Unilateral Damage Research Articles

The evaluation value of 18F-AV-133 PET/CT imaging in the Parkinson's disease crab-eating monkey model.

To investigate the diagnostic value of fluorine-18-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV-133) positron emission tomography/computed tomography (PET/CT) for Parkinson's disease (PD) and the metabolic parameter changes in the PD macaque model. Sixty three macaques were divided into an experimental group (n=55) and a normal group (n=8) for 18F-AV-133 PET/CT imaging. In the experimental group, the macaques were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) solution into one side of the neck artery 2-3 months before imaging to induce unilateral striatal damage for self-control, while the normal group received no special treatment. After imaging, two nuclear medicine doctors conducted image analysis to determine the damaged side using visual inspection and compared the data with the actual damaged side to evaluate the model construction. The standardized uptake value (SUV) semi-quantitative analysis method was used to process the images, obtaining metabolic information of the damaged and preserved sides of the striatum, thalamus, occipital lobe, frontal lobe, parietal lobe, temporal lobe, and cerebellum in different sides of the normal group. Data analysis was performed using SPSS 25 to compare metabolic differences between different sides and evaluate the impact of modeling on the metabolism of other regions of the brain, with a significance level set at P<0.05. Fluorine-18-AV-133 PET/CT imaging showed that the normal group of macaques exhibited relatively symmetrical radiotracer uptake in the bilateral striatal regions; the experimental group of PD macaque models showed completely asymmetrical radiotracer uptake in the left and right striatal regions, with model construction success rate of 100%. Semi-quantitative analysis using SUV revealed that the metabolic parameters SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) in the damaged striatal region of the experimental group of PD macaques were lower than those in the preserved side, with statistically significant differences (t/z=8.277, 12.032, 8.827, 8.744, P<0.001). The SUVmean in the damaged thalamus of the PD macaques was lower than in the preserved side (1.327±0.354 vs. 1.490±0.374), with a statistically significant difference (t=2.352, P=0.02).The metabolic parameters SUVmax, SUVmean, MTV, and TLG in the striatum of the normal group were higher than those in the preserved striatum of the experimental group, with P<0.05. Fluorine-18-AV-133 PET/CT can accurately assess the construction of PD macaque models and visualize the differences in metabolic parameters between different sides, making it useful for detecting monoaminergic terminal reduction in PD patients and providing a theoretical basis for the diagnosis and follow-up treatment of PD.

Concordance of Freehand 3D Ultrasound Muscle Measurements With Sarcopenia Parameters in a Geriatric Rehabilitation Ward.

Sarcopenia is a devastating disease for older adults, but it lacks accessible and reliable tools for measuring total appendicular skeletal muscle mass (ASMM). Two-dimensional muscle ultrasound (US) has been developed for its bedside clinical advantages and feasibility but lacks standardization and prediction performance. We previously validated a new 3D-US technique to measure muscle volume (MV) at bedside and applied it in a geriatric rehabilitation setting. Objectives were to analyse the concordance between 3D-US MV and ASMM and compare concordance between 3D-US MV and 2D-US parameters with ASMM. Participants were recruited in a Geriatric rehabilitation ward in Nantes, France, from May to October 2022. Exclusion criteria were as follows: oedema in the lower limbs or recent history of unilateral lower limb damage or stroke. ASMM was measured with bioelectrical impedance analysis; 3D-US and 2D-US acquisitions were performed on three muscles of the right lower limb. Measures of strength (hand grip, knee extension and ankle dorsiflexion) were also recorded. Reliability of 3D-US MV measurements on 10 participants was high (ICC = 0.99). We used Lin's concordance correlation coefficients (CCC) and bias correction factor for agreement between variables and linear regression models for prediction equations. Fifty-eight participants had an interpretable ASMM of whom 17 (29%) had a diagnosis of sarcopenia. Volumes of TA, RF and VL were all significantly concordant with ASMM measured by BIA (all p values < 0.001), with CCCs respectively of 0.72, 0.61 and 0.60. MV were all significantly concordant with isometric strength (p values < 0.001). Concordance and correlation with ASMM were higher with 3D-US than 2D-US measurements regardless of the muscle. Prediction of ASMM reached an adjusted R2 of 0.8 with tibialis anterior volume, biometrics and 2D measurements. This study was the first to use 3D-US in a geriatric setting and develop a model to predict ASMM in very old hospitalized patients. MV measurements with 3D-US proved to be reliable and more concordant with appendicular muscle mass and strength than 2D parameters.

Wall-Eyed Internuclear Ophthalmoplegia: History and Hypothesis.

Most patients with internuclear ophthalmoplegia (INO) are orthotropic, although a subset is exotropic. When INO is bilateral, this is termed wall-eyed bilateral internuclear ophthalmoplegia (WEBINO). In 1979, Sharpe described his "first case" of wall-eyed monocular internuclear ophthalmoplegia (WEMINO) as "a unique clinical syndrome" characterized by unilateral INO and ipsilateral exotropia. WEMINO was clinically identified in seven patients, with oculographic correlation in six and neuropathological confirmation in one. Oculographic features of exotropic INO patients were compared with those of six orthotropic INO patients using magnetic search coil and infrared oculography. All clinically defined WEMINO patients showed slowed, hypometric ipsilateral saccades by oculography. Six patients had ipsilateral exotropia, and three had ipsilateral hypertropia. Ipsilateral abducting saccades had faster peak velocities for smaller saccades, more so for orthotropic patients. Exotropic patients had normal sinusoidal mean vestibulo-ocular reflex (VOR) gains and phases; orthotropic patients had subnormal mean VOR gains and phase leads. WEMINO is a clinical ocular motor syndrome characterized by unilateral slow, hypometric adducting saccades with exotropia and hypertropia of the ipsilateral eye. We propose that it results from discrete unilateral damage to burst-tonic fibers in the medial longitudinal fasciculus (MLF) with sparing of the adjacent extrafascicular pathways. Paradoxically, orthotropic INO results from more extensive damage to ascending pathways lateral, ventral and caudal to the MLF. Direct injury to the medial rectus subnucleus is not required. This manuscript was in preparation at the time of Dr Sharpe's death in 2013 and is an acknowledgement of his forward-thinking, as his hypotheses have stood the test of time.

Cerebral ptosis: An ominous sign in stroke—A retrospective study

AbstractIntroductionCerebral ptosis is defined as the drooping of eyelids due to lesions in the cerebral hemispheres. Cerebral ptosis is due to either unilateral or bilateral hemispheric damage without brainstem involvement. Ischemic strokes are the most common etiology leading to hemispheric damage.AimsTo assess the prevalence of cerebral ptosis in ischemic strokes and to correlate the presence of cerebral ptosis with the outcome of the patients. To also assess the demographic profile of these patients.Materials and MethodsThis is a retrospective study from June 2022 to August 2024. All patients diagnosed as acute stroke presenting with cerebral ptosis within day 3 of stroke were included. Patients with a reduced level of consciousness, brainstem involvement, and those with signs of impending herniation were excluded. The modified Rankin scale (mRS) on the day of admission and the day of discharge were compared.ResultsThere were 26 patients with cerebral ptosis among 649 patients admitted with anterior circulation stroke (prevalence 4.01%). 84.6% (n = 12) had right hemisphere involvement and 15.4% (n = 4) had left side involvement. 88.5% (n− = 23) had middle cerebral artery territory involvement and 7.7% (n = 2) had internal carotid artery territory involvement. The mean mRS on admission was 4.42 and 4.81 on discharge (paired t‐test 0.015). mRS 6 (death) was observed in four patients.ConclusionCerebral ptosis is a supranuclear disorder with the most common etiology being vascular insult to the cerebral hemisphere. It is an ominous and rare clinical sign. Identification of this entity is important, and it is not to be confused with a reduced level of consciousness.

Correlation of the severity of the clinical presentation of SARS-CoV-2 pneumonia with respiratory function parameters in the post-COVID period.

Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity.

The insular cortex, autonomic asymmetry and cardiovascular control: looking at the right side of stroke.

Evidence from animal and human studies demonstrates that cortical regions play a key role in autonomic modulation with a differential role for some brain regions located in the left and right brain hemispheres. Known as autonomic asymmetry, this phenomenon has been demonstrated by clinical observations, by experimental models, and currently by combined neuroimaging and direct recordings of sympathetic nerve activity. Previous studies report peculiar autonomic-mediated cardiovascular alterations following unilateral damage to the left or right insula, a multifunctional key cortical region involved in emotional processing linked to autonomic cardiovascular control and featuring asymmetric characteristics. Based on clinical studies reporting specific damage to the insular cortex, this review aims to provide an overview of the prognostic significance of unilateral (left or right hemisphere) post-insular stroke cardiac alterations. In addition, we review experimental data aiming to unravel the central mechanisms involved in post-insular stroke cardiovascular complications. Current clinical and experimental data suggest that stroke of the right insula can present a worse cardiovascular prognosis.

Advanced progress of vestibular compensation in vestibular neural networks.

Vestibular compensation is the natural process of recovery that occurs with acute peripheral vestibular lesion. Here, we summarize the current understanding of the mechanisms underlying vestibular compensation, focusing on the role of the medial vestibular nucleus (MVN), the central hub of the vestibular system, and its associated neural networks. The disruption of neural activity balance between the bilateral MVNs underlies the vestibular symptoms after unilateral vestibular damage, and this balance disruption can be partially reversed by the mutual inhibitory projections between the bilateral MVNs, and their top-down regulation by other brain regions via different neurotransmitters. However, the detailed mechanism of how MVN is involved in vestibular compensation and regulated remains largely unknown. A deeper understanding of the vestibular neural network and the neurotransmitter systems involved in vestibular compensation holds promise for improving treatment outcomes and developing more effective interventions for vestibular disorders.

Sound-seeking before and after hearing loss in mice

How we move our bodies affects how we perceive sound. For instance, head movements help us to better localize the source of a sound and to compensate for asymmetric hearing loss. However, many auditory experiments are designed to restrict head and body movements. To study the role of movement in hearing, we developed a behavioral task called sound-seeking that rewarded freely moving mice for tracking down an ongoing sound source. Over the course of learning, mice more efficiently navigated to the sound. Next, we asked how sound-seeking was affected by hearing loss induced by surgical removal of the malleus from the middle ear. After bilateral hearing loss sound-seeking performance drastically declined and did not recover. In striking contrast, after unilateral hearing loss mice were only transiently impaired and then recovered their sound-seek ability over about a week. Throughout recovery, unilateral mice increasingly relied on a movement strategy of sequentially checking potential locations for the sound source. In contrast, the startle reflex (an innate auditory behavior) was preserved after unilateral hearing loss and abolished by bilateral hearing loss without recovery over time. In sum, mice compensate with body movement for permanent unilateral damage to the peripheral auditory system. Looking forward, this paradigm provides an opportunity to examine how movement enhances perception and enables resilient adaptation to sensory disorders.

The Motor Optimality Score-Revised Improves Early Detection of Unilateral Cerebral Palsy in Infants with Perinatal Cerebral Stroke.

Neonatal cerebral stroke includes a range of focal and multifocal ischemic and hemorrhagic brain lesions, occurring in about one of 3000 live births. More than 50% of children with neonatal stroke develop adverse outcomes, mainly unilateral cerebral palsy. Asymmetries in segmental movements at three months have been proven to be an early sign of CP in infants with unilateral brain damage. Recognition of additional early signs could enhance prognostic assessment and enable an early and targeted intervention. The aim of the study was to assess early signs of CP in infants with arterial cerebral stroke through the General Movements Assessment and the Motor Optimality Score-Revised (MOS-R). Twenty-four infants born at term (12 females and 12 males) diagnosed with ACS, and 24 healthy infants (16 females and 8 males) were assessed. The GMs (fidgety movements) and MOS-R were assessed from videos recorded at 11-14 weeks of post-term age. Cognitive and motor outcomes were assessed at 24 months using the Griffiths III developmental quotient and Amiel-Tison neurological examination. The gross motor function classification system expanded and revised (GMFCS-E&R) was adopted to categorize CP. Among infants with ACS, 21 (87.5%) developed unilateral CP. Most of them showed non-disabling CP (14 had GMFCS-E&R grade 1 [66.6%], 6 grade 2 [28.6%], and 1 grade 5 [4.8%]). Fidgety movements (FMs) were absent in 17 (70.8%), sporadic in 4 (16.7%) infants, and normal in 3 (12.5%). Segmental movement asymmetry was found in 22/24 (91.7%). According to the MOS-R, motor items (kicking, mouth movements), postural patterns (midline centered head, finger posture variability), and movement character (monotonous and stiff) were statistically different among infants with ACS and healthy infants. The MOS-R median global score was lower in the group with ACS compared to the control group (6 vs 26; p < 0.01). FMs, segmental movement asymmetry, and MOS-R global score were significantly correlated with abnormal outcome. MOS-R global scores less than or equal to 13 had 100% specificity and sensitivity in predicting GMFCS-E&R grade ≥ 2 CP in infants with ACS. The rate of CP was high among infants with ACS, but in most cases it showed low GMFCS-E&R grades. The study highlighted a significant correlation between MOS-R, together with absent FMs and unilateral CP in infants with ACS. Moreover, the MOS-R showed high sensitivity and specificity in the prediction of CP. Combined assessment of FMs and MOS-R could help to better identify infants at high risk of developing UCP in a population of infants with ACS. Early identification of precocious signs of unilateral CP is fundamental to providing an early individualized intervention.

The impact of bilateral versus unilateral anterior temporal lobe damage on face recognition, person knowledge and semantic memory.

The functional importance of the anterior temporal lobes (ATLs) has come to prominence in two active, albeit unconnected literatures-(i) face recognition and (ii) semantic memory. To generate a unified account of the ATLs, we tested the predictions from each literature and examined the effects of bilateral versus unilateral ATL damage on face recognition, person knowledge, and semantic memory. Sixteen people with bilateral ATL atrophy from semantic dementia (SD), 17 people with unilateral ATL resection for temporal lobe epilepsy (TLE; left = 10, right = 7), and 14 controls completed tasks assessing perceptual face matching, person knowledge and general semantic memory. People with SD were impaired across all semantic tasks, including person knowledge. Despite commensurate total ATL damage, unilateral resection generated mild impairments, with minimal differences between left- and right-ATL resection. Face matching performance was largely preserved but slightly reduced in SD and right TLE. All groups displayed the familiarity effect in face matching; however, it was reduced in SD and right TLE and was aligned with the level of item-specific semantic knowledge in all participants. We propose a neurocognitive framework whereby the ATLs underpin a resilient bilateral representation system that supports semantic memory, person knowledge and face recognition.

Altered thalamus functional connectivity in patients with acute unilateral vestibulopathy: a resting-state fMRI study.

Acute unilateral vestibulopathy (AUVP) is the second leading cause of peripheral vestibular vertigo. Full recovery of AUVP is related to sufficient central vestibular compensation. It has been confirmed that the vestibular nucleus and vestibular cortex are involved in the process of vestibular compensatory in AUVP patients. However, few studies have focused on the functional compensation of thalamus in patients with AUVP. This study aimed to explore the alterations of resting-state functional connectivity (FC) focused on thalamus using functional magnetic resonance imaging (fMRI) in AUVP patients. Data of 3D-T1 and resting-state fMRI were collected from 40 AUVP patients and 35 healthy controls (HC). Seeds-based (bilateral thalamus) FC was analyzed to investigate the changes in FC between the two groups. Furthermore, we evaluated the associations between altered thalamus FC and clinical features in AUVP patients using Pearson's partial correlation. Compared with HC, AUVP patients showed decreased FC between bilateral thalamus and left insula. We also observed decreased FC between right thalamus and left supramarginal gyrus. Additionally, we found increased FC between left thalamus and right postcentral gyrus (PCG), as well as increased FC between right thalamus and regions of bilateral PCG, right middle frontal gyrus and right middle occipital gyrus in AUVP patients. Furthermore, the FC between left thalamus and left insula was negatively correlated with values of canal paresis in patients with AUVP (p = 0.010, r = -0.434). Our results provided first evidence for the decreased thalamo-vestibular cortex pathway, as well as increased thalamo-somatosensory and thalamo-visual cortex pathway in AUVP patients. These findings help us better understand the underlying mechanisms of central dynamic compensatory following an acute unilateral peripheral vestibular damage.

Brachial Plexus Injury Influences Efferent Transmission on More than Just the Symptomatic Side, as Verified with Clinical Neurophysiology Methods Using Magnetic and Electrical Stimulation.

The variety of sources of brachial plexus injuries (BPIs) and the severity and similarity of their clinical symptoms with those of other injuries make their differential diagnosis difficult. Enriching their diagnosis with objective high-sensitivity diagnostics such as clinical neurophysiology may lead to satisfactory treatment results, and magnetic stimulation (MEP) might be an advantageous addition to the diagnostic standard of electrical stimulation used in electroneurography (ENG). The asymptomatic side in BPI cases sometimes shows only subclinical neurological deficits; this study aimed to clarify the validity and utility of using MEP vs. ENG to detect neural conduction abnormalities. Twenty patients with a BPI and twenty healthy volunteers with matching demographic and anthropometric characteristics were stimulated at their Erb's point in order to record the potentials evoked using magnetic and electrical stimuli to evaluate their peripheral motor neural transmission in their axillar, musculocutaneous, radial, and ulnar nerves. MEP was also used to verify the neural transmission in participants' cervical roots following transvertebral stimulations, checking the compatibility and repeatability of the evoked potential recordings. The clinical assessment resulted in an average muscle strength of 3-1 (with a mean of 2.2), analgesia that mainly manifested in the C5-C7 spinal dermatomes, and a pain evaluation of 6-4 (mean of 5.4) on the symptomatic side using the Visual Analog Scale, with no pathological symptoms on the contralateral side. A comparison of the recorded potentials evoked with magnetic versus electrical stimuli revealed that the MEP amplitudes were usually higher, at p = 0.04-0.03, in most of the healthy volunteers' recorded muscles than in those of the group of BPI patients, whose recordings showed that their CMAP and MEP amplitude values were lower on their more symptomatic than asymptomatic sides, at p = 0.04-0.009. In recordings following musculocutaneous and radial nerve electrical stimulation and ulnar nerve magnetic stimulation at Erb's point, the values of the latencies were also longer on the patient's asymptomatic side compared to those in the control group. The above outcomes prove the mixed axonal and demyelination natures of brachial plexus injuries. They indicate that different types of traumatic BPIs also involve the clinically asymptomatic side. Cases with predominantly median nerve lesions were detected in sensory nerve conduction studies (SNCSs). In 16 patients, electromyography revealed neurogenic damage to the deltoid and biceps muscles, with an active denervation process at work. The predominance of C5 and C6 brachial plexus injuries in the cervical root and upper/middle trunk of patients with BPI has been confirmed. A probable explanation for the bilateral symptoms of dysfunction detected via clinical neurophysiology methods in the examined BPI patients, who showed primarily unilateral damage, maybe the reaction of their internal neural spinal center's organization. Even when subclinical, this may explain the poor BPI treatment outcomes that sometimes occur following long-term physical therapy or surgical treatment.

Rehabilitation for Unilateral Spatial Neglect

Unilateral spatial neglect (USN) is a symptom of unilateral brain damage resulting in failure to report sensory phenomena in the contra-lesional space. It is associated with motor impairment as well as sensory deficits. Recent research suggests that USN, may be caused by a disruption in the interhemispheric balance of the visual attention network. Based on this hypothesis, non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), is utilized in the rehabilitation of USN patients. Presently, inhibitory stimulation by continuous theta burst stimulation (cTBS) on contra-lesional parietal cortex are believed to be the most promising method. Conversely, compensation by attentional network of the non-lesioned hemisphere plays an important role in the recovery of USN. Recent imaging studies revealed that functional and structural connectivity of attentional networks within a lesioned hemisphere and between lesioned and non-lesioned hemispheres affects spontaneous recovery and effectiveness of rehabilitation approach such as prism adaptation therapy. These findings are useful in elucidating the pathophysiology of USN and predicting functional outcome. Furthermore, we hope that understanding the pathophysiology will enable the development of new rehabilitation strategies and appropriate treatment selection.

Clinical course of respiratory tuberculosis relapses in the Kazakh population depending on HLA-DRB1 gene alleles.

The study aimed to ascertain the prevalence and frequency of relapses of respiratory tuberculosis (TB) and examine the characteristics of its clinical progression in members of the Kazakh population based on the alleles of the HLA-DRB1 gene. Methods of clinical and genetic research, statistical processing and analysis of the obtained data were used to achieve this goal. The research led to an analysis of the statistical processing of clinical and genetic investigations that found out how often TB in the respiratory tract is found and how different HLA-DRB1 gene alleles affect the disease's progression. To find out how exposure to certain HLA-DRB1 gene alleles affects the chance of relapse, the number of times they were found was compared between people who had relapsed and people who had just been diagnosed with TB. The impact of these alleles on the progression of the disease was assessed based on their frequency of detection of different clinical forms of TB (infiltrative, fibro-cavernous, generalised, disseminated), unilateral and bilateral lung damage, lung tissue deterioration, and the presence of bacterial secretions. The highest detection rate for all comparisons had gene alleles HLA-DRB1*01 (9.5%), *08 (4.2%), *15 (3.9%), *09 (1.6%), *12 (1.3%), *13 (0.9%), *11 (0.2%). The study found that Kazakhs with the HLA-DRB1*01, *08, and 15 gene alleles are more likely to develop recurrent respiratory TB. The study's practical value lies in its potential to utilise its findings for the prompt identification and eradication of genetic variables contributing to the recurrence of TB.

Testing the Adaptive Sterilization Hypothesis in mice inoculated with Chlamydia muridarum.

The "adaptive sterilization hypothesis" argues that the tendency of sexually transmitted infections (STIs) to cause infertility likely reflects an evolutionary adaptation of these pathogens. For example, some STIs can lead to bilateral occlusions of the oviducts and sterile matings. Cycling females that do not spend time gestating and lactating are ready to mate sooner than fertile females, and therefore, likely to mate more frequently and possibly more promiscuously. These sexual activities are associated with enhanced transmissibility of STIs, and tubal occlusion is a proximate mechanism by which STIs can increase fitness. Our principal objectives were to determine whether female mice inoculated with Chlamydia muridarum mate more frequently than mice inoculated with sterile saline and to test the hypothesis that tubal occlusion following C. muridarum infection modulates mating behavior in a manner that might increase transmissibility of Chlamydia. Similar to C. trachomatis infections in human females, C. muridarum can ascend the reproductive tract of mice, damage and occlude the oviducts, and cause infertility. However, ovarian function and mating activity are maintained following tubal occlusion. Twenty C57Bl/6 mice with regular estrous cycles were given intra-vaginal inocula of C. muridarum and 32 days later paired with a male for 90 days. Nine saline-treated females served as controls. Three Chlamydia-inoculated females were rendered infertile due to bilateral oviductal damage and mated 8 (±0.0) times. Control females mated on average 4.6 (±0.3) times, and 17 Chlamydia-inoculated fertile females, including six females with only a single oviduct occluded, mated on average 4.7 (±0.2) times. Chlamydia-inoculated fertile females with unilateral oviductal damage had significantly smaller average litter sizes as compared to females inoculated with saline. Females with unilateral tubal occlusion also tended to wean fewer pups than saline controls over the course of 90 days. Female mice with Chlamydia-induced tubal infertility mated more frequently (approximately every 11 d) than did fertile females (approximately every 20 d), which is consistent with the adaptive sterilization hypothesis. To determine whether Chlamydia-induced sterilization is truly adaptive, future studies will need to demonstrate increased sexual transmissibility, and possibly increased promiscuity, within populations of freely breeding mice.

CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome.

Introduction: The acute respiratory distress syndrome (ARDS), secondary to viral pneumonitis, is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019)-ongoing SARS-CoV-2 infection- reached more than 0.7 billion registered cases. Methods: Recently, we elaborated a non-surgical and reproducible method of the unilateral total diffuse alveolar damage (DAD) of the left lung in ICR mice-a publicly available imitation of the ARDS caused by SARS-CoV-2. Our data read that two C-C chemokine receptor 5 (CCR5) ligands, macrophage inflammatory proteins (MIPs) MIP-1α/CCL3 and MIP-1β/CCL4, are upregulated in this DAD model up to three orders of magnitude compared to the background level. Results: Here, we showed that a nonpeptide compound TAK-779, an antagonist of CCR5/CXCR3, readily prevents DAD in the lung with a single injection of 2.5mg/kg. Histological analysis revealed reduced peribronchial and perivascular mononuclear infiltration in the lung and mononuclear infiltration of the wall and lumen of the alveoli in the TAK-779-treated animals. Administration of TAK-779 decreased the 3-5-fold level of serum cytokines and chemokines in animals with DAD, including CCR5 ligands MIP-1α/β, MCP-1, and CCL5. Computed tomography revealed rapid recovery of the density and volume of the affected lung in TAK-779-treated animals. Discussion: Our pre-clinical data suggest that TAK-779 is more effective than the administration of dexamethasone or the anti-IL6R therapeutic antibody tocilizumab, which brings novel therapeutic modality to TAK-779 and other CCR5 inhibitors for the treatment of virus-induced hyperinflammation syndromes, including COVID-19.

Measuring Optokinetic Reflex and Vestibulo-Ocular Reflex in Unilateral Vestibular Organ Damage Model of Zebrafish.

One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.

Microporomechanics of quasi-brittle rocks: Theoretical formulations and analytical simulations

Hydromechanical coupling is one of the essential theoretical and practical issues in rock mechanics and rock engineering. In geological context, it is critically important to incorporate the effect of pore pressure into the constitutive equations with full account of cracking-induced material anisotropies and friction-related plastic deformation. Focus here is put on poromechanical formulations for quasi-brittle rocks weakened by microcracks and saturated with pore fluid pressure. The linear homogenization method applied to derive the effective properties and system free energy is combined with the irreversible thermodynamics and the problem decomposition. Constitutive derivations include the determination of the system free energy, state equations associated with and evolution laws of the internal variables, closed-form failure criterion, etc. Inherent coupling between anisotropic unilateral damage, friction-induced plastic deformation and the fluid pressure constitutes one of significant novelties of the work. Continuities required for the total free energy, macroscopic stress and the global porosity are guaranteed at any opening-closure transition of cracks. Through strength and deformation coupling analyses, the effects of fluid pressure on material strength and deformation are elucidated and also validated by experiments we performed upon a sandstone.

Contralateral Astrocyte Response to Acute Optic Nerve Damage Is Mitigated by PANX1 Channel Activity.

Glial reactivity is considered a hallmark of damage-induced innate immune responses in the central nervous system. In the visual system, unilateral optic nerve damage elicits dramatic glial reactivity in the retina directly affected by the lesion and a similar, albeit more modest, effect in the contralateral eye. Evaluation of astrocyte changes in a mouse model of optic nerve crush indicates that astrocyte reactivity, as a function of retinal coverage and cellular hypertrophy, occurs within both the experimental and contralateral retinas, although the hypertrophic response of the astrocytes in the contralateral eyes is delayed for at least 24 h. Evaluation of astrocytic reactivity as a function of Gfap expression indicates a similar, muted but significant, response in contralateral eyes. This constrained glial response is completely negated by conditional knock out of Panx1 in both astrocytes and Müller cells. Further studies are required to identify if this is an autocrine or a paracrine suppression of astroglial reactivity.

Cross-modal exposure restores multisensory enhancement after hemianopia.

Hemianopia is a common consequence of unilateral damage to visual cortex that manifests as a profound blindness in contralesional space. A noninvasive cross-modal (visual-auditory) exposure paradigm has been developed in an animal model to ameliorate this disorder. Repeated stimulation of a visual-auditory stimulus restores overt responses to visual stimuli in the blinded hemifield. It is believed to accomplish this by enhancing the visual sensitivity of circuits remaining after a lesion of visual cortex; in particular, circuits involving the multisensory neurons of the superior colliculus. Neurons in this midbrain structure are known to integrate spatiotemporally congruent visual and auditory signals to amplify their responses, which, in turn, enhances behavioral performance. Here we evaluated the relationship between the rehabilitation of hemianopia and this process of multisensory integration. Induction of hemianopia also eliminated multisensory enhancement in the blinded hemifield. Both vision and multisensory enhancement rapidly recovered with the rehabilitative cross-modal exposures. However, although both reached pre-lesion levels at similar rates, they did so with different spatial patterns. The results suggest that the capability for multisensory integration and enhancement is not a pre-requisite for visual recovery in hemianopia, and that the underlying mechanisms for recovery may be more complex than currently appreciated.