Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study.

OBJECTIVES: Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however, hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for and quantification of these events is required for safe use. This study aimed to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting. METHODS: Patients prescribed cotrimoxazole were identified using electronic healthcare records over 3 years (1 April 2016 to 31 March 2019). Individual risk factors were recognized. Serum creatinine and potassium trends were analysed over the subsequent 21 days. AKI and patients with hyperkalaemia were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed. RESULTS: Among 214 patients prescribed cotrimoxazole, 42 (19.6%, 95% confidence interval (CI) 14.6-25.7) met AKI criteria and 33 (15.4%, 95% CI 11.0-21.1) developed hyperkalaemia. Low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m2, odds ratio (OR) 7.78, 95% CI 3.57-16.13, p < 0.0001) and cardiac disorders (OR 2.40, 95% CI 1.17-4.82, p 0.011) predicted AKI, while low baseline estimated glomerular filtration rate (<60 mL/min/1.73 m2, OR 6.80, 95% CI 3.09-15.06, p < 0.0001) and higher baseline serum potassium (p 0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920 mg/d) was associated with lower AKI and hyperkalaemia risk (p 0.007 and 0.019 respectively). Early (within the first 2-4 days of therapy) serum creatinine changes predicted AKI (OR 3.65, 95% CI 1.73-7.41, p 0.001), and early serum potassium changes predicted hyperkalaemia (>0.6 mmol/L, OR 2.47, 95% CI 1.14-5.27, p 0.0236). CONCLUSIONS: Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose dependent. Renal function, serum potassium and preexisting cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2 to 4 days of treatment to identify susceptible patients is recommended, and the lowest effective dose ought to be prescribed.

Photoresponse of the protonated Schiff-base retinal chromophore in the gas phase.

The fragmentation, initiated by photoexcitation as well as collisionally-induced excitation, of several retinal chromophores was studied in the gas phase. The chromophore in the protonated Schiff-base form (RPSB), essential for mammalian vision, shows a remarkably selective photoresponse. The selectivity of the gas-phase chromophore is triggered by a series of fast trans to cis isomerizations followed by a Diels-Alder cyclization with subsequent slow statistical fragmentation, leading to one specific fragment ion. The pattern of the final statistical fragmentation may be altered by chemical modifications of the chromophore. We propose that isomerizations play an important role in the photoresponse of gas-phase retinal chromophores and guide internal conversion through conical intersections. The role of protein interactions is then to control the specificity of the photoisomerization in the primary step of vision and possibly to diminish thermal noise by suppressing spontaneous isomerization by heat.

Inter-relationship of intelligence-quotient and self-concept with dental caries amongst socially handicapped orphan children.

CONTEXT: India has been the focus of many health surveys among normal, physically, and mentally handicapped children. However, the data, concerning oral health conditions of socially handicapped children living in orphanages, are scanty. AIMS: To study the effect of parental inadequacy, environmental deprivation, and emotional disturbances on dental caries through intelligence quotient (IQ) and self-concept in orphan children and also to co-relate dental caries with different levels of IQ and self-concept. SETTINGS AND DESIGN: The study was carried out amongst socially handicapped children living in orphanages. PATIENTS AND METHODS: 100 children in the age group of 10-14 years from orphanages were selected. Malin's Intelligence Scale for Indian Children (MISIC) was used to assess the intelligence quotient; self-concept questionnaire to assess self-concept of the child and recording of dental caries status of children was done as per WHO Index (1997). STATISTICAL ANALYSIS USED: To assess the relationship of dental caries with IQ, student's unpaired t-test was used and; to find the relationship between self-concept and dental caries, Karl-Pearson's coefficient of co-relation was applied. RESULTS: the children in orphanages had a lower IQ and high caries experience but had an above average self-concept. There was also no co-relation between dental caries and self-concept. CONCLUSIONS: Orphan children, being socially handicapped, are at an increased risk for dental caries due to a lower IQ level, parental deprivation, and institutionalization. Moreover, lack of co-relation between dental caries and self-concept could be explained by the fact that dental caries is a lifelong process whereas different dimensions of self-concept are in a state of constant flux.

Photodissociation pathways and lifetimes of protonated peptides and their dimers.

Photodissociation lifetimes and fragment channels of gas-phase, protonated YA(n) (n = 1,2) peptides and their dimers were measured with 266 nm photons. The protonated monomers were found to have a fast dissociation channel with an exponential lifetime of ~200 ns while the protonated dimers show an additional slow dissociation component with a lifetime of ~2 µs. Laser power dependence measurements enabled us to ascribe the fast channel in the monomer and the slow channel in the dimer to a one-photon process, whereas the fast dimer channel is from a two-photon process. The slow (1 photon) dissociation channel in the dimer was found to result in cleavage of the H-bonds after energy transfer through these H-bonds. In general, the dissociation of these protonated peptides is non-prompt and the decay time was found to increase with the size of the peptides. Quantum RRKM calculations of the microcanonical rate constants also confirmed a statistical nature of the photodissociation processes in the dipeptide monomers and dimers. The classical RRKM expression gives a rate constant as an analytical function of the number of active vibrational modes in the system, estimated separately on the basis of the equipartition theorem. It demonstrates encouraging results in predicting fragmentation lifetimes of protonated peptides. Finally, we present the first experimental evidence for a photo-induced conversion of tyrosine-containing peptides into monocyclic aromatic hydrocarbon along with a formamide molecule both found in space.

An electrostatic deceleration lens for highly charged ions.

The design and implementation of a purely electrostatic deceleration lens used to obtain beams of highly charged ions at very low energies is presented. The design of the lens is such that it can be used with parallel as well as diverging incoming beams and delivers a well focused low energy beam at the target. In addition, tuning of the final energy of the beam over a wide range (1 eV/q to several hundred eV/q, where q is the beam charge state) is possible without any change in hardware configuration. The deceleration lens was tested with Ar(8+), extracted from an electron cyclotron resonance ion source, having an initial energy of 30 keV/q and final energies as low as 70 eV/q have been achieved.

Sub-microsecond photodissociation pathways of gas phase adenosine 5'-monophosphate nucleotide ions.

The sub-microsecond dissociation pathways for the protonated and deprotonated forms of adenosine 5'-monophosphate were probed in the gas phase using a linear time of flight spectrometer. The studies show two dissociation pathways for the AMP ions indicating dominant ergodic pathways in the photodissociation of these species. The photofragmentation was determined to be a single photon process for the AMP ions. Photodetachment of the AMP anion excited at 266 nm was not observed, leaving dissociation as the prominent pathway for relaxation of the excess energy in the biomolecule. The photofragments were analysed at the electrostatic ion storage ring (ELISA) and found to be similar to collision induced fragments in the case of anions but different in the case of cations.

Spectral tuning of the photoactive yellow protein chromophore by H-bonding.

Spectral tuning in the photoactive yellow protein (PYP) is investigated by performing gas-phase absorption measurements on a PYP-model chromophore with two water molecules hydrogen-bonded to it. The photoabsorption maximum shows an unusually large blue shift of 0.71 eV in going from the bare to the hydrogen-bonded chromophore. It is concluded that several interactions within the PYP protein are mutually cancelling each other, yielding an absorption maximum that is close to the absorption maximum of the bare chromophore. The system breaks apart upon photoexcitation in the gas phase by releasing the two water molecules, leaving the chromophore itself intact. The hydrogen-bonding interactions thus play an important role in stabilizing the gas phase chromophore against photofragmentation. The relaxation dynamics for the breakup process was also studied, and the timescale of relaxation via fragmentation was found to be < 25 ns.

Photoabsorption studies of neutral green fluorescent protein model chromophores in vacuo.

We report on gas-phase experimental and theoretical studies on the neutral form of the green-fluorescent protein (GFP) chromophore using six different models, each carrying a spectator positive charge. Theoretical studies were carried out to quantify the effect of the spectator charge on the absorption maximum of the true neutral. The study also includes models having the possibility of forming intra-molecular hydrogen bonds, and their effect on the absorption profile is analyzed. The charge redistribution caused by a strong intra-molecular hydrogen bond was found to give rise to a red shift in going from non-hydrogen bonded to hydrogen bonded models. For the non-hydrogen bonded models, the length of the side chain as well as the group carrying the spectator charge, was varied to explore the possibility of shifts in absorption maximum due to these variations. No shifts were observed. The implications of these results in tuning the absorption maximum of the neutral form of the GFP chromophores are discussed.

Disruption of fungal and bacterial biofilms by lauroyl glucose.

AIM: The ability of enzymatically synthesized lauroyl glucose to disrupt fungal (Candida albicans, Candida lipolytica) and bacterial (Pseudomonas aeruginosa PAO1, Pseudomonas aureofaciens) biofilms was investigated. METHODS AND RESULTS: Preformed biofilms of C. albicans and C. lipolytica in polystyrene microtitre plates were disrupted upto 45% and 65%, respectively, while P. aeruginosa and P. aureofaciens biofilms were disrupted by 51% and 57%. Precoating of the microtitre wells with lauroyl glucose affected cell attachment and biofilm growth of all the cultures to a lesser extent. With C. albicans and C. lipolytica, there was 11% and 32% decrease in the development of biofilms, respectively. With P. aeruginosa and P. aureofaciens, the reduction was 21% and 12% after 48 h. Lauroyl glucose effectively inhibited the formation of biofilms on glass slide surfaces when added along with the inoculum. Analysis by confocal laser scanning microscopy showed that the growth of the biofilms was lesser as compared with the control experiments. Lauroyl glucose displayed minimum inhibitory concentration values >500 microg ml(-1) for the test cultures and was comparable to that obtained with acetyl salicylate. CONCLUSION: Lauroyl glucose reduces biofilm growth of all the four test cultures on polystyrene and glass surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: This report is a novel application of the enzymatically synthesized, environmental-friendly nonionic surfactant.

Evaluation of fungal culture filtrate containing chitinase as a biocontrol agent against Helicoverpa armigera.

AIMS: To evaluate the biocontrol efficacy of culture filtrate containing chitinase from Trichoderma harzianum against Heliothis. METHODS AND RESULTS: T. harzianum was cultured by submerged fermentation using colloidal chitin as sole carbon source. The ability of the culture filtrate to hydrolyse colloidal chitin indicated the presence of chitinase as one of its components. Biocontrol assay on Heliothis showed that the culture filtrate is a potent antifeedant as it reduced the feeding rate and body weight of the larvae. It reduced the successful pupation and increased larval and pupal mortality in a dosage-dependent manner when applied topically. The highest mortalities (70%) were recorded for groups treated with 2000 U ml(-1) chitinase activity. The percentage of adult emergence was zero for the highest chitinase concentration (2000 U ml(-1)) tried. CONCLUSIONS: The studies showed that the culture filtrate containing chitinase from T. harzianum is capable of negatively affecting the growth and metamorphosis of Heliothis larvae. SIGNIFICANCE AND IMPACT OF THE STUDY: In view of the need for safer and environmentally friendly pest management tools, the present study could help in the development of enzyme-based biopesticides against Heliothis.

An evaluation of sealing ability of endodontic materials as root canal sealers.

An in vitro dye leakage study was carried out to compare the apical microleakage of vitapex (calcium hydroxide based paste) when used with single gutta percha cone with that of dentalis KEZ (calcium hydroxide and zincoxide eugenol based sealer) and zincoxide-eugenol sealer when used with laterally condensed gutta percha obturation technique. One hundred single rooted human anterior teeth were instrumented and randomly divided into three experimental groups of 30 teeth each and two control groups of 5 teeth each. Teeth in the first group were obturated using a single master gutta percha cone and vitapex as root canal sealer and those of second group were obturated with laterally condensed gutta percha using dentalis KEZ as sealer. Third experimental group was filled with laterally condensed gutta-percha using zinc-oxide eugenol as sealer. Teeth were then suspended in 2% methylene blue. After this, teeth were demineralized dehydrated and cleared. Linear dye penetration was determined under stereomicroscope (x10) with calibrated eye piece. Results of this study showed that calcium hydroxide based endodontic material leaked comparatively less as compared to zinc oxide Eugenol sealer. Vitapex with single gutta-percha cone provided an adequate apical Seal against dye penetration.

Helminth parasites of dogs from two resource-limited communities in South Africa.

Biological samples were collected from dogs in resource-limited communities in the North-West and Gauteng Provinces of South Africa to assess the prevalence of helminth parasitism. These samples included adhesive tape peri-anal skin swabs and fresh faecal samples for helminth examination, and thick and thin blood films (smears) and whole-blood samples in anticoagulant for examination of filarial nematode microfilariae and haemoprotozoa. The eggs of Ancylostoma caninum, Toxocara canis, Toxascaris leonina, Dipylidium caninum and taeniids were identified. None of the blood samples and smears tested positive for microfilariae of Dirofilaria immitis or Dipetalonema spp. or for haemoprotozoa. The adhesive tape swabs were negative for cestode eggs and segments. Most of the helminth parasites identified in this study are zoonotic and consequently are regarded as a public health hazard.