bluuebunny/crossref_metadata_2025 huggingface dataset:
Should knee extension strength testing be implemented as a screening test for identifying probable and confirmed sarcopenia in older T2DM patients?
Authors: kis Ofer , Buch Assaf , Eldor Roy , Rubin Amir , Dunsky Ayelet , Stern Naftali , Moran Daniel S.
Published: January 2022

Background

The accelerated loss of muscle strength and mass observed in older type 2 diabetes mellitus (T2DM) patients due to the combined effects of diabetes and obesity, greatly increases their risk for sarcopenia. Early detection and treatment of probable and confirmed sarcopenia is paramount to delay mobility disability. Using low handgrip strength cut-off points for the initial identification of sarcopenia according to the new European Working Group on Sarcopenia in Older People (EWGSOP2) guidelines may mask the presence of sarcopenia. Relative knee extension strength cut-off points using a simple hand-held dynamometer can assist clinicians in the diagnosis of probable and confirmed sarcopenia by possibly reducing false negative results.

Methods

A cohort of one hundred T2DM older patients (60% women) (mean age 74.5 years) mostly obese community dwelling older adults were evaluated for body composition by Bioelectrical impedance analysis (BIA), yielding appendicular skeletal mass index (ASMI) results. Patients underwent handgrip strength (HGS) and knee extension strength (KES) tests as well as functional ability tests. Prevalence of probable and confirmed sarcopenia using HGS and KES cut-off points were calculated. Pearson correlations were performed to evaluate the relationship between ASMI and limbs strength. A regression analysis was conducted to examine which variables best predict ASMI values. A multivariate analysis of covariance was performed to assess the effect of independent variables on KES and HGS.

Results

Using cutoff points for low KES identified 24 patients with probable sarcopenia and two with confirmed sarcopenia. Conversely, using the EWGSOP2 cut off points for low HGS, identified only one patient with probable sarcopenia and none of the patients with confirmed sarcopenia.

Conclusion

KES cut-off points using a simple hand-held dynamometer can assist in the identification of probable and confirmed sarcopenia using EWGSOP2 cut off points for low muscle mass in a population of older T2DM patients for further analysis and early treatment. This is notably true in patients possessing high body mass index (BMI) alongside normal ASMI and HGS, potentially reducing false positive sarcopenia screening results.

Trial registration

ClinicalTrials.gov PRS: NCT03560375. Last registration date (last update): 06/06/2018. The trial was a-priori registered before actual recruitment of subjects.
Progesterone differentially affects the transcriptomic profiles of cow endometrial cell types
Authors: Pereira Gonçalo , Guo Yongzhi , Silva Elisabete , Bevilacqua Claudia , Charpigny Gilles , Lopes-da-Costa Luís , Humblot Patrice
Published: January 2022

Background

The endometrium is a heterogeneous tissue composed of luminal epithelial (LE), glandular epithelial (GE), and stromal cells (ST), experiencing progesterone regulated dynamic changes during the estrous cycle. In the cow, this regulation at the transcriptomic level was only evaluated in the whole tissue. This study describes specific gene expression in the three types of cells isolated from endometrial biopsies following laser capture microdissection and the transcriptome changes induced by progesterone in GE and ST cells.

Results

Endometrial LE, GE, and ST cells show specific transcriptomic profiles. Most of the differentially expressed genes (DEGs) in response to progesterone are cell type-specific (96%). Genes involved in cell cycle and nuclear division are under-expressed in the presence of progesterone in GE, highlighting the anti-proliferative action of progesterone in epithelial cells. Elevated progesterone concentrations are also associated with the under-expression of estrogen receptor 1 (ESR1) in GE and oxytocin receptor (OXTR) in GE and ST cells. In ST cells, transcription factors such asSOX17andFOXA2,known to regulate uterine epithelial-stromal cross-talk conveying to endometrial receptivity, are over-expressed under progesterone influence.

Conclusions

The results from this study show that progesterone regulates endometrial function in a cell type-specific way, which is independent of the expression of its main receptor PGR. These novel insights into uterine physiology present the cell compartment as the physiological unit rather than the whole tissue.
Genome-wide association study for seedling biomass-related traits in Gossypium arboreum L.
Authors: Hu Daowu , He Shoupu , Jia Yinhua , Nazir Mian Faisal , Sun Gaofei , Geng Xiaoli , Pan Zhaoe , Wang Liru , Chen Baojun , Li Hongge , Ge Yuting , Pang Baoyin , Du Xiongming
Published: January 2022

Background

Seedling stage plant biomass is usually used as an auxiliary trait to study plant growth and development or stress adversities. However, few molecular markers and candidate genes of seedling biomass-related traits were found in cotton.

Result

Here, we collected 215 Gossypium arboreum accessions, and investigated 11 seedling biomass-related traits including the fresh weight, dry weight, water content, and root shoot ratio. A genome-wide association study (GWAS) utilizing 142,5003 high-quality SNPs identified 83 significant associations and 69 putative candidate genes. Furthermore, the transcriptome profile of the candidate genes emphasized higher expression of Ga03G1298, Ga09G2054, Ga10G1342, Ga11G0096, and Ga11G2490 in four representative cotton accessions. The relative expression levels of those five genes were further verified by qRT-PCR.

Conclusions

The significant SNPs, candidate genes identified in this study are expected to lay a foundation for studying the molecular mechanism for early biomass development and related traits in Asian cotton.
Impact of home healthcare on end-of-life outcomes for people with dementia: a systematic review
Authors: Chen Ping-Jen , Smits Lisanne , Miranda Rose , Liao Jung-Yu , Petersen Irene , Van den Block Lieve , Sampson Elizabeth L.
Published: January 2022

Background

Home healthcare (HHC) comprises clinical services provided by medical professionals for people living at home with various levels of care needs and health conditions. HHC may reduce care transitions from home to acute hospitals, but its long-term impact on homebound people living with dementia (PLWD) towards end-of-life remains unclear. We aim to describe the impact of HHC on acute healthcare utilization and end-of-life outcomes in PLWD.

Methods

Design: Systematic review of quantitative and qualitative original studies which examine the association between HHC and targeted outcomes. Interventions: HHC. Participants: At least 80% of study participants had dementia and lived at home. Measurements: Primary outcome was acute healthcare utilization in the last year of life. Secondary outcomes included hospice palliative care, advance care planning, continuity of care, and place of death. We briefly reviewed selected national policy to provide contextual information regarding these outcomes.

Results

From 6831 articles initially identified, we included five studies comprising data on 4493 participants from USA, Japan, and Italy. No included studies received a “high” quality rating. We synthesised core properties related to HHC at three implementational levels. Micro-level: HHC may be associated with a lower risk of acute healthcare utilization in the early period (e.g., last 90 days before death) and a higher risk in the late period (e.g. last 15 days) of the disease trajectory toward end-of-life in PLWD. HHC may increase palliative care referrals. Advance care planning was an important factor influencing end-of-life outcomes. Meso-level: challenges for HHC providers in medical decision-making and initiating palliative care for PLWD at the end-of-life may require further training and external support. Coordination between HHC and social care is highlighted but not well examined. Macro-level: reforms of national policy or financial schemes are found in some countries but the effects are not clearly understood.

Conclusions

This review highlights the dearth of dementia-specific research regarding the impact of HHC on end-of-life outcomes. Effects of advance care planning during HHC, the integration between health and social care, and coordination between primary HHC and specialist geriatric/ palliative care services require further investigation.
Post-acute COVID-19 syndrome in patients after 12 months from COVID-19 infection in Korea
Authors: Kim Yoonjung , Bitna-Ha  , Kim Shin-Woo , Chang Hyun-Ha , Kwon Ki Tae , Bae Sohyun , Hwang Soyoon
Published: January 2022

Background

As the coronavirus disease 2019 (COVID-19) pandemic continues to progress, awareness about its long-term impacts has been growing. To date, studies on the long-term course of symptoms, factors associated with persistent symptoms, and quality of life after 12 months since recovery from acute COVID-19 have been limited.

Methods

A prospective online survey (First: September 8, 2020–September 10, 2020; Second: May 26, 2021–June 1, 2021) was conducted on recovered patients who were previously diagnosed with COVID-19 between February 13, 2020 and March 13, 2020 at Kyungpook National University Hospital. Responders aged between 17 and 70 years were included in the study. Overall, 900 and 241 responders were followed up at 6 and 12 months after recovery from COVID-19 in the first and second surveys, respectively. Clinical characteristics, self-reported persistent symptoms, and EuroQol-5-dimension (EQ5D) index score were investigated for evaluating quality of life.

Results

The median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 454 (interquartile range [IQR] 451–458) days. The median age of the responders was 37 (IQR 26.0–51.0) years, and 164 (68.0%) responders were women. Altogether, 11 (4.6%) responders were asymptomatic, and 194 (80.5%), 30 (12.4%), and 6 (2.5%) responders had mild, moderate, and severe illness, respectively. Overall, 127 (52.7%) responders still experienced COVID-19-related persistent symptoms and 12 (5.0%) were receiving outpatient treatment for such symptoms. The main symptoms were difficulty in concentration, cognitive dysfunction, amnesia, depression, fatigue, and anxiety. Considering the EQ5D index scores, only 59.3% of the responders did not have anxiety or depression. Older age, female sex, and disease severity were identified as risk factors for persistent neuropsychiatric symptoms.

Conclusion

COVID-19-related persistent symptoms improved over time; however, neurological symptoms can last longer than other symptoms. Continuous careful observation of symptom improvement and multidisciplinary integrated research on recovered COVID-19 patients are required.
The role of first-trimester HbA1c in the early detection of gestational diabetes
Authors: Valadan Mehrnaz , Bahramnezhad Zeinab , Golshahi Fatemeh , Feizabad Elham
Published: January 2022

Background

We aimed to assess the utility of HbA1c in the early detection of gestational diabetes (GDM) in the first trimester.

Methods

This prospective study was performed on 700 pregnant women in the perinatology clinic at a tertiary university hospital from March 2018 to March 2020. For all pregnant women, HbA1c and fasting blood glucose (FBG) levels were examined during the first trimester. Then, a GDM screening test was done within 24–28 weeks of pregnancy using a 100 g oral glucose tolerance test (OGTT) as the gold standard test. The GDM diagnosis was made according to the American Diabetes Association (ADA) criteria. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of HbA1c and FBG were calculated using the receiver operating characteristic (ROC) curve.

Results

Of 700 participants, one hundred and fifteen (16.4%) women had GDM. The GDM patients were significantly older and had a higher pre-gestational body mass index and pregnancy weight gain compared to the non-GDM participants. The sensitivity and specificity for ruling out GDM at an HbA1c cut-off value of 4.85% was 92.2 and 32.8%, respectively, with a 95.5% NPV and a 21.2% PPV. Furthermore, sensitivity and specificity for diagnosing GDM at an HbA1c cut-off value of 5.45% was 54.8 and 96.8%, respectively, with a 91.5% NPV and a 76.8% PPV. Using HbA1c could decline OGTT in 40.4% of the pregnant women (28.7% with HbA1c < 4.85 and 11.7% with HbA1c ≥ 5.45%).

Conclusion

It seems that the first-trimester HbA1c cannot replace OGTT for the diagnosis of GDM because of its insufficient sensitivity and specificity. However, women with higher first-trimester HbA1c had a high risk for GDM incidence.
Valproate prescription to women of childbearing age in English primary care: repeated cross-sectional analyses and retrospective cohort study
Authors: Gaudio Mariangela , Konstantara Emmanouela , Joy Mark , van Vlymen Jeremy , de Lusignan Simon
Published: January 2022

Background

Valproate is a teratogenic drug that should be avoided during the preconception period and pregnancy. The aim was to explore general practitioners’ (GPs) prescription patterns over time, describe trends, and explore inter-practice variation within primary care.

Methods

We identified women of childbearing age (12–46 years old) in the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network. We performed repeated cross-sectional analyses from 2004 to 2018 to determine rates of prescription and a retrospective cohort estimated the prevalence of use of valproate during pregnancy.

Results

In 2004, 0.31% (95% Confidence Interval (95%CI):0.18 to 0.44%) women were prescribed valproate, decreasing to 0.16% (95%CI:0.07 to 0.24%) by 2018. Among women with epilepsy, the rate fell from 15.2% (95%CI:14.4 to 16.0%) to 8.8% (95% CI:8.2 to 9.7%) over the same period. In 2018, almost two thirds (62.2%) of women who were prescribed valproate had epilepsy only, whereas bipolar disorder and migraine accounted for 15.8% and 7.4% respectively. Contraceptive prescriptions did not increase over time, and only in 2018 was there greater odds of being prescribed contraception (OR 1.41, 95%CI:1.08 to 1.45). Just under a fifth (19.7%) of women were prescribed valproate during their pregnancy; two out of three of these pregnancies were preceded by folic acid prescription (5 mg). While some practices reduced their rate of valproate prescription, others did not.

Conclusions

Regulatory guidelines have changed GPs' prescription patterns in women of childbearing potential for valproate but not for contraception. Further research is needed to identify the barriers of GPs and women of childbearing potential to undertaking contraception.
Preconceptional evaluation of women with recurrent pregnancy loss: the additional value of assessing vascular and metabolic status
Authors: Habets Denise H. J. , Schiffer Veronique M. M. M. , Kraneburg Lisa P. A. , de Krom Femke J. W. , Gürtekin Irem , van Bree Bo E. , van Golde Ron J. T. , Wieten Lotte , Spaanderman Marc E. A. , Al-Nasiry Salwan
Published: January 2022

Background

A majority of recurrent pregnancy loss cases (RPL) remains unexplained. We hypothesized that complications in vascular and metabolic status may guide towards underlying problems that also predispose to RPL and that the number of pregnancy losses is related.

Methods

A retrospective study in 123 women with either a history of low-order RPL (2–3 pregnancy losses) or high-order RPL (≥ 4 pregnancy losses) and 20 women with a history of uncomplicated pregnancy (controls) was performed. Vascular status was assessed by measuring hemodynamic parameters, determining abnormal parameters and analyzing their contribution to the circulatory risk profile (CRP). In a similar way, metabolic status was assessed. Metabolic parameters were measured, used to determine abnormal parameters and analyzed for their contribution to the metabolic syndrome (MetS).

Results

No major differences were observed in vascular or metabolic parameters between women with RPL and controls. There was no relation with the number of pregnancy losses. However, when analyzing the presence of abnormal constituents, more than 80% of women with RPL had at least one abnormal constituent of the CRP. While only 27% had one or more abnormal constituent of the MetS.

Conclusions

The presence of abnormal circulatory factors prior to pregnancy, and to lesser extent constituents of the metabolic syndrome, may predispose to RPL and offer new insights to its pathophysiology.
Exclusive breastfeeding among women with type 1 and type 2 diabetes mellitus
Authors: Cordero Leandro , Stenger Michael R. , Landon Mark B. , Nankervis Craig A.
Published: January 2022

Objective

To compare exclusive breastfeeding (BF) and BF initiation among 185 women with Type 1 and 212 women with Type 2 pregestational diabetes who intended exclusive or partial BF and delivered at ≥34 weeks of gestation.

Methods

Retrospective cohort study. At discharge, exclusive BF is direct BF or BF complemented with expressed breast milk. BF initiation is defined by exclusive or partial BF.

Results

Type 1 and Type 2 groups were similar in prior BF experience (69 vs 67%) but were different in intention to BF exclusively (92 vs 78%) and partially (8 vs 22%). Women in the Type 1 group were younger (median age 30 vs 33y), likely to be primiparous (47 vs 25%), have a lower median BMI (32 vs 36 kg/m2) and deliver by primary cesarean (37 vs 26%). Infants born to Type 1 women were more likely to be admitted to the NICU (44 vs 18%) and to have hypoglycemia (59 vs 41%). At discharge, exclusive BF among Type 1 was higher (34 vs 23%), partial BF was similar (47 vs 46%) while FF (formula feeding) was lower (19 vs 31%) than in the Type 2 group. BF initiation occurred in 81% of Type 1 and 69% of Type 2 women.

Conclusion

Intention to BF exclusively was higher in Type 1 women compared to Type 2. At discharge, exclusive BF and BF initiation were lower and FF higher in the Type 2 group highlighting the need for different strategies if lactation in this special population is to be improved.
An interventional pilot of customized adherence enhancement combined with long-acting injectable antipsychotic medication (CAE-L) for poorly adherent patients with chronic psychotic disorder in Tanzania
Authors: Mbwambo Jessie , Kaaya Sylvia , Lema Isaac , Burant Christopher J. , Magwiza Catherine , Madundo Kim , Njiro Godwin , Blixen Carol E. , Cassidy Kristin A. , Levin Jennifer B. , Sajatovic Martha
Published: January 2022

Background

Chronic psychotic disorders (CPD) impose a particularly significant burden in resource-limited settings. Combining long-acting antipsychotic medication (LAI) with a customized adherence enhancement intervention (CAE-L) has potential to advance care.

Methods

Nineteen adults ≥ age 18 with CPD who self-reported missing ≥20% of antipsychotic medication within the last month were stabilized on oral haloperidol prior to transitioning to monthly haloperidol decanote for 25 weeks. Outcome evaluations were conducted at baseline and Week 25. Primary outcomes were oral medication adherence assessed via the Tablet Routines Questionnaire (TRQ) and LAI injection frequency. Secondary outcomes included CPD symptoms measured by the Brief Psychiatric Rating Scale and Clinical Global Impressions, functioning evaluated using the Social and Occupational Functioning Scale, and medication attitudes assessed with the Drug Attitudes Inventory.

Results

Mean sample age was 38.79 (SD = 9.31) with 18 individuals completing the study. There was one serious adverse event, a relapse into substance use, not deemed study-related. Mean endpoint LAI dosage was 65.79 mg (SD = 22.38). TRQ mean scores were 21.84 (SD =13.83) and 12.94 (SD = 11.93) at screen and baseline respectively. For only two individuals who were on concomitant oral medication at 25 weeks, TRQ change was not calculated. LAI injection frequency was 100%. Medication attitudes scores significantly improved from 7.89 (SD = 2.72) to 9.83 (SD = 0.52) (p = .001.) Changes in CPD symptoms and functioning were non-significant.

Conclusions

CAE-L appears to be preliminarily feasible and acceptable in Tanzanians with CPD.

Trial registration

The study was registered on ClinicalTrials.gov (NCT04327843) on March 31, 2020.
Socioeconomic inequalities in non- coverage of full vaccination among children in Bangladesh: a comparative study of Demographic and Health Surveys, 2007 and 2017–18
Authors: Srivastava Shobhit , Muhammad T. , Rashmi Rashmi , Kumar Pradeep
Published: January 2022

Background

Vaccination is considered as a powerful and cost-effective weapon against many communicable diseases. An increase in full vaccination among the most vulnerable populations in Bangladesh was observed in the last decade. This study aimed to capture the socioeconomic inequalities in non-coverage of full vaccination among children aged 12–23 months using the nationally representative data from the Bangladesh Demographic and Health Surveys (BDHS).

Methods

Data for this study have been drawn from the 2007 and 2017–18 BDHS, which covered 10,996 and 20,127 ever-married women aged 15–49 years in 2007 and 2017–18, respectively. Binary logistic regression analysis was performed to find the factors associated with children who did not receive full vaccination. Further, the concentration index was used to observe the socioeconomic inequality for the outcome variable.

Results

The proportion of children who did not get fully vaccinated decreased by more than 6 points (18.2 percent to 11.8 percent) between the years 2007 and 2017–18. In 2017–18, the odds of children who were not fully vaccinated were 58 percent and 53 percent less among mothers who had primary education in 2007 [adjusted odds ratio (AOR): 0.42; confidence interval (CI): 0.24–0.73] and 2017–18 [AOR: 0.47; CI: 0.23–0.94] respectively, compared to mothers with no education. The inequality for children who were not fully vaccinated had declined between two survey periods [concentration index (CCI) value of − 0.13 in 2007 and -0.08 in 2017–18]. The concentration of inequality in children with higher parity who did not receive full vaccination had increased from 5 percent in 2007 to 16.9 percent in 2017–18. There was a drastic increase in the socioeconomic inequality contributed by place of delivery from 2.9 percent (2007) to 60.5 percent (2017–18) among children who did not receive full vaccination.

Conclusions

The present study provide eminent evidence that non-coverage of full vaccination is more prevalent among children from poor households in Bangladesh, which is mainly associated with factors like mother’s education, father’s education and working status and household wealth index across the two rounds. These factors suggest multifaceted pro-poor interventions that will protect them from hardship and reduce their socioeconomic inequalities in coverage of full vaccination.
Pregnancy loss and Income in the Republic of Korea using National Health Insurance Service Data, 2008–2014
Authors: Lim Ga-Young , Jung Na Young , Jun Kyo Yeon , Kang Ji Yeon , Kim Mi Kyung , Lee Hye-Eun , Kim Myoung-Hee , Song Jaechul , Kim Inah , Kim Yu-Mi
Published: January 2022

Background

Although unintentional pregnancy loss is common, national representative statistics are lacking in high-income East Asian countries undergoing rapid demographic changes. It is necessary to confirm the income inequality of pregnancy loss even in universal national health insurance.

Method

Using National Health Insurance Service data between 2008 and 2014, the annual prevalence of pregnancy loss was enumerated, and differences in pregnancy loss according to age and income levels were assessed by multivariable Poisson regression. Joint-point regression was used to examine the trend of pregnancy loss.

Result

On average, there was a 15.0% annual pregnancy loss among 3,941,020 pregnancy cases from 2008 to 2014. Pregnancy loss inequality increased stepwise with income levels except for the highest income group. After adjusting for income levels, the annual percent change of age-standardized prevalence significantly increased by 2.6% every year since 2011.

Conclusion

Even in high-income countries with universal national health insurance, income inequality in pregnancy loss is observed. Further appraisal is needed to explain the increasing trend of pregnancy loss between 2011 and 2014 even after adjusting income.
Vacuum phenomenon as a predictor of kyphosis after implant removal following posterior pedicle screw fixation without fusion for thoracolumbar burst fracture: a single-center retrospective study
Authors: Hirahata Masahiro , Kitagawa Tomoaki , Yasui Youichi , Oka Hiroyuki , Yamamoto Iwao , Yamada Kazuaki , Fujita Muneyoshi , Kawano Hirotaka , Ishii Keisuke
Published: January 2022

Background

Posterior pedicle screw fixation without fusion has been commonly applied for thoracolumbar burst fracture. Implant removal is performed secondarily after bone union. However, the occurrence of secondary kyphosis has recently attracted attention. Secondary kyphosis results in poor clinical outcomes. The purpose of this was to determine predictors of kyphosis after implant removal following posterior pedicle screw fixation without fusion for thoracolumbar burst fracture.

Methods

This retrospective study reviewed 59 consecutive patients with thoracolumbar burst fracture who underwent implant removal following posterior pedicle screw fixation without fusion. Inclusion criteria were non-osteoporotic fracture and T11-L3 burst fracture. Old age, sex, initial severe wedge deformity, initial severe kyphosis, and vacuum phenomenon were examined as factors potentially associated with final kyphotic deformity (defined as kyphotic angle greater than 25°) or loss of correction. Logistic regression analysis was performed using propensity score matching.

Results

Among the 31 female and 28 male patients (mean age 38 years), final kyphotic deformity was found in 17 cases (29%). Multivariate analysis showed a significant association with the vacuum phenomenon. Loss of correction was found in 35 cases (59%) and showed a significant association with the vacuum phenomenon. There were no significant associations with other factors.

Conclusions

The findings of this study suggest that the vacuum phenomenon before implant removal may be a predictor of secondary kyphosis of greater than 25° after implant removal following posterior pedicle screw fixation without fusion for thoracolumbar burst fracture, but that old age, sex, initial severe kyphosis, and initial severe wedge deformity may not be predictors.
Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1β-induced osteoarthritis by downregulating the MAPK and NF-κB pathways
Authors: Xu Fang , Zhao Liang-Jun , Liao Ting , Li Zhao-Cong , Wang Lei-Lei , Lin Pan-Yu , Jiang Rui , Wei Qing-Jun
Published: January 2022

Background

Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear.

Methods

In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1β)-induced chondrocyte inflammation model.

Results

Our results verified that ononin alleviated the IL-1β-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways.

Conclusion

Our findings suggested that ononin could inhibit the IL-1β-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.
Creating a win-win for the health system and health Profession’s education: a direct observation clinical experience with feedback iN real-time (DOCENT) for low acuity patients in the emergency department
Authors: Clay Alison S. , Leiman Erin R. , Theiling Brent Jason , Song Yao , Padilla Blanca Blanca Iris , Hudak Nicholas M. , Hartman Ann Michelle , Hoder Jeffrey M. , Waite Kathleen A. , Lee Hui-Jie , Buckley Edward G.
Published: January 2022

Background

Clinical education across the professions is challenged by a lack of recognition for faculty and pressure for patient throughput and revenue generation. These pressures may reduce direct observation of patient care provided by students, a requirement for both billing student-involved services and assessing competence. These same pressures may also limit opportunities for interprofessional education and collaboration.

Methods

An interprofessional group of faculty collaborated in a sequential quality improvement project to identify the best patients and physical location for a student teaching clinic. Patient chief complaint, use of resources, length of stay, estimated severity of illness and student participation and evaluation of the clinic was tracked.

Results

Clinic Optimization and Patient Care: Five hundred and thirty-two emergency department (ED) patients were seen in the first 19 months of the clinic. A clinic located near the ED allowed for patients with higher emergency severity index and greater utilization of imaging. Patients had similar or lower lengths of stay and higher satisfaction than patients who remained in the ED (p < 0.0001). In the second clinic location, from October 2016–June 2019, 644 patients were seen with a total of 667 concerns; the most common concern was musculoskeletal (50.1%).

Student Interprofessional Experience: A total of 991 students participated in the clinic: 68.3% (n = 677) medical students, 10.1% (n = 100) physician assistant students, 9.7% (n = 96) undergraduate nursing students, 9.1% (n = 90) physical therapy students, and 2.8% (n = 28) nurse practitioner students. The majority (74.5%, n = 738) of student participants worked with students from other professions. More than 90% of students reported that faculty set a positive learning environment respectful of students. However, 20% of students reported that faculty could improve provision of constructive feedback.

Direct Observation: Direct observation of core entrustable professional activities for medical students was possible. Senior medical students were more likely to be observed generating a differential diagnosis or management plan than first year medical students.

Conclusions

Creation of a DOCENT clinic in the emergency department provided opportunities for interprofessional education and observation of student clinical skills, enriching student experience without compromising patient care.
Modernising physician resource planning: a national interactive web platform for Canadian medical trainees
Authors: Bourcier D. , Collins B. W. , Tanya S. M. , Basu M. , Sayal A. P. , Moolla S. , Dong A. , Balas M. , Molcak H. , Punchhi G.
Published: January 2022

Background

Healthcare systems rely heavily upon human resources to ensure high-quality access to care for the general population. With significant health worker shortages predicted worldwide in the coming decades, maximizing the current workforce by means of a physician resource planning (PRP) strategy that ensures the right number, mix, and distribution of physicians to meet population needs is warranted. In Canada, there is an insufficient number of primary care providers, and disproportionately low numbers of specialist physicians in rural compared to urban regions. Currently, Canadian medical students are not effectively included in PRP strategy and lack the required information for career orientation to help rebalance the population’s workforce needs. This paper present theHealth Human Resource (HHR) Platform, a comprehensive web tool that includes relevant workforce data to empower medical students in choosing a discipline based on both personal interests and social accountability.

Results

Physician workforce data, comments from Canadian residency program directors, and career planning resources were collected by the Canadian Federation of Medical Student’s (CFMS) HHR Task Force. This information was consolidated to create a national interactive platform that uses a map, comparison table, and trend graphs to illustrate over 500,000 unique data points from 37 datasets, including specific information and resources spanning 62 medical specialties from 2015 onwards. There was a 24.6% response rate for program director comments. During the first 4 months of theHHR Platformlaunch, there were 2434 different users, of which 985 were returning, with an average of 20.0 users per day spending on average 3 min on the platform.

Conclusions

TheHHR Platformconstitutes a national approach to PRP informing medical students on the mix and distribution of physicians needed to meet the future healthcare demands of the Canadian population.
Human placental mesenchymal stromal cells are ciliated and their ciliation is compromised in preeclampsia
Authors: Romberg Sophia Indira , Kreis Nina-Naomi , Friemel Alexandra , Roth Susanne , Souto Alice Steglich , Hoock Samira Catharina , Fischer Kyra , Nowak Thorsten , Solbach Christine , Louwen Frank , Ritter Andreas , Yuan Juping
Published: January 2022

Background

The development of the human placenta is tightly coordinated by a multitude of placental cell types, including human chorionic villi mesenchymal stromal cells (hCV-MSCs). Defective hCV-MSCs have been reported in preeclampsia (PE), a gestational hypertensive disease characterized by maternal endothelial dysfunction and systemic inflammation. Our goal was to determine whether hCV-MSCs are ciliated and whether altered ciliation is responsible for defective hCV-MSCs in preeclamptic placentas, as the primary cilium is a hub for signal transduction, which is important for various cellular activities.

Methods

In the present work, we collected placental tissues from different gestational stages and we isolated hCV-MSCs from 1st trimester, term control, and preeclamptic placentas. We studied their ciliation, functionality, and impact on trophoblastic cell lines and organoids formed from human trophoblast stem cells (hTSCs) and from the trophoblastic cell line JEG-3 with various cellular and molecular methods, including immunofluorescence staining, gene analysis, spheroid/organoid formation, motility, and cellular network formation assay. The statistical evaluation was performed using a Student’s t test (two-tailed and paired or homoscedastic) or an unpaired Mann–Whitney U test (two-tailed).

Results

The results show that primary cilia appeared abundantly in normal hCV-MSCs, especially in the early development of the placenta. Compared to control hCV-MSCs, the primary cilia were truncated, and there were fewer ciliated hCV-MSCs derived from preeclamptic placentas with impaired hedgehog signaling. Primary cilia are necessary for hCV-MSCs’ proper signal transduction, motility, homing, and differentiation, which are impaired in preeclamptic hCV-MSCs. Moreover, hCV-MSCs derived from preeclamptic placentas are significantly less capable of promoting growth and differentiation of placental organoids, as well as cellular network formation.

Conclusions

These data suggest that the primary cilium is required for the functionality of hCV-MSCs and primary cilia are impaired in hCV-MSCs from preeclamptic placentas.
Healthy lifestyle, metabolomics and incident type 2 diabetes in a population-based cohort from Spain
Authors: Delgado-Velandia Mario , Gonzalez-Marrachelli Vannina , Domingo-Relloso Arce , Galvez-Fernandez Marta , Grau-Perez Maria , Olmedo Pablo , Galan Iñaki , Rodriguez-Artalejo Fernando , Amigo Nuria , Briongos-Figuero Laisa , Redon Josep , Martin-Escudero Juan Carlos , Monleon-Salvado Daniel , Tellez-Plaza Maria , Sotos-Prieto Mercedes
Published: January 2022

Background

The contribution of metabolomic factors to the association of healthy lifestyle with type 2 diabetes risk is unknown. We assessed the association of a composite measure of lifestyle with plasma metabolite profiles and incident type 2 diabetes, and whether relevant metabolites can explain the prospective association between healthy lifestyle and incident type 2 diabetes.

Methods

A Healthy Lifestyle Score (HLS) (5-point scale including diet, physical activity, smoking status, alcohol consumption and BMI) was estimated in 1016 Hortega Study participants, who had targeted plasma metabolomic determinations at baseline examination in 2001–2003, and were followed-up to 2015 to ascertain incident type 2 diabetes.

Results

The HLS was cross-sectionally associated with 32 (out of 49) plasma metabolites (2.5% false discovery rate). In the subset of 830 participants without prevalent type 2 diabetes, the rate ratio (RR) and rate difference (RD) of incident type 2 diabetes (n cases = 51) per one-point increase in HLS was, respectively, 0.69 (95% CI, 0.51, 0.93), and − 8.23 (95% CI, − 16.34, − 0.13)/10,000 person-years. In single-metabolite models, most of the HLS-related metabolites were prospectively associated with incident type 2 diabetes. In probit Bayesian Kernel Machine Regression, these prospective associations were mostly driven by medium HDL particle concentration and phenylpropionate, followed by small LDL particle concentration, which jointly accounted for ~ 50% of the HLS-related decrease in incident type 2 diabetes.

Conclusions

The HLS showed a strong inverse association with incident type 2 diabetes, which was largely explained by plasma metabolites measured years before the clinical diagnosis.
Explaining variable effects of an adaptable implementation package to promote evidence-based practice in primary care: a longitudinal process evaluation
Authors: Glidewell Liz , Hunter Cheryl , Ward Vicky , McEachan Rosemary R. C. , Lawton Rebecca , Willis Thomas A. , Hartley Suzanne , Collinson Michelle , Holland Michael , Farrin Amanda J. , Foy Robbie ,   on behalf of the ASPIRE programme team, Alderson Sarah , Carder Paul , Clamp Susan , West Robert , Rathfelder Martin , Hulme Claire , Richardson Judith , Stokes Tim , Watt Ian
Published: January 2022

Background

Implementing evidence-based recommendations is challenging in UK primary care, especially given system pressures and multiple guideline recommendations competing for attention. Implementation packages that can be adapted and hence applied to target multiple guideline recommendations could offer efficiencies for recommendations with common barriers to achievement. We developed and evaluated a package of evidence-based interventions (audit and feedback, educational outreach and reminders) incorporating behaviour change techniques to target common barriers, in two pragmatic trials for four “high impact” indicators: risky prescribing; diabetes control; blood pressure control; and anticoagulation in atrial fibrillation. We observed a significant, cost-effective reduction in risky prescribing but there was insufficient evidence of effect on the other outcomes. We explored the impact of the implementation package on both social processes (Normalisation Process Theory; NPT) and hypothesised determinants of behaviour (Theoretical Domains Framework; TDF).

Methods

We conducted a prospective multi-method process evaluation. Observational, administrative and interview data collection and analyses in eight primary care practices were guided by NPT and TDF. Survey data from trial and process evaluation practices explored fidelity.

Results

We observed three main patterns of variation in how practices responded to the implementation package. First, in integration and achievement, the package “worked” when it was considered distinctive and feasible. Timely feedback directed at specific behaviours enabled continuous goal setting, action and review, which reinforced motivation and collective action. Second, impacts on team-based determinants were limited, particularly when the complexity of clinical actions impeded progress. Third, there were delivery delays and unintended consequences. Delays in scheduling outreach further reduced ownership and time for improvement. Repeated stagnant or declining feedback that did not reflect effort undermined engagement.

Conclusions

Variable integration within practice routines and organisation of care, variable impacts on behavioural determinants, and delays in delivery and unintended consequences help explain the partial success of an adaptable package in primary care.
Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects
Authors: Romito Ilaria , Porru Manuela , Braghini Maria Rita , Pompili Luca , Panera Nadia , Crudele Annalisa , Gnani Daniela , De Stefanis Cristiano , Scarsella Marco , Pomella Silvia , Mortera Stefano Levi , de Billy Emmanuel , Conti Adrian Libenzio , Marzano Valeria , Putignani Lorenza , Vinciguerra Manlio , Balsano Clara , Pastore Anna , Rota Rossella , Tartaglia Marco , Leonetti Carlo , Alisi Anna
Published: January 2022

An amendment to this paper has been published and can be accessed via the original article.
Phentermine–topiramate extended release for the dual treatment of obesity and sleep-related eating disorder: a case report
Authors: Grunvald Eduardo , DeConde Jennifer
Published: January 2022

Background

Obesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine–topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports.

Case presentation

A 35-year-old Caucasian male with a body mass index of 41.7 kg/m2 presented for obesity treatment. History revealed nocturnal episodes of hyperphagia associated with amnesia of overeating and other features of sleep-related eating disorder. Treatment was initiated with phentermine–topiramate extended release. Five months later he lost 5% of his body weight and demonstrated resolution of sleep-related eating disorder behaviors. He reported no adverse side effects. Upon self-discontinuation of the medication, his eating disorder recurred.

Conclusions

Clinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine–topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population.
Inhalable antibiotic resistomes emitted from hospitals: metagenomic insights into bacterial hosts, clinical relevance, and environmental risks
Authors: Wu Dong , Jin Ling , Xie Jiawen , Liu Hang , Zhao Jue , Ye Dan , Li Xiang-dong
Published: January 2022

Background

Threats of antimicrobial resistance (AMR) to human health are on the rise worldwide. Airborne fine particulate matter (PM2.5), especially those emitted from hospitals, could serve as a substantial yet lesser-known environmental medium of inhalable antibiotic resistomes. A genome-centric understanding of the hosting bacterial taxa, mobility potential, and consequent risks of the resistomes is needed to reveal the health relevance of PM2.5-associated AMR from clinical settings.

Results

Compared to urban ambient air PM2.5, the hospital samples harbored nearly twice the abundance of antibiotic resistantance genes (ARGs, ~ 0.2 log10(ARGs/16S rRNA gene)) in the summer and winter sampled. The profiled resistome was closely correlated with the human-source-influenced (~ 30% of the contribution) bacterial community (Procrustes test,P< 0.001), reflecting the potential antibiotic-resistant bacteria (PARB), such as the human commensalsStaphylococcusspp. andCorynebacteriumspp. Despite the reduced abundance and diversity of the assembled metagenomes from summer to winter, the high horizontal transfer potential of ARGs, such as the clinically relevantblaOXAandbacA, in the human virulent PARB remained unaffected in the hospital air PM samples. The occurring patterns of β-lactam resistance genes and their hosting genomes in the studied hospital-emitting PM2.5were closely related to the in-ward β-lactam-resistant infections (SEM, std = 0.62,P< 0.01). Featured with more abundant potentially virulent PARB (2.89 genome copies/m3-air), the hospital samples had significantly higher resistome risk index scores than the urban ambient air samples, indicating that daily human exposure to virulent PARB via the inhalation of PM2.5was ten times greater than from the ingestion of drinking water.

Conclusions

The significance of AMR in the studied hospital-emitting PM2.5was highlighted by the greater abundance of ARGs, the prevalence of potentially virulent PARB, and the close association with hospital in-ward β-lactam infections. A larger-scale multi-source comparison of genome-resolved antibiotic resistomes is needed to provide a more holistic understanding to evaluate the importance of airborne AMR from the “One-Health” perspective.
Targeting interleukin-1β and inflammation in lung cancer
Authors: Zhang Jun , Veeramachaneni Nirmal
Published: January 2022

Inflammation is a process that protects organs against various potentially harmful stimuli and enables repair. Dysregulated inflammation, however, damages tissues and leads to disease, including cancer. Cancer-related inflammation is characterized by cytokine production, leukocyte infiltration, angiogenesis, and tissue remodeling—all critical processes in modulating the tumor microenvironment (TME). The TME is known to play a key role in tumor progression, and targeting its immune component to achieve a better anti-tumor response is the basis of immunotherapy. Despite the critical role cytokines play in the TME and tumor progression, there is currently only one therapy approved by the FDA that directly involves cytokine signaling: human recombinant interleukin-2 protein, aldesleukin. The recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial evaluated the use of anti-interleukin-1β therapy in atherosclerotic disease; however, it also revealed interleukin-1β (IL-1β) blockade with canakinumab led to a significantly lower incidence of lung cancer. This has opened a promising new avenue for lung cancer therapy, and strategies using anti-IL-1β therapy alone or in combination with chemotherapy and/or immune checkpoint blockade are currently being evaluated in several clinical trials.