OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

OBJECTIVES

Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.

METHODS

This was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.

RESULTS

Two hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.

CONCLUSION

Overall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.

Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce

BACKGROUND

Penetrating brain injury (PBI) is a leading cause of combat mortality but local outcome data is limited. The authors examined combat-related PBI cases to describe patient characteristics and identify clinical and radiologic predictors of functional recovery

METHODS

This is a retrospective cohort study of military personnel aged 18–56 years with combat-related PBI referred to VLGH AFPMC between January 2017 to June 2022. The authors collected demographics data, injury mechanism, pre-hospital and transfer details, admission clinical and radiologic findings, treatments, and follow-up outcomes. The Glasgow Outcome Scale (GOS), dichotomized into unfavorable (GOS 1–3) and favorable (GOS 4–5), was used to assess functional status. Associations were tested with Fisher’s Exact Test.

RESULTS

Thirty-seven patients met inclusion criteria: 31 survivors with follow-up and 6 who died in hospital. All were male; gunshot wounds accounted for 81% of injuries. At a median follow-up of 27 months, among survivors, 74% had a Glasgow Coma Scale (GCS) of 15 and 45% achieved good recovery (GOS 5). Pre-hospital timing measures (evacuation time, interval to surgery, and transfer delays) were not significantly associated with outcome. Favorable outcomes correlated strongly with higher admission GCS (p < 0.001), preserved baseline motor function (p < 0.001), smaller hemorrhage volume (p = 0.01), and injury limited to a single lobe (p < 0.001). Unfavorable outcomes were associated with intracranial infection, post-traumatic seizures, and need for multiple surgeries (all p < 0.001).

CONCLUSION

Functional recovery after combat-related PBI in this cohort was principally determined by initial neurologic status, injury extent, and subsequent complications The lack of association with pre-hospital timing possibly reflects survivorship bias and incomplete capture of early fatalities.

Human ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Wounds, Gunshot ; Brain Injuries, Traumatic

Introduction: Steroid-responsive encephalopathy associated with thyroiditis (STREAT) is a rare clinical entity. Clinical presentations of STREAT can range from a strokelike presentation to psychiatric symptoms. STREAT is diagnosed based on four major criteria which include altered cognitive function, new or worsening psychiatric symptoms, elevated antithyroid antibodies, and exclusion of infectious, toxic, metabolic, or neoplastic causes. Corticosteroids are the cornerstone of treatment, with reported excellent response in neurocognitive symptoms resolution. Case: This was a case of a 48-year-old male with Graves’s disease who underwent radioiodine therapy 4 months earlier and was started on levothyroxine 100 mcg 2 weeks prior to presentation. He presented with 4 days of behavioral symptoms, irritable mood with auditory and visual hallucinations. There was no history of fever, headache, limb weakness, or seizure. On general appearance, the patient was agitated, talking incoherently, and disorientated with normal vitals. There was no delayed relaxation of the reflex. The examination of the cranial nerve, motor, sensory, and cerebellar system was normal. A lumbar puncture showed normal opening pressure with a high protein CSF content of 1,596 mg/L. The thyroid-stimulating hormone (TSH) was elevated at 72.7 uIU/mL and T4 at 9.56 pmol/L. Serum antithyroid peroxidase was elevated at 877.42 IU/mL, and antiTSH receptor antibody at 21.30 IU/L. CSF oligonal band, serum aquaporin-4, and viral screening were negative; noncontrasted computed tomography brain revealed normal findings. Based on the clinical history and examination, a diagnosis of STREAT was made at the emergency department. The patient was initiated on hydrocortisone 100 mg three times a day. Within 24–48 hours of steroid therapy, marked improvement and subsequent resolution of the mental status and behavioral symptoms were seen. Conclusion Hashimoto’s thyroiditis can rarely lead to STREAT, a condition with diverse neurological manifestations, where early recognition and prompt corticosteroid therapy are essential for favorable outcomes.
Brain Diseases ; Thyroiditis ; Steroids

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury. METHODS: A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot. RESULTS: After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001). CONCLUSION EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Rats ; Forkhead Box Protein O3/genetics* ; Reperfusion Injury/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Brain Ischemia/complications* ; Mitochondria/genetics* ; Autophagy ; Protein Kinases/genetics* ; Sirtuin 1/genetics* ; Humans ; Memory Disorders/psychology* ; Signal Transduction

In the era of big data, neuroimaging and algorithmic analyses have propelled brain science research and brain mapping. Acupuncture, widely recognized as an effective surface stimulation therapy, has demonstrated therapeutic efficacy for various brain conditions such as stroke and depression. However, the mechanisms linking acupuncture to brain function and its modulatory effects on brain activity require systematic exploration. Additionally, there is an urgent need to scientifically reinterpret traditional meridian theory and enhance its clinical applicability. Therefore, we propose the initiative of constructing a "brain mapping atlas of meridian, collateral and body surface stimulation" to explore the patterns linking the therapeutic effects of stimulating the twelve meridians, eight extraordinary vessels, divergent channels, collateral channels, sinew channels, and skin regions to brain function. This initiative aims to provide a scientific interpretation of traditional Chinese medicine meridian theory and enhance its practical applicability. This paper begins by reviewing the current state of brain mapping. It then summarizes existing research on the relationship between acupuncture and the brain, highlighting the necessity of constructing this atlas. The paper further analyzes the methodologies and technical challenges involved. Finally, the potential applications of the brain mapping atlas of meridian, collateral and body surface stimulation, and its main significance in advancing traditional meridian theory to keep pace with the times are prospected.
Humans ; Acupuncture Therapy ; Meridians ; Big Data ; Brain/physiology* ; Brain Mapping

The correlation between meridians and zangfu organs is one of the core contents of the theory of zangfu organs and meridians, which has significant research value and clinical application potential. In this paper, the research literature on correlation between meridians and zangfu organs in the past five years is sorted out and summarized, and it is found that more clinical application basis is added in meridian-diagnosis, and a new situation of high-quality evidence-based medicine is opened in the aspect of meridian-treatment. In terms of internal connection and biological mechanism, the neurobiological characteristics and regulatory mechanism represented by "heart meridian-heart" are illustrated. The research model of the relationship between the meridians-zangfu organs and the brain, which combines the functional connection of the brain network in clinic and the basic neural circuit mechanism under the premise of the "effect law", is clearly proposed.
Meridians ; Humans ; Brain/physiology*

OBJECTIVE: To screen the population for acupuncture treatment of neck pain, using functional magnetic resonance imaging (fMRI) technology and based on machine learning algorithms. METHODS: Eighty patients with neck pain were recruited. Using FPX25 handheld pressure algometer, the tender points were detected in the areas with high-frequent onset of neck pain and high degree of acupoint sensitization. Acupuncture was delivered at 4 tender points with the lowest pain threshold, once every two days; and the treatment was given 3 times a week and for 2 consecutive weeks. The amplitude of low-frequency fluctuation (ALFF) of the brain before treatment was taken as a predictive feature to construct support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN) models to predict the responses of neck pain patients to acupuncture treatment. A longitudinal analysis of the ALFF features was performed before and after treatment to reveal the potential biological markers of the reactivity to the acupuncture therapy. RESULTS: The SVM model could successfully distinguish high responders (48 cases) and low responders (32 cases) to acupuncture treatment, and its accuracy rate reached 82.5%. Based on the SVM model, the ALFF values of 4 brain regions were identified as the consistent predictive features, including the right middle temporal gyrus, the right superior occipital gyrus, and the bilateral posterior cingulate gyrus. In the patients with high acupuncture response, the ALFF value in the left posterior cingulate gyrus decreased after treatment (P<0.05), whereas in the patients with low acupuncture response, the ALFF value in the right superior occipital gyrus increased after treatment (P<0.01). The longitudinal functional connectivity (FC) analysis found that compared with those before treatment, the high responders showed the enhanced FC after treatment between the left posterior cingulate gyrus and various regions, including the bilateral Crus1 of the cerebellum, the right insula, the bilateral angular gyrus, the left medial superior frontal gyrus, and the left middle cingulate gyrus (GRF: corrected, voxel level: P<0.05, mass level: P<0.05). In contrast, the low responders exhibited the enhanced FC between the left posterior cingulate gyrus and the left Crus2 of the cerebellum, the left middle temporal gyrus, the right posterior cingulate gyrus, and the left angular gyrus; besides, FC was reduced in low responders between the left posterior cingulate gyrus and the right supramarginal gyrus (GRF: corrected, voxel level: P<0.05, mass level: P<0.05). CONCLUSION This study validates the practicality of pre-treatment ALFF feature prediction for acupuncture efficacy on neck pain. The therapeutic effect of acupuncture on neck pain is potentially associated with its impact on the default mode network, and then, alter the pain perception and emotional regulation.
Humans ; Neck Pain/physiopathology* ; Acupuncture Therapy ; Female ; Male ; Adult ; Middle Aged ; Machine Learning ; Magnetic Resonance Imaging ; Young Adult ; Brain/physiopathology* ; Acupuncture Points ; Aged

Electroencephalography (EEG) and magnetic resonance imaging (MRI), as neuroimaging technologies, provided objective and visualized technical tools for analyzing the brain effect mechanisms of acupuncture and moxibustion from the perspectives of brain structure, function, metabolism, and hemodynamics. The advancement of artificial intelligence (AI) algorithms can compensate for issues such as the large and scattered nature of neuroimaging data, inconsistent quality, and high heterogeneity of image information. The integration of AI with neuroimaging can facilitate individualized, intelligent, and precise prediction of acupuncture and moxibustion effects, enable intelligent classification of differential acupuncture responses, and identify brain activation patterns. This paper focuses on EEG and MRI, analyzing how machine learning and deep learning optimize multimodal neuroimaging data and their applications in the study of acupuncture and moxibustion brain effects mechanisms. Furthermore, it highlights current research gaps and limitations to provide insights for future studies on acupuncture brain effects mechanisms.
Humans ; Acupuncture Therapy ; Brain/physiology* ; Moxibustion ; Neuroimaging/methods* ; Artificial Intelligence ; Magnetic Resonance Imaging ; Electroencephalography

This paper explores the research progress of acupuncture for the prevention and treatment of Alzheimer's disease (AD) based on the "kidney-governor vessel-brain" axis. According to the fundamental pathogenesis of AD in traditional Chinese medicine (TCM), which attributes to kidney deficiency, marrow depletion, and impaired mental faculties, as well as the governor vessel's connection between the kidney and brain, the concept of the "kidney-governor vessel-brain" axis is proposed. The theoretical basis of the "kidney-governor vessel-brain" axis is analyzed based on the meridian pathway and physiological functions of the governor vessel, as well as the interdependent and mutually reinforcing relationships among the kidney, governor vessel, and brain. The relationship between AD and the "kidney-governor vessel-brain" axis is elucidated from both traditional medical theories and modern biological perspectives. Integrating clinical and mechanistic research on AD prevention and treatment based on this axis, it is suggested that the "kidney-governor vessel-brain" axis provides valuable insights and references for future research on AD prevention and treatment.
Humans ; Alzheimer Disease/physiopathology* ; Acupuncture Therapy ; Kidney/blood supply* ; Brain/blood supply* ; Meridians ; Blood Vessels/physiopathology*