The spectrum of bacterial infections in febrile neutropenic patients: effect on empiric antibiotic therapy

The aim of this retrospective analysis was to look at the spectrum of bacterial isolates and their resistance patterns to the commonly used antIbiotics in the settmg of febrile neutropenia. A total of 127 bacteria were isolated from patients with acute leukemias, lymphoproliferative disorders, aplastic anaemia and various solid tumours. Fifty-four percent organisms were gram negative; while the rest were gram positive. E. coli, pseudomónas aeruginosa, staphylococcus aureus, enterococcus and streptococci were the commonly isolated organisms. Forty-eight percent organisms were isolated from blood, 16% from urine, 13% from wounds and superficial abscesses and 11% from respiratory tract. E. coli exhibited a great degree of resistance to the commonly used antibiotics, such as pipericillin (70%), ofloxacin (50%) and aztreonam (50%). Pseudomonas and kiebsiella also showed varying degree of resistance against the antibiotics. Staphylococcus aureus and staphylococcus epidennidis were almost universally resistant to penicillin and showed a variable degree of resistance to other antibiotices too. Compared to the previous reports, the pattern of bacterial isolates and their resistance to antibiotics has changed over the past years. Aminolgy­cosides and third generation cephalosporins seem to be the choice of antibiotics for the upfront manage­ment of febrile neutropenic patients (JPMA 48:364,1998)

Phenotypes of Alpha 1 Antitrypsin in Karachi, Pakistan

Objective: To determine serum level of the protease inhibitor, to identify phenotypes and determine their frequencies. Study Design: A prospective study. Setting: PMRC Research Centre, JPMC and the Aga Khan University Hospital Karachi. Subjects: Healthy aduIts without history ol peptic ulcer disease and a normal endoscopy. Methodology: Quantitive measurement of serum alpha 1 AT was carried out by radial immunodiffusion. phenotyping by iso-electric focusing and confirmation of phenotypes by immunofixation and DNA analysis technique. Results:Serum alpha I AT was low in 13.4% of the subjects. Ni MM phenotype predominated followed by SZ SS, MZ and ZZ. DNA diagnosis accurately resolved the phenotypes as S and Z. Conclusion: Frequency by phenotype associated with total and intermediate deficiency is less in the populatio

The awareness and usage of orthodontic apps and social media by orthodontists in the UK: A questionnaire-based study

OBJECTIVE: To assess the awareness and usage of mobile apps and social media among orthodontic clinicians to support patients with orthodontic treatment, support the professional development of orthodontists, and identify any relevant apps and social media platforms currently recommended to patients. DESIGN: Cross-sectional questionnaire-based study. SETTING: United Kingdom. METHODS: A questionnaire was developed and distributed to members of the British Orthodontic Society (BOS). To increase the response rate, the questionnaire was circulated at three time points between January and March 2020. RESULTS: A total of 149 orthodontists responded to the questionnaire (15% response rate) with 113 orthodontists completing all questions (11.4%). Of those who answered, 81% (n = 111) had been qualified for >10 years, 35% worked in practice (n = 48), 34% worked in a hospital (n = 47) and 26% worked in both hospital and practice (n = 36). The results indicated that 20% of clinicians (n = 22) used apps to support patients and 33% (n = 37) reported using apps for professional purposes. Brush DJ appeared to be the most popular patient focused app (39%, n = 18) whereas the IOTN (17%, n = 8), Invisalign (17%, n = 8) and Dental Monitoring apps (9%, n = 4) were the most popular clinician-focused apps. With regard to social media, 53% (n = 60) of respondents reported that they used social media to communicate generic orthodontic information and promote their practice to patients. The most commonly used social media platforms were Facebook and Instagram. Of respondents, 96% expressed a willingness to recommend an evidence-based mobile app to patients if available, and 88% were willing to recommend an evidence-based social media platform. CONCLUSIONS: Orthodontic clinicians are utilising mobile apps and social media to support both patients and their own professional development. There is a willingness to increase the use of evidence-based platforms and apps to support patients

RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry

The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents

Symptom Domain Groups of the Patient-Reported Outcomes Measurement Information System Tools Independently Predict Hospitalizations and Re-hospitalizations in Cirrhosis

Background Patient-Reported Outcomes Measurement Information System (PROMIS) tools can identify health-related quality of life (HRQOL) domains that could differentially affect disease progression. Cirrhotics are highly prone to hospitalizations and re-hospitalizations, but the current clinical prognostic models may be insufficient, and thus studying the contribution of individual HRQOL domains could improve prognostication. Aim Analyze the impact of individual HRQOL PROMIS domains in predicting time to all non-elective hospitalizations and re-hospitalizations in cirrhosis. Methods Outpatient cirrhotics were administered PROMIS computerized tools. The first non-elective hospitalization and subsequent re-hospitalizations after enrollment were recorded. Individual PROMIS domains significantly contributing toward these outcomes were generated using principal component analysis. Factor analysis revealed three major PROMIS domain groups: daily function (fatigue, physical function, social roles/activities and sleep issues), mood (anxiety, anger, and depression), and pain (pain behavior/impact) accounted for 77% of the variability. Cox proportional hazards regression modeling was used for these groups to evaluate time to first hospitalization and re-hospitalization. Results A total of 286 patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths (IQR 22–47), during which 31% were hospitalized [median IQR mths 12.5 (3–27)] and 12% were re-hospitalized [10.5 mths (3–28)]. Time to first hospitalization was predicted by HE, HR 1.5 (CI 1.01–2.5, p = 0.04) and daily function PROMIS group HR 1.4 (CI 1.1–1.8, p = 0.01), independently. In contrast, the pain PROMIS group were predictive of the time to re-hospitalization HR 1.6 (CI 1.1–2.3, p = 0.03) as was HE, HR 2.1 (CI 1.1–4.3, p = 0.03). Conclusions Daily function and pain HRQOL domain groups using PROMIS tools independently predict hospitalizations and re-hospitalizations in cirrhotic patients

Eco-Friendly, Green Approach for Synthesis of Bio-Active Novel 3-Aminoindazole Derivatives

In present chapter we have reported green and highly efficient method for synthesize novel series of substituted -1H-indazol-3-amine derivative (3a-h) by cyclocondensation reaction of substituted benzonitrile (1a-h) and substituted Hydrazine (2a-h) using ceric (IV) ammonium nitrate (CAN) as a catalyst, EtOH-H2O as a ecofriendly media and reaction was carried out under ultrasound irradiation green method. The structures of newly synthesized indazole derivative (3a-h) were corroborated through spectral investigation such as elemental analysis and spectral studies like IR, C13 NMR, Mass spectra and 1H NMR. The compounds were assessed for their in-vitro antimicrobial activity with pathogenic microbe comprising Gram positive bacterial strains, S. aureus and Gram negative strains E.coli, P.vulgaris, and S. typhi at different concentration. The consequence of bioassay is compared with standard drug Chloramphenicol

Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri

Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at a lower effective concentration (2.5 and 5 μM) compared to the drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and its nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood–brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain-eating amoebic infections

Phytochemical Analysis, Antioxidant, and Antimicrobial Activities of Ducrosia flabellifolia: A Combined Experimental and Computational Approaches

Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography-electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent