bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations among drinking water quality, dyslipidemia, and cognitive function for older adults in China: evidence from CHARLS
Authors: Pan Xi , Luo Ye , Zhao Dandan , Zhang Lingling
Published: August 2022

Background

The current study aimed to examine the association between drinking water quality and cognitive function and to identify the direct and indirect effects of drinking water quality and dyslipidemia on cognitive function among older adults in China.

Methods

Primary data for the study were selected from China Health and Retirement Longitudinal Study (CHARLS, 2015) and 4,951 respondents aged 60 and above were included. Data on drinking water quality were selected from the 2015 prefectural water quality data from the Institute of Public and Environment Affairs in China and measured by the Blue City Water Quality Index. Dyslipidemia was measured by self-reported dyslipidemia diagnosis and lipid panel. Three composite measures of cognitive function included mental status, episodic memory, and global cognition. Mixed effects models were conducted to assess the associations between drinking water quality or dyslipidemia and cognitive function. The mediation effects of dyslipidemia were examined by path analyses.

Results

Exposure to high quality drinking water was significantly associated with higher scores in mental status, episodic memory, and global cognition (β = 0.34, p < 0.001 for mental status; β = 0.24, p < 0.05 for episodic memory; β = 0.58, p < 0.01 for global cognition). Respondents who reported dyslipidemia diagnosis had higher scores in the three composite measures of cognitive function (β = 0.39, p < 0.001 for mental status; β = 0.27 p < 0.05 for episodic memory; β = 0.66, p < 0.001 for global cognition). An elevated blood triglycerides was only associated with higher scores in mental status (β = 0.21, p < 0.05). Self-reported dyslipidemia diagnosis was a suppressor, which increased the magnitude of the direct effect of drinking water quality on mental status, episodic memory, and global cognition.

Conclusion

Drinking water quality was associated with cognitive function in older Chinese and the relationship was independent of natural or socioeconomic variations in neighborhood environments. Improving drinking water quality could be a potential public health effort to delay the onset of cognitive impairment and prevent the dementia pandemic in older people.
Using CUSUM in real time to signal clinically relevant decreases in estimated glomerular filtration rate
Authors: Zafarnejad Reyhaneh , Dumbauld Steven , Dumbauld Diane , Adibuzzaman Mohammad , Griffin Paul , Rutsky Edwin
Published: August 2022

Background

The electronic health record (EHR), utilized to apply statistical methodology, assists provider decision-making, including during the care of chronic kidney disease (CKD) patients. When estimated glomerular filtration (eGFR) decreases, the rate of that change adds meaning to a patient’s single eGFR and may represent severity of renal injury. Since the cumulative sum chart technique (CUSUM), often used in quality control and surveillance, continuously checks for change in a series of measurements, we selected this statistical tool to detect clinically relevant eGFR decreases and developed CUSUMGFR.

Methods

In a retrospective analysis we applied an age adjusted CUSUMGFR, to signal identification of eventual ESKD patients prior to diagnosis date. When the patient signaled by reaching a specified threshold value, days from CUSUM signal date to ESKD diagnosis date (earliness days) were measured, along with the corresponding eGFR measurement at the signal.

Results

Signaling occurred by CUSUMGFR on average 791 days (se = 12 days) prior to ESKD diagnosis date with sensitivity = 0.897, specificity = 0.877, and accuracy = .878. Mean days prior to ESKD diagnosis were significantly greater in Black patients (905 days) and patients with hypertension (852 days), diabetes (940 days), cardiovascular disease (1027 days), and hypercholesterolemia (971 days). Sensitivity and specificity did not vary by sociodemographic and clinical risk factors.

Conclusions

CUSUMGFR correctly identified 30.6% of CKD patients destined for ESKD when eGFR was > 60 ml/min/1.73 m2 and signaled 12.3% of patients that did not go on to ESKD (though almost all went on to later-stage CKD). If utilized in an EHR, signaling patients could focus providers’ efforts to slow or prevent progression to later stage CKD and ESKD.
A predictive model of macrosomic birth based upon real-world clinical data from pregnant women
Authors: Jing Gao , Huwei Shi , Chao Chen , Lei Chen , Ping Wang , Zhongzhou Xiao , Sen Yang , Jiayuan Chen , Ruiyao Chen , Lu Lu , Shuqing Luo , Kaixiang Yang , Jie Xu , Weiwei Cheng
Published: August 2022

Background

Fetal macrosomia is associated with an increased risk of several maternal and newborn complications. Antenatal predication of fetal macrosomia remains challenging. We aimed to develop a nomogram model for the prediction of macrosomia using real-world clinical data to improve the sensitivity and specificity of macrosomia prediction.

Methods

In the present study, we performed a retrospective, observational study based on 13,403 medical records of pregnant women who delivered singleton infants at a tertiary hospital in Shanghai from 1 January 2018 through 31 December 2019. We split the original dataset into a training set (n = 9382) and a validation set (n = 4021) at a 7:3 ratio to generate and validate our model. The candidate variables, including maternal characteristics, laboratory tests, and sonographic parameters were compared between the two groups. A univariate and multivariate logistic regression was carried out to explore the independent risk factors for macrosomia in pregnant women. Thus, the regression model was adopted to establish a nomogram to predict the risk of macrosomia. Nomogram performance was determined by discrimination and calibration metrics. All the statistical analysis was analyzed using R software.

Results

We compared the differences between the macrosomic and non-macrosomic groups within the training set and found 16 independent risk factors for macrosomia (P < 0.05), including biparietal diameter (BPD), head circumference (HC), femur length (FL), amniotic fluid index (AFI) at the last prenatal examination, pre-pregnancy body mass index (BMI), and triglycerides (TG). Values for the areas under the curve (AUC) for the nomogram model were 0.917 (95% CI, 0.908–0.927) and 0.910 (95% CI, 0.894–0.927) in the training set and validation set, respectively. The internal and external validation of the nomogram demonstrated favorable calibration as well as discriminatory capability of the model.

Conclusions

Our model has precise discrimination and calibration capabilities, which can help clinical healthcare staff accurately predict macrosomia in pregnant women.
Real-world patient characteristics and treatment outcomes among nontransplanted multiple myeloma patients who received Bortezomib in combination with Lenalidomide and Dexamethasone as first line of therapy in the United States
Authors: Medhekar Rohan , Ran Tao , Fu Alex Z. , Patel Sharmila , Kaila Shuchita
Published: August 2022

Background

There is limited real-world evidence that describes patients with newly diagnosed multiple myeloma (NDMM) treated with the bortezomib, lenalidomide, and dexamethasone (VRd) triplet regimen. We evaluated patient characteristics and treatment outcomes among nontransplanted NDMM patients who received VRd as their first line of therapy (LOT) in US oncology practice settings.

Methods

This retrospective observational cohort study evaluated patients from the Flatiron MM Core Registry who received VRd as first LOT between November 1, 2015, and February 28, 2021. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Associations between patient demographic and clinical characteristics and PFS were evaluated using a multivariable Cox proportional hazards model.

Results

A total of 2342 eligible patients with VRd as first LOT were identified (mean age, 67.0 years). Among all identified patients, 64.3% were ≥ 65 years of age, 25.5% were elderly (≥75 years), and 47.9% were frail. Among patients with available data, 21.2% had high-risk cytogenetics, and the majority had International Staging System (ISS) stage I/II disease (71.8%), and Eastern Cooperative Oncology Group performance status (ECOG PS) score 0/1 (81.2%). Median duration of therapy was 5.5 months. With median follow-up of 21.0 months, median PFS and time-to-next-treatment were 26.5 and 16.1 months, respectively. Higher risk of disease progression or death was seen in patients categorized as elderly (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.13-1.66 vs patients < 65 years), having high-risk cytogenetics (HR = 1.44; 95% CI: 1.19-1.75 vs standard risk), having ISS disease stages II and III (HR = 1.31; 95% CI: 1.06-1.63 and HR = 1.37; 95% CI: 1.10-1.70 versus stage I, respectively), and having worse ECOG PS score (≥2) (HR = 1.49; 95% CI: 1.22-1.81 versus functionally active patients).

Conclusions

The majority of patients treated with VRd in this study were ≥ 65 years of age, were ISS stage I/II, had an ECOG PS score of 0/1, and had standard cytogenetic risk. Median PFS observed in real-world practice was notably shorter than that observed in the SWOG S0777 clinical trial. In nontransplanted patients treated with VRd as first LOT, a higher risk of disease progression or death was associated with older age, having high-risk cytogenetics, worse disease stage, and worse ECOG PS score.
Colorectal cancer risk in association with colorectal cancer as a second malignancy in relatives: a nationwide cohort study
Authors: Zheng Guoqiao , Sundquist Jan , Sundquist Kristina , Ji Jianguang
Published: August 2022

Background

Increasing number of individuals will have first-degree relatives (FDRs) diagnosed with colorectal cancer (CRC), as a second primary malignancy (CRCa-2) after a non-CRC cancer. We aimed to estimate whether and to what extent a family history of CRCa-2 is associated with an increased CRC risk.

Methods

In this Swedish nationwide cohort study, rate ratio (RR) and cumulative incidence of CRC were estimated among 172,531 individuals with a family history of CRC as a first primary malignancy (CRCa-1) and 17,830 with a family history of CRCa-2, respectively, using individuals without cancer family history as the reference group.

Results

A cumulative incidence of CRC by age 80 was 6.3 and 5.6% for individuals with a parental and a sibling family history of CRCa-2, respectively. RRs of CRC for one FDR diagnosed with CRCa-1 and CRCa-2 were respectively 1.72 (95% CI, 1.65–1.79) and 1.50 (1.32–1.70); the latter RR was lower than the former (P = 0.0356), but no difference was observed after adjusting age of diagnosis of CRC in FDR and family relationship (P = 0.6898). Increased RRs were found to be associated with a CRCa-2 diagnosis in FDR that occured after cancers in upper aerodigestive tract, breast, prostate, kidney and nervous system.

Conclusions

Individuals who have relatives with CRCa-2 have an increased risk of CRC, but the magnitude is lower than those having relatives with CRCa-1, which is related to different ages of diagnosis of CRC in FDR and family relationships.
Tight adherent feature on optical coherence tomography predict postoperative visual outcome in epiretinal membrane eyes
Authors: Lai Tzu-Ting , Wu Li-Li , Hsieh Yi-Ting , Lee Chia-Chen , Peng Yi-Jie
Published: August 2022

Background

To identify the predictive parameter among preoperative measurements that best predicts postoperative visual outcome in the epiretinal membrane (ERM).

Methods

Thirty-three consecutive patients with idiopathic unilateral ERM patients between 2015 and 2018 were enrolled. Nineteen healthy normal eyes were selected as an independent age-matched group. Based on preoperative optical coherence tomography (OCT), we further divided the patients with ERM into two groups: type 1, loosely attached ERM, and type 2, tight adherent ERM. We documented the vision and thickness of various retinal layers: nerve fiber layer, ganglion cell layer, inner plexiform layer (GCL + IPL), inner nuclear layer (INL), outer retinal layer (ORL), and retinal pigment epithelium/Bruch complex layer before and after the surgery. The association between postoperative visual acuity and these variables was analyzed using multiple linear regression analysis.

Results

All retinal layers of ERM eyes were thicker than the normal eyes (P < 0.05). Among ERMs, we identified 11 eyes with type 1 adhesions and 22 eyes with type 2 adhesions. The preoperative GCL + IPL layers were significantly thicker in type 2 patients than in type 1 patients (93.67 ± 33.03 um vs 167.71 ± 13.77 um; P = 0.023). Greater GCL + IPL thickness was correlated with a worse postoperative visual acuity and multiple linear regression analysis showed that GCL + IPL thickness was an independent predictor of postoperative visual acuity (VA) (beta value = 0.689; P = 0.012). A greater thickness of GCL + IPL layers of type 2 patients had worse postoperative best-corrected visual acuity (BCVA) (P = 0.028). Ectopic inner foveal layers with disappearance of fovea pit were persistently presented in OCT profiles of both groups.

Conclusion

Idiopathic ERM demonstrated significantly thicker inner retinal layers (GCL + IPL and INL). However, the ORL thickness was similar between the normal eyes and ERM eyes. The preoperative GCL + IPL layers were significantly thicker in patients with type 2 ERM than that in patients with type 1 ERM. The increase in GCL + IPL thickness was significantly correlated with worse postoperative visual outcomes.
Treatment patterns among children and adolescents with attention-deficit/hyperactivity disorder in the United States – a retrospective claims analysis
Authors: Schein Jeff , Childress Ann , Adams Julie , Gagnon-Sanschagrin Patrick , Maitland Jessica , Qu Wendi , Cloutier Martin , Guérin Annie
Published: August 2022

Background

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder affecting approximately 10.0% of children and 6.5% of adolescents in the United States (US). A comprehensive assessment of the current treatment landscape is warranted to highlight potential unmet needs of children and adolescents with ADHD. Therefore, this study described treatment patterns and healthcare costs among commercially insured children and adolescents with ADHD in the US.

Methods

Children and adolescents with ADHD initiating pharmacological treatment indicated for ADHD were identified from IBM MarketScan Commercial Database (2014–2018). A treatment sequence algorithm was used to examine treatment patterns, including discontinuation (≥ 180 days following the last day of supply of any ADHD treatment), switch, add-on, and drop (discontinuation of an agent in combination therapy), during the 12-month study period following the index date (i.e., first observed ADHD treatment). Total adjusted annual healthcare costs were compared between patients with and without treatment changes.

Results

Among 49,756 children and 29,093 adolescents included, mean age was 9 and 15 years, respectively, and 31% and 38% were female. As the first treatment regimen observed, 92% of both children and adolescents initiated a stimulant and 11% initiated combination therapy. Over half of the population had a treatment change over 12 months—59% of children and 68% of adolescents. Treatment discontinuation over 12 months was common in both populations—21% of children and 36% of adolescents discontinued treatment. Healthcare costs increased with the number of treatment changes observed; children and adolescents with treatment changes (i.e., 1, 2, or ≥ 3) incurred an incremental annual cost of up to $1,443 and $2,705, respectively, compared to those without a treatment change (p < 0.001). Costs were largely driven by outpatient visits.

Conclusions

Over a 12-month period, treatment changes were commonly observed and were associated with excess costs, highlighting the unmet treatment needs of children and adolescents with ADHD in the US.
Preoperative prediction of sagittal imbalance in kyphosis secondary to ankylosing spondylitis after one-level three-column osteotomy
Authors: Luo Jianzhou , Yang Kai , Yang Zili , Chen Jiayi , Huang Zhengji , Luo Zhenjuan , Tao Huiren , Duan Chunguang , Wu Tailin
Published: August 2022

Background

This study aimed to determine preoperative predictors for sagittal imbalance in kyphosis secondary to ankylosing spondylitis (AS) after one-level three-column osteotomy.

Methods

A total of 55 patients with AS who underwent one-level three-column osteotomy were enrolled. The patients were divided into two groups according to sagittal vertical axis (SVA) value at the final follow-up (group A: SVA > 5 cm; group B: SVA ≤ 5 cm). The radiographic measures included global kyphosis, lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope, T1 pelvic angle (TPA), SVA, osteotomized vertebral angle and PI and LL mismatch (PI − LL). Postoperative clinical outcomes were evaluated using Scoliosis Research Society-22 questionnaire (SRS-22) and Oswestry Disability Index (ODI).

Results

Fifty-five AS patients had an average follow-up of 30.6 ± 10.2 months (range 24–84 months). Group A had larger preoperative and postoperative LL, PT, PI − LL, TPA and SVA values compared with group B (P < 0.05), and no significant differences were found in ODI and SRS-22 scores between the two groups (P > 0.05). Preoperative LL, PT, PI − LL, TPA, and SVA values were positively correlated with the follow-up SVA value (P < 0.05). Among them, TPA > 40.9°, PI − LL > 32.5° and SVA > 13.7 cm were the top three predictors with the best accuracy to predict sagittal imbalance. Immediate postoperative SVA value of ≤ 7.4 cm was a key factor in reducing the risk of sagittal imbalance during follow-up.

Conclusions

Preoperative TPA > 40.9°, PI − LL > 32.5° and SVA > 13.7 cm could predict sagittal imbalance in AS kyphosis after one-level three-column osteotomy, and additional osteotomies were recommended for this condition. Immediate postoperative SVA ≤ 7.4 cm was an optimal indicator for preventing sagittal imbalance.

Level of evidence

IV.
High burden of invasive and non-invasive cancer among women aged 20–49 years: the situation in Geneva, Switzerland
Authors: Rapiti Elisabetta , Fournier Evelyne , Schaffar Robin
Published: August 2022

Background

The pattern of cancer among young adults aged 20–49 years is different than that observed in other age groups, most notably women present higher rates than those observed among men. Estimations of the burden of cancer disease among women of this age group, however, rarely include both invasive and non-invasive disease.

Methods

We calculated incidence rates of invasive and non-invasive cancers for women and men aged 20–49 years and by cancer site for the period 2014–2018 in the canton of Geneva, Switzerland using data from the population-based cancer registry.

Results

Between 2014 and 2018, the incidence rates of invasive and non-invasive cancers among women were 177.6/100,000 and 166.4/100,000, respectively. The rates among men of the same age were 110.6/100,000 and 31.8/100,000, respectively. Just three cancers, breast, thyroid and melanoma accounted for 70% of all invasive cancers among women. In situ cervical cancer represented over 70% of non-invasive disease.

Conclusion

Cancer among women aged 20–49 years is quite frequent. This is primarily a result of increasing risk, increased diagnosis or both and highlights the need for better primary prevention strategies, personalized risk assessment and tailored screening, as well as increased awareness of women and health professionals about health risks in young adults.
Empathy as a learning objective in medical education: using phenomenology of learning theory to explore medical students’ learning processes
Authors: Assing Hvidt Elisabeth , Ulsø Anne , Thorngreen Cecilie Valentin , Søndergaard Jens , Andersen Christina Maar
Published: August 2022

Background

Clinical empathy has been associated with a range of positive patient- and clinician outcomes. Educating medical students to become empathic physicians has in recent years become a clearly pronounced learning objective in medical education in many countries worldwide. Research knowledge about how medical students experience the learning processes conveyed by empathy-enhancing educational interventions is lacking. Our study aimed to explore Danish medical students’ perspectives on which experiences allowed learning processes to take place in relation to empathy and empathic communication with patients.

Methods

We conducted a qualitative research study, involving semi-structured interviews with twenty-three Danish medical students across years of curriculum and universities. Braun and Clarke’s reflexive thematic analysis (RTA) guided the analytical process, moving on a continuum from inductive to deductive, theoretical approaches. Key concepts in regard to learning processes deriving from Amadeo Giorgi’s learning theory were applied to analyse the data.

Results

Learning processes in relation to clinical empathy occured: 1. when theoretical knowledge about empathy became embodied and contextualied within a clinical context 2. through interpersonal interactions, e.g., with peers, faculty members and clinicians, that conveyed behavior-mobilizing positive and negative affect and 3. when new learning discoveries in 2. and 3. were appropriated as a personalized and adequate behavior that transcends the situational level.

Conclusion

Rather than being an immediate product of knowledge transmission, skill acquisition or training, learning clinical empathy is experienced as a dynamic, temporal process embedded in a daily clinical lifeworld of becoming an increasingly human professional.
Perceptions, practices and barriers to reporting of adverse drug reactions among HIV infected patients and their doctors in 3 public sector hospitals of the Ethekwini Metropolitan, Kwa-Zulu Natal: a cross sectional and retrospective analysis
Authors: Zondi Sindiswa , Naidoo Panjasaram
Published: August 2022

Background

Adverse drug reactions (ADRs) remain a global public health concern. Pharmacovigilance practises are essential in ensuring patients safety and post drug marketing surveillance. This study aimed to describe practices, perceptions and barriers towards ADR reporting practices amongst People Living with HIV/AIDS (PLWHA), who are on Highly Active Anti-Retroviral Therapy (HAART) and their doctors.

Methods

The study took place at 3 public sector hospitals. The first phase of the study was a quantitative cross-sectional study using a closed ended questionnaire that was given to PLWHA. Phase two was a retrospective analysis of these patients’ medical files, whilst phase 3 included a descriptive statistics to determine the frequencies and percentages for variables such as ADR reporting practices by doctors.

Results

Spontaneous reporting, was evident with 202 patients (48%) indicating that they reported experiencing ADRs to their doctors. Ten doctors (77%) indicated that they received PV training. Eight (62%) doctors indicated that the completed ADR reporting forms were submitted to the pharmacy manager in the hospital for forwarding to the regulatory authority, with 2 (15%) indicating that they submitted directly to the South African Health Products Regulatory Authority. Four (31%) doctors stated that the system of reporting ADRs is ineffective with the majority of the doctors 12 (92%) responding that the reporting of ADRs is very important/critical. A barrier cited by 4 patients (0.9%) for non-reporting of their ADRs was transport cost. Whilst doctors' barriers included reporting being time consuming (31%), and a lack of availability of reporting forms (31%).

Conclusion

Patients and doctors are reporting ADRs but more education and easier reporting process should be available to strengthen the knowledge and reporting of ADRs. Doctors agree that it is critical to report ADRs. Electronic reporting should be encouraged to lessen the time it takes to report ADRs.
The trust and insurance models of healthcare purchasing in the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana in India: early findings from case studies of two states
Authors: Furtado Kheya Melo , Raza Arif , Mathur Devasheesh , Vaz Nafisa , Agrawal Ruchira , Shroff Zubin Cyrus
Published: August 2022

Background

The Pradhan Mantri Jan Arogya Yojana (PMJAY), a publicly funded health insurance scheme for the poor in India, was launched in 2018. Early experiences of states with various purchasing arrangements can provide valuable insights for its future performance. We sought to understand the institutional agencies and performance of the trust and insurance models of purchasing with respect to; a) Provider contracting b) Claim management c) Implementation costs.

Methods

A mixed methods case study design was adopted. Two states, Uttar Pradesh (representing a trust model) and Jharkhand (representing the insurance model) were purposively selected. Data sources included document reviews, key informant interviews, quantitative scheme data from the provider empanelment and claims database, and primary data on costs. Descriptive statistics were reported for quantitative data, content analysis was used for thematic reporting of qualitative data.

Results

In both models, the state was the final authority on empanelment decisions, with no significant influence of the insurance company. Private hospitals constituted the majority of empanelled providers, with wide variations in district-wise distribution of bed capacities in both states. The urgency of completing empanelment in the early days of the scheme created the need for both states to re-review hospitals and de-empanel those not meeting requirements. Very few quality- accredited private hospitals were empaneled. The trust displayed more oversight of support agencies for claim management, longer processing times, a higher claim rejection rate and numbers of queries raised, as compared to the insurance model. Support agencies in both states faced challenges in assessing the clinical decisions of hospitals. Cost-effectiveness showed mixed results; the trust cost less than the insurance model per beneficiary enrolled, but more per claim generated.

Conclusions

Efforts are required to enable a better distribution and ensure quality of care in empanelled hospitals. The adoption of standard treatment guidelines is needed to support hospitals and implementing agencies in better claim management. The oversight of agencies through enforcement of contracts remains vital in both models. Assessing the comparative performance of trusts and insurance companies in more states at later stages of scheme implementation, would be further useful to determine their cost-effectiveness as purchasers.
The A’-helix of CYP11A1 remodels mitochondrial cristae
Authors: Rosal Karen G. , Chen Wei-Yi , Chung Bon-chu
Published: August 2022

Background

CYP11A1 is a protein located in the inner membrane of mitochondria catalyzing the first step of steroid synthesis. As a marker gene for steroid-producing cells, the abundance of CYP11A1 characterizes the extent of steroidogenic cell differentiation. Besides, the mitochondria of fully differentiated steroidogenic cells are specialized with tubulovesicular cristae. The participation of CYP11A1 in the change of mitochondrial structure and the differentiation of steroid-producing cells, however, has not been investigated.

Methods

We engineered nonsteroidogenic monkey kidney COS1 cells to express CYP11A1 upon doxycycline induction and examined the mitochondrial structure of these cells. We also mapped the CYP11A1 domains that confer structural changes of mitochondria. We searched for CYP11A1-interacting proteins and investigated the role of this interacting protein in shaping mitochondrial structure. Finally, we examined the effect of CYP11A1 overexpression on the amount of mitochondrial contact site and cristae organizing system.

Results

We found that CYP11A1 overexpression led to the formation of tubulovesicular cristae in mitochondria. We also identified the A’-helix located at amino acid #57–68 to be sufficient for membrane insertion and crista remodeling. We identified heat shock protein 60 (Hsp60) as the CYP11A1-interacting protein and showed that Hsp60 is required for CYP11A1 accumulation and crista remodeling. Finally, we found that the small MIC10 subcomplex of the mitochondrial contact site and cristae organizing system was reduced when CYP11A1 was overexpressed.

Conclusions

CYP11A1 participates in the formation of tubulovesicular cristae in the mitochondria of steroidogenic cells. Its A’-helix is sufficient for the formation of tubulovesicular cristae and for protein integration into the membrane. CYP11A1 interacts with Hsp60, which is required for CYP11A1 accumulation. The accumulation of CYP11A1 leads to the reduction of MIC10 complex and changes mitochondrial structure.
Elevated cholesteryl ester transfer and phospholipid transfer proteins aggravated psoriasis in imiquimod-induced mouse models
Authors: Chen Jun , Qi Haihua , Liu Lijun , Niu Yandong , Yu Shuping , Qin Shucun , He Lei
Published: August 2022

Background

Psoriasis is a chronic inflammatory skin disorder related to dyslipidemia, with decreased high-density lipoprotein (HDL). Various cell types express phospholipid transfer protein (PLTP) as well as cholesteryl ester transfer protein (CETP). Their elevated levels among transgenic (Tg) mice led to reduced HDL and a higher risk of atherosclerosis (AS). This study examined whether elevated CETP and PLTP could aggravate psoriasis in a psoriasis vulgaris mouse model.

Methods

The back skins of CETP-Tg, PLTP-Tg, and C57BL/6 male mice, aged six to 8 weeks, were shaved for imiquimod cream (IMQ) (5%) treatment for five consecutive days. The clinical pathological parameters were rated independently using the modified target lesion psoriasis severity score. The skin sections stained with hematoxylin-eosin were scored by the Baker score. Epidermal thickening and differentiation and inflammatory factor infiltration were determined by immunohistochemistry. Inflammatory cytokine levels were measured using quantitative reverse transcription-polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA) kits. This work employed SPSS Statistics Version to conduct statistical analyses.

Results

In this study, CETP-Tg and PLTP-Tg mice had higher clinical and histological scores than wild-type (WT) mice. Immunohistochemistry of the epidermis and dermis revealed a high proportion of proliferating cell nuclear antigen (PCNA) positivity within psoriatic skin lesions of CETP-Tg and PLTP-Tg mice compared with WT mice. Interferon-α (IFN-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-17F, IL-22, and IL-23p19 mRNA levels increased within CETP-Tg and PLTP-Tg mice compared with WT counterparts. In comparison with WT mice, plasma tumor necrosis factor-α (TNF-α) levels, rather than IL-6 levels, were increased in CETP-Tg and PLTP-Tg mice.

Conclusions

Elevated CETP and PLTP aggravate psoriasis in a imiquimod-induced mouse model.
CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-inflammatory cytokine production
Authors: Gaur Rajula , Mensah Kofi A. , Stricker Jason , Adams Mary , Parton Anastasia , Cedzik Dorota , Connarn Jamie , Thomas Michael , Horan Gerald , Schafer Peter , Mair Stuart , Palmisano Maria , Ramírez-Valle Francisco
Published: August 2022

Background

Mitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MK2) is activated downstream of p38 MAPK and regulates stability of mRNAs encoding inflammatory cytokines. CC-99677 is a novel, irreversible, covalent MK2 inhibitor under development for the treatment of ankylosing spondylitis (AS) and other inflammatory diseases. As part of a phase I clinical trial to assess safety and tolerability, we evaluated target engagement, pharmacokinetics, and pharmacodynamics of CC-99677.

Methods

The MK2 inhibitor CC-99677 was evaluated for its effect on cytokine expression in vitro in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with a definitive AS diagnosis. A novel in vitro model was developed to compare the potential for tachyphylaxis of CC-99677 and p38 inhibitors in THP-1 cells. The effect of CC-99677 on tristetraprolin (TTP) and cytokine mRNA was assessed in stimulated human monocyte-derived macrophages. In a first-in-human study, thirty-seven healthy volunteers were randomly assigned to daily oral doses of CC-99677 or placebo, and blood was collected at pre-specified time points before and after dosing. CC-99677 concentrations were assessed in the plasma, and CC-99677 binding to MK2 was evaluated in PBMCs. Ex vivo stimulation of the whole blood was conducted from participants in the first-in-human study to assess the pharmacodynamic effects.

Results

In vitro, CC-99677 inhibited tumor necrosis factor (TNF), interleukin (IL)-6, and IL-17 protein production in samples of monocytes and macrophages from AS patients and healthy volunteers via an mRNA-destabilization mechanism. In the in vitro model of tachyphylaxis, CC-99677 showed a differentiated pattern of sustained TNF protein inhibition compared with p38 inhibitors. CC-99677 reduced TTP phosphorylation and accelerated the decay of inflammatory cytokine mRNA in lipopolysaccharide-stimulated macrophages. Administration of CC-99677 to healthy volunteers was safe and well-tolerated, with linear pharmacokinetics and sustained reduction of ex vivo whole blood TNF, IL-6, and chemokine synthesis.

Conclusions

CC-99677 inhibition of MK2 is a promising approach for the treatment of inflammatory diseases and may overcome the limitations of p38 MAPK inhibition.

Trial registration

ClinicalTrials.gov NCT03554993.
Low apparent diffusion coefficient in an extracranial brain tumor: a case report
Authors: Tuan Ho Xuan , Hung Nguyen Duy , Minh Nguyen Dinh , Quang Nguyen Nhat , Duy Ngo Quang , Duc Nguyen Minh
Published: August 2022

Background

Medulloblastoma is well known as the most common malignant brain tumor identified in children, frequently found at an intra-axial location in the posterior cranial fossa. Extra-axial medulloblastoma is uncommon and often misdiagnosed. We believe that a thorough understanding of atypical medulloblastoma cases is important in daily practice.

Case presentation

We present the unique case of a 39-year-old woman of Asian descent who suffered from headaches and right-sided hearing impairment. A right extra-axial medulloblastoma with an extremely low apparent diffusion coefficient of 0.404 × 10−3 mm2/second was detected on magnetic resonance imaging. The initial diagnosis suggested schwannoma or hemangioblastoma. However, the postoperative histopathologic findings indicated medulloblastoma (World Health Organization grade IV). Pre- and postoperative magnetic resonance imaging revealed no drop metastasis, but adjuvant radiation therapy was still required as a standard treatment therapy

Conclusions

Extra-axial medulloblastoma is an uncommon tumor that is often mistaken for other cerebellopontine angle neoplasms. We describe a rare example of extra-axial medulloblastoma, characterized by a low apparent diffusion coefficient. When evaluating an atypical cerebellopontine angle neoplasm, the apparent diffusion coefficient should be considered a relevant indicator.
Mental distress among university students in the Eastern Cape Province, South Africa
Authors: Mutinta Given
Published: August 2022

Introduction

Mental distress is a global health concern. Studies show that the prevalence of mental distress is higher in students’ population than in the general population. Therefore, there is need to understand the extent and factors associated with mental distress among students to help policymakers and practitioners in South Africa.

Aim of the study

The study was designed to investigate into the prevalence and factors associated with mental distress among students at universities in the Eastern Cape Province, South Africa.

Methods

A cross-sectional study was conducted among students from four universities in the Eastern Cape Province. The data were collected from 844 students using an online self-reporting questionnaire-20 to assess mental distress of students. Multivariable logistic regression modelling determined the association between socio-demographic and psychosocial factors with students’ mental distress.

Findings

The prevalence of mental distress among students was 53.3% (95% CI 47.0%, 58.1%). Female students were more prone to mental distress than male students ([AOR]: 4.67; 95% CI 2.82, 7.72, P = 0.001). Field of study ([AOR]: 3.9; 95% CI 1.74, 5.50, P = 0.010), year of study ([AOR]: 4.29; 95% CI 0.86, 21.46, P = 0.002), academic workload ([AOR]: 4.66; 95% CI 2.81, 7.71, P = 0.003), poor sleep quality ([AOR]: 2.24; 95% CI 1.13, 3.67, P = 0.010) and using cannabis ([AOR]: 3.10; 95% CI 1.755, 5.51, P = 0.020) were other factors significantly correlated with students’ mental distress.

Conclusions and recommendations

The study found the level of mental distress to be higher among students than what is reported in most of the previous studies on the student population in South Africa. Being a female student, a user of cannabis, and field of study, academic workload and having poor sleep quality were predictors of mental distress. Findings point to the need to devise evidence-driven interventions and strategies to prevent and reduce the problem of mental distress among students.
How the Big Five personality traits related to aggression from perspectives of the benign and malicious envy
Authors: Jiang Xinsheng , Li Xiaojun , Dong Xia , Wang Lan
Published: August 2022

Background

Prior studies have indicated the link between the Big Five personality traits and aggression. Based on the general aggression model, the purpose of this study is to reveal the formation mechanism of aggression from the people’s internal emotional perspective. Envy is a typical negative emotion that can be divided into benign/malicious envy. Therefore, we aim to explore the intrinsic role of benign/malicious envy within the Big Five personality traits in its connection to aggression.

Methods

We recruited 839 participants [229 men (27.29%) and 610 women (72.71%); mean age ± SD = 19.45 ± 2.39] who we tested with the NEO Personality Inventory, the Benign and Malicious Envy Scale, and the Aggression Questionnaire.

Results

The results of suggested that neuroticism was significantly and positively associated with aggression, while agreeableness was negatively related to aggression. Moreover, mediation analysis revealed that malicious envy works both in the relationship of neuroticism-aggression and agreeableness-aggression.

Conclusions

The current study advanced knowledge of the general aggression model. Most importantly, it reveals that malicious envy, as a type of envy, plays an important mediating role between neuroticism, agreeableness and aggression. Meanwhile, the cross-gender path analysis supports the stability of the mediating role of malicious envy. This finding provides new insights into the intervention of aggression from the perspective of envy.
Determinants of male involvement in family planning services in Abia State, Southeast Nigeria
Authors: Amuzie Chidinma Ihuoma , Nwamoh Uche Ngozi , Ukegbu Andrew , Umeokonkwo Chukwuma David , Azuogu Benedict Ndubueze , Agbo Ugonma Okpechi , Balogun Muhammad Shakir
Published: August 2022

Background

Male involvement in family planning (FP) remains low in male-dominant communities. Family planning contributes to the regulation of fertility and population growth in Nigeria. Increasing male involvement in family planning services is crucial in reducing maternal morbidity and mortality in patriarchal societies such as Nigeria. This study identified the determinants of male involvement in family planning services in Abia State, Nigeria.

Methods

This was a cross-sectional study conducted in twelve communities of Abia State, Nigeria. A total of 588 married men who met the eligibility criteria were recruited using a multistage sampling technique. An interviewer-administered semi-structured questionnaire was used to collect data on the variables. Univariate, bivariate and multivariate analysis was done. The level of significance was set at 5%.

Results

The overall level of active male involvement in family planning services was 55.1% (95% CI:51.0–59.2%). The mean age of the respondents was 42.4 ± 8.0 years. Access to television (aOR = 1.58, 95% CI: 1.05–2.39), spouse employment status (aOR = 2.02, 95% CI: 1.33–2.06), joint decision-making (aOR = 1.66, 95% CI: 1.05–2.62), and accompanying spouse to the FP clinic (aOR = 3.15, 95% CI: 2.16–4.62) were determinants of active male involvement.

Conclusion

At least, one out of every two men was actively involved in family planning services. This was determined by access to television, employment status of spouse, joint decision-making, and accompanying spouse to the FP clinic. There is a need to focus on the identified factors in order to further improve the active involvement of men in FP services.
Cardiovascular complications and predictors of mortality in hospitalized patients with COVID-19: a cross-sectional study from the Indian subcontinent
Authors: Lalani Kanhai , Seshadri Sneha , Samanth Jyothi , Thomas Jaimin Jose , Rao M. Sudhakar , Kotian Nisha , Satheesh Jijin , Nayak Krishnananda
Published: August 2022

Background

COVID-19 has spread rapidly across the world, producing significant morbidity and mortality. We investigated the cardiovascular complications and association of laboratory parameters with severity and mortality predictors in COVID-19 hospitalized patients.

Methods

Between May 2020 and June 2021, 730 COVID-19 patients were included in this retrospective observational study in the Coastal Karnataka region of South India. Acute coronary syndrome (ACS), myocarditis, arrhythmias, and all-cause mortality were reported as cardiovascular consequences. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), serum creatinine, D-dimer, troponin T, N-terminal pro-brain natriuretic peptide (NT-ProBNP), serum ferritin, and serum lactate dehydrogenase (LDH) were among the laboratory parameters measured.

Results

Most common electrocardiogram (ECG) changes were prolonged QTc interval (45.6%) followed by ST-T changes (40.7%) and sinus tachycardia (24.2%). 9.2% patients presented with ACS, with 38.8% having ST-elevation myocardial infarction (STEMI) and 61.2% having non-ST elevation myocardial infarction (NSTEMI). In non-survivors, NLR (p < 0.001) and PLR (p = 0.001) were significantly higher. Multivariable regression analysis showed that age (OR:1.019, 95% CI 1.003–1.034; p = 0.017), acute kidney injury (OR:3.562, 95% CI 1.737–7.301; p = 0.001), white blood cell count (WBC) (OR = 1.100, 95% CI 1.035–1.169; p = 0.002), platelet count (OR = 0.994, 95% CI 0.990–0.997; p = 0.001), PLR (OR = 1.002, 95% CI 1.000–1.004; p = 0.023) and severe COVID-19 (OR = 9.012, 95% CI 3.844–21.129; p = 0.001) were independent predictors of mortality in COVID-19 patients.

Conclusions

Age, WBC count, neutrophil%, NLR, PLR, creatinine, D-dimer, ferritin, LDH, tachycardia, and lymphocytes% strongly correlated with the severity of the disease. Age, acute kidney injury, elevated WBC count, a greater PLR, low platelet count, and COVID-19 severity were independent predictors of mortality.
Survey of control techniques to alleviate repercussions of shock-wave and boundary-layer interactions
Authors: Jana Tamal , Kaushik Mrinal
Published: August 2022

The primary focus of the present survey is to categorize the results of various investigations on the Shock/Boundary-Layer Interactions (SBLIs), their repercussions, and the effective ways to control them. The interactions of shock waves with the boundary layer are an important area of research due to their ubiquity in several applications ranging from transonic to hypersonic flows. Therefore, there is a need for a detailed inspection to understand the phenomena to predict its characteristics with certain accuracy. Considering this in mind, this article presents some key features of the physical nature of SBLIs, their consequences, and the control techniques in a sequential manner; in particular, the passive control techniques for the supersonic and hypersonic intakes are reviewed in detail.
Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results
Authors: Kennecke Hagen F. , O'Callaghan Chris J. , Loree Jonathan M. , Moloo Hussein , Auer Rebecca , Jonker Derek J. , Raval Manoj , Musselman Reilly , Ma Grace , Caycedo-Marulanda Antonio , Simianu Vlad V. , Patel Sunil , Pitre Lacey D. , Helewa Ramzi , Gordon Vallerie L. , Neumann Katerina , Nimeiri Halla , Sherry Max , Tu Dongsheng , Brown Carl J.
Published: August 2022

PURPOSE

Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES).

METHODS

This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid–fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin). Those with evidence of response proceeded to transanal endoscopic surgery 2-6 weeks later. The primary end point was protocol-specified organ preservation rate, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery.

RESULTS

Of 58 patients enrolled, all commenced chemotherapy and 56 proceeded to surgery. A total of 33/58 patients had tumor downstaging to ypT0/1N0/X on the surgery specimen, resulting in an intention-to-treat protocol-specified organ preservation rate of 57% (90% CI, 45 to 68). Of 23 remaining patients recommended for TME surgery on the basis of protocol requirements, 13 declined and elected to proceed directly to observation resulting in 79% (90% CI, 69 to 88) achieving organ preservation. The remaining 10/23 patients proceeded to recommended TME of whom seven had no histopathologic residual disease. The 1-year and 2-year locoregional relapse-free survival was, respectively, 98% (95% CI, 86 to 100) and 90% (95% CI, 58 to 98), and there were no distant recurrences or deaths. Minimal change in quality of life and rectal function scores was observed.

CONCLUSION

Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.
Physical organogenesis of the gut
Authors: Chevalier Nicolas R.
Published: August 2022

The gut has been a central subject of organogenesis since Caspar Friedrich Wolff’s seminal 1769 work ‘De Formatione Intestinorum’. Today, we are moving from a purely genetic understanding of cell specification to a model in which genetics codes for layers of physical–mechanical and electrical properties that drive organogenesis such that organ function and morphogenesis are deeply intertwined. This Review provides an up-to-date survey of the extrinsic and intrinsic mechanical forces acting on the embryonic vertebrate gut during development and of their role in all aspects of intestinal morphogenesis: enteric nervous system formation, epithelium structuring, muscle orientation and differentiation, anisotropic growth and the development of myogenic and neurogenic motility. I outline numerous implications of this biomechanical perspective in the etiology and treatment of pathologies, such as short bowel syndrome, dysmotility, interstitial cells of Cajal-related disorders and Hirschsprung disease.