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1.
Adv Mater ; 36(28): e2402723, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38665115

ABSTRACT

Magnetism in two dimensions is traditionally considered an exotic phase mediated by spin fluctuations, but far from collinearly ordered in the ground state. Recently, 2D magnetic states have been discovered in layered van der Waals compounds. Their robust and tunable magnetic state by material composition, combined with reduced dimensionality, foresee a strong potential as a key element in magnetic devices. Here, a class of 2D magnets based on metallic chlorides is presented. The magnetic order survives on top of a metallic substrate, even down to the monolayer limit, and can be switched from perpendicular to in-plane by substituting the metal ion from iron to nickel. Using functionalized STM tips as magnetic sensors, local exchange fields are identified, even in the absence of an external magnetic field. Since the compounds are processable by molecular beam epitaxy techniques, they provide a platform with large potential for incorporation into current device technologies.

2.
PLoS Pathog ; 19(11): e1011741, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37956166

ABSTRACT

A genomic signature for endosporulation includes a gene coding for a protease, YabG, which in the model organism Bacillus subtilis is involved in assembly of the spore coat. We show that in the human pathogen Clostridioidesm difficile, YabG is critical for the assembly of the coat and exosporium layers of spores. YabG is produced during sporulation under the control of the mother cell-specific regulators σE and σK and associates with the spore surface layers. YabG shows an N-terminal SH3-like domain and a C-terminal domain that resembles single domain response regulators, such as CheY, yet is atypical in that the conserved phosphoryl-acceptor residue is absent. Instead, the CheY-like domain carries residues required for activity, including Cys207 and His161, the homologues of which form a catalytic diad in the B. subtilis protein, and also Asp162. The substitution of any of these residues by Ala, eliminates an auto-proteolytic activity as well as interdomain processing of CspBA, a reaction that releases the CspB protease, required for proper spore germination. An in-frame deletion of yabG or an allele coding for an inactive protein, yabGC207A, both cause misassemby of the coat and exosporium and the formation of spores that are more permeable to lysozyme and impaired in germination and host colonization. Furthermore, we show that YabG is required for the expression of at least two σK-dependent genes, cotA, coding for a coat protein, and cdeM, coding for a key determinant of exosporium assembly. Thus, YabG also impinges upon the genetic program of the mother cell possibly by eliminating a transcriptional repressor. Although this activity has not been described for the B. subtilis protein and most of the YabG substrates vary among sporeformers, the general role of the protease in the assembly of the spore surface is likely to be conserved across evolutionary distance.


Subject(s)
Clostridioides difficile , Peptide Hydrolases , Humans , Peptide Hydrolases/metabolism , Clostridioides difficile/genetics , Clostridioides difficile/metabolism , Clostridioides , Spores, Bacterial/metabolism , Transcription Factors/metabolism , Endopeptidases/metabolism , Bacterial Proteins/metabolism , Bacillus subtilis/metabolism
3.
Eur J Obstet Gynecol Reprod Biol ; 289: 19-22, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37611537

ABSTRACT

OBJECTIVE: The primary objective of this study was to determine if immediate post-operative use of virtual reality impacts pain scores or opioid consumption following hysterectomy. STUDY DESIGN: A randomized controlled trial was performed at a university associated tertiary referral hospital in the United States among patients undergoing laparoscopic hysterectomy for benign indications. Prior to surgery, participants were randomized to use a VR program versus routine care postoperatively in the post anesthesia care unit. Postoperative pain was measured using visual analogue scale, and morphine milligram equivalent to quantify narcotic usage. Patient satisfaction was assessed with a survey. A total of 15 patients were randomized to the virtual reality intervention and 15 to the standard care group. The test statistic was a one-sided T-test, with a significance level targeted of 0.05. Categorical variables were analyzed using chi-square analysis and t-test for continuous variables. Pain score differences between the virtual reality and standard care groups at each time assessment were compared using the Wilcoxon Rank Sum test. RESULTS: The use of virtual reality did not significantly affect pain scores or postoperative narcotics required; however, it did have a positive impact on the subject's perception of their postoperative course. No adverse events were reported. CONCLUSION: Although virtual reality use following hysterectomy did not improve pain scores or decrease narcotic usage, it was well received by patients.


Subject(s)
Laparoscopy , Virtual Reality , Female , Humans , Laparoscopy/adverse effects , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Hysterectomy/adverse effects , Narcotics
4.
J Neurosci ; 43(1): 14-27, 2023 01 04.
Article in English | MEDLINE | ID: mdl-36384682

ABSTRACT

In the neocortex, fast synaptic inhibition orchestrates both spontaneous and sensory-evoked activity. GABAergic interneurons (INs) inhibit pyramidal neurons (PNs) directly, modulating their output activity and thus contributing to balance cortical networks. Moreover, several IN subtypes also inhibit other INs, forming specific disinhibitory circuits, which play crucial roles in several cognitive functions. Here, we studied a subpopulation of somatostatin-positive INs, the Martinotti cells (MCs) in layer 2/3 of the mouse barrel cortex (both sexes). MCs inhibit the distal portion of PN apical dendrites, thus controlling dendrite electrogenesis and synaptic integration. Yet, it is poorly understood whether MCs inhibit other elements of the cortical circuits, and the connectivity properties with non-PN targets are unknown. We found that MCs have a strong preference for PN dendrites, but they also considerably connect with parvalbumin-positive, vasoactive intestinal peptide-expressing, and layer 1 (L1) INs. Remarkably, GABAergic synapses from MCs exhibited clear cell type-specific short-term plasticity. Moreover, whereas the biophysical properties of MC-PN synapses were consistent with distal dendritic inhibition, MC-IN synapses exhibited characteristics of fast perisomatic inhibition. Finally, MC-PN connections used α5-containing GABAA receptors (GABAARs), but this subunit was not expressed by the other INs targeted by MCs. We reveal a specialized connectivity blueprint of MCs within different elements of superficial cortical layers. In addition, our results identify α5-GABAARs as the molecular fingerprint of MC-PN dendritic inhibition. This is of critical importance, given the role of α5-GABAARs in cognitive performance and their involvement in several brain diseases.SIGNIFICANCE STATEMENT Martinotti cells (MCs) are a prominent, broad subclass of somatostatin-expressing GABAergic interneurons, specialized in controlling distal dendrites of pyramidal neurons (PNs) and taking part in several cognitive functions. Here we characterize the connectivity pattern of MCs with other interneurons in the superficial layers (L1 and L2/3) of the mouse barrel cortex. We found that the connectivity pattern of MCs with PNs as well as parvalbumin, vasoactive intestinal peptide, and L1 interneurons exhibit target-specific plasticity and biophysical properties. The specificity of α5-GABAARs at MC-PN synapses and the lack or functional expression of this subunit by other cell types define the molecular identity of MC-PN connections and the exclusive involvement of this inhibitory circuits in α5-dependent cognitive tasks.


Subject(s)
Parvalbumins , Vasoactive Intestinal Peptide , Female , Male , Animals , Vasoactive Intestinal Peptide/metabolism , Parvalbumins/metabolism , Neurons , Pyramidal Cells/physiology , Interneurons/physiology , Somatostatin/metabolism , Synapses/physiology , gamma-Aminobutyric Acid/metabolism
5.
NPJ Biofilms Microbiomes ; 8(1): 94, 2022 11 30.
Article in English | MEDLINE | ID: mdl-36450806

ABSTRACT

The Clostridioides difficile pathogen is responsible for nosocomial infections. Germination is an essential step for the establishment of C. difficile infection (CDI) because toxins that are secreted by vegetative cells are responsible for the symptoms of CDI. Germination can be stimulated by the combinatorial actions of certain amino acids and either conjugated or deconjugated cholic acid-derived bile salts. During synthesis in the liver, cholic acid- and chenodeoxycholic acid-class bile salts are conjugated with either taurine or glycine at the C24 carboxyl. During GI transit, these conjugated bile salts are deconjugated by microbes that express bile salt hydrolases (BSHs). Here, we surprisingly find that several C. difficile strains have BSH activity. We observed this activity in both C. difficile vegetative cells and in spores and that the observed BSH activity was specific to taurine-derived bile salts. Additionally, we find that this BSH activity can produce cholate for metabolic conversion to deoxycholate by C. scindens. The C. scindens-produced deoxycholate signals to C. difficile to initiate biofilm formation. Our results show that C. difficile BSH activity has the potential to influence the interactions between microbes, and this could extend to the GI setting.


Subject(s)
Clostridioides difficile , Clostridioides , Substrate Specificity , Bile Acids and Salts , Cholic Acids , Deoxycholic Acid , Biofilms
6.
Cell Rep ; 40(8): 111202, 2022 08 23.
Article in English | MEDLINE | ID: mdl-36001978

ABSTRACT

Perisomatic inhibition of pyramidal neurons (PNs) coordinates cortical network activity during sensory processing, and this role is mainly attributed to parvalbumin-expressing basket cells (BCs). However, cannabinoid receptor type 1 (CB1)-expressing interneurons are also BCs, but the connectivity and function of these elusive but prominent neocortical inhibitory neurons are unclear. We find that their connectivity pattern is visual area specific. Persistently active CB1 signaling suppresses GABA release from CB1 BCs in the medial secondary visual cortex (V2M), but not in the primary visual cortex (V1). Accordingly, in vivo, tonic CB1 signaling is responsible for higher but less coordinated PN activity in the V2M than in the V1. These differential firing dynamics in the V1 and V2M can be captured by a computational network model that incorporates visual-area-specific properties. Our results indicate a differential CB1-mediated mechanism controlling PN activity, suggesting an alternative connectivity scheme of a specific GABAergic circuit in different cortical areas.


Subject(s)
Endocannabinoids , Neocortex , Interneurons/physiology , Neurons/physiology , Pyramidal Cells/physiology , Receptor, Cannabinoid, CB1 , gamma-Aminobutyric Acid/physiology
7.
Gut Microbes ; 14(1): 2094672, 2022.
Article in English | MEDLINE | ID: mdl-35793402

ABSTRACT

The nosocomial pathogen Clostridioides difficile is a burden to the healthcare system. Gut microbiome disruption, most commonly by broad-spectrum antibiotic treatment, is well established to generate a state that is susceptible to CDI. A variety of metabolites produced by the host and/or gut microbiota have been shown to interact with C. difficile. Certain bile acids promote/inhibit germination while other cholesterol-derived compounds and amino acids used in the Stickland metabolic pathway affect growth and CDI colonization. Short chain fatty acids maintain intestinal barrier integrity and a myriad of other metabolic compounds are used as nutritional sources or used by C. difficile to inhibit or outcompete other bacteria in the gut. As the move toward non-antibiotic CDI treatment takes place, a deeper understanding of interactions between C. difficile and the host's gut microbiome and metabolites becomes more relevant.


Subject(s)
Clostridioides difficile , Clostridium Infections , Gastrointestinal Microbiome , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bile Acids and Salts , Clostridioides , Clostridium Infections/microbiology , Humans
9.
Radiol Case Rep ; 17(5): 1445-1449, 2022 May.
Article in English | MEDLINE | ID: mdl-35265238

ABSTRACT

Mucinous carcinoma of the breast is a type of well-differentiated adenocarcinoma, a rare subtype of infiltrating ductal carcinoma. It represents approximately 2% of all invasive breast carcinomas. The mean age of presentation is 65 years, with an incidence of 1% in women younger than 35 years. Depending on the mucin content of the carcinoma, they are described as pure or mixed; the distinction between the 2 is important for prognosis and treatment. The treatment of special types of breast cancer is still controversial due to the limited amount of evidence, however, the main treatment for breast cancer is still surgery. We present a case of a 29-year-old patient with mucinous carcinoma of the breast with a delay in its management, but with a favorable postoperative result.

10.
Protein Eng Des Sel ; 342021 02 15.
Article in English | MEDLINE | ID: mdl-34882774

ABSTRACT

Clostridioides difficile is an enteric bacterium whose exotoxins, TcdA and TcdB, inactivate small GTPases within the host cells, leading to bloody diarrhea. In prior work, our group engineered a panel of potent TcdB-neutralizing designed ankyrin repeat proteins (DARPin) as oral therapeutics against C. difficile infection. However, all these DARPins are highly susceptible to digestion by gut-resident proteases, i.e. trypsin and chymotrypsin. Close evaluation of the protein sequence revealed a large abundance of positively charged and aromatic residues in the DARPin scaffold. In this study, we significantly improved the protease stability of one of the DARPins, 1.4E, via protein engineering. Unlike 1.4E, whose anti-TcdB EC50 increased >83-fold after 1-hour incubation with trypsin (1 mg/ml) or chymotrypsin (0.5 mg/ml), the best progenies-T10-2 and T10b-exhibit similar anti-TcdB potency as their parent in PBS regardless of protease treatment. The superior protease stability of T10-2 and T10b is attributed to the removal of nearly all positively charged and aromatic residues except those directly engaged in target binding. Furthermore, T10-2 was found to retain significant toxin-neutralization ability in ex vivo cecum fluid and can be easily detected in mouse fecal samples upon oral administration. Both T10-2 and T10b enjoy a high thermo- and chemo-stability and can be expressed very efficiently in Escherichia coli (>100 mg/l in shaker flasks). We believe that, in additional to their potential as oral therapeutics against C. difficile infection, T10-2 and T10b can also serve as a new generation DARPin scaffold with superior protease stability.


Subject(s)
Bacterial Toxins , Clostridioides difficile , Animals , Bacterial Proteins/genetics , Designed Ankyrin Repeat Proteins , Enterotoxins , Mice , Peptide Hydrolases
11.
PLoS Pathog ; 17(10): e1010015, 2021 10.
Article in English | MEDLINE | ID: mdl-34665847

ABSTRACT

Clostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the protective mechanism by which C. difficile is excluded. These 7α-dehydroxylated secondary bile acids are highly toxic to C. difficile vegetative growth, and antibiotic treatment abolishes the bacteria that perform this metabolism. However, the data that supports the hypothesis that secondary bile acids protect against C. difficile infection is supported only by in vitro data and correlative studies. Here we show that bacteria that 7α-dehydroxylate primary bile acids protect against C. difficile infection in a bile acid-independent manner. We monoassociated germ-free, wildtype or Cyp8b1-/- (cholic acid-deficient) mutant mice and infected them with C. difficile spores. We show that 7α-dehydroxylation (i.e., secondary bile acid generation) is dispensable for protection against C. difficile infection and provide evidence that Stickland metabolism by these organisms consumes nutrients essential for C. difficile growth. Our findings indicate secondary bile acid production by the microbiome is a useful biomarker for a C. difficile-resistant environment but the microbiome protects against C. difficile infection in bile acid-independent mechanisms.


Subject(s)
Bile Acids and Salts/metabolism , Clostridium Infections/metabolism , Disease Resistance/physiology , Gastrointestinal Microbiome/physiology , Animals , Mice , Mice, Knockout
12.
J Bacteriol ; 203(12): e0000821, 2021 05 20.
Article in English | MEDLINE | ID: mdl-33820795

ABSTRACT

The endospore-forming pathogen Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and is a significant burden on the community and health care. C. difficile, like all forms of life, incorporates selenium into proteins through a selenocysteine synthesis pathway. The known selenoproteins in C. difficile are involved in a metabolic process that uses amino acids as the sole carbon and nitrogen source (Stickland metabolism). The Stickland metabolic pathway requires the use of two selenium-containing reductases. In this study, we built upon our initial characterization of the CRISPR-Cas9-generated selD mutant by creating a CRISPR-Cas9-mediated restoration of the selD gene at the native locus. Here, we use these CRISPR-generated strains to analyze the importance of selenium-containing proteins on C. difficile physiology. SelD is the first enzyme in the pathway for selenoprotein synthesis, and we found that multiple aspects of C. difficile physiology were affected (e.g., growth, sporulation, and outgrowth of a vegetative cell post-spore germination). Using transcriptome sequencing (RNA-seq), we identified multiple candidate genes which likely aid the cell in overcoming the global loss of selenoproteins to grow in medium which is favorable for using Stickland metabolism. Our results suggest that the absence of selenophosphate (i.e., selenoprotein synthesis) leads to alterations to C. difficile physiology so that NAD+ can be regenerated by other pathways. IMPORTANCE C. difficile is a Gram-positive, anaerobic gut pathogen which infects thousands of individuals each year. In order to stop the C. difficile life cycle, other nonantibiotic treatment options are in urgent need of development. Toward this goal, we find that a metabolic process used by only a small fraction of the microbiota is important for C. difficile physiology: Stickland metabolism. Here, we use our CRISPR-Cas9 system to "knock in" a copy of the selD gene into the deletion strain to restore selD at its native locus. Our findings support the hypothesis that selenium-containing proteins are important for several aspects of C. difficile physiology, from vegetative growth to spore formation and outgrowth postgermination.


Subject(s)
Clostridioides difficile/enzymology , Clostridioides difficile/genetics , Phosphotransferases/genetics , Phosphotransferases/metabolism , CRISPR-Cas Systems , Gene Deletion , Gene Editing , Gene Expression Regulation, Bacterial , Gene Expression Regulation, Enzymologic , Genome, Bacterial , RNA, Bacterial/genetics , RNA-Seq
13.
Elife ; 92020 08 12.
Article in English | MEDLINE | ID: mdl-32783810

ABSTRACT

Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABAAR antagonists led to hypothesize an excessive activity of inhibitory circuits in this condition. Nonetheless, whether over-inhibition is present in DS and whether this is due to specific alterations of distinct GABAergic circuits is unknown. In the prefrontal cortex of Ts65Dn mice (a well-established DS model), we found that the dendritic synaptic inhibitory loop formed by somatostatin-positive Martinotti cells (MCs) and pyramidal neurons (PNs) was strongly enhanced, with no alteration in their excitability. Conversely, perisomatic inhibition from parvalbumin-positive (PV) interneurons was unaltered, but PV cells of DS mice lost their classical fast-spiking phenotype and exhibited increased excitability. These microcircuit alterations resulted in reduced pyramidal-neuron firing and increased phase locking to cognitive-relevant network oscillations in vivo. These results define important synaptic and circuit mechanisms underlying cognitive dysfunctions in DS.


Down syndrome is a genetic disorder caused by the presence of a third copy of chromosome 21. Affected individuals show delayed growth, characteristic facial features, altered brain development; with mild to severe intellectual disability. The exact mechanisms underlying the intellectual disability in Down syndrome are unclear, although studies in mice have provided clues. Drugs that reduce the inhibitory activity in the brain improve cognition in a mouse model of Down syndrome. This suggests that excessive inhibitory activity may contribute to the cognitive impairments. Many different neural circuits generate inhibitory activity in the brain. These circuits contain cells called interneurons. Sub-types of interneurons act via different mechanisms to reduce the activity of neurons. Identifying the interneurons that are affected in Down syndrome would thus improve our understanding of the brain basis of the disorder. Zorrilla de San Martin et al. compared mice with Down syndrome to unaffected control mice. The results revealed an increased activity in two types of inhibitory brain circuits in Down syndrome. The first contains interneurons called Martinotti cells. These help the brain to combine inputs from different sources. The second contains interneurons called parvalbumin-positive basket cells. These help different areas of the brain to synchronize their activity, which in turn makes it easier for those areas to exchange information. By mapping the changes in inhibitory circuits in Down syndrome, Zorrilla de San Martin et al. have provided new insights into the biological basis of the disorder. Future studies should examine whether targeting specific circuits with pharmacological treatments could ultimately help reduce the associated impairments.


Subject(s)
Down Syndrome/physiopathology , Interneurons/metabolism , Parvalbumins/metabolism , Prefrontal Cortex/physiopathology , Pyramidal Cells/metabolism , Somatostatin/metabolism , Animals , Disease Models, Animal , Female , Male , Mice
14.
Cell Rep ; 30(3): 630-641.e5, 2020 01 21.
Article in English | MEDLINE | ID: mdl-31968242

ABSTRACT

In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer (L) 2/3 pyramidal neurons (PNs) elicits strong feedforward inhibition (FFI) onto L5 PNs. We find that FFI involving parvalbumin (PV)-expressing cells is strongly potentiated by postsynaptic PN burst firing. FFI plasticity modifies the PN excitation-to-inhibition (E/I) ratio, strongly modulates PN gain, and alters information transfer across cortical layers. Moreover, our LTPi-inducing protocol modifies firing of L5 PNs and alters the temporal association of PN spikes to γ-oscillations both in vitro and in vivo. All of these effects are captured by unbalancing the E/I ratio in a feedforward inhibition circuit model. Altogether, our results indicate that activity-dependent modulation of perisomatic inhibitory strength effectively influences the participation of single principal cortical neurons to cognition-relevant network activity.


Subject(s)
Neocortex/physiology , Neural Inhibition/physiology , Neuronal Plasticity/physiology , Synapses/physiology , Action Potentials/physiology , Action Potentials/radiation effects , Animals , Female , Gamma Rhythm/radiation effects , Light , Long-Term Potentiation/physiology , Long-Term Potentiation/radiation effects , Mice, Inbred C57BL , Models, Neurological , Neural Inhibition/radiation effects , Neuronal Plasticity/radiation effects , Pyramidal Cells/physiology , Pyramidal Cells/radiation effects , Synapses/radiation effects , Time Factors , gamma-Aminobutyric Acid/metabolism
15.
J Robot Surg ; 14(2): 343-347, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31256328

ABSTRACT

The objectives of the study were to compare the cephalad migration of two patient positioning pads used in robotic gynecologic surgery and to determine if any correlation exists between cephalad movement and time in Trendelenburg position or body mass index. This was a prospective randomized controlled open-label trial (Canadian Task Force classification I). Sixty women undergoing robotic-assisted laparoscopic gynecologic surgery were randomized to the Pink Pad® system or egg-crate foam pre-operatively. Patients were placed under general anesthesia and then positioned in dorsal lithotomy. The locations of the iliac crest, acromion process, and buttock were marked on the table before and after surgery to calculate cephalad migration during surgery. The primary outcome was centimeters of cephalad migration at the three anatomic landmarks. Comparing the Pink Pad® (n = 24) to the egg-crate group (n = 26) revealed similar mean cephalad migration at the iliac crest (4.8 cm vs 4.3 cm, p = 0.56) and the shoulder (4.6 cm vs 3.9 cm, p = 0.39), and less cephalad migration at the buttock (median 3.0 cm vs 2.0 cm, p = 0.041). The total time in Trendelenburg was not correlated with cephalad migration at any anatomic landmark. Body mass index was positively correlated with cephalad migration only at the iliac crest (p = 0.032) regardless of pad type. The egg-crate foam resulted in less cephalad migration at all anatomic sites and significantly less migration at the buttocks compared to the Pink Pad®. This suggests that the less-costly egg-crate foam is noninferior to the Pink Pad® system and trends at superiority.


Subject(s)
Gynecologic Surgical Procedures/methods , Laparoscopy/methods , Movement , Patient Positioning/methods , Robotic Surgical Procedures/methods , Body Mass Index , Buttocks/physiology , Female , Head-Down Tilt , Humans , Patient Positioning/adverse effects , Patient Safety , Prospective Studies , Time Factors
16.
PLoS Biol ; 17(9): e3000419, 2019 09.
Article in English | MEDLINE | ID: mdl-31483783

ABSTRACT

Parvalbumin (PV)-positive interneurons modulate cortical activity through highly specialized connectivity patterns onto excitatory pyramidal neurons (PNs) and other inhibitory cells. PV cells are autoconnected through powerful autapses, but the contribution of this form of fast disinhibition to cortical function is unknown. We found that autaptic transmission represents the most powerful inhibitory input of PV cells in neocortical layer V. Autaptic strength was greater than synaptic strength onto PNs as a result of a larger quantal size, whereas autaptic and heterosynaptic PV-PV synapses differed in the number of release sites. Overall, single-axon autaptic transmission contributed to approximately 40% of the global inhibition (mostly perisomatic) that PV interneurons received. The strength of autaptic transmission modulated the coupling of PV-cell firing with optogenetically induced γ-oscillations, preventing high-frequency bursts of spikes. Autaptic self-inhibition represents an exceptionally large and fast disinhibitory mechanism, favoring synchronization of PV-cell firing during cognitive-relevant cortical network activity.


Subject(s)
Interneurons/physiology , Neocortex/physiology , Synapses , Synaptic Transmission , Animals , Female , Male , Mice, Inbred C57BL
17.
Infectio ; 23(3): 234-239, jul.-sept. 2019. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1002156

ABSTRACT

Introducción. La Bronquiolitis secundaria al Virus Sincitial Respiratorio, se han asociado con episodios sibilantes recurrentes y desarrollo de asma, incluso en la adultez. Sin embargo, la relación entre estas patologías es controvertida, y aun no se conoce el comportamiento de este fenómeno en Colombia. El objetivo de este estudio fue describir la evolución clínica a cinco años, de los niños con antecedente de bronquiolitis que requirieron hospitalización Materiales y métodos. Estudio descriptivo de cohorte retrospectiva de menores de dos años, con diagnóstico de Bronquiolitis atendidos en la Clínica Universitaria Colombia en los años 2008 a 2011 con seguimiento de hospitalizaciones por patologías respiratorias hasta el año 2016. Se revisaron 306 historias clínicas de pacientes y se analizaron características socio- demográficas, aislamientos virales y manejo farmacológico. Resultados. Los años con mayor número de hospitalizaciones por episodios sibilantes posterior al episodio bronquiolitis fueron el 2009 y 2011 con una incidencia acumulada de 15,6% y 9,9%. La edad promedio de hospitalización fue 6 meses y más frecuente en hombres. El virus sincital fue aislado con mayor frecuencia en los años de seguimiento, y la mayoría de los casos requirió manejo antibiótico; la ampicilina sulbactam (28,5%) y la ampicilina (22,6%).


Introduction. Bronchiolitis secondary to Respiratory Syncytial Virus, have been associated with recurrent wheezing episodes and development of asthma, even in adulthood. However, the relationship between these pathologies is controversial, and the behavior of this phenomenon in Colombia is not yet known. The aim of this study was to describe the five-year clinical course of children with a history of bronchiolitis who required hospitalization Materials and methods. Descriptive study of a retrospective cohort of children under two years of age, with a diagnosis of Bronchiolitis attended at the University Clinic Colombia in the years 2008 to 2011 with follow-up of hospitalizations for respiratory pathologies up to 2016. 306 patient clinical histories were reviewed and characteristics were analyzed. socio-demographic, viral isolates and pharmacological management. Results. The years with the highest number of hospitalizations for wheezing episodes after the bronchiolitis episode were 2009 and 2011 with an accumulated incidence of 15.6% and 9.9%. The average age of hospitalization was 6 months and more frequent in men. The syncytial virus was isolated more frequently in the years of follow-up, and most of the cases required antibiotic management; ampicillin sulbactam (28.5%) and ampicillin (22.6%).


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Respiratory Syncytial Viruses , Bronchiolitis , Hospitalization , Asthma , Respiratory Sounds , Respiratory Sounds/diagnosis , Demography , Colombia
18.
JSLS ; 23(2)2019.
Article in English | MEDLINE | ID: mdl-31148914

ABSTRACT

BACKGROUND AND OBJECTIVES: Physicians typically have little information of surgical device pricing, although this trend has not been studied in the field of obstetrics and gynecology. We therefore aimed to determine how accurately obstetrician-gynecologists estimate surgical device prices, and to identify factors associated with accuracy. METHODS: An anonymous survey was emailed to all obstetrician-gynecologist attendings, fellows, and residents at 3 teaching hospitals in a single healthcare system in Arizona. We obtained demographic data, perceptions of price transparency and self-rated price knowledge, and price estimates for 31 surgical devices. RESULTS: After participants provided consent and demographics, they then estimated the purchasing price of 31 devices. We defined price accuracy as being within ±10% of the hospital's purchasing price. Fifty-six of the 170 (32.9%) invitees completed the survey and 48 (28.2%) provided price estimates. On average, participants identified 1.9 items correctly (6.1%; range, 0-7 items) out of 31 with no difference in accuracy based on seniority, surgical volume, physician reimbursement structure, nor subspecialty practice-focus. All (100%) respondents felt pricing should be transparent, and only 1.8% felt it is at least somewhat transparent. CONCLUSION: We found that price-estimate accuracy was very low and had no association with any of the demographics. Also notable was the perception that pricing is not transparent despite a unanimous desire for transparency. Although physicians reported a preference for using less-expensive surgical devices, we conclude that physicians are unequipped to make cost-conscious decisions highlighting a large potential for education.


Subject(s)
Attitude of Health Personnel , Gynecology/economics , Hospitals, Teaching , Obstetrics/economics , Physicians , Surgical Equipment/economics , Adult , Awareness , Cost-Benefit Analysis , Education, Medical, Graduate , Female , Gynecology/education , Humans , Male , Obstetrics/education , Surveys and Questionnaires
19.
Elife ; 72018 12 18.
Article in English | MEDLINE | ID: mdl-30561327

ABSTRACT

In the neocortex, critical periods (CPs) of plasticity are closed following the accumulation of perineuronal nets (PNNs) around parvalbumin (PV)-positive inhibitory interneurons. However, how PNNs tune cortical function and plasticity is unknown. We found that PNNs modulated the gain of visual responses and γ-oscillations in the adult mouse visual cortex in vivo, consistent with increased interneuron function. Removal of PNNs in adult V1 did not affect GABAergic neurotransmission from PV cells, nor neuronal excitability in layer 4. Importantly, PNN degradation coupled to sensory input potentiated glutamatergic thalamic synapses selectively onto PV cells. In the absence of PNNs, increased thalamic PV-cell recruitment modulated feed-forward inhibition differently on PV cells and pyramidal neurons. These effects depended on visual input, as they were strongly attenuated by monocular deprivation in PNN-depleted adult mice. Thus, PNNs control visual processing and plasticity by selectively setting the strength of thalamic recruitment of PV cells.


Subject(s)
Cell Adhesion Molecules/metabolism , Extracellular Matrix/metabolism , Neuronal Plasticity , Neurons/physiology , Proteoglycans/metabolism , Visual Pathways/physiology , Animals , Mice , Thalamus/physiology , Visual Cortex/physiology
20.
Biota Neotrop. (Online, Ed. ingl.) ; 18(4): e20170497, 2018. tab, graf
Article in English | LILACS | ID: biblio-951210

ABSTRACT

Abstract: The Ilhabela State Park (PEIb, for Parque Estadual Ilhabela in Portuguese)-located between 23º 46' 28" south latitude and 45º 21' 20" west latitude-is responsible for the conservation of one of the most important, and most devastated, fragments of insular Atlantic Forest. To catalog the arboreal species along the trails of the Conservation Unit, and to provide a practical instrument to facilitate the recognition of these species, we aimed with this work to conduct a floristic and photographic survey of distinct life forms and create an identification key for arboreal dicotyledonous species based on vegetative characters. We cataloged 123 species belonging to 99 genera and 46 botanical families. The best-represented families were Rubiaceae (15 spp.), Fabaceae (10), Piperaceae (10), Myrtaceae (8), Melatomataceae (7) and Lauraceae (7). We found three species threatened with extinction, two new occurrences for the state of São Paulo, and one plant species new to science, demonstrating the floristic importance of the region. We developed three vegetative dichotomous identification keys: to species with compound leaves; simple and opposite leaves; and alternate simple leaves. The dichotomous keys presents 97 arboreal species, distributed among 37 families, and was based on vegetative characters such as phyllotaxis, composition and shape of the limbus, presence or absence of stipules, exudate, lenticels, indument, glands and dots. We also elaborated a photographic board with 118 species as a supplementary material to support the use of the identification key.


Resumo: O Parque Estadual de Ilhabela - PEIb (23º 46' e 28" de latitude sul e 45º 21' 20" de latitude oeste) é responsável pela conservação de um dos mais importantes e devastados fragmentos de Mata Atlântica insular. Como forma de listar as espécies arbóreas nas trilhas da Unidade de Conservação e fornecer um instrumento prático para auxiliar no reconhecimento dessas espécies, objetivamos nesse trabalho realizar um levantamento florístico e fotográfico com distintas formas de vida para elaborar uma chave de identificação das espécies de Dicotiledôneas arbóreas com base em caracteres vegetativos. Listamos 123 espécies, presentes em 99 gêneros e 46 famílias botânicas. As famílias mais bem representadas foram Rubiaceae (15 spp.), Fabaceae (10), Piperaceae (10), Myrtaceae (8), Melatomataceae (7) e Lauraceae (7). Encontramos três espécies ameaçadas de extinção, duas novas ocorrências para o estado de São Paulo e uma nova espécie de planta para a ciência, demonstrando a importância florística do local. Elaboramos três chaves dicotômicas vegetativas de identificação sendo elas: para espécies com folhas compostas; folhas simples e opostas; e folhas simples e alternas. As chaves apresentando 97 espécies arbóreas, distribuídas em 37 famílias, baseadas em caracteres vegetativos tais como filotaxia, composição e formato do limbo, presença ou ausência de estípulas, exsudado, lenticelas, indumento, glândulas e pontuações. Nós também elaboramos pranchas fotográficas como um material suplementar de auxílio à utilização da chave de identificação.

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