Light sheet microscopy-based 3-dimensional histopathology of the lymphatic vasculature in Emberger syndrome

Abstract Introduction Lymphovascular diseases represent a heterogenous group of inherited and sporadic disorders and refer to a range of possible underlying pathologies and pathogenesis.Emberger Syndrome, an inherited form of lymphedema, is characterized by bilateral lower limb lymphedema, however, upper limbs do not show any signs of swelling.To identify disease-associated histopathological alterations in patients with Emberger Syndrome and to elucidate potential histological differences between the lymphatic vasculature of upper and lower limbs, a detailed knowledge on the 3-dimensional tissue and vessel architecture is essential. However, the current gold standard in 2-dimensional histology provides only very limited spatial information. Material and methods To elucidate the underlying vascular pathology in Emberger Syndrome on the cellular level, we applied the 3-dimensional visualization and analysis approach VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction) to entire wholemount immunofluorescence-stained human tissue samples. VIPAR is a light sheet microscopy-based imaging technique, which allows 3-dimensional reconstruction of entire tissue biopsies followed by automated and semi-automated analysis of vascular parameters in 3-dimensional space. Results Using VIPAR we could show that in Emberger Syndrome the dermal lymphatic vasculature is intact and non-disrupted.However, lower limbs showed an hypoplastic lymphatic vasculature with absence of lymphatic valves in pre-collecting and collecting vessels. In contrast to the lower limbs, the lymphatic vasculature of the upper limbs showed no morphological alterations of lymphatic vessels and lymphatic valves compared to healthy controls. Discussion Based on the 3-dimensional histopathological analysis we were able to perform a detailed phenotyping of lymphatic vessels in the upper and lower limb in Emberger Syndrome and to identify the underlying vascular pathology. In addition, we could show vascular alteration between the upper and lower limbs indicating a vascular heterogeneity of dermal lymph vessels causing the lower limb lymphedema.

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Cross-Sectional Survey of Musculoskeletal Disorders in Workers Practicing Traditional Methods of Underground Coal Mining

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17072566 ◽

2020 ◽

Vol 17 (7) ◽

pp. 2566

Author(s):

Madiha Ijaz ◽

Sajid Rashid Ahmad ◽

Muhammad M. Akram ◽

Steven M. Thygerson ◽

Falaq Ali Nadeem ◽

...

Keyword(s):

Coal Mining ◽

Upper Limb ◽

Lower Limb ◽

Lower Limbs ◽

Underground Mines ◽

Upper Limbs ◽

Underground Coal Mining ◽

Cross Sectional Survey ◽

Cross Sectional ◽

R Programming

Background: In subcontinental underground mines, coal mining is carried out manually and requires many laborers to practice traditional means of coal excavation. Each task of this occupation disturbs workers’ musculoskeletal order. In order to propose and practice possible ergonomic interventions, it is necessary to know what tasks (drilling and blasting, coal cutting, dumping, transporting, timbering and supporting, loading and unloading) cause disorder in either upper limbs, lower limbs, or both. Methods: To this end, R-programming, version R 3.1.2 and SPSS, software 20, were used to calculate data obtained by studying 260 workers (working at different tasks of coal mining) from 20 mines of four districts of Punjab, Pakistan. In addition, a Standard Nordic Musculoskeletal Questionnaire (SNMQ) and Rapid Upper Limb Assessment (RULA) sheet were used to collect data and to analyze postures respectively. Results: In multi regression models, significance of the five tasks for upper and lower limb disorder is 0.00, which means that task based prevalence of upper and lower limb disorders are common in underground coal mines. The results of the multiple bar chart showed that 96 coal cutters got upper limb disorders and 82 got lower limb disorders. The task of timbering and supporting was shown to be dangerous for the lower limbs and relatively less dangerous for the upper limbs, with 25 workers reporting pain in their lower limbs, and 19 workers reporting pain in their upper limbs. Documented on the RULA sheet, all tasks got the maximum possible score (7), meaning that each of these tasks pose a threat to the posture of 100% of workers. The majority of participants (182) fell in the age group of 26 to 35 years. Of those workers, 131 reported pain in the lower limbs and slight discomfort (128) in the upper limbs. The significance value of age was 0.00 for upper limb disorder and was 0.012 for lower limb disorder. Frequency graphs show age in direct proportion to severity of pain while in inverse proportion with number of repetitions performed per min. Conclusions: All findings infer that each task of underground coal mining inflicts different levels of disorder in a workers’ musculoskeletal structure of the upper and lower limbs. It highlighted the need for urgent intervention in postural aspects of each task.

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Interlimb neural interactions in corticospinal and spinal reflex circuits during preparation and execution of isometric elbow flexion

Journal of Neurophysiology ◽

10.1152/jn.00705.2019 ◽

2020 ◽

Vol 124 (3) ◽

pp. 652-667

Author(s):

Atsushi Sasaki ◽

Naotsugu Kaneko ◽

Yohei Masugi ◽

Matija Milosevic ◽

Kimitaka Nakazawa

Keyword(s):

Lower Limb ◽

Elbow Flexion ◽

Motor Preparation ◽

Lower Limbs ◽

Spinal Reflex ◽

Upper Limbs ◽

Limb Muscle ◽

Motor Execution ◽

Lower Limb Muscles ◽

Neural Interactions

We found that upper limb muscle contractions facilitated corticospinal circuits controlling lower limb muscles even during motor preparation, whereas motor execution of the task was required to facilitate spinal circuits. We also found that facilitation did not depend on whether contralateral or ipsilateral hands were contracted or if they were contracted bilaterally. Overall, these findings suggest that training of unaffected upper limbs may be useful to enhance facilitation of affected lower limbs in paraplegic individuals.

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Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics Without Renal Dysfunction

Journal of the American Society of Nephrology ◽

10.1681/asn.2021010061 ◽

2021 ◽

pp. ASN.2021010061

Author(s):

Hao Liu ◽

Chitkale Hiremath ◽

Quinten Patterson ◽

Saumya Vora ◽

Zhiguo Shang ◽

...

Keyword(s):

Renal Function ◽

Kidney Disease ◽

Lymphatic Vessels ◽

Light Sheet ◽

Heterozygous Mutation ◽

Blood Capillaries ◽

Developmental Abnormalities ◽

Cortical Volume ◽

Light Sheet Microscopy ◽

Lymphatic Density

Background: Lymphatic abnormalities are observed in several types of kidney disease, but the relationship between the renal lymphatic system and renal function is unclear. The discovery of lymphatic-specific proteins, advances in microscopy, and available genetic mouse models provide the tools to help elucidate the role of renal lymphatics in physiology and disease. Methods: We utilized a mouse model containing a missense mutation in Vegfr3 (dubbed Chy) that abrogates its kinase ability. Vegfr3Chy/+ mice were examined for developmental abnormalities and kidney specific outcomes. Control and Vegfr3Chy/+ mice were subjected to cisplatin-mediated injury. We characterized renal lymphatics using tissue clearing, light-sheet microscopy, and computational analyses. Results: In the kidney, VEGFR3 is expressed not only in lymphatic vessels, but also in various blood capillaries. Vegfr3Chy/+ mice had severely reduced renal lymphatics with 100% penetrance, but we found no abnormalities in blood pressure, serum creatinine, BUN, albuminuria, and histology. There was no difference in the degree of renal injury after low dose cisplatin (5 mg/kg), although Vegfr3Chy/+ mice developed perivascular inflammation. Cisplatin-treated controls had no difference in total cortical lymphatic volume and length, but showed increased lymphatic density due to decreased cortical volume. Conclusions: We demonstrate that VEGFR3 is required for development of renal lymphatics. Our studies reveal that reduced lymphatic density does not impair renal function at baseline and induces only modest histological changes after mild injury. We introduce a novel quantification method to evaluate renal lymphatics in 3D and demonstrate that accurate measurement of lymphatic density in chronic kidney disease requires assessment of changes to cortical volume.

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Inter-Limb Coordination Variability in Ice Climbers of Different Skill Level

Baltic Journal of Sport and Health Sciences ◽

10.33607/bjshs.v1i80.342 ◽

2018 ◽

Vol 1 (80) ◽

Author(s):

Ludovic Seifert ◽

Leo Wattebled ◽

Maxime L’Hermette ◽

Romain Herault

Keyword(s):

Lower Limb ◽

Skill Level ◽

Lower Limbs ◽

Upper Limbs ◽

Environmental Constraint ◽

Research Results ◽

Grade 5 ◽

Limb Coordination ◽

Left And Right ◽

Mode Of Coordination

Research background and hypothesis. Ice climbers determine their own ascent paths by creating holes with their crampons and ice tools. The coupling of upper and lower limbs thus emerges from the icefall environment without prescriptions for one mode of coordination. Research aim. The aim of this study was to analyse the upper / lower limb coordination of ice climbers of different skill level and to explore how the environmental constraint (ice fall shape) is used by the climbers to adapt their motor behaviour.Research methods. Six elite ice climbers and ﬁ ve beginners climbed a 30m icefall, respectively in grade 5 / 5+ and grade 4. Frontal camera videotaped the ﬁ rst 15m of the ascent, then the left and right ice tools and the left and right crampons were digitalised in order to analyse the upper limbs coupling, the lower limbs coupling and the upper / lower limb coordination. Research results. The results indicated that in-phase mode of upper / lower limb coordination was the main attractor for both groups. However, elite climbers showed greater variability in their behaviour, exploring larger range of upper and lower angles (particularly vertical and crossed positions) and types of movement (ice tool swinging and ice hole hooking). Discussion and conclusions. It was concluded that holes in ice fall, and more globally ice fall shape, were affordances that induced variable upper / lower limb coordination in elite climbers, whereas beginners used a basic and stable motor organization in order to maintain body equilibrium.Keywords: upper / lower limb coordination, environmental constrains, types of movement.

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Neural coupling between upper and lower limbs during recumbent stepping

Journal of Applied Physiology ◽

10.1152/japplphysiol.01350.2003 ◽

2004 ◽

Vol 97 (4) ◽

pp. 1299-1308 ◽

Cited By ~ 67

Author(s):

Helen J. Huang ◽

Daniel P. Ferris

Keyword(s):

Upper Limb ◽

Lower Limb ◽

Lower Limbs ◽

Gait Rehabilitation ◽

Upper Limbs ◽

Neurologically Impaired ◽

Resistance Level ◽

Neuromuscular Activation ◽

Lower Limb Muscles ◽

Robotic Devices

During gait rehabilitation, therapists or robotic devices often supply physical assistance to a patient's lower limbs to aid stepping. The expensive equipment and intensive manual labor required for these therapies limit their availability to patients. One alternative solution is to design devices where patients could use their upper limbs to provide physical assistance to their lower limbs (i.e., self-assistance). To explore potential neural effects of coupling upper and lower limbs, we investigated neuromuscular recruitment during self-driven and externally driven lower limb motion. Healthy subjects exercised on a recumbent stepper using different combinations of upper and lower limb exertions. The recumbent stepper mechanically coupled the upper and lower limbs, allowing users to drive the stepping motion with upper and/or lower limbs. We instructed subjects to step with 1) active upper and lower limbs at an easy resistance level (active arms and legs); 2) active upper limbs and relaxed lower limbs at easy, medium, and hard resistance levels (self-driven); and 3) relaxed upper and lower limbs while another person drove the stepping motion (externally driven). We recorded surface electromyography (EMG) from six lower limb muscles. Self-driven EMG amplitudes were always higher than externally driven EMG amplitudes ( P < 0.05). As resistance and upper limb exertion increased, self-driven EMG amplitudes also increased. EMG bursts during self-driven and active arms and legs stepping occurred at similar times. These results indicate that active upper limb movement increases neuromuscular activation of the lower limbs during cyclic stepping motions. Neurologically impaired humans that actively engage their upper limbs during gait rehabilitation may increase neuromuscular activation and enhance activity-dependent plasticity.

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EFFECT OF CORVITIN ON OXYGEN TRANSPORT FUNCTION OF THE BLOOD AND GAS TRANSMITTERS IN ISCHEMIA-REPERFUSION OF THE LOVER LIMBS

Journal of the Grodno State Medical University ◽

10.25298/2221-8785-2021-19-2-194-201 ◽

2021 ◽

Vol 19 (2) ◽

pp. 194-201

Author(s):

V. N. Zasimovich ◽

◽

V. V. Zinchuk ◽

N. N. Ioskevich ◽

◽

...

Keyword(s):

Hydrogen Sulfide ◽

Oxygen Transport ◽

Lower Limb ◽

Ischemia Reperfusion ◽

Venous Blood ◽

Nitrogen Monoxide ◽

Lower Limbs ◽

Upper Limbs ◽

Transport Function ◽

Group I

Background. Ischemia-reperfusion of the lower limbs in atherosclerosis of their arteries is accompanied by impaired oxygen transport function (OTF) and the content gas transmitters (GT) of blood, which needs adequate correction. Purpose. To study the effect of corvitin on the parameters of OTF and GT of nitrogen monoxide and hydrogen sulfide in venous blood after revascularization of the lower limb in chronic atherosclerotic occlusion of the superficial femoral artery (SFA). Material and methods. Revascularization of the lower limbs in 103 patients was performed by loop endaterectomy from SFA. Patients of group I (n=52) received traditional medication support, II (n=51) - corvitin. The indices of OTFB and GT in the venous blood of the lower and upper limbs were determined before the operation, on the 3rd and 8th days after it. Results. The increase in the parameters of hyperoxemia, hypocapnemia and GT concentration in the postoperative period decreases with the use of corvitin. Conclusions. The use of corvitin reduces disturbances in OTFB and GT content during ischemia-reperfusion of the lower limbs.

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Heterozygous mutation of Vegfr3 decreases renal lymphatics but is dispensable for renal function

10.1101/2021.01.17.427041 ◽

2021 ◽

Author(s):

Hao Liu ◽

Chitkale Hiremath ◽

Quinten Patterson ◽

Saumya Vora ◽

Zhiguo Shang ◽

...

Keyword(s):

Renal Function ◽

Kidney Disease ◽

Lymphatic Vessels ◽

Light Sheet ◽

Structure And Function ◽

Heterozygous Mutation ◽

Light Sheet Microscopy ◽

Perivascular Inflammation ◽

Lymphatic Density ◽

And Function

ABSTRACTBackgroundLymphatic abnormalities are observed in several types of kidney disease, but the relationship between the renal lymphatic system and renal function is unclear. The discovery of lymphatic-specific proteins, advances in microscopy, and available genetic mouse models provide the tools to help elucidate the role of renal lymphatics in physiology and disease.MethodsWe utilized a mouse model containing a missense mutation in Vegfr3 (dubbed Chy) that abrogates its kinase ability. Vegfr3Chy/+ mice were examined for developmental abnormalities and kidney-specific outcomes. Control and Vegfr3Chy/+ mice were subjected to cisplatin-mediated injury. We characterized renal lymphatics using a combination of tissue clearing, light-sheet microscopy and computational analyses.ResultsIn the kidney, we found Vegfr3 is expressed not only in lymphatic vessels, but also various blood vessels. Vegfr3Chy/+ mice had severely reduced renal lymphatics with 100% penetrance, but we found no abnormalities in blood pressure, renal function and histology. Similarly, there was no difference in the degree of renal injury after cisplatin, although Vegfr3Chy/+ mice developed more perivascular inflammation by histology. Control mice treated with cisplatin had a measurable increase in cortical lymphatic density despite no change in cortical lymphatic volume and length.ConclusionsWe demonstrate that Vegfr3 is required for development of renal lymphatics, but a reduction in lymphatic density does not alter renal function and induces only modest histological changes after injury. Our data suggests that an increase in lymphatic density after cisplatin injury may reflect the loss of cortical volume associated with chronic kidney disease rather than growth of lymphatic vessels.SIGNIFICANCE STATEMENTDefects in renal lymphatics occur in various kidney diseases, but their role in maintaining kidney structure and function is unknown. We combine tissue clearing, light-sheet microscopy and computational analysis to characterize lymphatics and find that mice with a heterozygous mutation in Vegfr3 (Vegfr3Chy/+) have severely reduced renal lymphatics. Strikingly, these mice have indistinguishable renal function and histology compared with controls. Even after cisplatin injury, there are no differences in renal function, although Vegfr3Chy/+ mice developed more perivascular inflammation. Our data present a novel method of lymphatic quantification and suggest that a normal complement of renal lymphatics is dispensable for renal structure and function.

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Monoclonal Gammopathy Presenting as Peripheral Neuropathy

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/47090.14800 ◽

2021 ◽

Author(s):

Vishaka Agarwal ◽

Koukutla Soundarya Rajeshwari ◽

KT Jayakumar ◽

. Satish ◽

Chetan Somu

Keyword(s):

Upper Limb ◽

Lower Limb ◽

Chronic Inflammatory Demyelinating Polyneuropathy ◽

Position Sense ◽

Joint Position Sense ◽

Lower Limbs ◽

Foot Drop ◽

Thigh Muscle ◽

Upper Limbs ◽

Long Duration

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a disorder of peripheral nervous system, which presents with a long duration (eight weeks) of sensory and/or motor, symmetric/asymmetric symptoms. Aetiology ranges from infections, inflammations, autoimmune disorders, to vasculitis and malignancies. Hereby, authors report a case of a male patient who presented with complains of bilateral lower limb numbness and weakness, and bilateral upper limb numbness, since two months, which was gradually progressive. On examination, he was found to have muscle wasting in his bilateral upper limb web spaces, left anterior thigh muscle, decreased tone in bilateral upper limbs and lower limbs, decreased power in both his upper limbs distally and decreased power in both his lower limbs (distal>>proximal) was seen. Superficial reflexes were normal with bilateral plantar being equivocal. Deep tendon reflexes were absent in bilateral upper and lower limbs. Tremors of bilateral upper limbs on extension were present. Loss of vibration sense throughout, loss of joint position sense at bilateral big toe and ankle joint and foot drop of his left lower limb were noticed. A diagnosis of CIDP with underlying plasma cell disorder was made after serum electrophoresis, immune-fixation and electrodiagnostic studies. The patient was started on prednisone 60 mg once daily, discharged and advised for monthly follow-up. Diagnosis of CIDP and the underlying cause is multifactorial, which can be misdiagnosed, presenting as a challenge. Hence, a detailed clinical examination, appropriate investigations are very crucial in diagnosing and treating a case of CIDP and its underlying cause. Treatment includes glucocorticoids like prednisone, IV Ig (Intravenous Immunoglobulin), plasma exchange, treating the underlying cause.

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MUSCULAR DYSTROPHIES

The Professional Medical Journal ◽

10.29309/tpmj/2016.23.09.1707 ◽

2016 ◽

Vol 23 (09) ◽

pp. 1110-1117

Author(s):

Nadia Naseem ◽

Saqib Mahmood ◽

Afzal Hussain ◽

Mumtaz Hussain ◽

Miss Ayesha Munir ◽

...

Keyword(s):

Family History ◽

Lower Limb ◽

Positive Family History ◽

Lower Limbs ◽

Clinical Severity ◽

Muscular Dystrophies ◽

Upper Limbs ◽

Muscle Involvement ◽

Mild Phenotype ◽

Different Types

Objectives: Muscular dystrophies are classified into different types based ontheir age of onset, clinical severity, rate of progression, distribution of muscles weakness,pattern of inheritance and the genes involved. As muscular dystrophies are relativelyuncommon disorders, very little work has been done in Pakistan. This study has classified (forthe first time in Pakistan) the patients with different types of muscular dystrophies by clinicaland biochemical correlation. Study Design: Observational, descriptive study. Setting:Departments of Morbid Anatomy and Histopathology and Human Genetics and MolecularBiology at University of Health Sciences Lahore. Period: Three years’ (March, 2012-March2015). Methodology: A total of 100 patients comprising of all age groups and both gendersand with strong clinical suspicion of muscular dystrophy, with or without positive family history,were included. Detailed clinical history and physical examination findings were recordedfollowed by estimation of serum Creatine Phosphokinase (CPK), Lactate Dehyrogenase(LDH) and Aldolase levels. Results: A total of 77 males (M) and 23 females (F) were included.Mean age of the patients was 12.1990 + 6.69913 years. Parents of 76 patients reported withconsanguineous marriages while positive family history was reported in 31 patients. Eightytwo cases managed to ambulate with support of other persons while n= 14 patients weretotally non ambulatory. Symmetrical muscle involvement (lower limb followed by upper limb)was shown by 87 cases (including all males and n=22 females). Involvement of the lowerlimbs as a primary weakness followed by symmetrical and severe involvement of the upperlimb girdle and lower limb girdle suggested limb girdle muscle dystrophy (LGMD) in 9 (6F,3M)patients. Involvement of shoulders and upper limbs as a primary weakness followed by facialmuscles and infrequent involvement of lower limbs suggested fascioscapulohumeral muscledystrophy (FSHMD) in 2 cases. Involvement of upper limbs as a primary weakness followedby lower limbs with a moderate rise in CPK levels and mild phenotype was seen in two femalepatient which was quite suggestive of dysferlinopathy. Only two male patients reported onsetof weakness and ambulation loss before 1 year of age that may represent congenital muscledystrophy (CMD), dystroglycanopathy or congenital onset of LGMD (cLGMD). Mean serumCPK, LDH and Aldolase levels were 2376.6364 + 910.78963 U/L, 1030.7800 + 180.1620 U/Land 10.089 + 1.525 U/L respectively that demonstrated significant association (p<0.05) withcharacteristic clinical features. Conclusion: Muscular dystrophies are not only restrictedto dystrophinopathies in our population. Apart from clinical and biochemical parameters,appropriate histological and/or gene mutation analysis is mandatory for precise classificationof these disorders.

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