Interactions between arm and leg neuronal circuits following paired cervical and lumbosacral transspinal stimulation in healthy humans.

Transspinal (or transcutaneous spinal cord) stimulation is a promising noninvasive method that may strengthen the intrinsic spinal neural connectivity in neurological disorders. In this study we assessed the effects of cervical transspinal stimulation on the amplitude of leg transspinal evoked potentials (TEPs), and the effects of lumbosacral transspinal stimulation on the amplitude of arm TEPs. Control TEPs were recorded following transspinal stimulation with one cathode electrode placed either on Cervical 3 (21.3 ± 1.7 mA) or Thoracic 10 (23.6 ± 16.5 mA) vertebrae levels. Associated anodes were placed bilaterally on clavicles or iliac crests. Cervical transspinal conditioning stimulation produced short latency inhibition of TEPs recorded from left soleus (ranging from - 6.11 to -3.87% of control TEP at C-T intervals of -50, -25, -20, -15, -10, 15 ms), right semitendinosus (ranging from - 11.1 to -4.55% of control TEP at C-T intervals of -20, -15, 15 ms), and right vastus lateralis (ranging from - 13.3 to -8.44% of control TEP at C-T intervals of -20 and - 15 ms) (p < 0.05). Lumbosacral transspinal conditioning stimulation produced no significant effects on arm TEPs. We conclude that in the resting state, cervical transspinal stimulation affects the net motor output of leg motoneurons under the experimental conditions used in this study. Further investigations are warranted to determine whether this protocol may reactivate local spinal circuitry after stroke or spinal cord injury and may have a significant effect in synchronization of upper and lower limb muscle synergies during rhythmic activities like locomotion or cycling.

Soleus H-reflex amplitude modulation during walking remains physiological during transspinal stimulation in humans.

The soleus H-reflex modulation pattern was investigated during stepping following transspinal stimulation over the thoracolumbar region at 15, 30, and 50 Hz with 10 kHz carry-over frequency above and below the paresthesia threshold. The soleus H-reflex was elicited by posterior tibial nerve stimulation with a single 1 ms pulse at an intensity that the M-wave amplitudes ranged from 0 to 15% of the maximal M-wave evoked 80 ms after the test stimulus, and the soleus H-reflex was half the size of the maximal H-reflex evoked on the ascending portion of the recruitment curve. During treadmill walking, the soleus H-reflex was elicited every 2 or 3 steps, and stimuli were randomly dispersed across the step cycle which was divided in 16 equal bins. For each subject and condition, the soleus M-wave and H-reflex were normalized to the maximal M-wave. The soleus background electromyographic (EMG) activity was estimated as the linear envelope for 50 ms duration starting at 100 ms before posterior tibial nerve stimulation for each bin. The gain was determined as the slope of the relationship between the soleus H-reflex and the soleus background EMG activity. The soleus H-reflex phase-dependent amplitude modulation remained unaltered during transspinal stimulation, regardless frequency, or intensity. Similarly, the H-reflex slope and intercept remained the same for all transspinal stimulation conditions tested. Locomotor EMG activity was increased in knee extensor muscles during transspinal stimulation at 30 and 50 Hz throughout the step cycle while no effects were observed in flexor muscles. These findings suggest that transspinal stimulation above and below the paresthesia threshold at 15, 30, and 50 Hz does not block or impair spinal integration of proprioceptive inputs and increases activity of thigh muscles that affect both hip and knee joint movement. Transspinal stimulation may serve as a neurorecovery strategy to augment standing or walking ability in upper motoneuron lesions.

Effects of virtual reality versus motor imagery versus routine physical therapy in patients with parkinson's disease: a randomized controlled trial.

BACKGROUND: Parkinson's Disease (PD) is the second most common progressive neurodegenerative disorder, mostly affecting balance and motor function caused mainly by a lack of dopamine in the brain. The use of virtual reality (VR) and motor imagery (MI) is emerging as an effective method of rehabilitation for people with Parkinson's disease. Motor imagery and virtual reality have not been compared in patients with Parkinson's disease. This randomized clinical trial is unique to compare the effects of virtual reality with routine physical therapy, motor imagery with routine physical therapy, and routine physical therapy alone on balance, motor function, and activities of daily living in patients with Parkinson's disease. METHODS: A total of sixty patients with Parkinson's disease were randomized into three groups using lottery method; twenty with virtual reality therapy in addition to physical therapy (group A = VR + RPT), twenty with imagery therapy in addition to physical therapy (group B = MI + RPT), and twenty were treated with only routine physical therapy (group C = RPT). All patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) for motor function and activities of daily living, the Berg balance scale (BBS) for balance, and the Activities-specific Balance Confidence Scale (ABCs) for balance confidence at baseline, six and twelve weeks, and one month after treatment discontinuation. The one-way ANOVA was used to compare the outcomes between three groups, and the repeated measures ANOVA was used to compare the outcomes within each of the three groups at a significance level of p-value = 0.05. RESULTS: According to UPDRS III, the VR + RPT group showed significant improvement in motor function, compared to the MI + RPT and RPT groups, as the Mean ± SD at baseline was 33.95 ± 3.501 and at the 12-week assessment was 17.20 ± 9.451 with a p-value = 0.001. In the VR + RPT group, the BBS score at baseline was 37.15 ± 3.437 and at 12th week was 50.10 ± 4.897 with a p-value = 0.019. Among the VR + RPT group, the ABCS score showed significant improvement as the M ± SD at baseline was 57.95 ± 4.629, and at the 12th week was 78.59 ± 6.386 with a p-value = 0.010. At baseline, the UPDRS II for activities of daily living in the VR + RPT group was 25.20 ± 3.036 and at 12th week it was 15.30 ± 2.364 with p-value of 0.000. CONCLUSION: The current study found that the combination of VR and RPT proved to be the most effective treatment method for improving balance, motor function, and activities of daily living in patients with Parkinson's disease when compared to MI + RPT or RPT alone.

Insights into the involvement of male Hyalomma anatolicum ticks in transmitting Anaplasma marginale, lumpy skin disease virus and Theileria annulata.

Ticks can transmit viruses, bacteria, and parasites to humans, livestock, and pet animals causing tick-borne diseases (TBDs) mechanically or biologically in the world. Lumpy skin disease virus, Anaplasma marginale, and Theileria annulata inflict severe infections in cattle, resulting in significant economic losses worldwide. The study investigated the potential transmissions of LSDV, A. marginale, and T. annulata through male Hyalomma anatolicum ticks in cattle calves. Two 6-month-old Holstein crossbred calves designated as A and B were used. On day 1, 15 uninfected female ticks (IIa) and infected batch of 40 male ticks (I) were attached on calf A for 11 days. Filial transmission of the infections was observed in female ticks (IIb) collected from calf A, where 8 female ticks had been co-fed with infected male ticks. The blood sample of calf B was found positive through PCR for the infections. The larvae and egg pools obtained from the infected ticks were also tested positive in PCR. The study confirmed the presence of these mixed pathogens and potential intra-stadial and transovarial transmissions of A. marginale, T. annulata, and LSDV in male and female ticks of H. anatolicum and experimental calves to establish the feasibility of infections through an in vivo approach.

Adherence to the Mediterranean Diet in Saudi Arabia and Its Association with Socioeconomic Status and Depression.

Background and Objectives: Several RCTs have reported significant reductions in depression symptoms with the Mediterranean diet (MedDiet), but observational studies have reported inconsistent findings. Moreover, studies have rarely investigated the mediating role of socioeconomic status (SES), including objective material status, in adherence to the MedDiet and its impact on depressive symptoms in the same population. Therefore, this cross-sectional study investigated the relationship between adherence to the MedDiet, socioeconomic factors, and depression severity. Materials and Methods: A cross-sectional online survey was conducted between June and December 2022 across Saudia Arabia. The snowball sampling technique was used to recruit participants aged ≥18 years. Mediterranean diet adherence screener (MEDAS) and Patient Health Questionnaire-9 (PHQ-9) were used to assess adherence to the MedDiet and depression severity. An SES index, validated in the Saudi Arabian context, was used to assess SES. The data were analyzed using the Chi-square and Pearson's correlation tests. Results: Only 21% of our study population (n = 467) was MedDiet adherent. Adherence was significantly associated with education (p = 0.014) but not employment status among traditional SES indicators. Similarly, only television ownership (p = 0.009) was associated with MedDiet adherence among the 20 objective material possessions investigated. Nonetheless, the MedDiet-adherent group had a significantly lower PHQ-9 score than the non-adherent group (6.16 ± 0.68 vs. 8.35 ± 0.31, p = 0.002). A moderate but significantly negative correlation between MEDAS and PHQ-9 scores (r = -0.16, p = 0.001) was noted. Conclusions: MedDiet adherence was associated with lower depression severity scores. In addition to education and television ownership, adherence was not associated with any objective indicators of SES.

Lipid extraction and analysis of microalgae strain pectinodesmus PHM3 for biodiesel production.

The current study is focused on the lipid extract of microalgae; Pectinodesmus strain PHM3 and its general analysis in terms of chemical contents. Combinations of both chemical and mechanistic approaches were applied to obtain the maximum yield of lipids which was recorded to be 23% per gram through continuous agitation using Folch solution. The extraction methods used in this study included: Bligh and Dyers method, Continuous agitation method, Extraction using Soxhlet and Acid base extraction method. Lipid quantification of ethanol and Folch solution lipid extract was performed through gravimetric methods and qualification was done through Fourier Transmission Infrared Spectroscopy (FTIR) and Gas Chromatographymass spectrometry (GC-MS). Phytochemical analysis identified other compounds in ethanol extract and the results confirmed the presence of steroids, coumarins, tannins, phenols and carbohydrates. Transesterification of lipids showed 7% per gram dry weight yield of Pectinodesmus PHM3. GC-MS studies of extracted biodiesel suggested that 72% of biofuels was in the form of dipropyl ether, ethyl butyl ethers, methyl butyl ether and propyl butyl ether. Lipid processing of acid-base extract showed that oily nature of lipid shifted to a more precipitated form which is a common observation when mixture of lipids is converted to phosphatides.

Bosniak classification version 2019: a prospective comparison of CT and MRI.

OBJECTIVE: To assess the diagnostic accuracy and agreement of CT and MRI in terms of the Bosniak classification version 2019 (BCv2019). MATERIALS AND METHODS: A prospective multi-institutional study enrolled 63 patients with 67 complicated cystic renal masses (CRMs) discovered during ultrasound examination. All patients underwent CT and MRI scans and histopathology. Three radiologists independently assessed CRMs using BCv2019 and assigned Bosniak class to each CRM using CT and MRI. The final analysis included 60 histopathologically confirmed CRMs (41 were malignant and 19 were benign). RESULTS: Discordance between CT and MRI findings was noticed in 50% (30/60) CRMs when data were analyzed in terms of the Bosniak classes. Of these, 16 (53.3%) were malignant. Based on consensus reviewing, there was no difference in the sensitivity, specificity, and accuracy of the BCv2019 with MRI and BCv2019 with CT (87.8%; 95% CI = 73.8-95.9% versus 75.6%; 95% CI = 59.7-87.6%; p = 0.09, 84.2%; 95% CI = 60.4-96.6% versus 78.9%; 95% CI = 54.4-93.9%; p = 0.5, and 86.7%; 95% CI = 64.0-86.6% versus 76.7%; 95% CI = 75.4-94.1%; p = 0.1, respectively). The number and thickness of septa and the presence of enhanced nodules accounted for the majority of variations in Bosniak classes between CT and MRI. The inter-reader agreement (IRA) was substantial for determining the Bosniak class in CT and MRI (k = 0.66; 95% CI = 0.54-0.76, k = 0.62; 95% CI = 0.50-0.73, respectively). The inter-modality agreement of the BCv219 between CT and MRI was moderate (κ = 0.58). CONCLUSION: In terms of BCv2019, CT and MRI are comparable in the classification of CRMs with no significant difference in diagnostic accuracy and reliability. KEY POINTS: • There is no significant difference in the sensitivity, specificity, and accuracy of the BCv2019 with MRI and BCv2019 with CT. • The number of septa and their thickness and the presence of enhanced nodules accounted for the majority of variations in Bosniak classes between CT and MRI. • The inter-reader agreement was substantial for determining the Bosniak class in CT and MRI and the inter-modality agreement of the BCv219 between CT and MRI was moderate.

Impact of trans-anal versus laparoscopic total mesorectal excision on the surgical and pathologic outcomes of patients with rectal cancer: meta-analysis of randomized controlled trials.

BACKGROUND: Despite its profound impact on the oncologic outcomes of rectal cancer, the most optimal surgical approach to total mesorectal excision (TME) has not been identified yet. All previous meta-analyses on this subject have been based on observational studies. This meta-analysis was conducted to assess the surgical and oncologic outcomes of laparoscopic TME (LaTME) compared to trans-anal TME (TaTME), utilizing only randomized controlled trials. DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: We searched electronic databases (MEDLINE, Cochrane CENTRAL, Clinicaltials.gov) from 2010 onwards, for all published clinical trials comparing TaTME to LaTME. Results are presented as risk ratios, with 95% CI, and pooled using the random effects model. RESULTS: A total of 1691 patients, from 6 eligible randomized controlled trials, were included for analysis. Analyzed data showed no significant difference in morbidity (RR: 0.85, p = 0.15), mortality (RR: 0.50, p = 0.44), conversion to open (RR: 0.40, p = 0.07), or anastomotic leakage (RR: 0.73, p = 0.10) between TaTME and LaTME. There was also no difference in the rate of positive distal resection margin (DRM) (RR: 0.55, p = 0.10) or positive circumferential resection margin (CRM) (RR: 0.67, p = 0.30). Patients undergoing TaTME were more likely to have a complete TME (RR: 1.06, p = 0.002) and shorter hospital stays (RR: - 0.97, p < 0.00001). CONCLUSIONS: Patients undergoing TaTME for rectal cancer were more likely to have a complete TME when compared to LaTME, though this did not translate into improved distal or circumferential resection margin. Additionally, TaTME and LaTME had similar surgical outcomes except for shorter length of stay with TaTME.

DOCUMENTATION OF TRYPANOSOMA EVANSI IN CAPTIVE TIGERS AND LIONS IN PUNJAB (2016-2018), PAKISTAN.

Trypanosoma evansi is an important hemoparasite of a variety of animal species worldwide. This parasite is a threat to the health of domestic animals as well as wild animals, particularly those managed in captivity. The current study investigated the presence of T. evansi in captive tigers (Panthera tigris tigris) and lions (Panthera leo) in Pakistan. In total, 24 blood samples from 11 tigers and 3 lions (n = 14) were collected during the course of roughly 3 yr (2016-2018). Eighteen samples were subjected to both microscopic and molecular evaluation for the presence of T. evansi; the remaining 6 samples were processed for PCR only. Of the 18 samples tested by both methods, 3 (16%) and 8 (44%) were positive by microscopy and PCR, respectively. This highlights the higher sensitivity of PCR over microscopy for detection of trypanosomes. Of the 24 total samples evaluated by PCR, 12 (50%) were positive. The three sequences obtained showed 99% identity with variant surface glycoprotein genes of the different isolates of T. evansi. The sensitivity, specificity, positive predictive value, and negative predictive value of microscopy in identifying T. evansi was 37.5, 100, 100, and 66.7%, respectively, considering PCR as the gold standard. We recommend rigorous monitoring of captive tigers and lions for hemoparasites, particularly in winter and early spring in areas with high infection rate of this parasite, preferably via PCR.

Performance and limitations of automated ECG interpretation statements in patients with suspected acute coronary syndrome.

BACKGROUND: The 12­lead ECG plays an important role in triaging patients with symptomatic coronary artery disease, making automated ECG interpretation statements of "Acute MI" or "Acute Ischemia" crucial, especially during prehospital transport when access to physician interpretation of the ECG is limited. However, it remains unknown how automated interpretation statements correspond to adjudicated clinical outcomes during hospitalization. We sought to evaluate the diagnostic performance of prehospital automated interpretation statements to four well-defined clinical outcomes of interest: confirmed ST- segment elevation myocardial infarction (STEMI); presence of actionable coronary culprit lesions, myocardial necrosis, or any acute coronary syndrome (ACS). METHODS: An observational cohort study that enrolled consecutive patients with non-traumatic chest pain transported via ambulance. Prehospital ECGs were obtained with the Philips MRX monitor from the medical command center and re-processed using manufacturer-specific diagnostic algorithms to denote the likelihood of >>>Acute MI<<< or >>>Acute Ischemia<<<. Two independent reviewers retrospectively adjudicated the study outcomes and disagreements were resolved by a third reviewer. RESULTS: Our study included 2400 patients (age 59 ± 16, 47% females, 41% Black), with 190 (8%) patients with documented automated diagnostic statements of acute MI or acute ischemia. The sensitivity/specificity of the automated algorithm for detecting confirmed STEMI (n = 143, 6%); presence of actionable coronary culprit lesions (n = 258, 11%), myocardial necrosis (n = 291, 12%), or any ACS (n = 378, 16%) were 62.9%/95.6%; 37.2%/95.6%; 38.5%/96.4%; and 30.7%/96.3%, respectively. CONCLUSION: Although being very specific, automated interpretation statements of acute MI/acute ischemia on prehospital ECGs are not satisfactorily sensitive to exclude symptomatic coronary disease. Patients without these automated interpretation statements should be considered further for significant underlying coronary disease based on the clinical context. TRIAL REGISTRATION: ClinicalTrials.gov # NCT04237688.

Identifying the most important ECG predictors of reduced ejection fraction in patients with suspected acute coronary syndrome.

BACKGROUND: Non-invasive screening tools of cardiac function can play a significant role in the initial triage of patients with suspected acute coronary syndrome. Numerous ECG features have been previously linked with cardiac contractility in the general population. We sought to identify ECG features that are most predictive for real-time screening of reduced left ventricular ejection fraction (LVEF) in the acute care setting. METHODS: We performed a secondary analysis of a prospective, observational cohort study of patients evaluated for suspected acute coronary syndrome. We included consecutive patients in whom an echocardiogram was performed during indexed encounter. We evaluated 554 automated 12-lead ECG features in multivariate linear regression for predicting LVEF. We then used regression trees to identify the most important predictive ECG features. RESULTS: Our final sample included 297 patients (aged 63 ± 15, 45% females). The mean LVEF was 57% ± 13 (IQR 50%-65%). In multivariate analysis, depolarization dispersion in the horizontal plane; global repolarization dispersion; and abnormal temporal indices in inferolateral leads were all independent predictors of LVEF (R2 = 0.452, F = 6.679, p < 0.001). Horizontal QRS axis deviation and prolonged ventricular activation time in left ventricular apex were the most important determinants of reduced LVEF, while global QRS duration was of less importance. CONCLUSIONS: Poor R wave progression in precordial leads with dominant QS pattern in V3 is the most predictive feature of reduced LVEF in suspected ACS. This feature constitutes a simple visual marker to aid clinicians in identifying those with impaired cardiac function.

Carbon monoxide attenuates vasospasm and improves neurobehavioral function after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating form of hemorrhagic stroke and is a serious medical condition caused by bleeding usually due to a ruptured aneurysm. Oxidative stress and inflammation from hemoglobin and heme released from lysed red blood cells are some postulated causes of vasospasm during SAH, which could lead to delayed cerebral ischemia. At low amounts, carbon monoxide (CO) gas may be neuroprotective through anti-inflammation, anti-cell death, and restoration of normal blood flow. Hence, this study focuses on a noninvasive strategy to treat SAH by using CO as a therapeutic medical gas. Mice were treated with 250 ppm CO or air for 1h started at 2h after SAH. Various anatomical and functional outcomes were monitored at 1 and 7d after SAH. CO decreased neurological deficit score (47.4 ±â€¯10.5%) and increased activity (30.0 ±â€¯9.1%) and stereotypic counts (261.5 ±â€¯62.1%) at 7d. There was a significant increase in lumen area/wall thickness ratio in the middle cerebral artery (173.5 ±â€¯19.3%), which tended to increase in the anterior cerebral artery (25.5 ±â€¯4.3%) at 7d. This is the first report to demonstrate that CO minimizes delayed SAH-induced neurobehavioral deficits, which suggests that post-treatment with CO gas or CO-donors can be further tested as a potential therapy against SAH.

Molecular characterization of Hepatozoon canis from farm dogs in Pakistan.

Hepatozoon canis is a tick-borne pathogen of canids, which is distributed worldwide. However, very little is known about this protozoan parasite in Pakistan. This study provides the first molecular evidence of H. canis from farm dogs from three agro-ecological zones of Punjab, Pakistan. A conventional PCR targeting the 18S rRNA gene was used to characterize H. canis from farm dogs from three districts, namely Kasur, Rawalpindi, and Muzaffargarh, in Punjab. Of 341 blood samples tested, 155 (45.5%) were positive for H. canis, 73 (61.3%) from Kasur, 46 (42.5%) from Rawalpindi, and 36 (31.5%) from Muzaffargarh. Phylogenetic analyses revealed that 18S rRNA sequences of H. canis from this study clustered in three clades with those of H. canis from previously published studies to the exclusion of all other Hepatozoon spp. included in the analysis. This study provides the first insight into H. canis from farm dogs in Pakistan. Furthermore, it lays a foundation for future studies of the parasite to assess the impact of canine hepatozoonosis in dogs from various agro-ecological zones in Pakistan where pet ownership of dogs is increasing.

Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old mice.

The consumption of flavan-3-ol-containing foods, including (-)-epicatechin (EC), has been linked to lower incidence of cardiovascular disease and stroke. We previously demonstrated nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) -dependent EC efficacy in reducing stroke-induced deficits in 2-mo-old mice; yet stroke is primarily a disease of the elderly. Because neuroinflammation, oxidative stress, and vascular dysfunction are hallmarks of aging, we tested whether Nrf2 mediates EC efficacy in aging mice through modulation of glial responses and blood brain barrier permeability. First, we compared anastomosis in naïve wild-type and C57BL/6 Nrf2(-/-) mice to identify potential differences in cerebrovascular architecture. Data showed no significant differences in the number of anastomoses or mean intersection points, indicating similar gross vascular physiology. To assess efficacy and mechanisms of protection, wild-type or Nrf2(-/-) mice were administered the minimum effective EC dose established in our previous studies before the permanent distal middle cerebral artery occlusion. Similar to previous results with young mice, 12-mo-old wild types also showed significant reductions in infarct volume (41.01 ± 29.57%) and improved performance in removing adhesive tape relative to vehicle-treated controls, whereas a trend toward protection was observed in Nrf2(-/-). However, EC did not reduce immunoreactivity for the microglia/macrophage marker anti-ionized calcium-binding adapter molecule 1, suggesting that dampened activation/recruitment did not account for EC protection. Furthermore, there were no differences in mouse IgG extravasation or spontaneous hemorrhage between EC-treated groups. These data demonstrate that EC protection occurs independent of microglia/macrophage modulation or blood brain barrier preservation, suggesting that the glial cell responses in young mice are compensatory to another, and potentially novel, protective mechanism.

Intracerebral hemorrhage outcomes following selective blockade or stimulation of the PGE2 EP1 receptor.

BACKGROUND: Inflammation following intracerebral hemorrhage (ICH) significantly contributes to secondary brain damage and poor outcomes. Prostaglandin E2 (PGE2) is known to modulate neuroinflammatory responses and is upregulated in response to brain injury as a result of changes in inducible cyclooxygenase 2 (COX-2) and the membrane-bound type of PGE synthase. Inhibition of COX-2 activity has been reported to attenuate ICH-induced brain injury; however, the clinical utility of such drugs is limited due to the potential for severe side effects. Therefore, it is now important to search for downstream targets capable of preferentially modulating PGE2 signaling, and the four E prostanoid receptors, EP1-4, which are the main targets of PGE2, remain a viable therapeutic option. We have previously shown that EP1 receptor deletion aggravates ICH-induced brain injury and impairs functional recovery, thus the current study aimed to elaborate on these results by including a pharmacologic approach targeting the EP1 receptor. RESULTS: Chronic post-treatment with the selective EP1 receptor antagonist, SC-51089, increased lesion volume by 30.1 ± 14.5% (p < 0.05) and treatment with the EP1 agonist, 17-pt-PGE2, improved neuromuscular functional recovery on grip strength (p < 0.01) and hanging wire (p < 0.05) behavioral testing. To begin identifying the mechanisms involved in EP1-mediated neuroprotection after ICH, histology was performed to assess ferric iron content, neuroinflammation, leukocyte transendothelial migratory potential, and peripheral neutrophil and immunoglobulin infiltration. Following ICH, mice treated with the antagonist displayed increased ferric iron (p < 0.05) and cortical microgliosis (p < 0.05), whereas treatment with the agonist decreased cortical (p < 0.01) and striatal (p < 0.001) astrogliosis, leukocyte transendothelial migratory potential (p < 0.01), neutrophil infiltration (p < 0.05), and blood brain barrier breakdown (p < 0.05). CONCLUSIONS: In agreement with our previous results, selective antagonism of the EP1 receptor aggravated ICH-induced brain injury. Furthermore, EP1 receptor agonism improved anatomical outcomes and functional recovery. Thus, the present data continues to reinforce a putative role for EP1 as a new and more selective therapeutic target for the treatment of ICH that could reduce the side effects associated with COX-2 inhibition while still exploiting the beneficial effects.

Carl Wernicke of the Wernicke Area: A Historical Review.

The Wernicke area, also known as Brodmann area 22, is located in the posterior segment of the superior temporal gyrus in the dominant hemisphere. Carl Wernicke, a German neurologist, described this area in 1874. The life story of Carl Wernicke, a 19th-century medical genius, remains an inspiration for all neuroscientists even a hundred years later. We outline Wernicke's life story and academic achievements in neurosurgery, neurology, and psychiatry. We explore his remarkable ability to turn his many setbacks into steps forward, his controversial foray into psychiatry, and his wide-ranging set of contributions, including his work on external ventricular drainage for hydrocephalus and encephalopathy; his description of the eponymous Wernicke area; and his field-defining work on aphasia. This historical review attempts to bring to life a seminal figure in the neurosciences, providing an insight into his visionary thought process.

Loss of AMPK potentiates inflammation by activating the inflammasome after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a significant public health concern characterized by a complex cascade of cellular events. TBI induces adenosine monophosphate-activated protein kinase (AMPK) dysfunction impairs energy balance activates inflammatory cytokines and leads to neuronal damage. AMPK is a key regulator of cellular energy homeostasis during inflammatory responses. Recent research has revealed its key role in modulating the inflammatory process in TBI. Following TBI the activation of AMPK can influence various important pathways and mechanisms including metabolic pathways and inflammatory signaling. Our study investigated the effects of post-TBI loss of AMPK function on functional outcomes inflammasome activation, and inflammatory cytokine production. Male C57BL/6 adult wild-type (WT) and AMPK knockout (AMPK-KO) mice were subjected to a controlled cortical impact (CCI) model of TBI or sham surgery. The mice were tested for behavioral impairment at 24 h post-TBI thereafter, mice were anesthetized, and their brains were quickly removed for histological and biochemical evaluation. In vitro we investigated inflammasome activation in mixed glial cells stimulated with lipopolysaccharides+ Interferon-gamma (LI) (0.1 µg/20 ng/ml LPS/IFNg) for 6 h to induce an inflammatory response. Estimating the nucleotide-binding domain, leucine-rich-containing family pyrin domain containing western blotting ELISA and qRT-PCR performed 3 (NLRP3) inflammasome activation and cytokine production. Our findings suggest that TBI leads to reduced AMPK phosphorylation in WT mice and that the loss of AMPK correlates with worsened behavioral deficits at 24 h post-TBI in AMPK-KO mice as compared to WT mice. Moreover compared with the WT mice AMPK-KO mice exhibit exacerbated NLRP3 inflammasome activation and increased expression of proinflammatory mediators such as IL-1b IL-6 TNF-a iNOS and Cox 2. These results align with the in vitro studies using brain glial cells under inflammatory conditions, demonstrating greater activation of inflammasome components in AMPK-KO mice than in WT mice. Our results highlighted the critical role of AMPK in TBI outcomes. We found that the absence of AMPK worsens behavioral deficits and heightens inflammasome-mediated inflammation thereby exacerbating brain injury after TBI. Restoring AMPK activity after TBI could be a promising therapeutic approach for alleviating TBI-related damage.

A case report of primary hydatidosis of ulna and adjacent soft tissue.

Hydatidosis, is a zoonotic disease prevalent in sheep-raising regions globally. Musculoskeletal hydatidosis is uncommon and usually remains asymptomatic over a long period. The detection of musculoskeletal hydatidosis often signifies extensive cyst spread within the bone marrow cavity, making treatment difficult with a high recurrence rate. Unlike the conventional surgical approach for visceral hydatid cysts, treating osseous hydatidosis requires a strategy akin to oncologic therapy. We report a rare case of primary hydatidosis affecting the ulna and adjacent soft tissue in a 58-year-old woman. She presented with a painless forearm mass evolving over six years, accompanied by recent onset tenderness and restricted elbow joint mobility. Imaging revealed a cystic mass in the forearm, an intra-ulnar bone lesion, and an olecranon fracture. The primary diagnosis of musculoskeletal hydatidosis was made based on clinical findings and radiological imaging. Treatment involved resection of 2/3 of the proximal ulna and pericystectomy for the soft tissue hydatid cyst. Diagnosis of musculoskeletal hydatidosis is vital for effective preoperative planning, as internal fixation often fails without eradicating the infestation. Treatment typically involves radical operation with wide excision of the affected bone and adjacent joint structures, coupled with chemotherapy. Clinicians in endemic regions should consider musculoskeletal hydatidosis in the differential diagnosis of osteolytic lesions and slow-growing cystic masses. Diagnosis relies on clinical, serological, and radiological assessments.

Zuranolone for treatment of major depressive disorder: a systematic review and meta-analysis.

Background: Current treatment modalities for Major Depressive Disorder have variable efficacies and a variety of side effects. To amend this, many trials for short term, well tolerated monotherapies are underway. One such option is Zuranolone (SAGE-217), which is a recent FDA approved antidepressant for Post Partum depression (PPD) and is undergoing clinical trials for PPD, major depressive disorder (MDD) and essential tremors (ET). Objectives: Pool currently available data that compare Zuranolone to Placebo for the treatment of Major Depressive Disorder and evaluate its efficacy and safety profile. Methods: We retrieved data from PUBMED and SCOPUS from inception to July 2023. We included articles comparing Zuranolone or SAGE 217 with placebo in patients suffering from Major Depressive Disorder. Review Manager 5.4 was used to analyze the outcomes including changes in the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline as well as any treatment emergent adverse events (TEAEs) and severe adverse events. Results: Our review analyzed 4 trials and the data of 1,357 patients. Patients treated with Zuranolone indicated a statistically significant effect in the change from baseline in HAM-D score (p = 0.0009; MD [95% CI]: -2.03 [-3.23, -0.84]) as well as in MADRS score (p = 0.02; MD [95% CI]: -2.30[-4.31, -0.30]) and HAM-A score (p = 0.03; MD [95% CI]: -1.41[-2.70, -0.11]) on 15th day when compared to the Placebo group. Zuranolone was also significantly associated with a higher response rate (p = 0.0008; OR [95% CI]: 1.63[1.14, 2.35]) and higher remission rate (p = 0.03; OR [95% CI]: 1.65[1.05, 2.59]) when compared with the placebo. As for safety, Zuranolone was significantly associated with 1 or more TEAE (p = 0.006; RR [95% CI]: 1.14[1.04, 1.24]) but an insignificant association with side effects that lead to drug discontinuation (p = 0.70; RR [95% CI]: 1.18[0.51, 2.76]) and serious adverse events (p = 0.48; RR [95% CI]: 1.46 [0.52, 4.10]) when compared with placebo. Conclusion: Zuranolone is an effective and safe drug for short course major depressive disorder monotherapy. It shows results in 14 days (compared to 2-4 weeks that SSRI's take) and has anti-anxiolytic effects as well. However, only 4 trials have been used for the analysis and the sample size was small. The trials reviewed also cannot determine the long-term effects of the drug. More trials are needed to determine long term effects.