Porphyrin-BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect.

A porphyrin-BODIPY dyad (P-BDP) was obtained through covalent bonding, featuring a two-segment design comprising a light-harvesting antenna system connected to an energy acceptor unit. The absorption spectrum of P-BDP resulted from an overlap of the individual spectra of its constituent parts, with the fluorescence emission of the BODIPY unit experiencing significant quenching (96 %) due to the presence of the porphyrin unit. Spectroscopic, computational, and redox investigations revealed a competition between photoinduced energy and electron transfer processes. The dyad demonstrated the capability to sensitize both singlet molecular oxygen and superoxide radical anions. Additionally, P-BDP effectively induced the photooxidation of L-tryptophan. In suspensions of Staphylococcus aureus cells, the dyad led to a reduction of over 3.5 log (99.99 %) in cell survival following 30 min of irradiation with green light. Photodynamic inactivation caused by P-BDP was also extended to the individual bacterium level, focusing on bacterial cells adhered to a surface. This dyad successfully achieved the total elimination of the bacteria upon 20 min of irradiation. Therefore, P-BDP presents an interesting photosensitizing structure that takes advantage of the light-harvesting antenna properties of the BODIPY unit combined with porphyrin, offering potential to enhance photoinactivation of bacteria.

Association of Polymorphisms of the IL-17A and IL-17F Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.

Diketopyrrolopyrrole Derivatives as Photosensitizing Agents against Staphylococcus aureus.

Diketopyrrolopyrrole (DPP) derivatives containing sulfonamide (Sulfonamide-DPP), pyridyl (Dipyridyl-DPP) and N-methylpyridyl (MePyridyl-DPP) substituents were assessed as antibacterial photosensitizers. Non-charged DPPs showed an intense absorption band centered at about 480 nm and green fluorescence emission (ΦF ~ 0.7) in acetonitrile. The absorption of MePyridyl-DPP was bathochromically shifted at 510 nm, with decreased fluorescence emission. Sulfonamide-DPP and Dipyridyl-DPP photosensitized the formation of O2 (1 Δg ) (ΦΔ ~ 0.15-0.17), while the production induced by MePyridyl-DPP was at least 10 times lower. Furthermore, these DPPs produced a photoreduction of NBT similar to that of the control. Photodynamic inactivation induced by DPPs was first investigated at the single-bacterium level of Staphylococcus aureus attached to a surface. After 30 min irradiation, MePyridyl-DPP produced a complete eradication of the bacteria. In bacterial cell suspensions, dicationic DPP induced more than 7 log10 decrease in S. aureus cell survival after 30 min irradiation. Potentiation with iodide anions allowed a complete elimination of bacteria after 15 min therapy. This compound was also effective to eliminate S. aureus cells on biofilms. The results show that MePyridyl-DPP bearing two positive groups provides an amphiphilic character to the structure that improves the interaction with the cell envelop. This effect enhances the photocytotoxic activity of MePyridyl-DPP against bacteria.

Acute psychophysiological responses during exercise while using resistive respiratory devices: A systematic review.

Different studies have observed that respiratory muscle training (RMT) improve the endurance and strength of the respiratory muscles, having a positive impact on performance of endurance sports. Nevertheless, it remains to be clarified how to improve the efficiency of such training. The objective of this systematic review was to evaluate the acute physiological responses produced by training the respiratory muscles during exercise with flow resistive devices because such information may support us improve the efficiency of this type of training. A search in the Medline, Science Direct, Web of Science and Scopus databases was conducted, following the PRISMA guidelines. The methodological quality of the articles was assessed using the PEDro scale. Nineteen studies met the inclusion criteria and a total of 212 subjects were included in the studies. The RMT method used in all studies was flow resistive loading, whereas the constant load exercise was the most common type of exercise among the studies. The results obtained seem to indicate that the use of this type of training during exercise reduces the performance, the lactate (La-) values and the ventilation, whereas the end - tidal partial pressure of carbon dioxide (PCO2) is increased.

Rare Choristoma of the Tarsal Conjunctiva: Critical Inspection Prevents Unnecessary Mutilation.

We report a case of a 26-year-old male patient with an incidental finding of a flesh-colored tumor with few vellus hairs on its surface, located on the fornix and the tarsal conjunctiva of the left lower eyelid. Histology of the biopsy showed a choristoma consisting of abundant vellus hairs, sebaceous glands, and sparse lacrimal gland tissue. Recognition of conjunctival vellus hairs is significant and raises the suspected diagnosis of choristoma, which can be confirmed by a small sample biopsy. A complete excision is unnecessary and possible surgical complications can be prevented. Choristomas of the tarsal conjunctiva are very rare and, to our knowledge, this is the first histological documentation of a choristoma containing vellus hair located on the tarsal conjunctiva. In addition, we review the histopathological findings of choristomas and their differential diagnoses.

Psychophysiological Responses During a Cycling Test to Exhaustion While Wearing the Elevation Training Mask.

ABSTRACT: López-Pérez, ME, Romero-Arenas, S, Colomer-Poveda, D, Keller, M, and Márquez, G. Psychophysiological responses during a cycling test to exhaustion while wearing the elevation training mask. J Strength Cond Res 36(5): 1282-1289, 2022-The aim of this study was to investigate the psychophysiological effects of wearing the elevation training mask (ETM). Twelve men performed time-to-exhaustion (TTE) tests at 75% of peak power output with and without wearing the ETM. Heart rate (HR), rating of perceived exertion (RPE), breathing discomfort (BD), and oxygen saturation (SpO2) were measured during the TTE. Prefrontal cortex (PFC) and vastus lateralis oxygenated, deoxygenated, and total hemoglobin were monitored using near-infrared spectroscopy. At the end of each test, blood lactate values (La-) were collected, and subjects completed the Beck Anxiety Inventory (BAI). The mask caused a reduction in the TTE (-37.7%; p < 0.001) and in the SpO2 (-2%; p < 0.001). Beck Anxiety Inventory scores were negatively correlated with the changes observed in the TTE (r = -0.77; p < 0.01). La-, HR, and muscle oxygenation displayed similar results across conditions. In conjunction with an increased hemodynamic response in the PFC, subjects reported higher RPE and BD values in the ETM condition (p < 0.01). Finally, BAI scores were negatively correlated with the changes observed in the TTE (r = -0.77; p < 0.01). This study suggests that wearing the ETM induces psychophysiological alterations affecting the exercise tolerance and limiting the performance.

Porphyrin-Schiff Base Conjugates Bearing Basic Amino Groups as Antimicrobial Phototherapeutic Agents.

New porphyrin-Schiff base conjugates bearing one (6) and two (7) basic amino groups were synthesized by condensation between tetrapyrrolic macrocycle-containing amine functions and 4-(3-(N,N-dimethylamino)propoxy)benzaldehyde. This approach allowed us to easily obtain porphyrins substituted by positive charge precursor groups in aqueous media. These compounds showed the typical Soret and four Q absorption bands with red fluorescence emission (ΦF ~ 0.12) in N,N-dimethylformamide. Porphyrins 6 and 7 photosensitized the generation of O2(1Δg) (ΦΔ ~ 0.44) and the photo-oxidation of L-tryptophan. The decomposition of this amino acid was mainly mediated by a type II photoprocess. Moreover, the addition of KI strongly quenched the photodynamic action through a reaction with O2(1Δg) to produce iodine. The photodynamic inactivation capacity induced by porphyrins 6 and 7 was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans. Furthermore, the photoinactivation of these microorganisms was improved using potentiation with iodide anions. These porphyrins containing basic aliphatic amino groups can be protonated in biological systems, which provides an amphiphilic character to the tetrapyrrolic macrocycle. This effect allows one to increase the interaction with the cell wall, thus improving photocytotoxic activity against microorganisms.

Vedolizumab Experience in Children and Adolescents With Inflammatory Bowel Disease: A Multicenter Observational Study.

Background: Vedolizumab is increasingly used off-label to treat children and adolescents with inflammatory bowel disease (IBD). In the absence of rigorous clinical trial experience, multicenter observational data are important to establish expectations for efficacy and safety. We examined 1-year outcomes following vedolizumab therapy in a large multicenter pediatric IBD cohort. Methods: We performed a retrospective study of 159 pediatric patients (4-17 years old) with IBD [78, Crohn disease (CD); 81, ulcerative colitis/IBD-unspecified (UC/IBD-U)] treated with vedolizumab for 1 year at 8 pediatric medical centers in the United States. Demographics, clinical outcomes, laboratory data, and vedolizumab dosing were recorded. The primary outcome was corticosteroid (CS)-free clinical remission at 1 year. Other measured outcomes were clinical remission at 12 and/or 24 weeks, laboratory outcomes at 1 year, and endoscopy/histology results at 1 year. Results: Among the 159 patients (mean age, 14.5 ± 2.4 years; 86% anti-TNF experienced), 68/159 (43%) achieved CS-free clinical remission at 1 year (CD, 35/78, 45%; UC/IBD-U, 33/81, 40%). Vedolizumab therapy failed and was discontinued in 33/159 (21%) patients prior to 1 year (CD, 18/78, 23%; UC/IBD-U, 15/81, 19%). While week 12 clinical remission was not predictive of 1-year clinical remission in either CD or UC/IBD-U, week 24 clinical remission was predictive of 1-year clinical remission only in CD patients. No infusion reactions or serious side effects were noted. Conclusions: Vedolizumab was safe and effective in this pediatric population with approximately 43% achieving CS-free clinical remission at 1 year. Similar efficacy was noted in both CD and UC.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

Evolutionary history of Mexican domesticated and wild Meleagris gallopavo.

BACKGROUND: The distribution of the wild turkey (Meleagris gallopavo) extends from Mexico to southeastern Canada and to the eastern and southern regions of the USA. Six subspecies have been described based on morphological characteristics and/or geographical variations in wild and domesticated populations. In this paper, based on DNA sequence data from the mitochondrial D-loop, we investigated the genetic diversity and structure, genealogical relationships, divergence time and demographic history of M. gallopavo populations including domesticated individuals. RESULTS: Analyses of 612 wild and domesticated turkey mitochondrial D-loop sequences, including 187 that were collected for this study and 425 from databases, revealed 64 haplotypes with few mutations, some of which are shared between domesticated and wild turkeys. We found a high level of haplotype and nucleotide diversity, which suggests that the total population of this species is large and stable with an old evolutionary history. The results of genetic differentiation, haplotype network, and genealogical relationships analyses revealed three main genetic groups within the species: mexicana as a population relict (C1), merriami (C2), and mexicana/intermedia/silvestris/osceola (C3). Haplotypes detected in domesticated turkeys belong to group C3. Estimates of divergence times agree with range expansion and diversification events of the relict population of M. gallopavo in northwestern Mexico during the Pliocene-Pleistocene and Pleistocene-Holocene boundaries. Demographic reconstruction showed that an expansion of the population occurred 110,000 to 130,000 years ago (Kya), followed by a stable period 100 Kya and finally a decline ~ 10 Kya (Pleistocene-Holocene boundary). In Mexico, the Trans-Mexican Volcanic Belt may be responsible for the range expansion of the C3 group. Two haplotypes with different divergence times, MGMDgoB/MICH1 and MICH2, are dominant in domesticated and commercial turkeys. CONCLUSIONS: During the Pleistocene, a large and stable population of M. gallopavo covered a wide geographic distribution from the north to the center of America (USA and Mexico). The mexicana, merriami, and mexicana/intermedia/silvestris/osceola genetic groups originated after divergence and range expansion from northwestern Mexico during the Pliocene-Pleistocene and Pleistocene-Holocene boundaries. Old and new maternal lines of the mexicana/intermedia/silvestris/osceola genetic group were distributed within the Trans-Mexican Volcanic Belt where individuals were captured for domestication. Two haplotypes are the main founder maternal lines of domesticated turkeys.

New primate locality from the early Miocene of Patagonia, Argentina.

OBJECTIVES: The purpose of this work is to present a new primate locality with evidence that increases the knowledge on the radiation of the extinct platyrrhine primates. MATERIALS AND METHODS: We studied the new specimen and compared it to specimens identified as Mazzonicebus almendrae. RESULTS: The new first and second molars were comparable to Mazzonicebus almendrae in all morphological details, allowing us to allocate the new specimen to M. almendrae and add comments on morphological variation in this species regarding the orientation of the labial cristae and development of the anterolingual cingulum. This new maxilla also present the first known M3 for the species. DISCUSSION: The new specimen increases our knowledge of the extinct platyrrhines from Patagonia. Their age and geographical distribution ranges from early to middle Miocene in an area between 40° to 47° of southern latitude.

TubZ filament assembly dynamics requires the flexible C-terminal tail.

Cytomotive filaments are essential for the spatial organization in cells, showing a dynamic behavior based on nucleotide hydrolysis. TubZ is a tubulin-like protein that functions in extrachromosomal DNA movement within bacteria. TubZ filaments grow in a helical fashion following treadmilling or dynamic instability, although the underlying mechanism is unclear. We have unraveled the molecular basis for filament assembly and dynamics combining electron and atomic force microscopy and biochemical analyses. Our findings suggest that GTP caps retain the filament helical structure and hydrolysis triggers filament stiffening upon disassembly. We show that the TubZ C-terminal tail is an unstructured domain that fulfills multiple functions contributing to the filament helical arrangement, the polymer remodeling into tubulin-like rings and the full disassembly process. This C-terminal tail displays the binding site for partner proteins and we report how it modulates the interaction of the regulator protein TubY.

Social signals and aversive learning in honey bee drones and workers.

The dissemination of information is a basic element of group cohesion. In honey bees (Apis mellifera Linnaeus 1758), like in other social insects, the principal method for colony-wide information exchange is communication via pheromones. This medium of communication allows multiple individuals to conduct tasks critical to colony survival. Social signaling also establishes conflict at the level of the individual who must trade-off between attending to the immediate environment or the social demand. In this study we examined this conflict by challenging highly social worker honey bees, and less social male drone honey bees undergoing aversive training by presenting them with a social stress signal (isopentyl acetate, IPA). We utilized IPA exposure methods that caused lower learning performance in appetitive learning in workers. Exposure to isopentyl acetate (IPA) did not affect performance of drones and had a dose-specific effect on worker response, with positive effects diminishing at higher IPA doses. The IPA effects are specific because non-social cues, such as the odor cineole, improve learning performance in drones, and social homing signals (geraniol) did not have a discernible effect on drone or worker performance. We conclude that social signals do generate conflict and that response to them is dependent on signal relevance to the individual as well as the context. We discuss the effect of social signal on learning both related to its social role and potential evolutionary history.

Optimization of radiation doses received by personnel in PET uptake rooms.

Reduction of dose to exposed personnel during positron emission tomography (PET) installation usually relies on physical shielding. While the major contribution of shielding is unquestioned, it is usually the only method applied. Other methods of reduction, such as working procedure optimization, the position of the furniture, and rooms are usually disregarded in these installations. This paper presents a design and work optimization procedure used in a particular institution. The influence on the dose received by personnel due to the positioning of injection chairs, injection room configuration, and working procedures is studied. Using this optimization strategy, it is possible to reduce the technician dose due to patients by a factor of 0.59. Injection room design is much more important for optimizing the received dose than is work-flow management. The influence of the order of patient entrance on received dose was the aspect that produced the smallest variation in received doses. It is recommended that the optimization be carried out for the installation proposed in the design phase, when no additional cost is required, because the position of the doors of the injection rooms depends on the where the injection chairs are situated.

Dependability of posterior-segment spectral domain optical coherence tomography for measuring central corneal thickness.

PURPOSE: The aim of this study was to assess the intersession and interobserver reliability of central corneal thickness (CCT) measurements using a posterior-segment spectral domain optical coherence tomography (SD-OCT). METHODS: Sixty patients were examined with a posterior-segment SD-OCT system (Topcon 3D-OCT). To analyze intersession reproducibility, 1 examiner measured CCT in 60 eyes 2 times 1 week apart, and to study interobserver reproducibility, a second examiner obtained another measurement during the first session. Within-subject reproducibility, coefficient of reproducibility (CR), and intraclass correlation coefficients (ICC) were calculated. Agreement between Topcon 3D OCT and ultrasound pachymetry (USP) was also assessed. RESULTS: Posterior-segment SD-OCT showed an intersession reproducibility of 12.7 µm (CR = 2.4%) and an excellent ICC (0.96). No systematic difference between sessions was found (average difference, 1.7 µm; P = 0.15). We found no significant bias between observers (mean difference, -1.5 µm; P = 0.29). The interobserver reproducibility was 16.4 µm (CR = 3.1%), and the ICC was 0.94. Topcon 3D OCT CCT values were lower than USP readings (mean difference, 7.6 ± 8.1 µm; 95% confidence interval, 9.9-5.3 µm; P < 0.001). CONCLUSIONS: With a commercially available retinal SD-OCT system, reliable intersession and interobserver CCT measurements can be feasibly obtained. The criteria for a significant change, which would be the one exceeding the reproducibility, indicate that intersession and interobserver variations in CCT of more than 13 and 16 µm, respectively, may reflect true corneal change with this particular device. These estimates should help investigators and clinicians differentiate actual CCT modification from measurement random error. The slight CCT underestimation with respect to USP is within the range of other OCT devices.