Feasibility and efficacy of delayed pharmacoinvasive therapy for STelevation myocardial infarction

BACKGROUND ST-elevation myocardial infarction(STEMI)refers to a clinical syndrome that features symptoms of myocardial ischemia with consequent ST-elevation on electrocardiography and an associated rise in cardiac biomarkers.Rapid restoration of brisk flow in the coronary vasculature is critical in reducing mortality and morbidity.In patients with STEMI who could not receive primary percutaneous coronary intervention(PCI)on time,pharmacoinvasive strategy(thrombolysis followed by timely PCI within 3-24 h of its initiation)is an effective option.AIM To analyze the role of delayed pharmacoinvasive strategy in the window period of 24-72 h after thrombolysis.METHODS This was a physician-initiated,single-center prospective registry between January 2017 and July 2017 which enrolled 337 acute STEMI patients with partially occluded coronary arteries.Patients received routine pharmacoinvasive therapy(PCI within 3-24 h of thrombolysis)in one group and delayed pharmacoinvasive therapy(PCI within 24-72 h of thrombolysis)in another group.The primary endpoint was major adverse cardiac and cerebrovascular events(MACCE)within 30 d of the procedure.The secondary endpoints included major bleeding as defined by Bleeding Academic Research Consortium classification,angina,and dyspnea within 30 d.RESULTS The mean age in the two groups was comparable(55.1±10.1 years vs 54.2±10.5 years,P=0.426).Diabetes was present among 20.2%and 22.1%of patients in the routine and delayed groups,respectively.Smoking rate was 54.6%and 55.8%in the routine and delayed groups,respectively.Thrombolysis was initiated within 6 h of onset of symptoms in both groups(P=0.125).The mean time from thrombolysis to PCI in the routine and delayed groups was 16.9±5.3 h and 44.1±14.7 h,respectively.No significant difference was found for the occurrence of measured clinical outcomes in the two groups within 30 d(8.7%vs 12.9%,P=0.152).Univariate analysis of demographic characteristics and risk factors for patients who reported MACCE in the two groups did not demonstrate any significant correlation.Secondary endpoints such as angina,dyspnea,and major bleeding were non-significantly different between the two groups.CONCLUSION Delayed PCI pharmacoinvasive strategy in a critical diseased but not completely occluded artery beyond 24 h in patients who have been timely thrombolyzed seems a reasonable strategy.

Single-use flexible ureteroscopes: Comparative in vitro analysis of four scopes

Objective:Single-use flexible ureteroscopes(fURSs)have recently been introduced by different companies.Goal of this in-vitro study was to compare four fURSs.Methods:We performed in vitro analysis of Uscope 7.5 Fr and Uscope 9.5 Fr(Pusen Ltd.,Zhuhai,China),LithoVue 9.5 Fr(LithoVue
,Boston Scientific,MA,USA),and Indoscope 9.5 Fr(Bioradmedisys
,Pune,India).Optical characteristics(image resolution,color representation,and luminosity)were compared at various distances of 10 mm,20 mm,and 50 mm.Deflection and irrigation were evaluated with and without accessories.Results:Color perception was comparable for all scopes at 10 mm(p<0.05),while Lithovue 9.5 Fr was comparable with Indoscope 9.5 Fr at the distances of 20 mm and 50 mm.Both scopes were statistically better than both Uscopes at the distances of 20 mm and 50 mm.Image resolution powers were comparable amongst all fURSs at the distances of 10 mm and 20 mm(3.56 line pairs per millimeter[lp/mm]).However,Indoscope(3.56 lp/mm)was superior to LithoVue and Uscope scopes(3.17 lp/mm)at the distance of 50 mm.Luminosity at the distance of 10 mm was comparable for LithoVue and Uscope 9.5 Fr.However,at the distances of 20 mm and 50 mm,LithoVue had the highest luminosity while Uscope 7.5 Fr had the lowest one.Indoscope had lower luminosity than other 9.5 Fr scopes at all distances.With empty working channel and 200 mm laser fiber,Indoscope had the maximum deflection(285
).With basket,Uscope 7.5 Fr had the maximum loss of deflection(30
)while Indoscope had no deflection loss.With empty working channel,all scopes had comparable irrigation flow rates in both deflected and undeflected state.Similarly,with 200 mm laser or basket,irrigation flow rates were comparable in all scopes.Conclusion:Color representation was equivalent for Indoscope and LithoVue,while being better than Uscope 7.5 Fr and Uscope 9.5 Fr.Image resolution was comparable in all scopes at the distances of 10 mm and 20 mm.Beyond the distance of 10 mm,luminosity of LithoVue was the highest and that of Uscope 7.5 Fr was the lowest.Deflection loss was the minimum with Indoscope and the maximum with 7.5 Fr Uscope.Under all scenarios,irrigation flow rates were comparable in all scopes.

Disciplined sleep for healthy living: Role of noradrenaline

Sleep is essential for maintaining normal physiological processes. It has been broadly divided into rapid eye movement sleep(REMS) and non-REMS(NREMS); one spends the least amount of time in REMS. Sleep(both NREMS and REMS) disturbance is associated with most altered states, disorders and pathological conditions. It is affected by factors within the body as well as the environment, which ultimately modulate lifestyle.Noradrenaline(NA) is one of the key molecules whose level increases upon sleep-loss, REMS-loss in particular and it induces several REMS-loss associated effects and symptoms. The locus coeruleus(LC)-NAergic neurons are primarily responsible for providing NA throughout the brain. As those neurons project to and receive inputs from across the brain, they are modulated by lifestyle changes, which include changes within the body as well as in the environment. We have reviewed the literature showing how various inputs from outside and within the body integrate at the LC neuronal level to modulate sleep(NREMS and REMS) and vice versa. We propose that these changes modulate NA levels in the brain, which in turn is responsible for acute as well as chronic psychosomatic disorders and pathological conditions.

Clinical characteristics of COVID-19 patients who underwent tracheostomy and its effect on outcome:A retrospective observational study

BACKGROUND The exponential rise in Coronavirus disease 2019(COVID-19)cases has resulted in an increased number of patients requiring prolonged ventilatory support and subsequent tracheostomy.With the limited availability of literature regarding the outcomes of COVID-19 patients with tracheostomy,we attempted to study the clinical characteristics and multiple parameters affecting the outcomes in these patients.AIM To determine all-cause mortality following tracheostomy and its association with various risk factors in COVID-19 patients.METHODS This retrospective study included 73 adult COVID-19 patients admitted to the ICU between 1 April,2020 and 30 September,2021 who underwent tracheostomy as a result of acute respiratory failure due to COVID-19.The data collected included demographics(age,sex),comorbidities,type of oxygen support at admission,severity of COVID-19,complications,and other parameters such as admission to tracheostomy,intubation to tracheostomy,ICU stay,hospital stay,and outcome.RESULTS This study included 73 adult patients with an average age of 52±16.67 years,of which 52%were men.The average time for admission to tracheostomy was 18.12±12.98 days while intubation to tracheostomy was 11.97±9 days.The mortality rate was 71.2%and 28.8%of patients were discharged alive.The mean duration of ICU and hospital stay was 25±11 days and 28.21±11.60 days,respectively.Greater age,severe COVID-19,mechanical ventilation,shock and acute kidney injury were associated with poor prognosis;however,early tracheostomy in intubated patients resulted in better outcomes.CONCLUSION Patients with severe COVID-19 requiring mechanical ventilation have a poor prognosis but patients with early tracheostomy may benefit with no added risk.We recommend that the timing of tracheostomy be decided on a case-by-case basis and a well-designed randomised controlled trial should be performed to elucidate the potential benefit of early tracheostomy in such patients.

Up to 70 THz bandwidth from an implanted Ge photoconductive antenna excited by a femtosecond Er:fibre laser

Phase-stable electromagnetic pulses in the THz frequency range offer several unique capabilities in time-resolved spectroscopy.However,the diversity of their application is limited by the covered spectral bandwidth.In particular,the upper frequency limit of photoconductive emitters-the most widespread technique in THz spectroscopy-reaches only up to 7 THz in the regular transmission mode due to absorption by infrared-active optical phonons.Here,we present ultrabroadband(extending up to 70 THz)THz emission from an Au-implanted Ge emitter that is compatible with mode-locked fibre lasers operating at wavelengths of 1.1 and 1.55μm with pulse repetition rates of 10 and 20 MHz,respectively.This result opens up the possibility for the development of compact THz photonic devices operating up to multi-THz frequencies that are compatible with Si CMOS technology.

Randomized controlled trial of topical EMLA and vapocoolant spray for reducing pain during wDPT vaccination

Background:Intramuscular vaccination is among the most common source of iatrogenic pain in infants.Vapocoolant sprays are rapid-acting alternative to topical anesthetics.They provide transient anesthesia via evaporation induced skin cooling,and reduce pain due to vaccine injection in children and adults.The objective was to compare the synergistic analgesic effect of eutectic mixture of local anesthetics (EMLA) with breastfeeding (EB group) and vapocoolant spay with breastfeeding (VB group) to that of only breastfeeding (BO group) during whole cell diptheria,pertussis and tetanus (wDPT) vaccination.Methods:A double blind randomized controlled trial was done to include infants up to 3 months of age who came for their first wDPT vaccination.The primary outcome variable was the duration of cry after vaccination.Secondary outcome variables were Modified Facial Coding Score,Neonatal Infant Pain Scale and latency of onset of cry.Results:Of the 201 eligible participants,111 babies were excluded and remaining 90 babies were randomized into three groups of thirty each.The groups did not differ significantly in baseline characteristics.Median (interquartile range,IQR) of duration of cry was lesser [35.86 (21.07-107.75) seconds] in babies receiving EMLA cream with breast feeding (EB group) and in babies receiving vapocoolant spray with breast feeding (VB group) [32.58 (21.25-106.21) seconds] as compared to babies receiving only breast feeding (BO group) [67.5 (27.6-180) seconds] (P=-0.147).Difference in median (IQR) of latency of cry was not statistically significant.Modified Facial Coding Score and Neonatal Infant Pain Scale at 1 minute and 3 minutes was significantly lower in the EB and VB group,as compared to the BO group (P<0.05).Conclusions:Addition of topical EMLA application or vapocoolant spray to breastfeeding during wDPT vaccination does not reduce duration of cry in infants up to 3 months of age.However,they are able to show reduction in pain score and further studies are warranted to assess their efficacy as pain relief measures in infants and children.

点突变对胶原纤维结构和机械性能的影响：分子动力学研究

现代人对胶原机械性能和结构的理解程度，对于生物医学材料以及纳米技术的应用至关重要。而且，点突变与许多胶原类疾病有关，其中包括成骨不全症（OI）。我们进行一系列传统研究以及能够操纵原子的分子动力学模拟，以便检测点突变对于胶原纤维结构和机械性能的影响，包括甘氨酸到丙氨酸、天冬氨酸、半胱氨酸和丝氨酸的突变以及羟脯氨酸到精氨酸、天冬酰胺、谷酰胺和赖氨酸的突变。研究发现，所有点突变均能分散胶原纤维的结构，并降低其强度，从而影响纤维的层堆积。相对于羟脯氨酸突变（wT〉Arg〉Glu〉Asn〉Lys），甘氨酸突变（wT〉Ala〉ser〉cys〉Asp）对纤维的机械强度的影响更为有害。甘氨酸突变的临床表现与通过分子模拟预言纤维可拉伸强度降低的趋势相一致。大体上，胶原纤维机械性能的降低能够预言点突变的临床表现。

Cellulose synthase ‘class specific regions’ are intrinsically disordered and functionally undifferentiated

Cellulose synthases （CESAs） are glycosyltransferases that catalyze formation of cellulose microfibrils in plant cell walls. Seed plant CESA isoforms cluster in six phylogenetic clades, whose non-interchangeable members play distinct roles within cellulose synthesis complexes （CSCs）. A ＇class specific region＇ （CSR）, with higher sequence similarity within versus between functional CESA classes, has been suggested to contribute to specific activities or interactions of different isoforms. We investigated CESA isoform specificity in the moss, Physcomitrella patens （Hedw.） B. S. G. to gain evolutionary insights into CESA structure/function relationships. Like seed plants, P. patens has oligomeric rosette-type CSCs, but the PpCESAs diverged independently and form a separate CESA clade. We showed that P. patens has two functionally distinct CESAs classes, based on the ability to complement the gametophore-negative phenotype of a ppcesa5 knockout line. Thus, non-interchangeable CESA classes evolved separately in mosses and seed plants. However, testing of chimeric moss CESA genes for complementation demonstrated that functional classspecificity is not determined by the CSR. Sequence analysis and computational modeling showed that the CSR is intrinsically disordered and contains predicted molecular recognition features, consistent with a possible role in CESA oligomerization and explaining the evolution of class-specific sequences without selection for class-specific function.