Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants.

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10µm and <5µm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5µm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.

Overcoming small-bandgap charge recombination in visible and NIR-light-driven hydrogen evolution by engineering the polymer photocatalyst structure.

Designing an organic polymer photocatalyst for efficient hydrogen evolution with visible and near-infrared (NIR) light activity is still a major challenge. Unlike the common behavior of gradually increasing the charge recombination while shrinking the bandgap, we present here a series of polymer nanoparticles (Pdots) based on ITIC and BTIC units with different π-linkers between the acceptor-donor-acceptor (A-D-A) repeated moieties of the polymer. These polymers act as an efficient single polymer photocatalyst for H2 evolution under both visible and NIR light, without combining or hybridizing with other materials. Importantly, the difluorothiophene (ThF) π-linker facilitates the charge transfer between acceptors of different repeated moieties (A-D-A-(π-Linker)-A-D-A), leading to the enhancement of charge separation between D and A. As a result, the PITIC-ThF Pdots exhibit superior hydrogen evolution rates of 279 µmol/h and 20.5 µmol/h with visible (>420 nm) and NIR (>780 nm) light irradiation, respectively. Furthermore, PITIC-ThF Pdots exhibit a promising apparent quantum yield (AQY) at 700 nm (4.76%).

Response of Moringa oleifera trees to salinity stress conditions in Tabuk region, Kingdom of Saudi Arabia.

Moringa oleifera is an amazing tree with various applications. Salinity is a world major barrier to crop productivity. This study was conducted to investigate salinity and seaweed extract's effect on Moringa oleifera's growth and yields. Measurements were made of growth characteristics, fresh and dried leaf, inflorescence, mature pod and seed weight, and yield per tree, as well as chemical parameters. Seasons had no substantial effect on any of these traits. In terms of seaweed concentrations, the treatment containing 20% seaweed outperformed the treatment containing 0% seaweed in all measurements. Concerning the salinity levels, the maximum level of all studied attributes was at 18.75 mmol/L NaCl, while the level of 70.31 mmol/L NaCl has the lowest values. The interaction between salinity levels and seaweed revealed that T4 (18.75 mmol/L NaCl plus 20 % seaweed) was the highest for all traits and T9 (70.31 mmol/L NaCl plus 0 % seaweed) was the lowest for all traits except for the potassium content. Concerning potassium content, T7 (54.69 mmol/L NaCl plus 0 % seaweed) was the lowest. These findings could help to develop efficient breeding methods for Moringa oleifera in the future.

Exogenously Supplemented Proline and Phenylalanine Improve Growth, Productivity, and Oil Composition of Salted Moringa by Up-Regulating Osmoprotectants and Stimulating Antioxidant Machinery.

Salinity is linked to poor plant growth and a reduction in global food output. Therefore, there is an essential need for plant adaptation and mitigation of salinity stress conditions. Plants combat salinity stress influences by promoting a set of physiological, biochemical, and molecular actions. Tremendous mechanisms are being applied to induce plant stress tolerance, involving amino acid application. For evaluating the growth and productivity of Moringa oleifera trees grown under salt stress conditions, moringa has been cultivated under different levels of salinity and subjected to a foliar spray of proline (Pro) and phenylalanine (Phe) amino acids. Moringa plants positively responded to the lowest level of salinity as the leaves, inflorescences, seeds, and oil yields have been increased, but the growth and productivity slightly declined with increasing salinity levels after that. However, Pro and Phe applications significantly ameliorate these effects, particularly, Pro-treatments which decelerated chlorophyll and protein degradation and enhanced vitamin C, polyphenols, and antioxidant activity. A slight reduction in mineral content was observed under the high levels of salinity. Higher osmoprotectants (proline, protein, and total soluble sugars) content was given following Pro treatment in salted and unsalted plants. A significant reduction in oil yield was obtained as affected by salinity stress. Additionally, salinity exhibited a reduction in oleic acid (C18:1), linoleic (C18:2), and linolenic (C18:3) acids, and an increase in stearic (C18:0), palmitic (C16:0), eicosenoic (C20:2), and behenic (C22:0) acids. Generally, Pro and Phe treatments overcome the harmful effects of salinity in moringa trees by stimulating the osmoprotectants, polyphenols, and antioxidant activity, causing higher dry matter accumulation and better defense against salinity stress.

Impact of planting density and soaking seeds in melatonin solution on yield, secondary products content and antimicrobial activity of lovage plant.

Many studies worldwide have been done on the effect of medicinal uses of lovage plant but, very little works have been done on its production. In this study the effect of different planting density and soaking seeds in different concentration of melatonin solution as well as their combination treatments on yield, secondary products content and antimicrobial activity of lovage plant were studied. It was observed that using planting space of 15 cm gave the maximum mean values of total phenolic and antioxidant content and essential oil percentage. Using 30 cm planting space gave the maximum mean values of plant height, yield of herb fresh and dry weight per hectare, yield of roots dry weight and essential oil per hectare. While the plant space of 45 cm recorded the maximum mean values of fresh and dry weight of herb and roots fresh weight per plant and chlorophyll content. For melatonin levels, using 100 µM melatonin solution had the minimum mean values of number of days to emergence. While, soaking seeds in 75 µM melatonin solution recorded the best results of all studied parameters. Regarding the combination treatments, measurements comprising of herb fresh and dry weight as well as essential oil yield per hectare showed that the combination treatment of 30 cm between plants in row plus soaking seeds in 75 µM melatonin solution was able to achieve the maximum values of these parameters. While the combination treatment of 15 cm between plants in row plus soaking solution of 75 µM melatonin is recommended for getting the maximum yield of root fresh and dry weight per hectare and the maximum total phenolic and antioxidant contents per herb in both cuts of both studied season. The first major compound of lovage essential oil of herb is α-terpinyle acetate followed by ß-Phellandrene. The percentages of these compounds were affected by the applied treatments. The volatile oil of lovage plant exhibits high antibacterial and antifungal properties in the concentrations range of 75-100 µg mL-1.

Response of Growth, Yield, and Phytochemical Behavior of Jojoba Genotypes to Azolla filiculoides Plant Extract.

A unique storage lipid wax found in jojoba seeds can be employed as a chemical feedstock. Alternative safe and natural sources of plant nutrients are constantly sought to preserve both human health and the environment. As a result, EAI1, EAI2, and EAI3 jojoba genotypes' growth, yield, and phytochemical behavior in response to Azolla extract at concentrations of 0, 10, and 30% were studied. Maximum productivity was found with EAI1, followed by EAI3 then EAI2 across all Azolla extracts. In relation to the Azolla extract concentrations in the two seasons, the concentration of 30% delivered the most pronounced results across all the studied genotypes. During the two seasons, administration of a combined treatment of the EAI1 jojoba genotype with 30% Azolla extract produced the highest mean values of growth, flowering, and fruiting, as well as chemical composition parameters. This means that the treatment of EAI1 genotype with 30% Azolla filiculoides Lam. plant extract yielded the highest significant seed yield (3748 and 3839 kg ha-1) and oil yield per hectare (1910 and 2002 L ha-1). The combination treatment of the EAI1 jojoba genotype with 10% Azolla extract yielded the highest proportion of gadoleic fatty acid (49.83%).

Maximizing Leaves, Inflorescences, and Chemical Composition Production of Moringa oleifera Trees under Calcareous Soil Conditions.

One of the main issues limiting plant productivity is a lack of soil nutrient resources, especially in calcareous soil, which covers more than one third of the world's land surface area. On the other hand, despite rising demand for all parts of the Moringa oleifera tree, several studies have focused on its leaf production as an herbaceous plant, rather than as a tree, and no extensive research has been carried out on leaf and inflorescence production in the mature tree. As a result, the influence of vermicompost and NPK (minerals and nanoparticles), as well as their combination, under calcareous soil conditions, was investigated in this study. The experiment was set up as a split plot in Randomized Complete Block Design (RCBD) with three replicates. In both seasons considered in this study, it was discovered that increasing the quantity of vermicompost and employing NPK fertilization, as well as their combination treatments, greatly enhanced all parameters and yield of distinct Moringa oleifera tree parts. Furthermore, the combination treatment T21 yielded the highest mean values of growth, leaves, and chemical composition parameters, as well as the highest yield from the Moringa oleifera tree. In both seasons, the highest number of inflorescences per tree, as well as the yield of fresh and dry inflorescences, was measured using combination treatment T18. In both seasons, however, increasing the level of vermicompost, NPK, and their combination treatments significantly reduced the total phenolic and flavonoid content and antioxidant activity of dry Moringa oleifera leaves.

An Evaluation of Oxidative Stress With Thiol/Disulfide Homeostasis in Patients With Persistent Allergic Rhinitis.

BACKGROUND: We evaluated the efficacy of medical treatment on thiol-disulfide balance despite ongoing allergic stimulation. METHODS: The research design was a prospective observational study that included 35 persistent allergic rhinitis (AR) patients. All patients who were diagnosed with persistent AR were included. A skin prick test was applied to all patients, and the Sino-nasal Outcome Test-22 was used to evaluate sinonasal symptoms. Thiol/disulfide homeostasis balance parameters were measured using a novel automatic and spectrophotometric method and compared statistically. Serum total thiol (TT), native thiol (SH), disulphide (SS), disulphide/native thiol (SS/SH), disulphide/total thiol (SS/TT), and native thiol/total thiol (SH/TT) ratios were measured after the second month of the treatment. RESULTS: The 35 patients included 20 (58%) females and 15 (42%) males. The mean age of the patients was 33.17 ± 9.9 years. Disulphide, SS/SH, and SS/TT ratios decreased significantly after the treatment (P < .05), while SH and SH/TT increased significantly (P < .05). The mean SH measurement increased significantly in the second month (P = .001), but TT mean measurements showed no difference after the treatment (P = .058). The mean SS measurements, on the other hand, decreased significantly in the second month (P = .003). CONCLUSION: Thiol/disulfide homeostasis may be used as a marker to evaluate the efficacy of persistent AR treatments. After the treatment, the increase in SH levels suggested the decrease in oxidative stress, even though allergen exposure continued.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Response of Moringa oleifera Seeds and Fixed Oil Production to Vermicompost and NPK Fertilizers under Calcareous Soil Conditions.

A shortages of soil nutrients resources and a lack of accessibility to them especially in calcareous soil are considered some of the main factors that limit plant production. In particular, the cultivation of the Moringa oleifera trees in this type of soil is of special interest given the increasing demand for every part of this tree. Several studies have focused on the production of its leaves as an herbaceous plant and not as a tree, but there has not been extensive research on its pods, seeds, and fixed oil production. In this sense, in this study, we provide an assessment of the use of fertilizers, vermicompost and NPK (as traditional minerals and as nanoparticles), in order to improve pods, seeds, and fixed oil contents, as indicators of the quality of the production of the Moringa oleifera trees in calcareous soil conditions. In this experiment, it was observed that all parameters and the yield of pods, seeds, and fixed oil of the Moringa oleifera tree were significantly improved by increasing the level of vermicompost and using NPK fertilization and combination treatments in both seasons of the study. The combination treatments of 10 and 20 ton ha-1 vermicompost plus NPK control produced the highest percentage of oleic acid with insignificant differences between them.

Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts.

BACKGROUND: There are no data comparing the 6-9 month oral three-drug Nix regimen (bedaquiline, pretomanid and linezolid [BPaL]) to conventional regimens containing bedaquiline (B, BDQ) and linezolid (L, LZD).METHODS: Six-month post end-of-treatment outcomes were compared between Nix-TB (n = 109) and 102 prospectively recruited extensively drug-resistant TB patients who received an ˜18-month BDQ-based regimen (median of 8 drugs). A subset of patients received BDQ and LZD (n = 86), and a subgroup of these (n = 75) served as individually matched controls in a pairwise comparison to determine differences in regimen efficacy.RESULTS: Favourable outcomes (%) were significantly better with BPaL than with the B-L-based combination regimen (98/109, 89.9% vs. 56/86, 65.1%; adjusted relative risk ratio [aRRR] 1.35; P < 0.001) and in the matched pairwise analysis (67/75, 89.3% vs. 48/75, 64.0%; aRRR 1.39; P = 0.001), despite significantly higher baseline bacterial load and prior second-line drug exposure in the BPaL cohort. Time to culture conversion (P < 0.001), time to unfavourable outcome (P < 0.01) and time to death (P < 0.03) were significantly better or lower with BPaL than the B-L-based combinations.CONCLUSION: The BPaL regimen (and hence substitution of multiple other drugs by pretomanid and/or higher starting-dose LZD) may improve outcomes in drug-resistant TB patients with poor prognostic features. However, prospective controlled studies are required to definitively answer this question.

Clinicopathological correlation of stem cell markers expression in oral squamous cell carcinoma; relation to patients` outcome.

Background: Squamous cell carcinoma (OSCC) is the commonest oral malignancy.The overall 5 year survival of OSCC has remained at 50%, largely unchanged for 40 years. CSCs are important within the development, invasion, drug resistance, and prediction of carcinomas treatment outcome. ALDH1 and CD44 are commonly used epithelial tumors cancer stem-like cells surface markers. Materials: Our study aimed to judge CD44 and ALDH1 immunohistochemical expressions in 44 cases of OSCC and relates the expression to patients' survival. Results: High CD44 & ALDH1 expressions were significantly expressed in variable histologic grades of OSCCs, large sized carcinomas, presence lymph vascular invasion, presence of nodal and distant metastasis, advanced TNM clinical stage, recurrence and death during follow up period (P ≤ 0.05). Reduced DFS and three years overall survival were significantly recorded in cases with high CD44 expression, and high ALDH1 expression (p < 0.05). CD44 & ALDH1 expressions, histologic grade, tumor size were the independent predictors of DFS and three years OS. Conclusion: CD44 and ALDH1 expressions are valuable prognostic factors in OSCC and could be well considered predictors for patients' 3 years OS and DFS.

Next steps in dermatology training: choosing to enter higher speciality training and the transition from trainee to consultant dermatologist.

BACKGROUND: Junior doctors are required to make career decisions at an early stage in their postgraduate training. Trainees also feel inadequately prepared for the transition to consultant roles. AIM: To explore the key factors influencing the choice of dermatology as a postgraduate medical career and to identify the training needs required for transition from trainee to consultant. METHODS: An online questionnaire was designed to identify (i) why trainees chose a postgraduate medical career in dermatology, and (ii) the training required for transition from trainee to consultant. RESULTS: In total, 46 responses were received from trainees in their first to final years (ST3-6), of whom 89% had undertaken an undergraduate dermatology placement, with a median duration of 2 weeks. Dermatology was considered as a career during medical school by 61% of trainees, and 41% confirmed their decision to pursue a career in dermatology during foundation training. The most influential factors involved in speciality selection were first, enjoyment of the work, second, postgraduate experience and equal third, the variety of the speciality and the regularity of working hours (P < 0.05). Mentoring was pivotal to career decision-making. Significant numbers of trainees expressed a need for training in medical leadership, such as running an outpatient clinic and supervising clinical multidisciplinary teams. Although larger numbers of trainees had training in management of dermatology services, such as service improvement (52%) and local governance/National Health Service structures (43%), significant numbers of trainees had no training in writing job plans (89%) or business plans (85%). Training was significantly deficient for personal management and self-awareness. CONCLUSION: Our study highlights important considerations in career decision-making for trainees. Training in medical leadership, management and self-awareness could be enhanced to ensure that trainees feel adequately equipped for consultant roles.

KN95 filtering facepiece respirators distributed in South Africa fail safety testing protocols.

BACKGROUND: Given the global shortage of N95 filtering facepiece respirators (FFP2 in Europe) during the COVID-19 pandemic, KN95 masks (Chinese equivalent of the N95 and FFP2) were imported and distributed in South Africa (SA). However, there are hardly any published independent safety data on KN95 masks. OBJECTIVES: To evaluate the seal, fit and filtration efficiency of several brands of KN95 masks marketed for widespread use in SA healthcare facilities, using standardised testing protocols. METHODS: The verifiability of manufacturer and technical details was first ascertained, followed by evaluation of the number of layers comprising the mask material. The testing protocol involved a directly observed positive and negative pressure user seal check, which if passed was followed by qualitative fit testing (sodium saccharin) in healthy laboratory or healthcare workers. Quantitative fit testing (3M) was used to validate the qualitative fit testing method. The filtration efficacy and integrity of the mask filter material were evaluated using a particle counter-based testing rig utilising aerosolised saline (expressed as filtration efficacy of 0.3 µm particles). Halyard FLUIDSHIELD 3 N95 and 3M 1860 N95 masks were used as controls. RESULTS: Twelve KN95 mask brands (total of 36 masks) were evaluated in 7 participants. The mask type and manufacturing details were printed on only 2/12 brands (17%) as per National Institute of Occupational Safety and Health and European Union regulatory requirements. There was considerable variability in the number of KN95 mask layers (between 3 and 6 layers in the 12 brands evaluated). The seal check pass rate was significantly lower in KN95 compared with N95 masks (1/36 (3%) v. 12/12 (100%); p<0.0001). Modification of the KN95 ear-loop tension using head straps or staples, or improving the facial seal using Micropore 3M tape, enhanced seal test performance in 15/36 KN95 masks evaluated (42%). However, none of these 15 passed downstream qualitative fit testing compared with the control N95 masks (0/15 v. 12/12; p<0.0001). Only 4/8 (50%) of the KN95 brands tested passed the minimum filtration requirements for an N95 mask (suboptimal KN95 filtration efficacy varied from 12% to 78%, compared with 56% for a surgical mask and >99% for the N95 masks at the 0.3 µm particle size). CONCLUSIONS: The KN95 masks tested failed the stipulated safety thresholds associated with protection of healthcare workers against airborne pathogens such as SARS-CoV-2. These preliminary data have implications for the regulation of masks and their distribution to healthcare workers and facilities in SA.

Random telegraph signal analysis with a recurrent neural network.

We use an artificial neural network to analyze asymmetric noisy random telegraph signals, and extract underlying transition rates. We demonstrate that a long short-term memory neural network can outperform other methods, particularly for noisy signals and measurements with limited bandwidths. Our technique gives reliable results as the signal-to-noise ratio approaches one, and over a wide range of underlying transition rates. We apply our method to random telegraph signals generated by quasiparticle poisoning in a superconducting double dot, allowing us to extend our measurement of quasiparticle dynamics to new temperature regimes.

Diagnosis of COVID-19: Considerations, controversies and challenges.

Coronavirus disease 2019 (COVID-19) due to a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has resulted in over 1.5 million confirmed cases and close to 100 000 deaths. In the majority of symptomatic cases, COVID-19 results in a mild disease predominantly characterised by upper respiratory tract symptoms. Reverse transcription polymerase chain reaction (RT-PCR) using a nasopharyngeal sample is the mainstay of diagnosis, but there is an ~30% false negative rate early in the disease and in patients with mild disease, and therefore repeat testing may be required. RT-PCR positivity can persist for several days after resolution of symptoms. IgM and IgG antibody responses become positive several days after the onset of symptoms, and robust antibody responses are detectable in the second week of illness. Antibody-based immunoassays have a limited role in the diagnosis of early symptomatic disease. However, their incremental benefit over RT-PCR in the first 2 weeks of illness is currently being clarified in ongoing studies. Such assays may be useful for surveillance purposes. However, their role in potentially selecting individuals who may benefit from vaccination, or as a biomarker identifying persons who could be redeployed into essential employment roles, is being investigated. Rapid antibody-based immunoassays that detect viral antigen in nasopharyngeal samples are being developed and evaluated.

Home-Based Extended Low-Dose Oral Misoprostol in Management of First-Trimester Pregnancy Loss in Low-Resource Communities: A Randomized Trial.

OBJECTIVE: To investigate the efficacy, safety and tolerability of a home-based extended low-dose oral misoprostol for management of first-trimester pregnancy loss. MATERIALS AND METHODS: A randomized trial that was conducted in the Woman's Health University Hospital and El-eman Maternity Hospital, Assiut, Egypt. One hundred and sixty patients were included. They were randomly assigned to receive four tablets of 200 µg misoprostol vaginally (max. 800 µg-hospital group) or 12 tablets orally, one every 3 h, over 2 consecutive days (max. 2400 µg-extended low-dose home group). For failed first dose, another similar second dose was given. Primary outcome measure was the percentage of patients with 'medically completed miscarriages' in each group (including complete miscarriages + incomplete miscarriages with successful post-miscarriage misoprostol). RESULTS: The total number of patients with 'medically completed miscarriages' in home group was 65/79 (82.3%), which was comparable to the hospital group (52/71 or 73.2%) (P = 0.182). However, the majority of patients in home group had significantly successful miscarriages after a single course of low-dose oral misoprostol, experienced much less heavy bleeding attacks and had less systemic side effects. CONCLUSION: In low-resource communities, the home-based extended low-dose oral misoprostol protocol proved high efficacy, safety and tolerability in management of first-trimester pregnancy loss.