Proteomics and metabolic burden analysis to understand the impact of recombinant protein production in E. coli.

The impact of recombinant protein production (RPP) on host cells and the metabolic burden associated with it undermine the efficiency of the production system. This study utilized proteomics to investigate the dynamics of parent and recombinant cells induced at different time points for RPP. The results revealed significant changes in both transcriptional and translational machinery that may have impacted the metabolic burden, growth rate of the culture and the RPP. The timing of protein synthesis induction also played a critical role in the fate of the recombinant protein within the host cell, affecting protein and product yield. The study identified significant differences in the expression of proteins involved in fatty acid and lipid biosynthesis pathways between two E. coli host strains (M15 and DH5⍺), with the E. coli M15 strain demonstrating superior expression characteristics for the recombinant protein. Overall, these findings contribute to the knowledge base for rational strain engineering for optimized recombinant protein production.

The MUC1-HIF-1α signaling axis regulates pancreatic cancer pathogenesis through polyamine metabolism remodeling.

Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 (SAT1), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation. We further identified a regulatory axis whereby MUC1 stabilized hypoxia-inducible factor (HIF-1α), leading to increased SAT1 expression, which in turn induced carbon flux into the tricarboxylic acid cycle. MUC1-mediated stabilization of HIF-1α enhanced the promoter occupancy of the latter on SAT1 promoter and corresponding transcriptional activation of SAT1, which could be abrogated by pharmacological inhibition of HIF-1α or CRISPR/Cas9-mediated knockout of HIF1A. MUC1 knockdown caused a significant reduction in the levels of SAT1-generated metabolites, N1-acetylspermidine and N8-acetylspermidine. Given the known role of MUC1 in therapy resistance, we also investigated whether inhibiting SAT1 would enhance the efficacy of FOLFIRINOX chemotherapy. By utilizing organoid and orthotopic pancreatic cancer mouse models, we observed that targeting SAT1 with pentamidine improved the efficacy of FOLFIRINOX, suggesting that the combination may represent a promising therapeutic strategy against pancreatic cancer. This study provides insights into the interplay between MUC1 and polyamine metabolism, offering potential avenues for the development of treatments against pancreatic cancer.

Metabolomic Investigations into Hypoxia-Mediated Metabolic Reprogramming of Pancreatic Cancer Cells.

Hypoxia is a crucial microenvironmental factor that defines tumor cell growth and aggressiveness. Cancer cells adapt to hypoxia by altering their metabolism. These alterations impact various cellular and physiological functions, including energy metabolism, vascularization, invasion and metastasis, genetic instability, cell immortalization, stem cell maintenance, and resistance to chemotherapy (Li et al. Technol Cancer Res Treat 20:15330338211036304, 2021). Hypoxia-inducible factor-1α (HIF-1α) is known to be a critical regulator of glycolysis that directly regulates the transcription of multiple key enzymes of the glycolysis pathway. Moreover, HIF-1α stabilization can be directly modulated by TCA-derived metabolites, including 2-ketoglutarate and succinate (Infantino et al, Int J Mol Sci 22(22), https://doi.org/10.3390/ijms22115703 , 2021). Overall, the molecular mechanisms underlying the adaptation of cellular metabolism to hypoxia impact the metabolic phenotype of cancer cells. Such adaptations include increased glucose uptake, increased lactate production, and increased levels of other metabolites that stabilize HIF-1α, leading to a vicious circle of hypoxia-induced tumor growth.

Methotrexate-based PROTACs as DHFR-specific chemical probes.

Methotrexate (MTX) is a tight-binding dihydrofolate reductase (DHFR) inhibitor, used as both an antineoplastic and immunosuppressant therapeutic. MTX, like folate undergoes folylpolyglutamate synthetase-mediated γ-glutamylation, which affects cellular retention and target specificity. Mechanisms of MTX resistance in cancers include a decrease in MTX poly-γ-glutamylation and an upregulation of DHFR. Here, we report a series of potent MTX-based proteolysis targeting chimeras (PROTACs) to investigate DHFR degradation pharmacology and one-carbon biochemistry. These on-target, cell-active PROTACs show proteasome- and E3 ligase-dependent activity, and selective degradation of DHFR in multiple cancer cell lines. By comparison, treatment with MTX increases cellular DHFR protein expression. Importantly, these PROTACs produced distinct, less-lethal phenotypes compared to MTX. The chemical probe set described here should complement conventional DHFR inhibitors and serve as useful tools for studying one-carbon biochemistry and dissecting complex polypharmacology of MTX and related drugs. Such compounds may also serve as leads for potential autoimmune and antineoplastic therapeutics.

C1QA and COMP: plasma-based biomarkers for early diagnosis of pancreatic neuroendocrine tumors.

Pancreatic Neuroendocrine tumors (PanNET) are challenging to diagnose and often detected at advanced stages due to a lack of specific and sensitive biomarkers. This study utilized proteomics as a valuable approach for cancer biomarker discovery; therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 5 Grade I, 4 Grade II PanNET patients) to identify potential proteins capable of effectively distinguishing PanNET from healthy controls. Data are available via ProteomeXchange with the identifier PXD045045. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis. Further, 5 proteins (C1QA, COMP, HSP90B1, ITGA2B, and FN1) were selected by pathway analysis and were validated using Western blot analysis. Significant downregulation of C1QA (p = 0.001: within groups, 0.03: control vs. grade I, 0.0013: grade I vs. grade II) and COMP (p = 0.011: within groups, 0.019: control vs grade I) were observed in PanNET Grade I & II than in controls. Subsequently, ELISA on 38 samples revealed significant downregulation of C1QA and COMP with increasing disease severity. This study shows the potential of C1QA and COMP in the early detection of PanNET, highlighting their role in the search for early-stage (Grade-I and Grade-II) diagnostic markers and therapeutic targets for PanNET.

Role of MMP1 and MMP10 in local invasion and distant metastasis in different levels of oral squamous cell carcinoma - A immunohistochemical comparative study.

Background: Matrix metalloproteinases (MMPs) are basically a part of a large family of proteolytic enzymes. They play an important role in degrading extracellular matrix and basement membrane, which is a basic mechanism in local invasion and tumour metastasis. The aim of this study was to evaluate immunohistochemically the expression of MMP1 and MMP10 in tumour invasion locally and at distant levels, including lymph nodes at different levels in oral squamous cell carcinoma (OSCC). Materials and Methods: A total of 50 tissue samples with clinically confirmed OSCC and 15 normal oral mucosal tissues will be included in the study. Immunohistochemical staining will be performed for the demonstration of MMP1 and MMP10 in lesional tissue, perilesional tissue, and lymph nodes of different levels that were evaluated with respect to microscopic features. Results: All OSCC cases had MMP1 and MMP10 expression levels. The expression increased as the nodal level increased from level I to level V. This difference was statistically significant at P < 0.001 Both MMPs were not expressed in normal epithelial cells. There was no significant correlation between MMP1 and MMP10 expression. Conclusion: This study showed that MMP1 and MMP10 are expressed in the tissues of OSCC and may serve as prognostic indicators for the disease.

Role of hypoxia and epithelial-mesenchymal transition in the formation and maintenance of oral cancer stem cells in oral squamous cell carcinomas and metastatic lymph node: An immunohistochemical analysis.

Background: Inspite of having advanced treatment modalities the overall survival rate in oral squamous cell carcinoma (OSCC) remains poor. This is considered to be mainly due to local recurrence and distant metastasis. Various studies have concentrated on the role of oral cancer stem cells (OCSCs) in the progression and metastasis of OSCC. However, the role of tumor microenvironment components has been less delved into. Hence clarity on cell biology and metastatic potential OCSCs is essential for the development of more effective anti-cancer treatment. Aim: To establish the role of OCSCs in different grades of OSCC and metastatic lymph nodes through the expression of cluster of differentiation 44 (CD44). To demonstrate and correlate the role of hypoxia and Epithelial mesenchymal transition (EMT) in the various grades and metastatic lymph nodes in the formation and maintenance of OCSCs by employing Hypoxia-inducible factor-1 Alpha (HIF 1α) and Snail respectively. Method and Material: A total of 36 cases of OSCC, 12 from each grade and 12 normal oral mucosal tissues were included in the study. Immunohistochemical staining was performed for the demonstration of CD44, HIF1α, and Snail. Statistics: Descriptive analysis, Chi-square, and Spearman's rank correlation were used to analyze frequency and proportion, to compare expression and correlate between lesion proper and lymph node in each group respectively. Results: Significant expression of CD44, HIF1 α, and Snail among advancing grades of OSCC and their metastatic lymph node were observed. A positive correlation was seen between them. Conclusions: The prognosis of OSCC can be improved by better understanding and targeting the molecules involved in the formation and maintenance of OCSCs.

Molecular characterization and antifungal activity of lipopeptides produced from Bacillus subtilis against plant fungal pathogen Alternaria alternata.

Over 380 host plant species have been known to develop leaf spots as a result of the fungus Alternaria alternata. It is an aspiring pathogen that affects a variety of hosts and causes rots, blights, and leaf spots on different plant sections. In this investigation, the lipopeptides from the B. subtilis strains T3, T4, T5, and T6 were evaluated for their antifungal activities. In the genomic DNA, iturin, surfactin, and fengycin genes were found recovered from B. subtilis bacterium by PCR amplification. From different B. subtilis strains, antifungal Lipopeptides were extracted, identified by HPLC, and quantified with values for T3 (24 g/ml), T4 (32 g/ml), T5 (28 g/ml), and T6 (18 g/ml). To test the antifungal activity, the isolated lipopeptides from the B. subtilis T3, T4, T5, and T6 strains were applied to Alternaria alternata at a concentration of 10 g/ml. Lipopeptides were found to suppress Alternaria alternata at rates of T3 (75.14%), T4 (75.93%), T5 (80.40%), and T6 (85.88%). The T6 strain outperformed the other three by having the highest antifungal activity against Alternaria alternata (85.88%).

Fast pain relief in exercise-induced acute musculoskeletal pain by turmeric-boswellia formulation: A randomized placebo-controlled double-blinded multicentre study.

BACKGROUND: Plant extracts with analgesic properties are seldom considered for treatment of acute musculoskeletal pain due to delay in onset of analgesia. Turmeric (Curcuma longa) and boswellia (Boswellia serrata) extracts are well-studied anti-inflammatory compounds gaining in popularity and used as an alternative to conventional treatments for musculoskeletal pain. This study analyzed the analgesic effect of a formulation of turmeric and boswellia extracts in sesame oil (Rhuleave-K, TBF) in reducing exercise-induced acute musculoskeletal pain in healthy participants. METHODS: In this randomized double-blinded placebo-controlled, single-dose, single-day, multicentre study, a total of 232 participants (TBF n = 116; placebo n = 116) having moderate-to-severe exercise-induced acute musculoskeletal pain were randomized in an allocation concealed 1:1 ratio to receive a single dose of 1000 mg of TBF or placebo. The outcome measures were numerical rating scale (NRS), categorical pain relief scale (PRS), onset of analgesia, and short form of McGill questionnaire (SF-MPQ). NRS and PRS were measured from predose to every 30 minutes interval of postdose up to 6 hours at rest, with movement and applying pressure on the affected part. The onset of analgesia was measured from the time of dosage and censored at 6 hours of postdose. The sum of pain intensity difference (SPID6) and total pain relief (TOTPAR6) at 6 hours was, respectively, analyzed from NRS and PRS scores. RESULTS: TBF showed a significant reduction in pain intensity (SPID6rest) with 97.85% improvement in cumulative responder analysis compared with 2.46% in placebo. The onset of pain relief was fast and highly significant in the TBF group with 99% of participants having a mean perceptible pain relief at 68.5 minutes (95% confidence interval, 59.5-77.4) and 96% of participants having a mean meaningful pain relief at 191.6 minutes (95% confidence interval, 176.7-206.4) compared to the placebo group. Highly significant and continuous improvement in pain relief was observed in the TBF group with 93% of participants having ≥ 50% of maximum TOTPAR6 with a number needed to treat of 1.1 at rest. CONCLUSION: Exercise-induced acute musculoskeletal pain can be effectively relieved by TBF (Rhuleave-K) in about 3 hours signifying its strong analgesic activity.

COVID-19 Associated Mucormycosis (CAM): A Single Hospital-Based Study.

Background: Opportunistic fungal infections like Mucormycosis in Coronavirus Disease 2019 (COVID-19) patients have posed a great challenge to health care professionals, especially in developing countries like India. Hence, there is a need to understand the biological behaviour of COVID-19 associated Mucormycosis (CAM) to establish standard treatment Protocols and to reduce mortality. Aims: This study aims is to assess the type of Mucormycosis among COVID-19 patients in study population and compare the findings with clinical, radiological and haematological parameters along with treatment and surgical management. Methods and Material: This retrospective, observational study included 60 cases of CAM reported to the Department of Oral and Maxillofacial Surgery at the tertiary care centre, Karnataka Institute of Medical Sciences, Hubli. Data about various parameters were tabulated and analysed statistically. Statistical Analysis Used: Bivariate analysis was done using the Chi-Square test to assess the relationship between the type of Mucormycosis and other variables. Spearman's Correlation test was used to assess the correlation between types of Mucormycosis with the other variables. Linear regression analysis was performed to assess the response variable related to the type of Mucormycosis. Results: About 50% of subjects presented with "Rhino orbital" type of Mucormycosis. Palatal discoloration and palatal erosion was the most common oral manifestation among "only Sinus" and "Rhino orbital" types of Mucormycosis (P = 0.00). Significant association (P = 0.29) was found between the type of Diabetes mellitus and Mucormycosis. Conclusions: The study indicates that DM is the most commonly associated comorbidity in CAM patients. Hence, a thorough understanding of the underlying comorbidity and its close monitoring during and after COVID-19 infection is mandatory for successful treatment outcomes.

Senescent Fibroblast in Oral Submucous Fibrosis Aids in Disease Progression and Malignant Transformation.

Aim: To study the role of senescent fibroblasts (SFs) and its secretory phenotypes promoting fibrosis and malignancy in oral submucous fibrosis (OSMF). Material Methods: A total of 20 cases of OSMF and 20 normal oral mucosal tissues were taken for the study. The tissue sections were stained for IHC-immunohistochemistry with senescent cell marker p16INK4a. The supernatant solution of the transport medium was studied for leached out senescent associated secretory proteins (SASP): matrix metalloproteinases 9 (MMP9), interleukins 6 (IL6), vascular endothelial growth factor (VEGF). Tissues were studied for malignant transformation with p53 and Ki67. Fibrosis in the OSMF was tested with lysyloxidase (LOX). The Statistical Package for the Social Sciences (SSPS) statistical software was used to analyze the data. Results: IHC staining for p16INK4ashowed positivity in the connective tissue of OSMF cases which was statistically significant. Antibody assay using enzyme-linked immunosorbent assay (ELISA) showed elevated levels of secretoproteins IL6, MMP9, VEGF in OSMF cases. LOX enzyme levels were also significantly increased in OSMF cases. Proliferative markers Ki67 and p53 were positive in IHC staining in the epithelium of OSMF. Conclusion: This study confirms the presence of SF and its secreto phenotypes in OSMF and showed increased LOX expression which is implicated in fibrosis. These findings suggest that SF may contribute to fibrosis in OSMF. The study also confirms the malignant transformation of the overlying epithelium as shown by p53 and Ki67 positivity.

Finite Element Analysis of Cornea and Lid Wiper during Blink, with and without Contact Lens.

Ocular surface disorders such as Lid Wiper Epitheliopathy (LWE), Superior Epithelial Arcuate Lesion (SEAL), and contact lens-induced Limbal Stem Cell Deficiency (LSCD) as well as Superior Limbic Keratoconjunctivitis (SLK) affect one's quality of life. Hence, it is imperative to investigate the underlying causes of these ocular surface disorders. During blink, the undersurface of the eyelid tends to interact with the cornea and the conjunctiva. The presence of a contact lens can add to the biomechanical frictional changes on these surfaces. To estimate these changes with and without a contact lens, a finite element model (FEM) of the eyelid wiper, eyeball, and contact lens was developed using COMSOL Multiphysics. Biomechanical properties such as von Mises stress (VMS) and displacement were calculated. Our study concluded that (a) maximum VMS was observed in the lid wiper in the absence of contact lens in the eye and (b) maximum VMS was observed in the superior 1.3 mm of the cornea in the presence of the contact lens in the eye. Thus, the development of friction-induced ocular surface disorders such as LWE, SLK, SEAL, and LSCD could be attributed to increased VMS. FEA is a useful simulation tool that helps us to understand the effect of blink on a normal eye with and without CL.

Metabolomic Profiling Revealed Diversion of Cytidinediphosphate-Diacylglycerol and Glycerol Pathway towards Denovo Triacylglycerol Synthesis in Rhodosporidium toruloides.

Oleaginous yeast Rhodosporidium toruloides has great biotechnological potential and scientific interest, yet the molecular rationale of its cellular behavior to carbon and nitrogen ratios with concurrent lipid agglomeration remains elusive. Here, metabolomics adaptations of the R. toruloides in response to varying glucose and nitrogen concentrations have been investigated. In preliminary screening we found that 5% glucose (w/v) was optimal for further analysis in Rhodosporidium toruloides 3641. Hereafter, the effect of complementation to increase lipid agglomeration was evaluated with different nitrogen sources and their concentration. The results obtained illustrated that the biomass (13 g/L) and lipid (9.1 g/L) production were maximum on 5% (w/v) glucose and 0.12% (NH4)2SO4. Furthermore, to shed lights on lipid accumulation induced by nitrogen-limitation, we performed metabolomic analysis of the oleaginous yeast R. toruloides 3641. Significant changes were observed in metabolite concentrations by qualitative metabolomics through gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), which were mapped onto the governing metabolic pathways. Notable finding in this strain concerns glycerol and CDP-DAG metabolism wherein reduced production of glycerol and phospholipids induced a bypass leading to enhanced de-novo triacylglyceride synthesis. Collectively, our findings help in understanding the central carbon metabolism of R. toruloides which may assist in developing rationale metabolic models and engineering efforts in this organism.

Accessory enzymes of hypercellulolytic Penicillium funiculosum facilitate complete saccharification of sugarcane bagasse.

BACKGROUND: Sugarcane bagasse (SCB) is an abundant feedstock for second-generation bioethanol production. This complex biomass requires an array of carbohydrate active enzymes (CAZymes), mostly from filamentous fungi, for its deconstruction to monomeric sugars for the production of value-added fuels and chemicals. In this study, we evaluated the repertoire of proteins in the secretome of a catabolite repressor-deficient strain of Penicillium funiculosum, PfMig188, in response to SCB induction and examined their role in the saccharification of SCB. RESULTS: A systematic approach was developed for the cultivation of the fungus with the aim of producing and understanding arrays of enzymes tailored for saccharification of SCB. To achieve this, the fungus was grown in media supplemented with different concentrations of pretreated SCB (0-45 g/L). The profile of secreted proteins was characterized by enzyme activity assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 280 proteins were identified in the secretome of PfMig188, 46% of them being clearly identified as CAZymes. Modulation of the cultivation media with SCB up to 15 g/L led to sequential enhancement in the secretion of hemicellulases and cell wall-modifying enzymes, including endo-ß-1,3(4)-glucanase (GH16), endo-α-1,3-glucanase (GH71), xylanase (GH30), ß-xylosidase (GH5), ß-1,3-galactosidase (GH43) and cutinase (CE5). There was ~ 122% and 60% increases in ß-xylosidase and cutinase activities, respectively. There was also a 36% increase in activities towards mixed-linked glucans. Induction of these enzymes in the secretome improved the saccharification performance to 98% (~ 20% increase over control), suggesting their synergy with core cellulases in accessing the recalcitrant region of SCB. CONCLUSION: Our findings provide an insight into the enzyme system of PfMig188 for degradation of complex biomass such as SCB and highlight the importance of adding SCB to the culture medium to optimize the secretion of enzymes specific for the saccharification of sugarcane bagasse.

Biophysical and structural studies reveal marginal stability of a crucial hydrocarbon biosynthetic enzyme acyl ACP reductase.

Acyl-ACP reductase (AAR) is one of the two key cyanobacterial enzymes along with aldehyde deformylating oxygenase (ADO) involved in the synthesis of long-chain alkanes, a drop-in biofuel. The enzyme is prone to aggregation when expressed in Escherichia coli, leading to varying alkane levels. The present work attempts to investigate the crucial structural aspects of AAR protein associated with its stability and folding. Characterization by dynamic light scattering experiment and intact mass spectrometry revealed that recombinantly expressed AAR in E. coli existed in multiple-sized protein particles due to diverse lipidation. Interestingly, while thermal- and urea-based denaturation of AAR showed 2-state unfolding transition in circular dichroism and intrinsic fluorescent spectroscopy, the unfolding process of AAR was a 3-state pathway in GdnHCl solution suggesting that the protein milieu plays a significant role in dictating its folding. Apparent standard free energy [Formula: see text] of ~ 4.5 kcal/mol for the steady-state unfolding of AAR indicated borderline stability of the protein. Based on these evidences, we propose that the marginal stability of AAR are plausible contributing reasons for aggregation propensity and hence the low catalytic activity of the enzyme when expressed in E. coli for biofuel production. Our results show a path for building superior biocatalyst for higher biofuel production.

Bone replacement grafts with guided tissue regeneration in treatment of grade II furcation defects: a systematic review and meta-analysis.

AIM: The present systematic review appended with meta-analysis aimed to evaluate the efficacy of bone replacement graft (BRG) with guided tissue regeneration (GTR) over BRG or open flap debridement (OFD) alone in the treatment of grade II furcation defects. MATERIALS AND METHODS: An electronic literature search of PubMed, Cochrane Library and Google Scholar databases accompanied with manual searching was done. Randomized controlled trials (RCTs) up to October 2019, comparing BRG+GTR with BRG or OFD in grade II furcation defects, were identified. Clinical attachment level (CAL) gain, changes in gingival marginal level (GML), vertical defect fill (VDF), horizontal defect fill (HDF) and reduction in defect volume were the outcome parameters. RESULTS: Of a total of 12, 9 studies compared BRG+GTR vs BRG while 3 compared BRG+GTR vs OFD. Meta-analysis was carried out for CAL gain, VDF, HDF and GML changes. In the BRG+GTR vs BRG comparison group, out of 9 studies, 6 RCTs showed standardized mean difference (SMD) of 0.513 for VDF, 9 RCTs showed SMD of 0.83 for HDF and 2 RCTs showed SMD of 0.651 for CAL gain, whereas only 2 studies in the same group reported reduction in defect volume. Three studies of the BRG+GTR vs OFD group exhibited significant VDF and CAL gain with SMD of 2.002 and 1.161 respectively. However, no significant change was recorded for GML in both groups. CONCLUSION: The present systematic review indicates supplemental benefits of combination therapy of BRG+GTR over monotherapy in resolving grade II furcation defects. CLINICAL RELEVANCE: In our quest to achieve maximum regeneration in grade II furcation defects, combination therapies such as BRG+GTR have been accepted as treatment choices over other modalities. Clinical situations warranting near-complete regeneration of the tissues in such defects are better suited for combination therapies.

Efficacy of high-dissolution turmeric-sesame formulation for pain relief in adult subjects with acute musculoskeletal pain compared to acetaminophen: A randomized controlled study.

BACKGROUND: Acetaminophen (paracetamol) is one of the most commonly used over-the-counter for pain relief. Management of acute pain with plant-based nutrients has remained suboptimal due to an absence of data supporting acute relief of pain. In the present study, it was hypothesized that high-dissolution liquid treatment of black sesame extract oil, Curcuma longa and Boswellia serrata may provide pain relief in people with acute musculoskeletal pain as quickly as acetaminophen. METHODS: In this randomized active controlled open label study, 88 healthy subjects with acute musculoskeletal pain were randomized to receive treatment capsule (Rhuleave-K; 1,000 mg/d) or 1,000 mg/d acetaminophen for 7 days. Change in pain intensity and pain relief at first 6 hours, 3 days, and 7 days were measured. The onset of analgesia was measured by perceptible pain relief and meaningful pain relief. Other measures were McGill Pain Questionnaire and Patient Global Impression Change. RESULTS: The treatment formulation resulted in average magnitude of pain relief comparable to the acetaminophen. Sixty-six percent of subjects in the treatment group reported positive response in pain relief (≥50% max TOTPAR; total pain relief) after 6 hours, compared to 73% of control. Seventy-three percent of subjects on treatment were considered positive responders, compared to 80% in the control group. The average time of onset of analgesia was 1 hour for the treatment group, versus 0.83 hour for control. At the end of day 3 and 7, there was significant improvement (P < .001 for day 3 and day 7) in the pain condition of treatment group and was comparable to control (P = .436 for day 3 and P = .529 for day 7). The total McGill Pain score showed significant reduction in pain with the treatment irrespective of the pain intensity statistically equal (P = .468) to control. Both the groups were equal in providing sensory pain relief (P = .942), but the treatment was 8.57 times significantly better (P = .027) than acetaminophen in reducing the unpleasantness and emotional aspects (affective domain) involved with acute pain. CONCLUSION: The results showed that the treatment used in the study may act as a natural, fast acting, and safe alternative for acute pain relief comparable to acetaminophen.

Summary of Proceedings and Expert Consensus Statements From the International Summit "Lipids in Parenteral Nutrition".

BACKGROUND: The 2018 Lipids in Parenteral Nutrition summit involved a panel of experts in clinical nutrition, lipid metabolism, and pharmacology, to assess the current state of knowledge and develop expert consensus statements regarding the use of intravenous lipid emulsions in various patient populations and clinical settings. The main purpose of the consensus statements is to assist healthcare professionals by providing practical guidance on common clinical questions related to the provision of lipid emulsions as part of parenteral nutrition (PN). METHODS: The summit was designed to allow interactive discussion and consensus development. The resulting consensus statements represent the collective opinion of the members of the expert panel, which was informed and supported by scientific evidence and clinical experience. RESULTS: The current article summarizes the key discussion topics from the summit and provides a set of consensus statements designed to complement existing evidence-based guidelines. Lipid emulsions are a major component of PN, serving as a condensed source of energy and essential fatty acids. In addition, lipids modulate a variety of biologic functions, including inflammatory and immune responses, coagulation, and cell signaling. A growing body of evidence suggests that lipid emulsions containing ω-3 fatty acids from fish oil confer important clinical benefits via suppression of inflammatory mediators and activation of pathways involved in the resolution of inflammation. CONCLUSIONS: This article provides a set of expert consensus statements to complement formal PN guideline recommendations.

Comparative evaluation of the left ventricular mass in patients with chronic kidney disease in periodontally healthy, chronic gingivitis, and chronic periodontitis patients.

OBJECTIVES: Emerging evidence suggests that inflammation due to periodontal diseases may not be limited to adjacent oral tissues but may have influence on systemic diseases such as chronic kidney diseases (CKD) and cardiovascular diseases. Hence, this study was aimed to evaluate and compare left ventricular mass (LVM) in patients with CKD undergoing hemodialysis (CKDH) in periodontally healthy, chronic gingivitis, and chronic periodontitis. METHODOLOGY: A total of 60Â patients diagnosed with CKDH were divided equally into three groups based on periodontal status as CKDH patients with healthy periodontium (Group I), CKDH patients with chronic gingivitis (Group II), and CKDH patients with chronic periodontitis (Group III). These patients were assessed clinically, biochemically, and echocardiographically. LVM in each of these patients was calculated according to Devereux formula and was indexed to height. RESULTS: Group II and Group III patients exhibited higher mean LVM of 199.51 ± 40.17 g and 200.35 ± 65.04Â g, respectively, as compared to Group I of 161.56 ± 27.99Â g. Similarly, LVM index (LVMI) was found to be more in Group II and Group III at 59.36 ± 13.14Â g/m2.7 and 57.83 ± 19.94Â g/m2.7, respectively, while it was 45.99 ± 11.87 g/m2.7 for Group I patients. CONCLUSION: Increasing the severity of periodontal diseases in CKDH patients is associated with increase in LVM and LVMI. Periodontal screening and intervention would enable the clinician to refine cardiovascular risk assessment in such patients.