bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol
Authors: Janssen Daalen Jules M. , Meinders Marjan J. , Mathur Soania , van Hees Hieronymus W.H. , Ainslie Philip N. , Thijssen Dick H.J. , Bloem Bastiaan R.
Published: June 2024

Background

Parkinson’s disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD.

Methods/Design

: This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction.

Discussion

This trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD.

Trial registration

ClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).
Correlation of bilateral M1 hand area excitability and overall functional recovery after spinal cord injury: protocol for a prospective cohort study
Authors: Dai Chunqiu , Lin Xiaodong , Xue Baijie , Xi Xiao , Gao Ming , Liu Xinyu , Han Tao , Li Qiaozhen , Yuan Hua , Sun Xiaolong
Published: June 2024

Background

After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown.

Objective

To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation.

Methods

This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment.

Discussion

The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI.

Trial registration number

ChiCTR2300068831.
Serum sickness-like reaction to D-mannose supplement: a case report
Authors: Plante Emma R. , Ekwunwa Charles , Maciag Michelle C. , Illanes Diego
Published: June 2024

Background

Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly attributed to antibiotics, anticonvulsants, and anti-inflammatory agents.

Case presentation

A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. She was evaluated by her pediatrician and started on a 7-day course of prednisone, as well as antihistamines. Her CBC, basic metabolic panel, liver function panel, Lyme titers, and urinalysis were all within normal limits. With concern for hypersensitivity reaction to medication, all medications were discontinued. Nine days after symptom onset, the patient was evaluated by an allergist, who confirmed her presentation was consistent with serum sickness-like reaction. Her symptoms resolved, and her medications were re-introduced sequentially over several months. Restarting UQora, however, triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free.

Conclusions

This case report describes the first documented case of serum sickness-like reaction caused by UQora (active ingredient D-mannose). D-mannose is a monosaccharide, and it is frequently promoted to prevent urinary tract infections. While the clinical features and timeline in this case were typical of serum sickness-like reaction, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of serum sickness-like reaction and the importance of prompt identification and management to enhance patient safety. Further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.
Relationship between body mass index and residential segregation in large cities of Latin America
Authors: Doberti Herrera Tamara , Rodríguez Osiac Lorena , Flores-Alvarado Sandra , Pérez Ferrer Carolina , Higuera Diana , de Oliveira Cardoso Leticia
Published: June 2024

Background

Obesity is a global health problem, and its connection with social and environmental factors is well-established. Social factors, such as urban segregation, may impact obesity through various mechanisms, including food and physical activity environments, as well as social norms and networks. This multilevel study aims to examine the effect of socio-economic residential segregation of Latin American cities on the obesity of individuals within those cities.

Methods

We analyzed data from national surveys for a total of 59,340 individuals of 18–70 years of age, conducted in 156 cities across Brazil, Chile, Colombia, and Mexico between 2007 and 2013. We adjusted two-level linear mixed models for body mass index (BMI) stratified by sex and country, controlling for age, educational level and poverty. Separate models were built for dissimilarity and isolation segregation indices.

Results

The relationships between segregation indices and BMI were mostly not statistically significant, and in some cases, they were opposite to what was expected. The only significant relationships were observed in Colombian men, using the dissimilarity index (-7.5 [95% CI: -14.4, -0.5]) and in Colombian women, using the isolation index (-7.9 [95% CI: -14.1, -1.7]).

Conclusions

While individual-level factors cannot fully explain differences among people in the same city, segregation indices may help. However, we found that in some cases, the relationship between BMI and segregation indices is opposite to what is expected based on prior literature. This should be considered in examining the phenomenon. Further research on obesogenic environments in segregated neighborhoods could provide valuable evidence.
Preconception health and care policies, strategies and guidelines in the UK and Ireland: a scoping review
Authors: Cassinelli Emma H. , McKinley Michelle C. , Kent Lisa , Eastwood Kelly-Ann , Schoenaker Danielle A. J. M. , Trew David , Stoikidou Theano , McGowan Laura
Published: June 2024

Background

Preconception health has the potential to improve parental, pregnancy and infant outcomes. This scoping review aims to (1) provide an overview of the strategies, policies, guidelines, frameworks, and recommendations available in the UK and Ireland that address preconception health and care, identifying common approaches and health-influencing factors that are targeted; and (2) conduct an audit to explore the awareness and use of resources found in the scoping review amongst healthcare professionals, to validate and contextualise findings relevant to Northern Ireland.

Methods

Grey literature resources were identified through Google Advanced Search, NICE, OpenAire, ProQuest and relevant public health and government websites. Resources were included if published, reviewed, or updated between January 2011 and May 2022. Data were extracted into Excel and coded using NVivo. The review design included the involvement of the “Healthy Reproductive Years” Patient and Public Involvement and Engagement advisory panel.

Results

The searches identified 273 resources, and a subsequent audit with healthcare professionals in Northern Ireland revealed five additional preconception health-related resources. A wide range of resource types were identified, and preconception health was often not the only focus of the resources reviewed. Resources proposed approaches to improve preconception health and care, such as the need for improved awareness and access to care, preconceptual counselling, multidisciplinary collaborations, and the adoption of a life-course approach. Many behavioural (e.g., folic acid intake, smoking), biomedical (e.g., mental and physical health conditions), and environmental and social (e.g., deprivation) factors were identified and addressed in the resources reviewed. In particular, pre-existing physical health conditions were frequently mentioned, with fewer resources addressing psychological factors and mental health. Overall, there was a greater focus on women’s, rather than men’s, behaviours.

Conclusions

This scoping review synthesised existing resources available in the UK and Ireland to identify a wide range of common approaches and factors that influence preconception health and care. Efforts are needed to implement the identified resources (e.g., strategies, guidelines) to support people of childbearing age to access preconception care and optimise their preconception health.
Deleterious impact of trivial to severe interstitial pneumonia and emphysema on mortality and acute exacerbation of interstitial pneumonia in patients with lung cancer: a retrospective cohort study
Authors: Tomishima Yutaka , Kitamura Atsushi , Imai Ryosuke , Ohde Sachiko
Published: June 2024

Background

Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer.

Methods

This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates.

Results

Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18–1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39–2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63–3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01–1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP.

Conclusion

Our results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones.
Retrieval analysis of PEEK rods pedicle screw system: three cases analysis
Authors: Xu Xiaoduo , Wang Lei , Wang Jingming , Yu Xiuchun , Huang Weimin
Published: June 2024

Purpose

To analyze the characteristics of PEEK rods retrieved in vivo, specifically their wear and deformation, biodegradability, histocompatibility, and mechanical properties.

Method

Six PEEK rods were retrieved from revision surgeries along with periprosthetic tissue. The retrieved PEEK rods were evaluated for surface damage and internal changes using Micro-CT, while light and electron microscopy were utilized to determine any histological changes in periprosthetic tissues. Patient history was gathered from medical records. Two intact and retrieved PEEK rods were used for fatigue testing analysis by sinusoidal load to the spinal construct.

Results

All implants showed evidence of plastic deformation around the screw-rod interface, while the inner structure of PEEK rods appeared unchanged with no visible voids or cracks. Examining images captured through light and electron microscopy indicated that phagocytosis of macrophages around PEEK rods was less severe in comparison to the screw-rod interface. The results of an energy spectrum analysis suggested that the distribution of tissue elements around PEEK rods did not differ significantly from normal tissue. During fatigue testing, it was found that the retrieved PEEK rods cracked after 1.36 million tests, whereas the intact PEEK rods completed 5 million fatigue tests without any failure.

Conclusion

PEEK rods demonstrate satisfactory biocompatibility, corrosion resistance, chemical stability, and mechanical properties. Nevertheless, it is observed that the indentation at the junction between the nut and the rod exhibits relatively weak strength, making it susceptible to breakage. As a precautionary measure, it is recommended to secure the nut with a counter wrench, applying the preset torque to prevent overtightening.
The use of laser photobiomodulation as pre-anesthetic tissue management technique in reducing injection pain in children
Authors: Hamouda Aliaa Abdelsalam , El-Habashy Laila M. , Khalil Amani
Published: June 2024

Background

One of the main goals for pediatric dentists is to offer a painless anesthesia experience. Laser photobiomodulation is among the suggested strategies to decrease injection pain. So, this study aimed to assess the impact of laser photobiomodulation on local anesthesia (LA) injection pain in children and its effect on the efficacy of LA during pulpotomy and SSC procedures.

Methods

The research was carried out as a randomized controlled clinical trial with two parallel group design. It involved 64 cooperative healthy children, age range from 5 to 7 years, each having at least one maxillary molar indicated for pulpotomy. Children were randomly allocated to one of the two groups based on the pre-anesthetic tissue management technique used: test group received laser photobiomodulation, while control group received topical anesthetic gel. Pain during injection, pulpotomy, and SSC procedures was assessed using physiological measures (Heart Rate (HR)), subjective evaluation (modified Face-Pain‐Scale (FPS), and objective analysis (Sound‐Eye‐Motor scale (SEM)).

Results

A total of 64 children with mean age 6.23 ± 0.78 participated in this research. The mean HR scores were significantly lower in the laser PBM group during buccal and palatal infiltration injections. The SEM mean scores were significantly lower in the laser PBM group during both injections. For the FPS scale, the number of children who recorded satisfaction during injection was significantly higher in laser PBM group. There was no statistically significant difference in mean HR as well as in SEM and FPS scores between the two groups during pulpotomy and SSC procedures. Comparisons between the two study groups were performed using independent samples t- and Mann-Whitney U tests. Significance was set at p value < 0.05.

Conclusion

Laser photobiomodulation is a promising non-pharmacological pre-anesthetic tissue management technique in children that offered less painful injection compared to topical anesthetic gel without compromising the effectiveness of LA.

Trial Registration

ClinicalTrials.gov Identifier: NCT05861154. Registered on 16/5/2023.

Graphical Abstract
Nomogram based on immune-inflammatory indicators and age-adjusted charlson comorbidity index score to predict prognosis of postoperative parotid gland carcinoma patients
Authors: Cheng Hao , Xu Jin-Hong , He Jia-Qi , Wu Chen-Chen , Li Jia-Fan , Xu Xue-Lian
Published: June 2024

Background

Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis.

Method

All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots.

Result

The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p < 0.001), pathology (p = 0.019), tumor location (p < 0.001), extranodal extension (ENE) (p < 0.001), systemic immune-inflammation index (SII) (p = 0.004), prognostic nutrition index (PNI) (p = 0.003), ACCI (p < 0.001), and Glasgow prognostic Score (GPS) (p = 0.001) were independent indicators for disease free survival (DFS). Additionally, the independent prognostic factors for overall survival (OS) including AJCC stage (p = 0.015), pathology (p = 0.004), tumor location (p < 0.001), perineural invasion (p = 0.009), ENE (p < 0.001), systemic immune-inflammation index (SII) (p = 0.001), PNI (p = 0.001), ACCI (p = 0.003), and GPS (p = 0.033). The nomogram models for predicting DFS and OS in PGC patients were generated based on these independent risk factors. All nomogram models show good discriminative capability with area under curves (AUCs) over 0.8 (DFS 0.802, and OS 0.825, respectively). Decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) show good clinical net benefit of the two nomograms in both training and validation cohorts. Kaplan-Meier survival analyses showed superior discrimination of DFS and OS in the new risk stratification system compared with the AJCC stage system. Finally, postoperative patients with PGC who underwent adjuvant radiotherapy had a better prognosis in the high-, and medium-risk subgroups (p < 0.05), but not for the low-risk subgroup.

Conclusion

The immune-inflammatory-nutrition indicators and ACCI played an important role in both DFS and OS of PGC patients. Adjuvant radiotherapy had no benefit in the low-risk subgroup for PGC patients who underwent surgical resection. The newly established nomogram models perform well and can provide an individualized prognostic reference, which may be helpful for patients and surgeons in proper follow-up strategies.
Polycystic ovarian syndrome elevates the distress of sexual pain in Iranian women with infertility
Authors: Tahmasbi Bita , Eshraghi Reza , Amini-Tehrani Mohammadali , Zamanian Hadi , Ilami Ashkan
Published: June 2024

Background

Sexual dysfunction may lead to sexual distress in women with infertility, while polycystic ovarian syndrome (PCOS) may escalate this distress. This study aimed to investigate the role of PCOS in the relationship between sexual dysfunction and sexual distress in Iranian women with infertility.

Methods

The Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and Depression and Anxiety modules of the DASS-21 were cross-sectionally investigated in 190 women with infertility (103 women with PCOS and 87 women without PCOS).

Results

There were negative correlations between sexual function domains and sexual distress (P < .001) in the total sample. Moderation analysis revealed that higher levels of impaired desire, arousal, and pain elevated sexual distress in the PCOS group. After adjusting for depression and anxiety, only the association between sexual pain and sexual distress was moderated by PCOS condition (P = .008).

Conclusions

The findings suggest that impaired sexual function is associated with increased levels of sexual distress in infertile female patients. Importantly, comorbid PCOS renders patients susceptible to sexual distress where sexual pain is increased. Further research may shed light on the physiological, psychological, and relational aspects of sexual pain and associated distress in infertile female patients with comorbid PCOS.
The role of neoadjuvant chemotherapy before radical surgery in stage IB2/IIA2 squamous cell cervical cancers
Authors: ALCI Aysun , Aytekin Okan , Ersak Burak , Kilic Fatih , Oktar Okan , Caner Cakır , Korkmaz Vakkas , Comert Gunsu Kimyon , Selcuk İlker , Toptas Tayfun , Boran Nurettin , Tasci Tolga , Karalok Alper , Basaran Derman , Tekin Ozlem Moraloglu , Ustun Yaprak Engin , Turan Taner , Ureyen Isin
Published: June 2024

Background

This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior to radical hysterectomy compared to those who did not receive NACT before surgery.

Materials and methods

This is a multicenter study including data of 6 gynecological oncology departments. The study is approved from one of the institution’s local ethics committee. Patients were stratified into two cohorts based on the receipt of NACT preceding their surgical intervention. Clinico-pathological factors and progression-free survival were analyzed.

Results

Totally 87 patients were included. Lymphovascular space invasion (LVSI) was observed as 40% in the group receiving NACT, while it was 66.1% in the group not receiving NACT (p = 0.036). Deep stromal invasion (> 50%) was 56% in the group receiving NACT and 84.8% in the group not receiving NACT (p = 0.001). In the univariate analysis, application of NACT is statistically significant among the factors that would be associated with disease-free survival. Consequently, a multivariate analysis was conducted for progression-free survival, incorporating factors such as the depth of stromal invasion, the presence of LVSI, and the administration of NACT. Of these, only the administration of NACT emerged as an independent predictor associated with decreased progression-free survival. (RR:5.88; 95% CI: 1.63–21.25; p = 0.07).

Conclusions

NACT shouldn’t be used routinely in patients with stage IB2/IIA2 cervical cancer before radical surgery. Presented as oral presentation at National Congress of Gynaecological Oncology & National Congress of Cervical Pathologies and Colposcopy (2022/ TURKEY).
Reducing economic burden through split-shared care model for people living with uncontrolled type 2 diabetes and polypharmacy: a multi-center randomized controlled trial
Authors: Lum Zheng Kang , Tan Jia Yeong , Wong Cynthia Sze Mun , Kok Zi Yin , Kwek Sing Cheer , Tsou Keith Yu Kei , Gallagher Paul John , Lee Joyce Yu-Chia
Published: June 2024

Background

Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy.

Method

This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control). People with uncontrolled type 2 diabetes, defined as HbA1c > 7.0% and taking ≥ 5 chronic medications were included while people with missing baseline economic data (such as consultation costs, medication costs) were excluded. Direct medical costs were extracted from the institution’s financial database while indirect costs were calculated from self-reported gross income and productivity loss, using Work Productivity Activity Impairment Global Health questionnaire. Separate generalized linear models with log link function and gamma distribution were used to analyze changes in direct and indirect medical costs.

Results

A total of 175 patients (intervention = 70, control = 105) completed the trial and were included for analysis. The mean age of the participants was 66.9 (9.2) years, with majority being male and Chinese. The direct medical costs were significantly lower in the intervention than the control group over 6 months (intervention: -US$70.51, control: -US$47.66, p < 0.001). Medication cost was the main driver in both groups. There were no significant changes in productivity loss and indirect costs in both groups.

Conclusion

Implementation of split-shared visits with frontline community partners may reduce economic burden for patient with uncontrolled type 2 diabetes and polypharmacy.

Trial registration

Clinicaltrials.gov Reference Number: NCT03531944 (Date of registration: June 6, 2018).
Effect of thyme, ginger, and their nano-particles on growth performance, carcass characteristics, meat quality and intestinal bacteriology of broiler chickens
Authors: Hassan Amal H. A. , Youssef Ibrahim M. I. , Abdel-Atty Nasser S. , Abdel-Daim Asmaa S. A.
Published: June 2024

This study was conducted to evaluate the effects of thyme, ginger, and their nano-particles, as alternatives to antibiotic growth promotors (AGP), on productive performance, carcass traits, meat quality and gut health of broiler chickens. A total of 270 one-day-old broiler chicks were randomly distributed into 6 groups, each consisting of 3 replicates (n = 15 chicks/replicate). The birds in group 1 were fed the control diet which contained neither antibiotic growth promotors nor phytogenic feed additives (PFA). Birds in group 2 were fed diets containing 0.05% of AGP (Bacitracin methylene disalicylate). Chicks in group 3 and 4 were fed diets supplemented with 1.0% of thyme and ginger, respectively, whereas birds in group 5 and 6 were offered diets including 0.10% of nano-thyme and nano-ginger, respectively. The experiment lasted for 35 days. It was found that thyme and ginger with their nano-products, like the antibiotic, improved the body weight, weight gain and feed conversion rate of birds. The effect of ginger and nano-ginger on body weight and weight gain was greater than other treatments. During the overall feeding period, the feed cost of production was the highest in antibiotic group, but was the lowest in ginger and nano-ginger treatments. There was no effect of dietary treatments on carcass yield or organs weight except bursa of Fabricius and abdominal fat. Thyme, ginger and their nano-composites increased the weight of bursa and reduced the abdominal fat amount. The phytogenic additives and their nano-particles improved the colour, water holding capacity, and flavor of meat. Moreover, these additives reduced the total intestinal bacterial count as well as the total aerobic mesophilic count of meat. The effect of PFA and their nano-particles on the bacterial count was similar to that of antibiotic. In conclusion, thyme and ginger with their nano- particles can be considered as promising agents in feeding of broilers to improve the growth performance, gut health and meat quality. Moreover, these additives can be used as alternatives to AGP to overcome its health hazards and the high cost. The nanotechnology of herbal plants enables them to be added in smaller amounts in poultry diets with producing the same effect of raw ingredients, and this could be due to the higher bioavailability.
An epidemiological analysis of severe imported malaria infections in Sri Lanka, after malaria elimination
Authors: Seneviratne Shilanthi , Fernando Deepika , Wickremasinghe Rajitha , Senarathne Sujai , Chulasiri Pubudu , Thenuwara Nethmini , Aluthweera Champa , Mohotti Iromi , Jayakuru Shamila , Fernando Thilan , Wijesundara Anula , Fernandopulle Rohini , Mendis Kamini
Published: June 2024

Background

Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria.

Methods

Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients’ general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented.

Results

532 imported malaria cases were diagnosed over 11 years (2013–2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26–60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died.

Conclusions

The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.
Pulse wave signal-driven machine learning for identifying left ventricular enlargement in heart failure patients
Authors: Wu Dandan , Ono Ryohei , Wang Sirui , Kobayashi Yoshio , Sughimoto Koichi , Liu Hao
Published: June 2024

Background

Left ventricular enlargement (LVE) is a common manifestation of cardiac remodeling that is closely associated with cardiac dysfunction, heart failure (HF), and arrhythmias. This study aimed to propose a machine learning (ML)-based strategy to identify LVE in HF patients by means of pulse wave signals.

Method

We constructed two high-quality pulse wave datasets comprising a non-LVE group and an LVE group based on the 264 HF patients. Fourier series calculations were employed to determine if significant frequency differences existed between the two datasets, thereby ensuring their validity. Then, the ML-based identification was undertaken by means of classification and regression models: a weighted random forest model was employed for binary classification of the datasets, and a densely connected convolutional network was utilized to directly estimate the left ventricular diastolic diameter index (LVDdI) through regression. Finally, the accuracy of the two models was validated by comparing their results with clinical measurements, using accuracy and the area under the receiver operating characteristic curve (AUC-ROC) to assess their capability for identifying LVE patients.

Results

The classification model exhibited superior performance with an accuracy of 0.91 and an AUC-ROC of 0.93. The regression model achieved an accuracy of 0.88 and an AUC-ROC of 0.89, indicating that both models can quickly and accurately identify LVE in HF patients.

Conclusion

The proposed ML methods are verified to achieve effective classification and regression with good performance for identifying LVE in HF patients based on pulse wave signals. This study thus demonstrates the feasibility and potential of the ML-based strategy for clinical practice while offering an effective and robust tool for diagnosing and intervening ventricular remodeling.
7-MEGA™ inhibits adipogenesis in 3T3-L1 adipocytes and suppresses obesity in high-fat-diet-induced obese C57BL/6 mice
Authors: Won Yeong-Seon , Bak Seon-Gyeong , Chandimali Nisansala , Park Eun Hyun , Lim Hyung-Jin , Kwon Hyuck Se , Park Sang-Ik , Lee Seung Jae
Published: June 2024

Background

Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community.

Method

This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes.

Results

7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate.

Conclusion

In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.
MiR-223 enhances lipophagy by suppressing CTSB in microglia following lysolecithin-induced demyelination in mice
Authors: Ma Hao , Ou Zhi-lin , Alaeiilkhchi Nima , Cheng Yong-quan , Chen Kai , Chen Jia-yu , Guo Ru-qin , He Min-yue , Tang Shi-yi , Zhang Xin , Huang Zhi-ping , Liu Junhao , Liu Jie , Zhu Qing-an , Huang Zu-cheng , Jiang Hui
Published: June 2024

Background

Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved.

Methods

C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM.

Results

Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1β.

Conclusion

These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.
Cargo-eliminated osteosarcoma-derived small extracellular vesicles mediating competitive cellular uptake for inhibiting pulmonary metastasis of osteosarcoma
Authors: Lin Shanyi , Shu Longqiang , Guo Yuhang , Yuan Ji , Zhang Juntao , Wang Yang , Yang Yunlong , Yuan Ting
Published: June 2024

Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs’ function by CE-sEVs.
Associations between a normal-range free thyroxine concentration and ovarian reserve in infertile women undergoing treatment via assisted reproductive technology
Authors: Zhang Qiaoling , Zhang Dandan , Liu Haoyuan , Fu Jinyun , Tang Li , Rao Meng
Published: June 2024

Background

Some recent studies have shown that female subclinical hypothyroidism (SCH) is associated with diminished ovarian reserve (DOR). In this study, we aimed to investigate whether serum-free thyroxine (fT4) concentrations within the reference range are associated with ovarian reserve in women.

Methods

This cross-sectional study included 4933 infertile women with normal-range fT4 concentrations who received assisted reproductive technology treatment in our clinic. The data of women in different fT4 concentration tertiles (namely 12–15.33, 15.34–18.67, and 18.68–22 pmol/L) were compared with ovarian reserve markers, namely the anti-Müllerian hormone (AMH) concentration, the antral follicle count (AFC), and the number of aspirated oocytes. The primary outcomes were the AMH concentration and the risk of DOR, diagnosed as an AMH concentration < 1.1 ng/mL.

Results

The average ages of women in the low-normal, middle-normal, and high-normal fT4 tertiles were 33.20 (standard deviation [SD]: 5.11), 32.33 (SD: 5.13), and 31.61 (SD: 5.10) years, respectively (p < 0.0001). AMH concentrations (adjusted mean: 3.32 [95% confidence interval {CI}: 3.16 to 3.50] vs. 3.51 [3.40 to 3.62] vs. 3.64 [3.50 to 3.80] ng/mL, p = 0.022) were significantly different between the fT4 concentration tertiles. The risk of DOR was significantly increased in the low-normal (adjusted odds ratio: 1.61 [95% CI: 1.01 to 2.58]) and middle-normal (1.47 [95% CI: 1.00 to 2.16]) tertiles compared with the high-normal tertile. Subgroup analysis showed that AMH concentrations were significantly different among the fT4 concentration tertiles in women aged < 35 years (adjusted mean: 3.94 [95% CI: 3.70 to 4.20] vs. 4.25 [4.11 to 4.39] vs. 4.38 [4.18 to 4.58], p = 0.028), whereas this difference was not significant in women aged ≥ 35 years (p = 0.534). The general additive models using fT4 as a continuous variable indicated that a lower fT4 concentration within the normal range was significantly associated with a lower AMH concentration (p = 0.027), a lower AFC (p = 0.018), a lower number of aspirated oocytes (p = 0.001), and a higher risk of DOR (p = 0.007).

Conclusion

Low-normal fT4 concentrations are associated with lower ovarian reserve in infertile women.
Single-cell landscape of immunological responses in elderly patients with sepsis
Authors: He Wanxue , Yao Chen , Wang Kaifei , Duan Zhimei , Wang Shuo , Xie Lixin
Published: June 2024

Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell–cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.
Ecological study of the reach of congregate vs. grab-and-go summer meals in New York City
Authors: Harb Amanda A. , Koch Pamela A. , Roberts Katherine J. , McGuirt Jared T. , Cadenhead Jennifer W. , Wolf Randi L.
Published: June 2024

Participation in school meals is associated with many benefits. However, participation in school meals served in the summer through the Summer Food Service Program (SFSP) is low due to many barriers, including program requirements such as congregate feeding. During COVID-19, these requirements were waived, allowing grab-and-go meals. The purpose of this study is to compare the number of SFSP breakfast and lunch meals served during the summers of grab-and-go meals (2020 and 2021) to prior summers of congregate feeding (2014–2019) in New York City (NYC). This study is an ecological study of NYC public school geographic districts (n = 32). The primary outcome is the total number of SFSP meals served per student. Using the repeated-measures ANOVA, the results show a significant increase in the number of SFSP meals served per student during the first summer (2020) of grab-and-go meals compared to summers 2016–2019 (p ≤ 0.01) but no significant differences during the second summer (2021) of grab-and-go meals compared to summers 2014–2019. However, there was a significant increase in the number of breakfast meals served in August per student during both the first and second summer of grab-and-go meals compared to summers 2014–2019 (p < 0.05). Among NYC public schools, the waivers may increase the reach of breakfast meals served in August, when there are fewer summer school activities. While there is a need for more research, policymakers may consider making waivers that allow grab-and-go meals permanent flexibilities for the SFSP to increase access to summer meals.