Significant Pathology Research Articles

TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

Gastroprotective Effect of Quercus infectoria Olivier Galls on Ethanol-Induced Gastritis in Rats.

One of the common inflammatory disorders that substantially affects the stomach and its mucosa is gastritis. It can be induced by non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, alcohol, Helicobacter pylori infection, and stress. These factors affect cellular regeneration, mucus production, and bicarbonate secretion, resulting finally in inflammation and ulceration. Ethanol-induced gastritis is one of the commonly used models for studying the pathology of gastritis and investigating the effect of drugs in managing the disease. Several drugs, such as proton pump inhibitors (PPIs), are available to control and correct the pathological signs of gastritis; however, the side effects of such drugs represent an obstacle to their applications in many cases. Quercus infectoria(QI) Olivier galls are formed as a pathological response to wasp insults to the tree. They are rich in several bioactive molecules, e.g., gallotannins that have been shown to be effective in several inflammatory conditions due to their antioxidant and anti-inflammatory potentials. In this study, we aimed to evaluate the therapeutic potential of QI gall extract (QIGE) in treating ethanol-induced gastritis in rats. To test this, 20 adult male Swiss rats were divided into four groups: healthy control, ethanol-treated (80% in water, 5 ml/kg, per oral gavage), ethanol + omeprazole (20 mg/kg, per oral gavage), and ethanol + QIGE (300 mg/kg, per oral gavage). QIGE was administered for seven days before ethanol administration, which took place three hours after the last QIGE dose. Three hours after ethanol intake, animals were euthanized, gastric content was collected, and stomach tissue was examined for macroscopic changes and then fixed to be further utilized for histological assessment by hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Masson's trichrome staining. Ethanol treatment significantly decreased gastric pH and increased gastric acidity compared to healthy control. It also induced clear morphological and histological damage and ulceration, depleted mucus on the gastric epithelium, and induced edema and collagen deposition in gastric submucosa. The QIGE treatment ameliorated the changes in gastric pH and total acidity. It also protected stomach tissue from ethanol-induced ulceration, histopathological changes, edema, and collagen deposition. The protective effects of QIGE were comparable to those of omeprazole. In conclusion, QI gall extract possesses a promising gastroprotective effect against ethanol-induced gastritis.

Risk Factors for Bone Fractures in Patients With Comorbid Pathology

Patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), leading to macrophage activation, impaired microvascular function, changes in muscle contraction and fibrosis development. In addition, these proinflammatory cytokines promote bone resorption, thereby increasing the incidence of bone fractures. The aim of the study is to evaluate the effect of tumor necrosis factor-alpha receptor types 1 and 2 (TNF-α-SR1 and TNF-α-SR2) on fracture probability in individuals with osteoporosis who have concurrent chronic heart failure (HF) and type 2 diabetes mellitus (T2DM). The study was conducted on 178 women aged 50 to 65 years. Among these women, 48 were in group 1 and had both heart failure and type 2 diabetes. Group 2 included 93 patients with osteoporosis and heart failure and group 3 included 37 women with osteoporosis, heart failure and type 2 diabetes. Thirty-five postmenopausal women without any clinical and instrumental signs of cardiovascular pathology or osteoporosis were selected as the control group. The levels of TNF-α-SR1 and TNF-α-SR2 receptors in patient groups 1-3 were significantly higher (p<0.01) than in the control group, as were their concentrations. In addition, it was found that the levels of both receptors were significantly higher in group 3 than in patients in groups 1 and 2. To evaluate the levels of TNF-α-SR1 and TNF-α-SR2, the data were divided into four quartiles (Q1-Q4) based on the increase in the concentrations of these markers. For TNF-α-SR2, an increasing risk gradient was observed, with the odds ratio (OR) for osteoporosis events increasing from 1.4 to 12.83, but the risk was statistically significant only for Q3-Q4. For Q4 TNF-α-SR1 levels, a significant increase in the risk of an adverse osteoporosis outcome at 36 months was also found (OR=5.25, p=0.038). In addition, the use of loop diuretics was found to be a predictor of high risk of osteoporotic fractures in patients with chronic HF (JR=6.29, 95% CI=1.45-17.26, p=0.015). Postmenopausal women with chronic HF and elevated levels of soluble TNF-α-SR1 and TNF-α-SR2 receptors are at higher risk for osteoporosis and adverse disease progression. In addition, the use of loop diuretics in these individuals is associated with an increased risk of osteoporotic fractures.

RADIOLOGICAL FEATURES OF THE LOCATION OF CYSTIC FORMATIONS IN THE MAXILLARY SINUS AND THEIR RELATIONSHIP WITH ALVEOLAR BONE PATHOLOGY OF THE UPPER JAW

The aim of the study. To study the features of the location of cystic formations in the maxillary sinus based on CT scans and to determine their relationship with the pathology of the upper jaw teeth.
 Materials and methods. The study involved the analysis of 552 head computed tomography scans of patients referred for examination by an otolaryngologist or dentist. The total number of individuals examined was 552, comprising 44.7% females and 55.3% males, aged 18-74 years. The investigation was conducted using the NewTom GO device with a measurement range of 155-172 mGy/cm±10%, with an error of ±4.24%. Statistical processing of data was carried out using the STATISTICA v.12.6 software.
 Results. Out of 552 computed tomography images analyzed, 92 images of individual maxillary sinuses (MS) of 79 patients with single cysts were selected. They were divided into two groups. Group 1 involved patients with cysts on the lower wall of MS (n=76). Group 2 included patients with cysts on other walls (n=16). The assessment of the ratio of 4, 5, 6, 7 tooth roots of the upper jaw to the lower wall of the upper jaw showed that the protrusion frequency in Group 1 was significantly higher (42.1%) compared to Group 2 (18.7%). Meanwhile, the average thickness of the bone over these teeth in Group 2 was significantly greater (3.4 ± 1.09 mm) than in Group 1 (1.9 ± 0.92 mm) (p=0.0003). In both patient groups, the greatest thickness was observed over tooth 4, and the smallest over tooth 7. Additionally, in 33.7% of cases, the cyst was associated with involvement of deep structures of the projecting teeth and the spread of inflammation to the lower wall of MS.
 Conclusions. Among patients referred by an otolaryngologist or dentist for CT examination to radiologically verify pathological processes in the nasal cavity, paranasal sinuses, and the upper jaw teeth, MS cysts were detected in 19.6% of cases, with 83% of them being localized in its lower parts. In patients with cysts located in the lower parts of MS, the roots protruding into the sinus cavity and a thinner layer of bone over them are more frequently observed compared to those where cysts are located in other areas of MS. In patients with cystic formations in the alveolar recess of MS, radiological signs of pathology of the upper jaw teeth are detected in 34% of cases.

Lymphatic malformations: mechanistic insights and evolving therapeutic frontiers.

The lymphatic vascular system is gaining recognition for its multifaceted role and broad pathological significance. Once perceived as a mere conduit for interstitial fluid and immune cell transport, recent research has unveiled its active involvement in critical physiological processes and common diseases, including inflammation, autoimmune diseases, and atherosclerosis. Consequently, abnormal development or functionality of lymphatic vessels can result in serious health complications. Here, we discuss lymphatic malformations (LMs), which are localized lesions that manifest as fluid-filled cysts or extensive infiltrative lymphatic vessel overgrowth, often associated with debilitating, even life-threatening, consequences. Genetic causes of LMs have been uncovered, and several promising drug-based therapies are currently under investigation and will be discussed.

Circular RNA circNCOA3 promotes tumor progression and anti-PD-1 resistance in colorectal cancer.

Aim: Circular RNAs (circRNAs) have been found to be involved in tumor progression, but their role in colorectal cancer (CRC) immune escape remains to be elucidated. Methods: circRNAs differentially expressed in responsive and resistant CRC tissues to programmed cell death 1 (PD-1) antibody therapy were identified by microarray analysis. The clinical and pathological significance of circNCOA3 was validated in a separate cohort of CRC samples. The function of circNCOA3 was explored experimentally. RNA immunoprecipitation and luciferase activity assays were conducted to identify downstream targets of circNCOA3. Results: The circNCOA3 was markedly overexpressed in CRC samples resistant to PD-1 blockade. circNCOA3 expression was significantly correlated with adverse tumor phenotypes and poor outcomes in CRC patients. Knockdown of circNCOA3 expression markedly suppressed the proliferative and invasive capability of CRC cells. Moreover, knockdown of circNCOA3 increased the proportion of CD8+ T cells while decreasing the proportion of myeloid-derived suppressor cells (MDSCs). Knockdown of circNCOA3 inhibited tumor growth and increased the sensitivity to PD-1 antibody treatment in mouse tumor models. Further studies revealed that circNCOA3 acted as a competing endogenous RNA (ceRNA) for miR-203a-3p.1 to influence the level of CXCL1. Conclusion: Our findings indicate that circNCOA3 might be useful as a potential biomarker to predict the efficacy and prognosis of CRC patients treated with anti-PD-1 therapy.

Frequency of Clinically Significant Findings in the Surgical Pathology Specimen Following Laparoscopic Sleeve Gastrectomy and Concordance with Preoperative Endoscopy: Insights from a Large Single-Center Experience.

Endoscopy prior to bariatric surgery is not always performed, and in sleeve gastrectomy (SG), the surgical specimen is not always sent for pathological examination. There is limited data on the frequency of clinically significant findings in SG specimens or correlation with preoperative endoscopy. We reviewed 426 consecutive SG patients to determine the concordance of preoperative endoscopy findings in patients with clinically significant postoperative pathology. Preoperative endoscopy was performed on 397 patients (93.2%). Three hundred seventy-three patients had preoperative endoscopy and surgical pathology results available. Then, 20/373 (5.4%) patients had potentially significant postoperative pathology, including intestinal metaplasia, autoimmune metaplastic atrophic gastritis (AMAG), gastrointestinal stromal tumors, and/or gastric cancer. The overall incidence of AMAG in the entire cohort was 2.3%. Preoperative gastric biopsies (to include gastric body) identified AMAG in nearly 1/2 of patients. Patients with clinically significant postoperative pathology results had a median [interquartile range] of 3 [3-5] tissue blocks examined as compared to 3 [1-3] for the remainder of the cohort (p < 0.001). This is one of the largest studies describing clinically significant postoperative pathology after SG. AMAG, in particular, is of particular importance as it is associated with a 3-fivefold increase in risk for gastric cancer. The incidence of significant postoperative pathology in this population is small but potentially clinically significant and requires validation in larger studies. We recommend wider sampling in preoperative endoscopy (body and antrum), especially in patients being planned for gastric bypass, consideration for routine pathological examination of SG surgical specimens, with careful gross examination and targeted sampling.

Pathogenetic aspects of the autoreactive form of spontaneous urticaria in adult patients

Objective: to study the parameters of the immune status and the spectrum of autoimmune markers of patients suffering from an autoreactive form of chronic spontaneous urticaria. Materials and methods: the study involved 67 patients with an autoreactive form of chronic spontaneous urticaria, with clinical and laboratory signs of autoimmune pathology, aged 18 to 65 years, who were observed on an outpatient or inpatient basis in the period from 2019 to 2022. Healthy donors without signs of chronic spontaneous urticaria (n=35) were considered as a control group. The results were evaluated according to the dynamics of clinical and functional, immunological examination. Results: when assessing the immune status of patients with autoreactive chronic spontaneous urticaria, a violation of the differentiation processes of immune-competent cells was revealed, with a predominance of T-lymphocytes with helper-inductive activity, entailing an inversion of the immune-regulatory index, activation of the humoral link of the immune system was noted: an increase in B-lymphocytes, immunoglobulins of classes A, M, G, increase of circulating immune complexes. The indicators of total IgE did not differ fundamentally from the level of donors. Changes in the parameters of the monocyte-macrophage link in patients with autoreactive form of chronic spontaneous urticaria indicated an increase in the functional activity of phagocytic cells and depletion of their reserves. Conclusion: in the autoimmune genesis of chronic spontaneous urticaria, there are significant changes in the autoimmune markers corresponding to the concomitant autoimmune disease (rheumatoid factor, antibodies (Ab) to nDNA, Ab to cardiolipin, Ab to β2-glycoprotein, Ab to neutrophils), there is a high percentage of correlation with a positive test result with autologous serum, there are features of immune status of patients with autoreactive form of chronic spontaneous urticaria.

But We Do Not Know Anything, We Were Born in This Predicament: Experiences of Learners Facing Xenophobia in South Africa

In this article, we discuss the experiences of learners who face xenophobia in South Africa. While extensive research has been conducted on xenophobia, few studies have specifically examined its impact on school-going children, whose presence at school is not by design in South Africa. We explore their lived experiences within the curriculum, thus exposing various trajectories that hinder effective teaching and learning. To theorise our findings, we tap into Whitehouse and Lanman’s notion of social cohesion. For data collection, we used a participatory action research approach. Through a series of interviews and group discussions, we engaged with a diverse group of 13 participants, which consisted of 10 migrant learners and 3 teachers. The study found that xenophobia is a significant social pathology in South Africa which found its way into the classroom walls, thereby affecting the performance of migrant learners. It affects the victim’s identity and has profound consequences for the perpetrators. Ultimately, the effects of xenophobia contribute to a cycle of school violence. We assert the imperative of addressing the distressing impact of xenophobia on children within classrooms. Based on our findings, we argue that initial teacher education programmes are key in fostering a non-violent society through promoting cohesion and cultural responsiveness.

Acetabular "Fleck" Sign: Outcomes of Surgical Repair.

Traumatic, posterior hip dislocations in the pediatric population are typically managed by closed reduction to achieve a concentric hip joint. The presence of an acetabular "fleck" sign, despite concentric reduction, has been shown to signify significant hip pathology. The purpose of this study was to evaluate the outcomes of open labral repair through a surgical hip dislocation (SHD) in a consecutive series of patients with an acetabular "fleck" sign associated with a traumatic hip dislocation/subluxation. A retrospective review of patients between 2008 and 2022 who presented to a single, level 1 pediatric trauma center with a traumatic posterior hip dislocation/subluxation was performed. Patients were included if they had an acetabular "fleck" sign on advanced imaging and underwent open labral repair through SHD. Medical records were reviewed for sex, age, laterality, mechanism of injury (MOI), and associated orthopaedic injuries. The modified Harris hip score (mHHS) was utilized as the primary clinical outcomes measure. Patients were assessed for the presence of heterotopic ossification (HO) and complications, including implant issues, infection, avascular necrosis (AVN), and post-traumatic dysplasia. Twenty-nine patients (23 male, average age: 13.0±2.7 y; range: 5.2 to 17.3) were identified. Eighteen injuries were sports related, 9 caused by motor vehicle accidents, and 1 pedestrian struck. All patients were found to have an acetabular "fleck" sign on CT (26 patients) or MRI (5 patients). Associated injuries included: femoral head fracture (n=6), pelvic ring injury (n=3), ipsilateral femur fracture (n=2), and ipsilateral PCL avulsion (n=1). At the latest follow-up (2.2±1.4y), all patients had returned to preinjury activity/sport. Three patients developed asymptomatic, grade 1 HO in the greater trochanter region. There was no incidence of AVN. One patient developed post-traumatic acetabular dysplasia due to early triradiate closure. mHHS scores showed excellent outcomes (n=21, 94.9±7.4, range: 81 to 100.1). The acetabular "fleck" sign indicates a consistent pattern of osteochondral avulsion of the posterior/superior labrum. Restoring native hip anatomy and stability is likely to improve outcomes. SHD with open labral repair in these patients produces excellent clinical outcomes, with no reported cases of AVN. Level IV-therapeutic.

A pilot screening project for the detection of hip dysplasia in young patients

ABSTRACT Hip dysplasia in young adults is underdiagnosed and can cause pain and discomfort. Progression to osteoarthritis (OA) is common, necessitating total hip arthroplasty at an early age. When discovered early, symptomatic patients can be offered physiotherapy and/or hip-preserving surgery to alleviate pain and decrease the risk of early OA. A pilot project to screen radiograms for hip dysplasia was started across the Swedish region of Örebro Län in January 2019, comparing the incidence of dysplasia before and after initiation of the screening program. All elective conventional radiograms of the hip (age 12–44 years), requested by primary care physicians, were analyzed by consultant radiologists according to a pre-established algorithm to identify hip abnormalities. If the hip radiograms showed dysplastic changes, or other pathological signs, the radiologist advised referral to a specialized Youth Hip Clinic for further work-up and treatment. A total of 1056 radiograms were requested by clinicians during the study periods (601 and 455 during 2018 and 2020, respectively). A total of 457 trauma-related cases were excluded, resulting in 599 available for analysis (348 and 251 during 2018 and 2020, respectively). During 2018, 17 patients (4.9%) received the radiologic diagnosis of dysplasia, compared with 44 patients (17.5%) during 2020 (P &amp;lt; 0. 001). A three-fold increase of patients diagnosed with hip dysplasia was detected as a result of the implementation of the screening program. The advantage of screening is early referral to an orthopedic department for evaluation and consideration for physiotherapy and/or surgical intervention.

Male–female disparity in clinical features and significance of mild vertebral fractures in community-dwelling residents aged 50 and over

This investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant’s criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman’s rho: 0.23 to 0.36, P < 0.05). Our study showed that Grade 1 mild vertebral fractures in males lacked pathological significance, while in females they potentially indicated fragility fractures and were related to poor lumbopelvic alignment.

Indicators of cerebral venous drainage with non-thrombotic disorders in extracranial veins

The growing number of studies on cerebral venous circulation disorders associated with extrinsic stenosis of the internal jugular veins, as well as attempts to surgically influence the restoration of blood flow, are an indicator of the importance of this problem. Studies show that extracranial outflow disorders are associated with a wide range of neurological clinical manifestations and may contribute to the development of congestive intracranial hypertension. Anatomical variants of the development of the extracranial venous system, constitutional insufficiency and stenosis often play similar roles in the development of disorders of the cerebral venous outflow, but differ parametrically. There are no standard diagnostic criteria for differential diagnosis, normal and pathological parameters are contradictory, and the diagnosis largely depends on the combined use of imaging techniques. The history of attempts to study disorders of the cerebral venous circulation is quite long, associated with the technical innovations in every period of time. The most non-invasive, accessible and safe tools for diagnosing non-thrombotic lesions and anomalies of the internal jugular veins are currently recognized as ultrasound scanning and MR venography in tandem. Researchers note both local hemodynamic disturbances at the level of stenosis and changes in the overall picture of the venous vascular network of the neck with certain patterns of its remodeling. The pathological significance of the compensatory expansion of nonjugular outflow tracts (vertebral, paraspinal collateral, spinal epidural veins, etc.) is still a controversial issue. MRI and ultrasound combined show a high degree of agreement between the results, which should stimulate further research into the pathophysiology and differentiation of various causes and severity of non-thrombotic lesions of the jugular veins.

(271) Assessment of Varicocele Bilaterality in Infertile Men

Abstract Introduction Varicocele is the most common correctable cause of male factor infertility. It has always been a debatable subject as regard how it affects fertility and the best way to treat. However, there is a wide consensus nowadays that varicocelectomy improve male fertility potentials. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. Objective The primary outcome measure was to assess disease bilaterality and the secondary outcome measure was to report on improvement in semen 3 and 6 months post varicocelectomy and pregnancy rate 1 year post surgery. Methods This prospective study was conducted between January 2019 and January 2022. Infertile males with varicoceles underwent microsurgical subinguinal varicocelectomy by expert uroandrologists. Patients who were referred as unilateral varicoceles had their CDUS repeated for assessment of missed concomitant contralateral varicocele. Then, patients who were diagnosed with bilateral varicoceles underwent bilateral subinguinal ligation straight away. Those who were referred with unilateral varicocele had their palpable sides operated on first; then the contralateral side was also explored using an intraoperative Doppler device and the maximal vein diameter was measured. Patients came for follow for at least 6 months after surgery to evaluate any complications and assess improvement in semen parameters. Gynecologists also reported on normal pregnancy rate 1 year after surgery. Results A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). This is statistically significantly higher than initial US (P&amp;lt;0.001). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter [r=0.9, P&amp;lt;0.001]. Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). Conclusions Varicocele bilaterality is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome. Disclosure No.

α-Methylacyl-CoA Racemase from Mycobacterium tuberculosis-Detailed Kinetic and Structural Characterization of the Active Site.

α-Methylacyl-CoA racemase in M. tuberculosis (MCR) has an essential role in fatty acid metabolism and cholesterol utilization, contributing to the bacterium's survival and persistence. Understanding the enzymatic activity and structural features of MCR provides insights into its physiological and pathological significance and potential as a therapeutic target. Here, we report high-resolution crystal structures for wild-type MCR in a new crystal form (at 1.65 Å resolution) and for three active-site mutants, H126A, D156A and E241A, at 2.45, 1.64 and 1.85 Å resolutions, respectively. Our analysis of the new wild-type structure revealed a similar dimeric arrangement of MCR molecules to that previously reported and details of the catalytic site. The determination of the structures of these H126A, D156A and E241A mutants, along with their detailed kinetic analysis, has now allowed for a rigorous assessment of their catalytic properties. No significant change outside the enzymatic active site was observed in the three mutants, establishing that the diminution of catalytic activity is mainly attributable to disruption of the catalytic apparatus involving key hydrogen bonding and water-mediated interactions. The wild-type structure, together with detailed mutational and biochemical data, provide a basis for understanding the catalytic properties of this enzyme, which is important for the design of future anti-tuberculosis drug molecules.

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum.

The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.

Mechanoregulation and function of calponin and transgelin.

It is well known that chemical energy can be converted to mechanical force in biological systems by motor proteins such as myosin ATPase. It is also broadly observed that constant/static mechanical signals potently induce cellular responses. However, the mechanisms that cells sense and convert the mechanical force into biochemical signals are not well understood. Calponin and transgelin are a family of homologous proteins that participate in the regulation of actin-activated myosin motor activity. An isoform of calponin, calponin 2, has been shown to regulate cytoskeleton-based cell motility functions under mechanical signaling. The expression of the calponin 2 gene and the turnover of calponin 2 protein are both under mechanoregulation. The regulation and function of calponin 2 has physiological and pathological significance, as shown in platelet adhesion, inflammatory arthritis, arterial atherosclerosis, calcific aortic valve disease, post-surgical fibrotic peritoneal adhesion, chronic proteinuria, ovarian insufficiency, and tumor metastasis. The levels of calponin 2 vary in different cell types, reflecting adaptations to specific tissue environments and functional states. The present review focuses on the mechanoregulation of calponin and transgelin family proteins to explore how cells sense steady tension and convert the force signal to biochemical activities. Our objective is to present a current knowledge basis for further investigations to establish the function and mechanisms of calponin and transgelin in cellular mechanoregulation.

Migraine is a risk factor for pseudophakic positive dysphotopsia following monofocal lens implantation

ObjectiveTo identify neuroadaptation-related risk factors for persistent positive dysphotopsia (>6 months) following monofocal lens implantation. DesignRetrospective cohort study. ParticipantsPatients of an academic institution and a private practice in Saint Louis, Missouri. Inclusion criteria were adults with cataract extraction between January 2010 and April 2021 with monofocal intraocular lens implantation. Exclusion criteria included dementia, <20/40 acuity, visual pathway damage, visual field loss, and significant pathology causing photopsia. MethodsParticipants were surveyed via telephone. ResultsThere were 385 participants (385 eyes), of whom 66 had persistent dysphotopsia (58 positive), 298 had none, and 21 had nonpersistent dysphotopsia. Among the 58 who had positive persistent dysphotopsia, mean Pseudophakic Dysphotopsia Questionnaire 6 (PDQ-6) score was 14.11 (SD, 8.46). There were no significant differences in sex or race. Migraine prevalence was greater among those with dysphotopsia (21.2%) than among those without (11.4%; p = 0.054). History of migraine was associated with an increase in PDQ-6 score of 2.76 points (p = 0.006). Six people in each group had Visual Aura Rating Scale (VARS) scores greater than zero. Mean VARS score was 0.48 for those with dysphotopsia and 0.14 for those without (p = 0.03). History of migraine or increased VARS score, younger age, and female sex were associated with lower satisfaction. ConclusionHistory of migraine was associated with increased dysphotopsia severity and decreased patient satisfaction. Although further study with a larger sample size is warranted, these preliminary results highlight the potential of simple questions to individualize lens choice, reduce the risk of dysphotopsia, and improve patient satisfaction.

Incidental Tc-99m MIBI Lung Uptake in Parathyroid Scintigraphy.

Diffuse Tc-99m MIBI uptake in the lungs during parathyroid scintigraphy is exceptional, and only a few cases have described this unusual aspect. The differential diagnostic of this funding is a challenge when interpreting the examination, since it can be a sign of serious pathology. We report the case of unexpected diffusely increased Tc-99m MIBI uptake in bilateral lung fields in a patient with left cardiac dysfunction.

Missed abortion in the 11–21-week period: Fetal autopsy and placental histopathological analysis of 794 cases

IntroductionMissed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 – week 20 + 6). Material and methodsThis retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. ResultsThe cases were divided into two groups according to gestational length; gestational week 11 + 0–14 + 6 (group A) and 15 + 0–20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DiscussionFetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. ConclusionCord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.