Metal-Free Catalysis in C-C Single-Bond Cleavage: Achievements and Prospects.

This review article emphasizes the C-C bond cleavage in organic synthesis via metal-free approach. Conventional organic synthesis mainly deals with the reactive π bonds and polar σ bonds. In contrast, the ubiquitous C-C single bonds are inherently stable and are less reactive, which poses a challenge to synthetic chemists. Although inert, such C-C single-bond cleavage reactions have gained attention amongst synthetic chemists, as they provide unique and more straightforward routes, with significantly fewer steps. Several review articles have been reported regarding the activation and cleavage of C-C bonds using different transition metals. However, given the high cost and toxicity of many of these metals, the development of strategies under metal-free conditions is of utmost importance. Though many research articles have been published in this area, no review article has been reported so far. Herein, we discuss the reactions in a more concise way from the year 2012 to today, with emphasis on important reactions. Mechanisms of all the reactions are also well addressed. We believe that this review will be beneficial for the readers who work in this field.

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicated in advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2 positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-East India and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of 68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examination from September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational (epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved, standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters. Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantly higher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patients with well differentiated histology and was more common in patients with stage II and III diseases, but neither of the associations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours (56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patients with locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlated significantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expression is recommended to provide a therapeutic advantage in Indian patients.

Effect of probiotic Pediococcus acidilactici FT28 on growth performance, nutrient digestibility, health status, meat quality, and intestinal morphology in growing pigs.

AIM: The experiment was conducted to evaluate the effect of swine-origin probiotic Pediococcus acidilactici FT28 on growth, nutrient utilization, health status, meat quality and intestinal morphology in growing female pigs. MATERIALS AND METHODS: Pigs (n=27) were distributed into three groups (3 replicates of 3 each) and supplemented with basal diet either without probiotics (C) or with a probiotic of dairy-based (Lactobacillus acidophilus NCDC-15; TLact) or swine based (P. acidilactici FT28; TPedic). The probiotics were fed as fermented feed at 200 g/pig/day. At the end of the trial, six pigs from each group were selected for metabolism trial and then sacrificed to determine meat quality and intestinal morphology. RESULTS: Supplementation of both probiotics improved growth performance, whereas feed intake, digestibility of CP and N retention were better (p<0.05) in P. acidilactici FT28-fed group. However , the digestibility of dry matter (DM), organic matter (OM), ether extracts (EE), crude fiber and nitrogen free extract did not show any significant effect on probiotic supplementation. The serum A: G ratio, triglyceride, and cholesterol level were also improved (p<0.05) in TPedic group compared to other treatment groups. Both probiotic supplementations showed lower (p<0.05) serum glucose level with similar protein and albumin value, which indicated good utilization of feed as well as health status of growing pigs. Dressing percentage, vital organ weight, and EE of loin meat were higher (p<0.05) in probiotic-supplemented groups compared to control. However, P. acidilactici FT28-fed animals showed higher (p<0.05) CP and total ash percentage of meat without affecting pH, water holding capacity, and extract release volume of loin muscle. The villi height and crypt depth were better in both supplemented groups compared to control. CONCLUSION: Results of the present study revealed that P. acidilactici FT28 could serve as better probiotic source in swine production for the better utilization of CP and N-retention in meat with improved health status and intestinal morphology.

Development of a novel surface assisted volume negative hydrogen ion source.

H- ion based neutral beam injector is a critical heating and current drive system in a fusion reactor. However, the present H- ion source configuration has limitations in terms of production, extraction, cesium (Cs) inventory and management. To overcome these limitations, a proof-of-principle experiment based on a novel concept regarding surface assisted volume H- ions production by sprinkling Cs coated tungsten (W) dust grains (low work function surface) into a hydrogen plasma is carried out. Four different diagnostics have been used to validate the concept. The H- ion fraction is estimated from (a) Langmuir probe diagnostic, (b) phase velocity of ion acoustic waves, (c) dust current and confirmed by the measurement of (d) Balmer line ratio. The measured H- ion fraction with respect to the plasma density for different discharge conditions varies from ~0.2 to 0.3 in presence of Cs coated W dust particles. The experimental results show good agreement with the theoretical estimation.

Correlation between salivary and serum anti-desmoglein 1 and 3 antibody titres using ELISA and between anti-desmoglein levels and disease severity in pemphigus vulgaris.

ELISA for anti-desmoglein antibodies (Dsg) is commonly used for diagnosis and assessment of treatment response in pemphigus vulgaris (PV). The present study was conducted to assess the relationship between salivary and serum Dsg1 and Dsg3 levels, and whether salivary Dsg1 and Dsg3 levels correlate with clinical disease severity of oral mucosal lesions in PV. In total 43, patients with PV with predominantly mucosal involvement were recruited. Both serum and salivary samples were collected from the cases, and salivary samples were also collected from five controls. There was a statistically significant correlation between serum and salivary Dsg1 levels and between serum and salivary Dsg3 levels. There was no correlation between serum or salivary Dsg1 and Dsg3 levels with the objective component of the oral mucosal Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Serum Dsg1 levels significantly correlated with cutaneous ABSIS, but there was no correlation between cutaneous ABSIS and either salivary Dsg1, salivary Dsg3 or serum Dsg3. As salivary Dsg titres correlate with serum levels, saliva can serve as a simple and noninvasive alternative to serum for Dsg ELISA.

Effect of testicular tissue lysate on developmental competence of porcine oocytes matured and fertilized in vitro.

The objective of the present study was to investigate the effect of testicular tissue lysate (TTL) on developmental competence of germinal vesicle (GV) stage porcine oocytes. Two types of TTL were prepared through repeated freeze-thaw in liquid nitrogen, one from whole testicular tissue (wTTL) and other from either of four different sections of testes, namely just beneath the tunica albuginea (TA), from the transitional area between the seminiferous cord/tubules and the mediastinum testis (TR) and from the intermediate area (parenchymal tissue origin) and CE (cauda epididymis origin). The whole or section-wise TTL treatments were given for 44 hr during in vitro maturation (IVM). Oocyte maturation was done in either of the two media, namely defined (high-performance basic medium for porcine oocyte maturation, commercially available) and serum containing (TCM199). After maturation, oocytes were co-incubated with fresh spermatozoa for 6 hr and then transferred to embryo culture media. Treatment of GV stage oocytes with wTTL (1 mg/ml) increased the cleavage and morula percentage rate (69.23 ± 6.23 and 48.15 ± 6.77, respectively) than that of their control (58.33 ± 8.08 and 32.54 ± 5.53, respectively) in defined media, and in serum-containing media, cleavage and morula percentage rate were almost equal in both treatment (54.56 ± 7.79 and 34.70 ± 6.78, respectively) and control (59.52 ± 8.21 and 38.52 ± 6.54, respectively). However, effect of wTTL was not significant. In case of section-wise TTL supplements, TR section significantly (p < .01) improved cleavage and morula rate (58.43 ± 7.98 and 36.14 ± 6.89, respectively) followed by TA. In conclusion, present study indicates that IVM, in vitro fertilization and in vitro culture of embryo are improved in the presence of TTL, particularly its TR section. Further study is expected to reveal the principal components of TTL which may prove useful for IVM.

Circulating T-helper 17 cells and associated cytokines in psoriasis.

BACKGROUND: Recently, a new population of IL-17-producing CD4 T helper (Th) cells, named Th17, was identified and shown to be involved in various inflammatory and autoimmune diseases, including psoriasis. AIM: To determine the frequency of Th17 cells and related cytokines in peripheral blood of patients with psoriasis, and to analyse their association with disease severity. METHODS: This was a prospective study comprising 34 patients with psoriasis and 24 healthy controls. Clinicoepidemiological details of patients were recorded, and severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index. Circulating Th1 and Th17 cells in untreated patients with psoriasis and healthy controls were quantified by flow cytometry. In sera collected from patients with psoriasis and healthy controls, concentrations of IL-17A and IL-23 were examined by ELISA. RESULTS: Increased frequencies of CD4+ IL-17A+ T cells were seen in peripheral blood of patients with psoriasis vulgaris (P < 0.001). Although serum IL-17A and IL-23 concentrations were higher in patients with psoriasis than in controls, the results did not reach statistical significance. We could not find any correlation between the studied T cells or related cytokines and the disease severity. CONCLUSION: Increased serum levels of circulating Th17 cells and related cytokines may contribute to the cutaneous pathology of psoriasis, as well as the inflammatory process that is a hallmark of psoriasis.

Cancer and cure: A critical analysis.

Cancer is one of the most dreaded diseases of the 20th century and spreading further with continuance and increasing incidence in the 21st century. The situation is so alarming that every fourth person is having a lifetime risk of cancer. India registers more than 11 lakh new cases of cancer every year, whereas, this figure is above 14 million worldwide. Is cancer curable? The short answer to this question is "Yes." In fact, all cancers are curable if they are caught early enough. Cancer cells continue to grow unless one of four things occur: (1) The cancerous mass is removed surgically; (2) using chemotherapy or another type of cancer-specific medication, such as hormonal therapy; (3) using radiation therapy; or (4) the cancer cells shrink and disappear on their own.

Optic nerve involvement in childhood onset systemic lupus erythematosus: Three cases and a review of the literature.

The ocular system can be affected in systemic lupus erythematosus (SLE) in one third of patients. However, optic nerve involvement is relatively uncommon, but is more so in pediatric SLE patients, where it can occur in 1% of cases. We report three children with SLE who presented with optic nerve involvement. Two children had optic neuritis, with optic neuritis being the first manifestation in one child. The third child had ischaemic optic neuropathy secondary to antiphospholipid syndrome. A careful work up for SLE should be performed in every child with optic nerve disease. Prompt diagnosis and early treatment results in a better prognosis.

Childhood lupus nephritis in a developing country-24 years' single-center experience from North India.

OBJECTIVE: Data on outcome of childhood lupus nephritis from developing countries are sparse. This study looks at outcome in children with lupus nephritis from a federal government-funded teaching hospital in North India. METHODS: This study included children less than 14 years of age with lupus nephritis who presented to a single center during a period of 24 years (1991 to 2013). Data on clinical characteristics and outcome were extracted from medical records. The primary outcome was actuarial survival (time-to-death) and secondary outcome was actuarial renal survival using Kaplan-Meier analysis. A worst-case scenario that assumed children who were lost to follow-up as having either died or gone into end-stage renal disease was also calculated. Log-rank test and Cox-regression were used to assess difference in survival by histological class and predictors of poor outcome, respectively. RESULTS: This study included 72 children, with a female:male ratio of 3:1, mean (±SD) age at onset of lupus 9.3 (±2.4) years and mean (±SD) time from onset-to-nephritis being 9.4 (±12.6) months. Renal biopsy was conducted in 53 children. The most common histological class was class IV (35 children). Mortality occurred in 22 children (30%), with half of these occurring at presentation. The two important causes of death were infection and end-stage renal disease. Actuarial survival was 81%, 67% and 59% at one, five and 10 years, respectively. In the worst-case scenario, actuarial survival was 72%, 53% and 38%, respectively. Renal survival was 96%, 89% and 78% (worst-case scenario 86%, 73% and 52%) at one, five and 10 years, respectively. There was no difference in survival by histological class. On univariate analysis, serum creatinine at presentation (hazard ratio = 2.2 (95% CI 1.3-3.9)) and serious infection (hazard ratio 7.9 (95% CI 2.6-23.5)) were statistically significant predictors of time-to-death. CONCLUSION: Outcome of children with lupus nephritis from India is worse than developed countries. Nearly one-third of the children died, half at presentation, with common causes being infection and end-stage renal disease.

Prevalence of Aspergillus sensitisation in pulmonary tuberculosis-related fibrocavitary disease.

SETTING: Aspergillus complicates the course of healed pulmonary tuberculosis (PTB), causing aspergilloma and chronic pulmonary aspergillosis. Whether Aspergillus also causes allergic sensitisation in PTB-related fibrocavitary disease and bronchiectasis remains unknown. OBJECTIVE: To investigate the prevalence of Aspergillus sensitisation in healed fibrocavitary PTB. DESIGN: In a case-control design, consecutive symptomatic new referrals with PTB-related fibrocavitary disease underwent spirometry, Aspergillus skin test and computed tomography of the chest, determination of serum IgE levels (total and Aspergillus fumigatus-specific), serum precipitins against A. fumigatus and eosinophil count. Aspergillus sensitisation was defined as either a positive Aspergillus skin test or A. fumigatus IgE >0.35 kUA/l. RESULTS: A total of 100 subjects (50 PTB-related fibrocavitary disease, 50 controls) with a mean age of 40.8 years (standard deviation [SD] 12.2) were enrolled. Aspergillus sensitisation was present in 16 (32%) cases and two (4%) controls. Fourteen cases (one control) had IgE values >1000 IU/ml, while two cases manifested eosinophilia. Aspergillus precipitins were positive in 13 cases (two controls); of these, 8 did not have Aspergillus sensitisation. The presence of airflow obstruction on spirometry was significantly associated with Aspergillus sensitisation on univariate analysis (OR 4.96, 95%CI 1.36-18.03). CONCLUSIONS: There is a high prevalence of Aspergillus sensitisation in PTB-related fibrocavitary disease. The clinical relevance and therapeutic implications of this finding require further investigation.

Slow progressor of human immunodeficiency virus: 20 years follow-up of a case from North India.

A case of human immunodeficiency virus (HIV) infection from North India is described with a 20-year follow-up. Patient first reported in 1993 when he was detected HIV positive, remained healthy without treatment, married in 1999 and did not transmit the disease to his children or his wife and was lost to follow-up. He was thought to be an elite controller. After 15 years of the initial visit, his CD4 cells, however, were found to be low, with a viral load of 10,000/copies/ml. He was negative for human leukocyte antigen B57 and B27 alleles with a normal expression of CCR5 and CXCR4 on CD4 cells. Lymphocytes showed a significant production of tumour necrosis factor alpha and interferon γ, but not of interleukin (IL)-2, IL4 or IL10. It is possible that gut infection, common in India, could have triggered T cell activation in the ensuing years, resulting in activation of HIV. The case illustrates the significance of long-term follow-up of these patients for timely institution of anti-retroviral therapy.

Regulatory role of adrenergic neurotransmitters on the spontaneous muscular activity in the ruminant trematode Paramphistomum cervi (Paramphistomatidae).

The neuromuscular system of helminths is an important area for target identification and drug development. Many anthelmintics, namely ivermectin, levamisole, piperazine, pyrantel, praziquantel and organophosphates, produce paralysis of helminths by affecting their neuromuscular systems. The neuromuscular system of helminths is also an important area of research to identify some of the important differences between the neuromuscular physiology of helminths and mammals. The identification of differences would help in developing newer target-specific, safe and effective anthelmintics. The present study was carried out to investigate the effects of different adrenergic neurotransmitters (epinephrine, norepinephrine, dopamine, l-dopa) and their antagonists (propranolol and haloperidol) on the spontaneous muscular activity of isometrically mounted Paramphistomum cervi.

Antimicrobial potential of metabolites extracted from bacterial symbionts associated with marine sponges in coastal area of Gulf of Mannar Biosphere, India.

UNLABELLED: Marine coastal areas of India have vast diversity of sponges which harbours many endosymbiotic bacteria which are the source of many potential antimicrobial metabolites. This study focuses the screening and characterization of drug-producing bacteria symbiotically which are associated with marine sponges collected from Gulf of Mannar, South Coast India. Six different sponges were collected and they were identified on the basis of their morphology. The drug-producing isolates were screened by agar overlay method towards various clinical strains. The secondary metabolites were characterized and were found to be quinones, alkaloids, flavanoids and flavonyl glycosides. The metabolites showed significant inhibitory properties against clinical strains that were further identified as chromophoric and fluorophoric in nature. Ethyl acetate extracts of chromophore and floureophore substances showed significant inhibitory properties against Methicillin resistant Staphylococcus aureus (MRSA) and Salmonella typhi respectively. 16S rRNA gene sequencing of theses isolates revealed that chomophore-producing strain were closely related to Pseudomonas spp. RHLB12, isolated from Callyspongia spp. and floureophore-producing bacteria was related to Bacillus licheniformis T6-1 which was isolated from Haliclona spp. Hence, our study demonstrated that antimicrobial metabolites extracted from symbiotic bacteria associated with marine sponges have high therapeutic potential against many bacterial pathogens including multidrug-resistant strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study demonstrating antimicrobial potential of flurophoric and chromophoric metabolites extracted from bacterial biosymbionts associated with marine sponges. Our study has significant scope as Indian coastal area especially harbours vast varieties of sponges with novel secondary metabolites-producing organisms. The natural metabolites extracted from sponge-derived bacteria pave novel therapeutic remedy against various pathogens when most of them are emerged as extreme drug resistant superbugs.

Effect of propofol in altering pentylenetetrazol induced seizure threshold in rats.

The present study was undertaken to evaluate the role of propofol in altering pentylenetetrazol induced seizure threshold in rats. Total 42 Wistar rats were used to evaluate different parameters (onset of action, duration of seizure, seizure severity score and number of seizure) following propofol injection. The present results showed that there was significant reduction in the time required for onset of seizure in propofol treated groups following PTZ treatment. If treated with propofol alone (2 and 5 mg/kg), there was no significant difference as compared to controls. In seizure severity score assessment, there was no significant difference with various doses of propofol alone treated groups, but the difference was observed in propofol (2 and 5 mg/kg) treated groups following PTZ treatment. Duration of seizure also significantly increased in propofol (5 mg/kg) treated group, but at 2 mg/kg of propofol treatment, no significant difference was observed. The present results showed that propofol ameliorate seizure threshold and caused prolongation of duration of seizure. However, further study and trials are needed to confirm the present results.

Gender bias in renal transplantation: are women alone donating kidneys in India?

Previous studies have shown that women not only donate live-related and unrelated kidneys more often, but are also less likely to receive a live kidney than men. Few data are, however, available from developing countries. To study a possible gender imbalance in living donor (LD) renal transplantation in India, we retrospectively analyzed all LD renal transplantations performed at a single center between 2001 and 2005. Of the 682 recipients, 606 (88.9%) were males and 76 (11.1%) were females (P<.0001). There were 552 biologically related, 118 spousal, and 12 unrelated nonspousal donors. Among the donors, there were 451 (66.1%) females and 231 (33.9%) males (P<.001). Most of the live donations were contributed by mothers (32.1%). In the spousal group, the greatest gender disparity was observed with predominantly wives donating for their husbands (90.7% vs 9.3%). Complex social and economic factors are responsible for the overall gender imbalance. In conclusion, women represent a highly vulnerable group in LD renal transplantation. Awareness and changes in attitudes of the public as well as physicians are needed to eliminate this gender inequity.

Oncological emergencies--management guidelines for clinicians.

The authors in the present article have given a brief outline of oncological emergencies and discussed the management guidelines from clinical stand point.

Image-guided fine-needle aspiration cytology of deep-seated enlarged lymph nodes.

PURPOSE: To evaluate the role of image-guided fine-needle aspiration cytology (FNAC) of deep-seated lymph nodes. MATERIAL AND METHODS: Image-guided FNACs were performed on 242 patients of deep-seated lymph nodes which included thoracic, retroperitoneal and abdominal nodes. A sterile 3.5/5-MHz micro convex sector probe was used for localisation of the node. The FNAC was performed using a 0.7- to 0.9-mm needle with the stylet removed and attached to a 20-ml syringe and FNAC handle after the needle was visualised in the lesion. For each case a minimum of 4-5 smears were made, and two observers without bias interpreted the smears. RESULTS: A total of 242 patients were aspirated, of which 216 (90%) aspirations were US-guided and the remaining 26 (10%) were CT-guided. Adequate material for cytologic diagnosis was obtained in 208 (86%) patients with a similar diagnostic accuracy. The aspirate material was non-representative or scanty in 34 (14%) patients. The most common cytological diagnosis was tuberculosis/consistent with tuberculosis seen in 108 (45%) patients followed by metastasis (17%) and reactive hyperplasia (10%). Non-Hodgkin lymphoma was diagnosed in 22 (9%) patients. All patients were briefly followed for a period of 1 1/2 to 2 years (mean 1 year). CONCLUSION: Image-guided FNAC has a pivotal role, and is a cost-effective tool for establishing tissue diagnosis as a primary investigative modality. It is also helpful and accurate in follow-up of patients with a known malignant disease, thereby avoiding surgical intervention.

Fine needle aspiration cytology of metastatic scalp nodules.

OBJECTIVE: To analyze cases of palpable cutaneous/ subcutaneous scalp nodules and evaluate the clinical features and role of fine needle aspiration cytology (FNAC) in their diagnosis. STUDY DESIGN: A total of 1,022 cases of metastatic malignancies at various sites were analyzed over a period of two years. FNAC was performed as a routine outpatient procedure for palpable lesions and under ultrasound or computed tomographic guidance for nonpalpable, internal sites. Histologic correlation was done when possible. RESULTS: Eighteen cases were found to be metastatic scalp nodules. The scalp as a metastatic site constituted 1.76% of all metastatic sites, 7.72% of extranodal sites, and 15.3% of extranodal and extrahepatic sites. Of the 18 cases, 7 (38.9%) had primaries in the head and neck region (thyroid, 3; orbit, 1; tonsil, 1; tongue, 1; and parathyroid, 1). Cutaneous/subcutaneous metastasis was encountered in 58 patients, and the 18 cases of scalp metastasis constituted 31.03% of all cutaneous sites. CONCLUSION: Careful examination of the skin on the entire body, with particular attention to the scalp, should be done when a primary internal malignancy or recurrence is suspected. FNAC is a very helpful and cost-effective modality in determining the nature of such lesions.