bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of late-life depression with cognitive impairment: evidence from a cross-sectional study among older adults in India
Authors: Muhammad T. , Meher Trupti
Published: June 2021

Background

Late-life depression (LLD) is considered as a prodrome to dementia and plays a major role in the development of long-term cognitive disabilities. We aimed to estimate the prevalence and correlates of LLD and cognitive impairment and to explore their associations among older adults in India.

Methods

Data for this study was derived from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017-18). The total sample included 31,464 (15,098 male and 16,366 female) older individuals aged 60 years and above. Cognitive impairment measured from various domains derived from the cognitive module of the Health and Retirement Study (HRS), and major depression measured by the CIDI-SF (Composite International Diagnostic Interview- Short Form) were the outcome variables. Descriptive, bivariate, and multivariable analyses were performed to fulfill the objectives of the study.

Results

The overall prevalence of LLD and cognitive impairment for the current sample was 8.7% and 13.7 % respectively. Among older individuals who have rated their health status as poor were 2.59 times more likely to suffer from LLD [OR: 2.59, CI: 2.24–2.99] as compared to their counterparts. The older adults who had difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL) were 74% and 69 % more likely to suffer from LLD. Similarly, older adults who were depressed had higher odds of cognitive impairment [OR: 1.22, CI: 1.01–1.48] compared to their counterparts. Also, older adults who were depressed and belonged to rural areas were 2.58 times [AOR: 2.58, CI: 1.95–3.41] more likely to be cognitively impaired than those who were not depressed and resided in urban areas.

Conclusions

Depression is linked to an increased risk of cognitive decline and dementia; therefore, failing to diagnose and treat LLD in later life may have significant health implications. Moreover, treatment under the care of a cognitive neurologist or geriatric psychiatrist is recommended for people with LLD and cognitive disability due to both the disorders' complex existence.
Case report: first symptomatic Candidatus Neoehrlichia mikurensis infection in Slovenia
Authors: Lenart Mitja , Simoniti Miha , Strašek-Smrdel Katja , Špik Vesna Cvitković , Selič-Kurinčič Tanja , Avšič-Županc Tatjana
Published: June 2021

Background

Candidatus Neoehrlichia mikurensis (CNM) is an emerging tick-born pathogen and usually causes symptomatic infection only in immunocompromised patients. Apart from one described case found in the literature where cultivation was successful, all cases so far were diagnosed by using broad-range 16S rDNA PCR.

Case presentation

Our patient presented with a prolonged febrile state of unknown origin. Clinical presentation, extensive medical workup and classic microbiologic testing were non-conclusive. Several infectious agents and other causes for the febrile state were excluded. In the end, a broad-range 16S rDNA PCR was to be performed to confirm the diagnosis of CNM infection. Treatment was successful with doxycycline.

Conclusions

Due to the obscurity of the pathogen, diagnostic workup in CNM is prolonged and challenging. More awareness is need about this emerging infectious disease in countries with high prevalence of tick-borne diseases as standard microbiological methods are not successful in confirming the diagnosis.
Short-term survival and safety of apatinib combined with oxaliplatin and S-1 in the conversion therapy of unresectable gastric cancer
Authors: Ye Zaisheng , Zeng Yi , Wei Shenghong , Wang Yi , Lin Zhitao , Chen Shu , Wang Zhiwei , Chen Shanshan , Chen Luchuan
Published: June 2021

Background

We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer.

Patients and methods

Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430 (01/12/2016–01/12/2022).

Results

A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%).

Conclusion

Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.
Hydrocele in a case of atypical Kawasaki disease: case report and review of diagnostic criteria
Authors: Tan Y. R. L. , Chow C.-T. C. , Ganesan I. , Leow H. M. E.
Published: June 2021

Background

Kawasaki Disease (KD) is a self-limiting vasculitis of unknown etiology. Although there are well-recognized clinical features associated with classic KD, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete KD.

Case presentation

We report on a child who was initially treated for Escherichia coli left pyelonephritis and Influenza A and Rhinovirus / Enterovirus upper respiratory tract infection. The child developed an acute hydrocele and a maculopapular rash during the illness course, which prompted further evaluation for concomitant atypical KD, although there were no other physical signs suggestive of classic KD at the time. Subsequent diagnosis of atypical KD was made with confirmation on echocardiography, with timely administration of intravenous immunoglobulin.

Conclusions

Although there are well recognized clinical features associated with classic Kawasaki Disease, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete Kawasaki Disease. This case report highlights the importance of considering a diagnosis of KD in a child with prolonged fever and unexplainable symptoms suggestive of inflammation, in this case, the rare presentation of an acute hydrocele. We recommend that for any child with prolonged unexplained fever, Kawasaki Disease should be considered.

Trial registration

Not applicable.
The psychotropic effect of vitamin D supplementation on schizophrenia symptoms
Authors: Neriman Aras , Hakan Yilmaz , Ozge Ucuncu
Published: June 2021

Background

Schizophrenia is a multifactorial disease involving interactions between genetic and environmental factors. Vitamin D has recently been linked to many metabolic diseases and schizophrenia. Vitamin D plays essential roles in the brain in the context of neuroplasticity, neurotransmitter biosynthesis, neuroprotection, and neurotransmission. Vitamin D receptors are demonstrated in most brain regions that are related to schizophrenia. However, very few studies in the literature examine the effects of 25-hydroxyvitamin D (25OHD) on schizophrenia symptoms.

Methods

This study aimed to examine the effects of vitamin D replacement on positive, negative, and cognitive symptoms of schizophrenia. Serum 25OHD levels of 52 schizophrenia patients were measured. SANS and SAPS were used to evaluate the severity of schizophrenia symptoms, and the Wisconsin Card Sorting Test: CV4 was used for cognitive assessment. The study was completed with 40 patients for various reasons. The patients whose serum 25OHD reached optimal levels after vitamin D replacement were reevaluated with the same scales in terms of symptom severity. The SPSS 25 package program was used for statistical analysis. The Independent-Samples t-test was used to examine the relationship between the variables that may affect vitamin D levels and the vitamin D level and to examine whether vitamin D levels had an initial effect on the scale scores.

Results

The mean plasma 25OHD levels of the patients was 17.87 ± 5.54. A statistically significant relationship was found only between the duration of sunlight exposure and 25 OHD level (p < 0.05). The mean SANS and SAPS scores of the participants after 25OHD replacement (23.60 ± 15.51 and 7.78 ± 8.84, respectively) were statistically significantly lower than mean SANS and SAPS scores before replacement (51.45 ± 17.96 and 18.58 ± 15.59, respectively) (p < 0.001 for all). Only the total attention score was significantly improved after replacement (p < 0.05).

Conclusion

The data obtained from our study suggest that eliminating the 25OHD deficiency together with antipsychotic treatment can improve the total attention span and positive and negative symptoms in schizophrenia. The 25OHD levels should be regularly measured, replacement should be started when necessary, and the patients should be encouraged to get sunlight exposure to keep optimal 25OHD levels.
Emotional responses and perceived stressors of frontline medical staffs in case of COVID-19 treatment centers and obstetrics emergency in Ethiopia
Authors: Kebede Mebratu Abraha , Demissie Dereje Bayissa , Guddu Dessalegn Kenay , Haile Michael Temane , Bitew Zebenay Workneh , Muleta Mahteme Bekele
Published: June 2021

Background

the rapid spread of COVID-19, its lethality in severe cases and the absence of specific medicine poses a huge threat to human life and health, as well as huge impact on the mental health. Facing this critical situation, health care workers on the front line who are directly involved in the diagnosis, treatment, and care of patients with COVID-19 are at risk of developing psychological distress and other mental health symptoms including emotional disturbance.

Objective

the aim of this study will be to assess the current state of emotional responses and perceived stressors of frontline medical staffs in case of Addis Ababa COVID-19 Treatment Centers and obstetrics emergency and abortion care, Ethiopia 2020.

Methods

Hospital based comparative cross-section study design was conducted by using self-administered questionnaire survey from June 1st to 30th of 2020 among 133 and 266 frontline medical staffs from obstetric emergency and abortion care clinic and COVID-19 treatment centers respectively. The data were collected after getting written consent from each participant and it entered into the computer using Epi-data version 7, then exported to SPSS version 20 for further analysis. Descriptive analysis was done using frequencies & percent. All independent determinants with P-value < 0.05 were used to identify important predictors of emotional responses and perceived stressors.

Result

A total of 399 frontline medical staffs were included in the study. The mean age of the respondents of those who were working in obstetrics emergency and abortion care clinic was 27.47 (SD, 3.46) years and it was 28.12 (SD, 4.09) years for the other groups. This study revealed that, 72.9 and 5.6% of the study participant from obstetrics emergency and abortion clinic and COVID-19 treatment centers had a positive emotional response, respectively. Factors such as having a low level of motivational factors (AOR 2.78, 95% CI (1.13, 6.84)), being a nurse (AOR 10.53, 95% CI (1.31, 85.26)) and working at triage (AOR 8.61, 95% CI (1.15, 64.81))) had statistically significant association with negative emotional response.

Conclusion

The current study revealed that a high proportion of front line a negative emotional responses had negative emotional response. Further, almost all of the medical staffs working in COVID-19 treatment centers and at obstetrics emergency and abortion care unit had perceived the outbreak related stressors. So, providing comprehensive psychological support is warranted for health care providers working in such kinds of department or units.
Effects of hormone replacement therapy on glucose and lipid metabolism in peri- and postmenopausal women with a history of menstrual disorders
Authors: Li Saisai , Ma Linjuan , Song Yang , Zheng Jiehong , Cai Yuqun , Xu Hong , Chen Peiqiong , Xu Wenxian , Huang Yizhou , Qi Tongyun , Li Chunming , Chu Ketan , Lan Yibing , Xu Ling , Zhou Jianhong
Published: June 2021

Background

Previous studies have indicated that women with a history of menstrual disorders have an increased risk of metabolic and cardiovascular diseases. This has been attributed to the high proportion of polycystic ovary syndrome (PCOS) among this group. The favorable effects of hormone replacement therapy (HRT) on serum lipid profiles and glucose homeostasis in postmenopausal women is widely accepted. Whether HRT can also show positive effects on metabolic homeostasis in menopausal women with prior menstrual disorders (a putative PCOS phenotype) has not been reported yet. The aim of the study was to compare the effects of HRT on glucose and lipid metabolism in peri- and postmenopausal women with prior menstrual disorders and controls who did not have prior menstrual disorders.

Methods

A retrospective multicenter study was conducted including 595 peri- and postmenopausal women who received HRT at four hospitals in the Zhejiang Province from May 31, 2010 to March 8, 2021. Participants were divided into the Normal menstruation group and the Menstrual disorders group according to their prior usual menstrual cycle pattern. Glucose and lipid metabolism indicators were assessed at baseline and after HRT. The results were compared between and within the groups, and data from peri- and postmenopausal women were analyzed separately.

Results

HRT significantly decreased fasting insulin and homeostasis model assessment of insulin resistance in perimenopausal users, and fasting plasma glucose levels in postmenopausal users with prior menstrual disorders, compared with baseline. Furthermore, HRT decreased low-density lipoprotein cholesterol, total cholesterol, fasting insulin, fasting plasma glucose and homeostasis model assessment of insulin resistance in both peri- and postmenopausal controls, compared with baseline. Nevertheless, no significant differences were observed in any of the glucose or lipid metabolism indicators at baseline and follow-up, as well as changes from baseline levels between menopausal women with and without prior menstrual disorders.

Conclusions

HRT shows more obvious within-group improvements in glucose and lipid metabolism in controls, but there is no significant between-group difference. Further prospective studies are required for confirmation.
Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation
Authors: Xu Chang , Zhou Xiaoqin , Zorzela Liliane , Ju Ke , Furuya-Kanamori Luis , Lin Lifeng , Lu Cuncun , Musa Omran A. H. , Vohra Sunita
Published: June 2021

Backgrounds

Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events.

Methods

We conducted a survey of systematic reviews published in two periods: January 1, 2015, to January 1, 2020, and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews.

Results

We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant (proportion difference=−0.09, 95% CI −0.21 to 0.03, p = 0.12).

Conclusion

Systematic review authors routinely treated studies with zero-events in both arms as “non-informative” carriers and excluded them from their reviews. Whether studies with no events are “informative” or not largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.
Clinically-diagnosed vitamin deficiencies and disorders in the entire United States military population, 1997–2015
Authors: Knapik Joseph J. , Farina Emily K. , Fulgoni Victor L. , Lieberman Harris R.
Published: June 2021

Background

This study examined incidence rates, temporal trends, and demographic factors associated with vitamin deficiencies/disorders in all United States military personnel from 1997 to 2015 (mean N = 1,382,266/year).

Methods

Employing an ecological study design, the Defense Medical Epidemiological Database and specific International Classification of Diseases codes were used to determine incidence rates for clinically-diagnosed vitamin deficiencies/disorders. Associations with demographic factors were examined.

Results

The overall incidence rate of vitamin deficiencies/disorders was 92.7 cases/100,000 person-years (p-yr). Highest rates were for vitamin D (53.7 cases/100,000 p-yr), other B-complex vitamins (20.2 cases, 100,000 p-yr), vitamin B12 anemia (7.6 cases/100,000 p-yr), deficiencies of “other vitamins” (5.9 cases/100,000 p-yr), and vitamin A (2.5 cases/100,000 p-yr). Thiamin, riboflavin, niacin, pyridoxine, folate, vitamin C, and vitamin K deficiencies and hypervitaminoses A and D had < 1 case/100,000 p-yr. Rates for vitamin D, other B-complex, “other vitamin”, and thiamin deficiencies increased over time, while vitamin A and C deficiencies decreased. Women had higher incidence rates for all examined deficiencies/ disorders except niacin and vitamin C. Incidence rates rose with age in 8 of 15 deficiency/disorder categories and blacks had higher incidence rates in 9 of 15 deficiency/disorder categories.

Conclusions

The overall rate of clinically-diagnosed vitamin deficiencies and disorders was low but higher in women and minority subgroups. As for most illnesses, the diagnosed incidence of such disorders may be an underestimate of the actual incidence. These findings can guide clinical decision making with regard to testing for nutritional deficiencies and delivering public health information to at risk populations.

Clinical trial registration

(No. ISRCTN58987177). Registration date 9 October 2019.
Aspergillosis of central nervous system in patients with leukemia and stem cell transplantation: a systematic review of case reports
Authors: Shariati Aref , Didehdar Mojtaba , Rajaeih Shahin , Moradabadi Alireza , Ghorbani Mohammad , Falahati Vahid , Chegini Zahra
Published: June 2021

Background

Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT).

Methods

Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline.

Results

Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%).

Conclusion

CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.
Risk factors of thrombosis in Chinese subjects with acute promyelocytic leukemia
Authors: Zhang Xueya , Guo Xizhe
Published: June 2021

Background

Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia Thrombosis is at increased risk complication in patients with this disease. However, the risk factors of thrombosis related to Chinese APL patients are not fully understood.

Methods

In this study, clinical and laboratory data of 44 consecutively Chinese APL patients were collected and analyzed.

Results

One arterial and 6 venous thrombosis occurred in 44 patients, including 22 males and 22 females, with a median age of 44 years (range from 18 to 74 years). The ratio of male and female gender, age, white blood cell count, hemoglobin, platelets, disease risk stratification, CD2, Khorana score, differentiation syndrome (DS) and gene mutation related to prognosis of APL, including DNMT3A, TET2, IDH1, IDH2, NRAS and ASXL1 in the two groups with and without thrombosis were not statistically significant. The detection rate of PAI-1 genotype 4G4G was 71.4% (5/7) in 7 patients with thrombosis, while the detection rate of PAI-1 genotype 4G4G in 37 patients without thrombosis was 8.1% (3/37). The differences between the two groups in WT-1 (P = 0.01), PAI-1 4G4G (P = 0.0009), bcr3 (P = 0.027), CD15 (P = 0.005), and FLT3-ITD mutation (P = 0.0008) were statistically significant. Using multivariate analysis, the risk factors of venous thrombosis in APL were CD15 (P = 0.043), PAI-1 4G4G (P = 0.009), WT-1 (P = 0.043) and FLT3/ITD (P = 0.013), respectively.

Conclusion

Our results suggested the PAI-1 gene 4G4G type, CD15, WT-1 and FLT3-ITD mutations excluding DNMT3A, TET2, IDH1/2, NRAS and ASXL1 are risk factors of thrombotic events in Chinese APL patients.
Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis
Authors: Wang Hui-Na , Ji Kunmei , Zhang Li-Na , Xie Chu-Chu , Li Wei-Yong , Zhao Zhen-Fu , Chen Jia-Jie
Published: June 2021

Background

Activator protein-1 (AP1), a c-Fos–JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (FcεRI) binding. This study examined c-Fos involvement in MC activation and tested the effects of the c-Fos/AP1 inhibitor T-5224 on MCs activation and allergic responses.

Methods

In vitro studies were conducted with two MC model systems: rat basophilic leukemia cells (RBLs) and mouse bone marrow derived mast cells (BMMCs). MC degranulation and effector functions were examined with β-hexosaminidase release and cytokine secretion assays. c-Fos/AP1 was inhibited with T-5224. c-Fos activity was suppressed with short hairpin RNA targeting c-Fos (shFos). In vivo immune responses were evaluated in passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models, as well as in an oxazolone (OXA)-induced model of atopic dermatitis, a common allergic disease.

Results

c-Fos expression was elevated transcriptionally and translationally in IgE-stimulated MCs. c-Fos binding of the Egr1 (early growth response 1) promoter upregulated Egr1 transcription, leading to production of interleukin (IL)4. T-5224 reduced FcεRI-mediated MC degranulation (evidenced by β-hexosaminidase activity and histamine levels) and diminished EGR1 and IL4 expression. T-5224 attenuated IgE-mediated allergic responses in PCA and ASA models, and it suppressed MC-mediated atopic dermatitis in mice.

Conclusion

IgE binding can activate MCs via a c-Fos/Egr1/IL-4 axis. T-5224 suppresses MC activation in vitro and in vivo and thus represents a promising potential strategy for targeting MC activation to treat allergic diseases.
Microglia RAGE exacerbates the progression of neurodegeneration within the SOD1G93A murine model of amyotrophic lateral sclerosis in a sex-dependent manner
Authors: MacLean Michael , Juranek Judyta , Cuddapah Swetha , López-Díez Raquel , Ruiz Henry H. , Hu Jiyuan , Frye Laura , Li Huilin , Gugger Paul F. , Schmidt Ann Marie
Published: June 2021

Background

Burgeoning evidence highlights seminal roles for microglia in the pathogenesis of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). The receptor for advanced glycation end products (RAGE) binds ligands relevant to ALS that accumulate in the diseased spinal cord and RAGE has been previously implicated in the progression of ALS pathology.

Methods

We generated a novel mouse model to temporally delete Ager from microglia in the murine SOD1G93A model of ALS. Microglia Ager deficient SOD1G93A mice and controls were examined for changes in survival, motor function, gliosis, motor neuron numbers, and transcriptomic analyses of lumbar spinal cord. Furthermore, we examined bulk-RNA-sequencing transcriptomic analyses of human ALS cervical spinal cord.

Results

Transcriptomic analysis of human cervical spinal cord reveals a range of AGER expression in ALS patients, which was negatively correlated with age at disease onset and death or tracheostomy. The degree of AGER expression related to differential expression of pathways involved in extracellular matrix, lipid metabolism, and intercellular communication. Microglia display increased RAGE immunoreactivity in the spinal cords of high AGER expressing patients and in the SOD1G93A murine model of ALS vs. respective controls. We demonstrate that microglia Ager deletion at the age of symptomatic onset, day 90, in SOD1G93A mice extends survival in male but not female mice. Critically, many of the pathways identified in human ALS patients that accompanied increased AGER expression were significantly ameliorated by microglia Ager deletion in male SOD1G93A mice.

Conclusions

Our results indicate that microglia RAGE disrupts communications with cell types including astrocytes and neurons, intercellular communication pathways that divert microglia from a homeostatic to an inflammatory and tissue-injurious program. In totality, microglia RAGE contributes to the progression of SOD1G93A murine pathology in male mice and may be relevant in human disease.
How many trials are needed in kinematic analysis of reach-to-grasp?—A study of the drinking task in persons with stroke and non-disabled controls
Authors: Frykberg Gunilla Elmgren , Grip Helena , Alt Murphy Margit
Published: June 2021

Background

Kinematic analysis of the 3D reach-to-grasp drinking task is recommended in stroke rehabilitation research. The number of trials required to reach performance stability, as an important aspect of reliability, has not been investigated for this task. Thus, the aims of this study were to determine the number of trials needed for the drinking task to reach within-session performance stability and to investigate trends in performance over a set of trials in non-disabled people and in a sample of individuals with chronic stroke. In addition, the between-sessions test–retest reliability in persons with stroke was established.

Methods

The drinking task was performed at least 10 times, following a standardized protocol, in 44 non-disabled and 8 post-stroke individuals. A marker-based motion capture system registered arm and trunk movements during 5 pre-defined phases of the drinking task. Intra class correlation statistics were used to determine the number of trials needed to reach performance stability as well as to establish test–retest reliability. Systematic within-session trends over multiple trials were analyzed with a paired t-test.

Results

For most of the kinematic variables 2 to 3 trials were needed to reach good performance stability in both investigated groups. More trials were needed for movement times in reaching and returning phase, movement smoothness, time to peak velocity and inter-joint-coordination. A small but significant trend of improvement in movement time over multiple trials was demonstrated in the non-disabled group, but not in the stroke group. A mean of 3 trials was sufficient to reach good to excellent test–retest reliability for most of the kinematic variables in the stroke sample.

Conclusions

This is the first study that determines the number of trials needed for good performance stability (non-disabled and stroke) and test–retest reliability (stroke) for temporal, endpoint and angular metrics of the drinking task. For most kinematic variables, 3–5 trials are sufficient to reach good reliability. This knowledge can be used to guide future kinematic studies.
Consanguinity-based analysis of exome sequencing yields likely genetic causes in patients with inherited retinal dystrophy
Authors: Shen Ren-Juan , Wang Jun-Gang , Li Yang , Jin Zi-Bing
Published: June 2021

Background

Consanguineous families have a relatively high prevalence of genetic disorders caused by bi-allelic mutations in recessive genes. This study aims to evaluate the effectiveness and efficiency of a consanguinity-based exome sequencing approach to capturing genetic mutations in inherited retinal dystrophy families with consanguineous marriages.

Methods

Ten unrelated consanguineous families with a proband affected by inherited retinal dystrophy were recruited in this study. All participants underwent comprehensive ophthalmic examinations. Whole exome sequencing was performed, followed by a homozygote-prior strategy to rapidly filter disease-causing mutations. Bioinformatic prediction of pathogenicity, Sanger sequencing and co-segregation analysis were carried out for further validation.

Results

In ten consanguineous families, a total of 10 homozygous mutations in 8 IRD genes were identified, including 2 novel mutations, c.1654_1655delAG (p. R552Afs*5) in gene FAM161A in a patient diagnosed with retinitis pigmentosa, and c.830T > C (p.L277P) in gene CEP78 in a patient diagnosed with cone and rod dystrophy.

Conclusion

The genetic etiology in consanguineous families with IRD were successfully identified using consanguinity-based analysis of exome sequencing data, suggesting that this approach could provide complementary insights into genetic diagnoses in consanguineous families with variant genetic disorders.
TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
Authors: Miao Chenkui , Liang Chao , Li Pu , Liu Bianjiang , Qin Chao , Yuan Han , Liu Yiyang , Zhu Jundong , Cui Yankang , Xu Aiming , Wang Shangqian , Su Shifeng , Li Jie , Shao Pengfei , Wang Zengjun
Published: June 2021

Background

Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive.

Methods

RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism.

Results

We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications.

Conclusions

Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies.
MdFRK2-mediated sugar metabolism accelerates cellulose accumulation in apple and poplar
Authors: Su Jing , Zhang Chunxia , Zhu Lingcheng , Yang Nanxiang , Yang Jingjing , Ma Baiquan , Ma Fengwang , Li Mingjun
Published: June 2021

Background

Cellulose is not only a common component in vascular plants, but also has great economic benefits for paper, wood, and industrial products. In addition, its biosynthesis is highly regulated by carbohydrate metabolism and allocation in plant. MdFRK2, which encodes a key fructokinase (FRK) in apple, showed especially high affinity to fructose and regulated carbohydrate metabolism.

Results

It was observed that overexpression ofMdFRK2in apple decreased sucrose (Suc) and fructose (Fru) with augmented FRK activity in stems, and caused the alterations of many phenotypic traits that include increased cellulose content and an increase in thickness of the phloem region. To further investigate the involved mechanisms, we generatedFRK2-OE poplar lines OE#1, OE#4 and OE#9 and discovered (1) that overexpression ofMdFRK2resulted in the huge increased cellulose level by shifting the fructose 6-phosphate or glucose 6-phsophate towards UDPG formation, (2) a direct metabolic pathway for the biosynthesis of cellulose is that increased cleavage of Suc into UDP-glucose (UDPG) for cellulose synthesis via the increased sucrose synthase (SUSY) activity and transcript levels ofPtrSUSY1, (3) that the increased FRK activity increases the sink strength overall so there is more carbohydrate available to fuel increased cambial activity and that resulted in more secondary phloem. These results demonstrated thatMdFRK2overexpression would significantly changes the photosynthetic carbon flux from sucrose and hexose to UDPG for increased cellulose synthesis.

Conclusions

The present data indicated thatMdFRK2overexpression in apple and poplar changes the photosynthetic carbon flux from sucrose and hexose to UDPG for stem cellulose synthesis. A strategy is proposed to increase cellulose production by regulating sugar metabolism as a whole.
Geographic distribution of the cagA, vacA, iceA, oipA and dupA genes of Helicobacter pylori strains isolated in China
Authors: Xue Zhijing , Yang Hong , Su Dongxing , Song Xiangfeng , Deng Xin , Yu Changhong , Sun Chunhua , He Lihua , You Yuanhai , Gong Yanan , Fan Dongjie , Sun Lu , Han Xiurui , Fan Ruyue , Zhang Maojun , Yan Xiaomei , Qian Jiaming , Zhang Jianzhong
Published: June 2021

Background

There are geographic variations in the genotypes of Helicobacter pylori (H. pylori) cagA, vacA, iceA, oipA and dupA. The aim of the study was to investigate the distribution of these genotypes among H. pylori strains from five regions of China and their association with clinical outcomes.

Materials and methods

Gastric biopsy specimens were obtained from 348 patients with different gastrointestinal diseases in the five regions of China. The regional distribution was 89 patients from Shandong, 91 from Guangxi, 57 from Hunan, 58 from Qinghai and 53 from Heilongjiang. The presence of cagA, vacA, iceA, oipA and dupA genotypes was determined by polymerase chain reaction (PCR) from H. pylori DNA.

Results

A total of 269 H. pylori isolates were obtained, of which 74 isolates were from Shandong, 78 from Guangxi, 46 from Hunan, 33 from Qinghai and 38 from Heilongjiang. The cagA-positive status was predominant in the five regions. The predominant vacA genotypes were s1c (73.4%), m2 (70.6%) and i1 (92.9%). In strains from Shandong, s1a and m1 were dominant. By contrast, s1c was dominant in Guangxi and i1 was dominant in Hunan and Heilongjiang. The prevalence of m2 subtype in Qinghai (78.8%) was significantly higher than that in other regions (P < 0.05). The predominant iceA genotype was iceA1 and the frequency of iceA1 was significantly more prevalent in Hunan than in other regions (P < 0.05). The oipA status “on” gene was more frequent in Shandong (91.9%) and Guangxi (91%) than in Heilongjiang (71.7%) (P < 0.05). Conversely, the dupA-positive status was less than half in Shandong (31.1%) and Guangxi (15.4%), whereas it was 73.9% in Hunan and 81.8% in Qinghai (P < 0.001). There were no significant associations between the cagA, vacA, iceA, oipA genotypes and clinical outcomes. The dupA-positive strains were more common in peptic ulcer disease (PUD) patients than in non-ulcer dyspepsia (NUD) patients in Shandong and Guangxi (P < 0.05), but the association was not observed in other geographic regions.

Conclusions

There was significant geographic diversity of H. pylori genotypes in different regions of China and the presence of dupA gene can be considered as a marker for the development of gastroduodenal diseases. However, the cagA, iceA, vacA and oipA genes cannot be regarded for prediction of the clinical presentation of H. pylori infection in China.
Identification and functional characterization of a fish-specific tlr19 in common carp (Cyprinus carpio L.) that recruits TRIF as an adaptor and induces ifn expression during the immune response
Authors: Shan Shijuan , Liu Rongrong , Feng Hanxiao , Meng Fei , Aizaz Muhanmmad , Yang Guiwen
Published: June 2021

Toll-like receptor 19 (Tlr19) is a fish-specific TLR that plays a critical role in innate immunity. In the present study, we aimed to identify tlr19 from common carp (Cyprinus carpio L.) and explored its expression profile, localization, adaptor, and signaling pathways. A novel tlr19 cDNA sequence (Cctlr19) was identified in common carp. Phylogenetic analysis revealed that CcTlr19 was most closely related to Danio rerio Tlr19. Subcellular localization analysis indicates that CcTlr19 was synthesized in the free ribosome and then transported to early endosomes. Cctlr19 was constitutively expressed in all the examined tissues, with the highest expression in the brain. After poly(I:C) and Aeromonas hydrophila injection, the expression of Cctlr19 was significantly upregulated in immune-related organs. In addition, the expression of Cctlr19 was upregulated in head kidney leukocytes (HKL) upon stimulation with different ligands. Immunofluorescence and luciferase analyses indicate that CcTlr19 recruited TRIF as an adaptor. Furthermore, CcTlr19 can activate the expression of ifn-1 and viperin. Taken together, these findings lay the foundation for future research to investigate the mechanisms underlying fish tlr19.
A numerical and analytical study of SE(Is)(Ih)AR epidemic fractional order COVID-19 model
Authors: Khan Hasib , Begum Razia , Abdeljawad Thabet , Khashan M. Motawi
Published: June 2021

This article describes the corona virus spread in a population under certain assumptions with the help of a fractional order mathematical model. The fractional order derivative is the well-known fractal fractional operator. We have given the existence results and numerical simulations with the help of the given data in the literature. Our results show similar behavior as the classical order ones. This characteristic shows the applicability and usefulness of the derivative and our numerical scheme.
Simplified and improved criteria for oscillation of delay differential equations of fourth order
Authors: Moaaz O. , Muhib A. , Baleanu D. , Alharbi W. , Mahmoud E. E.
Published: June 2021

An interesting point in studying the oscillatory behavior of solutions of delay differential equations is the abbreviation of the conditions that ensure the oscillation of all solutions, especially when studying the noncanonical case. Therefore, this study aims to reduce the oscillation conditions of the fourth-order delay differential equations with a noncanonical operator. Moreover, the approach used gives more accurate results when applied to some special cases, as we explained in the examples.
The everyday life situation of caregivers to family members who have had a stroke and received the rehabilitation intervention F@ce in Uganda
Authors: Eriksson Gunilla Margareta , Kamwesiga Julius Tunga , Guidetti Susanne
Published: June 2021

Background

Stroke is increasing in Africa and consequences such as limitations in the performance of activities in everyday life persist a long time. A family member might need to care for and assist the person who has had a stroke. The life situation of these caregivers thereby changes, which could lead to increased workload and new responsibilities in caring for which they lack but request knowledge. During the F@ce rehabilitation program, the caregivers received counseling, which is uncommon in the African context. The aim of the study was twofold; (1) to investigate the perceived caregiver burden and life satisfaction and, (2) to explore and describe the life situation for caregivers to persons that have had a stroke and received the mobile phone supported rehabilitation F@ce in urban areas in Uganda.

Method

A mixed method design was used. Twelve caregivers took part in a semi-structured interview regarding their everyday life situation and responded to questionnaires on caregiver burden and life satisfaction. Latent qualitative content analysis was used to analyse the interviews.

Results

Five categories were identified in the caregivers’ experiences of their life situation: Feels obligated but is just a natural commitment; a tightly scheduled everyday life; being the supporting relative; the caregivers´ approach as rehabilitators; and being supported by the rehabilitation intervention. The caregivers rated relatively high on the Caregiver Burden Scale and two thirds of the sample rated their satisfaction with life as a whole as dissatisfying. Further ratings on the Life Satisfaction checklist revealed that the financial, vocational, leisure and family situations were dissatisfying.

Conclusions

Even if it was viewed as a natural commitment to be a caregiver when a family member had had a stroke, the life situation changed substantially for those who took on the caregiving role. Caregiving responsibilities were challenging as well as a heavy workload and a strained financial situation as many were giving up on jobs. The participants felt burdened and rated a low life satisfaction. The F@ce intervention was, however, expressed as valued and involved support and advice in their caregiving situation as well as information on stroke which relieved stress among them.
Patient perspectives on endoscopic sinus surgery for chronic rhinosinusitis
Authors: Saydy Nadim , Moubayed Sami Pierre , Desrosiers Martin
Published: June 2021

Background

Through shared decision-making, physicians and patients can elect endoscopic sinus surgery (ESS) when maximal medical therapy fails in patients with chronic rhinosinusitis (CRS). In this study, we aim to explore the most important themes with regards to patients’ perspectives on ESS. Our objective was to define the patient experience and ensure that we have congruent physician and patient goals for obtaining success.

Methods

Semi-structured face-to-face interviews were conducted with 22 patients at a tertiary-care institution in Montreal. Three themes were established a priori: living with CRS, objectives and expectations and criteria for success. This thematic approach allowed the identification, analysis and reporting of patterns found across the data set. A phenomenological methodological orientation was used. Interviews were audio-recorded and transcribed verbatim for continuous analysis. These were coded by hand by a single coder who read the transcripts multiple times and relistened to the recordings.

Results

Exploration of themes on patients’ perspectives on ESS for CRS yielded multiple anecdotal findings, and some recurring patterns. There is a tendency for patients to focus on one principal symptom that drives their decrease in QoL. Headaches and nasal congestion seemed to impact patients’ QoL the most amongst rhinologic symptoms. Hyposmia was rarely spontaneously by patients but was often a significant source of distress when prompted during interviews. Objectives and expectations seemed to be inversely proportional to number of previous surgeries and severity of symptoms preoperatively. There was a clear association between preoperative expectations and postoperative satisfaction. There was no clear pattern in the improvement magnitude or time improved postoperatively for patients to consider the surgery a success.

Conclusions

Patients’ level of satisfaction postoperatively and with their care in general is multifactorial. We believe the topic of goals and expectations regarding ESS should be discussed preoperatively for every patient with CRS. This includes patients with seemingly minor disease and patients naive to surgery, as can sometimes have exceedingly high expectations. Preoperative counselling must also include an assessment of what symptom is the most cumbersome to that particular patient, as patients tend to focus a lot on one or two symptoms. Postoperatively, we encourage clinicians to be attentive to the change in each patient's principal complaints within the context of a personalized approach and to refer back to patients’ preoperative goals in their assessment of operative success.

Graphical Abstract