Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaginal swabs of women with acute SARS-CoV-2 infection: a prospective study.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vaginal secretions of both reproductive-aged and postmenopausal women during acute SARS-CoV-2 infection. DESIGN: Prospective study. SETTING: A single tertiary, university-affiliated medical centre in Israel. Time period, 1 June 2020 through to 31 July 2020. POPULATION: Women who were hospitalised in a single tertiary medical centre, who were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. METHODS: Women were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. Vaginal RT-PCR swabs were obtained from all study participants after a proper cleansing of the perineum. MAIN OUTCOME MEASURES: Detection of SARS-CoV-2 in vaginal RT-PCR swabs. RESULTS: Vaginal and nasopharyngeal swabs were obtained from 35 women, aged 21-93 years. Twenty-one women (60%) were in their reproductive years, of whom, five were in their third trimester of pregnancy. Most of the participants (57%) were healthy without any underlying medical conditions. Of the 35 patients sampled, 2 (5.7%) had a positive vaginal RT-PCR for SARS-CoV-2, one was premenopausal and the other was a postmenopausal woman. Both women had mild disease. CONCLUSION: Our findings contradict most previous reports, which did not detect the presence of viral colonisation in the vagina. Although passage through the birth canal exposes neonates to the vaginal polymicrobial flora, an acquisition of pathogens does not necessarily mandate neonatal infection or clinical disease. Nevertheless, when delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation, even if it is uncommon. TWEETABLE ABSTRACT: When delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation.

Prediction of data stream parameters in atmospheric turbulent wireless communication links.

A unified approach for calculation of information data stream parameters in the atmospheric optical communication channel is presented based on irradiance fluctuations of optical wave propagation through turbulence and on a generalized Ricean K-parameter distribution. The effects of turbulence are described via the well-known Kolmogorov scheme of turbulent structure relaxation in terms of stochastic scintillation theory described by the gamma-gamma distribution along with measurements of the values of the refractive index structure parameter, C(n)(2). The relation between the Ricean parameter K and the signal scintillation parameter sigma(I)(2) is considered to develop a unified description of the corresponding probability density function (pdf) of signal fading within an atmospheric wireless communication link. Through the corresponding pdf and parameter K, signal data stream parameters such as the signal-to-noise ratio (SNR), bit error rate (BER), and capacity of the optical atmospheric channel (C) are estimated. Such an approach permits the reliable prediction of the effects of fading caused by different levels of turbulence and agrees with experimental data observed at different atmospheric levels, at the heights of both 100-200 m and above 1-2 km. It is shown that at heights of 100-200 m, effects of fading, caused by turbulence, occur much more frequently than those at the heights of 1-2 km. Data stream parameters such as channel capacity, SNR, and spectral efficiency become stronger at higher altitudes, while at the same time the BER becomes relatively negligible.

The expression of SR calcium transport ATPase and the Na(+)/Ca(2+)Exchanger are antithetically regulated during mouse cardiac development and in Hypo/hyperthyroidism.

The mouse has been used extensively for generating transgenic animal models to study cardiovascular disease. Recently, a number of transgenic mouse models have been created to investigate the importance of sarcoplasmic reticulum (SR) Ca(2+)transport proteins in cardiac pathophysiology. However, the expression and regulation of cardiac SR Ca(2+)ATPase and other Ca(2+)transport proteins have not been studied in detail in the mouse. In this study, we used multiplex RNase mapping analysis to determine SERCA2, phospholamban (PLB), and Na(+)/Ca(2+)-exchanger (NCX-1) gene expression throughout mouse heart development and in hypo/hyperthyroid animals. Our results demonstrate that the expression of SERCA2 and PLB mRNA increase eight-fold from fetal to adult stages, indicating that SR function increases with heart development. In contrast, the expression of the Na(+)/Ca(2+)-exchanger gene is two-fold higher in fetal heart compared to adult. Our study also makes the important observation that in hypothyroidic hearts the NCX-1 mRNA and protein levels were upregulated, whereas the SERCA2 mRNA/protein levels were downregulated. In hyperthyroidic hearts, however, an opposite response was identified. These findings are important and point out that the expression of NCX-1 is regulated antithetically to that of SERCA2 during heart development and in response to alterations in thyroid hormone levels.

Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina.

Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.

Premedication with Xylocaine spray does not lead to a false positive rapid urease test.

Rapid urease tests are used for quick identification of Helicobacter pylori during upper gastrointestinal endoscopy. Rapid urease test solutions contain urea, which in the presence of H. pylori urease, generates ammonia, which changes the test medium color to indicate a positive result. Theoretically, Xylocaine spray (ASTRA, Södertalje, Sweden), which has a basic pH value, could cause a similar positive reaction in the test medium. To determine whether patients premedicated with Xylocaine spray have a higher rate of false positive urease tests, we compared the results of a rapid urease test and histologic stains in 107 patients, 54 premedicated with Xylocaine spray and 53 premedicated with intravenous midazolam but not Xylocaine spray. There were no significant differences in test sensitivity, specificity, or predictive values between the study groups. We conclude that patients can be premedicated with Xylocaine spray without concern that the false positive rate of rapid urease tests will increase.

Evolutionarily conserved promoter region containing CArG*-like elements is crucial for smooth muscle myosin heavy chain gene expression.

In recent years, significant progress has been made toward understanding skeletal muscle development. However, the mechanisms that regulate smooth muscle development and differentiation are presently unknown. To better understand smooth muscle-specific gene expression, we have focused our studies on the smooth muscle myosin heavy chain (SMHC) gene, a highly specific marker of differentiated smooth muscle cells. The goal of the present study was to isolate and characterize the mouse SMHC gene promoter, since the mouse promoter would be particularly suited for in vivo promoter analyses in transgenic mice and would serve as a tool for targeting genes of interest into smooth muscle cells. We report here the isolation and characterization of the mouse SMHC promoter and its 5' flanking region. DNA sequence analysis of a 2.6-kb portion of the promoter identified several potential binding sites for known transcription factors. Transient transfection analysis of promoter deletion constructs in primary cultures of smooth muscle cells showed that the region between -1208 and -1050 bp is critical for maximal SMHC promoter activity. A comparison of SMHC promoter sequences from mouse, rat, and rabbit revealed the presence of a highly conserved region located between -967 and -1208 bp. This region includes three CArG/CArG*-like elements, two SP-1 binding sites, a NF-1-like element, an Nkx2-5 binding site, and an Elk-1 binding site. Gel mobility shift assay and DNase I footprinting analyses show that all three CArG/CArG*-like elements can form DNA-protein complexes with nuclear extract from vascular smooth muscle cells. Protein binding to the CArG* elements can be competed out by either serum response element or by an authentic CArG element from the cardiac alpha-actin gene. Using a serum response factor (SRF) antibody, we demonstrate that SRF is part of the protein complex. In addition, we show that cotransfection with the SRF dominant-negative mutant expression vector abolishes SMHC promoter activity, suggesting that SRF protein plays a critical role in SMHC gene regulation.

Open access endoscopy for hospitalized patients.

OBJECTIVES: Most requests for gastroenterology consultations for hospitalized patients are for endoscopic procedures. Open access endoscopy has been evaluated in several institutions for outpatients. Our aim was to evaluate an open access policy for hospitalized patients. METHODS: Since April of 1996, patients hospitalized in the Soroka Medical Center have been referred directly for upper endoscopy (esophagogastroduodenoscopy, EGD) and flexible sigmoidoscopy (FS). The numbers of procedures and consultation requests between July 1, 1996, and September 30, 1996, were compared with the corresponding months of 1995. A survey of physician satisfaction with the new open access system was conducted. RESULTS: The mean number of monthly consultations during the study period was 30.7 +/- 2.4, compared with 119.3 +/- 5.4 during the same months in 1995 (p = 0.006). Open access endoscopy was performed on 114 patients during the study period. Upper GI bleeding (n = 41) and abdominal pain (n = 33) were the most common indications for EGD. There were nine duodenal ulcers, five gastric ulcers, and eight gastric carcinomas. Sixteen patients (21%) had normal EGDs. The most common indications for FS were rectal bleeding (n = 24) and diarrhea (n = 13). Seven patients had colorectal cancer; 12 FSs were normal. In all, 286 EGDs and FSs were conducted in the study period compared with 253 in 1995 (not significant). All physicians expressed satisfaction with the new system and favored its continuation. CONCLUSIONS: The open access policy for hospitalized patients led to a considerable reduction in requests for consultations, with no significant increase in the number of endoscopies. The majority of patients referred directly for endoscopy had appropriate indications.

Identification of functional promoter elements in the rabbit smooth muscle myosin heavy chain gene.

Despite the importance of smooth muscle cell proliferation in vascular pathophysiological states, the mechanisms regulating smooth muscle cell growth and differentiation are poorly understood. Previous studies have shown that adult rabbit smooth muscles express two types of myosin heavy chain (MHC) isoforms, SM1 and SM2, which are generated through alternative RNA splicing from a single smooth muscle MHC (SMHC) gene. In the present study, we isolated and characterized the rabbit SMHC gene promoter. DNA sequence analysis of the upstream region of the SMHC gene revealed several putative cis-DNA regulatory elements proximal to the transcription start site. Most notably, cis-acting regulatory elements that closely resemble CC(A/T)6GG (CArG box) and myocyte enhancer binding factor 2 (MEF-2)-type sequence motifs were found in the SMHC 5'-flanking region. In addition, six E-box motifs were found in the 5'-flanking region of the SMHC gene between -374 and -2109 base pairs from the transcription start site. A series of transient transfection assays using SMHC promoter deletion constructs indicated that a promoter fragment extending to 2266 base pairs upstream of the transcription start site has the highest reporter activity in cultured rat aortic smooth muscle cells. Gel mobility shift analyses using the MEF-2-like sequence located at -1540 revealed a specific DNA protein complex, whereas the CArG-like element located at -1275 did not show protein binding. The SMHC promoter construct, p509-CAT, which included neither the CArG- nor MEF-2-type motifs, conferred 32% of chloramphenicol acetyltransferase activity in the same cells, whereas the construct p188-CAT, which contained the minimal promoter elements (TATA box), was significantly less active (7%; 2.0-fold over background). This is the first report describing the promoter elements of a gene whose expression is restricted to smooth muscle cells.

Evidence for the formation of a functional complex between vasoactive intestinal peptide, its receptor, and Gs in lung membranes.

The molecular weight of the vasoactive intestinal peptide (VIP) receptor in rat lung and its interaction with the stimulatory guanine nucleotide-binding protein (Gs) were assessed by covalent cross-linking, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunological techniques. Studies with two cross-linking agents indicated that the VIP receptor in this tissue is a single polypeptide of Mr = 54,000. The VIP-occupied receptor could be cross-linked to neighboring proteins after detergent solubilization; higher molecular weight complexes of Mr = 114,000 and 184,000 were formed. Immunoblotting with antisera against G-protein subunits demonstrated that both complexes contained the alpha-subunit of Gs as well as the 125I-VIP cross-linked receptor whereas only the Mr = 184,000 complex contained the beta-subunit. Pretreatment with GTP reduced the prominence of these complexes, verifying the functional nature of this receptor-Gs association. Studies with a third cross-linking agent, ethylene glycol bis(succinimidyl succinate), provided direct evidence of physically associated, ternary VIP-receptor-Gs complexes actually in the membrane milieu. That these complexes were functionally associated with shown by their inhibition by anti-Gs alpha anti-serum. Since treatment of membranes with guanosine 5'-O-(3-thiotriphosphate) resulted in the separation of the VIP-cross-linked receptor from Gs such that no cross-linking could occur, we conclude that the binding of GTP analogs induces a conformational change in Gs in the membrane milieu.

Effects of nisoldipine on myocardial ischemia during exercise and during daily activity.

The antiischemic properties of nisoldipine, a dihydropyridine calcium antagonist, were assessed in a multicenter, double-blind, placebo-controlled trial by repeated exercise testing and 72-hour ambulatory electrocardiographic monitoring in 82 patients with coronary artery disease. Patients with positive treadmill stress test results and greater than or equal to 2 ischemic episodes per 24 hours were included in this study. Administration of all chronic antiischemic medications except beta blockers were discontinued. During the first week all patients received placebo twice daily. During the second and third weeks, 41 patients received nisoldipine 10 mg and 41 patients received placebo twice daily. In the placebo group there were no changes in exercise parameters or in ambulatory electrocardiographic parameters. In the nisoldipine group, exercise duration increased from 403 to 448 seconds (p = 0.0035), time to 1 mm of ST depression increased from 224 to 298 seconds (p = 0.002), time to pain increased from 241 to 321 seconds (p = 0.01), and maximal ST depression was reduced from 2.6 to 2.3 mm (p = 0.002). Among the ambulatory electrocardiographic parameters in the nisoldipine group, only the number of episodes was reduced, from 14.4 to 11.6 (p = 0.0013) per patient. There was no significant reduction in total ischemic time (132 vs 120 minutes per patient). No significant side effects were observed. This is the largest clinical trial to date on the effects of nisoldipine on myocardial ischemia. The results indicate that nisoldipine was effective in improving all exercise parameters and only partially effective in suppressing ischemia during daily activity.

Hemodynamic evaluation of common cardiac arrhythmias.

Hemodynamic effects of arrhythmias are considered to be relatively unimportant unless the heart rate is very slow or very rapid. The present study describes a simple method which enables determination of beat-to-beat changes in stroke volume, cardiac output, double product and cardiac efficiency expressed as the interrelationship between the last two parameters. It is obtained by calculating stroke volume from directly measured values of arterial pressure, using a modification of a formula described for irregular rhythms. The calculated parameters are expressed as the percentage of the values of the sinus beat or state occurring with normal cardiac rhythm. The results confirmed that atrial ectopic beats have a less deleterious effect on myocardial function than those from ventricular or nodal origin. The change in stroke volume or cardiac output may be accompanied by either a decreased or increased double product and/or cardiac efficiency. This depends on the type of arrhythmia, the number of ectopic beats per minute and the condition of the patient's heart. The method provides measurement of this parameter in a given patient at a given state as well as at other different frequencies of the same arrhythmia. It demonstrates then which frequency induces hemodynamic changes of sufficient degree to justify antiarrhythmic therapy. The method may be useful in optimising care of patients in units for critical care, or even in outpatient departments.

The effect of verapamil in patients with asymptomatic stress-induced ischemia.

In 25 patients with asymptomatic exercise-induced positive stress tests heart rate, blood pressure, double product, exercise duration, and ST-segment changes were studied prior to and 4 weeks after administration of 120 mg of verapamil therapy three times a day. Significant improvement was observed at rest and at peak exercise in heart rate, pressure values, double product, and maximal ST depression with a prolongation of exercise duration. Measurements at the same work load in the post-verapamil test as at the pretreatment peak exercise showed a slower heart rate, lower blood pressure, less double product, and less ST depression as a more pronounced expression of drug efficacy. There was no deterioration in any parameter. In conclusion, improved myocardial performance can be demonstrated in asymptomatic ischemic patients when treated with verapamil, and this effect is particularly evident when data are compared with equal exercise duration in the posttreatment test as with peak exercise prior to therapy.

Scanning electron microscopy of human Fallopian tube in ectopic pregnancy.

The scanning electron microscopy by virtue of its high resolution topographic reproduction of epithelial surfaces lining the female genital tract, provides unique information toward understanding the anatomy and physiology of the female reproductive system. The human Fallopian ectopic pregnancy is an urgent gynecologic event, which was and still is a diagnostic challenge. There is an increase in the incidence of ectopic pregnancy in recent years. With the purpose of exploring the etiology of tubal ectopic pregnancy from the ultrastructure point of view, we examined 7 cases of tubal pregnancy and compared them to a similar number of normal tubes. We do not find evidence to the pathophysiology of tubal pregnancy by examination of the ultrastructure of the human tube with scanning electron microscopy.

Experience with combined individualized method of hMG/hCG therapy.

The introduction of powerful ovulation induction agents, such as gonadotropins, has made an important contribution to the temporary elimination of the anovulation syndrome. Since the treatment is expensive and not without significant medical complication, it is vitally important to conduct therapy according to a well-defined monitoring system. In the past, clinicians have tended to monitor gonadotropin therapy by biophysical signs, but they were found to be insufficient monitors if used alone. Estrogen secretion from the ovaries does reflect the follicular maturation process. In this study a combined individualized method for hMG/hCG therapy is presented. Fifty-one infertile anovulatory women were treated for a total of 124 treatment cycles. All courses of therapy were judged to have induced ovulation. There was a good clinical correlation between cervical score and increasing estrogen levels. The pregnancy rate was 62.7%, with 60% of patients becoming pregnant within the first three cycles of treatment. In spite of the complications of less than 1% of severe hyperstimulation, 15.5% multiple gestation, and 28% of abortion rate, gonadotropin therapy is a most efficient tool in the treatment of infertility due to anovulation.

Corrosion of a new copper-gold or copper-platinum intrauterine device.

It has been shown previously that supplementing plastic intrauterine devices (IUDs) with copper wire enhances the antifertility effect of the device. The use of copper intrauterine contraceptive devices, however, is currently limited to two to three years, mainly because of wire fragmentation, which was observed as early as after eight months of use. In the resulting search for a long-lasting device, two new systems of duplex wire, with gold and platinum cores electrolytically coated with copper, were devised and studied. Initially, duplex wires and controls were exposed to physiological solution. Copper dissolution rate and corrosion morphology were studied by weight-loss measurements and optical metallography. Similar systems were then surgically implanted in rat uteri for varying periods of up to 26 weeks. Electron microanalysis of corrosion products, in addition to weight-loss measurements and metallography, was performed. The results showed that a uniform and ductile copper coating is obtainable by electroplating on gold and platinum wires. Rate of copper dissolution is similar to that of solid copper wire. No dissolution of gold and platinum in the controls or coated wires was detected by weight loss, metallography, or atomic absorption measurements. Microanalysis of the deposits and corrosion products on the wires in the uteri environment showed sulfur, chlorine, and calcium, in addition to copper. The results of this study suggest that supplementing IUDs with copper-coated gold or platinum wires may result in significant prolongation of the life span of the device by preventing uncontrolled loss of copper caused by wire fragmentation.

A copper-based intrauterine device with gold or platinum core: in vitro and in vivo studies.

The use of copper intrauterine contraceptive devices is currently limited to 2-3 years, mainly due to wire fragmentation, which was observed as early as after 8 months of use. In the resulting search for a long-lasting device, two new systems of duplex wire, with gold and platinum cores electrolytically coated with copper, were devised and studied. Initially, duplex wires and controls were exposed to physiological solution. Copper dissolution rate, and corrosion morphology were studied by weight-loss measurements and optical metallography. Similar systems were then surgically implanted in rat uteri for varying periods up to 26 weeks. Electron microanalysis of corrosion products in addition to weight-loss measurements and metallography was performed. The results showed that a uniform and ductile copper coating is obtainable by electroplating on gold and platinum wires. The rate of copper dissolution is similar to that of solid copper wire. No dissolution of gold and platinum in the controls or coated wires was detected by weight loss, metallography or atomic absorption measurements. Microanalysis of the deposits and corrosion products on the wires in the uterine environment showed the presence of compounds containing sulphur, chlorine, calcium and copper. The results of this study suggest that supplementing IUDs with copper-coated gold or platinum wires may result in significant prolongation of the life-span of the device by preventing uncontrolled loss of copper caused by wire fragmentation.

The significance of fetal electrocardiography in the diagnosis of intrauterine bradyarrhythmia.

From 11 cases of fetal bradycardia diagnosed by monitoring of 130 fetal electrocardiograms (ECG's) in high-risk pregnancies we have presented our experience in three selected cases of fetal bradyarrthythmia. Case 1 revealed on ECG blocked atrial premature beats simulating an extreme sinus bradycardia sequentially followed by conducted atrial premature beats. In case 2 we diagnosed ventricular premature beats in the form of persistent bigeminy which was controlled by intravenous propranolol. The last case illustrated the phenomenon of aberrant ventricular conduction known to occur in adult cardiology. The electrophysiologic basis of the variable arrhythmias was discussed. Detailed analysis of repeated direct fetal ECG's provided us with the diagnosis and understanding of the electrophysiologic mechanisms underlying the rhythm disturbances. This consequently determined the pharmacologic therapy and the obstetric approach relevant to each case. We have shown that by direct fetal electrocardiography it is possible to analyze accurately the rhythm disturbances. Persistent fetal bradycardia does not always signify fetal distress. We hope that this will lead to closer teamwork between the obstetrician and the cardiologist which will give an impetus to the future development of "fetal cardiology," thereby enhancing our understanding of the electrophysiology of the fetal heart.