Prospective comparative evaluation of intraoperative joint stability and component placement between posterior approach to hip and its quadriceps coxae sparing modification for primary hip arthroplasty.

Background: Efforts at minimizing the propensity of posterior approach of hip for post-operative dislocation after total hip arthroplasty have been a subject of continual research. We comparatively evaluated the posterior approach to hip and its quadriceps coxae sparing (QCS) modification with regard to joint stability and component placement.Questions/Purposes: (1) Does sparing of Quadriceps Coxae tendons vis a vis their sectioning in posterior approach help in achieving better intraoperative stability? (2) Does sparing of Quadriceps Coxae tendons come in the way of adequate surgical exposure sufficient to place hip components accurately? (3) Does sparing of Quadriceps Coxae tendons result in better early functional outcome? Methods: Seventy-two patients requiring THA were enrolled prospectively and randomized into two groups: group A (posterior approach) and group B quadriceps coxae sparing (QCS) approach. They were compared for intraoperative joint stability, accuracy of component placement, duration of surgery, blood loss, any event of hip dislocation, and functional outcome. Results: QCS approach resulted in better intraoperative hip stability as the hips tolerated a higher value of 43.50±3.5° mean internal rotation (at 90° of flexion and 20° of adduction) in this group versus a mean value of 33.50±5.5° in posterior approach group (p < 0.01). No significant difference was observed for femoral version, acetabular inclination, and acetabular version in the two groups (p > 0.05). There was no difference between the two groups in terms of duration of surgery, intraoperative blood loss, and functional outcome at one year (p > 0.05). No event of hip dislocation was observed in QCS approach, whereas, one such event happened in the posterior-approach group. Conclusion: Preservation of the QC tendons improves the intraoperative stability of THA and they do not cause any hindrance in the exposure required for optimum component placement.

A Comparative Evaluation of Combined Nerve Block Versus Periarticular Infiltration on Postoperative Pain Relief in Total Hip Arthroplasty.

Introduction: To minimize the side effects of the central neuraxial blockade to obtain postoperative pain relief, there has been an increasing preference for targeting the peripheral structures in patients undergoing total hip arthroplasty (THA). Patients and Methods: This prospective study was performed between September 2019 and September 2021 and involved 30 patients that were randomized to two groups. One group (n = 15) received combined nerve block (CNB) [obturator nerve, nerve to quadratus femoris, superior gluteal nerve, and femoral nerve], while another group (n = 15) received periarticular infiltrative analgesia (PIA). All the patients were given the same volume and composition of the drug cocktail (20 ml 0.5% ropivacaine, 1 ml (100 mcg) dexmedetomidine, and 29 ml normal saline). Results: The patients in group CNB had a significantly lower visual analog score (VAS) at 6, 12, 18, 24, 30, 36, 42 and 48 h after surgery (p < 0.05). Patients in group CNB required fewer (p < 0.001) doses of the rescue analgesic (1.67 ± 0.90 doses) as compared to group PIA (3.53 ± 0.64 doses). Time to the first rescue analgesia was significantly longer (p = 0.01) in group CNB (6.71 ± 2.36 h) as compared to group PIA (4.80 ± 1.26 h). However, patients in group PIA had significantly faster sensory (p < 0.001) and motor recovery (p < 0.001) as compared to group CNB. It took significantly longer (p < 0.001) to administer the nerve block (16.87 ± 1.80 min) as compared to periarticular infiltration (6.53 ± 1.18 min). There were no complications in either group. Conclusion: CNB registered significant superiority over PIA with respect to postoperative pain relief and time to rescue analgesia. However, the time taken to administer CNB was significantly higher and the patients in the PIA group had early recovery in sensory and motor modalities. Level of Evidence: III (therapeutic).

Influence of exopolysaccharide EPSKar1-iron complexation on iron bioavailability and alleviating iron deficiency anaemia in Wistar rats.

The prevalence of iron deficiency anaemia is a significant issue worldwide, affecting individuals of all ages and often associated with inadequate iron bioavailability. Despite the use of ferrous salt supplements to address anaemia, their limited bioaccessibility and bioavailability in human GIT and adverse impact on food properties remain significant challenges. Hence, this study aims to explore the iron chelation mechanism of an exopolysaccharide EPSKar1 to enhance iron bioaccessibility, bioavailability, and anti-anaemic effects using cell culture and an anaemic rat model. EPSKar1 was extracted from Lacticaseibacillus rhamnosus Kar1 and complexed with FeSO4 to form "EPSKar1-iron". This novel complex, besides being bio-accessible after in vitro gastric digestion, demonstrated 61.27 ± 1.96% iron bioavailability to the Caco-2 cells. In line with these in vitro findings, intragastric administration of the EPSKar1-iron complex to anaemic Wistar rats at 25 and 50 mg per kg body weight significantly restored blood haemoglobin levels and re-established the morphological features of red blood cells. Furthermore, the apparent digestibility co-efficient and iron uptake improved significantly without adversely affecting the serum biochemical parameters in these anaemic rats. The levels of iron-transport proteins including serum transferrin and ferritin in tissue and plasma have increased remarkably upon oral administration of EPSKar1-iron at a higher dose of 50 mg per kg body weight. Oral supplementation of EPSKar1-iron did not foster adverse histological changes in the liver, kidneys, and spleen. In fact, the treatment with the EPSKar1-iron complex had a restitution effect on the tissue architecture, thereby ameliorating the tissue lesions. These findings collectively indicate that the EPSKar1-iron complex shows nutraceutical potential in enhancing the bioavailability of iron and could be a promising approach to tackle iron deficiency anaemia.

Accuracy of Patient-Specific, 3D-Printed Laminofacetal Based Trajectory-Guide for Pedicle Screw Placement in Subaxial Cervical and Thoracic Spine.

Background: Conventional methods of pedicle-screw placement have higher breach rates due to variations in pedicle trajectories. Objective: We studied the accuracy of patient-specific, three-dimensional (3D)-printed laminofacetal-based trajectory guide for pedicle-screw placement in the subaxial-cervical and thoracic spine. Materials and Methods: We enrolled 23 consecutive patients who underwent subaxial cervical and thoracic pedicle-screw instrumentation. They were divided into two groups: group A (cases without spinal deformity) and group B (cases with pre-existing spinal deformity). Patient-specific, 3D-printed laminofacetal-based trajectory guide for each instrumented level was designed. The accuracy of screw placement was assessed on postoperative computed tomography (CT) using the Gertzbein-Robbins grading. Results: A total of 194 pedicle screws (114 cervical and 80 thoracics) were placed using trajectory guides, of which 102 belonged to group B (34 cervical and 68 thoracics). Out of a total of 194 pedicle screws, 193 had clinically acceptable placement (grade A: 187; grade B: 6; and grade C: 1). In the cervical spine, 110 pedicle screws out of a total of 114 had grade A placement (grade B: 4). In the thoracic spine, 77 pedicle screws out of a total of 80 had grade A placement (grade B: 2; grade C: 1). Out of a total of 92 pedicle screws in group A, 90 had grade A placement, and the rest 2 had grade B breach. Similarly, 97 out of a total of 102 pedicle screws in group B were placed accurately, 4 had grade B and another had a grade C breach. Conclusions: Patient-specific, 3D-printed laminofacetal-based trajectory guide may help in accurate placement of subaxial cervical and thoracic pedicle screws. It may help reduce surgical time, blood loss, and radiation exposure.

Evaluation of vertebral shortening and interbody fusion with short segment pedicle screw fixation for unstable thoracolumbar fractures.

Background: Various operative procedures have been described for the treatment of traumatic paraplegia caused by unstable thoracolumbar fractures. We prospectively evaluated interbody fusion (IBF) with SS-PSF in these cases with regard to clinico-radiological outcome with the objectives: (1) Does IBF and short segment pedicle screw fixation (SS-PSF) prevent progression of kyphotic angle after surgery? (2) Can this procedure be safely performed in the setting of acute trauma?. Methods: Sixteen patients suffering from traumatic paraplegia caused by acute unstable thoracolumbar fractures were enrolled prospectively and underwent IBF with SS-PSF. They were evaluated for magnitude of shortening in spine, progression of kyphotic angle, and neurological improvement by American spinal injury association scale (ASIA). Results: Out of total sixteen, 14 patients were ASIA grade A and 2 were grade C, at the time of presentation. Thirteen out of these 14 remained grade A and one improved to B. Both the patients who had grade C involvement at the time of presentation improved to grade D at one-year follow-up. The mean blood loss was 750 ml (range; 650 ml-1150 ml). Mean kyphotic angle decreased from 20.6° (range; 13° to 37°) preoperatively to 6.2° (range; 3° to 10°) at postoperative day 2 (p = 0.002). Its mean value after 6 months was 6.5° (range; 3° to 11°). The procedure resulted in mean spinal column shortening of 18 mm (range; 16 mm-22 mm) in the spinal column. All the patients achieved bony union by a mean duration of 3.9 months (range; 3 months-6 months). Conclusions: IBF with SS-PSF has the shortest possible instrumented construct for thoracolumbar junction fusion done by posterior approach. The interbody fusion for unstable thoracolumbar junction fractures prevents the progression of kyphotic angle post-operatively. Level of evidence: Level 4.

Shortening dome osteotomy for correction of severe cubitus varus secondary to malunited supracondylar fractures in children.

The results of conventional corrective procedures remain suboptimal for severe cubitus varus deformities (> 30°) in children. We present the results of shortening dome osteotomy for the correction of such deformities. PATIENTS AND METHODS: We present retrospective review of prospectively collected data of 18 patients (11 boys and 7 girls) who underwent shortening dome osteotomy between January 2011 and December 2019 for severe cubitus varus deformities (> 30°) secondary to malunited supracondylar fracture. The procedure involved the removal of convexo-concave bone (5-8 mm wide) between the two domes. Humero-ulnar angles, lateral condylar prominence index (LCPI), and elbow range of movements were recorded preoperatively and postoperatively. RESULTS: Mean age was 7.5 years (range 5 years-11 years). Indication for surgery was poor cosmesis in all the patients and tardy ulnar nerve symptoms in three patients. Mean preoperative humero-ulnar angle was 26.1° varus (range 22°-34°), while it was 7.1° valgus (range 0°-12°) for contralateral normal elbow. They were followed for a mean duration of 2.2 years (range 12 months-5.8 years). The mean postoperative valgus angle achieved was 7.3° (range 2°-12°) as total angular correction achieved was 34.4° (range 30°-44°) (p < 0.001). Radiological healing was observed in all the patients at mean duration of 7.1 weeks (range 5 weeks-9 weeks). Mean preoperative and postoperative LCPI were - 2.4 (range +4.7 to - 10.5) and - 1.7 (range +4.5 to - 5.1), respectively (p = 0.595). Three patients had pin tract infections and two of them responded to aseptic dressings and oral antibiotics, while another required early pin removal and additional protection in splint. All patients regained preoperative arc of motion within 6 months after the procedure. CONCLUSION: Shortening dome osteotomy is a safe and effective method for correcting severe cubitus varus deformities (> 30°) secondary to malunited supracondylar fracture in children.

Bone defect classifications in revision total knee arthroplasty, their reliability and utility: a systematic review.

BACKGROUND: There are various classification systems described in the literature for managing bone defects in revision knee arthroplasty (RTKA). We analysed the reliability and usefulness of these classification systems. QUESTIONS/PURPOSES: (1) To review and critique the various classification systems proposed for bone loss in RTKA. (2) Among all the proposed classifications which one is the most commonly used by surgeons to report their results. (3) What is the reliability of various bone defect classification systems for RTKA. In this review, we have assessed the studies validating those classifications with a detailed description of the limitations and the proposed modifications. METHODS: This systematic review was conducted following PRISMA guidelines. Pubmed/Medline, CINAHL, EMBASE, Scopus, Cochrane databases and Web of Science databases were searched using multiple search terms and MeSH terms where possible. Studies meeting inclusion criteria were assessed for statistical parameters of reliability of a classification system. RESULTS: We found 16 classification systems for bone defects in RTKA. Six studies were found evaluating a classification system with reporting their reliability parameters. Fifty-four studies were found which classified bone loss using AORI classification in their series. AORI classification is most commonly reported for classifying bone defects. Type T2B and F2B are the most common bone defects in RTKA. The average kappa value for AORI classification for femoral bone loss was 0.38 (0.27-0.50) and 0.76 (0.63-1) for tibial bone loss assessment. CONCLUSION: None of the available classification systems is reliably established in determining the bone loss and treatment plans in RTKA. Among all, AORI classification is the most widely used system in clinical practice. The reliability of AORI Classification is fair for femoral bone loss and substantial for tibial bone loss.

Prospecting for Cressa cretica to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2.

The severe acute respiratory syndrome COVID-19 declared as a global pandemic by the World Health Organization has become the present wellbeing worry to the whole world. There is an emergent need to search for possible medications. Cressa cretica is reported to show antitubercular, antibacterial and expectorant property. In this research, we aim to prospect the COVID-19 main protease crystal structure (Mpro; PDB ID: 6LU7) and the active chemical constituents from Cressa cretica in order to understand the structural basis of their interactions. We examined the binding potential of active constituents of Cressa cretica plant to immensely conserved protein Mpro of SARS-CoV-2 followed by exploration of the vast conformational space of protein-ligand complexes by molecular dynamics (MD) simulations. The results suggest the effectiveness of 3,5-Dicaffeoylquinic acid and Quercetin against standard drug Remdesivir. The active chemical constituents exhibited good docking scores, and interacts with binding site residues of Mpro by forming hydrogen bond and hydrophobic interactions. 3,5-Dicaffeoylquinic acid showed the best affinity towards Mpro receptor which is one of the target enzymes required by SARS CoV-2 virus for replication suggesting it to be a novel research molecule. The potential of the active chemical constituents from Cressa cretica against the SARS-CoV-2 virus has best been highlighted through this study. Therefore, these chemical entities can be further scrutinized and provides direction for further consideration for in-vivo and in-vitro validations for the treatment of covid-19. Communicated by Ramaswamy H. Sarma.

Spectrum of malignancies among human immunodeficiency virus-infected patients at a tertiary level human immunodeficiency virus-anti-retroviral therapy center in a North Indian hospital.

INTRODUCTION: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of some types of cancer. A chronic immunodeficiency state, increased survival in the highly active antiretroviral therapy (HAART) era and predisposition to certain oncogenic viral infections have been postulated as the main reasons. While, the incidence of acquired immunodeficiency syndrome (AIDS) defining cancers (ADCs) is declining in the post-HAART era, non-AIDS-defining cancers (NADCs) are becoming an important cause of mortality in these patients. MATERIALS AND METHODS: Analysis of the data of HIV-infected patients registered at an apex centre was done for 7 years. All patients were subjected to routine investigations on presentation (baseline) and during follow-up for the occurrence of any malignant disease. CD4 cell counts before starting anti-retroviral therapy and before the diagnosis of malignancy were noted. The date of the last review and the current status/outcome were recorded. RESULTS: Out of 1258, 17 patients were diagnosed with various malignancies. Seven patients (41.2%) had ADCs and the remaining 10 (58.8%) had NADCs. The mean duration between diagnosis of HIV infection and diagnosis of malignancy was 59.53 months. The mean survival duration from the diagnosis of malignancy for all cases was 21 months. The mean survival duration was 29 months and 15 months for ADC and NADC group respectively. CONCLUSIONS: NADCs are on the rise in the era of effective use of HAART and increasing life span of HIV patients. The index of suspicion for cancer should be higher in such patients, especially compared to opportunistic infections in view of good immunovirologic status.

Evaluation of pancreatic regeneration activity of Tephrosia purpurea leaves in rats with streptozotocin-induced diabetes.

BACKGROUND AND AIM: Flavonoid rich plant Tephrosia purpurea (T. purpurea), commonly known as Sarpunkha has been used in traditional systems of medicine to treat diabetes mellitus. However, its effectiveness in promoting regeneration of pancreas in diabetes has not been investigated. Therefore, the present study was undertaken to evaluate pancreatic ß-cells regeneration, antioxidant and antihyperlipidemic potentials of T. purpurea leaves extract, its fractions and main constituent Rutin in diabetic rats. EXPERIMENTAL PROCEDURE: The leaves extract and its fractions were first screened for acute and sub-chronic antidiabetic activity in a dose range of 250-500 mg/kg orally. Further, fractions with potent antidiabetic activity were screened for pancreatic ß-cells regeneration activity using histopathological studies and morphometric analysis, which was followed by estimation of biochemical parameters. RESULTS AND CONCLUSION: The most significant antidiabetic, pancreatic regeneration and antihyperlipidemic activity was exhibited by n-butanol soluble fraction of ethanol extract at the dose level of 500 mg/kg. Histopathology revealed that treatment with this fraction improved the ß-cell granulation of islets and prevented the ß-cells damage which was further confirmed by morphometric analysis. Thus, the present study validated the traditional use of T. purpurea plant in the treatment of diabetes, which might be attributed to pancreatic ß-cells regeneration potential of its active constituent Rutin. TAXONOMY CLASSIFICATION BY EVISE: Traditional Medicine; Metabolic Disorder; Experimental Design; Cell Regeneration and Histopathology.

Tuberculous osteomyelitis of tibial diaphysis following saphenous vein graft harvest for coronary artery bypass: a case report.

Tuberculosis in the tibial diaphysis following saphenous vein graft harvest for coronary artery bypass grafting has not been reported, to the best of authors' knowledge. We report the first such clinical case in view of its clinical rarity and as a complication of the simple procedure like saphenous vein graft harvest.

Epineurotomy for leprous, high ulnar neuropathy: defining a safe corridor based on the epineural vascular anatomy.

BACKGROUND: Leprous neuropathy is treatable but still a source of disability worldwide. Multidrug therapy (MDT) and oral steroids are the main stay of treatment. Ulnar nerve, at the elbow, is commonly involved. Nerve decompression may be required in selected cases by an epineurotomy (internal neurolysis). The preferred surface of ulnar nerve for performing this procedure to minimize iatrogenic vascular compromise is a matter of debate. QUESTIONS/PURPOSES: We describe the epineural vessel arrangement on the medial and lateral surface of ulnar nerve around the medial epicondyle while performing epineurotomy for leprous neuropathy. METHODS: We enrolled patients of symptomatic leprous ulnar neuropathy of less than one year duration on MDT that did not respond to steroids, for surgical decompression. Ten patients underwent epineurotomy of ulnar nerves (N = 11) around medial epicondyle. The epineural vessels were classified as per Sunderland's classification of arteriae nervorum. The number of epineural vessels was assessed on the medial and lateral surface of the ulnar nerve adjoining the medial epicondyle. The epineurotomy incision was placed over the surface of ulnar nerve having relatively less vessels. RESULTS: The mean number of epineural vessels on the medial surface was 9.72 (range; 7-14) and on the lateral surface were 4.72 (range; 3-6). The average number of vessels per cm2 of the medial and lateral surface of the nerve was 0.94 and 0.48, respectively. The most common type of epineural vessel was type 3 on both medial and lateral surface of the nerve. Lateral epineurotomy was performed in all 11 cases. All the patients had relief from neuropathic pain. The mean VAS score improved from 3.20 ± 0.89 to 0.50 ± 0.34 at 2 years follow-up (p = 0.02). The mean motor score improved from 9.31 ± 4.12 to 15.42 ± 3.10 and sensory score improved from 40.0 ± 30.70 to 85 ± 9.90 at two years follow-up (p < 0.01). CONCLUSION: Lateral surface (facing the medial epicondyle) of ulnar nerve has a lesser density of epineural vessels in comparison to its medial (subcutaneous) surface. CLINICAL RELEVANCE: This anatomical understanding may be helpful in minimizing the iatrogenic vascular compromise of ulnar nerve while performing its epineurotomy around the medial epicondyle for leprous neuropathy. The findings may be extrapolated to other clinical indications of epineurotomy of ulnar nerve, for example, in cubital tunnel syndrome, traumatic ulnar neuroma in continuity, and benign ulnar nerve tumors.

Primary Aneurysmal Bone Cyst of the Distal Tibia Crossing the Open Physis.

Crossing the barrier of an open physis by primary aneurysmal bone cyst is an exceptional phenomenon. We present a rare case of primary active aneurysmal bone cyst of the distal tibia in a 15-year-old boy in whom the lesion had crossed the open lateral distal tibia physis. The diagnosis was confirmed by radiographs, computed tomography, magnetic resonance imaging, and histopathologic findings. The lesion was successfully treated by extended curettage and allograft impaction. The patient was asymptomatic when last seen at 30 months.

Shortening Dome Osteotomy for Correction of Complex Multiplanar Elbow Deformities: A New Surgical Technique.

Despite surgical advances in fracture management, it is not uncommon to find pediatric or adolescent patients with elbow deformities. Correction of severe deformities, often leaves the ingenuity of the treating surgeon asking for more. Various osteotomy techniques have been described in the literature for the correction of elbow deformities. Although, the concept of dome osteotomy did address certain inadequacies of the existing osteotomy techniques for distal humerus, but correction of complex deformities associated with deformation of trochlea and olecranon fossa still remain a surgical challenge which has not been adequately addressed in the literature so far. Our experience with the existing osteotomies for distal humerus led to the development of a new surgical technique of shortening dome osteotomy for correction of such complex multiplanar elbow deformities. Surgical steps, indications, and expected outcome is described.

Functional Outcome of Early, Selective Surgical Nerve Decompression in Leprous Neuropathy.

Background: Leprous neuropathy is a significant, yet preventable, cause of disability worldwide. Decompressive surgery and oral steroids have been used along with Multi Drug Therapy (MDT) for treating leprous neuropathy with varied success as reported in literature. Methods: We prospectively studied 16 peripheral nerves in 10 patients with leprous neuropathy of less than a year duration and not responding to steroid therapy in 3 weeks. The patients were divided into 2 groups: Group-A (decompressive nerve surgery was done within 12 weeks of onset of neurological deficit), and Group-B (nerve decompression was performed after 12 weeks from onset of neurological deficit). Post-operatively patients were assessed for regression of deformity, sensory, motor, vasomotor recovery and neuropathic pain. Results: Median age of patients was 32 years (range; 18 years to 46 years). Mean motor score and mean grip strength was significantly better for group A patients at 2 years follow-up (p < 0.05). Mean sensory score improved significantly in both the groups (p < 0.05). Similarly, mean VAS score for neuropathic pain improved significantly in both the groups (p < 0.05). Recovery of autonomic function was observed in 3 nerves in group A and 1 in group B. Conclusions: The cases who underwent nerve decompression surgery within 12 weeks had better functional outcomes, especially in terms of motor recovery, than those who were operated after that. Studies involving larger number of patients are required to draw firm conclusions.

Prevalence of fatty liver in metabolic syndrome.

BACKGROUND: In Western world, non-alcohlic fatty liver disease (NAFLD) is considered to be the commonest liver problem, and it is being recognised as a major cause of liver-related morbidity and mortality. As the prevalence of overweight/obesity and metabolic syndrome increases, NASH may become one of the more common causes of end stage liver disease and hepatocellular carcinoma. But much information is not available in this association. So an attempt has been made to correlate both. AIMS: The aims of this study are: 1. to study the prevalence of non-alcoholic fatty liver in metabolic syndrome; and 2. to study the correlation between the non-alcoholic fatty liver and metabolic syndrome along with its individual components. MATERIALS AND METHODS: The study was an observational and analytical study of patients attending OPD and indoor patients of the Department of Medicine, G.G.S. Medical College and Hospital Faridkot. In total, 100 patients diagnosed as metabolic syndrome according to the NCEP ATP III criteria were subjected to ultrasonography; age and sex matched 100 controls were also taken; and the relationship between metabolic syndrome and NAFLD was studied. RESULTS: In total, 73% cases of metabolic syndrome according to NCEP ATPIII were having fatty liver, while in controls 38% persons were having fatty liver which is statistically significant. CONCLUSIONS: Fatty liver was found to be highly prevalent in metabolic syndrome, and the early detection of fatty liver can help in modifying the disease course and delaying more serious complications like cirrhosis of liver and hepatocellular carcinoma.

Co-targeting of CXCR4 and hedgehog pathways disrupts tumor-stromal crosstalk and improves chemotherapeutic efficacy in pancreatic cancer.

Pancreatic cancer (PC) remains a therapeutic challenge because of its intrinsic and extrinsic chemoresistance mechanisms. Here, we report that C-X-C motif chemokine receptor 4 (CXCR4) and hedgehog pathways cooperate in PC chemoresistance via bidirectional tumor-stromal crosstalk. We show that when PC cells are co-cultured with pancreatic stellate cells (PSCs) they are significantly more resistant to gemcitabine toxicity than those grown in monoculture. We also demonstrate that this co-culture-induced chemoresistance is abrogated by inhibition of the CXCR4 and hedgehog pathways. Similarly, the co-culture-induced altered expression of genes in PC cells associated with gemcitabine metabolism, antioxidant defense, and cancer stemness is also reversed upon CXCR4 and hedgehog inhibition. We have confirmed the functional impact of these genetic alterations by measuring gemcitabine metabolites, reactive oxygen species production, and sphere formation in vehicle- or gemcitabine-treated monocultures and co-cultured PC cells. Treatment of orthotopic pancreatic tumor-bearing mice with gemcitabine alone or in combination with a CXCR4 antagonist (AMD3100) or hedgehog inhibitor (GDC-0449) displays reduced tumor growth. Notably, we show that the triple combination treatment is the most effective, resulting in nearly complete suppression of tumor growth. Immunohistochemical analysis of Ki67 and cleaved caspase-3 confirm these findings from in vivo imaging and tumor measurements. Our findings provide preclinical and mechanistic evidence that a combination of gemcitabine treatment with targeted inhibition of both the CXCR4 and hedgehog pathways improves outcomes in a PC mouse model.

A novel approach to detect highly manipulated fat adulterant as Reichert-Meissl value-adjuster in ghee (clarified butter) through signature peaks by gas chromatography of triglycerides.

Ghee, the clarified butter fat being the costliest fat among other edible oils and fats in India, prone to adulteration with highly manipulated cheaper oils/fats, especially during lean season. The present investigation carried on triglycerides profile of one of the latest components of the adulterant fat i.e. RM (Reichert-Meissl)-adjuster, has been exploited to check the adulteration of ghee with a newly emerged highly manipulated fat. Using standardized (S)-limits specified by the ISO/IDF for cow milk fat, the minimum level of detection of the adulterant fat was observed as 7.5%. However, in case of buffalo ghee, due to non-availability of the ISO/IDF limits, the detection of this adulterant fat in buffalo ghee was not possible. Gas chromatograms showed specific signature peaks of large size in the retention time region of 4.5 to 6.5 min for RM-adjuster and adulterant fat, whereas no such peaks were observed in pure cow and buffalo ghee samples. The new approach of zooming in and superimposing of selected peaks in the chromatograms of triglycerides of suspected ghee has been used as a strategy to find adulterant fat's presence. Through this approach, the addition of RM-adjusted highly manipulated foreign fat (adulterant fat) to the tune of even 0.5% could be achieved in both cow as well as buffalo ghee.

Dietary intake of pearl millet based weaning food supplemented with iron and vitamin A enhances bioavailability of vitamin A in anemic rats.

The study was aimed to assess vitamin A bioavailability and allergenicity of pearl millet (Pennisetum glaucum) based weaning food (PMWF) fortified with iron and retinyl acetate in male Wistar albino rats. Animals (n = 64) were divided into Normal (NG) and Anemic (AG) groups; further sub-divided into 4 sub-groups having 8 animals each receiving synthetic diet, commercial diet, iron fortified PMWF diet and iron (150.00 ± 0.73 ppm) plus retinyl acetate (393.00 ± 3.07 µg/100 g) fortified PMWF diet (Final diet). Results revealed that anemic sub-groups showed apparent digestibility coefficient (ADC) in the range of 69.5 ± 0.40-93.2 ± 0.79%, which was significantly (P < 0.01) higher than normal sub-groups (65.5 ± 0.62-84.6 ± 0.33%). In both groups, rats fed final diet presented significantly (P < 0.01) higher ADC (84.6 ± 0.33-93.2 ± 0.79%) than that of animals received iron fortified diet (69.0 ± 0.59-76.1 ± 1.02%), indicating higher bioavailability of vitamin A in final diet. Moreover, hepatic vitamin A replenished rapidly in anemic groups (1.79-27.8) when compared to normal rats (1.11-19.4 µg/g liver). Immunoglobulins IgG, IgE in blood serum and IgA in intestinal fluid ranged from 574 ± 6.48 to 603 ± 9.76 µg/ml, 287 ± 4.46 to 309 ± 5.70 ng/ml and 204 ± 10.33 to 255 ± 13.22 µg/ml, respectively. However, no significant (P > 0.05) difference was observed between the groups and/or subgroups, suggesting no allergic response of final diet. Stimulation index triggered by lipopolysaccharide (LPS) ranged from 1.22 ± 0.06 to 1.45 ± 0.09 µg ml-1 in normal sub-groups and 1.16 ± 0.02 to 1.33 ± 0.03 µg ml-1 in anemic sub-groups with no significant (P > 0.05) difference among them. Overall, it can be concluded that retinyl acetate could be an effective fortificant to improve the status of vitamin A in anemic models.

Bioavailability assessment of zinc enriched lactobacillus biomass in a human colon carcinoma cell line (Caco-2).

The present study utilizes lactobacilli strains having the potential to accumulate a significant amount of Zinc (Zn) in their biomass and ability to deliver the same mineral in a highly bioavailable form. A human origin Lactobacillus fermentum SR4 and Lactobacillus rhamnosus GG (LGG) were studied for their ability to accumulate Zn by growing them in the medium containing Zn salt. Further, Zn enriched cell lysates were prepared by Ultrasonication, as an organic Zn source. Various functional groups involved in bacterial Zn binding were identified by FT-IR spectroscopy and elemental Zn in bio-chelated cell lysate complex was confirmed by SEM and Energy Dispersive X-ray Spectrometry (EDX). Experimental data demonstrated a significantly higher (P < 0.05) bioavailability of Zn chelated by SR4 followed by LGG i.e., 57% and 48%, as compared to the commercially available inorganic (ZnSo4) and even organic (Zinc gluconate) forms tested which has 15.6% and 21.7% respectively.