Efficacy of a culturally adapted, cognitive behavioural therapy-based intervention for postnatal depression in British south Asian women (ROSHNI-2): a multicentre, randomised controlled trial.

BACKGROUND: Postnatal depression necessitates timely and effective interventions to mitigate adverse maternal and child outcomes in the short term and over the life course. British south Asian women with depression are often underserved and undertreated due to stigma, language barriers, and cultural barriers. This trial aimed to test the clinical efficacy of a culturally adapted, group cognitive behavioural therapy (CBT)-based intervention, the Positive Health Programme (PHP), delivered by non-specialist health workers for postnatal depression in British south Asian women. METHODS: This study was a randomised controlled trial, with culturally adapted recruitment and an internal pilot, comparing the PHP (intervention group) with treatment as usual (control group) in British south Asian women with postnatal depression. The study was conducted at five centres across the UK. Participants were aged 16 years or older, met the DSM-5 criteria for depression, and had infants aged 0-12 months. Randomisation (1:1) was stratified by centre, with a block size of 18, and was done through an independent remote telephone service. The PHP was delivered over 12 group sessions in 4 months. The primary outcome was recovery from depression (defined as a Hamilton Depression Rating Scale [HDRS] score ≤7) at 4 months after randomisation, and an assessment was also done at 12 months. Analysis was on an intention-to-treat basis including only participants with non-missing outcome data; we used a random-effects logistic regression model including fixed covariates for study site, baseline depression severity (HDRS score), parity, and years in education and a random coefficient for therapy group. This trial is registered with the ISRCTN (ISRCTN10697380). FINDINGS: Of the 9136 individuals approached for recruitment between Feb 8, 2017, and March 29, 2020, 4296 women were eligible for and consented to screening, among whom 732 screened positive and were randomly allocated: 368 (50%) to the PHP group and 364 (50%) to the control group. Participants were mostly of Pakistani (397 [55%] of 719 with available data), Indian (176 [24%]), or Bangladeshi ethnicity (127 [18%]), with an overall mean age of 31·4 years (SD 5·2), with their youngest infants having a mean age of 23·6 weeks (14·2). At 4 months from randomisation, the proportion of participants who showed recovery from depression on the HDRS was significantly higher in the PHP group (138 [49%] of 281) than in the control group (105 [37%] of 281; adjusted odds ratio 1·97 [95% CI 1·26-3·10]). At the 12-month follow-up, this difference was no longer significant (1·02 [95% CI 0·62-1·66]). INTERPRETATION: In British south Asian women with postnatal depression, a culturally adapted group CBT-based intervention could aid in quicker recovery from depression compared with treatment as usual. Further research is needed to identify how to sustain the treatment effect and establish strategies for scale-up. FUNDING: UK National Institute for Health and Care Research.

Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.

BACKGROUND: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. OBJECTIVE: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. MATERIALS AND METHODS: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. RESULTS: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1ß) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. CONCLUSION: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI.

Understanding zebrafish sleep and wakefulness physiology as an experimental model for biomedical research.

Sleep is a globally observable fact, or period of reversible distracted rest, that can be distinguished from arousal by various behavioral criteria. Although the function of sleep is an evolutionarily conserved behavior, its mechanism is not yet clear. The zebrafish (Danio rerio) has become a valuable model for neurobehavioral studies such as studying learning, memory, anxiety, and depression. It is characterized by a sleep-like state and circadian rhythm, making it comparable to mammals. Zebrafish are a good model for behavioral studies because they share genetic similarities with humans. A number of neurotransmitters are involved in sleep and wakefulness. There is a binding between melatonin and the hypocretin system present in zebrafish. The full understanding of sleep and wakefulness physiology in zebrafish is still unclear among researchers. Therefore, to make a clear understanding of the sleep/wake cycle in zebrafish, this article covers the mechanism involved behind it, and the role of the neuromodulator system followed by the mechanism of the HPA axis.

The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach.

Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases. The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur.

Pharmacological evaluation of the effects of enzymatically liberated fish oil on eosinophilic inflammation in animal models.

The inappropriate activation of eosinophils is a well-recognized driver of various human inflammatory diseases including asthma, chronic rhinitis, and various gastrointestinal diseases, including eosinophilic esophagitis. Steroids, both topical and systemic, remain a cornerstone of treatment and can be highly effective. However, some individuals suffer side effects, unresolved symptoms, or both. OmeGo, an enzymatically liberated fish oil, has demonstrated anti-inflammatory and antioxidant properties as well the reduction of the activation, migration, and survival of eosinophils. Two animal models of eosinophilic inflammation were used to further assess OmeGo's profile. A house dust mite model of induced asthma showed a significant reduction in eosinophilic lung inflammation compared to the negative control, linoleic acid. The CRTH2 antagonist fevipiprant showed a similar eosinophilic inhibitory profile to OmeGo. In contrast, cod liver oil had no impact on any measure of inflammation. A guinea pig model of mild intraperitoneal eosinophilia showed a significant reduction in eosinophil activity by OmeGo, assessed by chemotaxis and chemokinesis. Apolipoprotein A-IV, an endogenous human protein with anti-inflammatory actions, showed a similar but numerically lower effect. OmeGo therefore combines a consistent antieosinophilic action with the known anti-inflammatory effects of polyunsaturated fatty acids. Proof-of-concept studies in asthma are warranted.

Predictive and diagnostic test accuracy of ultrasonography in differentiating severe dengue from nonsevere dengue.

Diagnosing severe dengue from those who do not develop complication is important to prevent death. The objective of this systematic review was to evaluate the diagnostic test accuracy of ultrasonography in differentiating severe dengue from nonsevere dengue; and to assess if ultrasonography/ultrasound can be used as a predictive (screening) and diagnostic tool in the course of dengue infection. An electronic search was conducted in different databases via OvidSP platform. The included studies were cohort studies between 1995 and 2016 wherein cases were confirmed by dengue blood test. Severity of dengue was assessed and compared using standard WHO references. The methodological quality of the paper was assessed by two independent reviewers by using QUADAS-2 tool. In total 12 studies were included in this review after suitable screening. Overall, the studies included had a low and unclear risk of bias. Seven out of nine studies that compared severe dengue and nonsevere dengue, performed an ultrasonography on gallbladder (wall thickness cutoff-3 mm) with a sensitivity of 24.2-100% and a specificity of 13.2-98.7%. Other parameters such as splenic subcapsular fluid collection, pericardial fluid and hepatic subcapsular fluid collection had a specificity of >90%, though the sensitivity was poor. There were insufficient evidence that ultrasonography is able to differentiate severe dengue from nonsevere dengue accurately. The predictive and diagnostic value of ultrasonography could not be concluded due to insufficient reporting on the temporality of the ultrasonography performed with regard to the diagnosis. However, it might serve as an adjunct investigation to support the clinical diagnosis.

Single step in situ synthesis and optical properties of polyaniline/ZnO nanocomposites.

Polyaniline/ZnO nanocomposites were prepared by in situ oxidative polymerization of aniline monomer in the presence of different weight percentages of ZnO nanostructures. The steric stabilizer added to prevent the agglomeration of nanostructures in the polymer matrix was found to affect the final properties of the nanocomposite. ZnO nanostructures of various morphologies and sizes were prepared in the absence and presence of sodium lauryl sulphate (SLS) surfactant under different reaction conditions like in the presence of microwave radiation (microwave oven), under pressure (autoclave), under vacuum (vacuum oven), and at room temperature (ambient condition). The conductivity of these synthesized nanocomposites was evaluated using two-probe method and the effect of concentration of ZnO nanostructures on conductivity was observed. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and UV-visible (UV-VIS) spectroscopy techniques were used to characterize nanocomposites. The optical energy band gap of the nanocomposites was calculated from absorption spectra and ranged between 1.5 and 3.21 eV. The reported values depicted the blue shift in nanocomposites as compared to the band gap energies of synthesized ZnO nanostructures. The present work focuses on the one-step synthesis and potential use of PANI/ZnO nanocomposite in molecular electronics as well as in optical devices.

Role of Autophagy and Mitophagy in Neurodegenerative Disorders.

Autophagy is a self-destructive cellular process that removes essential metabolites and waste from inside the cell to maintain cellular health. Mitophagy is the process by which autophagy causes disruption inside mitochondria and the total removal of damaged or stressed mitochondria, hence enhancing cellular health. The mitochondria are the powerhouses of the cell, performing essential functions such as ATP (adenosine triphosphate) generation, metabolism, Ca2+ buffering, and signal transduction. Many different mechanisms, including endosomal and autophagosomal transport, bring these substrates to lysosomes for processing. Autophagy and endocytic processes each have distinct compartments, and they interact dynamically with one another to complete digestion. Since mitophagy is essential for maintaining cellular health and using genetics, cell biology, and proteomics techniques, it is necessary to understand its beginning, particularly in ubiquitin and receptor-dependent signalling in injured mitochondria. Despite their similar symptoms and emerging genetic foundations, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have all been linked to abnormalities in autophagy and endolysosomal pathways associated with neuronal dysfunction. Mitophagy is responsible for normal mitochondrial turnover and, under certain physiological or pathological situations, may drive the elimination of faulty mitochondria. Due to their high energy requirements and post-mitotic origin, neurons are especially susceptible to autophagic and mitochondrial malfunction. This article focused on the importance of autophagy and mitophagy in neurodegenerative illnesses and how they might be used to create novel therapeutic approaches for treating a wide range of neurological disorders.

Exploratory RCT of a group psychological intervention for postnatal depression in British mothers of South Asian origin - ROSHNI-D.

BACKGROUND: Postnatal depression (PND) is a global public health problem. There is a high prevalence of PND amongst ethnic minority women and major ethnic inequalities in mental health care in the U.K. Language and cultural barriers pose a significant challenge for access to timely treatment and interventions for British South Asian (BSA) women with PND. METHODS: The study, carried out in Manchester and Lancashire, England, was a two-arm single-blind exploratory randomised controlled trial. BSA women (N = 83) having a baby <12 months were randomised either to the group receiving the culturally adapted Positive Health Programme (PHP) (n = 42) or to the group receiving treatment as usual (TAU) (n = 41). Follow-up assessments were at 3 months (end of intervention) and 6 months after randomisation. RESULTS: Using an intention to treat analysis, there was no significant difference between PHP intervention and TAU groups in depression measured using Hamilton Depression Rating Scale both at 3 and 6 months follow up. Using modified intention to treat analysis, women who attended four or more sessions showed significant reduction in depression in the PHP group compared to the TAU group and the greater number of sessions attended was associated with greater reductions in depression scores. LIMITATIONS: The sample was relatively small and the study was conducted in one geographical area in Northwest England; hence, these results may not be generalizable to other regions and populations. CONCLUSION: The recruitment and trial retention figures highlighted the ability of the research team to engage with BSA women, having implications in planning services for this group. TRIAL REGISTRATION: Clinicaltrials.govNCT01838889.

Organosulphur and organoselenium compounds as emerging building blocks for catalytic systems for O-arylation of phenols, a C-O coupling reaction.

Diaryl ethers form an important class of organic compounds. The classic copper-mediated Ullmann diaryl ether synthesis has been known for many years and involves the coupling of phenols with aryl halides. However, the use of high reaction temperature, high catalyst loading and expensive ligands has created a need for the development of alternative catalytic systems. In the recent past, organosulphur and organoselenium compounds have been used as building blocks for developing homogeneous, heterogeneous and nanocatalysts for this C-O coupling reaction. Homogeneous catalytic systems include preformed complexes of metals with organosulphur and organoselenium ligands. The performance of such complexes is influenced dramatically by the nature of the chalcogen (S or Se) donor site of the ligand. Nanocatalytic systems (including Pd17Se15, Pd16S7 and Cu1.8S) have been designed using a single-source precursor route. Heterogeneous catalytic systems contain either metal (Cu or Pd) or metal chalcogenides (Pd17Se15 or Cu1.8S) as catalytically active species. This article aims to cover the simple and straightforward methodologies and approaches that are adopted for developing catalytically relevant organosulfur and organoselenium ligands, their homogeneous metal complexes, heterogeneous and nanocatalysts. The effects of chalcogen (S or Se) donor, halogen (Cl/Br/I) of aryl halide, nature (electron withdrawing or electron donating) of substituents present on the aromatic ring of aryl halides or substituted phenols and position (ortho or para) of substitution on the results of catalytic reactions have been critically analyzed and summarized. The effect of composition (Pd17Se15 or Pd16S7) on the performance of nanocatalytic systems is also highlighted. Substrate scope has also been discussed in all three types of catalysis. The superiority of heterogeneous catalytic systems (e.g., Pd17Se15 immobilised on graphene oxide) indicates the bright future possibilities for the development of efficient catalytic systems using similar or tailored ligands for this reaction.

Organosulphur, organoselenium and organotellurium compounds for the development of heterogeneous and nanocatalytic systems for Suzuki coupling.

Suzuki-Miyaura cross-coupling (SMC) is an extremely useful reaction in organic syntheses. During the last two decades, many researchers across the world have employed organochalcogen compounds in various ways for the development of catalytic systems for this reaction. Chalcogen-ligated molecular complexes have been designed using such compounds as ligands, and applied as homogeneous catalytic systems. During the period 2013-2022, various heterogeneous and nano-catalytic systems have also been developed using organosulphur, organoselenium and organotellurium compounds. The main advantages associated with such systems are their easy synthesis and air- and moisture-insensitivity. This article aims to provide insights into the synthetic methodologies pertaining to the preparation of (i) these catalytically relevant and useful compounds and (ii) the heterogeneous and nano-catalytic systems designed using them. Another major focus of the article is to rationalize and critically analyse the effect of chalcogen donor on the size, composition, morphology and shape of the nanostructure. A critical analysis of the applications of all such catalytic systems in Suzuki-Miyaura coupling is presented in detail. Various factors (e.g., temperature) which affect the catalytic performance are also rationalized. The effects of binding mode, ligand framework, chalcogen donor atom and metal are also covered, along with all other factors that influence the catalytic potential of the systems. Various other aspects such as green catalysis (in aqueous medium and in air), and use of non-conventional (ultrasonic radiation) energy sources are analysed. Applications of heterogeneous and nanocatalytic systems apart from Suzuki coupling are also highlighted, and challenges and future scope are elaborated.

Analysis of molecular genetic diversity in a representative collection of foxtail millet [Setaria italica (L.) P. Beauv.] from different agro-ecological regions of India.

Foxtail millet [Setaria italica (L.) P. Beauv.], an important crop of East Asia is known for its drought tolerance and was once an indispensible crop of vast rainfed areas in semi-arid regions in India. In India it is cultivated in Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu, Rajasthan, Madhya Pradesh, Uttar Pradesh and north eastern states. The grain finds use in several local recipes such as roti (bread), jaula, singal, sirol. Foxtail millet grain contains 12.3 % protein, 4.7 % fat, 60.6 % carbohydrates, and 3.2 % ash. The present study was conducted to analyse the genetic diversity among foxtail accessions from different states of India and a few exotic accessions using RAPD and ISSR techniques and identify diverse accessions for use in variety improvement programmes. A set of 125 foxtail millet accessions selected from 11 different agro-ecological regions of India were analyzed using random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) marker techniques. A total of 146 (115 RAPD and 31 ISSR) scoreable markers were generated with 16 RAPD and four ISSR primers. The dendrogram generated using Nei's genetic distances and principal component analyses revealed presence of two clusters and two subclusters in group I. The accessions from Andhra Pradesh, Karnataka, Maharashtra and Uttarakhand were more diverse since they were distributed in both the clusters. There was no clear geographical differentiation observable. The bootstrap support for the major groups identified was strong (above 80 %) indicating good statistical support. The average value of Nei and Li's genetic distance was lowest (0.081) for accessions from West Bengal while the collections from Karnataka showed highest dissimilarity (average genetic distance = 0.239). The average genetic distance for all 125 accessions together was 0.177 indicating presence of only moderate genetic diversity in the collections. The analysis of molecular variance indicated that only 2.76 % variation was explained by variations among the groups and 11.55 % among populations within groups. However the percentage of variation observed within populations was high (85.68). The value of Fst was observed to be very low (0.028) indicating low differentiation of the accessions analysed. The population genetic analysis carried out indicates that highest number of alleles per locus (1.745 ± 0.438) was observed for Andhra Pradesh with 35 accessions. When four eco-geographic regions were considered, the southern region comprising AP, Karnataka and TN showed the highest number of alleles per locus (1.787 ± 0.411). The value of Gst was lowest for south (0.123) and highest for central west (0.455). This indicated that all the landraces from south share common alleles. The gene flow between the accessions from different regions was also observed to be high with the highest migration (3.557) recorded for south.

Modeling of neotame and fructose thermochemistry: Comparison with mono and divalent metal ions by Computational and experimental approach.

The metal complexes can demonstrate various interesting biological activities in the human body. However, the role of certain metal ions for specific cell activities is still subject to debate. This study is aimed at comparing the thermochemical properties of neotame (artificial sweetener) and α, ß-fructose in gas phase and water medium. The interaction of α and ß-fructose, neotame with monovalent and divalent metal ions was studied and comprehended by density functional theory (DFT) using B3LYP functional, 6-311 + G (d, p) and D3 basis set. Metal ion affinities (MIA) values depicted that ionic radius of metal ions played an important role in the interaction of α, ß-fructose and neotame. The ∆G parameter was calculated to predict and understand the interaction of metal ions with α and ß-fructose, neotame. The results suggested that the presence of hydroxyl groups and oxygen atoms in sugar molecules acted as preferred sites for the binding and interaction of mono and divalent ions. For the first time computational study has been introduced in the present study to review the progress in the application of metal binding with sugar molecules especially with neotame. Moreover, voltammetric behaviour of neotame-Zn2+ was studied using cyclic and differential pulse voltammetry. The obtained results suggest that the peak at -1.13 V is due to the reduction of Zn2+ in 0.1 M phosphate buffer medium at pH 5.5. Whereas, addition of 6-fold higher concentration of neotame to the ZnCl2.2H2O resulted in a new irreversible cathodic peak at -0.83, due to the reduction of neotame-Zn2+ complex. The Fourier transform infrared spectroscopy (FTIR) results indicates that the ß-amino group (-NH) and carboxyl carbonyl (-C = O) groups of neotame is participating in the chelation process, which is further supported by DFT studies. The findings of this study identify the efficient chelation factors as major contributors into metal ion affinities, with promising possibilities to determine important biological processes in cell wall and glucose transmembrane transport.

Radium and other alpha emitters in prostate cancer.

223Radium (223Ra) is the first alpha-emitting therapy proven effective in human cancer. Prospective randomized trials indicate that 223Ra, which concentrates after intravenous injection in areas of osteoblastic metastatic disease, can prolong survival in bone-dominant castrate resistant prostate cancer patients. Though radium isotopic therapy is conceptually critical to demonstrate that alpha emitters can be safe and effective, 223Ra has inherent limitations given its restriction to bone metastatic disease. To overcome this limitation, targeted alpha therapy (TAT) is now being actively evaluated in prostate cancer, and other neoplasms. Key to TAT in prostate tumors in current studies is the overexpression of prostate specific membrane antigen (PSMA), a folate hydrolase expressed on the cell surface of malignant adenocarcinomas of the prostate. Using PSMA targeting (small molecules or antibodies), alpha emitting agents such as 225Actinium (225Ac) or 213Bismuth (213Bi) can be delivered to PSMA expressing tumors regardless of their metastatic location. Initial results from TAT in prostate cancer are highly promising and rapid development of these agents is anticipated in the years ahead assuming adequacy of isotope availability and appropriate clinical trial design. TAT may be develop as an independent approach, or synergize with a variety of other approaches including external beam radiation, hormonal therapies, chemotherapies, various radiation sensitizers, DNA repair inhibitors, and/or immune modulators. Clinical investigation opportunities in this field will rapidly increase in the years ahead.

Hyperbaric Oxygen Therapy: Side Effects Defined and Quantified.

Significance: Hyperbaric oxygen therapy (HBOT) is an important advanced therapy in the treatment of problem wounds, including diabetic foot ulcers and late effect radiation injury. HBOT remains among the safest therapies used today. Nonetheless, there are side effects associated with HBOT. It is important for providers to be able to identify, understand, and quantify these side effects for prevention, management, and informed consent. Recent Advances: The past two decades have seen significant advancements in our understanding of the underlying mechanisms of HBOT. This has led to a better understanding of the underlying reason for clinical benefit. It has also led to a better understanding of its side effects. Moreover, more recent literature allows for better quantification of these side effects. This review will highlight these side effects. Critical Issues: Wound healing in the case of problem nonhealing wounds requires the use of various advanced treatment modalities, including HBOT. HBOT has been shown to significantly improve healing rates in certain problem wounds, including advanced diabetic foot ulcers and late effect radiation injury. It is provided in a variety of clinical settings by providers with varying levels of expertise. It is important for those providing this therapy to understand the potential side effects. Future Directions: Research in HBOT has led to significant advancements in the area of wound healing. At the same time, there remains a variety of treatment protocols used at different institutions. It is important to quantify risk and benefit at different treatment pressures and times to better standardize treatment and improve patient care.

Interplay of the Quality of Ciprofloxacin and Antibiotic Resistance in Developing Countries.

Ciprofloxacin, a second generation broad spectrum fluoroquinolone, is active against both Gram-positive and Gram-negative bacteria. Ciprofloxacin has a high oral bioavailability and a large volume of distribution. It is used for the treatment of a wide range of infections including urinary tract infections caused by susceptible bacteria. However, the availability and use of substandard and spurious quality of oral ciprofloxacin formulations in the developing countries has been thought to have contributed toward increased risk of treatment failure and bacterial resistance. Therefore, quality control and bioequivalence studies of the commercially available oral ciprofloxacin formulations should be monitored. Appropriate actions should be taken against offending manufacturers in order to prevent the sale of substandard and spurious quality of ciprofloxacin formulations.

Electrochemical sensing platform amplified with a nanobiocomposite of L-phenylalanine ammonia-lyase enzyme for the detection of capsaicin.

The present study involves the development of a sensitive electrochemical biosensor for the determination of capsaicin extracted from chilli fruits, based on a novel signal amplification strategy using enzyme technology. For the first time, platinum electrode modified with multiwalled carbon nanotubes where phenylalanine ammonia-lyase enzyme was immobilized using nafion was characterized by attenuated total reflectance infrared spectroscopy, transmittance electron microscopy and thermo-gravimetric analysis supported by computational methods. Cyclic and differential pulse voltammetry measurements were performed to better understand the redox mechanism of capsaicin. The performance of the developed electrochemical biosensor was tested using spiked samples with recoveries ranging from 98.9 to 99.6%. The comparison of the results obtained from bare and modified platinum electrodes revealed the sensitivity of the developed biosensor, having a detection limit (S/N=3) of 0.1863µgmL(-1) and electron transfer rate constant (ks) of 3.02s(-1). Furthermore, adsorption and ligand-enzyme docking studies were carried out to better understand the redox mechanisms supported by density functional theory calculations. These results revealed that capsaicin forms hydrogen bonds with GLU355, GLU541, GLU586, ARG and other amino acids of the hydrophobic channel of the binding sites thereby facilitating the redox reaction for the detection of capsaicin.

Biosynthesis of ZnO nanoparticles using Jacaranda mimosifolia flowers extract: Synergistic antibacterial activity and molecular simulated facet specific adsorption studies.

The naturally occurring biomolecules present in the plant extracts have been identified to play an active role in the single step formation of nanoparticles with varied morphologies and sizes which is greener and environmentally benign. In the present work, spherical zinc oxide nanoparticles (ZnO NPs) of 2-4nm size were synthesized using aqueous extract of fallen Jacaranda mimosifolia flowers (JMFs), treated as waste. The microwave assisted synthesis was completed successfully within 5min. Thereafter, phase identification, morphology and optical band gap of the synthesized ZnO NPs were done using X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) and UV-Visible spectroscopy techniques. The composition of JMFs extract was analyzed by gas chromatography-mass spectrometry (GC-MS) and the ZnO NPs confirmation was further explored with fourier transform infrared spectroscopy (FTIR). The GC-MS results confirmed the presence of oleic acid which has high propensity of acting as a reducing and capping agent. The UV-Visible data suggested an optical band gap of 4.03eV for ZnO NPs indicating their small size due to quantum confinement. Further, facet specific adsorption of oleic acid on the surface of ZnO NPs was studied computationally to find out the impact of biomolecules in defining the shape and size of NPs. The viability of gram negative Escherichia coli and gram positive Enterococcus faecium bacteria was found to be 48% and 43%, respectively at high concentration of NPs.

Studies on Bacterial Proteins Corona Interaction with Saponin Imprinted ZnO Nanohoneycombs and Their Toxic Responses.

Molecular imprinting generates robust, efficient, and highly mesoporous surfaces for biointeractions. Mechanistic interfacial interaction between the surface of core substrate and protein corona is crucial to understand the substantial microbial toxic responses at a nanoscale. In this study, we have focused on the mechanistic interactions between synthesized saponin imprinted zinc oxide nanohoneycombs (SIZnO NHs), average size 80-125 nm, surface area 20.27 m(2)/g, average pore density 0.23 pore/nm and number-average pore size 3.74 nm and proteins corona of bacteria. The produced SIZnO NHs as potential antifungal and antibacterial agents have been studied on Sclerotium rolfsii (S. rolfsii), Pythium debarynum (P. debarynum) and Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), respectively. SIZnO NHs exhibited the highest antibacterial (∼50%) and antifungal (∼40%) activity against Gram-negative bacteria (E. coli) and fungus (P. debarynum), respectively at concentration of 0.1 mol. Scanning electron spectroscopy (SEM) observation showed that the ZnO NHs ruptured the cell wall of bacteria and internalized into the cell. The molecular docking studies were carried out using binding proteins present in the gram negative bacteria (lipopolysaccharide and lipocalin Blc) and gram positive bacteria (Staphylococcal Protein A, SpA). It was envisaged that the proteins present in the bacterial cell wall were found to interact and adsorb on the surface of SIZnO NHs thereby blocking the active sites of the proteins used for cell wall synthesis. The binding affinity and interaction energies were higher in the case of binding proteins present in gram negative bacteria as compared to that of gram positive bacteria. In addition, a kinetic mathematical model (KMM) was developed in MATLAB to predict the internalization in the bacterial cellular uptake of the ZnO NHs for better understanding of their controlled toxicity. The results obtained from KMM exhibited a good agreement with the experimental data. Exploration of mechanistic interactions, as well as the formation of bioconjugate of proteins and ZnO NHs would play a key role to interpret more complex biological systems in nature.