bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary analysis and functional characterization of SiBRI1 as a Brassinosteroid receptor gene in foxtail millet
Authors: Zhao Zhiying , Tang Sha , Zhang Yiming , Yue Jingjing , Xu Jiaqi , Tang Wenqiang , Sun Yanxiang , Wang Ruiju , Diao Xianmin , Zhang Baowen
Published: June 2021

Brassinosteroids (BRs) play important roles in plant growth and development. Although BR receptors have been intensively studied in Arabidopsis, those in foxtail millet remain largely unknown. Here, we show that the BR signaling function of BRASSINOSTEROID INSENSITIVE 1 (BRI1) is conserved between Arabidopsis and foxtail millet, a new model species for C4 and Panicoideae grasses. We identified four putative BR receptor genes in the foxtail millet genome: SiBRI1, SiBRI1-LIKE RECEPTOR KINASE 1 (SiBRL1), SiBRL2 and SiBRL3. Phylogenetic analysis was used to classify the BR receptors in dicots and monocots into three branches. Analysis of their expression patterns by quantitative real-time PCR (qRT-PCR) showed that these receptors were ubiquitously expressed in leaves, stems, dark-grown seedlings, roots and non-flowering spikelets. GFP fusion experiments verified that SiBRI1 localized to the cell membrane. We also explored the SiBRI1 function in Arabidopsis through complementation experiments. Ectopic overexpression of SiBRI1 in an Arabidopsis BR receptor loss-of-function mutant, bri1-116, mostly reversed the developmental defects of the mutant. When SiBRI1 was overexpressed in foxtail millet, the plants showed a drooping leaf phenotype and root development inhibition, lateral root initiation inhibition, and the expression of BR synthesis genes was inhibited. We further identified BRI1-interacting proteins by immunoprecipitation (IP)-mass spectrometry (MS). Our results not only demonstrate that SiBRI1 plays a conserved role in BR signaling in foxtail millet but also provide insight into the molecular mechanism of SiBRI1.
Quantitative trait loci (QTL) analysis of leaf related traits in spinach (Spinacia oleracea L.)
Authors: Liu Zhiyuan , She Hongbing , Xu Zhaosheng , Zhang Helong , Li Guoliang , Zhang Shifan , Qian Wei
Published: June 2021

Background

Spinach (Spinacia oleracea L.) is an important leafy vegetable crop, and leaf-related traits including leaf length, leaf width, and petiole length, are important commercial traits. However, the underlying genes remain unclear. The objective of the study was to conduct QTL mapping of leaf-related traits in spinach.

Results

A BC1 population was used to construct the linkage map and for QTL mapping of leaf length, leaf width, petiole length, and the ratio of leaf length to width in 2015 and 2019. Two genetic linkage maps were constructed by specific locus amplified fragment sequencing (SLAF-seq), and kompetitive allele specific PCR (KASP) technology, respectively using BC1 population in 2015. Based on the results of 2015, the specific linkage groups (LG) detected QTLs were generated using BC1 population in 2019. A total of 13 QTLs were detected for leaf-related traits, only five QTLs being repeatedly detected in multiple years or linkage maps. Interestingly, the major QTLs of leaf length, petiole length, and the ratio of leaf length to width were highly associated with the same SNP markers (KM3102838, KM1360385 and KM2191098). A major QTL of leaf width was mapped on chromosome 1 from 41.470−42.045 Mb. And 44 genes were identified within the region. Based on the GO analysis, these genes were significantly enriched on ribonuclease, lyase activity, phosphodiester bond hydrolysis process, and cell wall component, thus it might change cell size to determine leaves shape.

Conclusions

Five QTLs for leaf-related traits were repeatedly detected at least two years or linkage maps. The major QTLs of leaf length, petiole length, and the ratio of leaf length to width were mapped on the same loci. And three genes (Spo10792, Spo21018, and Spo21019) were identified as important candidate genes for leaf width.
Consultations and antibiotic treatment for urinary tract infections in Norwegian primary care 2006–2015, a registry-based study
Authors: Haugom Lars Emil Aga , Ruths Sabine , Emberland Knut Erik , Eliassen Knut Eirik Ringheim , Rortveit Guri , Wensaas Knut-Arne
Published: June 2021

Background

Extensive use of antibiotics and the resulting emergence of antimicrobial resistance is a major health concern globally. In Norway, 82% of antibiotics is prescribed in primary care and one in four prescriptions are issued for the treatment of urinary tract infections (UTI). The aim of this study was to investigate time trends in antibiotic treatment following a consultation for UTI in primary care.

Methods

For the period 2006–2015 we linked data from the Norwegian Registry for Control and Payment of Health Reimbursements on all patient consultations for cystitis and pyelonephritis in general practice and out-of-hours (OOH) services, and data from the Norwegian Prescription Database on all dispensed prescriptions of antibiotics.

Results

Altogether 2,426,643 consultations by attendance for UTI took place in the study period, of these 94.5% for cystitis and 5.5% for pyelonephritis. Of all UTI consultations, 79.4% were conducted in general practice and 20.6% in OOH services. From 2006 to 2015, annual numbers of cystitis and pyelonephritis consultations increased by 33.9 and 14.0%, respectively. The proportion of UTI consultations resulting in an antibiotic prescription increased from 36.6 to 65.7% for cystitis, and from 35.3 to 50.7% for pyelonephritis. These observed changes occurred gradually over the years. Cystitis was mainly treated with pivmecillinam (53.9%), followed by trimethoprim (20.8%). For pyelonephritis, pivmecillinam was most frequently used (43.0%), followed by ciprofloxacin (20.5%) and sulfamethoxazole-trimethoprim (16.3%). For cystitis, the use of pivmecillinam increased the most during the study period (from 46.1 to 56.6%), and for pyelonephritis, the use of sulfamethoxazole-trimethoprim (from 11.4 to 25.5%) followed by ciprofloxacin (from 18.2 to 23.1%).

Conclusions

During the 10-year study period there was a considerable increase in the proportion of UTI consultations resulting in antibiotic treatment. Cystitis was most often treated with pivmecillinam, and this proportion increased during the study period. Treatment of pyelonephritis was characterized by more use of broader-spectrum antibiotics, use of both sulfamethoxazole-trimethoprim and ciprofloxacin increased during the study period. These trends, indicative of enduring changes in consultation and treatment patterns for UTIs, will have implications for future antibiotic stewardship measures and policy.
Cancer incidence and mortality trends in France over 1990–2018 for solid tumors: the sex gap is narrowing
Authors: Defossez G. , Uhry Z. , Delafosse P. , Dantony E. , d’Almeida T. , Plouvier S. , Bossard N. , Bouvier A. M. , Molinié F. , Woronoff A. S. , Colonna M. , Grosclaude P. , Remontet L. , Monnereau A. ,   the French Network of Cancer Registries (FRANCIM), Amadeo Brice , Baldi Isabelle , Bara Simona , Bouvier Anne-Marie , Bouvier Véronique , Colonna Marc , Coureau Gaëlle , Cowppli-Bony Anne , Dabakuyo-Yonli Sandrine , d’Almeida Tania , Daubisse-Marliac Laetitia , Defossez Gautier , Delafosse Patricia , Desandes Emmanuel , Grosclaude Pascale , Guizard Anne-Valérie , Lacour Brigitte , Lapôtre-Ledoux Bénédicte , Hammas Karima , Molinié Florence , Nousbaum Jean-Baptiste , Plouvier Sandrine , Pouchieu Camille , Robaszkiewicz Michel , Schvartz Claire , Trétarre Brigitte , Velten Michel , Woronoff Anne-Sophie
Published: June 2021

Objective

To analyze trends in cancer incidence and mortality (France, 1990–2018), with a focus on men-women disparities.

Methods

Incidence data stemmed from cancer registries (FRANCIM) and mortality data from national statistics (CépiDc). Incidence and mortality rates were modelled using bidimensional penalized splines of age and year (at diagnosis and at death, respectively). Trends in age-standardized rates were summarized by the average annual percent changes (AAPC) for all-cancers combined, 19 solid tumors, and 8 subsites. Sex gaps were indicated using male-to-female rate ratios (relative difference) and male-to-female rate differences (absolute difference) in 1990 and 2018, for incidence and mortality, respectively.

Results

For all-cancers, the sex gap narrowed over 1990–2018 in incidence (1.6 to 1.2) and mortality (2.3 to 1.7). The largest decreases of the male-to-female incidence rate ratio were for cancers of the lung (9.5 to 2.2), lip - oral cavity - pharynx (10.9 to 3.1), esophagus (12.6 to 4.5) and larynx (17.1 to 7.1). Mixed trends emerged in lung and oesophageal cancers, probably explained by differing risk factors for the two main histological subtypes. Sex incidence gaps narrowed due to increasing trends in men and women for skin melanoma (0.7 to 1, due to initially higher rates in women), cancers of the liver (7.4 to 4.4) and pancreas (2.0 to 1.4). Sex incidence gaps narrowed for colon-rectum (1.7 to 1.4), urinary bladder (6.9 to 6.1) and stomach (2.7 to 2.4) driven by decreasing trends among men. Other cancers showed similar increasing incidence trends in both sexes leading to stable sex gaps: thyroid gland (0.3 to 0.3), kidney (2.2 to 2.4) and central nervous system (1.4 to 1.5).

Conclusion

In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends.
ADHD symptomatology of children with congenital heart disease 10 years after cardiac surgery: the role of age at operation
Authors: Czobor Nikoletta R. , Ocsovszky Zsófia , Roth György , Takács Szabolcs , Csabai Márta , Székely Edgár , Gál János , Székely Andrea , Konkolÿ Thege Barna
Published: June 2021

Background

The aim of the present study was to investigate the differences in ADHD symptomatology between healthy controls and children who underwent cardiac surgery at different ages.

Methods

Altogether, 133 children (54 patients with congenital heart disease undergoing first cardiac surgery under 3 years of age, 26 operated at the age of 3 or later, and 53 healthy controls) were examined. Patients completed the Youth Self Report (YSR), while their parents completed the Child Behaviour Checklist (CBCL) and the ADHD Rating Scale-IV.

Results

Children receiving surgery for the first time under the age of 3 years were more likely diagnosed with cyanotic type malformation and have undergone to a greater number of operations. However, ADHD symptoms of those treated surgically at or above 3 years of age were more severe than that of the control group or those who were treated surgically at a younger age. The control group and those treated surgically below the age of three did not differ across any of the ADHD symptom severity indicators.

Conclusions

The age at the time of cardiac surgery might be associated with later ADHD symptom severity – with lower age at operation associated with better outcomes. Further, adequately powered studies are needed to confirm these exploratory findings and investigate the moderators of this relationship.
Perspectives on COVID-19 testing policies and practices: a qualitative study with scientific advisors and NHS health care workers in England
Authors: Martindale Anne-Marie , Pilbeam Caitlin , Mableson Hayley , Tonkin-Crine Sarah , Atkinson Paul , Borek Aleksandra , Lant Suzannah , Gobat Nina , Solomon Tom , Sheard Sally
Published: June 2021

Background

As COVID-19 death rates have risen and health-care systems have experienced increased demand, national testing strategies have come under scrutiny. Utilising qualitative interview data from a larger COVID-19 study, this paper provides insights into influences on and the enactment of national COVID-19 testing strategies for health care workers (HCWs) in English NHS settings during wave one of the COVID-19 pandemic (March–August 2020). Through the findings we aim to inform learning about COVID-19 testing policies and practices; and to inform future pandemic diagnostic preparedness.

Methods

A remote qualitative, semi-structured longitudinal interview method was employed with a purposive snowball sample of senior scientific advisors to the UK Government on COVID-19, and HCWs employed in NHS primary and secondary health care settings in England. Twenty-four interviews from 13 participants were selected from the larger project dataset using a key term search, as not all of the transcripts contained references to testing. Framework analysis was informed by the non-adoption, abandonment, scale-up, spread, and sustainability of patient-facing health and care technologies implementation framework (NASSS) and by normalisation process theory (NPT).

Results

Our account highlights tensions between the communication and implementation of national testing developments; scientific advisor and HCW perceptions about infectiousness; and uncertainties about the responsibility for testing and its implications at the local level.

Conclusions

Consideration must be given to the implications of mass NHS staff testing, including the accuracy of information communicated to HCWs; how HCWs interpret, manage, and act on testing guidance; and the influence these have on health care organisations and services.
Zoledronic acid and teriparatide have a complementary therapeutic effect on aseptic loosening in a rabbit model
Authors: Wang Peng , Shang Guang-qian , Xiang Shuai , Zhang Hai-ning , Wang Ying-zhen , Xu Hao
Published: June 2021

Background

Revisions are mainly caused by wear debris-induced aseptic loosening. How to effectively suppress debris-induced periprosthetic osteolysis has become an urgent problem. Both zoledronic acid and teriparatide can increase the bone mass around prostheses and increase the stability of prostheses. A hypothesis was proposed: the combination of the two drugs may have a better treatment effect than the use of either drug alone.

Methods

We created a rabbit model to study the effect and mechanism of the combination of zoledronic acid and teriparatide in the treatment of aseptic loosening. Thirty-two adult male New Zealand white rabbits were selected and treated with TKA surgery, and a titanium rod prosthesis coated evenly with micrometre-sized titanium debris was implanted into the right femoral medullary cavity. All rabbits were randomized into four groups (control group = 8, zoledronic acid group = 8, teriparatide group = 8, and zoledronic acid + teriparatide group = 8). All the animals were sacrificed in the 12th week, and X-ray analyses, H&E staining, Goldner-Masson trichrome staining, von Kossa staining, and RT-PCR and Western blotting of the mRNA and protein of OCN, OPG, RANKL and TRAP5b in the interface membrane tissues around the prostheses were immediately carried out.

Results

The results shown that both zoledronic acid and teriparatide could inhibit debris-induced peri-prosthetic osteolysis and promote new bone formation. Zoledronic acid was more capable of inhibiting osteoclast activation and peri-prosthetic osteolysis, while teriparatide was more capable of promoting osteoblast function and peri-prosthetic bone integration.

Conclusion

This research confirmed that the combination of zoledronic acid and teriparatide could prevent and treat aseptic loosening of the prosthesis more effectively. However, the safety of this combination and the feasibility of long-term application have not been ensured, and the clinical application requires further experiments and clinical research support.
Clinical observation of two bone cement distribution modes after percutaneous vertebroplasty for osteoporotic vertebral compression fractures
Authors: Li Qiujiang , Long Xingxia , Wang Yinbin , Guan Tao , Fang Xiaomin , Guo Donggeng , Lv Jinhan , Hu Xuehua , Jiang Xiaocheng , Cai Lijun
Published: June 2021

Background

Current findings suggest that percutaneous vertebroplasty(PVP) is a suitable therapeutic approach for osteoporotic vertebral compression fractures (OVCFs). The present retrospective study aimed to investigate the differences in clinical efficacy and related complications between the two bone cement distribution modes.

Methods

We retrospectively reviewed the medical records of the patients with single-segment OVCFs who underwent bilateral percutaneous vertebroplasty. Patients were divided into blocky and spongy group according to the type of postoperative bone cement distribution. Clinical efficacy and related complications was compared between the two bone cement distribution modes on 24 h after the operation and last follow-up.

Results

A total of 329 patients with an average follow up time of 17.54 months were included. The blocky group included 131 patients, 109 females(83.2 %) and 22 males(16.8 %) with a median age of 72.69 ± 7.76 years, while the Spongy group was made up of 198 patients, 38 females(19.2 %) and 160 males(80.8 %) with a median age of 71.11 ± 7.36 years. The VAS and ODI after operation improved significantly in both two groups. The VAS and ODI in the spongy group was significantly lower than that in the blocky group, 24 h postoperatively, and at the last follow-up. There were 42 cases (12.8 %) of adjacent vertebral fractures, 26 cases (19.8 %) in the blocky group and 16 cases (8.1 %) in the spongy group. There were 57 cases (17.3 %) of bone cement leakage, 18 cases (13.7 %) in blocky group and 39 cases (19.7 %) in the spongy group. At 24 h postoperatively and at the last follow-up, local kyphosis and anterior vertebral height were significantly corrected in both groups, but gradually decreased over time, and the degree of correction was significantly higher in the spongy group than in the block group. The change of local kyphosis and loss of vertebral body height were also less severe in the spongy group at the last follow-up.

Conclusions

Compared with blocky group, spongy group can better maintain the height of the vertebral body, correct local kyphosis, reduce the risk of the vertebral body recompression, long-term pain and restore functions.
Support received by family members before, at and after an ill person’s death
Authors: O’Sullivan Anna , Alvariza Anette , Öhlén Joakim , Larsdotter Cecilia
Published: June 2021

Background

It is widely recognised, that family members are central to care of people with advanced illness, and that support should be provided to all family members in need thereof. The aim of this study was to investigate family members’ experiences of support received during the last three months of life, at the time of death and after the death of a person with advanced illness.

Methods

A retrospective cross-sectional survey design was employed, using the VOICES(SF) questionnaire and multiple methods for data analyses. The sample consisted of 485 bereaved family members (aged: 20–90 years old, 70% women) of people who died in hospital between August 2016-April 2017.

Results

Of the family members, 58,8% reported they had received enough help and support during the illness, whereas 30,2% had not. Family members’ comments about support during the illness were mainly related to care the ill person had or had not received, rather than about support they themselves received. Of all family members, 52,8% reported having had enough support at the time of the ill person’s death. Related to support at death, 14,6% reported that the imminence of death was not clear, which was described as having affected their opportunity to be with the dying person at the time of death. Of all, 25,2% had a follow-up conversation after the death, 48% did not and did not want to, and 21% had no follow-up conversation, but would have liked one. A follow-up conversation was described as helpful for the bereavement process, and disappointment was expressed when not receiving support after the death.

Conclusions

Family members’ experiences of support were partly related to whether the ill person’s care needs were fulfilled. Healthcare staff expressing empathy and respect in the care of dying people and their family members were important for family members’ experiences of support. Family members’ difficulty recognising that death was imminent and the importance of healthcare staff providing them with clear information were expressed in connection with support at death. Follow-up conversations were valued by family members, especially if with a healthcare professional who was present at the time of death.
Patient-controlled admissions to inpatient care: A twelve-month naturalistic study of patients with schizophrenia spectrum diagnoses and the effects on admissions to and days in inpatient care
Authors: Skott Maria , Durbeej Natalie , Smitmanis-Lyle Maria , Hellner Clara , Allenius Emelie , Salomonsson Sigrid , Lundgren Tobias , Jayaram-Lindström Nitya , Rozental Alexander
Published: June 2021

Background

Patients with schizophrenia spectrum diagnoses have a poor prognostic outlook and rates of recovery. Inpatient care is common, but the decision to initiate such care is not solely up to the patient but also influenced by the healthcare providers. Recent ideas about shared decision-making however challenges this idea. Patient-Controlled Admissions (PCA) refers to a care model where a patient signs a contract that allows the decision for admission into inpatient care to be transferred onto the patient.

Methods

In Region Stockholm’s public healthcare PCA was introduced to patients with schizophrenia spectrum diagnoses deemed to have the greatest care needs. Outcomes of a 12-month naturalistic within-group follow-up was analyzed using Wilcoxon signed-rank test.

Results

In total, 56 patients fulfilled the study’s inclusion criteria, with between 20 to 42 patients having complete data and being able to analyze statistically, depending on the variable. Number of admissions, inpatient days, number of involuntary admissions, and involuntary admission days decreased, but only significantly so for inpatient days, p < .01 (a mean reduction of 11.5 days). Neither self-rated well-being, as assessed using the EQ5D-3L, or a clinician-administered rating of overall health status, the Clinical Global Impression Scale, demonstrated a significant change.

Conclusions

The use of PCA points towards a trend in decreased hospitalization for patients with schizophrenia spectrum diagnoses, although this needs to be explored further in larger samples and over a longer follow-up.
Afterload-related reference values for myocardial work indices
Authors: Li Qiancheng , Wang Hui , Feng Haiyan , Wu Tingfan , Yang Ying , Gao Dongmei , Sun Lina
Published: June 2021

Background

The novel noninvasive pressure-strain loop (PSL) is a reliable tool that reflects myocardial work (MW). Systolic blood pressure (SBP) is the only independent factor for MW indices. However, afterload-related reference values have not been previously reported. The aim of the present study was to establish reference values for MW parameters by wide range SBP grading.

Methods

We prospectively selected healthy individuals and subjects with SBP ≥ 140 mmHg at the time of study without myocardial remodeling. MW parameters were collected and the reference values achieved were grouped by SBP in 10-mmHg.

Results

Significant differences were noted among the SBP-groups for global work index (GWI) and global constructive work (GCW). The majority of statistical comparisons of the differences in GWI and GCW were significant at each SBP-group. With SBP ranging from 90 to 189 mmHg, the parameters GWI and GCW tended to increase linearly with afterload. Overall, the global wasted work (GWW) tended to rise as SBP was increased, but not all of the differences noted in GWW were significant for each SBP-group. Global work efficiency (GWE) remained stable across all SBP-groups, with the exception of a slight drop noted when it exceeded 160 mmHg.

Conclusions

The amount of MW but not the work efficiency varied greatly according to the different afterload. This finding cannot be ignored during clinical research or diagnosis and afterload-related reference values are required to make a reasonable judgment on the myocardial function.
Phthalide derivative CD21 attenuates tissue plasminogen activator-induced hemorrhagic transformation in ischemic stroke by enhancing macrophage scavenger receptor 1-mediated DAMP (peroxiredoxin 1) clearance
Authors: Liu Dong-Ling , Hong Zhi , Li Jing-Ying , Yang Yu-Xin , Chen Chu , Du Jun-Rong
Published: June 2021

Background

Hemorrhagic transformation (HT) is a critical issue in thrombolytic therapy in acute ischemic stroke. Damage-associated molecular pattern (DAMP)-stimulated sterile neuroinflammation plays a crucial role in the development of thrombolysis-associated HT. Our previous study showed that the phthalide derivative CD21 attenuated neuroinflammation and brain injury in rodent models of ischemic stroke. The present study explored the effects and underlying mechanism of action of CD21 on tissue plasminogen activator (tPA)-induced HT in a mouse model of transient middle cerebral artery occlusion (tMCAO) and cultured primary microglial cells.

Methods

The tMCAO model was induced by 2 h occlusion of the left middle cerebral artery with polylysine-coated sutures in wildtype (WT) mice and macrophage scavenger receptor 1 knockout (MSR1−/−) mice. At the onset of reperfusion, tPA (10 mg/kg) was intravenously administered within 30 min, followed by an intravenous injection of CD21 (13.79 mg/kg/day). Neuropathological changes were detected in mice 3 days after surgery. The effect of CD21 on phagocytosis of the DAMP peroxiredoxin 1 (Prx1) in lysosomes was observed in cultured primary microglial cells from brain tissues of WT and MSR1−/− mice.

Results

Seventy-two hours after brain ischemia, CD21 significantly attenuated neurobehavioral dysfunction and infarct volume. The tPA-infused group exhibited more severe brain dysfunction and hemorrhage. Compared with tPA alone, combined treatment with tPA and CD21 significantly attenuated ischemic brain injury and hemorrhage. Combined treatment significantly decreased Evans blue extravasation, matrix metalloproteinase 9 expression and activity, extracellular Prx1 content, proinflammatory cytokine mRNA levels, glial cells, and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway activation and increased the expression of tight junction proteins (zonula occludens-1 and claudin-5), V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, and MSR1. MSR1 knockout significantly abolished the protective effect of CD21 against tPA-induced HT in tMCAO mice. Moreover, the CD21-induced phagocytosis of Prx1 was MSR1-dependent in cultured primary microglial cells from WT and MSR1−/− mice, respectively.

Conclusion

The phthalide derivative CD21 attenuated tPA-induced HT in acute ischemic stroke by promoting MSR1-induced DAMP (Prx1) clearance and inhibition of the TLR4/NF-κB pathway and neuroinflammation.
Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice
Authors: Shao Shuai , Xu Cheng-Bo , Chen Cheng-Juan , Shi Gao-Na , Guo Qing-Lan , Zhou Yu , Wei Ya-Zi , Wu Lei , Shi Jian-Gong , Zhang Tian-Tai
Published: June 2021

Background

Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative of 4,4′-dihydroxydibenzyl sulfoxide from a traditional Chinese medicine Gastrodia elata with anti-nociceptive effects, significantly alleviated neuropathic pain following intrathecal injection. Here, we aimed to investigate the underlying mechanisms of DS against neuropathic pain.

Methods

A chronic constrictive injury (CCI) mouse model of neuropathic pain induced by sciatic nerve ligation was performed to evaluate the effect of DS by measuring the limb withdrawal using Von Frey filament test. Immunofluorescence staining was used to assess the cell localizations and expressions of Iba-1, ASC, NLRP3, and ROS, the formation of autolysosome. The levels of NLRP3-related proteins (caspase-1, NLRP3, and IL-1β), mitophagy-related proteins (LC3, Beclin-1, and p62), and apoptosis-related proteins (Bcl-XL and Bax) were detected by Western blotting. The apoptosis of BV-2 cell and caspase activity were evaluated by flow cytometry.

Results

DS significantly alleviated the neuropathic pain by increasing the mechanical withdrawal threshold and inhibiting the activation of NLRP3 in CCI-induced model mice. Our findings indicated that DS promoted the mitophagy by increasing the LC3II and Beclin 1 and decreasing the levels of p62 protein in BV-2 cell. This is accompanied by the inhibition of NLRP3 activation, which was shown as inhibited the expression of NLRP3 in lysates as well as the secretion of mature caspase-1 p10 and IL-1β p17 in supernatants in cultured BV-2 microglia. In addition, DS could promote mitophagy-induced improvement of dysfunctional mitochondria by clearing intracellular ROS and restoring mitochondrial membrane potential.

Conclusion

Together, our findings demonstrated that DS ameliorate chronic neuropathic pain in mice by suppressing NLRP3 inflammasome activation induced by mitophagy in microglia. DS may be a promising therapeutic agent for chronic neuropathic pain.
Sexual and reproductive health of Syrian refugee adolescent girls: a qualitative study using focus group discussions in an urban setting in Lebanon
Authors: Korri Rayan , Hess Sabine , Froeschl Guenter , Ivanova Olena
Published: June 2021

Background

The war in Syria caused the forced displacement of millions of Syrians to neighboring countries. Lebanon is the host country with the largest overall number of Syrian refugees per capita. Adolescent refugee girls experience a unique level of vulnerability during human emergencies and are at increased risk of suffering from poor sexual and reproductive health (SRH) outcomes. We conducted an exploratory qualitative study to learn about the SRH perceptions and experiences of refugee adolescent girls living in Bourj Hammoud, an urban setting in Lebanon.

Methods

We employed a qualitative design with eight focus group discussions (FGDs) conducted with 40 Syrian Arab and Syrian Kurdish adolescent girls between January and March 2020. Every FGD consisted of five participants aged 13 to 17 years. A semi-structured guide was used covering multiple themes: menstruation, puberty, SRH awareness, and sexual harassment. FGDs were transcribed and analyzed using thematic analysis.

Findings

The participants discussed adolescent girls’ health and named six elements of good health, such as healthy activities and self-protection. The majority of the FGD participants reported a lack of awareness about menstruation when they experienced it for the first time and the social stigma associated with menstruation. When defining puberty, they indicated its social link to a girl’s readiness for marriage and her need to become cautious about sexual harassment. Most FGD participants had very poor knowledge of the female reproductive system. Mothers were the most approached persons to receive information on SRH issues; however, the girls indicated a wish to receive advice from specialists in a comfortable and private atmosphere. All the girls reported that either they themselves, or an acquaintance, had experienced some type of sexual harassment. The girls rarely reported those incidents due to fear of being blamed or subjected to mobility restrictions, or forced to drop out of school.

Conclusions

The findings show the refugee girls need for satisfactory knowledge on SRH issues and interventions to prevent sexual and gender-based violence that take into consideration the complexity of urban settings.
Adolescent sexual behaviour in a refugee setting in Uganda
Authors: Bukuluki Paul , Kisaakye Peter , Mwenyango Hadijah , Palattiyil George
Published: June 2021

Background

Children under 18 years old constituted more than half (52%) of the refugee population in 2017. Adolescent Sexual and reproductive health is an essential component of primary health care. Yet, not every refugee adolescent is able to access sexual and reproductive health services.

Methods

Using quantitative data from 356 refugee adolescents and qualitative data (17 in-depth interviews and nine key informant interviews), we examine refugee adolescent sexual behaviour in Bidibidi settlement—the largest refugee settlement in Uganda using a binary logistic regression model.

Results

The results show that 25% of refugee adolescents in Bidibidi refugee settlement had ever had sex. After controlling for all factors, results show that refugee adolescents aged 16–18 years (OR  =  3.47; 95% CI  =  1.09–10.94), males (OR  =  17.59; 95% CI  =  4.48–69.07), not in school (OR  =  14.57; 95% CI  =  2.20–96.35) were more likely to engage in sexual behaviour than their counterparts. Refugee adolescents who do not agree that a girl cannot get pregnant if she has sex while standing up (knowledge about getting pregnant) were significantly less associated with sexual behaviour (OR  =  0.30; 95% CI  =  0.10–0.85).

Conclusions

Results from this study show that keeping refugee adolescents in school and providing sexual and reproductive health information are likely to delay refugee adolescents’ engagement in sexual behaviour. Therefore, there is need to promote keeping refugee adolescents in school in order to improve sexual and reproductive health of adolescent refugees living in low-income countries such as Uganda.
The yield of HIV testing during pregnancy and postnatal period, Uganda, 2015–2018: analysis of surveillance data
Authors: Wibabara Yvette , Lukabwe Ivan , Kyamwine Irene , Kwesiga Benon , Ario Alex R. , Nabitaka Linda , Bulage Lilian , Harris Julie , Mudiope Peter
Published: June 2021

Background

Uganda has registered a reduction in new HIV infections among children in recent years. However, mother-to-child transmission of HIV still occurs, especially among pregnant women who present late. To eliminate this transmission, all HIV-positive pregnant women should be identified during antenatal HIV testing. We described women newly identified HIV-positive during pregnancy and postnatal period 2015–2018.

Methods

We extracted surveillance data for women identified as HIV-positive during pregnancy and the postnatal period reported through the Health Management Information System from 2015–2018. We calculated proportions newly positive at antenatal, labor, and postnatal periods nationally and at district levels. We disaggregated data into ‘tested early’ (during antenatal care) and ‘tested late’ (during labor or postnatal period) and calculated the proportion positive. We evaluated trends in these parameters at national and district levels.

Results

Overall, 8,485,854 mothers were tested for HIV during this period. Of these, 2.4% tested HIV-positive for the first time. While the total number of mothers tested increased from 1,327,022 in 2015 to 2,514,212 in 2018, the proportion testing HIV-positive decreased from 3.0% in 2015 to 1.7% in 2018 (43% decline over the study period, p < 0.001). Of 6,781,047 tested early, 2.2% tested HIV-positive. The proportion positive among those tested early dropped from 2.5% in 2015 to 1.7% in 2018. Of 1,704,807 tested late, 3.2% tested HIV-positive. The proportion positive among those tested late dropped from 5.2% in 2015 to 1.6% in 2018. At the district level, Kalangala District had the highest proportion testing positive at 13% (909/11,312) in 2015; this dropped to 5.2% (169/3278) in 2018.

Conclusion

The proportion of women newly testing HIV-positive during pregnancy and postnatal declined significantly during 2015–2018. A higher proportion of mothers who tested late vs early were HIV-positive. Failure to identify HIV early represents an increased risk of transmission. Ministry of Health should strengthen Elimination of Mother to Child Transmission (eMTCT) services to sustain this decrease through targeted interventions for poorly-performing districts. It should strengthen community-based health education on antenatal care and HIV testing and enhance the implementation of other primary prevention strategies targeting adolescents and young women.
Clinical value of assessing motor performance in postacute stroke patients
Authors: Flury D. , Massé F. , Paraschiv-Ionescu A. , Aminian K. , Luft A. R. , Gonzenbach R.
Published: June 2021

Background

Rehabilitative treatment plans after stroke are based on clinical examinations of functional capacity and patient-reported outcomes. Objective information about daily life performance is usually not available, but it may improve therapy personalization.

Objective

To show that sensor-derived information about daily life performance is clinically valuable for counseling and the planning of rehabilitation programs for individual stroke patients who live at home. Performance information is clinically valuable if it can be used as a decision aid for the therapeutic management or counseling of individual patients.

Methods

This was an observational, cross-sectional case series including 15 ambulatory stroke patients. Motor performance in daily life was assessed with body-worn inertial sensors attached to the wrists, shanks and trunk that estimated basic physical activity and various measures of walking and arm activity in daily life. Stroke severity, motor function and activity, and degree of independence were quantified clinically by standard assessments and patient-reported outcomes. Motor performance was recorded for an average of 5.03 ± 1.1 h on the same day as the clinical assessment. The clinical value of performance information is explored in a narrative style by considering individual patient performance and capacity information.

Results

The patients were aged 59.9 ± 9.8 years (mean ± SD), were 6.5 ± 7.2 years post stroke, and had a National Institutes of Health Stroke Score of 4.0 ± 2.6. Capacity and performance measures showed high variability. There were substantial discrepancies between performance and capacity measures in some patients.

Conclusions

This case series shows that information about motor performance in daily life can be valuable for tailoring rehabilitative therapy plans and counseling according to the needs of individual stroke patients. Although the short recording time (average of 5.03 h) limited the scope of the conclusions, this study highlights the usefulness of objective measures of daily life performance for the planning of rehabilitative therapies. Further research is required to investigate whether information about performance in daily life leads to improved rehabilitative therapy results.
Secretory carcinoma of the breast with multiple distant metastases in the brain and unfavorable prognosis: a case report and literature review
Authors: Tang Hongping , Zhong Lihua , Jiang Hongbing , Zhang Yan , Liang Guannan , Chen Guoyan , Xie Gui’e
Published: June 2021

Background

Secretory carcinoma of the breast is one of the rarest entities, accounting for less than 0.15 % of all infiltrating breast carcinomas. It has characteristic histopathological and molecular features and, in general, a more favorable prognosis. In this case report, we describe a local, advanced secretory carcinoma of the breast with aggressive course and an unfavorable outcome.

Case presentation

A hard, painless, and palpably bossed mass approximately 12.0 cm in diameter occupied most of the left breast of a 39-year-old woman with fixation to the overlying skin. Breast ultrasonography and magnetic resonance imaging (MRI) scans gave the same grading as BI-RADS IV. A needle biopsy was performed, and the pathological diagnosis was secretory carcinoma. Neoadjuvant chemotherapy (NAC) was then performed, after which ultrasonography and MRI scans revealed chemo-resistance of the tumor to NAC. Left breast mastectomy and axillary lymphadenectomy were subsequently performed. Tumor cells were triple-negative and positive for S-100 and periodic acid-Schiff (PAS) staining. Fluorescence in-situ hybridization (FISH) analysis indicated a fusion arrangement of the ETV6-NTRK3 gene. The patient developed multiple distant metastases in the brain and died of these metastases 19 months after initial diagnosis.

Conclusions

Secretory carcinomas of the breast have been described as a low-grade histologic subtype with a favorable prognosis. This case showed chemo-resistance to neoadjuvant chemotherapy, multiple distant metastases, and a final unfavorable outcome. Further research is needed to better understand the behavior and treatment of this rare tumor.
Video-assisted minimal access surgery for complicated mitral valve endocarditis, tricuspid valve insufficiency and progressive coronary disease after previous CABG - in the time of COVID-19: a case report
Authors: Andrási Terézia B. , Abudureheman Nunijiati , Glück Alannah , Vondran Maximilian , Dinges Gerhard , Talipov Ildar , Rastan Ardawan J.
Published: June 2021

Background

The timing for heart surgery following cerebral embolization after cardiac valve vegetation is vital to postoperative recovery being uneventful, additionally Covid-19 may negatively affect the outcome. Minimally invasive methods and upgraded surgical instruments maximize the benefits of surgery also in complex cardiac revision cases with substantial perioperative risk.

Case presentation

A 68 y.o. patient, 10 years after previous sternotomy for OPCAB was referred to cardiac surgery on the 10th postoperative day after neurosurgical intervention for intracerebral bleeding with suspected mitral valve endocarditis. Mitral valve vegetation, tricuspid valve insufficiency and coronary stenosis were diagnosed and treated by minimally invasive revision cardiac surgery on the 14th postoperative day after neurosurgery.

Conclusion

The present clinical case demonstrates for the first time that the minimally invasive approach via right anterior mini-thoracotomy can be safely used for concomitant complex mitral valve reconstruction, tricuspid valve repair and aorto-coronary bypass surgery, even as a revision procedure in the presence of florid endocarditis after recent neurosurgical intervention. The Covid-19 pandemic and prophylactic patient isolation slow down the efficacy of pulmonary weaning and mobilisation and prolong the need for ICU treatment, without adversely affecting long-term outcome.
Healthcare needs, expectations, utilization, and experienced treatment effects in patients with hereditary spastic paraplegia: a web-based survey in the Netherlands
Authors: Kerstens Hans C. J. W. , Van Lith Bas J. H. , Nijkrake Maarten J. , De Swart Bert J. M. , Van den Bemd Laura A. C. , Smeets Rob J. E. M. , Klemens Fheodoroff , Van de Warrenburg Bart P. C. , Van der Wees Philip J. , Geurts Alexander C. H.
Published: June 2021

Background

We aimed to identify healthcare needs, expectations, utilization, and the experienced treatment effects in a population of Dutch patients with hereditary spastic paraplegia (HSP).

Methods

We distributed an online questionnaire among 194 adult persons with HSP in the Netherlands, of which 166 returned a fully completed version. After applying predefined exclusion criteria, 109 questionnaires from persons with pure HSP were analysed.

Results

Healthcare needs and expectations were primarily focused on the relief of muscle stiffness and reduction of balance and gait impairments (65–80%), but many participants also expressed needs regarding relief of non-motor symptoms (e.g. pain, fatigue), emotional problems, impaired sleep and self-care capacity, and participation problems (> 60%). Remarkably, despite these frequent needs, relatively few participants (< 33%) expected to be able to improve in these additional domains. Rehabilitation physicians and physiotherapists were more frequently consulted than neurologists and occupational therapists, respectively. Physiotherapy was the most often proposed non-pharmacological intervention (85%), followed by orthopedic footwear (55%) and splints (28%). Approximately one third of the participants was never offered any pharmacological (spasmolytic) treatment. Spasmolytic oral drugs, injections, and intrathecal baclofen were given to 41%, 26%, and 5% of the participants, respectively. Independent of the type of pharmacological intervention, 35–46% of these participants experienced decreased spastiticy and improved general fitness. Other experienced effects differed per type of intervention.

Conclusions

Based on this web-based survey in the Netherlands, there seems to be ample room for improvement to meet and attune the healthcare needs and expectations of people with HSP concerning both their motor and non-motor symptoms and functional limitations. In addition, the provision of adequate information about non-pharmacological and pharmacological interventions seems to be insufficient for many patients to allow shared decision making. These conclusions warrant a more pro-active attitude of healthcare providers as well as an interdisciplinary approach for a substantial proportion of the HSP population, also involving professionals with a primary occupational and/or psychosocial orientation.
Causative variant profile of collagen VI-related dystrophy in Japan
Authors: Inoue Michio , Saito Yoshihiko , Yonekawa Takahiro , Ogawa Megumu , Iida Aritoshi , Nishino Ichizo , Noguchi Satoru
Published: June 2021

Background

Collagen VI-related dystrophy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy. This disease is caused by causative variants in COL6A1, COL6A2, or COL6A3. Most reported causative variants are de novo; therefore, to identify possible associated causative variants, comprehensive large cohort studies are required for different ethnicities.

Methods

We retrospectively reviewed clinical information, muscle histology, and genetic analyses from 147 Japanese patients representing 130 families, whose samples were sent for diagnosis to the National Center of Neurology and Psychiatry between July 1979 and January 2020. Genetic analyses were conducted by gene-based resequencing, targeted panel resequencing, and whole exome sequencing, in combination with cDNA analysis.

Results

Of a total of 130 families with 1–5 members with collagen VI-related dystrophy, 120 had mono-allelic and 10 had bi-allelic variants in COL6A1, COL6A2, or COL6A3. Among them, 60 variants were in COL6A1, 57 in COL6A2, and 23 in COL6A3, including 37 novel variants. Mono-allelic variants were classified into four groups: missense (69, 58%), splicing (40, 33%), small in-frame deletion (7, 6%), and large genomic deletion (4, 3%). Variants in the triple helical domains accounted for 88% (105/120) of all mono-allelic variants.

Conclusions

We report the causative variant profile of a large set of Japanese cases of collagen VI-related dystrophy. This dataset can be used as a reference to support genetic diagnosis and variant-specific treatment.
The parabrachial-to-amygdala pathway provides aversive information to induce avoidance behavior in mice
Authors: Ito Mariko , Nagase Masashi , Tohyama Suguru , Mikami Kaori , Kato Fusao , Watabe Ayako M.
Published: June 2021

The neuronal circuitry for pain signals has been intensively studied for decades. The external lateral parabrachial nucleus (PB) was shown to play a crucial role in nociceptive information processing. Previous work, including ours, has demonstrated that stimulating the neuronal pathway from the PB to the central region of the amygdala (CeA) can substitute for an actual pain signal to drive an associative form of threat/fear memory formation. However, it is still unknown whether activation of the PB–CeA pathway can directly drive avoidance behavior, escape behavior, or only acts as strategic freezing behavior for later memory retrieval. To directly address this issue, we have developed a real-time Y-maze conditioning behavioral paradigm to examine avoidance behavior induced by optogenetic stimulation of the PB–CeA pathway. In this current study, we have demonstrated that the PB–CeA pathway carries aversive information that can directly trigger avoidance behavior and thereby serve as an alarm signal to induce adaptive behaviors for later decision-making.