bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis
Authors: Sagard Jonas , Olofsson Tor , Mogard Elisabeth , Marsal Jan , Andréasson Kristofer , Geijer Mats , Kristensen Lars Erik , Lindqvist Elisabet , Wallman Johan K.
Published: February 2022

Background

Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity.

The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain.

Methods

Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA).

Results

Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2–0.9); BASDAI 1.6 (0.8–2.4); evaluator’s global disease activity assessment (Likert scale 0–4) 0.3 (0.1–0.5), BASFI 1.5 (0.6–2.4), and VAS pain (cm) 1.3 (0.4–2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis.

Conclusion

Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.
Amyloid PET imaging and dementias: potential applications in detecting and quantifying early white matter damage
Authors: Pietroboni Anna M. , Colombi Annalisa , Carandini Tiziana , Sacchi Luca , Fenoglio Chiara , Marotta Giorgio , Arighi Andrea , De Riz Milena A. , Fumagalli Giorgio G. , Castellani Massimo , Bozzali Marco , Scarpini Elio , Galimberti Daniela
Published: February 2022

Purpose

Positron emission tomography (PET) with amyloid tracers (amy-PET) allows the quantification of pathological amyloid deposition in the brain tissues, including the white matter (WM). Here, we evaluate amy-PET uptake in WM lesions (WML) and in the normal-appearing WM (NAWM) of patients with Alzheimer’s disease (AD) and non-AD type of dementia.

Methods

Thirty-three cognitively impaired subjects underwent brain magnetic resonance imaging (MRI), Aβ1-42 (Aβ) determination in the cerebrospinal fluid (CSF) and amy-PET. Twenty-three patients exhibiting concordant results in both CSF analysis and amy-PET for cortical amyloid deposition were recruited and divided into two groups, amyloid positive (A+) and negative (A−). WML quantification and brain volumes’ segmentation were performed. Standardized uptake values ratios (SUVR) were calculated in the grey matter (GM), NAWM and WML on amy-PET coregistered to MRI images.

Results

A+ compared to A− showed a higher WML load (p = 0.049) alongside higher SUVR in all brain tissues (p < 0.01). No correlations between CSF Aβ levels and WML and NAWM SUVR were found in A+, while, in A−, CSF Aβ levels were directly correlated to NAWM SUVR (p = 0.04). CSF Aβ concentration was the only predictor of NAWM SUVR (adj R2 = 0.91; p = 0.04) in A−. In A+ but not in A− direct correlations were identified between WM and GM SUVR (p < 0.01).

Conclusions

Our data provide evidence on the role of amy-PET in the assessment of microstructural WM injury in non-AD dementia, whereas amy-PET seems less suitable to assess WM damage in AD patients due to a plausible amyloid accrual therein.
Effect of chronic intermittent hypoxia (CIH) on neuromuscular junctions and mitochondria in slow- and fast-twitch skeletal muscles of mice—the role of iNOS
Authors: Bannow L. I. , Bonaterra G. A. , Bertoune M. , Maus S. , Schulz R. , Weissmann N. , Kraut S. , Kinscherf R. , Hildebrandt W.
Published: February 2022

Background

Obstructive sleep apnea (OSA) imposes vascular and metabolic risks through chronic intermittent hypoxia (CIH) and impairs skeletal muscle performance. As studies addressing limb muscles are rare, the reasons for the lower exercise capacity are unknown. We hypothesize that CIH-related morphological alterations in neuromuscular junctions (NMJ) and mitochondrial integrity might be the cause of functional disorders in skeletal muscles.

Methods

Mice were kept under 6 weeks of CIH (alternating 7% and 21% O2 fractions every 30 s, 8 h/day, 5 days/week) compared to normoxia (NOX). Analyses included neuromuscular junctions (NMJ) postsynaptic morphology and integrity, fiber cross-sectional area (CSA) and composition (ATPase), mitochondrial ultrastructure (transmission-electron-microscopy), and relevant transcripts (RT-qPCR). Besides wildtype (WT), we included inducible nitric oxide synthase knockout mice (iNOS−/−) to evaluate whether iNOS is protective or risk-mediating.

Results

In WT soleus muscle, CIH vs. NOX reduced NMJ size (− 37.0%, p < 0.001) and length (− 25.0%, p < 0.05) together with fiber CSA of type IIa fibers (− 14%, p < 0.05) and increased centronucleated fiber fraction (p < 0.001). Moreover, CIH vs. NOX increased the fraction of damaged mitochondria (1.8-fold, p < 0.001). Compared to WT, iNOS−/− similarly decreased NMJ area and length with NOX (− 55%, p < 0.001 and − 33%, p < 0.05, respectively) or with CIH (− 37%, p < 0.05 and − 29%, p < 0.05), however, prompted no fiber atrophy. Moreover, increased fractions of damaged (2.1-fold, p < 0.001) or swollen (> 6-fold, p < 0.001) mitochondria were observed with iNOS−/− vs. WT under NOX and similarly under CIH. Both, CIH- and iNOS−/− massively upregulated suppressor-of-cytokine-signaling-3 (SOCS3) > 10-fold without changes in IL6 mRNA expression. Furthermore, inflammatory markers like CD68 (macrophages) and IL1β were significantly lower in CIH vs. NOX. None of these morphological alterations with CIH- or iNOS−/− were detected in the gastrocnemius muscle. Notably, iNOS expression was undetectable in WT muscle, unlike the liver, where it was massively decreased with CIH.

Conclusion

CIH leads to NMJ and mitochondrial damage associated with fiber atrophy/centronucleation selectively in slow-twitch muscle of WT. This effect is largely mimicked by iNOS−/− at NOX (except for atrophy). Both conditions involve massive SOCS3 upregulation likely through denervation without Il6 upregulation but accompanied by a decrease of macrophage density especially next to denervated endplates. In the absence of muscular iNOS expression in WT, this damage may arise from extramuscular, e.g., motoneuronal iNOS deficiency (through CIH or knockout) awaiting functional evaluation.
Phytochemical analysis and anti-microbial activities of Artemisia spp. and rapid isolation methods of artemisinin
Authors: Mohammed Seid , Dekabo Aman , Hailu Tilahun
Published: February 2022

Artemisia species are important traditional medicinal plants of Ethiopia which are used for the treatment of infection and non-infection health problems. The genus Artemisia (Astraceae) consists of about 500 species worldwide. In this study, the main aim was to investigate chemical components ofArtemisiaspp. (A. abyssinica,A.absinthiumand A.annua) and evaluate their antimicrobial activities against bacterial strains. The results indicated that the crude extract of these plants was effective against selected bacterial strains. Here we isolated the well-known antimalarial drug artemisinin (7 mg, 0.004%) fromArtemisia annualeaves using a rapidn-hexane fractionation method.Then-hexane extract ofA. abyssinica,ethyl acetate extract ofA. absinthiumandn-hexane ofA.annuashowed varying degrees of inhibiting effect against bacterial strains such as Staphylococcus aureusATCC 25923 T,Salmonella enteritidisATCC13076T,Klebsiella pneumoniaeATCC1053T,boydiiATCC1233T,Escherichia coliATCC 25922 T, hospital acquiredAcinetobacter baumannii.The ethyl acetate extract ofArtemisia absinthium(A.abe) showed the maximum inhibiting effect (35 mm) againstA. baumannii. The minimum zone of inhibition (< 3 mm) was recorded for test extract of A.ap againstKlebsiella pneumoniaeATCC1053T. Ethyl acetate extract ofA, absinthium(A.abe) was more effective against these selected bacterial strains and the zone of inhibition ranged from 5 to 35 mm. The minimum inhibition zone (8 mm) was detected againstS. typhimuriumATCC 13311 Tfor both A.ac and n-hexane- EtOAc fraction (8:2) ofA, abyssinica. The maximum zone of inhibition (25 mm) for fraction (A.ach F4) ofA, abyssinicaobtained by column chromatography was recorded againstS. pyogen ATCC19,615. However, there was no zone of inhibition detected forboydiiATCC1233Tdue to these test extracts. Significant variations (P ≥ 0.05) were observed between all test extracts of these medicinal plants at 95% of confidence intervals. In this study, clear zones of inhibition were detected for the positive control (standard impregnated disks). Based on our results we recommend that various species of Artemisiaspp. seem to have the potential for in-depth investigation for various antimicrobial activities that assisting the effort in searching for antimicrobial lead compounds.
Specific anti-SARS-CoV-2 S1 IgY-scFv is a promising tool for recognition of the virus
Authors: Ge Shikun , Wu Rao , Zhou Tingting , Liu Xiang , Zhu Jin , Zhang Xiaoying
Published: February 2022

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, a series of vaccines, antibodies and drugs have been developed to combat coronavirus disease 2019 (COVID-19). High specific antibodies are powerful tool for the development of immunoassay and providing passive immunotherapy against SARS-CoV-2 and expected with large scale production. SARS-CoV-2 S1 protein was expressed in E. coli BL21 and purified by immobilized metal affinity chromatography, as antigen used to immunize hens, the specific IgY antibodies were extracted form egg yolk by PEG-6000 precipitation, and the titer of anti-S1 IgY antibody reached 1:10,000. IgY single chain variable fragment antibody (IgY-scFv) was generated by using phage display technology and the IgY-scFv showed high binding sensitivity and capacity to S1 protein of SARS-CoV-2, and the minimum detectable antigen S1 protein concentration was 6 ng/µL. The docking study showed that the multiple epitopes on the IgY-scFv interacted with multiple residues on SARS-CoV-2 S1 RBD to form hydrogen bonds. This preliminary study suggests that IgY and IgY-scFv are suitable candidates for the development of immunoassay and passive immunotherapy for COVID-19 to humans and animals.
Sequential lateral positioning as a new lung recruitment maneuver: an exploratory study in early mechanically ventilated Covid-19 ARDS patients
Authors: Roldán Rollin , Rodriguez Shalim , Barriga Fernando , Tucci Mauro , Victor Marcus , Alcala Glasiele , Villamonte Renán , Suárez-Sipmann Fernando , Amato Marcelo , Brochard Laurent , Tusman Gerardo
Published: February 2022

Background

A sequential change in body position from supine-to-both lateral positions under constant ventilatory settings could be used as a postural recruitment maneuver in case of acute respiratory distress syndrome (ARDS), provided that sufficient positive end-expiratory pressure (PEEP) prevents derecruitment. This study aims to evaluate the feasibility and physiological effects of a sequential postural recruitment maneuver in early mechanically ventilated COVID-19 ARDS patients.

Methods

A cohort of 15 patients receiving lung-protective mechanical ventilation in volume-controlled with PEEP based on recruitability were prospectively enrolled and evaluated in five sequentially applied positions for 30 min each: Supine-baseline; Lateral-1st side; 2nd Supine; Lateral-2nd side; Supine-final. PEEP level was selected using the recruitment-to-inflation ratio (R/I ratio) based on which patients received PEEP 12 cmH2O for R/I ratio ≤ 0.5 or PEEP 15 cmH2O for R/I ratio > 0.5. At the end of each period, we measured respiratory mechanics, arterial blood gases, lung ultrasound aeration, end-expiratory lung impedance (EELI), and regional distribution of ventilation and perfusion using electric impedance tomography (EIT).

Results

Comparing supine baseline and final, respiratory compliance (29 ± 9 vs 32 ± 8 mL/cmH2O; p < 0.01) and PaO2/FIO2 ratio (138 ± 36 vs 164 ± 46 mmHg; p < 0.01) increased, while driving pressure (13 ± 2 vs 11 ± 2 cmH2O; p < 0.01) and lung ultrasound consolidation score decreased [5 (4–5) vs 2 (1–4); p < 0.01]. EELI decreased ventrally (218 ± 205 mL; p < 0.01) and increased dorsally (192 ± 475 mL; p = 0.02), while regional compliance increased in both ventral (11.5 ± 0.7 vs 12.9 ± 0.8 mL/cmH2O; p < 0.01) and dorsal regions (17.1 ± 1.8 vs 18.8 ± 1.8 mL/cmH2O; p < 0.01). Dorsal distribution of perfusion increased (64.8 ± 7.3% vs 66.3 ± 7.2%; p = 0.01).

Conclusions

Without increasing airway pressure, a sequential postural recruitment maneuver improves global and regional respiratory mechanics and gas exchange along with a redistribution of EELI from ventral to dorsal lung areas and less consolidation.

Trial registration ClinicalTrials.gov, NCT04475068. Registered 17 July 2020, https://clinicaltrials.gov/ct2/show/NCT04475068
Cell cycle arrest biomarkers for predicting renal recovery from acute kidney injury: a prospective validation study
Authors: Jia Hui-Miao , Cheng Li , Weng Yi-Bing , Wang Jing-Yi , Zheng Xi , Jiang Yi-Jia , Xin Xin , Guo Shu-Yan , Chen Chao-Dong , Guo Fang-Xing , Han Yu-Zhen , Zhang Tian-En , Li Wen-Xiong
Published: February 2022

Background

Acute kidney injury (AKI) is a common disease in the intensive care unit (ICU). AKI patients with nonrecovery of renal function have a markedly increased risk of death compared with patients with recovery. The current study aimed to explore and validate the utility of urinary cell cycle arrest biomarkers for predicting nonrecovery in patients who developed AKI after ICU admission.

Methods

We prospectively and consecutively enrolled 379 critically ill patients who developed AKI after admission to the ICU, which were divided into a derivation cohort (194 AKI patients) and a validation cohort (185 AKI patients). The biomarkers of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected at inclusion immediately after AKI diagnosis (day 0) and 24 h later (day 1). The optimal cut-off values of these biomarkers for predicting nonrecovery were estimated in the derivation cohort, and their predictive accuracy was assessed in the validation cohort. The primary endpoint was nonrecovery from AKI (within 7 days).

Results

Of 379 patients, 159 (41.9%) patients failed to recover from AKI onset, with 79 in the derivation cohort and 80 in the validation cohort. Urinary [TIMP-2]*[IGFBP7] on day 0 showed a better prediction ability for nonrecovery than TIMP-2 and IGFBP7 alone, with an area under the reciever operating characteristic curve (AUC) of 0.751 [95% confidence interval (CI) 0.701–0.852, p < 0.001] and an optimal cut-off value of 1.05 ((ng/mL)2/1000). When [TIMP-2]*[IGFBP7] was combined with the clinical factors of AKI diagnosed by the urine output (UO) criteria, AKI stage 2–3 and nonrenal SOFA score for predicting nonrecovery, the AUC was significantly improved to 0.852 (95% CI 0.750–0.891, p < 0.001), which achieved a sensitivity and specificity of 88.8% (72.9, 98.7) and 92.6% (80.8, 100.0), respectively. However, urine [TIMP-2]*[IGFBP7], TIMP-2 alone, and IGFBP7 alone on day 1 performed poorly for predicting AKI recovery.

Conclusion

Urinary [TIMP-2]*[IGFBP7] on day 0 showed a fair performance for predicting nonrecovery from AKI. The predictive accuracy can be improved when urinary [TIMP-2]*[IGFBP7] is combined with the clinical factors of AKI diagnosed by the UO criteria, AKI stage 2–3 and nonrenal SOFA score.
Antimicrobial resistance among bacteria isolated from urinary tract infections in females in Namibia, 2016–2017
Authors: Haindongo Erastus H. , Funtua Binta , Singu Boni , Hedimbi Marius , Kalemeera Francis , Hamman Jana , Vainio Olli , Hakanen Antti J. , Vuopio Jaana
Published: February 2022

Background

The emergence of antimicrobial resistance (AMR) among bacterial pathogens demands a local understanding of the epidemiological situation. This information is needed both for clinical treatment decision-making purposes as well as for the revision of current care guidelines. Clinical AMR data from Namibia is sparse, whilst urinary tract infections remain not only widespread but they disproportionally affect females. This paper aims to describe the national antimicrobial resistance situation of major bacterial uropathogens in females within the 14 Namibian regions.

Method

Retrospective countrywide information on clinical urine cultures performed in females in Namibia in 2016–2017 was obtained from the national public health laboratory, Namibia Institute of Pathology (NIP). The data set included both microbiological findings as well as antimicrobial susceptibility test (AST) results. The AST was done as per the Clinical and Laboratory Standards Institute (CLSI) guidelines. Resistance to 3rd generation cephalosporins was indicative of Extended Spectrum-ß-lactamase (ESBL) production. Data analysis was done with WHONET using expert interpretation rules.

Results

In total, 22,259 urinary cultures were performed, of which 13,673 (61.4%) were culture positive. Gram-negative bacterial species accounted for 72.6% of the findings. The most common pathogens identified were Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. Most of these were from young females, with a median age ranging from 28 to 32 years for the various pathogens. Resistance to ampicillin was 77.7% in E. coli and 84.9% in K. pneumoniae. In E. coli, resistance to 1st line empiric therapy antibiotic, nitrofurantoin, was below 13%, except for one region that showed 59.2% resistance. Resistance to third generation cephalosporin (3GC) was used as a proxy for ESBL production. By year 2017, 3GC resistance was 22%, 31.4% and 8.3% for E. coli, K. pneumoniae and P. mirabilis, respectively.

Conclusion

We report high resistance to ampicillin, quinolones and sulfamethoxazole-trimethoprim amongst E. coli. Resistance rates to third-generation cephalosporins was also concerningly high at 22%. Resistance to carbapenems was low. However, superiority of nitrofurantoin was found, which provides rational support for the usefulness of nitrofurantoin as an empiric therapy regimen for the treatment of urinary tract infections in this setting.
Determining the elastography strain ratio cut off value for differentiating benign from malignant breast lesions: systematic review and meta-analysis
Authors: Mutala Timothy Musila , Mwango Gladys N. , Aywak Angeline , Cioni Dania , Neri Emanuele
Published: February 2022

Background

Elastography is an addition to grey-scale ultrasonic examination that has gained substantial traction within the last decade. Strain ratio (SR) has been incorporated as a semiquantitative measure within strain elastography, thus a potential imaging biomarker. The World Federation for Ultrasound in Medicine and Biology (WFUMB) published guidelines in 2015 for breast elastography. These guidelines acknowledge the marked variance in SR cut-off values used in differentiating benign from malignant lesions. The objective of this review was to include more recent evidence and seek to determine the optimal strain ratio cut off value for differentiating between benign and malignant breast lesions.

Methods

Comprehensive search of MEDLINE and Web of Science electronic databases with additional searches via Google Scholar and handsearching set from January 2000 to May 2020 was carried out. For retrieved studies, screening for eligibility, data extraction and analysis was done as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Diagnostic Test Accuracy (PRISMA-DTA) Statement guidelines of 2018. Quality and risk of bias assessment of the studies were performed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.

Results

A total of 424 articles, 412 from electronic database and 12 additional searches were retrieved and 65 studies were included in the narrative synthesis and subgroup analysis. The overall threshold effect indicated significant heterogeneity among the studies with Spearman correlation coefficient of Logit (TPR) vs Logit (FPR) at − 0.301, p-value = 0.015. A subgroup under machine model consisting seven studies with 783 patients and 844 lesions showed a favourable threshold, Spearman’s correlation coefficient,0.786 (p = 0.036).

Conclusion

From our review, currently the optimal breast SR cut-off point or value remains unresolved despite the WFUMB guidelines of 2015. Machine model as a possible contributor to cut-off value determination was suggested from this review which can be subjected to more industry and multi-center research determination.
Social capital undergirds coping strategies: evidence from two informal settlements in Nairobi
Authors: Mpanje Desire , Gibbons Pat , McDermott Ronan , Omia Dalmas Ochieng’ , Olungah Charles Owuor
Published: February 2022

Understanding the nature and scope of existing social capital is essential to building the resilience of people living in vulnerable urban settings. This paper explores the question of how aid organisations can better utilise social capital to build the resilience of communities in slums. It specifically examines the relationship between social capital and urban vulnerability. The study used a mixed-methods approach to understand the diverse perspectives of social capital and uncover relationships that exist between social capital, absorptive and adaptive coping strategies in Kibera and Kawangware slums in Nairobi, Kenya. The findings show that coping is not a community or a societal issue; people living in slums resort to either absorptive or adaptive coping strategies or a combination of both due to the precariousness of livelihoods in such contexts. Measures of bonding, bridging, and linking social capital in slums are significantly associated with adaptive coping strategies. Families that had more dependents, were taking care of ill members or that had no regular source of income were more likely to resort to withdrawing children from school, begging, selling assets, amongst others. Livelihood studies overlook critical aspects of social capital such as bridges and linkages, which are essential for building the transformative capacities of slum dwellers. Therefore, aid actors should focus on social capital if they are to build the capacities of people living in slums. More attention should be given to the role of local organisations and initiatives in establishing bridges and linkages so as not to undermine communities’ existing capacities and resource base.
An Approach to a Patient With Primary Hyperparathyroidism and a Suspected Ectopic Parathyroid Adenoma
Authors: Glasgow Clark , Lau Eunice Y C , Aloj Luigi , Harper Ines , Cheow Heok , Das Tilak , Berman Laurence , Powlson Andrew S , Bashari Waiel A , Challis Benjamin G , Marker Alison , Moyle Penelope , Mohamed Isra Ahmed , Schoenmakers Nadia , Broomfield Jonathan , Oddy Sue , Moran Carla , Gurnell Mark , Jani Piyush , Masterson Liam , Fish Brian , Casey Ruth T
Published: February 2022

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance. Solitary hyperfunctioning parathyroid adenomas account for 85% to 90% of PHPT cases. The remaining 10% to 15% include cases of multiglandular disease (multiple adenomas or hyperplasia) and, rarely, parathyroid carcinoma (1%). Ectopic parathyroid adenomas may arise due to abnormal embryological migration of the parathyroid glands and can be difficult to localize preoperatively, making surgical cure challenging on the first attempt.

The potential existence of multiglandular disease should be considered in all patients in whom preoperative localization fails to identify a target adenoma or following unsuccessful parathyroidectomy. Risk factors for multiglandular disease include underlying genetic syndromes (eg, MEN1/2A), lithium therapy, or previous radiotherapy. In addition to multifocal disease, the possibility of an ectopic parathyroid gland should also be considered in patients requiring repeat parathyroid surgery. In this article, we use illustrative clinical vignettes to discuss the approach to a patient with primary hyperparathyroidism (PHPT) and a suspected ectopic parathyroid adenoma.
The Kynurenine Pathway Metabolites in Cord Blood Positively Correlate With Early Childhood Adiposity
Authors: Tan Karen Mei-Ling , Tint Mya-Thway , Kothandaraman Narasimhan , Michael Navin , Sadananthan Suresh Anand , Velan S Sendhil , Fortier Marielle V , Yap Fabian , Tan Kok Hian , Gluckman Peter D , Chong Yap-Seng , Chong Mary F F , Lee Yung Seng , Godfrey Keith M , Eriksson Johan G , Cameron-Smith David
Published: February 2022

Context

The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth.

Objective

In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years.

Methods

Liquid chromatography–tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age.

Results

Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years.

Conclusion

Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity.
Approach to the Patient With Prader–Willi Syndrome
Authors: Höybye Charlotte , Tauber Maithé
Published: February 2022

Prader–Willi syndrome (PWS) is a rare, multisystemic, genetic disorder involving the hypothalamus. It is caused by loss of expression of paternally inherited genes in chromosome 15 q11-13 region. The estimated incidence is around 1 in 20.000 births. PWS is characterized by a complex lifelong trajectory involving neurodevelopmental, nutritional, endocrine, metabolic, and behavioral changes. The major symptoms are hypotonia, short stature, hypogonadism, and eating disorders ranging from anorexia in infancy to hyperphagia, a deficit of satiety, and a high risk of severe obesity. The patients display intellectual disability comprising cognitive deficit, delayed motor and language development, learning deficits, impaired social skills, and emotional regulation. Behavioral features including temper outbursts, anxiety, obsessive–compulsive symptoms and rigidity are common and become more apparent with increasing age. Almost all have hypogonadism and growth hormone deficiency. Central adrenal insufficiency is rare whereas central hypothyroidism occurs in up to 30% of children with PWS. The prevalence of obesity increases with age from almost none in early childhood to more than 90% in adulthood. Up to 25% of adults with obesity have type 2 diabetes. Obesity and its complications are the major causes of comorbidity and mortality in PWS. As there is no specific treatment, care consists of comprehensive management of feeding disorders, a restricted, controlled diet, regular exercise, hormone substitution, and screening and treatment of comorbidities. Here we present the course of PWS from birth to adulthood in 2 patients and discuss their symptoms in relation to the literature.
PROBLEMS OF STABILITY, VIABILITY, RESILIENCE OF THE STATE AND SOCIETY. ELECTRONIC TUTORIAL
Authors:   Lomonosov Moscow State University, Kokurina O.Yu.
Published: February 2022

This manual contains a critical generalization of the problem of the viability and resilience of the state and the socio-political system, based on an interdisciplinary systems approach to its solution. The author reveals the problem of the viability of the state and the resilience of public administration and legal regulation as complex social systems. Modern approaches to ensuring the stability of complex systems with control based on the balance of diversity and complexity, control processes and self-organization are presented. It is shown that the viable systems model (VSM) can serve as a useful tool for conceptual simplification, helping to find the necessary balance between the complexity and resilience of public administration and regulation systems. The imperative of mutual responsibility of the individual, society and public authorities as a political and legal regulator of ensuring the stability of the socio-political system is substantiated. The study was supported by the RFBR and EISI within the framework of the scientific project No. 21-011-31155.
Keeping warfarin patients safe during the COVID-19 pandemic: review of an INR self-testing programme
Authors: Gee Emma , Pol Angeline , Kittoe Kwesi , Coker Folusho , Speed Victoria
Published: February 2022

Background:

Anticoagulation clinics faced an unprecedented challenge during the COVID-19 pandemic to safely manage patients on warfarin therapy.

Methods:

A London teaching hospital trust received INR point-of-care (POC) testing devices from its clinical commissioning group. The Trust distributed the devices to patients who were cognitively and physically able to self-test and evaluated clinical outcomes and patient experience.

Findings:

A significant improvement in warfarin control (mean time in therapeutic range (TTR) before POC 52%, standard deviation (SD) 24.8, vs mean after 60.7%, SD 19.7; P>0.009) and a 39% reduction in missed appointments were seen in self-testing patients. Positive patient satisfaction and lifestyle outcomes were identified through a telephone survey. A minority of patients struggled with the technique, leading to frustration. Some patients used many test strips through unsuccessful and additional tests.

Conclusion:

POC testing in a carefully selected group of patients on warfarin therapy resulted in positive clinical and patient satisfaction outcomes. Appropriate governance processes are needed, and clinical expertise is required to support patients. Cost-effectiveness of POC testing needs careful monitoring.
Antiseptic versus non-antiseptic solutions for preventing infection in acute traumatic wounds: a systematic review
Authors: Soeselo Daniel Ardian , Yolanda Rennie , Zita Maria , Theresia Sandy , Astiarani Yunisa , Santi Bryany Titi
Published: February 2022

Objective:

To compare the effectiveness of antiseptic solutions to that of non-antiseptic solutions in reducing wound infection rate, reducing bacterial load and improving wound healing.

Method:

We searched PubMed MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), ProQuest Medical Database and medRxiv for randomised controlled trials (RCTs) comparing antiseptic solutions with non-antiseptic solutions in simple, uncomplicated acute traumatic wounds. Qualitative data synthesis was employed. Risk of bias was assessed and GRADE assessment was used to evaluate quality of evidence.

Results:

In this systematic review, four studies with a total of 875 participants were included, of which two studies showed a significant reduction of wound infection rate using povidone-iodine (p=0.001 and p=0.03). The use of non-antiseptic solutions significantly increased bacterial load on acute traumatic wounds (p=0.0001). The quality of evidence was very low. No studies reported on wound healing outcome.

Conclusion:

No robust conclusions can be implemented in clinical practice. Future studies are needed to compare the use of antiseptic and non-antiseptic solutions in acute traumatic wounds.
Effect ofPseudomonascolonisation on lower limb venous ulcer healing: a systematic review
Authors: Toale Conor , Kelly Aisling , Leahy Fiona , Meagher Helen , Stapleton Patrick J , Moloney Michael A , Kavanagh Eamon G
Published: February 2022

Objective:

Pseudomonas aeruginosa is a Gram-negative bacillus that commonly colonises lower limb venous ulcers. Its effects on venous ulcer healing are widely debated. It produces exotoxins and elastase, as well as forming biofilms in hard-to-heal wounds. It is postulated that these virulence factors lead to slower healing times in patients with lower limb venous ulcers colonised with Pseudomonas. This review aimed to summarise the available evidence pertaining to this topic.

Method:

A systematic review was performed in August 2019, where the Pubmed, Cochrane and Embase databases were searched for relevant literature according to PRISMA guidelines. Retrospective and prospective studies examining the effect of Pseudomonas colonisation on any measure of ulcer healing were included.

Results:

Some 282 articles were screened, of which seven studies including 491 patients were ultimately included for analysis. Of these, no study demonstrated a significant association between Pseudomonas colonisation and delayed healing of venous ulcers. In five of the seven studies, the effect of Pseudomonas aeruginosa on initial ulcer size at presentation was recorded.

Conclusion:

All the studies demonstrated an association between ulcer size and the presence of Pseudomonas aeruginosa. While Pseudomonas aeruginosa may colonise larger ulcers or those with a worse prognosis, no evidence was found to support the hypothesis that this colonisation had a negative impact on lower limb venous ulcer healing.
A 24-hour interval compression plan for managing chronic oedema: part 1—the science and theory behind the concept
Authors: Bock Karen J , Muldoon Jeanette
Published: February 2022

Compression, skin care, manual lymph drainage and exercise form the mainstays of treatment of chronic limb oedema. The compression aspect of the regimen is often prescribed and used without conscious concern for the patient's ability for self-adjustment and skin hygiene. This article will focus on the action of compression therapy using a new concept of encouraging patients to apply and reapply an adjustable compression garment or multiple garment types during a 24-hour interval. The benefits of this focus on interval compression therapy on all aspects of care will be explained and case studies presented.
A novel dressing with silver to treat meticillin-resistant Staphylococcus aureus biofilm infection in a pig model
Authors: Davis Stephen C , Li Jie , Gil Joel , Valdes Jose , Solis Michael , Higa Alex
Published: February 2022

Objective:

The purpose of this study was to use an in vivo biofilm porcine model to examine a new polyvinyl alcohol-based gelling fibre dressing with silver and compare it to other commercial dressings containing: polyvinyl alcohol-based gelling fibre without silver; carboxymethyl cellulose-based fibre with silver, benzethonium chloride and ethylenediaminetetraacetic acid; and untreated control.

Methods:

A total of 52 deep partial-thickness wounds (10x7x0.5mm) were created on each of three animals and inoculated with 25µl of meticillin-resistant Staphylococcus aureus (MRSA) (106 colony forming units (CFU)/ml). Wounds were covered for 24 hours to allow biofilm formation and were randomly designated to one of the four treatments. Samples were recovered for microbiological and histological analysis on days 3, 5 and 7 post-treatment.

Results:

Polyvinyl alcohol-based gelling fibre dressing with silver was able to significantly reduce biofilm more effectively than the other treatment groups. By day 7, wounds treated with the dressing had a 2.72±0.01 log CFU/g reduction in MRSA count versus untreated control wounds and a 2.59±0.01 log CFU/g reduction versus baseline counts. For histology analysis, all wounds reached 100% re-epithelialisation by day 5.

Conclusion:

The results of this study indicated that polyvinyl alcohol-based gelling fibre dressing with silver was effective against biofilm of antibiotic-resistant staphylococcal strains without inhibiting the wound healing process, and may have important clinical implications when treating acute and/or hard-to-heal wounds.
Prescribing for respiratory disease
Authors: Robertson Deborah
Published: February 2022

Deborah Robertson provides an overview of recently published articles that may be of interest to non-medical prescribers. Should you wish to look at any of the papers in more detail, a full reference is provided
Ozanimod for relapsing remitting multiple sclerosis and how Brexit changed the journey
Authors: Daykin Nicola
Published: February 2022

This article will focus on ozanimod, a medication that has been put forward for relapsing-remitting multiple sclerosis (RRMS). It will look at ozanimod's characteristics, including the pharmacokinetics and pharmacodynamics of the medication, and follow ozanimod's journey from clinical trials through the different licencing agencies, allowing ozanimod to be used as a treatment in multiple sclerosis (MS). Finally, this article will look at its journey through the National Institute for Clinical Excellence (NICE) to seek approval to be used as a medication to treat RRMS on the NHS. The article will also briefly reflect on the marketing authorisation changes in the UK since leaving the European Union (EU) and the impact of these changes.
Lacticaseibacillus spp.; Probiotic candidates from Palmyra palm sugar, possess antimicrobial, and anti-biofilm activities against methicillin-resistant Staphylococcus aureus
Authors: Mitsuwan Watcharapong , Sornsenee Phoomjai , Romyasamit Chonticha
Published: February 2022

Background and Aim: Probiotics are beneficial microorganisms that play important roles by adhering to the gut and producing antimicrobial substances to inhibit pathogens. The objective of this study was to isolate and characterize the probiotic lactic acid bacteria (LAB) from Palmyra palm sugar, which can produce antimicrobial compounds against methicillin-resistant Staphylococcus aureus (MRSA), a new zoonotic and food-borne pathogens.

Materials and Methods: Twenty-six LAB isolates were isolated from 30 Palmyra palm sugar samples. Three selected LAB were further characterized as probiotics. In addition, the antibacterial and anti-biofilm-forming activities of the probiotics' culture supernatants against MRSA and food-borne pathogens were investigated. Finally, the selected probiotics were identified by aligning 16S rRNA sequences.

Results: The three confirmed probiotics, WU 0904, WU 2302, and WU 2503, showed strong antibacterial activities against S. aureus, MRSA, Escherichia coli O157:H7, and Listeria monocytogenes, as measured by a broth microdilution assay. Among the LAB isolates, 82.22-86.58%, 91.83-96.06%, and 64.35-74.93% exhibited resistance to low pH, pancreatin treatment, and bile salts, respectively. It was found that 59.46% and 83.33% auto-aggregation was observed in 2 and 24 h, respectively. Moreover, 50.25-57.24% adhesion was detected after the incubation of the bacterial cells to Caco-2 cells. . Biofilm inhibition (82.81-87.24%) was detected after the treatment of MRSA with the culture supernatants, when compared with that to the control. By the alignment of 16S rRNA sequences, the isolate WU 2302 was identified as Lacticaseibacillus spp. with 98.82% homology when compared to the GenBank database.

Conclusion: This study indicates that isolated probiotics can produce antimicrobial compounds against MRSA and food-borne pathogens. The obtained results strongly suggest that these probiotics are promising candidates for pharmaceutical products.
Improved Priority-based Congestion Control Protocol for Multi-Access Edge Computing (MAEC) Using IoT-based Wearable Devices for Neurological Diseases Diagnosis
Authors: Kalaivaani P.T. , Krishnamoorthy Raja , Naidu Apparao , Harikrishna Ponnam
Published: February 2022

Stroke is one of the fatal diseases that affect the brain and causes death within 3 to 10 hours. However, most of the deaths caused by a stroke can be avoided with the identification of the nature of stroke and react to it in a timely manner by intelligent health systems. Internet of Things (IoT) has become an important aspect in medical industry for monitoring of stroke related data/information using various wearable devices. Moreover, Multiple-Access Edge Computing (MAEC) is playing a major role for processing, analysing, and storing of data which leads to several researchers to compete in improving the mechanism of congestion control. In this paper, an improved Priority-based Congestion Control Protocol (iPCCP) is proposed for obtaining increased throughput, decreasing delay, effective resource utilization, and longer network lifetime by optimal energy consumption among IoT based sensor nodes. The proposed method categorizes the data-traffic into emergency and normal data. The packet delivery rate is considered for the normal data-traffic and retains the size of the buffer to improve the throughput and avoids the packet drops due to congestion. The energy consumption and network traffic load is reduced using the data aggregation and filtration technique. For emergency situations, priority-based routing scheme is used to have greater throughput and lesser delay. The performance of the proposed technique outperforms in term of traffic load, lifespan, energy consumption, and network throughput and simulation results are compared with other existing methods to show the improvement of the proposed work.
Supply and Demand Characteristics of Palm Kernel Shell as a Renewable Energy Source for Industries
Authors: Handaya Handaya , Susanto Herry , Indrawan Dikky , Marimin Marimin
Published: February 2022

Depleting stockpile of fossil fuels and rising global temperature due to the greenhouse effect are probably the two most threatening factors to civilization sustainability. Converting biomass into a readily available energy source will help reduce dependency on fossil fuels, whilst at the same time moderating greenhouse gas emmissions due to its carbon neutrality. Palm oil industry is the largest source of biomass in Indonesia and the available quantity to be utilized is growing inline with the steady growth of the generating industry. Among various wastes from palm oil processing, palm kernel shell is an oil palm biomass with high potential to be applied as a source of energy, given its high caloric value and distinctive physical properties. This source of renewable energy can be utilized by industries with thermal conversion processes. As a prerequisite, a feasibility study on technical, environmental, and economic aspects needs to be carried out. From long term perspective, supply, demand, and regulatory situational analysis will also be required. Lastly, a review on the existing palm kernel shell supply chain will help to understand its current situation. Based on literature studies and field observations, we have identified supply and demand characteristics that will be valuable in constructing an effective, efficient, and sustainable supply chain model of palm kernel shell. Understanding these characteristics is a precursor in realizing this massive potential of renewable energy source in the industrial context.
Point-of-care testing in primary healthcare: a scoring system to determine the frequency of performing internal quality control
Authors: Gidske Gro , Sandberg Sverre , Fossum Anne L. , Binder Stein , Langsjøen Eva C. , Solsvik Anne E. , Stavelin Anne
Published: February 2022

Objectives

Internal quality control (IQC) plays an important role in quality assurance in laboratory medicine. However, there is no universal consensus or guideline on when and how IQC should be analyzed on point-of-care testing (POCT) devices. The aim of this study was to develop a scoring system to determine how often IQC should be analyzed in primary healthcare on the various POCT devices.

Methods

Based on a systematic literature review and a thorough process involving the whole Noklus, a nationwide POC organization, a scoring system for when to analyze IQC was developed. Four factors were considered to significantly impact IQC frequency: The importance of the analyte in diagnosing and monitoring patients, type of POCT device, user-friendliness, and number of patient samples. For each POCT device, the first three factors were given a score, and the sum of the scores determined the general recommended IQC frequency. The number of patient samples determined whether and how to adjust these frequencies in each individual general practice.

Results

The scoring system was applied to 17 analytes and 134 different POCT devices (153 analyte-device combinations). Most of the devices analyzing high-risk analytes (71 out of 74) obtained daily or weekly IQC frequency. For example, all blood-cell counters and all glucose meters should undergo IQC daily and weekly, respectively.

Conclusions

This study presents a consensus-based scoring system for differentiated and device-specific recommendations for IQC frequency on POCT devices in primary healthcare. The scoring system can easily be adopted to other local environments and is easy to use.