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Background Alport Syndrome and IgA Nephropathy (IgAN) are both disorders that can cause hematuria. Alport syndrome is most commonly an X-linked disease, caused by COL4A5 mutation. Mutations of COL4A3 and COL4A4 on chromosome two are also common causes of Alport syndrome. IgAN is the most common glomerulonephritis worldwide. Though IgAN is usually sporadic, an estimated 15% of cases have an inheritable component. These cases of Familal IgA Nephropathy (FIgAN) can have mutations on genes which are known to cause Alport Syndrome. Case presentation We report a case of a 27-year-old man with strong family history of renal disease, who presented with hematuria and new non-nephrotic range proteinuria. Physical exam showed no abnormalities. His creatinine remained persistently elevated, and renal ultrasound exhibited bilaterally increased echogenicity consistent with Chronic Kidney Disease. Twenty-four-hour urinary collection revealed non-nephrotic range proteinuria of 1.4 g, with otherwise negative workup. On biopsy, he had IgA positive immunofluorescent staining as well as moderate interstitial fibrosis and tubular atrophy. Electron microscopy showed a basket-weave pattern of thickening and splitting of the lamina densa-consistent with Alport Syndrome, as well as mesangial expansion with electron-dense deposits -consistent with IgAN. Conclusions Mutations of COL4A5 on the X chromosome, as well as mutations of COL4A3 and COL4A4 on chromosome 2, can cause both Alport Syndrome and FIgAN. Genome wide association studies identified certain Angiotensin Converting Enzyme gene polymorphisms as independent risk factors for progression of IgAN. Our Presentation with this co-occurring pathology suggests a new paradigm where Alport Syndrome and FIgAN may represent manifestations of a single disease spectrum rather than two disparate pathologies. Appreciating hematuria through this framework has implications for treatments and genetic counseling. Further genome wide association studies will likely increase our understanding of Alport Syndrome, FIgAN, and other causes of hematuria.

Humans can perform complex movements with speed and agility in the face of constantly changing task demands. To accomplish this, motor plans are adapted to account for errors in our movements because of changes in our body (e.g., growth or injury) or in the environment (e.g., walking on sand vs ice). It has been suggested that adaptation that occurs in response to changes in the state of our body will generalize across different movement contexts and environments, whereas adaptation that occurs with alterations in the external environment will be context-specific. Here, we asked whether the ability to form generalizable versus context-specific motor memories develops during childhood. We performed a cross-sectional study of context-specific locomotor adaptation in 35 children (3-18 years old) and 7 adults (19-31 years old). Subjects first adapted their gait and learned a new walking pattern on a split-belt treadmill, which has two belts that move each leg at a different speed. Then, subjects walked overground to assess the generalization of the adapted walking pattern across different environments. Our results show that the generalization of treadmill after-effects to overground walking decreases as subjects' age increases, indicating that age and experience are critical factors regulating the specificity of motor learning. Our results suggest that although basic locomotor patterns are established by two years of age, brain networks required for context-specific locomotor learning are still being developed throughout youth.

Background. Step asymmetries during gait in persons after stroke can occur in temporal or spatial domains. Prior studies have shown that split-belt locomotor adaptation can temporarily mitigate these asymmetries. Objective. We investigated whether baseline gait asymmetries affected how patients adapt and store new walking patterns. Methods. Subjects with stroke and age-matched controls were studied walking at a 2:1 speed ratio on the split-belt during adaptation and assessed for retention of the learned pattern (the after-effect) with both belts at the same speed. Results. Those with stroke adapted more slowly ( P < .0001), though just as much as healthy older adults. During split-belt walking, the participants with stroke adapted toward their baseline asymmetry (eg, F = 14.02, P < .01 for step symmetry), regardless of whether the subsequent after-effects improved or worsened their baseline step asymmetries. No correlation was found between baseline spatial and temporal measures of asymmetry ( P = .38). Last, the initial spatial and temporal asymmetries predicted after-effects independently of one another. The after-effects in the spatial domain (ie, center of oscillation difference) are only predicted by center of oscillation difference baseline ( F = 15.3, P = .001), while all other parameters were nonsignificant (all Ps > .17). Temporal coordination (ie, phasing) after-effects showed a significant effect only from phasing baseline ( F = 26.92, P < .001, all others P > .33). Conclusion. This work demonstrates that stroke patients adapt toward their baseline temporal and spatial asymmetries of walking independently of one another. We define how a given split-belt training session would affect asymmetries in these domains, which must be considered when developing rehabilitation interventions for stroke patients.

The healthy aging process affects the ability to learn and remember new facts and tasks. Prior work has shown that motor learning can be adversely affected by non-motor deficits, such as time. Here we investigated how age, and a dual task influence the learning and forgetting of a new walking pattern. We studied healthy younger (30 yo) and older adults (50 yo) as they alternated between 5-min bouts of split-belt treadmill walking and resting. Older subjects learned a new walking pattern at the same rate as younger subjects, but forgot some of the new pattern during the rest breaks. We tested if forgetting was due to reliance on a cognitive strategy that was not fully engaged after rest breaks. When older subjects performed a dual cognitive task to reduce strategic control of split-belt walking, their adaptation rate slowed, but they still forgot much of the new pattern during the rest breaks. Our results demonstrate that the healthy aging process is one component that weakens motor memories during rest breaks and that this phenomenon cannot be explained solely by reliance on a conscious strategy in older adults.

Adaptation is an error-driven motor learning process that can account for predictable changes in the environment (e.g., walking on ice) or in ourselves (e.g., injury). Our ability to recall and build upon adapted motor patterns across days is essential to this learning process. We investigated how different training paradigms affect the day-to-day memory of an adapted walking pattern. Healthy human adults walked on a split-belt treadmill, and returned the following day to assess recall, relearning rate, and performance. In the first experiment, one group adapted and de-adapted (i.e., washed-out the learning) several times on day 1 to practice the initial stage of learning where errors are large; another group adapted only one time and then practiced in the adapted (“learned”) state where errors were small. On day 2, they performed washout trials before readapting. The group that repeatedly practiced the initial portion of adaptation where errors are large showed the fastest relearning on the second day. In fact, the memory was nearly as strong as that of a third group that was left overnight in the adapted state and was not washed-out before reexposure on the second day. This demonstrates that alternating exposures to early adaptation and washout can enhance readaptation. In the second experiment, we tested whether the opposite split-belt pattern interferes with day 2 relearning. Surprisingly, it did not, and instead was similar to practicing in the adapted state. These results show that the structure of the initial phase of learning influences the ease of motor relearning.

Control of the human walking pattern normally requires little thought, with conscious control used only in the face of a challenging environment or a perturbation. We have previously shown that people can adapt spatial and temporal aspects of walking to a sustained perturbation generated by a split-belt treadmill. Here we tested whether conscious correction of walking, versus distraction from it, modifies adaptation. Conscious correction of stepping may expedite the adaptive process and help to form a new walking pattern. However, because walking is normally an automatic process, it is possible that conscious effort could interfere with adaptation, whereas distraction might improve it by removing competing voluntary control. Three groups of subjects were studied: a control group was given no specific instructions, a conscious correction group was instructed how to step and given intermittent visual feedback of stepping during adaptation, and a distraction group performed a dual-task during adaptation. After adaptation, retention of aftereffects was assessed in all groups during normal treadmill walking without conscious effort, feedback, or distraction. We found that conscious correction speeds adaptation, whereas distraction slows it. Subjects trained with distraction retained aftereffects longest, suggesting that the training used during adaptation predicts the time course of deadaptation. An unexpected finding was that these manipulations affected the adaptation rate of spatial but not temporal elements of walking. Thus conscious processes can preferentially access the spatial walking pattern. It may be that spatial and temporal controls of locomotion are accessible through distinct neural circuits, with the former being most sensitive to conscious effort or distraction.