The addition of blood flow restriction during resistance exercise does not increase prolonged low-frequency force depression.

At a given exercise intensity, blood flow restriction (BFR) reduces the volume of exercise required to impair post-exercise neuromuscular function. Compared to traditional exercise, the time course of recovery is less clear. After strenuous exercise, force output assessed with electrical muscle stimulation is impaired to a greater extent at low versus high stimulation frequencies, a condition known as prolonged low-frequency force depression (PLFFD). It is unclear if BFR increases PLFFD after exercise. This study tested if BFR during exercise increases PLFFD and slows recovery of neuromuscular function compared to regular exercise. Fifteen physically active participants performed six low-load sets of knee-extensions across four conditions: resistance exercise to task failure (RETF), resistance exercise to task failure with BFR applied continuously (BFRCONT) or intermittently (BFRINT), and resistance exercise matched to the lowest exercise volume condition (REVM). Maximal voluntary contraction (MVC) force output, voluntary activation and a force-frequency (1-100 Hz) curve were measured before and 0, 1, 2, 3, 4 and 24 h after exercise. Exercise to task failure caused similar reductions at 0 h for voluntary activation (RETF = 81.0 ± 14.2%, BFRINT = 80.9 ± 12.4% and BFRCONT = 78.6 ± 10.7%) and MVC force output (RETF = 482 ± 168 N, BFRINT = 432 ± 174 N, and BFRCONT = 443 ± 196 N), which recovered to baseline values between 4 and 24 h. PLFFD occurred only after RETF at 1 h supported by a higher frequency to evoke 50% of the force production at 100 Hz (1 h: 17.5 ± 4.4 vs. baseline: 15 ± 4.1 Hz, P = 0.0023), BFRINT (15.5 ± 4.0 Hz; P = 0.03), and REVM (14.9 ± 3.1 Hz; P = 0.002), with a trend versus BFRCONT (15.7 ± 3.5 Hz; P = 0.063). These findings indicate that, in physically active individuals, using BFR during exercise does not impair the recovery of neuromuscular function by 24 h post-exercise.

Can we enable individuals to reach further down without rounding their backs before beginning a lift? Examining the influence of starting foot and trunk position on reach depth.

There is disagreement regarding the efficacy of 'safe' lifting recommendations for reducing low back disorder risk. These recommendations commonly focus on minimising lumbar spine flexion, which limits the range of allowable starting lift positions for that person. This study evaluated whether starting postural adaptations could allow a person to reach down further without rounding their lumbar spine before beginning a lift. Reach displacement was measured as participants performed a series of maximal reach tasks under different combinations of stance width, foot orientation and trunk inclination, with their lumbar spine motion restricted. There were no interactions between any of the three postural adaptations or any effect of stance width or trunk inclination. Seventy-nine percent of participants achieved their greatest reach displacement with their feet externally rotated, which contributed to a 4 cm greater reach displacement compared to a neutral foot orientation (p < 0.001).Practitioner summary: This study examined whether aspects of initial posture could influence the ability to adhere to 'safe' lifting recommendations across a range of lift heights. As a component of lifting (re)training interventions, practitioners should consider starting lift posture adaptations (e.g. manipulating foot external rotation) to improve capacity to adhere to recommendations.

Functional Movement Screen Task Scores and Joint Range-of-motion: A Construct Validity Study.

Little is known about the construct validity of the Functional Movement Screen (FMS). We aimed to assess associations between FMS task scores and measures of maximum joint range-of-motion (ROM) among university varsity student-athletes from 4 sports (volleyball, basketball, ice hockey, and soccer). Athletes performed FMS tasks and had their maximum ankle, hip and shoulder ROM measured. Multivariable linear regression was used to estimate associations between FMS task scores and ROM measurements. 101 university student-athletes were recruited (52 W/49 M; mean age 20.4±1.9 years). In general, athletes with higher FMS task scores had greater ROM compared to those with lower task scores. For example, athletes who scored 2 on the FMS squat task had 4° (95% CI, 1° to 7°) more uni-articular ankle dorsiflexion ROM compared with those who scored 1, while those who scored 3 on the FMS squat task had 10° (4° to 17°) more uni-articular ankle dorsiflexion ROM compared with those who scored 1. Large variation in ROM measurements was observed. In sum, substantial overlap in joint ROM between groups of athletes with different FMS task scores weakens the construct validity of the FMS as an indicator of specific joint ROM.

Mechanical Energy Expenditure at Lumbar Spine and Lower Extremity Joints During the Single-Leg Squat Is Affected by the Nonstance Foot Position.

ABSTRACT: Hirsch, SM, Chapman, CJ, Frost, DM, and Beach, TAC. Mechanical energy expenditure at lumbar spine and lower extremity joints during the single-leg squat is affected by the nonstance foot position. J Strength Cond Res 36(9): 2417-2426, 2022-Previous research has shown that discrete kinematic and kinetic quantities during bodyweight single-leg squat (SLS) movements are affected by elevated foot positioning and sex of the performer, but generalizations are limited by the high-dimensional data structure reported. Using a 3D inverse dynamical linked-segment model, we quantified mechanical energy expenditure (MEE) at each joint in the kinetic chain, the total MEE (sum of MEE across aforesaid joints), and the relative contribution of each joint to total MEE during SLSs performed with elevated foot positioned beside stance leg (SLS-Side), and in-front of (SLS-Front) and behind (SLS-Back) the body. Total MEE differed between SLS variations ( p = 0.002), with the least amount observed in the SLS-Back (effect size [ES] = 0.066-0.069). Approximately 50% of total MEE was contributed by the knee joint in each SLS variation, whereas MEE at the ankle, hip, and lumbar spine (in absolute and relative terms) varied complexly as a function of the elevated foot position. Total MEE ( p = 0.0192, ES = 0.852) and the absolute MEE at the knee and spine was greater in men across the SLS variations performed ( p = 0.025-0.036, ES = 0.715-0.766), but only the lumbar spine contribution to total MEE was larger in men across all SLS variations ( p = 0.045, ES = 0.607). Otherwise, there were no other sex-specific responses observed. Biomechanically, SLS movements are generally "knee-dominant," but changing elevated foot position effectively redistributes MEE among other joints in the linkage. Consistent with the previous conclusions reached based on discrete kinematic and kinetic data, not all SLSs are equal.

Comparison of 5 Normalization Methods for Knee Joint Moments in the Single-Leg Squat.

Ratio scaling is the most common magnitude normalization approach for net joint moment (NJM) data. Generally, researchers compute a ratio between NJM and (some combination of) physical body characteristics (eg, mass, height, limb length, etc). However, 3 assumptions must be verified when normalizing NJM data this way. First, the regression line between NJM and the characteristic(s) used passes through the origin. Second, normalizing NJM eliminates its correlation with the characteristic(s). Third, the statistical interpretations following normalization are consistent with adjusted linear models. The study purpose was to assess these assumptions using data collected from 16 males and 16 females who performed a single-leg squat. Standard inverse dynamics analyses were conducted, and ratios were computed between the mediolateral and anteroposterior components of the knee NJM and participant mass, height, leg length, mass × height, and mass × leg length. Normalizing NJM-mediolateral by mass × height and mass × leg length satisfied all 3 assumptions. Normalizing NJM-anteroposterior by height and leg length satisfied all 3 assumptions. Therefore, if normalization of the knee NJM is deemed necessary to address a given research question, it can neither be assumed that using (any combination of) participant mass, height, or leg length as the denominator is appropriate nor consistent across joint axes.

Considerations for Velocity-Based Training: The Instruction to Move "As Fast As Possible" Is Less Effective Than a Target Velocity.

ABSTRACT: Hirsch, SM and Frost, DM. Considerations for velocity-based training: the instruction to move "as fast as possible" is less effective than a target velocity. J Strength Cond Res 35(2S): S89-S94, 2021-In addition to the potential benefits with monitoring training intensity with velocity-measuring tools during exercise, these devices also provide an opportunity for researchers and practitioners to provide feedback and instruction to performers in a new way. The purpose of this study was to assess the influence of instructing athletes with a target velocity vs. instructing them to move "as fast as possible" during a free-weight bench press. In addition, the effects of each instruction on future repetition maximum (RM) test performance was compared. Thirteen male powerlifters were recruited and performed 4 sets of 5 repetitions with 45% 1RM while being instructed to attain a target velocity of 1.0 m·s-1 or to move as fast as possible. The maximum mean velocity attained in each set was compared with a repeated measures analysis of variance and Tukey's post-hoc test. After these 4 sets of 5 repetitions, the number of repetitions performed during an RM test with 75% 1RM was compared with a Wilcoxon Signed-Rank test. Participants moved faster when they received the target velocity instruction (0.84 ± 0.10 m·s-1) than when they received the "move as fast as possible" instruction (0.82 ± 0.09 m·s-1) (p < 0.001) with no differences in the number of repetitions performed in the following RM test between the 2 testing sessions (p = 0.43). An instruction to attain a challenging velocity target may be a more effective strategy to use when attempting to elicit maximum barbell velocities during training relative to the traditional instruction to move as fast as possible.

Fibrillary astrocytes are decreased in the subgenual cingulate in schizophrenia.

Decreases in astrocyte density and in glial fibrillary acid protein (GFAP) mRNA in the anterior cingulate cortex have been reported changed in mood and affective disorders. Our study examines the relative density and frequency of fibrillary and gemistocytic astrocytes in the white matter of the subgenual cingulate cortex in 11 schizophrenia, 16 bipolar disorder, 20 major depression and 20 normal control cases. Serial coronal sections were stained with H&E for anatomical guidance and GFAP immunohistochemistry for astrocyte identification. Astrocyte density was measured using systematic anatomical distinctions and randomised counting methods previously reported. Astrocytes were classified as fibrillary or gemistocytic based on staining and morphometric criteria and were measured in the crown and base of the gyral white matter. Fibrillary astrocytes were decreased in the base of the cingulate white matter in schizophrenia (p = 0.046), with no change in the density of gemistocytic astrocytes. There was no change in density of gemistocytic astrocytes. This suggests that the previously reported decrease in astrocytes in schizophrenia in the subgenual cingulate is accounted for only by a change in fibrillary astrocytes. With recent findings suggesting fibrillary astrocytes regulate synaptic glutamate this morphological change may relate to disregulation of function of the subgenual cingulate cortex.

Restricting lumbar spine flexion redistributes and changes total mechanical energy expenditure during lifting.

Minimizing lumbar spine flexion during lifting requires greater lower extremity joint motion. However, the effects of these kinematic changes on lumbar and lower extremity joint kinetics are unknown. Further, it is unclear whether the distribution of biomechanical demands throughout the lumbar spine and lower extremity during lumbar spine flexion restricted lifting are modulated by task factors like lift origin height and object mass. This study examined the influence of restricting lumbar spine flexion during lifting on the distribution of biomechanical demands, operationalized as mechanical energy expenditure (MEE), across the lumbar spine and lower extremity joints during lifting tasks. Twenty participants performed a series of lifting tasks that varied by lift origin height, object mass and presence or absence of lumbar spine motion restricting harness. MEE was quantified for the lumbar spine and lower extremity joints and summed across all joints to represent the total MEE. Distributions of MEE were compared across combinations of the three task factors. Total MEE was greater when lifting with restricted spine motion (p < 0.001). MEE was redistributed away from the lumbar spine and predominantly to the hips in the spine restricted conditions (p < 0.001). The nature and magnitude of this effect was modulated by lift origin height for the lumbar spine (p < 0.001) and hips (p < 0.001). Findings demonstrated that biomechanical demands can be shifted from the lumbar spine to the lower extremity when lifting with restricted spine flexion, which might help mitigate overuse injuries through coordinative variability.

Astrocyte decrease in the subgenual cingulate and callosal genu in schizophrenia.

Decreases in glial cell density and in GFAP mRNA in the anterior cingulate cortex have been reported in schizophrenia, bipolar disorder and major depressive disorder. Our study examines astrocyte and oligodendrocyte density in the white and grey matter of the subgenual cingulate cortex, and at the midline of the genu of the corpus callosum, in schizophrenia, bipolar disorder, depression and normal control cases. Serial coronal sections were stained with H and E for anatomical guidance, cresyl haematoxylin for oligodendrocyte identification and GFAP immunohistochemistry for astrocyte identification. Oligodendrocyte and astrocyte density was measured using systematic anatomical distinctions and randomised counting methods. A significant decrease in astrocyte density was observed in schizophrenia compared with normal controls in the cingulate grey matter, cingulate white matter and the midline of the corpus callosum (p = 0.025). Bipolar disorder and depression cases showed no significant changes in astrocyte density. Oligodendrocytes did not show any changes between diagnostic groups. In subgenual cingulate cortex, the ratio of oligodendrocytes to astrocytes was decreased between the controls and the three disease groups, suggesting a specific glial cell type specific change in schizophrenia.

A comparison of five methods to normalize joint moments during running.

BACKGROUND: Net joint moments (NJM) are typically normalized for a (combination of) physical body characteristics such as mass, height, and limb length using ratio scaling to account for differences in body characteristics between individuals. Four assumptions must be met when normalizing NJM data this way to ensure valid conclusions. First, the relationship between the non-normalized NJM and participant characteristic should be linear. Second, the regression line between NJM and the characteristic(s) used should pass through the origin. Third, scaling should not significantly perturb the statistical distribution of the data. Fourth, normalizing a NJM should eliminate its correlation with the characteristic(s) normalized for. RESEARCH QUESTION: This study assessed these assumptions using data collected among 59 individuals running at 10 km h-1. METHODS: Standard inverse dynamics analyses were conducted, and ratios were computed between the sagittal-plane hip, knee and ankle NJM's and the participant's mass, height, leg length, mass × height, and mass × leg length. RESULTS: The most important finding of this study was that none of the scaling variables fulfilled all assumptions across all joints. However, scaling by mass, mass*height and mass*leg length satisfied the assumptions for the knee joint moment and log-transformed hip joint moment, suggesting these methods generally performed best. SIGNIFICANCE: Our findings suggests that scaling by mass, mass*height and mass*leg length may be considered to normalize joint moments during running. Nevertheless, we urge researchers to check the statistical assumptions to ensure valid conclusions. We provide supplementary code to check the statistical assumptions, and discuss consequences of inappropriate scaling.

Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia.

The molecular basis of schizophrenia is poorly understood; however, different brain regions are believed to play distinct roles in disease symptomology. We have studied gene expression in the superior temporal cortex (Brodmann area 22; BA22), which may play a role in positive pathophysiology, and compared our results with data from the anterior prefrontal cortex (BA10), which shows evidence for a role in negative symptoms. Genome-wide mRNA expression was determined in the BA22 region in 23 schizophrenics and 19 controls and compared with a BA10 data set from the same subjects. After adjustments for confounding sources of variation, we carried out GeneGO pathway enrichment analysis in each region. Significant differences were seen in age-related transcriptional changes between the BA22 and the BA10 regions, 21.8% and 41.4% of disease-associated transcripts showing age association, respectively. After removing age associated changes from our data, we saw the highest enrichment in processes mediating cell adhesion, synaptic contact, cytoskeletal remodelling, and apoptosis in the BA22 region. For the BA10 region, we observed the strongest changes in reproductive signalling, tissue remodelling, and cell differentiation. Further exploratory analysis also identified potentially disease-relevant processes that were undetected in our more stringent primary analysis, including autophagy in the BA22 region and the amyloid process in the BA10 region. Collectively, our analysis suggests disruption of many common pathways and processes underpinning synaptic plasticity in both regions in schizophrenia, whereas individual regions emphasize changes in certain pathways that may help to highlight pathway-specific therapeutic opportunities to treat negative or positive symptoms of the disease.

Investigation of G72 (DAOA) expression in the human brain.

BACKGROUND: Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO), supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. METHODS: The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. RESULTS: Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis) human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala), spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. CONCLUSION: Our results suggest that native G72 protein is not normally present in the tissues that we analysed in this study. We also conclude that the lack of demonstrable G72 expression in relevant brain regions does not support a role for G72 in modulation of DAO activity and the pathology of schizophrenia via a DAO-mediated mechanism. In silico analysis suggests that G72 is not robustly expressed and that the transcript is potentially labile. Further studies are required to understand the significance of the G72/30 locus to schizophrenia.

Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).

UNLABELLED: Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. METHODS: mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. RESULTS: overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. DISCUSSION: overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.

Mismatch negativity indexes illness-specific impairments of cortical plasticity in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease.

Cognitive impairment is an important predictor of functional outcome in patients with schizophrenia, yet its neurobiology is still incompletely understood. Neuropathological evidence of impaired synaptic connectivity and NMDA receptor-dependent transmission in superior temporal cortex motivated us to explore the correlation of in vivo mismatch negativity (MMN) with cognitive status in patients with schizophrenia. MMN elicited in a roving stimulus paradigm displayed a response proportional to the number of stimulus repetitions (memory trace effect). Preliminary evidence in patients with chronic schizophrenia suggests that attenuation of this MMN memory trace effect was correlated with the degree of neuropsychological memory dysfunction. Here we present data from a larger confirmatory study in patients with schizophrenia, bipolar disorder, probable Alzheimer's disease and healthy controls. We observed that the diminution of the MMN memory trace effect and its correlation with memory impairment was only found in the schizophrenia group. Recent pharmacological studies using the roving paradigm suggest that attenuation of the MMN trace effect can be understood as abnormal modulation of NMDA receptor-dependent plasticity. We suggest that the convergence of the previously identified synaptic pathology in supragranular cortical layers with the intracortical locus of MMN generation accounts for the remarkable robustness of MMN impairments in schizophrenia. We further speculate that this layer-specific synaptic pathology identified in supragranular neurons plays a pivotal computational role, by weakening the encoding and propagation of prediction errors to higher cortical modules. According to predictive coding theory such breakdown will have grave implications not only for perception, but also for higher-order cognition and may thus account for the MMN-cognition correlations observed here. Finally, MMN is a sensitive and specific biomarker for detecting the early prodromal phase of schizophrenia and is well suited for the exploration of novel cognition-enhancing agents in humans.

A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia.

BACKGROUND: Ziprasidone is a novel antipsychotic with a unique pharmacologic profile. This study compared ziprasidone with the conventional antipsychotic haloperidol in outpatients with stable schizophrenia. METHOD: Three hundred one outpatients with stable chronic or subchronic schizophrenia (DSM-III-R) were randomized and participated in this double-blind, multicenter, parallel-group clinical study comparing flexible-dose oral ziprasidone, 80-160 mg/day (N = 148), with haloperidol, 5-15 mg/day (N = 153), over 28 weeks. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity of Illness scale, the Montgomery-Asberg Depression Rating Scale, the Simpson-Angus Scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale. RESULTS: Modal doses at endpoint were 80 mg/day for ziprasidone and 5 mg/day for haloperidol. Improvements in all mean efficacy variables with both ziprasidone and haloperidol were observed. Significantly more patients were categorized as negative symptom responders (> or = 20% reduction in PANSS negative subscale score) in the ziprasidone group (48%) compared with the haloperidol group (33%) (p < .05). Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders. Changes in body weight were negligible with both treatments. No pattern of laboratory or cardiovascular changes was observed. CONCLUSION: Ziprasidone and haloperidol were both effective in reducing overall psychopathology; ziprasidone demonstrated effective treatment of negative symptoms and was better tolerated than haloperidol. Ziprasidone appears to offer an effective alternative to haloperidol in the long-term treatment of stable outpatients with schizophrenia.

Mismatch negativity potentials and cognitive impairment in schizophrenia.

Cognitive impairment in schizophrenia is an important predictor of clinical and social outcome. In this preliminary study, the correlation between cognitive status and deficits in mismatch negativity (MMN) generation was explored. The MMN response to tone duration deviants was recorded using a new stimulation protocol with continuously changing ('roving') standard stimuli in order to measure the effect of standard repetitions on MMN (memory trace effect). Cognitive status of the patient group (n=28) was assessed using neuropsychological screening. Healthy participants (n=20) served as age-matched comparison group. In patients, MMN amplitude in frontal electrodes as well as the MMN memory trace effect was diminished compared to controls. While both measures were inversely related to patient's age and disease severity, only the MMN memory trace effect was robustly correlated with the degree of neuropsychological impairment. This suggests that ERP measures of auditory system adaptability more appropriately characterise the pathophysiological processes underlying cognitive impairment in schizophrenia than static measures of ERP magnitude.

A volumetric biochemical niacin flush-based index that noninvasively detects fatty acid deficiency in schizophrenia.

(1) It is possible to investigate aspects of phospholipid-related signal transduction in humans noninvasively using the niacin skin flush test. (2) Patients with schizophrenia have previously been reported to show a reduced flushing response. (3) The aim of this study was to devise a comprehensive index of cutaneous response to the niacin test, incorporating aqueous methyl nicotinate concentration and time, and to test this index in schizophrenia. (4) A discrete approximation to a continuous volumetric index, which we have named the volumetric niacin response (VNR), was devised. Its value was measured in 27 patients with DSM-IV schizophrenia and 26 age- and sex-matched normal controls. (5) The mean value of the VNR in the patients with schizophrenia (16.26) was significantly smaller than that of 26.77 in the normal controls (P<.0004). (6) With a threshold value for the VNR of 21, the test differentiated well between schizophrenia and normal controls (P=.002) with a sensitivity of 78% and a specificity of 65%. (7) The present results confirm that the flushing response is reduced in schizophrenia, and show that calculation of the VNR is an effective means of allowing the total response in different patients or patient groups to be readily compared.

Impairment in frontal but not temporal components of mismatch negativity in schizophrenia.

Impairment in mismatch negativity (MMN) potentials is a robust finding in schizophrenia. While previous studies suggested that MMN in man is generated by a single dipole source bilaterally in the primary auditory cortex, more recent data modified this assumption by showing differential modulation of MMN components over the frontal and temporal scalp. Here we used a roving standard experiment to record mismatch potentials to tone duration deviants with the aim to detect robust temporal and frontal mismatch components. Fourteen schizophrenic patients with normal intelligence and without overt cognitive deficits and age- and sex-matched controls were studied. In agreement with previous findings MMN recorded from the frontal scalp was markedly attenuated in patients. However, in contrast to previous reports, positive mismatch potentials of normal magnitude were recorded from temporal (mastoid) electrodes. This finding raises the possibility of a selective impairment in multiple mismatch generators in schizophrenia and may lend support for the notion of impaired cortico-cortical connectivity in schizophrenia.

Recombinant human platelet-derived growth factor: biology and clinical applications.

The abilities of bone to remodel, fractures to repair, and bone grafts to incorporate are all fundamental reflections of the bone remodeling cycle. This process is characterized by the recruitment and differentiation of osteoblastic and osteoclastic cell populations, whose cellular activities are coordinated and regulated by an elaborate system of growth factors and cytokines. One of the crucial biological factors responsible for reparative osseous activity is platelet-derived growth factor (PDGF). The potent stimulatory effects of PDGF as a chemoattractant and mitogen for mesenchymal cells (including osteogenic cells), along with its ability to promote angiogenesis, have been demonstrated in a variety of preclinical models predicting maxillofacial, spine and appendicular skeletal, and soft-tissue applications. The biological profile of PDGF, including its ability to recruit osteoprogenitor cells, makes it particularly suited to address the skeletal defects that are seen with comorbid conditions such as osteoporosis, diabetes, and the effects of smoking. The clinical success and safety that have been demonstrated with use of recombinant human PDGF (rhPDGF) in the repair of periodontal defects have led to U.S. Food and Drug Administration (FDA) approval of rhPDGF for this indication. Ongoing pilot and pivotal trials in the United States and internationally will continue to clarify the promising role of PDGF in the treatment of challenging skeletal disorders.