bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pilot Study of Nicotine Replacement Therapy Sampling and Selection to Increase Medication Adherence in Low-Income Smokers
Authors: Cropsey Karen L , Wolford-Clevenger Caitlin , Sisson Michelle L , Chichester Keith R , Hugley Mickeah , Azuero Andres , Businelle Michael S , Hendricks Peter S , Shelton Richard C , Carpenter Matthew J
Published: February 2021

Introduction

Adherence to smoking cessation medications remains suboptimal, particularly among low-income smokers. Guided, experiential sampling of nicotine replacement therapies (NRTs) may increase NRT adherence and smoking cessation over gold standard counseling plus NRT. The present pilot study aimed to examine feasibility, acceptability, and preliminary efficacy of a novel experiential intervention.

Aims and Methods

This pilot randomized controlled trial (N = 83) compared gold standard smoking cessation treatment (four weekly sessions of behavioral counseling followed by self-selected combination NRT in week 5) to a novel experiential approach (ie, In Vivo; four weekly sessions of sampling each short form of NRT-gum, lozenge, inhaler, nasal spray-in-session while wearing the nicotine patch followed by NRT selection in week 5). Both groups received 8 weeks of nicotine patch plus their selected additional short form NRT for smoking cessation followed by a 1-month assessment.

Results

Screening and enrollment rates supported feasibility. In Vivo was comparable in acceptability with the gold standard of care intervention; however, there was greater attrition in the In Vivo group compared with the gold standard of care group. Results suggested higher medication adherence and improvements in smoking behavior in the In Vivo intervention; with generally small-to-medium effect sizes.

Conclusions

This experiential approach to sampling NRT is feasible and acceptable to low-income people who smoke. This intervention may increase adherence and reduce harmful smoking behavior but needs to be tested on a larger scale.

Implications

Medication adherence remains a significant impediment to the successful smoking cessation. The results of this study suggest that guided sampling of NRT products improves adherence among low-income smokers. Additionally, this approach yielded greater improvements in smoking behavior compared with gold standard smoking cessation treatment. This intervention shows promise as a feasible smoking cessation treatment for low-income smokers.
Histochemical Techniques in Plant Science: More Than Meets the Eye
Authors: Yadav Vaishali , Arif Namira , Singh Vijay Pratap , Guerriero Gea , Berni Roberto , Shinde Suhas , Raturi Gaurav , Deshmukh Rupesh , Sandalio Luisa M , Chauhan Devendra Kumar , Tripathi Durgesh Kumar
Published: February 2021

Histochemistry is an essential analytical tool interfacing extensively with plant science. The literature is indeed constellated with examples showing its use to decipher specific physiological and developmental processes, as well as to study plant cell structures. Plant cell structures are translucent unless they are stained. Histochemistry allows the identification and localization, at the cellular level, of biomolecules and organelles in different types of cells and tissues, based on the use of specific staining reactions and imaging. Histochemical techniques are also widely used for the in vivo localization of promoters in specific tissues, as well as to identify specific cell wall components such as lignin and polysaccharides. Histochemistry also enables the study of plant reactions to environmental constraints, e.g. the production of reactive oxygen species (ROS) can be traced by applying histochemical staining techniques. The possibility of detecting ROS and localizing them at the cellular level is vital in establishing the mechanisms involved in the sensitivity and tolerance to different stress conditions in plants. This review comprehensively highlights the additional value of histochemistry as a complementary technique to high-throughput approaches for the study of the plant response to environmental constraints. Moreover, here we have provided an extensive survey of the available plant histochemical staining methods used for the localization of metals, minerals, secondary metabolites, cell wall components, and the detection of ROS production in plant cells. The use of recent technological advances like CRISPR/Cas9-based genome-editing for histological application is also addressed. This review also surveys the available literature data on histochemical techniques used to study the response of plants to abiotic stresses and to identify the effects at the tissue and cell levels.
Providing Epidemiological Data in Lumbar Spine Imaging Reports Did Not Affect Subsequent Utilization of Spine Procedures: Secondary Outcomes from a Stepped-Wedge Randomized Controlled Trial
Authors: Suri Pradeep , Meier Eric N , Gold Laura S , Marcum Zachary A , Johnston Sandra K , James Kathryn T , Bresnahan Brian W , O’Reilly Michael , Turner Judith A , Kallmes David F , Sherman Karen J , Deyo Richard A , Luetmer Patrick H , Avins Andrew L , Griffith Brent , Heagerty Patrick J , Rundell Sean D , Jarvik Jeffrey G , Friedly Janna L
Published: February 2021

Objective

To evaluate the effect of inserting epidemiological information into lumbar spine imaging reports on subsequent nonsurgical and surgical procedures involving the thoracolumbosacral spine and sacroiliac joints.

Design

Analysis of secondary outcomes from the Lumbar Imaging with Reporting of Epidemiology (LIRE) pragmatic stepped-wedge randomized trial.

Setting

Primary care clinics within four integrated health care systems in the United States.

Subjects

238,886 patients ≥18 years of age who received lumbar diagnostic imaging between 2013 and 2016.

Methods

Clinics were randomized to receive text containing age- and modality-specific epidemiological benchmarks indicating the prevalence of common spine imaging findings in people without low back pain, inserted into lumbar spine imaging reports (the “LIRE intervention”). The study outcomes were receiving 1) any nonsurgical lumbosacral or sacroiliac spine procedure (lumbosacral epidural steroid injection, facet joint injection, or facet joint radiofrequency ablation; or sacroiliac joint injection) or 2) any surgical procedure involving the lumbar, sacral, or thoracic spine (decompression surgery or spinal fusion or other spine surgery).

Results

The LIRE intervention was not significantly associated with subsequent utilization of nonsurgical lumbosacral or sacroiliac spine procedures (odds ratio [OR] = 1.01, 95% confidence interval [CI] 0.93–1.09; P = 0.79) or any surgical procedure (OR = 0.99, 95 CI 0.91–1.07; P = 0.74) involving the lumbar, sacral, or thoracic spine. The intervention was also not significantly associated with any individual spine procedure.

Conclusions

Inserting epidemiological text into spine imaging reports had no effect on nonsurgical or surgical procedure utilization among patients receiving lumbar diagnostic imaging.
Innervation of the Human Intervertebral Disc: A Scoping Review
Authors: Groh Adam M R , Fournier Dale E , Battié Michele C , Séguin Cheryle A
Published: February 2021

Objective

Back pain is an elusive symptom complicated by a variety of possible causes, precipitating and maintaining factors, and consequences. Notably, the underlying pathology remains unknown in a significant number of cases. Changes to the intervertebral disc (IVD) have been associated with back pain, leading many to postulate that the IVD may be a direct source of pain, typically referred to as discogenic back pain. Yet despite decades of research into the neuroanatomy of the IVD, there is a lack of consensus in the literature as to the distribution and function of neural elements within the tissue. The current scoping review provides a comprehensive systematic overview of studies that document the topography, morphology, and immunoreactivity of neural elements within the IVD in humans.

Method

Articles were retrieved from six separate databases in a three-step systematic search and were independently evaluated by two reviewers.

Results

Three categories of neural elements were described within the IVD: perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors. Nerves were consistently localized within the outer layers of the annulus fibrosus. Neural ingrowth into the inner annulus fibrosus and nucleus pulposus was found to occur only in degenerative and disease states.

Conclusion

While the pattern of innervation within the IVD is clear, the specific topographic arrangement and function of neural elements in the context of back pain remains unclear.
Are remission and low disease activity state ideal targets for pregnancy planning in systemic lupus erythematosus? A multicentre study
Authors: Tani Chiara , Zucchi Dina , Haase Isabell , Larosa Maddalena , Crisafulli Francesca , Strigini Francesca A L , Monacci Francesca , Elefante Elena , Mucke Johanna , Choi May Y , Andreoli Laura , Iaccarino Luca , Tincani Angela , Doria Andrea , Fischer-Betz Rebecca , Mosca Marta
Published: February 2021

Objectives

To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome.

Methods

Pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to the Definition of Remission in SLE (DORIS) criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death.

Results

A total of 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. Seventy-three flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking HCQ were less likely to have disease flare, while a history of LN increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on HCQ resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed.

Conclusions

Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetric complications in SLE pregnancies.
Systemic sclerosis skin is a primed microenvironment for soft tissue calcification—a hypothesis
Authors: Burgess Kyle A , Herrick Ariane L , Watson Rachel E B
Published: February 2021

Calcinosis cutis, defined as sub-epidermal deposition of calcium salts, is a major clinical problem in patients with SSc, affecting 20–40% of patients. A number of recognized factors associated with calcinosis have been identified, including disease duration, digital ischaemia and acro-osteolysis. Yet, to date, the pathogenesis of SSc-related calcinosis remains unknown, and currently there is no effective disease-modifying pharmacotherapy. Following onset of SSc, there are marked changes in the extracellular matrix (ECM) of the skin, notably a breakdown in the microfibrillar network and accumulation of type I collagen. Our hypothesis is that these pathological changes reflect a changing cellular phenotype and result in a primed microenvironment for soft tissue calcification, with SSc fibroblasts adopting a pro-osteogenic profile, and specific driving forces promoting tissue mineralization. Considering the role of the ECM in disease progression may help elucidate the mechanism(s) behind SSc-related calcinosis and inform the development of future therapeutic interventions.
Familial Mediterranean fever and asthma
Authors: Tsur Avishai M , Watad Abdulla , Gendelman Omer , Nissan Daniel , Cohen Arnon D , Amital Howard
Published: February 2021

Objective

To assess the association between FMF and asthma.

Methods

This study was designed as a cross-sectional study. All patients diagnosed with FMF between 1 January 2000 and 31 December 2016 who were prescribed colchicine were included in the study. Controls were matched by sex, date of birth, residential socioeconomic status and country of birth. Logistic regression models were used to determine the odds ratio for asthma in FMF patients and controls.

Results

A total of 7098 FMF patients who were prescribed colchicine were identified. Of them, 3547 (50%) were females, 3632 (51%) were of low residential socioeconomic status and 6160 (87%) were born in Israel. Their median age at the end of follow-up was 37 years (23–54). In an unadjusted logistic regression, FMF was associated with asthma [odds ratio (OR)=1.33, 95% CI: 1.17, 1.51; P <0.001]. The association persisted after adjusting for sex, socioeconomic status and country of birth (OR=1.33, 95% CI: 1.18, 1.52; P <0.001)

Conclusion

FMF is positively associated with asthma. Further research is required to validate our results and explore possible explanations of this association. These findings cast doubt on previous studies implying FMF to be a protective factor from asthma.
COSMIC RADIATION EXPOSURE TO THE AUSTRALIAN PUBLIC
Authors: Tate Brendan , Carpenter Julia , Tinker Rick , Orr Blake
Published: February 2021

A component of natural background radiation is exposure to galactic cosmic radiation (GCR). Annual GCR doses to the Australian public at ground levels and at altitudes of commercial domestic and international flights were estimated using the cosmic radiation dose modelling tool CARI-6. The annual population weighted average dose to Australians from GCR was estimated to be 342 μSv, of which 14.7 μSv (5%) was from domestic travel, 30.7 μSv (10%) was from international travel and 297 μSv (85%) of the dose was received at ground level. This study showed that critical population groups that are frequent flyers may exceed reference levels where additional awareness or protection should be considered. The GCR dose portion is ~25% of the total annual background radiation dose received by the Australian public.
Insomnia symptom severity is associated with increased suicidality and death by suicide in a sample of patients with psychiatric disorders
Authors: Simmons Zach , Burlingame Gary , Korbanka Juergen , Eastman Kevin , Thomas Douglas , Christensen Jeremy , Jenson Michelle , Nadorff Michael R , Kay Daniel B
Published: February 2021

Study Objectives

Insomnia is a risk factor for suicidal behavior including attempts and death by suicide. We investigated whether insomnia symptom severity was associated with suicidality and death by suicide in patients with psychiatric disorders.

Methods

The sample included 180 deceased patients with psychiatric disorders seen at Weber Human Services between 2008 and 2018 who completed the Outpatient Questionnaire-45.2 (OQ) prior to death. Insomnia symptom severity was assessed using item 41 from the OQ. Manner of death was determined by death records and autopsy reports. History of suicidality was determined through electronic medical records. Cases were grouped into four lifetime categories: non-suicidal (n = 30), suicidal ideation (n = 36), suicide attempt (n = 95), and death by suicide (n = 19). Demographic, medical, and psychiatric features of each group were compared using linear regression. Logistic regression was used to determine whether insomnia symptom severity was associated with lifetime suicidality severity grouping, adjusting for psychiatric disorders commonly linked to suicidality.

Results

Lifetime suicidality was associated with sleep problems, fatigue, headaches, and psychiatric disorders (i.e. depressive, personality, and trauma-related disorders). Referenced to the non-suicidal group, greater insomnia symptom severity was significantly associated with suicide attempts and death by suicide, with odds ratios (OR) of OR = 2.67, p = 0.011, and OR = 5.53, p = 0.002, respectively, even after adjusting important psychiatric diagnoses.

Conclusions

Results suggest that insomnia symptom severity endorsed during a clinical visit is associated with heightened suicidality, especially suicidal behavior. The presence of insomnia symptoms in patients with psychiatric disorders may indicate risk for suicide and is a target for suicide prevention.
Transcriptional control of Clostridium autoethanogenum using CRISPRi
Authors: Fackler Nicholas , Heffernan James , Juminaga Alex , Doser Damien , Nagaraju Shilpa , Gonzalez-Garcia R Axayacatl , Simpson Séan D , Marcellin Esteban , Köpke Michael
Published: February 2021

Gas fermentation by Clostridium autoethanogenum is a commercial process for the sustainable biomanufacturing of fuels and valuable chemicals using abundant, low-cost C1 feedstocks (CO and CO2) from sources such as inedible biomass, unsorted and nonrecyclable municipal solid waste, and industrial emissions. Efforts toward pathway engineering and elucidation of gene function in this microbe have been limited by a lack of genetic tools to control gene expression and arduous genome engineering methods. To increase the pace of progress, here we developed an inducible CRISPR interference (CRISPRi) system for C. autoethanogenum and applied that system toward transcriptional repression of genes with ostensibly crucial functions in metabolism.
Modelling trachoma post-2020: opportunities for mitigating the impact of COVID-19 and accelerating progress towards elimination
Authors: Borlase Anna , Blumberg Seth , Callahan E Kelly , Deiner Michael S , Nash Scott D , Porco Travis C , Solomon Anthony W , Lietman Thomas M , Prada Joaquin M , Hollingsworth T Dèirdre
Published: February 2021

Background

The COVID-19 pandemic has disrupted planned annual antibiotic mass drug administration (MDA) activities that have formed the cornerstone of the largely successful global efforts to eliminate trachoma as a public health problem.

Methods

Using a mathematical model we investigate the impact of interruption to MDA in trachoma-endemic settings. We evaluate potential measures to mitigate this impact and consider alternative strategies for accelerating progress in those areas where the trachoma elimination targets may not be achievable otherwise.

Results

We demonstrate that for districts that were hyperendemic at baseline, or where the trachoma elimination thresholds have not already been achieved after three rounds of MDA, the interruption to planned MDA could lead to a delay to reaching elimination targets greater than the duration of interruption. We also show that an additional round of MDA in the year following MDA resumption could effectively mitigate this delay. For districts where the probability of elimination under annual MDA was already very low, we demonstrate that more intensive MDA schedules are needed to achieve agreed targets.

Conclusion

Through appropriate use of additional MDA, the impact of COVID-19 in terms of delay to reaching trachoma elimination targets can be effectively mitigated. Additionally, more frequent MDA may accelerate progress towards 2030 goals.
WRKY Transcription Factors Actively Respond to Fusarium oxysporum in Lilium regale
Authors: Li Shan , Liu Guanze , Pu Limei , Liu Xuyan , Wang Zie , Zhao Qin , Chen Hongjun , Ge Feng , Liu Diqiu
Published: February 2021

The WRKY transcription factors form a plant-specific superfamily important for regulating plant development, stress responses, and hormone signal transduction. In this study, many WRKY genes (LrWRKY1–35) were identified in Lilium regale, which is a wild lily species highly resistant to Fusarium wilt. These WRKY genes were divided into three classes (I to III) based on a phylogenetic analysis. The Class-II WRKY transcription factors were further divided into five subclasses (IIa, IIb, IIc, IId, and IIe). Moreover, the gene expression patterns based on a quantitative real-time PCR analysis revealed the WRKY genes were differentially expressed in the L. regale roots, stems, leaves, and flowers. Additionally, the expression of the WRKY genes was affected by an infection by Fusarium oxysporum as well as by salicylic acid, methyl jasmonate, ethephon, and hydrogen peroxide treatments. Moreover, the LrWRKY1 protein was localized to the nucleus of onion epidermal cells. The recombinant LrWRKY1 protein purified from Escherichia coli bound specifically to DNA fragments containing the W-box sequence, and a yeast one-hybrid assay indicated that LrWRKY1 can activate transcription. A co-expression assay in tobacco (Nicotiana tabacum) confirmed LrWRKY1 regulates the expression of LrPR10-5. Furthermore, the overexpression of LrWRKY1 in tobacco and the Oriental hybrid ‘Siberia’ (susceptible to F. oxysporum) increased the resistance of the transgenic plants to F. oxysporum. Overall, LrWRKY1 regulates the expression of the resistance gene LrPR10-5 and is involved in the defense response of L. regale to F. oxysporum. This study provides valuable information regarding the expression and functional characteristics of L. regale WRKY genes.
Comparative study of small-incision lenticule extraction with and without prophylactic corneal crosslinking: 1-year outcomes
Authors: Liu Chunlei , Fang Xuejun , Wang Zheng , Zhao Xinheng , Zou Haohan , Jhanji Vishal , Wang Yan
Published: February 2021

Purpose:

To compare myopia and astigmatic correction after small-incision lenticule extraction (SMILE) with or without prophylactic crosslinking (SMILE Xtra).

Setting:

Shenyang Aier Eye Hospital, Central South University, China.

Design:

Retrospective study.

Methods:

Patients with comparable manifest sphere and cylinder undergoing SMILE Xtra or SMILE were enrolled. The crosslinking (CXL) energy was 2.7 J/cm2. Only right eyes were selected. Visual and refractive changes were evaluated for 1 year. Astigmatic correction was analyzed using Alpins method.

Results:

Thirty-six eyes undergoing SMILE Xtra and 40 eyes undergoing SMILE were enrolled. The uncorrected distance visual acuity at 1-day visit was lower after SMILE Xtra than that after SMILE (P = .01). At 12 months, the mean manifest refraction spherical equivalent (MRSE) and manifest cylinder were 0.08 ± 0.32 diopters (D) and −0.29 ± 0.23 D in SMILE Xtra group, whereas −0.25 ± 0.29 D and −0.22 ± 0.19 D in SMILE group (P < .01 and P = .135), respectively. Thirty-four eyes (94%) and 32 eyes (89%) in SMILE Xtra group and 36 eyes (91%) and 39 eyes (98%) in SMILE group exhibited target MRSE and manifest cylinder within ±0.50 D (P = .771 and P = .294), respectively. Compared with SMILE group, spherical correction index (SCI), correction index (CI), and difference vector were higher in SMILE Xtra group since 1-week follow-up (all P < .05). SCI and CI were slightly more than 1.0 after SMILE Xtra even at postoperative 12-month follow-up.

Conclusions:

With CXL protocol of 30 mW/cm2 for 90 seconds, SMILE Xtra exhibited comparable astigmatic correction with SMILE up to 1-year follow-up, although slight spherical equivalent and astigmatic overcorrection were evident after SMILE Xtra.
Trocar blade-assisted scleral fixation for an incomplete dislocated intraocular lens
Authors: Liu Laura , Wang Nan-Kai , Chen Yen-Po , Chen Kuan-Jen , Chou Hung-Da , Yu-Chuan Kang Eugene , Yeung Ling , Hwang Yih-Shiou , Chen Tun-Lu , Chen Yi-Hsing , Wu Wei-Chi , Lai Chi-Chun , Liu Jorn-Hon
Published: February 2021

An incomplete dislocated intraocular lens (IOL) is often treated with IOL exchange because the IOL subluxates posteriorly during surgery and makes it difficult to fixate the IOL in situ. A trocar blade used for 23-gauge vitrectomy was used to lift and stabilize the IOL–capsular complex. The IOL can then be fixated using a suture loop fixation technique, which was originally limited to patients with decentered IOL. The advantage of this technique is that it allows the remaining zonular fibers and IOL to be preserved. The modified technique using a trocar blade to assist scleral fixation allows the incomplete dislocated IOL to be retrieved and fixated with a simplified surgical procedure.
Menstrual Dysfunction in Women With Schizophrenia During Risperidone Maintenance Treatment
Authors: Bo Qijing , Xing Xiaomeng , Li Tian , Mao Zhen , Zhou Fuchun , Wang Chuanyue
Published: February 2021

Background

A percentage of women patients with schizophrenia may suffer from menstrual dysfunction associated with antipsychotic medication. This study evaluated menstrual dysfunction in women with schizophrenia given maintenance risperidone, and investigated the association between menstrual dysfunction and the duration and dose of risperidone and clinical symptoms.

Methods

The data of 161 women were obtained from the Risperidone Maintenance Treatment in Schizophrenia study, including patients' characteristics, menstrual conditions, and duration and dosage of risperidone. Qualitative data regarding menstrual health were evaluated at baseline (clinical stabilization after 4–8 weeks maintenance treatment with a standard risperidone dose 4–8 mg/d) and follow-up interviews up to 52 weeks.

Results

At baseline, 73.2% (119/161) of the patients were eumenorrheic; specific rates of menstrual dysfunction were 14.3% (23/161) irregular menstruation, 6.8% (11/161) oligomenorrhea, and 5.0% (8/161) amenorrhea. At the end of follow-up, 16.0% (19/119) of those with eumenorrhea at baseline reported menstrual dysfunction. During the entire risperidone maintenance treatment, 37.9% (61/161) experienced menstrual dysfunction. The range of onset time from the beginning of risperidone treatment to menstrual dysfunction was 64 to 243 days. Risperidone dose was positively associated with menstrual dysfunction (r = 0.187, P = 0.046). The total Positive and Negative Syndrome Scale score was significantly associated with menstrual dysfunction (r = 0.274, P = 0.001).

Conclusions

Attention should be given to menstrual dysfunction of women with schizophrenia that is an adverse effect of risperidone maintenance treatment. Menstrual dysfunction may occur early or late during maintenance treatment, partly depending on the dose.

ClinicalTrials.gov
identifier: NCT00848432
Atomoxetine Reduced Binge/Purge Symptoms in a Case of Anorexia Nervosa Binge/Purge Type
Authors: Wilfahrt Robert P. , Wilfahrt Lucy G. , Matthews Hamburg Abigail
Published: February 2021

Psychopharmacologic treatments for eating disorders (EDs) remain unclear, particularly for anorexia nervosa. As in attention-deficit hyperactivity disorder, a dopaminergic mechanism has been implicated in EDs, prompting our use of atomoxetine in an 18-year-old woman with anorexia nervosa, binge/purge type. Atomoxetine is a highly selective norepinephrine reuptake inhibitor with nonaddictive properties and limited effects of appetite suppression. Doses followed those used in a previous trial of atomoxetine in the treatment of binge ED, and response was assessed over 4 months, with significant improvement in ED behaviors and mood. Larger-scale, randomized studies that assess the efficacy of atomoxetine in the treatment of anorexia nervosa, binge/purge type are warranted.
Molecular and biochemical characterization of the bicarbonate-sensing soluble adenylyl cyclase from a bony fish, the rainbow troutOncorhynchus mykiss
Authors: Salmerón Cristina , Harter Till S. , Kwan Garfield T. , Roa Jinae N. , Blair Salvatore D. , Rummer Jodie L. , Shiels Holly A. , Goss Greg G. , Wilson Rod W. , Tresguerres Martin
Published: February 2021

Soluble adenylyl cyclase (sAC) is aHCO3 −-stimulated enzyme that produces the ubiquitous signalling molecule cAMP, and deemed an evolutionarily conserved acid–base sensor. However, its presence is not yet confirmed in bony fishes, the most abundant and diverse of vertebrates. Here, we identified sAC genes in various cartilaginous, ray-finned and lobe-finned fish species. Next, we focused on rainbow trout sAC (rtsAC) and identified 20 potential alternative spliced mRNAs coding for protein isoforms ranging in size from 28 to 186 kDa. Biochemical and kinetic analyses on purified recombinant rtsAC protein determined stimulation byHCO3 −at physiologically relevant levels for fish internal fluids (EC50∼ 7 mM). rtsAC activity was sensitive to KH7, LRE1, and DIDS (established inhibitors of sAC from other organisms), and insensitive to forskolin and 2,5-dideoxyadenosine (modulators of transmembrane adenylyl cyclases). Western blot and immunocytochemistry revealed high rtsAC expression in gill ion-transporting cells, hepatocytes, red blood cells, myocytes and cardiomyocytes. Analyses in the cell line RTgill-W1 suggested that some of the longer rtsAC isoforms may be preferentially localized in the nucleus, the Golgi apparatus and podosomes. These results indicate that sAC is poised to mediate multiple acid–base homeostatic responses in bony fishes, and provide cues about potential novel functions in mammals.
CO
2
sensing by connexin26 and its role in the control of breathing
Authors: Dale Nicholas
Published: February 2021

Breathing is essential to provide the O
2
required for metabolism and to remove its inevitable CO
2
by-product. The rate and depth of breathing is controlled to regulate the excretion of CO
2
to maintain the pH of arterial blood at physiological values. A widespread consensus is that chemosensory cells in the carotid body and brainstem measure blood and tissue pH and adjust the rate of breathing to ensure its homeostatic regulation. In this review, I shall consider the evidence that underlies this consensus and highlight historical data indicating that direct sensing of CO
2
also plays a significant role in the regulation of breathing. I shall then review work from my laboratory that provides a molecular mechanism for the direct detection of CO
2
via the gap junction protein connexin26 (Cx26) and demonstrates the contribution of this mechanism to the chemosensory regulation of breathing. As there are many pathological mutations of Cx26 in humans, I shall discuss which of these alter the CO
2
sensitivity of Cx26 and the extent to which these mutations could affect human breathing. I finish by discussing the evolution of the CO
2
sensitivity of Cx26 and its link to the evolution of amniotes.
CO
2
diffusion in tobacco: a link between mesophyll conductance and leaf anatomy
Authors: Clarke Victoria C. , Danila Florence R. , von Caemmerer Susanne
Published: February 2021

The partial pressure of CO
2
at the sites of carboxylation within chloroplasts depends on the conductance to CO
2
diffusion from intercellular airspace to the sites of carboxylation, termed mesophyll conductance (
g
m
). We investigated how
g
m
varies with leaf age and through a tobacco (
Nicotiana tabacum
) canopy by combining gas exchange and carbon isotope measurements using tunable diode laser spectroscopy. We combined these measurements with the anatomical characterization of leaves. CO
2
assimilation rate,
A
, and
g
m
decreased as leaves aged and moved lower in the canopy and were linearly correlated. This was accompanied by large anatomical changes including an increase in leaf thickness. Chloroplast surface area exposed to the intercellular airspace per unit leaf area (
S
c
) also decreased lower in the canopy. Older leaves had thicker mesophyll cell walls and
g
m
was inversely proportional to cell wall thickness. We conclude that reduced
g
m
of older leaves lower in the canopy was associated with a reduction in
S
c
and a thickening of mesophyll cell walls.
Implementation of an in-house real-time reverse transcription-PCR assay to detect the emerging SARS-CoV-2 N501Y variants
Authors: Bedotto Marielle , Fournier Pierre-Edouard , Houhamdi Linda , Colson Philippe , Raoult Didier
Published: February 2021

The SARS-CoV-2 pandemic has been associated with the emergence of several variants with a mutated spike glycoprotein that are of substantial concern regarding their transmissibility and ability to evade immune responses. This warrants implementing strategies for their detection and surveillance. We have set up an in-house one-step real-time reverse transcription-PCR (qPCR) assay that specifically detects SARS-CoV-2 spike N501Y variants. Our assay was positive for all 6 patients found spike N501Y-positive by genome sequencing. Ten cDNA samples for each of the 10 Marseille variants identified by genome sequencing and three nasopharyngeal samples of a spike N501Y-negative variant (Marseille-4) that predominates locally tested negative. All negative controls among which 5 SARS-CoV-2-negative nasopharyngeal samples tested negative. First use in the setting of diagnosis on 51 nasopharyngeal samples from SARS-CoV-2-positive but Marseille-4-negative patients showed positivity in 5 cases further confirmed by sequencing as from spike N501Y variant-infected patients. Thus, our in-house qPCR system was found reliable for the detection of the N501Y substitution and allowed estimating preliminarily that spike N501Y variant prevalence was 4% among SARS-CoV-2 diagnoses since January 2020.
Estimating real-world COVID-19 vaccine effectiveness in Israel using aggregated counts
Authors: Aran Dvir
Published: February 2021

The vaccination roll-out of the COVID-19 vaccines in Israel has been highly successful. By February 22th, approximately 47% of the population has already been administered at least one dose of the BNT162b2 vaccine. Efforts to estimate the true real-world effectiveness of the vaccine have been hampered by disease dynamics and social-economic discrepancies. Here, using counts of positive and hospitalized cases of vaccinated individuals, we conduct a sensitivity analysis of the vaccine effectiveness. Under an assumption of no effectiveness on the first two weeks after the 1st dose, we observe very low effectiveness on the third week. After the 2nd dose, on weeks 1 and 2 we find 73-85% effectiveness in reducing positive cases, hospitalizations, and severe cases, which increase to 89-97% effectiveness 14 days after the 2nd dose. As more granular data will be available, it will be possible to extract more exact estimates; however, the emerging evidence suggests that the vaccine is highly effective.
ADIPOSE-DERIVED STROMAL VASCULAR FRACTION AND FAT GRAFTS VERSUS MEDICAL TREATMENT FOR TREATING THE HANDS OF PATIENTS WITH SYSTEMIC SCLEROSIS. A RANDOMIZED CRONTOLLED TRIAL
Authors: Iglesias Martin , Torre-Villalvazo Iván , Butrón-Gandarillas Patricia , Rodríguez-Reyna Tatiana S. , Torre-Anaya Erik A. , Tovar-Palacio Armando R. , Zentella-Dehesa Alejandro , Guevara-Cruz Martha , Hérnandez-Campos Alan M
Published: February 2021

Background

In the hand, the Systemic Sclerosis (SS) is characteristically evidenced by Raynaud’s phenomenon (RP) and fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment not always cure these complications. Local adipose-derived stromal vascular fraction (ADSVF) administration into the hands has been proposed as an emerging treatment for these complications, due to its proangiogenic, antifibrotic, and immunoregulatory activities. The objective of this controlled trial was to evaluate the safety and clinical effects of fat micrografts plus ADSVF administration into the hands of patients with SS.

Methods

This was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with SS were enrolled and assigned to the experimental or control group. Fat micrografts plus the ADSVF were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon (RP), digital ulcer healing (DUH), mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, Serologic antibodies, hand function, and quality of life scores were evaluated in both groups. The mean follow-up period was 168 days.

The differences between before and after the intervention were analyzed with the Wilcoxon range test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann–Whitney U test.

Results

Adverse events were not observed in both groups. There were no changes in disease severity, serologic antibodies, nailfold capillaroscopy patterns, mobility, and hand function in both groups. There were significant improvements in pain, DUH and quality of life scores in the experimental group. RP improved significantly in both groups. However, on statistically comparing the results at 168 days between the groups, significant improvements were only observed in pain levels (p = 0.02) and DUH (p=0.003).

Conclusions

The injection of ADSVF plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with SS can be treated with this treatment.

Trial Registration

Retrospectively registered in ClinicalTrials.gov with identifier NCT04387825
Amyloid deposition in granuloma of tuberculosis patients: A pilot study
Authors: Ghosh Shreya , Kala Chayanika , Garg Akansha , Thakur Ashwani Kumar
Published: February 2021

The formation of granuloma is one of the characteristic features of tuberculosis. Besides, rise in the concentration of serum amyloid A (SAA) protein is the indicator for chronic inflammation associated with tuberculosis. The predisposition of SAA driven secondary amyloidosis in tuberculosis is well documented. However, SAA derived amyloid onset and deposition start sites are not well chracterised in tuberculosis and other chronic inflammatory conditions. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of SAA protein and proteases that cleave SAA into aggregation prone fragments. 150 tuberculosis patients were screened and biopsies were collected from the affected organs of these patients. 20 patients showed eosinophilic hyaline rich deposits within and surrounding granuloma respectively. They were further screened for the presence of amyloid deposits. The hyaline material, upon Congo red staining exhibited characteristic apple green birefringence under polarized light, confirming deposition of amyloid. Further upon immuno histochemical staining with anti-SAA antibody, the amyloid enriched areas showed positive immunoreactivity. In this pilot study, wexx have shown granuloma as a potential site for serum amyloid A derived amyloid deposition in tuberculosis patients. This study would set a stage to expxand the clinical and fundamental research for understanding the mechanism of amyloid formation in granuloma underlying tuberculosis and other chronic inflammatory conditions.
Country specific mutational profile of SARS-CoV-2 in pre- and post-international travel ban: Effect on vaccine efficacy
Authors: Laha Sayantan , Chatterjee Raghunath
Published: February 2021

In order to curb the rapid transmission of SARS-CoV-2, nation-wide lockdowns were implemented as a preliminary measure. Since most countries enforced travel-bans during end of March 2020, the country-specific patterns should be discernible in the subsequent months. We identified frequently mutated non-synonymous mutations in ∼2,15,000 SARS-CoV-2 sequences during pre- and post-travel-ban periods in 35 countries. We further investigated the mutational profile on a bi-monthly basis and traced the progress over the time. Several new mutations have emerged post-travel-ban and on the rise in specific countries, chief among them being A222V and S477N in Spike, and A220V in Nucleocapsid protein. Consequently, we examined the Spike protein epitopes to inspect whether any of these country-specific mutations overlapped with these epitopes. Several mutations were found to be contained within one or more epitopes, including the highly mutated residues of Spike protein, advocating the requirement of active monitoring of vaccine efficacies in respective countries.
SARS-CoV-2 re-infection risk in Austria
Authors: Pilz Stefan , Chakeri Ali , Ioannidis John PA , Richter Lukas , Theiler-Schwetz Verena , Trummer Christian , Krause Robert , Allerberger Franz
Published: February 2021

Background

A key question concerning coronavirus disease 2019 (COVID-19) is how effective and long lasting immunity against this disease is in individuals who were previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the risk of SARS-CoV-2 re-infections in the general population in Austria.

Methods

This is a retrospective observational study using national SARS-CoV-2 infection data from the Austrian epidemiological reporting system. As the primary outcome, we aim to compare the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February to April 30, 2020) versus the odds of first infections in the remainder general population by tracking polymerase chain reaction (PCR)-confirmed infections of both groups during the second wave from September 1 to November 30, 2020. Re-infection counts are tentative, since it cannot be excluded that the positive PCR in the first and/or second wave might have been a false positive.

Results

We recorded 40 tentative re-infections in 14,840 COVID-19 survivors of the first wave (0.27%) and 253,581 infections in 8,885,640 individuals of the remaining general population (2.85%) translating into an odds ratio (95% confidence interval) of 0.09 (0.07 to 0.13).

Conclusions

We observed a relatively low re-infection rate of SARS-CoV-2 in Austria. Protection against SARS-CoV-2 after natural infection is comparable to the highest available estimates on vaccine efficacies. Further well-designed research on this issue is urgently needed for improving evidence-based decisions on public health measures and vaccination strategies.
SARS-CoV-2 Seroprevalence Among Antenatal Clinic Attendees in Kingston, Jamaica, September-November 2020
Authors: Chisolm Te’Anne , Walker Jerome P. , Leys Ynolde , Butterfield Tiffany R. , Medley Candice , Thompson Tamara K. , Reynolds-Campbell Glendee , Mulder Willem H. , Mitchell Michelle Campbell , Anzinger Joshua J.
Published: February 2021

SARS-CoV-2 seroprevalence in an antenatal population in Kingston, Jamaica was assessed for September-November 2020 in a repeated cross-sectional study using the Abbott Architect SARS-CoV-2 IgG assay. After adjusting for test performance, seroprevalence was 6.9% for September, 16.9% for October, and 24.0% for November. Of the 37 pregnant women testing SARS-CoV-2 IgG positive, only 3 were symptomatic. One symptomatic woman testing SARS-CoV-2 IgG positive had multiple co-morbidities and succumbed to COVID-19 pneumonia. Up to January 31, 2021, 8 women identified as SARS-CoV-2 IgG positive delivered, all without complications. Comparison of test adjusted seroprevalence data with cumulative PCR-confirmed COVID-19 cases within the Kingston Metropolitan Area indicated that as many as 44.4 times more people were infected with SARS-CoV-2 than identified with PCR testing. These findings provide the first evidence for the extent of SARS-CoV-2 infections in Jamaica and will inform future SARS-CoV-2 testing strategies.
Workplace sexual harassment in sexual and reproductive services: a preliminary cross-sectional study
Authors: Costanzo Italo
Published: February 2021

INTRODUCTION

Sexual harassment at the workplace in health care is most prevalent in Anglo regions, although is an emerging problem globally. No research has yet focused on the prevalence of the phenomenon within the area of sexual and reproductive health care in Anglo regions. The aim of this study is therefore to measure the prevalence of sexual harassment in sexual and reproductive health care setting and compare it with other clinical areas.

METHOD

A web survey to health care workers of various NHS Trusts in the United Kingdom was carried out and a cross-sectional study was conducted to measure observed counts, expected frequencies and prevalence from a total of 90 questionnaires received.

RESULTS

The prevalence of workplace sexual harassment within the sexual and reproductive health services is lower compared to other clinical areas.

CONCLUSIONS

Working in sexual and reproductive services could be a protective factor for workplace sexual harassment, therefore this study originates a new line of research aiming to identify the protective factors against sexual harassment at the workplace in sexual and reproductive health and the ways they could be used to protect every health care worker from sexual harassment in the workplace.

KEY POINTS

The prevalence of workplace sexual harassment in sexual and reproductive health services is lower compared to other clinical areas.

Working in sexual and reproductive services could be a protective factor for workplace sexual harassment.
Epidemic dynamics in inhomogeneous populations and the role of superspreaders
Authors: Kawagoe K. , Rychnovsky M. , Chang S. , Huber G. , Li L. M. , Miller J. , Pnini R. , Veytsman B. , Yllanes D.
Published: February 2021

A variant of the SIR model for an inhomogeneous population is introduced in order to account for the effect of variability in susceptibility and infectiousness across a population. An initial formulation of this dynamics leads to infinitely many differential equations. Our model, however, can be reduced to a single first-order one-dimensional differential equation. Using this approach, we provide quantitative solutions for different distributions. In particular, we use GPS data from ∼ 107 cellphones to determine an empirical distribution of the number of individual contacts and use this to infer a possible distribution of susceptibility and infectivity. We quantify the effect of superspreaders on the early growth rate ℛ0 of the infection and on the final epidemic size, the total number of people who are ever infected. We discuss the features of the distribution that contribute most to the dynamics of the infection.
A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic
Authors: Bugembe Daniel Lule , V.T.Phan My , Ssewanyana Isaac , Semanda Patrick , Nansumba Hellen , Dhaala Beatrice , Nabadda Susan , O’Toole Áine Niamh , Rambaut Andrew , Kaleebu Pontiano , Cotten Matthew
Published: February 2021

Introductory paragraph

SARS-CoV-2 genomic surveillance in Uganda provides an opportunity to provide a focused description of the virus evolution in a small landlocked East African country. Here we show a recent shift in the local epidemic with a newly emerging lineage A.23 evolving into A.23.1 which is now dominating the Uganda cases and has spread to 26 other countries. Although the precise changes in A.23.1 as it has adapted are different from the changes in the variants of concern (VOC), the evolution shows convergence on a similar set of proteins. The A.23.1 spike protein coding region has accumulated changes that resemble many of the changes seen in VOC including a change at position 613, a change in the furin cleavage site that extends the basic amino acid motif, and multiple changes in the immunogenic N-terminal domain. In addition, the A.23.1lineage encodes changes in non-spike proteins that other VOC show (nsp6, ORF8 and ORF9). The clinical impact of the A.23.1 variant is not yet clear, however it is essential to continue careful monitoring of this variant, as well as rapid assessment of the consequences of the spike protein changes for vaccine efficacy.