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Clinical endometritis (CE) is common in post-partum dairy cows and is associated with impaired reproductive performance. The aim of the study was to evaluate the effect of subclinical endometritis (SE) in cows clinically cured of CE on their fertility. The study was performed on 215 Holstein Friesian cows with CE diagnosed by vaginoscopy and ultrasound between 21 and 28 days after parturition. All cows were clinically examined three times at an interval of 2 weeks. Cows without signs of CE were considered cured, and endometrial samples from the uteri were collected by cytobrush to diagnose SE using cytological evaluation of polymorphonuclear neutrophils (PMNs) percentage. The threshold for SE was set at ≥ 5% PMNs. Intervals calving to oestrus and calving to conception, first AI pregnancy rate, pregnancy rate 200 days after artificial insemination (AI), the number of AI per pregnancy (AI/P), pregnancy loss, and culling rate were calculated. SE was diagnosed in 40.9% of cows clinically cured of CE. There were significant differences in the AI/P (3.2 vs. 2.6; p < 0.027) and the pregnancy loss (18.2% vs. 4.7%; p < 0.002) between cows with SE and without SE. Cows with SE showed a tendency towards longer interval calving to conception, lower pregnancy rate 200 days after AI, and higher culling rate. In conclusion, SE after a clinical cure of CE may reduce fertility in dairy cows., (© 2024. The Author(s).)

This study profiled various levels of engagement and related communication behaviours among 50 Asian Indian Tamil autistic children (AUT) and their mothers. The interaction was compared with two groups of mother-child dyads of non-autistic (NA) children, 50 in each group, matched for chronological age (CA), and for language level (LL). Results indicated that despite mother's efforts to engage with their children, autistic children were often 'engaged with objects' or remained 'unengaged' due to children's preference for solitary play, while NA children were often engaged in 'co-ordinated' and 'people engagement'. Across the three groups, mothers predominantly took the lead and dominated the interaction, irrespective of children's language levels. These initiations by the mothers were often to provide instructions and to ask 'What' questions. Autistic children initiated communication predominantly to ask for an object and responded often in the form of negations and protests with limited verbal output or non-verbally. Most of the communication behaviours of both children and mothers in AUT group was quantitatively and qualitatively different when compared to those in both the NA groups, indicating unique nature of interactions despite matching for CA or LL. The observations from the study highlights the need for considering adult's contingent behaviours also, while assessing communication skills of autistic children in order to provide effective intervention., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The endocannabinoid system (ECS) plays a crucial role in reproductive health, but its function in postpartum dairy cows remains poorly understood. This study investigated the expression patterns of ECS-related genes in the endometrium of postpartum dairy cows and their associations with endometrial health and the presence of fatty liver. Endometrial biopsies were collected from 22 Holstein Friesian cows at 4 and 7 weeks postpartum. Gene expression was analyzed using RT-qPCR, focusing on key ECS components including CNR2 , MGLL , FAAH1 , NAAA , NAPEPLD , PADI4 and PTGDS. The results reveal dynamic changes in ECS gene expression associated with endometritis and fatty liver. MGLL expression was significantly upregulated in cows with endometritis at 7 weeks postpartum, while NAAA expression was consistently downregulated in cows with fatty liver. CNR2 showed a time-dependent pattern in endometritis, and PTGDS expression was elevated in clinical endometritis at 4 weeks postpartum. The presence of fatty liver was associated with altered expression patterns of several ECS genes, suggesting a link between metabolic stress and endometrial ECS function. These findings indicate a potential role for the ECS in postpartum uterine health and recovery, offering new insights into the molecular mechanisms underlying reproductive disorders in dairy cows and paving the way for novel therapeutic approaches.

Geopolymer materials, considered to be an alternative to Portland cement-based concretes, can be produced from various types of waste aluminosilicate raw materials. This article presents the results of research related to the use of diatomite as an additive in geopolymers. The results of testing geopolymer composites with 1%, 3%, and 5% additions of diatomite with a grain size of 0-0.063 mm after and without thermal treatment were presented. This article presents the physical properties of the diatomite additive, the morphology of diatomite particles SEMs, thermal analysis, and compressive strength test results. In this research, diatomite was treated as a substitute for both fly ash and metakaolin (replaced in amounts of 1 and 3%) and as a substitute for sand introduced as a filler (in this case, 5% of diatomite was added). As a result of this research, it was found that the addition of diatomite instead of the main geopolymerization precursors in amounts of 1 and 3% had a negative impact on the strength properties of geopolymers, as the compressive strength was reduced by up to 28%. The introduction of crushed diatomite instead of sand in an amount of 5% contributed to an increase in strength of up to 24%.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

The lack of specific and sensitive early diagnostic options for pancreatic cancer (PC) results in patients being largely diagnosed with late-stage disease, thus inoperable and burdened with high mortality. Molecular spectroscopic methodologies, such as Raman or infrared spectroscopies, show promise in becoming a leader in screening for early-stage cancer diseases, including PC. However, should such technology be introduced, the identification of differentiating spectral features between various cancer types is required. This would not be possible without the precise extraction of spectra without the contamination by necrosis, inflammation, desmoplasia, or extracellular fluids such as mucous that surround tumor cells. Moreover, an efficient methodology for their interpretation has not been well defined. In this study, we compared different methods of spectral analysis to find the best for investigating the biomolecular composition of PC cells cytoplasm and nuclei separately. Sixteen PC tissue samples of main PC subtypes (ductal adenocarcinoma, intraductal papillary mucinous carcinoma, and ampulla of Vater carcinoma) were collected with Raman hyperspectral mapping, resulting in 191,355 Raman spectra and analyzed with comparative methodologies, specifically, hierarchical cluster analysis, non-negative matrix factorization, T-distributed stochastic neighbor embedding, principal components analysis (PCA), and convolutional neural networks (CNN). As a result, we propose an innovative approach to spectra classification by CNN, combined with PCA for molecular characterization. The CNN-based spectra classification achieved over 98% successful validation rate. Subsequent analyses of spectral features revealed differences among PC subtypes and between the cytoplasm and nuclei of their cells. Our study establishes an optimal methodology for cancer tissue spectral data classification and interpretation that allows precise and cognitive studies of cancer cells and their subcellular components, without mixing the results with cancer-surrounding tissue. As a proof of concept, we describe findings that add to the spectroscopic understanding of PC., (© 2023. The Author(s).)

Objective: Pressure ulcers (PUs) are a significant healthcare problem with a negative impact on patients' quality of life and incurring substantial healthcare expenses. Our study aimed to analyse the costs of treating PUs in hospitalised patients in the Czech Republic, in the context of current treatment procedures and price levels, and to pilot-test the detailed methodology developed., Method: A prospective, observational, non-interventional study was conducted at the Clinic of Anesthesiology, Resuscitation and Intensive Medicine, the Internal Medicine Department and the Surgical Department of the University Hospital Ostrava. The study included all hospitalised patients with a PU from March-May 2021. Data were collected using the hospital information system. A bottom-up, person-based approach to cost analysis was used, based on a comprehensive cost structure using accurate patient-specific consumption records., Results: The length of hospitalisations ranged from 1-31 (mean: 12.7) days. The average cost of PU treatment per hospitalisation was calculated at €1579. The average daily cost of PU treatment was €179, including antibiotic therapy (ATB) and €112 without ATB. Most of the costs were associated with ATB (38.6%) and caregivers' time (35.9%). Based on the results, a predictive model was developed to estimate the cost of treating a hospitalised patient with a PU, which could be used in future research to assess the costs of treating these patients., Conclusion: We have faced many challenges in the methodology of preparation of cost analysis (e.g., how to count amorphous topical agents and sprays, how to properly identify PUs, how to price the positioning aids and mattresses, and how to relate the ATB treatment to the PU). This analysis provides important input for developing a comprehensive and more accurate methodology for monitoring PU costs in hospitalised patients, applicable in clinical practice for inpatient healthcare providers., Competing Interests: Declaration of interest: This work was supported by the Ministry of Health of the Czech Republic under grant no. NU20-09-00094 ‘Cost analysis of pressure ulcers treatment – determinant of care.’ All rights reserved. The authors have no conflicts of interest to declare.

Na V 1.1 (SCN1A) is a voltage-gated sodium channel mainly expressed in GABAergic neurons. Loss of function mutations of Na V 1.1 lead to epileptic disorders, while gain of function mutations cause a migraine in which cortical spreading depolarizations (CSDs) are involved. It is still debated how these opposite effects initiate two different manifestations of neuronal hyperactivity: epileptic seizures and CSD. To investigate this question, we previously built a conductance-based model of two neurons (GABAergic and pyramidal), with dynamic ion concentrations (Lemaire et al. in PLoS Comput Biol 17(7):e1009239, 2021. https://doi.org/10.1371/journal.pcbi.1009239 ). When implementing either Na V 1.1 migraine or epileptogenic mutations, ion concentration modifications acted as slow processes driving the system to the corresponding pathological firing regime. However, the large dimensionality of the model complicated the exploitation of its implicit multi-timescale structure. Here, we substantially simplify our biophysical model to a minimal version more suitable for bifurcation analysis. The explicit timescale separation allows us to apply slow-fast theory, where slow variables are treated as parameters in the fast singular limit. In this setting, we reproduce both pathological transitions as dynamic bifurcations in the full system. In the epilepsy condition, we shift the spike-terminating bifurcation to lower inputs for the GABAergic neuron, to model an increased susceptibility to depolarization block. The resulting failure of synaptic inhibition triggers hyperactivity of the pyramidal neuron. In the migraine scenario, spiking-induced release of potassium leads to the abrupt increase of the extracellular potassium concentration. This causes a dynamic spike-terminating bifurcation of both neurons, which we interpret as CSD initiation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nature confines hundreds of millimolar of amphiphilic neurotransmitters, such as serotonin, in synaptic vesicles. This appears to be a puzzle, as the mechanical properties of lipid bilayer membranes of individual major polar lipid constituents of synaptic vesicles [phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS)] are significantly affected by serotonin, sometimes even at few millimolar concentrations. These properties are measured by atomic force microscopy, and their results are corroborated by molecular dynamics simulations. Complementary 2 H solid-state NMR measurements also show that the lipid acyl chain order parameters are strongly affected by serotonin. The resolution of the puzzle lies in the remarkably different properties displayed by the mixture of these lipids, at molar ratios mimicking those of natural vesicles (PC:PE:PS:Cholesterol = 3:5:2:5). Bilayers constituting of these lipids are minimally perturbed by serotonin, and show only a graded response at physiological concentrations (>100 mM). Significantly, the cholesterol (up to 33% molar ratio) plays only a minor role in dictating these mechanical perturbations, with PC:PE:PS:Cholesterol = 3:5:2:5 and 3:5:2:0 showing similar perturbations. We infer that nature uses an emergent mechanical property of a specific mixture of lipids, all individually vulnerable to serotonin, to appropriately respond to physiological serotonin levels.

The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) were randomized and 320 were treated (162 with rivipansel, 158 with placebo) with an IV loading dose, followed by up to 14 additional 12-hourly maintenance doses of rivipansel or placebo, in addition to standard care. Rivipansel was similarly administered during subsequent VOCs in the Open-label Extension (OLE) study. In the full analysis population, the median time to readiness for discharge (TTRFD), the primary end point, was not different between rivipansel and placebo (-5.7 hours, P = .79; hazard ratio, 0.97), nor were differences seen in secondary end points of time to discharge (TTD), time to discontinuation of IV opioids (TTDIVO), and cumulative IV opioid use. Mean soluble E-selectin decreased 61% from baseline after the loading dose in the rivipansel group, while remaining unchanged in the placebo group. In a post hoc analysis, early rivipansel treatment within 26.4 hours of VOC pain onset (earliest quartile of time from VOC onset to treatment) reduced median TTRFD by 56.3 hours, reduced median TTD by 41.5 hours, and reduced median TTDIVO by 50.5 hours, compared with placebo (all P < .05). A similar subgroup analysis comparing OLE early-treatment with early-treatment RESET placebo showed a reduction in TTD of 23.1 hours (P = .062) and in TTDIVO of 30.1 hours (P = .087). Timing of rivipansel administration after pain onset may be critical to achieving accelerated resolution of acute VOC. Trial Registration: Clinicaltrials.gov, NCT02187003 (RESET), NCT02433158 (OLE)., (© 2023 by The American Society of Hematology.)

In the case of historic buildings, especially those under protection, it is important to replace elements of the roof covering, while maintaining current technical standards, to meet the requirements of the conservator. The authors of the article present alternatives to commonly used solutions, based on their experience with replacing historic building roofing with ceramic tiles made according to the production and firing technology of the nineteenth century. They emphasize that the correct/specialized restoration of existing tiles in a building makes it possible to preserve and reuse them, which is in line with the principles of historic preservation. However, due to the preservation of the roof tiles, it is not always possible to revitalize them. As a solution to the problem, the use of clay roof tiles manufactured according to 19th-century firing technology, including handmade methods, is presented, which preserves the geometry of the historic roof tiles. The approach presented by the authors meets both the requirements of conservation theory and the building standards for roofing elements. Although it is much more expensive than the solutions currently commonly used that result from modern technical requirements and tile-manufacturing technology, in the case of objects of significant cultural heritage, it is a solution that meets modern technical requirements while not compromising the original appearance of the monument.

An important function of the brain is to predict which stimulus is likely to occur based on the perceived cues. The present research studied the branching behavior of a computational network model of populations of excitatory and inhibitory neurons, both analytically and through simulations. Results show how synaptic efficacy, retroactive inhibition and short-term synaptic depression determine the dynamics of selection between different branches predicting sequences of stimuli of different probabilities. Further results show that changes in the probability of the different predictions depend on variations of neuronal gain. Such variations allow the network to optimize the probability of its predictions to changing probabilities of the sequences without changing synaptic efficacy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To assess the pharmacokinetic profile of ivermectin in Biłgorajska geese ( Anser anser domesticus ) after single I/V or oral administration, in order to compare these routes of administration and assess oral bioavailability., Methods: Ten healthy male geese were used in a single-dose, two-phase study with a 3-month washout period between phases. In the first phase, all geese were given 0.2 mg/kg I/V ivermectin, while in the second phase they were treated orally with the same dosage. Blood samples were collected at selected time points up to 480 hours after each administration. Samples were purified using protein precipitation and drug concentration was quantified using HPLC. The analytical method was validated on blank goose plasma and was characterised by an optimal linearity and a limit of quantification of 0.025 μg/mL. The pharmacokinetic analysis was carried out using a non-compartmental approach., Results: The drug was quantifiable up to 240 hours after I/V administration, while after oral treatment it was quantifiable up to 144 hours in most of the geese. The elimination half-life of ivermectin was approximately 3.8 (95% CI = 1.98-7.92; p = 0.027) times higher after I/V administration compared to oral administration. Moreover, the area under the curve from zero to the last detectable timepoint was 6.4 (95% CI = 4.65-8.74; p < 0.001) hours greater after I/V than oral administration. This difference led to a bioavailability of 20.38 (SD 5.92) %., Conclusions: Following oral administration in geese, ivermectin has a bioavailability of approximately 20%. Further research on the action of ivermectin in the gastrointestinal tract is required along with assessment of tissue residues to allow calculation of withdrawal time to ensure consumer safety., Abbreviations: AUC: Area under the concentration-time curve; AUC last : Area under the curve from zero to the last detectable timepoint; AUMC: Area under the first moment curve; C max : Maximum concentration; T max : Time at maximum plasma concentration.

Background: A diagnosis by magnetic resonance imaging (MRI) is often necessary before surgery of degenerative spine diseases. This can lead to a possible conflict with an inserted implant of the hip or knee. Heat generation or movement could be caused by the magnetic field. The aim of this study is to investigate temperature development in vitro in a 1.5T MRI of a ceramic knee arthroplasty., Methods: A full ceramic, complete metal-free non-constrained primary total knee arthroplasty is investigated. Temperature change was measured between platinum resistors before and after each MRI sequence by change of resistance. The knee implant was placed in a plastic container after the sensors were attached. Then the container was completely filled with ultrasound gel. To document any possible movement of the implant, a grid was placed under the container to document the position of the implant before and after the scans., Results: A total of four standard knee sequences were performed. The temperature at sites 1 to 5 per implant was always documented in the as-is state before MRI and then after each sequence. A total of 5 temperature measurement points were taken per implant. It was found that there were extremely small temperature variations. These were always in the range of less than 1°C. There was no case of movement of the implant triggered by the MRI scan., Conclusions: The experimental investigations carried out here showed homogeneous results with this experimental setup. It is concluded that, at least in vitro, that this ceramic knee implant can be used in MRI examinations without heating or movement., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self-modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

Platelets express P2X1 receptors and our data also show the expression of P2X7 receptors. We studied the role of both receptors in platelet apoptosis by incubation of PRP with P2X agonists, then centrifuged to remove viable platelets, and analyzed the supernatant by flow cytometry to identify a sparse platelet-derived population that stained with MitoTracker dyes and CD41. BzATP, a potent agonist of P2X receptors, and ABT737, an activator of intrinsic apoptosis, produced altered platelets that stained moderately for annexin V and corresponded to an early stage apoptotic platelet (ESAP). Over a range of BzATP concentrations, we observed a dose-dependent formation of ESAPs between 5 and 500 uM BzATP, together with a variable formation of ESAPs at nanomolar ATP or BzATP (50-200 nM). Production of ESAPs occurred with αβ-meATP, while responses with either BzATP or αβ-meATP showed desensitization at a higher agonist concentration. Formation of ESAPs by either 100 nM or 0.5 mM BzATP was inhibited by preincubation of platelets with latrunculin A, an inhibitor of the actin cytoskeleton that prevents apoptosis. ESAP production was totally inhibited by preincubation of platelets with methyl-beta-cyclodextrin, which removes cholesterol from lipid rafts. Our data show that both P2X1 and P2X7 receptors are localized in platelet lipid rafts where P2X-agonists act to produce early stage apoptotic platelets.

Spreading depolarizations (SDs) are involved in migraine, epilepsy, stroke, traumatic brain injury, and subarachnoid hemorrhage. However, the cellular origin and specific differential mechanisms are not clear. Increased glutamatergic activity is thought to be the key factor for generating cortical spreading depression (CSD), a pathological mechanism of migraine. Here, we show that acute pharmacological activation of NaV1.1 (the main Na+ channel of interneurons) or optogenetic-induced hyperactivity of GABAergic interneurons is sufficient to ignite CSD in the neocortex by spiking-generated extracellular K+ build-up. Neither GABAergic nor glutamatergic synaptic transmission were required for CSD initiation. CSD was not generated in other brain areas, suggesting that this is a neocortex-specific mechanism of CSD initiation. Gain-of-function mutations of NaV1.1 (SCN1A) cause familial hemiplegic migraine type-3 (FHM3), a subtype of migraine with aura, of which CSD is the neurophysiological correlate. Our results provide the mechanism linking NaV1.1 gain of function to CSD generation in FHM3. Thus, we reveal the key role of hyperactivity of GABAergic interneurons in a mechanism of CSD initiation, which is relevant as a pathological mechanism of Nav1.1 FHM3 mutations, and possibly also for other types of migraine and diseases in which SDs are involved.

Crotamine, a toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus , has been reported to have antinociceptive effects. We purified recombinant crotamine expressed in Escherichia coli and investigated its antinociceptive and anti-inflammatory effects using the hot-plate test, acetic-acid-induced writhing method, and formalin test in mice. Recombinant crotamine was administered intraperitoneally (0.04-1.2 mg kg -1 ) or intraplantarly (0.9-7.5 μg 10 μL -1 ) before the tests. The paw volume was measured with a plethysmometer. To evaluate the antagonistic and anti-inflammatory effects of naloxone, subcutaneous naloxone (4 mg kg -1 ) or intraplantar naloxone (5 μg 10 μL -1 ) was administered before recombinant crotamine. For tumor necrosis factor (TNF)-α assays, blood was drawn 3 h after formalin injection and measured using enzyme-linked immunosorbent assay. Intraperitoneal and intraplantar recombinant crotamine had antinociceptive and anti-inflammatory effects, neither of which were affected by pre-treatment with naloxone. The mean serum TNF-α levels were significantly lower in the intraperitoneal recombinant crotamine (0.4 and 1.2 mg kg -1 ) or intraplantar (2.5 and 7.5 μg 10 μL -1 ) recombinant crotamine groups than in the saline group and were not affected by naloxone pre-treatment. In conclusion, recombinant crotamine possesses significant antinociceptive and anti-inflammatory effects that do not appear to be related to the opioid receptor. The antinociceptive and anti-inflammatory effects of intraperitoneal or intraplantar recombinant crotamine are related to TNF-α.

Loss of function mutations of SCN1A, the gene coding for the voltage-gated sodium channel NaV1.1, cause different types of epilepsy, whereas gain of function mutations cause sporadic and familial hemiplegic migraine type 3 (FHM-3). However, it is not clear yet how these opposite effects can induce paroxysmal pathological activities involving neuronal networks' hyperexcitability that are specific of epilepsy (seizures) or migraine (cortical spreading depolarization, CSD). To better understand differential mechanisms leading to the initiation of these pathological activities, we used a two-neuron conductance-based model of interconnected GABAergic and pyramidal glutamatergic neurons, in which we incorporated ionic concentration dynamics in both neurons. We modeled FHM-3 mutations by increasing the persistent sodium current in the interneuron and epileptogenic mutations by decreasing the sodium conductance in the interneuron. Therefore, we studied both FHM-3 and epileptogenic mutations within the same framework, modifying only two parameters. In our model, the key effect of gain of function FHM-3 mutations is ion fluxes modification at each action potential (in particular the larger activation of voltage-gated potassium channels induced by the NaV1.1 gain of function), and the resulting CSD-triggering extracellular potassium accumulation, which is not caused only by modifications of firing frequency. Loss of function epileptogenic mutations, on the other hand, increase GABAergic neurons' susceptibility to depolarization block, without major modifications of firing frequency before it. Our modeling results connect qualitatively to experimental data: potassium accumulation in the case of FHM-3 mutations and facilitated depolarization block of the GABAergic neuron in the case of epileptogenic mutations. Both these effects can lead to pyramidal neuron hyperexcitability, inducing in the migraine condition depolarization block of both the GABAergic and the pyramidal neuron. Overall, our findings suggest different mechanisms of network hyperexcitability for migraine and epileptogenic NaV1.1 mutations, implying that the modifications of firing frequency may not be the only relevant pathological mechanism., Competing Interests: The authors have declared that no competing interests exist.

The global growth of electronic media usage among children has caused concerns regarding screen time (ST) impact on child development. No previous population-based studies have evaluated ST and child development in India. This study aimed to determine the burden of ST, associated sociodemographic factors, and its impact on domains of child development. A population-based cross-sectional study was conducted in the field practice area of rural and urban health centers in Tamil Nadu, India. A total of 718 children (396 rural and 322 urban) were selected, using a cluster random sampling method. ST estimates were obtained from parents/guardian after a 7-day observation period. The Communication DEALL Developmental Checklist was used to assess child development. The mean ST was 2.39 hours/day (95% confidence interval [CI]: 2.23-2.54), and the prevalence of excessive ST was 73% (95% CI: 69.2-76.8). Excessive ST was significantly associated with the mothers' ST, screen usage at bedtime, birth order (in children < 2 years), and attending school (in children ≥ 2 years). Increased ST was significantly associated with developmental delay, in particular, in the domains of language acquisition and communication. In children aged ≥ 2 years, a delay in ≥ 3 domains was associated with ST (adjusted odds ratio [AOR] = 17.75, 95% CI: 5.04-62.49, p < 0.001), as was language delay (AOR = 52.92, 95% CI: 12.33-227.21, p < 0.001). In children aged < 2 years, a delay in ≥ 2 domains was associated with ST (AOR = 16.79, 95% CI: 2.26-124.4, p < 0.001), as was language delay (AOR = 20.93, 95% CI: 2.68-163.32, p < 0.01). A very high prevalence of excessive ST was identified, with a significant association with developmental delay in children. There is an urgent need to include education on ST limits at the primary healthcare level., Competing Interests: The authors have declared that no competing interests exist.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4)  MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

We study experimentally the effect of linear plasma density gradients on the self-modulation of a 400 GeV proton bunch. Results show that a positive or negative gradient increases or decreases the number of microbunches and the relative charge per microbunch observed after 10 m of plasma. The measured modulation frequency also increases or decreases. With the largest positive gradient we observe two frequencies in the modulation power spectrum. Results are consistent with changes in wakefields' phase velocity due to plasma density gradients adding to the slow wakefields' phase velocity during self-modulation growth predicted by linear theory.

The study analyzes the influence of plant growth promoters and biological control agents on the chemical composition and antioxidant activity (AA) in the sprouts of buckwheat. The AA of cv. Kora sprouts was higher than cv. Panda, with 110.0 µM Fe 2+ /g (FRAP-Ferric Reducing Antioxidant Power), 52.94 µM TRX (Trolox)/g (DPPH-1,1-diphenyl-2-picrylhydrazyl), 182.7 µM AAE (Ascorbic Acid Equivalent)/g (Photochemiluminescence-PCL-ACW-Water-Soluble Antioxidant Capacity) and 1.250 µM TRX/g (PCL-ACL-Lipid-Soluble Antioxidant Capacity). The highest AA was found in the sprouts grown from seeds soaked in Ecklonia maxima extract and Pythium oligandrum (121.31 µM Fe 2+ /g (FRAP), 56.33 µM TRX/g (DPPH), 195.6 µM AAE/g (PCL-ACW) and 1.568 µM TRX/g (PCL-ACL). These values show that the antioxidant potential of buckwheat sprouts is essentially due to the predominant hydrophilic fraction of antioxidants. The AA of the sprouts was strongly correlated with total polyphenol content.

In this article we present a biologically inspired model of activation of memory items in a sequence. Our model produces two types of sequences, corresponding to two different types of cerebral functions: activation of regular or irregular sequences. The switch between the two types of activation occurs through the modulation of biological parameters, without altering the connectivity matrix. Some of the parameters included in our model are neuronal gain, strength of inhibition, synaptic depression and noise. We investigate how these parameters enable the existence of sequences and influence the type of sequences observed. In particular we show that synaptic depression and noise drive the transitions from one memory item to the next and neuronal gain controls the switching between regular and irregular (random) activation., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The mechanism of fast inspiratory flow rate (V I ') induced lung injury is unclear. As fast V I ' increases hysteresis, a measure of surface tension at the air-liquid interface, surfactant release or function may be important. This experimental study examines the contribution of impaired surfactant release or function to dynamic-VILI., Methods: Isolated perfused lungs from male Sprague Dawley rats were randomly allocated to four groups: a long or short inspiratory time (Ti = 0.5 s; slow V I ' or Ti = 0.1 s; fast V I ') at PEEP of 2 or 10 cmH 2 O. Tidal volume was constant (7 ml/kg), with f = 60 breath/min. Forced impedance mechanics (tissue elastance (Htis), tissue resistance (Gtis) and airway resistance (Raw) were measured at 30, 60 and 90 min following which the lung was lavaged for surfactant phospholipids (PL) and disaturated PL (DSP)., Results: Fast V I ' resulted in a stiffer lung. Concurrently, PL and DSP were decreased in both tubular myelin rich and poor fractions. Phospholipid decreases were similar with PEEP. In a subsequent cohort, laser confocal microscopy-based assessment demonstrated increased cellular injury with increased V I ' at both 30 and 90 min ventilation., Conclusion: Rapid V I ' may contribute to ventilator induced lung injury (VILI) through reduced surfactant release and/or more rapid reuptake despite unchanged tidal stretch.

The main objective of this article is to develop ceramic-based materials for additive layer manufacturing (3D printing technology) that are suitable for civil engineering applications. This article is focused on fly ash-based fiber-reinforced geopolymer composites. It is based on experimental research, especially research comparing mechanical properties, such as compressive and flexural strength for designed compositions. The comparison includes various composites (short fiber-reinforced geopolymers and plain samples), different times of curing (investigation after 7 and 28 days), and two technologies of manufacturing (casted and injected samples-simulations of the 3D printing process). The geopolymer matrix is based on class F fly ash. The reinforcements were green tow flax and carbon fibers. The achieved results show that the mechanical properties of the new composites made by injection methods (simulations of 3D technology) are comparable with those of the traditional casting process. This article also discusses the influence of fiber on the mechanical properties of the composites. It shows that the addition of short fibers could have a similar influence on both of the technologies., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Cortical spreading depression (CSD) is a wave of transient intense neuronal firing leading to a long lasting depolarizing block of neuronal activity. It is a proposed pathological mechanism of migraine with aura. Some forms of migraine are associated with a genetic mutation of the Na v1.1 channel, resulting in its gain of function and implying hyperexcitability of interneurons. This leads to the counterintuitive hypothesis that intense firing of interneurons can cause CSD ignition. To test this hypothesis in silico, we developed a computational model of an E-I pair (a pyramidal cell and an interneuron), in which the coupling between the cells in not just synaptic, but takes into account also the effects of the accumulation of extracellular potassium caused by the activity of the neurons and of the synapses. In the context of this model, we show that the intense firing of the interneuron can lead to CSD. We have investigated the effect of various biophysical parameters on the transition to CSD, including the levels of glutamate or GABA, frequency of the interneuron firing and the efficacy of the KCC2 co-transporter. The key element for CSD ignition in our model was the frequency of interneuron firing and the related accumulation of extracellular potassium, which induced a depolarizing block of the pyramidal cell. This constitutes a new mechanism of CSD ignition.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Background and Purpose: There is no consensus on whether patients undergoing myelography should discontinue medications that could lower their seizure threshold. The purpose of this study was to document the most commonly prescribed seizure threshold-lowering medications in patients undergoing myelography and determine whether withholding such medications decreases the incidence of seizures., Materials and Methods: We performed a retrospective observational study of all the myelograms obtained in 2016 at 2 affiliated hospitals. At hospital A, seizure threshold-lowering medications are discontinued before myelography, and prophylactic diazepam is given for all cervical myelograms. At hospital B, seizure threshold-lowering medications are not withheld before the procedure, and medical seizure prophylaxis is not implemented. The seizure threshold-lowering medications the patients were taking at the time of the procedure and postmyelographic seizure incidence were documented., Results: A total of 311 patients underwent myelography during 2016. One hundred eleven patients (36%) were on at least 1 seizure threshold-lowering medication, and 30 (10%) were on at least 2. The most common medications were duloxetine, sertraline, venlafaxine, bupropion, and trazodone. The most common tricyclic antidepressant was amitriptyline. Three patients across both sites had a controlled seizure disorder and were on antiepileptics. None of the patients at either hospital had seizures during or within 3 hours following any of the myelograms during the study period., Conclusions: Continuing seizure threshold-lowering medications during myelography does not increase the risk of seizures. Screening for and withholding seizure threshold-lowering medications are not indicated for routine myelography., (© 2019 by American Journal of Neuroradiology.)

Three right-handed patients diagnosed with Holmes tremor (HT), who suffered from pharmacotherapy-refractory tremor, were eligible for unilateral posterior subthalamic area deep brain stimulation (PSA-DBS). All patients were evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Clinical Global Impression scale (CGI) before DBS, 6, and 12 months after the PSA-DBS as well as at the last follow-up. In all patients, we observed a significant improvement of tremor control as demonstrated by changes in the FTMTRS and the CGI scales. Mean improvement of tremor in all patients was 56% for the FTMRTS with a corresponding change in the CGI scale. Our study demonstrates that PSA-DBS is efficacious in the treatment of HT. Indeed, PSA is a promising target for DBS for intractable proximal and distal tremor, even in cases of previous, suboptimal functional neurosurgery. The beneficial effect lasts over a long-term follow-up. PSA-DBS may be considered as an alternative target of DBS in tremor treatment., (© 2019 S. Karger AG, Basel.)

Introduction: The aim of the study was the application and evaluation of real-time PCRs based on the fluorescence of SYBR Green I intercalating dye for the detection of three Bacillus anthracis genes in contaminated liver and blood samples. The goals for detection were rpoB gene as a chromosomal marker, pag gene located on plasmid pXO1, and capC gene located on plasmid pXO2., Material and Methods: Five B. anthracis strains were used for the experiments. Additionally, single strains of other species of the genus Bacillus , i.e . B. cereus , B. brevis , B. subtilis , and B. megaterium , and strains of six other species were used for evaluation of the specificity of the tests. Three SYBR Green I real-time PCRs were conducted allowing confirmation of B. anthracis in the biological samples., Results: The observation of amplification curves in real-time PCRs enabled the detection of the chromosomally encoded rpoB gene, pag gene, and capC gene of B. anthracis . The specificity of the tests was confirmed by estimation of the melting temperature of the PCR products. The sensitivity and linearity of the reactions were determined using regression coefficients. Strains of other microbial species did not reveal real-time PCR products., Conclusion: All real-time PCRs for the detection of B. anthracis in biological samples demonstrated a significant sensitivity and high specificity., Competing Interests: Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article.

Background: Aphasia is a neurogenic communication disorder with significant deficits in various domains of language and communication. One such type of aphasia, which impacts the quality of life significantly is Broca's aphasia, where the individual is aware of the communication difficulty., Objective: To compare the Quality of Communication Life (QoCL) between individuals with Broca's aphasia and normal individuals., Methods: The first phase of the study translated and validated QCL scale in Tamil. The second phase involved administration of the Tamil QCL scale on 12 individuals with Broca's aphasia and 12 age matched normal adults. The marked responses were analysed on a visual analogue scale independently., Statistical Analysis: Three domains of QoCL were compared between the two groups using Mann-Whitney U-test., Results: The QoCL scores across three domains were observed to be lower in individuals with Broca's aphasia, when compared to normal adults. Individuals with Broca's aphasia expressed greater challenges in socialization/activities domain of QoCL than confidence/self-concept and roles and responsibilities domains., Conclusions: Information obtained on self-reported QCL scale in familiar or native language will facilitate in planning client-oriented management of aphasia., Competing Interests: There are no conflicts of interest.

We analyzed a generic relaxation oscillator under moderately strong forcing at a frequency much greater that the natural intrinsic frequency of the oscillator. Additionally, the forcing is of the same sign and, thus, has a nonzero average, matching neuroscience applications. We found that, first, the transition to high-frequency synchronous oscillations occurs mostly through periodic solutions with virtually no chaotic regimes present. Second, the amplitude of the high-frequency oscillations is large, suggesting an important role for these oscillations in applications. Third, the 1:1 synchronized solution may lose stability, and, contrary to other cases, this occurs at smaller, but not at higher frequency differences between intrinsic and forcing oscillations. We analytically built a map that gives an explanation of these properties. Thus, we found a way to substantially "overclock" the oscillator with only a moderately strong external force. Interestingly, in application to neuroscience, both excitatory and inhibitory inputs can force the high-frequency oscillations.

Combating bacterial pathogens has become a global concern especially when the antibiotics and chemical agents are failing to control the spread due to its resistance. Bacteriophages act as a safe biocontrol agent by selectively lysing the bacterial pathogens without affecting the natural beneficial microflora. The present study describes the screening of prominent enteric pathogens NDK1, NDK2, NDK3, and NDK4 (Escherichia, Klebsiella, Enterobacter, and Serratia) mostly observed in domestic wastewater; against which KNP1, KNP2, KNP3, and KNP4 phages were isolated. To analyze their potential role in eradicating enteric pathogens and toxicity issue, these bacteriophages were sequenced using next-generation sequencing and characterized based on its genomic content. The isolated bacteriophages were homologous to Escherichia phage (KNP1), Klebsiella phage (KNP2), Enterobacter phage (KNP3), Serratia phage (KNP4), and belonged to Myoviridae family of Caudovirales except for the unclassified KNP4 phage. Draft genome analysis revealed the presence of lytic enzymes such as holing and lysozyme in KNP1 phage, endolysin in KNP2 phage, and endopeptidase with holin in KNP3 phage. The absence of any lysogenic and virulent genes makes this bacteriophage suitable candidate for preparation of phage cocktail to combat the pathogens present in wastewater. However, KNP4 contained a virulent gene rendering it unsuitable to be used as a biocontrol agent. These findings make the phages (KNP1-KNP3) as a promising alternative for the biocontrol of pathogens in wastewater which is the main culprit to spread these dominated pathogens in different natural water bodies. This study also necessitates for genomic screening of bacteriophages for lysogenic and virulence genes prior to its use as a biocontrol agent.

Introduction: The aim of the study was the application and comparison of real-time PCR methods based on the fluorescence of SYBR Green I intercalating dye and TaqMan probes for the detection of the 23S rDNA gene of Listeria spp. and the hly A gene of Listeria monocytogenes in biological samples of the liver, brain, and blood., Material and Methods: Five strains of L. monocytogenes and single strains of each species L. ivanovii , L. innocua , L. grayi , L. welshimeri , and L. seeligeri were used for the experiments. Additionally, five strains of other species of bacteria were used for evaluation of the specificity of tests. In the first stage of the study SYBR Green I real-time PCRs, one allowing detection of the 23S rDNA gene and two based on the amplification the hly A gene, were performed. In the next part, three TaqMan probe-based real-time PCRs allowing confirmation of belonging to Listeria spp. and L. monocytogenes were conducted., Results: The observation of amplification curves in real-time PCRs enabled the detection of both genes. A high regression coefficient of 0.99 was found for all reactions. Specific amplification products were obtained for the 23S rDNA and hly A genes which confirm their belonging to Listeria spp. and L. monocytogenes , respectively. Other microbial species did not reveal real-time PCR products., Conclusion: Both real-time PCR methods for the detection of Listeria spp. and L. monocytogenes in biological samples demonstrated a significant sensitivity and high specificity., Competing Interests: Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article. Financial Disclosure Statement: This work was financed with the funds of the National Veterinary Research Institute in Pulawy, Poland. Animal Rights Statement: None required.

A subcritical pattern-forming system with nonlinear advection in a bounded domain is recast as a slow-fast system in space and studied using a combination of geometric singular perturbation theory and numerical continuation. Two types of solutions describing the possible location of stationary fronts are identified, whose origin is traced to the onset of convective and absolute instability when the system is unbounded. The former are present only for non-zero upstream boundary conditions and provide a quantitative understanding of noise-sustained structures in systems of this type. The latter correspond to the onset of a global mode and are present even with zero upstream boundary conditions. The role of canard trajectories in the nonlinear transition between these states is clarified and the stability properties of the resulting spatial structures are determined. Front location in the convective regime is highly sensitive to the upstream boundary condition, and its dependence on this boundary condition is studied using a combination of numerical continuation and Monte Carlo simulations of the partial differential equation. Statistical properties of the system subjected to random or stochastic boundary conditions at the inlet are interpreted using the deterministic slow-fast spatial dynamical system., Competing Interests: We have no competing interests.

Prediction is the ability of the brain to quickly activate a target concept in response to a related stimulus (prime). Experiments point to the existence of an overlap between the populations of the neurons coding for different stimuli, and other experiments show that prime-target relations arise in the process of long term memory formation. The classical modelling paradigm is that long term memories correspond to stable steady states of a Hopfield network with Hebbian connectivity. Experiments show that short term synaptic depression plays an important role in the processing of memories. This leads naturally to a computational model of priming, called latching dynamics; a stable state (prime) can become unstable and the system may converge to another transiently stable steady state (target). Hopfield network models of latching dynamics have been studied by means of numerical simulation, however the conditions for the existence of this dynamics have not been elucidated. In this work we use a combination of analytic and numerical approaches to confirm that latching dynamics can exist in the context of a symmetric Hebbian learning rule, however lacks robustness and imposes a number of biologically unrealistic restrictions on the model. In particular our work shows that the symmetry of the Hebbian rule is not an obstruction to the existence of latching dynamics, however fine tuning of the parameters of the model is needed.

Two unknown impurities were observed during the process development for multigram-scale synthesis of eplerenone (Inspra ® ). The new process-related impurities were identified and fully characterized as the corresponding (7β,11α,17α)-11-hydroxy- and (7α,11β,17α)-9,11-dichloroeplerenone derivatives 12a and 13 . Seven other known but poorly described in the literature eplerenone impurities, including four impurities A, B, C and E listed in the European Pharmacopoeia 8.4 were also detected, identified and fully characterized. All these contaminants result from side reactions taking place on the steroid ring C of the starting 11α-hydroxy-7α-(methoxycarbonyl)-3-oxo-17α-pregn-4-ene-21,17-carbolactone ( 12 ) and the key intermediate (7α,17α)-9(11)-enester 7 , including epimerization of the C-7 asymmetric center, oxidation, dehydration, chlorination and lactonization. The impurities were isolated and/or synthesized and fully characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry/electrospray ionization (HRMS/ESI). Their ¹H- and 13 C-NMR signals were fully assigned. The molecular structures of the eight impurities, including the new (7β,11α,17α)-11-hydroxy- and (7α,11β,17α)-9,11-dichloroeplerenone related substances 12a and 13 , were solved and refined using single-crystal X-ray diffraction (SCXRD). The full identification and characterization of these impurities should be useful for the quality control and the validation of the analytical methods in the manufacture of eplerenone., Competing Interests: The authors declare no conflict of interest.

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10 - 6 ) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10 -5 ) and near ZNF697 (combined P-value 8.15 × 10 -5 ).

Innovations in next-generation sequencing technology have introduced new avenues in microbial studies through "omics" approaches. This technology has considerably augmented the knowledge of the microbial world without isolation prior to their identification. With an enormous volume of bacterial "omics" data, considerable attempts have been recently invested to improve an insight into virosphere. The interplay between bacteriophages and their host has created a significant influence on the biogeochemical cycles, microbial diversity, and bacterial population regulation. This review highlights various concepts such as genomics, transcriptomics, proteomics, and metabolomics to infer the phylogenetic affiliation and function of bacteriophages and their impact on diverse microbial communities. Omics technologies illuminate the role of bacteriophage in an environment, the influences of phage proteins on the bacterial host and provide information about the genes important for interaction with bacteria. These investigations will reveal some of bio-molecules and biomarkers of the novel phage which demand to be unveiled.

The spread of multidrug-resistant (MDR) bacteria is an emerging threat to the environment and public wellness. Inappropriate use and indiscriminate release of antibiotics in the environment through un-metabolized form create a scenario for the emergence of virulent pathogens and MDR bugs in the surroundings. Mechanisms underlying the spread of resistance include horizontal and vertical gene transfers causing the transmittance of MDR genes packed in different host, which pass across different food webs. Several controlling agents have been used for combating pathogens; however, the use of lytic bacteriophages proves to be one of the most eco-friendly due to their specificity, killing only target bacteria without damaging the indigenous beneficial flora of the habitat. Phages are part of the natural microflora present in different environmental niches and are remarkably stable in the environment. Diverse range of phage products, such as phage enzymes, phage peptides having antimicrobial properties, and phage cocktails also have been used to eradicate pathogens along with whole phages. Recently, the ability of phages to control pathogens has extended from the different areas of medicine, agriculture, aquaculture, food industry, and into the environment. To avoid the arrival of pre-antibiotic epoch, phage intervention proves to be a potential option to eradicate harmful pathogens generated by the MDR gene flow which are uneasy to cure by conventional treatments.

There is a current and pressing need for improved cancer therapies. The use of small molecule kinase inhibitors and their application in combinatorial regimens represent an approach to personalized targeted cancer therapy. A number of AGC kinases, including atypical Protein Kinase C enzymes (PKCs), are validated drug targets for cancer treatment. Most drug development programs for protein kinases focus on the development of drugs that bind at the ATP-binding site. Alternatively, allosteric drugs have great potential for the development of future innovative drugs. However, the rational development of allosteric drugs poses important challenges because the compounds not only must bind to a given site but also must stabilize forms of the protein with a desired effect at a distant site. Here we describe the development of a new class of compounds targeting a regulatory site (PIF-pocket) present in the kinase domain and provide biochemical and crystallographic data showing that these compounds allosterically inhibit the activity of atypical PKCs. PS432, a representative compound, decreased the rate of proliferation of non-small cell lung cancer cells more potently than aurothiomalate, an atypical PKCι inhibitor currently under evaluation in clinical trials, and significantly reduced tumor growth without side effects in a mouse xenograft model. The druglike chemical class provides ample possibilities for the synthesis of derivative compounds, with the potential to allosterically modulate the activity of atypical PKCs and other kinases.

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.