Oxidative Functionalization of Cinnamaldehyde Derivatives: Control of Chemoselectivity by Organophotocatalysis and Dual Organocatalysis.

The catalytic and chemoselective oxidation of cinnamaldehyde derivatives having a C═C bond and formyl group was studied by using two organocatalysts. The visible-light-induced catalysis using rhodamine 6G as an organophotocatalyst promoted the methoxyhydroxylation of the C═C bond in a chemoselective manner. In contrast, the cooperation between rhodamine 6G and N-heterocyclic carbene (NHC) allowed the oxidative esterification of formyl group.

Hippocampal MicroRNA-124 Enhances Chronic Stress Resilience in Mice.

UNLABELLED: Chronic stress-induced aberrant gene expression in the brain and subsequent dysfunctional neuronal plasticity have been implicated in the etiology and pathophysiology of mood disorders. In this study, we examined whether altered expression of small, regulatory, noncoding microRNAs (miRNAs) contributes to the depression-like behaviors and aberrant neuronal plasticity associated with chronic stress. Mice exposed to chronic ultra-mild stress (CUMS) exhibited increased depression-like behaviors and reduced hippocampal expression of the brain-enriched miRNA-124 (miR-124). Aberrant behaviors and dysregulated miR-124 expression were blocked by chronic treatment with an antidepressant drug. The depression-like behaviors are likely not conferred directly by miR-124 downregulation because neither viral-mediated hippocampal overexpression nor intrahippocampal infusion of an miR-124 inhibitor affected depression-like behaviors in nonstressed mice. However, viral-mediated miR-124 overexpression in hippocampal neurons conferred behavioral resilience to CUMS, whereas inhibition of miR-124 led to greater behavioral susceptibility to a milder stress paradigm. Moreover, we identified histone deacetylase 4 (HDAC4), HDAC5, and glycogen synthase kinase 3ß (GSK3ß) as targets for miR-124 and found that intrahippocampal infusion of a selective HDAC4/5 inhibitor or GSK3 inhibitor had antidepressant-like actions on behavior. We propose that miR-124-mediated posttranscriptional controls of HDAC4/5 and GSK3ß expressions in the hippocampus have pivotal roles in susceptibility/resilience to chronic stress. SIGNIFICANCE STATEMENT: Depressive disorders are a major public health concern worldwide. Although a clear understanding of the etiology of depression is still lacking, chronic stress-elicited aberrant neuronal plasticity has been implicated in the pathophysiology of depression. We show that the hippocampal expression of microRNA-124 (miR-124), an endogenous small, noncoding RNA that represses gene expression posttranscriptionally, controls resilience/susceptibility to chronic stress-induced depression-like behaviors. These effects on depression-like behaviors may be mediated through regulation of the mRNA or protein expression levels of histone deacetylases HDAC4/5 and glycogen synthase kinase 3ß, all highly conserved miR-124 targets. Moreover, miR-124 contributes to stress-induced dendritic hypotrophy and reduced spine density of dentate gyrus granule neurons. Modulation of hippocampal miR-124 pathways may have potential antidepressant effects.

Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure.

Variation in the chromatographic, material, and chemical characteristics of methacrylate-based polymer monoliths during photoinitiated low-temperature polymerization.

Both the separation behavior and the structure of a polymer monolith column depends on both the reaction solution composition and the polymerization conditions. In photoinitiated low-temperature polymerization, polymerization temperature, irradiation intensity, and polymerization time were key factors to control the monolith characteristics. In this study, the effect of polymerization time on the chromatographic, material, and chemical characteristics of poly(butyl methacrylate-co-ethylene dimethacrylate) monoliths was studied using pyrolysis-gas chromatography, Raman spectroscopy, inverse size exclusion chromatography, scanning electron microscopy, and chromatographic methods. Both butyl methacrylate and ethylene dimethacrylate monomers were incorporated into the monolith as the polymerization time increased, and it resulted in increases in both the flow resistance (decrease in both permeability and total/through pore porosities) and retention factors. The longer polymerization time led to lower relative amounts of free methacrylate functional groups in the monolith, i.e. cross-linking was enhanced. The increase of the polymerization time from 8 to 12 min significantly reduced the separation efficiency for the retained analyte, whereas an increase in the fraction of the mesoporosity was observed.

Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1.

Aberrant transcriptional regulation in the brain is thought to be one of the key components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Heat shock factors (HSFs) modulate cellular homeostasis through the control of gene expression. However, the roles of HSFs in brain function have yet to be elucidated fully. In the present study, we attempted to clarify the role of HSF1-mediated gene regulation in neuronal and behavioral development using HSF1-deficient (HSF1(-/-)) mice. We found granule neurons of aberrant morphology and impaired neurogenesis in the dentate gyrus of HSF1(-/-) mice. In addition, HSF1(-/-) mice showed aberrant affective behavior, including reduced anxiety and sociability but increased depression-like behavior and aggression. Furthermore, HSF1 deficiency enhanced behavioral vulnerability to repeated exposure to restraint stress. Importantly, rescuing the HSF1 deficiency in the neonatal but not the adult hippocampus reversed the aberrant anxiety and depression-like behaviors. These results indicate a crucial role for hippocampal HSF1 in neuronal and behavioral development. Analysis of the molecular mechanisms revealed that HSF1 directly modulates the expression of polysialyltransferase genes, which then modulate polysialic acid-neural cell adhesion molecule (PSA-NCAM) levels in the hippocampus. Enzymatic removal of PSA from the neonatal hippocampus resulted in aberrant behavior during adulthood, similar to that observed in HSF1(-/-) mice. Thus, these results suggest that one role of HSF1 is to control hippocampal PSA-NCAM levels through the transcriptional regulation of polysialyltransferases, a process that might be involved in neuronal and behavioral development in mice.

Isolation of vapB-positive Rhodococcus equi from submaxillary lymph nodes with or without granulomatous lesions in growing-finishing pigs in Japan.

To investigate the etiological role of vapB-positive Rhodococcus equi in pigs, R. equi was isolated from the submaxillary lymph nodes with or without macroscopically detectable lesions of apparently healthy growing-finishing pigs at a slaughterhouse in Toyama Prefecture, Japan. R. equi was isolated from 57 (24.6%) of 232 pigs with macroscopically detectable lymph node lesions, and 56 (98.2%) of the 57 isolates were vapB-positive. R. equi was isolated from 10 (2.4%) of 420 pigs without lymph node lesions, and six (60%) of the 10 isolates were vapB-positive. Plasmid DNA was isolated from the 62 vapB-positive isolates and digested with EcoRI and NsiI to obtain the plasmid profile. Fifty-two (83.9%), three (4.8%), and four (6.5%) isolates contained pVAPB subtypes 1, 2, and 3, respectively, while the remaining three isolates were of pVAPB subtypes 9, 13, and 14, respectively. Twelve specimens from lymph nodes with macroscopically detectable lesions were randomly selected for histopathological staining. Granulomatous lesions resembling tuberculosis were found in 11 of the 12 specimens, and the remaining specimen showed typical foci of malakoplakia in the lymph node. The isolation rates of R. equi and vapB-positive R. equi from lymph nodes with macroscopically detectable lesions were significantly higher (P<0.05) than those of lymph nodes without lesions, suggesting an etiologic association between vapB-positive R. equi and macroscopically detectable granulomatous lesions in porcine submaxillary lymph nodes. Previous reports on the prevalence of vapB-positive R. equi in pigs are reviewed and discussed.

Physical and Mental Effects of Foot Baths Among Women in Labor: Protocol for a Pre-Post Test Experimental Design.

BACKGROUND: Foot baths are used in complementary and alternative therapy to improve the duration and quality of sleep and reduce tension, anxiety, fatigue, and confusion. They are also known to improve the frequency of labor contractions and to increase their duration in women; thus, they are commonly used by midwives in clinical settings in Japan. However, the physical and mental effects of foot baths during labor are unknown. OBJECTIVE: This study aims to assess the physical and mental effects of foot baths based on biomarker levels and self-administered questionnaires. METHODS: A single-arm pre-post test trial design is being used in this study, and the study is being conducted at a general hospital in Tochigi Prefecture, Japan. The target study population is women in the first stage of labor, the phase when the uterus starts to contract and when the cervix dilates to 10 cm, or those undergoing labor induction. Participants who meet the eligibility criteria are recruited, and written informed consent is obtained from them. They are asked to answer the questionnaire and to collect 1.5 mL of saliva in 2 microtubes each, before and after the intervention. The intervention is foot baths for 15-20 minutes using a foot bath device. Data on delivery, such as gestational age, gravidity, parity, diagnosis following the last vaginal examination, and presence or absence of membrane rupture, are retrieved from the medical records. The primary outcomes are salivary cortisol levels before and after the foot baths. The secondary outcomes are levels of relaxation and comfort, labor pain, body warmth, vital signs, and interval of labor pain before and after the foot baths, which are assessed using a numerical rating scale. A paired t test or Wilcoxon signed-rank test will be performed to compare the data for salivary cortisol levels and numerical rating scale scores. RESULTS: Data collection started on April 1, 2022. As of October 2022, we had enrolled 10 participants. Because of the COVID-19 pandemic in Japan, it is difficult for medical personnel to freely interact with women in labor until the results of the COVID-19 polymerase chain reaction test are available in the research facility, complicating the recruitment process. CONCLUSIONS: This is the first prospective study to assess the effects of foot baths using a biomarker during the first stage of labor. The findings on the effects of foot baths on women in labor will provide novel insights that may improve the outcomes of delivery. A randomized controlled trial to investigate the effects of foot baths to obtain robust evidence should be conducted in the future. TRIAL REGISTRATION: University Hospital Medical Information Network-Clinical Trial Registry UMIN000046539; https://tinyurl.com/2wwj7dns. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39985.

Interferon signaling and hypercytokinemia-related gene expression in the blood of antidepressant non-responders.

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant responsiveness using a novel data-driven approach based on statistical pattern recognition. We retrospectively divided patients with major depressive disorder into antidepressant responder and non-responder groups. Comprehensive gene expression analysis was performed using peripheral blood without narrowing the genes. We designed a classifier according to our own discrete Bayes decision rule that can handle categorical data. Nineteen genes showed differential expression in the antidepressant non-responder group (n = 15) compared to the antidepressant responder group (n = 15). In the training sample of 30 individuals, eight candidate genes had significantly altered expression according to quantitative real-time polymerase chain reaction. The expression of these genes was examined in an independent test sample of antidepressant responders (n = 22) and non-responders (n = 12). Using the discrete Bayes classifier with the HERC5, IFI6, and IFI44 genes identified in the training set yielded 85% discrimination accuracy for antidepressant responsiveness in the 34 test samples. Pathway analysis of the RNA sequencing data for antidepressant responsiveness identified that hypercytokinemia- and interferon-related genes were increased in non-responders. Disease and biofunction analysis identified changes in genes related to inflammatory and infectious diseases, including coronavirus disease. These results strongly suggest an association between antidepressant responsiveness and inflammation, which may be useful for future treatment strategies for depression.

Possible action of vasohibin-1 as an inhibitor in the regulation of vascularization of the bovine corpus luteum.

The development of the corpus luteum (CL), which secretes large amounts of progesterone to establish pregnancy, is accompanied by active angiogenesis, vascularization, and lymphangiogenesis. Negative feedback regulation is a critical physiological mechanism. Vasohibin-1 (VASH1) was recently discovered as a novel endothelium-derived negative feedback regulator of vascularization. We therefore investigated the expression of VASH1 in the bovine CL. Expression of VASH1 mRNA and protein was predominantly localized to luteal endothelial cells (LECs). VASH1 expression in the CL was constant through the early to late luteal phases and decreased during CL regression relating with the action of luteolytic prostaglandin F(2)(α) in vivo. To investigate the role of VASH1, we determined whether VASH1 treatment affects angiogenesis and/or lymphangiogenesis using LECs and lymphatic endothelial cells (LyECs) in vitro. Vascular endothelial growth factor A (VEGFA) stimulated the expression of VASH1 in LECs but not in LyECs, and VASH1 completely blocked VEGFA-induced formation of capillary-like tube structures of LECs and LyECs in vitro. In summary, VASH1 is predominantly located on LECs in the bovine CL and inhibits the angiogenic and lymphangiogenic actions of VEGFA. Bovine CL therefore has a VEGFA-VASH1 system that may be involved in regulation of luteal function, especially in the development of the CL. The results indicate that VASH1 has the potential to act as a negative feedback regulator of angiogenesis and lymphangiogenesis in the CL in cows.

Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents.

There is growing evidence suggesting that early life events have long-term effects on the neuroendocrine and behavioral developments of rodents. However, little is known about the involvement of early life events in the susceptibility to subsequent stress exposure during adulthood. The present study characterized the effect of maternal separation, an animal model of early life adversity, on the behavioral response to repeated restraint stress in adult rats and investigated the molecular mechanism underlying behavioral vulnerability to chronic stress induced by the maternal separation. Rat pups were separated from the dams for 180 min per day from postnatal day 2 through 14 (HMS180 rats). We found that, as young adults, HMS180 rats showed a greater hypothalamic-pituitary-adrenal axis response to acute restraint stress than nonseparated control rats. In addition, repeatedly restrained HMS180 rats showed increased depression-like behavior and an anhedonic response compared with nonrestrained HMS180 rats. Furthermore, HMS180 rats showed increased expression of REST4, a neuron-specific splicing variant of the transcriptional repressor REST (repressor element-1 silencing transcription factor), and a variety of REST target gene mRNAs and microRNAs in the medial prefrontal cortex (mPFC). Finally, REST4 overexpression in the mPFC of neonatal mice via polyethyleneimine-mediated gene transfer enhanced the expression of its target genes as well as behavioral vulnerability to repeated restraint stress. In contrast, REST4 overexpression in the mPFC of adult mice did not affect depression-like behaviors after repeated stress exposure. These results suggest that the activation of REST4-mediated gene regulation in the mPFC during postnatal development is involved in stress vulnerability.

Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow.

BACKGROUND: After ovulation in the cow, the corpus luteum (CL) rapidly develops within a few days with angiogenesis and progesterone production. CL formation resembles an inflammatory response due to the influx of immune cells. Neutrophils play a role in host defense and inflammation, and secrete chemoattractants to stimulate angiogenesis. We therefore hypothesized that neutrophils infiltrate in the developing CL from just after ovulation and may play a role in angiogenesis of the CL. METHODS AND RESULTS: Polymorphonuclear neutrophils (PMN) were detected in CL tissue by Pas-staining, and interleukin-8 (IL-8, a neutrophil-specific chemoattractant) was measured in supernatant of the CL tissue culture: considerable amounts of PMNs and the high level of IL-8 were observed during the early luteal phase (days 1-4 of the estrous cycle). PMNs and IL-8 were low levels in the mid and late luteal phases, but IL-8 was increased during luteal regression. The PMN migration in vitro was stimulated by the supernatant from the early CL but not from the mid CL, and this activity was inhibited by neutralizing with an anti-IL-8 antibody, indicating the major role of IL-8 in inducing active PMN migration in the early CL. Moreover, IL-8 stimulated proliferation of CL-derived endothelial cells (LECs), and both the supernatant of activated PMNs and IL-8 stimulated formation of capillary-like structures of LECs. CONCLUSION: PMNs migrate into the early CL partially due to its major chemoattractant IL-8 produced at high levels in the CL, and PMNs is a potential regulator of angiogenesis together with IL-8 in developing CL in the cow.

A novel mouse model of postpartum depression using emotional stress as evaluated by nesting behavior.

Postpartum depression is an important mental health issue not only for the mother but also for the child's development, other family members, and the society. An appropriate animal model is desired to elucidate the pathogenesis of postpartum depression. However, methods for stress loading during pregnancy have not been established. Behavioral experiments to investigate postpartum depression-like behaviors should be conducted without stress because behavioral tests affect rearing behaviors such as lactation. Therefore, we developed a new mouse model of postpartum depression using a psychological stress method. Mating partners were made to witness their partners experiencing social defeat stress and then listen to their cries. Emotional stress loading during pregnancy significantly increased postpartum depression-like behaviors. Postpartum depression also affected nurturing behaviors and caused disturbances in pup care. Furthermore, nesting behavior was impaired in the stressed group, suggesting that the observation of nesting behavior may be useful for assessing social dysfunction in postpartum depression. These results demonstrate the utility of this new mouse model of postpartum depression.

The Mood-Improving Effect of Viewing Images of Nature and Its Neural Substrate.

It has been recently suggested that contact with nature improves mood via reducing the activity of the prefrontal cortex. However, the specific regions within the prefrontal cortex that underlie this effect remain unclear. In this study, we aimed to identify the specific regions involved in the mood-improving effect of viewing images of nature using a 52-channel functional near-infrared spectroscopy (fNIRS). Specifically, we focused on the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (dlPFC), two regions associated with affective processing and control. In a randomized controlled crossover experiment, we assigned thirty young adults to view images of nature and built environments for three minutes each in a counterbalanced order. During image viewing, participants wore a fNIRS probe cap and had their oxyhemoglobin (oxy-Hb) measured. Immediately following each image viewing, participants indicated their mood in terms of comfortableness, relaxation, and vigor. Results showed that viewing images of nature significantly increased comfortableness and relaxation but not vigor compared to viewing images of built environments, with a large effect size. Meanwhile, the concentration of oxy-Hb in only the right OFC and none of the other regions significantly decreased while viewing the images of nature compared to built environments, with a medium effect size. We speculate that viewing images of nature improves mood by reducing the activity of or calming the OFC. Since the OFC is hyperactive in patients with depression and anxiety at rest, contact with nature might have therapeutic effects for them.

Distinct epigenetic signatures between adult-onset and late-onset depression.

The heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.

Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients.

In HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.

Optimized protocol for the extraction of RNA and DNA from frozen whole blood sample stored in a single EDTA tube.

Cryopreservation of whole blood is useful for DNA collection, and clinical and basic research. Blood samples in ethylenediaminetetraacetic acid disodium salt (EDTA) tubes stored at - 80 °C are suitable for DNA extraction, but not for high-quality RNA extraction. Herein, a new methodology for high-quality RNA extraction from human blood samples is described. Quickly thawing frozen whole blood on aluminum blocks at room temperature could minimize RNA degradation, and improve RNA yield and quality compared with thawing the samples in a 37 °C water bath. Furthermore, the use of the NucleoSpin RNA kit increased RNA yield by fivefold compared with the PAXgene Blood RNA Kit. Thawing blood samples on aluminum blocks significantly increased the DNA yield by ~ 20% compared with thawing in a 37 °C water bath or on ice. Moreover, by thawing on aluminum blocks and using the NucleoSpin RNA and QIAamp DNA Blood kits, the extraction of RNA and DNA of sufficient quality and quantity was achieved from frozen EDTA whole blood samples that were stored for up to 8.5 years. Thus, extracting RNA from frozen whole blood in EDTA tubes after long-term storage is feasible. These findings may help advance gene expression analysis, as well as biomarker research for various diseases.

Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aß) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aß1-42, Aß1-40, Aß1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aß1-38, Aß1-40, Aß1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

Massive subcutaneous emphysema developing before surgery for mandibular fracture: a case report.

Preoperative massive subcutaneous emphysema before intubation is extremely rare. However, this complication may be potentially lethal, depend on the condition of air spreading. Subcutaneous emphysema which occurs intra- or postoperative period is sometimes iatrogenic because the air is introduced into the tissue space through the hole injured by the operation. But the emphysema in this case occurred preoperatively by the pressure of the bag valve mask, because the patient had an intra-oral wound, which reaches the submental space. In this report, we describe an extremely rare case of preoperative massive emphysema of the patient with the mandibular fracture.

Prevalence and Characterization of Carbapenem-Hydrolyzing Class D ß-Lactamase-Producing Acinetobacter Isolates From Ghana.

Multidrug resistance, especially carbapenem resistance in Acinetobacter bacteria is a global healthcare concern. However, available data on the phenotypic and genotypic characteristics of Acinetobacter isolates from West Africa, including Ghana is scanty. Our aim was to investigate the antibiotic resistance profile and genotypic characteristics of Acinetobacter isolates from Ghana and to characterize carbapenemase producers using whole-genome sequencing (WGS). A total of 36 Acinetobacter isolates collected at three hospitals in Ghana between 2016 and 2017 were analyzed. MICs were determined by commercial antibiotic plates. Acinetobacter baumannii MLST was determined using the Pasteur scheme. WGS of OXA-carbapenemase producers was performed using short- and long-read sequencing strategies. The resistance rate was highest for trimethoprim/sulfamethoxazole (n = 22; 61%). Six (16.7%) and eight (22.2%) isolates were resistant to ceftazidime and colistin, respectively. Two (5.6%) isolates were resistant and one (2.8%) isolate had intermediate sensitivity to three carbapenems. Fifteen STs were identified in 24 A. baumannii isolates including six new STs (ST1467 ∼ ST1472). ST78 was the predominant (n = 6) followed by ST1469 (n = 3). Four carbapenemase-producing A. baumannii isolates also were identified. Isogenic ST103 isolates Ab-B004d-c and Ab-D10a-a harbored bla OXA- 23 within Tn2007 on identical plasmids, pAb-B004d-c_3, and pAb-D10a-a_3. ST1472 isolate Ab-C102 and ST107 isolate Ab-C63 carried bla OXA- 58 and bla OXA- 420, a rare bla OXA- 58 variant, respectively, within novel genetic contexts. Our results show that A. baumannii isolates of diverse and unique genotypes, including OXA-carbapenemase producers, are circulating in Ghana highlighting the need for a wider surveillance of antimicrobial resistance.