The impact of phosphodiesterase inhibition on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury: a systematic review.

Study design: Systematic review. Objective: The objective of this study was to evaluate the impact of phosphodiesterase (PDE) inhibitors on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury (SCI). Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered with PROSPERO (CRD42019150639). Searches were performed in MEDLINE and Embase. Studies were included if they evaluated the impact of PDE inhibitors on neurobehavioral outcomes in preclinical models of traumatic or non-traumatic SCI. Data were extracted from relevant studies, including sample characteristics, injury model, and neurobehavioral assessment and outcomes. Risk of bias was assessed using the SYRCLE checklist. Results: The search yielded a total of 1,679 studies, of which 22 met inclusion criteria. Sample sizes ranged from 11 to 144 animals. PDE inhibitors used include rolipram (n = 16), cilostazol (n = 4), roflumilast (n = 1), and PDE4-I (n = 1). The injury models used were traumatic SCI (n = 18), spinal cord ischemia (n = 3), and degenerative cervical myelopathy (n = 1). The most commonly assessed outcome measures were Basso, Beattie, Bresnahan (BBB) locomotor score (n = 13), and grid walking (n = 7). Of the 22 papers that met the final inclusion criteria, 12 showed a significant improvement in neurobehavioral outcomes following the use of PDE inhibitors, four papers had mixed findings and six found PDE inhibitors to be ineffective in improving neurobehavioral recovery following an SCI. Notably, these findings were broadly consistent across different PDE inhibitors and spinal cord injury models. Conclusion: In preclinical models of traumatic and non-traumatic SCI, the administration of PDE inhibitors appeared to be associated with statistically significant improvements in neurobehavioral outcomes in a majority of included studies. However, the evidence was inconsistent with a high risk of bias. This review provides a foundation to aid the interpretation of subsequent clinical trials of PDE inhibitors in spinal cord injury. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150639, identifier: CRD42019150639.

Clinical and Laboratory Profile of Patients Visiting the Post-COVID-19 Clinic at a Tertiary Care Hospital: A Cross-Sectional Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) survivors may continue experiencing diverse symptoms. This study portrays the clinical and laboratory profile of patients with post-acute sequelae of COVID-19'(PASC) at a tertiary care hospital in India.  Methodology: This cross-sectional study enrolled patients visiting the post-COVID-19 clinic three weeks after their acute COVID-19 illness. Their clinical, serological, and radiological characteristics were collected and analyzed. RESULTS: Of the 259 participants (age: 48.02±15.27 years; 62.25% men), 168 had PASC manifestations. The most frequently reported symptoms were fatigue (n=71(42.26%)), breathlessness (n=38(22.61%)), and cough (n=35(20.83%)). Patients with PASC had higher body mass index (28.24±5.02 vs. 26.26±3.65; p=0.002), history of hypertension (52 (30.95%) vs. 17 (18.6%); p=0.039), uncontrolled systolic blood pressure (37 (22.03) vs. 14 (15.38); p=0.042), and persistent chest x-ray abnormalities (34 (20.23) vs. 10 (10.98); p=0.048). CONCLUSION: Fatigue, breathlessness, and cough are common PASC symptoms. Hypertension, obesity, and abnormal chest x-ray findings at follow-up are potential risk factors for developing PASC.

Temporal variations in patterns of Escherichia coli strain diversity and antimicrobial resistance in the migrant Egyptian vulture.

Aims: Multiple antimicrobial resistance in Escherichia coli of wild vertebrates is a global concern with scarce assessments on the subject from developing countries that have high human-wild species interactions. We studied the ecology of E. coli in a wintering population of Egyptian Vultures in India to understand temporal changes in both E. coli strains and patterns of antimicrobial resistance. Methods and Results: We ribotyped E. coli strains and assessed antimicrobial resistance from wintering vultures at a highly synanthropic carcass dump in north-west India. Both E. coli occurence (90.32%) and resistance to multiple antimicrobials (71.43%) were very high. Clear temporal patterns were apparent. Diversity of strains changed and homogenized at the end of the Vultures' wintering period, while the resistance pattern showed significantly difference inter-annually, as well as between arrival and departing individuals within a wintering cycle. Significance of study: The carcass dump environment altered both E. coli strains and multiple antimicrobial resistance in migratory Egyptian Vultures within a season. Long-distance migratory species could therefore disseminate resistant E. coli strains across broad geographical scales rendering regional mitigation strategies to control multiple antimicrobial resistance in bacteria ineffective.

Development of METAL-ACTIVE SITE and ZINCCLUSTER tool to predict active site pockets.

The advent of whole genome sequencing leads to increasing number of proteins with known amino acid sequences. Despite many efforts, the number of proteins with resolved three dimensional structures is still low. One of the challenging tasks the structural biologists face is the prediction of the interaction of metal ion with any protein for which the structure is unknown. Based on the information available in Protein Data Bank, a site (METALACTIVE INTERACTION) has been generated which displays information for significant high preferential and low-preferential combination of endogenous ligands for 49 metal ions. User can also gain information about the residues present in the first and second coordination sphere as it plays a major role in maintaining the structure and function of metalloproteins in biological system. In this paper, a novel computational tool (ZINCCLUSTER) is developed, which can predict the zinc metal binding sites of proteins even if only the primary sequence is known. The purpose of this tool is to predict the active site cluster of an uncharacterized protein based on its primary sequence or a 3D structure. The tool can predict amino acids interacting with a metal or vice versa. This tool is based on the occurrence of significant triplets and it is tested to have higher prediction accuracy when compared to that of other available techniques.

Characterization of probiotic potential of Bacillus species isolated from a traditional brine pickle.

Fermented foods are known for their potential as main source of probiotics. The present study aimed at investigating the probiotic properties of bacteria isolated from fermented mango pickle. Non-hemolytic fermenting microbiota isolated from mango pickle was screened in vitro for their basic probiotic properties such as acid tolerance, bile salt, lysozyme and salt tolerance. They were also tested for their beneficial characters like cholesterol removal, bacterial adhesion to hydrocarbons, auto-aggregation, antimicrobial activity, ß-galactosidase activity, exopolysaccharide production and adhesion to HT-29 cell line. Outputs of these parameters were subjected to principal component analysis (PCA) and these results were interpreted to select prospective bacterial isolates that can be used as potential probiotics. Out of eight isolates, PUFSTP35 (Bacillus licheniformis), PUFSTP38 (Bacillus amyloliquefaciens) and PUFSTP39 (Bacillus subtilis) showed similar trend to Weissella cibaria (MTCC 9814) that was used as a reference strain for profiling probiotic properties. B. licheniformis PUFSTP35 from fermented mango pickle appear to be the most potential candidate for use as a beneficial probiotic.

Exercise-based interventions for cancer survivors in India: a systematic review.

Existing literature suggests that cancer survivors present with high rates of morbidity due to various treatment and disease induced factors. Research globally has shown exercise to be beneficial in improving treatment outcomes and quality of life. India has a high prevalence of cancer and not much is known about exercise interventions for cancer survivors in India. This review was planned to review the state of exercise based interventions for cancer survivors in India. A comprehensive literature search was performed in PubMed, CINAHL, EMBASE, Scopus, Cochrane Library, PEDro, IndMed, and Shoda Ganga. The search results were screened and data extracted by two independent reviewers. All eligible studies were assessed for methodological quality rating using Downs and Black checklist. Data was extracted using a pilot tested pro forma to summarize information on site and stage of cancer, type of exercise intervention and outcome measures. The review identified 13 studies, published from 1991 to 2013, after screening 4060 articles. Exercise interventions fell into one of three categories: (1) yoga-based, (2) physiotherapy-based and (3) speech therapy based interventions; and exclusively involved either breast or head and neck cancers. Studies were generally of low to moderate quality. A broad range of outcomes were found including symptoms, speech and swallowing, and quality of life and largely supported the benefits of exercise-based interventions. At present, research involving exercise-based rehabilitation interventions in India is limited in volume, quality and scope. With the growing burden of cancer in the country, there is an immediate need for research on exercise based interventions for cancer survivors within the sociocultural context of India.

Formulation of essential oil-loaded chitosan-alginate nanocapsules.

Naturally occurring polymers such as alginate (AL) and chitosan (CS) are widely used in biomedical and pharmaceutical fields in various forms such as nanoparticles, capsules, and emulsions. These polymers have attractive applications in drug delivery because of their biodegradability, biocompatibility, and nontoxic nature. The pharmaceutical applications of essential oils such as turmeric oil and lemongrass oil are well-known, and their active components, ar-turmerone and citral, respectively, are known for their antibacterial, antifungal, antioxidant, antimutagenic, and anticarcinogenic properties. However, these essential oils are unstable, volatile, and insoluble in water, which limits their use for new formulations. Therefore, this study focuses on developing a CS-AL nanocarrier for the encapsulation of essential oils. The effects of process parameters such as the effect of heat and the concentrations of AL and CS were investigated. Various physicochemical characterization techniques such as scanning electron microscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible spectroscopy were performed. Results of characterization studies showed that 0.3 mg/mL AL and 0.6 mg/mL CS produced minimum-sized particles (<300 nm) with good stability. It was also confirmed that the oil-loaded nanocapsules were hemocompatible, suggesting their use for future biomedical and pharmaceutical applications. Furthermore, the antiproliferative activity of turmeric oil- and lemongrass oil-loaded nanocapsules was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in A549 cell lines and it was found that both the nanoformulations had significant antiproliferative properties than the bare oil.

Metformin-loaded BSA nanoparticles in cancer therapy: a new perspective for an old antidiabetic drug.

Clinical and experimental data suggest that there is a strong association between type II diabetic mellitus and pancreatic cancer. The present study focuses on exploring the anticancer and antidiabetic properties of metformin-loaded bovine serum albumin nanoparticles (BSA NPs) on (MiaPaCa-2) pancreatic carcinoma cell lines. Albumin nanoparticles were synthesized using coacervation method and the average size of the particles was found to be 97 nm. The particles were stable and showed a spherical morphology with narrow size distribution. We investigated the impact of two stages characterized in type II diabetes mellitus (hyperglycemia and hyperinsulinemia) on the proliferation of MiaPaCa-2 cells and compared the inhibitory effects of bare metformin to that of MET-BSA NPs. Further, different concentrations of insulin and glucose were added along with bare metformin, bare BSA, and metformin encapsulated BSA carrier on MiaPaCa-2 cells to check the strong association between type II diabetes and pancreatic cancer. The results revealed that MET-BSA NPs showed more toxicity when compared with drug and carrier individually.

Psidium guajava Linn confers gastro protective effects on rats.

BACKGROUND AND OBJECTIVES: The best alternatives to synthetic medicines, available, for the treatment of gastric ulcer disorders, are the natural products found in plants. They are known to exhibit a variety of activities. The present study is aimed at the screening of Psidium (P.) guajava Linn for its gastro protective effect. MATERIAL AND METHODS: The methanol extracts of the leaves of P. guajava were tested in three different ulcer models viz. aspirin (ASP), pyloric ligation (PL) and ethanol (EtoH) induced ulcer models in rats. RESULTS AND DISCUSSION: The treatment of P. guajava at varying doses (100 mg/kg and 200 mg/kg) significantly (p < 0.001) inhibited the gastric lesions induced by ASP (70.5%), PL (65.07%) and EtoH (70.4%) respectively and the potency was found to be equivalent as compared to the standard drug, omeprazole. Reduction in the gastric secretory volume, acid secretion and increased gastric pH were the factors observed in treated rats. The presence of volatile oil, flavonoids and saponins present in the extracts of P. guajava may be responsible for the anti-ulcer property exhibited. CONCLUSIONS: The results further suggest that P. guajava possess gastro protective as well as ulcer healing properties which might also be due to its anti-secretory properties.

Bioremoval of trivalent chromium using Bacillus biofilms through continuous flow reactor.

Present study deals with the applicability of bacterial biofilms for the bioremoval of trivalent chromium from tannery effluents. A continuous flow reactor was designed for the development of biofilms on different substrates like glass beads, pebbles and coarse sand. The parameters for the continuous flow reactor were 20 ml/min flow rate at 30°C, pH4. Biofilm biomass on the substrates was in the following sequence: coarse sand>pebbles>glass beads (4.8 × 10(7), 4.5 × 10(7) and 3.5 × 10(5)CFU/cm(2)), which was confirmed by CLSM. Biofilms developed using consortium of Bacillus subtilis and Bacillus cereus on coarse sand had more surface area and was able to remove 98% of Cr(III), SEM-EDX proved 92.60% Cr(III) adsorption on biofilms supported by coarse sand. Utilization of Bacillus biofilms for effective bioremoval of Cr(III) from chrome tanning effluent could be a better option for tannery industry, especially during post chrome tanning operation.

Cr (III) bioremoval capacities of indigenous and adapted bacterial strains from Palar river basin.

The effluents from tanning industries in and around Palar river basin are the major cause of Cr (III) pollution. Forty-five chromium (III) tolerant bacterial strains were isolated from the Palar river basin. Bacillus subtilis VITSCCr01 showed tolerance up to 1500 mg/l and its Cr (III) bioremoval capacity was 64%. Increasing the concentration of Cr (III) increased exopolysaccharide (EPS) production by the bacteria. FT-IR spectral studies confirmed the presence of polysaccharides in the Cr (III) treated bacteria. Adaptation of Bacillus subtilis VITSCCr01 with higher Cr (III) concentration improved the bioremoval capacity to 85%. SEM-EDX showed that the adapted bacteria accumulated high concentration of chromium. Bacillus subtilis VITSCCr01 could be used as a tool for in situ removal of Cr (III) especially in the tannery polluted environment.

Role of components of the phagocytic NADPH oxidase in oxygen sensing.

It has been hypothesized that O(2) sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91(phox)-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47(phox)-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 +/- 18.0 vs. 20.0 +/- 13.0% (n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47(phox)-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47(phox)-null mutant than in wild-type mice: 109.61 +/- 13.29 vs. 72.54 +/- 7.65 impulses/s (n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was approximately 58% larger in p47(phox)-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91(phox)- and p47(phox)-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91(phox) component of the phagocytic NADPH oxidase does not alter the O(2)-sensing mechanism of the carotid body. However, absence of the p47(phox) component significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O(2) sensing in EPO-producing cells of the kidney appears to be independent of the gp91(phox) and p47(phox) components of the phagocytic NADPH oxidase.

Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice.

Various heme-containing proteins have been proposed as primary molecular O(2) sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91(phox)) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O(2)-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K(+) currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca(2+) concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91(phox) gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O(2) sensor in arterial chemoreception.

Granulomatous pneumonitis following bone marrow transplantation.

We describe the rare occurrence of a granulomatous pneumonitis seen in a patient following allogeneic bone marrow transplantation. Interestingly sarcoidosis was diagnosed in the marrow donor less than a year after donating his bone marrow.

Tetracycline aspiration. Case report and review of the literature.

A 74-year-old woman presented with a 2-day history of cough, dyspnea and wheezing following aspiration of a tetracycline tablet. She developed a left lower lobe pneumonitis, and bronchoscopy revealed left main bronchus narrowing and exudate. The course of this patient is discussed in reference to the available literature on toxic aspirations.

Unusual presentation of thoracic Pneumocystis carinii infection in a patient with acquired immunodeficiency syndrome.

Pleura-based masses and hilar adenopathy were seen on a chest radiograph of a patient with acquired immunodeficiency syndrome who had a history of Pneumocystis carinii infection. The differential diagnosis of such a presentation is discussed in light of atypical and extrapulmonary manifestations of P. carinii infection in a patient receiving prophylaxis with dapsone.