Liquid diet induces memory impairment accompanied by a decreased number of hippocampal neurons in mice

It is suggested that masticatory dysfunction affects the central nervous system; however, the underlying mechanism remains unknown. Brain‐derived neurotrophic factor (BDNF) and its receptor, TrkB, are known to play important roles in memory and learning. In this study, we examined the effects of mastication on memory, the expression levels of BDNF and TrkB, and the number of neurons in the hippocampus of mice. Male C57 BL/6J mice (3 weeks old) were randomly divided into the control group (N = 7) fed chow pellets and the experimental group (N = 7) fed a liquid diet, which reduces mastication during eating. At 14 weeks of age, we performed a passive avoidance test and found that memory and learning ability were impaired in the experimental group compared with the control group. After the behavioral experiment, brains were harvested and analyzed morphologically and biochemically. In the hippocampus of the experimental group, the expression levels of BDNF were significantly higher, whereas those of TrkB were lower than those of the control group. In the cerebral cortex, these levels remained unchanged between the two groups. The ratio of phospho‐p44/42 ERK/pan ERK, a downstream molecule of BDNF/TrkB signaling, in the experimental group was significantly lower than that of the control group in the cortex and hippocampus. The number of pyramidal neurons in the hippocampus was lower in the experimental group than in the control group. These findings suggest that reduced mastication induced by a liquid diet in early childhood may impair memory and learning ability, accompanied by neuronal loss in the hippocampus. © 2014 Wiley Periodicals, Inc.     

Reduced Frontal Glutamate + Glutamine and N-Acetylaspartate Levels in Patients With Chronic Schizophrenia but not in Those at Clinical High Risk for Psychosis or With First-Episode Schizophrenia

Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy (¹H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in ¹H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent ¹H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in ¹H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.Key words: anterior cingulate cortex, at-risk mental state, biomarkers, frontal lobe, magnetic resonance imaging, neurochemical abnormality     

Randomised trial comparing Lichtenstein vs Trabucco vs Valenti techniques in inguinal hernia repair

Purpose

Following Lichtenstein’s technique, over the last 15 years several variation have been proposed, such as Trabucco’s sutureless technique and the use of two self-regulating prostheses, proposed by Valenti that have given excellent results. The aim of this prospective and randomised study was to determine whether there are differences in the results obtained with these three techniques.

Methods

Of 812 patients submitted to inguinal hernia repair, we selected and randomised 162 patients into three groups of 54 patients each: Lichtenstein (Group L), Trabucco (Group T) and Valenti (Group V). Surgical procedures were performed in all cases by residents in surgery using local anaesthesia. Primary endpoint was intensity of postoperative pain. Median follow-up was 8 years.

Results

The primary analysis of postoperative pain at 48 h did not report any significant difference between the three groups as for secondary analyses except that the Trabucco procedure took less operative time than the Lichtenstein, and the Valenti group was more painful than the Lichtenstein group at the third postoperative day. In our series median operation time was 60 min. Recurrence rate was 1.85 %.

Conclusions

Surgical repair of inguinal hernia according to the Lichtenstein, Trabucco and Valenti techniques is safe and easy to perform regardless of the surgical experience of the operator, with excellent results and no differences due to technique used as regards almost all of the parameters studied.     

Effect of UV Irradiation and TiO2-Photocatalysis on Airborne Bacteria and Viruses: An Overview

Current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put a spotlight on the spread of infectious diseases brought on by pathogenic airborne bacteria and viruses. In parallel with a relentless search for therapeutics and vaccines, considerable effort is being expended to develop ever more powerful technologies to restricting the spread of airborne microorganisms in indoor spaces through the minimization of health- and environment-related risks. In this context, UV-based and photocatalytic oxidation (PCO)-based technologies (i.e., the combined action of ultraviolet (UV) light and photocatalytic materials such as titanium dioxide (TiO₂)) represent the most widely utilized approaches at present because they are cost-effective and ecofriendly. The virucidal and bactericidal effect relies on the synergy between the inherent ability of UV light to directly inactivate viral particles and bacteria through nucleic acid and protein damages, and the production of oxidative radicals generated through the irradiation of the TiO₂ surface. In this literature survey, we draw attention to the most effective UV radiations and TiO₂-based PCO technologies available and their underlying mechanisms of action on both bacteria and viral particles. Since the fine tuning of different parameters, namely the UV wavelength, the photocatalyst composition, and the UV dose (viz, the product of UV light intensity and the irradiation time), is required for the inactivation of microorganisms, we wrap up this review coming up with the most effective combination of them. Now more than ever, UV- and TiO₂-based disinfection technologies may represent a valuable tool to mitigate the spread of airborne pathogens.     

cDNA clone for the heavy chain of the human B cell alloantigen DC1: strong sequence homology to the HLA-DR heavy chain.

A cDNA library has been constructed from a B cell mRNA fraction enriched for HLA-DR sequences, and cDNA clones corresponding to sequences specifically expressed in B lymphocytes have been isolated by a differential screening procedure. Analysis of these clones with probes specific for the HLA-DR heavy chain gene allowed the characterization of HLA-DR heavy chain-related sequences. One clone, pDCH1, was demonstrated to encode the DC1 heavy chain because the amino acid sequence predicted from its nucleotide sequence matches eight out of nine residues available for comparison in the amino-terminal sequence of the DC1 heavy chain. The heavy chain of the DC1 alloantigen is composed of 232 amino acids and can be divided into two external domains, alpha 1 (amino acids 1-87) and alpha 2 (amino acids 88-181), a connecting peptide (amino acids 182-194), a hydrophobic transmembrane region (amino acids 195-217), and an intracytoplasmic region (amino acids 218-232). Comparison with the HLA-DR heavy chain reveals strong sequence homology in the second external Ig-like domain (alpha 2) and the transmembrane region. In contrast, the first external domain, the connecting peptide, and the intracytoplasmic region are less conserved.     

Anti-V3 loop spectrotype in HIV-infected individuals during zidovudine therapy

Summary In order to investigate the role played by zidovudine (ZDV) as immune modulator, particularly on B-cell response, the anti-V₃ loop spectrotype in 115 sera from 26 HIV-infected individuals was evaluated, prior to and during treatment with ZDV, by isoelectric focusing and reverse blotting (IEF-RB), a technique useful for indirectly measuring the activity and the number of B-cell clones. All 18 patients showing seroreactivity by IEFRB displayed a clear oligoclonal banding pattern, with no change in the spectrotype (i.e. new bands), in sequential analysis over the course of therapy. Only minor changes in band intensity were found, without any correlation with ZDV treatment or CD4⁺ cell count. In addition, among the sera reactive in spectrotypic analysis, the percentage of those with p24 antigen positivity was significantly lower than those with no detectable p24 antigen (19.8% vs 80.2%, respectively, p=<0.0001, Fisher's exact test). In conclusion, it could not be demonstrated by IEFRB that there was any effect of ZDV on the activity and the number of anti-V₃ specific B-cell clones. This data is in line with previous studies showing the constancy of anti-gp120 antibody spectrotype over the long course of the disease.

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Anti-V3-Loop Spektrotyp bei HIV-Infizierten während Zidovudin-Behandlung

Zusammenfassung Der Anti-V3-Loop-Spektrotyp wurden in 115 Seren von 26 HIV-Infizierten vor und nach Zidovudin-Therapie bestimmt, um die Rolle von Zidovudin als Immunmodulator, vor allem der B-Zell-Antwort, zu prüfen. Als Methoden wurden isoelektrische Fokussierung und reverses Blotting (IEFRB) eingesetzt, die sich für die indirekte Bestimmung der Aktivität und der Zahl der B-Zell-Klone als brauchbar erwiesen haben. Bei allen 18 seroreaktiven Patienten stellten sich eindeutige oligoklonale Bandenmuster dar. In Verlaufsanalysen während der Therapie war keine Änderung im Spektrotyp, d. h. keine neuen Banden, zu erkennen. Die Bandenintensität änderte sich nur wenig, wobei keine Beziehung zur Zidovudin-Therapie oder den CD4⁺ Zellzahlen bestand. In den Spektrotyp-positiven Seren war nur bei einem kleinen Anteil auch p24-Antigen nachzuweisen (19,8% positive gegen 80,2% p-24-Antigen negative Seren; p0,0001, Fisher's exakter Test). Zusammenfassend fand sich mit IEFRB kein Einfluß von Zidovudin auf die Aktivität und die Zahl anti-V₃-spezifischer B-Zell-Klone. Dies stimmt mit den Ergebnissen früherer Studien überein, in denen Konstanz des anti-gp120-Antikörper-Spektrotyps im Langzeitverlauf der Erkrankung festgestellt wurde.

     

Histological features of primary tumors after induction or high-dose chemotherapy in high-risk neuroblastoma

Purpose

In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the “delayed local treatment (DL)” policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL.

Patients

From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed.

Results

Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, ¹²³I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation.

Conclusions

Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter.     

Infrequent alterations of the p16INK4A gene in liver cancer

We examined the genomic status of the p16^INK4A (inhibitor of cyclin-dependent kinase 4 A) and cyclin-dependent kinase 4 (CDK4) genes in 62 human hepatocellular carcinomas (HCCs), 5 cholangiocellular carcinomas and 6 cell lines derived from human liver cancers. Although no samples showed the homozygous deletion of the p16^INK4A gene, we detected intragenic mutations of the p16^INK4A gene in 3 HCCs and one HCC cell line, which led to an amino-acid substitution or a frameshift. In 2 HCC samples with mis-sense mutations of the p16^INK4A gene, loss of heterozygosity on 9p22 was also detected, suggesting that the loss of function of p16 was induced during hepatocarcinogenesis. On the other hand, amplification or rearrangement of the CDK4 gene was not detected in any samples examined in this study. These results indicated that the mutations or deletions of the p16^INK4A gene are not frequent, but may play a role in a sub-set of human HCC. © 1996 Wiley-Liss, Inc.     

Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner

Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.