the industrialized world. A steady increase in the use of Swedish oral moist snuff, snus, has occurred in parallel. This development is neither solicited by authorities nor the medical establishment, but rather has occurred along with increased awareness of the dangers of smoking, and has been promoted by product development and marketing of snus.

OBJECTIVE
To evaluate time trends in patterns of tobacco use in northern Sweden during 1990-2007.

DESIGN
Cross-sectional (99,381 subjects) and longitudinal (26,867 subjects) data from the Västerbotten Intervention Programme (VIP) 1990-2007 were analyzed. All adults in Västerbotten County are invited to a VIP health examination at ages 40, 50, and 60 years, and until 1995 also 30 years. Smoking and use of snus were evaluated by gender, age and educational groups. Intermittent smoking was categorized as smoking.

RESULTS
From the period 1990-1995 to the period 2002-2007, smoking prevalence decreased from 26 to 16% among men and from 27 to 18% among women. The differences in prevalence increased between educational groups. The decline in smoking was less and the increase of snus use was greater among those with basic education. The use of snus among basic-educated 40-year-olds reached 35% among men and 14% among women during 2002-2007. Dual smoking and snus use increased among men and women with basic education. Smoking without snus use was more prevalent among women. Gender differences in total smoking prevalence (smoking only plus dual use) were small in all age groups, but increased among those with basic education reaching 7.3% during 2002-2007, with women being more frequent smokers. Smoking prevalences were similar among never, former and current snus users. Among the 30,000 former smokers, 38% of men and 64% of women had never used snus. Longitudinal data showed a decline in total tobacco use from baseline until follow-up and this was mainly due to a smoking cessation rate of<1% a year. Snus use was started by 6.2% of the 30-year-old women (age at baseline), and this contributed to a stable prevalence of total tobacco use in this group. Seventy percent of baseline snus users still used snus at follow-up. Among smokers, 55% continued smoking, 12% of men and 7% of women switched to snus. Among those with dual tobacco use at baseline, a third of men and a fourth of women remained dual users 10 years later.

CONCLUSION
There are increasing differences in tobacco use between educational groups. Higher smoking and snus use prevalence are found among those with basic education, and this is most pronounced in the younger group of this middle-aged population. In spite of a higher prevalence of smoking without snus use among women, total smoking prevalence is similar in men and women due to a higher prevalence of dual tobacco use, i.e. snus and cigarettes, among men. The increase in snus use is being paralleled by a slight increase in dual use and the smoking prevalence does not seem to be influenced by snus. This should be the subject of further studies and also have implications for tobacco control policies.

Norberg|Margareta|M| Lundqvist|Gunnar|G| Nilsson|Maria|M| Gilljam|Hans|H| Weinehall|Lars|L|

tobacco
snus
smoking
prevalence
Swedish moist snuff
smokeless tobacco
socioeconomic factors/education


Population genetic data for 15 autosomal STR markers in Turkish Cypriots from Cyprus.

Abstract: Fifteen autosomal short tandem repeat (STR) markers [D8S1179, D21S11, D7S820, CSF1PO, D3S1358, THO1, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA] were analyzed in 501 unrelated, randomly selected Turkish Cypriot individuals from the island of Cyprus. While no locus duplications or null alleles were detected in these samples, eight allelic variants were observed in total, 75% of which were intermediate allelic variants that were absent in the system allelic ladder. Allelic frequencies and statistical parameters of forensic interest were calculated at each locus. For the 15 STR loci tested, combined matching probability (pM) was 2.15717 × 10(-18) and combined power of exclusion (PE) was 0.9999995213. No deviations from the Hardy-Weinberg equilibrium were observed, except for the vWA locus, which became insignificant after the Bonferroni correction for multiple testing. Locus-by-locus comparisons of the Turkish Cypriot allelic frequencies with those published for the neighboring and/or historically related populations with similar loci coverage (Turkish, Greek, Greek Cypriot, Italian and Lebanese) revealed some statistically significant differences at one to five loci. In general, an increase in the number of such significant differences between the Turkish Cypriot data and those for other populations correlated closely with an increase in the geographic distance and/or a decrease in the amount of historical contact. The Turkish Cypriot autosomal STR population study will find immediate use in the Committee on Missing Persons in Cyprus Project on the "Exhumation, Identification and Return of Remains of Missing Persons" and it will also be available for criminal, parentage and other missing person investigations.

Gurkan|Cemal|C|
Demirdov|Damla Kanliada|DK|
Yamaci|Rezan Fahrioglu|RF|
Sevay|Huseyin|H|

Autosomal
Turkish Cypriot
Cyprus
Short tandem repeat (STR)
Identifiler


Addressing care-seeking as well as insurance-seeking selection biases in estimating the impact of health insurance on out-of-pocket expenditure.

Abstract: Health Insurance (HI) programmes in low-income countries aim to reduce the burden of out-of-pocket (OOP) health care expenditure. However, if the decisions to purchase insurance and to seek care when ill are correlated with the expected health care expenditure, the use of naïve regression models may produce biased estimates of the impact of insurance membership on OOP expenditure. Whilst many studies in the literature have accounted for the endogeneity of the insurance decision, the potential selection bias due to the care-seeking decision has not been taken into account. We extend the Heckman selection model to account simultaneously for both care-seeking and insurance-seeking selection biases in the health care expenditure regression model. The proposed model is illustrated in the context of a Vietnamese HI programme using data from a household survey of 1,192 individuals conducted in 1999. Results were compared with those of alternative econometric models making no or partial allowance for selection bias. In this illustrative example, the impact of insurance membership on reducing OOP expenditures was underestimated by 21 percentage points when selection biases were not taken into account. We believe this is an important methodological contribution that will be relevant to future empirical work.

D010342:Patient Acceptance of Health Care

Health insurance
Low-income countries
Endogeneity
Selection bias
Heckman model
Vietnam


Leishmania infantum 5'-Methylthioadenosine Phosphorylase presents relevant structural divergence to constitute a potential drug target.

Abstract:
BACKGROUND
The 5'-methylthioadenosine phosphorylase (MTAP), an enzyme involved in purine and polyamine metabolism and in the methionine salvage pathway, is considered as a potential drug target against cancer and trypanosomiasis. In fact, Trypanosoma and Leishmania parasites lack de novo purine pathways and rely on purine salvage pathways to meet their requirements. Herein, we propose the first comprehensive bioinformatic and structural characterization of the putative Leishmania infantum MTAP (LiMTAP), using a comparative computational approach.

RESULTS
Sequence analysis showed that LiMTAP shared higher identity rates with the Trypanosoma brucei (TbMTAP) and the human (huMTAP) homologs as compared to the human purine nucleoside phosphorylase (huPNP). Motifs search using MEME identified more common patterns and higher relatedness of the parasite proteins to the huMTAP than to the huPNP. The 3D structures of LiMTAP and TbMTAP were predicted by homology modeling and compared to the crystal structure of the huMTAP. These models presented conserved secondary structures compared to the huMTAP, with a similar topology corresponding to the Rossmann fold. This confirmed that both LiMTAP and TbMTAP are members of the NP-I family. In comparison to the huMTAP, the 3D model of LiMTAP showed an additional α-helix, at the C terminal extremity. One peptide located in this specific region was used to generate a specific antibody to LiMTAP. In comparison with the active site (AS) of huMTAP, the parasite ASs presented significant differences in the shape and the electrostatic potentials (EPs). Molecular docking of 5'-methylthioadenosine (MTA) and 5'-hydroxyethylthio-adenosine (HETA) on the ASs on the three proteins predicted differential binding modes and interactions when comparing the parasite proteins to the human orthologue.

CONCLUSIONS
This study highlighted significant structural peculiarities, corresponding to functionally relevant sequence divergence in LiMTAP, making of it a potential drug target against Leishmania.

D000241:Adenosine
D020816:Amino Acid Motifs
D000595:Amino Acid Sequence
D000906:Antibodies
D001666:Binding Sites, Antibody
D020134:Catalytic Domain
D003839:Deoxyadenosines
D006801:Humans
D018314:Leishmania infantum
D062105:Molecular Docking Simulation
D010446:Peptide Fragments
D011485:Protein Binding
D011487:Protein Conformation
D011683:Purine-Nucleoside Phosphorylase
D017422:Sequence Analysis, DNA
D017385:Sequence Homology
D055672:Static Electricity
D013379:Substrate Specificity
D013872:Thionucleosides
D014346:Trypanosoma brucei brucei

Leishmania
MTAP
Homology modeling
Antibody
Molecular docking


Cubical Shape Enhances the Interaction of Layer-by-Layer Polymeric Particles with Breast Cancer Cells.

Abstract: Blood-borne objects display a nonspherical shape with in-flow dimensions much larger than the vascular endothelial fenestrations, yet, at the diseased state, are able to traverse through these fenestrations owing to their elasticity. The role of physical parameters including shape and elasticity in the behavior of objects found in the tumor microenvironment needs to be understood to ultimately enhance chemotherapy and minimize its side effects. In this study, sphere- and cube-shaped biocompatible elastic microparticles (EM) made via layer-by-layer assembly of hydrogen-bonded tannic acid/poly(N-vinylpyrrolidone) (TA/PVPON) as hollow polymer shells and their rigid core-shell precursors (RM) are explored. In contrast to rigid five-bilayer (TA/PVPON) core shells, hollow elastic shells are unrecognized by J774A.1 macrophages, yet interact with endothelial and breast cancer cells. Internalization of cubical shells is fivefold more efficient by HMVEC (human microvascular endothelial cells) and sixfold and 2.5-fold more efficient by MDA-MB-231 and by SUM159 (breast cancer cells), respectively, compared to spherical shells. The interaction of cubical (TA/PVPON)5 shells with endothelial cells is similar under 10 s(-1) (characteristic of tumor vasculature) and 100 s(-1) shear rate (normal vasculature) while it is decreased at 100 s(-1) shear rate for the spherical shells. Our data suggest that cubical geometry promotes interaction of particles with breast cancer cells, while elasticity prevents engulfment by phagocytic cells in the tumor microenvironment.

Alexander|Jenolyn F|JF|
Kozlovskaya|Veronika|V|
Chen|Jun|J|
Kuncewicz|Thomas|T|
Kharlampieva|Eugenia|E|
Godin|Biana|B|

shape
particles
elasticity
tumor microenvironment
multilayer capsules


Cognition, comprehension and application of biostatistics in research by Indian postgraduate students in periodontics.

Abstract:
BACKGROUND
Biostatistics is an integral part of research protocols. In any field of inquiry or investigation, data obtained is subsequently classified, analyzed and tested for accuracy by statistical methods. Statistical analysis of collected data, thus, forms the basis for all evidence-based conclusions.

AIM
The aim of this study is to evaluate the cognition, comprehension and application of biostatistics in research among post graduate students in Periodontics, in India.

MATERIALS AND METHODS
A total of 391 post graduate students registered for a master's course in periodontics at various dental colleges across India were included in the survey. Data regarding the level of knowledge, understanding and its application in design and conduct of the research protocol was collected using a dichotomous questionnaire. A descriptive statistics was used for data analysis.

RESULTS
Nearly 79.2% students were aware of the importance of biostatistics in research, 55-65% were familiar with MS-EXCEL spreadsheet for graphical representation of data and with the statistical softwares available on the internet, 26.0% had biostatistics as mandatory subject in their curriculum, 9.5% tried to perform statistical analysis on their own while 3.0% were successful in performing statistical analysis of their studies on their own.

CONCLUSION
Biostatistics should play a central role in planning, conduct, interim analysis, final analysis and reporting of periodontal research especially by the postgraduate students. Indian postgraduate students in periodontics are aware of the importance of biostatistics in research but the level of understanding and application is still basic and needs to be addressed.

Swetha|Jonnalagadda Laxmi|JL|
Arpita|Ramisetti|R|
Srikanth|Chintalapani|C|
Nutalapati|Rajasekhar|R|

Cognition comprehension biostatistics periodontics questionnaire


Clinical characteristics of patients with persistent postural-perceptual dizziness.

Abstract:
INTRODUCTION
Persistent postural-perceptual dizziness is the dizziness that lasts for over three months with no clinical explanation for its persistence. The patient's motor response pattern presents changes and most patients manifest significant anxiety.

OBJECTIVE
To evaluate the clinical characteristics of patients with persistent postural and perceptual dizziness.

METHODS
statistical analysis of clinical aspects of patients with persistent postural-perceptual dizziness.

RESULTS
81 patients, average age: 50.06±12.16 years; female/male ratio: 5.7/1; main reasons for dizziness: visual stimuli (74%), body movements (52%), and sleep deprivation (38%). The most prevalent comorbidities were hypercholesterolemia (31%), migraine headaches (26%), carbohydrate metabolism disorders (22%) and cervical syndrome (21%). DHI, State-Trait Anxiety Inventory - Trait, Beck Depression Inventory, and Hospital Anxiety and Depression Scale questionnaires were statistically different (p<0.05) when compared to controls. 68% demonstrated clinical improvement after treatment with serotonin reuptake inhibitors.

CONCLUSION
Persistent postural-perceptual dizziness affects more women than men, with a high associated prevalence of metabolic disorders and migraine. Questionnaires help to identify the predisposition to persistent postural-perceptual dizziness. The prognosis is good with adequate treatment.

Bittar|Roseli Saraiva Moreira|RS|
Lins|Eliane Maria Dias von Söhsten|EM|

Dizziness Anxiety Comorbidity Depression Ansiedade Comorbidade Depressão Tontura


Aberrant circulating levels of purinergic signaling markers are associated with several key aspects of peripheral atherosclerosis and thrombosis.

Abstract:
RATIONALE
Purinergic signaling plays an important role in inflammation and vascular integrity, but little is known about purinergic mechanisms during the pathogenesis of atherosclerosis in humans.

OBJECTIVE
The objective of this study is to study markers of purinergic signaling in a cohort of patients with peripheral artery disease.

METHODS AND RESULTS
Plasma ATP and ADP levels and serum nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) and ecto-5'-nucleotidase/CD73 activities were measured in 226 patients with stable peripheral artery disease admitted for nonurgent invasive imaging and treatment. The major findings were that ATP, ADP, and CD73 values were higher in atherosclerotic patients than in controls without clinically evident peripheral artery disease (P<0.0001). Low CD39 activity was associated with disease progression (P=0.01). In multivariable linear regression models, high CD73 activity was associated with chronic hypoxia (P=0.001). Statin use was associated with lower ADP (P=0.041) and tended to associate with higher CD73 (P=0.054), while lower ATP was associated with the use of angiotensin receptor blockers (P=0.015).

CONCLUSIONS
Purinergic signaling plays an important role in peripheral artery disease progression. Elevated levels of circulating ATP and ADP are especially associated with atherosclerotic diseases of younger age and smoking. The antithrombotic and anti-inflammatory effects of statins may partly be explained by their ability to lower ADP. We suggest that the prothrombotic nature of smoking could be a cause of elevated ADP, and this may explain why cardiovascular patients who smoke benefit from platelet P2Y12 receptor antagonists more than their nonsmoking peers.

Jalkanen|Juho|J|
Yegutkin|Gennady G|GG|
Hollmén|Maija|M|
Aalto|Kristiina|K|
Kiviniemi|Tuomas|T|
Salomaa|Veikko|V|
Jalkanen|Sirpa|S|
Hakovirta|Harri|H|

D058921:Purinergic P2Y Receptor Antagonists

atherosclerosis
thrombosis
smoking
adenosine
adenosine diphosphate
adenosine triphosphate
receptors, purinergic P1


Regional Anaesthetic Techniques and Their Implications During the COVID Pandemic.

Abstract: The current pandemic has highlighted the need to protect both patients and medical staff. The increased use of regional anaesthesia as a primary anaesthetic modality for operations and other invasive procedures has limited the number of aerosol-generating procedures performed during general anaesthesia. Its use is further characterized by decreases in postoperative pain and length of hospitalization. This article provides an overview of regional anaesthetic techniques (peripheral nerve locks, epidural and spinal anaesthesia) and their uses during the COVID pandemic.

Mehmood|Raafay|R|0000-0002-9213-2291
McGuire|Ainsley John|AJ|
Mansoor|Zainab|Z|
Fink|Adam Benjamin|AB|
Atanasov|Gabriel|G|

Regional anaesthesia
Spinal anaesthesia
Epidural anaesthesia
Peripheral nerve block


Selecting efficient methodologies for estimation of As and Hg availability in a brownfield.

Abstract: The determination of soil metal(loid) availability presents controversy and there is no consensus or uniformity on used analytical methods. In this study nine single extraction methods (H2O, CaCl2, NaNO3, NH4NO3, DTPA, EDTA, HCl, LMWOA, TCLP) and four sequential extraction procedures (Tessier, BCR, Wenzel and Fernández-Martínez) have been compared to estimate the availability of As and Hg in two soils from a highly polluted brownfield, especially with As. The metal(loid) concentrations were also determined in three native plant species (Lotus corniculatus, Betula celtiberica and Dactylis glomerata) collected in the habitat under study. Each single extractant showed a particular capacity of As/Hg extraction because they do not extract the same forms of each element. The availability of As and Hg depended on the element characteristics, soil properties, type of extractant and degree of pollution, thus the use of a single extraction procedure provides limited information of metal(loid) availability and to reach general conclusions is difficult. Regarding the sequential extractions, each procedure showed a specific pattern for As and Hg regardless of the soil. Thus, the choice of one or other method depends on the environmental conditions, metal(loid) and soil properties. In risk assessment studies it would be recommendable to select one of the more aggressive extractants, so as not to underestimate the environmental risk. In this regard, the sequential extraction procedures render more detailed information about metal(loid) potential availability in relation to soil properties. The analysis of native plant species showed higher metal(loid) concentrations in roots than in aerial parts and differences were observed depending on the metal(loid) and the species. In general, plants showed a higher BCFs for Hg than As even though the total and available As concentrations were higher than those found for Hg, which highlights the influence of plant species on the metal(loid) uptake.

Gil-Díaz|M|M|
Luchsinger-Heitmann|A|A|
García-Gonzalo|P|P|
Alonso|J|J|
Lobo|M C|MC|

Single extraction methods
Sequential extraction procedures
Arsenic
Mercury
Polluted soil


Serum Helicobacter pylori CagA antibody titer as a useful marker for advanced inflammation in the stomach in Japan.

Abstract:
BACKGROUND AND AIM
Subjects infected with Helicobacter pylori containing cagA do not always induce serum CagA antibody. Our previous meta-analysis showed that serum CagA seropositivity was associated with gastric cancer even in East Asian countries. However, it remains unclear why serum CagA-positive status is associated with gastric cancer. In this study, we aimed to examine the relationship between anti-CagA antibody titer and the levels of pepsinogen (PG), and histological score.

METHODS
Eighty-eight H. pylori-positive Japanese patients with gastritis were included. Serum CagA antibody titer, PG I, and PG II were evaluated by ELISA. Histological scores were evaluated according to Update Sydney System. CagA expression was examined by immunoblot.

RESULTS
Seroprevalence of CagA antibody was found in 75.0%. Interestingly, serum CagA antibody titer was significantly correlated with PG I and PG II levels (P = 0.003 and 0.004, respectively). Serum CagA antibody titer was also significantly correlated with mucosal inflammation in the corpus (P = 0.04). On the other hand, bacterial density was not related with CagA antibody titer. CagA expression level of the strains was irrespective of the status of PG and serum CagA antibody.

CONCLUSIONS
Subjects with higher serum CagA antibody titer can be considered as high-risk population for the development of gastric cancer from the point of strong gastric inflammatory response even in Japan. Host recognition rather than bacterial colonization might be associated with the difference of serum CagA antibody titer.

Shiota|Seiji|S| Murakami|Kazunari|K| Okimoto|Tadayoshi|T| Kodama|Masaaki|M| Yamaoka|Yoshio|Y|

Helicobacter pylori
CagA
pepsinogen
serum antibody


Alkaline conditions in hydrophilic interaction liquid chromatography for intracellular metabolite quantification using tandem mass spectrometry.

Abstract: Modeling of metabolic networks as part of systems metabolic engineering requires reliable quantitative experimental data of intracellular concentrations. The hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry (HILIC-ESI-MS/MS) method was used for quantitative profiling of more than 50 hydrophilic key metabolites of cellular metabolism. Without prior derivatization, sugar phosphates, organic acids, nucleotides, and amino acids were measured under alkaline and acidic mobile phase conditions with pre-optimized multiple reaction monitoring (MRM) transitions. Irrespective of the polarity mode of the acquisition method used, alkaline conditions achieved the best quantification limits and linear dynamic ranges. Fully 90% of the analyzed metabolites presented detection limits better than 0.5pmol (on column), and 70% presented 1.5-fold higher signal intensities under alkaline mobile phase conditions. The quality of the method was further demonstrated by absolute quantification of selected metabolites in intracellular extracts of Escherichia coli. In addition, quantification bias caused by matrix effects was investigated by comparison of calibration strategies: standard-based external calibration, isotope dilution, and standard addition with internal standards. Here, we recommend the use of alkaline mobile phase with polymer-based zwitterionic hydrophilic interaction chromatography (ZIC-pHILIC) as the most sensitive scenario for absolute quantification for a broad range of metabolites.

D002853:Chromatography, Liquid
D048168:Escherichia coli K12
D006863:Hydrogen-Ion Concentration
D053719:Tandem Mass Spectrometry


Crystal structure of rac-(3aR,4S,5aR,6S,9R,10aS,10bR)-3a,5a,9-tri-methyl-tetra-deca-hydro-6,9-ep-oxy-cyclo-hepta-[e]inden-4-ol monohydrate.

Abstract: The title hydrate, C17H28O2·H2O, was synthesized in order to determine the relative configuration of the tetra-cyclic framework. The fused 5,6,7-tricarbocyclic core exhibits an entire cis-annulation, featuring a 1,4-cis-relation of the angular methyl groups in the six-membered ring. The oxa bridge of the ep-oxy-cyclo-heptane moiety is oriented towards the concave face of the boat-shaped mol-ecule, whereas the angular methyl groups are directed towards the convex face. The asymmetric unit of the crystal contains two nearly identical formula units, which are related via a pseudo-centre of symmetry. The structure could be solved in the space groups I-4 and I41/a. The refinement in the acentric space group, however, gave significantly better results and these are used in this paper. O-H⋯O hydrogen bonds are observed between the organic mol-ecules, between the organic mol-ecules and the water mol-ecules, and between the water mol-ecules, forming a chain along the c-axis direction.

Schäfer|Andreas|A| Golz|Christopher|C| Preut|Hans|H| Strohmann|Carsten|C| Hiersemann|Martin|M|

crystal structure
hydrate
hydrogen bonding
diterpenoid synthesis


The Validated Embryonic Stem Cell Test with Murine Embryonic Stem Cells.

Abstract: Birth defects are the leading cause of infant mortality in the USA, yet the causes of most of these conditions are unknown. While a combination of genetic and environmental factors are suspected in most cases, little information exists about the health risks that prenatal exposure to many common chemicals poses for the fetus. Thus, development and refinement of procedures that can accurately predict embryotoxicity of compounds is important for curtailing the number of infants born with birth defects. The embryonic stem cell test (EST) is a procedure that utilizes comparison of cytotoxicity in embryonic and adult cells and inhibition of differentiation to predict embryotoxicity of compounds tested. Because of its use of existing cell lines, the EST dramatically reduces the need for animal test subjects in toxicity testing. In addition, because of its use of inhibition of differentiation as an endpoint, the EST is extremely versatile in the range of complications it can test for. In this chapter, procedures for use of the validated embryonic stem cell test with the traditional cardiomyocyte differentiation endpoint are explained. The protocol includes discussion of routine stem cell culture, the cardiomyocyte differentiation procedure, and methods for utilization of molecular endpoints for assessing embryotoxicity of compounds.

Walker|Lauren M|LM|
McClelland-Descalzo|Darcie L V|DLV|
Zur Nieden|Nicole I|NI|

Embryonic stem cell test
Embryotoxicity
Cardiomyocyte
Contraction counting
Developmental toxicity
Quantitative gene expression analysis


Condom Use at First Vaginal Intercourse Among Adolescents and Young Adults in the United States, 2002-2017.

Abstract:
PURPOSE
The purpose of this study was to describe trends in vaginal intercourse (VI) and condom use during first VI from 2002 to 2017 among never-married 15- to 24-year-olds in the United States.

METHODS
Data come from the National Survey of Family Growth. We used logistic regression and Stata's margins package to estimate the percentage reporting VI and condom use at first VI and to conduct statistical comparisons across time.

RESULTS
VI was stable for 20- to 24-year-old men, but their condom use increased after 2002. For 15- to 19-year-old men, VI declined after 2011-2015 but condom use increased (83%). Among women, the overall percentage reporting VI and partner's condom use was stable, despite a significant increase in condom use among 15- to 19-year-olds between 2006-2010 and 2011-2015 (69%-75%).

CONCLUSIONS
Condom use at first intercourse increased among young men, but a similar pattern was not observed for young women. Understanding why is crucial to the formulation of strategies to increase condom uptake.

Holway|Giuseppina Valle|GV|
Brewster|Karin L|KL|
Tillman|Kathryn Harker|KH|

Condom use
Intercourse
Adolescents
Young adults
Contraceptive use
NSFG


Impact of Candida auris Infection in a Neutropenic Murine Model.

Abstract: Candida auris has become a global public health threat due to its multidrug resistance and persistence. Currently, there are limited murine models to study C. auris infection. Those models use a combination of cyclophosphamide and cortisone acetate, suppressing both innate and adaptive immunity. Here, we compare C. auris infection in two neutrophil-depleted murine models in which innate immunity is targeted using the monoclonal antibodies 1A8 and RB6-8C5.

Torres|Steven R|SR|
Pichowicz|Amber|A|
Torres-Velez|Fernando|F|
Song|Renjie|R|
Singh|Navjot|N|
Lasek-Nesselquist|Erica|E|
De Jesus|Magdia|M|0000-0002-0713-8462

Candida auris
Ly6C
Ly6G
microbiome
neutrophil depletion
torticollis


Lipid Signaling in Tumorigenesis.

Abstract: Lipids are important cellular building blocks and components of signaling cascades. Deregulation of lipid metabolism or signaling is frequently linked to a variety of human diseases such as diabetes, cardiovascular diseases, and cancer. It is widely believed that lipid molecules or their metabolic products are involved in tumorigenic inflammation and thus, lipids are implicated as significant contributors or even primary triggers of tumorigenesis. Lipids are believed to directly or indirectly activate growth promoting signals such as those involving LPA, insulin, IGF-1 and EGF to promote cancer cell growth. Cellular levels of certain lipids, including sphingosine-1-phosphate and ceramide, maintain a delicate balance between cell death and survival and alterations in their levels lead to unfavorable consequences including tumorigenesis. This article provides an overview of current knowledge that implicates lipids in tumorigenesis and explores the potential mechanisms that support a positive link between obesity and cancer.

Lipid metabolism
Cancer
Sphingosine-1-phosphate
Ceramide
Obesity
Monoglyceride lipase


Caregiver-Teacher Concordance of Challenging Behaviors in Children with Autism Spectrum Disorder Served in Community Mental Health Settings.

Abstract: Children with autism spectrum disorder (ASD) exhibit high rates of challenging behaviors that impair functioning and represent the primary presenting problem in mental health (MH) services. Obtaining symptom reports from multiple informants is critical for treatment planning. This study evaluated caregiver-teacher concordance of ratings of the intensity of challenging behaviors in children with ASD receiving MH services, and identified child clinical factors associated with concordance. This sample included 141 children (M = 9.07 years), their caregivers, and teachers. Caregiver-teacher concordance of challenging behaviors was low and impacted by the degree and type of child psychiatric comorbidity. Findings support need for increased attention to the range of psychiatric problems children with ASD present to tailor treatment recommendations and service delivery.

Caregiver-teacher concordance
Challenging behaviors
Autism spectrum disorder
Psychiatric comorbidity
School-age children


Targeting the p53 Pathway in CLL: State of the Art and Future Perspectives.

Abstract: The p53 pathway is a desirable therapeutic target, owing to its critical role in the maintenance of genome integrity. This is exemplified in chronic lymphocytic leukemia (CLL), one of the most common adult hematologic malignancies, in which functional loss of p53 arising from genomic aberrations are frequently associated with clonal evolution, disease progression, and therapeutic resistance, even in the contemporary era of CLL targeted therapy and immunotherapy. Targeting the 'undruggable' p53 pathway therefore arguably represents the holy grail of cancer research. In recent years, several strategies have been proposed to exploit p53 pathway defects for cancer treatment. Such strategies include upregulating wild-type p53, restoring tumor suppressive function in mutant p53, inducing synthetic lethality by targeting collateral genome maintenance pathways, and harnessing the immunogenicity of p53 pathway aberrations. In this review, we will examine the biological and clinical implications of p53 pathway defects, as well as our progress towards development of therapeutic approaches targeting the p53 pathway, specifically within the context of CLL. We will appraise the opportunities and pitfalls associated with these therapeutic strategies, and evaluate their place amongst the array of new biological therapies for CLL.

Kwok|Marwan|M|0000-0002-3985-5079 Agathanggelou|Angelo|A| Davies|Nicholas|N| Stankovic|Tatjana|T|

p53
synthetic lethality
ATM
ATR
CDK
DNA-PK
MDM2
PARP
USP7
immunity


Enhancing resistance of Sesamum indicum against Alternaria sesami through Bacillus velezensis AR1.

Abstract:
BACKGROUND
Considerable yield loss and poor quality of sesame seed are attributed to fungal pathogens including Alternaria sesami. The use of agrochemicals and few biocontrol agents have been employed to at least minimize the problem. Thus, this research work was initiated to mitigate the impact of the disease using Bacillus velezensis AR1. A total of four treatments, A. sesami alone, sole fungicide, AR1, and alternate application of AR1 with dithianon (fungicide) were applied with six replications.

RESULTS
The results indicate that the sole and alternate application of AR1 with fungicide reduced disease severity to less than 10%. Plant physiological traits also improved due to the plant growth promoting AR1. Induced plant defense-related biochemicals, i.e. total phenolic and flavonoid contents, were maximum in the plant subjected to AR1 and alternate application with a fungicide. In addition, the concentration of leaf amino acid proline was doubled due to AR1 compared to the control. The concentration of the plant growth-regulating hormones gibberellic acid and indole acetic acid (IAA), as well as leaf chlorophyll, total nitrogen and phosphorus contents were also significantly increased by 203.86, 7.79, 0.31 mg gFW-1 , 0.15 and 0.13%, respectively, due to the treatments. Furthermore, postharvest soil chitinase, cellulase and 1,3-β-glucanase activity results indicated the biological control and rapid soil colonization trends of AR1.

CONCLUSION
From these in vitro and in vivo experiment findings, B. velezensis AR1 can be recommended for biological control of plant fungal diseases for environmentally safe and quality crop production. © 2020 Society of Chemical Industry.

biological control
plant disease resistance
plant hormones
soil enzymes


Quantitative Sensory Testing in Patients with Multisomatoform Disorder with Chronic Pain as the Leading Bodily Symptom-a Matched Case-Control Study.

Abstract:
OBJECTIVE
Chronic pain is a debilitating condition of multifactorial origin, often without physical findings to explain the presenting symptoms. Of the possible etiologies of persisting painful symptoms, somatoform disorders and functional somatic syndromes (FSS) are among the most challenging, with a prevalence of 8-20%. Many different somatoform disorders and FSS have overlapping symptoms, with pain being the most prevalent one. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We hypothesized that the concept of MSD will be reflected in a distinct sensory profile of patients compared with healthy controls and possibly provide insight into the type and pathophysiology of the pain commonly experienced by patients.

DESIGN
We performed comprehensive quantitative sensory testing (QST) in 151 patients and 149 matched controls.

RESULTS
There were significant differences in the sensory profiles of patients compared with controls. Patients with MSD showed a combination of tactile and thermal hypesthesia combined with mechanical and cold hyperalgesia. This was true for measurements at test and control sites, with the exception of vibration detection threshold and mechanical pain threshold. Among the observed changes, a marked sensory loss of function, as evidenced by an increase in cold detection threshold, and a marked gain of function, as evidenced by a decrease of pressure pain threshold, were most notable. There was no evidence of concurrent medication influencing QST results.

CONCLUSIONS
The observed somatosensory profile of patients with MSD resembles that of patients suffering from neuropathic pain with evidence of central sensitization.

Achenbach|Johannes|J| Tran|Anh-Thu|AT| Jaeger|Burkhardt|B| Kapitza|Karl|K| Bernateck|Michael|M| Karst|Matthias|M|

Quantitative sensory testing
multisomatoform disorder
functional somatic syndrome
hyperalgesia
small fibre neuropathy


Immunochromatography test for rapid diagnosis of Mycoplasma pneumoniae infection.

Abstract: The sensitivity and specificity of a new rapid Mycoplasma pneumoniae antigen immunochromatography (IC) test, DK-MP-001, were determined using particle agglutination (PA) antibody response and loop-mediated isothermal amplification (LAMP) gene detection as the gold standard. Of 165 patients, 59 were diagnosed with M. pneumoniae infection based on a ≥fourfold rise of serum PA antibody during the course of the illness. Of the first visit swabs, 60 were positive for M. pneumoniae on LAMP, and 49 were positive for M. pneumoniae antigen on IC test. Compared with PA antibody and LAMP, the sensitivity/specificity of the IC test were 81.4% (48/59) and 99.1% (105/106); and 81.7% (49/60) and 100% (105/105), respectively. IC test detected antigen in pharyngeal swabs more sensitively than in nasal swabs for the same subjects (P < 0.05). The IC test performs well enough to be used with pharyngeal swabs at the first examination.

immunochromatography
rapid diagnosis
Mycoplasma pneumoniae
Mycoplasma pneumoniae pneumonia


Crystal structure of Ralstonia eutropha polyhydroxyalkanoate synthase C-terminal domain and reaction mechanisms.

Abstract: Polyhydroxyalkanoates (PHAs) are natural polyesters synthesized by numerous microorganisms as energy and reducing power storage materials, and have attracted much attention as substitutes for petroleum-based plastics. Here, we report the first crystal structure of Ralstonia eutropha PHA synthase at 1.8 Å resolution and structure-based mechanisms for PHA polymerization. RePhaC1 contains two distinct domains, the N-terminal (RePhaC1ND ) and C-terminal domains (RePhaC1CD ), and exists as a dimer. RePhaC1CD catalyzes polymerization via non-processive ping-pong mechanism using a Cys-His-Asp catalytic triad. Molecular docking simulation of 3-hydroxybutyryl-CoA to the active site of RePhaC1CD reveals residues involved in the formation of 3-hydroxybutyryl-CoA binding pocket and substrate binding tunnel. Comparative analysis with other polymerases elucidates how different classes of PHA synthases show different substrate specificities. Furthermore, we attempted structure-based protein engineering and developed a RePhaC1 mutant with enhanced PHA synthase activity.

Kim|Jieun|J|
Kim|Yeo-Jin|YJ|
Choi|So Young|SY|
Lee|Sang Yup|SY|
Kim|Kyung-Jin|KJ|

D000214:Acyl Coenzyme A
D000217:Acyltransferases
D020134:Catalytic Domain
D002942:Circular Dichroism
D018360:Crystallography, X-Ray
D020118:Cupriavidus necator
D008958:Models, Molecular
D062105:Molecular Docking Simulation
D016296:Mutagenesis
D000072417:Protein Domains
D013050:Spectrometry, Fluorescence
D013379:Substrate Specificity

Crystal structure
Ralstonia eutropha
Polyhydroxyalkanoates
PHA synthase
Enzyme mechanism


Time determines the neural circuit underlying associative fear learning.

Abstract: Ultimately associative learning is a function of the temporal features and relationships between experienced stimuli. Nevertheless how time affects the neural circuit underlying this form of learning remains largely unknown. To address this issue, we used single-trial auditory trace fear conditioning and varied the length of the interval between tone and foot-shock. Through temporary inactivation of the amygdala, medial prefrontal-cortex (mPFC), and dorsal-hippocampus in rats, we tested the hypothesis that different temporal intervals between the tone and the shock influence the neuronal structures necessary for learning. With this study we provide the first experimental evidence showing that temporarily inactivating the amygdala before training impairs auditory fear learning when there is a temporal gap between the tone and the shock. Moreover, imposing a short interval (5 s) between the two stimuli also relies on the mPFC, while learning the association across a longer interval (40 s) becomes additionally dependent on a third structure, the dorsal-hippocampus. Thus, our results suggest that increasing the interval length between tone and shock leads to the involvement of an increasing number of brain areas in order for the association between the two stimuli to be acquired normally. These findings demonstrate that the temporal relationship between events is a key factor in determining the neuronal mechanisms underlying associative fear learning.

Guimarãis|Marta|M|
Gregório|Ana|A|
Cruz|Andreia|A|
Guyon|Nicolas|N|
Moita|Marta A|MA|

single-trial
trace fear conditioning
amygdala
mPFC
hippocampus
muscimol