LIVER FIBROSIS: PATHOPHYSIOLOGY, DIAGNOSIS, AND EMERGING THERAPEUTIC TARGETS FOR A COMMON COMPLICATION OF CHRONIC LIVER DISEASES.

Fibrosis of the liver, which can be caused by either viral or chemical chronic liver illnesses, is a serious issue for the world's health. Collagen is crucial for the development of the illness and the possibility of developing hepatocellular carcinoma (HCC), which is linked to the progression of liver damage. Although there are various mechanisms for acute liver injury and diseases-specific cells response, almost all of fatty liver aetiologies share similar trends in the development of fibrous liver damage. The scientific community's knowledge of the fundamental causes of fibrosis of the liver has undergone a significant shift during the last ten years. It has been shown that the fundamental trigger, such as the control or management of an infectious disease, can be eradicated or eliminated in order to reverse liver fibrosis. Reversing frequently occurs prematurely or too rarely, particularly in severe fibrosis, to avoid possibly fatal effects. Therefore, there is an urgent need for anti-fibrotic medications to halt the progression of liver damage and the appearance of HCC. Even though various anti-fibrotic medication options have shown strong anti-fibrotic effects in lab animals, research studies have only seen a small amount or none of these advantages. There is not an approved remedy for the condition as a result. In this article, we give a general overview of the physiological and molecular origins of collagen in chronic liver disease and investigate how these causes can impact the quickly developing field of anti-fibrotic treatments.

Effects of oral probiotic and lactoferrin interventions on iron-zinc homeostasis, oxidant/antioxidant equilibrium and diarrhoea incidence of neonatal piglets.

The objective of this study was to examine the effects of early-life host specific probiotic and lactoferrin (LF) supplementations on diarrhoea incidence, iron (Fe)-zinc (Zn) balance and antioxidant capabilities in serum of neonatal piglets. A total of eight sow litters obtained from parity matched sows were randomly divided into four groups and assigned to one of the four interventions: control (2.0 ml normal saline), bovine lactoferrin (bLF) (100 mg bLF in normal saline), probiotic (Pb) (1×109 cfu of swine origin Pediococcus acidilactici FT28 strain) and bLF+Pb (both 100 mg bLF and 1×109 cfu of P. acidilactici FT28). All the piglets received supplementations once daily orally for first 7 days of life. The incidence of diarrhoea markedly decreased in bLF group compared to control group. Notably, no incidences of diarrhoea were recorded in Pb and bLF+Pb groups. The Zn and Fe concentrations were significantly increased from day 7 to 21 in bLF and on day 21 in bLF+Pb group. No such changes were noted in Pb group. Total antioxidant capacity (TAC) in serum was significantly increased on days 7 and 15 in bLF group and on days 7 and 21 in bLF+Pb group. Malonaldehyde concentration was markedly reduced from day 7 to 21 in bLF and bLF+Pb groups. The concentrations of nitrate on days 15 and 21 and malonaldehyde on day 7 were significantly higher in Pb group, but mean TAC was unaltered from day 0 to 21. Although no correlation between the incidence of diarrhoea and Zn/Fe and oxidant/antioxidant homeostasis was noted in the Pb group, the supplementation of P. acidilactici FT28 alone was sufficient to prevent the incidence of diarrhoea in neonatal piglets. Taken together, it is concluded that strategic supplementation of P. acidilactici FT28 in early life could help in preventing diarrhoea until weaning of piglets.

Grading of Anatomopathological Disparity in the Cases of Invasive Pulmonary Aspergillosis in wild avian species as recorded in Pigeons (Columba livia), Peafowls (Pavo cristatus), and Griffon Vultures (Gyps fulvus).

Aspergillosis which is caused by Aspergillus fumigatus, a fungal pathogen, can vary from a localized infection to severe life-threatening invasive or disseminated systemic diseases in birds. The present study aimed to evaluate and grade the anatomopathological disparity in the cases of invasive pulmonary aspergillosis (IPA) in Columba livia (pigeons), Pavo cristatus (peafowls), and Gyps fulvus (Griffon vultures). Necropsy gross lesions varied from mere congestion of lungs in P. cristatus, congestion and large necrotizing masses surrounded by a zone of hyperemia (10 mm dia) in lungs of C. livia, and typically disseminated granuloma in the lungs, air sacs, and organs of other serous membranes in G. fulvus. Histopathology varied from extensive parenchymal necrosis amidst exuberant fungal invasion in P. cristatus, multifocal to focally extensive tissue necrosis with colonies of fungal hyphae surrounded by heterophils and lymphocytes in C. livia, as well as typical mycotic granuloma embedded in the lungs, air sacs, and thoracoabdominal serous membranes with angio-invasion in G. fulvus. Based on gross and histopathological findings, we diagnosed the cases as Acute Invasive Pulmonary Aspergillosis (AIPA) in peafowls and pigeons, as well as Chronic Invasive Pulmonary Aspergillosis (CIPA) in Griffon vultures. There is a paucity of case reports on aspergillosis in wild avian species, and this report strived to document the cases of IPA in peafowls, pigeons, and vultures. This is the first report of its kind which evaluated anatomopathological disparity of IPA in pigeons, peafowls, and vultures with a proposed anatomopathological grading system which would help to understand and investigate the nature of aspergillosis in different avian hosts.

Starch bio-based composite active edible film functionalized with Carum carvi L. essential oil: antimicrobial, rheological, physic-mechanical and optical attributes.

In the present study, the antimicrobial, rheological, mechanical, barrier and optical properties of Carrageenan and Manihot esculenta (composite) starch biobased edible film incorporated with caraway (Carum carvi L.) essential oil (EO) were investigated. The Minimum Inhibitory Concentration (MIC) of caraway oil against B. cereus, E. coli, P. aeruginosa and S. aureus were found to be 0.6, 1.4, 1.4 and 0.8% respectively. The Gas Chromatography- Mass Spectroscopy (GC-MS) of caraway EO expressed a distinct chromatogram peak for phenolic compounds. Rheological results of Film-Forming Solution (FFS) revealed solid-like viscoelastic behavior. Incorporation of caraway EO in the film caused significant (P < 0.05) increase in moisture, moisture absorption, bio-degradability in terms of film solubility, L value, total color difference (ΔE), haziness and transparency value, however, significantly (P < 0.05) decreased tensile strength and whiteness index were observed. The zone of inhibition of caraway EO incorporated films against all test bacteria were highly significant (P < 0.01) than control whereas antibacterial activity was found more towards gram-positive bacteria than gram-negative bacteria. No significant (P>0.05) changes in thickness, density, water activity, swelling, elongation at break, water vapor transmission rate, a and b value were observed with increasing caraway EO concentration. These results with some good rheological, physic-mechanical, antimicrobial and optical characteristics suggest the application of such active film into a variety of foods with improved food safety and quality. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05028-1.

Intra-operative pain and patient satisfaction during lichtenstein repair under local anesthesia versus spinal anesthesia: an open-label randomized controlled trial.

PURPOSE: To compare pain during surgery among patients undergoing Lichtenstein inguinal hernia repair (LIHR) under local anaesthesia (LA) and spinal anaesthesia (SA). METHOD: Patients were randomized to undergo LIHR under LA or SA. Both intra-operative and postoperative pain was measured by NRS (numerical rating scale). Postoperative pain was managed similarly in both groups using intravenous diclofenac and paracetamol. Postoperative recovery, time to discharge, and early complications were recorded. Postoperative pain was assessed at 2, 6 and 24 h from the time of skin incision. Patient satisfaction was recorded on 5-point Likert scale 24 h after surgery. RESULTS: Data of 30 patients of each group were analyzed. All patients successfully underwent operation using anaesthesia technique allocated. Median intra-operative pain was 0 (0,3) in SA and 2.5 (0,5) in LA group. In SA group, intra-operative pain did not exceed NRS 3, while in LA, pain greater than NRS 3 was reported in 30% patients. No patient required tramadol in either group during postoperative period. Minor postoperative complications were reported 9/30 (30%) in SA compared to 1/30 (3.33%) in LA group. The satisfaction rate was 67% in LA group, whereas 37% in SA group. CONCLUSION: LA should be strongly considered for all patients with unilateral inguinal hernia undergoing open repair. In spite of a slightly more severe pain during surgery, patient satisfaction was higher using LA. TRIAL REGISTRATION: This study was conducted as a part of a postgraduate thesis research work. The protocol was submitted to the University of Delhi after approval of the IEC. Registration with the Clinical Trials Registry of India was not successfully done.

Compact X-Band Electron Linac for Radiotherapy and Security Applications.

RadiaBeam has developed a 6 MeV accelerator that is compact and light enough to be placed on a robotic arm or light truck. The main drivers of size and weight in conventional accelerators are the power source and the shielding. Small dimensions are enabled by operation at 9.3 GHz frequency (X-band), which allows reducing the size and weight of all accelerator components. Thanks to the robust design of the accelerating structure, the accelerator can be used as a source for novel cargo inspection and radiotherapy techniques. In this paper, we present the linac design and its components, as well the results of the experimental demonstration of beam acceleration.

Surgical management of the odontogenic keratocyst: A 20-year experience.

The objective of this study was to describe the authors' long-term experience with the management of odontogenic keratocysts (OKCs). All OKC cases treated at the study centre between 1999 and 2015, with a minimum of 5 years of follow-up by December 2019, were reviewed retrospectively. Operative procedures including decompression/marsupialization, enucleation (E), E+Carnoy's solution (CS), E+CS+peripheral ostectomy (PO), and resection were assessed for complete resolution, partial resolution, and recurrence rates. In the parakeratinized non-syndromic group, E+CS+PO resulted in the lowest recurrence rate among the minimally invasive procedures (4.3%), while enucleation resulted in the highest rate (60%). Regarding the other modalities, recurrence was 12.5% for decompression, 11.5% for marsupialization, 16.7% for E+CS, 26.7% for E+PO, and 0% for resection. In the syndromic group, marsupialization resulted in a significantly higher recurrence (23.1%), while E+CS+PO cases showed no recurrence. No recurrence was observed in the orthokeratinized group patients treated with marsupialization or with E+CS. Based on clinico-radiographic features and observed results, it is concluded that OKC, although having a high recurrence rate, is a benign lesion and responds well to conservative procedures in most cases. Radical procedures should be reserved for unresponsive lesions and those with extensive tissue destruction.

Anterior segmental osteotomies without orthodontics: practicability of the correction of dentoalveolar deformities.

We designed this study to determine the efficiency and stability of anterior segmental osteotomies (ASO) without orthodontics for various dentofacial deformities. Records of patients treated with maxillary or mandibular ASO, or both, without orthodontics in the past 15 years were analysed. The assessment included postoperative analysis of patients' aesthetics and functional satisfaction using a questionnaire and grading (score 0 - 4) system, and the amount of relapse calculated from 12-month postoperative cephalograms. A total of 26 ASO subjects (age range 13- 31 years) were studied (14 maxillary, two mandibular, and 10 bimaxillary). Long-term stability was acceptable in all cases with no significant relapse (p>0.05). No major complications were encountered. All patients reported good to excellent (score=3 to 4) satisfaction following surgery. Using meticulous planning and a careful surgical technique, ASO without orthodontics is a simple, quick, safe, and stable option for the correction of dentofacial deformities.

Stress and Molecular Drivers for Cancer Progression: A Longstanding Hypothesis.

Stress management is becoming very important part of cancer patient care. Chronic stressors lead to boost tumorigenesis and promote cancer development, recurrence, and drug resistant leading to poor health outcomes. The Hypothalamic-Pituitary-Adrenal (HPA) axis, which is activated by stress, also regulates Hypothalamic-Pituitary-Thyroid (HPT) axis. Stress related changes in immune function and inflammatory response also leads to reduced immune surveillance resulting in tumorigenesis. This article explores the hormonal axis impacted by stress and how chronic stress can lead to poor outcome of a cancer patient.

Possible treatment and strategies for COVID-19: review and assessment.

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.

Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?

BACKGROUND: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT). PATIENTS AND METHODS: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate. RESULTS: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40-56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3). CONCLUSIONS: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.

Expression of MTNR1A, steroid (ERα, ERß, and PR) receptor gene transcripts, and the concentration of melatonin and steroid hormones in the ovarian follicles of buffalo.

High ambient temperature exhibits a retrograde effect on buffalo reproduction because of heat stress. Moreover, melatonin is known to regulate reproductive changes in seasonally reproductive animals by binding to high affinity, G protein-coupled receptors. The MTNR1A gene is a prime receptor, mediating the effect of melatonin at the neuroendocrine level to control seasonal reproduction. In sheep, the role of melatonin is well known; however, studies have not been conducted in buffalo to determine its effect during favorable and unfavorable breeding seasons. Therefore, the present study aimed to (1) determine the expression of MTNR1A, ERα, ERß, and PR gene transcripts in the ovarian follicles of buffalo during the summer and winter seasons and (2) analyze melatonin, 17ß-estradiol, and progesterone concentrations in the follicular fluid of buffalo during both seasons. Murrah buffalo ovaries were collected during both the summer (May-June) and winter (December-January) seasons. All visible ovarian follicles were allocated into one of three groups: (1) small (8-9.9 mm); (2) medium (10-11.9 mm); and (3) large (12-14 mm). Follicular fluid was aspirated from each group of follicles for hormone analyses. The granulosa cells were processed for RNA extraction. Furthermore, they were subjected to real-time quantitative PCR to analyze the expression (relative quantification) of MTNR1A, ERα, ERß, and PR in each follicular group. The expression of MTNR1A gene transcript decreased with the increasing size of the follicle and intrafollicular melatonin concentration. Expression of ERα and PR remained unaffected by the season and was similar (P > 0.05) in all groups. Expression of ERß was higher (P < 0.05) in summer than winter; nevertheless, small-sized follicles from the summer exhibited higher (P < 0.05) expressions than medium- and large-sized follicles. The overall intrafollicular melatonin concentration was positively correlated (P < 0.05) with 17ß-estradiol and progesterone concentrations. In conclusion, the decreased expression of MTNR1A and increased concentration of intrafollicular melatonin with the increasing size of the follicle indicates a probable role in folliculogenesis and ovulation in buffalo.

Interplay of oxidative stress and antioxidant bio markers in oil adjuvant Brucella melitensis vaccinated and challenged mice.

The intracellular nature of Brucella leads to rise in oxidative stress due to bacterial invasion, particularly at the site of predilection spleen and lymph nodes. The present study aimed to evaluate the erythrocytic and tissue specific oxidative stress responses induced during oil adjuvant killed Brucella melitensis vaccination. The results of the study clearly implicated a significant increase in level of catalase, and superoxide dismutase (SOD) activity and lipid peroxidation (LPO), and total protein content in erythrocytes after vaccination. The activity of glutathione-S-transferase (GST) was unaltered during the period of experiment. The catalase activity and GSH content was significantly increased in lung and spleen tissues. The tissues GST levels increased significantly in all tissues, while tissue SOD level increased significantly only in lung tissues. Thus, it can be inferred that oil adjuvant based Brucella vaccine induces negligible signs of inflammatory pathophysiology and supports the development of significant level of protection against virulent Brucella challenge.

Outcome of 150 Consecutive Blumgart's Pancreaticojejunostomy After Pancreaticoduodenectomy.

Postoperative pancreatic fistula (POPF) is the most feared complication after pancreaticoduodenectomy (PD) that leads to intra-abdominal abscess, sepsis, or bleeding and remains the single most important source of morbidity and mortality after PD. To minimize this dreaded complication, various surgical techniques and modifications of pancreaticoenteric reconstruction have been proposed. However, still POPF does occur even in experienced hands. We herein describe the outcome of 150 post PD patients who underwent duct-to-mucosa (DM) pancreaticojejunostomy (PJ) using a special technique, Blumgart's "through & through" U transpancreatic sutures. The technique is described in detail. Postoperative octreotide and metoclopramide were used in all patients for 3 days. An enhanced recovery (ERAS) protocol was followed in a subset of patients. All patients were ASA grade 1 and had adenocarcinoma of the periampullary region/pancreatic head and underwent standard pylorus resecting PD after due optimization. Eighty-eight (58.7%) patients had pancreatic duct < 3 mm and pancreatic texture was soft to very soft in 112 (74.6%) patients. There was only one International Study Group of Pancreatic Surgery (ISGPS) grade C POPF with concomitant hemorrhage. Five patients developed ISGPS grade B and two grade C, delayed gastric emptying (DGE). There was no 30-day mortality. The average length of hospital stay was 7.3 ± 4.2 days with a median of 6 days in the ERAS subset of patients. Blumgart's "through & through" DMPJ technique is very helpful in reducing the POPF and other complications even in high-risk pancreas (i.e., soft with a small pancreatic duct) and is easy to learn and perform.

The Impact of Uniform Capsular Dissection Technique of Total Thyroidectomy on Postoperative Complications: An Experience of More Than 1000 Total Thyroidectomies from an Endocrine Surgery Training Centre in North India.

BACKGROUND: Total thyroidectomy (TT) with a uniform technique of capsular dissection (CD) is the preferred technique worldwide. The aim of study is to analyze the impact of uniform technique of CD for done as primary surgery at an endocrine surgery training centre. PATIENTS AND METHODS: Retrospective review from 1995 to 2009. Data collected from hospital records and follow-up. RESULTS: One thousand and thirty-eight cases were included, with mean age 42.91 ± 13.48 years; male:female - 1:2.2; mean duration of goiter - 99.83 ± 105.1 months; 67.8% were euthyroid and 30.7% - hyperthyroid at initial presentation; 35.5% were malignant. Surgery includes TT alone - 77.7% and TT with lymph nodes dissection - 22.3%; sternotomy required in 1.2% and thoracotomy in 0.1%; tracheomalacia present in 3.9%; however, tracheostomy required in 4.5% and parathyroid autotransplantation in 21%; Peroperative mean gross gland weight was 124.34 ± 129.85 g. Complications include hypocalcemia (temporary - 35.9%; permanent - 1.3%); recurrent laryngeal nerve palsy (temporary - 2.7%; permanent - 91%); hemorrhage - 1.3%; and various others. CONCLUSION: TT with uniform technique of CD is a safe procedure. Certain risk factors may predispose to complications, which can be avoided and managed adequately if anticipated beforehand.