Risk factors for suicide reattempt: a systematic review and meta-analysis.

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

Nerve Injury Triggers Time-dependent Activation of the Locus Coeruleus, Influencing Spontaneous Pain-like Behavior in Rats.

BACKGROUND: Dynamic changes in neuronal activity and in noradrenergic locus coeruleus (LC) projections have been proposed during the transition from acute to chronic pain. Thus, the authors explored the cellular cFos activity of the LC and its projections in conjunction with spontaneous pain-like behavior in neuropathic rats. METHODS: Tyrosine hydroxylase:Cre and wild-type Long-Evans rats, males and females, were subjected to chronic constriction injury (CCI) for 2 (short-term, CCI-ST) or 30 days (long-term, CCI-LT), evaluating cFos and Fluoro-Gold expression in the LC, and its projections to the spinal cord (SC) and rostral anterior cingulate cortex (rACC). These tests were carried out under basal conditions (unstimulated) and after noxious mechanical stimulation. LC activity was evaluated through chemogenetic and pharmacologic approaches, as were its projections, in association with spontaneous pain-like behaviors. RESULTS: CCI-ST enhanced basal cFos expression in the LC and in its projection to the SC, which increased further after noxious stimulation. Similar basal activation was found in the neurons projecting to the rACC, although this was not modified by stimulation. Strong basal cFos expression was found in CCI-LT, specifically in the projection to the rACC, which was again not modified by stimulation. No cFos expression was found in the CCI-LT LCipsilateral (ipsi)/contralateral (contra)→SC. Chemogenetics showed that CCI-ST is associated with greater spontaneous pain-like behavior when the LCipsi is blocked, or by selectively blocking the LCipsi→SC projection. Activation of the LCipsi or LCipsi/contra→SC dampened pain-like behavior. Moreover, Designer Receptor Exclusively Activated by Designer Drugs (DREADDs)-mediated inactivation of the CCI-ST LCipsi→rACC or CCI-LT LCipsi/contra→rACC pathway, or intra-rACC antagonism of α-adrenoreceptors, also dampens pain-like behavior. CONCLUSIONS: In the short term, activation of the LC after CCI attenuates spontaneous pain-like behaviors via projections to the SC while increasing nociception via projections to the rACC. In the long term, only the projections from the LC to the rACC contribute to modulate pain-like behaviors in this model.

Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi→spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.

Short mindfulness meditation training: does it really reduce perceived stress?

To study whether an 8-week mindfulness meditation training program truly reduces perceived stress without designing a stress reduction program. An experimental study was performed in which we studied the effects of 8 weeks of MM training on attention and awareness, as measured by the MAAS (mindfulness attention awareness scale) and perceived stress, as measured by the PSQ (perceived stress questionnaire), in 80 volunteers from the general public recruited by email from university centers. An increase in the individual's dispositional capacity to be attentive and aware of the experience of the present moment in everyday life was observed in the experimental group versus the control group; F (2, 156) = 14.30, p = .000, η2 partial = .155. Perceived stress showed no significant differences between groups in: social acceptance; F (2, 156) = 2.30, p = .103, overload; F (2, 156) = 2.32, p = .101, irritability, tension and fatigue; F (2, 156) = 2.27, p = .106, energy and joy; F (2, 156) = 2.79, p = .065. MM practice for 8 weeks of training increases the individual's dispositional capacity to be attentive and aware of the experience of the present moment in everyday life but may not reduce perceived stress.

A comparative study of climacteric symptoms among two populations of mid-aged women.

The purpose of this study was to compare climacteric symptoms associated with health-related quality of life (HRQOL) among women from Madrid (Spain) and Belgrade (Serbia). A cross-sectional study included 461 women from Madrid and 513 women from Belgrade aged 40-65 years. Climacteric symptoms and HRQOL were examined using the Menopause Rating Scale (MRS). There were no differences in MRS total score (p = 0.873), somato-vegetative and urogenital domain scores regarding country groups. However, women from Belgrade had poorer psychological domain score than women from Madrid (p = 0.027). Madrilenian women were more likely to have worse MRS score if they were coupled, had gynaecological complaints and longer duration of amenorrhoea. In Belgradian women, having higher level of education and using hormone-replacement therapy was associated with worse MRS score. Midlife women from Madrid and Belgrade had similar perception of intensity of urogenital and somato-vegetative climacteric symptoms. Belgradian women, however, perceived psychological symptoms as more severe.IMPACT STATEMENTWhat is already known on this subject? Social and cultural meanings of menopause vary across countries. It is quite delicate to strike a balance between two or more populations of women that can be compared, but also have specific features that are unique to their area. Similarities such as position of women in the society, access to education, contraception and safe induced abortion can facilitate this comparison.What do the results of this study add? Spanish and Serbian women rated similarly somato-vegetative and urogenital complaints, but Serbian women had worse psychological symptoms compared to Spanish women. Spanish women were more likely to endure climacteric symptoms until they withdraw spontaneously. Serbian women of higher education were more likely to use hormone-replacement therapy to manage climacteric complaints.What are the implications of these findings for clinical practice and/or further research? This study is the first to compare climacteric symptoms between women in Spain and Serbia. Despite the universality of menopause, culture seems to play a major role in differences in the perception of specific climacteric symptoms. Examination of quality of life in menopausal transition is an important measure of health status and should become a part of the routine health care in midlife.

Women in a situation of homelessness and violence: a single-case study using the photo-elicitation technique.

BACKGROUND: Violence against women places them in a vulnerable position with regard to homelessness. Although sometimes invisible, women's homelessness is a complex reality shrouded in dramatic biographies that should be sensitively addressed to avoid revictimization. METHODS: With the aim of understanding the chaotic discourse of homeless women's experiences of violence, a qualitative single-case study was conducted using the photo-elicitation technique. Data were analyzed in accordance with grounded theory. RESULTS: The participant's discourse could be summarized in the following categories: "Living in a spiral of violence", "Confronting vulnerability and violence", "Being a strong woman", "New family networks", "Re-building mother-child relationships", and "Nurturing spiritual wellbeing". CONCLUSIONS: Supporting homelessness women requires an approach that focuses on the prevention of re-victimization and the consequences of violence in terms of physical and mental health. Shelters are spaces of care for recovery and represent referential elements for the re-construction of self.

Biochemical and Genomic Characterization of the Cypermethrin-Degrading and Biosurfactant-Producing Bacterial Strains Isolated from Marine Sediments of the Chilean Northern Patagonia.

Pesticides cause severe environmental damage to marine ecosystems. In the last ten years, cypermethrin has been extensively used as an antiparasitic pesticide in the salmon farming industry located in Northern Patagonia. The objective of this study was the biochemical and genomic characterization of cypermethrin-degrading and biosurfactant-producing bacterial strains isolated from cypermethrin-contaminated marine sediment samples collected in southern Chile (MS). Eleven strains were isolated by cypermethrin enrichment culture techniques and were identified by 16S rDNA gene sequencing analyses. The highest growth rate on cypermethrin was observed in four isolates (MS13, MS15a, MS16, and MS19) that also exhibited high levels of biosurfactant production. Genome sequence analyses of these isolates revealed the presence of genes encoding components of bacterial secondary metabolism, and the enzymes esterase, pyrethroid hydrolase, and laccase, which have been associated with different biodegradation pathways of cypermethrin. These novel cypermethrin-degrading and biosurfactant-producing bacterial isolates have a biotechnological potential for biodegradation of cypermethrin-contaminated marine sediments, and their genomes contribute to the understanding of microbial lifestyles in these extreme environments.

The Effect of Resveratrol on Cell Viability in the Burkitt's Lymphoma Cell Line Ramos.

Resveratrol is a polyphenolic natural compound produced by a variety of crops. Currently, resveratrol is considered a multi-target anti-cancer agent with pleiotropic activity, including the ability to prevent the proliferation of malignant cells by inhibiting angiogenesis and curtailing invasive and metastatic factors in many cancer models. However, the molecular mechanisms mediating resveratrol-specific effects on lymphoma cells remain unknown. To begin tackling this question, we treated the Burkitt's lymphoma cell line Ramos with resveratrol and assessed cell survival and gene expression. Our results suggest that resveratrol shows a significant anti-proliferative and pro-apoptotic activity on Ramos cells, inducing the DNA damage response, DNA repairing, and modulating the expression of several genes that regulate the apoptotic process and their proliferative activity.

Papular Epidermal Nevus with Skyline Basal Cell Layer (PENS): Three New Cases and Review of the Literature.

BACKGROUND/OBJECTIVE: Papular epidermal nevus with skyline basal cell layer (PENS) is a recently described type of epidermal nevus with characteristic histopathologic findings, mainly regular, rectangular acanthosis and a well-demarcated basal cell layer with clear palisading and separation between basal cell nuclei and the first row of Malpighian cell nuclei. Although the first reports described randomly distributed lesions appearing sporadically in otherwise healthy patients, cases of Blaschkoid distribution, lesions associated with extracutaneous manifestations, and familial cases have been reported. METHODS: We performed a review of the clinical charts of all patients with histologic diagnosis of PENS in our hospital. We evaluated epidemiologic, clinical, and histologic features. We then reviewed the literature with a particular emphasis on the presence or absence of extra-cutaneous associations. RESULTS: Three patients with PENS are described. One had a single lesion, one had three lesions, and one, a patient with mild developmental delay, a curved penis, and hypospadias, had multiple lesions. CONCLUSION: The probability of having extracutaneous manifestations is 6.3 times as great in individuals with more than four lesions. Therefore these patients may need closer follow-up.

Understanding the kinetics of ligand binding to globins with molecular dynamics simulations: the necessity of multiple state models.

Residue conformational changes and internal cavity migration processes play a key role in regulating the kinetics of ligand migration and binding events in globins. Molecular dynamics simulations have demonstrated their value in the study of these processes in different haemoglobins, but derivation of kinetic data demands the use of more complex techniques like enhanced sampling molecular dynamics methods. This review discusses the different methodologies that are currently applied to study the ligand migration process in globins and highlight those specially developed to derive kinetic data.

Psychological Impact of the Volcanic Eruption in La Palma Spanish Island: Predictors of Depression, Anxiety, Stress, and Well-being.

Natural disasters, such as the eruption of the "Tajogaite" volcano on the Spanish island of La Palma, might have a high impact on the mental health of those who experience them. This study aims to evaluate the mental state of La Palma's population on the acute phase of the event as well as two and seven months later. The main hypothesis was that levels of anxiety will decrease in time, while depression and perceived stress levels will remain stable. Levels of depression, anxiety, perceived stress and psychological well-being were measured, as well as their relationship and certain demographic variables such as age, gender and residential situation. Results showed that anxiety and perceived stress significantly decreased with time, but depression and well-being remained stable. Moreover, higher levels of depression could be partly explained by higher anxiety and perceived stress, previous pharmacological treatment, and lower levels of well-being. Also, being a woman, higher levels of perceived stress, living in a region affected by the eruption, and previous pharmacological treatment significantly predicted higher anxiety; being a woman, higher levels of anxiety and lower levels of well-being significantly predicted higher perceived stress. Finally, higher levels of well-being could be partly explained by lower levels of depression and perceived stress, and not living alone. This study was able to identify particularly vulnerable groups during natural disasters, such as the eruption of a volcano. This is important to provide early psychological care to those who need it in these situations.

Rubus urticifolius Compounds with Antioxidant Activity, and Inhibition Potential against Tyrosinase, Melanin, Hyaluronidase, Elastase, and Collagenase.

In our study, using chromatographic techniques, we isolated three bioactive compounds, which were structurally elucidated as (E)-2-(3-(3,4-dimethoxyphenyl)acrylamido)-N-methylbenzamide (1), 4-Hydroxyquinoline-2-carboxylic acid (2), and (E)-2-Cyano-3-(4-hydroxyphenyl)acrylic acid (3), using spectroscopic methods. The anti-melanogenic, anti-inflammatory, antioxidant, and anti-aging properties were evaluated in vitro by measuring the activity of pharmacological targets including tyrosinase, melanin, NF-κB, hyaluronidase, elastase, collagenase, and Nrf2. Our results show that compound 1 is the most active with IC50 values of 14.19 µM (tyrosinase inhibition), 22.24 µM (melanin inhibition), 9.82-12.72 µM (NF-κB inhibition), 79.71 µM (hyaluronidase inhibition), 80.13 µM (elastase inhibition), 76.59 µM (collagenase inhibition), and 116-385 nM (Nrf2 activation) in the THP-1, HEK001, WS1, and HMCB cells. These findings underscore the promising profiles of the aqueous extract of R. urticifolius at safe cytotoxic concentrations. Additionally, we report, for the first time, the isolation and characterisation of these nitrogenous compounds in the R. urticifolius species. Finally, compound 1, isolated from R. urticifolius, is a promising candidate for the development of more effective and safer compounds for diseases related to skin pigmentation, protection against inflammation, and oxidative stress.

Carbon dioxide insufflation safety in double-balloon enteroscopy: an experimental animal study.

AIM: The aim of the present study was to assess the safety and efficacy of CO(2) during double-balloon enteroscopy (DBE) in an experimental animal model study. In this study, insufflation with room air and with CO(2) was compared. METHODS: Twenty healthy swines were used. The animals were randomly allocated to two groups. The room air-DBE group was insufflated with room air, whereas the CO(2)-DBE group was insufflated with CO(2). Endoscopy duration was 90 min. The following parameters were measured during the study (basal, 30 min, 60 min, 90 min): invasive hemodynamic parameters, ventilatory parameters, arterial blood gases, exploration depth, as well as biochemical tests. Residual gas was evaluated at the end of DBE, at 180 min and 24 h after DBE. RESULTS: During the endoscopic exploration none of the animals showed hemodynamic, ventilatory or arterial blood gas alterations in the normal reference range for the swine species. The CO(2) group showed statistically significant differences over the room air group with lower post-procedure residual gas and greater depth of the small bowel explored. CONCLUSION: The use of CO(2) for insufflation during DBE was safe and no complications associated with CO(2) were observed. In addition, the use of CO(2) offers benefits over the use of room air for insufflation during DBE.

Exploring Pathways and Obstacles to Well-Being in Victims of Terrorism: A Qualitative Approach.

On March 11, 2004, Madrid suffered one of the worst terrorist attacks in the history of Spain, leaving more than 190 dead and 2,000 injured. For years, the psychological consequences of the attacks have been studied; however, its long-term effects on symptomatology and especially on well-being remains unknown. This study aims to explore, through a qualitative approach, pathways and obstacles to the well-being of those affected directly or indirectly by the attacks of March 11 in Madrid. Two focus groups were held, one for indirect victims and one for direct victims. Subsequently, a thematic analysis of the materials obtained was carried out. More than 10 years after the attacks, most of the participants reported great difficulty in achieving well-being. Acceptance and victims' associations seemed to act as key facilitators, while symptoms, political institutions and the media were the main obstacles. Direct and indirect victims presented similar data although aspects such as guilt and family relationships played a different role in their well-being.

Factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women in Metro Manila, Philippines: a multicentre longitudinal cohort study.

OBJECTIVE: To determine the potential risk factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women. DESIGN: A multicentre prospective cohort study among eligible women in Metro Manila, Philippines, from 2020 to 2022. SETTING: Five national and local hospital research sites altogether recruited and screened 500 consenting eligible individuals. PARTICIPANTS: Pregnant and non-pregnant participants meeting the eligibility criteria were admitted for a reverse-transcription PCR determination of SARS-CoV-2, pregnancy testing and ultrasound, and an interview with an administered questionnaire. EXPOSURES: Primary exposure was pregnancy; secondary exposures involve sociodemographic, lifestyle and obstetric-gynaecologic factors. OUTCOME MEASURE: Outcome being measured was COVID-19 status. RESULTS: The significant COVID-19 risk factors were: pregnancy (PR=1.184, 95% CI 1.096, 1.279), having a white-collar job (PR=1.123, 95% CI 1.02, 1.235), travelling abroad (PR=1.369, 95% CI 1.083, 1.173) and being infected by at least one vaccine-preventable disease (VPD) (PR=1.208, 95% CI 1.113, 1.310). Protective factors included having graduate-level education (PR=0.787, 95% CI 0.649, 0.954), immunisation against a VPD (PR=0.795, 95% CI 0.733, 0.862) and practising contraception (PR=0.889, 95% CI 0.824, 0.960). CONCLUSION: This study is the first in the country to determine the risks influencing COVID-19 infection among unvaccinated pregnant and non-pregnant women. Pregnancy is a significant risk for COVID-19 among women in Metro Manila. Educational attainment and positive health behaviours seem to confer protection. Occupations and activities that increase the frequency of interactions, as well as history of communicable diseases may predispose women to COVID-19. Further studies are needed to elucidate the development of the disease in pregnant women, including the maternal and neonatal effects of COVID-19 via potential vertical mechanisms of transmission.

Herpes simplex virus type 1 induces simultaneous activation of Toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes.

Herpes simplex virus type 1 (HSV-1) is the most common pathogenic cause of sporadic acute encephalitis and it produces latent persistent infection lifelong in infected individuals. Brain inflammation is associated with activation of glial cells, which can detect pathogen-associated molecular patterns (PAMPs) through a variety of pattern-recognition receptors (PRR), including Toll-like receptors (TLRs). In this study, we evaluated the expression and activation of TLR2, TLR3, and TLR4 in HSV-1-infected astrocyte and neuronal primary cultures. Our results showed a clear induction in TLR2 and TLR4 expression in astrocytes as early as 1 h after HSV-1 infection, whereas no significant change was observed in neurons. In addition, infected astrocytes showed increased levels of interferon regulatory factors IRF3 and IRF7, interferon ß (INFß), interleukin 6 (IL6), and serum amyloid A (SAA3) transcripts, as well as phospho-IRF3 protein. These effects seemed to be dependent on viral replication since previous treatment of the cells with acyclovir resulted in low levels of TLRs expression and activation even after 4 h post-infection. These results suggest that reactivation of HSV-1 at the central nervous system (CNS) would likely induce and activate TLR2 and TLR4 receptors directly through interaction of astrocytes with the pathogen and also indirectly by endogenous ligands produced locally, such as serum amyloid protein, potentiating the neuroinflammatory response.

Nerve injury induces transient locus coeruleus activation over time: role of the locus coeruleus-dorsal reticular nucleus pathway.

ABSTRACT: The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. Using the chronic constriction injury of the sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats, we identified time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion, hypothesizing that the LC→dorsal reticular nucleus (DRt) pathway is involved in the pathological nociception associated with chronic pain. LCipsi inactivation with lidocaine increased cold allodynia 2 days after nerve injury but not later. However, similar blockade of LCcontra reduced cold allodynia 7 and 30 days after inducing neuropathy but not earlier. Furthermore, lidocaine blockade of the LCipsi or LCcontra reversed pain-induced depression 30 days after neuropathy. Long-term pain enhances phosphorylated cAMP-response element binding protein expression in the DRtcontra but not in the DRtipsi. Moreover, inactivation of the LCcontra→DRtcontra pathway using dual viral-mediated gene transfer of designer receptor exclusively activated by designer drugs produced consistent analgesia in evoked and spontaneous pain 30 days postinjury. This analgesia was similar to that produced by spinal activation of α2-adrenoreceptors. Furthermore, chemogenetic inactivation of the LCcontra→DRtcontra pathway induced depressive-like behaviour in naïve animals, but it did not modify long-term pain-induced depression. Overall, nerve damage activates the LCipsi, which temporally dampens the neuropathic phenotype. However, the ensuing activation of a LCcontra→DRtcontra facilitatory pain projection contributes to chronic pain, whereas global bilateral LC activation contributes to associated depressive-like phenotype.

New combined approach in metallic ureteral stenting to avoid urothelial hyperplasia: study in swine model.

PURPOSE: We assessed the therapeutic value of a new treatment option for ureteral strictures that may avoid urothelial hyperplasia, which is the main cause of metallic stent failure. MATERIALS AND METHODS: We used 24 pigs in this study. An experimental model of ureteral stricture was induced in all animals. Obstruction was confirmed by ultrasound and retrograde ureteropyelogram 6 weeks after model creation. The pigs were then randomly allocated to 2 experimental groups. Therapy involved placement of a 6 × 30 mm metallic ureteral covered stent in the ureteral stricture in group 1 and subsequent endoureterotomy at the ureteral segments adjacent to the 2 ends of the stent in group 2. A double pigtail stent was then deployed for 3 weeks. Completion studies 6 months after therapy included retrograde ureteropyelogram, endoluminal ultrasound and ureteroscopy to assess urothelial hyperplasia formation. RESULTS: At the end of the study evidence of urothelial hyperplasia was seen in 50% of the pigs in group 1 and in 29% in group 2. Four and 2 cases of cranial stent migration in groups 1 and 2, respectively, were seen at 6 months. Hyperplasia and renal involvement were statistically significantly different between the groups with more damage in group 1 than in group 2. CONCLUSIONS: Hyperplasia was markedly reduced when ureteral peristalsis was inhibited by endoureterotomy at the area of interaction between the stent and the ureter.

[Herpes simplex virus type 1 as risk factor associated to Alzheimer disease]. / Herpes simplex virus tipo 1 como factor de riesgo asociado con la enfermedad de Alzheimer.

Herpes simplex virus type 1 (HSV-1) is ubiquitous, neurotropic, and the most common pathogenic cause of sporadic acute encephalitis in humans. Herpes simplex encephalitis is associated with a high mortality rate and significant neurological, neuropsychological, and neurobehavioral sequels. HSV-1 infects limbic system structures in the central nervous system (CNS), and has been suggested as an environmental risk factor for Alzheimer's disease. The possibility that HSV-1 reactivates in CNS neurons causing chronic progressive damage at cellular level and altering the neuronal functionality has not been thoroughly investigated. Currently it is ignored if recurrent reactivation of HSV-1 in asymptomatic patients involves some risk of progressive deterioration of the CNS functions caused, in example, by a neuroinflammatory response against the virus or by direct toxicity of the pathogen on neurons. Therefore, studies regarding the routes of dissemination of HSV-1 from the peripheral ganglions to the CNS, as well as the possible cellular and molecular mechanisms implied in generating neuronal damage during latent and productive infection, are of much relevance.

Aging and neuroinflammation: Changes in immune cell responses, axon integrity, and motor function in a viral model of progressive multiple sclerosis.

Although aggravated multiple sclerosis (MS) disability has been reported in aged patients, the aging impact on immune cells remodeling within the CNS is not well understood. Here, we investigated the influence of aging on immune cells and the neuroinflammatory and neurodegenerative processes that occur in a well-established viral model of progressive MS. We found an anomalous presence of CD4+ T, CD8+ T, B cells, and cells of myeloid lineage in the CNS of old sham mice whereas a blunted cellular innate and adaptive immune response was observed in Theiler's murine encephalomyelitis virus (TMEV) infected old mice. Microglia and macrophages show opposite CNS viral responses regarding cell counts in the old mice. Furthermore, enhanced expression of Programmed Death-ligand 1 (PD-L1) was found in microglia isolated from old TMEV-infected mice and not in isolated CNS macrophages. Immunocytochemical staining of microglial cells confirms the above differences between young and old mice. Age-related axonal loss integrity in the mouse spinal cord was found in TMEV mice, but a less marked neurodegenerative process was present in old sham mice compared with young sham mice. TMEV and sham old mice also display alterations in innate and adaptive immunity in the spleen compared to the young mice. Our study supports the need of new or adapted pharmacological strategies for MS elderly patients.