Role of Transcerebellar Diameter and Transcerebellar Diameter/Abdominal Circumference Ratio in Assessing Fetal Growth and Diagnosing Intrauterine Growth Restriction.

Background In obstetrics, accurately determining gestational age (GA) is a critical aspect of managing pregnancy and evaluating fetal growth and development. Intrauterine growth restriction (IUGR) is characterized by the failure of the fetus to reach its potential growth. Early detection of IUGR is crucial for optimal obstetric care to reduce fetal complications and neonatal morbidity and mortality. The purpose of the current research is to determine the role of transcerebellar diameter (TCD) and the TCD/abdominal circumference (AC) ratio in assessing fetal growth and diagnosing IUGR. Methods In the sample, there were 600 expectant mothers with GA exceeding 28 weeks. We measured TCD and AC and then calculated the TCD/AC ratio. We used IBM SPSS Statistics for Windows, V. 22.0 (IBM Corp., Armonk, NY), for statistical analysis. The data was subjected to statistical tests, including Pearson's correlation coefficient, coefficient of determination, and tests of validity. Results The current research demonstrates a strong linear correlation between TCD and GA. Additionally, there was no notable disparity in TCD measurements between normal and IUGR fetuses with the same GA. There was an insignificant relationship between the TCD/AC ratio and GA, with a constant TCD/AC ratio in the third trimester of pregnancy in normal fetuses. The mean TCD/AC ratio was 14.72±0.89 (mean±standard deviation), and a cut-off value of 16.5 was determined to diagnose IUGR. Conclusion TCD can serve as a reliable measure for GA estimation during the third trimester in pregnant women with uncertain last menstrual period (LMP) or no dating scan and IUGR fetuses. In diagnosing IUGR, the TCD/AC ratio has demonstrated greater sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The TCD/AC ratio is a GA-independent measure that can be used to diagnose IUGR.

Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD.

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

A Comparative Study of Transcranial Color-Coded Doppler (TCCD) and Transcranial Doppler (TCD) Ultrasonography Techniques in Assessing the Intracranial Cerebral Arteries Haemodynamics.

Cerebrovascular disease (CVD) poses a major public health and socio-economic burden worldwide due to its high morbidity and mortality rates. Accurate assessment of cerebral arteries' haemodynamic plays a crucial role in the diagnosis and treatment management of CVD. The study compared a non-imaging transcranial Doppler ultrasound (TCD) and transcranial color-coded Doppler ultrasound (with (cTCCD) and without (ncTCCD)) angle correction in quantifying middle cerebral arteries (MCAs) haemodynamic parameters. A cross-sectional study involving 50 healthy adults aged ≥ 18 years was conducted. The bilateral MCAs were insonated via three trans-temporal windows (TTWs-anterior, middle, and posterior) using TCD, cTCCD, and ncTCCD techniques. The MCA peak systolic velocity (PSV) and mean flow velocity (MFV) were recorded at proximal and distal imaging depths that could be visualised on TCCD with a detectable spectral waveform. A total of 152 measurements were recorded in 41 (82%) subjects with at least one-sided open TTW across the three techniques. The mean PSVs measured using TCD, ncTCCD, and cTCCD were 83 ± 18 cm/s, 81 ± 19 cm/s, and 93 ± 21 cm/s, respectively. There was no significant difference in PSV between TCD and ncTCCD (bias = 2 cm/s, p = 1.000), whereas cTCCD yielded a significantly higher PSV than TCD and ncTCCD (bias = -10 cm/s, p < 0.001; bias = -12 cm/s, p ≤ 0.001, respectively). The bias in MFV between TCD and ncTCCD techniques was (bias = -0.5 cm/s; p = 1.000), whereas cTCCD demonstrated a higher MFV compared to TCD and ncTCCD (bias = -8 cm/s, p < 0.001; bias = -8 cm/s, p ≤ 0.001, respectively). TCCD is a practically applicable imaging technique in assessing MCA blood flow velocities. cTCCD is more accurate and tends to give higher MCA blood flow velocities than non-imaging TCD and ncTCCD techniques. ncTCCD is comparable to non-imaging TCD and should be considered in clinical cases where using both TCD and TCCD measurements is needed.

New evidence for fractional pressure ratio prediction by pulsatility index from transcranial Doppler in patients with symptomatic cerebrovascular stenosis disease.

Background: The pulsatility index (PI) derived from transcranial Doppler (TCD) assessment may represent the cerebral resistance and altered cerebral blood flow. The purpose of this study was to assess the performance of the TCD PI in correlation with wire-based fractional pressure ratio (FPR). Methods: This study included 33 patients with symptomatic atherosclerotic lesions of the extracranial and intracranial large arteries, specifically the internal carotid artery, middle cerebral artery (MCA), vertebral artery (VA) V4 segment, and basilar artery (BA), all of which exhibited luminal stenosis ranging from 50% to 70%. TCD was performed prior to angiography in order to determine the flow distal to the lesion. We performed cerebrovascular angiography with a pressure wire to measure the FPR of vessels with stenotic lesions. Bland-Altman analysis and ordinal least square (OLS) linear regression were used to quantify the correlation between PI and FPR. Results: A total of 42 TCD data points were analyzed. At the TCD locations distal to the lesions, the correlation coefficients were no less than 0.90%, with almost all P values <0.001, which indicated very strong positive correlations; the exception to this was the distal TCD for MCA segment lesions (r=0.897; P=0.015) and VA V4 segment (r=0.964; P=0.036). The Bland-Altman plot demonstrated a small difference (0.003) between the distal TCD PI and the FPR, with an acceptable 95% confidence interval [95% confidence interval (CI): 0.06-0.12]. Conclusions: The PI obtained through TCD assessment distal to the stenotic lesion exhibited a correlation with the FPR computed using pressure wire measurements.

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients.

BACKGROUND: Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8+ T cells and CD8+T/CD4+T cell ratio in advanced gastric cancer patients receiving immunotherapy. METHODS: A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier methods and Cox proportional hazards regression models. RESULTS: The optimal cutoff values for percentages of CD8+ T cells, naive CD8+ T cells (CD8+ Tn) and memory CD8+ T cells (CD8+ Tm) expressing programmed cell death -1(PD-1) as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy. CONCLUSION: The circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence.

Differential gene expression of cytokines, receptors, and miRNAs in individuals living with HIV-1 and vaccinated against yellow fever.

Between 2016 and 2018, Brazil faced a yellow fever (YF) outbreak, which led to an expansion of vaccination coverage. The coexistence of the YF outbreak and the HIV-1 epidemic in Brazil raised concerns regarding the immune response and vaccine effectiveness in individuals living with HIV (PLWH). The aim of this study was to investigate the immune response to YF vaccination in PLWH and HIV-uninfected individuals as controls. Transcript levels of immunomodulatory molecules, including IL-6, IL-10, IL-21, TGF-ß, CD19, CD163, miR-21, miR-146, and miR-155, were measured using RTqPCR. TCD4+ cells were evaluated by cytometry, and neutralizing antibody (Nab) titers were detected by a micro plaque-reduction neutralization test. The findings of our study revealed several noteworthy observations. First, there was a notable reduction in the circulation of TCD4+ cells postvaccination. Among people living with HIV (PLWH), we observed an increase in the expression of IL-10 following vaccination, while IL-6 expression was diminished in PLWH with lower TCD4+ counts. Furthermore, we identified the downregulation of CD19 and TGF-ß, along with the upregulation of IL-21 and CD163. Notably, we observed positive correlations between the levels of IL-10/IL-21, IL-10/CD163, and IL-6/CD19. Additionally, there was a positive correlation between miRNAs 146 and 155. It is important to emphasize that all participants exhibited robust neutralizing antibody responses after receiving 17DD YF vaccination. In this context, the gene expression data presented can be useful for biomarker studies of protective antibodies induced by YF vaccination. This study sheds light on immune mechanisms in individuals living with HIV and YF vaccination.

Hyper-acute effects of sub-concussive soccer headers on brain function and hemodynamics.

Introduction: Sub-concussive head impacts in soccer are drawing increasing research attention regarding their acute and long-term effects as players may experience thousands of headers in a single season. During these impacts, the head experiences rapid acceleration similar to what occurs during a concussion, but without the clinical implications. The physical mechanism and response to repetitive impacts are not completely understood. The objective of this work was to examine the immediate functional outcomes of sub-concussive level impacts from soccer heading in a natural, non-laboratory environment. Methods: Twenty university level soccer athletes were instrumented with sensor-mounted bite bars to record impacts from 10 consecutive soccer headers. Pre- and post-header measurements were collected to determine hyper-acute changes, i.e., within minutes after exposure. This included measuring blood flow velocity using transcranial Doppler (TCD) ultrasound, oxyhemoglobin concentration using functional near infrared spectroscopy imaging (fNIRS), and upper extremity dual-task (UEF) neurocognitive testing. Results: On average, the athletes experienced 30.7 ± 8.9 g peak linear acceleration and 7.2 ± 3.1 rad/s peak angular velocity, respectively. Results from fNIRS measurements showed an increase in the brain oxygenation for the left prefrontal cortex (PC) (p = 0.002), and the left motor cortex (MC) (p = 0.007) following the soccer headers. Additional analysis of the fNIRS time series demonstrates increased sample entropy of the signal after the headers in the right PC (p = 0.02), right MC (p = 0.004), and left MC (p = 0.04). Discussion: These combined results reveal some variations in brain oxygenation immediately detected after repetitive headers. Significant changes in balance and neurocognitive function were not observed in this study, indicating a mild level of head impacts. This is the first study to observe hemodynamic changes immediately after sub-concussive impacts using non-invasive portable imaging technology. In combination with head kinematic measurements, this information can give new insights and a framework for immediate monitoring of sub-concussive impacts on the head.

Case report: Intensive statin and PCSK-9 inhibitor combo reduces plaque volume and stenosis in ischemic stroke patient.

Intracranial atherosclerotic ischemic stroke dramatically impacts the quality of life among the elderly. Statins therapy has been proven to be effective in plaque stabilization and alleviation in patients with intracranial atherosclerotic ischemic stroke. According to recent studies, these effects may be directly related to lipid levels rather than specific lipid-lowering drugs. Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK-9 inhibitor) are newer effective lipid-lowering drugs increasingly prescribed to patients at high cardiovascular risk to lower LDL cholesterol. Studies have provided evidence that PCSK9 inhibitor combined with statin therapy can lead to a decrease in the plaque volume measured by intravascular ultrasound in coronary heart disease patients. But the efficacy of combination of the two drugs in symptomatic intracranial artery stenosis has been unknown. Here we provide a case which was reported to suggest that a combination of Evolocumab and intensive statin therapy might reverse or alleviate symptomatic intracranial artery stenosis.

Regional disparity in continuously measured time-domain cerebrovascular reactivity indices: a scoping review of human literature.

Objective: Cerebral blood vessels maintaining relatively constant cerebral blood flow (CBF) over wide range of systemic arterial blood pressure (ABP) is referred to as cerebral autoregulation (CA). Impairments in CA expose the brain to pressure-passive flow states leading to hypoperfusion and hyperperfusion. Cerebrovascular reactivity (CVR) metrics refer to surrogate metrics of pressure-based CA that evaluate the relationship between slow vasogenic fluctuations in cerebral perfusion pressure/ABP and a surrogate for pulsatile CBF/cerebral blood volume.Approach: We performed a systematically conducted scoping review of all available human literature examining the association between continuous CVR between more than one brain region/channel using the same CVR index.Main Results: In all the included 22 articles, only handful of transcranial doppler (TCD) and near-infrared spectroscopy (NIRS) based metrics were calculated for only two brain regions/channels. These metrics found no difference between left and right sides in healthy volunteer, cardiac surgery, and intracranial hemorrhage patient studies. In contrast, significant differences were reported in endarterectomy, and subarachnoid hemorrhage studies, while varying results were found regarding regional disparity in stroke, traumatic brain injury, and multiple population studies.Significance: Further research is required to evaluate regional disparity using NIRS-based indices and to understand if NIRS-based indices provide better regional disparity information than TCD-based indices.

Transcranial doppler velocities in a large healthy population of African children.

Background and purpose: Transcranial doppler ultrasound (TCD) is a tool that diagnoses and monitors pathophysiological changes to the cerebrovasculature. As cerebral blood flow velocities (CBFVs) increase throughout childhood, interpretation of TCD examinations in pediatrics requires comparison to age matched normative data. Large cohorts of healthy children have not been examined to develop these reference values in any population. There is a complete absence of normative values in African children where, due to lack of alternate neuroimaging techniques, utilization of TCD is rapidly emerging. Materials and methods: A prospective study of 710 healthy African children 3 months-15 years was performed. Demographics, vital signs, and hemoglobin values were recorded. Participants underwent a complete, non-imaging TCD examination. Systolic (Vs), diastolic (Vd), and mean (Vm) flow velocities and pulsatility index (PI) were calculated by the instrument for each measurement. Results: Vs, Vd, and Vm increased through early childhood in all vessels, with the highest CBFVs identified in children 5-5.9 years. There were few significant gender differences in CBFVs in any vessels in any age group. No correlations between blood pressure or hemoglobin and CBFVs were identified. Children in the youngest age groups had CBFVs similar to those previously published, whereas nearly every vessel in children ≥3 years had significantly lower Vs, Vd, and Vm. Conclusions: For the first time, reference TCD values for African children are established. Utilization of these CBFVs in the interpretation of TCD examinations in this population will improve the overall accuracy of TCD as a clinical tool on the continent.

Agitated saline with 10% blood increases number and stability of microbubbles in detection right-to-left shunt by contrast-enhanced transcranial Doppler: an in vitro and in vivo observational study.

Background: Agitated saline (AS) with blood has been shown to have good tolerance and increased efficacy when used in contrast-enhanced transcranial Doppler (c-TCD) to detect right-to-left shunt (RLS). However, little is known about the effects of blood volume on c-TCD results. Our study investigated the characterization of AS with different blood volumes in vitro and compared the c-TCD results in vivo. Methods: In vitro, AS without blood, AS with 5% blood (5% BAS), and AS with 10% blood (10% BAS) were prepared based on previous studies and observed under microscopy. The numbers and sizes of the microbubbles from different contrast agents were compared immediately, 5 min, and 10 min post-agitation. In vivo, 74 patients were recruited. c-TCD was repeated 3 times using AS with different blood volumes in each patient. Signal detection times, positive rates, and classifications of RLS were compared among the 3 groups. Results: In vitro, the AS without blood produced 5.4±2.4/field microbubbles after agitation, the 5% BAS produced 30.4±4.2/field, and the 10% BAS produced 43.9±12.7/field. More microbubbles remained in the 10% BAS than the 5% BAS within 10 min (18.5±6.1 vs. 7.1±2.0/field, P<0.001). The size of the microbubbles from the 5% BAS increased from 9.2±8.2 to 22.1±10.6 µm within 10 min post-agitation (P=0.014), while the 10% BAS changed insignificantly. In vivo, the signal detection times of the 5% BAS (1.1±0.7 s) and 10% BAS (1.0±0.8 s) were significantly shorter than the AS without blood (4.0±1.5 s, P<0.0001). The RLS positive rates were 63.5%, 67.6% and 71.6% in AS without blood, 5% BAS and 10% BAS respectively; however, the differences were not statistically significant. The AS without blood reached 12.2% level III RLS, while the 5% BAS reached 25.7%, and the 10% BAS reached 35.1% (P=0.005). Conclusions: The 10% BAS would be suggested in c-TCD as it addressed larger RLS by increasing the number and stability of microbubbles, and it improves the diagnosis of patent foramen ovale (PFO).

Thoracoabdominal normothermic regional perfusion in donation after circulatory death does not restore brain blood flow.

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.

Clinical significance of MRA, TCD and electroencephalogram in the diagnosis of intracranial artery stenosis in ischemic cerebrovascular disease.

The clinical value of magnetic resonance angiography (MRA), transcranial Doppler ultrasound (TCD) and electroencephalogram (EEG) in the diagnosis of intracranial artery stenosis in ischemic cerebrovascular disease (ICVD) was explored. The clinical data of TCD, MRA and EEG in 98 patients with ICVD were retrospectively analyzed. The clinical value of TCD, MRA combined with EEG in the diagnosis of intracranial artery stenosis in ICVD was analyzed based on the results of digital subtraction angiography (DSA) as the gold standard. A total of 98 patients were diagnosed with 27 cases of normal intracranial artery, 32 cases of mild stenosis, 25 cases of moderate stenosis, and 14 cases of severe stenosis DSA examination. TCD was detected in 23 cases of normal, 25 cases of mild stenosis, 23 cases of moderate stenosis and 13 cases of severe stenosis. MRA showed 24 cases of normal, 28 cases of mild stenosis, 21 cases of moderate stenosis and 12 cases of severe stenosis. EEG examination detected that there were 25 cases of normal, 24 cases of mild stenosis, 22 cases of moderate stenosis, and 14 cases of severe stenosis. Sensitivity, accuracy and negative predictive value had significant differences between combined diagnosis and single diagnosis. The combined detection of TCD, MRA and EEG is consistent with DSA detection in the diagnosis of ICVD intracranial artery stenosis.

Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status.

Background: The lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. Methods: A cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio™ COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with p<0.05 considered statistically significant. Results: The median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (≥500 cells/µL) versus 1.8% (200-499 cells/µL), (OR=3.5; p=0.04) and 0.6% (<200 cells/µL), (OR=17.7; p<0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (≥40 copies/mL) versus 4.9% (<40 copies/mL), (OR= 3.8; p<0.01). Conclusion: Before COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination.

Efficacy of PF-06651600 in alleviating the pro-inflammatory capacity of CD4+ T cells in rheumatoid arthritis patients.

INTRODUCTION: PF-06651600 is a highly specific inhibitor of Janus-activated kinase 3 and the Tec family of kinases. Regarding its dual function in the inhibition of both γc cytokine receptors and T cell receptor signaling, the present study aimed at evaluating the impact of PF-06651600 on the status of T-helper cells (Th) as the central game players in the pathogenesis of rheumatoid arthritis (RA). METHOD: TCD4+ cells were isolated from 34 RA patients and 15 healthy control individuals and were evaluated after treatment with PF-06651600. RESULTS: RA patients had higher percentages of TCD4+ cells, CD4+ PD-1+ cells, and CD4+ PD-1+ TIGIT+ cells compared to a healthy control group and the TCD4+ cells of these patients showed higher interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17 secretion along with higher messenger RNA (mRNA) expressions of T-bet. The percentage of CD4+ PD-1+ TIGIT+ cells showed a reverse correlation with the Disease Activity Score of 28 joints of the RA patients. PF-06651600 caused a significant decrease in the mRNA expressions of T-bet and RAR-related orphan receptor γt and the secretion of interferon (IFN)-γ and TNF-α in TCD4+ cells of RA patients. On the other hand, the population of CD4+ PD-1+ TIGIT+ cells was expanded under the influence of PF-06651600. This treatment also reduced the proliferation of TCD4+ cells. CONCLUSION: PF-06651600 demonstrated a potential to modulate the activity of TCD4+ cells in RA patients and to reduce the commitment of Th cells to the pathogenic Th1 and Th17 subsets. Further, it caused TCD4+ cells to gain an exhausted phenotype which is associated with better prognosis in RA patients.

Effect of Interventional Therapy Unexplained Dizziness and Relationship Between Dizziness Handicap Inventory and Right-to-Left Shunt Grading.

Objective: Unexplained dizziness remains a clinical challenge. Our previous studies have shown that unexplained dizziness may be related to patent foramen ovale (PFO). This study aims to explore whether the degree of shunt is correlated with the degree of unexplained dizziness and looking for the possible clinical intervention for patients with unexplained dizziness. Methods: This study was a large single-center, prospective, controlled study. From March 2019 to March 2022, patients with unexplained dizziness and explained dizziness and healthy controls were recruited. Contrast-enhanced transcranial Doppler sonography (c-TCD) was performed to detect the existence of right-to-left shunt (RLS) and shunt grading. The dizziness handicap inventory (DHI) was completed to evaluate the dizziness. Unexplained dizziness patients with large amount of PFO were volunteered to receive medication treatment and transcatheter PFO closure and followed up six months. Results: A total of 387 patients (132 unexplained, 123 explained and 132 controls) were enrolled. There was a statistical difference in the RLS grading with three groups (p < 0.001). The Spearman correlation coefficient of RLS grading and DHI scores in unexplained dizziness patients (r=0.122, p=0.163) and explained dizziness patients (r=0.067, p=0.460). In the unexplained group, there were 49 cases with massive grading RLS. Of which 25 patients received percutaneous PFO closure treatment and 24 cases received medication treatment. Followed up six months after treatment, the amount of DHI scores change in patients who received the percutaneous PFO closure was significantly higher than that in the medication treatment group (p < 0.001). Conclusion: RLS may play an important role in unexplained dizziness. For unexplained dizziness patients, PFO closure may contribute to better outcomes. In the future, large-scale randomized controlled studies are still needed.

Thousand Cankers Disease in Walnut Trees in Europe: Current Status and Management.

Thousand cankers disease (TCD) is a new deadly disease in walnut trees (Juglans spp.), which is plaguing commercial plantations, natural groves, and ornamental black walnut trees (Juglans nigra) in their native and invasion areas in the US and, more recently, in artificial plantations and amenity trees in the newly-invaded areas in Europe (Italy). This insect/fungus complex arises from the intense trophic activity of the bark beetle vector Pityophthorus juglandis in the phloem of Juglans spp. and the subsequent development of multiple Geosmithia morbida cankers around beetles' entry/exit holes. After an analysis of the main biological and ecological traits of both members of this insect/fungus complex, this review explores the options available for TCD prevention and management. Special focus is given to those diagnostic tools developed for disease detection, surveillance, and monitoring, as well as to existing phytosanitary regulations, protocols, and measures that comply with TCD eradication and containment. Only integrated disease management can effectively curtail the pervasive spread of TCD, thus limiting the damage to natural ecosystems, plantations, and ornamental walnuts.

Effect of Baduanjin exercise on cerebral blood flow and cognitive frailty in the community older adults with cognitive frailty: A randomized controlled trial.

Objectives: Regular Baduanjin exercise training has been shown to be beneficial to the physical and cognitive health of older adults, but the underlying mechanisms remain to be investigated. This study examined the influence of Baduanjin on cerebral hemodynamics in community-dwelling older adults with cognitive frailty. Design: Randomized controlled trial. Methods: A total of 102 eligible participants were randomly allocated into the Baduanjin exercise intervention group (BEG) or usual physical activity control group (CG) for 24 weeks. Cerebral hemodynamic parameters of bilateral middle/anterior cerebral artery and basilar artery, cognitive ability and physical frailty were assessed using Transcranial Doppler (TCD), Montreal Cognitive Assessment (MoCA) and Edmonton Frailty Scale (EFS) at baseline and 24 weeks post-intervention. Results: After 24 weeks intervention, the changes in peak systolic velocity (PSV), mean blood flow velocity (MBFV), and end diastolic velocity (EDV) in the right middle cerebral artery and basilar artery were better in the BEG than in the CG; the increase in MoCA scores and the decrease in EFS scores were significantly higher in the BEG than in the CG. Moreover, the interaction of exercise and time on those variables showed obvious significance. Conclusions: The 24 weeks Baduanjin exercise training had a positive beneficial effect on cerebral blood flow in community-dwelling older adults with cognitive frailty. This may be a potential mechanism by which Baduanjin exercise improves the cognitive frailty in older adults. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800020341. Date of registration: December 25, 2018, http://www.chictr.org.cn/showproj.aspx?proj=29846.

Ultrasound-guided cerebral resuscitation in patients with severe traumatic brain Injury.

Traumatic brain injury (TBI) is a worldwide public health concern given its significant morbidity and mortality, years of potential life lost, reduced quality of life and elevated healthcare costs. The primary injury occurs at the moment of impact, but secondary injuries might develop as a result of brain hemodynamic abnormalities, hypoxia, and hypotension. The cerebral edema and hemorrhage of the injured tissues causes a decrease in cerebral perfusion pressure (CPP), which leads to higher risk of cerebral ischemia, herniation and death. In this setting, our role as physicians is to minimize damage by the optimization of the CPP and therefore to reduce mortality and improve neurological outcomes. Performing a transcranial doppler ultrasound (TCD) allows to estimate cerebral blood flow velocities and identify states of low flow and high resistance. We propose to include TCD as an initial assessment and further monitoring tool for resuscitation guidance in patients with severe TBI. We present an Ultrasound-Guided Cardio-cerebral Resuscitation (UGCeR) protocol in Patients with Severe TBI.