Effects of COVID-19 variation on the treatment response and disease severity in critical illness: a retrospective observational cohort study.

OBJECTIVE: Even though the treatment of the original variant was not fully determined, variants of COVID-19 emerged. Whether the clinic of COVID-19 has changed because of variation is controversial. The present study aimed to examine the COVID-19 severity and treatment responsiveness of critically ill patients between the original virus and emergent variations with a more comprehensive set of measures. PATIENTS AND METHODS: Treatment responses, laboratory findings, and clinical conditions of critically ill patients with COVID-19 who were identified with variants between February 1st, and May 30th, 2021, were examined in two medical Intensive Care Units (ICUs) in tertiary care centers. Each patient received treatment in the ICU for at least one week. RESULTS: Sixty-five (30 patients with the original variant: POV) critically ill patients were included in the study. SOFA scores, blood glucose, total bilirubin, urea-creatinine and lactate dehydrogenase levels decreased significantly in POV (p=.031, p=.002, p=.002, p=.008, and p=.007, respectively). Overall, patients with emergent variants (PEV) (M = 76.58, SD = 8.64) had lower partial-pressure-of-oxygen/fraction-of-inspired-oxygen ratios (P/F) than POV (M = 123.16, SD = 9.49). Use of the prone position and steroid therapy did not result in significant improvements in oxygenation of critically ill PEV. Hypertension was identified as the common comorbidity in PEV (OR=5.287). CONCLUSIONS: We showed that the state of PEV was more severe than POV at the time of ICU admission. However, the prone position and steroids were not efficient in improving the P/F ratios. P/F ratios of PEV were significantly lower in non-invasive ventilation. These results suggest that early intubation might be necessary for PEV.

DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription.

Post-translational modifications of histone variant H2A.Z accompany gene transactivation, but its modifying enzymes still remain elusive. Here, we reveal a hitherto unknown function of human KAT2A (GCN5) as a histone acetyltransferase (HAT) of H2A.Z at the promoters of a set of transactivated genes. Expression of these genes also depends on the DNA repair complex XPC-RAD23-CEN2. We established that XPC-RAD23-CEN2 interacts both with H2A.Z and KAT2A to drive the recruitment of the HAT at promoters and license H2A.Z acetylation. KAT2A selectively acetylates H2A.Z.1 versus H2A.Z.2 in vitro on several well-defined lysines and we unveiled that alanine-14 in H2A.Z.2 is responsible for inhibiting the activity of KAT2A. Notably, the use of a nonacetylable H2A.Z.1 mutant shows that H2A.Z.1ac recruits the epigenetic reader BRD2 to promote RNA polymerase II recruitment. Our studies identify KAT2A as an H2A.Z.1 HAT in mammals and implicate XPC-RAD23-CEN2 as a transcriptional co-activator licensing the reshaping of the promoter epigenetic landscape.

In vitro water resistance testing using SPF simulation based on spectroscopic analysis of rinsed sunscreens.

OBJECTIVE: Water resistance retention (WRR) is the third performance attribute of sunscreens. Today, the standardized method for testing WRR is performed in vivo. For screening purposes, an in vitro method is highly preferable. Up to now, however, available methods have failed in accurately predicting in vivo WRR. In this study, we examine a novel in vitro approach aimed at enhancing in vivo prediction of WRR. METHODS: We investigated two approaches, including a traditional procedure referred to as the 'plate method', which involves measuring in vitro sun-protection factor (SPF) before and after water immersion, and a new approach termed the 'solution method'. The latter employed a computational method to calculate the SPF using UV transmittance measurements of a sunscreen solution, obtained by rinsing the substrate without water immersion and with water immersion. It also had a model function for describing film irregularity. The aim was to avoid the effect of substrate-to-product affinity on the film distribution, which impacts the measured absolute value of the in vitro SPF occurring in the conventional approach. For both methodologies, we assessed two substrates for the sunscreen application based on different polymers, the widely used polymethylmethacrylate (PMMA) and the ethylene methacrylate acid copolymer (EMA). RESULTS: The agreement between in vivo and in vitro WRR values obtained from each of the four test conditions was analysed using different sunscreens. No correlation was found between in vivo and in vitro WRR using the plate method, independently of the plate type. In contrast, the solution method, using EMA plates, revealed a significant correlation between in vivo and in vitro results, with an especially high correlation for in vivo non-water-resistant sunscreens. The results of two operators were comparable. The solution method was unsuitable for PMMA plates. CONCLUSION: Despite the small discrepancy remaining between WRR values obtained from the in vitro solution method and in vivo method, which itself shows variability in results, this work provided a new insight into the in vitro testing of water resistance of sunscreens.

5-HT receptor-mediated modulation of granule cell inhibition after juvenile stress recovers after a second exposure to adult stress.

Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior. Similarly, the 5-HT1A receptor-mediated inhibition of evoked inhibitory postsynaptic currents (IPSCs) of granule cells was only reduced in single stress exposed animals. This was also true for the number of granule cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3 receptors are expressed on cholecystokinin (CCK)+ basket cells in the hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+ basket cell markers after single juvenile or adult stress and partial recovery after combined stress, thus matching the electrophysiological findings. Adaptive changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells in the DG may help to maintain normal levels of anxiety after single juvenile or adult stress exposure, as indicated by the increased anxiety that accompanies the loss of this regulation upon combined stress.

The assessment of carcass traits of Awassi lambs by real-time ultrasound at different body weights and sexes.

The objectives of this experiment were to evaluate the accuracy of ultrasonography to measure subcutaneous fat thickness (SFT) and LM traits (area, depth, and width) in live Awassi lambs of different sexes, predict actual SFT and LM traits without damage to the carcass, and improve carcass classification. Data were obtained from ultrasound scans of 20 female and 10 male lambs. Female lambs were randomly divided into light (FL; n = 10) and heavy (FH; n = 10) finishing groups. Slaughter weights of lambs in FL were 30 kg and for FH and male groups were 40 kg. Subcutaneous fat thickness and LM traits, cross-sectional area between the 12th and 13th rib were measured using real-time ultrasound in vivo and on the carcass after slaughter. All ultrasound and carcass measurements were different (P > 0.05) except carcass yield and carcass LM width in female lambs (FL and FH). Between different sex groups, all ultrasound and carcass measurements were the same except ultrasound SFT (USFT; P = 0.04) and carcass SFT (CSFT; P = 0.03). Significant correlation coefficients were between USFT and CSFT (0.93, P < 0.01; 0.76, P = 0.02), ultrasound LM depth (ULMD) and carcass LM depth (CLMD; 0.64, P = 0.05; 0.77, P < 0.01), and ultrasound LM area (ULMA) and carcass LM area (CLMA; 0.88, 0.84; P < 0.01) for female lambs in FL and FH groups. Also, similar correlations were determined significantly between USFT and CSFT (0.84, P < 0.01; 0.76, P = 0.02), ULMD and CLMD (0.69, P = 0.03; 0.77, P < 0.01), and ULMA and CLMA (0.88, 0.84; P < 0.01) for male lambs in male and FH groups. The introduction of USFT and ULMA as independent variables in addition to BW in the multiple regression equations further improved the variations for CSFT (88, 75, and 81%) and CLMA (78, 90, and 80%) for lambs in FL, FH, and male groups, respectively, whereas no improvement was observed for cold carcass weight with the exception of the FH group and carcass yield. These results indicate that in vivo USFT and ULMA in association with BW could be used to estimate CSFT, CLMA, and cold carcass weight ultrasound findings about LM, and SFT can be included to the selection programs for different BW and sex of Awassi lambs.

The assessment of carcass composition of Awassi male lambs by real-time ultrasound at two different live weights.

The accuracy of ultrasonography to measure fat thickness (FT) and longissimus dorsi muscle (LM) traits (area, depth and width) in live Awassi male lambs and predict carcass FT and LM traits was studied. Twenty six Awassi male lambs were randomly divided into light (L) (n=13) and heavy (H) (n=13) finishing lambs. Slaughter weight of lambs in L and H groups were 40 and 45kg, respectively. FT and LM traits, cross-sectional area between the 12th and 13th rib were measured using real-time ultrasound in vivo and on the carcass after slaughter. All ultrasound and carcass measurements were the same except live weight (LW) (P<0.001), cold carcass weight (CCW) (P<0.001) and carcass LM width (P<0.05). Overall, correlation coefficients between ultrasound and carcass FT, LM depth, width and area were 0.79, 0.82 (P<0.001); 0.60, 0.58 (P<0.05); 0.48, -0.17 (P>0.05) and 0.89, 0.87 (P<0.001), respectively, for lambs in L and H groups. The introduction of ultrasound FT and ultrasound LM area as independent variables in addition to LW in the multiple regression equations further improved the variations for carcass FT (84%, 71%), carcass LM area (79%, 79%), CCW (72%, 65%) for lambs in light and heavy groups whereas no improvement was observed for carcass yield. These results indicate that in vivo ultrasound FT and measurement of the LM area in association with LW could be used to estimate carcass FT, carcass LM area and CCW in different LW Awassi lambs.

Sonographically guided fine-needle biopsy of thyroid nodules: the effects of nodule characteristics, sampling technique, and needle size on the adequacy of cytological material.

AIM: To evaluate the effects of sonographic characteristics of thyroid nodules, the diameter of needle used for sampling, and sampling technique on obtaining sufficient cytological material (SCM). MATERIALS AND METHODS: We performed sonography-guided fine-needle biopsy (FNB) in 232 solid thyroid nodules. Size-, echogenicity, vascularity, and localization of all nodules were evaluated by Doppler sonography before the biopsy. Needles of size 20, 22, and 24 G were used for biopsy. The biopsy specimen was acquired using two different methods after localisation. In first method, the needle tip was advanced into the nodule in various positions using a to-and-fro motion whilst in the nodule, along with concurrent aspiration. In the second method, the needle was advanced vigorously using a to-and-fro motion within the nodule whilst being rotated on its axis (capillary-action technique). RESULTS: The mean nodule size was 2.1+/-1.3 cm (range 0.4-7.2 cm). SCM was acquired from 154 (66.4%) nodules by sonography-guided FNB. In 78 (33.6%) nodules, SCM could not be collected. There was no significant difference between nodules with different echogenicity and vascularity for SCM. Regarding the needle size, the lowest rate of SCM was obtained using 20 G needles (56.6%) and the highest rate of adequate material was obtained using 24 G needles (82.5%; p=0.001). The SCM rate was 76.9% with the capillary-action technique versus 49.4% with the aspiration technique (p<0.001). CONCLUSION: Selecting finer needles (24-25 G) for sonography-guided FNB of thyroid nodules and using the capillary-action technique decreased the rate of inadequate material in cytological examination.

Persistence length changes dramatically as RNA folds.

We determine the persistence length l(p) for a bacterial group I ribozyme as a function of concentration of monovalent and divalent cations by fitting the distance distribution functions P(r) obtained from small angle x-ray scattering intensity data to the asymptotic form of the calculated P(WLC)(r) for a wormlike chain. The l(p) values change dramatically over a narrow range of Mg(2+) concentration from approximately 21 Angstroms in the unfolded state (U) to approximately 10 Angstroms in the compact (I(C)) and native states. Variations in l(p) with increasing Na(+) concentration are more gradual. In accord with the predictions of polyelectrolyte theory we find l(p) alpha 1/kappa(2) where kappa is the inverse Debye-screening length.

Protein and solvent dynamics: how strongly are they coupled?

Analysis of Raman and neutron scattering spectra of lysozyme demonstrates that the protein dynamics follow the dynamics of the solvents glycerol and trehalose over the entire temperature range measured 100-350 K. The protein's fast conformational fluctuations and low-frequency vibrations and their temperature variations are very sensitive to behavior of the solvents. Our results give insight into previous counterintuitive observations that protein relaxation is stronger in solid trehalose than in liquid glycerol. They also provide insight into the effectiveness of glycerol as a biological cryopreservant.

Histological evaluation of teeth with hyperplastic pulpitis caused by trauma or caries: case reports.

AIM: The purpose of this histological study was to examine teeth with hyperplastic pulpitis caused by trauma or caries. SUMMARY: The pulp tissue of one young permanent incisor with a complicated crown-root fracture and a hyperplastic pulpitis, which had been contaminated with oral microflora for 40 days, and pulp polyps from four permanent first molars whose crowns were destroyed by extensive caries were prepared for standard histological examination. Histologically, normal pulp tissue organization was observed in the tooth with a complicated crown-root fracture in the cervical radicular region. Irregular calcification was seen in the coronal and radicular portion of the pulp in the four carious teeth with pulp polyps. Radicular pulp tissue in the middle and apical third of root canals beneath irregular calcification showed intensive fibrosis but was free from inflammatory cells. KEY LEARNING POINTS: Hyperplastic pulpitis is a type of irreversible chronic open pulpitis. Young permanent teeth with hyperplastic pulpitis caused by trauma or caries have a great inherent defensive capacity to heal.