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Abstract Background Immigrants to Germany and their children are at particular risk for tuberculosis (TB). Methods 35 Patients (10 male/25 female aged 2 - 59 years (median 33 years) originating mostly from high incidence countries in Asia (19 [54.3%]) in Africa (14 [40.0%] and East Europe (2 [5.7%]), attended at the Tropical Medicine unit were analysed. Results Primary clinical presentation was most frequently lymphadenitis (13 [37.1%]). other organs involved included bones (7 [20.0%]), central nervous system (5 [14.3%]), urogenital organs (3 [8.6%]), lung (3 [8.6%]), mediastinum, (2 [5.7%]) and abdomen (2 [5.7%]). ESR was abnormal in 21/28 (75.0%), CRP in 20/35 (57.1%), and protein electrophoresis in 22/26 (84.6%) cases. The tuberculin skin test was strongly positive in all 15 cases where the test had been performed. Tuberculosis interferon gamma release assay (TB-IGRA) was positive in all 35 cases (100%). PCR for nucleic acids of Mycobacterium (M.) tuberculosis complex was positive in only 7/20 (35.0%) cases. M. tuberculosis was identified in 32/35 (91.4%), M. bovis in 2 (5.7%) cases. 1 case was diagnosed clinically. All patients were negative for HIV. Typical histopathology was seen in the 29 cases, where biopsies had been taken. Chest-X-ray did not reveal specific pulmonary lesions in the majority of cases (22/35 [62.9%]). Diagnosis of TB was mostly delayed (4 to 299 weeks, [median 8]). The most frequent primary suspicion was a malignancy (17/35 [48.6%]) while TB was initially suspected in 5 cases only. Diagnosis of TB is impeded by its multifaceted presentation especially in immigrants.

A new anthraquinone, 1-methyl-2-(3'-methyl-but-2'-enyloxy)-anthraquinone (1) has been isolated from seeds of Aegle marmelos Correa and was characterized on the basis of spectral analysis (UV, IR, 1H NMR, 13C NMR, 2D NMR and mass spectroscopy). The compound exhibited significant antifungal activity against pathogenic strains of Aspergillus species and Candida albicans in disc diffusion assay (MIC value of 6.25 microg/disc), microbroth dilution and percent spore germination inhibition assays (MIC value of 31.25-62.5 microg/ml). [ABSTRACT FROM AUTHOR]

Lectins are sugar interacting proteins which bind specific glycans reversibly and have ubiquitous presence in all forms of life. They have diverse biological functions such as cell signaling, molecular recognition, etc. C-type lectins (CTL) are a group of proteins from the lectin family which have been studied extensively in animals and are reported to be involved in immune functions, carcinogenesis, cell signaling, etc. The carbohydrate recognition domain (CRD) in CTL has a highly variable protein sequence and proteins carrying this domain are also referred to as C-type lectin domain containing proteins (CTLD). Because of this low sequence homology, identification of CTLD from hypothetical proteins in the sequenced genomes using homology based programs has limitations. Machine learning (ML) tools use characteristic features to identify homologous sequences and it has been used to develop a tool for identification of CTLD. Initially 500 sequences of well annotated CTLD and 500 sequences of non CTLD were used in developing the machine learning model. The classifier program Linear SVC from sci kit library of python was used and characteristic features in CTLD sequences like dipeptide and tripeptide composition were used as training attributes in various classifiers. A precision, recall and multiple correlation coefficient (MCC) value of 0.92, 0.91 and 0.82 respectively were obtained when tested on external test set. On fine tuning of the parameters like kernel, C value, gamma, degree and increasing number of non CTLD sequences there was improvement in precision, recall and MCC and the corresponding values were 0.99, 0.99 and 0.96. New CTLD have also been identified in the hypothetical segment of human genome using the trained model. The tool is available on our local server for interested users., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Type 2 diabetes (T2D) is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease (CVD). The pathogenesis of both diseases shares common risk factors and mechanisms, and both are significant contributors to global morbidity and mortality. Supplements of natural products for T2D mellitus (T2DM) and CVD can be seen as a potential preventive and effective therapeutic strategy., Aim: To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease (CAD)., Methods: By using specific keywords, we strategically searched the PubMed database. Randomized controlled trials (RCTs) were searched as the primary focus that examined the effect of natural products on glycemic control, oxidative stress, and antioxidant levels. We focused on outcomes such as low blood glucose levels, adjustment on markers of oxidative stress and antioxidants. After screening full-length papers, we included 9 RCTs in our review that met our inclusion criteria., Results: In the literature search on the database, we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD. American ginseng, sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure, which are key factors in managing T2DM and CVD. In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention. Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers, suggesting benefits for both conditions. The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula , which is significant for the management of cardiovascular risk factors in T2DM. Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM., Conclusion: The high level of antioxidant, anti-inflammatory, and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD, with the potential benefit of lowering the risk of CAD., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Computational algorithms and tools have retrenched the drug discovery and development timeline. The applicability of computational approaches has gained immense relevance owing to the dramatic surge in the structural information of biomacromolecules and their heteromolecular complexes. Computational methods are now extensively used in identifying new protein targets, druggability assessment, pharmacophore mapping, molecular docking, the virtual screening of lead molecules, bioactivity prediction, molecular dynamics of protein-ligand complexes, affinity prediction, and for designing better ligands. Herein, we provide an overview of salient components of recently reported computational drug-discovery workflows that includes algorithms, tools, and databases for protein target identification and optimized ligand selection., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Uncontrolled high sugar levels lead to advanced glycation end products (AGEs), which affects several metabolic pathways by its receptor of advanced glycation end products (RAGE) and causes diabetic complication. MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis, and target tissues, influencing health and disease processes., Aim: To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications., Methods: We systematically searched the electronic database PubMed using keywords. We included free, full-length research articles that evaluate the role of miRNAs in T2DM and its complications, focusing on genetic and molecular disease mechanisms. After assessing the full-length papers of the shortlisted articles, we included 12 research articles., Results: Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications. miR-96-5p, miR-7-5p, miR-132, has_circ_0071106, miR-143, miR-21, miR-145-5p, and more are associated with various aspects of T2DM, including disease risk, diagnostic markers, complications, and gene regulation., Conclusion: Targeting the AGE/RAGE axis, with a focus on miRNA regulation, holds promise for managing T2DM and its complications. MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE, potentially reducing inflammation, oxidative stress, and vascular complications. Additionally, miRNAs may serve as early diagnostic biomarkers for T2DM. Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis., Aim: To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes., Methods: We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide., Results: Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 ( r = 0.596, P = 0.001) and TNF-α ( r = 0.337, P = 0.001) and a negative correlation with nitric oxide ( r =-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates., Conclusion: CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. All authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Allium sativum agglutinin (ASA) is an important lectin isolated from garlic bulbs and has shown promising therapeutic potential in earlier reports. It has a bulb-type lectin domain, and members of this protein family have been investigated for anti-cancer, antimicrobial and other effects. In our earlier study, we have reported ASA as an anti-cancer agent, and in the present study, we have evaluated it for its antifungal and antimicrobial effects. The effects of ASA on the opportunistic pathogens in humans Candida auris and Candida glabrata fungal strains have been evaluated, and efforts are made to evaluate the mechanistic basis of these antifungal effects. The antifungal activity of ASA on different strains of C. glabrata and C. auris was found with MIC 50 concentration range of 30-70 µg/ml. Fungal growth was significantly suppressed upon treatment with ASA at MIC 50 and 2MIC 50 . Hydrogen peroxide production was detected after ASA treatment in fungal cells and cell morphology, and integrity was affected when analysed through FE-SEM. Further, the anti-biofilm effect of ASA was investigated against Candida and three bacterial strains (Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae), and promising results were obtained with maximal effect in case of K. pneumoniae among the bacterial strains. These results can form the basis for the development of ASA as antimicrobial agent., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Severe acute malnutrition (SAM) is a significant public health problem in developing countries, including India, where a significant proportion of children suffer from malnutrition., Objective: This research aims to investigate the factors contributing to severe acute malnutrition (SAM). Additionally, the study seeks to explore the relationship between micronutrient levels and pro-inflammatory cytokines in SAM children with and without clinical complications. Furthermore, the effectiveness of antibiotic treatment in SAM children without complications is evaluated., Methods: The study involved three groups comprising 66 subjects each: a healthy control group, SAM children with complications, and SAM children without complications. Blood samples were collected, and various analyses were conducted, including biochemical, hematological, micronutrient, and pro-inflammatory marker quantification. The data were analyzed using SPSS version 22.0., Results: The results indicate that the levels of IL-6, CRP, and TNF-α were significantly higher in the SAM group with complications compared to both the control group and the SAM group without complications. Zinc and copper levels were significantly lower in both SAM groups compared to the control group, and a negative correlation was observed between zinc levels and inflammatory markers. The study also assessed the efficacy of antibiotic treatment in SAM children without complications by comparing their weight, height, weight-for-height, and weight-for-age at baseline and after a 15-day follow-up period. Significant improvements in these parameters were observed in both the group receiving antibiotic treatment and the group not receiving antibiotic treatment., Conclusion: The findings suggest that a combination of antibiotic treatment and nutritional support can lead to significant clinical improvements in SAM children without complications. This study has important implications for the management and treatment of SAM in India and other developing countries.

Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.

Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Various investigations are being conducted to overcome these challenges using RNA, DNA, and proteins for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as a novel target to treat the multistep process of TNBC. LncRNAs regulate epigenetic expression levels, cell proliferation and apoptosis, and tumour invasiveness and metastasis. Thus, lncRNA-based early diagnosis and treatment options could be helpful, especially for patients with severe TNBC. lncRNAs are expressed in a highly specific manner in cells and tissues and are involved in TNBC progression and development. lncRNAs could be used as sensitive and specific targets for diagnosis, treatment, and monitoring of patients with TNBC. Therefore, the exploration of novel diagnostic and prognostic biomarkers is of extreme importance. Here, we discuss the molecular advances on lncRNA regulation of TNBC and lncRNA-based early diagnosis, treatment, and drug resistance.

SARS-CoV-2 (severe acute respiratory syndrome) is highly infectious and causes severe acute respiratory distress syndrome (SARD), immune suppression, and multi-organ failure. For SARS-CoV-2, only supportive treatment options are available, such as oxygen supportive therapy, ventilator support, antibiotics for secondary infections, mineral and fluid treatment, and a significant subset of repurposed effective drugs. Viral targeted inhibitors are the most suitable molecules, such as ACE2 (angiotensin-converting enzyme-2) and RBD (receptor-binding domain) protein-based inhibitors, inhibitors of host proteases, inhibitors of viral proteases 3CLpro (3C-like proteinase) and PLpro (papain-like protease), inhibitors of replicative enzymes, inhibitors of viral attachment of SARS-CoV-2 to the ACE2 receptor and TMPRSS2 (transmembrane serine proteinase 2), inhibitors of HR1 (Heptad Repeat 1)-HR2 (Heptad Repeat 2) interaction at the S2 protein of the coronavirus, etc. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Even with the tremendous progress made, creating effective drugs remains difficult. To develop COVID-19 treatment alternatives, clinical studies are examining a variety of therapy categories, including antibodies, antivirals, cell-based therapy, repurposed diagnostic medicines, and more. In this article, we discuss recent clinical updates on SARS-CoV-2 infection, clinical characteristics, diagnosis, immunopathology, the new emergence of variant, SARS-CoV-2, various approaches to drug development and treatment options. The development of therapies has been complicated by the global occurrence of many SARS-CoV-2 mutations. Discussion of this manuscript will provide new insight into drug pathophysiology and drug development.

Breast cancer (BC) is caused by epigenetic modifications and genetic heterogeneity and exhibits various histological feature. HER2+ (Human epidermal growth factor receptor 2) is a more aggressive type of breast cancer, diagnosis and prognosis are difficult for HER2+ BC. Anti-HER2+ inhibitors have been effectively used for patient treatment. High mortality rate is reported in HER2+ BC, due to availability of limited therapeutic options. Despite advances in systemic medications to treat metastatic breast cancer (MBC), HER2-positive MBC is still challenging for patients and treating clinicians. The clinical characteristics of the disease have changed after treatment with HER2-targeted therapy. Various types of Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with HER2+ BC including afatinib, lapatinib, neratinib, tucatinib, and pyrotinib, have been developed as HER2-targeted therapies. The antibody-drug conjugates adotrastuzumab, emtansine, famtrastuzumab, and deruxtecan, as well as the anti-HER2 monoclonal antibody pertuzumab are used in both early-stage and metastatic situations, either alone or in conjunction with chemotherapy and other HER2-targeting therapies. The emergence of drug resistance in anti-HER2 therapies has been observed. To overcome drug resistance and limited efficacy in current treatment options, nano formulations can be used in patients with HER2+ BC treatment. Anti-HER2 ligands can be used in various nano formulations to target HER2 receptors. Here we will discuss, targeted TKIs in patients with HER2+ BC, clinical studies of HER2+ targeted TKIs, mechanisms of resistance to HER2-directed therapies with new implications of TKIs in HER2+ MBC (metastatic breast cancer) and anti-HER2 ligand in various nano formulations to target HER2 receptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Singh, Lee and Yadav.)

Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction. If insulin has neuroprotective properties, insulin resistance may interfere with those properties. Risk factors have a significant impact on the development of diseases, such as diabetes, obesity, stroke, and other conditions. Analysis of risk factors of importance for the association between diabetes and dementia is important because they may impede clinical management and early diagnosis. We discuss the pathological and physiological mechanisms behind the association between Type 2 diabetes mellitus and dementia, such as insulin resistance, insulin signaling, and sporadic forms of dementia; the relationship between insulin receptor activation and TAU phosphorylation; dementia and mRNA expression and downregulation of related receptors; neural modulation due to insulin secretion and glucose homeostasis; and neuronal apoptosis due to insulin resistance and Type 2 diabetes mellitus. Addressing these factors will offer clinical outcome-based insights into the mechanisms and connection between patients with type 2 diabetes and cognitive impairment. Furthermore, we will explore the role of brain insulin resistance and evidence for anti-diabetic drugs in the prevention of dementia risk in type 2 diabetes.

The incidence of obesity and over bodyweight is emerging as a major health concern. Obesity is a complex metabolic disease with multiple pathophysiological clinical conditions as comorbidities are associated with obesity such as diabetes, hypertension, cardiovascular disorders, sleep apnea, osteoarthritis, some cancers, and inflammation-based clinical conditions. In obese individuals, adipocyte cells increased the expression of leptin, angiotensin, adipocytokines, plasminogen activators, and C-reactive protein. Currently, options for treatment and lifestyle behaviors interventions are limited, and keeping a healthy lifestyle is challenging. Various types of phytochemicals have been investigated for antiobesity potential. Here, we discuss pathophysiology and signaling pathways in obesity, epigenetic regulations, regulatory mechanism, functional ingredients in natural antiobesity products, and therapeutic application of phytochemicals in obesity., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Vikram Kumar et al.)

Objective: Type 2 Diabetes is a glucose metabolic disorder occurred by insulin insensitivity in which folate metabolism plays an important role. it is believed that polymorphism of Methylenetetrahydrofolate reductase (MTHFR) C677T linked with type 2 diabetes mellitus. However, results are conflicted. therefore, in this study we re-examine the relationship between MTHFR C677T in type 2 diabetes mellitus patients., Methods: Present research work included 100 newly diagnosed type 2 diabetic mellitus (T2DM) cases and 100 healthy individuals. After the blood sample collection all the biochemical parameters were evaluated among the T2DM cases and healthy individuals. DNA and RNA extraction from whole blood was done to study the MTHFR gene polymorphism by allele specific polymerase chain reaction method and its expression analysis was done by quantitative real time polymerase chain reaction method., Results: The significant difference was observed in genotype distribution among case and control group ( p =0.0002). Compared with wildtype CC genotype, CT heterozygous (OR=2.95, 95% Cl=1.62-5.38) and TT homozygous (OR=3.20, CI=1.79-5.73) suggest to have effect of MTHFR polymorphism on type 2 mellitus risk. Moreover, relative MTHFR mRNA expression was found for wild type CC genotype 3.02-fold, CT heterozygous genotype 2.57 fold and mutant TT homozygous genotype 0.50-fold which is down regulated ( p <0.0001)., Conclusion: Our results indicates that the polymorphism in MTHFR C677T plays significant role in type II diabetes risk. MTHFR CT heterozygous and mutant TT genotype showed reduced mRNA expression among the T2DM patients. However, large scale case-control studies are needed to strengthen such conclusion in the future., Competing Interests: Conflict of InterestThe authors declare that they have no competing interests., (© Springer Nature Switzerland AG 2022.)

Multiple variants of SARS-CoV-2 have emerged and are now prevalent at the global level. Currently designated variants of concern (VOCs) are B.1.1.7, B1.351, P.1, B.1.617.2 variants and B.1.1.529. Possible options for VOC are urgently required as they carry mutations in the virus spike protein that allow them to spread more easily and cause more serious illness. The primary targets for most therapeutic methods against SARS-CoV-2 are the S (Spike) protein and RBD (Receptor-Binding Domain), which alter the binding to ACE2 (Angiotensin-Converting Enzyme 2). The most popular of these strategies involves the use of drug development targeting the RBD and the NTD (N-terminal domain) of the spike protein and multiple epitopes of the S protein. Various types of mutations have been observed in the RBDs of B.1.1.7, B1.351, P. and B.1.620. The incidence of RBD mutations increases the binding affinity to the ACE2 receptor. The high binding affinity of RBD and ACE2 has provided a structural basis for future evaluation of antibodies and drug development. Here we discuss the variants of SARS-CoV-2 and recent updates on the clinical evaluation of antibody-based treatment options. Presently, most of the antibody-based treatments have been effective in patients with SARS-CoV-2. However, there are still significant challenges in verifying independence, and the need for further clinical evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Singh, Sharma, Lee and Yadav.)

Background: Garlic (Allium sativum) from the family Amaryllidaceae is widely used in culinary and is reported to have potential anticancer, anti-diabetic, antimicrobial, and cardioprotective activities. Allium sativum agglutinin (ASA) is a bulb-type lectin (BTL) domaincontaining lectin isolated from garlic and has been studied for its various biological functions. Previous studies have reported the anti-cancer effects of ASA on histiocytic lymphoma (U937), promyelocytic leukemia (HL60), and oral cancer (KB)., Methods: In this study, we have purified and characterized ASA and evaluated it for its anticancer effects on other cancer cell lines. MTT assay and FACS analysis was done to corroborate the anticancer findings against cervical (HeLa) and lung cancer (A549) cell lines., Results: IC 50 value of 37 μg/ml in HeLa and a weak activity (26.4 ± 1.9% cellular inhibition at 100μg/ml treatment) in A549 were found in the MTT assay. FACS analysis further corroborated these findings and showed the apoptotic effects of ASA in these cell lines., Conclusion: Anticancer activity for members of bulb-type lectin (BTL) domain-containing lectins has been widely reported, and we hope that our study forms a basis for the development of ASA as a therapeutic agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The emergence of SARS-CoV-2 variants may cause resistance at the immunity level against current vaccines. Some emergent new variants have increased transmissibility, infectivity, hospitalization, and mortality. Since the administration of the first SARS-CoV-2 vaccine to a human in March 2020, there is an ongoing global race against SARS-CoV-2 to control the current pandemic situation. Spike (S) glycoprotein of SARS-CoV-2 is the main target for current vaccine development, which can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. The effectiveness of SARS-CoV-2 vaccines and other therapeutics developments are limited by the new emergent variants at the global level. We have discussed the emergent variants of SARS-CoV-2 on the efficacy of developed vaccines. Presently, most of the vaccines have been tremendously effective in severe diseases. However, there are still noteworthy challenges in certifying impartial vaccines; the stories of re-infections are generating more stressful conditions, and this needs further clinical evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Singh, Parveen and Yadav.)

Objectives: This retrospective study compared two mandibular reconstruction procedures-conventional reconstruction plates (CR) and patient-specific implants (PSI)-and evaluated their accuracy of reconstruction and clinical outcome., Methods: Overall, 94 patients had undergone mandibular reconstruction with CR ( n = 48) and PSI ( n = 46). Six detectable and replicable anatomical reference points, identified via computer tomography, were used for defining the mandibular dimensions. The accuracy of reconstruction was assessed using pre- and postoperative differences., Results: In the CR group, the largest difference was at the lateral point of the condyle mandibulae (D2) -1.56 mm (SD = 3.8). In the PSI group, the largest difference between preoperative and postoperative measurement was shown at the processus coronoid (D5) with +1.86 mm (SD = 6.0). Significant differences within the groups in pre- and postoperative measurements were identified at the gonion (D6) [ t (56) = -2.217; p  = .031 <.05]. In the CR group, the difference was 1.5 (SD = 3.9) and in the PSI group -1.04 (SD = 4.9). CR did not demonstrate a higher risk of plate fractures and post-operative complications compared to PSI., Conclusion: For reconstructing mandibular defects, CR and PSI are eligible. In each case, the advantages and disadvantages of these approaches must be assessed. The functional and esthetic outcome of mandibular reconstruction significantly improves with the experience of the surgeon in conducting microvascular grafts and familiarity with computer-assisted surgery. Interoperator variability can be reduced, and training of younger surgeons involved in planning can be reaching better outcomes in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Möllmann, Apeltrath, Karnatz, Wilkat, Riedel, Singh and Rana.)

The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been proposed. These medicines include inhibitors of serine protease TMPRSS2 and angiotensin converting enzyme 2 (ACE2). The S protein of SARS-CoV-2 binds to the receptor in host cells. ACE2 inhibitors block TMPRSS2 and S protein priming, thus preventing SARS-CoV-2 entry to host cells. Moreover, antiviral medicines (including the nucleotide analogue remdesivir, the HIV protease inhibitors lopinavir and ritonavir, and wide-spectrum antiviral antibiotics arbidol and favipiravir) have been shown to reduce the dissemination of SARS-CoV-2 as well as morbidity and mortality associated with COVID-19.

Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA -mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1 - or BRCA2 -associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer. This review covers the current results of clinical trials testing and future directions for the field of PARP inhibitor development.

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.

The current study was designed to analyse the effects of experimental induction of enterotoxaemia through intra-duodenal inoculation of C. perfringens type D culture isolated from spontaneous outbreaks in goats. Twenty goats (6-9 month age) were divided into four groups and C. perfringens type D culture was inoculated intra-duodenally as per following: Group-I (whole cultures-WC), group-II (culture supernatant-CS), group-III (washed cells-WS), and group-IV (uninfected control-C). The treated animals were sacrificed after 72 h post infection (hpi), and necropsy showed gross changes including haemorrhages and congestion in the ileal and colon mucosa, pulmonary congestion and edema in lung. Kidney, brain and spleen exhibited severe to moderate congestion. Microscopic changes like haemorrhages, degenerative and necrotic changes in the mucosal epithelium of intestine and haemorrhages in kidney parenchyma were observed in the H&E stained sections. Lung alveolar sacs were filled with proteinaceous fluid. Immunohistochemistry revealed positive immunolabelling for etx (epsilon toxin) in the mucosa of intestine in WC and CS group. Control animals did not exhibit any significant gross or microscopic changes. PCR amplification of DNA extracted from intestinal tissues of WC and CS groups showed positive for etx gene demonstrating the production of epsilon toxin. Transcriptional responses in experimental groups were assessed by quantitative reverse transcription real time PCR (qRT-PCR). Genes including IL-1β and IL2 showed up-regulation in all the experimental groups (WC, CS&WS). Specifically the toxin-based experimental groups (WC&CS) showed up-regulation of the gene responsible for chemotaxis viz. IL-8, while the washed cells group (WS) showed higher transcriptional response to Cathepsin-L (Cat-L) gene denoting the acute inflammatory response due to neutrophil elastase activity. These results take a cue on the evolving nature of the enterotoxaemia in goats due to various strains circulating in the field. The host response and its modulation due to the novel enterotoxaemia strains throws light on the current challenges in efficient control of the disease in goats., (© 2021 Published by Elsevier Ltd.)

Since December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a global health concern. The transmission method is human-to-human. Since this second wave of SARS-CoV-2 is more aggressive than the first wave, rapid testing is warranted to use practical diagnostics to break the transfer chain. Currently, various techniques are used to diagnose SARS-CoV-2 infection, each with its own set of advantages and disadvantages. A full review of online databases such as PubMed, EMBASE, Web of Science, and Google Scholar was analyzed to identify relevant articles focusing on SARS-CoV-2 and diagnosis and therapeutics. The most recent article search was on May 10, 2021. We summarize promising methods for detecting the novel Coronavirus using sensor-based diagnostic technologies that are sensitive, cost-effective, and simple to use at the point of care. This includes loop-mediated isothermal amplification and several laboratory protocols for confirming suspected 2019-nCoV cases, as well as studies with non-commercial laboratory protocols based on real-time reverse transcription-polymerase chain reaction and a field-effect transistor-based bio-sensing device. We discuss a potential discovery that could lead to the mass and targeted SARS-CoV-2 detection needed to manage the COVID-19 pandemic through infection succession and timely therapy., (©2021 JOURNAL of MEDICINE and LIFE.)

COVID-19 induced pandemic situations have put the bio-medical waste (BMW) management system, of the world, to test. Sudden influx, of COVID-infected patients, in health-care facilities, has increased the generation of yellow category BMW (Y-BMW) and put substantial burden on the BMW-incineration units of India. This study presents the compromising situation of the BMW-incineration units of India, in the wake of COVID-19 pandemic, from 21st March 2020 to 31st August 2020. This analysis revealed that on an average each COVID-infected patient in India generates approximately 3.41 kg/d of BMW and average proportion of Y-BMW in it is 50.44%. Further, it was observed that on 13th July 2020, the total Y-BMW, generated by both the normal and COVID-infected patients, fully utilized the BMW-incineration capacity of India. Also, it was made evident that, during the study period, BMW-incineration emitted several pollutants and their concentration was in the order: NO x  > CO > SO x  > PM > HCl > Cd > Pb > Hg > PCBs > Ni > Cr > Be > As. Subsequently, life time cancer risk assessment depicted that with hazard quotient >10 -6 , Cd may induce carcinogenic health impacts on both the adults and children of India. Therefore, to mitigate the environmental-health impacts associated with the incineration of BMW, evaluation of various options, viz., alternative technologies, substitution of raw materials and separate treatment of specific wastes, was also done. It is expected that the findings of this study may encourage the global auditory comprising scientific community and authorities to adopt alternate BMW-management strategies during the pandemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of the present study was to analyze the size of the preoperatively calculated defect volume of MRONJ patients (medication-related osteonecrosis of the jaw) and to develop a computer-aided tool based on techniques of AI (artificial intelligence) that facilitates diagnostics of MRONJ. For this purpose, on the basis of 3D (three-dimensional) data sets of 175 MRONJ patients, the outline of the necrosis was marked with the software iPlan 3.0.5 (BrainLAB AG) thus determining the respective volume. The correlation of this volume with other 31 collected parameters was analyzed retrospectively. There was a significant correlation between the defect volume on the one hand, and the MRONJ stage, the number of performed operations, and the therapy invasiveness on the other hand. Furthermore, it could be shown that in one third of the cases no defects could be recognized in the 2D imaging by panoramic radiograph,  while in the 3D data sets defects already had been demarcated. On the basis of these data, a computer-aided tool based on the principles of AI was developed and validated, which might allow the automated calculation of the 3D defect extension and classification of the MRONJ cases into a ranking system. In conclusion, preparation of a 3D image can be recommended for reliably making the diagnosis "MRONJ." Moreover, knowledge of the exact defect volume serves as a decision-making aid with regard to the choice of therapy, ensures intraoperative certitude, and allows an assessment of the prognosis., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Study Design: This study presents a case-control study of 33 patients who underwent secondary orbital reconstruction, evaluating techniques and outcome., Objective: Adequate functional and aesthetical appearance are main goals for secondary orbital reconstruction. Insufficient premorbid orbital reconstruction can result in hypoglobus, enophthalmos, and diplopia. Computer-assisted surgery and the use of patient-specific implants (PSIs) is widely described in the literature. The authors evaluate the use of selective laser-melted PSIs and hypothesize that PSIs are an excellent option for secondary orbital reconstruction., Methods: The sample was composed of 33 patients, previously treated with primary orbital reconstruction, presenting themselves with indications for secondary reconstruction (i.e. enophthalmos, diplopia, or limited eye motility). Computed tomography and/or cone beam data sets were assessed before and after secondary reconstruction comparing intraorbital volumes, infraorbital angles, and clinical symptoms. Clinical outcomes were assessed using a standardized protocol., Results: Results show a significant change in intraorbital volumes and a reduction of clinical symptoms after secondary reconstruction., Conclusions: Outcomes of this study suggest that secondary orbital reconstruction can be performed routinely using selective laser-melted PSIs and titanium spacers., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Lockdown is one of the prevalent tools that are used to control the spread of COVID-19 virus in India. Under the circumstances created during lockdown period, children are deprived from the social interaction and companionship; because of which, they are susceptible to psychiatric disorders. Therefore, in this study, efforts were to understand the impacts of lockdown on the mental status of the children of India and their specific causes., Study Design: It is a questionnaire-based study., Methods: A web-based questionnaire was prepared, and 400 parents from four districts of Punjab, India, namely, Ludhiana, Sahibzada Ajit Singh (SAS) Nagar, Sangrur and Ferozepur, were telephonically interviewed. Further, the information collected from the interviews was statistically analysed using Statistical Package for the Social Sciences (SPSS) software., Results: Findings from this study revealed that 73.15% and 51.25% of the children were having signs of increased irritation and anger, respectively; 18.7% and 17.6% of the parents also mentioned the symptoms of depression and anxiety, respectively, among their children, which were also augmented by the changes in their diet, sleep, weight and more usage of the electronic equipment. Children (~76.3%) persistently urge to go outdoors and play with their friends; therefore, they could lag in social development. Further, observations from Pearson's correlation revealed that during lockdown, children's mental health is significantly related to the area of their house, number of children in the family, qualification of their mother and socio-economic status of their family., Conclusions: This study made it evident that the mental health of the children residing in Punjab, India, was compromised during the lockdown period induced by the COVID-19 pandemic. Findings of this study may also trigger the international authorities to frame the guidelines of lockdown in the interest of mental health of their native children., (© 2020 John Wiley & Sons, Ltd.)

Breast cancer (BC) is the second most commonly diagnosed cancer in the world. BC develops due to dysregulation of transcriptional profiles, substantial interpatient variations, genetic mutations, and dysregulation of signaling pathways in breast cells. These events are regulated by many genes such as BRCA1/2, PTEN, TP53, mTOR, TERT, AKT, PI3K and others genes. Treatment options for BC remain a hurdle, which warrants a comprehensive understanding that establishes an interlinking connection between these genes in BC tumorigenesis. Consequently, there is an increasing demand for alternative treatment approaches and the design of more effective treatments. In this regard, it is crucial to build the corresponding transcriptional regulatory networks governing BC by using advanced genetic tools and techniques. In the past, several molecular editing technologies have been used to edit genes with several limitations. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR Associated Protein 9 (CRISPR/Cas9) recently received wise attention due to its potential in biomedical and therapeutic applications. Here, we review the role of various molecular signalling pathways dysregulated in BC development such as PTEN/PI3K/AKT/mTOR as well as BRCA1/BRCA2/TP53/TERT and their interplay between the related gene networks in BC initiation, progression and development of resistance against available targeted therapeutic agents. Use of CRISPR/Cas9 gene-editing technology to generate BC gene-specific transgenic cell lines and animal models to decipher their role and interactions with other gene products has been employed successfully. Moreover, the significance of using CRISPR/Cas9 technology to develop early BC diagnostic tools and treatments is discussed here., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pandemic causing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally infected more than 50 million people and ∼1.2 million have succumbed to this deadly pathogen. With the vaccine trials still in clinical phases, mitigation of Coronavirus Disease 2019 (COVID-19) relies primarily on robust virus detection methods and subsequent quarantine measures. Hence, the importance of rapid, affordable and reproducible virus testing will serve the need to identify and treat infected subjects in a timely manner. Based on the type of diagnostic assay, the primary targets are viral genome (RNA) and encoded proteins. Currently, COVID-19 detection is performed using various molecular platforms as well as serodiagnostics that exhibit approximately 71% sensitivity. These methods encounter several limitations including sensitivity, specificity, availability of skilled expertise and instrument access. Saliva-based COVID-19 diagnostics are emerging as a superior alternative to nasal swabs because of the ease of sample collection, no interaction during sampling, and high viral titers during early stages of infection. In addition, SARS-CoV-2 is detected in the environment as aerosols associated with suspended particulate matter. Designing virus detection strategies in diverse samples will allow timely monitoring of virus spread in humans and its persistence in the environment. With the passage of time, advanced technologies are overcoming limitations associated with detection. Enhanced sensitivity and specificity of next-generation diagnostics are key features enabling improved prognostic care. In this comprehensive review, we analyze currently adopted advanced technologies and their concurrent use in the development of diagnostics for SARS-CoV-2 detection.

Brain function activity is regulated by several mechanisms of genetic and epigenetic factors such as histone modelling, DNA methylation, and non-coding RNA. Alterations in these regulatory mechanisms affect the normal development of neurons that causes Neuropsychiatric Disorders (ND). However, it is required to analyse the functional significance of neuropsychiatric disorders associated with a molecular mechanism to bring about therapeutic advances in early diagnosis and treatment of the patients. The CRISPR/Cas 9 (Clustered Regularly Interspaced Short Palindromic Repeats) genome editing tools have revolutionized multiple genome and epigenome manipulation targets the same time. This review discussed the possibilities of using CRISPR/Cas 9 tools during molecular mechanism in the ND as a therapeutic approach to overcome ND that is caused due to genetic and epigenetic abnormalities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The coronavirus (SARS-CoV-2) pandemic is a rapidly transmitting and highly pathogenic disease. The spike protein of SARS-CoV-2 binds to the surface of angiotensin-converting enzyme-2 (ACE2) receptors along the upper respiratory tract and intestinal epithelial cells. SARS-CoV-2 patients develop acute respiratory distress, lymphocytic myocarditis, disseminated intravascular coagulation, lymphocytic infiltration, and other serious complications. A SARS-CoV-2 diagnosis is conducted using quantitative reverse-transcription PCR and computed tomography (CT) imaging. In addition, IgM or IgG antibodies are used to identify acute and convalescent illness. Recent clinical data have been generated by health workers and researchers and have shown that there is an urgent requirement in the effective clinical and treatment of patients, as well as other developments for dealing with SARS-CoV-2 infection. A broad spectrum of clinical trials of different vaccines and drug treatment has been evaluated for use against SARS-CoV-2. This review includes the emergence of SARS-CoV-2 pneumonia as a way to recognize and eliminate any barriers that affect rapid patient care and public health management against the SARS-CoV-2 epidemic based on the natural history of the disease, its transmission, pathogenesis, immune response, epidemiology, diagnosis, clinical presentation, possible treatment, drug and vaccine development, prevention, and future perspective., (Copyright © 2020 Singh, Han, Choi and Yadav.)

Mastalgia affects premenopausal in which cyclical mastalgia affects up to 40% of women. In approximately 8% of these women, pain will be severe and interfere with their normal activities. oral tamoxifen widely used in the treatment of mastalgia is associated with a wide range of side effects. Topical tamoxifen has the potential to be a more efficacious and safer alternative with lower blood drug levels hence having lower systemic side effects. To compare reduction in the pain, nodularity and blood drug levels of tamoxifen using topical verus oral tamoxifen in cyclical mastalgia. Patients who presented to the surgery outpatient department with complaints of breast pain were provided with a breast pain evaluation questionnaire. Patients were randomized using a computer generated sequence into two groups with 75 participants in each group. In Group 1, the participants received topical tamoxifen gel and a placebo tablet for 3 months, and in Group 2, the participants received Oral Tab Tamoxifen 10 mg OD and a placebo gel for 3 months. They were provided with a Cardiff Breast Pain assessment chart and asked to mark the severity of their pain and response to treatment in the following month and asked to report to the investigator. Patients were called for review every month, and the pain chart was monitored and documented. The response to therapy (relief of pain) was assessed after 3 months of treatment and once more at the end of 6 months for recurrence. After completion of 1 month of treatment, blood sample was drawn to check for the blood drug levels. There is a significant difference of mean pain score between oral and topical tamoxifen groups (P < .001) at the end of 1 month, 3 months (P < .001), and 6 months (P < .001). There is a significant difference in the Nodularity found between oral and topical groups at presentation (P = .004), at 1 month (P = .003) and at 6 months (P < .001). There is a significant difference of mean blood tamoxifen level (ng/mL) in oral and topical tamoxifen groups (P < .001). From this study, we conclude that topical tamoxifen is more effective than oral tamoxifen treatment in reducing cyclical breast pain and decreasing breast nodularity with lesser side effects and lower recurrence rates., (© 2019 Wiley Periodicals, Inc.)

Coronaviruses are a group of enveloped RNA viruses that are diversely found in humans and now declared a global pandemic by the World Health Organization in March 2020. The population's susceptibility to these highly pathogenic coronaviruses has contributed to large outbreaks, evolved into public health events, and rapidly transmitted globally. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In the primary stage of severe acute respiratory syndrome coronavirus (SARS-COV-2) infection, the signs and symptoms are nonspecific, and many more cases have been observed than initially expected. Genome sequencing is performed regularly to identify genetic changes to SARS-COV-2, and vaccine development is focused on manufacture, production, and based on specific problems, and very few are available on recent developments in the prevention of outbreaks. The aim of this review article to explore recent updates on SARS-COV-2 in the context of pathogenesis during disease progression, and innate acquired mechanisms of defense, This includes advances in diagnostics, susceptibility, and severity of host-virus genome interactions, modes of transmission, active compounds being used in pre-clinical and clinical trials for the treatment of patients, vaccine developments, and the effectiveness of SARS-COV-2 prevention and control measures. We have summarized the importance of pathophysiology immune response, Diagnostics, vaccine development currently approaches explored for SARS-COV-2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

The latest breakthrough towards the adequate and decisive methods of gene editing tools provided by CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR Associated System), has been repurposed into a tool for genetically engineering eukaryotic cells and now considered as the major innovation in gene-related disorders. Nanotechnology has provided an alternate way to overcome the conventional problems where methods to deliver therapeutic agents have failed. The use of nanotechnology has the potential to safe-side the CRISPR/Cas9 components delivery by using customized polymeric nanoparticles for safety and efficacy. The pairing of two (CRISPR/Cas9 and nanotechnology) has the potential for opening new avenues in therapeutic use. In this review, we will discuss the most recent advances in developing nanoparticle-based CRISPR/Cas9 gene editing cargo delivery with a focus on several polymeric nanoparticles including fabrication proposals to combat microbial infections., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recent developments in the nucleic acid editing technologies have provided a powerful tool to precisely engineer the genome and epigenome for studying many aspects of immune cell differentiation and development as well as several immune mediated diseases (IMDs) including autoimmunity and cancer. Here, we discuss the recent technological achievements of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based RNA-guided genome and epigenome editing toolkit and provide an insight into how CRISPR/Cas9 (CRISPR Associated Protein 9) toolbox could be used to examine genetic and epigenetic mechanisms underlying IMDs. In addition, we will review the progress in CRISPR/Cas9-based genome-wide genome and epigenome screens in various cell types including immune cells. Finally, we will discuss the potential of CRISPR/Cas9 in defining the molecular function of disease associated SNPs overlapping gene regulatory elements., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Sialolithiasis is the most common cause of chronic sialadenitis of the submandibular gland (SMG). Symptomatic superficial lobe stones are often treated by submandibulectomy. A gland preserving operation allows for transoral stone removal through endoscopically assisted sialolithotomy. Herein, we provide clinical and sonographical follow-up data in patients who underwent sialolithotomy under general anesthesia., Materials and Methods: Sixty patients treated at the Department of Oral and Maxillofacial Surgery at Düsseldorf University Hospital for superficial lobe sialolithiasis of SMG were included in this study. All received transoral sialolithotomy under general anesthesia. Follow-up was conducted via standardized patient questionnaires, clinical examination, and B-mode and color Doppler sonography., Results: Mean patient age was 48.9 years. 56.6% of right and 43.4% of left SMG were affected. Mean follow-up was 45 months. Fifty-five of 59 detected stones could be removed. Mean operation time was 71 min. 3.3% of patients reported recurrent episodes of postoperative pain and 10% felt recurrent episodes of gland swelling. Persistent postoperative lingual nerve hypesthesia was described in one patient. No facial nerve damages occurred. Salivary flow rates remained reduced in most of the affected glands upon stone removal. Sonographical follow-up data of the previously affected SMG after intraoral endoscopy-assisted sialolithotomy showed a regular gland size in 70.8% of cases, a parenchyma free of inflammation in 93.8%, and without signs of fibrosis in 72.9% of cases. 68.7% of patients showed a regular structure of Wharton's duct at time of follow-up. In total, 89.6% of patients were diagnosed stone-free within both glands on follow-up. No case required subsequent submandibulectomy., Conclusions: Sialolithotomy of Wharton's duct for removal of stones from the SMG's superficial lobe is a promising alternative to submandibulectomy., Clinical Relevance: Reduction of postoperative morbidity through endoscopically assisted sialolithotomy for removal of superficial lobe stones from SMG., Trial Registration: Ethics Committee of Heinrich-Heine-University Düsseldorf (no. 5586).

Contemporary advances in technology have enabled the transfer of industrial laser melting technology to surgery, and its use can improve the accuracy of orbital restoration. The aim of this study therefore was to evaluate the accuracy of primary orbital reconstruction with the use of selective laser melted, patient-specific implants and navigation. A total of 100 patients with complex orbital fractures were included. Planned orbital volumes were compared with those achieved, and angles were compared with the unaffected side. Analysis included the overlay of postoperative on planned images (iPlan ® 3.0.5, Brainlab). The mean (SD) orbital volume of the unaffected side was 27.2 (2.8)ml in men and 25.0 (2.6)ml in women. Fractures that involved the posterior third of the orbital floor and comminuted fractures showed significant orbital enlargement (p=0.026). The mean (SD) reconstructed orbital volume was 26.9 (2.7)ml in men and 24.26 (2.5)ml in women. Three-dimensional analysis of the colour mapping showed minor deviations when compared with the unaffected side. The results suggest that a high degree of accuracy can be routinely achieved in these complex cases., (Copyright © 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Coenurus cerebralis is the larval stage of Taenia multiceps, which infects the muscles and brain of goats and, to a lesser extent, sheep. The resulting cerebral and non-cerebral infections caused by the larval form (metacestode) of this cestode are commonly known as coenurosis. A weak emaciated carcass of five months old female goat, on necropsy, revealed numerous parasitic cysts (n = 56, grossly visible) in the visceral cavity including heart, diaphragm, thoracic cavity, abdominal cavity and pelvic inlet. A large number of variable sized parasitic cysts were also observed embedded in the pericardium and myocardium causing functional damage to the heart. The parasite caused extensive tissue damage at gross and microscopic levels in the heart including traumatic destruction of the myocardium with degenerative and necrotic changes and infiltration of mononuclear cells. On parasitological examination, the cysts were identified as Coenurus cerebralis, as the scolices had characteristic four suckers and a rostellum with a double crown of hooks. Further confirmation was done using polymerase chain reaction targeting specific ND1 and CO1 genes. Phylogenetic analysis of CO1 and ND1 genes showed a major branch comprising two clades of T. multiceps grouped as separate entities with the first clade showing T. multiceps/Coenurus cerebralis native CIRG strain (cerebral) being placed in proximity to T. multiceps/Coenurus cerebralis CIRG strain (non-cerebral/visceral) compared to the Chinese strains of T. multiceps. The phylogenetic analysis of ND1 and CO1 genes of C. cerebralis of cerebral and non-cerebral isolates revealed close proximity but expressed in two different disease forms (i.e., visceral coenurosis and neural coenurosis) which indicated that they were very close divergent from a common ancestor. On the basis of the observations it was concluded that goat died due to cardiac dysfunction resulting from severe systemic infection of metacestode of T. multiceps was closely related to isolate that caused neural coenurosis in another goat. Based on the sequencing analysis and phylogenetic information, the possible differences in the clinical manifestation (neural or visceral) could be attributed to the pathogenesis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The authors hypothesize that histopathological characteristics of basal cell carcinomas of the head and neck (BCCHN) have changed over time and the correlation of BCCHN localization and histological tumour type can help improving the number and quality of necessary therapeutic interventions. Information of 222 patients with 344 BCCHN was gained. Descriptive measures were compared to prior studies to prove whether or not characteristics of basal cell carcinomas or patients have changed over time. Afterwards descriptive measures were correlated with number of conducted operations to evaluate if tumour localization, histological tumour type and number of operations depend on one another. Aggravating factors which lead to a higher number of operations were older age, greater size of BCCHN, adjacent elastosis, the localizations eye, ear and nose and histological tumour types morpheaform and nodularulcerated . In comparison to earlier studies characteristics of BCCHN and patients showed positive developments because of grown awareness of BCCHN. Furthermore, our correlations demonstrate that therapeutic results of BCCHN treatment are continuously improving. Nevertheless, treatment of aggressive morpheaform BCCHN in combination with distinctive patient characteristics still needs improvement., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.