bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between muscle quality index and pulmonary function in post-COVID-19 subjects
Authors: González-Islas Dulce , Robles-Hernández Robinson , Flores-Cisneros Laura , Orea-Tejeda Arturo , Galicia-Amor Susana , Hernández-López Nadia , Valdés-Moreno Mariana I. , Sánchez-Santillán Rocío , García-Hernández Juan Carlos , Castorena-Maldonado Armando
Published: November 2023

Background

The SARS-CoV2 pandemic impacted many critically ill patients, causing sequelae, affecting lung function, and involving the musculoskeletal system. We evaluated the association between lung function and muscle quality index in severely ill post-COVID-19 patients.

Methods

A cross-sectional study was conducted on a post-COVID-19 cohort at a third-level center. The study included patients who had experienced severe-to-critical COVID-19. Anthropometric measurements, such as body mass index (BMI) and handgrip strength, were obtained to calculate the muscle quality index (MQI). Additionally, spirometry, measurements of expiratory and inspiratory pressure, and an assessment of DLCO in the lungs were performed. The MQI was categorized into two groups: low-MQI (below the 50th percentile) and high-MQI (above the 50th percentile), based on sex. Group differences were analyzed, and a multivariate linear regression analysis was performed to assess the association between respiratory function and MQI.

Results

Among the 748 patients analyzed, 61.96% required mechanical ventilation, and the median hospital stay was 17 days. In patients with a low MQI, it was observed that both mechanical respiratory function and DLCO were lower. The multivariate analysis revealed significantly lower findings in mechanical respiratory function among patients with a low MQI.

Conclusion

The Low-MQI is an independent predictor associated with pulmonary function parameters in subjects with Post-COVID-19 syndrome.
Early results of a novel modular knee arthrodesis implant after uncontrolled periprosthetic knee joint infection
Authors: Büyükdoğan Kadir , Öztürkmen Yusuf , Goker Barlas , Oral Melih , Atay Tolga , Özkan Korhan , Çağlar Ömür , Ayvaz Mehmet
Published: November 2023

Aim

The aim of this study is to evaluate the functional outcomes and complications after non-fusion knee arthrodesis with a modular segmental intramedullary implant used for infected total knee arthroplasty revisions.

Methods

A retrospective review of the patients who had been surgically treated with a modular intramedullary arthrodesis implant for recurrent infection after revision TKA between January 2016 and February 2020 were included. The indications for arthrodesis were failed infected TKA with massive bone loss, deficient extensor mechanism and poor soft tissue coverage that precluded joint reconstruction with revision TKA implants. Clinical outcomes were assesed with visual analogue scale for pain (pVAS), Oxford knee score (OKS) and 12-item short form survey (SF-12). Full-length radiographs were used to verify limb length discrepancies (LLD).

Results

Fourteen patients (4 male and 10 female) patients with a mean age of 69.3 (range, 59 to 81) years at time of surgery were available for final follow-up at a mean of 28.8 months (range, 24–35 months). All clinical outcome scores improved at the final follow-up (pVAS, 8.5 to 2.6, p = .01; OKS, 12.6 to 33.8, p = .02; SF-12 physical, 22.9 to 32.1, p = .01 and SF-12 mental, 27.7 to 40.2, p = .01). The mean LLD was 1.0 cm (range, + 15 – 2.3 cm). Re-infection was detected in three patients (21.4%). Two patients were managed with suppressive antibiotic treatment and a third patient required repeat 2-stage revision procedure. In one patient, a periprosthetic femur fracture was observed and treated with plate osteosynthesis.

Conclusion

Uncontrolled infection after total knee arthroplasty can be effectively treated with arthrodesis using a modular intramedullary nail and satisfactory functional results can be obtained.

Level of evidence

Level 4, Retrospective cohort study.
Effect of Uncaria tomentosa aqueous extract on the response to palmitate-induced lipotoxicity in cultured skeletal muscle cells
Authors: de Freitas-Marchi Bruna Leticia , dos Santos Jeniffer Farias , Reigado Gustavo Roncoli , Fernandes Myrian Thiago Pruschinski , Alcalde Felipe Santiago Chambergo , de Oliveira Carvalho Carla Roberta , Nunes Viviane Abreu
Published: November 2023

Background

Type 2 diabetes mellitus (T2DM) is frequently associated with dyslipidemia, which corresponds to the increase in the triglycerides and fatty acid concentrations in tissues, such as the skeletal muscle. Also, T2DM molecular mechanism involves increasing in reactive oxygen species (ROS) production and oxidative stress. The use of herbal medicines such as Uncaria tomentosa (Ut) has been proposed as an auxiliary treatment for patients with T2DM. In this study, it was evaluated the effect of Ut aqueous extract on cell viability and ROS production, in skeletal myoblasts from C2C12 lineage exposed to the free fatty acid palmitate (PA).

Methods

Cells were incubated with PA in different concentrations ranging from 10 to 1000 μM, for 24 or 48 h, for cytotoxicity assay. Cell death, DNA fragmentation and ROS production assays were performed in cell cultures incubated with PA for 24 h, in the pre (preventive condition) or post treatment (therapeutic condition) with 250 μg/ml Ut aqueous extract, for 2 or 6 h. Cell death was evaluated by MTT method or flow cytometry. ROS generation was measured by fluorescence spectroscopy using the DCFDA probe.

Results

Cell viability was reduced to approximately 44% after the incubation with PA for 24 h from the concentration of 500 µM. In the incubation of cells with 500 μM PA and Ut extract for 6 h, in both conditions (preventive or therapeutic), it was observed an increase of 27 and 70% in cell viability respectively, in comparison to the cultures incubated with only PA. Also, the incubation of cultures with 500 μM PA, for 24 h, increased 20-fold the ROS formation, while the treatment with Ut extract, for 6 h, both in the preventive or therapeutic conditions, promoted decrease of 21 and 55%, respectively.

Conclusion

The Ut extract was efficient in promoting cell protection against PA lipotoxicity and ROS generation, potentially preventing oxidative stress in C2C12 skeletal muscle cells. Since T2DM molecular mechanism involves oxidative stress condition and it is often associated with dyslipidemia and fatty acid accumulation in muscle tissue, these results open perspectives for the use of Ut as an auxiliary strategy for T2DM management.
Afterhours telehealth in Australian residential aged care facilities: a mixed methods evaluation
Authors: Trankle Steven A. , Reath Jennifer
Published: November 2023

Background

The aged care system in Australia is under pressure. Residential aged care facilities (RACFs) and general practitioners (GPs) have difficulty providing the care needed by their residents, particularly after hours. Many residents are given ambulance support and transferred to hospital emergency departments (EDs) for care that could be provided at RACFs. The MyEmergencyDoctor (MED) service was commissioned in a 12-month program (February 2020-February 2021) using ED physicians to provide afterhours telehealth care in six RACFs.

Methods

Using the NASSS framework, we synthesised descriptive analyses of statistical data from the MED service, RACFs and the ambulance service and a thematic analysis of interview data collected from GPs, RACF and MED service staff, and family members of residents.

Results

Most calls to MED (179/209) were resolved with in-house treatment thereby reducing ambulance usage and hospital admissions. Interviews further revealed that MED enabled timely care for residents who were unwell but did not need hospital transfer. Technology, training, and rapid access to MED assisted RACF staff and complemented usual GP care. MED potentially reduced GP burnout. Refresher training was considered important especially in RACFs with high staff turnover, as was greater afterhours access to medications.

Conclusions

The afterhours telehealth model provided in-house care and reduced ambulance transfers, and GPs and RACF staff generally felt supported. The service was easy to use and fostered good communications with GPs and RACF staff. Some GPs preferred to provide their own care, commenting on the need for a good understanding of patient and family needs and of the local context. Other stakeholders suggested this model could be extended to palliative care settings and to normal business hours when GPs were unavailable. The reduced ambulance and hospital use suggested benefits to wider health systems, however policies and funding that remunerate GPs, support community-based care and provide additional staffing in RACFs are needed to sustain afterhours telehealth in RACFs. Use of the NASSS (non-adoption, abandonment, scale-up, spread, and sustainability) Framework provided a valuable explanatory lens for our analyses.
Socioecological systems analysis of potential factors for cholera outbreaks and assessment of health system’s readiness to detect and respond in Ilemela and Nkasi districts, Tanzania
Authors: Ngingo Baraka L. , Mchome Zaina S. , Bwana Veneranda M. , Chengula Augustino , Mwanyika Gaspary , Mremi Irene , Sindato Calvin , Mboera Leonard E.G.
Published: November 2023

Background

Cholera outbreaks are a recurrent issue in Tanzania, with Ilemela and Nkasi districts being particulary affected. The objective of this study was to conduct a socio-ecological system (SES) analysis of cholera outbreaks in these districts, identifying potential factors and assessing the preparedness for cholera prevention and control.

Methods

A cross-sectional study was carried out in Ilemela and Nkasi districts of Mwanza and Rukwa regions, respectively in Tanzania between September and October 2021. A SES framework analysis was applied to identify potential factors associated with cholera outbreaks and assess the readiness of the districts to cholera prevention and control.

Results

Ilemela is characterised by urban and peri-urban ecosystems while Nkasi is mainly rural. Cholera was reported to disproportionately affect people living along the shores of Lake Victoria in Ilemela and Lake Tanganyika in Nkasi, particularly fishermen and women involved infish trading. The main potential factors identified for cholera outbreaks included defecation in the shallow ends and along the edges of lakes, open defecation, bathing/swimming in contaminated waters and improper waste disposal. The preparedness of both districts for cholera prevention and response was found to be inadequate due to limited laboratory capacity, insufficient human resources, and budget constraints.

Conclusion

People of Ilemela and Nkasi districts remain at significant risk of recurrent cholera outbreaks and the capacity of the districts to detect the disease is limited. Urgent preventive measures, such as conducting considerable community awareness campaigns on personal hygiene and environmental sanitation are needed to alleviate the disease burden and reduce future cholera outbreaks.
Relationship between the cumulative exposure to atherogenic index of plasma and ischemic stroke: a retrospective cohort study
Authors: Zheng Huancong , Wu Kuangyi , Wu Weiqiang , Chen Guanzhi , Chen Zekai , Cai Zefeng , Cai Zhiwei , Lan Yulong , Wu Shouling , Chen Youren
Published: November 2023

Background

Atherogenic index of plasma (AIP) has been demonstrated as a surrogate marker for ischemic stroke, but there is limited evidence for the effect of long-term elevation of AIP on ischemic stroke. Therefore, we aimed to characterize the relationship between cumulative exposure to AIP and the risk of ischemic stroke.

Methods

A total of 54,123 participants in the Kailuan Study who attended consecutive health examinations in 2006, 2008, and 2010 and had no history of ischemic stroke or cancer were included. The time-weighted cumulative AIP (cumAIP) was calculated as a weighted sum of the mean AIP values for each time interval and then normalized to the total duration of exposure (2006–2010). Participants were divided into four groups according to quartile of cumAIP: the Q1 group, ≤−0.50; Q2 group, − 0.50 to − 0.12; Q3 group, − 0.12 to 0.28; and Q4 group, ≥ 0.28. Cox proportional hazard models were used to evaluate the relationship between cumAIP and ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

After a median follow-up of 11.03 years, a total of 2,742 new ischemic stroke events occurred. The risk of ischemic stroke increased with increasing quartile of cumAIP. After adjustment for potential confounders, Cox regression models showed that participants in the Q2, Q3, and Q4 groups had significantly higher risks of ischemic stroke than those in the Q1 group. The HRs (95% CIs) for ischemic stroke in the Q2, Q3, and Q4 groups were 1.17 (1.03, 1.32), 1.33 (1.18, 1.50), and 1.45 (1.28, 1.64), respectively. The longer duration of high AIP exposure was significantly associated with increased ischemic stroke risk.

Conclusions

High cumulative AIP is associated with a higher risk of ischemic stroke, which implies that the long-term monitoring and maintenance of an appropriate AIP may help prevent such events.
Erythrocyte–brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo
Authors: Zhang Hai , Sumbria Rachita K. , Chang Rudy , Sun Jiahong , Cribbs David H. , Holmes Todd C. , Fisher Mark J. , Xu Xiangmin
Published: November 2023

Background

Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC–brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported.

Methods

RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC–brain endothelial interactions associated with oxidatively stressed RBC. Their relationship with microglial activation and CMH was examined with post-mortem histology.

Results

Oxidatively stressed RBC stall significantly and rapidly in cerebral vessels in mice, accompanied by decreased blood flow velocity which recovers at 5 days. Post-mortem histology confirms significantly greater RBC–cerebral endothelial interactions and microglial activation at 24 h after t-BHP-treated RBC injection, which persist at 7 days. Furthermore, significant CMH develop in the absence of blood–brain barrier leakage after t-BHP-RBC injection.

Conclusions

Our in vivo and ex vivo findings show the stalling and clearance of oxidatively stressed RBC in cerebral capillaries, highlighting the significance of microglial responses and altered RBC–brain endothelial interactions in CMH development. Our study provides novel mechanistic insight into CMH associated with pathological conditions with increased RBC–brain endothelial interactions.
Targeting the conserved coronavirus octamer motif GGAAGAGC is a strategy for the development of coronavirus vaccine
Authors: Lin Ching-Hung , Hsieh Feng-Cheng , Chang Yu-Chia , Yang Cheng-Yao , Hsu Hsuan-Wei , Yang Chun-Chun , Tam Hon-Man-Herman , Wu Hung-Yi
Published: November 2023

Background

Coronaviruses are pathogens of humans and animals that cause widespread and costly diseases. The development of effective strategies to combat the threat of coronaviruses is therefore a top priority. The conserved coronavirus octamer motif 5’GGAAGAGC3’ exists in the 3’ untranslated region of all identified coronaviruses. In the current study, we aimed to examine whether targeting the coronavirus octamer motif GGAAGAGC is a promising approach to develop coronavirus vaccine.

Methods

Plaque assays were used to determine the titers of mouse hepatitis virus (MHV)-A59 octamer mutant (MHVoctm) and wild-type (wt) MHV-A59 (MHVwt). Western blotting was used for the determination of translation efficiency of MHVoctm and MHVwt. Plaque assays and RT-qPCR were employed to examine whether MHVoctm was more sensitive to interferon treatment than MHVwt. Weight loss, clinical signs, survival rate, viral RNA detection and histopathological examination were used to evaluate whether MHVoctm was a vaccine candidate against MHVwt infection in BALB/c mice.

Results

In this study, we showed that (i) the MHVoctm with mutation of coronavirus octamer was able to grow to high titers but attenuated in mice, (ii) with the reduced multiplicity of infection (MOI), the difference in gene expression between MHVoctm and MHVwt became more evident in cultured cells, (iii) MHVoctm was more sensitive to interferon treatment than MHVwt and (iv) mice inoculated with MHVoctm were protected from MHVwt infection.

Conclusions

Based on the results obtained from cultured cells, it was suggested that the synergistic effects of octamer mutation, multiplicity of infection and immune response may be a mechanism explaining the distinct phenotypes of octamer-mutated coronavirus in cell culture and mice. In addition, targeting the conserved coronavirus octamer motif is a strategy for development of coronavirus vaccine. Since the conserved octamer exists in all coronaviruses, this strategy of targeting the conserved octamer motif can also be applied to other human and animal coronaviruses for the development of coronavirus vaccines, especially the emergence of novel coronaviruses such as SARS-CoV-2, saving time and cost for vaccine development and disease control.
Molecular characterization of a reptarenavirus detected in a Colombian Red-Tailed Boa (Boa constrictor imperator)
Authors: Abouelkhair Mohamed A. , Roozitalab Ashkan , Elsakhawy Ola K.
Published: November 2023

The global decline in biodiversity is a matter of great concern for members of the class Reptilia. Reptarenaviruses infect snakes, and have been linked to various clinical conditions, such as Boid Inclusion Body Disease (BIBD) in snakes belonging to the families Boidae and Pythonidae. However, there is a scarcity of information regarding reptarenaviruses found in snakes in both the United States and globally. This study aimed to contribute to the understanding of reptarenavirus diversity by molecularly characterizing a reptarenavirus detected in a Colombian Red-Tailed Boa (Boa constrictor imperator). Using a metagenomics approach, we successfully identified, and de novo assembled the whole genomic sequences of a reptarenavirus in a Colombian Red-Tailed Boa manifesting clinically relevant symptoms consistent with BIBD. The analysis showed that the Colombian Red-Tailed Boa in this study carried the University of Giessen virus (UGV-1) S or S6 (UGV/S6) segment and L genotype 7. The prevalence of the UGV/S6 genotype, in line with prior research findings, implies that this genotype may possess specific advantageous characteristics or adaptations that give it a competitive edge over other genotypes in the host population. This research underscores the importance of monitoring and characterizing viral pathogens in captive and wild snake populations. Knowledge of such viruses is crucial for the development of effective diagnostic methods, potential intervention strategies, and the conservation of vulnerable reptilian species. Additionally, our study provides valuable insights for future studies focusing on the evolutionary history, molecular epidemiology, and biological properties of reptarenaviruses in boas and other snake species.
Free and open-source software for object detection, size, and colour determination for use in plant phenotyping
Authors: Wright Harry Charles , Lawrence Frederick Antonio , Ryan Anthony John , Cameron Duncan Drummond
Published: November 2023

Background

Object detection, size determination, and colour detection of images are tools commonly used in plant science. Key examples of this include identification of ripening stages of fruit such as tomatoes and the determination of chlorophyll content as an indicator of plant health. While methods exist for determining these important phenotypes, they often require proprietary software or require coding knowledge to adapt existing code.

Results

We provide a set of free and open-source Python scripts that, without any adaptation, are able to perform background correction and colour correction on images using a ColourChecker chart. Further scripts identify objects, use an object of known size to calibrate for size, and extract the average colour of objects in RGB, Lab, and YUV colour spaces. We use two examples to demonstrate the use of these scripts. We show the consistency of these scripts by imaging in four different lighting conditions, and then we use two examples to show how the scripts can be used. In the first example, we estimate the lycopene content in tomatoes (Solanum lycopersicum) var. Tiny Tim using fruit images and an exponential model to predict lycopene content. We demonstrate that three different cameras (a DSLR camera and two separate mobile phones) are all able to model lycopene content. The models that predict lycopene or chlorophyll need to be adjusted depending on the camera used. In the second example, we estimate the chlorophyll content of basil (Ocimum basilicum) using leaf images and an exponential model to predict chlorophyll content.

Conclusion

A fast, cheap, non-destructive, and inexpensive method is provided for the determination of the size and colour of plant materials using a rig consisting of a lightbox, camera, and colour checker card and using free and open-source scripts that run in Python 3.8. This method accurately predicted the lycopene content in tomato fruit and the chlorophyll content in basil leaves.
Tendon stem/progenitor cells are promising reparative cell sources for multiple musculoskeletal injuries of concomitant articular cartilage lesions associated with ligament injuries
Authors: Yin Heyong , Mao Kelei , Huang Yufu , Guo Ai , Shi Lin
Published: November 2023

Background

Trauma-related articular cartilage lesions usually occur in conjunction with ligament injuries. Torn ligaments are frequently reconstructed with tendon autograft and has been proven to achieve satisfactory clinical outcomes. However, treatments for the concomitant articular cartilage lesions are still very insufficient. The current study was aimed to evaluate whether stem cells derived from tendon tissue can be considered as an alternative reparative cell source for cartilage repair.

Methods

Primary human tendon stem/progenitor cells (hTSPCs) were isolated from 4 male patients (32 ± 8 years) who underwent ACL reconstruction surgery with autologous semitendinosus and gracilis tendons. The excessive tendon tissue after graft preparation was processed for primary cell isolation with an enzyme digestion protocol. Decellularization cartilage matrix (DCM) was used to provide a chondrogenic microenvironment for hTSPCs. Cell viability, cell morphology on the DCM, as well as their chondrogenic differentiation were evaluated.

Results

DAPI staining and DNA quantitative analysis (61.47 μg per mg dry weight before and 2.64 μg/mg after decellularization) showed that most of the cells in the cartilage lacuna were removed after decellularization process. Whilst, the basic structure of the cartilage tissue was preserved and the main ECM components, collagen type II and sGAG were retained after decellularization, which were revealed by DMMB assay and histology. Live/dead staining and proliferative assay demonstrated that DCM supported attachment, survival and proliferation of hTSPCs with an excellent biocompatibility. Furthermore, gene expression analysis indicated that chondrogenic differentiation of hTSPC was induced by the DCM microenvironment, with upregulation of chondrogenesis-related marker genes, COL 2 and SOX9, without the use of exogenous growth factors.

Conclusion

DCM supported hTSPCs attachment and proliferation with high biocompatibility. Moreover, TSPCs underwent a distinct chondrogenesis after the induction of a chondrogenic microenvironment provided by DCM. These results indicated that TSPCs are promising reparative cell sources for promoting cartilage repair. Particularly, in the cohort that articular cartilage lesions occur in conjunction with ligament injuries, autologous TSPCs can be isolated from a portion of the tendon autograph harvested for ligaments reconstruction. In future clinical practice, combined ligament reconstruction with TSPCs- based therapy for articular cartilage repair can to be considered to achieve superior repair of these associated injuries, in which autologous TSPCs can be isolated from a portion of the tendon autograph harvested for ligaments reconstruction.
Short-term study of atrial shunt and improvement of functional mitral regurgitation
Authors: Shang Xiaoke , Liu Mei , Zhong Yucheng , Wang Xueli , Chen Song , Fu Xiaojuan , Sun Ming , Li Geng , Xie Mingxing , Song Guangyuan , Zhu Da , Zhang Changdong , Dong Nianguo
Published: November 2023

Background

This study used an atrial septal shunt to compare the treatment progress and prognosis for patients with heart failure (HF) who have different ejection fractions.

Methods

Twenty HF patients with pulmonary hypertension, who required atrial septal shunt therapy, were included in this study. The patients underwent surgery between December 2012 and December 2020. They were divided into two groups based on their ejection fraction: a group with reduced ejection fraction (HFrEF) and a group with preserved ejection fraction(HFpEF) + mid-range ejection fraction (HfmrEF). Echocardiography was utilized to evaluate parameters such as left ventricular dimension (LVD), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume (LVEDV). Hemodynamic parameters were measured using cardiac catheterization. The patient's cardiac function was assessed using the six-minute walking test (6MWT), KCCQ score, NYHA classification, and the degree of functional mitral regurgitation (FMR). Followed-up visits were conducted at 1, 3, and 6 months, and any adverse effects were recorded.

Results

The LVEF values were consistently higher in the HFpEF+HFmrEF group than HFrEF group at all periods (P < 0.05). Differences in LVD were observed between the two groups before the surgery. Statistically, significant differences were found at the preoperative stage, 1 month, and 3 months (P < 0.05, respectively). However, the LVEDV showed a significant difference between the two groups only at 3 months (P = 0.049). Notably, there were notable variations in LAPm, LAPs, and the pressure gradient between the LA-RA gradient at baeline, after implantation, and during the 6 months follow-up (all P < 0.05).

Conclusion

Following treatment, the HFpEF+HFmrEF group exhibited more significant improvements in echocardiographic and cardiac catheterization indices than the HFrEF group. However, there was no statistically significant difference between the two groups regarding the 6MWT and KCCQ scores. It is important to note that the findings of this study still require further investigation in a large sample size of patients.
The relation between vaccination status and referral to a consultation–liaison psychiatry service for hospitalized patients with COVID-19
Authors: Nishihara Tomoe , Shibata Mao , Ohashi Ayako , Hiyama Kazutoshi , Yamashita Takafumi , Kuroiwa Mika , Sudo Nobuyuki
Published: November 2023

Background

Previous studies have shown that patients with Coronavirus Disease 2019 (COVID-19) are likely to be affected by delirium and other psychiatric complications. We aimed to evaluate the relation between COVID-19 vaccination status and referral of patients hospitalized with COVID-19 for consultation–liaison psychiatry services.

Method

From the medical records used for this retrospective, single hospital-based study, 576 patients were identified who were over 18 years-of-age and hospitalized with a diagnosis of COVID-19 between March 2020 and March 2022. The data of 531 for whom the vaccine history was obtained from the medical records were available for analysis: 455 without and 76 with referral to consultation–liaison psychiatry. A history of COVID-19 vaccination at least two times was used in the analysis of the odds for referral to liaison psychiatric consultation: 95% confidence interval (CI) in multivariable logistic regression. The adjustment factors included sex, age, body mass index (BMI), severity of COVID-19, C-reactive protein level, medical history, and therapeutic factors such as the use of remdesivir, steroids, or mechanical ventilation.

Results

The prevalence of psychiatric consultation was 14.3%. Patients without vaccination had a 7-times greater OR (95%CI:2.08–23.58) than vaccinated patients for a referral for consultation–liaison psychiatry services after adjusting for confounding factors.

Conclusion

Non-vaccination was associated with a greater likelihood of referral for consultation–liaison psychiatry service among these hospitalized Japanese patients with COVID-19, even after adjusting for clinical and therapeutic factors. It is possible that vaccination greatly lessens the need for the referral of COVID-19 patients for consultation–liaison psychiatry services.
Cauda equina syndrome in a patient with human immunodeficiency virus and secondary central nervous system lymphoma: a case report
Authors: Tang Alexander , Di Fonzo David , Redha Mohammed , Churchill-Smith Michael
Published: November 2023

Background

Secondary central nervous system lymphoma (SCNSL) is a known complication of immunocompromised patients with most cases involving the brain parenchyma. Reports of cauda equina syndrome (CES) caused by SCNSL are exceedingly scarce as involvement of this anatomical region is extremely uncommon.

Case presentation

We report a case of a 46-years-old, African, female patient with human immunodeficiency virus (HIV) who developed CES in the context of SCNSL. There were no blasts present in the peripheral blood smear. We provide a review of the literature, discussion of the clinical evolution of this patient and the radiological/histopathological findings. The patient ultimately responded well to induction chemotherapy and high dose methotrexate.

Conclusion

This case report demonstrates that CES, while a rare occurrence in this clinical context, should be considered in at-risk patients especially those presenting with abnormal neurological findings. Prompt recognition may prevent permanent neurological injury and obviate the need for more invasive therapeutic interventions.
The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response
Authors: Zafardoust Simin , Kazemnejad Somaieh , Fathi-Kazerooni Mina , Darzi Maryam , Sadeghi Mohammad Reza , Sadeghi Tabar Ali , Sehat Zahra
Published: November 2023

Background

Assisted reproduction faces a significant obstacle in the form of poor ovarian response (POR) to controlled ovarian stimulation. To address this challenge, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. Our previous research has demonstrated that menstrual blood-derived-mesenchymal stromal cells (MenSCs) injected into the ovaries of women with POR can increase pregnancy rates. The objective of this study was to examine whether MenSC therapy could enhance ovarian reserve parameters and pregnancy outcomes in a larger population of individuals with POR.

Method

This study consisted of 180 infertile individuals with POR who declined oocyte donation. Participants were divided into two groups: those who received bilateral MenSCs intraovarian injection and those who received no intervention. Our primary aim was to compare the rates of spontaneous pregnancy between the two groups, followed by an investigation of any alterations in the ovarian reserve parameters, such as serum FSH, AMH, and AFC levels, as well as the ICSI/IVF outcomes, in both groups of participants.

Results

The MenSC therapy exhibited a favourable tolerability profile and did not raise any safety concerns. Following the 2-month follow-up period, women who received MenSC treatment demonstrated a significantly higher rate of spontaneous pregnancy (P < 0.005) and an improvement in anti-Müllerian hormone (AMH) levels (P = 0.0007) and antral follicle count (AFC) (P < 0.001), whereas the control group demonstrated a considerable decline in these parameters (Both P < 0.001). The MenSC therapy led to a greater number of mature oocytes and embryos among women who underwent ICSI/IVF. Our age subgroup analysis demonstrated a significant difference in the number of spontaneous pregnancies and ICSI/IVF outcomes between the treatment and control groups only among individuals below 40 years of age.

Conclusion

The results of our study indicate that MenSCs treatment may be a viable option for treating women experiencing POR. However, in order to be widely implemented in clinical practice, the clinical effectiveness of MenSCs therapy will need to be established through rigorous prospective randomized clinical trials.

Trial registration: ClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308. IRCT, IRCT20180619040147N4. Registered 08/01/2020.
Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor
Authors: Nguyen Lan Phuong , Cho Minyeong , Nguyen Thai Uy , Park Hee-Kyung , Nguyen Huong Thi , Mykhailova Kateryna , Hurh Sunghoon , Kim Hong-Rae , Seong Jae Young , Lee Cheol Soon , Ham Byung-Joo , Hwang Jong-Ik
Published: November 2023

Background

Tachykinins and their cognate receptors, neurokinin receptors (NKs) including NK1, NK2, and NK3 play vital roles in regulating various physiological processes including neurotransmission, nociception, inflammation, smooth muscle contractility, and stimulation of endocrine and exocrine gland secretion. Their abnormal expression has been reported to be associated with neurological disorders, inflammation, and cancer. Even though NKs are expressed in the same cells with their expression being inversely correlated in some conditions, there is no direct evidence to prove their interaction. Understanding the functional crosstalk between NKs in mediated downstream signaling and cellular responses may elucidate the roles of each receptor in pathophysiology.

Results

In this study, we showed that NKs were co-expressed in some cells. However, different from NK3, which only forms homodimerization, we demonstrated a direct interaction between NK1 and NK2 at the protein level using co-immunoprecipitation and NanoBiT-based protein interaction analysis. Through heterodimerization, NK2 downregulated substance P-stimulated NK1 signals, such as intracellular Ca2+ mobilization and ERK phosphorylation, by enhancing β-arrestin recruitment, even at the ligand concentration that could not activate NK2 itself or in the presence of NK1 specific antagonist, aprepitant. In A549 cells with receptors deleted and reconstituted, NK2 exerted a negative effect on substance P/NK1-mediated cell migration.

Conclusion

Our study has provided the first direct evidence of an interaction between NK1 and NK2, which highlights the functional relevance of their heterodimerization in cellular responses. Our findings demonstrated that through dimerization, NK2 exerts negative effects on downstream signaling and cellular response mediated by NK1. Moreover, this study has significant implications for understanding the complexity of GPCR dimerization and its effect on downstream signaling and cellular responses. Given the important roles of tachykinins and NKs in pathophysiology, these insights may provide clues for developing NKs-targeting drugs.
A sialyltransferases-related gene signature serves as a potential predictor of prognosis and therapeutic response for bladder cancer
Authors: Cao Penglong , Chen Mingying , Zhang Tianya , Zheng Qin , Liu Mulin
Published: November 2023

Background

Aberrant glycosylation, catalyzed by the specific glycosyltransferase, is one of the dominant features of cancers. Among the glycosyltransferase subfamilies, sialyltransferases (SiaTs) are an essential part which has close linkages with tumor-associated events, such as tumor growth, metastasis and angiogenesis. Considering the relationship between SiaTs and cancer, the current study attempted to establish an effective prognostic model with SiaTs-related genes (SRGs) to predict patients’ outcome and therapeutic responsiveness of bladder cancer.

Methods

RNA-seq data, clinical information and genomic mutation data were downloaded (TCGA-BLCA and GSE13507 datasets). The comprehensive landscape of the 20 SiaTs was analyzed, and the differentially expressed SiaTs-related genes were screened with “DESeq2” R package. ConsensusClusterPlus was applied for clustering, following with survival analysis with Kaplan–Meier curve. The overall survival related SRGs were determined with univariate Cox proportional hazards regression analysis, and the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to generate a SRGs-related prognostic model. The predictive value was estimated with Kaplan–Meier plot and the receiver operating characteristic (ROC) curve, which was further validated with the constructed nomogram and decision curve.

Results

In bladder cancer tissues, 17 out of the 20 SiaTs were differentially expressed with CNV changes and somatic mutations. Two SiaTs_Clusters were determined based on the expression of the 20 SiaTs, and two gene_Clusters were identified based on the expression of differentially expressed genes between SiaTs_Clusters. The SRGs-related prognostic model was generated with 7 key genes (CD109, TEAD4, FN1, TM4SF1, CDCA7L, ATOH8 and GZMA), and the accuracy for outcome prediction was validated with ROC curve and a constructed nomogram. The SRGs-related prognostic signature could separate patients into high- and low-risk group, where the high-risk group showed poorer outcome, more abundant immune infiltration, and higher expression of immune checkpoint genes. In addition, the risk score derived from the SRGs-related prognostic model could be utilized as a predictor to evaluate the responsiveness of patients to the medical therapies.

Conclusions

The SRGs-related prognostic signature could potentially aid in the prediction of the survival outcome and therapy response for patients with bladder cancer, contributing to the development of personalized treatment and appropriate medical decisions.
Multi-electrolyte disturbance and supplementation in severely malnourished hospitalized adolescents with restrictive eating disorders
Authors: Dunbar Eva-Molly Petitto , Pribble Chase , Cueto Jennifer , Goldschmidt Andrea B. , Tortolani Christina , Donaldson Abigail A.
Published: November 2023

Background

This study describes the prevalence of hypophosphatemia, hypokalemia, and/or hypomagnesemia and resulting electrolyte supplementation during refeeding in severely malnourished youths hospitalized for restrictive eating disorders.

Methods

Hospitalized patients between 11-26y (N = 81) at < 75% treatment goal weight (TGW) were assessed through retrospective chart review. Outcomes were compared between participants < 70% TGW and those 70–75% TGW. Nutritional rehabilitation started at 1750 kcals/day and advanced by 500 kcal every other day until target intake was achieved. Associations between %TGW on admission; hypophosphatemia, hypokalemia, and/or hypomagnesemia; and electrolyte supplementation were examined.

Results

Of the 24 (29.6%) participants with hypophosphatemia, hypokalemia, and/or hypomagnesemia, 7 (8.6%) received supplementation; the remainder corrected without supplementation. Participants < 70% TGW did not differ from those 70–75% TGW on rates of these conditions or need for supplementation.

Conclusions

Hospital-based nutritional rehabilitation did not confer increased rates of hypophosphatemia, hypokalemia, and/or hypomagnesemia or need for electrolyte supplementation in patients < 70% TGW compared to those 70–75% TGW. While additional research is needed to establish clinical practice guidelines on electrolyte management in this population, our findings suggest that nutritional rehabilitation may be reasonably undertaken without prophylactic electrolyte supplementation, even in patients < 70% TGW.
A rare congenital anomaly in a female child with acute urinary retention—female hypospadias: a case report
Authors: Tan Hooi Hooi , Tan Shung Ken
Published: November 2023

Background

Female hypospadias is a rare congenital anomaly and defined as a female urethral opening on the anterior vaginal wall. Diagnosis is challenging due to its rarity. Different anatomical variations exist depending on the location of the urethral opening. Clinical presentation can vary from asymptomatic until end-stage renal disease due to lower urinary tract obstruction. This case highlights the important clinical and radiological features of female hypospadias. Surgical treatment remains the mainstay management for this entity.

Case presentation

We report a case of a 5-year-old girl presented with 3 days of lower abdominal pain, vomiting and difficulty in voiding. She was previously well. Abdominal examination revealed a palpable suprapubic mass arising from the pelvis up to the umbilicus. Perineal examination showed a single opening at the introitus. Ultrasound showed a grossly distended urinary bladder and bilateral mild hydroureteronephrosis. Catheterization of the opening failed to decompress the bladder, and a suprapubic catheter was inserted which drained 500 cc of clear urine. She also developed acute kidney injury which resolved after suprapubic drainage. Cystogram and genitogram failed to delineate the communication between the urinary bladder and vagina. However, cystovaginoscopy revealed a normal vagina opening, and the urethral meatus entered the anterior wall of the vagina distally. She underwent a meatoplasty and recovered well after surgery.

Conclusion

Attention to important clinical and radiological features helps in the diagnosis of female hypospadias. Female hypospadias should be suspected in female patient with single opening at the introitus, acute urinary retention and failed urinary catheterization. Cystovaginoscopic examination is required to diagnose this condition. Urethroplasty is curative with good outcome for low type of female hypospadias.
Implementation matters: assessing the effectiveness and sustainment of an obstetric triage program at a high-volume facility in Ghana
Authors: Ramaswamy Rohit , Bogdewic Stephanie , Williams Caitllin R. , Deganus Sylvia , Bonzi Gifty Ama , Boakye Joana , Koranteng Emelia , Mensah Rosemond , Amanor Alice , Bryce Fiona , Owen Medge D.
Published: November 2023

Background

Maternal mortality remains stubbornly high in Ghana. Current national efforts are focused on improving the quality of care offered in health facilities. Obstetric triage is one intervention that has been proposed to improve the timeliness and appropriateness of care, two key elements of quality. In this study, we describe and evaluate a theory-based implementation approach to introduce obstetric triage into Tema General Hospital, a high-volume maternity hospital in Greater Accra, that blends concepts from implementation science and quality improvement. This implementation project was a first attempt to scale this intervention into a new facility, following initial development in the Greater Accra Regional Hospital (formerly Ridge Hospital) in Accra.

Methods

This was a retrospective mixed-methods evaluation of two stages of implementation: active implementation and sustainment. We triangulated monitoring data captured during active implementation with clinical outcome data (timeliness of first assessment, accuracy of diagnosis, and appropriateness of care plan) from direct observation or patient obstetric triage assessment forms at baseline, at the completion of the active implementation stage, and following a 12-month “washout” period with no contact between hospital staff and the purveyor organization. Finally, we assessed embeddedness of the new triage procedures using the NoMad, a quantitative assessment of constructs from normalization process theory (NPT).

Results

Patient waiting time decreased substantially during the study. At baseline, the median arrival-to-assessment waiting time was 70.5 min (IQR: 30.0–443.0 min). Waiting time decreased to 6.0 min (IQR: 3.0–15.0 min) following active implementation and to 5.0 min (IQR: 2.0–10.0 min) during the sustainment period. Accuracy of diagnosis was high at the end of active implementation (75.7% correct) and improved during the sustainment period (to 77.9%). The appropriateness of care plans also improved during the sustainment period (from 66.0 to 78.9%). Per NoMad data, hospital staff generally perceive obstetric triage to be well integrated into the facility.

Conclusions

This theory-based implementation approach proved to be successful in introducing a novel obstetric triage concept to a busy high-volume hospital, despite resource constraints and a short implementation window. Results proved long-lasting, suggesting this approach has high potential for engendering sustainability in other facilities as well. Our approach will be useful to other initiatives that aim to utilize program data to create and test implementation theories.
Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM)
Authors: Vasudev Naveen S. , Ainsworth Gemma , Brown Sarah , Pickering Lisa , Waddell Tom , Fife Kate , Griffiths Richard , Sharma Anand , Katona Eszter , Howard Helen , Velikova Galina , Maraveyas Anthony , Brown Janet , Pezaro Carmel , Tuthill Mark , Boleti Ekaterini , Bahl Amit , Szabados Bernadett , Banks Rosamonde E. , Brown Joanne , Venugopal Balaji , Patel Poulam , Jain Ankit , Symeonides Stefan N. , Nathan Paul , Collinson Fiona J. , Powles Thomas
Published: November 2023

PURPOSE

Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile.

METHODS

Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy.

RESULTS

Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively.

CONCLUSION

Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.