Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.

Clinical, Microbiological, Serological and Radiological Profile of Patients With Mild-Moderate and Severe Allergic Bronchopulmonary Aspergillosis (ABPA).

Objective Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus antigen mostly Aspergillus fumigatus that occurs almost exclusively in patients with asthma and cystic fibrosis. ABPA is an underdiagnosed and undertreated disease because of its presentation with various grades of severity in asthma patients. Data available regarding the clinical, serological, and radiological profile of ABPA patients is limited due to lack of consensus on diagnostic criteria and treatment guidelines. Thus ABPA is a significant disease, especially in the Indian population where the incidence of allergic diseases like asthma is on the rise. Methods This prospective study was conducted in the Department of Pulmonary Medicine at one of the tertiary centers of north India. All consecutive patients diagnosed with allergic bronchopulmonary aspergillosis (ABPA) from 1st January 2017 to 30th September 2017 were included in the study. A total of 67 consecutive patients diagnosed with bronchial asthma were included in the study. The diagnosis of ABPA was based upon either criterion given by Rosenberg and Paterson or the International Society of Human and Animal Mycology (ISHAM) criteria. Patients diagnosed with ABPA were finally divided into mild, moderate, and severe. Results The majority of patients showed an obstructive pattern on spirometry and moderate to severe obstruction was the most common pattern observed among patients who had an obstructive pattern on spirometry. Also, all three patients with the mixed pattern on spirometry had severe disease. Serological analysis revealed that patients in the moderate category had a higher level of absolute eosinophil count (AEC), total IgE, and Aspergillus-specific IgE antibodies, especially in patients who had either high attenuation mucus (HAM) or centrilobular nodules on their high-resolution computed tomography (HRCT) scan. Conclusion ABPA is a disease of divergent presentation. We concluded to have alternate or add-on criteria for the classification of ABPA which was not based on the sequelae of chronic inflammatory changes in the lungs.

The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5.

Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane. Other studies using TRPC5 gain-of-function transgenic mice have questioned the pathogenic role of TRPC5 in podocytes. Here, we show that TRPC5 over-expression or inhibition does not ameliorate proteinuria induced by the expression of constitutively active Rac1 in podocytes. Additionally, single-cell patch-clamp studies did not detect functional TRPC5 channels in primary cultures of podocytes. Thus, we conclude that TRPC5 plays a role redundant to that of TRPC6 in podocytes and is unlikely to be a useful therapeutic target for podocytopathies.

Adherence to spinal imaging guidelines and utilization of lumbar spine diagnostic imaging for low back pain at a Canadian Chiropractic College: a historical clinical cohort study.

BACKGROUND: Diagnostic imaging is useful for assessing low back pain (LBP) when a clinician suspects a specific underlying pathology. Evidence-based imaging guidelines assist clinicians in appropriately determining the need for imaging when assessing LBP. A previous study reported high adherence to three clinical guidelines, with utilization rate of 12.3% in imaging of LBP patients attending a chiropractic teaching clinic. A new imaging guideline for spinal disorders has been published and used in teaching. Thus, the aims of our study were to assess the adherence to the new guideline and X-ray utilization in new episodes of LBP. METHODS: We conducted a historical clinical cohort study using patient electronic health record audits at seven teaching clinics over a period of 20 months. Records of patients who were at least 18 years of age, presented with a new onset of LBP, and consented to data collection were included. Abstracted data included patient demographics, the number and type of red flags, and the decision to image. Rate of guideline adherence (proportion of those not recommended for imaging, given no red flags) and rate of image utilization were descriptively analyzed. RESULTS: We included 498 patients in this study. At least 81% of included patients had one or more red flags reported. The most commonly reported individual red flag was age ≥ 50 (43.8%) followed by pain at rest (15.7%). In those referred for imaging, age ≥ 50 (93.3%) was the most frequently reported red flag. No red flag(s) were identified in 93 patient records, and none were referred for imaging of their LBP, yielding an adherence rate of 100% (95% CI 96, 100%). A total of 17 of 498 patients were recommended for imaging for their low back pain, resulting in an imaging utilization rate of 3.4% (95% CI 1.8, 5.0%). CONCLUSION: The imaging utilization rate was 3.4%, lower than 12.3% previously reported at a chiropractic teaching clinic. None without red flags were referred for imaging, yielding a 100%, adherence rate to current LBP imaging guidelines. Future research should consider currency of guideline, accuracy of red flags and factors influencing clinicians' decision, when assessing imaging adherence rates.

Role of Immunohistochemistry and serology in subclassifying the Inflammatory Bowel Disease cases diagnosed as Inflammatory Bowel Diseases---unclassified on colonic biopsies.

Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and ß-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for ß-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.

Prevalence of precursor lesions (P53 signature, SCOUT, STIL, STIC) in fallopian tubes resected for non-neoplastic causes.

Background: High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. Objective: 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Materials and Methods: Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Results: Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Conclusion: Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.

Role of C4d in the Diagnosis and Prognosis of Native Renal Diseases.

Introduction: C4d is a biomarker of the complement cascade and has a primary role in the diagnosis of antibody-mediated rejection in solid organ transplantation. The present study was undertaken to investigate the role of C4d in the diagnosis and prognosis of native renal diseases. Methods: An observational cross-sectional study was conducted in the Department of Pathology from September 2017 to September 2019. In this study, we applied C4d staining by immunohistochemistry in 51 native renal biopsies. Semiquantitative scoring was done on the basis of intensity of C4d staining along the glomerular capillary wall (0-3) and mesangium (0-3), tubules (0-3), and arteries (0-3). These individual scores were added to get the total C4d score (0-12) which was correlated with chronicity index, serum urea and creatinine levels. Glomerular C4d score was correlated with 24 h urinary protein as well as with immunofluorescence deposition of immunoglobulins and complements. Results: We found a linear positive correlation (P < 0.05) between the total C4d score and serum creatinine; tubular C4d score and serum creatinine; and glomerular C4d score along capillary wall and 24 h urinary protein. A positive correlation (P < 0.05) was found between glomerular C4d score along the capillary wall with immunofluorescence deposits of immunoglobulins and complements, suggesting the efficacy of C4d as a surrogate marker in the diagnosis of native renal diseases. Conclusions: C4d deposition is associated with a poor prognosis in renal diseases and an accelerated deterioration of renal function. It also plays a role as a surrogate marker in diagnosis of native renal diseases.

COVID-19-associated mucormycosis of head-and-neck region: A systematic review.

BACKGROUND AND AIM: With the second wave of COVID-19, there has been a substantial rise in opportunistic infections like mucormycosis. Mucormycosis is a fatal fungal infection and understanding the associated risk factors and their management plays a key role to reduce mortality and morbidity caused due to such infections. This systematic review was conducted to assess the risk factors, clinical characteristics and to understand the pathogenesis of COVID-19-associated mucormycosis (CAM) affecting the head-and-neck region. METHODS: The PubMed database was searched with the keywords; ((Mucormycosis) OR (invasive fungal sinusitis)) AND (COVID-19) and the PRISMA chart was prepared for the selection of the reports based on the inclusion and exclusion criteria. RESULTS: A total of 261 cases of CAM affecting the head-and-neck region were analyzed in this systematic review. Most of the patients presented with rhino-orbital/rhino-orbito-cerebral form of mucormycosis (rhino-orbital mucormycosis/rhino-orbital-cerebral mucormycosis). Pulmonary mucormycosis along with rhino-orbital form, involvement of hard palate, and maxillary sinus was seen in one case each. A total of 224 (85.8%) patients were diabetic, 68 (30.3%) of them had poor glycemic control. Steroids were administered in 210 (80.4%) patients. Except for two, antifungal treatment was given to all patients. Follow-up data revealed 67 (25.6%) deaths and 193 (73.9%) were alive with one patient lost during follow-up. CONCLUSION: The findings of this systematic review suggested that the occurrence of mucormycosis in COVID-19 patients is related to the inherent effects of COVID-19 infection on the immune system, comorbidities especially diabetes, and treatment aspects. Hence, a detailed understanding of these factors may aid in the personalized management of CAM and improve the disease outcome. RELEVANCE FOR PATIENTS: The risk factors in patients affected by CAM should be recognized and closely monitored in post-COVID-19 patients. A multidisciplinary team must be in place to reduce the mortality and morbidity in such patients.

Novel mechanisms of action contributing to benralizumab's potent anti-eosinophilic activity.

BACKGROUND: Benralizumab is a humanised, anti-interleukin-5 receptor α monoclonal antibody with anti-eosinophilic activity. Lack of fucose (afucosylation) increases its affinity to CD16a and significantly enhances antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells. Although benralizumab proved clinically efficacious in clinical trials for patients with severe asthma and hypereosinophilic syndrome, in-depth characterisation of its anti-eosinophilic mechanisms of action remains elusive. METHODS: Here, we further investigated the mechanisms involved in benralizumab's anti-eosinophilic activities by employing relevant primary human autologous cell co-cultures and real-time-lapse imaging combined with flow cytometry. RESULTS: In the presence of NK cells, benralizumab induced potent eosinophil apoptosis as demonstrated by the upstream induction of Caspase-3/7 and upregulation of cytochrome c. In addition, we uncovered a previously unrecognised mechanism whereby benralizumab can induce eosinophil phagocytosis/efferocytosis by macrophages, a process called antibody-dependent cellular phagocytosis. Using live cell imaging, we unravelled the stepwise processes leading to eosinophil apoptosis and uptake by activated macrophages. Through careful observations of cellular co-culture assays, we identified a novel role for macrophage-derived tumour necrosis factor (TNF) to further enhance benralizumab-mediated eosinophil apoptosis through activation of TNF receptor 1 on eosinophils. TNF-induced eosinophil apoptosis was associated with cytochrome c upregulation, mitochondrial membrane depolarisation and increased Caspase-3/7 activity. Moreover, activated NK cells were found to amplify this axis through the secretion of interferon-γ, subsequently driving TNF expression by macrophages. CONCLUSIONS: Our data provide deeper insights into the timely appearance of events leading to benralizumab-induced eosinophil apoptosis and suggest that additional mechanisms may contribute to the potent anti-eosinophilic activity of benralizumab in vivo. Importantly, afucosylation of benralizumab strongly enhanced its potency for all mechanisms investigated.

Transcriptome and IgH Repertoire Analyses Show That CD11chi B Cells Are a Distinct Population With Similarity to B Cells Arising in Autoimmunity and Infection.

A distinct B cell population marked by elevated CD11c expression is found in patients with systemic lupus erythematosus (SLE). Cells with a similar phenotype have been described during chronic infection, but variable gating strategies and nomenclature have led to uncertainty of their relationship to each other. We isolated CD11chi cells from peripheral blood and characterized them using transcriptome and IgH repertoire analyses. Gene expression data revealed the CD11chi IgD+ and IgD- subsets were highly similar to each other, but distinct from naive, memory, and plasma cell subsets. Although CD11chi B cells were enriched in some germinal center (GC) transcripts and expressed numerous negative regulators of B cell receptor (BCR) activation, they were distinct from GC B cells. Gene expression patterns from SLE CD11chi B cells were shared with other human diseases, but not with mouse age-associated B cells. IgH V-gene sequencing analysis showed IgD+ and IgD- CD11chi B cells had somatic hypermutation and were clonally related to each other and to conventional memory and plasma cells. However, the IgH repertoires expressed by the different subsets suggested that defects in negative selection during GC transit could contribute to autoimmunity. The results portray a pervasive B cell population that accumulates during autoimmunity and chronic infection and is refractory to BCR signaling.

Serum CA 19-9 and CA 125 as a diagnostic marker in carcinoma of gallbladder.

BACKGROUND: Gall bladder carcinoma is endemic in North India along the Ganges belt. Most of the cases usually present in late stage when prognosis is poor. That mandates a necessity for proper screening in these areas for gall bladder lesions. Tumor markers CA 19-9 and CA 125 have been studied in various GI cancers and may also help in the screening, diagnosis and evaluation of gall bladder carcinoma. Aims: To assess serum CA19-9 and serum CA125 in patients with gall bladder lesions and find out a cut off value for diagnosis of carcinoma gallbladder. METHODS AND MATERIAL: Study included 118 cases, with female: male ratio of 4:1.Out of it, 91 (77 %) cases were benign and 27 (23 %) were malignant. Patients' sera was collected and analyzed for CA19-9 and CA 125 by CMIA method. RESULTS: The Mean (SD) value of CA19-9 for benign and malignant cases was found to be 12.86 (17.54) and 625.35(186.52) U/ml. For CA 125 it was found to be 17.98(13.69) and 239.63(73.72) U/ml respectively. The difference was statistically significant (P< 0.001). When Mean - 2SD value of malignant lesions were taken as cut off a value of CA 19-9 and CA 125 were found be 252.31 U/ml & 92.19U/ml respectively, found to be significant to suggest /diagnose a case of carcinoma gall bladder along with clinicoradiological findings. Taking these value as cut off Sensitivity & Specificity for CA 19-9 and CA 125 in detecting malignant cases were found to be 100% & 98.90% and 100% & 94.50% respectively. CONCLUSIONS: It is concluded that both serum CA 19-9 and serum CA 125 may act as a good adjunct for diagnosis of cases of carcinoma gallbladder along with imaging studies. However, changes in CA19-9 are more significant than CA 125.

Promoting Interfacial Interactions with the Addition of Lignin in Poly(Lactic Acid) Hybrid Nanocomposites.

In this paper, the calorimetric response of the amorphous phase was examined in hybrid nanocomposites which were prepared thanks to a facile synthetic route, by adding reduced graphene oxide (rGO), Cloisite 30B (C30B), or multiwalled carbon nanotubes (MWCNT) to lignin-filled poly(lactic acid) (PLA). The dispersion of both lignin and nanofillers was successful, according to a field-emission scanning-electron microscopy (FESEM) analysis. Lignin alone essentially acted as a crystallization retardant for PLA, and the nanocomposites shared this feature, except when MWCNT was used as nanofiller. All systems exhibiting a curtailed crystallization also showed better thermal stability than neat PLA, as assessed from thermogravimetric measurements. As a consequence of favorable interactions between the PLA matrix, lignin, and the nanofillers, homogeneous dispersion or exfoliation was assumed in amorphous samples from the increase of the cooperative rearranging region (CRR) size, being even more remarkable when increasing the lignin content. The amorphous nanocomposites showed a signature of successful filler inclusion, since no rigid amorphous fraction (RAF) was reported at the filler/matrix interface. Finally, the nanocomposites were crystallized up to their maximum extent from the glassy state in nonisothermal conditions. Despite similar degrees of crystallinity and RAF, significant variations in the CRR size were observed among samples, revealing different levels of mobility constraining in the amorphous phase, probably linked to a filler-dimension dependence of space filling.

Hip pain in an elite cyclist with Non-Hodgkin's Follicular Lymphoma: a case report.

OBJECTIVE: We present a case of an elite cyclist that hesitated to follow the medical advice from her practitioners, as she was determined to train and compete resulting in delayed diagnosis and management of a rare hip pathology. CASE PRESENTATION: A 51-year old elite female cyclist had a history of years of hip pain with insidious onset. The chiropractor in this case observed a lack of response to treatment, and advised the patient to get an MRI with suspicion of a labral tear. She eventually agreed to further investigations and was diagnosed with Non-Hodgkin's follicular lymphoma and a labral tear. SUMMARY: Elite athletes are not immune to serious pathology. Chiropractors should be vigilant and ensure to investigate any patients with a lack of response to conservative management. Chiropractors should be aware of the risk of athletic patients that continue to train and compete when advised not to.

OBJECTIF: Nous présentons le cas d'une cycliste d'élite qui a hésité à suivre les conseils médicaux de ses praticiens, car elle était déterminée à s'entraîner et à participer à des compétitions, ce qui a retardé le diagnostic et la prise en charge d'une pathologie rare de la hanche. PRÉSENTATION DU CAS: Une cycliste d'élite de 51 ans avait des antécédents de douleurs à la hanche depuis des années; le début de ses douleurs avait été insidieux. Le chiropraticien a observé une absence de réponse au traitement et a conseillé à la patiente de subir un examen par IRM en soupçonnant une déchirure du labrum. La patiente a fini par accepter de subir des examens complémentaires. Un lymphome folliculaire non hodgkinien et une déchirure labrum ont été diagnostiqués. RÉSUMÉ: Les athlètes d'élite ne sont pas à l'abri d'une pathologie grave. Les chiropraticiens doivent être vigilants et s'assurer d'examiner tous les patients réfractaires à un traitement conservateur. Les chiropraticiens doivent être conscients du risque que représentent les patients sportifs qui continuent à s'entraîner et à participer à des compétitions alors qu'on leur a conseillé de ne pas le faire.

Use of Nucleic Acid Amplification Testing for Rapid Detection of Mycobacterium tuberculosis Complex Among US Tuberculosis Patients, 2011‒2017.

Background: Nucleic acid amplification (NAA) tests rapidly detect Mycobacterium tuberculosis complex directly from clinical specimens, providing valuable results for those evaluated for tuberculosis. Methods: We analyzed characteristics of cases with NAA testing performed, compared cases with positive and negative NAA test results, and calculated turnaround time and time to treatment for all verified cases reported to the National Tuberculosis Surveillance System in the United States during 2011-2017. Results: Among 67082 verified tuberculosis cases with NAA testing information, 30820 (45.9%) were reported as not having an NAA test performed; the proportion without NAA testing declined annually, from 60.5% in 2011 to 33.6% in 2017. Of 67082 verified cases, 27912 (41.6%) had positive, 8215 (12.2%) had negative, and 135 (0.2%) had indeterminate NAA test results. Among the 33937 cases with an acid-fast bacilli (AFB) smear-positive result, 24093 (70.9%) had an NAA test performed; 11490 of the 30244 (38.0%) with an AFB smear-negative result had an NAA test performed. Although sputum was the most common specimen type tested, 79.8% (7023/8804) of nonsputum specimen types had a positive NAA test result. Overall, 63.7% of cases with laboratory testing had NAA test results reported <6 days following specimen collection; for 13891 cases not yet on treatment, median time to treatment after the laboratory report date was 2 days. Conclusions: Our analyses demonstrate increased NAA test utilization between 2011 and 2017. However, a large proportion of cases did not have an NAA test performed, reflecting challenges in broader uptake, suggesting an opportunity to expand use of this diagnostic methodology.

Role of Hematological Indices as a Screening Tool of Beta Thalassemia Trait in Eastern Uttar Pradesh: An Institutional Study.

A large majority of microcytic hypochromic anemia have defects in cellular hemoglobin synthesis due to either iron deficiency or thalassemia trait; both differing in management and prognosis. HPLC and serum iron profile as confirmatory tests are unavailable at health care centers. Blanket therapy of iron supplements is therefore given in all such cases which may cause iron overload in thalassemia cases. Easy to use and cost effective screening methods are desirable. The present study was undertaken to evaluate the diagnostic accuracy of twelve indices to effectively screen cases of thalassemia trait and differentiate them from iron deficiency anemia. Routine samples from the hematology lab with Hb < 13 gm/dl, MCV < 80 fl and MCH < 27 pg were screened. Taking HPLC and serum ferritin as gold standard, out of total 1353 cases, 98 cases of thalassemia trait (HbA2 > 3.5 on HPLC) and 1102 cases of iron deficiency anemia (serum ferritin < 12 g/ml) were evaluated using discrimination indices. Diagnostic accuracy for each index was calculated. While few indices showed a sensitivity of 100%, their specificity was low which meant more number of false positive cases. Based on Youden's Index, which measures the diagnostic tests ability to balance sensitivity and specificity, the best three indices in the decreasing order of their efficacy in our study were Ricerca Index (RI), Green and King Index (GKI) and Mentzer Index (MI). MI is considered a reliable index by many clinicians since a long time, however RI and GKI were found to have a better diagnostic accuracy based on our study.

The clinical utility of routine spinal radiographs by chiropractors: a rapid review of the literature.

INTRODUCTION: When indicated by signs or symptoms of potentially serious underlying pathology (red flags), chiropractors can use radiographs to inform their diagnosis. In the absence of red flags, the clinical utility of routine or repeat radiographs to assess the structure and function of the spine is controversial. OBJECTIVES: To determine the diagnostic and therapeutic utility of routine or repeat radiographs (in the absence of red flags) of the cervical, thoracic or lumbar spine for the functional or structural evaluation of the spine. Investigate whether functional or structural findings on repeat radiographs are valid markers of clinically meaningful outcomes. The research objectives required that we determine the validity, diagnostic accuracy and reliability of radiographs for the structural and functional evaluation of the spine. EVIDENCE REVIEW: We searched MEDLINE, CINAHL, and Index to Chiropractic Literature from inception to November 25, 2019. We used rapid review methodology recommended by the World Health Organization. Eligible studies (cross-sectional, case-control, cohort, randomized controlled trials, diagnostic and reliability) were critically appraised. Studies of acceptable quality were included in our synthesis. The lead author extracted data and a second reviewer independently validated the data extraction. We conducted a qualitative synthesis of the evidence. FINDINGS: We identified 959 citations, screened 176 full text articles and critically appraised 23. No relevant studies assessed the clinical utility of routine or repeat radiographs (in the absence of red flags) of the cervical, thoracic or lumbar spine for the functional or structural evaluation of the spine. No studies investigated whether functional or structural findings on repeat radiographs are valid markers of clinically meaningful outcomes. Nine low risk of bias studies investigated the validity (n = 2) and reliability (n = 8) of routine or repeat radiographs. These studies provide no evidence of clinical utility. CONCLUSION: We found no evidence that the use of routine or repeat radiographs to assess the function or structure of the spine, in the absence of red flags, improves clinical outcomes and benefits patients. Given the inherent risks of ionizing radiation, we recommend that chiropractors do not use radiographs for the routine and repeat evaluation of the structure and function of the spine.

Lymph node stromal CCL2 limits antibody responses.

Nonhematopoietic stromal cells in lymph nodes such as fibroblastic reticular cells (FRCs) can support the survival of plasmablasts and plasma cells [together, antibody-forming cells (AFCs)]. However, a regulatory function for the stromal compartment in AFC accumulation has not been appreciated. Here, we show that chemokine ligand 2 (CCL2)-expressing stromal cells limit AFC survival. FRCs express high levels of CCL2 in vessel-rich areas of the T cell zone and the medulla, where AFCs are located. FRC CCL2 is up-regulated during AFC accumulation, and we use lymph node transplantation to show that CCL2 deficiency in BP3+ FRCs and lymphatic endothelial cells increases AFC survival without affecting B or germinal center cell numbers. Monocytes are key expressers of the CCL2 receptor CCR2, as monocyte depletion and transfer late in AFC responses increases and decreases AFC accumulation, respectively. Monocytes express reactive oxygen species (ROS) in an NADPH oxidase 2 (NOX2)-dependent manner, and NOX2-deficient monocytes fail to reduce AFC numbers. Stromal CCL2 modulates both monocyte accumulation and ROS production, and is regulated, in part, by manipulations that modulate vascular permeability. Together, our results reveal that the lymph node stromal compartment, by influencing monocyte accumulation and functional phenotype, has a regulatory role in AFC survival. Our results further suggest a role for inflammation-induced vascular activity in tuning the lymph node microenvironment. The understanding of stromal-mediated AFC regulation in vessel-rich environments could potentially be harnessed to control antibody-mediated autoimmunity.