bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low sodium intake is associated with low birth weight and size only when given in the second half of gestation
Authors: de Siqueira Flavia Ramos , de Souza Regiane Machado , de Oliveira Ivone Braga , Furukawa Luzia Naoko S. , Heimann Joel Claudio 
Published: June 2021

This study examined the effects of maternal low sodium intake during different periods of pregnancy on dams and male (M) and female (F) offspring.MethodsFemale Wistar rats (n= 6 ‐ 8/group) were fed low (LS ‐ 0.15%) or normal (NS ‐ 1.3% NaCl) sodium diet since the 1st day of gestation until delivery or LS during the 1st (LS10) or 2nd half of gestation (LS20).Results(mean±SEM, p< 0.05): Maternal body weight (g) was lower in LS and LS20 than in NS and LS10 at the 3rd week of gestation (LS = 380±8.1; LS20 = 406±13.2; NS = 435±6.1, LS10 = 461±12.9). No difference was found in water and food intake among the groups. Also, no differences were observed in the litter size among experimental groups and no correlation between the number of pups and maternal body weight at the 3rd week of gestation. At birth, body weight (g, n=14 to 27/group) (M: NS = 6.5±0.1, LS = 5.5±0.1, LS10 = 6.1±0.1, LS20 = 4.8±0.1, F: NS = 6.1±0.2, LS = 5.2±0.1, LS10 = 5.6±0.1, LS20 = 4.1±0.1) and naso‐anal length (cm, n=14 to 27) (M: NS = 5.1±0.02, LS = 4.9±0.03, LS10 = 5.0±0.03, LS20 = 4.6±0.03, F: NS = 4.9±0.05, LS = 4.8±0.04, LS10 = 4.9±0.03, LS20 = 4.4±0.03) were lower in LS and LS20 than in NS offspring.ConclusionAlthough maternal dietary intake was not influenced by dietary sodium content, maternal low sodium diet during the second half of gestation induced lower birth weight and size. Supported by CAPES and FAPESP
Specific targeting of pancreatic β‐cells by simultaneous binding of GLP‐1 and α2‐adrenergic receptors with a multivalent ligand
Authors: Ananthakrishnan Kameswari , Weber Craig , Hart Nathaniel , Vagner Josef , Limesand Sean , Lynch Ronald 
Published: June 2021

Diabetes Mellitus is characterized by a decline in β‐cell mass and function. The lack of specificity of β‐cell targeting agents poses a challenge to observe changes in β‐cell mass and thus monitor disease progression. We propose β‐cell specificity can be enhanced by using multivalent ligands that simultaneously bind to multiple unique surface receptors that, as a combination, identify a cell type of interest. We synthesized a ligand composed of Yohimbine (Yhb) (α2 adrenergic receptor (α2AR) antagonist) linked to Glucagon‐like Peptide 1(GLP‐1). Receptors to both ligands are expressed on βTC3 cells at a ratio of ~ 1.5:1 (GLP‐1R/α2AR). Microscopy of a fluorophore tagged ligand indicated that binding was rapid with removal of ligand from the cell surface seen within 2–3 min. From population based competition assays, the binding affinity for monovalent GLP‐1 was ~10 nM, whereas GLP‐1/Yhb exhibited 2 distinct binding sites. The high affinity binding (9 pM) is correlated to MVL crosslinking the complementary receptors causing a decrease in ligand off rate, resulting in a 1000X increase in apparent affinity. The low affinity binding (225 nM) is consistent with weak binding of the GLP‐1 moiety in the MVL to the spare GLP‐1 receptors in βTC3 cells. Our findings suggest that GLP‐1/Yhb acts as a specific targeting agent to β‐cells as it exhibits enhanced binding to and retention in β‐cells compared to other cells in the imaging field.Supported by: Juvenile Diabetes Research Foundation, and the Arizona Biomedical Research Commission
Are they really just big boned?: How increased body mass in human juveniles affects bone joint morphology in the lower limb
Authors: Kelso Rebecca K Scopa 
Published: June 2021

With higher incidence of childhood obesity in the United States, it is clinically important to understand the long‐term mechanical effects of increased loadbearing on joints of the lower limb throughout ontogeny. As part of this documentation, this study looks at the relationship between increased mass and femoral and proximal tibia dimensions. A clinical sample of juveniles considered to have normal mass was used as a control in comparison with juveniles considered clinically obese. Radiographic measurements of the femoral head, distal femur, and proximal tibia were taken, and measurements obtained from the images after correcting for parallax. Preliminary results indicate a high correlation between dimensions from these three regions and observed body mass, but that the femoral head breadth— commonly thought to be a good indicator of body mass—was not the most highly correlated in either the normal‐weight or obese groups. Rather, femoral epicondylar breadth has higher correlations with mass. Furthermore, there is some indication that joint sizes may be adaptive and outpacing weight gain in older children (10–17 yrs). This may indicate overcompensating in joint size growth among obese juveniles, most likely in response to high mechanical loads. The limitations of the data leave the timing of the onset of obesity unknown, however, and therefore the ontogeny of joint hypertrophy cannot yet be established.Grant Funding Source : n/a
Bifid median nerve variations: A cadaveric study
Authors: Warren Kelly , Norbury John 
Published: June 2021

Bifid median nerve (BMN) is an anatomical variation that occurs when the main median nerve trunk splits into medial and lateral trunks prior to entering the hand within the carpal tunnel (CT). The classification of BMN can be further divided into subcategories, which are based on associated abnormalities and location of branching. In this study, the upper extremities of twenty‐nine cadaveric specimens were examined for the presence of BMN in the flexor forearm and hand regions (14 females, 15 males). Of the 58 upper extremities examined, 6 exhibited BMN patterns (10.3%; 4 female, 2 male), with both trunks traveling within the CT into the hand. Two distinct bifid branching patterns were also observed: (B1) mid‐forearm, proximal to carpal tunnel (n=2 females) and (B2) wrist level, within CT (n=2 females, 2 males). In both B1 cases, the smaller medial trunk pierced the flexor digitorum superficialis muscle, traveled within the CT with the larger lateral trunk, and gave off communicating branches to both the lateral trunk and superficial branch of the ulnar nerve after entering the left hand. Incidence of BMN was found to be higher in female cadavers (67%), and in left upper extremities (67%). Knowledge of variable median nerve branching patterns, especially as it is associated with the CT, is important for diagnostic and surgical interventions.Grant Funding Source: n/a
The fabellofibular and arcuate ligaments of the knee joint: attachments, functional and clinical implicationsfor the posterolateral aspect of the knee joint
Authors: Ghosh Tamojit 
Published: June 2021

Summary Of ResultsThe fabellofibular ligament is attached proximally to the fabella (bony or cartilaginous, found in 8–16 % of human knees) and distally to the lateral basal aspect of the fibular head anterolateral to the insertion of the popliteofibular ligament. It's an independent ligament proven that the lateral inferior genicular blood vessels separate it from the femoral condyle. The Y‐SHAPED arcuate ligament's base is attached to base of the apex of the fibular head ( deep to the fabellopopliteal ligament when it is present), the medial limb courses up and merges with posterior part of the knee joint capsule and the oblique popliteal ligament. It has fibres attached to the lateral knee joint mensicus too adding to its posterior mobility. Its lateral limb courses upwards to be attached to the lateral femoral condyle. The arcuate ligament's relationships with the fabellopopliteal ligament, the deeper part of the lateral collateral ligament and with the absence or presence of fabellae are discussed in detail. Attachments of the popliteofibular ligament and the superior & inferior popliteomeniscal fibres are also discussed.Summary of conclusionsAll the ligaments of the posterolateral aspect of the human knee develop relative to the larger phylogenetic evolution event in which the fibular head regresses downwards and loses it primitive articulation with the lateral condyle of the femur. In posterolateral knee joint injuries the above ligaments should be visually sought out and attempts made to repair them individually. This is especially true for repairs of injuries of the lateral meniscus and lateral collateral ligament where associated injuries of the above smaller ligaments exist.Grant Funding Source : Indian Institute of Morphology
Lateral and longitudinal ultrastructural study of the recurrent laryngeal nerve in adult rats
Authors: da Silva Ferreira Renata , de Barros Oliveti Maria Carolina Dal Bem , Fazan Valéria Paula Sassoli 
Published: June 2021

Despite the importance of the recurrent laryngeal nerve (RLN) in terms of respiration and phonation functions, studies on the normal histology of this nerve in rats are still scanty. The RLN is asymmetric in length, because the different origin on both sides but neither a longitudinal ultrastrucutral study nor information about ultrastructural lateral asymmetry of this nerve is available in rats. Male adult Wistar rats (N=5), had their RLN prepared for transmission electron microscopy and morphometry. Comparisons were made between segments on the same side and same levels between sides. The RLN fascicles are significantly larger proximally, on both sides as is the myelinated fiber number. No other longitudinal differences were observed. Unmyelinated fiber number and density is larger on right, compared to proximal left segment. This lateral difference was not present on the distal segments. No other lateral differences were observed. Our results indicate that the RLN are asymmetric not only macroscopically (origin and length, between sides) but also on its microscopic anatomy, not only between sides but also between proximal and distal segments. This information is crucial for those studies investigating RLN neuropathies since results can vary according to the nerve site studied.Grant Funding Source: FAPESP, CNPq, CAPES and FAEPA
Does hypertension affect morphometric parameters of phrenic nerves?
Authors: Rodrigues Anaceres Ribeiro , da Silva Ferreira Renata , Salgado Helio Cesar , Fazan Valéria Paula Sassoli 
Published: June 2021

We previously reported [1] important differences in phrenic nerve morphology between normotensive Wistar‐Kyoto and spontaneoulsy hypertensive rats (SHR) but the question whether the differences are due to hypertension or intrinsic to the rat strains still remains. We aimed to investigate the phrenic nerve morphology in young normotensive SHR and adult SHR with well established hypertension. Female SHR aged 5 (N=6) or 20 (N=6) weeks were anesthetized for arterial pressure (AP) recording. Proximal and distal segments of the right and left phrenic nerves were removed and prepared for epoxy resin embedding and light microscopy morphometry. Adult rats showed significantly higher body weight and AP, compared to young animals. Phrenic nerves showed morphologic and morphometric lateral and longitudinal symmetry for both groups but were significantly larger on older animals. Myelinated fiber area and diameter were also larger on older animals but their number was not different between groups. Myelinated axons were larger on older animals but the G ratio was not different between groups. As expected, aging affected phrenic nerve fascicle and myelinated fibers size with no alteration in fiber number. Also, hypertension development did not affect morphological parameters considered important for myelinated fiber function.Grant Funding Source : FAPESP, CNPq, CAPES and FAEPA
Neuronal counting in the spinal cord dorsal horn of male adult Wistar rats after noxious stimuli during neonatal period
Authors: Machado Nathalia Leilane Berto , Sanada Luciana Sayuri , do Carmo Elisabete Cássia , de Oliveira Alexandre Leite Rodrigues , Fazan Valéria Paula Sassoli 
Published: June 2021

The aim of the present study was to analyze the effects of noxious stimuli during neonatal period in the neuronal distribution in the spinal cord dorsal horn in adult rats. Six male Wistar rats with 180 days of life were separated in 2 groups: pain group (n=3) and control group (n=3). The pain group was stimulated with a needle on the right paw and the control group was stimulated with a cotton swab on the right paw, being both groups stimulated twice a day for 15 days. Were evaluate the hyperalgesia of both groups with Von Frey Monofilament and a specific calibrated forceps; the analysis of the neuronal distribution was performed by counting Nissl stained neurons with a specific software. Statistic tests were applied, and p value was considered significant when p was less than 0,05. We observed that the pain group presented a hyperalgesia in the right hindpaw when compared to the control group, but no differences were found in the neuronal counting in the spinal cord between groups. Our results suggest that noxious stimuli during neonatal period are capable of changing the sensorimotor system in the long term, but this change does not involve changes in the neuronal distribution in the dorsal horn.Grant Funding Source : FAPESP, CNPq and FAEPA
Zygapophyseal joint space gapping following spinal manipulation in low back pain patients
Authors: Cramer Gregory D , Cambron Jerrilyn A , Cantu Joe A , Dexheimer Jennifer , Pocius Judith D , Gregerson Douglas , Fergus Michael , McKinnis Ray A 
Published: June 2021

This study quantified lumbar zygapophyseal (Z) joint space separation (therapeutic gapping) in acute low back pain subjects after spinal manipulative therapy (SMT) or side‐posture positioning (SPP).MethodsThis IRB‐approved project enrolled 112 acute low back pain subjects. After 2 weeks of treatment all subjects received an MRI scan (supine position) of the L4/L5 and L5/S1 Z joints. Subjects were then randomized into SPP (non‐manipulation) Groups 1 or 4 (n=28, 26) or SMT (manipulation) Groups 2 or 3 (n=26, 26). SMT and SPP were performed with the most painful side of the lumbar region up. After the SMT or SPP procedure/intervention, a second MRI scan was taken with subjects either supine (Groups 2 and 4) or maintaining the SPP (Groups 1 and 3). Observers blinded to group and MRI scan (first or second) measured the central anterior‐posterior (A‐P) joint space on the scans. Difference between A‐P measurements taken post‐ and pre‐intervention was the Z joint “gapping difference.” Gapping differences were compared among and between groups (ANOVA).ResultsFinal data analysis was performed on 106 subjects (51 male and 55 female). Differences were significant (p=0.0005; Group 1=0.6 +0.9mm, Group 2=0.2 +0.4, Group 3=0.9 +0.7, Group 4=0.4 +0.3).ConclusionsSMT (Group 3) resulted in the greatest amount of therapeutic gapping in acute low back pain subjects. Funding: NIH/NCCAM Grant # 2R01AT000123.
Genetic depletion of the phosphatase PHLPP1 upregulates receptor tyrosine kinase signaling
Authors: Reyes Gloria Ximena , Newton Alexandra 
Published: June 2021

The PH‐domain leucine rich repeat protein phosphatase PHLPP1 is a Ser/Thr phosphatase that negatively regulates Akt signaling. This pathway controls many cellular processes; loss of PHLPP leads to hyperactivation of Akt and an imbalance in cell homeostasis, triggering many diseases. Using cells derived from a phlpp1−/− mouse, we show that PHLPP1 suppresses the amplitude of the ERK pathway through an Akt‐independent mechanism. phlpp1−/− cells have increased receptor tyrosine kinase levels leading to augmented activation of downstream signaling. In these cells, the effects on ERK are due to an increased rate of receptor biosynthesis, not defective receptor degradation. Neither pharmacological inhibition of the PI3K‐Akt pathway, nor the MEK‐Erk pathway affects receptor levels, indicating that the PHLPP1 target is not Akt nor ERK. Furthermore, the catalytic and leucine rich repeat regions are critical to regulate receptor levels in normal cells. To find the mechanism controlling receptor levels, we performed pharmacological and PCR arrays to dissect the components responsible for this phenotype in phlpp1−/− cells. Our data indicate that general transcriptional machinery rather than only one transcriptional factor are involved. These data unveil an additional function of PHLPP1 in suppressing receptor tyrosine kinase signaling in cells by a transcriptional mechanism.This work was funded by NIH GM067946.
Targeting the Metastasis Suppressor NDRG1: A New Strategy for the Treatment of Pancreatic Cancer
Authors: Richardson Des R , Chikhani Sherin , Lui Goldie , Sivagurunathan Sutharshani , Kovacevic Zaklina 
Published: June 2021

AimsThe metastasis suppressor, N‐myc downstream regulated gene‐1 (NDRG1), is negatively correlated with tumor progression in pancreatic cancer. Moreover, NDRG1 is an iron‐regulated gene that is markedly up‐regulated by cellular iron‐depletion using novel anti‐tumor agents such as the chelator, Dp44mT, in pancreatic cancer cells. However, the exact molecular function(s) of NDRG1 remain to be established.ResultsUsing gene‐array analysis together with NDRG1 over‐expression and silencing, we identified molecular targets of NDRG1 in 3 pancreatic cancer cell lines. For the first time, we demonstrate that NDRG1 up‐regulates neural precursor cell expressed developmentally down‐regulated 4‐like (NEDD4L) and GLI‐similar 3 (GLIS3). Further studies examining the down‐stream effects of NEDD4L led to the discovery that NDRG1 affects the transforming growth factor β (TGF‐β) pathway, leading to up‐regulation of two key tumor suppressor proteins, namely phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and mothers against decapentaplegic homolog 4 (SMAD4) in multiple cell lines. Moreover, NDRG1 inhibited the phosphatidylinositol 3‐kinase (PI3K) and Ras oncogenic pathways.ConclusionThe identified target genes of NDRG1 and their effect on the TGF‐â signaling pathway reveal its molecular function in pancreatic cancer and a novel therapeutic avenue.
Control of cortical actin assembly and cadherin‐catenin localization by GPCRs and RhoGTPases
Authors: Jimenez-Dalmaroni Maximiliano Javier , Heasman Janet , Wylie Christopher 
Published: June 2021

Many common and permanently disabling human birth defects, such as spina bifida, are caused by the loss of cell shape changes and tissue movements in the early embryo. Therefore, it is important to understand how these cell shape changes are regulated during embryonic development. It has been previously shown that the actin cytoskeleton is required for normal tissue movements at these stages. Furthermore, the expression and localization of cadherin‐catenin complex are relevant for cell adhesion and F‐actin assembly and their lost can increase risk of metastasis in carcinomas and alter normal cell movements during embryonic development.Using the Xenopus laevis embryo and human embryonic stem cells as models, we are currently investigating the mechanisms by which cortical actin assembly is regulated during development and the signaling pathways relevant for the cadherin‐catenin localization. We have identified two G‐protein couple receptors, a novel GPCR receptor termed xFlop and xLPA, and the small GTPase Rac1, as key molecules involved in this process. We hope this research could lead us to not only better understanding of cortical actin assembly and remodeling in early stages of Xenopus laevis embryos and humans, but also to develop novel treatments for spina bifida and human cancer metastasis.
Clinically Oriented Anatomy and Physiology for a Master Physician Assistant Program
Authors: Escobar-Poni Bertha Corina 
Published: June 2021

All that hard work behind a syllabus is very rarely perfection; in the end, is just ‘clay’ to be reshaped by the needs and expectations of both students and teachers. The previous statement summarizes my recent experience teaching a clinically oriented anatomy and physiology course to students in our Master Degree program for Physician Assistant. My first quarter was a disappointment, but the 2nd quarter was a success (based on student's evaluations). Although I did little changes in the online physiology modules, the greatest change was in the clinical anatomy section. The hallmark of the success revolved around two aspects: teamwork, and empowering through active learning. The implementation of three learning methods made a big difference: rotating teaching stations, training experts, and peer teaching. A student from each team was trained to become an expert in specific anatomic territory including clinical applications, thus be a resource in their teams. Each student took seriously the responsibility for their peers learning. Students left every lab with a sense of accomplishment, confident about how much they learned and making plans to meet after hours. Last year's learned lessons of dos and don'ts were pivotal to a great start with this new class. I am looking forward to our mutual learning and sharing.Support: Henry Gray/Elsevier Distinguished Educator Award Plenary Symposium
Factors associated with weight change up to 12 months postpartum in HIV‐infected women: findings from the HIV prevention of mother‐to‐child transmission (PMTCT) Kesho Bora trial
Authors: Cames Cecile , Cournil Amandine , Bork Kirsten 
Published: June 2021

Data on postpartum weight change (PWC) in HIV‐infected women are sparse and inconsistent. This study analyzed, according to antiretroviral prophylaxis (ARV), clinical and infant feeding (IF) characteristics, PWC from 1 to 12 months in HIV‐infected women participating in a PMTCT trial in 5 study sub‐Saharan African sites.Women with 200–500 CD4+ cells/mm3 were randomized to receive from 28–36 weeks gestation either a triple ARV (3 ARV), continued up to 6 months postpartum (PP) or a standard ARV (STANDARD) until 1 week PP.Among 792 women, 78% breastfed for a median duration of 5.1 months (IQR: 2.8–6.0). At delivery, viral load (VL) was undetectable in 64% of 3 ARV women vs. 30% in STANDARD group (P<0.0001) and median CD4 count was 463 and 414 cells/mm3, respectively (P<0.0001). At 1 month PP, less than 3% were underweight while 49% were overweight or obese. Mean PWC at 12 months was +1.4kg in 3 ARV group and −0.7kg in STANDARD group (P<0.0001). In mixed linear model analyses, 3 ARV, baseline overweight or obesity and C‐section were independently associated with PWC (+65, +54 and +56 g/month, P<0.0001, <0.001 and =0.02, respectively). No association was found between either IF or CD4 count or VL and PWC.3 ART increased weight gain over the first year PP and IF had no impact on PWC among these HIV‐infected women with intermediate advanced disease.Funding: ANRS, DFID, ECDTP, Trasher Research Fund, GSK Fund, CDC, NIH, WHO