Category: Nevin Manimala

Fungal Biol. 2023 Jul-Aug;127(7-8):1241-1249. doi: 10.1016/j.funbio.2023.04.003. Epub 2023 Apr 14.

ABSTRACT

Candidiasis is a significant fungal infection with high mortality and morbidity rates worldwide. Candida albicans is the most dominant species responsible for causing different manifestations of candidiasis. Certain virulence traits as well as its resistance to antifungal drugs contribute to the pathogenesis of this yeast. This study was designed to determine the production of some virulence factors, such as biofilm formation and extracellular hydrolytic enzymes (esterase, coagulase, gelatinase, and catalase) by this fungus, as well as its antifungal resistance profile. A total of 304 clinical C. albicans isolates obtained from different clinical specimens were identified by a conventional diagnostic protocol. The antifungal susceptibility of C. albicans strains was determined by disk diffusion technique against commercially available antifungal disks, such as nystatin 50 μg, amphotericin B 100 unit, fluconazole 25 μg, itraconazole 10 μg, ketoconazole 10 μg, and voriconazole 1 μg. The assessment of biofilm formation was determined by the tube staining assay and spectrophotometry. Gelatinase, coagulase, catalase, and esterase enzyme production was also detected using standard techniques. A total of 66.1% (201/304) and 28.9% (88/304) of C. albicans strains were susceptible-dose dependent (SDD) to nystatin and itraconazole, respectively. Among the antifungal drugs, C. albicans strains showed high resistance to ketoconazole 24.7% (75/304); however, no statistically significant relationship between the clinical origin of C. albicans isolates and antifungal drug resistance pattern was detected. For virulence factors, the majority of the C. albicans strains actively produced biofilm and all hydrolytic enzymes. Biofilm formation was demonstrated by 88% (267/304) of the strains with a quantitative mean value 0.1762 (SD ± 0.08293). However, 100% (304/304) of isolates produced catalase enzyme, 69% (211/304) produced coagulase, 66% (197/304) produced gelatinase, and 52% (157/304) produced esterase enzyme. A significant relationship between the source of specimens and biofilm formation by C. albicans was observed; nevertheless, there was no significant relationship between different sources of C. albicans strains and the production of different enzymatic virulence factors. The study found that C. albicans strains have excellent potential to produce virulence markers and resistance to antifungals, which necessitates surveillance of these opportunistic pathogens to minimize the chances of severe invasive infections.

PMID:37495314 | DOI:10.1016/j.funbio.2023.04.003

J Am Coll Cardiol. 2023 Aug 1;82(5):401-410. doi: 10.1016/j.jacc.2023.05.042.

ABSTRACT

BACKGROUND: The RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial examined the effects of combination therapy with moderate-intensity statin and ezetimibe in patients with atherosclerotic cardiovascular disease compared with high-intensity statin monotherapy.

OBJECTIVES: This observational study was conducted to evaluate the impact of 2 treatment strategies used in the RACING trial in clinical practice.

METHODS: After stabilized inverse probability of treatment weighting, a total of 72,050 patients who were prescribed rosuvastatin after drug-eluting stent implantation were identified from a nationwide cohort database: 10,794 patients with rosuvastatin 10 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 61,256 patients with rosuvastatin 20 mg monotherapy. The primary endpoint was the 3-year composite event of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke in accordance with the RACING trial.

RESULTS: Combination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint (11.6% vs 15.2% for those with high-intensity statin monotherapy; HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Compared with high-intensity statin monotherapy, combination lipid-lowering therapy was associated with fewer discontinuations of statin (6.5% vs 7.6%; HR: 0.85; 95% CI: 0.78-0.94: P < 0.001) and a lower occurrence of new-onset diabetes requiring medication (7.7% vs 9.6%; HR: 0.80; 95% CI: 0.72-0.88; P < 0.001).

CONCLUSIONS: In clinical practice, combination lipid-lowering therapy with ezetimibe and moderate-intensity statin was associated with favorable clinical outcomes and drug compliance in patients treated with drug-eluting stent implantation. (CONNECT DES Registry; NCT04715594).

PMID:37495276 | DOI:10.1016/j.jacc.2023.05.042

J Dent. 2023 Jul 24:104631. doi: 10.1016/j.jdent.2023.104631. Online ahead of print.

ABSTRACT

OBJECTIVES: Tooth grinding produces a significant amount of aerosol particles. The aim of this study was to quantitatively assess particle contamination produced from tooth grinding with a speed-increasing handpiece across a real-world clinical setting.

METHODS: The crowns of all molars were pretreated into cylinders with a uniform cross-section diameter of 10 mm and a height of 5 mm. A novel computer-assisted numerical control system was used to fix the feed rate at 10 mm/min and the grinding depth at 30 μm, and to parametrically study the bur speed: from 20,000 (20 K) to 200,000 (200 K) revolutions per minute (rpm) at 20 K rpm intervals. 5-minute tooth grinding was performed in triplicate at each speed setting in a real dental operation room with the air conditioning off, and the window closed. Three online real-time particle counters (ORPC; TR-8301, TongrenCo.) with six particle-size channels (0.3, 0.5, 1.0, 2.5, 5.0, and 10.0 µm) were placed at 3 positions (0.5 m, 1.0 m, and 1.5 m) to evaluate particle production. All experimental instruments were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Scheirer-Ray-Hare and Kruskal-Wallis/ Dunn-Bonferroni tests, p < 0.05).

RESULTS: The concentration level of aerosol particles production during the grinding experiment was elevated above the control group for all conditions, and increased with bur speed at any location (the maximum peak, reaching 5.59 × 10⁷ particles/m³, at 200 K and 1 m), with differences between conditions. We noted that the effect of speed on the increment of particles across different channels compared to the control group was statistically significant among locations (p < 0.001). The simple main effect of location was not significant for the distribution difference of increment in 0.3 µm particles at 120 K (H = 4.314, p = 0.116), 0.5 µm at 180 K (H = 1.855, p = 0.396), and 5 µm at 40 K (H = 1.259, p = 0.533), while increments in other sizes particles at any speed setting showed significant differences (p < 0.05). Out of 171 post hoc pairwise comparisons of location, 130 showed significant differences (p < 0.05), with 50 between 0.5 m and 1.5 m (0.5 m – 1.5 m), and 40 in both the 1.5 m – 1 m and 0.5 m – 1 m. The simple main effect of speed was significant for the distribution difference of particle increment across all channels at any sampling location. In the post hoc pairwise comparisons of speed, there were 810 comparison groups, and those with speed differences below 80 K tended to show non-significant differences (p > 0.05), but all groups with a speed difference above 140 K showed significant differences (p < 0.05).

CONCLUSIONS: Statistically significant particle contamination was produced using a speed-increasing handpiece, but the contamination level for each experimental condition was reduced to baseline within 30 min, and most particles with a diameter greater than 1 μm produced at low speeds (80 K or lower) tended to settle within 1 m.

CLINICAL RELEVANCE: Our study suggested that the use of a speed-increasing handpiece below 80 K and 30 minutes of fallow time may lead to an adequate reduction in the health effects of particle contamination.

PMID:37495202 | DOI:10.1016/j.jdent.2023.104631

Osteoarthritis Cartilage. 2023 Jul 24:S1063-4584(23)00861-0. doi: 10.1016/j.joca.2023.07.005. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine whether pain sensitization is associated with hand and lower extremity function in people with hand osteoarthritis (OA) in the Nor-Hand study.

DESIGN: Pain sensitization was assessed by pressure pain thresholds (PPTs) and temporal summation (TS). Hand function was assessed by Australian/Canadian Osteoarthritis Hand Index (range: 0-36), grip strength and Moberg pick-up test, and lower extremity function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (range: 0-68), 30-second chair stand test, and 40-meter walk test. We examined whether sex-standardized PPT and TS values were cross-sectionally associated with measures of physical function using linear regression analyses. Beta coefficients were presented per sex-specific standard deviation of PPT and TS. The mediating effect of pain was examined by causal-inference based mediation analysis.

RESULTS: In 206 participants, higher PPTs at/near the hand, indicative of less peripheral and/or central pain sensitization, were associated with greater grip strength and better self-reported hand function (beta for PPT at finger joint on AUSCAN function: -1.41, 95% CI -2.40, -0.42). Higher PPTs at/near the hand, near the knee and at trapezius were associated with lower extremity function, although not statistically significant for all outcomes. Self-reported pain severity mediated the effect of PPT on self-reported function. TS was not associated with hand or lower extremity function.

CONCLUSION: Peripheral sensitization, and possibly central sensitization, was associated with impaired function. Effects of PPTs on self-reported function were mediated by self-reported pain, whereas there might be a direct effect of sensitization or effects through other mediators on performance-based function.

PMID:37495183 | DOI:10.1016/j.joca.2023.07.005

Appetite. 2023 Jul 24:106980. doi: 10.1016/j.appet.2023.106980. Online ahead of print.

ABSTRACT

Behaviour change interventions for weight management have found varied effect sizes and frequent weight re-gain after weight loss. There is interest in exploring whether differences in eating behaviour can be used to develop tailored weight management programs. This secondary analysis of an 18-month weight maintenance randomised controlled trial (RCT) aimed to investigate the association between individual variability in weight maintenance success and change in eating behaviour traits (EBT). Data was analysed from the NoHoW trial (Scott et al., 2019), which was designed to measure processes of change after weight loss of ≥5% body weight in the previous year. The sample included 1627 participants (mean age = 44.0 years, SD = 11.9, mean body mass index (BMI) = 29.7 kg/m², SD = 5.4, gender = 68.7% women/31.3% men). Measurements of weight (kg) and 7 EBTs belonging to domains of reflective, reactive, or homeostatic eating were taken at 4 time points up to 18-months. Increases in measures of ‘reactive eating’ (binge eating, p < .001), decreases in ‘reflective eating’ (restraint, p < .001) and changes in ‘homeostatic eating’ (unlimited permission to eat, p < .001 and reliance on hunger and satiety cues, p < .05) were significantly and independently associated with concomitant weight change. Differences in EBT change were observed between participants who lost, maintained, or re-gained weight for all EBTs (p < .001) except for one subscale of intuitive eating (eating for physical reasons, p = .715). Participants who lost weight (n = 322) exhibited lower levels of reactive eating and higher levels of reflective eating than participants who re-gained weight (n = 668). EBT domains can identify individuals who need greater support to progress in weight management interventions. Increasing reflective eating and reducing reactive eating may enhance weight management success.

PMID:37495176 | DOI:10.1016/j.appet.2023.106980

J Am Acad Dermatol. 2023 Jul 24:S0190-9622(23)02395-2. doi: 10.1016/j.jaad.2023.06.059. Online ahead of print.

NO ABSTRACT

PMID:37495174 | DOI:10.1016/j.jaad.2023.06.059

J Thorac Cardiovasc Surg. 2023 Jul 24:S0022-5223(23)00624-4. doi: 10.1016/j.jtcvs.2023.07.019. Online ahead of print.

ABSTRACT

INTRODUCTION: Right heart output in heart failure can be compensated through increasing systemic venous pressure. We determined whether this “Passive Cardiac Output” magnitude can predict LVAD outcomes.

METHODS: Retrospective review of 383 patients who received a continuous flow LVAD at the University of Michigan from 2012 to 2021. Pre-LVAD cardiac output driven by venous pressure was determined by dividing right atrial by mean pulmonary artery pressure, multiplied by total cardiac output. Normalization to body surface area derives the “Passive Cardiac Index (PasCI)”. Youden J statistics identified the PasCI threshold which predicted LVAD death by 2 years.

RESULTS: Increased preoperative PasCI was associated with reduced survival (HR=2.27, P<0.01), and increased risk of right ventricular failure (RVF) (HR=3.46, P=0.04). Youden analysis showed that a preoperative PasCI >0.5 (n=226) predicted LVAD death (P=0.10). Patients with Passive CI >0.5 had poorer survival (P=0.02), with a trend toward more heart failure readmission days (45.09+67.64 vs 35.13+45.02 days, P=0.084) and increased gastrointestinal bleeding (29.2% vs 20.4%, P=0.052). Additionally, of the 97 patients who experienced readmissions for heart failure, those with pre-LVAD implantation Passive CI >0.5 were more likely to have >1 readmission (P= 0.05).

CONCLUSIONS: While right heart output can be augmented by raising venous pressure, this negatively impacts end-organ function and increases heart failure readmission days. Patients with a pre-LVAD PasCI >0.5 have worse post-LVAD survival and increased RVF. Utilizing the PasCI metric in isolation or incorporation into a predictive model may improve the management of LVAD candidates with RV dysfunction.

PMID:37495169 | DOI:10.1016/j.jtcvs.2023.07.019

J Pharmacol Toxicol Methods. 2023 Jul 24:107299. doi: 10.1016/j.vascn.2023.107299. Online ahead of print.

ABSTRACT

The cardiovascular safety pharmacology (SP) study conducted to satisfy ICH S7A and S7B has commonly used a cross-over study design where each animal receives all treatments. In an increasing number of cases, cross-over designs are not possible and parallel studies have to be used. These can seldom be as large as 8 animals/treatment to match an n = 8 cross-over. Animals in parallel designs receive only one treatment. Parallel studies will have a different sensitivity to detect changes. This sensitivity is a critical question in using nonclinical QTc evaluations to support an integrated proarrhythmic risk assessment under the newly released ICH E14/S7B Q&As. The current analysis used a study large enough (n = 48) to be analyzed both as a parallel and as a cross-over design to directly compare the performance of the two experimental designs coupled to different statistical models, while all other study conduct aspects were the same. A total of 48 nonhuman primates (NHP) received 2 different treatments twice: vehicle, moxifloxacin (80 mg/kg), vehicle, moxifloxacin (80 mg/kg). Post-dose QTc interval data were recorded for 48 h for each treatment. Data were analyzed using 12 animals randomly selected for each treatment in a parallel design or as an n = 48 animal cross-over study. Different statistical models were used. The primary endpoint was the residual deviation (sigma) from the models applied to hourly time intervals. The sigma was used to determine the minimal detectable difference (MDD) for the study design-statistical model combination. Two statistical models were applicable to either study design. They gave similar sigma and resulting MDD values. In cross-over designs, the individual animal identification (ID) can be used in the statistical model. This enabled the smallest MDD value. Simple statistical models for analysis were identified: Treatment + Baseline for parallel designs and Treatment + ID for cross-over designs. The statistical sensitivity of NHP parallel study designs is reasonable (MDD for n = 6 of 12.7 ms), and in combination with testing exposures higher than likely to be necessary in man could be used in an integrated risk assessment. Where sensitivity of the NHP in vivo QTc assessment is critical, the cross-over design enabled a higher sensitivity (MDD 12.2 ms for n = 4; 8 ms for n = 8).

PMID:37495163 | DOI:10.1016/j.vascn.2023.107299

Sci Total Environ. 2023 Jul 24:165740. doi: 10.1016/j.scitotenv.2023.165740. Online ahead of print.

ABSTRACT

BACKGROUND: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy.

METHODS: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models.

RESULTS: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (β 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele).

CONCLUSIONS: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.

PMID:37495132 | DOI:10.1016/j.scitotenv.2023.165740

World Neurosurg. 2023 Jul 24:S1878-8750(23)01023-9. doi: 10.1016/j.wneu.2023.07.083. Online ahead of print.

ABSTRACT

BACKGROUND: Pain relief in lumbar disc hernias is a challenging condition. This study retrospectively compared particulate steroids, methylprednisolone acetate (mid-term effective), against betamethasone acetate (Long-term effective) on ultrasound-guided caudal epidural injection for lumbar disc herniation (LDH).

METHODS: A total of 40 patients with L4-5 and/or L5-S1 disc herniation were treated with ultrasound-guided caudal epidural injection between September 2021 and June 2022. Nine-teen patients who were given methylprednisolone acetate (group A) as a steroid and a total of 21 patients who were used betamethasone acetate (Group B) were retrospectively collected, and their pain levels and functional improvement were compared retrospectively before, immediately after, and 3 weeks after the injection in terms of the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) as the efficacy value.

RESULTS: There was no statistically significant difference between the groups regarding age, gender, and BMI (p >0.05). In group A, pre-op VAS was 8.84 ± 0.76, immediate post-op period 3.10 ± 1.37, and post-op 3rd week was 4.73 ± 2.32. In group B, the pre-op VAS was 8.76 ±0.76, the post-op early period was 3.14 ± 1.27, and the post-op 3rd week was 3.12 ± 1.30. In group A pre-op ODI was 49.84 ± 9.11 and post-op 3rd week was 22.84 ± 6.44. In group B, the pre-op ODI was 46.71 ± 16.15 and post-op 3rd week was 30.80 ± 17.65. Significant changes were observed in the reduction of VAS values after the procedure in both groups during the early postoperative period and the third week (p-value < 0.05). However, a significant difference was not found between the changes in VAS values between the groups (p-value > 0.005). Similarly, significant changes were observed in the decrease of ODI values after the procedure in both groups during the early postoperative period and the third week (p-value < 0.05). However, no significant difference was observed in the ODI scores between the two groups.

CONCLUSIONS: No significant difference was observed between betamethasone and methylprednisolone. Both steroid groups showed a substantial improvement in the preoperative pain scores of the patients.

PMID:37495099 | DOI:10.1016/j.wneu.2023.07.083