bluuebunny/crossref_metadata_2025 huggingface dataset:
Biobanks in the low- and middle-income countries of the Arab Middle East region: challenges, ethical issues, and governance arrangements—a qualitative study involving biobank managers
Authors: Abdelhafiz Ahmed Samir , Ahram Mamoun , Ibrahim Maha Emad , Elgamri Alya , Gamel Ehsan , Labib Rania , Silverman Henry
Published: August 2022

Background

Biobanks have recently been established in several low- and middle-income countries (LMICs) in the Arab region of the Middle East. We aimed to explore the views of biobank managers regarding the challenges, ethical issues, and governance arrangements of their biobanks.

Methods

In-depth semi-structured qualitative interviews were conducted with a purposive sample of eight biobank managers from Egypt (6), Jordan (1), and Sudan (1). Interviews were performed either face-to-face, by phone, or via Zoom and lasted approximately 45–75 min. After verbal consent, interviews were recorded and then transcribed. The authors performed a thematic analysis of the transcripts independently and then integrated the themes via a consensus process.

Results

Biobank managers discussed the main challenges in establishing their biobanks. These included the staff’s lack of experience and training, limited funds, deficit awareness of biobanks, obtaining funding from different sources. Only four reported they were active in distributing biospecimens and health data to researchers. Six biobanks used a broad consent model, one used tiered consent, and another allowed participants to opt-out of being recontacted. Five managers avoided partnerships with pharmaceutical companies due to concerns with unfavorable reactions from the community. Five managers did not have clear policies for returning research results to the donors. Five expressed challenges with sample and data sharing with international collaborators; all five used material transfer agreements. The biobank managers revealed variable governance arrangements and activities with community involving awareness and educational efforts rather than active engagement. Several expressed the importance of transparency with the operations of their biobanks and gaining the trust of their stakeholders.

Conclusion

Managers of biobanks in LMICs in the Arab Middle East encounter financial, operational, and social challenges toward their sustainability efforts. Discussions with key stakeholders are warranted to manage ethical issues involving informed consent, privacy, data sharing, and the return of results. We recommend that biobank managers in the Arab Middle East form collaborative networks within the region and internationally, develop trusting governance relationships with their stakeholders, and pursue engagement activities with their communities to enhance trust.
Homozygous mutation of the LRRK2 ROC domain as a novel genetic model of parkinsonism
Authors: Chen Meng-Ling , Wu Ruey-Meei
Published: August 2022

Background

Parkinson’s disease (PD) is one of the most important neurodegenerative disorders in elderly people. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are found in a large proportion of the patients with sporadic and familial PD. Mutations can occur at different locations in theLRRK2. Patients with LRRK2 ROC-COR mutations face an increased risk of typical motor symptoms of PD, along with cognitive decline. An animal model with a monogenicLRRK2gene mutation is a suitable model for exploring the pathophysiology of PD and identifying potential drug therapies. However, the effect of homozygous (HOM)LRRK2in PD pathophysiology is unclear.

Methods

We established humanLRRK2(hLRRK2) R1441G HOM transgenic (Tg) mice to explore the phenotype and pathological features that are associated withhLRRK2R1441G Tg mouse models and discuss the potential clinical relevance. The open field test (OFT) was performed to examine motor and nonmotor behaviors. A CatWalk analysis system was used to study gait function. [18F]FDOPA PET was used to investigate functional changes in the nigrostriatal pathway in vivo. Transmission electron microscopy was used to examine the morphological changes in mitochondria and lysosomes in the substantia nigra.

Results

The R1441G HOM Tg mice demonstrated gait disturbance and exhibited less anxiety-related behavior and exploratory behavior than mice withhLRRK2at 12 months old. Additionally, [18F]FDOPA PET showed a reduction in FDOPA uptake in the striatum of the HOM Tg mice. Notably, there was significant lysosome and autophagosome accumulation in the cytoplasm of dopaminergic neurons in R1441G hemizygous (HEM) and HOM mice. Moreover, it was observed using transmission electron microscopy (TEM) that the mitochondria of R1441G Tg mice were smaller than those ofhLRRK2mice.

Conclusion

This animal provides a novel HOMhLRRK2R1441G Tg mouse model that reproduces some phenotype of Parkinsonism in terms of both motor and behavioral dysfunction. There is an increased level of mitochondrial fission and no change in the fusion process in the group of HOMhLRRK2R1441G Tg mouse. This mutant animal model of PD might be used to study the mechanisms of mitochondrial dysfunction and explore potential new drug targets.
Evaluating surface EMG control of motorized wheelchairs for amyotrophic lateral sclerosis patients
Authors: Manero Albert C. , McLinden Shea L. , Sparkman John , Oskarsson Björn
Published: August 2022

Background

This study evaluated a novel control method for patients unable to independently control powered wheelchairs. Patients with amyotrophic lateral sclerosis often require a wheelchair but struggle with sufficient hand dexterity required for joystick control making them a population that needs this type of control method.

Methods

The study employed a novel control mechanism, using electromyography surface sensors applied to temporalis muscles able to measure the myoelectric voltage. Pattern and magnitude control of muscle contraction allowed for steering intention recognition and were used to manipulate their power wheelchair joystick. Four patients ages 51 to 69, two female and two male with amyotrophic lateral sclerosis, conducted Wheelchair Skills Test developed by Dalhousie University and were surveyed on the experience’s Clinical Global Impression of Change.

Results

Findings showed independent steering was capable for patients without hand function and provided recommendations for improved human-machine interface. All patients demonstrated the ability to engage the system, with varying precision, for driving their wheelchair in a controlled environment.

Conclusions

Three patients in the pilot trial reported the highest score of clinical global impression of change, all of whom had lost independent control of their wheelchair joystick. Patient four retained impaired hand dexterity for joystick control and reported negative impression of change, comparatively. Feedback from the study will be leveraged to improve training outcomes.

Trial registration Subjects provided signed informed consent according to the Declaration of Helsinki to enter the study that was approved by the Mayo Clinic Institutional Review Board in Rochester, Minnesota. The study is registered on ClinicalTrials.gov under identifier NCT04800926 as of March 14, 2021 retrospectively registered.
Circular RNA circ-BNC2 (hsa_circ_0008732) inhibits the progression of ovarian cancer through microRNA-223-3p/ FBXW7 axis
Authors: Liu Ting , Yuan Li , Zou Xiaofeng
Published: August 2022

Background

Circular RNAs (circRNAs) are reported to be key regulators in the progression of human cancers. This work focuses on the function and molecular mechanism of circRNA-BNC2 (circ-BNC2) (also known as hsa_circ_0008732) in ovarian cancer (OC).

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect circ-BNC2, microRNA-223-3p (miR-223-3p) and F-box and WD repeat domain containing 7 (FBXW7) mRNA expressions in OC tissues and cells. Besides, cell counting kit 8 (CCK-8), transwell assay and cell cycle assays were executed to assess the proliferative, migrative, invasive abilities, and cell cycle progression of OC cells, respectively. Dual-luciferase reporter gene assay and RNA pull-down assay were used to validate the targeting relationships between miR-223-3p and circ-BNC2 or FBXW7. Western blot was adopted to determine FBXW7 protein levels in OC cells.

Results

Circ-BNC2 expression was downregulated in OC tissues and cell lines, which was associated with higher FIGO stage and lymph node metastasis of OC patients. Circ-BNC2 overexpression repressed the proliferation, migration, invasion of OC cells and induced cell cycle arrest, while silencing circ-BNC2 worked oppositely. Mechanistically, circ-BNC2 could upregulate FBXW7 expression in OC cells via sponging miR-223-3p.

Conclusion

Circ-BNC2 suppresses the progression of OC via regulating miR-223-3p / FBXW7 axis. Our findings provided potential biomarker for OC therapy.
Osteoclast-derived extracellular vesicles are implicated in sensory neurons sprouting through the activation of epidermal growth factor signaling
Authors: Neto Estrela , Leitão Luís , Mateus José C. , Sousa Daniela M. , Alves Cecília J. , Aroso Miguel , Monteiro Ana C. , Conceição Francisco , Oreffo Richard O. C. , West Jonathan , Aguiar Paulo , Lamghari Meriem
Published: August 2022

Background

Different pathologies, affecting the skeletal system, were reported to display altered bone and/or cartilage innervation profiles leading to the deregulation of the tissue homeostasis. The patterning of peripheral innervation is achieved through the tissue-specific expression of attractive or repulsive axonal guidance cues in specific space and time frames. During the last decade, emerging findings attributed to the extracellular vesicles (EV) trading a central role in peripheral tissue innervation. However, to date, the contribution of EV in controlling bone innervation is totally unknown.

Results

Here we show that sensory neurons outgrowth induced by the bone resorbing cells—osteoclasts—is promoted by osteoclast-derived EV. The EV induced axonal growth is achieved by targeting epidermal growth factor receptor (EGFR)/ErbB2 signaling/protein kinase C phosphorylation in sensory neurons. In addition, our data also indicate that osteoclasts promote sensory neurons electrophysiological activity reflecting a possible pathway in nerve sensitization in the bone microenvironment, however this effect is EV independent.

Conclusions

Overall, these results identify a new mechanism of sensory bone innervation regulation and shed the light on the role of osteoclast-derived EV in shaping/guiding bone sensory innervation. These findings provide opportunities for exploitation of osteoclast-derived EV based strategies to prevent and/or mitigate pathological uncontrolled bone innervation.
D-dopachrome tautomerase drives astroglial inflammation via NF-κB signaling following spinal cord injury
Authors: Li Hui , He Bingqiang , Zhang Xingyuan , Hao Huifei , Yang Ting , Sun Chunshuai , Song Honghua , Wang Yingjie , Zhou Yue , Zhu Zhenjie , Hu Yuming , Wang Yongjun
Published: August 2022

Background

Reactive astrocytes are increasingly recognized as crucial regulators of innate immunity in degenerative or damaged central nervous system (CNS). Many proinflammatory mediators have been shown to drive inflammatory cascades of astrocytes through activation of NF-κB, thereby affecting the functional outcome of the insulted CNS. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of proinflammatory macrophage migration inhibitory factor (MIF), has been revealed to share receptor and overlapping functional spectrum with MIF, but little is known about its roles in the neuropathological progression of the CNS and relevant regulatory mechanisms.

Results

D-DT protein levels were significantly elevated within neurons and astrocytes following SCI. Analysis of transcriptome profile revealed that D-DT was able to activate multiple signal pathways of astrocytes, which converged to NF-κB, a hub regulator governing proinflammatory response. Rat D-DT recombinant protein was efficient in inducing the production of inflammatory cytokines from astrocytes through interaction with CD74 receptor. Activation of mitogen-activated protein kinases (MAPKs) and NF-κB was observed to be essential for the transduction of D-DT signaling. Administration of D-DT specific inhibitor at lesion sites of the cord resulted in significant attenuation of NF-κB activation and reduction of the inflammatory cytokines following SCI, and accordingly improved the recovery of locomotor functions.

Conclusion

Collectively, D-DT is a novel proinflammatory mediator of astrocytes following SCI. Insights of its cell-specific expression and relevant proinflammatory mechanisms will provide clues for the control of CNS inflammation.
Functions and mechanisms of protein disulfide isomerase family in cancer emergence
Authors: Rahman Nisa Syakila A. , Zahari Syazalina , Syafruddin Saiful Effendi , Firdaus-Raih Mohd , Low Teck Yew , Mohtar M. Aiman
Published: August 2022

The endoplasmic reticulum (ER) is a multi-layered organelle that is essential for the synthesis, folding, and structural maturation of almost one-third of the cellular proteome. It houses several resident proteins for these functions including the 21 members of the protein disulfide isomerase (PDI) family. The signature of proteins belonging to this family is the presence of the thioredoxin domain which mediates the formation, and rearrangement of disulfide bonds of substrate proteins in the ER. This process is crucial not only for the proper folding of ER substrates but also for maintaining a balanced ER proteostasis. The inclusion of new PDI members with a wide variety of structural determinants, size and enzymatic activity has brought additional epitomes of how PDI functions. Notably, some of them do not carry the thioredoxin domain and others have roles outside the ER. This also reflects that PDIs may have specialized functions and their functions are not limited within the ER. Large-scale expression datasets of human clinical samples have identified that the expression of PDI members is elevated in pathophysiological states like cancer. Subsequent functional interrogations using structural, molecular, cellular, and animal models suggest that some PDI members support the survival, progression, and metastasis of several cancer types. Herein, we review recent research advances on PDIs, vis-à-vis their expression, functions, and molecular mechanisms in supporting cancer growth with special emphasis on the anterior gradient (AGR) subfamily. Last, we posit the relevance and therapeutic strategies in targeting the PDIs in cancer.
Presenilin-1 F105C mutation leads to tau accumulation in human neurons via the Akt/mTORC1 signaling pathway
Authors: Chong Cheong-Meng , Tan Yuan , Tong Jiaqi , Ke Minjing , Zhang Ke , Yan Lingli , Cen Xiaotong , Lu Jia-Hong , Chen Guobing , Su Huanxing , Qin Dajiang
Published: August 2022

Background

The mammalian target of rapamycin (mTOR) plays a critical role in controlling cellular homeostasis, and its dysregulation has been implicated in Alzheimer’s disease (AD). Presenilin-1 (PS1) mutations account for the most common causes of familial Alzheimer’s disease (FAD); however, whether PS1 mutation causes mTOR dysregulation in human neurons remains a key unresolved issue.

Methods

We generated heterozygotes and homozygotes of PS1 F105C knock-in mutation in human induced pluripotent stem cells (iPSCs) via CRISPR/Cas9/piggyback-based gene editing and differentiated them into human neurons. Secreted Aβ and tau accumulation were determined by ELISA assay, immunofluorescence staining, and western blotting analysis. mTOR signaling was evaluated by western blotting analysis, immunofluorescence staining, and co-immunoprecipitation. Autophagy/lysosome activities were determined by LC3-based assay, LysoTracker Red staining, and DQ-Red BSA staining.

Results

Through comparison among these isogenic neurons, PS1 F105C mutant neurons exhibited elevated Aβ and tau accumulation. In addition, we found that the response of mTORC1 to starvation decreases in PS1 F105C mutant neurons. The Akt/mTORC1/p70S6K signaling pathway remained active upon EBSS starvation, leading to the co-localization of the vast majority of mTOR with lysosomes. Consistently, PS1 F105C neurons displayed a significant decline in starvation-induced autophagy. Notably, Torin1, a mTOR inhibitor, could efficiently reduce prominent tau pathology that occurred in PS1 F105C neurons.

Conclusion

We demonstrate that Chinese PS1 F105C mutation causes dysregulation of mTORC1 signaling, contributing to tau accumulation in human neurons. This study on inherited FAD PS1 mutation provides unprecedented insights into our understanding of the molecular mechanisms of AD. It supports that pharmaceutical blocking of mTOR is a promising therapeutic strategy for the treatment of AD.
The effectiveness of teachers’ written and verbal corrective feedback (CF) during formative assessment (FA) on male language learners’ academic anxiety (AA), academic performance (AP), and attitude toward learning (ATL)
Authors: Patra Indrajit , Alazemi Asmaa , Al-Jamal Dina , Gheisari Asma
Published: August 2022

Although corrective feedback (CF) has been studied, more studies still need to be conducted on this variable to check its effects on language learning. Therefore, this study aimed to investigate the effectiveness of teachers’ written and verbal CF during the formative assessment (FA) on English as a foreign language (EFL) learners’ academic anxiety (AA), academic performance (AP), and attitude toward learning (ATL) in Ahvaz, Iran. Using the convenience sampling method, 76 students were chosen and divided into the experimental group (EG) and control group (CG). The EG received CF during FA, but CG was taught traditionally. After analyzing the data through descriptive and inferential statistics, the results indicated that the teachers’ written and verbal CF during FA positively affected the experimental language learners’ AP. In addition, the results showed that teachers’ CF significantly diminished the EG’s level of anxiety. Regarding the learners’ ATL English, the results showed that there was a significant change in the pre-test and post-test due to the feedback received from the teacher, which means that learners’ ATL enhanced remarkably. Considering the results of this study, a number of conclusions are drawn, and several implications are put forward.
Accuracy of the digital workflow for guided insertion of orthodontic palatal TADs: a step-by-step 3D analysis
Authors: Pozzan Lucia , Migliorati Marco , Dinelli Luca , Riatti Riccardo , Torelli Lucio , Di Lenarda Roberto , Contardo Luca
Published: August 2022

Background

The introduction in the orthodontic field of the digital workflow for guided insertion of palatal TADs and the development of the 1-visit protocol led to the reduction of chair time and the possibility of complete customization of designs and materials. Conversely, the reduction of operative steps implicates a lower tolerance of deviations between the planned and the actual position of the miniscrews, particularly when the orthodontic device is fixed on 4 palatal TADs or has a rigid structure. This study aims to analyze the influence of each step of the digital workflow on the deviation of the miniscrews’ axis of insertion in a bicortical sample. The null hypothesis is that there are no significant differences in the deviations among the operative steps.

Methods

33 subjects were selected for insertion of bicortical palatal miniscrews with a 1-visit protocol. Digital files were collected at the three stages of the workflow (i.e., digital planning, laboratory prototype, post-insertion impression). A 3D software analysis was performed on a total of 64 miniscrews. After automatic shape recognition of the guiding holes of the digital plan and the scanbodies of the laboratory prototype and post-insertion impression as geometric cylinders, their three-dimensional longitudinal axis was traced and the deviation among them was calculated. Friedman test with Bonferroni correction was performed to assess the significance of the deviations among the three steps, with significance set at p < 0.05.

Results

The laboratory step has a significantly lower degree of deviations (2.12° ± 1.62) than both the clinical step (6.23° ± 3.75) and the total deviations (5.70° ± 3.42). No significant differences were found between miniscrews inserted on the left or the right side.

Conclusions

This study suggests that laboratory procedures such as surgical guide production or rapid prototyping don’t play a significant role in the degree of deviations between the planned and the positioned palatal TADs. Conversely, the clinical steps have a bigger influence and need to be carefully evaluated. Despite this difference, there is a cumulative effect of deviations that can lead to the failure of the 1-visit protocol.
Lifetime history of TBI with loss of consciousness and disability among Appalachian and rural residents: 2016–2019 Ohio BRFSS
Authors: Feiss Robyn , Corrigan John D. , Ding Kele , Beaulieu Cynthia L. , Bogner Jennifer , Yang Jingzhen
Published: August 2022

Background

While lifetime history of traumatic brain injury (TBI) is associated with increased risk of disabilities, little is known about disability and TBI among Appalachian and other rural residents. This study aimed to examine if the relationship between lifetime history of TBI with loss of consciousness (LOC) and disability differs by location of living (Appalachian vs. non-Appalachian; rural vs. urban).

Methods

We obtained data on lifetime history of TBI with LOC, location of living, and six sources of disability (auditory, visual, cognitive, mobility, self-care related, and independent living-related impairments) from the 2016–2019 Ohio Behavioral Risk Factor Surveillance System. We modeled the disability outcomes with Appalachian living (or rural living), lifetime history of TBI with LOC, and their interaction as independent variables.

Results

Of the 16,941 respondents included, 16.9% had a lifetime history of TBI with LOC, 19.5% were Appalachian residents and 22.9% were rural residents. Among Appalachian residents, 56.1% lived in a rural area. Appalachian (ARR = 1.92; 95%CI = 1.71–2.13) and rural residents (ARR = 1.87; 95%CI = 1.69–2.06) who had a lifetime history of TBI with LOC were at greater risk for having any disability compared to non-Appalachian and urban residents without lifetime history of TBI with LOC, respectively.

Conclusions

Appalachian and rural living and lifetime history of TBI with LOC are risk factors for disability. Future research and health policies should address mechanisms for this risk as well as access to healthcare services following a TBI among Appalachian and rural residents.
A multidimensional approach to wearability assessment of an electronic wrist bracelet for the criminal justice system
Authors: Lee Soo-Min , Lee So-Hyun , Park Juyeon
Published: August 2022

Electronic monitoring systems have been globally adopted to track criminals to ensure public safety efficiently. In this study, we aimed to assess the wearability of an electronic bracelet using multiple evaluation methods, including the evaluation of range of motion (ROM), air gap (AG), and clothing pressure (CP) at the wearer’s wrist, as well as self-scoring of subjective comfort (SC). We recruited eight Korean male participants (N = 8) who were in their 30 s and did not have any musculoskeletal problems at data collection. We compared the test results collected on the first day with those obtained after wearing the electronic wrist bracelet for 5 consecutive days. We also examined the differences between the normal-weight and overweight groups. Overall, the data evinced a decrease in the wrist ROM, AG, and SC, but an increase in the CP after it was worn for 5 days. And, the results were more observable in the overweight group, as compared to the normal-weight group. Furthermore, this study proposed a novel and effective assessment tool that could be used to measure the wearability of devices or systems intended to be worn on the human body—not only the electronic wrist bracelet for criminal monitoring but also popular commercial electronic bracelets for sportswear or health-related monitoring system.
Vaccines platforms and COVID-19: what you need to know
Authors: Acosta-Coley Isabel , Cervantes-Ceballos Leonor , Tejeda-Benítez Lesly , Sierra-Márquez Lucellys , Cabarcas-Montalvo María , García-Espiñeira María , Coronell-Rodríguez Wilfrido , Arroyo-Salgado Bárbara
Published: August 2022

Background

The novel SARS-CoV-2, responsible for the COVID-19 pandemic, is the third zoonotic coronavirus since the beginning of the 21 first century, and it has taken more than 6 million human lives because of the lack of immunity causing global economic losses. Consequently, developing a vaccine against the virus represents the fastest way to finish the threat and regain some "normality."

Objective

Here, we provide information about the main features of the most important vaccine platforms, some of them already approved, to clear common doubts fostered by widespread misinformation and to reassure the public of the safety of the vaccination process and the different alternatives presented.

Methods

Articles published in open access databases until January 2022 were identified using the search terms "SARS-CoV-2," "COVID-19," "Coronavirus," "COVID-19 Vaccines," "Pandemic," COVID-19, and LMICs or their combinations.

Discussion

Traditional first-generation vaccine platforms, such as whole virus vaccines (live attenuated and inactivated virus vaccines), as well as second-generation vaccines, like protein-based vaccines (subunit and viral vector vaccines), and third-generation vaccines, such as nanoparticle and genetic vaccines (mRNA vaccines), are described.

Conclusions

SARS-CoV-2 sequence information obtained in a record time provided the basis for the fast development of a COVID-19 vaccine. The adaptability characteristic of the new generation of vaccines is changing our capability to react to emerging threats to future pandemics. Nevertheless, the slow and unfair distribution of vaccines to low- and middle-income countries and the spread of misinformation are a menace to global health since the unvaccinated will increase the chances for resurgences and the surge of new variants that can escape the current vaccines.
Exploring the relationship between computational thinking and learning satisfaction for non-STEM college students
Authors: Liao Chien Hsiang , Chiang Chang-Tang , Chen I-Chuan , Parker Kevin R.
Published: August 2022

While various studies have focused on the significance of computational thinking (CT) for the future career paths of individuals in science, technology, engineering, and mathematics (STEM), few studies have focused on computational thinking for non-STEM college students. This study explores the relationship between computational thinking and learning satisfaction for non-STEM-major college students. A conceptual model is proposed to examine the structural relationships among computational thinking, self-efficacy, self-exploration, enjoyment and learning satisfaction in an AppInventor-based liberal education course. Collecting data from 190 undergraduate students from Taiwan and analyzing the data by using partial least squares (PLS) methods, the research framework confirms the six proposed hypotheses. These results show that both computational thinking and enjoyment play significant roles in both self-exploration and digital self-efficacy. Moreover, digital self-efficacy and self-exploration also have a significant positive influence on learning satisfaction. These findings have implications for influencing the learning outcomes of non-STEM-major college students, computational thinking course instructors, and computational thinking relevant policies.
Combined modality PET/MR for the detection of severe large vessel vasculitis
Authors: Cerne John W. , Liu Sophia , Umair Muhammad , Pathrose Ashitha , Moore Jackson E. , Allen Bradley D. , Markl Michael , Carr James C. , Savas Hatice , Wilsbacher Lisa , Avery Ryan
Published: August 2022

Background

Large vessel vasculitis (LVV) can be characterized based on symptom severity, and this characterization helps clinicians decide upon treatment approach. Our aim was to compare the imaging findings of combined modality positron emission tomography/magnetic resonance (PET/MR) and inflammatory markers between severe and non-severe LVV. A retrospective query was performed to identify all patients with LVV who underwent PET/MR at our institution between January 2015 and January 2021.

Results

Eleven patients (nine females; age 62.2 ± 16.4 years) underwent 15 PET/MR scans. Positivity was defined by findings indicative of active LVV on each modality: PET positive if vessel metabolic activity > liver metabolic activity; MR positive if wall thickening or contrast enhancement. When positive PET or positive MR findings were considered a positive scan, LVV patients with severe disease (n = 9 scans) showed a higher number of positive scans (n = 9) compared to the number of positive scans in non-severe patients (n = 3) (p < 0.05). The sensitivity and specificity for the detection of severe LVV were 1.00 and 0.50, respectively. When only the presence of both positive PET and positive MR findings were considered a positive scan, inflammatory marker levels were not significantly different between severe and non-severe LVV groups (severe: erythrocyte sedimentation rate (ESR) = 9.8 ± 10.6 mm/h; C-reactive protein (CRP) = 0.6 ± 0.4 mg/dL) (non-severe: ESR = 14.3 ± 22.4 mm/h; CRP = 0.5 ± 0.6 mg/dL). Blood- and liver-normalized maximum standardized uptake values were not significantly different between severe and non-severe patients (1.4 ± 0.3 vs 1.5 ± 0.4; 1.1 ± 0.4 vs 1.0 ± 0.3, respectively).

Conclusions

Because of the differences observed, PET/MR appears to be better suited to facilitate the characterization of LVV as severe or non-severe compared to inflammatory marker measurements and quantitative measurements of metabolic activity. Qualitative assessment of PET and MR positivity by 18F-fluorodeoxyglucose PET/MR may be able to supplement clinical symptoms-based LVV classification decisions and may be helpful when clinical symptoms overlap with other disease processes.
Influence of CYP2D6, CYP2C19 and CYP3A5 polymorphisms on plasma levels of tamoxifen metabolites in Algerian women with ER+ breast cancer
Authors: Boucenna Amira , Boudaoud Khadidja , Hireche Ahmed , Rezgoune Mohamed Larbi , Abadi Noureddine , Filali Taha , Satta Dalila
Published: August 2022

Background

Tamoxifen, a selective estrogen receptor modulator, is indicated for breast cancer developed in response to estrogen.

Findings

In the current study we explored the relationship between the different variants of CYP2D6, CYP2C19, CYP3A5 and plasma Endoxifen levels in Algerian patients with ER + breast cancer. We further conducted the relationship between the candidate genes and the recurrences rate. Endoxifen levels differed significantly (p < .005) between carriers of two functional alleles and patients genotyped as CYP2D6*10, CYP2D6*17, CYP2D6*41 or CYP2D6*5/*5. Patients with elevated Endoxifen concentrations were significantly more likely to not report recurrences than patients with reduced or nul alleles. Such nul/nul, red/red, and red/nul diplotypes have been associated with a higher rate of recurrences than other genotypes during treatment.

Conclusion

Our findings suggest that the CYP2D6 genotype should be considered in tamoxifen-treated women. While quantitatively, CYP2D6 represents only a minor fraction of the total drug metabolizing capacity of the liver, it is polymorphic and, therefore, may alter the balance of metabolism of tamoxifen toward the activation pathways. Breast cancer patients with the CYP2D6 nul/nul or red/nul diplotype may benefit less from Tamoxifen treatment and are more likely to develop recurrences. Comprehensive CYP2D6 genotyping has a good predictive value for CYP2D6 activity. Common variants in CYP2C19 and CYP3A5 did not have a significant impact on the recurrences in this cohort of patients with ER + breast cancer.
Cannabis use and effect of cannabis abstinence on cognitive functioning in young people — an observational case-control follow-up study from rehabilitation centre in Andhra Pradesh
Authors: Goud Sripathi Santhosh , Radhika M. S. , Indla Vishal , Kolli Nagasaritha
Published: August 2022

Background

Cannabis is the most commonly used illicit substance globally, in India particularly. In recent times, younger people started abusing cannabis, resulting in academic decline and psychological disorders. Research from developed countries had shown that abstinence from cannabis reverses cognitive decline in the young population to a certain extent. Studies on this topic have been very few in India. We intended to assess the effects of cannabis use and abstinence from cannabis on the cognitive functioning of young adults.

The study was an observational study including 50 consecutive young male patients, who got admitted to our rehabilitation centre with cannabis use disorder (group A). The Montreal Cognitive Assessment (MoCA) test was used to assess the baseline cognitive functioning of these patients initially after 1 week of abstinence and compared with 50 graduate students with no history of cannabis use (group B). The MoCA test was re-administered to group A subjects after 3 months of strict abstinence from cannabis use.

Results

There was a statistically significant difference between the baseline MoCA score of cannabis users and the controls (P < 0.001). Both the duration (r = −0.296, P = 0.036) and the quantity (r= −0.491, P < 0.001) of cannabis use had a negative correlation with the MoCA score. When the MoCA test was re-administered after 3 months of abstinence, we found a statistically significant improvement in cognitive functioning in cannabis users (P < 0.001), but the mean score was still less than the mean score of the control group (24.08 ± 2.66 vs 28.62 ± 0.85, P < 0.001) showing only partial improvement.

Conclusion

This study showed that cognitive deficits were seen in cannabis users as compared to nonusers. It also had shown that abstinence from cannabis had partially reversed the impairment, but still some deficits were remaining. There is an urgent need for primary prevention strategies at community level to decrease the prevalence of cannabis use.
A study of elevated red cell distribution width (RDW) in early-onset neonatal sepsis
Authors: Hodeib Mahmoud , Morgan Dalia , Hedaya Aya , Waked Nevien
Published: August 2022

Background

Neonatal sepsis is a serious infection occurring within the first 28 days of life. It is a significant cause of mortality and morbidity. Red cell distribution width (RDW) is estimated within the standard CBC profile and considered a simple tool for the diagnosis of neonatal sepsis without additional cost. Our aim in this study is to investigate the potential role of red cell distribution width (RDW) in the diagnosis of early-onset neonatal sepsis (EONS). The aim of our study is to detect the role of red cell distribution width (RDW) in the diagnosis and prognosis of early-onset neonatal sepsis (EONS).

Results

This case-control study was conducted at the NICU of Beni-Suef University Hospital and revealed that RDW% was highly significantly higher among cases than among controls (16.65 ± 4.28, 11.13 ± 0.62, respectively); regarding the severity of neonatal sepsis, we divided our cases into three groups (sepsis group includes 21 neonates, severe sepsis group includes 31 neonates, and septic shock group includes 48 neonates), there were statistically significant differences between the three groups (sepsis, severe sepsis, and septic shock) regarding RDW (15.15 ± 1.65, 16.78 ± 2.01, 17.02 ± 2.02, respectively) as P value (0.027).

Conclusion

This study revealed that RDW is associated with the diagnosis and prognosis of early-onset neonatal sepsis, so further study is needed to prove causation as it is being simple, less expensive, available, and easily repeated as it is routinely done with CBC, so it will be a good indicator for prognosis of neonatal sepsis.
Outcomes of acute appendicitis in patients younger than age 4: a descriptive study
Authors: Camacho-Cruz Jhon , Padilla Patricia Ocampo , Sánchez Daniela Guerrero , Mongui Diana Milena , Hoyos Laura Katherine , Porras María Lucia , Hoyos Pablo Vásquez , Polo Fernando , Castro Carlos Alberto
Published: August 2022

Background

Acute appendicitis is an infrequent pathology in children under 4 years of age, and its diagnosis is a clinical challenge that can lead to late detection. The intention of this study is to describe the clinical and surgical findings and to explore factors and outcomes associated with appendiceal perforation in patients under 4 years of age with histologically confirmed acute appendicitis. Cross-sectional study of historical data is on patients with a pathologic diagnosis of appendicitis. Clinical, surgical, and pathological variables were described. The relationship between the presence of perforation and associated factors and outcomes was explored using odds ratios (OR) and 95% confidence intervals.

Results

Seventy-five patients were found between 2013 and 2019. Seventy-four cases presented with pain on palpation, 56 (75%) with signs of peritoneal irritation, and 70 (93%) with sepsis on admission to the emergency room. An ultrasound was done on 57 patients (76%), and only 26 (45%) were suggestive of appendicitis. Forty-one (55%) cases were operated on by open surgery and 34 (45%) by laparoscopy. In 61 (81%), they were perforated, and 48 (64%) presented peritonitis. Perforation was associated with increased hospital days (OR = 2.54 [1.60−4.03]), days of antibiotics (OR = 4.40 [2.09−9.25]), and admission to intensive care (OR = 9.65 [1.18−78.57]).

Conclusions

Abdominal pain reported by parents, pain on abdominal palpation, and clinical criteria of sepsis on admission to the emergency room are common features. Acute appendicitis complicated by perforation leads to high morbidity due to longer antibiotic treatment, hospitalization days, admission to PICU, and postoperative ileus.
Prediction of Covid-19 infection severity using ABO blood group types and Rh factor
Authors: Shah Syed Asim Ali , Arshad Naveed , Asim Fareena , Nadeem Muhammad
Published: August 2022

Background & Objective: Biological markers for the prediction of acquiring Covid-19 risk are deficient and there is a dire need of immediate research data. The objective of the study was to predict the link of ABO blood group types along with Rh factor distribution with the severity of Covid-19.

Methods: This was an observational cross-sectional survey conducted in medicine department of Pakistan Ordnance Factory Hospital, Wah Cantt Pakistan, from August 2020 to December 2020 after approval of IRB. Participants tested positive for presence of Covid-19 infection by polymerase chain reaction (PCR) were included in the study. Covid-19 infection severity was measured through mild, moderate and severe disease categories and analyzed. ABO blood group and Rh subgroups data for all the Covid-19 infected patients were obtained from the laboratory section of the hospital and analyzed. Data was entered in SPSS v 26 and analyzed. Cox regression model was used to find out the severity of Covid-19.

Results: Total 248 patients were included; 75% patients were male and 25% were females. The mean age of the patients was 52.77±15.58 years. A very significant association was found between ABO blood group types, Rh factor antigen and severity of Covid-19 (p=0.001). When stratified ABO, Rh antigen blood group with health status of all patients there was a very significant association between them (p=0.013). An insignificant association between male and female odds ratio of ABO blood group types but blood group B, Rh positive antigen was more susceptible in Covid-19 positive patients.

Conclusion: There is a link between ABO blood group types along with Rh factor antigen (B+ and O+) with the severity of Covid-19 positive patients. ABO blood group types and Rh factor can be used as a potential marker/tool to predict the susceptibility of acquiring Covid-19 infection as well as for severity of the infection.

doi: https://doi.org/10.12669/pjms.38.7.5128

How to cite this:Shah SAA, Arshad N, Asim F, Nadeem M. Prediction of Covid-19 infection severity using ABO blood group types and Rh factor. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.5128

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Medical colleges’ challenges and coping strategies in implementing accreditation standards in Pakistan
Authors: GUL FOUZIA , MAHBOOB USMAN , WAJID GOHAR , SHERIN AKHTAR
Published: August 2022

Objectives: To explore the challenges faced by medical colleges and coping strategies used in implementing accreditation standards by Pakistan Medical Commission during accreditation inspection 2019.

Methods: In this qualitative case study, four medical colleges and their affiliated hospitals from three cities in Khyber Pakhtunkhwa province of Pakistan were selected through purposive sampling. Data was collected through focus group discussions (FGD) through Open-ended questions, based on CIPP (context, input, process, and product) model. Each focus group comprised of Dean, the Director Department of Medical Education (DME) and the Medical Director of the hospital. Data were thematically analyzed and results were based on the CIPP model.

Results: Three themes identified were administrative challenges, accreditation challenges and resource challenges. The administrative challenges theme was further explained under subthemes of rules and regulation challenges, documentation and record challenges, and DME-related challenges. The accreditation-related challenges theme was explored in-depth with subthemes of accreditation process-related challenges, accreditation standards-related challenges and curriculum-related challenges. The resource challenges theme was described under sub-themes of infrastructure-related challenges, human resources and financial challenges. The commonest coping strategies adopted by medical colleges were establishing DME, emergency preparatory meetings of staff, and hiring staff on an emergency basis, to overcome administrative, accreditation and resource challenges respectively. Future suggestions for improving the accreditation process in the local context were highlighted.

Conclusion: Main challenges identified were administrative challenges, accreditation challenges and resource challenges. Coping strategies by the medical colleges for these challenges are highlighted. The accreditation body should harmonize the process of accreditation with medical colleges and other stakeholders.

doi: https://doi.org/10.12669/pjms.38.7.6121

How to cite this:Gul F, Mahboob U, Wajid G, Sherin A. Medical colleges’ challenges and coping strategies in implementing accreditation standards in Pakistan. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.6121

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effect of CYP3A4 and PPARA polymorphism on concentration-to-dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients
Authors: Azam Fahad , Khan Moosa , Shaheen Abida , Bhatti Abu Bakar Hafeez
Published: August 2022

Objectives: Polymorphism in cytochrome P450 3A4 (CYP3A4) and its regulatory gene peroxisome proliferator activated receptor (PPARA) may significantly affect the metabolism of tacrolimus. This study aims to explore the effect of the single nucleotide polymorphisms (SNP) of cytochrome P450 3A4 and PPARA on the pharmacological variables of adverse effects and the concentration-to-dose ratio (CDR) of the immune suppressant drug tacrolimus in Pakistani liver transplant recipients.

Methods: Eighty-one liver transplant patients were included and their demographic and clinical data were recorded. Dosages and trough levels of tacrolimus measured by electrochemiluminescence (ECLIA) were recorded daily. Genotyping for transplant recipients was performed for CYP3A4 rs35599367, PPARA rs4253728 and rs4823613. Incidence of sepsis, acute cellular rejection (ACR) and other adverse effects were recorded.

Results: Liver transplant recipients with CYP3A4 rs35599367 CT and TT genotype reported higher tacrolimus CDR compared to the CC genotype during week-1 (p<0.001) and week-2 (p =0.03) post-transplantation period. CYP3A4 rs35599367 polymorphism presented a significant association with nephrotoxicity, sepsis, seizures and psychosis. Significant association of PPARA rs4253728 and PPAARA rs4823613 polymorphism with ACR was observed.

Conclusion: Genotyping for CYP3A4 rs35599367 polymorphism during dose titration may shorten the duration to reach optimal tacrolimus trough levels and may help predict adverse events in transplant recipients receiving tacrolimus; genotyping for PPARA rs4253728 and rs4823613 may predict the incidence of ACR.

doi: https://doi.org/10.12669/pjms.38.7.6180

How to cite this:Azam F, Khan M, Shaheen A, Bhatti AH. Effect of CYP3A4 and PPARA polymorphism on concentration-to-dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.6180

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
CPP-ACP complex as a solution to the problem of complications after teeth bleaching - a literature review
Authors: Kula Łucja , Mocny-Pachonska Katarzyna
Published: August 2022

Introductions and purpose: Teeth bleaching is an increasingly popular procedure that comes with its specific set of complications including damaged enamel, dentin hypersensitivity, and increased vulnerability to bacterial colonization. CPP-ACP complex possesses remineralizing and bacteriostatic properties as well as the ability to abolish dentin hypersensitivity. The aim of this study is to systematise the state of current knowledge on the use of casein phosphopeptide with amorphous calcium phosphate in combating complications after tooth bleaching.

Description of the state of knowledge: The CPP-ACP complex used alone or in a protocol with a bleaching agent, in a way that is comparable to other products, abolishes post-operative dentin hypersensitivity by blocking the flow of dentino-pulpal tubular fluid. It restores the morphological properties of the tooth, by increasing the hardness of the bleached enamel, more effectively than fluoride agents. Casein phosphopeptide with amorphous calcium phosphate limits the penetration of the bleaching agent into the tooth chamber, thereby preventing the development of pulp inflammation. Moreover, because of its buffering properties, it prevents the development of caries on surfaces weakened by the bleaching process.