Accelerated long-term forgetting in patients with acquired brain injury.

OBJECTIVE: Recent research suggests that patients with neurological disorders without overt seizures may also experience accelerated long-term forgetting (ALF). This term describes unimpaired learning and memory performance after standard retention intervals, but an excessive rate of forgetting over delays of days or weeks. The objective of this retrospective study was to investigate ALF in patients with an acquired brain injury (ABI) and to associate memory performance with executive functions. METHODS: Verbal memory performance (short-term recall, 30-min recall, 1-week recall) was assessed in 34 adult patients with ABI and compared to a healthy control group (n = 54) using an auditory word learning and memory test. RESULTS: Repeated measure analysis showed significant effects of time and group as well as interaction effects between time and group regarding recall and recognition performance. Patients with ABI had a significantly impaired 1-week recall and recognition performance compared to the healthy control group. Correlations between recall performance and executive functions were nonsignificant. DISCUSSION: Our results demonstrate that non-epileptic patients with ABI, especially patients with frontal and fronto-temporal lesions, are prone to ALF. Additionally, our data support the assumption that ALF results from a consolidation impairment since verbal recall and recognition were impaired in patients with ABI.

Comparison of consumer knowledge about Campylobacter, Salmonella and Toxoplasma and their transmissibility via meat: results of a consumer study in Germany.

BACKGROUND: Campylobacter is the most commonly reported causative agent of foodborne bacterial infection in Germany, and contaminated chicken meat is an important source of this zoonotic agent. The aim of this study was to determine the knowledge of consumers in Germany about Campylobacter, Salmonella and Toxoplasma and their transmissibility via meat. In addition, we investigated the level of knowledge between selected consumer groups and whether the results coincided with those of international studies. METHODS: We conducted a cross-sectional survey of 1008 consumers in Germany via an online panel to record, analyse and evaluate the state of knowledge about Campylobacter, Salmonella and Toxoplasma. The participants were selected according to age, gender and federal states to be representative of the German population. RESULTS: Overall, 68.3% of the respondents had never heard of Campylobacter, 20.2% had heard of Campylobacter but did not know how to protect themselves, and only 11.5% knew how to protect themselves from Campylobacter infections. Slightly more than half (52.2%) of the respondents who had at least heard of Campylobacter knew that Campylobacter was transmissible via meat. Knowledge increased significantly with age. Participants over 60 years old knew about Campylobacter almost three times as often as the 16- to 19-year-old comparison group (OR = 2.982). Consumers who had at least a secondary school certificate were almost twice as likely to know about Campylobacter as those who had no school certificate or a lower secondary school certificate (OR = 1.899). Participants who were not actors in the food chain were significantly less frequently informed about Campylobacter than were those who were actors in the food chain. Consumer knowledge of Toxoplasma was better than that of Campylobacter. Consumers have the most knowledge about Salmonella. CONCLUSIONS: Consumers in Germany are predominantly poorly informed about Campylobacter and the transmission route via meat. General knowledge of Toxoplasma is better than that of Campylobacter. Among the three pathogens, consumers are best informed about Salmonella. This finding highlights the importance of making existing information materials more accessible to consumers in the future to increase their knowledge, with the objective of reducing the incidence of Campylobacter infections.

A role for G protein-coupled receptor 137b in bone remodeling in mouse and zebrafish.

G protein-coupled receptor 137b (GPR137b) is an orphan seven-pass transmembrane receptor of unknown function. In mouse, Gpr137b is highly expressed in osteoclasts in vivo and is upregulated during in vitro differentiation. To elucidate the role that GPR137b plays in osteoclasts, we tested the effect of GPR137b deficiency on osteoclast maturation and resorbing activity. We used CRISPR/Cas9 gene editing in mouse-derived ER-Hoxb8 immortalized myeloid progenitors to generate GPR137b-deficient osteoclast precursors. Decreasing Gpr137b in these precursors led to increased osteoclast differentiation and bone resorption activity. To explore the role of GPR137b during skeletal development, we generated zebrafish deficient for the ortholog gpr137ba. Gpr137ba-deficient zebrafish are viable and fertile and do not display overt morphological defects as adults. However, analysis of osteoclast function in gpr137ba-/- mutants demonstrated increased bone resorption. Micro-computed tomography evaluation of vertebral bone mass and morphology demonstrated that gpr137ba-deficiency altered the angle of the neural arch, a skeletal site with high osteoclast activity. Vital staining of gpr137ba-/- fish with calcein and alizarin red indicated that bone formation in the mutants is also increased, suggesting high bone turnover. These results identify GPR137b as a conserved negative regulator of osteoclast activity essential for normal resorption and patterning of the skeleton. Further, these data suggest that coordination of osteoclast and osteoblast activity is a conserved process among vertebrates and may have similar regulation.

miR-139-5p controls translation in myeloid leukemia through EIF4G2.

MicroRNAs (miRNAs) are crucial components of homeostatic and developmental gene regulation. In turn, dysregulation of miRNA expression is a common feature of different types of cancer, which can be harnessed therapeutically. Here we identify miR-139-5p suppression across several cytogenetically defined acute myeloid leukemia (AML) subgroups. The promoter of mir-139 was transcriptionally silenced and could be reactivated by histone deacetylase inhibitors in a dose-dependent manner. Restoration of mir-139 expression in cell lines representing the major AML subgroups (t[8;21], inv[16], mixed lineage leukemia-rearranged and complex karyotype AML) caused cell cycle arrest and apoptosis in vitro and in xenograft mouse models in vivo. During normal hematopoiesis, mir-139 is exclusively expressed in terminally differentiated neutrophils and macrophages. Ectopic expression of mir-139 repressed proliferation of normal CD34(+)-hematopoietic stem and progenitor cells and perturbed myelomonocytic in vitro differentiation. Mechanistically, mir-139 exerts its effects by repressing the translation initiation factor EIF4G2, thereby reducing overall protein synthesis while specifically inducing the translation of cell cycle inhibitor p27(Kip1). Knockdown of EIF4G2 recapitulated the effects of mir-139, whereas restoring EIF4G2 expression rescued the mir-139 phenotype. Moreover, elevated miR-139-5p expression is associated with a favorable outcome in a cohort of 165 pediatric patients with AML. Thus, mir-139 acts as a global tumor suppressor-miR in AML by controlling protein translation. As AML cells are dependent on high protein synthesis rates controlling the expression of mir-139 constitutes a novel path for the treatment of AML.

Intracranial EEG correlates of implicit relational inference within the hippocampus.

Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g., "winter-red," "red-cat") such that an indirect relation was established in following word pairs (e.g., "winter-cat"). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster "fit" judgments while the absence of indirect relations fostered "do not fit" judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post-stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1,500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future decision making.

Gender-related effects on substrate utilization and metabolic adaptation in hairless spontaneously hypertensive rat.

Cold exposure of rats leads to ameliorated glucose and triglyceride utilization with females displaying better adaptation to a cold environment. In the current study, we used hairless rats as a model of increased thermogenesis and analyzed gender-related effects on parameters of lipid and glucose metabolism in the spontaneously hypertensive (SHR) rats. Specifically, we compared hairless coisogenic SHR-Dsg4 males and females harboring mutant Dsg4 (desmoglein 4) gene versus their SHR wild type controls. Two way ANOVA showed significant Dsg4 genotype (hairless or wild type) x gender interaction effects on palmitate oxidation in brown adipose tissue (BAT), glucose incorporation into BAT determined by microPET, and glucose oxidation in skeletal muscles. In addition, we observed significant interaction effects on sensitivity of muscle tissue to insulin action when Dsg4 genotype affected these metabolic traits in males, but had little or no effects in females. Both wild type and hairless females and hairless males showed increased glucose incorporation and palmitate oxidation in BAT and higher tissue insulin sensitivity when compared to wild type males. These findings provide evidence for gender-related differences in metabolic adaptation required for increased thermogenesis. They are consistent with the hypothesis that increased glucose and palmitate utilization in BAT and muscle is associated with higher sensitivity of adipose and muscle tissues to insulin action.

Fish is Fish: the use of experimental model species to reveal causes of skeletal diversity in evolution and disease.

Fishes are wonderfully diverse. This variety is a result of the ability of ray-finned fishes to adapt to a wide range of environments, and has made them more specious than the rest of vertebrates combined. With such diversity it is easy to dismiss comparisons between distantly related fishes in efforts to understand the biology of a particular fish species. However, shared ancestry and the conservation of developmental mechanisms, morphological features and physiology provide the ability to use comparative analyses between different organisms to understand mechanisms of development and physiology. The use of species that are amenable to experimental investigation provides tools to approach questions that would not be feasible in other 'non-model' organisms. For example, the use of small teleost fishes such as zebrafish and medaka has been powerful for analysis of gene function and mechanisms of disease in humans, including skeletal diseases. However, use of these fish to aid in understanding variation and disease in other fishes has been largely unexplored. This is especially evident in aquaculture research. Here we highlight the utility of these small laboratory fishes to study genetic and developmental factors that underlie skeletal malformations that occur under farming conditions. We highlight several areas in which model species can serve as a resource for identifying the causes of variation in economically important fish species as well as to assess strategies to alleviate the expression of the variant phenotypes in farmed fish. We focus on genetic causes of skeletal deformities in the zebrafish and medaka that closely resemble phenotypes observed both in farmed as well as natural populations of fishes.

miR-9 is a tumor suppressor in pediatric AML with t(8;21).

MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of acute myeloid leukemia (AML) with t(8;21), inv(16) or mixed lineage leukemia (MLL) rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor-suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor-suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner.

A genome-wide survey of human short-term memory.

Recent advances in the development of high-throughput genotyping platforms allow for the unbiased identification of genes and genomic sequences related to heritable traits. In this study, we analyzed human short-term memory, which refers to the ability to remember information over a brief period of time and which has been found disturbed in many neuropsychiatric conditions, including schizophrenia and depression. We performed a genome-wide survey at 909 622 polymorphic loci and report six genetic variations significantly associated with human short-term memory performance after genome-wide correction for multiple comparisons. A polymorphism within SCN1A (encoding the α subunit of the type I voltage-gated sodium channel) was replicated in three independent populations of 1699 individuals. Functional magnetic resonance imaging during an n-back working memory task detected SCN1A allele-dependent activation differences in brain regions typically involved in working memory processes. These results suggest an important role for SCN1A in human short-term memory.

Standard test of labelling for efficiency for quality control of no carrier added 90YCL3 / Prueba estándar de la eficiencia del marcaje para el control de la calidad del 90YCI3 sin portador añadido

ABSTRACT Particle emitting radionuclides (e.g. b--emitters 90Y and 177Lu, b-emitter 149Tb, Auger electron emitter 165Er or positron emitter 86Y) are more and more frequently used in research and clinical practice for imaging and radionuclide targeted therapy in nuclear medicine. These radiometals, altogether threevalent lanthanides or actinides with high specific radioactivity, coupled to biomolecule carriers (peptides or monoclonal antibodies) through chelating link (e.g. DTPA or DOTA) bind to specific antigens and/or receptors of diseased tissues, which enables the imaging (positron emitters) or destruction (b--, a-, and Auger electron emitter) of the diseased tissue releasing the antigens or carrying the receptors. The radionuclide precursor 90YCl3 (solution of hard b--emitter 90Y in diluted HCl) with high purity and specific activity is already commercially produced and succesfully used in nuclear medicine, e.g. for radioimmunotherapy (RIT) of Lymphoma. Specification and purity of our product obtained using extraction 90Sr/90Y generator (using technology of centrifuge extractors with di-2-ethylhexylphosphoric acid, D2EHPA) is examined and compared to other similar products in this contribution. A standard method for determination of labelling efficiency of the 90YCl3 precursor based on its reaction with DOTA-Tyr3-Octreotide (DOTA-TOC) and ITLC-SG chromatographic separation is described and proposed for the quality control.

Los radionucleidos emisores de partículas (ej. emisores b 90Y y 177Lu, emisores a 149Tb, emisor de electrones Auger 165Er o emisor de positrones 86Y) se emplean cada vez más en la investigación, en la práctica clínica para el procesamiento de imágenes y en la terapia dirigida de radionuclidos en medicina nuclear. Estos radiometales junto con actínidos o lantánidos trivalentes con alta actividad específica, asociados a portadores de biomoléculas (péptidos o anticuerpos monoclonales) por medio de un enlace con quelatos (ej. DTPA o DOTA) se unen a antígenos específicos receptores de tejidos afectados que permiten el procesamiento de imágenes (emisores de positrones) o la destrucción (b--, a-, y emisores de electrones de Auger) de los tejidos afectados que liberan los antígenos o portan los receptores. El precursor del radionucleido 90YCI3 (solución de emisor b- duro - 90Y en HCI diluido) con elevada pureza y actividad específica ya se produce comercialmente y se usa exitosamente en la medicina nuclear, por ejemplo, para la radioinmunoterapia (RIT) del linfoma. En esta contribución se examina la especificación y la pureza de nuestro producto, obtenido mediante extracción con generador 90Sr/90Y (empleando la tecnología de extractores por centrifugado con ácido di-2-ethylhexyl phosphoric D2EHPA) y se compara con otros productos similares. Se describe y propone para el control de la calidad un método estándar para determinar la eficiencia en el marcaje del precursor del 90YCI3 basado en su reacción con DOTA-Tyr3-ostreotido (DOTA-TOC) y separación cromatográfica ITLC-SG.

[What are the economic advantages of Integrated Health Care?]. / Wo liegen die Chancen der Integrierten Versorgung aus ökonomischer Sicht?

Integrated Health Care and Managed Health Care are both tools to implement broader responsibilities of health care providers for the economic efforts of their activities. While Managed Care is quite common in the United States of America, experiences with such systems are sparse in Europe and Germany. With Integrated Health Care, new types of markets will emerge: not only a market for health care services, but also for insurance contracts, and for provision of care. The paper discusses different incentives arising from different health care systems.

[Cost of illness studies as a basis for decision making]. / Die Krankheitskostenrechnung als Entscheidungshilfe.

Definitions and methods for cost of illness studies are explained: costs, direct costs, indirect costs, intangible costs, the human capital method and the willingness to pay approach. Devaluing the long-term health benefits from prevention by constant discount rates is questioned. The development and the state of the art of cost of illness studies at a national level in Germany are discussed. As an example the newly developed cost of illness study of the Federal Statistical Office with direct and indirect costs of circulatory diseases is presented. Reasons for the benefit of cost of illness studies for decision making are given in the context of costs of illness and aging.

Inhibition of neutrophil elastase and thrombin activity by caffeic acid esters.

Natural and synthetic caffeic acid esters were assayed for their enzymatic activity versus neutrophil elastase (EC 3.4.21.37) and thrombin (EC 3.4.21.5). Lipophilic caffeic acid esters inhibited neutrophil elastase activity and the inhibition rate was enhanced with increasing length of the aliphatic chain of the alcohol component. The geometry of the chain seems to be more important than the number of carbon atoms. The most inhibitory compound was n-octylcaffeic acid ester with an IC50 value of 1.0 microM. Thrombin activity was only weakly inhibited by the caffeic acid esters thus demonstrating a specificity for neutrophil elastase. Because of its critical role in inflammatory processes, inhibition of neutrophil elastase by caffeic acid esters might be of importance in the treatment of inflammation.

Aqueous leaching properties and environmental implications of cadmium, lead and zinc trimercaptotriazine (TMT) compounds.

2,4,6-Trimercaptotriazine, trisodium salt nonahydrate (TMT-55) is a commercial product that is widely used to chemically precipitate cadmium, lead, zinc and other heavy metals from wastewaters and contaminated natural waters. When mixed with aqueous solutions of TMT-55, aqueous solutions of either reagent-grade zinc, cadmium, or lead salts precipitate crystalline "Zn-TMT", amorphous or crystalline "Cd-TMT" or amorphous "Pb-TMT" (M3[S3C3N3]2.nH2O, where M=Cd2+, Pb2+, and Zn2+ and n> or = 0) that may eventually crystallize if stored in air. Laboratory aqueous leaching studies over 78-106 days using pH 3 HCl, distilled water (pH 6) and pH 9-10 NaOH evaluated the stability of the Cd-, Pb-, and Zn-TMT precipitates. Under pH 3 conditions, the amorphous Cd- and Pb-TMT compounds converted to their crystalline forms and amorphous Cd-TMT also crystallized in distilled water. Otherwise, no decomposition products were detected in the leached solid residues. When compared with the aqueous solubilities of corresponding sulfides and most hydroxides, the TMT compounds were significantly more soluble in distilled water and pH 3 HCl.

Chemistry of 2,4,6-trimercapto-1,3,5-triazine (TMT): acid dissociation constants and group 2 complexes.

The acid dissociation constants of 2,4,6-trimercaptotriazine (H(3)TMT, 1) were determined and now can be employed in the preparation of complexes having specific M-TMT (M = divalent metal; TMT = 2,4,6-trimercapto-1,3,5-triazinide, C(3)N(3)S(3)(3-)) ratios. For example, the combination of H(3)TMT (1) with Mg(OH)(2) at pH 7.1 leads to the crystallization of Mg(H(2)TMT)(2).6H(2)O (4). With the appropriate pH adjustment, the contiguous series of compounds Ba(3)(TMT)(2).8H(2)O (3), Ba(H(2)TMT)(2).7H(2)O (5), and BaHTMT.3H(2)O (6) can be isolated. The compounds were characterized by mp, IR, TGA, elemental analysis, and, in the cases of 4, 5, and 6, crystallography. The comparison of 4 with 5 and 6 offers an interesting view of the difference in hard and soft bonding with TMT. In the saltlike Mg structure of 4, there is extensive hydrogen bonding, but in the Ba structures, 5 and 6, covalent Ba-S bonding dominates.

Effect of nasal continuous positive airway pressure on neuropsychological function in sleep apnea-hypopnea syndrome. A randomized, placebo-controlled trial.

A placebo-controlled, partial cross-over, double-blind, randomized study was performed with 46 adults with sleep apnea-hypopnea syndrome (SAHS) to determine the effect of therapeutic and subtherapeutic (0-1 cm H(2)O) nasal continuous positive airway pressure (CPAP) treatment on polysomnographic and neuropsychological testing. The following neuropsychological tests were administered: Geriatric Depression Scale, Trail Making A and B, Digit Span Test Forward and Backward, Epworth Sleepiness Scale, SteerClear, Digit Symbol, Controlled Oral Word Association, and Complex Figure Recall. Compared with results without CPAP, subtherapeutic CPAP did not affect any measured polysomnographic parameter. Comparison of neuropsychological test results obtained between the initial periods of effective treatment (Group 1, 16.1 d; Group 2, 19.6 d; p = NS) in all subjects showed significant improvements in Digit Symbol, Digit Span Backward, and Complex Figure tests. However, there were no group differences in changes in test results during the period when one group was on effective CPAP and the other on ineffective CPAP (Group 1, 16.1 d; Group 2, 13.9 d; p = NS). The results indicate the feasibility and importance of using ineffective CPAP as a placebo treatment and the importance of including a placebo control in studies evaluating the effect of treatment on neuropsychological function in SAHS.

A pyridine-thiol ligand with multiple bonding sites for heavy metal precipitation.

There are immediate concerns with current commercial ligands that are used for heavy metal precipitation, especially the limited arrays of bonding sites. Previous research has indicated that not only do commercial reagents lack sufficient bonding criteria, but they also fail to provide long-term stability as ligand-metal complexes. For this reason, we have developed a pyridine-based thiol ligand (DTPY) which not only offers multiple bonding sites for heavy metals but also should form stable metal-ligand precipitates. In this study, we used the divalent metals cadmium and copper to model the reactivity and pH stability of divalent metal complexes with the DTPY ligand. Using inductively-coupled plasma spectrometry (ICP), results indicate that a 50.00ppm (parts per million) copper solution, pH of 4.5, can be reduced to below the ICP detection limits of 0.00093ppm (>99.99% removal), and a 50.00ppm cadmium solution, pH of 6.0, can be reduced to 0.06ppm (99.88%).

An oral elastic mandibular advancement device for obstructive sleep apnea.

Oral mandibular advancement devices are becoming an increasingly important treatment alternative for obstructive sleep apnea (OSA). The first aim of the study was to determine whether a new oral elastic mandibular advancement device (EMA) prevents pharyngeal airway closure during sleep in patients with OSA. The second aim of the study was to determine if the polysomnographic response to the oral mandibular advancement device was dependent on the site of airway closure. Overnight polysomnograms were performed in 28 untreated OSA subjects with and without EMA. A third polysomnogram was performed in 12 of the subjects to determine the site of airway closure without the device. Site of airway closure above or below the oropharynx was determined by measuring the respective presence or absence of respiratory fluctuations in oropharyngeal pressure during induced occlusions in non-rapid eye movement (NREM) sleep. Mean apnea-hypopnea index (AHI) was 52.6 +/- 28.2 (SD) events/h without the device and 21.2 +/- 19.3 events/h with the device. Nineteen subjects (68%) had at least a 50% reduction in AHI with the device. The change in AHI with the device (AHI without device - AHI with device) was directly related to the AHI without the device. All three subjects with airway closure in the lower pharyngeal airway had a greater than 80% reduction in AHI with the device. Two of the nine subjects with airway closure in the velopharynx had a similar therapeutic response. The results show the effectiveness of EMA in the treatment of OSA. The results also indicate that polysomnographic severity of OSA and the site of airway closure should not be used to exclude patients from this oral device treatment.

[Control of health care by the economist?]. / Steuerung des Gesundheitswesens durch den Okonomen?

Although the health care system has to deal with huge financial problems one cannot neglect that this labour-intensive service branch creates the most jobs with social security obligations. Corrective strategies will have to increase the orientation of health care to patients' needs which requires better information and more decision-making autonomy for the insured people as well as a maximising of efficiency. Competition needs to be strengthened in order to improve quality and reduce costs. This requires more contractual freedom for insurance funds and a dismantling of the current monopolistic structures. Finally, adequate remuneration schedules and patients' individual responsibility play a major role to meet the future challenges in the European internal market.

Memory lost and regained following bilateral hippocampal damage.

We present a longitudinal neuropsychological study (31 examinations over a period of 18 months) of patient DE DF demonstrated bilateral atrophy of the hippocampal formation and globus pallidus resulting from carbon monoxide poisoning. Eighteen months after the event, the volume of the hippocampal formation was reduced by 42% on the left side and 28% on the right. The patient initially presented with a severe global amnesia. Then, he showed a gradual, yet selective recovery of episodic memory function. Verbal free recall and spatial memory performance remained reduced, whereas immediate word recall and recognition memory, as well as picture learning and memory, improved to levels at the lower range of normal performance. Interestingly, nonspatial associative learning was never much impaired and recovered completely by the end of testing. These data are taken as evidence that the human hippocampal formation does not equally support different forms of episodic memory.