bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Ki-67 Proliferative Index Assessment of Human B-Cell Lymphomas By Flow Cytometry
Authors: Castillo Felipe , Morales Constanza , Iruretagoyena Mirentxu , Díaz Schmidt Joaquin , Ernst Daniel
Published: December 2023

Background:

The Ki-67 proliferative index is used as a diagnostic and prognostic marker in the classification of B-cell non-Hodgkin lymphomas (NHL). Despite its semiquantitative nature, immunohistochemistry (IHC) evaluation of Ki-67 in histologic specimens is the gold standard. The aim of this study was to determine the correlation of quantitative Ki-67 expression by flow cytometry (FCM) with standard IHC in samples of B-cell NHL.

Methods:

We performed a retrospective observational study of bone marrow and tissue biopsies evaluated for routine lymphoma screening between January 2021 and December 2022. FCM analysis was performed according to Euroflow standard LST screening. Positive samples were further characterized, and Ki-67 expression was integrated using a PerCP-Cy5.5 fluorochrome-conjugated monoclonal antibody after cell fixation and permeabilization. The Ki-67 proliferative index was calculated as all positive events among the neoplastic population (%). Ki-67 proliferative index by flow cytometry was compared with Ki-67 proliferative index by IHC. Clinical data were retrieved from the electronic database. This study was approved by the institutional IRB and clinical ethics committee.

Results:

A total of 51 samples from 50 patients were evaluated: 4 bone marrow aspirates, 8 fine-needle aspirations (FNA) and 39 tissue biopsies. Median age at diagnosis was 67 years (interquartile range [IRQ], 60-79 years), and 45% were female. A low-grade lymphoma was diagnosed in 27 cases (52.9%; 20/27 follicular lymphoma), a high-grade lymphoma case in 23 cases (45.1%; 20/23 diffuse large B-cell lymphoma), and mantle cell lymphoma in 1 case.

Median Ki-67 proliferative index by FCM was 41.4% (range, 1 - 100%) and 54.8% (range, 5 - 100%) by IHC. Overall, the Ki-67 proliferation index by FCM showed a significant correlation coefficient of 0.925 with IHC (95% IC 0.870 - 0.957, p < 0.0001). There was a negative constant bias of -13.35% (-46.87 to 20.16), which was greater in the range of 30-80% of Ki-67 expression by IHC.

Indolent lymphomas displayed a lower proliferative index by FCM compared with IHC (5 vs 20%, p<0.001). No difference was seen among aggressive lymphomas. Fourteen cases had a difference in the proliferative index >20%, 10/14 were follicular lymphoma, 2/14 were indolent lymphoma transformations and 2 were large B-cell NHL. In all cases FCM displayed lower results compared with IHC.

Conclusions:

Our data suggest that the Ki-67 proliferative index can be accurately assessed by flow cytometry. A correlation bias seems clinically meaningful in intermediate values of Ki-67. The quantitative nature of FCM-based proliferative index may improve the prognostic potential of Ki-67, especially for indolent or borderline histologies. Further validation studies are warranted.
The Biodistribution of the Novel Heme and Hemoglobin Scavenger Apohemoglobin-Haptoglobin Complex in Healthy C57BL/6 Mice
Authors: Lucas Daniela , Munoz Carlos J , Muller Cynthia R , Gopal Srila , Cabrales Pedro
Published: December 2023

Background: Apohemoglobin-haptoglobin (apoHb-Hp) complex represents a bioengineered complex designed to scavenge hemoglobin and heme. These substances are released into the intravascular space during hemolysis, leading to vasoconstriction, inflammation, and disease progression. The use of apoHb-Hp complex has already demonstrated promising results in sickle cell and beta-thalassemia mouse models, highlighting its potential as a therapeutic agent. However, there are still crucial aspects that remain poorly understood, particularly concerning the biodistribution and pharmacokinetics associated during chronic administration. Understanding how the drug is distributed throughout the body is essential for optimizing its therapeutic potential, ensuring patient safety, and guiding both drug development and clinical use.

Methods: To address these critical questions of apoHb-Hp biodistribution and pharmacokinetics, we conducted a study using twenty C57BL/6 mice from Jackson Laboratory. The mice were treated with the apoHb-Hp complex via daily injection every other day for different periods: 24 hours, one week, three weeks, and six weeks, with five mice in each subgroup. The dosage used was 80 mg/kg, and the concentration was 33.6 mg/mL. To evaluate the half-life and biodistribution of the complex, the last dose in each subgroup was radiolabeled with technetium-99m (99mTc-ApoHb-Hp).The intravascular 99mTc-ApoHb-Hp levels were measured after 30 minutes, 1 hour, 4 hours, and 24 hours to establish the drug's half-life. After the final tail vein sample collection, the mice were sacrificed, and their hearts, livers, spleens, lungs, and kidneys were weighed and collected to determine the amount of 99mTc-ApoHb-Hp present in each organ.

Results: The results indicate that a significant portion of the 99mTc-ApoHb-Hp was accumulated in the liver, and regardless of the duration of dosing, the half-life for the 24 hour group was 10 hours, for the 1 week it was 6.5hrs, and for the 3 weeks it was 9hrs, showing no significant difference between the groups. hours. Liver accumulation favors the hepatocytes metabolism degradation of the apoHb-Hp complex from the body. There was no significant differences in half life based on dosing chronicity, likely suggesting that there was no additional degradation of ApoHb-Hp by immune mediated mechanisms such as antibody formation.

In conclusion, Biodistribution of ApoHb-Hp was predominantly in the liver in both acute setting ( single dose) and chronic setting ( multiple doses). The average half life of the infusion was 5 hours and the predominant clearance mechanism was likely via hepatic elimination. Further research and development may help improve our understanding of the biodistribution of the apo Hb- Hp complex, therapy opening new doors for the treatment of hemolytic anemias using the ApoHb-Hp complex.
Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients
Authors: Fregonese Beatrice , Hajj Carla , Gonzalez Silvano , Lee Jisun , Boe Lily , Imber Brandon S. , Yahalom Joachim
Published: December 2023

Background/Objectives: Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy.

Materials/Methods: 285 consecutive pts with PG lymphomas treated with RT between 1/2000-1/2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE v4.0.

Results: Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 years (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-year OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT.

Conclusion: Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.
Changes in Immune-Related Indicators in Patients with Hematopoietic Abnormalities and Their Impact on Clinical Symptoms
Authors: Chen Mengran , Zhao Lei , Yang Jinjun , Wu Yu
Published: December 2023

Background: The pathogenesis of myelodysplastic syndrome (MDS) is mainly driven by specific genetic lesions involving stem cell compartments. But recent studies have found that MDS also appears to be related to immune mechanisms. There is still no consensus on which immune pathway is involved. As a result, we investigated the potential implications of various immune cell subpopulations on hematopoietic abnormalities disease occurrence and development.

Methods: 69 MDS patients in our hospital and 31 normal controls are involved. Clinical data were collected and immune-related indicators were detected through blood routine testing, flow cytometry, ELISA, and other testing methods. Then we analyzed the differences between immune groups in patients and normal individuals, as well as the correlation between the immune group and clinical symptoms.

Results: In lymphocytes, the activated T cell population was significantly increased in patients with MDS (p<0.01), with CD4 + T cell being the most significantly elevated (p<0.01). In atypical T cell subtypes, NK-T was the most significantly reduced (p<0.01). Among immune cell receptors, the NK-P46 was significantly increased (p<0.01). And there was a significant decrease in immune cell activity experiments (p<0.01). In the correlation study, we found a negative correlation between neutrophils and NK-NKG2D cells (r=-0.52, p<0.01), and a positive correlation between bone marrow progenitor cells and Th17 (r=0.47, p<0.05). (figure 1)

Conclusion: It has been confirmed that the immune mechanism has indeed had an impact on MDS. We found a significant increase in the T cell population but a decrease in immune cell function in patients with MDS. Indicating a new direction for studying immune mechanisms in MDS patients.
Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience
Authors: Béranger Nicolas , Coppo Paul , Tsatsaris Vassilis , Boisseau Pierre , Provôt François , Delmas Yahsou , Poullin Pascale , Vanhoorelbeke Karen , Veyradier Agnès , Joly Bérangère S.
Published: December 2023

Pregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary teams. The mechanisms responsible for a deficiency in the disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) leading to pregnancy-onset TTP may be congenital or acquired, and studying ADAMTS13 conformation could be of interest. The differential diagnosis between TTP and other pregnancy-associated thrombotic microangiopathies (TMA) is often challenging. Our retrospective multicenter study highlights the significance and the challenges associated with pregnancy-onset TTP and childbirth in terms of diagnosis, obstetric management, and follow-up aspects. Among 1174 pregnancy-onset TMA enrolled in the French Registry for TMA from 2000 to 2020, we identified 108 pregnancy-onset TTP: 52 immune-mediated TTP (iTTP, 48.1%), 27 acquired TTP of unidentified mechanism (uTTP, 25%), and 29 congenital TTP (cTTP, 26.9%). Data show that maternal outcome is good (survival rate: 95%) and fetal outcome is linked to the gestational age at the onset of the disease (survival rate: 75.5%). Three distinct entities with different natural histories emerged: pregnancy-onset iTTP appears similar to idiopathic iTTP, with an open ADAMTS13 conformation, and is marked by a relapse risk independent of subsequent pregnancies; pregnancy-onset uTTP appears to have a different pathophysiology with an unexpected open ADAMTS13 conformation and a very low relapse risk independent of subsequent pregnancies; finally, pregnancy-onset cTTP is characterized by the necessity of pregnancy as a systematic and specific trigger and a need for prophylactic plasmatherapy for subsequent pregnancies. This trial was registered at www.clinicaltrials.gov as #NCT00426686, and at the Health Authority and the French Ministry of Health (P051064/PHRC AOM05012).
Psychological characteristics and emotional difficulties underlying school refusal in adolescents using functional near-infrared spectroscopy
Authors: Li Gaizhi , Niu Ying , Liang Xiumei , Andari Elissar , Liu Zhifen , Zhang Ke-Rang
Published: December 2023

Background

This study aims to explore the psychological characteristics, related emotional problems and potential NIR brain function mechanism of adolescents who refuse to attend school.

Methods

The study included 38 adolescents (12–18 years old) who were not attending school and 35 healthy controls (12–18 years old) who are attending school regularly. Participants completed (1) general demographics, (2) Eysenck Personality Questionnaire (EPQ), (3) Zung Self-Rating Depression Scale (SDS), (4) Zung Self-Rating Anxiety Scale (SAS), and (5) Symptom Checklist-90 (SCL-90). In addition to the clinical tests, participants completed functional near-infrared spectroscopy (fNIRS). Mental health, personality, and emotional state were evaluated in both groups to explore the differences and to understand the underlying mechanisms of school refusal during adolescence.

Results

Adolescents who did not attend school had higher neuroticism scores on the Eysenck Personality Questionnaire than healthy controls (p(FDR) < 0.001), introversion and concealment scores were lower than those of healthy controls (p(FDR) < 0.001), there was no significant difference in psychoticism scores between groups. SDS, SAS, SCL-90 scores and factor scores were higher than those of healthy control group (p(FDR) < 0.001), NIR functional brain imaging was different from healthy control group in the 12 and 27 channels (p(FDR) = 0.030, p(FDR) = 0.018), and no difference was found in the remaining channels (p(FDR) > 0.05). There were statistically significant differences in age and gender between the adolescents who refused school and the control group (p(FDR) < 0.001).

Conclusion

School refusal adolescents are relatively introverted and sensitive and need more attention in daily life. Although the adolescents’ emotional problems did not reach the diagnostic criteria of depressive disorder and anxiety disorder, their scores were still higher than those of the control group, suggesting that we should pay more attention to their emotional problems in order to better help them return to school. Using fNIRS, it was found that abnormalities in frontal lobe regions in adolescents with school refusal behaviors, which would contribute to early diagnosis and timely intervention of school refusal behaviors.
Prevalence of and factors associated with scrub typhus exposure among the hill tribe population living in high incidence areas in Thailand: a cross-sectional study
Authors: Tasak Nidanuch , Apidechkul Tawatchai , Law Andrew C. K. , Abdad Mohammad Yazid , Srichan Peeradone , Perrone Carlo , Tanganuchitcharnchai Ampai , Wongsantichon Jantana , Blacksell Stuart D.
Published: December 2023

Background

Scrub typhus is a significant tropical disease, occurring in rural settings and therefore usually afflicting remote agricultural populations who have lower socioeconomic status and limited access to medical care. A large proportion of the hill tribe people in Thailand are financially poor, have limited education, and do not have adequate health care access. This study aimed to estimate the prevalence of and determine factors associated with scrub typhus exposure among the hill tribe population living in high-incidence areas in northern Thailand.

Methods

A cross-sectional study design was used to gather information from hill tribe people aged 18 years and over living in ten hill tribe villages in Mae Fah Luang, Chiang Rai Province, Thailand. Participants who met the inclusion criteria were invited to participate in the study. A validated questionnaire was used as the research instrument, and 5 mL blood samples were taken.Orientia tsutsugamushiIgM and IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and then confirmed by immunofluorescence assay (IFA). Logistic regression was used to detect associations between variables at a significance level of α = 0.05.

Results

A total of 485 hill tribe people participated in the study; 57.1% were female, 29.9% were over 60 years of age, 46.4% were from the Akha tribe, and 74.2% had never attended school. The overall prevalence of scrub typhus exposure was 48.0%. In the multivariate model, five variables were found to be associated with scrub typhus exposure. Participants aged over 60 years had a 4.31-fold increased risk (95% CI = 1.73–10.72) of scrub typhus exposure compared to those who were younger than 30 years. Those who were illiterate had a 3.46-fold increased risk (95% CI = 1.93–6.21) of scrub typhus exposure than those who had at least a primary education level. Participants from the Akha tribe had a 2.20-fold increased risk (95% CI = 1.31–3.72) of scrub typhus exposure than those from the Lahu tribe. Subjects who had a history of cutting grass had a 1.85-fold increased risk (95% CI = 1.20–2.84) of scrub typhus exposure. Those who never wore gloves for farming had a 2.12-fold increased risk (95% CI = 1.28–3.49) of scrub typhus exposure than those who wore gloves daily.

Conclusions

There is a high prevalence of scrub typhus exposure among the hill tribe in Thailand. Effective public health interventions to promote scrub typhus awareness and prevention are urgently needed in these populations.
Effects of “fixation-fusion” sequence of lumbar surgery on surgical outcomes for patients with lumbar spinal stenosis: study protocol for a multicenter randomized controlled trial
Authors: Pan Weicheng , Jiang Jialin , Zhang Weihang , Mei Zijian , Sun Kaiqiang , Zheng Bing , Meng Yake , Bai Yushu , He Zhimin , Shi Jiangang , Guo Yongfei
Published: December 2023

Background

New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis.

Methods and analysis

This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis populations in the study.

Conclusion

This study is designed to investigate the clinical outcomes of modified LIF sequences in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified “fixation-fusion” sequence of LIF surgery is effective in treating lumbar spinal stenosis.

Trial registration

http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507.
The larger patellar tilt angle and lower intercondylar notch angle might increase posterior cruciate ligament injury risk: a retrospective comparative study
Authors: Huo Zhenhui , Hao Kuo , Fan Chongyi , Li Kehan , Li Ming , Wang Fei , Niu Yingzhen
Published: December 2023

Background

Posterior cruciate ligament (PCL) injuries are common ligament injuries of the knee, and previous studies often focused on the associations between the morphology of the knee and PCL injuries. Studies on the correlation between PCL injuries and patellofemoral alignment are limited.

Methods

This retrospective study included 92 patients with PCL injured and 92 patients with PCL intact. Measurement parameters were compared between the two groups, including patellar tilt angle, congruence angle, patellar height, hip-knee-ankle angle, lateral trochlear inclination, femoral condyle ratio, bicondylar width, intercondylar notch width and index, notch angle, trochlear facet asymmetry, and trochlear sulcus depth and angle. Independent risk factors associated with PCL injuries were identified by logistic regression analyses.

Results

In the PCL injured group, the patellar tilt angle was significantly larger (13.19 ± 5.90° vs. 10.02 ± 4.95°, P = 0.04); the intercondylar notch angle was significantly lower (60.97 ± 7.83° vs. 67.01 ± 6.00°, P = 0.004); the medial and lateral femoral condyle ratio were significantly larger (0.63 ± 0.64 vs. 0.60 ± 0.56, P = 0.031; 0.65 ± 0.60 vs. 0.58 ± 0.53, P = 0.005) than in the PCL intact group. There were 11 patients with patellar dislocation in the PCL injured group, accounting for 12%. In these patients, the patellar height was higher (1.39 ± 0.17 vs. 1.09 ± 0.25, P = 0.009); the trochlear sulcus angle was larger (157.70 ± 8.7° vs. 141.80 ± 8.78°, P < 0.001); and the trochlear sulcus depth was shallower (3.10 ± 1.20mm vs. 5.11 ± 1.48mm, P = 0.003) than those in the patients without patellar dislocation. Multivariate analyses showed that patellar tilt angle (each increase 1 degree, OR = 1.14) and intercondylar notch angle (each increase 1 degree, OR = 0.90) were independent risk factors for PCL injuries.

Conclusion

The patients with PCL injuries had larger patellar tilt angles, lower intercondylar notch angles, and longer posterior femoral condyles than patients with PCL intact. The larger patellar tilt angle and lower intercondylar notch angle might be risk factors for PCL injuries.
Application of density functional theory for evaluating the mechanical properties and structural stability of dental implant materials
Authors: Saini Ravinder Singh , Mosaddad Seyed Ali , Heboyan Artak
Published: December 2023

Background

Titanium is a commonly used material for dental implants owing to its excellent biocompatibility, strength-to-weight ratio, corrosion resistance, lightweight nature, hypoallergenic properties, and ability to promote tissue adhesion. However, alternative materials, such as titanium alloys (Ti–Al-2 V) and zirconia, are available for dental implant applications. This study discusses the application of Density Functional Theory (DFT) in evaluating dental implant materials' mechanical properties and structural stability, with a specific focus on titanium (Ti) metal. It also discusses the electronic band structures, dynamic stability, and surface properties. Furthermore, it presents the mechanical properties of Ti metal, Ti–Al-2 V alloy, and zirconia, including the stiffness matrices, average properties, and elastic moduli. This research comprehensively studies Ti metal's mechanical properties, structural stability, and surface properties for dental implants.

Methods

We used computational techniques, such as the CASTEP code based on DFT, GGA within the PBE scheme for evaluating electronic exchange–correlation energy, and the BFGS minimization scheme for geometry optimization. The results provide insights into the structural properties of Ti, Ti–Al-2 V, and zirconia, including their crystal structures, space groups, and atomic positions. Elastic properties, Fermi surface analysis, and phonon studies were conducted to evaluate the tensile strength, yield strength, ductility, elastic modulus, Poisson's ratio, hardness, fatigue resistance, and corrosion resistance.

Results

The findings were compared with those of Ti–Al-2 V and zirconia to assess the advantages and limitations of each material for dental implant applications. This study demonstrates the application of DFT in evaluating dental implant materials, focusing on titanium, and provides valuable insights into their mechanical properties, structural stability, and surface characteristics.

Conclusions

The findings of this study contribute to the understanding of dental implant material behavior and aid in the design of improved materials with long-term biocompatibility and stability in the oral environment.
Knowledge, attitude, and perceptions of healthcare professionals towards complementary and alternative medicine: a cross-sectional survey from twin cities of Pakistan
Authors: Tahir Azhar Hussain , Tanveer Maria , Shahnaz Gul , Saqlain Muhammad , Ayub Shagufta , Ahmed Ali
Published: December 2023

Background

The growing popularity and use of complementary and alternative medicine (CAM) products among the general public worldwide has been well documented. This study aimed to investigate the knowledge, attitude, and perceptions (KAP) of Pakistani healthcare professionals (HCP) toward CAM and to document their views on integrating CAM education with the curriculum of undergraduate health science programs.

Method

A cross-sectional study using simple random sampling was conducted for a duration of ten months among HCPs from Pakistan’s twin cities: Islamabad and RawalpindiThe data were collected using a self-administered and validated (Cronbach’s alpha: 0.71) questionnaire. This questionnaire consisted of five sections, namely; demographic, attitude, perception, integration and knowledge.

Result

The response rate was 91.20% (500/456). The participants included 160 physicians, 155 nurses,and 141 pharmacists. The majority of the respondents were females, 67.50%, and unmarried (60.50%).The majority of HCPs participating in this study agreed that CAM modalities may benefit conventional medicine system. Likewise, most HCPs perceived different CAM therapies aseffective treatment options. More than 50% HCPs suggested CAM elective courses in the curriculum of the health sciences program.Overall, 79.17% of the HCPs have poor knowledge of CAM. Physicians have the highest knowledge score 25.63%, followed by pharmacists 21.99%, and nurses 12.26%. Knowledge status was significantly associated with age, profession, and experience of practice (p = 0.001,0.001 & 0.019).

Conclusion

This study revealed that despite the overall positive attitude of HCPs toward CAM, the score of knowledge is low. Therefore, the survey recommends evidence-based guidelines for the rationale use of CAM and updated syllabi of undergraduate health programs which will assist the future HCPs in increasing professionals’ knowledge toachieve better health outcomes for the general public.
Comparison of chitosan nanoparticles containing Lippia citriodora essential oil and citral on the induction of apoptosis in A375 melanoma cells
Authors: Karimivaselabadi Abolfazl , Osanloo Mahmoud , Ghanbariasad Ali , Zarenezhad Elham , Hosseini Hossein
Published: December 2023

Background

Using nanoparticles containing L. citriodora EO and citral has shown potential in treating skin disorders such as melanoma.

Methods

In this study, GC‒MS was used to analyze the chemical composition of L. citriodora essential oil (EO). The ion gelation method prepared free chitosan nanoparticles and chitosan nanoparticles containing L. citriodora EO and citral. The successful loading of the EO and citral was evaluated using ATR-FTIR. The DPPH assay measured the antioxidant effect of citral, L. citriodora EO, Citral-ChiNPs, L. citriodora-ChiNPs, and Free-ChiNPs. A375 melanoma cell viability was assessed using the MTT assay. The qPCR technique was employed to evaluate the expression of apoptotic genes, and flow cytometry was used to detect apoptosis.

Results

This study showed that in equal concentrations, the antioxidant properties of chitosan nanoparticles containing citral were greater than those of chitosan nanoparticles containing L. citriodora. The IC50 values of chitosan nanoparticles containing citral, L. citriodora EO, and their nonformulated states were 105.6, 199.9, 136.9, and 240 µg/ml, respectively. The gene expression results showed that the ratio of the expression of the apoptosis gene to the inhibitory gene was higher than 1 in all the samples, indicating that the conditions for apoptosis were present. Flow cytometry confirmed cell apoptosis, with 93.5 ± 0.3% in chitosan nanoparticles containing citral, 80 ± 0.2% in chitosan nanoparticles containing L. citriodora EO, 63 ± 0.3 in citral, and 42.03% in L. citriodora EO-treated cells.

Conclusion

The results showed that using the Nano form of L. citriodora and citral increased their efficiency in apoptosis pathways and their toxicity against 375 melanoma cancer cells.
Tailored implementation of the FICUS multicomponent family support intervention in adult intensive care units: findings from a mixed methods contextual analysis
Authors: Verweij Lotte , Oesch Saskia , Naef Rahel
Published: December 2023

Background

The Family in Intensive Care UnitS (FICUS) trial investigates the clinical effectiveness of a multicomponent, nurse-led interprofessional family support intervention (FSI) and explores its implementation in intensive care units (ICUs). The local context of each ICU strongly influences intervention performance in practice. To promote FSI uptake and to reduce variation in intervention delivery, we aimed to develop tailored implementation strategies.

Methods

A mixed method contextual analysis guided by the Consolidated Framework for Implementation Research (CFIR) was performed from March to June 2022 on eight ICUs assigned to the intervention group. ICU key clinical partners were asked to complete a questionnaire on CFIR inner setting measures (i.e., organizational culture, resources, learning climate and leadership engagement) and the Organizational Readiness for Implementing Change (ORIC) scale prior to group interviews, which were held to discuss barriers and facilitators to FSI implementation. Descriptive analysis and pragmatic rapid thematic analysis were used. Then, tailored implementation strategies were developed for each ICU.

Results

In total, 33 key clinical partners returned the questionnaire and 40 attended eight group interviews. Results showed a supportive environment, with CFIR inner setting and ORIC measures each rated above 3 (scale: 1 low—5 high value), with leadership engagement scoring highest (median 4.00, IQR 0.38). Interview data showed that the ICU teams were highly motivated and committed to implementing the FSI. They reported limited resources, new interprofessional information exchange, and role adoption of nurses as challenging.

Conclusion

We found that important pre-conditions for FSI implementation, such as leadership support, a supportive team culture, and a good learning climate were present. Some aspects, such as available resources, interprofessional collaboration and family nurses’ role adoption were of concern and needed attention. An initial set of implementation strategies were relevant to all ICUs, but some additions and adaptation to local needs were required. Multi-component interventions are challenging to implement within complex systems, such as ICUs. This pragmatic, theory-guided, mixed methods contextual analysis demonstrated high readiness and commitment to FSI implementation in the context of a clinical trial and enabled the specification of a tailored, multifaceted implementation strategy.
Novel intragenic deletion within the FXN gene in a patient with typical phenotype of Friedreich ataxia: may be more prevalent than we think?
Authors: Aguilera Cinthia , Esteve-Garcia Anna , Casasnovas Carlos , Vélez-Santamaria Valentina , Rausell Laura , Gargallo Pablo , Garcia-Planells Javier , Alía Pedro , Llecha Núria , Padró-Miquel Ariadna
Published: December 2023

Background

Friedreich ataxia is the most common inherited ataxia in Europe and is mainly caused by biallelic pathogenic expansions of the GAA trinucleotide repeat in intron 1 of the FXN gene that lead to a decrease in frataxin protein levels. Rarely, affected individuals carry either a large intragenic deletion or whole-gene deletion of FXN on one allele and a full-penetrance expanded GAA repeat on the other allele.

Case presentation

We report here a patient that presented the typical clinical features of FRDA and genetic analysis of FXN intron 1 led to the assumption that the patient carried the common biallelic expansion. Subsequently, parental sample testing led to the identification of a novel intragenic deletion involving the 5’UTR upstream region and exons 1 and 2 of the FXN gene by MLPA.

Conclusions

With this case, we want to raise awareness about the potentially higher prevalence of intragenic deletions and underline the essential role of parental sample testing in providing accurate genetic counselling.
Prediction of the number of asthma patients using environmental factors based on deep learning algorithms
Authors: Hwang Hyemin , Jang Jae-Hyuk , Lee Eunyoung , Park Hae-Sim , Lee Jae Young
Published: December 2023

Background

Air pollution, weather, pollen, and influenza are typical aggravating factors for asthma. Previous studies have identified risk factors using regression-based and ensemble models. However, studies that consider complex relationships and interactions among these factors have yet to be conducted. Although deep learning algorithms can address this problem, further research on modeling and interpreting the results is warranted.

Methods

In this study, from 2015 to 2019, information about air pollutants, weather conditions, pollen, and influenza were utilized to predict the number of emergency room patients and outpatients with asthma using recurrent neural network, long short-term memory (LSTM), and gated recurrent unit models. The relative importance of the environmental factors in asthma exacerbation was quantified through a feature importance analysis.

Results

We found that LSTM was the best algorithm for modeling patients with asthma. Our results demonstrated that influenza, temperature, PM10, NO2, CO, and pollen had a significant impact on asthma exacerbation. In addition, the week of the year and the number of holidays per week were an important factor to model the seasonality of the number of asthma patients and the effect of holiday clinic closures, respectively.

Conclusion

LSTM is an excellent algorithm for modeling complex epidemiological relationships, encompassing nonlinearity, lagged responses, and interactions. Our study findings can guide policymakers in their efforts to understand the environmental factors of asthma exacerbation.
Plasmodium infections and associated risk factors among parturients in Jawi district, northwest Ethiopia: a cross-sectional study
Authors: Tamir Zemenu , Animut Abebe , Dugassa Sisay , Belachew Mahlet , Abera Adugna , Tsegaye Aster , Erko Berhanu
Published: December 2023

Background

Pregnant women have an increased risk of Plasmodium infections and disease. Malaria in pregnancy is a major public health problem in endemic areas. Assessment of the burden and risk factors of malaria in pregnancy across different malaria transmission settings is required to guide control strategies and for malaria elimination. Thus, the current study is generating such evidence from parturient women in northwest Ethiopia.

Methods

A cross-sectional study was conducted among 526 pregnant women admitted to the delivery rooms of selected health facilities in Jawi district, northwest Ethiopia, between November 2021 and July 2022. Data on the socio-demographic, clinical, obstetric, and malaria prevention practices of pregnant women were collected using interviewer-administered questionnaires and from women’s treatment cards. Malaria was diagnosed by light microscopy, rapid diagnostic test, and multiplex real-time polymerase chain reaction. Risk factors for malaria were evaluated using bivariable and multivariable logistic regression models. A P-value of < 0.05 was considered statistically significant.

Results

Among the examined parturient women, 14.3% (95% CI 11.4–17.5%) had Plasmodium infections. The prevalence of peripheral, placental, and congenital malaria was 12.2% (95% CI 9.5–15.3%), 10.9% (95% CI 8.2–14.1%), and 3.7% (95% CI 2.3–6.1%), respectively. About 90.6% of peripheral and 92% of placental Plasmodium infections were asymptomatic. Plasmodium infection at parturiency was independently predicted by maternal illiteracy (AOR = 2.03, 95% CI 1.11–3.74), primigravidity (AOR = 1.88, 95% CI 1.01–3.49), lack of antenatal care follow-up (AOR = 2.28, 95% CI 1.04–5.03), and history of symptomatic malaria during pregnancy (AOR = 4.2, 95% CI 2.32–7.59). Moreover, the blood group O phenotype was significantly associated with placental malaria among the primiparae.

Conclusions

Overall, asymptomatic Plasmodium infections were prevalent among parturients in northwest Ethiopia. Maternal illiteracy, primigravidity, lack of antenatal care follow-up, and history of symptomatic malaria during pregnancy were the risk factors for malaria during parturiency. Thus, promotion of a healthy pregnancy through ANC follow-up, strengthening malaria prevention and control practices, and screening of malaria in asymptomatic pregnant women are suggested to reduce its burden in pregnancy.
A comprehensive multiomics approach reveals that high levels of sphingolipids in cardiac cachexia adipose tissue are associated with inflammatory and fibrotic changes
Authors: Qu Yiwei , Wang Yong , Wu Tao , Liu Xue , Wang Huaizhe , Ma Dufang
Published: December 2023

Cardiac cachexia is a deadly consequence of advanced heart failure that is characterised by the dysregulation of adipose tissue homeostasis. Once cachexia occurs with heart failure, it prevents the normal treatment of heart failure and increases the risk of death. Targeting adipose tissue is an important approach to treating cardiac cachexia, but the pathogenic mechanisms are still unknown, and there are no effective therapies available. Transcriptomics, metabolomics, and lipidomics were used to examine the underlying mechanisms of cardiac cachexia. Transcriptomics investigation of cardiac cachexia adipose tissue revealed that genes involved in fibrosis and monocyte/macrophage migration were increased and strongly interacted. The ECM-receptor interaction pathway was primarily enriched, as shown by KEGG enrichment analysis. In addition, gene set enrichment analysis revealed that monocyte chemotaxis/macrophage migration and fibrosis gene sets were upregulated in cardiac cachexia. Metabolomics enrichment analysis demonstrated that the sphingolipid signalling pathway is important for adipose tissue remodelling in cardiac cachexia. Lipidomics analysis showed that the adipose tissue of rats with cardiac cachexia had higher levels of sphingolipids, including Cer and S1P. Moreover, combined multiomics analysis suggested that the sphingolipid metabolic pathway was associated with inflammatory-fibrotic changes in adipose tissue. Finally, the key indicators were validated by experiments. In conclusion, this study described a mechanism by which the sphingolipid signalling pathway was involved in adipose tissue remodelling by inducing inflammation and fat fibrosis in cardiac cachexia.
Determinants for hesitancy in human papillomavirus (HPV) vaccine uptake among school girls in Jimma Town, Ethiopia. A mixed approach: quantitative and qualitative
Authors: Dera Meron , Wondimagegnehu Abigiya , Asfaw Zeytu G.
Published: December 2023

Background

The human papillomavirus (HPV) vaccination helps the body fight off certain types of the virus. Despite being one of the top 10 health hazards in the world, vaccination hesitancy has received little attention in Ethiopia. In Jimma Town, Ethiopia, the current study aims to identify the variables that affect HPV vaccine resistance and evaluate HPV uptake resistance and related variables among female school students.

Methods

A mixed study of quantitative and qualitative data collection and analysis were considered. An institution-based cross-sectional study was conducted from December 2022 to June 2023. Following a thorough random sampling process, 373 respondents were selected using stratified sampling techniques. The necessary information was gathered using an in-depth interview, a structured questionnaire administered using Kobotoolbox tools, and an interviewer who had undergone training. Models of multivariable and bivariate logistic regression were both used.

Result

A total of 369 respondents participated in the study and the response rate was 98.9%. The hesitancy of the HPV vaccine in Jimma Town female school students was 39.02%. Female students who have a mobile phone, (OR = 0.46, 95% CI (1.16, 45.89), mothers educational status ($$\ge$$
≥
Secondary) (OR = 0.53, 95% CI (1.11, 2.44), older sister vaccinated (OR = 0.19, 95% CI (0.004, 0.42), previously vaccinated two doses of HPV (OR=0.64, 95% CI (0.006, 0.137), Confidence (worried in safety and efficacy of vaccine) (OR = 3.42, 95% CI (0.30, 0.87), Not Belief in rumors (HPV vaccine ruins girls fertility) (OR = 0.21, 95% CI (0.43, 0.96), and Complacency (Distrust in health care information ) (OR = 0.24, 95% CI (0.37, 0.94), were found to be statistically significant with HPV Vaccine Hesitancy.

Conclusion

Due to widespread misinformation in the community, both schoolgirls and parents had high levels of hesitancy for the HPV vaccine in this study compared to a similar study. As a result, the HPV vaccine program, with the help of the appropriate health care professionals, should work hard to maximize community awareness in order to significantly increase the uptake of the HPV vaccine.
Association of TNF-α, IGF-1, and IGFBP-1 levels with the severity of osteopenia in mice with nonalcoholic fatty liver disease
Authors: Wang Tong-Hao , Li Jian-Biao , Tian Yong-Gang , Zheng Jin-Xin , Li Xiao-Dong , Guo Shu-zhang
Published: December 2023

Backgrounds

Nonalcoholic fatty liver disease (NAFLD) exhibits a close association with osteoporosis. This work aims to assess the potential effects of NAFLD on the progression of osteopenia in animal models.

Methods

Forty-eight C57BL/6 female mice were randomly divided to wild-type (WT) group and high-fat diet (HFD) group. The corresponding detections were performed after sacrifice at 16, 24 and 32 weeks, respectively.

Results

At 16 weeks, an remarkable increase in body weight and lipid aggregation in the hepatocytes of HFD group was observed compared to the WT group, while the bone structure parameters showed no significant difference. At 24 weeks, the levels of TNF-α and IL-6 in NAFLD mice were significantly increased, while the level of osteoprotegerin mRNA in bone tissue was decreased, and the level of receptor activator of nuclear factor Kappa-B ligand mRNA was increased. Meanwhile, the function of osteoclasts was increased, and the bone microstructure parameters showed significant changes. At 32 weeks, in the HFD mice, the mRNA levels of insulin-like growth factor-1 (IGF-1), runt-related transcription factor 2, and osterix mRNA were reduced, while the insulin-like growth factor binding protein-1 (IGFBP-1) level was increased. Simultaneously, the osteoblast function was decreased, and the differences of bone structure parameters were more significant, showing obvious osteoporosis.

Conclusions

The bone loss in HFD mice is pronounced as NAFLD progresses, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles at the different stages of NAFLD in HFD.
Ecofriendly single-step HPLC and TLC methods for concurrent analysis of ternary antifungal mixture in their pharmaceutical products
Authors: Abdelrahman Maha M. , Naguib Ibrahim A. , Zaazaa Hala E. , Nagieb Hend M.
Published: December 2023

Two accurate, sensitive, and selective methods for simultaneous determination of miconazole nitrate (MIC), nystatin (NYS), and metronidazole (MET) in pure state or drug product were established and verified. First, RP-HPLC-DAD was designed. Separation was accomplished using a ZOBRAX Eclipse Plus RP-C8 column that was running under an isocratic elution of methanol: 0.05% aqueous solution of sodium dodecyl sulphate (40: 60 v/v), with a flow rate that was regulated at 0.8 mL/min. The column temperature was adjusted at 25 °C and diode array detector was monitored at 220 nm. The linearity range of the proposed method was achieved at the concentration of 5–50, 4–50, and 4–40 µg/mL and the attained retention time for the studied drugs was 2.52, 3.52 and 4.99 min for MIC, NYS, and MET, correspondingly. Second, a TLC-densitometric approach was used to resolve the three compounds. Resolution of the three cited drugs was carried out using TLC aluminum plates pre-coated with 0.25 mm silica gel 60 F254. A developing solvent comprised ethyl acetate: toluene: methanol: triethyl amine: formic acid (3: 1: 7: 0.3: 0.1 by volume) (pH = 5.5) was utilized and scanning of the resolved bands at 215 nm. Linearity of the developed TLC method was evaluated and evident to be 0.4–2, 0.4–2.2, and 0.4–2 μg/band for MIC, NYS, and MET, in that order. The suggested chromatographic methods were verified according to ICH directives. The findings of the developed chromatographic procedures were statistically compared with the results of the reported ones using student’s t-test and F-test. Furthermore, two green assessment tools evaluated the indicated methods' level of greenness (GAPI and AGREE).