Acute Behavioral Changes Research Articles

Diagnostic Identification of Acute Brain Dysfunction in Pediatric Sepsis and Septic Shock in the Electronic Health Record: A Comparison of Four Definitions in a Reference Dataset.

Acute brain dysfunction (ABD) in pediatric sepsis has a prevalence of 20%, but can be difficult to identify. Our previously validated ABD computational phenotype (CP ABD ) used variables obtained from the electronic health record indicative of clinician concern for acute neurologic or behavioral change. We tested whether the CP ABD has better diagnostic performance to identify confirmed ABD than other definitions using the Glasgow Coma Scale or delirium scores. Diagnostic testing in a curated cohort of pediatric sepsis/septic shock patients. Quaternary freestanding children's hospital. The test dataset comprised 527 children with sepsis/septic shock managed between 2011 and 2021 with a prevalence (pretest probability) of confirmed ABD of 30% (159/527). CP ABD was based on use of neuroimaging, electroencephalogram, and/or administration of new antipsychotic medication. We compared the performance of the CP ABD with three GCS/delirium-based definitions of ABD-Proulx et al, International Pediatric Sepsis Consensus Conference, and Pediatric Organ Dysfunction Information Update Mandate. The posttest probability of identifying ABD was highest in CP ABD (0.84) compared with other definitions. CP ABD also had the highest sensitivity (83%; 95% CI, 76-89%) and specificity (93%; 95% CI, 90-96%). The false discovery rate was lowest in CP ABD (1-in-6) as was the false omission rate (1-in-14). Finally, the prevalence threshold for the definitions varied, with the CP ABD being the definition closest to 20%. In our curated dataset of pediatric sepsis/septic shock, CP ABD had favorable characteristics to identify confirmed ABD compared with GCS/delirium-based definitions. The CP ABD can be used to further study the impact of ABD in studies using large electronic health datasets.

Occult Lung Cancer-Associated Autoimmune Encephalitis Presenting as Acute Psychosis.

During deployment, a 52-year-old male developed acute behavioral changes. Though initially considered to have PTSD and related agitation and confusional state, his evaluation was consistent with acute encephalopathy. Magnetic resonance imaging of the brain showed T2 hyperintensities, and CSF analysis was positive for anti-N-methyl-D-aspartate receptor antibody. A nuclear protein in testis carcinoma midline carcinoma was discovered in the lung. Immunotherapy and surgical resection led to steady improvement prior to adjuvant chemotherapy. Autoimmune encephalitis due to anti-N-methyl-D-aspartate receptor antibodies is increasingly being recognized as causal of acute behavioral change.

A rare case of anti-DPPX encephalitis combined with neuroleptospirosis

BackgroundNeuroleptospirosis and anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis are both very rare and have only been reported in the form of respective case reports. There are no reports of anti-DPPX encephalitis combined with neuroleptospirosis in the literature. We reported the first case of neuroleptospirosis combined with elevated DPPX antibodies in serum and cerebrospinal fluid (CSF).Case presentationA previously healthy 53-year-old Chinese male farmer with a history of drinking raw stream water and flood sewage exposure was brought to the hospital due to an acute onset of neuropsychiatric symptoms. No fever or meningeal irritation signs were detected on physical examination. Routine laboratory investigations, including infection indicators, leukocyte and protein in CSF, electroencephalogram and gadolinium-enhanced magnetic resonance imaging of the brain, all revealed normal. While metagenomic next-generation sequencing (mNGS) identified the DNA genome of Leptospira interrogans in the CSF. Anti-DPPX antibody was detected both in blood and in CSF. A diagnosis of neuroleptospirosis combined with autoimmune encephalitis associated with DPPX-Ab was eventually made. He resolved completely after adequate amount of penicillin combined with immunotherapy.ConclusionWe highlight that in patients with acute or subacute behavioral changes, even in the absence of fever, if the most recent freshwater exposure is clear, physicians should pay attention to leptospirosis. Due to the low sensitivity of routine microscopy, culture, polymerase chain reaction and antibody testing, mNGS may have more advantages in diagnosing neuroleptospirosis. As autoimmune encephalitis can be triggered by various infections, neuroleptospirosis may be one of the causes of autoimmune encephalitis. Since neuronal antibody measurements themselves are not that common in neuroleptospirosis, future studies are needed to determine whether the detection of anti-DPPX antibodies is a rare event in leptospirosis. Early identification of autoimmune encephalitis and timely administration of immunotherapy may lead to a better outcome.

Acute and sub-acute toxicity study of anti-obesity herbal granules in Sprague Dawley rats.

Toxicological studies are essential for developing novel medications in pharmaceutical industries including ayurvedic preparation. Hence, the present study is aimed to evaluate acute and 28-days repeated dose oral toxicity of anti-obesity polyherbal granules (PHG) in Sprague Dawley rats by OECD guidelines No 425 and 407, respectively. In an acute oral toxicity study, a single dose of 2 g/kg PHG was administered to rats and mortality, body weight, and clinical observations were noted for fourteen days. However, in the subacute oral toxicity study, the PHG was administered orally at doses of 0.3, 0.5 and 1 g/kg daily for 28 days to rats. Food intake and body weight were recorded weekly. On the 29th day, rats were sacrificed and subjected to haematological, biochemical, urine, necropsy, and histopathological analysis. In an acute oral toxicity study, no treatment-related, mortality, behavioral changes, and toxicity were found throughout fourteen days. Likewise, in the sub-acute toxicity study, no mortality and toxic effects were found in haematology, biochemical, urine, necropsy and histopathological analysis in rats for 28 days of treatment with PHG. Based on these results, the LD50 of PHG was found to be greater than 2 g/kg and the no-observed-adverse-effect level (NOAEL) of PHG for rats was found to be 0.5 g/kg/day. Thus, anti-obesity polyherbal granules showed a good safety profile in animal studies and can be considered an important agent for the clinical management of obesity.

CSF1R Inhibition Promotes Neuroinflammation and Behavioural Deficits during Graft-Versus-Host Disease in Mice

Chronic graft-versus-host disease (cGVHD) remains a significant complication of allogeneic hematopoietic stem cell transplantation. Central nervous system (CNS) involvement is becoming increasingly recognised, where brain-infiltrating donor MHC class II + bone marrow-derived macrophages (BMDM) are implicated mediators of pathology. Colony-stimulating factor 1 receptor (CSF1R)-dependent BMDM are established mediators of cutaneous and pulmonary cGVHD, and clinical trials assessing the efficacy of CSF1R antibody blockade to deplete macrophages are promising. We hypothesized that CSF1R antibody blockade may also be a useful strategy to prevent/treat CNS cGVHD. We leveraged studies in acute GVHD (aGVHD) to determine the feasibility of an antibody-based approach for depleting brain microglia and macrophages. Moreover, we queried whether CSF1R blockade may be a viable therapy for CNS aGVHD, which has been shown to be mediated by host microglia. Increased blood-brain barrier permeability during aGVHD facilitated CNS antibody access. However, CSF1R blockade early post-transplant induced region-specific microglia depletion and was associated with unexpected exacerbation of aGVHD neuroinflammation, including increased T cell and inflammatory monocyte infiltration, and whole brain cytokine levels. In established cGVHD, vascular changes and anti-CSF1R efficacy was more limited. Anti-CSF1R-treated mice retained donor BMDM, activated microglia, CD8 + and CD4 + T cells, and local cytokine expression in the brain. These findings were recapitulated in GVHD recipients where CSF1R was conditionally depleted in donor CX3CR1 + BMDM. Notably, inhibition of CSF1R signalling post-transplant failed to reverse either acute or chronic GVHD-induced behavioral changes. Taken together, these data suggest that ongoing clinical trials of CSF1R inhibition should assess neurological adverse events in patients. In contrast to the lack of efficacy with CSF1R inhibition, transfer of Ifngr-/- grafts reduced MHC class II + BMDM infiltration, resulting in improved behaviour. Furthermore, single nuclei RNA sequencing of brains from mice receiving wild-type or Ifngr-/- allografts revealed a disease-associated interferon-inducible mature oligodendrocyte population in the cGVHD brain. This was markedly reduced in recipients of Ifngr-/- grafts, indicating that targeting this axis can promote brain repair beyond the myeloid compartment during cGVHD. In summary, our findings reveal unexpected neurological immune toxicity during CSF1R blockade and highlight the IFNGR pathway as an alternative target for the treatment of cGVHD within the CNS.

Excluded and ashamed: Shame proneness interacts with social exclusion and testosterone reactivity to predict behavioral aggression

Exclusion from social relationships is a painful experience that may threaten an individual’s status and dominance. The steroid hormone testosterone, which fluctuates rapidly in response to such threats, may be implicated in subsequent behavioral action (e.g., aggressive or prosocial responses) that aims to protect or enhance one’s status after exclusion. Past research, however, indicates that the link between acute changes in testosterone and behavior depend on context-relevant individual dispositions. In the context of social exclusion, an individual’s level of shame proneness—characterized by a tendency to experience shame and to react submissively—is theoretically relevant to the testosterone-induced aggression relationship but has yet to be examined empirically. Here, men (n = 167) were randomly assigned to be socially included or excluded in the virtual ball-tossing game, Cyberball, after which aggressive behavior was examined using the Point Subtraction Aggression Paradigm (PSAP). Testosterone reactivity was measured via salivary hormone samples collected pre- and post-game. Moderated multiple regression analyses were run to examine the extent to which testosterone reactivity and shame proneness moderated the effect of Cyberball condition on aggression. Results revealed a significant two-way interaction between Cyberball condition and testosterone reactivity, as well as a three-way interaction including shame proneness. For individuals low in shame proneness, exclusion was associated with higher post-cyberball aggression among those who experienced a rise in testosterone but was associated with lower post-cyberball aggression among those who experienced a decrease in testosterone. For individuals high in shame proneness, however, exclusion did not meaningfully affect aggressive responses, regardless of whether they experienced an increase or decrease in testosterone. These findings extend our understanding of the moderating roles of context and disposition on the neuroendocrinology of aggression in social interaction

A Pediatric Case of LGI1 Autoimmune Encephalitis Presenting with Faciobrachial Dystonic Seizures (P5-5.014)

<h3>Objective:</h3> NA <h3>Background:</h3> 15-year-old male presented with acute behavioral changes (agitation, confusion, declining grades), frequent falls, and abnormal movements involving the right corner of the mouth, cheek, arm and hand. His lower face appeared to be pulling to the right with concomitant flexion of the ipsilateral elbow and wrist in a motion that brought his hand close to his face <h3>Design/Methods:</h3> NA <h3>Results:</h3> Continuous EEG demonstrated approximately 70 seizures with either right or left rhythmic delta activity and superimposed spikes with associated twitching or dystonia in the contralateral arm or hand. MRI imaging showed T2 hyperintensity of the left hippocampus and amygdala. His seizures were controlled after loading 3 ASM’s (lacosamide, levetiracetam, valproate) followed by IVIG and methyl prednisolone administration. The diagnosis was confirmed by Mayo autoimmune encephalitis panel that was positive in the CSF and serum for LGI1 (leucine-rich glioma-inactivated 1) antibody. <h3>Conclusions:</h3> LGI1 autoimmune encephalitis is the second most common autoimmune encephalitis after NMDA(N-Methyl-D-aspartate). It is most commonly seen in middle aged men and estimated to occur in 0.83 per million. LGI1 autoimmune encephalitis is associated with multiple seizure types including focal seizures and tonic clonic seizures. The most distinctive feature of LGI1 autoimmune encephalitis is faciobrachial dystonic seizures that have been reported extensively in adult patients. LGI1 autoimmune encephalitis with seizures is exceedingly rare in the pediatric population. We found only 6 reported cases. Our case is the first reported faciobrachial dystonic seizures at presentation in a pediatric patient. <b>Disclosure:</b> Dr. Fields has nothing to disclose. Dr. Dalvi has nothing to disclose. Dr. Duberstein Coad has nothing to disclose. Dr. Eizadkhah has nothing to disclose. Dr. Moshe has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier/Neurobiology Of Disease. Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Moshe has received publishing royalties from a publication relating to health care. Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as a Reviewer of study sections with NINDS.

Long-term and short term effects of elevated underwater sound on oyster toadfish (Opsanus tau)

The effects of underwater sound on fishes are of increasing concern for managers, regulators, and researchers. While there has been work which demonstrated changes in behavior, these studies have generally evaluated of immediate or near-term responses. Understanding acute changes in behavior is necessary, but questions about long-term responses to underwater sound, including any habituation and the relative influence of environmental conditions versus anthropogenic sound must also be investigated. To further elucidate potential response to chronic underwater vessel generated sound, passive acoustic monitoring was used to measure the response of vocalizing oyster toadfish (Opsanus tau) to vessel sounds within the Chesapeake Bay. An automatic detector was configured which allowed for counting of vessel passages and toadfish vocalizations. The response of vocalizing toadfish individual vessel movement was then evaluated. Next the response of toadfish to elevated sound levels across a 30-day period was measured and compared to short-term response. In addition, the influence of environmental variables and contrasted effects of these on the effects of increased anthropogenic sound was investigated.

Thermoregulatory, metabolic and stress responses to spring shearing of aged ewes born to undernourished mothers

Maternal undernutrition during gestation affects the behaviour, metabolism, and sensitivity to stressors of the offspring. Shearing is a stressor that triggers physiological and behavioural changes and augments the thermoregulatory demands in sheep. The aim of this study was to compare the thermoregulatory, metabolic, and behavioural responses to spring shearing of aged ewes born to mothers who grazed different pasture allowances during gestation. Nineteen non-gestating six-year-old Corriedale ewes born to mothers who grazed two pasture allowances from 23 days before conception until 122 days of gestation were used. The pasture allowance offered to the mothers was high [HPA group; n = 11; 10–12 kg of dry matter (DM)/100 kg of body weight (BW)/day] or low [LPA group: n = 8; 5–8 kg of DM/100 kg of BW/day]. The adult offspring of both experimental groups were sheared during spring (Day 0), and remained outdoors, grazing natural grassland, and the behaviour, the surface temperature and the rectal temperature were recorded. Blood concentrations of albumin, total protein, glucose, and insulin were also determined. Data were compared with a mixed model. The LPA ewes had lower ear and nose maximum and minimum surface temperatures before shearing (P < 0.05). On Day 15, the average surface temperature of the vulva was lower in LPA than in HPA ewes (P < 0.05). After shearing, rumination frequency was greater in HPA than in LPA ewes (P = 0.01), and LPA ewes were observed more time standing up than HPA ewes (P < 0.0001). Insulin concentration tended to be greater in LPA than HPA ewes (P = 0.06). Maternal undernutrition during gestation modified the thermoregulatory responses and the acute behavioural changes after shearing in aged female offspring, whilst the metabolism was affected to a lesser degree. The long-term effects noticed in this study highlight the importance of providing proper nutrition to pregnant ewes.

Fear, anxiety, and production in laying hens with healed keel bone fractures

For laying hens, the immediate aftermath and healing period of a keel fracture (KF) is characterized by reduced ability to perform species-specific behavior, access resources, and pain. However, the longer-term impacts, once the fracture is completely healed, are less clear. As well as acute pain and behavioral changes, a negative experience can shape future responses to putatively threatening stimuli, raising future fear, and anxiety levels during husbandry-related events. We aimed to determine whether hens that had previously sustained keel bone fractures, but were now outside of the peak age range for new fractures, showed higher fear and anxiety levels compared to intact hens. We also determined if healed keel bone fractures were associated with reduced production, changes in behavior and resource use. One hundred and fifty hens with a palpation score of 1 ( "KF") and 150 hens with a palpation score of 0 (keel fracture free, "KFF") were selected from a commercial farm at 63 wk of age and housed in 6 groups (3×KF and 3×KFF). We compared production (hen weight and feed consumption, egg quantity, quality and weight, floor eggs, shell thickness, and weight) and home pen behavior (behaviors and transitional movements) in both groups. Finally, we measured the responses of KF (n=75) and KFF (n=75) during tonic immobility, novel arena, and novel object tests. KF and KFF hens did not differ in their responses to the tonic immobility, novel arena, and novel object tests, nor were there differences between the 2 groups in home pen behavior and transitional movements. KFF birds were lighter and laid eggs with less eggshell membrane compared KF birds, but no differences were found between KF and KFF in any other production measures. We found no evidence that healed KFs were associated with detrimental welfare effects in laying hens, but further work is required to determine the mechanisms and implications of the lower body weight and egg shell membrane.

RARE CASE REPORT -AUTOIMMUNE LGI1 LIMBIC ENCEPHALITIS IN ELDERLY

Autoimmune encephalitis is one of the main causes of noninfectious encephalitis. Can be broadly classied into non-paraneoplastic, paraneoplastic and vasculitis associated encephalopathy. It can be triggered by tumors and infections. Autoimmune encephalitis presents with variety of clinical features such as acute onset behavioral changes, psychiatric symptoms, memory loss, movement disorders, dystonia, mutism and seizures. Neuronal antibodies are directed against cell surface Ag(CSAab) ,synaptic antigen (SyAab), intraneuronal Ag(INAab). Anti LG1 and CASPR2 encephalitis are usually non-neoplastic autoimmune encephalopathy where antibodies are directed against proteins associated with Voltage gated k channel. About 50% patients with anti-VGKC encephalitis do not present antibodies against LGI1 or CASPR-2. Anually 1 case is detected amongst 100000 patients. This is a case report of a patient presented to Geriatrics OPD and the series of evaluation which led to diagnosis and treatment outcome.

1241: IDENTIFICATION OF ACUTE BRAIN DYSFUNCTION IN PEDIATRIC SEPSIS USING FOUR DEFINITIONS

Introduction: Studies of acute brain dysfunction (ABD) in sepsis are limited by imprecise clinical variables suggestive of neurologic/behavioral dysfunction. We previously validated a new computational phenotype of ABD indicative of clinician concern for an acute change in neurologic/behavioral function. We hypothesized that this computational phenotype would identify ABD with higher sensitivity and specificity than common ABD criteria, including Proulx, Goldstein and the Pediatric Organ Dysfunction Information Update Mandate (PODIUM). Methods: We performed a retrospective study of 527 randomly selected pediatric sepsis episodes in a research sepsis registry from a single institution between 2011 and 2019. The reference standard for ABD was established using chart review for diagnosis of acute neurologic or behavioral change during sepsis. The computational phenotype defined ABD as completion of either brain imaging (CT or MRI) or electroencephalogram (EEG) irrespective of results and/or new antipsychotic administration. Proulx and Goldstein criteria defined ABD as Glasgow Coma Scale (GCS) < 5 and ≤11, respectively. PODIUM defined ABD as total GCS ≤8, motor GCS ≤4, Cornell Assessment of Pediatric Delirium (CAPD) score ≥9, or seizures, attenuation or suppression on EEG. Missing data were assumed to be normal (ie, not ABD). We used the probability test of proportions to compare sensitivity and specificity of the four criteria to identify ABD against the reference standard. Results: The 527 sepsis patients has a median age of 6.6 years [1.6-13.9] and were 54% male. 64% had more than one complex chronic condition and 36% had more than one non-neurologic organ dysfunctions. The computational phenotype was more sensitive to identify ABD (83%, 95%CI 76-89%) compared to Proulx (22%, 16-29%; p< 0.05), Goldstein (40%, 33-48%; p< 0.05), and PODIUM (73%, 66-80%; p=0.03). Specificity to exclude ABD was significantly higher for the computational phenotype (93%, 95% CI 90-96%) compared to Goldstein (73%, 68-77%; p< 0.05) and PODIUM (68%, 63-80%; p< 0.05), but not Proulx (93%, 90-95%; p=1.00). Conclusions: The computational phenotype identified ABD in pediatric sepsis with a higher combination of sensitivity and specificity than other commonly used criteria that rely heavily on GCS.

Teenager with acute psychosis due to non-paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis with a successful recovery: A case report

IntroductionAnti NMDAR encephalitis is a neuropsychiatric syndromic disease caused by an immunological response. Acute behavioral changes, psychosis, and catatonia are common clinical manifestations, are seizures, amnesia, speech difficulties, dyskinesia, and autonomic dysregulation.Case presentationWe discuss the case of a 14-year-old girl who had psychotic symptoms and tested positive for anti-NMDAR antibodies.DiscussionPatients present with psychiatric symptoms such as delusions, hallucinations, agitation, changes in speech mania, disorganized thinking, catatonia, insomnia, and often seizures. Anti-NMDAR encephalitis should be suspected in teenage patient with acute psychotic symptoms and seizure episodes. A multidisciplinary treatment strategy is required.ConclusionThe delayed treatment can lead to complications and delayed recovery complicating the disease process so multidisciplinary approach of treatment is necessary.

Acute Changes In Sedentary Behavior Following Aerobic Exercise In Overweight And Obese Females

Introduction: As the obesity epidemic continues to progress, the importance of participating in regular physical activity and maintaining a healthy diet is being emphasized more than ever. Exercise is often recommended to create a daily energy deficit in hopes that this deficit will result in weight loss. The reality is that weight loss due to an exercise induced energy deficit is typically less than predicted. It is hypothesized that the body attempts to counter balance the exercise induced energy deficit by reducing daily energy expenditure through an increase in daily sedentary behavior. Only a few studies have attempted to investigate this compensatory and many of these studies did not use technology that was specifically designed to measure sedentary behaviors. This study will utilize the activPal accelerometer which is designed to measure sedentary behaviors. Purpose: The purpose of this study was to compare acute changes in daily sedentary behavior between overweight (BMI ≥ 25) and obese (BMI ≥ 30) sedentary, college-age women over a 24-hour period, following either a 200 or 400 kcal bout of aerobic exercise (walking). Methods: Thirty-five participants completed three trials: control (no exercise), 200 kcal of exercise, and 400 kcal of exercise. The exercise consisted of walking on a treadmill at 70% of their heart rate reserve. The order of these trials were randomized. For the 200 and 400 kcal sessions, indirect calorimetry was used to measure energy expenditure. For 24 hours following each trial, changes in sedentary behavior were recorded using the activPal accelerometer. Data was analyzed using a repeated measures ANOVA. Results: There were no significant differences between the control, 200 kcal, or 400 kcal trials for sit/lie time (p = 0.230, 574.8 ± 145.5, 614.8 ± 108.4, 573.4 ± 150.9 min, respectively), standing time (p = 0.062, 231.4 ± 117.8, 185.5 ± 80.1, 219 ± 84.2 minutes respectively) or steps (p = 0.928, 7797.3 ± 3788.9, 7965.0 ± 3423.8, 7701.8 ± 3682.7 steps respectively). Conclusion: The results of this study show that daily sedentary behaviors in overweight/obese college age females does not significantly change following a single bout of aerobic exercise.

Koebner Phenomenon: a Clinical Clue of Systemic Sarcoidosis

We have a 57 year old female with past medical history significant only for hypothyroidism and generalized lymphadenopathy who presents with acute behavioral changes. She was minimally responsive on exam, nonverbal, and only weakly able to follow basic commands such as squeezing her hands. Her physical exam was notable for scarring of bilateral eyebrows (figures 1 and 2), which occurred three years ago when she had cosmetic tattooing of her eyebrows. She was accompanied by her husband who states that she does not take any medications at home other than levothyroxine. Clinical testing including neuroimaging with CT and MRI, EEG, CBC/CMP, TSH, HIV, RPR, urine drug screen, and CSF analysis were all normal. On a previous admission, patient had a full-body CT performed which showed extensive lymphadenopathy throughout the neck, bilateral hila, mesentery, and retroperitoneum. Bronchoscopy was performed at that time which did not yield any pathology. In addition, there are innumerable hypodense lesions invading the liver and spleen parenchyma, which was not worked up at this point. A biopsy of multiple liver lesions performed this admission showed noncaseating granulomas with no evidence of malignancy (figure 3). A diagnosis of neurosarcoidosis was made based on compatible clinical presentation, pathologic evidence of noncaseating granulomas, and exclusion of infection or malignancy. The patient was started on high-dose systemic corticosteroids with rapid return to baseline neurologic function. Isomorphic responses to skin trauma, such as in cosmetic tattooing in our patient, is known as Koebner phenomenon and can present as early clues of systemic sarcoidosis in the appropriate clinical context.

Rare neurological and neuropsychiatric manifestations of scrub typhus: a case series of 10 cases

IntroductionScrub typhus is a potentially life-threatening but curable disease that can produce multi-organ failure. Neurological manifestations in scrub typhus have gained attention recently, where the entire neural axis except the myoneural junction can be involved. Although the pathogenesis of neurological involvement has not been established, immune-mediated mechanisms are suspected. This article reports the clinicopathological features of scrub typhus cases presenting several rare neurological and neuropsychiatric manifestations. MethodsThree hundred fifty-four serologically confirmed scrub typhus cases were admitted to the Department of General Medicine of Burdwan Medical College and Hospital (West Bengal, India) between May 2018 and May 2022. There were 50 patients who had predominantly neurological manifestations. Of these 50 cases, ten patients presented with extremely rare neurological manifestations. ResultsWe report 10 cases of scrub typhus (four men and six women) who presented with complex neurological pictures (posterior reversible encephalopathy syndrome, Opalski syndrome, parkinsonism, cerebellitis, isolated opsoclonus, acute transverse myelitis, myositis, polyradiculoneuropathy with cranial neuropathy, acute transient behavioral changes, and fibromyalgia). Immune-mediated mechanisms might have mediated the pathogenesis of most cases following scrub typhus infection. ConclusionFrom a clinicopathological point of view, each case was unique in its presentation and treatment response. In any acute onset neurological disorders associated with febrile illness in the tropics or subtropics, scrub typhus infection should be included in the differential diagnosis, despite the absence of eschar and unremarkable neuroimaging findings. This otherwise curable disease may result in multi-organ dysfunction syndrome and death if the diagnosis is delayed.

Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain.

Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive signals in neonates. The current study aims to attenuate acute and long-term hypersensitivity associated with neonatal procedural pain using ondansetron (a 5-HT3 antagonist) and buspirone (a 5-HT1a agonist) in a well-established rat model of repetitive needle pricking. Sprague-Dawley rat pups of both sexes received ondansetron (3 mg/kg), buspirone (3 mg/kg) or saline prior to repetitive needle pricks into the left hind-paw from postnatal day 0–7. Control animals received tactile stimulation or were left undisturbed. Acute, long-term, and post-operative mechanical sensitivity as well as adult anxiety were assessed. Neonatal 5-HT1a receptor agonism completely reverses acute hypersensitivity from P0-7. The increased duration of postoperative hypersensitivity after re-injury in adulthood is abolished by 5-HT3 receptor antagonism during neonatal repetitive needle pricking, without affecting baseline sensitivity. Moreover, 5-HT1a and 5-HT3 receptor modulation decreases adult state anxiety. Altogether, our data suggests that targeted pharmacological treatment based on the modulation of spinal serotonergic network via the 5-HT1a and 5-HT3 receptors in neonates may be of use in treatment of neonatal procedural pain and its long-term consequences. This may result in a new mechanism-based therapeutic venue in treatment of procedural pain in human neonates.

Cytotoxicity and Acute Oral Toxicity Effects of Parkia Speciosa Seeds Extract in C57bl/6 Mice

Parkia speciosa is frequently consumed as a raw salad due to the notion that the plant exhibits numerous pharmacological activities that could benefit health particularly among Asians. This study was aimed to investigate the cytotoxicity and acute oral toxicity consequences of Parkia speciosa seeds extract against 4T1 mouse mammary cancer cells on C57BL/6 female mice. The antiproliferative effect of aqueous and ethanolic extracts was studied using the in-vitro antiproliferative assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Meanwhile, for acute toxicity study, twenty female mice were categorized into 5 groups, each with three aqueous extract treatment groups: 50 mg/kg, 300 mg/kg, 2000 mg/kg, meanwhile one vehicle group (treated with sterile distilled water), and one control group (no treatment given). Changes in behavioural signs, mortality rate, relative body weight, haematology, serum biochemistry, and organ histological evaluation were observed. Based on the MTT assay, the aqueous extract of Parkia speciosa was weakly active (IC50 = 312.5 ± 1.20 ug/ml) against 4T1 mammary cancer cells. In the acute study, no mortality, behavioural and physical changes were observed in any of the mice groups throughout the 14-day experiment. The haematological and serum biochemistry results of the treated and control groups showed no alteration. The kidney and liver were histopathologically evaluated and found to have normal organ architectures. Analyzed results could conclude that aqueous extract of Parkia speciosa has weakly active against cancer cells but has no deleterious effects on C57BL/6 mice given at high doses up to 2000 mg/kg.

Immunometabolic Stress and Ketone Bodies in Disorders of the Aging Brain

Delirium is an acute confusional state that is a common complication of acute illness in older adults, and is associated with increased risk of death, disability, and dementia. Delirium in older adults is an example of a geriatric syndrome, with multifactorial, multi-system causes that include existing aging-related physiological changes as well as external acute stressors. Its pathophysiology delirium is not well understood but may include glycolytic energy deficits associated with acute inflammation in the brain. The endogenous ketogenic system provides ketone bodies as a lipid-derived alternative to glucose for cellular energy, and ketone bodies are increasingly understood to have immunomodulatory effects particularly on innate immune cells. We used a mouse model of acute inflammation-associated behavioral change to investigate how age-related differences in energy utilization in the brain affect delirium-like phenotypes, focusing on energy metabolism and innate immune activation in the brain as an example of immunometabolic approaches to geriatric syndromes.

Antioxidant property, haematinic and biosafety effect of Ipomoea batatas lam. leaf extract in animal model

BackgroundPlant medicine was dated back for decades and has immensely contributed to the health care system in several countries. This present study evaluated in vitro antioxidant, anti-anaemic and biosafety properties of n-hexane leaf extract of Ipomoea batatas L. in an animal model. The antioxidant property of the extract was expressed by 1, 1-diphenyl-1-picrylhydrazyl (DPPH) with an appropriate method. The extract was orally administered at graded doses (125, 250 and 500 mg/kg body weight) to determine its effect on 40 mg/kg phenylhydrazine hydrochloride-induced anaemia in rats at days 1, 7 and 14 using a standard protocol. Acute and subacute toxicological evaluations were based on initial behaviour, mortality and histological examination of the organs.ResultsThe antioxidant study of the extract showed 60.14% in the presence of DPPH and ascorbic acid. The haematological parameters (RBC, HGB, HCT, MCV, MCH and MCHC) significantly increased at p value < 0.05 in the treated groups compared with control groups. Specifically, there is a significant increase in the treatment groups, namely red blood cells (5.93, 6.78, 6.75), haematocrit (40.75, 44.05, 44.63) and haemoglobin (13.35, 14.70, 14.73), when compared with untreated control. Also, the results of the myeloid/erythroid ratio of the treated groups (20: 40, 21.7: 43.4 ratio) and (23. 3: 46.6 ratio) are compared with (15.0: 25.0 ratio) of 40 mg/kg phenylhydrazine and 25: 50 normal control of the bone marrow at day 14. No acute behavioural change or mortality was observed. Histological analysis exhibited normal physiological state of the visceral organs.ConclusionsThese findings support the folklore use of Ipomoea batatas L. leaf extract to reduce oxidative stress, treat anaemia and exhibit its safety at the highest doses of 500 mg/kg body weight.