Prognostic Significance of Pre-Treatment Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Head and Neck Malignancies.

Introduction: Carcinoma is the second most common cause of death worldwide. The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are essential markers of inflammation and tumorigenesis in various cancers including head and neck cancers. Pretreatment platelet- lymphocytic ratio can be used as an independent predictor of mortality whereas neutrophil- lymphocytic ratio is an independent predictor of recurrence. The main aim of this study is to compare the pre-treatment neutrophil lymphocyte ratio and platelet-lymphocyte ratio in the patients of head and neck malignancies with those of the control group. Material and Method: 100 patients with histologically diagnosed cases of head and neck malignancies. Age and sex matched healthy subjects attending Otorhinolaryngology out-patient department for any other complaints (100 control subjects). Complete blood count had been done to calculate absolute neutrophil count and absolute lymphocyte count. Results: The mean age of the subjects in the study group was 55.73 ± 11.56 years. In control group, the mean age group was 54.11 ± 10.46 years. NLR and PLR significantly increased in cases than controls. NLR associated with T stage, histological type and histological grade but not with site and nodal involvement. PLR associated with T stage, metastasis but not with the histological grade, histological type, site and nodal involvement. Conclusion: From this study, we conclude that pre-treatment NLR and PLR were closely associated both with the size of primary tumor and also with the stage of malignant disease in patients of head and neck malignancies.

Every lid swelling is not stye: A rare presentation of scrub typhus eschar.

A 17-year-old female patient presented to us with complaints of diffuse swelling in her left upper eyelid with preauricular lymphadenopathy for three days. She was diagnosed with a case of hordeolum externum and was treated on the same line. However, during follow-up, she developed a mild- to moderate-grade fever, which did not subside with treatment. On further investigation, her IgM rapid ELISA for Scrub typhus was positive, which was further confirmed by the Weil-Fellix test (OXK=1:360). She was treated with systemic doxycycline. Within a week, her fever returned to normal baseline, with resolution of local eye lid swelling, and her black scab was also gone. We have reported a case of scrub typhus as a rare manifestation with lid swelling and subsequently eschar formation on the upper eye lid. The patient was promptly treated with oral antibiotics without any morbidity.

Upregulation of Somatostatin Receptor Type 2 Improves 177Lu-DOTATATE Therapy in Receptor-Deficient Pancreatic Neuroendocrine Tumor Model.

Pancreatic neuroendocrine tumors (PNET) express high levels of somatostatin receptor type 2 (SSTR2), a unique target for both tumor imaging and therapy. This surface expression is lost in metastatic high-grade PNETs, making patients ineligible for SSTR2-targeted 177 Lutetium (Lu)-DOTATATE peptide receptor radionuclide therapy (PRRT), and represents an unmet clinical need. Here, we aimed to restore SSTR2 expression through the reversal of inhibitory epigenetic gene silencing to improve tumor responsiveness to PRRT. We first assessed human SSTR2 promoter methylation and expression levels in 96 patient samples. We then used three NET cell lines (QGP-1, BON-1, GOT-1) with variable SSTR2 expression profiles for functional in vitro studies using histone deacetylase inhibitors (HDACi). Finally, the QGP-1 xenograft mouse model, with low basal SSTR2 expression, was used to assess the therapeutic efficacy of combined HDACi and 177Lu-DOTATATE therapies. We confirm that SSTR expression is decreased and correlates with SSTR2 promoter methylation in patients with high-grade NETs. When exposed to HDACis, SSTR2 surface expression is increased in three NET cell lines in vitro. In an in vivo PNET xenograft model with low basal SSTR2 expression, our studies demonstrate significantly higher tumor uptake of SSTR2-targeted 177Lu-DOTATATE in animals pretreated with HDACis compared with controls. For the first time, we show that this higher tumor uptake results in significant antitumor response when compared with standard PRRT alone. These preclinical results provide a rationale for utilizing HDACi pretreatment to improve targeted radionuclide therapy in patients with SSTR2-negative, metastatic PNETs.

Recognizing Ethyl Chloride Neurotoxicity: Inhalant Abuse Hidden in Plain Sight.

Ethyl chloride is a common topical anesthetic. However, when abused as an inhalant, effects can range from headaches and dizziness to debilitating neurotoxicity requiring intubation. While previous case reports describe the short-term reversible neurotoxicity of ethyl chloride, ours show chronic morbidity and mortality outcome. During the initial evaluation, it is essential to consider the rising trend of commercially available inhalants being used as recreational drugs. We present a case of a middle-aged man presenting with subacute neurotoxicity due to repeated abuse of ethyl chloride.

Relationship Between Lipid Profile and Sensorineural Hearing Loss: An Institution Based Study.

Sensorineural hearing loss is the most frequent problem worldwide and is the most neglected condition. Thus, it is essential to understand the etiology and pathophysiology of SNHL. The main objective of the study is to find whether serum lipid parameters have any correlation with SNHL. 68 patients within the age group of 20-60 years with clinically diagnosed sensorineural hearing loss were included in this study. Informed written consent, otoscopy, pure tone audiometry were done on all patients. The subjects were subjected to Serum lipid profile. The mean age of subjects in this study was 53.25 ± 13.78 years and male to female ratio was found to be 1.125:1. The serum total cholesterol and serum triglyceride also showed significant relationship with the degree of hearing loss (p value < 0.001). With an increase in the serum LDL there was increase in the severity of hearing loss which was statistically significant (p value < 0.001) where as serum HDL level showed statistically insignificant and negative correlation with severity of hearing loss. Serum lipid profile can be used as important biomarker for assessing the severity of hearing loss. Subjects with deranged lipid parameters had higher degress of hearing impairement.

A Systematic Review of updated mechanistic insights towards Alzheimer's disease.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a degenerative neurological disorder that impairs memory, cognitive abilities, and the ability to do even most everyday activities. This neurodegenerative disease is growing increasingly common as the world's population ages. Here we reviewed some of the key findings that have shown the function of Aß peptide, oxidative stress, free radical damage Triggering Receptors Expressed on Myeloid Cells 2 (TREM2), Nitric Oxide (NO), and gut microbiota in the aetiology of AD. METHODOLOGY: The potentially relevant online medical databases, namely, PubMed, Scopus, Google Scholar, Cochrane Library, and JSTOR were exhaustively researched. In addition, the data reported in the present study were primarily intervened on the basis of the timeline selected from 1 January 2000 to 31 October 2021. The whole framework was designed substantially based on key terms and studies selected by virtue of their relevance to our investigations. RESULTS: Findings suggested that channels of free radicals, such as transition metal accumulation, and genetic factors are mainly accountable for the redox imbalance that assist to understand better the pathogenesis of AD and incorporate new therapeutic approaches. Moreover, TREM2 might elicit a protective function for microglia in AD. NO causes an increase in oxidative stress and mitochondrial damage, compromising cellular integrity and viability. The study also explored that the gut and CNS communicate with one another and that regulating gut commensal flora might be a viable therapeutic for neurodegenerative illnesses like AD. CONCLUSION: There are presently no viable therapies for Alzheimer's disease, but recent breakthroughs in our knowledge of the disease's pathophysiology may aid in the discovery of prospective therapeutic targets.

Cutaneous ectopia of lung, located on back and neck: Hitherto undescribed presentation.

Ectopia is defined as the presence of a normal-appearing tissue in an abnormal location, where it is not normally found. In the literature, it is also referred to as heterotopia and is described as choristoma when it forms a mass. Lung tissue ectopia is a rare anomaly and is characterized by the presence of mature lung tissue comprising well-formed bronchi, bronchioles, and alveoli at an abnormal location. Occurrence of ectopic lung tissue in the skin is an extremely rare entity and the diagnosis is mostly established by histopathologic examination. This report documents a rare occurrence of cutaneous ectopic lung tissue at two locations (neck and back). Cutaneous ectopia at multiple sites has not been described in the literature till date.

Alteration in biochemical constituents and nutrients partitioning of Asparagus racemosus in response to elevated atmospheric CO2 concentration.

Understanding the response of medicinal plants to elevated CO2 concentrations is crucial to evaluate the climate change impacts on medicinal plant's productivity together with the accumulation of biochemical constituents counting nutrients wealth. The present study investigated the effect of elevated CO2 concentrations (ambient-~400±4, 600±12, and 800±16 µmol CO2 mol-1) on the biochemical constituents (viz. chlorophyll, carotenoids, ascorbic acid, protein, total sugars, and carbon partitioning) and accumulation of mineral nutrients (viz. potassium, phosphorus, and magnesium) in different plant parts (viz. leaf, stem, and root) of Asparagus racemosus Willd., an endangered medicinal plant species. The results confirmed that the elevated CO2 concentration significantly (p ≤ 0.05) enhanced the leaves biochemical constituents, viz. chlorophyll, protein, total sugars, and carbon content while conversely diminishes the ascorbic acid content in leaf. The accumulation of nutrients especially potassium and magnesium were significantly (p ≤ 0.05) improved while it is reverse in case of phosphorus under the elevated CO2 concentration. Moreover, elevated CO2 notably altered protein, sugars, carbon, and nutrients partitioning in leaf, stem, and root tissues. This study will be helpful in anticipating the effect of rising atmospheric CO2 concentration on medicinal and threatened plants and require further intensive studies to comprehend the effects of elevated CO2 concentration.

A Study to Grade the Severity of Tinnitus and its Psychological Impact Using Tinnitus Functional Index (tfi).

Background: Chronic tinnitus has a lot impact on the quality of life of person by affecting his/ her physical health, occupational health and social relations. It can lead to sleep interference, cognitive difficulties, lack of concentration, anxiety, frustration, anger and depression. The present study showed the severity and impact of tinnitus on quality of life of subjects with or without hearing loss using tinnitus functional index (TFI). Methods: Subjects with history of tinnitus with or without hearing loss including informed consent, otoscopy, pure tone audiometry (PTA) were done. Grading of tinnitus was done by using tinnitus functional index score. Results: The mean age of participants were 50.20 ± 4.2 years and male to female ratio were found to be 1.05:1. On PTA, 122 participants had hearing loss and 28 had no hearing loss. 49 patients had mild TFI score, 85 had moderate TFI score and 16 had severe hearing loss. The difference in the severity of tinnitus using TFI between normal hearing and sensorineural hearing loss individual was statistically significant. On the other hand, the severity of tinnitus and degree of hearing loss were also found to be statistically significant with p value < 0.0001 chi. Sq = 77.39. This shows that with increase in increase in hearing loss there is increase in TFI sore. Conclusion: Tinnitus has a negative impact on the quality of life like pshycological, emotional and physical effects. The effects of tinnitus is more in those with co-existing hearing loss.

A Clinical Study to Evaluate the Role of Vitamin D3 in Allergic Rhinitis.

Allergic rhinitis is a common and chronic immunoglobulin E-mediated inflammation of nasal mucosa induced after allergen exposure. Allergic rhinitis is a global health problem that causes major illness and affects patient's social life, sleep, school and work performance. Various studies have implicated the association between low serum vitamin D levels and allergic diseases. Active form of Vitamin D3 has been shown to have immunoregulatory effect on both innate and adaptive immunity, which can significantly affect the outcome of allergic responses in allergic rhinitis. The study aims to evaluate effectiveness of Oral Vitamin D3 supplementation as an adjunct to standard therapy, in the management of allergic rhinitis. The present study is a prospective study in which 80 subjects were recruited and were randomly divided into two groups. The study group received oral vitamin D3 (60,000 IU) along with intranasal steroid spray while control group received only intranasal steroid spray for 4 weeks. The response in both the groups was compared by evaluating total nasal symptom score (TNSS). Subjects of allergic rhinitis showed deficiency in vitamin D indicated by mean serum vitamin D levels of 15 ± 2.42 ng/ml in the study group and 14.72 ± 2.64 ng/ml in the control group. The pre treatment mean TNSS score was 10.45 ± 3.1 in the study group and 11.43 ± 2.35 in the control group. The post treatment mean TNSS score was 2.1 ± 0.21 in the study group and 3.85 ± 0.76 in the control group. A significant reduction in symptoms score was observed after 4 weeks of oral vitamin D3 supplementation. The difference between two groups was found to be statistically significant (p value < 0.05).

The regulatory roles of progesterone and estradiol on emotion processing in women.

Emotion processing is known to interact with memory. Ovarian steroid hormones, such as progesterone and estradiol, modulate emotion processing and memory. However, it is unclear how these hormones influence brain activity when emotion processing is integrated with working memory (WM). Therefore, the objective of this study was to examine the relationship between endogenous hormonal concentration and brain activity during emotion processing in the context of a WM n-back task in 74 young women using functional magnetic resonance imaging (fMRI). Results show that positive emotion processing activates reward-related areas, such as the caudate and putamen, whereas negative emotion processing activates a corticolimbic network, including the amygdala and hippocampus. Furthermore, our findings provide evidence that progesterone modulates more bottom-up brain activation during both positive and negative emotion processing, whereas estradiol activates lateralized, top-down regulation. These findings provide insight on the neural correlates of emotion processing during an n-back task in young women and highlight how important it is to consider women's endogenous hormonal concentration in neurobiological and cognition research.

Oral contraceptive use, especially during puberty, alters resting state functional connectivity.

Millions of women worldwide use oral contraceptives (OCs), often starting during puberty/adolescence. It is, however, unknown how OC use during this critical period of development affects the brain. The objective of the current study was to examine resting state functional connectivity (FC) in the default mode network (DMN), central executive network (CEN), salience network (SN), reward network (RN), and subcortical limbic network of the brain using independent component analysis (ICA) between pubertal- and adult-onset OC users (n = 27) and naturally cycling women (n = 48). It was hypothesized that OC use would result in network-specific increases and decreases in FC and that pubertal-onset OC use would result in differences to the aforementioned networks compared to adult-onset OC use. Pubertal-onset OC use is related to heightened FC in the SN compared to adult-onset OC users. In general, OC use also increases connectivity in the SN, CEN, RN, and subcortical limbic network compared to NC women. No significant differences in connectivity were observed in the DMN between OC users and NC women. These findings provide a mechanistic insight for the altered executive functioning and emotion/reward processing previously seen in OC users, which may then increase their vulnerability to mental health conditions.

Use of the birth control pill affects stress reactivity and brain structure and function.

Millions of women worldwide use oral contraceptives (i.e., birth control pill; OCs), often starting during puberty/adolescence; however, it is unknown how OC use during this critical period of development affects the brain, especially with regard to emotional working memory. Here, we examined stress reactivity, and brain structure and function in OC users using the Trier Social Stress Test and structural and functional magnetic resonance imaging (MRI). Our results show that OC use during puberty/adolescence gives rise to a blunted stress response and alters brain activation during working memory processing. OC use, in general, is also linked to increased prefrontal brain activation during working memory processing for negatively arousing stimuli. OC use is also related to significant structural changes in brain regions implicated in memory and emotional processing. Together, these findings highlight that OC use induces changes to brain structure and function and alters stress reactivity. These findings may provide a mechanistic insight for the increased vulnerability to mood-related mental illness in women after OC use.

Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes.

Long-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In this study, we found that mice exposed to chronic HA (5000 m for 12 weeks) exhibited deficits in learning and memory associated with hippocampal function and were linked with changes in the expression of synaptic proteins across various regions of the brain. Specifically, we found decreased levels of synaptophysin (SYP) (p < 0.05) and spinophilin (SPH) (p < 0.05) in the olfactory cortex, post synaptic density-95 (PSD-95) (p < 0.05), growth associated protein 43 (GAP43) (p < 0.05), glial fibrillary acidic protein (GFAP) (p < 0.05) in the cerebellum, and SYP (p < 0.05) and PSD-95 (p < 0.05) in the brainstem. Ultrastructural analyses of synaptic density and morphology in the hippocampus did not reveal any differences in CEHA mice compared to SL mice. Our data are novel and suggest that CEHA exposure leads to cognitive impairment in conjunction with neuroanatomically-based molecular changes in synaptic protein levels and astroglial cell marker in a region specific manner. We hypothesize that these new findings are part of highly complex molecular and neuroplasticity mechanisms underlying neuroadaptation response that occurs in brains when chronically exposed to HA.

Ethnic differences in diurnal cortisol profiles in healthy adults: A meta-analysis.

PURPOSE: Cortisol is a well-known biomarker of the physiological stress system; atypical cortisol patterns have been linked to many psychological and physiological illnesses. Previous studies have found vast health disparities among ethnic groups; however, studies examining the relationship between cortisol and ethnicity have found mixed results. This meta-analysis investigated whether there are differences in diurnal cortisol outcomes among ethnic groups, while considering the moderating roles of various individual factors and methodological approaches. METHODS: Search phrases were entered into MEDLINE, PsycINFO, EMBASE, Cochrane Library, CINAHL, Scopus, and Web of Science. Effect sizes were extracted for ten diurnal cortisol outcomes, including waking, 30 min after waking, cortisol awakening response, slope, area under the curve, urinary twenty-four-hour secretion, total cortisol output, and midday, evening, and bedtime concentrations, for eight ethnic group comparisons, including Asians, Blacks, Hispanics, Indigenous people, Whites, Minority and Majority groups, and Multiethnic groups. Moderator analyses, including variables such as gender, age, and number of cortisol collection time points, were conducted. RESULTS: There were significant ethnic differences in diurnal cortisol profiles, including cortisol awakening responses, with more robust differences in ethnic comparisons that included White participants. Differences in diurnal cortisol profiles were also moderated by gender, mean age, and sample size. CONCLUSIONS: This meta-analysis supports the notion that ethnic groups exhibit distinct diurnal cortisol profiles, which, according to the biopsychosocial model of health, may be a result of unique sociocultural experiences. The limitations of this meta-analysis and future directions for stress research with various ethnic groups are discussed. Statement of contribution What is already known on this subject? Studies have found vast health disparities among ethnic groups. Psychological and physiological illnesses and atypical diurnal cortisol profiles are strongly correlated. Studies have examined the relationship between diurnal cortisol rhythms and ethnicity, but findings are mixed. What does this study add? This study is a systematic examination of the relationship between diurnal cortisol rhythm and ethnicity. Psychosocial and methodological factors moderate the relationship between diurnal cortisol output and ethnicity. This study provides insight on factors that contribute to health disparities among ethnic groups.

Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner.

Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner.

The adaptive immune and stress responses of adult female CD1 mice following exposure to a viral mimetic.

Exposure to a bacterial endotoxin during puberty induces long-term changes to reproductive and non-reproductive behaviours. While the underlying mechanisms remain unknown, we have recently shown that there are age and sex differences in acute immune and stress responses following immune challenge. Given that it is unclear whether viral infections result in similar age and sex differences, the objective of this study was to examine the acute immune and stress responses following exposure to polyinosinic:polycytidylic acid (poly(I:C)), a viral mimetic, in CD1 mice and to investigate the role of gonadal hormones in these responses. CD1 male and female mice underwent sham-surgery or gonadectomy at 5 or 9 weeks of age. Following one week of recovery, at 6 (pubertal group) or 10 (adult group) weeks of age, mice were treated with either saline or poly(I:C). Poly(I:C) treatment induced greater sickness behaviour in males compared to females and increased peripheral corticosterone in adult mice relative to their pubertal counterparts. Changes in body temperature and central c-Fos expression were more prominent in adult females. Gonadectomy worsened poly(I:C)-induced sickness behaviour and altered body temperature in both sexes. The results demonstrate that adult females display the most pronounced acute changes in body temperature, corticosterone release, and c-Fos expression but show the fastest recovery in sickness behavior, indicating that, compared to males, females display an adaptive physiological response following immune stress due to higher circulating estradiol and progesterone.

Programming Effects of Pubertal Lipopolysaccharide Treatment in Male and Female CD-1 Mice.

Puberty is a critical period of development marked by sexual, immune, and neural maturation. Exposure to stress during this period can lead to enduring changes in brain functioning and in behavior; however, the underlying mechanisms and the programming effects of stress during puberty remain unknown. Therefore, the objective of this study was to investigate the programming effects of pubertal immune challenge in response to a homotypic stressor later in life in CD-1 mice. Age and sex differences in the peripheral and central cytokine levels, along with sickness behavior and telemetry data, were analyzed following the secondary treatment. The results showed that pretreatment with LPS attenuated the immune response to a second homotypic challenge. Males pretreated with LPS during puberty and in early adulthood displayed an attenuated hypothermic response following the second LPS treatment compared with saline-pretreated controls, which is consistent with the attenuated peripheral IL-6 and IFN-γ concentrations. Females pretreated with LPS during puberty displayed lower IL-1ß, TNF-α, and IL-6 mRNA expression in the prefrontal cortex following the secondary immune challenge compared with saline controls. The results of this study show that exposure to LPS during puberty programs the peripheral and central immune responses, resulting in an attenuated immune response following a subsequent homotypic stressor. Thus, exposure to an immune challenge during puberty affects immune function later in life, which could permanently affect brain function and have implications on mental health.

A safe and efficacious Pt(ii) anticancer prodrug: design, synthesis, in vitro efficacy, the role of carrier ligands and in vivo tumour growth inhibition.

Diaminocyclohexane-Pt(ii)-phenalenyl complexes (1 and 2) showed an appropriate balance between efficacy and toxicity. Compound 2 showed nearly two-fold higher tumour growth inhibition than oxaliplatin in a murine NSCLC tumour model, when a combined drug development approach was used. The fluorescent properties of phenalenone were utilized to understand the mechanistic details of the drug.

Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD-1 mice.

Puberty is a critical developmental period that is characterized by significant brain development. Exposure to stress during this time can alter brain functioning setting the stage for long-lasting behavioural outcomes. The objective of this study was to investigate age and sex differences in the peripheral and central immune responses, along with sickness behaviour, following immune stress. The results showed that LPS treatment increased serum cytokine levels and sickness symptoms in all mice. Pubertal males displayed increased IL-1ß concentrations at 2 h and increased IL-6 concentrations at 8 h post-treatment whereas increased concentrations of TNFα, IL-10, IL-12, IL-1ß, IFNγ, and IL-6 persisted at 8 and 24 h in adult females. Consistent with peripheral cytokines, pubertal males displayed greater IL-1ß, TNFα, and IL-6 mRNA expression in the prefrontal cortex at 2 h, whereas adult males expressed more of the aforementioned cytokines at 8 h compared to saline controls. Adult males also displayed greater IL-1ß mRNA expression compared to their female counterparts, and adult females displayed greater TNFα mRNA expression compared to their male counterparts. These results not only provide a better understanding of the age and sex differences in acute immune response, but also show important region- and time-specific differences in the response to an immune challenge, and that the peripheral immune response differs from the central response. This highlights the need to examine immune markers in both the periphery and the central nervous system for an accurate depiction of acute immune response following an immune challenge.