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The article presents the case of a 48-year-old man with rapidly progressing parkinsonism, cognitive impairment, and sleep abnormalities, resembling anti-Immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease but linked to anti-amphiphysin antibodies.Topics include antibody-mediated parkinsonism, rapidly progressive parkinsonism associated with underlying malignancy, and the role of immunotherapy in treating immune-related parkinsonism.

Introduction: Cabozantinib is a multikinase inhibitor agent used in the treatment of hepatocellular, renal, and thyroid cancers. The development of heart failure after cabozantinib initiation is an extremely rare side effect, with only four case reports published in the literature. We describe a case of cabozantinib-induced cardiac failure in a patient with thyroid cancer refractory to standard treatment. Case report: Fifty-seven-year-old woman had no history of cardiovascular disease. Echocardiography prior to chemotherapy revealed normal cardiac function. However, she developed pretibial edema and shortness of breath after 2 months of cabozantinib treatment. Ejection fraction was found to be 30% in the echocardiography of the patient, and global hypokinesia was detected in cardiac functions. Management and outcome: Cabozantinib treatment of the patient was discontinued. After discontinuation of treatment, the patient's cardiac functions did not return to normal. Heart failure due to cabozantinib treatment was thought to be permanent. Discussion: There are only four cases on this subject in the literature. Although the use of cabozantinib rarely causes heart failure, this side effect can have extremely serious consequences. Even if it is a rare condition, cardiological evaluations should be performed before and after cabozantinib therapy because it can be reversible after discontinuation of the treatment. [ABSTRACT FROM AUTHOR]

Assessing regional wall motion abnormalities (RWMA) in the myocardium may provide early diagnosis and treat chronic remodeling in STEMI patients. We assessed RWMA in 217 subjects with anterior STEMI admitted to Era University Hospital in Lucknow, UP, India. Besides abnormalities in the LAD territory, sub-sets of patients exhibited diffuse regional myocardial dysfunction. Interestingly, variations in serum electrolytes, specifically sodium and potassium, significantly affected the distribution and frequency of RWMA. Notably, RWMA occurred in the basal septum, apical septum, apex, and lateral wall in the anterior STEMI group. Additionally, the rate of regional dysfunction varied with serum urea and creatinine levels. This suggests that anterior STEMI can manifest myocardial abnormalities beyond the LAD territory. These findings indicate that ST-segment elevation might not be specific, possibly influenced by electrolyte changes affecting cardiac rhythm. Therefore, diagnosing and correcting region-specific wall motion abnormalities and electrolyte imbalances may improve outcomes in STEMI patients.

Background: It is well known that motor features of Parkinson’s disease (PD) commonly begin on one side of the body and extend to the other side with disease progression. The onset side generally remains more severely affected over the course of the disease. However, the pathophysiology underlying the asymmetry of motor manifestations remains unclear. The purpose of the present study is to examine whether alterations in neuronal activity in the subthalamic nucleus (STN) associate with PD severity. Methods: Microelectrode recording was performed in the STN during targeting for 30 patients in the treatment of deep brain stimulation. The mean spontaneous firing rate (MSFR), power density spectral analysis, and correlations were calculated. Characteristics of subthalamic oscillatory activity were compared between two hemispheres. UPDRS III scores during “Off” and “On” states were obtained for the body side of initial symptoms (BSIS) and the body side of extended symptoms (BSES). Results: There were significant differences of MSFR (41.3 ± 11.0 Hz vs 35.2 ± 10.0 Hz) and percentage of ß frequency oscillatory neurons (51.3% vs 34.9%) between BSIS and BSES. The percentage of ß frequency oscillatory neurons correlated with the bradykinesia/rigidity scores for both sides (p < 0.05). In contrast, the percentage of tremor frequency oscillatory neurons was significantly higher in the BSES than that in the BSIS. In particular, these neurons only correlated with the tremor scores of the BSES (p < 0.05). Conclusion: The results suggest that increased neuronal firing rate and ß frequency oscillatory neurons in the STN are associated with contralateral side motor severity and its progression. Tremor frequency oscillatory neurons are less observed in the STN of the BSIS suggesting that ß oscillatory activity dominates and tremor frequency oscillatory activity reciprocally declines. [ABSTRACT FROM AUTHOR]

Background: Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals. Objective: Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals. Methods: We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group. Results: The inter-rater agreement was fair (Fleiss K = 0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (p < 0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all ps < 0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients. Conclusion: Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients. [ABSTRACT FROM AUTHOR]

Achondroplasia (ACH) is the most common skeletal dysplasia and characterized by shorter long bones relative to the torso. Concerning the upper body, frequent features are cranio-cervical compression, thoracolumbar kyphosis, lumbar lordosis and stenosis [1,2]. Secondary symptoms can be lower back pain, claudication, weakness and paresthesias. What is the sagittal spinopelvic alignment during gait in ACH and which characteristics affect the pelvic tilt? 34 paediatric and juvenile patients with ACH (age:10.5±4.2 years, height: 108±15 cm) were statistically compared to 27 age-matched typically developing controls (age: 10.8±4.4 years, height: 145±23 cm). All underwent a 3D gait analysis [Vicon Nexus, mod. PiG-Model] to capture upper and lower body kinematics. Thorax, pelvic and lumbar spine rotations were extracted. All subjects were clinically examined for anthropometrics, passive RoM and manual strength. The presence of symptoms was documented. Correlations between clinical parameters, anthropometrics and pelvic tilt were analyzed. 17 of 34 patients reported back pain, sensory deficits or sudden leg weakness. During gait, patients with ACH showed +11.1° more anterior pelvic tilt (P<0.001), -4.0° less anterior thorax tilt (P= 0.005) and - 15.9° more lumbar extension (P<0.001). In both cohorts, subjects who took longer steps, had more pelvic tilt (Fig. 1), yet the tilt was still significantly larger in ACH, irrespective of longer relative steps (P<0.01). In ACH, negative correlations with anterior pelvic tilt were found for popliteal angles (r= -0.40, P=0.018) and for limb length to body height ratio (r=-0.65, P<0.001). Passive hip flexion contracture (Thomas-Test) in ACH was not related to anterior pelvic tilt (r=-0.14, P=0.43). ACH patients with symptoms walked with similarly severe spinopelvic malignment than asymptomatic patients, yet at 11.2% reduced speed (P=0.025). Upon clinical exam, patients with more tilt showed less knee extensor and plantarflexor strength (r=-0.45 and -0.40, both P< 0.027). No such correlations were found in controls. [Display omitted] Pelvic tilt and hyperlordosis in ACH was pronounced and the rate of symptoms hinting to neurological deficits and spinal compression was 50%. The link of pelvic tilt and reduced knee and ankle extensor strength fits within this considerations. Although anterior pelvic tilt was not a sole compensation to increase step length, it seems to some degree be a consequence of disproportionally short leg length. Notably, after surgical femoral lengthening, sagittal lumbar lordosis has been reported to decrease [3]. Next to leg growth promoting therapeutics and drugs, interventions that increase hamstrings tone in ACH may potentially also be beneficial for the upper body. [ABSTRACT FROM AUTHOR]

The debilitating symptoms of Parkinson's disease, including the hallmark slowness of movement, termed bradykinesia, were described more than 100 years ago. Despite significant advances in elucidating the genetic, molecular and neurobiological changes in Parkinson's disease, it remains conceptually unclear exactly why patients with Parkinson's disease move slowly. To address this, we summarize behavioural observations of movement slowness in Parkinson's disease and discuss these findings in a behavioural framework of optimal control. In this framework, agents optimize the time it takes to gather and harvest rewards by adapting their movement vigour according to the reward that is at stake and the effort that needs to be expended. Thus, slow movements can be favourable when the reward is deemed unappealing or the movement very costly. While reduced reward sensitivity, which makes patients less inclined to work for reward, has been reported in Parkinson's disease, this appears to be related mainly to motivational deficits (apathy) rather than bradykinesia. Increased effort sensitivity has been proposed to underlie movement slowness in Parkinson's disease. However, careful behavioural observations of bradykinesia are inconsistent with abnormal computations of effort costs due to accuracy constraints or movement energetic expenditure. These inconsistencies can be resolved when considering that a general disability to switch between stable and dynamic movement states can contribute to an abnormal composite effort cost related to movement in Parkinson's disease. This can account for paradoxical observations such as the abnormally slow relaxation of isometric contractions or difficulties in halting a movement in Parkinson's disease, both of which increase movement energy expenditure. A sound understanding of the abnormal behavioural computations mediating motor impairment in Parkinson's disease will be vital for linking them to their underlying neural dynamics in distributed brain networks and for grounding future experimental studies in well-defined behavioural frameworks. [ABSTRACT FROM AUTHOR]

Purpose: Infant regurgitation is associated with other functional gastrointestinal disorders and signs and symptoms that have a major impact on the quality of life of infants and their families. This study evaluated the safety, tolerance, and real-world effectiveness of an antiregurgitation formula containing locust bean gum (LBG), prebiotics, and postbiotics to alleviate digestive symptoms beyond regurgitation. Methods: This 3-month study involved infants with regurgitation requiring the prescription of an anti-regurgitation formula according to usual clinical practice. Outcomes included evaluation of the evolution of stool consistency and frequency; occurrence of colic, constipation, and diarrhea; and assessment of regurgitation severity. Infant crying, parental assessment of infant well-being, and parental satisfaction with the stool consistency were also evaluated. Results: In total, 190 infants (average age: 1.9±1.1 months) were included. After three months, stool frequency and consistency remained within the normal physiological range, with 82.7% of infants passing one or two stools per day and 90.4% passing loose or formed stools. There was no significant increase in the number of infants with diarrhea, whereas a decrease was observed in the number of infants with constipation after 1 month (p=0.001) and with colic after both 1 and 3 months (p<0.001). Regurgitation severity and crying decreased and parental satisfaction with stool consistency, formula acceptability, infant well-being, and sleep quality increased. Monitoring of adverse events did not reveal any safety concerns. Conclusion: Formulas containing LBG, prebiotics, and postbiotics were well tolerated and provided an effective strategy for managing infant regurgitation and gastrointestinal discomfort. [ABSTRACT FROM AUTHOR]

Background: Bradykinesia has been reported in patients with dystonia. Despite this, the pathophysiological mechanisms of bradykinesia in dystonia remain largely unknown. Methods: We here performed a comprehensive literature search and reviewed clinical and experimental studies on bradykinesia in patients with dystonia. Results: Many studies have documented the presence of bradykinesia in patients with idiopathic and inherited isolated dystonia, regardless of the presence of parkinsonism. In addition, bradykinesia has been observed as a side effect in dystonic patients who have undergone deep brain stimulation, in those with functional dystonia as well as in those with combined dystonia, e.g., dystonia-parkinsonism. These clinical and experimental findings support the hypothesis that dysfunction in a brain network involving the basal ganglia, primary sensorimotor cortex, and cerebellum may play a key role in the pathophysiology of both bradykinesia and dystonia. Conclusion: Bradykinesia is frequently observed in dystonia. We may gain insights into the pathophysiological underpinnings of two distinct movement disorders by investigating this issue. Furthermore, a deeper understanding of bradykinesia in dystonia may have terminological implications in this field. [ABSTRACT FROM AUTHOR]

Changes in motor activity are common in individuals with Frontotemporal dementia (FTD). Yet, it remains unclear why some individuals become motorically hyperactive, while others hypoactive even in early stages of the disease. This study aimed to examine the relationship between motor activity level and (1) FTD clinical subtype, and (2) cortical thickness and subcortical volumes. Eighty-two charts were retrospectively reviewed from patients meeting consensus criteria for one of the three main clinical subtypes of FTD: probable bvFTD, semantic variant Primary Progressive Aphasia (PPA), or non-fluent variant PPA. Participants were assigned to one of three groups: (1) hyperactive, (2) hypoactive, or (3) no record of change. Hyperactivity was prevalent among bvFTD (58.5%) and semantic PPA (68.8%) subtypes while hypoactivity was less common in both subtypes (29.3% and 18.8%, respectively). The majority of patients with non-fluent PPA showed no record of change in motor activity (66.7%). The analysis of cortical thickness and subcortical volumes did not identify significant associations with motor activity levels. In conclusion, increased motor activity is highly prevalent among individuals with FTD, especially bvFTD and svPPA subtypes. These findings may inform prognosis and prediction of changes in motor activity, and allow planning for appropriate environmental and behavioural interventions. Future studies with prospective, standardized longitudinal collection of information regarding the type and level of change in motor activity, including wearable measures of actigraphy, may help to further delineate the onset and progression of abnormal motor behaviours and determine neuroanatomic associations in FTD. [ABSTRACT FROM AUTHOR]

Aims: To determine the role of opioid and β‐adrenergic receptors in bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). Methods: In α‐chloralose anesthetized cats, 30‐min PNS was applied repeatedly for 3–9 times to induce poststimulation or persistent bladder underactivity. Then, naloxone (opioid receptor antagonist, 1 mg/kg, IV) or propranolol (β‐adrenergic receptor antagonist, 3 mg/kg, IV) was given to reverse the bladder underactivity. After the drug treatment, an additional 30‐min PNS was applied to counteract the drug effect. Repeated cystometrograms were performed by slowly (1–2 mL/min) infusing the bladder with saline via a urethral catheter to determine the bladder underactivity and the treatment effects. Results: Prolonged (2–4.5 h) PNS induced bladder underactivity evident as a large bladder capacity (169 ± 49% of control) and a reduced amplitude of bladder contraction (59 ± 17% of control). Naloxone fully reversed the bladder underactivity by reducing bladder capacity to 113 ± 58% and increasing the amplitude of bladder contraction to 104 ± 34%. After administration of naloxone an additional 30‐min PNS temporarily increased the bladder capacity to the underactive bladder level (193 ± 74%) without changing the amplitude of the bladder contraction. Propranolol had no effect on bladder underactivity. Conclusions: A tonic enkephalinergic inhibitory mechanism in the CNS plays a critical role in the bladder underactivity induced by prolonged PNS, while the peripheral β‐adrenergic receptor mechanism in the detrusor is not involved. This study provides basic science evidence consistent with the clinical observation that comorbid opioid usage may contribute to voiding dysfunction in patients with Fowler's syndrome. [ABSTRACT FROM AUTHOR]

Background: Very fewstudies have assessed the presence of a possible correlation between speech variables and limb bradykinesia in patients with Parkinson's disease (PD). The objective of this study was to find correlations between different speech variables and upper extremity bradykinesia under different medication conditions in advanced PD patients. Methods: Retrospective data were collected from a cohort of advanced PD patients before and after an acute levodopa challenge. Each patient was assessed with a perceptual-acoustic analysis of speech, which included several quantitative parameters [i.e., maximum phonation time (MPT) and intensity (dB)]; the Unified Parkinson's Disease Rating Scale (UPDRS) (total scores, subscores, and items); and a timed test (a tapping test for 20 s) to quantify upper extremity bradykinesia. Pearson's correlation coeffcient was applied to find correlations between the different speech variables and the tapping rate. Results: A total of 53 PD patients [men: 34; disease duration: 10.66 (SD 4.37) years; age at PD onset: 49.81 years (SD 6.12)] were included. Levodopa intake increased theMPT of sustained phonation (p<0.01), but it reduced the speech rate (p = 0.05). In the defined-OFF condition, MPT of sustained phonation positively correlated with both bilateral mean (p = 0.044, r-value:0.299) and left (p = 0.033, r-value:0.314) tapping. In the defined-ON condition, the MPT correlated positively with bilateral mean tapping (p = 0.003), left tapping (p = 0.003), and right tapping (p = 0.008). Conclusion: This study confirms the presence of correlations between speech acoustic variables and upper extremity bradykinesia in advanced PD patients. These findings suggest common pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Using existing transthoracic echocardiographic indices to quantify left ventricular wall motion abnormalities (WMAs) can be difficult due to the variations in the location of the abnormalities within the left ventricle, the quality of examinations, and the inter‐/intra‐observer variability of available indices. This study aimed to evaluate a new approach for measuring the extent of WMA by calculating the percentage of abnormal wall motion and comparing it to the wall motion score index (WMSI). The study also sought to assess inter‐ and intra‐observer variability. Methods: The study included 140 echocardiograms from 54 patients presenting with ST‐elevation myocardial infarction or Takotsubo syndrome. All patients underwent an echocardiographic examination according to a standard protocol and the images were used to measure the extent of akinesia (proportion akinesia, PrA), akinesia and hypokinesia (proportion akinesia/hypokinesia, PrAH), and WMSI. The inter‐observer variability between the two operators was analyzed. The intra‐observer analysis was performed by one observer using the same images at least 1 month after the first measurement. The agreement was analyzed using the Pearson correlation coefficient and Bland‐Altman plots. Results: Inter‐ and intra‐observer variability for PrA and PrAH were low and comparable to those for WMSI. Conclusion: PrA and PrAH are reliable and reproducible echocardiographic methods for the evaluation of left ventricular wall motion. [ABSTRACT FROM AUTHOR]

Background: The prevalence and incidence of Parkinson's disease (PD) is increasing due to a prolonged life expectancy. The cardinal features of PD include resting tremor, rigidity, bradykinesia, and postural instability. In rodents the 2,4,5-trihydroxyphenylethylamine [6-hydroxydopamine (6-OHDA)] induced lesion of the nigrostriatal system showed retrograde degeneration and structural changes in the corpus striatum under transmission the electron microscope (TEM). Aim and Objectives: To study the ultra-structure of normal and 6-OHDA lesioned corpus striatum in Wistar albino rats under the transmission electron microscope. Material and Methods: Wistar albino male adult rats received unilateral stereotaxical injection of 6-OHDA on the right side of striatum and were sacrificed after 120 days. The following stereotaxic co-ordinates were used to target the dorsolateral part of the striatum: AP = 0.2 mm, ML = 3.2 mm, DV = 4.5 mm from the bregma. Another target was the dorsomedial part of striatum: AP = 1.1 mm, ML = 2.4 mm and DV = 3.5 mm. The motor behavior was monitored in cylinder which was counted for a period of 60 min. Results and Conclusion: Our TEM finding in the control rats demonstrated that nucleus was round and comparatively large in proportion to the cell body and lies in the centre of the nerve cell in the striatum. Occasionally one or two dense nucleoli were located eccentrically in the nucleoplasm. Additionally, in the cytoplasm around the nucleus, the conspicuous organelles along with the numerous ribosomes which were mostly free and appear as rosettes or clusters, some of which were attached to the endoplasmic reticulum. Furthermore, few short of granular endoplasmic reticula were seen. Interestingly, the lesioned rats showed neuronal and glial cells damage at the ultra-structural level in striatum under TEM observation. [ABSTRACT FROM AUTHOR]

Background and objectives (Aim). To identify the features of the inflammatory status of the intestine in premature infants depending on gestational age. Materials and methods. The study included 36 premature babies. All children were divided into two groups, according to gestational age (GA): group 1-12 newborns with GA of 22 (0/7) 28 (6/7) weeks; and group 2-24 newborns with GA of 29(0/7) 32(6/7) weeks. The exclusion criteria were: the presence of congenital malformations, septic conditions, surgical pathologies. Results. The level of fecal calprotectin, as well as CRP in the 1st group of children was significantly higher than in the 2nd group, which demonstrates an inverse relationship between the severity of inflammation and the gestational age of premature newborns: the lower the gestational age, the higher the rates of inflammation in the intestines. The permeability of the intestinal barrier was high in both groups, which was reflected in increased values of fecal alpha-antitrypsin on the 3rd and 14th days of the examination, and did not have statistically significant differences between the groups. Children of group 1 required longer treatment than children of group 2, both in the ICU. Clinical manifestations of digestive disorders in premature infants were manifested by decreasing in body weight gain, the appearance of discharge from the tube with pathological impurities, while no significant difference was found between the groups. Conclusions. Premature neonates less than 28 weeks of age show greater signs of acute inflammation in the intestinal tract. [ABSTRACT FROM AUTHOR]

Diabetic bladder dysfunction (DBD) is a prevalent diabetic complication that is recalcitrant to glucose control. Using the Akita mouse model (type 1) bred to be NLR family pyrin domain containing 3 (NLRP3)+/+ or NLRP3-/-, we have previously found that females (mild hyperglycemia) progress from an overactive to underactive bladder phenotype and that this progression was dependent on NLRP3-induced inflammation. Here, we examined DBD in the male Akita mouse (severe hyperglycemia) and found by urodynamics only a compensated underactive-like phenotype (increased void volume and decreased frequency but unchanged efficiency). Surprisingly, this phenotype was still present in the NLRP3-/- strain and so was not dependent on NLRP3 inflammasome-induced inflammation. To examine the cause of the compensated underactive-like phenotype, we assessed overall nerve bundle density and afferent nerve bundles (Ad-fibers). Both were decreased in density during diabetes, but denervation was absent in the diabetic NLRP3 / strain so it was deemed unlikely to cause the underactive-like symptoms. Changes in bladder smooth muscle contractility to cell depolarization and receptor activation were also not responsible as KCl (depolarizing agent), carbachol (muscarinic agonist), and a,b-methylene-ATP (purinergic agonist) elicited equivalent contractions in denuded bladder strips in all groups. However, electrical field stimulation revealed a diabetes-induced decrease in contractility that was not blocked in the NLRP3-/- strain, suggesting that the bladder compensated underactive-like phenotype in the male Akita mouse is likely through a decrease in efferent neurotransmitter release. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TTCM) has been described as a new entity of cardiomyopathy at the turn of the century. Takotsubo, a Japanese word, denotes an "octopus pot," a fishing jar that has a narrow neck and wide base for trapping an octopus. This correlates with the shape of the heart on left ventriculography with apical ballooning and basal hypokinesia. The first case was defined in 1990 by Sato et al. and a plethora of literature exists about TTCM ever since. While believed to be an occurrence in elderly postmenopausal females, various reports have been found in recent literature highlighting its occurrence during the antenatal, perinatal, and postpartum periods. It is high time that TTCM is kept in the purview of diagnosing acute cardiopulmonary symptoms in pregnancy. Only an accurate and timely diagnosis of TTCM in pregnancy can lead to an early intervention and prevent countless morbidities and mortalities. A multidisciplinary approach with psychological rehabilitation is recommended to prevent recurrence. We present a concise review of the diagnosis, clinical features and management of this condition and the salient differentiating features from peripartum cardiomyopathy (PPCM). We found 26 cases of TTCM and 16 cases of reverse TTCM. There is a void in knowledge about estrogen levels and the corresponding levels of catecholamines in due course of pregnancy. Future studies to correlate between declining estrogen levels and catecholamine levels at the onset of symptoms of TTCM need to be done to get more insights into this phenomenon. [ABSTRACT FROM AUTHOR]

Potential cognitive and physiological alterations due to space environments have been investigated in long-term space flight and various microgravity-like conditions, for example, head-down tilt (HDT), confinement, isolation, and immobilization. However, little is known about the influence of simulated microgravity environments on visual function. Contrast sensitivity (CS), which indicates how much contrast a person requires to see a target, is a fundamental feature of human vision. Here, we investigated how the CS changed by 1-h −30° HDT and determined the corresponding mechanisms with a perceptual template model. A quick contrast sensitivity function procedure was used to assess the CS at ten spatial frequencies and three external noise levels. We found that (1) relative to the + 30° head-up tilt (HUT) position, 1-h −30° HDT significantly deteriorated the CS at intermediate frequencies when external noise was present; (2) CS loss was not detected in zero- or high-noise conditions; (3) HDT-induced CS loss was characterized by impaired perceptual template; and (4) self-reported questionnaires indicated that subjects felt less pleasure and more excitement, less comfort and more fatigued by screen light, less comfort in the area around the eye, and serious symptoms such as piercing pain, blur acid, strain, eye burning, and dizziness after HDT. These findings improve our understanding of the negative effects of simulated microgravity on visual function and elucidate the potential risks of astronauts during space flight. [ABSTRACT FROM AUTHOR]

Parenting interventions reduce antisocial behavior (ASB) in some children with conduct problems (CPs), but not others. Understanding the neural basis for this disparity is important because persistent ASB is associated with lifelong morbidity and places a huge burden on our health and criminal justice systems. One of the most highly replicated neural correlates of ASB is amygdala hypoactivity to another person's fear. We aimed to assess whether amygdala hypoactivity to fear in children with CPs is remediated following reduction in ASB after successful treatment and/or if it is a marker for persistent ASB. We conducted a prospective, case-control study of boys with CPs and typically developing (TD) boys. Both groups (ages 5–10 years) completed 2 magnetic resonance imaging sessions (18 ± 5.8 weeks apart) with ASB assessed at each visit. Participants included boys with CPs following referral to a parenting intervention group and TD boys recruited from the same schools and geographical regions. Final functional magnetic resonance imaging data were available for 36 TD boys and 57 boys with CPs. Boys with CPs were divided into those whose ASB improved (n = 27) or persisted (n = 30) following the intervention. Functional magnetic resonance imaging data assessing fear reactivity were then analyzed using a longitudinal group (TD/improving CPs/persistent CPs) × time point (pre/post) design. Amygdala hypoactivity to fear was observed only in boys with CPs who had persistent ASB and was absent in those whose ASB improved following intervention. Our findings suggest that amygdala hypoactivity to fear is a marker for ASB that is resistant to change following a parenting intervention and a putative target for future treatments. [ABSTRACT FROM AUTHOR]

BackgroundBeta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson's disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed.MethodsTo determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson's Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT).ResultsMean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=

Parkinson's disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed- loop neuromodulation. We examined neural activity in the basal ganglia and cortex of 31 subjects with PD during a quantitative motor task to decode tremor and bradykinesia -- two cardinal motor signs of PD -- and relatively asymptomatic periods of behavior. Support vector regression analysis of microelectrode and electrocorticography recordings revealed that tremor and bradykinesia had nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the signal type and location. Cortical decoding generally outperformed subcortical decoding. Within the subthalamic nucleus (STN), tremor and bradykinesia were better decoded from distinct subregions. These results demonstrate how to leverage neurophysiology to more precisely treat PD. [ABSTRACT FROM AUTHOR]

Marine cone snails have attracted researchers from all disciplines but early life stages have received limited attention due to difficulties accessing or rearing juvenile specimens. Here, we document the culture of Conus magus from eggs through metamorphosis to reveal dramatic shifts in predatory feeding behaviour between post-metamorphic juveniles and adult specimens. Adult C. magus capture fish using a set of paralytic venom peptides combined with a hooked radular tooth used to tether envenomed fish. In contrast, early juveniles feed exclusively on polychaete worms using a unique "sting-and-stalk" foraging behaviour facilitated by short, unbarbed radular teeth and a distinct venom repertoire that induces hypoactivity in prey. Our results demonstrate how coordinated morphological, behavioural and molecular changes facilitate the shift from worm- to fish-hunting in C. magus, and showcase juvenile cone snails as a rich and unexplored source of novel venom peptides for ecological, evolutionary and biodiscovery studies. Challenges rearing juvenile cone snails have limited our understanding of their developmental biology. This study cultured Conus magus cone snails and revealed how complex morphological, behavioural and molecular changes facilitate the ontogenetic shift from juvenile worm-hunters to fish-hunting adults. [ABSTRACT FROM AUTHOR]

The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC50 = 0.059 ± 0.008 μg/mL) or carbachol (EC50 = 0.068 ± 0.007 μg/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children. [ABSTRACT FROM AUTHOR]

Background: Bradykinesia is considered the fundamental motor feature of Parkinson's disease (PD). It is central to diagnosis, monitoring, and research outcomes. However, as a clinical sign determined purely by visual judgement, the reliability of humans to detect and measure bradykinesia remains unclear. Objective: To establish interrater reliability for expert neurologists assessing bradykinesia during the finger tapping test, without cues from additional examination or history. Methods: 21 movement disorder neurologists rated finger tapping bradykinesia, by Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Modified Bradykinesia Rating Scale (MBRS), in 133 videos of hands: 73 from 39 people with idiopathic PD, 60 from 30 healthy controls. Each neurologist rated 30 randomly-selected videos. 19 neurologists were also asked to judge whether the hand was PD or control. We calculated intraclass correlation coefficients (ICC) for absolute agreement and consistency of MDS-UPDRS ratings, using standard linear and cumulative linked mixed models. Results: There was only moderate agreement for finger tapping MDS-UPDRS between neurologists, ICC 0.53 (standard linear model) and 0.65 (cumulative linked mixed model). Among control videos, 53% were rated > 0 by MDS-UPDRS, and 24% were rated as bradykinesia by MBRS subscore combination. Neurologists correctly identified PD/control status in 70% of videos, without strictly following bradykinesia presence/absence. Conclusion: Even experts show considerable disagreement about the level of bradykinesia on finger tapping, and frequently see bradykinesia in the hands of those without neurological disease. Bradykinesia is to some extent a phenomenon in the eye of the clinician rather than simply the hand of the person with PD. [ABSTRACT FROM AUTHOR]

Bradykinesia is a cardinal hallmark of Parkinson's disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson's Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson's disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia. [ABSTRACT FROM AUTHOR]

Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females [ABSTRACT FROM AUTHOR]

Objective: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long‐term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13–30 Hz) dynamics or a wider bilateral network dysfunction. Methods: Twenty‐one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist‐flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN‐STN beta coherence. Results: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN‐STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. Interpretation: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029–1039 [ABSTRACT FROM AUTHOR]

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Pulmonary blastoma (PB) is a rare and invasive malignancy of the lungs with a poor prognosis. Although the mainstay treatment of PB is surgery, and radiotherapy and chemotherapy have been reported, no standard therapy exists for patients inoperable in advanced stages. Moreover, little is known about driver mutation status and immunotherapy efficacy. This paper presents a male patient diagnosed with classic biphasic PB using CT-guided lung biopsy pathology and immunohistochemistry. The patient’s symptoms included cough, chest pain, shortness of breath, hemoptysis, and hypodynamia. The primary focus of this paper is to discuss the impact of anti-PD-1 immunotherapy on PB. The patient experienced progression-free survival (PFS) of over 27 months following sintilimab second-line anti-PD-1 therapy. The patient has currently survived for nearly 40 months with a satisfactory quality of life. [ABSTRACT FROM AUTHOR]

Background: Correlations between dopamine transporter (DAT) availability and Parkinson's disease (PD) motor symptoms vary depending on the imaging modality, choice of regions of interest and clinical measures. We aimed to validate the PET radioligand [18F]FE-PE2I as a clinical biomarker in PD, hypothesizing negative correlations between DAT availability in specified nigrostriatal regions with symptom duration, disease stage and motor symptom scores. Methods: We included 41 PD patients (age 45–79 years; H&Y stage < 3) and 37 healthy control subjects in a cross-sectional study with dynamic [18F]FE-PE2I PET. Binding potential (BPND) was estimated in the caudate nucleus, putamen, ventral striatum, sensorimotor striatum, and substantia nigra using the cerebellum as reference region. Results: We found negative correlations (p < 0.02) between symptom duration and BPND in the putamen and sensorimotor striatum (rs = −.42; rs = −.51), and between H&Y stage and BPND in caudate nucleus, putamen, sensorimotor striatum, and substantia nigra (rs between −.40 and −.54). The first correlations were better described with exponential fitting. MDS-UPDRS-III in 'OFF' state correlated negatively (p < 0.04) with BPND in the sensorimotor striatum (rs = −.47), and excluding tremor score also in the putamen (rs = −.45). Conclusion: Results are in agreement with earlier findings in in vivo and post-mortem studies and validate [18F]FE-PE2I as a functional PD biomarker for PD severity. Trial registration: EudraCT 2011-0020050, Registered April 26 2011; EudraCT 2017-003327-29, Registered October 08 2017; EudraCT 2017-001585-19, Registered August 2 2017. https://eudract.ema.europa.eu/. [ABSTRACT FROM AUTHOR]

One of the modern challenges facing society is finding ways to counteract hypodynamia. This article discusses the ability of educational institutions to enrich the forms and means of extracurricular physical activity through sports-animation practice, in order to stimulate the active participation of adolescents and increase the volume of their motor activity. Presented is the regulatory conditioning for the formation of professional-pedagogical competence for the realization of sports-animation activity. The authors justify the fact that maximising the engagement of the free time of the younger generation will regressively affect its activities with negative health dependencies. [ABSTRACT FROM AUTHOR]

This article discusses the effect of acute and chronic immobilization stress on erythrocyte membranes. The intensive development of science and technology has brought into human life, along with positive phenomena, a number of unfavorable factors: hypodynamia, excessive nervous, physical exertion, professional and household stresses. Among them, hypodynamia is a lifestyle characterized by a decrease in motor activity, which negatively affects human health. This is a common situation nowadays. Hypodynamia leads to metabolic and energy disorders in the body, cardiovascular diseases, diseases of the gastrointestinal tract, overweight, early aging, a decrease in the body's ability to resist various diseases, changes in the general condition of the body, etc. Such a stressful effect is observed at the cellular and molecular level. As stress increases, metabolic disorders appear, activation of free radical oxidation leads to disruption of the main: barrier, receptor, catalytic functions of biological membranes. As a result, it leads the human body to various pathological conditions. Currently, more attention is being paid to an integrated approach to the treatment and prevention of diseases. This article discusses the effect of acute and chronic immobilization stress on erythrocyte membranes. As a result of the research, it was found that the effect of immobilization stress leads to a decrease in the osmotic and peroxide resistance of erythrocytes and an increase in the hemoglobin yield. The use of vitamin E reduces the damaging effect of both acute and chronic immobilization stress. Consequently, antioxidants can protect the body from the damaging effects of stress factors. [ABSTRACT FROM AUTHOR]

Delirium in the intensive care unit (ICU) is a common but serious condition that has been associated with in-hospital mortality and post-discharge psychological dysfunction. The aim of this before and after study is to determine the effect of a multidisciplinary care model entailing daily ICU rounds with a psychiatrist on the incidence of delirium and clinical outcomes. To assess the impact of a proactive psychiatry consultation model in the surgical ICU on the incidence and duration of delirium. This was a prospective, single institution, observational controlled cohort pilot study of adult patients admitted to a surgical ICU. A control group that received standard of care (SOC) with daily delirium prevention care bundles in the pre-intervention period was compared to an intervention group, which had a psychiatrist participate in daily ICU rounds (post-intervention period). The primary outcome was delirium incidence. The secondary outcomes were: delirium duration, ventilator days, hospital and ICU length of stay, and in-hospital mortality. A total of 104 patients were enrolled and equally split between SOC and intervention groups; 95 contributed to analysis. The overall incidence of ICU delirium was 19%. SOC and intervention groups had similar rates of delirium (21% vs 18%, p = 0.72). None of the secondary outcomes statistically significantly differed between the two groups. Delirium in ICU patients is a potentially preventable condition with serious sequelae. There was no difference in delirium incidence or duration between patients receiving SOC or patients who had multidisciplinary rounds with a psychiatrist. [ABSTRACT FROM AUTHOR]

The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Long-segment chronic total occlusion in femoropoplitial segment can be effectively treated with self-expandable stent especially when there are flow-limiting dissections created either while wiring the lesion or while predilating the lesions. Distortion of a self-expandable stent can during the procedure; hence, proper care should be taken in Plaque modification before stent deployment. Distortion can cause retention of the stent markers. Understanding the problem, the hardware we are using can guide us in bailing out the situation and also improving the long-term outcomes of the extremities. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is used to treat multiple neuropsychiatric disorders, including Parkinson's Disease (PD). Despite widespread clinical use, its therapeutic mechanisms are unknown. Here, we developed a mouse model of subthalamic nucleus (STN) DBS for PD, to permit investigation using cell type-specific tools available in mice. We found that electrical STN DBS relieved bradykinesia, as measured by movement velocity. In addition, our model recapitulated several hallmarks of human STN DBS, including rapid onset and offset, frequency dependence, dyskinesia at higher stimulation intensity, and associations between electrode location, therapeutic benefit, and side effects. We used this model to assess whether high frequency stimulation is necessary for effective STN DBS, or if low frequency stimulation can be effective when paired with compensatory adjustments in other parameters. We found that low frequency stimulation, paired with greater pulse width and amplitude, relieved bradykinesia. Moreover, a composite metric incorporating pulse width, amplitude, and frequency predicted therapeutic efficacy better than frequency alone. We found a similar relationship between this composite metric and movement speed in a retrospective analysis of human data, suggesting correlations observed in the mouse model may extend to human patients. Together, these data establish a mouse model for elucidating mechanisms of DBS.

Recognizing drug-induced parkinsonian bradykinesia in psychosis patients can be challenging due to overlapping presentation with psychomotor slowing associated with depression, negative symptoms, or cognitive disturbances. In this study, we apply prior findings on the pathophysiology of bradykinesia in Parkinson's disease to gain an understanding of motor slowing in psychosis patients. Handwriting movements from 57 healthy participants and 70 psychosis patients were recorded on a digitizing tablet. Temporal and kinematic features were extracted from handwritten loops and circles. An independent objective measure based on peak velocity for circles written at maximum speed was used to classify patients as bradykinetic. Using a statistical cut-point derived from normative data, 64% of the patients met criterion for bradykinesia compared with 46% using a conventional observer-based severity rating scale. Bradykinetic patients produced handwriting movements with longer stroke durations, smaller amplitudes and lower peak velocities compared with non-bradykinetic patients. Thirty-six percent of the pen strokes produced by the bradykinetic patients were non-ballistic compare with 20% for the non-bradykinetic patients. The proportion of nonballistic movements observed in handwriting was unrelated to current antipsychotic dose, severity of negative psychosis or depression. The ease-of-use and standardization of a tablet-based approach to quantifying parkinsonian bradykinesia can aid in diagnosing parkinsonian bradykinesia in patients treated with antipsychotics.