Decrease in CD8+CD45+CCR7+CD62L+ T cells in individuals vaccinated with Sinovac-CoronaVac following COVID-19 infection.

Vaccines induce antibodies, but T cell responses are also important for protection against Coronavirus disease 2019. Here, we analyzed the frequency of memory T cells in infected and/or vaccinated individuals and observed a decrease in central memory T cells in individuals who were vaccinated following COVID-19 infection.

Prevalence of Chagas disease among Latin American immigrants in non-endemic countries: an updated systematic review and meta-analysis.

Background: Chagas disease (CD), endemic in 21 Latin American countries, has gradually spread beyond its traditional borders due to migratory movements and emerging as a global health concern. We conducted a systematic review and meta-analysis of available data to establish updated prevalence estimates of CD in Latin American migrants residing in non-endemic countries. Methods: A systematic search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, Scopus, Web of Science, and LILACS via Virtual Health Library (Biblioteca Virtual em Saúde - BVS), including references published until November 1st, 2023. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated using random effect models. Heterogeneity was assessed by the chi-square test and the I2 statistic. Subgroup analyses were performed to explore potential sources of heterogeneity among studies. The study was registered in the PROSPERO database (CRD42022354237). Findings: From a total of 1474 articles screened, 51 studies were included. Studies were conducted in eight non-endemic countries (most in Spain), between 2006 and 2023, and involving 82,369 screened individuals. The estimated pooled prevalence of CD in Latin American migrants living in non-endemic countries was 3.5% (95% CI: 2.5-4.7; I2: 97.7%), considering studies in which screening was indicated simply because the person was Latin American. Per subgroups, the pooled CD prevalence was 11.0% (95% CI: 7.7-15.5) in non-targeted screening (unselected population in reference centers) (27 studies); in blood donors (4 studies), the pooled prevalence was 0.8% (95% CI: 0.2-3.4); among people living with HIV Latin American immigrants (4 studies) 2.4% (95% CI: 1.4-4.3) and for Latin American pregnant and postpartum women (14 studies) 3.7% (95 CI: 2.4-5.6). The pooled proportion of congenital transmission was 4.4% (95% CI: 3.3-5.8). Regarding the participants' country of origin, 7964 were from Bolivia, of which 1715 (21,5%) were diagnosed with CD, and 21,304 were from other Latin American countries of which 154 (0,72%) were affected. Interpretation: CD poses a significant burden of disease in Latin American immigrants in non-endemic countries, suggesting that CD is no longer a problem limited to the American continent and must be considered as a global health challenge. Funding: This study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

Suggestion Timing Moderates the Effects of Prior Pain Experiences on Pain Perception.

Two common elements in patient care are reoccurring painful events (eg, blood draws) and verbal suggestions from others for lessened pain. Research shows that verbal suggestions for lower pain can decrease subsequent pain perception from novel noxious stimuli, but it is less clear how these suggestions and prior painful experiences combine to influence the perception of a reoccurring painful event. The presented experiment tested the hypothesis that the order of these 2 factors influence pain perception for a reoccurring painful event. All participants (702 healthy college-student volunteers, 58% women, 85.5% White) experienced a novel painful event on one arm, then again on their other arm (now a familiar pain event). Participants who received the suggestion that they can tolerate more pain on the second arm relative to the first from the outset, before the initial pain event, perceived relatively less pain during the repeated event as compared to participants who received the same suggestion after the first painful event or no-suggestion (control). Given many pain events within medical contexts are, or become, familiar to patients, further researching the timing at which patients receive verbal suggestions for lower pain can inform practices to optimize the therapeutic, pain-reducing potential of such suggestions. PERSPECTIVE: Providing suggestions that a familiar pain event (ie, the second of 2) will be less painful than a prior event can reduce perceived pain for the familiar event depending on when it is presented. These findings can inform practices to optimize the therapeutic potential of verbal suggestions for reduced pain.

Blue light (470 nm) effectively inhibits bacterial and fungal growth.

UNLABELLED: Blue light (470 nm) LED antimicrobial properties were studied alone against bacteria and with or without the food grade photosensitizer, erythrosine (ERY) against filamentous fungi. Leuconostoc mesenteroides (LM), Bacillus atrophaeus (BA) or Pseudomonas aeruginosa (PA) aliquots were exposed on nutrient agar plates to Array 1 (AR1, 0·2 mW cm(-2)) or Array 2 (AR2, 80 mW cm(-2)), which emitted impure or pure blue light (0-300 J cm(-2)), respectively. Inoculated control (room light only) plates were incubated (48 h) and colonies enumerated. The antifungal properties of blue light combined with ERY (11·4 and 22·8 µmol l(-1)) on Penicillium digitatum (PD) and Fusarium graminearum (FG) conidia were determined. Conidial controls consisted of: no light, room light-treated conidia and ERY plus room light. Light-treated (ERY + blue light) conidial samples were exposed only to AR2 (0-100 J cm(-2)), aliquots spread on potato dextrose agar plates, incubated (48 h, 30°C) and colonies counted. Blue light alone significantly reduced bacterial and FG viability. Combined with ERY, it significantly reduced PD viability. Blue light is lethal to bacteria and filamentous fungi although effectiveness is dependent on light purity, energy levels and microbial genus. SIGNIFICANCE AND IMPACT OF THE STUDY: Light from two arrays of different blue LEDs significantly reduced bacterial (Leuconostoc mesenteroides, Bacillus atrophaeus and Pseudomonas aeruginosa) viabilities. Significant in vitro viability loss was observed for the filamentous fungi, Penicillium digitatum and Fusarium graminearum when exposed to pure blue light only plus a photosensitizer. F. graminearum viability was significantly reduced by blue light alone. Results suggest that (i) the amount of significant loss in bacterial viability observed for blue light that is pure or with traces of other wavelengths is genus dependent and (ii) depending on fungal genera, pure blue light is fungicidal with or without a photosensitizer.

A symptom-specific analysis of the effect of high-frequency left or low-frequency right transcranial magnetic stimulation over the dorsolateral prefrontal cortex in major depression.

BACKGROUND: We have investigated the efficacy of high-frequency left (HFL) versus low-frequency right (LFR) repetitive transcranial magnetic stimulation (rTMS) in depression, focusing on specific symptoms as possible predictors of outcome for these two different types of stimulation. METHOD: Seventy-four outpatients with a major depressive episode treated with an adequate antidepressant dosage for at least 4 weeks were included in our study and randomly assigned to two different groups: HFL or LFR rTMS. The Hamilton Rating Scale for Depression (HAM-D) items were pooled into 6 factors to evaluate specific symptoms as possible predictors of response. RESULTS: Twenty-one out of 32 patients (65.6%) and 24 out of 42 patients (57.1%) were responders in the HFL and LFR groups, respectively. No significant difference in response rate was observed. Considering the whole sample, we found an inverse correlation between activity and HAM-D score reduction and a significant positive relation between somatic anxiety and outcome. An inverse correlation between psychic anxiety and HAM-D score reduction emerged considering the HFL group. In the LFR group, there was a significant negative relationship between baseline activity and the outcome. CONCLUSION: These findings support the hypothesis that LFR rTMS could be as effective as HFL rTMS and more suitable for patients with a higher anxiety degree, particularly in bipolar patients.

Emerging targets for the development of novel antifungal therapeutics.

Invasive mycoses have become important causes of morbidity and mortality in immunocompromised patients. New approaches for antifungal therapy are required to meet the challenges imposed by these life-threatening infections. Such approaches are being developed through identification of novel biochemical and molecular targets of pathogenic fungi.

Role of nitric oxide in brain regions related to defensive reactions.

Nitric oxide synthase (NOS) positive neurons are located in most brain areas related to defensive reactions, including the dorsolateral periaqueductal grey (dlPAG). NOS inhibitors injected into this structure induce anxiolytic-like responses whereas NO donors promote flight reactions. Intra-dlPAG administration of carboxy-PTIO, a NO scavenger, or ODQ, a soluble guanylate cyclase inhibitor, produced anxiolytic-like effects on rats exposed to the elevated plus-maze (EPM). A double-staining experiment using NADPHd histochemistry and c-Fos immunohistochemistry in rats exposed to a cat or to the EPM showed increased activation of NO producing neurons in the dlPAG, paraventricular and lateral nuclei of hypothalamus and dorsal raphe nucleus. Cat exposure also increased activation of NOS neurons in the medial amygdala, dorsal pre-mammillary nucleus and bed nucleus of stria terminalis. Local infusion into the dlPAG of a glutamate NMDA-receptor antagonist (AP7) or a benzodiazepine agonist (midazolam) completely prevented the flight reactions induced by intra-dlPAG administration of SIN-1, a NO donor. The responses were also inhibited by the 5-HT2A/C agonist DOI but not by a 5-HT1A agonist. These results suggest a modulatory role for NO on brain areas related to defensive reactions, probably by interacting with glutamate, serotonin and/or GABA-mediated neurotransmission.

Biochemical investigation of histidinemia in schizophrenic patients.

Our results suggest that the association between the clinical diagnosis of schizophrenic disorder and heterozygosis for histidinemia is not a chance one. The real meaning of this relationship has to be further investigated.

Tryptophan depletion in obsessive-compulsive patients.

Twelve patients with obsessive-compulsive disorder were studied after the administration of a mixture of amino acids devoid of tryptophan (TRP) or a mixture containing all the essential amino acids, in a double-blind, crossover design. The TRP-free mixture caused a marked depletion of plasma TRP. After TRP decrease, mean ratings of obsessions and compulsions, measured by Visual Analogue Scales (VAS) ratings, did not worsen. In contrast with other reports in literature, TRP depletion also failed to alter mood in our subjects.

Antifungal peptides: potential candidates for the treatment of fungal infections.

Many diversely produced natural peptides, as well as those produced semisynthetically and synthetically, have been found to inhibit the growth or even be lethal to a wide range of fungi. Some of these have the potential to aid mankind in combating mycoses caused by emerging pathogens or as a result of the increasing number of antibiotic-resistant fungi. Antifungal peptides may also assist in non-medical fields such as agriculture. For example, introduction by transgenic research of antifungal peptides could improve crop production yields by increasing host resistance to fungal invasion. The aim of this review is to provide information on research on these important peptides.

Serine and glycine metabolism in schizophrenic patients.

1. The brain glycine is almost exclusively derived from serine via serine-hydroxymethyltransferase. 17 males schizophrenic inpatients and 10 males healthy volunteers were submitted to the serine tolerance test. 2. Plasma serine and glycine concentration were evaluated before and after 1, 2, 3, 4 hours of an oral load with L-serine to test the interconversion between the two amino acids. 3. The authors did not find any significant difference between schizophrenic patients and control group and concluded that the enzyme serine-hydroxymethyltransferase is not deficient in the conversion of serine to glycine in schizophrenic patients as suggested by other authors.

Neutral amino acid availability in two major psychiatric disorders.

1. Evidence suggests catecholamines and indoleamines may play a role in the pathogenesis of several psychiatric disorders. These neurotransmitters (i.e. dopamine, norepinephrine and serotonin) are synthesized within the human brain from their precursors, the aromatic large neutral amino acids tyrosine and tryptophan. Other large neutral amino acids, namely valine, isoleucine, leucine and phenylalanine affect precursor availability by competing with tryptophan and tyrosine for the transport system across the blood brain barrier. 2. The authors evaluated the brain availability of L-tryptophan and tyrosine in a sample of psychiatric patients with a diagnosis of major depression and schizophrenia. 3. The present results suggest a possible usefulness of Tryptophan/Large Neutral Amino Acids ratio in distinguishing major depression from schizophrenia, while Tyrosine/Large Neutral Amino Acids ratio shows a very limited usefulness. The absolute need of powerful and accurate statistical analysis to evaluate the power of a biological test clearly stands out from the present study.

Predictive value of tryptophan/large neutral amino acids ratio to antidepressant response.

The molar ratio of total plasma tryptophan to the sum of other large neutral amino acids (viz., valine, isoleucine, leucine, tyrosine, phenylalanine), thought to reflect brain serotonin formation, was estimated in 69 patients with major depression before and after 1 week of treatment with different serotonin reuptake inhibitors, fluvoxamine (n = 28), fluoxetine (n = 10), citalopram (n = 7), mixed serotonin-noradrenaline reuptake inhibitor amitriptyline (n = 11), clomipramine (n = 8) and the preferentially noradrenaline reuptake inhibitor, nortriptyline (n = 5). A significant difference among 'good', 'intermediate' and 'poor' responders for the percentual variation of tryptophan/large neutral amino acids ratio after 1 week of therapy was found, while pretreatment values of tryptophan/large neutral amino acids ratio, basal Hamilton Depression Rating Scale scores and its percentual variation after 1 week of therapy did not show any significant differences. These results suggest that the percentual variation of tryptophan/large neutral amino acids ratio could be a useful tool in predicting drug response.

Decrease in plasma phenylalanine and tyrosine after phenylalanine-tyrosine free amino acid solutions in man.

After an overnight fast, 5 male healthy subjects ingested increasing amounts of a solution containing a fixed proportion of seven essential amino acids (L-isoleucine, 13.3%; L-leucine, 21.0%; L-lysine, 15.2%; L-methionine, 21.0%; L-threonine, 9.5%; L-tryptophan, 4.8% and L-valine, 15.2%) and lacking phenylalanine and tyrosine. The solutions caused a rapid fall in plasma phenylalanine and tyrosine which was proportional to the total amount of amino acids ingested. Following the highest dose administered (31.5 g) plasma phenylalanine and tyrosine fell to a minimum of, respectively, 12.7% and 29.8% the initial levels and remained markedly reduced at 6 hours after treatment. The decrease of tyrosine and phenylalanine levels was associated with a decrease of systolic and diastolic arterial pressure.

Plasma tryptophan levels and plasma tryptophan/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects.

Fasting plasma tryptophan (TRP) levels and ratios of total plasma tryptophan to the sum of five large neutral amino acids (LNAAs)--tyrosine, phenylalanine, leucine, isoleucine, and valine--that compete with tryptophan for passage across the blood-brain barrier were found to be significantly lower in a group of 28 patients with major depression compared with 29 normal subjects and 21 patients with obsessive-compulsive disorder (OCD). The OCD group was divided in two subgroups: patients with OCD alone and patients with a co-diagnosis of major depression. Since it has been considered that these biological parameters reflect brain tryptophan and serotonin levels, our results suggest their importance in relation to the presence or absence of depressive symptoms. The values of the other LNAAs and their sum did not differ significantly among the groups.

Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression.

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients.

Amino acid patterns in schizophrenia: some new findings.

Blood concentrations of various amino acids were measured in schizophrenic patients and control subjects. Significantly higher blood concentrations of glycine, glutamate, and serine were found in the schizophrenic patients. Glycine was abnormally elevated in subjects with paranoid or undifferentiated schizophrenia, but not in disorganized patients. Since glutamate, glycine, and serine play a complex role in the regulation of N-methyl-D-aspartate (NMDA) receptors, which are important in the control of normal cognitive processes, we hypothesized that the elevated levels of these amino acids might disrupt the normal functioning of NMDA receptors and might be involved in the pathophysiology of schizophrenia.

Total sleep deprivation combined with lithium and light therapy in the treatment of bipolar depression: replication of main effects and interaction.

The clinical usefulness of total sleep deprivation (TSD) in the treatment of bipolar depression is hampered by a high-rate short-term relapse. Previous literature has suggested that both long-term lithium treatment and light therapy could successfully prevent relapse. We randomized 115 bipolar depressed inpatients to receive three cycles of TSD, alone or in combination with morning light exposure, given at an intensity of 150 or 2500 lux. Forty-nine patients were undergoing long-term treatment with lithium salts (at least 6 months), while 66 patients were taking no psychotropic medication. Mood was self-rated by the Visual Analogue Scale three times a day during treatment. The results showed that both light therapy and ongoing lithium treatment significantly enhanced the effects of TSD on the perceived mood, with no additional benefit when the two treatments were combined. Subjective sleepiness during TSD, as rated by the self-administered Stanford Sleepiness Scale, was significantly reduced by light exposure, and was correlated with the outcome. This study confirms the possibility of obtaining a sustained antidepressant response to TSD in bipolar patients.

Antifungal and peroxidative activities of nonheme chloroperoxidase in relation to transgenic plant protection.

Nonheme chloroperoxidase (CPO-P) of Pseudomonas pyrrocinia catalyzes the oxidation of alkyl acids to peracids by hydrogen peroxide. Alkyl peracids possess potent antifungal activity as found with peracetate: 50% killing (LD(50)) of Aspergillus flavus occurred at 25 microM compared to 3.0 mM for the hydrogen peroxide substrate. To evaluate whether CPO-P could protect plants from fungal infection, tobacco was transformed with a gene for CPO-P from P. pyrrocinia and assayed for antifungal activity. Leaf extracts from transformed plants inhibited growth of A. flavus by up to 100%, and levels of inhibition were quantitatively correlated to the amounts of CPO-P activity expressed in leaves. To clarify if the peroxidative activity of CPO-P could be the basis for the increased resistance, the antifungal activity of the purified enzyme was investigated. The LD(50) of hydrogen peroxide combined with CPO-P occurred at 2.0 mM against A. flavus. Because this value was too small to account for the enhanced antifungal activity of transgenic plants, the kinetics of the enzyme reaction was examined and it was found that the concentration of hydrogen peroxide needed for enzyme saturation (K(m) = 5.9 mM) was already lethal. Thus, the peroxidative activity of CPO-P is not the basis for antifungal activity or enhanced resistance in transgenic plants expressing the gene.

Evaluation of peracid formation as the basis for resistance to infection in plants transformed with haloperoxidase.

Nonheme haloperoxidase (HPO-P) isolated from Pseudomonas pyrrocinia catalyzed the peroxidation of alkyl acids to peracids. Among acids tested as substrates, acetic acid was most readily peroxidized. The reaction product peracetate possessed potent antifungal activity: 50% death (LD(50)) of Aspergillus flavus occurred at 25 microM peracetate. Viability of A. flavus was inhibited by up to 80% by leaf extracts of tobacco plants transformed with the HPO-P gene from P. pyrrocinia compared to viability of fungi exposed to extracts from controls. To elucidate if peracid formation by HPO-P was the basis for antifungal activity in transgenic leaf tissues, lethalities of hydrogen peroxide-acetate-HPO-P combinations against A. flavus were examined in vitro. LD(50) of A. flavus exposed to the combinations occurred at 30 mM acetate when concentrations of hydrogen peroxide and HPO-P were held constant. This value was identical to the LD(50) produced by 30 mM acetate in the absence of hydrogen peroxide-HPO-P and therefore did not account for enhanced antifungal activity in transgenic plants. For clarification, kinetics of the enzymic reaction were examined. According to the concentration of acetate needed for enzyme saturation (K(m) = 250 mM), acetate was lethal prior to its oxidation to peracetate. Results indicate that peracid generation by HPO-P was not the basis for enhanced antifungal activity in transgenic plants expressing the HPO-P gene.