Microbiological acceptance criteria, specifications of herbal drugs and herbal drug preparations in various pharmacopoeias: a global scenario.

PURPOSE: A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region. METHOD: In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated. RESULTS: It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination. CONCLUSION: From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Percutaneous electrical nerve stimulation in post-mastectomy neuropathic pain: A case report.

Post-mastectomy pain syndrome (PMPS) is a type of chronic postsurgical pain that can be severe, debilitating and frequently encountered in clinical practice. Multiple studies have focused on prevention, identifying risk factors and treating this condition. Nonetheless, PMPS remains a complex condition to treat effectively. In this case report, we describe the use of percutaneous electrical nerve stimulation in a breast cancer patient who experienced PMPS refractory to conventional treatments.

Numerical Analysis of Coronavirus Detection Using Photonic Crystal Fibre-Based SPR Sensor.

Coronavirus disease (COVID-19) is a worldwide health emergency caused by the coronavirus 2 (severe acute respiratory illness) (SARS-CoV-2). COVID-19 has a wide range of symptoms, making a definitive diagnosis difficult. The shortage of equipment for testing technology COVID-19 has resulted in long queues for COVID-19 testing, which is a major problem. COVID-19 testing is currently performed using sluggish and costly technology like single-photon emission computed tomography (SPECT), computed tomography (CT), positron emission tomography (PET), and enzyme-linked immunosorbent assay (ELISA). The gold standard test for diagnosing COVID-19 is real-time reverse transcriptase-polymerase chain reaction (RT-PCR), which necessitates highly skilled workers and has a lengthy turnaround time. However, rapid and affordable immunodiagnostic techniques (antigen or antibody tests) are also available with some trade off accuracy. Optical sensors are frequently employed in a variety of applications, because of their increased sensitivity, strong selectivity, rapid reaction times, and outstanding resolution. The use of photonic crystal fibre (PCF) is advantageous for the quick detection of the new coronavirus and is suggested with the use of a PCF-based (Au/BaTiO3/graphene) multilayered surface plasmon resonance (SPR) biosensor. The proposed sensor can quickly detect the COVID-19 virus in two different ligand-analyte environments: (i) the virus spike receptor-binding domain (RBD) as an analyte and monoclonal antibodies (mAbs) as a probe ligand, and (ii) monoclonal antibodies (IgG or IgM) as an analyte and the virus spike RBD as a probe ligand. The finite element method (FEM) is used to quantitatively examine the performance of the PCF-based multilayered SPR sensor.

An Extensive Review on ß-lactamase Enzymes and their Inhibitors.

ß-lactam antibiotics treat bacterial infections very effectively, but overuse and misuse have led to resistance. ß-lactamase enzymes hydrolyze ß-lactam antibiotics and are the primary cause of resistance in bacteria. Bacteria evolve and clinically mutate to produce such ß -lactamase enzymes, which could hydrolyze newly discovered antibiotics. Therefore, carbapenems are considered to be the last resort for antimicrobial treatment. Further, different inhibitors have been discovered to fight these evolving and mutating ß- lactamase enzyme resistance. These inhibitors are given in combination with the ß-lactam antibiotics to treat bacterial infections effectively. But in due course of time, it has been observed that bacteria develop resistance against this combination. This is an extensive review that discusses different classes of ß-lactamase enzymes, their mechanism of action, and the role of critical structural elements like loops and catalytically relevant mutations. Such mutations and structural modifications result in expanding the spectrum of activity, making these ß-lactamase enzymes resistant to the newly discovered ß-lactam antibiotics and their inhibitors. Detailed knowledge of such mutations, catalytically relevant structural modifications, related kinetics, and action mechanisms could help develop new inhibitors effectively. Further, a detailed discussion of available inhibitors against each class of ß-lactamase enzymes is also present.

Design and Characterization of Silver Nanoparticles of Different Species of Curcuma in the Treatment of Cancer Using Human Colon Cancer Cell Line (HT-29).

BACKGROUND: Cancer is a deadly disease responsible for worldwide mortality; usually, middle- and low-income countries have been more affected by cancer and are responsible for 70% of deaths. The present study was performed with the aim to design silver nanoparticles using three species of Curcuma, i.e., Curcuma longa, Curcuma aromatica, and Curcuma caesia. METHODS: The rhizomes of different plants were extracted with ethanol. The rhizome extracts were used to prepare silver nanoparticles. It was optimized at different pH, silver ion concentrations, and concentrations of plant extracts. The anticancer activity of prepared nanoparticles of C. longa, C. aromatica, and C. caesia was evaluated on a human colon cancer cell line (HT-29) using sulforhodamine B (SRB) assay. RESULTS: The percentage yield of C. longa, C. aromatica, and C. caesia was 11.34 g, 15.45 g, and 12.67 g, respectively. The results exhibited that the prepared nanoparticles were smooth and spherical. All the nanoparticles of rhizome extracts rescued the viability of HT-29 cells in a different extent. HT-29 cells were sensitive to prepared nanoparticles that induce more cytotoxicity towards cancer cells. CONCLUSION: Thus, the prepared silver nanoparticle of Curcuma species through green synthesis may help treat cancer with low toxicity.

Detailed investigation of catalytically important residues of class A ß-lactamase.

An increasing global health challenge is antimicrobial resistance. Bacterial infections are often treated by using ß-lactam antibiotics. But several resistance mechanisms have evolved in clinically mutated bacteria, which results in resistance against such antibiotics. Among which production of novel ß-lactamase is the major one. This results in bacterial resistance against penicillin, cephalosporin, and carbapenems, which are considered to be the last resort of antibacterial treatment. Hence, ß-lactamase enzymes produced by such bacteria are called extended-spectrum ß-lactamase and carbapenemase enzymes. Further, these bacteria have developed resistance against many ß-lactamase inhibitors as well. So, investigation of important residues that play an important role in altering and expanding the spectrum activity of these ß-lactamase enzymes becomes necessary. This review aims to gather knowledge about the role of residues and their mutations in class A ß-lactamase, which could be responsible for ß-lactamase mediated resistance. Class A ß-lactamase enzymes contain most of the clinically significant and expanded spectrum of ß-lactamase enzymes. Ser70, Lys73, Ser130, Glu166, and Asn170 residues are mostly conserved and have a role in the enzyme's catalytic activity. In-depth investigation of 69, 130, 131, 132, 164, 165, 166, 170, 171, 173, 176, 178, 179, 182, 237, 244, 275 and 276 residues were done along with its kinetic analysis for knowing its significance. Further, detailed information from many previous studies was gathered to know the effect of mutations on the kinetic activity of class A ß-lactamase enzymes with ß-lactam antibiotics.Communicated by Ramaswamy H. Sarma.

Insights into structure and activity relationship of clinically mutated PER1 and PER2 class A ß-lactamase enzymes.

PER1 and PER2 are among the class A ß-lactamase enzymes, which have evolved clinically to form antibiotic resistance and have significantly expanded their spectrum of activity. Hence, there is a need to study the clinical mutation responsible for such ß-lactamase mediated antibiotic resistance. Alterations in catalytic centre and Ω-loop structure could be the cause of antibiotic resistance in these ß-lactamase enzymes. Structural and functional alterations are caused due to mutations on or near the catalytic centre, which results in active site plasticity and are responsible for its expanded spectrum of activity in these class A ß-lactamase enzymes. Multiple sequence alignment, structure, kinetic, molecular docking, MMGBSA and molecular dynamic simulation comparisons were done on 38 clinically mutated and wild class A ß-lactamase enzymes. This work shows that PER1 and PER2 enzymes contains most unique mutations and have altered Ω-loop structure, which could be responsible for altering the structure-activity relationship and extending the spectrum of activity of these enzymes. Alterations in molecular docking, MMGBSA, kinetic values reveals the modification in the binding and activity of these clinically mutated enzymes with antibiotics. Further, the cause of these alterations can be revealed by active site interactions and H-bonding pattern of these enzymes with antibiotics. Met69Gln, Glu104Thr, Tyr105Trp, Met129His, Pro167Ala, Glu168Gln, Asn170His, Ile173Asp and Asp176Gln mutations were uniquely found in PER1 and PER2 enzymes. These mutations occurs at catalytic important residues and results in altered interactions with ß-lactam antibiotics. Hence, these mutations could be responsible for altering the structure-activity of PER1 and PER2 enzymes.Communicated by Ramaswamy H. Sarma.

Cervical Ectopic Pregnancy with Unsupervised Intake of Medications for Abortion: A Case Report.

Cervical ectopic pregnancy is the rarest form of ectopic pregnancy, where implantation occurs in the mucosa of the endocervical canal, below the internal os. Medical abortion is a safe and effective method of termination of early intrauterine pregnancies when carried out under the supervision of trained service providers. Unfortunately, unsupervised misuse of such methods can lead to grave morbidities, especially in ectopic pregnancies. We report a case of a 29-year-old female with cervical ectopic pregnancy, with a history of self-induced medical abortion. Her assumption that her pregnancy had been terminated caused a delay in seeking treatment, which led to complications during management. Ultrasonography revealed features suggestive of cervical ectopic pregnancy and evacuation of the fetus and placenta was done using curettage, during which she had uncontrolled severe vaginal bleeding leading to need of emergency hysterectomy. Keywords: case reports; cervical; ectopic pregnancy; hysterectomy; induced abortion.

Mutations responsible for the carbapenemase activity of SME-1.

SME-1 is a carbapenemase, produced by Serratia marcescens organism and causes nosocomial infections such as in bloodstream, wounds, urinary tract, or respiratory tract infections. Treatment of such infections becomes very complex due its resistance towards penicillins, cephalosporins, monobactams, and carbapenems. Resistance to such antibiotics is of great medical concern. The misuse and overuse of these antibiotics result in the clinical mutation and production of novel ß-lactamase enzymes such as SME-1, which show resistance to carbapenems. Class A contains most of the clinically significant extended spectrum of ß-lactamase enzymes and carbapenemases. In this study, class A ß-lactamase SME-1 sequence, structure, and binding were compared with naturally mutated class A ß-lactamase enzymes and a wild-type TEM-1. This study was performed for revealing mutations, which could be responsible for the carbapenemase activity of SME-1. The dynamic characteristics of SME-1 enzymes manifest a different degree of conservation and variability, which confers them to possess carbapenemase activities. Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations occur in SME-1 as compared to wild-type TEM-1. These mutated residues are present close to active site residues such as Ser70, Lys73, Ser130, Asn132, Glu166, and Asn170, which participate in the hydrolytic reaction of ß-lactam antibiotics. Furthermore, these mutated residues demonstrate altered interactions with the ß-lactam antibiotics (results in altered binding) and within themselves (results in active site structure alterations), which results in expanding the spectrum of activity of these enzymes. This study provides important insights into the structure and activity relationship of SME-1 enzymes. This is evident from the Ω-loop structure modification, which forms the wall of the active site and repositioning of residues involved in hydrolytic reactions, when present in the complex with meropenem in a stable state of MD simulation at 50 ns. Hence, Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations could result in an altered active site structure, binding, and activity of SME-1 with meropenem and thus become resistantant against meropenem, which is a carbapenem.

Prediction of suitable T and B cell epitopes for eliciting immunogenic response against SARS-CoV-2 and its mutant.

Spike glycoprotein of SARS-CoV-2 is mainly responsible for the recognition and membrane fusion within the host and this protein has an ability to mutate. Hence, T cell and B cell epitopes were derived from the spike glycoprotein sequence of wild SARS-CoV-2. The proposed T cell and B cell epitopes were found to be antigenic and conserved in the sequence of SARS-CoV-2 mutant (B.1.1.7). Thus, the proposed epitopes are effective against SARS-CoV-2 and its B.1.1.7 mutant. MHC-I that best interacts with the proposed T cell epitopes were found, using immune epitope database. Molecular docking and molecular dynamic simulations were done for ensuring a good binding between the proposed MHC-I and T cell epitopes. The finally proposed T cell epitope was found to be antigenic, non-allergenic, non-toxic and stable. Further, the finally proposed B cell epitopes were also found to be antigenic. The population conservation analysis has ensured the presence of MHC-I molecule (respective to the finally proposed T cell) in human population of most affected countries with SARS-CoV-2. Thus the proposed T and B cell epitope could be effective in designing an epitope-based vaccine, which is effective on SARS-CoV-2 and its B.1.1.7mutant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13721-021-00348-w.

Water activity and biomass estimation using digital image processing in solid-state fermentation.

Water activity in biotechnological applications plays a vital role. Estimation and precise control of water activity will enhance the product. The objective here is to use digital image processing technique in MATLAB for the quantification of the biomass and water condensate on a horizontal surface. A model has been developed with the data produced experimentally in this study in abiotic conditions. Also, a comparative study has been given for the estimation of the water condensate produced. It was observed that at a particular threshold value the error rate is less than 30%. The result of experimental study was good, and it showed a linear relation with proposed model. Also, the similar experimental estimation was done in biotic conditions, and results are showing good agreement between experimental observation and the model developed. Further, this method could be used in solid state fermentation process for water activity estimation and low-cost biomass estimation.

Serratus anterior plane block for upper abdominal incisions.

Regional anaesthetic techniques for patients undergoing laparotomy have been shown to provide optimal postoperative analgesia and allow early mobilisation, and thus, enhance recovery. The serratus anterior plane block, first documented in 2013, has been suggested as a potential alternative to thoracic paravertebral and central neuraxial blockade for chest wall and upper abdominal incisions as it can provide analgesia from T2 to T9. Although there are published cases of this block being used for chest wall analgesia, there are currently no published cases of this block being used for abdominal incisions. We report our experience with two patients, using ultrasound-guided serratus anterior plane blockade with catheter insertion following laparotomy.

Obstructive sleep apnea as a risk factor associated with difficult airway management - A narrative review.

STUDY OBJECTIVE: The association between obstructive sleep apnea (OSA) and difficult airway had been studied in various clinical trials but the relationship between the two conditions has not been clearly established. The objective of this narrative review is to determine if OSA is a risk factor associated with difficult airway. DESIGN: The OVID Medline in process, Medline (vis Pub Med), EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS were searched up to April 2016 using specific keywords. Inclusion criteria were: [1] airway management in patients with a diagnosis of OSA, [2] comparison of airway management between OSA and non-OSA patients, [3] publications or abstracts in the English language. The incidence of difficult airway between OSA and non-OSA patients was compared using Chi-square analysis or Fisher's exact test. MAIN RESULTS: Ten studies were included in the final review. Overall, the incidence of difficult tracheal intubation was higher in OSA patients versus non-OSA patients [56/386 (14.5%) vs. 69/897 (7.7%); P=0.0002]. OSA patients also have a higher incidence of difficult mask ventilation [115/4626 (2.5%) vs. 471/64,684 (0.7%); P<0.0001]. Compared to non-OSA patients, OSA was not associated with difficulty in the use of a supraglottic airway (SGA) device [10/663 (1.5%) vs. 162/15,171 (1.1%); P=0.38]. No studies compared difficult surgical airway in OSA and non-OSA patients. CONCLUSIONS: OSA was found to be a risk factor associated with difficult tracheal intubation and difficult mask ventilation. There was no association between OSA and difficult SGA use.

Molecular characterization of phytoplasma of 16SrI-B group association with Acalypha indica in India.

The typical phytoplasma symptoms of little leaf, yellowing, chlorosis, witches' broom, and stunting growth were observed on Acalypha indica plants during the field survey conducted at Lucknow and surrounding districts in year 2015-2016. To confirm the association and possibility of phytoplasma etiology, PCR assays were performed using universal primer pairs (P1/P6) and nested primer pairs (R16F2n/R2) in a total of five diseased samples along with control. A ~1.2 Kb amplicon was observed in nested PCR assay in diseased sample; however, no band was observed in control sample. The positive amplicons were sequenced for 16S rDNA and used for the virtual RFLP analysis and phylogenetic studies. BLASTn search showed 99-100% sequence identities with the 'Candidatus phytoplasma asteris' members (16SrI group) and phylogenetic analysis showed closest relationship with member of 16SrI group. The virtual RFLP assigned it as a member of 16SrI-B subgroup. This is the first record of phytoplasma association of 'Ca. P. asteris' subgroup B with A. indica in the world.

Accuracy in Blood Pressure Monitoring: The Effect of Noninvasive Blood Pressure Cuff Inflation on Intra-arterial Blood Pressure Values.

CONTEXT: Both invasive and noninvasive blood pressure (invasive arterial blood pressure [IABP] and noninvasive BP [NIBP]) monitors are used perioperatively; however, they often produce different values. The reason for this discrepancy is not clear, and it is possible that the act of cuff inflation itself might affect the IABP values, especially with the recurrent cycling of NIBP cuff. AIM: The aim of this study was to determine the effect of ipsilateral NIBP cuff inflation on the contralateral IABP values. SETTINGS AND DESIGNS: Prospective, observational study. MATERIALS AND METHODS: One hundred consecutive patients were studied. The NIBP device was set to cycle every 5 min for a total of 6 times. During each cuff inflation cycle, changes in IABP values from the arterial line in the contralateral arm were recorded. A total of 582 measurements were included for data analysis. STATISTICAL ANALYSIS: Chi-square, paired t-test, analysis of variance. RESULTS: Mean (± standard deviation) changes in systolic BP (SBP), diastolic BP, and mean BP with cuff inflation were 6.7 ± 5.9, 2.6 ± 4.0, and 4.0 ± 3.9 mmHg, respectively. We observed an increase of 0-10 mmHg in SBP in majority (73.4%) of cuff inflations. The changes in IABP did not differ between the patients with or without hypertension or with the baseline SBP. CONCLUSIONS: This study showed that there is a transient reactive rise in IABP values with NIBP cuff inflation. This is important information in the perioperative and intensive care settings, where both these measurement techniques are routinely used. The exact mechanism for this effect is not known but may be attributed to the pain and discomfort from cuff inflation.

Biodegradation and dissolution of polyaromatic hydrocarbons by Stenotrophomonas sp.

The aim of this work was to study the biodegradation capabilities of a locally isolated bacterium, Stenotrophomonas sp. strain IITR87 to degrade the polycyclic aromatic hydrocarbons and also check the preferential biodegradation of polycyclic aromatic hydrocarbons (PAHs). From preferential substrate degradation studies, it was found that Stenotrophomonas sp. strain IITR87 first utilized phenanthrene (three membered ring), followed by pyrene (four membered ring), then benzo[α]pyrene (five membered ring). Dissolution study of PAHs with surfactants, rhamnolipid and tritonX-100 showed that the dissolution of PAHs increased in the presence of surfactants.

The future of regional anesthesia education: lessons learned from the surgical specialty.

PURPOSE: Application of ultrasound in regional anesthesia has now become the standard of care and its use has shown to reduce complications. Nevertheless, gaining expertise in ultrasound-guided regional anesthesia requires the acquisition of new cognitive and technical skills. In addition, due to a reduction in resident working hours and enforcement of labour laws and directives across various states and countries, trainees perform and witness fewer procedures. Together, these issues create challenges in the teaching and learning of ultrasound-guided regional anesthesia in the time-based model of learning. PRINCIPAL FINDINGS: The challenges of teaching ultrasound-guided regional anesthesia are similar to those experienced by our surgical counterparts with the advent of minimally invasive surgery. In order to overcome these challenges, our surgical colleagues used theories of surgical skills training, simulation, and the concept of deliberate practice and feedback to shift the paradigm of learning from experience-based to competency-based learning. CONCLUSION: In this narrative review, we describe the theory behind the evolution of surgical skills training. We also outline how we can apply these learning theories and simulation models to a competency-based curriculum for training in ultrasound-guided regional anesthesia.

Fast-dissolving ocular films of riboflavin acetate conjugate for treatment of keratoconus in UVA-CXL procedure: ex vivo permeation, hemolytic toxicity and apoptosis detection.

BACKGROUND: Attempts to facilitate corneal epithelial penetration of riboflavin (Rb) without de-epithelization, so far, include the use of penetration enhancers, to devitalize corneal epithelium in order to disturb tight epithelial interjunctional complexes and zonulae occludentes. Though such approaches result in sufficient epithelial permeability of Rb to guarantee efficacy of CXL procedure, they lack the evidences of safety. Prodrug with improved lipophilicity targeted toward esterases and amidases has proven to be an effective and promising approach to overcome lipophilic corneal epithelial barrier. OBJECTIVES: Fast-dissolving ocular films of newly synthesized and characterized riboflavin lipid conjugate (RbLDC) were developed to overcome corneal epithelial barrier resistance for treatment of keratoconus. The safety concern of the film was assessed by in vitro hemolytic toxicity and in vitro apoptosis detection for its safe clinical use. RESULTS: The optimized film was tough, flexible and dissolved rapidly within 36.86 s in simulated tear fluid, pH 7.4. FE-SEM/EDX showed smooth surfaces of films and evidenced the quantitative elemental similarity, indicating drug homogeneity. The permeation profile of F18 demonstrated 13.28-fold increased permeation of RbLDC relative to Rb solution across intact cornea. Safety was confirmed by 3.74% hemolysis and 10% apoptosis. CONCLUSION: Safe and efficient RbLDC fast-dissolving ocular films capable of overcoming corneal epithelial barrier resistance to avoid surgical intervention of corneal epithelial debridement were developed.