Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

Psychiatric comorbidities in children with conduct disorder:a descriptive analysis of real-world data

To the editor:Two recent advisories from the US surgeon general have underscored the unprecedented public health crisis in youth mental health and emphasised the need for“timely data collection and research to identify and respond to youth mental health needs more rapidly”.1 Increased rates of suicidal behaviour,depression and anxiety symptoms and substance use.

Sex, ApoE4 and Alzheimer's disease: rethinking drug discovery in the era of precision medicine

Alzheimer's disease(AD) is the most common cause of dementia and presents with an insidious onset and long prodromal period. Despite billions spent on clinical trials and decades of research, there are currently no disease modifying therapies approved for AD.

Intraoperative hemodynamic parameters of middle cerebral artery and other artery aneurysms utilizing transcranial Doppler ultrasonography

BACKGROUND： Hemodynamic changes accompany the initiation, development and rupture of middle cerebral artery （MCA） aneurysms. The complexity of the intraaneurysmal hemodynamic factors has not been completely clarified by the indirect measures and methods used in previous studies. OBJECTIVE： To evaluate correlations of intraoperative hemodynamic factors to initiation and rupture of MCA aneurysms. DESIGN, TIME AND SETTING： A case-control study was performed at the Department of Neurosurgery, Tiantan Hospital Affiliated to Capital Medical University, China between March and October 2008. PARTICIPANTS： A total of 12 consecutive patients diagnosed with MCA aneurysms （MCA aneurysms group） and five patients without middle cerebral artery aneurysms （with aneurysms located at other arteries, control group） were enrolled at the Department of Neurosurgery, Tiantan Hospital Affiliated to Capital Medical University, China. METHODS： The proximal and distal arteries of MCA aneurysms were exposed visibly in the MCA aneurysm group. The M1 segment of MCA without the aneurysm and the aneurysm on other arteries were also exposed visibly in the control group. Hemodynamic indices were then measured using an intraoperative 16 MHz probe installed in a Multi-Dop TCD8X4 device. MAIN OUTCOME MEASURES： Mean （time-averaged velocity） difference, maximum mean, pulsatility index difference, maximum pulsatility index, resistance index difference, maximum resistance index; correlation of development and rupture of MCA aneurysms to intraoperative hemodynamic factors of the parent artery. RESULTS： A total of 12 patients underwent microsurgery for treatment to occlude 15 MCA aneurysms. Of the 15 MCA aneurysms, 12 were located at the bifurcation, two at the M1 segment and one at the M3 segment; eight of the aneurysms were unruptured and seven were ruptured. The whole indices with combination mean difference, maximum mean, and maximum pulsatility index of the aneurysms were important factors influencing the rupture of MCA aneurysms （t = 2.92, P = 0.03, constant）. A higher velocity intraaneurismal flow at the bifurcation was identified （t = 3.48, P = 0.01, constant）. After the aneurysm was completely occluded, global high-velocity flow could not be detected in the parent arteries （t = 2.57, P=0.03, constant）. CONCLUSION： When short-term high-velocity blood flow is present, aneurysms can be easily initiated and ruptured at the bifurcation of MCA.

Bacillary layer detachment presenting with posterior scleritis:case report

Background:Bacillary layer detachment(BALAD)is a phenomenon characterized by fluid accumulation at the myoid region of the inner photoreceptor segments identifiable on optical coherence tomography(OCT)imaging.This finding has been recently described in patients with diverse primary diagnoses which share the common feature of serous exudation in the posterior pole.However,thus far there have been very few reports in the literature of BALAD in patients with posterior scleritis.Case Description:A 16-year-old male presented with unilateral vision changes that acutely worsened overnight to significant unilateral vision loss.He was eventually diagnosed with idiopathic posterior scleritis with associated BALAD on OCT.Similar to other reported cases of BALAD,he experienced anatomic restoration of the outer retina followed by good visual recovery after treatment with high dose steroid,ultimately with complete recovery of both retinal anatomy and vision within 4 months.Conclusions:This case provides further evidence that posterior scleritis can be a cause of BALAD.The rapid presentation and excellent visual and anatomical outcome of this case is entirely consistent with known descriptions of BALAD in a variety of other conditions,further supporting the categorization of BALAD as an entity which retinal specialists should be able to recognize as distinct from other forms of intraretinal fluid,retinal detachment,and retinoschisis.

Application of optical coherence tomography in hereditary,toxic and metabolic optic neuropathies

Hereditary,metabolic and toxic optic neuropathies cause bilateral,central vision loss and therefore can result in severe impairment in visual function.Accurate,early diagnosis is critical,as nutritional and toxic optic neuropathies may be reversible if identified early,and diagnosis of hereditary optic neuropathies can prevent unnecessary invasive workup,provide prognostic information,and allow for effective genetic counseling.Optical coherence tomography(OCT)is a valuable tool that aids in the diagnosis and prognostication of optic neuropathies as it allows for quantification of changes in the retinal ganglion cells(RGCs)and retinal nerve fiber layer(RNFL)over time.We review the characteristic clinical presentations of hereditary,metabolic and toxic optic neuropathies,with an emphasis on OCT findings.

Gut-brain axis in traumatic brain injury: impact on neuroinflammation

The gastrointestinal track is inhabited by tens of trillions of microorganisms. The gut microbiota is involved in gut motility, nutrient absorption and synthesis of metabolites that influence hmeostasis, metabolism and immunefunction. Given the influence gut microbiota has on health, there is a growing body of literature describing the gut microbiota's impact on brain and behavior.

CD4-positive diffuse large B-cell lymphoma:A variant with aggressive clinical potential

CD4 expression is rare in diffuse large B-cell lymphoma(DLBCL), with 4 previously reported cases. Its significance is uncertain. We report five patients with CD4+ DLBCL and one CD4+ primary mediastinal large B-cell lymphoma. Cases were identified by searching the electronic database of the department; each was reviewed. Average age was 56 years. Neoplastic cells expressed CD20(5/6 tested cases). BCL2/BCL6 expression were seen in 3/3 tested cases, suggesting a germinal center origin. Additionally, expression of T-cell antigens CD2 and CD5 was noted in 2/2 and CD7 in 1/1 tested case. CD3 was negative in all. Lymph nodes were commonly involved(67%). Patients received chemotherapy +/- radiation(6/6) and bone marrow transplant(2/6). Average survival was 44.2 mo. CD4 expression in DLBCL raises questions of lineage commitment. CD4+ DLBCL is rare; care should be exercised not to diagnose these as T-cell lymphomas. A subset behaves aggressively.

Proteomic Portrait of Human Lymphoma Reveals Protein Molecular Fingerprint of Disease Specific Subtypes and Progression

An altered proteome in lymph nodes often suggests abnormal signaling pathways that may be associated with diverse lymphatic disorders.Current clinical biomarkers for histological classification of lymphomas have encountered many discrepancies,particularly for borderline cases.Therefore,we launched a comprehensive proteomic study aimed to establish a proteomic landscape of patients with various lymphatic disorders and identify proteomic variations associated with different disease subgroups.In this study,109 fresh-frozen lymph node tissues from patients with various lymphatic disorders(with a focus on Non-Hodgkin’s Lymphoma)were analyzed by data-independent acquisition mass spectrometry.A quantitative proteomic landscape was comprehensively characterized,leading to the identification of featured protein profiles for each subgroup.Potential correlations between clinical outcomes and expression profiles of signature proteins were also probed.Two representative signature proteins,phospholipid-binding proteins Annexin A6(ANXA6)and Phospholipase C Gamma 2(PLCG2),were successfully validated via immunohistochemistry.We also evaluated the capability of acquired proteomic signatures to segregate multiple lymphatic abnormalities and identified several core signature proteins,such as Sialic Acid Binding Ig Like Lectin 1(SIGLEC1)and GTPase of immunity-associated protein 5(GIMAP5).In summary,the established lympho-specific data resource provides a comprehensive map of protein expression in lymph nodes during multiple disease states,thus extending the existing human tissue proteome atlas.Our findings will be of great value in exploring protein expression and regulation underlying lymphatic malignancies,while also providing novel protein candidates to classify various lymphomas for more precise medical practice.

Diagnosis of pulmonary tuberculosis among asymptomatic HIV＋ patients in Guangxi, China

Background Pulmonary tuberculosis （PTB） among asymptomatic Chinese patients with HIV infection has not been investigated despite high tuberculosis burden in China. This study was aimed to evaluate the prevalence, risk factors and clinical outcomes of PTB among asymptomatic patients with HIV/AIDS in Guangxi to facilitate the development of diagnostic and treatment strategies.Methods All asymptomatic adult HIV-infected patients with CD4 ＜350 cells/μl who attended four HIV clinics in Guangxi between August 2006 and March 2008 were evaluated for active PTB with physical examination, chest X-ray （CXR）,sputum smear and/or sputum liquid culture. Data were described using median （interquartile range, IQR） and frequencies.Univariate and multivariate Logistic regression analyses were performed to identify risk factors associated with PTB.Results Among 340 asymptomatic subjects, 15 （4%） were diagnosed with PTB, with 4 （27%） sputum smear positive and 8 （53%） sputum culture positive. CXR has higher diagnostic sensitivity （87%） than sputum smear （25%） and sputum culture （67%）, but lower specificity （56%） compared with sputum smear （99%） and culture （100%）. In univariate analysis,injection drug user, body mass index （BMI） ＜18 kg/m2, CD4 ＜50 cells/μl and presence of peripheral lymphadenopathy were associated with an increased risk of asymptomatic PTB, while in multivariate analysis only peripheral lymphadenopathy maintained statistical significance （OR=7.6, 95% CI 1.4-40）. Patients with negative smear and minor or no abnormalities on CXR had longer interval between screening and TB treatment.Conclusions PTB was relatively common in this group of HIV＋ asymptomatic Chinese patients. Diagnosis is challenging especially where sputum culture is unavailable. These findings suggest that an enhanced evaluation for PTB needs to be integrated with HIV care in China and transmission prevention in China to control at both households and health care facilities, especially for patients with factors associated with a higher risk of PTB.

Genetic variants in the ADD1 and GNB3 genes and bloodpressure response to potassium supplementation

Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes.However,blood pressure(BP)responses to potassium supplementation vary among individuals.This study was designed to examine the association between 12 single nucleotide polymorphisms(SNPs)in the adducin 1 alpha(ADD1)and guanine nucleotide binding protein(G protein)beta polypeptide 3(GNB3)genes and systolic BP(SBP),diastolic BP(DBP),and mean arterial pressure(MAP)responses to potassium-supplementation.We conducted a 7-day high-sodium intervention(307.8 mmol sodium/day)followed by a 7-day high-sodium with potassium-supplementation(60 mmol potassium/day)among 1906 Han Chinese participants from rural north China.BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer.We identified significant associations between ADD1 variant rs17833172 and SBP,DBP,and MAP responses to potassium-supplementation(all P<0.0001)that remained significant after adjustment for multiple comparisons.In participants that were heterozygous or homozygous for the G allele of this marker,SBP,DBP,and MAP response to potassium-supplementation were–3.52(–3.82,–3.21),–1.41(–1.66,–1.15)and–2.12(–2.37,–1.87),respectively,as compared to the corresponding responses of 1.99(0.25,3.73),–0.65(–0.10,–0.21),and–0.23(–0.37,0.83),respectively,for those who were homozygous for A allele.In addition,participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation(P=0.0041 and 0.01,respectively),which was also significant after correction for multiple testing.DBP and MAP responses to potassiumsupplementation were–1.36(–1.63,–1.10)and–2.07(–2.32,–1.82)for those with at least G allele compared to corresponding responses of 0.86(–0.68,2.40)and–0.45(–1.74,0.84)for those who were homozygous for A allele.In summary,our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation,which could have important clinical and public health implications.Future studies aimed at replicating these novel findings are warranted.