Development of Mefloquine-Based Bifunctional Secondary Amine Organocatalysts for Enantioselective Michael and Friedel-Crafts Reactions.

The chiral framework based on 11-aminomefloquine has been utilized for the first time to construct bifunctional organocatalysts. These catalysts demonstrate high enantioselectivity in both Michael additions and Friedel-Crafts reactions across a variety of substrates, achieving up to >99% ee. The distinctive feature is the incorporation of a secondary amine group, offering unique tight hydrogen-bonding capabilities in the protonated state, as supported by DFT computation. The diversity of these organocatalysts suggests their broad applicability across multiple reaction classes.

Millennial processes of population decline, range contraction and near extinction of the European bison.

European bison (Bison bonasus) were widespread throughout Europe during the late Pleistocene. However, the contributions of environmental change and humans to their near extinction have never been resolved. Using process-explicit models, fossils and ancient DNA, we disentangle the combinations of threatening processes that drove population declines and regional extinctions of European bison through space and across time. We show that the population size of European bison declined abruptly at the termination of the Pleistocene in response to rapid environmental change, hunting by humans and their interaction. Human activities prevented populations of European bison from rebounding in the Holocene, despite improved environmental conditions. Hunting caused range loss in the north and east of its distribution, while land use change was responsible for losses in the west and south. Advances in hunting technologies from 1500 CE were needed to simulate low abundances observed in 1870 CE. While our findings show that humans were an important driver of the extinction of the European bison in the wild, vast areas of its range vanished during the Pleistocene-Holocene transition because of post-glacial environmental change. These areas of its former range have been climatically unsuitable for millennia and should not be considered in reintroduction efforts.

Effect of Intramuscular Tramadol on the Duration of Clinically Relevant Sciatic Nerve Blockade in Patients Undergoing Calcaneal Fracture Fixation: A Randomized Controlled Trial.

BACKGROUND: Calcaneal fracture fixation can generate severe postoperative pain and analgesia can be supported by a sciatic nerve block. However, following resolution of the sensory blockade, rebound pain may ensue. The aim of this study was to assess whether an incidental finding of two patients with an extension of the sciatic nerve block beyond 24 h following 100 mg of intramuscular tramadol administration could be confirmed. METHODS: Thirty-seven patients scheduled for a calcaneal intramedullary fixation (Calcanail®) were randomly divided into two groups. The tramadol group (n = 19) received a sciatic nerve block with 20 mL of 0.25% bupivacaine and a concomitant dose of 100 mg of intramuscular tramadol, while the control group (n = 18) received an identical sciatic nerve block with concomitant injection of normal saline (placebo). All patients had a spinal anesthesia with light sedation for the procedure. The time to first analgesic request defined as appearance of any pain (NRS > 0) was assessed as the primary endpoint with a clinically relevant expected result of at least 50% elongation in sensory blockade. RESULTS: The median time to first analgesic request from time of blockade in the tramadol group was 670 min compared with 578 min in the control group. The result was clinically not relevant and statistically not significant (p = 0.17). No statistical difference could be demonstrated in the time to first opioid request, although a trend for opioid sparing in the tramadol group could be seen. Total morphine consumption in the first 24 h was also statistically insignificant (the tramadol group 0.066 mg kg-1 compared with 0.125 mg kg-1 in the control group). In conclusion, intramuscular tramadol does not extend the duration of analgesia of a sciatic nerve block following a calcaneal fracture fixation beyond 2 h and an opioid sparing effect could not be demonstrated in this trial.

Efficacy and Side Effect Profile of Intrathecal Morphine versus Distal Femoral Triangle Nerve Block for Analgesia following Total Knee Arthroplasty: A Randomized Trial.

(1) Background: The management of postoperative pain after knee replacement is an important clinical problem. The best results in the treatment of postoperative pain are obtained using multimodal therapy principles. Intrathecal morphine (ITM) and single-shot femoral nerve block (SSFNB) are practiced in the treatment of postoperative pain after knee replacement, with the most optimal methods still under debate. The aim of this study was to compare the analgesic efficacy with special consideration of selected side effects of both methods. (2) Materials and methods: Fifty-two consecutive patients undergoing knee arthroplasty surgery at the Department of Orthopedics and Traumatology of the Medical University of Warsaw were included in the study. Patients were randomly allocated to one of two groups. In the ITM group, 100 micrograms of intrathecal morphine were used, and in the SSFNB group, a femoral nerve block in the distal femoral triangle was used as postoperative analgesia. The other elements of anesthesia and surgery did not differ between the groups. (3) Results: The total dose of morphine administered in the postoperative period and the effectiveness of pain management did not differ significantly between the groups (cumulative median morphine dose in 24 h in the ITM group 31 mg vs. SSFNB group 29 mg). The incidence of nausea and pruritus in the postoperative period differed significantly in favor of patients treated with a femoral nerve block. (4) Conclusions: Although intrathecal administration of morphine is similarly effective in the treatment of pain after knee replacement surgery as a single femoral triangle nerve block, it is associated with a higher incidence of cumbersome side effects, primarily nausea and pruritus.

Timing and synchrony of birth in Eurasian lynx across Europe.

The ecology and evolution of reproductive timing and synchrony have been a topic of great interest in evolutionary ecology for decades. Originally motivated by questions related to behavioral and reproductive adaptation to environmental conditions, the topic has acquired new relevance in the face of climate change. However, there has been relatively little research on reproductive phenology in mammalian carnivores. The Eurasian lynx (Lynx lynx) occurs across the Eurasian continent, covering three of the four main climate regions of the world. Thus, their distribution includes a large variation in climatic conditions, making it an ideal species to explore reproductive phenology. Here, we used data on multiple reproductive events from 169 lynx females across Europe. Mean birth date was May 28 (April 23 to July 1), but was ~10 days later in northern Europe than in central and southern Europe. Birth dates were relatively synchronized across Europe, but more so in the north than in the south. Timing of birth was delayed by colder May temperatures. Severe and cold weather may affect neonatal survival via hypothermia and avoiding inclement weather early in the season may select against early births, especially at northern latitudes. Overall, only about half of the kittens born survived until onset of winter but whether kittens were born relatively late or early did not affect kitten survival. Lynx are strict seasonal breeders but still show a degree of flexibility to adapt the timing of birth to surrounding environmental conditions. We argue that lynx give birth later when exposed to colder spring temperatures and have more synchronized births when the window of favorable conditions for raising kittens is shorter. This suggests that lynx are well adapted to different environmental conditions, from dry and warm climates to alpine, boreal, and arctic climates. This variation in reproductive timing will be favorable in times of climate change, as organisms with high plasticity are more likely to adjust to new environmental conditions.

[Comparison of intra-abdominal pressure, during spine surgeries, among two prone positional apparatuses in the same patient - a case report]. / Porównanie zmiany wartosci cisnienia sródbrzusznego podczas operacji kregoslupa przy zastosowaniu dwóch systemów ulozenia chorego w pozycji na brzuchu ­ opis przypadku.

Spinal surgeries often require prone positioning of the patient. This is associated with increased intra-abdominal pressure, which may increase the risk of intra- and postoperative complications. The described case enables the comparison of two prone positional apparatuses and their influence on changes in intra-abdominal pressure during spine surgeries. A CASE REPORT: A 74-year-old female patient underwent two spine surgeries due to a fracture of the Th12 vertebra and traumatic kyphosis. Both were performed in the prone position. During the first procedure, stabilization of the fracture, positioning was performed by placing the patient on the Allen table, whereas during the second procedure, laminectomy, by placing the patient on gel pads. During both surgeries the patient's intra-abdominal pressure was measured. The values measured while lying on the Allen table were found to be lower (mean 13.8 mmHg ± 0.66 mmHg) than the results obtained during the procedure utilizing gel pads (mean 24 mmHg ± 1.22 mmHg). Both surgeries were completed without complications. In both cases, creatinine, urea, and potassium concentrations as well as daily diuresis were measured to assess postoperative renal function. The results of these analyses did not indicate renal damage. CONCLUSIONS: The way the patient is positioned on the abdomen has a significant impact on intra-abdominal pressure. Compared to gel pads, the Allen table allows for a reduction in abdominal pressure, which corresponds with lower values of intra-abdominal pressure. This may help reduce the risk of complications during surgeries performed in the prone position.

Next-generation phylogeography resolves post-glacial colonization patterns in a widespread carnivore, the red fox (Vulpes vulpes), in Europe.

Carnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using genotyping by sequencing [GBS]) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g., Iberia). In addition, we tested multiple post-glacial recolonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to a larger mammalian community on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species.

Efficacy of Selenourea Organocatalysts in Asymmetric Michael Reactions under Standard and Solvent-Free Conditions.

By varying the steric and electronic surroundings of the hydrogen-bonding motif, the novel chiral Cinchona-alkaloid based selenoureas were developed. Acting as bifunctional catalysts, they were applied in the Michael reactions of dithiomalonate and nitrostyrene providing chiral adducts with up to 96% ee. The asymmetric Michael--hemiacetalization reaction of benzylidene pyruvate and dimedone, performed with the assistance of 5 mol% of selenoureas, furnished the product with up to 93% ee and excellent yields. The effectiveness of the new hydrogen-bond donors was also proved in solvent-free reactions under ball mill conditions, supporting the sustainability of the devised catalytic protocol.

Chiral Vicinal Diamines Derived from Mefloquine.

Novel 1,2-diamines based on the mefloquine scaffold prepared in enantiomerically pure forms resemble 9-amino-Cinchona alkaloids. Most effectively, 11-aminomefloquine with an erythro configuration was obtained by conversion of 11-alcohol into azide and hydrogenation. Alkylation of a secondary amine unit was needed to arrive at diastereomeric threo-11-aminomefloquine and to introduce diversity. Most of the substitution reactions of the hydroxyl group to azido group proceeded with net retention of the configuration and involved actual aziridine or plausible aziridinium ion intermediates. Enantiomerically pure products were obtained by the resolution of either the initial mefloquine or one of the final products. The evaluation of the efficacy of the obtained vicinal diamines in enantioselective transformations proved that erythro-11-aminomefloquine is an effective catalyst in the asymmetric Michael addition of nitromethane to cyclohexanone (up to 96.5:3.5 er) surpassing epi-aminoquinine in terms of selectivity.

The first description of the nymphal stages of Hoplopleura longula (Psocodea: Anoplura: Hoplopleuridae) from the harvest mouse Micromys minutus (Rodentia: Muridae).

BACKGROUND: Despite the widespread belief that an extensive body of knowledge exists for the sucking lice (Anoplura), some of their common, Eurasian or even cosmopolitan species still lack complete taxonomic descriptions, especially those for their nymphal stages. This applies especially to the most common rodent parasites: the lice of the genus Hoplopleura. In Europe, only two of the five most common Hoplopleura species have full taxonomic characteristics with a description of the nymphal stages. This study enriches the current state of knowledge for another species, Hoplopleura longula and presents the first description of its nymphal stages.The study includes five rare louse specimens (two nymphs I, one nymph II, two nymphs III) of H. longula collected from 63 Eurasian harvest mice Micromys minutus. The collected lice were fixed and preserved in 70% ethyl alcohol solution and then placed in polyvinyl-lactophenol to form total preparations. NEW INFORMATION: Only two of the five species found in Eurasia (H. acanthopus, H. affinis, H. captiosa, H. edentula and H. longula) have been given full taxonomic descriptions, including immature stages. This paper presents a description of the nymphal stages of H. longula (described for the first time).

Sex-biased polyparasitism in moose (Alces alces) based on molecular analysis of faecal samples.

Simultaneous infection with multiple parasite species in an individual host is often observed in wild populations. The understanding of parasite species distribution across populations of wild animals is of basic and applied importance, because parasites can have pronounced effects on the dynamics of host population. Here, we quantified prevalence and endoparasite species richness in moose and explored sex-biased polyparasitism using diagnostic PCR method coupled with DNA sequencing of moose faecal samples from the Biebrza River valley, North-Eastern Poland. This is the largest moose population in Central Europe that has not been harvested for almost 20 years. We also evaluated the appropriate quantity of faeces for detecting DNA of parasite species. Faecal samples were screened for molecular markers of 10 different species of endoparasites. Endoparasite prevalence was high in the studied population. Almost all of the samples (98%) tested positive for at least one parasite species, and we found polyparasitism in the majority of the tested individuals. The number of different parasite species found in a single individual ranged from 0 to 9. The parasite species richness was significantly higher in male than in female individuals. The most prevalent were liver fluke Parafasciolopsis fasciolaemorpha and gastrointestinal nematodes Ostertargia sp. Of the ten endoparasite species detected, only the prevalence of the tapeworm Moniezia benedeni was significantly higher in males than in females. Additionally, we identified co-occurrence associations of parasite species, which tended to be random, but we noted some evidence of both positive and negative associations. Our findings promote applications of molecular methods for parasite species identification from non-invasively collected faecal samples in management and scientific study of moose population, which should include investigation of parasite status, and in health monitoring programs for other wild cervids.

Multispecies reservoir of Spirometra erinaceieuropaei (Cestoda: Diphyllobothridae) in carnivore communities in north-eastern Poland.

BACKGROUND: Spirometra erinaceieuropaei is a diphylobothriid tapeworm with a complex life-cycle including definitive, intermediate and paratenic (transport) hosts. Multiple routes of parasite transmission often make it impossible to determine what type of host a specific infected animal is considered to be. Spargana larvae cause sparganosis, a severe food- and water-borne disease mainly found in Asia. In Poland, Spirometra sp. was reported in large carnivores in Bialowieza Primeval Forest for the first time in the 1940s and was recently confirmed as S. erinaceieuropaei in several mammals and snakes using molecular methods. METHODS: In total, 583 carcasses of 9 carnivore species were necropsied between 2013 and 2019 in north-eastern (NE) Poland. The larvae of S. erinaceieuropaei (spargana) were isolated from subcutaneous tissue, counted, and preserved for genetic analyses. We calculated the prevalence and intensity of infection. To assess spatial variation in S. erinaceieuropaei infection probability in NE Poland, we applied a generalized additive model (GAM) with binomial error distribution. To confirm the species affiliation of isolated larvae, we amplified a partial fragment of the 18S rRNA gene (240 bp in length). RESULTS: Spirometra larvae were found in the subcutaneous tissue of 172 animals of 7 species and confirmed genetically as S. erinaceieuropaei. The overall prevalence in all studied hosts was 29.5% with a mean infection intensity of 14.1 ± 33.8 larvae per individual. Native European badgers and invasive raccoon dogs were characterized by the highest prevalence. An analysis of parasite spread showed a spatially diversified probability of infection with the highest values occurring in the biodiversity hot spot, Bialowieza Primeval Forest. CONCLUSIONS: Our study revealed that various mammal species (both native and non-native) can serve as S. erinaceieuropaei reservoirs. The frequency and level of infection may differ between selected hosts and likely depend on host diversity and habitat structure in a given area. Further studies are needed to assess the distribution of the parasite throughout Europe and the environmental and biological factors influencing infection severity in wild mammals.

[Hypotension - a complication of subarachnoid anesthesia especially dangerous in patients aged]. / Hipotensja ­ powiklanie znieczulenia podpajeczynówkowego szczególnie grozne u chorych w podeszlym wieku.

Demographic data clearly show the progressive aging of societies. Problems and specificity of anaesthesia in the elderly becomes a particularly important issue in this context. Spinal anesthesia is a method often used to anesthetize elderly patients, and hypotension is one of its most common early complications. Untreated or improperly treated hypotension increases the risk of perioperative complications such as myocardial infarction, ischemic stroke or acute renal failure. The prevention of hypotension consists of intravenous fluid therapy and pre-emptive use of vasoconstrictor drugs. Among vasoconstrictors, ephedrine and phenylephrine are commonly used to treat hypotension due to spinal anaesthesia. Both drugs are available in Poland. Issues related to their use in the treatment of hypotension caused by spinal anaesthesia in the elderly, including the features of both drugs, their method of administration and dosage based on the literature and own experience are the subject of this study. It should be noted, however, that most studies in the use of ephedrine and phenylephrine as a targeted treatment for hypotension concern the obstetric patient population while the elderly population is underrepresented and the results are inconclusive.

The level of habitat patchiness influences movement strategy of moose in Eastern Poland.

Spatio-temporal variation in resource availability leads to a variety of animal movement strategies. In the case of ungulates, temporally unpredictable landscapes are associated with nomadism, while high predictability in the resource distribution favours migratory or sedentary behaviours depending on the spatial and temporal scale of landscape dynamics. As most of the surveys on moose (Alces alces) movement behaviours in Europe have been conducted on Scandinavian populations, little is known about the movement strategies of moose at the southern edge of the species' range. We expected that decreasing habitat patchiness in central Europe would be associated with the prevalence of migratory behaviours. To verify this hypothesis, we analysed 32 moose fitted with GPS collars from two study areas in eastern Poland which differed in a level of habitat patchiness. We classified moose movements using the net squared displacement method. As presumed, lower patchiness in the Biebrza study site was associated with the predominance of individuals migrating short-distance, while in more patchy landscape of Polesie, resident moose dominated. At the individual level, the propensity of moose to migrate decreased with increasing abundance of forest habitats in their summer ranges. In addition, the parameters (migration distance, timing and duration) for migratory individuals varied substantially between individuals and years. Yet, in spring individual moose expressed a consistent migration timing across years. There was little synchronization of migration timing between individuals from the same population both in spring and autumn, which may have been related to mild weather conditions. We observed that moose postponed their migrations and started movement toward summer ranges at a similar time window in years when spring was delayed due to harsh weather. Hence, in light of global warming, we presume further changes in animal movements will arise.

Patterns of parasite eggs, oocysts and larvae shedding by moose in the Biebrza marshland (NE Poland).

The study analyses patterns of endoparasite eggs, oocysts and larvae shedding by moose from the relict population in the Biebrza marshland, NE Poland, which has grown to be one of the largest in Central Europe since the ban on hunting imposed in 2001. The analysis identified 10 species or groups of parasites among 230 faecal moose samples collected over 16 consequent months. The most prevalent were the eggs of Trichostrongylidae, Trichuris spp., Nematodirella alcidis, Parafasciolopsis fasciolaemorpha and the larvae of Elaphostrongylus sp. Four parasite species were more prevalent in males, indicating male-biased parasitism, and the studied moose population exhibited a female-skewed sex ratio. Nematodirella alcidis eggs and Protostrongylid larvae were more prevalent during winter, which indicated their resistance to harsh weather conditions. The prevalence of Eimeria alces and Aonchotheca sp. increased during the growing season, as did the number of eggs per gram of faeces (EPG) of P. fasciolaemorpha, possibly due to the availability of water sources. Higher mean monthly temperature was also found to have a positive effect on the excretion of Trichostrongylidae and Moniezia spp. eggs. In addition, the time of infection and the specificity of the parasite life cycle, being sensitive to certain climatic conditions, also appeared to have a strong influence on eggs, oocysts and larvae shedding in this non-harvested moose population.

Open kidney cancer surgery and perioperative cardiac arrhythmias.

INTRODUCTION: Although cardiac arrhythmias during anesthesia are often observed, the literature focuses mainly on cardio-thoracic surgery. We aimed to evaluate the incidence of arrhythmias appearing in the perioperative period in patients undergoing urological surgery and furthermore to define whether combining general with epidural anesthesia prevents them. MATERIAL AND METHODS: The study included 50 adults, without a prior cardiac or arrhythmia history, undergoing an open kidney cancer surgery, who were randomly allocated to receive either general or combined epidural/general anesthesia. A Holter monitor was applied the evening before the surgery, tracing continuously for a period of 24 hours (7PM-7PM). ClinicalTrials.gov NCT02988219. RESULTS: There was no statistical difference in the arrhythmia occurrence between the randomization groups. Among 65.21% the following arrhythmias were observed: 27 - bradycardia, 4 - sinus pause, 6 - ventricular extrasystoles (>1000/24 hours), 3 - supraventricular extrasystoles (>200/24 hours). The patients with arrhythmia were older and often with hypertension (p <0.01). A longer surgery duration predisposed to arrhythmia appearance (122.5 vs. 99 minutes), (p <0.01). The temperature measured at the beginning and at the end of the surgery was significantly lower among the participants with arrhythmia (p = 0.02, p = 0.01). The gender, body mass index (BMI), laboratory tests and the intake of intravenous fluids did not influence the occurrence of arrhythmia. CONCLUSIONS: Perioperative cardiac arrhythmias (usually sinus arrhythmias) are common during an open kidney surgery and occur regardless of the anesthetic technique and usually do not require any treatment. Age, hypertension, long operation time or low body temperature predispose the patient to perioperative cardiac arrhythmias during surgery.

Widespread male sex bias in mammal fossil and museum collections.

A recent study of mammoth subfossil remains has demonstrated the potential of using relatively low-coverage high-throughput DNA sequencing to genetically sex specimens, revealing a strong male-biased sex ratio [P. Pecnerová et al., Curr. Biol. 27, 3505-3510.e3 (2017)]. Similar patterns were predicted for steppe bison, based on their analogous female herd-based structure. We genetically sexed subfossil remains of 186 Holarctic bison (Bison spp.), and also 91 brown bears (Ursus arctos), which are not female herd-based, and found that ∼75% of both groups were male, very close to the ratio observed in mammoths (72%). This large deviation from a 1:1 ratio was unexpected, but we found no evidence for sex differences with respect to DNA preservation, sample age, material type, or overall spatial distribution. We further examined ratios of male and female specimens from 4 large museum mammal collections and found a strong male bias, observable in almost all mammalian orders. We suggest that, in mammals at least, 1) wider male geographic ranges can lead to considerably increased chances of detection in fossil studies, and 2) sexual dimorphic behavior or appearance can facilitate a considerable sex bias in fossil and modern collections, on a previously unacknowledged scale. This finding has major implications for a wide range of studies of fossil and museum material.

Large-scale mitogenomic analysis of the phylogeography of the Late Pleistocene cave bear.

The cave bear (Ursus spelaeus) is one of the Late Pleistocene megafauna species that faced extinction at the end of the last ice age. Although it is represented by one of the largest fossil records in Europe and has been subject to several interdisciplinary studies including palaeogenetic research, its fate remains highly controversial. Here, we used a combination of hybridisation capture and next generation sequencing to reconstruct 59 new complete cave bear mitochondrial genomes (mtDNA) from 14 sites in Western, Central and Eastern Europe. In a Bayesian phylogenetic analysis, we compared them to 64 published cave bear mtDNA sequences to reconstruct the population dynamics and phylogeography during the Late Pleistocene. We found five major mitochondrial DNA lineages resulting in a noticeably more complex biogeography of the European lineages during the last 50,000 years than previously assumed. Furthermore, our calculated effective female population sizes suggest a drastic cave bear population decline starting around 40,000 years ago at the onset of the Aurignacian, coinciding with the spread of anatomically modern humans in Europe. Thus, our study supports a potential significant human role in the general extinction and local extirpation of the European cave bear and illuminates the fate of this megafauna species.