bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y6 receptor in mice
Authors: Milde Stefan , van Tartwijk Francesca W. , Vilalta Anna , Hornik Tamara C. , Dundee Jacob M. , Puigdellívol Mar , Brown Guy C.
Published: October 2021

Inflammation may contribute to multiple brain pathologies. One cause of inflammation is lipopolysaccharide/endotoxin (LPS), the levels of which are elevated in blood and/or brain during bacterial infections, gut dysfunction and neurodegenerative diseases, such as Parkinson’s disease. How inflammation causes neuronal loss is unclear, but one potential mechanism is microglial phagocytosis of neurons, which is dependent on the microglial P2Y6receptor. We investigated here whether the P2Y6receptor was required for inflammatory neuronal loss. Intraperitoneal injection of LPS on 4 successive days resulted in specific loss of dopaminergic neurons (measured as cells staining with tyrosine hydroxylase or NeuN) in thesubstantia nigraof wild-type mice, but no neuronal loss in cortex or hippocampus. This supports the hypothesis that neuronal loss in Parkinson’s disease may be driven by peripheral LPS. By contrast, there was no LPS-induced neuronal loss in P2Y6receptor knockout mice. In vitro, LPS-induced microglial phagocytosis of cells was prevented by inhibition of the P2Y6receptor, and LPS-induced neuronal loss was reduced in mixed glial–neuronal cultures from P2Y6receptor knockout mice. This supports the hypothesis that microglial phagocytosis contributes to inflammatory neuronal loss, and can be prevented by blocking the P2Y6receptor, suggesting that P2Y6receptor antagonists might be used to prevent inflammatory neuronal loss in Parkinson’s disease and other brain pathologies involving inflammatory neuronal loss.
Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial
Authors: Alfadhel Majid , Nashabat Marwan , Saleh Mohammed , Elamin Mohammed , Alfares Ahmed , Al Othaim Ali , Umair Muhammad , Ahmed Hind , Ababneh Faroug , Al Mutairi Fuad , Eyaid Wafaa , Alswaid Abdulrahman , Alohali Lina , Faqeih Eissa , Almannai Mohammed , Aljeraisy Majed , Albdah Bayan , Hussein Mohamed A. , Rahbeeni Zuhair , Alasmari Ali
Published: October 2021

Background

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias.

Methods

The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay.

Results

Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels.

Conclusion

Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.
Clipper: p-value-free FDR control on high-throughput data from two conditions
Authors: Ge Xinzhou , Chen Yiling Elaine , Song Dongyuan , McDermott MeiLu , Woyshner Kyla , Manousopoulou Antigoni , Wang Ning , Li Wei , Wang Leo D. , Li Jingyi Jessica
Published: October 2021

High-throughput biological data analysis commonly involves identifying features such as genes, genomic regions, and proteins, whose values differ between two conditions, from numerous features measured simultaneously. The most widely used criterion to ensure the analysis reliability is the false discovery rate (FDR), which is primarily controlled based onp-values. However, obtaining validp-values relies on either reasonable assumptions of data distribution or large numbers of replicates under both conditions. Clipper is a general statistical framework for FDR control without relying onp-values or specific data distributions. Clipper outperforms existing methods for a broad range of applications in high-throughput data analysis.
Catastrophic adult-onset Still’s disease as a distinct life-threatening clinical subset: case–control study with dimension reduction analysis
Authors: Wahbi Anaïs , Tessoulin Benoît , Bretonnière Cédric , Boileau Julien , Carpentier Dorothée , Decaux Olivier , Fardet Laurence , Geri Guillaume , Godmer Pascal , Goujard Cécile , Maisonneuve Hervé , Mari Arnaud , Pouchot Jacques , Ziza Jean-Marc , Georgin-Lavialle Sophie , Hamidou Mohamed , Néel Antoine
Published: October 2021

Objectives

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder. Diagnosing AOSD can be challenging, as disease presentation and clinical course are highly heterogeneous. For unclear reasons, a few patients develop life-threatening complications. Our objective was to determine whether these cases resulted from therapeutic delay or could represent a peculiar AOSD subset.

Methods

We conducted a multicentre retrospective study of 20 AOSD patients with organ failure requiring intensive care unit admission and 41 control AOSD patients without organ failure. Clinico-biological data at hospital admission were explored using supervised analyses and unsupervised dimension reduction analysis (factor analysis of mixed data, FAMD).

Results

Disease duration before admission was shorter in patients with life-threatening AOSD (median, 10 vs 20 days, p = 0.007). Disease duration before AOSD therapy initiation also tended to be shorter (median, 24 vs 32 days, p = 0.068). Despite this shorter disease duration, FAMD, hierarchical clustering and univariate analyses showed that these patients exhibited distinctive characteristics at first presentation, including younger age; higher frequency of splenomegaly, liver, cardiac and/or lung involvement; less frequent arthralgia; and higher ferritin level. In multivariate analysis, 3 parameters predicted life-threatening complications: lack of arthralgia, younger age and shorter time between fever onset and hospitalisation.

Conclusion

This study suggests that life-threatening complications of AOSD occur very early, in a peculiar subset, which we propose to name catastrophic adult-onset Still’s disease (CAOSD). Its exact burden may be underestimated and remains to be clarified through large multicentre cohorts. Further studies are needed to identify red flags and define the optimal therapeutic strategy.
Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services—part 1 of 6
Authors: Altomare Daniele , Molinuevo José Luis , Ritchie Craig , Ribaldi Federica , Carrera Emmanuel , Dubois Bruno , Jessen Frank , McWhirter Laura , Scheltens Philip , van der Flier Wiesje M. , Vellas Bruno , Démonet Jean-François , Frisoni Giovanni B. ,   on behalf of the European Task Force for Brain Health Services, Abramowicz Marc , Altomare Daniele , Barkhof Frederik , Berthier Marcelo , Bieler Melanie , Blennow Kaj , Brayne Carol , Brioschi Andrea , Carrera Emmanuel , Chételat Gael , Csajka Chantal , Demonet Jean-François , Dodich Alessandra , Dubois Bruno , Frisoni Giovanni B. , Garibotto Valentina , Georges Jean , Hurst Samia , Jessen Frank , Kivipelto Miia , Llewellyn David , McWhirter Laura , Milne Richard , Minguillón Carolina , Miniussi Carlo , Molinuevo José Luis , Nilsson Peter M. , Ranson Janice , Ribaldi Federica , Ritchie Craig , Scheltens Philip , Solomon Alina , van Der Flier Wiesje , van Duijn Cornelia , Vellas Bruno , Visser Leonie
Published: October 2021

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy.

An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population.

We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.
Protocols for cognitive enhancement. A user manual for Brain Health Services—part 5 of 6
Authors: Brioschi Guevara Andrea , Bieler Melanie , Altomare Daniele , Berthier Marcelo , Csajka Chantal , Dautricourt Sophie , Démonet Jean-François , Dodich Alessandra , Frisoni Giovanni B. , Miniussi Carlo , Molinuevo José Luis , Ribaldi Federica , Scheltens Philip , Chételat Gael
Published: October 2021

Cognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.

We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.

CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.

We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs (“smart drugs”, acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.

Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.
X-linked SCID with a rare mutation
Authors: Mahdavi Fatemeh Sadat , Keramatipour Mohammad , Ansari Sarina , Sharafian Samin , Karamzade Arezou , Tavakol Marzieh
Published: October 2021

Background

Severe combined immunodeficiency (SCID) is a group of relatively rare primary immunodeficiency disorders (PIDs), characterized by disturbed development of T cells and B cells, caused by several genetic mutations that bring on different clinical presentations. SCID may be inherited as an autosomal recessive or an X-linked genetic trait.

Case presentation

A 6-year-old male presented with a history of food allergy, productive coughs, and recurrent purulent rhinitis, poor weight gain and hypothyroidism. The total count of CD4+ T lymphocytes, along with their naïve and central memory subpopulations, as well as central memory CD8+ T cells were decreased in flow cytometry. A nucleotide substitution in exon one of interleukin 2 receptor gamma chain (IL-2RG) gene (c.115 G>A, p.D39N, ChrX: 70,331,275) was reported, based on which the diagnosis of X-liked SCID was confirmed. Antiviral and antibiotic prophylaxis, along with monthly IVIG (intravenous immunoglobulin) was started and the patient was subsequently referred for hematopoietic stem cell transplantation.

Conclusion

PIDs should be considered as the differential diagnosis in any patient with unexplained and bizarre symptoms associated with recurrent infections, allergic and autoimmune manifestations. Clinicians should also bear X-SCID in mind in case of approach to any patient with poor weight gain, unusual allergic or endocrine manifestations, even in the case of a normal or increased level of serum immunoglobulins or T and B cells numbers.
Median 10 years follow-up of patients with covert Cushing’s syndrome: a case series
Authors: Najafipour Farzad , Bahrami Amir , Niafar Mitra , Houshyar Jalil , Halimi Monireh , Sadra Vahideh
Published: October 2021

Background

Ectopic adrenocorticotropic hormone secretion syndrome occurs in 10% of all patients with adrenocorticotropic-hormone-dependent hypercortisolism. It is usually associated with overt malignancies or with occult and indolent tumors. This study aims to confirm the source of ectopic adrenocorticotropic hormone in four patients with ectopic Cushing’s syndrome over time.

Case presentation

A 38-year-old Iranian man with Cushing’s syndrome underwent bilateral adrenalectomy since the source of ectopic adrenocorticotropic hormone secretion was not localized and pituitary imaging was normal. A whole-body scan revealed a right-lung tumoral mass with mediastinal lymph node metastasis. The mass was assumed a lung carcinoid tumor with mediastinal adenopathy. Right-lung mid-zone lobectomy and mediastinal lymphadenectomy were done. In a 47-year-old Iranian man with Cushing’s syndrome, whole-body computed tomography scan revealed a pulmonary nodule in the posterior segment of the left lower lobe of the lung. The third case was a 25-year-old Iranian man who presented with symptoms and signs of Cushing’s syndrome. Pituitary magnetic resonance imaging revealed a microadenoma 5 × 9 mm. Whole-body scan showed abnormal focal somatostatin receptors analog avid lesion in the posterior aspect of inferior third of right lung, highly suggestive of ectopic adrenocorticotropic-hormone-producing tumor. The last case was a 43-year-old Iranian woman with Marfan syndrome with a history of mitral and aortic valve replacement and chronic dissection of the aorta, who presented with symptoms and signs of Cushing’s syndrome. She underwent bilateral adrenalectomy 1 year later owing to failure to locate ectopic adrenocorticotropic hormone syndrome. Whole-body scan showed abnormally increased radiotracer uptake in the midline of the skull base and posterior aspect of the middle zone of left hemithorax and bed of left lobe of thyroid.

Conclusion

The clinical spectrum of ectopic adrenocorticotropic hormone secretion syndrome is wide, and distinguishing Cushing’s disease from ectopic adrenocorticotropic hormone secretion syndrome is difficult. Initial failure to identify a tumor is common. Pulmonary carcinoid or occult source of ectopic adrenocorticotropic hormone secretion syndrome is usually the cause. In occult cases of ectopic adrenocorticotropic hormone in which the tumor cannot be localized, serial follow-up with serial computed tomography, magnetic resonance imaging, or scintigraphy is recommended for several years until the tumor can be localized and treated.
The generalized projection methods in countably normed spaces
Authors: Tawfeek Sarah , Faried Nashat , El-Sharkawy H. A.
Published: October 2021

Let E be a Banach space with dual space $E^{*}$

E
∗

, and let K be a nonempty, closed, and convex subset of E. We generalize the concept of generalized projection operator “$\Pi _{K}: E \rightarrow K$

Π
K

:
E
→
K
” from uniformly convex uniformly smooth Banach spaces to uniformly convex uniformly smooth countably normed spaces and study its properties. We show the relation between J-orthogonality and generalized projection operator $\Pi _{K}$

Π
K

and give examples to clarify this relation. We introduce a comparison between the metric projection operator $P_{K}$

P
K

and the generalized projection operator $\Pi _{K}$

Π
K

in uniformly convex uniformly smooth complete countably normed spaces, and we give an example explaining how to evaluate the metric projection $P_{K}$

P
K

and the generalized projection $\Pi _{K}$

Π
K

in some cases of countably normed spaces, and this example illustrates that the generalized projection operator $\Pi _{K}$

Π
K

in general is a set-valued mapping. Also we generalize the generalized projection operator “$\pi _{K}: E^{*} \rightarrow K$

π
K

:

E
∗

→
K
” from reflexive Banach spaces to uniformly convex uniformly smooth countably normed spaces and study its properties in these spaces.
The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review
Authors: Frost Madeline C. , Lampert Hannah , Tsui Judith I. , Iles-Shih Matthew D. , Williams Emily C.
Published: October 2021

Background

Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD.

Methods

We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes.

Results

Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples.

Conclusions

Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.
Rate of malignancy for thyroid nodules with AUS/FLUS cytopathology in a tertiary care center – a retrospective cohort study
Authors: Hathi Kalpesh , Rahmeh Tarek , Munro Vicki , Northrup Victoria , Sherazi Ali , Chin Christopher J.
Published: October 2021

Background

Thyroid nodules are stratified through fine-needle aspiration (FNA) and are often categorized using The Bethesda System for Reporting Thyroid Cytopathology, which estimates the risk of malignancy for six cytopathological categories. The atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) categories have varying malignancy rates reported in the literature which can range from 6 to 72.9%. Due to this heterogeneity, we assessed the malignancy rate and effectiveness of repeat FNA (rFNA) for AUS/FLUS thyroid cytopathology at our institution.

Methods

Electronic health records of patients with AUS/FLUS thyroid cytopathology on FNA at our center since the implementation of the Bethesda System on May 1, 2014–December 31, 2019 were retrospectively reviewed. Patient demographics, treatment pathway, and pathology results were collected. The treatment pathway of the nodules, the rFNA results, and the malignant histopathology results were reported. Malignancy rates were calculated as an upper and lower limit estimate.

Results

This study described 182 AUS/FLUS thyroid nodules from 177 patients. In total, 24 thyroid nodules were deemed malignant upon histopathology, yielding a final malignancy rate of 13.2–25.3%. All of the malignancies were variants of papillary thyroid carcinoma. The malignancy rate of the nodules which underwent resection without rFNA (21.5%) was lower than the malignancy rate of the nodules which underwent resection after rFNA (43.8%). 45.5% of the rFNA results were re-classified into more definitive categories.

Conclusion

The malignancy rate of AUS/FLUS thyroid cytopathology at our center is in line with the risk of malignancy stated by the 2017 Bethesda System. However, our malignancy rate is lower than some other Canadian centers and approximately half of our rFNAs were re-classified, highlighting the importance of establishing center-specific malignancy and rFNA re-classification rates to guide treatment decisions.
A survey of prevalence and phenotypic and genotypic assessment of antibiotic resistance in Staphylococcus aureus bacteria isolated from ready-to-eat food samples collected from Tehran Province, Iran
Authors: Mesbah Arash , Mashak Zohreh , Abdolmaleki Zohreh
Published: October 2021

Background

ResistantStaphylococcus aureus(S. aureus) bacteria are considered among the major causes of foodborne diseases. This survey aims to assess genotypic and phenotypic profiles of antibiotic resistance inS. aureusbacteria isolated from ready-to-eat food samples.

Methods

According to the previously reported prevalence ofS. aureusin ready-to-eat food samples, a total of 415 ready-to-eat food samples were collected from Tehran province, Iran.S. aureusbacteria were identified using culture and biochemical tests. Besides, the phenotypic antibiotic resistance profile was determined by disk diffusion. In addition, the genotypic pattern of antibiotic resistance was determined using the PCR.

Results

A total of 64 out of 415 (15.42%) ready-to-eat food samples were contaminated withS. aureus. Grilled mushrooms and salad olivieh harbored the highest contamination rate of (30%), while salami samples harbored the lowest contamination rate of 3.33%. In addition,S. aureusbacteria harbored the highest prevalence of resistance to penicillin (85.93%), tetracycline (85.93%), gentamicin (73.43%), erythromycin (53.12%), trimethoprim-sulfamethoxazole (51.56%), and ciprofloxacin (50%). However, all isolates were resistant to at least four antibiotic agents. Accordingly, the prevalence oftetK(70.31%),blaZ(64.06%),aacA-D(57.81%),gyrA(50%), andermA(39.06%) was higher than that of other detected antibiotic resistance genes. Besides,AacA-D + blaZ(48.43%),tetK + blaZ(46.87%),aacA-D + tetK(39.06%),aacA-D + gyrA(20.31%), andermA + blaZ(20.31%) were the most frequently identified combined genotypic patterns of antibiotic resistance.

Conclusion

Ready-to-eat food samples may be sources of resistantS. aureus,which pose a hygienic threat in case of their consumption. However, further investigations are required to identify additional epidemiological features ofS. aureusin ready-to-eat foods.
A short review on lymphatic endothelial cell heterogeneity
Authors: Miyasaka Masayuki
Published: October 2021

Recent single-cell RNA sequencing studies in mouse and human have clearly indicated that lymphatic endothelial cells (LECs) consist of multiple cell subsets, each expressing a unique set of genes, residing in distinct locations in the body. These studies have also revealed a conserved pattern of gene expression in LECs across animal species, as well as specialized sets of genes unique to each species. However, the extent to which this heterogeneity is adaptive to the external milieu surrounding LECs has remained unclear. The transcriptional and regulatory pathways that program the different subsets of LECs also remain unexplored.
Thyroid Status and Brain Circulation: The Rotterdam Study
Authors: Fani Lana , Roa Dueñas Oscar , Bos Daniel , Vernooij Meike W , Klaver Caroline C W , Ikram M Kamran , Peeters Robin P , Ikram M Arfan , Chaker Layal
Published: October 2021

Context

Whether thyroid dysfunction is related to altered brain circulation in the general population remains unknown.

Objective

We determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly people.

Methods

This was a population-based study of 3 subcohorts of the Rotterdam Study, starting in 1989, 2000, and 2006. A total of 5142 participants (mean age, 63.8 years; 55.4% women), underwent venipuncture to measure serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/minute). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non)linear regression models.

Results

FT4 (in pmol/L) levels had an inverse U-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion than middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P nonlinearity = .002) was up to –2.44 mL (95% CI –4.31; –0.56). Higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to –2.46 µm, 95% CI –4.98; 0.05 for lower FT4).

Conclusion

These results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through suboptimal brain circulation that is potentially modifiable.
On Living with Television
Authors: Holdsworth Amy
Published: October 2021

In On Living with Television, Amy Holdsworth examines the characteristics of intimacy, familiarity, repetition, and duration that have come to exemplify the medium of television. Drawing on feminist television studies, queer theory, and disability studies as well as autobiographical life-writing practices, Holdsworth shows how television shapes everyday activities, from eating and sleeping to driving and homemaking. Recounting her own life with television, she offers a sense of the joys and pleasures Disney videos brought to her disabled sister, traces how bedtime television becomes part of a daily routine between child and caregiver, explores her own relationship to binge-eating and binge-viewing, and considers the idea of home through the BBC family drama Last Tango in Halifax. By foregrounding the ways in which television structures our relationships, daily routines, and sense of time, Holdsworth demonstrates how television emerges as a potent vehicle for writing about life.
Swimming kinematics and performance of spinal transected lampreys with different levels of axon regeneration
Authors: Fies Jacob , Gemmell Brad J. , Fogerson Stephanie M. , Morgan Jennifer R. , Tytell Eric D. , Colin Sean P.
Published: October 2021

Axon regeneration is critical for restoring neural function after spinal cord injury. This has prompted a series of studies on the neural and functional recovery of lampreys after spinal cord transection. Despite this, there are still many basic questions remaining about how much functional recovery depends on axon regeneration. Our goal was to examine how swimming performance is related to degree of axon regeneration in lampreys recovering from spinal cord transection by quantifying the relationship between swimming performance and percent axon regeneration of transected lampreys after 11 weeks of recovery. We found that while swimming speeds varied, they did not relate to percent axon regeneration. In fact, swimming speeds were highly variable within individuals, meaning that most individuals could swim at both moderate and slow speeds, regardless of percent axon regeneration. However, none of the transected individuals were able to swim as fast as the control lampreys. To swim fast, control lampreys generated high amplitude body waves with long wavelengths. Transected lampreys generated body waves with lower amplitude and shorter wavelengths than controls, and to compensate, transected lampreys increased their wave frequencies to swim faster. As a result, transected lampreys had significantly higher frequencies than control lampreys at comparable swimming velocities. These data suggest that the control lampreys swam more efficiently than transected lampreys. In conclusion, there appears to be a minimal recovery threshold in terms of percent axon regeneration required for lampreys to be capable of swimming; however, there also seems to be a limit to how much they can behaviorally recover.
Physical Activity Promotion in a Safety-Net Clinic: Does the Provider Make a Difference? A Pilot Study
Authors: Bowen Pamela G. , Opoku-Agyeman William , Affuso Olivia , Levi Paula , Wingo Nancy
Published: October 2021

Background

Despite the long-term health benefits of physical activity, many Americans across the life span do not meet the recommended levels. However, physical activity discussions in the clinic setting may hold promise. The purpose of this study aimed to understand health care providers’ beliefs and practices about physical activity discussions being a part of patients’ health care treatment.

Methods

Semistructured, audiotaped interviews were conducted to elicit narratives from 10 health care providers. Interview data were transcribed verbatim, and then coded and analyzed by two qualitative researchers using NVivo12.

Results

Three major themes emerged were as follows: importance of regular physical activity counseling for vulnerable populations; patients’ lack of regular physical activity, including subthemes of lack of time, current health conditions, and social determinants of health; and health care provider’s reflections about their own physical activity.

Conclusions

Health care providers have an important role when it comes to promoting good health. Having physical activity discussions with patients at every clinic visit is a great opportunity to encourage patients to engage in healthy lifestyle behaviors such as regular physical activity. From this pilot study, implications for practice may include increased awareness of the health care providers to discuss physical activity at every visit, which may lead to improved provider–patient communications related to the benefits of daily physical activity behaviors. These discussions may even have a secondary gain of encouraging the providers themselves to adopt the healthy behavior and thereby serve as a role model for their patients.
Values in nursing and the virtues of the profession: a systematic critical review
Authors: Kosmidis Dimitrios , Koutsouki Sotiria , Theofanidis Dimitrios
Published: October 2021

Introduction: Values are the cornerstone of routine nursing practice. Yet, there is lack of clarity and controversies over the content of the term and its application in contemporary nursing practice.Aim: The main aim of this discussion paper to explore the concept of ‘values’ in nursing, provide insights into their application with specific relevance to nursing and contemplate on its consequences on contemporary nursing practice.Methodology: For this paper’s needs a critical literature search was undertaken within the past two decades whereby key terms and corresponding contexts were critically appraised with regards to the concepts involved. Search terms used included: nursing, values, deontology, caring, in both Pubmed and Greek databases. The Cohen's Kappa coefficient was used in order to assess inter-rater reliability.Results & Discussion: After close perusal, the search yielded 55 papers with a distinct content on values in contemporary nursing. These were categorized in 5 distinct subthemes i.e. Ethical and individual values, Professional values and virtues, The development of values, Integrity and Dignity which were subsequently addressed and discussed further. Cohen's Kappa was 0.85 (95% CI:0.776-0.922) reflecting a strong level of agreement among the two authors.Discussion: Professional values can be seen as tools that encourage nurses to become ethically sensitive professionals. Various studies on professional values in different countries have shown that the difference in the adoption and weight given to professional values is mainly due to the priorities given, rather than their nature per se. Ethical values significantly influence the scope of nursing practice, the way nurses think and act and consequently the care they provide with integrity and dignity being at the core of their practice delivery.Conclusions: Values in nursing science should be developed primarily by direct learning in basic education through raising awareness among nurses regarding ethics and the value of nursing. Integrity and respect for dignity are referred to as two of the most basic values which may affect both nursing practice and care providers. The way nurses behave is a reflection of their knowledge, experience, ability, personality and judgment. This reflects the professionalism of nurses based on agreed common values.
Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia
Authors: Navapurkar Vilas , Bartholdson Scott Josefin , Maes Mailis , Hellyer Thomas P , Higginson Ellen , Forrest Sally , Pereira-Dias Joana , Parmar Surendra , Heasman-Hunt Emma , Polgarova Petra , Brown Joanne , Titti Lissamma , Smith William PW , Scott Jonathan , Rostron Anthony , Routledge Matthew , Sapsford David , Török M. Estée , McMullan Ronan , Enoch David A , Wong Vanessa ,   VAP-Rapid investigators, Curran Martin D , Brown Nicholas M , Simpson A John , Herre Jurgen , Dougan Gordon , Conway Morris Andrew
Published: October 2021

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing.

Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable.

Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group.

Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)).

Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.
Liga Kobiet Polskich w okręgu łódzkim w latach 1982–1989. Główne kierunki działalności w świetle materiałów sprawozdawczych organizacji
Authors: Dajnowicz Małgorzata
Published: October 2021

Liga Kobiet Polskich, akceptowana przez władze komunistyczne organizacja kobieca, usiłowała umocnić swoje wpływy zwłaszcza wśród kobiet pracujących. Jako priorytetowy cel działalności wskazywała także upowszechnianie znaczenia szerokich działań Komitetu Gospodarstwa Domowego, w ramach którego organizowano szkolenia zawodowe, promowano gospodarność w prowadzeniu przez kobiety gospodarstw domowych. Schyłek jej działalności przypadł na koniec lat osiemdziesiątych, biorąc pod uwagę zarówno zmniejszającą się liczbę członkiń, jak i słabnącą pozycję jako oficjalnej reprezentacji kobiet polskich.
Iterative Coordination and Innovation: Prioritizing Value over Novelty
Authors: Ghosh Sourobh , Wu Andy
Published: October 2021

An innovating organization faces the challenge of how to prioritize distinct goals of novelty and value, both of which underlie innovation. Popular practitioner frameworks like Agile management suggest that organizations can adopt an iterative approach of frequent meetings to prioritize between these goals, a practice we refer to as iterative coordination. Despite iterative coordination’s widespread use in innovation management, its effects on novelty and value in innovation remain unknown. With the information technology firm Google, we embed a field experiment within a hackathon software development competition to identify the effect of iterative coordination on innovation. We find that iterative coordination causes firms to implicitly prioritize value in innovation: Although iteratively coordinating firms develop more valuable products, these products are simultaneously less novel. Furthermore, by tracking software code, we find that iteratively coordinating firms favor integration at the cost of knowledge-creating specialization. A follow-on laboratory study documents that increasing the frequency and opportunities to reprioritize goals in iterative coordination meetings reinforces value and integration, while reducing novelty and specialization. This article offers three key contributions: highlighting how processes to prioritize among multiple performance goals may implicitly favor certain outcomes; introducing a new empirical methodology of software code version tracking for measuring the innovation process; and leveraging the emergent phenomenon of hackathons to study new methods of organizing.

History: This paper has been accepted for the Organization Science Special Issue on Experiments in Organizational Theory.

Funding: The authors gratefully acknowledge financial support from Google LLC, the Harvard Business School Division of Research and Faculty Development, and the National Science Foundation [Grant 1122374].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.1499 .
PCOS Modulatory Activity of Tinospora cordifolia leaves – An Insilico Approach
Authors: Devi M. Sri , Muralidharan P.Muralidharan , Hari Rajeswary , Lavanya M. , Abiraamavalli T. Abiraamavalli
Published: October 2021

The polycystic ovarian syndrome affects women of all age groupsis mainly due to hyperinsulinemia and hyperandrogenism.The insulin action in the ovaries is mediated by binding to its receptor namely IRS (Insulin receptor substrate).The present investigation is undertaken to select a suitable antagonistic ligand from the bioactive phyto components of Tinosporacordifolialeaves to inhibit IRS1 and IRS 2 receptors to prevent the binding of insulin and subsequent hyperandrogenism.The phyto ligands used for the study were obtained from the previous literature and the IRS1 and IRS 2 receptor protein structure were retrieved from PDB (protein Data bank). Using the Corina 3D converter the ligand 3D structures were obtained. Molecular docking analysis was performed through Patch dock server to select a suitable ligand based on docking score for the IRS1 and IRS 2 receptor protein.Three ligands namely Berberine, Rumphioside I and Syringin showed better docking score among the ligand selectedand their inhibitory activity were analysed by intermolecular interactions using “LIGPLOT” analysis. It can be concluded that these three ligands can be used for the successful treatment of PCOS after proper preclinical and clinical studies.
Effectiveness Study of Typical and Atypical Antipsychotics on Patients with Schizophrenia using WHO Disability Assessment Schedule (WHODAS 2.0)
Authors: Agrawal Ratna , Rath Bhabagrahi
Published: October 2021

Background and Objectives: Schizophrenia is the commonest and one of the best known mental disorder which usually starts before 25 years of age, leading to significant disability in both behavioural and social life. Usually the person with any mental disability has to face social ignorance, this further leads to deterioration of their health and productivity. The deterioration of the health is not only due to the course of the disease but also may be due to treatment by some of the antipsychotics, which are the main drugs for the schizophrenia management. So, the present study has been designed to determine the effectiveness of typical and atypical antipsychotics in patients with schizophrenia in terms of disability reduction caused by them using WHODAS 2.0. Methods: After taking ethics committee approval and informed consent from study participants this prospective, observational, questionnaire based study has been conducted in the Department of Psychiatry and Pharmacology of V. S.S. Institute of Medical Sciences and Research, Burla, Odisha using WHODAS 2.0 in patients suffering from schizophrenia. Results: Atypical antipsychotics lead to more reduction in disability in patients with schizophrenia than typical antipsychotics both at 6 and 12 month duration. On comparing the various atypical antipsychotics used in the study, there was no significant difference among them. Conclusion: Based on the above findings, it can be concluded that atypical antipsychotics are more effective than typical antipsychotics in terms of disability reduction. The findings may help clinicians to get better insight in the management of schizophrenia.
Screening the Therapeutic Potential of Methanolic Stem Extract of Cissus arnottiana
Authors: Selvi P. , Murugesh S. , Yuvarajan R. Yuvarajan , Rajasekar A. Rajasekar
Published: October 2021

Modern lifestyle, pollution, food habit, and stress have intensively enhanced the evolution of several diseases on human being. Medicinal plants are used from the ancient times for the therapeutic needs to cure various diseases as well as less toxic in nature. One of such plant is Cissus arnottiana which is used from the olden days which has been identified as an important medicine plant by many researchers all over the world. Cissus arnottiana contains phytochemicals such as alkaloids, tannins, terpenoids, flavonoids, phenolic compounds etc. In this present work methanolic stem extract of Cissus arnottiana is used to evaluate the antibacterial activity of gram negative and gram positive human pathogenic bacteria. DPPH assay is used to investigate the antioxidant properties of the methanolic extract. The anti-inflammatory activity of the extract has been studied using anti proteinase assay. The MTT cell proliferation assay is carried out against HeLa cell line in which 44% of cells are viable for the concentration of 100 µg/mL. Interestingly, the methanolic stem extract can be used as a potential candidate for new therapeutic applications.
Two-Pore Channels in Cancer Hallmarks: An Update Review
Authors: Sediqi Nelofar , Jahidin Aisyah Hasyila , Hasan Mizaton Hazizul , Zakaria Yuslina
Published: October 2021

Cancer is one of the most disastrous diseases that leads to a serious threat to millions of people’s health worldwide. Cancer is distinguished by multiple common criteria, known as the “cancer hallmarks" which calcium signaling has either direct or indirect correlation with each of them. An emerging body of evidence suggests that two-pore channels/calcium signaling machinery has a crucial role in the promotion of diverse aspects of cancer, particularly in several cancer hallmarks including cell proliferation, angiogenesis, migration, invasion, metastasis, and metabolic reprogramming. Recent findings linked two-pore channels/calcium signaling machinery with autophagy, chemoresistance, and patients' survival in cancer. The present review provides current findings on the roles of two-pore channels in cancer, particularly in several cancer hallmarks, autophagy, and chemoresistance. Furthermore, a specific focus on recent data concerning the two-pore channels antagonists and novel inhibitors is discussed. This review will furnish readers with a more in-depth understanding of the significance of two-pore channel calcium signalling in cancer and its potential as a druggable target for cancer therapy