Response to Comment on "following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion" and "molecular Diffusivity of Click Reaction Components: The Diffusion Enhancement Question"

In their Comment (DOI: 10.1021/jacs.2c02965) on two related publications by our groups (J. Am. Chem. Soc. 2021, 143, 20884-20890; DOI: 10.1021/jacs.1c09455) and another (J. Am. Chem. Soc. 2022, 144, 1380-1388; DOI: 10.1021/jacs.1c11754), Huang and Granick discuss the diffusion NMR measurements of molecules during a copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click"reaction. Here we respond to these comments and maintain that no diffusion enhancement was observed for any species during the reaction. We show that the relaxation agent does not interfere with the CuAAC reaction kinetics nor the diffusion of the molecules involved. Similarly, the gradient pulse length and diffusion time do not affect the diffusion coefficients. Peak overlap was completely removed in our study with the use of hydrazine as the reducing agent. The steady-state assumption does not hold for these diffusion measurements that take several minutes, which is the reason monotonic gradient orders are not suitable. Finally, we discuss the other reactions where similar changes in diffusion have been claimed. Our conclusions are fully supported by the results represented in our original JACS Article and the corresponding Supporting Information

The effect of sex, stature, and limb length on the preferred walk-to-run transition speed

Background The preferred walk-to-run transition speed (PTS) for healthy adults is approximately 2 m∙s-1, however, PTS is influenced by anthropometric factors. Yet despite known sex differences in anthropometrics, studies have reported no sex differences in PTS. Research question Do stature and limb length affect PTS in the same way for both male and female healthy adults? Methods Thirty-seven (19 female) non-injured adults volunteered for this study. Participants completed a walk-to-run transition protocol, where the treadmill speed was increased from 1.2 m∙s-1 to 2.2 m∙s-1, in increments of 0.1 m∙s-1 every two minutes. An independent t-test compared PTS between sexes. Multiple regression analysis determined the effect of sex and stature and sex and limb length on PTS. Results Female participants transitioned at a lower PTS than male participants (1.8 (0.2) m∙s-1 versus 1.9 (0.1) m∙s-1; p ≤ 0.026). Sex and stature explained 19% of the variance in PTS, while sex and limb length explained 21% of the variance. Including interactions increased the variance explained by 23% and 2% for sex and stature and sex and limb length, respectively. The significant interaction between sex and stature showed PTS was inversely proportional to stature for male participants but directly proportional for female participants. Significance These findings suggest that the extent to which stature and limb length influence the preferred transition speed may differ between sexes

Supplementary Energy Increases Bone Formation during Arduous Military Training

Purpose: This study aimed to investigate the effect of supplementary energy on bone formation and resorption during arduous military training in energy deficit. Methods: Thirty male soldiers completed an 8-wk military combat course (mean ± SD, age = 25 ± 3 yr, height = 1.78 ± 0.05 m, body mass = 80.9 ± 7.7 kg). Participants received either the habitual diet (control group, n = 15) or an additional 5.1 MJ·d−1 to eliminate the energy deficit (supplemented group, n = 15). Circulating markers of bone formation and resorption, and reproductive, thyroid, and metabolic status, were measured at baseline and weeks 6 and 8 of training. Results: Bone-specific alkaline phosphatase decreased in controls (−4.4 ± 1.9 μg·L−1) and increased in the supplemented group (16.0 ± 6.6 μg·L−1), between baseline and week 8 (P < 0.001). Procollagen type 1 N-terminal propeptide increased between baseline and week 6 for both groups (5.6 ± 8.1 μg·L−1, P = 0.005). Beta carboxy-terminal cross-linking telopeptide of type 1 collagen decreased between baseline and week 8 for both groups (−0.16 ± 0.20 μg·L−1, P < 0.001). Prolactin increased from baseline to week 8 for the supplemented group (148 ± 151 IU·L−1, P = 0.041). The increase in adiponectin from baseline to week 8 was higher in controls (4.3 ± 1.8 mg·L−1, P < 0.001) than that in the supplemented group (1.4 ± 1.0 mg·L−1, P < 0.001). Insulin-like growth factor binding protein-3 was lower at week 8 than baseline for controls (−461 ± 395 ng·mL−1, P < 0.001). Conclusion: The increase in bone-specific alkaline phosphatase, a marker of bone formation, with supplementation supports a role of energy in osteoblastic activity; the implications for skeletal adaptation and stress fracture risk are unclear. The mechanism is likely through protecting markers of metabolic, but not reproductive or thyroid, function

Interaction of perceptual grouping and crossmodal temporal capture in tactile apparent-motion

Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can &quot;capture'' visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left-or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from -75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs-one short (75 ms), one long (325 ms)-were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an attentional modulation of apparent motion, which inhibits crossmodal temporal-capture effects

Role of sex and stature on the biomechanics of normal and loaded walking : implications for injury risk in the military

Load carriage and marching ‘in-step’ are routine military activities associated with lower limb injury risk in service personnel. The fixed pace and stride length of marching typically vary from the preferred walking gait and may result in overstriding. Overstriding increases ground reaction forces and muscle forces. Women are more likely to overstride than men due to their shorter stature. These biomechanical responses to overstriding may be most pronounced when marching close to the preferred walk-to-run transition speed. Load carriage also affects walking gait and increases ground reaction forces, joint moments and the demands on the muscles. Few studies have examined the effects of sex and stature on the biomechanics of marching and load carriage; this evidence is required to inform injury prevention strategies, particularly with the full integration of women in some defence forces. This narrative review explores the effects of sex and stature on the biomechanics of unloaded and loaded marching at a fixed pace and evaluates the implications for injury risk. The knowledge gaps in the literature, and distinct lack of studies on women, are highlighted, and areas that need more research to support evidence-based injury prevention measures, especially for women in arduous military roles, are identified

Sister Mary Joseph's Nodule at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 34 cases.

Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis

Sequentially based analysis versus image based analysis of Intima Media Thickness in common carotid arteries studies - Do major IMT studies underestimate the true relations for cardio- and cerebrovascular risk?

<p>Abstract</p> <p>Background</p> <p>Image-based B-mode ultrasound has gained popularity in major studies as a non-invasive method of measuring cardio- and cerebrovascular risk factors. However, none of the major studies appears to have paid sufficient attention to the variation in end diastolic wall process. By using sequentially based analyses (SBA) of Intima-Media Thickness (IMT), the general purpose of this study was to show that the current image based (ECG tracked) analysis (IBA) has some major variations and might underestimate the true relations for cardiovascular events and stroke for IMT measurement.</p> <p>Method</p> <p>The study group consisted of 2500 healthy male subjects aged between 35 to 55 years. 4 sequences (300 images) were analyzed per subject. 750,000 images were analysed throughout the course of this study.</p> <p>Results</p> <p>IBA showed significantly lower mean, maximal, and minimal values for IMT in CCA than for SBA. The correlation analysis between IBA and SBA with the cardio- and cerebrovascular risk factors showed a higher correlation of SBA for all risk factors. The Pearson coefficient was 0.81, p < 0.01, for SBA versus Framingham CHD risk level (FCRL) and 0.49, p = 0.01, for IBA versus FCRL.</p> <p>Conclusion</p> <p>IBA did not measure the true maximal values of the IMT in this study. Together with the correlation analysis, this indicates that IBA might underestimate the true relations for IMT and risk factors.</p

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Vitamin D metabolites are associated with musculoskeletal injury in young adults: a prospective cohort study

The relationship between vitamin D metabolites and lower body (pelvis and lower limb) overuse injury is unclear. In a prospective cohort study, we investigated the association between vitamin D metabolites and incidence of lower body overuse musculoskeletal and bone stress injury in young adults undergoing initial military training during all seasons. In 1637 men and 530 women (age, 22.6 ± 7.5 years; BMI, 24.0 ± 2.6 kg∙m-2 ; 94.3% white ethnicity), we measured serum 25-hydroxyvitamin D (25(OH)D) and 24,25- dihydroxyvitamin D (24,25(OH)2D) by high-performance liquid chromatography tandem mass spectrometry, and 1,25-dihydroxyvitamin D (1,25(OH)2D) by immunoassay during week 1 of training. We examined whether the relationship between 25(OH)D and 1,25(OH)2D:24,25(OH)2D ratio was associated with overuse injury. During 12 weeks training, 21.0% sustained ≥1 overuse musculoskeletal injury, and 5.6% sustained ≥1 bone stress injury. After controlling for sex, BMI, 2.4 km run time, smoking, bone injury history, and Army training course (Officer, standard, or Infantry), lower body overuse musculoskeletal injury incidence was higher for participants within the second lowest versus highest quartile of 24,25(OH)2D (OR: 1.62 [95%CI 1.13–2.32; P = 0.009]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2D:24,25(OH)2D (OR: 6.30 [95%CI 1.89–21.2; P = 0.003]). Lower body bone stress injury incidence was higher for participants within the lowest versus highest quartile of 24,25(OH)2D (OR: 4.02 [95%CI 1.82–8.87; P < 0.001]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2D:24,25(OH)2D (OR: 22.08 [95%CI 3.26–149.4; P = 0.001]), after controlling for the same covariates. Greater conversion of 25(OH)D to 24,25(OH)2D, relative to 1,25(OH)2D (i.e., low 1,25(OH)2D:24,25(OH)2D), and higher serum 24,25(OH)2D were associated with a lower incidence of lower body overuse musculoskeletal and bone stress injury. Serum 24,25(OH)2D may have a role in preventing overuse injury in young adults undertaking arduous physical training

Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1

Peer reviewedPublisher PD