Selective Targeting of α4ß7/MAdCAM-1 Axis Suppresses Fibrosis Progression by Reducing Proinflammatory T Cell Recruitment to the Liver.

Integrin α4ß7+ T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here, we report increased accumulation of α4ß7+ T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl4-induced liver fibrosis was associated with enrichment of intrahepatic α4ß7+ CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of α4ß7 or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl4-treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of α4ß7+ CD4 and CD8 T cells, suggesting that α4ß7/MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and α4ß7+ T cells promote hepatic fibrosis progression. Analysis of hepatic α4ß7+ and α4ß7- CD4 T cells revealed that α4ß7+ CD4 T cells were enriched for markers of activation and proliferation, demonstrating an effector phenotype. The findings suggest that α4ß7+ T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of α4ß7 or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases.

Rare Indication of Atlantoaxial Fusion-failed Conservative Management of Primary Atlantoaxial Osteoarthritis.

Introduction: Osteoarthritis of the atlantoaxial joint is a significant cause of occipitocervical pain, which is often missed and has an increasing prevalence with age. The patients typically present with occipitocervical pain and restricted and painful neck rotations. Despite the primary reliance on conservative management for this pathology, surgical intervention becomes crucial for those not responding to standard conservative treatment. The presented case series highlights the rarity of the requirement of surgical intervention in the management of Atlantoaxial osteoarthritis (AAOA) and the clinical outcomes of surgical management in AAOA. Case Report: This paper presents a case series of four patients who were managed surgically with atlantoaxial fusion, from a database of 108 patients with AAOA. The case series includes three males and one female with a mean age of presentation being 67.5 years. All four patients presented with occipitocervical pain, and painful neck movements and were diagnosed with AAOA on the anteroposterior open mouth view radiographs showing changes of osteoarthritis such as bone erosions, sclerosis, osteophytes. The patients were managed conservatively with non-steroidal anti-inflammatory drugs, intra-articular steroid injections, and cervical collar immobilization. Those not responding to conservative management and with incapacitating pain were managed surgically with atlantoaxial fusion procedures. Conclusion: In a group of patients with a painful and debilitating degenerative AAOA only a small proportion of cases require surgical intervention. In this cohort, only 3.70 % of patients required surgery, highlighting the rarity of surgical intervention required in the management of AAOA. Nevertheless, when conducted, atlantoaxial fusion has proved to be efficacious with a low rate of serious complications and the patient self-rated outcome in terms of post-operative visual analog scale score and neck disability index scores indicating a high degree of satisfaction with the procedures.

Antagonizing Activin A/p15INK4b Signaling as Therapeutic Strategy for Liver Disease.

BACKGROUND/AIM: Activin A is involved in the pathogenesis of human liver diseases, but its therapeutic targeting is not fully explored. Here, we tested the effect of novel, highly specific small-molecule-based activin A antagonists (NUCC-474/555) in improving liver regeneration following partial hepatectomy and halting fibrosis progression in models of chronic liver diseases (CLDs). METHODS: Cell toxicity of antagonists was determined in rat hepatocytes and Huh-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Hepatocytes and hepatic stellate cells (HSCs) were treated with activin A and NUCC-555 and analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry. Partial hepatectomized Fisher (F)344 rats were treated with NUCC-555, and bromodeoxyuridine (BrdU) incorporation was determined at 18/24/36/120/240 h. NUCC-555 was administered into thioacetamide- or carbon tetrachloride-treated F344 rats or C57BL/6 mice, and the fibrosis progression was studied. RESULTS: NUCC-474 showed higher cytotoxicity in cultured hepatic cells; therefore, NUCC-555 was used in subsequent studies. Activin A-stimulated overexpression of cell cycle-/senescence-related genes (e.g., p15INK4b, DEC1, Glb1) was near-completely reversed by NUCC-555 in hepatocytes. Activin A-mediated HSC activation was blocked by NUCC-555. In partial hepatectomized rats, antagonizing activin A signaling resulted in a 1.9-fold and 2.3-fold increase in BrdU+ cells at 18 and 24 h, respectively. Administration of NUCC-555 in rats and mice with progressing fibrosis significantly reduced collagen accumulation (7.9-fold), HSC activation indicated by reduced alpha smooth muscle actin+ and vimentin+ cells, and serum aminotransferase activity. CONCLUSIONS: Our studies demonstrate that activin A antagonist NUCC-555 promotes liver regeneration and halts fibrosis progression in CLD models, suggesting that blocking activin A signaling may represent a new approach to treating people with CLD.

Transforaminal Endoscopic Ventral Stenosis Decompression in Calcified Lumbar Disc Herniation: A Long Term Outcome in 79 Patients.

BACKGROUND: Calcified lumbar disc herniations (CLDH) causing calcified ventral stenosis pose a therapeutic challenge to the treating surgeon due to their neural adhesions, location, and hardness. METHODS: This retrospective study analyzed all the cases of CLDH/calcified ventral stenosis managed by transforaminal endoscopic lumbar discectomy with a minimum follow-up of 24 months. The preoperative images were analyzed for the level, migration; and grade (Lee's migration zones), and location (Michigan State University classification). Detailed surgical technique and intraoperative parameters including the duration of surgery and complications have been recorded. The clinical parameters including visual analog scale (VAS), Oswestry disability index (ODI), length of stay in hospital, days of return to basic work, and patient satisfaction index were analyzed. Postoperatively the images were analyzed for the adequacy of decompression. RESULTS: The mean VAS for back pain and leg pain was 4.7 ± 2.6 (0-9), and 7.45 ± 2.2 (1-10), respectively. The mean preoperative ODI was 78.2 ± 13.2 (63.2-95.6). Nineteen patients (24%) had neurological deficits preoperatively. The mean duration of surgery was 90.5 ± 15.8 (58-131) minutes. Postoperative magnetic resonance imaging revealed adequate decompression in 97.5% (n = 77). The mean duration of hospital stay was 1.05 ± 0.22 (1-2) days, and the postoperative back and leg pain VAS was 1.14 ± 1.2 (0-3) (P < 0.05) and 1.7 ± 0.5 (0-6) (P < 0.05), respectively. The ODI at final follow-up was 6.5 ± 3.7 (2.2-18) (P < 0.05). Neurological recovery occurred in 17 (89.5%) patients and they returned to basic work/jobs in 19.5 ± 3.3 (14-26) days. The mean patient satisfaction index was 1.18 ± 0.47 (1-2) at a mean follow-up of 5.52 ± 2.91 (2-12.75) years. CONCLUSIONS: Transforaminal endoscopic lumbar discectomy is a complete, safe, and efficacious procedure in patients with CLDH with earlier recovery considering the surgery is performed with the patient being awake.

Long-term functional and radiological outcomes of cervical disc arthroplasty at a tertiary level spine center in India: A retrospective cohort analysis with minimum 2 years of follow-up.

Context: Cervical disc arthroplasty (CDA) was developed for the treatment of cervical disc disease with the potential advantages of preservation of physiological motion at a discal level, thereby potentially reducing adjacent level stresses and degeneration, which were a known complication of anterior cervical arthrodesis. The objective of this study was the assessment of long-term functional and radiological outcomes overtime in all the patients who underwent CDA from 2011 to 2019 at our institute. Materials and Methods: Forty-eight patients who underwent CDA (2011-2019) with a minimum 2-year follow-up were retrospectively evaluated. The functional outcome included the Visual Analog Score (VAS) and Neck Disability Index (NDI). Radiographs were assessed for range of motion (ROM) at the index surgical level, presence of heterotopic ossification (HO), and adjacent segment degeneration. Results: The mean follow-up was 5.79 ± 2.96 (2.16-11.75) years. Significant improvement (P < 0.05) was observed in the VAS (8.91 ± 2.52 [preoperative] to 0.89 ± 1.27 [follow-up]) and NDI (65.5% ±23.06% [preoperative] to 4.79 ± 3.87 [follow-up]) score. Motion at index level increased significantly from 5.53° preoperatively to 7.47°, and 92% of the implanted segments were still mobile (referring to the threshold of ROM > 3°). HOs are responsible for the fusion of 4/50 (8%) levels at the last follow-up. Distal and proximal adjacent disc degeneration occurred in 36% and 28% of patients, respectively. No migration of the implant was observed on the radiograph. Conclusion: Our study showed favorable clinical outcome of CDA with preservation of ROM at the index surgical level. CDA can be a promising alternative to anterior cervical arthrodesis when properly indicated.

Comparative Study on Accuracy of Intra-Operative Computed Tomography-Navigation Based Pedicle Screw Placement With Skin vs Bone Fixed Dynamic Reference Frame in Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare the accuracy of intra-operative navigation-assisted percutaneous pedicle screw insertion between bone fixed and skin fixed dynamic reference frame (DRF) in Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: Between October 2018 and September 2022, patients who underwent MIS-TLIF were included in this study with DRF fixed either on bone (group B) or skin (group S). Pedicle screws were inserted under the guidance of intra-operative Cone bean Computed tomography (cbCT) based navigation. Accuracy of pedicle screw placement was immediately checked by a final intra-operative cbCT Spin. RESULTS: Among 170 patients, group B included 91 patients and group S included 79 patients. Out of total 680 screws, 364 screws (group B) and 316 screws (group S) were placed. Patient's demographic data and distribution of screws showed no statistically significant difference. The accuracy showed no significant difference between both the groups (94.5% in group B and 94.3% in group S). CONCLUSION: Skin fixed DRF can serve as an alternate way for placement and avoids extra incision with similar accuracy in pedicle screw insertions with bone fixed DRF using intra-operative CT guided navigation in MIS TLIF.

Does MR Signal Intensity Change have Prognostic Value in Multilevel Cervical Myelopathy? A Single-Center, Prospective Study.

Background and Objective: Neurological recovery in cervical myelopathy remains unpredictable. There is contradictory literature regarding the prognostic value of magnetic resonance imaging (MRI) in such cases. The objective of the present study is to evaluate the morphological changes in the spinal cord in cervical spondylotic myelopathy and compare them with clinical outcome. Materials and Methods: This is a single-center, prospective, observational study. All patients with multilevel (two or more levels) cervical spondylotic myelopathy undergoing anterior spine surgery were included in the study. Patient demographics and radiological findings were recorded. MRI was repeated immediately post-op and at 1-year follow-up. MRI classification system based on axial images was used to evaluate presurgery and postsurgery changes and correlate them with clinical information. Results: The study comprised 50 patients (40 males and 10 females) with a mean age of 59.5 years. Average duration of symptoms before surgery was 6.29 months. Thirty-four patients underwent two-level decompression, while 16 patients underwent more than two-level decompression. Average duration of follow-up was 26.82 months. Mean pre-op Nurick grade was 2.84, and mean recovery rate was 56.73. Most common pre-op MRI type was type 1. Analysis of data by logistic regression showed better recovery rate with lower age, lower pre-op Nurick grade, and lower pre-op MRI type. Conclusion: MR classification based on signal intensity changes in axial images have been found to correlate with recovery rate.

Selective targeting of α 4 ß 7 /MAdCAM-1 axis suppresses liver fibrosis by reducing proinflammatory T cell recruitment to the liver.

Integrin α 4 ß 7 + T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here we report increased accumulation of α 4 ß 7 + T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl 4 -induced liver fibrosis was associated with enrichment of intrahepatic α 4 ß 7 + CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of α 4 ß 7 or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl 4 treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of α 4 ß 7 + CD4 and CD8 T cells suggesting that α 4 ß 7 /MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and α 4 ß 7 + T cells promote hepatic fibrosis progression. Analysis of hepatic α 4 ß 7 + and α 4 ß 7 -CD4 T cells revealed that α 4 ß 7 + CD4 T cells enriched for markers of activation and proliferation demonstrating an effector phenotype. Notably, blockade of α 4 ß 7 or MAdCAM-1 did not affect the recruitment of Foxp3+ regulatory T cells, demonstrating the specificity of α 4 ß 7 /MAdCAM-1 axis in regulating effector T cell recruitment to the liver. The findings suggest that α 4 ß 7 + T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of α 4 ß 7 or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases.

Western diet dampens T regulatory cell function to fuel hepatic inflammation in nonalcoholic fatty liver disease.

Background and aims: The immunosuppressive T regulatory cells (Tregs) regulate immune responses and maintain immune homeostasis, yet their functions in nonalcoholic fatty liver disease (NAFLD) pathogenesis remains controversial. Methods: Mice were fed a normal diet (ND) or a western diet (WD) for 16 weeks to induce NAFLD. Diphtheria toxin injection to deplete Tregs in Foxp3 DTR mice or Treg induction therapy in WT mice to augment Treg numbers was initiated at twelve and eight weeks, respectively. Liver tissues from mice and NASH human subjects were analyzed by histology, confocal imaging, and qRT-PCR. Results: WD triggered accumulation of adaptive immune cells, including Tregs and effector T cells, within the liver parenchyma. This pattern was also observed in NASH patients, where an increase in intrahepatic Tregs was noted. In the absence of adaptive immune cells in Rag1 KO mice, WD promoted accumulation of intrahepatic neutrophils and macrophages and exacerbated hepatic inflammation and fibrosis. Similarly, targeted Treg depletion exacerbated WD-induced hepatic inflammation and fibrosis. In Treg-depleted mice, hepatic injury was associated with increased accumulation of neutrophils, macrophages, and activated T cells within the liver. Conversely, induction of Tregs using recombinant IL2/αIL2 mAb cocktail reduced hepatic steatosis, inflammation, and fibrosis in WD-fed mice. Analysis of intrahepatic Tregs from WD-fed mice revealed a phenotypic signature of impaired Treg function in NAFLD. Ex vivo functional studies showed that glucose and palmitate, but not fructose, impaired the immunosuppressive ability of Treg cells. Conclusions: Our findings indicate that the liver microenvironment in NAFLD impairs ability of Tregs to suppress effector immune cell activation, thus perpetuating chronic inflammation and driving NAFLD progression. These data suggest that targeted approaches aimed at restoring Treg function may represent a potential therapeutic strategy for treating NAFLD. Lay summary: In this study, we elucidate the mechanisms contributing to the perpetuation of chronic hepatic inflammation in nonalcoholic fatty liver disease (NAFLD). We show that dietary sugar and fatty acids promote chronic hepatic inflammation in NAFLD by impairing immunosuppressive function of regulatory T cells. Finally, our preclinical data suggest that targeted approaches aimed at restoring T regulatory cell function have the potential to treat NAFLD.

'Higher the grade-smaller the pedicle': a study of pedicle dimensional variations in 100 cases of high grade lytic spondylolisthesis.

PURPOSE: To measure the pedicle dimensions in high grade lytic spondylolisthesis (HGL) and to classify them, which helps the spine surgeon in proper selection of pedicle screws. METHODS: A study of CT scans in 100 consecutive patients between Jan 2017 and April 2021 diagnosed as single-level HGL on standing radiographs. Pedicle height (PH), Pedicle width (PW), Differential pedicle height (DPH), Screw length (SL) and Transverse pedicle angle (TPA) were measured and analyzed. PH and PW were classified into four grades as-grade A less than 5.0 mm, grade B between 5.0 and 6.0 mm, grade C between 6.0 and 7.0 mm, and grade D above 7.0 mm. RESULTS: 5 males and 95 females with mean age of 49.1 years. PH in 44% lytic vertebra were grade A, B (less than 6 mm) and the rest 56% had grade C, D (greater than 6 mm). PH averaged 6.6 mm in grade 3 HGL, 5.61 mm in grade 4 HGL. Change in PW, SL and TPA was not statistically significant with regards to grade or level of listhesis. A total of 37 cases were noted to have DPH (25 cases had a difference < 2 mm and 12 had a difference > 2 mm). CONCLUSION: 44% of the PH in lytic vertebra was grade A and B (less than 6 mm) that stresses the importance of pre-op CT assessment and planning the appropriate screw dimensions. Change in PH was statistically significant with regards to the grade of listhesis (P-value < 0.01). Differential pedicle height also need to be looked for.

An eco-friendly approach on green synthesis, bio-engineering applications, and future outlook of ZnO nanomaterial: A critical review.

Synthesizing ZnO nanostructures ranging from 1 nm to 4 nm confines the electron cloud and exhibits a quantum effect generally called as quantum confinement effect attracting many researchers in the field of electronics and optics. ZnO nanostructures are used in medical applications to formulate antioxidant, antibacterial, antifungal, anti-inflammatory, wound healing, and anti-diabetic medications. This work is a comprehensive study of green synthesis of ZnO nanomaterials using different biological sources and highlights different processes able to produce nanostructures including nanowires, nanorods, nanotubes and other nano shapes of ZnO nanostructures. Different properties of ZnO nanostructures and their targeted bioengineering applications are also described. The strategies and challenges of the eco-friendly approach to enhance the application span of ZnO nanomaterials are also summarized, with future prospects for greener design of ZnO nanomaterials are also suggested.

A comparative morphometric analysis of operative windows for performing OLIF among normal and deformity group in lower lumbar spine.

PURPOSE: To assess the radiological morphometric parameters of OLIF surgical technique in lower lumbar spine among normal and in patients with adult degenerative spine (levoscoliosis and dextroscoliosis). METHOD: Standing AP radiographs and MRI in supine position were taken. Patients were divided into 3 groups based on Cobbs' angle into normal, levo and dextro scoliosis. Moros classification was used to calculate bare window (BW), vascular window (VW), Psoas window (PW), psoas major height (pmh) and width (pmw) at lower lumbar levels and measurements were done on PACS. RESULTS: Seventy five patients (25 in each group) were assessed. BW has trend from L2-L3 > L3-L4 > L4-L5 in dextro and levoscoliosis. PW has trend from L3-L4 > L2-L3 > L4-L5 in levoscoliosis and normal group. VW has trend from L4-L5 > L3-L4 > L2-L3 in dextro and levoscoliosis; pmw has trend from L4-L5 > L3-L4 > L2-L3 in Levo and dextroscoliosis; pmh has trend from L4-L5 > L3-L4 > L2-L3 in levoscoliosis and normal group. CONCLUSION: BW was noted to be highest at L3-4, lowest at L4-5 in normal group. VW was constant, BW showed a reverse trend with PW across all the levels. Though levoscoliosis group of patients had significantly higher BW, psoas retraction issues are to be kept in mind in view of anatomically taught psoas.

Clinical characteristics and outcome of patients presenting to emergency department during the second wave of COVID-19.

Background: COVID 19 resurgence in multiple waves and the highly infectious variant of SARS-CoV-2 (B.1.617) has wreaked havoc across healthcare systems in India. We conducted a study to delineate the clinico-epidemiological profile of COVID-19 patients in this second wave of the pandemic. Methods: This was a retrospective, single centre, observational study at the Emergency Department(ED) of a teaching institute in North India. The ED health records were screened for patient files with the diagnosis of COVID -19, age > 14 years, presenting from 10th April to 30th of May. ED clinical notes, disposition, and mortality data were retrieved and analysed. Results: 1647 files were screened and 253 eligible patients of COVID-19 were included in the study. 60% patients were male, mean age (+ SD) was 54 (+ 14.8 years). Shortness of breath (74.7%), fever (71.9%), cough (57.7%) were the common presenting symptoms. 20% of patients were nil comorbid; Diabetes (44.7%) and Hypertension (41.5%) were the common comorbid illnesses. 73.1% patients had severe COVID illness, 39.9% had oxygen saturation <90% on arrival and 33.2% had <70%. More than 90% patients required respiratory support on arrival. 25% of people presented to hospital after home isolation, of which 81% had severe COVID at presentation. 39 % patients of mild illness had received corticosteroids. Conclusion: The second wave of COVID-19 with rapid upsurge of cases overwhelmed the healthcare system with a higher proportion of severe COVID-19 cases and higher mortality, thus stressing the need for prior planning, preparation and strengthening healthcare systems across tiers.

Intestinal Barrier Dysfunction in Fatty Liver Disease: Roles of Microbiota, Mucosal Immune System, and Bile Acids.

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of progressive liver diseases ranging from simple steatosis to steatohepatitis and fibrosis. Globally, NAFLD is the leading cause of morbidity and mortality associated with chronic liver disease, and NAFLD patients are at a higher risk of developing cirrhosis and hepatocellular carcinoma. While there is a consensus that inflammation plays a key role in promoting NAFLD progression, the underlying mechanisms are not well understood. Recent clinical and experimental evidence suggest that increased hepatic translocation of gut microbial antigens, secondary to diet-induced impairment of the intestinal barrier may be important in driving hepatic inflammation in NAFLD. Here, we briefly review various endogenous and exogenous factors influencing the intestinal barrier and present recent advances in our understanding of cellular and molecular mechanisms underlying intestinal barrier dysfunction in NAFLD.

RCC (reinforced criss-cross construct): an easy and effective multi-rod thoraco-lumbar posterior reconstruction technique.

STUDY DESIGN: Surgical technical note and literature review. OBJECTIVES: To describe a technique that uses 4 rod constructs in cases of complex thoracolumbar spinal deformity correction or revision surgeries based on the hybrid use of two different types of purchase points by a staggered pedicle screw fixation. It utilizes two rods on either side of the spine using a lateral and medial entry point of pedicle screws in the vertebral body. METHODS: Pedicle screws using extra-pedicular technique are more converging screws and are inserted alternately in the vertebral body and connected by rods. The left-out alternate vertebral bodies are fixed by a relatively straighter pedicle entry screw and connected to each other by a separate rod. So, two trajectories are independently used for a four-rod construct. This reconstruction has been named RCC (reinforced criss-cross construct). The screws in the index case were placed by free hand method, but we have increasingly utilized navigation guidance for placement of screws in recent times. RESULTS: We present a surgical technical note in a patient with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV-AIDS). He was diagnosed to have multi-drug-resistant (MDR) tuberculous spondylodiscitis, complicated with Immune reconstitution inflammatory syndrome (IRIS) and implant failure resulting in kyphosis and thoracic myelopathy. RCC with pharmacological management achieved healing and union, which was maintained at 4 years follow-up. Our method of four-rod construct provides a strong and lasting construct in the management of spinal deformities and three-column osteotomies. It provides good structural support to the spine till bony union is achieved. CONCLUSION: Hybrid multi-rod construct like RCC provides a rigid mechanical support to the instrumentation and reduces the chances of rod failure especially in complex thoraco-lumbar spinal deformity correction surgeries.

ß-Catenin-NF-κB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction.

Expansion of biliary epithelial cells (BECs) during ductular reaction (DR) is observed in liver diseases including cystic fibrosis (CF), and associated with inflammation and fibrosis, albeit without complete understanding of underlying mechanism. Using two different genetic mouse knockouts of ß-catenin, one with ß-catenin loss is hepatocytes and BECs (KO1), and another with loss in only hepatocytes (KO2), we demonstrate disparate long-term repair after an initial injury by 2-week choline-deficient ethionine-supplemented diet. KO2 show gradual liver repopulation with BEC-derived ß-catenin-positive hepatocytes and resolution of injury. KO1 showed persistent loss of ß-catenin, NF-κB activation in BECs, progressive DR and fibrosis, reminiscent of CF histology. We identify interactions of ß-catenin, NFκB, and CF transmembranous conductance regulator (CFTR) in BECs. Loss of CFTR or ß-catenin led to NF-κB activation, DR, and inflammation. Thus, we report a novel ß-catenin-NFκB-CFTR interactome in BECs, and its disruption may contribute to hepatic pathology of CF.

The liver has an incredible capacity to repair itself or 'regenerate' ­ that is, it has the ability to replace damaged tissue with new tissue. In order to do this, the organ relies on hepatocytes (the cells that form the liver) and bile duct cells (the cells that form the biliary ducts) dividing and transforming into each other to repair and replace damaged tissue, in case the insult is dire. During long-lasting or chronic liver injury, bile duct cells undergo a process called 'ductular reaction', which causes the cells to multiply and produce proteins that stimulate inflammation, and can lead to liver scarring (fibrosis). Ductular reaction is a hallmark of severe liver disease, and different diseases exhibit ductular reactions with distinct features. For example, in cystic fibrosis, a unique type of ductular reaction occurs at late stages, accompanied by both inflammation and fibrosis. Despite the role that ductular reaction plays in liver disease, it is not well understood how it works at the molecular level. Hu et al. set out to investigate how a protein called ß-catenin ­ which can cause many types of cells to proliferate ­ is involved in ductular reaction. They used three types of mice for their experiments: wild-type mice, which were not genetically modified; and two strains of genetically modified mice. One of these mutant mice did not produce ß-catenin in biliary duct cells, while the other lacked ß-catenin both in biliary duct cells and in hepatocytes. After a short liver injury ­ which Hu et al. caused by feeding the mice a specific diet ­ the wild-type mice were able to regenerate and repair the liver without exhibiting any ductular reaction. The mutant mice that lacked ß-catenin in hepatocytes showed a temporary ductular reaction, and ultimately repaired their livers by turning bile duct cells into hepatocytes. On the other hand, the mutant mice lacking ß-catenin in both hepatocytes and bile duct cells displayed sustained ductular reactions, inflammation and fibrosis, which looked like that seen in patients with liver disease associated to cystic fibrosis. Further probing showed that ß-catenin interacts with a protein called CTFR, which is involved in cystic fibrosis. When bile duct cells lack either of these proteins, another protein called NF-B gets activated, which causes the ductular reaction, leading to inflammation and fibrosis. The findings of Hu et al. shed light on the role of ß-catenin in ductular reaction. Further, the results show a previously unknown interaction between ß-catenin, CTFR and NF-B, which could lead to better treatments for cystic fibrosis in the future.

The Effect of Head Loading on Cervical Spine in Manual Laborers.

STUDY DESIGN: A prospective case-control study. PURPOSE: To determine the effect of axial loading on the cervical spine when weights are carried on the head. OVERVIEW OF LITERATURE: Traditionally, carrying weights on the head has been a common practice in developing countries. The laborers working in agriculture, construction, and other industries, as well as porters at railway platforms, are required to lift heavy weights. Since controversy exists regarding carrying weights on the head, we decided to evaluate its effect on the cervical spine. METHODS: The study comprised 62 subjects. Of this number, 32 subjects (group A) were unskilled laborers from the construction industry; the other 30 subjects (group B) were in the control group and had never previously carried heavy weights on their heads. Cervical spine radiographs were taken for all the 62 subjects. Subjects in group A were asked to carry a load (approximately 35 kg) on their heads and walk for about 65 m, with their cervical spine radiographs taken afterward. RESULTS: The mean ages of patients in groups A and B were 27.17 and 25.75 years, respectively. The mean cervical lordosis observed in group A (18.96°) was dramatically less compared with group B (25.40°), showing a further decrease in head loading (3.35°). Five subjects had a reversal of lordosis (-5.61°). A statistically significant reduction in disc height and listhesis was observed when the load was carried on the head with a further decrease after walking with the load. Accelerated degenerative changes, particularly affecting the upper cervical spine, were observed in head loaders. CONCLUSIONS: Carrying a load on the head leads to accelerated degenerative changes, which involve the upper cervical spine more than the lower cervical spine and predisposes it to injury at a lower threshold. Thus, alternative methods of carrying loads should be proposed.

The Effectiveness and Safety of Ultrasonic Bone Scalpel Versus Conventional Method in Cervical Laminectomy: A Retrospective Study of 311 Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The aim of this study was to compare the results of cervical laminectomy (CL) performed with ultrasonic bone scalpel (UBS) or conventional method (CM). METHOD: This study comprised 311 CL performed by a single surgeon between January 2004 and December 2017. Group A (GpA) comprised 124 cases of CL performed using UBS, while Group B (GpB) comprised 187 cases of CL performed using CM. These 2 groups were compared in terms of demographic characteristics of patients, duration of surgery, estimated blood loss, and surgical complications. RESULTS: GpA included 112 males and 12 females, mean age being 61.18 years. GpB comprised 166 males and 21 females, mean age being 62.04 years. Mean duration of surgery, estimated blood loss, and length of hospital stay was 65.52/70.87 minutes, 90.24/98.40 mL, and 4.80/4.87 days in GpA and GpB, respectively. Six patients were reported to have dural injuries in each group. In GpA, 2 cases of C5 palsy and 1 nerve root injury was observed, while in GpB, 3 cases of C5 palsy and no nerve root injury was reported. One patient had developed transient neurological deterioration postsurgery in GpA as against 11 patients in GpB. CONCLUSION: Neurological complications observed in CM leads to intensive care unit admission, additional morbidity, and additional expenditure, whereas UBS provides a safe, rapid, and effective means of performing CL, thereby decreasing the rate of surgical complications and postoperative morbidity.

Transforaminal Thoracic Interbody Fusion for Thoracic Disc Prolapse: Surgicoradiological Analysis of 18 Cases.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: Thoracic disc prolapse (TDP) surgeries have reported complications ranging from paraplegia to approach related complications. This study is to present a series of TDP patients surgically treated with transforaminal thoracic interbody fusion (TTIF). Emphasis on surgical technique and strategies to avoid complications are analyzed. METHODS: Eighteen patients with TDP were included. Imagings were analyzed for end-plate changes and calcification. Type of disc prolapse (central/para-central) and percentage of canal occupancy were noted. Objective outcome was quantified with Visual Analogue Scale (VAS), modified Nurick's grade, and ASIA (American Spinal Injury Association) score. All complications were noted. RESULTS: Eighteen patients (average age 43.65 years) having total 22 levels operated, that included double level (n = 2) and missed level (n = 2) are reported. All patients had myelopathy. Calcification of disc (n = 13), central disc prolapses (n = 9), para-central (n = 11) and more than 50% canal occupancy (n = 8) were noted. VAS back pain, modified Nurick's grade and ASIA grade improved significantly in all patients. One patient had postoperative transient deficit. The functional score achieved its maximum at 1 year follow-up and remained static at final follow-up of 65.05 months. Union was achieved in all patients. CONCLUSIONS: The most important factor for outcome in TDP is the technical aspect of avoiding cord manhandling and avoiding wrong level surgeries. TTIF is not devoid of complications but can give good results to posterior approach trained surgeons.

Age - Does it really count? A study of the Perioperative Morbidity and Long-Term Outcome in Patients Above 70 Years of Age Undergoing Spine surgery for Lumbar Degenerative Disorders.

Objective To assess the long-term outcome and perioperative morbidity in spine surgeries for lumbar degenerative disorders and, thereby, to evaluate the safety of surgery in the aging population. Methods Retrospective study of patients aged > 70 years, operated for degenerative lumbar disorders between 2011 and 2015. We evaluated patient demographic, clinical and surgical data; comorbidities, perioperative complications, pre & postoperative pain scores and Oswestry disability index (ODI) scores, patient satisfaction and overall mortality. Results A total of 103 patients (Males: Females55:48) with mean age 74.6 years (70-85yrs) were studied. 60 patients (58.2%) had decompression alone, while 43 (41.8%) had decompression & fusion. Mean hospital stay was 5.7days. Mean follow-up was 47.6months (24-73mnths). Patients reported significant improvement in backpain (Numerical pain score 7.7 vs 1.6; p < 0.001), leg pain (Numerical pain score 7.4 vs 1.7; p < 0.001), disability (ODI 82.3 vs 19.1; p < 0.001) and walking distance ( p < 0.001). 76% patients were satisfied with the results at the time of final follow-up. 26 patients (25.24%) had perioperative complications which were all minor, without mortality. Most common intraoperative & postoperative complications were dural tear (6.79%) & urinary tract infection (6.79%) respectively. Conclusions With meticulous perioperative care lumbar spine surgery is safe and effective in elderly population. Patients had longer mean hospital stay in view of the gradual and comprehensive rehabilitation program. Presence of comorbidities or minor perioperative complications did not increase the overall morbidity or affect the clinical outcomes of surgery in our study.