Aggregation-Induced Emission Enhancement and Solid-State Photoswitching of Crystalline Carbazole N-Salicylidene Anilines.

The development of fluorescent stimuli-responsive organic materials has attracted substantial interest due to their increasing optoelectronic applications. This study systematically introduces fluorine atoms on one end of carbazole-based N-salicylidene anilines 5a-5f to elucidate the impact in their solution and solid-state photophysics. The addition of fluorine atoms at one end of the molecule induced significant changes, for example, a reduction in the quantum yield (QY) fluorescence emission in solution, going from QY near unity in compound 5a (QY ∼ 100%) to a negligible emission in 5f (QY < 1%). Similarly, compound 5a showed a very strong aggregation-induced enhancement emission behavior, whereas compounds with a higher fluorine content were almost quenched. Furthermore, the crystalline solid-state photoisomerization in N-salicylidene anilines is not trivial, and only compounds with three (5e) and five fluorine atoms (5f) exhibited reversible solid-state photoisomerization under 405 nm light source irradiation. We propose that the presence of the arene-perfluoroarene interaction in the crystalline array facilitates the latter behavior. Our findings present a comprehensive study of crystal engineering for the obtention of photoswitchable crystalline materials and adjustable photophysics response, paving the way for its implementation in other systems.

Testicular torsion and ultrasound-assisted manual detorsion.

Testicular torsion is a medical emergency that requires an immediate and multidisciplinary approach from emergency, surgical, and radiological services. In this article, we discuss the current knowledge and growing value of ultrasound (US) for intravaginal testicular torsion diagnosis and our experience with manual testicular detorsion with US assistance. Testicular torsion requires prompt and accurate diagnosis and quick therapeutic action. Technological advances in US equipment and knowledge of this pathology place the radiologist in an excellent position for its diagnosis and management. During the same medical procedure, the radiologist can both confirm the intravaginal testicular torsion and attempt manual testicular detorsion. US-assisted manual testicular detorsion is a non-invasive, simple, quick, safe, and effective manoeuvre that can rapidly restore testicular blood flow, maximising testicular salvage, relieving the patient's symptoms, and facilitating surgery.

Ratphones: An Affordable Tool for Highly Controlled Sound Presentation in Freely Moving Rats.

Encoding and processing sensory information is key to understanding the environment and to guiding behavior accordingly. Characterizing the behavioral and neural correlates of these processes requires the experimenter to have a high degree of control over stimuli presentation. For auditory stimulation in animals with relatively large heads, this can be accomplished by using headphones. However, it has proven more challenging in smaller species, such as rats and mice, and has been only partially solved using closed-field speakers in anesthetized or head-restrained preparations. To overcome the limitations of such preparations and to deliver sound with high precision to freely moving animals, we have developed a set of miniature headphones for rats. The headphones consist of a small, skull-implantable base attached with magnets to a fully adjustable structure that holds the speakers and keeps them in the same position with respect to the ears.

The Use of a Brief Synchronization Treatment after Weaning, Combined with Superovulation, Has Moderate Effects on the Gene Expression of Surviving Pig Blastocysts.

The combination of estrus synchronization and superovulation (SS) treatments causes alterations in ovarian and endometrial gene expression patterns, resulting in abnormal follicle and oocyte growth, fertilization, and embryo development. However, the impact of combined SS treatments on the transcriptome of the surviving embryos remains unidentified. In this study, we examined gene expression changes in day 6 blastocysts that survived a brief regimen of synchronization treatment combined with superovulation. The sows were included in one of three groups: SS7 group (n = 6), sows were administered Altrenogest (ALT) 7 days from the day of weaning and superovulated with eCG 24 h after the end of ALT treatment and hCG at the onset of estrus; SO group (n = 6), ALT nontreated sows were superovulated with eCG 24 h postweaning and hCG at the onset of estrus; control group (n = 6), weaned sows displaying natural estrus. Six days after insemination, the sows underwent a surgical intervention for embryo collection. Transcriptome analysis was performed on blastocyst-stage embryos with good morphology. Differentially expressed genes (DEGs) between groups were detected using one-way ANOVA with an un-adjusted p-value < 0.05 and a fold change 1.5. The effect of SO treatment on the number of altered pathways and DEGs within each pathway was minimal. Only four pathways were disrupted comprising only a total of four altered transcripts, which were not related to reproductive functions or embryonic development. On the other hand, the surviving blastocysts subjected to SS7 treatments exhibited moderate gene expression changes in terms of DEGs and fold changes, with seven pathways disrupted containing a total of 10 transcripts affected. In this case, the up-regulation of certain pathways, such as the metabolic pathway, with two up-regulated genes associated with reproductive functions, namely RDH10 and SPTLC2, may suggest suboptimal embryo quality, while the down-regulation of others, such as the glutathione metabolism pathway, with down-regulated genes related to cellular detoxification of reactive oxygen species, namely GSTK1 and GSTO1, could depress the embryos' response to oxidative stress, thereby impairing subsequent embryo development. The gene expression changes observed in the present study in SS7 embryos, along with previous reports indicating SS7 can negatively affect fertilization, embryo production, and reproductive tract gene expression, make its use in embryo transfer programs unrecommendable.

Synthesis and Evaluation of Biological Activities for a Novel 1,2,3,4-Tetrahydroisoquinoline Conjugate with Dipeptide Derivatives: Insights from Molecular Docking and Molecular Dynamics Simulations.

Peptide synthesis has opened new frontiers in the quest for bioactive molecules with limitless biological applications. This study presents the synthesis of a series of novel isoquinoline dipeptides using advanced spectroscopic techniques for characterization. These compounds were designed with the goal of discovering unexplored biological activities that could contribute to the development of novel pharmaceuticals. We evaluated the biological activities of novel compounds including their antimicrobial, antibacterial, and antifungal properties. The results show promising activity against Escherichia coli and potent antibacterial activity against MTCC 443 and MTCC 1688. Furthermore, these compounds demonstrate strong antifungal activity, outperforming existing standard drugs. Computational binding affinity studies of tetrahydroisoquinoline-conjugated dipeptides against E. coli DNA gyrase displayed significant binding interactions and binding affinity, which are reflected in antimicrobial activities of compounds. Our integrative significant molecular findings from both wet and dry laboratories would help pave a path for the development of antimicrobial therapeutics. The findings suggest that these isoquinoline-conjugated dipeptides could be excellent candidates for drug development, with potential applications in the fight against bacterial and fungal infections. This research represents an exciting step forward in the field of peptide synthesis and its potential to discover novel bioactive molecules with significant implications for human health.

Immunological uterine response to pig embryos before and during implantation.

The establishment of a successful pregnancy can only occur through a concerted functioning of the entire female reproductive system, allowing for fertilization, subsequent embryo development and implantation of the conceptus. In this context, the uterine immunological responses responsible for rejection or tolerance of the conceptus are of critical importance. The aim of the present review is to summarize our current knowledge about those cellular and molecular immunological events occurring at the uterine level during pre-implantation and implantation stages of pregnancy in the pig. Advancing our understanding of the immune mechanisms involved in the success or failure of pregnancy will provide cues to develop novel strategies augmenting endometrial receptivity, finally increasing the efficiency of assisted reproductive technologies in pigs.

A Short-Term Altrenogest Treatment Post-weaning Followed by Superovulation Reduces Pregnancy Rates and Embryo Production Efficiency in Multiparous Sows.

Although embryo transfer (ET) is a biotechnology ready for the swine industry, there are factors to be solved, the availability of embryo donors as one. Multiparous sows as donors ought to be considered since weaning is a natural and efficient method for estrus synchronization. In addition, superovulation treatments at weaning are effective in increasing the efficiency of donor embryo production. However, ET programs typically require more donors than those available from a single weaning, imposing grouping several weanings to establish a batch for ET. Since short-term administration of Altrenogest is effective in delaying estrus after weaning without effects on ovulation and embryo development, we investigated how Altrenogest combined with superovulation would affect reproductive parameters and embryo quality and quantity of weaned multiparous donor sows. The sows were administered Altrenogest from the day of weaning for 14 (SS-14 group; N = 26), 7 (SS-7 group; N = 31) and 4 (SS-4 group; N = 32) days. The sows were superovulated with eCG 24 h after the last administration of Altrenogest and with hCG at the onset of estrus. Sows not treated with Altrenogest that were superovulated with eCG 24 h post-weaning and hCG at the onset of estrus (SC group; N = 37) and sows with natural estrus after weaning (C group; N = 34) were used as control groups. The percentage of sows showing estrus within 10 days was not affected by the treatment, but the interval from Altrenogest withdrawal to estrus was longer (P < 0.05) in the SS groups than the interval from weaning to estrus in the controls. SS treatments increased (P < 0.05) the percentage of sows with ovarian cysts and the development of polycystic ovaries. The pregnancy and the fertilization rates, and the overall embryo production efficiency were also negatively affected by the SS treatments (P < 0.05). Interestingly, almost 70% of the structures classified as unfertilized oocytes or degenerated embryos in sows from the SS groups were immature oocytes. In conclusion, although superovulation of weaned sows was highly efficient, short-term administration of Altrenogest in combination with superovulation had negative effects on most of the reproductive parameters assessed, particularly affecting the overall efficiency of pregnancy and embryo production.

Hyperthermia-Induced Changes in EEG of Anesthetized Mice Subjected to Passive Heat Exposure.

Currently, the role of hypothermia in electroencephalography (EEG) is well-established. However, few studies have investigated the effect of hyperthermia on EEG, an important physiological parameter governing brain function. The aim of this work was to determine how neuronal activity in anesthetized mice is affected when the temperature rises above the physiological threshold mandatory to maintain the normal body functions. In this study, a temperature-elevation protocol, from 37 to 42°C, was applied to four female mice of 2-3 months old while EEG was recorded simultaneously. We found that hyperthermia reduces EEG amplitude by 4.36% when rising from 37 to 38 degrees and by 24.33% when it is increased to 42 degrees. Likewise, increasing the body temperature produces a very large impact on the EEG spectral parameters, reducing the frequency power at the delta, theta, alpha, and beta bands. Our results show that hyperthermia has a global effect on the EEG, being able to change the electrical activity of the brain.

Point-of-Care Echocardiography: A Useful Tool for Assessing Complex Arrhythmias in the Pediatric Intensive Care Unit.

OBJECTIVE: To demonstrate that the analysis of the atrioventricular, intraventricular, and interventricular asynchrony by point-of-care ultrasound (POCUS) could be an alternative tool for assessing complex arrhythmias in pediatric patients with congenital heart diseases, mainly when an epicardial register or electrophysiology study is not available. DESIGN: Descriptive, retrospective case series study. SETTING: The pediatric intensive care unit of a university-affiliated tertiary hospital in Spain. PATIENTS: The authors included 12 patients with congenital heart disease younger than 18 years admitted to the authors' pediatric intensive care unit (PICU) from January 2018 to December 2019, with complex arrhythmias after surgery, managed by performing a bedside echocardiography when an electrophysiology test or epicardial auriculogram was unavailable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors included a total of 14 complex arrhythmias in 12 postsurgical patients in whom a comprehensive transthoracic electrocardiogram was not conclusive. The presence of atrioventricular, intraventricular, or interventricular asynchrony was assessed in standard echo views by performing M-mode and Doppler mitral inflow analysis, checking the heart motion. The final POCUS diagnoses were atrial flutter (n = 5), postsurgical atrioventricular block (n = 4), asynchrony induced by pacemaker (n = 2), junctional ectopic tachycardia (n = 1), nodal rhythm plus ventricular extrasystole (n = 1), and supraventricular tachycardia (n = 1). In all patients, regardless of the type of arrhythmia, detecting motion asynchrony was crucial for making the correct diagnosis. Offline cardiologist analysis of the POCUS scans showed full agreement. CONCLUSIONS: POCUS is a useful tool for initial diagnosis and management of complex arrhythmias in the PICU, mainly when epicardial auriculogram or electrophysiology studies are unavailable.

Implantable LENUS pro pump for treprostinil infusion in three pediatric patients.

BACKGROUND: Prostanoid treatment in patients with severe pulmonary arterial hypertension (PAH) has been proven safe and effective. Subcutaneous administration of treprostinil has side effects, which limits their use and acceptance. An implantable pump for continuous intravenous treprostinil infusion has been recently approved. We describe our experience with the implantable pump in three pediatric patients. DESCRIPTION OF CASES: The LENUS pro pump was implanted in three adolescents with severe PAH, who were treated with tadalafil, ambrisentan, and subcutaneous treprostinil. The indication of the Lenus pro pump implantation was the local side effects of subcutaneous treprostinil (pain, inflammation, and local infection) that were not well tolerated and that severely decreased their quality of life. The pump was surgically implanted under general anesthesia.One patient, in functional class IV, suffered postoperative hemodynamic instability and small pneumothorax, requiring an increase in treprostinil dose up to 85 ng/kg/min and a decrease 9 days after the pump implantation. The second patient who was discharged 4 days after surgery with treprostinil at 60 ng/kg/min reported improvement in his quality of life, but the dose requirement increased up to 92 ng/kg/min. After a 21-month follow-up, this patient received a lung transplant. The third patient presented a hematoma at the pump site with no other complications and had a follow-up of 9 months with an improvement in her quality of life. COMMENTS: Implantable pumps for continuous parenteral prostanoid infusion in pediatric patients are an alternative to external pumps, especially when familiar psychological or psychomotor issues hinder the use of external pumps.

Appendicitis or non-specific abdominal pain in pre-school children: When to request abdominal ultrasound?

AIM: The aim of this study is to determine the most useful diagnostic tools to differentiate appendicitis from non-specific abdominal pain (NSAP) in pre-school children. METHODS: We prospectively evaluated all children aged 5 years or younger admitted for suspected appendicitis at a paediatric emergency department during 5 years. Cases of NSAP and appendicitis were enrolled according to inclusion and exclusion criteria. The different variables collected were assessed by statistic and diagnostic accuracy studies. RESULTS: A total of 82 patients were studied: 27 cases of NSAP and 55 cases of appendicitis. We found no symptoms or signs with a high power of discrimination between both processes. Complicated cases of appendicitis begin to appear when the duration of symptoms exceeds 12 h. Among laboratory tests, C-reactive protein (CRP) value >34 mg/L was the variable with a greater association to appendicitis (odds ratio 9.8). Abdominal ultrasound (US) had high sensitivity and specificity to differentiate appendicitis, significantly improving its diagnostic accuracy when the duration of symptoms exceeds 12 h. CONCLUSIONS: A good history and physical examination are important in the diagnostic process, but reliable physical signs can be difficult to elicit in pre-school children. CRP and abdominal US are useful investigations that can improve diagnostic accuracy. According to our results, abdominal pain duration longer than 12 h or CRP value >34 mg/L should be an indication to perform an abdominal US in pre-school children with right lower quadrant tenderness.

Achievements and future perspectives of embryo transfer technology in pigs.

Commercial embryo transfer (ET) has unprecedented productive and economic implications for the pig sector. However, pig ET has been considered utopian for decades mainly because of the requirements of surgical techniques for embryo collection and embryo deposition into recipients, alongside challenges to preserve embryos. This situation has drastically changed in the last decade since the current technology allows non-surgical ET and short- and long-term embryo preservation. Here, we provide a brief review of the improvements in porcine ET achieved by our laboratory in the past 20 years. This review includes several aspects of non-surgical ET technology and different issues affecting ET programmes and embryo preservation systems. The future perspectives of ET technology are also considered. We will refer only to embryos produced in vivo since they are the only type of embryos with possible short-term use in pig production.

The mechanistic foundation of Weber's law.

Although Weber's law is the most firmly established regularity in sensation, no principled way has been identified to choose between its many proposed explanations. We investigated Weber's law by training rats to discriminate the relative intensity of sounds at the two ears at various absolute levels. These experiments revealed the existence of a psychophysical regularity, which we term time-intensity equivalence in discrimination (TIED), describing how reaction times change as a function of absolute level. The TIED enables the mathematical specification of the computational basis of Weber's law, placing strict requirements on how stimulus intensity is encoded in the stochastic activity of sensory neurons and revealing that discriminative choices must be based on bounded exact accumulation of evidence. We further demonstrate that this mechanism is not only necessary for the TIED to hold but is also sufficient to provide a virtually complete quantitative description of the behavior of the rats.

BODIPY as electron withdrawing group for the activation of double bonds in asymmetric cycloaddition reactions.

In this work we have found that a BODIPY can be used as an electron withdrawing group for the activation of double bonds in asymmetric catalysis. The synthesis of cyclohexyl derivatives containing a BODIPY unit can easily be achieved via trienamine catalysis. This allows a new different asymmetric synthesis of BODIPY derivatives and opens the door to future transformation of this useful fluorophore. In addition, the Quantum Chemistry calculations and mechanistic studies provide insights into the role of BODIPY as an EWG.

Prevention of hatching of porcine morulae and blastocysts by liquid storage at 20 °C.

Vitrification is the ideal method for long-lasting storage of porcine embryos. However, both strict airline regulations for transport of liquid nitrogen dewars and the technical problems experienced when vitrified embryos are transferred using non-surgical procedures have led to the introduction of alternative storage methods, such as preserving embryos in liquid state. This study evaluated whether a pH-stable medium containing high concentrations of either foetal calf serum (FCS; 50%) or BSA (4%) combined with storage at temperatures of 17 °C or 20 °C maintained in vivo-derived morulae and blastocysts alive and unhatched (a sanitary requirement for embryo transportation) during 72 h of storage. Neither FCS nor BSA supplements were able to counteract the negative effect of low temperatures (17 °C) on embryonic survival after storage. At 20 °C, the protective effect of FCS or BSA depended on embryo stage. While FCS successfully arrested embryo development of only blastocysts, BSA arrested the development of both morulae and blastocysts. Over 80% of BSA arrested embryos restarted development by conventional culture and progressed to further embryonic stages, including hatching. In conclusion, porcine morulae and blastocysts can survive and remain unhatched during at least 72 h when stored at 20 °C in a BSA-containing medium.

State-dependent geometry of population activity in rat auditory cortex.

The accuracy of the neural code depends on the relative embedding of signal and noise in the activity of neural populations. Despite a wealth of theoretical work on population codes, there are few empirical characterizations of the high-dimensional signal and noise subspaces. We studied the geometry of population codes in the rat auditory cortex across brain states along the activation-inactivation continuum, using sounds varying in difference and mean level across the ears. As the cortex becomes more activated, single-hemisphere populations go from preferring contralateral loud sounds to a symmetric preference across lateralizations and intensities, gain-modulation effectively disappears, and the signal and noise subspaces become approximately orthogonal to each other and to the direction corresponding to global activity modulations. Level-invariant decoding of sound lateralization also becomes possible in the active state. Our results provide an empirical foundation for the geometry and state-dependence of cortical population codes.

Analysis of some immunogenic properties of the recombinant Sporothrix schenckii Gp70 expressed in Escherichia coli.

AIM: Sporothrix schenckii is the causative agent of sporotrichosis. A 70-kDa glycoprotein, Gp70, is a candidate for the development of prophylactic alternatives to control the disease, and its gene (GP70) is predicted to encode for a protein of 43 kDa, contrasting with the molecular weight of the native protein. MATERIALS & METHODS: The GP70 was expressed in bacteria, the recombinant protein purified, used in immunoassays and injected to Galleria mellonella. RESULTS & CONCLUSION: The recombinant protein was detected by anti-Gp70 antibodies, confirming that the Gp70 backbone is a 43-kDa peptide. This protein showed enzyme activity of cyclase and was recognized by sera of patients with sporotrichosis. Although it was not useful for serodiagnosis of sporotrichosis, it conferred protection to animals against experimental sporotrichosis.

Synthetic Approach to Readily Accessible Benzofuran-Fused Borondipyrromethenes as Red-Emitting Laser Dyes.

We took advantage of the chemoselective meso-functionalization of 2,3,5,6-tetrabromo-8-methylthioBODIPY 6 to prepare a series of 2,3,5,6-tetrabromo-8-arylBODIPY derivatives suitable for SNAr substitution reactions with phenols exclusively at positions 3 and 5. Pd(0)-catalyzed intramolecular arylation reaction ensued on the remaining brominated positions 2 and 6 to give a new family of benzofuran-fused BODIPY dyes. This method utilizes readily available starting materials and allows for the preparation of the title compounds with excellent functional group tolerance. Moreover, it was demonstrated that the methodology described herein is amenable for the incorporation of biomolecules. The photophysical and lasing properties of the benzofuran-fused BODIPY dyes were thoroughly analyzed with the aid of electrochemical measurements and quantum mechanical simulations. These dyes show bright and intriguing emission (both fluorescence and laser) toward the red edge of the visible spectrum with remarkable tolerance under strong and continuous irradiation.

Using experience to improve: how errors shape behavior and brain activity in monkeys.

Previous works have shown that neurons from the ventral premotor cortex (PMv) represent several elements of perceptual decisions. One of the most striking findings was that, after the outcome of the choice is known, neurons from PMv encode all the information necessary for evaluating the decision process. These results prompted us to suggest that this cortical area could be involved in shaping future behavior. In this work, we have characterized neuronal activity and behavioral performance as a function of the outcome of the previous trial. We found that the outcome of the immediately previous trial (n-1) significantly changes, in the current trial (n), the activity of single cells and behavioral performance. The outcome of trial n-2, however, does not affect either behavior or neuronal activity. Moreover, the outcome of difficult trials had a greater impact on performance and recruited more PMv neurons than the outcome of easy trials. These results give strong support to our suggestion that PMv neurons evaluate the decision process and use this information to modify future behavior.

Stable bioemulsifiers are produced by Acinetobacter bouvetii UAM25 growing in different carbon sources.

Acinetobacter species are identified as producing surface-active and emulsifying molecules known as bioemulsifiers. Production, characterization and stability of bioemulsifiers produced by Acinetobacter bouvetii UAM25 were studied. A. bouvetii UAM25 grew in three different carbon and energy sources: ethanol, a glycerol-hexadecane mixture and waste cooking oil in an airlift bioreactor, showing that bioemulsifier production was growth associated. The three purified bioemulsifiers were lipo-heteropolysaccharides of high molecular weight (4866 ± 533 and 462 ± 101 kDa). The best carbon source and energy for bioemulsifier production was wasted cooking oil, with a highest emulsifying capacity (76.2 ± 3.5 EU mg-1) as compared with ethanol (46.6 ± 7.1 EU mg-1) and the glycerol-hexadecane mixture (49.5 ± 4.2 EU mg-1). The three bioemulsifiers in our study displayed similar macromolecular structures, regardless of the nature (hydrophobic or hydrophilic) of the carbon and energy source. Bioemulsifiers did not decrease surface tension, but the emulsifying capacity of all of them was retained under extreme variation in salinity (0-50 g NaCl L-1), pH (3-10) and temperature (25-121 °C), indicative of remarkable stability. These findings contribute to understanding of the relationship between: production, physical properties, chemical composition and stability of bioemulsifiers for their potential applications in biotechnology, such as bioremediation of hydrocarbon-contaminated soil and water.