Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.

BACKGROUND: The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection. METHODS: This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded. RESULTS: A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001). CONCLUSION: Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

Tau immunotherapy in Alzheimer's disease and progressive supranuclear palsy.

Tubulin-associated unit (tau) has been associated with more than 25 neurological disorders-the so-called tauopathies. Hence, finding a novel therapeutic agent targeting tau to halt the progression of diseases has been of interest. Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are the most studied tauopathies. AD is characterized by two cardinal pathological mechanisms: amyloid ß (Aß) plaques and neurofibrillary tangles (NFTs), leading to atrophy of the brain. Over the last few years, attention has been on NFTs composed of the hyperphosphorylated microtubule-associated protein tau. Tau contributes to the synaptic plasticity of axons; hyperphosphorylated and aggregated tau have been shown to increase the likelihood of cognitive impairments. PSP is also associated with tau accumulation in NFTs and neuropil threads, making this condition a candidate for tau-targeted therapies. Many tau-targeting therapies have been developed, and clinical trials are being conducted. Tau-targeting drugs are classified into four subgroups based on the pathological target: tau phosphorylation inhibitors, stabilizers of microtubules, enhancing tau clearance, and tau aggregation inhibitors. On the other hand, the desired specificity and sensitivity of tau immunotherapy agents without interrupting normal proteome are the fundamental point of tremendous attention. Starting with animal studies of these therapies to clinical trials, both are divided into passive and active immunotherapies, while passive immunotherapies are the method of desire. Targeting aggregation and phosphorylation sites of tau is the chief target of therapies. This article reviews the latest animal and clinical studies of tau-based immunotherapies and tau-targeted drugs for AD and PSP.

Comparison of Intravenous Paracetamol, Dexketoprofen Trometamol, or Topical Lidocaine Use for Pain Relief in Scorpion Stings: A Placebo-Controlled, Randomized Study.

INTRODUCTION: After a scorpion sting, patients commonly present to hospitals with pain. Our study sought to compare the analgesic efficacy of IV paracetamol, IV dexketoprofen trometamol, topical lidocaine, and placebo in patients reporting pain after presenting with a history of scorpion sting. METHODS: This double-blind, randomized, placebo-controlled study was conducted in the emergency department of a tertiary hospital. Adult patients who presented with the complaint of pain after a scorpion sting and did not have systemic findings were randomly assigned to 1 of the following 4 groups: IV paracetamol, IV dexketoprofen trometamol, topical lidocaine, and placebo. The visual analog scale scores were measured at the time of presentation to the emergency department and at 30 and 60 min to determine the pain intensity. RESULTS: The study included 106 patients, of whom 30 were in the paracetamol group, 26 in the dexketoprofen trometamol group, 25 in the topical lidocaine group, and 25 in the placebo group. We did not find a different analgesic effect among the groups in the first 30 min (P=0.185). IV paracetamol, dexketoprofen trometamol, and topical lidocaine did not show different analgesic effects in the first 60 min (P>0.05). IV paracetamol and dexketoprofen trometamol were found to provide a more effective analgesia than the placebo at 60 min (P<0.05). The analgesic effects of topical lidocaine and placebo did not differ (P=0.330). CONCLUSIONS: IV paracetamol and IV dexketoprofen trometamol provided analgesia in the first 60 min, similar to topical lidocaine but superior to placebo.

Side Effects Related to BNT162b2 and CoronaVac Vaccine Requiring Emergency Department Visit.

Background Currently, the most effective method in the fight against coronavirus disease 2019 (COVID-19) is vaccination against the disease. However, there are hesitations among society concerning the safety and side effects of COVID-19 vaccines. We aimed to determine the observed side effects that require an emergency room visit after taking the BNT162b2 and CoronaVac vaccines. Methods This prospective observational study was conducted with patients who presented to the emergency department due to vaccine-related complications after COVID-19 vaccination. The patients' symptoms at the time of presentation, time from vaccination to the onset of symptoms, and dose of the vaccine administered were determined. In addition, the demographic characteristics of the patients, whether they had a history of COVID-19 infection, and their vital signs at the time of presentation were recorded. The variables were compared according to the type of vaccine administered. Results The study included 182 patients who presented to the emergency department over a 6-month period. It was determined that 166 of these patients (91.2%) had received the BNT162b2 vaccine and 16 (8.8%) had received the CoronaVac vaccine. The majority of the patients did not have a history of COVID-19 infection (70.3%), and most presented to the hospital with complications after the second dose (61%). The onset of vaccine-related symptoms was mostly within 1 to 12 hours (39%). The majority of patients (97.8%) were discharged from the emergency department. The most common symptoms after vaccination were fatigue ( n = 70), followed by muscle/joint pain ( n = 52), headache ( n = 33), and fever ( n = 32). The rate of dizziness was found to be statistically significantly higher in the CoronaVac vaccine group than in the BNT162b2 vaccine group ( p = 0.008). There was no statistically significant difference between the two vaccine groups in relation to the remaining symptoms ( p > 0.005). Conclusion There were no serious complications related to the BNT162b2 or CoronaVac vaccine. The most common symptom after both vaccines was fatigue; therefore, the BNT162b2 and CoronaVac vaccines can be safely administered.

Transcutaneous Electrical Nerve Stimulation (TENS) for the Treatment of Renal Colic in the ED: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY OBJECTIVE: To determine the analgesic efficacy of TENS treatment in patients with renal colic in the emergency department (ED). METHODS: This double-blind, randomized controlled trial was conducted in a tertiary care ED. Patients with a definitive diagnosis of renal colic were assigned (1:1) as randomized to receive the real TENS with frequency 100 Hz, pulse width 200 microseconds, voltage 2 mA, or placebo with sham TENS. Pain intensity was measured using visual analog scales (VAS) at baseline, after 15 and 30th minutes. RESULTS: A total of 100 patients were included in the final analysis: 50 patients treated with real TENS and 50 patients treated with sham TENS. VAS scores in both groups were similar at baseline. The mean reduction in VAS score at 15 min was 33.3 ± 17.6 (95% Confidence interval (CI): 28.3 to 38.3) for the real TENS group and 14.9 ± 11.6 (95% CI 11.6 to 18.2) for the sham TENS group (mean difference: 18.4 (95% CI: 12.5 to 24.4, P < 0.0001). The mean reduction in VAS score at 30 min was 63.7 ± 21.1 (95% CI: 57.7 to 69.7) for the real TENS group and 14.9 ± 16.2 (95% CI: 19.5 to 10.3) for the sham TENS group (mean difference: 48.8, 95% CI: 41.4 to 56.3, P < 0.0001). Four patients (8%) in the real TENS group and 24 patients (48%) in the sham TENS group required the rescue medication after 30th minutes. CONCLUSIONS: TENS is effective for acute pain treatment in renal colic patients in the ED. TENS therapy could be a treatment option for renal colic.

Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19.

PURPOSE: Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency. METHODS: Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined. RESULTS: Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype. CONCLUSION: 25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients.

Biotransformation of 2,4-dinitrotoluene by the beneficial association of engineered Pseudomonas putida with Arabidopsis thaliana.

2,4-dinitrotoluene (2,4-DNT) is a priority environmental xenobiotic pollutant which has toxic, mutagenic, and carcinogenic properties. Thus, its biodegradation by applying recent approaches such as taking advantage of plant-bacteria interactions is crucial. In this work, the genes from Burkholderia sp. R34, necessary for 2,4-DNT degradation, were integrated into wild-type Pseudomonas putida (P. putida) KT2440 genome, and this strain, named KT.DNT, was inoculated to soil in in vitro conditions. To estimate the disappearance of 2,4-DNT in contaminated soil, samples were taken from different time intervals, extracted and analyzed using high-performance liquid chromatography (HPLC). Biotransformation of 2,4-DNT increased gradually and the degradation in soil after 14-days of treatment with the bacterium was found to be the 97.1%, indicating that the engineered strain could be a remarkable candidate for in situ bioremediation of 2,4-DNT-contaminated sites. In addition, in vitro interaction of this bacterium with a model plant, Arabidopsis thaliana (A. thaliana), enhanced lateral root and root hair formation together with dry root weight. Moreover, the initial 2,4-DNT concentration was decreased to 68% within 2 h with the plant-associated KT.DNT in liquid culture. Hence, the usage of this bacterium with plants could also be a promising application for the 2,4-DNT biotransformation.

Effects of Pure and Mixed Autochthonous Torulaspora delbrueckii and Saccharomyces cerevisiae on Fermentation and Volatile Compounds of Narince Wines.

The cultivar of Narince is a native white grape variety of Vitis vinifera, grown in Tokat city, the Mid-Black Sea Region of Anatolia. In this study, the effects of pure and mixed autochthonous Torulaspora delbrueckii-214 and Saccharomyces cerevisiae-1088 cultures on the fermentation behavior and aroma compounds of Narince wines were investigated. Volatile compounds formed in wines were extracted using a liquid⁻liquid extraction method and determined by GC-MS-FID. Narince grape must was fermented in duplicate, under the following three conditions. Two pure cultures of T. delbrueckii-214 and S. cerevisiae-1088 and a mixture of T. delbrueckii-214 and S. cerevisiae-1088 (1:1). The presence of the non-Saccharomyces T. delbrueckii-214 yeast slowed down the fermentation and produced a lower level of ethanol and a higher levels of glycerol and volatile acid. Only the pure culture of T. delbrueckii-214 was unable to finish fermentation. On the other hand, mixed culture fermentation improved the aroma intensity and complexity of wine due to increased levels of higher alcohols and esters. According to sensory analysis, wine fermented with mixed culture was the most preferred wine followed by wine inoculated with pure S. cerevisiae-1088. This study confirms the role of T. delbrueckii in wine aroma and the potential of non-Saccharomyces use in winemaking.

Complications of intrastromal corneal ring segment implantation using a femtosecond laser for channel creation: a survey of 850 eyes with keratoconus.

PURPOSE: To report complications after the implantation of intrastromal corneal ring segments (Keraring; Mediphacos, Belo Horizonte, Brazil) in keratoconic eyes using a femtosecond laser (IntraLase; Advanced Medical Optics, Santa Ana, California, USA) for channel creation. METHODS: Retrospective chart review of 531 patients (850 eyes) who underwent Keraring insertion using a femtosecond laser for channel creation. Intraoperative and postoperative complications were recorded. RESULTS: Intraoperatively, there were 22 (2.7%) cases of incomplete channel formation. The rest of the intraoperative complications were galvo lag error (system malfunction) [five eyes (0.6%)], endothelial perforation [five eyes (0.6%)] and incorrect entry of the channel [two eyes (0.2%)]. Postoperatively, there were 11 (1.3%) cases of segment migration, two (0.2%) cases of corneal melting and one (0.1%) case of mild infection. The overall complication rate was 5.7% (49 cases out of 850 eyes). CONCLUSION: In this study, intracorneal ring segment implantation using a femtosecond laser for channel creation was related to a number of complications. The most common complications were incomplete channel creation (intraoperatively) and segment migration (postoperatively).

INTACS followed by KeraRing intrastromal corneal ring segment implantation for keratoconus.

PURPOSE: To describe the visual and refractive outcomes in three eyes (two keratoconic patients) with previous intrastromal corneal ring segments (INTACS, Addition Technology Inc) that underwent adjuvant single KeraRing (Mediphacos) intrastromal corneal ring segment implantation. METHODS: Two keratoconic patients (three eyes) with implanted INTACS segments underwent an additional (without explanting previous INTACS) single KeraRing segment implantation. RESULTS: No intraoperative complications occurred. Six months postoperatively, uncorrected distance visual acuity improved from 20/100 and 20/200 to 20/32 and 20/40 in the right and left eyes, respectively, of patient 1, and from 20/400 to 20/50 in the treated right eye of patient 2. Corrected distance visual acuity improved from 20/50 and 20/100 to 20/30 and 20/32 in the right and left eyes, respectively, of patient 1 and from 20/200 to 20/40 in patient 2. Keratometric measurements improved from 51.00/45.70 to 47.00/44.60 diopters (D) and from 50.80/48.80 to 42.70/40.30 D in the right and left eyes, respectively, of patient 1, and from 49.30/45.70 to 45.60/44.10 D in patient 2. CONCLUSIONS: In keratoconic patients with INTACS in place, adjuvant single intrastromal corneal ring segment (KeraRing) implantation could improve visual and refractive outcome.

Effect of treatment sequence in combined intrastromal corneal rings and corneal collagen crosslinking for keratoconus.

PURPOSE: To compare 2 sequences of combined intrastromal corneal ring segment (ICRS) implantation and ultraviolet/riboflavin-mediated corneal collagen crosslinking (CXL) in progressive keratoconus. SETTING: Dunya Eye Hospital, Istanbul, Turkey. METHODS: In this prospective comparative randomized consecutive study, CXL was followed by ICRS implantation (Group 1) or ICRS implantation was followed by CXL (Group 2). Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, spherical equivalent (SE), manifest cylinder (cylinder), and mean keratometry (K) were compared preoperatively and postoperatively. RESULTS: The mean interval between treatments was 7 months +/- 2 (SD) (mean follow-up, 13 +/- 1 months). The mean UDVA and CDVA improved in both groups (UDVA: 0.07 +/- 0.09 to 0.25 +/- 0.12, Group 1, and 0.11 +/- 0.09 to 0.32 +/- 0.21, Group 2; CDVA: 0.24 +/- 0.11 to 0.41 +/- 0.20 and 0.22 +/- 0.16 to 0.55 +/- 0.2, respectively). The mean SE, cylinder, and mean K values decreased in both groups (SE: -7.13 +/- 3.34 D to -2.98 +/- 2.33 D, Group 1, and -7.05 +/- 5.54 D to -2.81 +/- 4.08 D, Group 2; cylinder: -4.38 +/- 2.03 D to -2.62 +/- 1.93 D and -4.68 +/- 2.60 D to -2.20 +/- 1.67 D, respectively; mean K: 52.47 +/- 4.01 D to 48.31 +/- 3.65 D and 52.06 +/- 4.93 D to 48.08 +/- 4.13 D, respectively). Overall, there was more improvement in CDVA, SE, and mean K in Group 2 than in Group 1. CONCLUSION: Implantation of ICRS followed by CXL resulted in greater improvement of keratoconus.

One-year results of intrastromal corneal ring segment implantation (KeraRing) using femtosecond laser in patients with keratoconus.

PURPOSE: To report the results of intrastromal corneal ring segment [ICRS] (KeraRing; Mediphacos, Belo Horizonte, Brazil) implantation using a femtosecond laser (IntraLase Corp, Irvine, California, USA) in keratoconic patients. DESIGN: Retrospective, noncomparative, interventional study. METHODS: Thirty-two keratoconic patients (50 eyes) who underwent ICRS insertion using a femtosecond laser for channel creation and completed at least one year of follow-up were included in this study. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, topographic findings, and adverse events were assessed. RESULTS: No intraoperative complications were demonstrated in this series of patients. At the first postoperative day, segment migration to the incision site was seen in three eyes (6%; early postoperative complication). To avoid melting, we repositioned the migrated segment away from the incision site. Serious second migration was not seen and we did not need to reposition any segment again. At the last postoperative examination, there was a statistically significant reduction in the spherical equivalent refractive error compared with that observed at the examination before implantation (mean +/- standard deviation, -5.62 +/- 4.15 diopters [D; range, -23.62 to 0.50 D] to -2.49 +/- 2.68 D [range, -11.12 to 3.5 D]; P < .001). The UCVA before implantation was 20/40 or worse in 47 eyes (94%; range, counting fingers to 20/30), whereas at the last follow-up examination, 14 (28%) of 50 eyes had a UCVA of 20/40 or better (range, counting fingers to 20/25). Nine eyes (18%) maintained the preimplantation BSCVA, whereas 39 eyes (68%) experienced a BSCVA gain of one to four lines at the last follow-up examination. Only in two eyes (4%; two patients) with advanced keratoconus (stage III) was there a decrease of up to two lines. Despite this deterioration in BSCVA, the patients did not want to remove the ICRSs, because there was an increase of UCVA. No late postoperative complications were observed during the follow-up period. CONCLUSIONS: ICRS (KeraRing) implantation using femtosecond laser for tunnel creation is a minimally invasive procedure for improving visual acuity (both UCVA and BSCVA) in keratoconic patients.

Combined Intacs and posterior chamber toric implantable Collamer lens implantation for keratoconic patients with extreme myopia.

PURPOSE: To evaluate the results of combined Intacs (Addition Technology, Fremont, California, USA) and posterior chamber toric implantable Collamer lens [ICLs] (Visian ICL; STAAR Surgical, Monrovia, California, USA) implantation in keratoconic patients with extreme myopia and irregular astigmatism. DESIGN: Prospective, single-center, noncomparative, interventional, consecutive case series. METHODS: Three eyes of two consecutive highly myopic keratoconic patients who had undergone posterior chamber toric ICLs implantation after Intacs implantation. Implantation of posterior chamber toric ICLs was performed at intervals between six and 10 months after Intacs implantation. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, topographic findings, adverse events, and postoperative complications were noted. RESULTS: No intraoperative or postoperative complications were observed. An improvement in UCVA and BSCVA was found after the Intacs and toric Visian ICL procedures in all eyes. All eyes were emmetropic within 1 diopter (D), whereas the mean manifest refractive spherical equivalent refraction reduced from -18.50 +/- 2.61 D (range, -16.75 to -21.50 D) to 0.42 D (range, plano to -0.75 D). The mean difference between preoperative and last follow-up UCVA and BSCA was a gain of 6.67 +/- 1.15 lines (range, gain of six to eight lines) and 4.33 +/- 2.52 lines (range, gain of two to seven lines), respectively. CONCLUSIONS: Combined Intacs and posterior chamber toric phakic Visian ICL implantation in a two-step procedure is an effective method for correcting keratoconic patients with extreme myopia.

Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation.

PURPOSE: To investigate the effect of the cumulative exposure to estradiol (E(2)) during the follicular phase on IVF outcome. METHODS: Patients were stimulated with recombinant FSH after GnRH agonist suppression and had a day 3-embryo transfer. Estrogen exposure was determined as the area under the curve (AUC) for serum E(2) levels measured from the first day of stimulation through the day after hCG administration. RESULTS: E(2) AUC thresholds for 10th and 90th percentiles were 4704 pg/ml and 16338 pg/ml, respectively. The pregnancy and implantation rates were highest in the 10th-90th percentile group, and were statistically higher in this group than in the >90th percentile group (54.6% vs. 33.3% and 24.8% and 12.9%, respectively, for pregnancy and implantation rates, P < 0.05). Recovered mature oocytes, fertilization, and number and mean score of transferred embryos were similar. CONCLUSIONS: High cumulative E(2) exposure during the follicular phase of IVF cycles has detrimental effects on implantation.

Predictive value of the hemizona assay for pregnancy outcome in patients undergoing controlled ovarian hyperstimulation with intrauterine insemination.

OBJECTIVE: The hemizona assay (HZA) is an established functional test that examines in vitro sperm-zona pellucida binding capacity with high predictive power for fertilization outcome in IVF. The objective of this study was to evaluate the value of the HZA as a predictor of pregnancy in patients undergoing controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI). DESIGN: Prospective clinical study. SETTING: Academic center. PATIENT(S): Eighty-two couples with unexplained or male factor infertility that underwent 313 IUI cycles. INTERVENTION(S): Basic semen analysis and HZA were performed within three months of starting COH/IUI therapy. MAIN OUTCOME MEASURE(S): Hemizona index (HZI) and clinical pregnancy. RESULT(S): Overall, patients with an HZI of <30 had a significantly lower pregnancy rate compared to patients with an HZI of > or =30 (11.1% vs. 40.6%, respectively; P<.05; relative risk for failure to conceive: 1.5 (confidence interval 1.2-1.9)). In all patients combined, and in the range of HZI 0-60, the duration of infertility (P=.000) and the HZI (P=.004) were significant determinants of conception (receiver operating characteristics (ROC) analysis). In couples with male infertility, the average path velocity and HZI were significant predictors of conception (P=.001 and P=.005, respectively, ROC analysis). The negative and positive predictive values of the HZA for pregnancy were 93% and 69%, respectively. Logistic regression analysis provided models of HZI (P=.021) and duration of infertility (P=.037) with highest predictability of conception in male factor and unexplained infertility groups, respectively. CONCLUSION(S): The HZA predicted pregnancy in the IUI setting with high sensitivity and negative predictive value in couples with male infertility. Results of this sperm function test are useful in counseling couples before allocating them into COH/IUI therapy.