Post-menopausal women are disproportionately affected by osteoarthritis (OA). As such, the purpose of this study was to (1) summarize the state-of-the-science aimed at understanding the effects of ...menopause on OA in animal models and (2) investigate how dosage and timing of initiation of estrogen treatment affect cartilage degeneration.
A systematic review identified articles studying menopausal effects on cartilage in preclinical models. A meta-analysis was performed using overlapping cartilage outcomes in conjunction with a rigor and reproducibility analysis. Ordinary differential equation models were used to determine if a relationship exists between cartilage degeneration and the timing of initiation or dosage of estrogen treatment.
Thirty-eight manuscripts were eligible for inclusion. The most common menopause model used was ovariectomy (92%), and most animals were young at the time of menopause induction (86%). Most studies did not report inclusion criteria, animal monitoring, protocol registration, or data accessibility. Cartilage outcomes were worse in post-menopausal animals compared to age-matched, non-menopausal animals, as evidenced by cartilage histological scoring 0.75, 1.72, cartilage thickness −4.96, −0.96, type II collagen −4.87, −0.56, and c-terminal cross-linked telopeptide of type II collagen (CTX-II) 2.43, 5.79 (95% CI of Effect Size (+greater in menopause, −greater in non-menopause)). Moreover, modeling suggests that cartilage health may be improved with early initiation and higher doses of estrogen treatment.
To improve translatability, animal models that consider aging and natural menopause should be utilized, and more attention to rigor and reproducibility is needed. Timing of initiation and dosage may be important factors modulating therapeutic effects of estrogen on cartilage.
The classical terrace-ledge-kink model of crystal growth is widely used to interpret mineral formation in biological and geological systems. A key assumption underlying application of the model is ...that thermal fluctuations of steps are sufficiently rapid to produce an abundance of kink sites for attachment of growth units. High-resolution in situ atomic force microscopy (AFM) studies and kinetic Monte Carlo simulations of step-edge structure and dynamics show this physical picture to be invalid for the common mineral calcite whose steps exhibit low kink density and weak step edge fluctuations. As a consequence, interactions of impurities with calcite step edges cannot be interpreted with traditional thermodynamic models based on minimization of the Gibbs free energy. Instead, impurity-step interactions follow a different mechanism determined by the kinetics of attachment and detachment. Step advance is unimpeded when the creation of new kinks by attachment of growth units to the step outpaces binding of impurities to the newly created kinks. This kink-limited model offers a plausible explanation for reports of “kinetic disequilibrium” of trace element signatures. Moreover, because kink density is tied to crystal solubility, these findings argue for a theory based on weak fluctuations to interpret growth of many common crystalline phases of importance in geochemical, biological, and technological settings.
Flow resistance along the rat renal tubule Gilmer, Gabrielle G; Deshpande, Venkatesh G; Chou, Chung-Lin ...
American journal of physiology. Renal physiology,
11/2018, Letnik:
315, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The Reynolds number in the renal tubule is extremely low, consistent with laminar flow. Consequently, luminal flow can be described by the Hagen-Poiseuille laminar flow equation. This equation ...calculates the volumetric flow rate from the axial pressure gradient and flow resistance, which is dependent on the length and diameter of each renal tubule segment. Our goal was to calculate the pressure drop along each segment of the renal tubule and to determine the points of highest resistance. When the Hagen-Poiseuille equation was used for rat superficial nephrons based on known tubule flow rates, lengths, and diameters, it was found that the maximum pressure drop occurred in two segments: the thin descending limbs of Henle and the inner medullary collecting ducts. The high resistance in the thin descending limbs is due to their small diameters. The steep pressure drop observed in the inner medullary collecting ducts is due to the convergent structure of the tubules, which channels flow into fewer and fewer tubules toward the papillary tip. For short-looped nephrons, the calculated glomerular capsular pressure matched measured values, even with the high collecting duct flow rates seen in water diuresis, provided that tubule compliance was taken into account. In long-looped nephrons, the greater length of thin limb segments is likely compensated for by a larger luminal diameter. Simulation of the effect of proximal diuretics, namely acetazolamide or type 2 sodium-glucose transporter inhibitors, predicts a substantial back pressure in Bowman's capsule, which may contribute to observed decreases in glomerular filtration rate.
Athletes who have sustained a tear of the anterior cruciate ligament (ACL) are at a greater risk of re-tear and of developing other adverse outcomes, such as knee osteoarthritis, compared with ...uninjured athletes. Relaxin, a peptide hormone similar in structure to insulin, has been shown to interfere with the structural integrity of the ACL in female individuals. The purpose of the present study was to evaluate dynamic knee valgus and the serum relaxin concentration (SRC) in athletes who had previously sustained a torn ACL and in those who had not.
The study included 22 female athletes, divided into 2 groups: those who had previously sustained a torn ACL (4 participants; torn ACL in the dominant leg in all cases) and those who had not (18 participants). Kinematic data were collected at 100 Hz. To assess dynamic knee valgus, participants performed a single-leg squat, a single-leg crossover dropdown, and a drop vertical jump at 2 time points in the menstrual cycle of the patient, pre-ovulatory and mid-luteal. SRC was determined with use of the Human Relaxin-2 Immunoassay using a blood sample obtained during the mid-luteal phase of the menstrual cycle.
Independent samples t tests were utilized to compare the differences in dynamic knee valgus and SRC between groups. For the single-leg squat, participants with a prior torn ACL were found to have significantly higher dynamic knee valgus at the mid-luteal phase but not at the pre-ovulatory phase. For the drop vertical jump and single-leg crossover dropdown, participants with a prior torn ACL were found to have significantly higher dynamic knee valgus at both the pre-ovulatory and mid-luteal phases. SRC was also significantly higher among participants with a prior torn ACL.
Participants who had previously sustained a torn ACL had higher SRC and more dynamic knee valgus compared with those who had not. Further investigation of the effects of hormones as a risk factor for reinjury in participants with a prior ACL tear may be worthwhile. In addition, it may be worth monitoring hormonal and biomechanical properties in athletes during the long-term recovery from ACL reconstruction.
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Background
Nutritional deficit and oral iron gastrointestinal intolerance may be a common cause of iron deficiency, which can be managed by pharmacists.
Aim
To understand the prevalence of iron ...deficiency in women of childbearing age with a self-reported history of intolerance to oral iron and the tolerability of three doses of an iron-whey-protein formulation in the care of these women.
Method
Ferritin and haemoglobin levels were documented in women of childbearing age with oral iron gastrointestinal intolerance. In those with iron deficiency (ferritin < 30 µg/L), adherence, gastrointestinal tolerability, ferritin, transferrin saturation and haemoglobin levels were compared between their prior oral iron product and iron-whey-protein microspheres randomised to three doses (14 mg daily, 25 mg daily and 50 mg daily) for 12 weeks.
Results
Most screened women had low iron stores (128 (62.7%); ferritin < 30 µg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin < 12 µg/L) and 33 (16.2%) had iron deficiency anaemia (ferritin < 30 µg/L, haemoglobin < 12 g/dL). Amongst the 59 women who participated in the prospective clinical study of iron-whey-protein microspheres over 12 weeks, 48 (81.4%) were classified as adherent/persistent and fewer instances of gastrointestinal intolerance were reported (0.59 ± 0.91) when compared to 12 (20.3%) and (4.0 ± 2.2) respectively while taking the prior oral iron (Fisher’s Exact and
T
-test respectively, both
p
< 0.001). There was no difference in adherence or tolerability of different iron-whey-protein formulation doses. Ferritin, haemoglobin and energy levels increased significantly over 12 weeks.
Conclusion
Undiagnosed iron deficiency is common in women of childbearing age with a history of intolerance to oral iron and iron-whey-protein microspheres can improve adherence, GI tolerability, iron stores, haemoglobin and energy levels in these women.
Clinical trial registration
Clinicaltrials.gov identifier (registration includes full trial protocol): NCT04778072.
The purpose of this study was to evaluate pitching mechanics between female softball pitchers with upper extremity pain and those without upper extremity pain. Specifically, the trunk, shoulder and ...elbow kinematics and shoulder kinetics during the change-up softball pitch were examined. Fifty-five collegiate softball pitchers participated, divided into those with upper extremity pain (20.0±1.3 yrs.; 174.4±6.9 cm; 82.9±12.4 kg; 11.1±2.6 yrs. of experience; n=23) and those who were pain-free (19.9±1.4 yrs.; 173.8±6.9 cm; 81.4±12.5 kg; 10.0±2.5 yrs. of experience; n=32). Pitching mechanics were obtained via the trakSTAR
electromagnetic tracking system (Ascension Technologies, Inc., Burlington, VT, USA). Mann-Whitney U tests revealed significant differences in shoulder horizontal abduction at foot contact (
0.014,
153,
2.450) and trunk lateral flexion at ball release (
0.012,
150,
-2.515); and between shoulder distraction force at ball release (
0.034,
168,
-2.124). The pain group illustrated greater shoulder horizontal abduction at foot contact, less trunk lateral flexion towards the throwing side at ball release, and greater shoulder distraction at ball release than the pain-free group. The differences in trunk and shoulder kinematics, and shoulder kinetics between groups allows for insight into further studies examining injury pervasiveness in softball pitching.
Lithium salts, used for treating bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI) thereby limiting therapeutic success. NDI is associated with loss of expression of the gene ...coding for the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use systems biology methods in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts (CCDs) of rats after 72 hours without or with initiation of lithium chloride administration. Transcriptome-wide changes in mRNA abundances were mapped to gene sets associated with curated canonical signaling pathways, showing evidence for activation of NF-κB signaling with induction of genes coding for multiple chemokines and most components of the Major Histocompatibility Complex Class I antigen-presenting complex. Administration of anti-inflammatory doses of dexamethasone to lithium chloride–treated rats countered the loss of aquaporin-2. RNA-Seq also confirmed prior evidence of a shift from quiescence into the cell cycle with arrest. Time course studies demonstrated an early (12 hour) increase in multiple immediate early response genes including several transcription factors. Protein mass spectrometry in microdissected CCDs provided corroborative evidence and identified decreased abundance of several anti-oxidant proteins. Thus, in the context of prior observations, our study can be best explained by a model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 transcription.
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Female athletes are at an elevated risk for tearing their anterior cruciate ligament, compared to their male counterparts. Though injury screening clinical tests and neuromuscular training programs ...have been widely implemented, injury rates remain high among female athletes. The purpose of this study was to examine the relationship between serum relaxin concentrations and knee valgus during three clinical tests (single leg squat, drop vertical jump, and single leg crossover dropdown). Twenty-two female athletes volunteered. Participants were scheduled for collection during the mid-luteal phase, when serum relaxin concentrations are known to be measurable. Blood samples were collected, and serum relaxin concentrations were quantified. Kinematic data were collected while participants performed the three clinical tests. Regression analyses revealed statistically significant relationships between serum relaxin concentrations and knee valgus throughout all tests. These findings suggest that serum relaxin concentrations and knee valgus are not independent of each other and more holistic approaches may be necessary to truly map out the risk for injury and ultimately reduce the rate of anterior cruciate ligament injuries. Thus, concluding that knee valgus, a highly utilized modifiable biomechanical risk factor, and relaxin, a hormone that has been associated with anterior cruciate ligament injury in female athletes, are related to each other.
The purpose of this study was to examine how lumbopelvic-hip complex (LPHC) stability, via knee valgus, affects throwing kinematics during a team handball jump shot.
LPHC stability was classified ...using the value of knee valgus at the instant of landing from the jump shot. If a participant displayed knee valgus of 17° or greater, they were classified as LPHC unstable. Stable and unstable athletes’ throwing mechanics were compared.
Twenty female team handball athletes (26.5±4.7years; 1.75±0.04m; 74.4±6.4kg; experience level: 4.8±4.1 years) participated. An electromagnetic tracking system was used to collect kinematic data while participants performed three 9-m jump shots. The variables considered were kinematics of the pelvis, trunk, and shoulder; and segmental speeds of the pelvis, torso, humeral, forearm, and ball velocities. Data were analyzed across four events: foot contact, maximum shoulder external rotation, ball release, and maximum shoulder internal rotation.
Statistically significant differences were found between groups in pelvis, trunk, humerus, and forearm velocities at all events (p≤0.05). Specifically, the unstable group displayed significantly slower speeds.
These findings suggest the difference in throwing mechanics are affected by LPHC instability for this select group of female team handball athletes. These differences infer an increased risk of injury in the upper and lower extremities when landing from a jump shot because of the energy losses throughout the kinetic chain and lack of utilization of the entire chain. It is recommended that further investigations also consider muscle activation throughout the throwing motion.
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