Displaced center of pressure on the treated side in individuals with essential tremor after radiofrequency ablation: a longitudinal case-control study.

Background: Essential tremor (ET) is a common involuntary movement disorder (IMD). Radiofrequency ablation (RFA) targeting the ventral intermediate nucleus (Vim) of the thalamus is a stereotactic neurosurgery performed in individuals with ET when pharmacotherapy is no longer effective. Though the reasons remain largely unclear, certain adverse events are known to appear post-RFA. These may be due to functional changes in the Vim, related to RFA-induced tremor reduction, or an adverse reaction to compensatory movement patterns used to perform movements in the presence of tremor symptoms. Objective: This study aimed to understand the characteristics of post-RFA symptoms in individuals with ET. Methods: In a longitudinal case-control study, we compared post-RFA symptoms between individuals with ET who underwent Vim-targeted RFA and those with IMD who underwent non-Vim-targeted RFA. Symptoms were compared preoperatively and 1-week and 1-month postoperatively. Quantitative assessments included center-of-pressure (COP) parameters, grip strength, Mini-Mental State Examination, two verbal fluency tests, and three types of physical performance assessments (upper extremity ability, balance ability, and gait ability). Results: Individuals with ET after RFA showed horizontal displacements of the COP to the treated side (the dominant side of the RFA target's hemisphere) at 1-week postoperatively compared to the preoperative period. The horizontal COP displacement was associated with balance dysfunction related to postural stability post-RFA. Other COP parameters did not significantly differ between the ET and IMD groups. Conclusion: COP displacement to the treated side may be due to a time lag in adjusting postural holding strategies to the long-standing lateral difference in tremor symptoms associated with tremor improvement after RFA.

Differences in psychosocial factors and sleep study findings between delayed sleep-wake phase disorder and hypersomnia in teenagers.

Central hypersomnia (HS) and delayed sleep-wake phase disorder (DSWPD) appear commonly in adolescents, and they severely reduce quality of life and have an enormous impact on academic performance and other aspects of development. Although these disorders are thought to be considerably different in etiology, it is sometimes difficult to distinguish them because of their similar clinical features. This study aimed to compare psychosocial factors and sleep study findings between HS and DSWPD in teenagers. The clinical data of 89 teenagers who visited the psychiatric section of the Sleep Medicine Center of Nihon University Itabashi Hospital from January 2013 to December 2019 were analyzed. Psychosocial factors were evaluated at the first visit, and polysomnography (PSG) and the multiple sleep latency test (MSLT) were performed for patients deemed to require definitive diagnosis. Compared with patients with HS, those with DSWPD had a higher rate of mother's employment, introversion, adjustment problems, events that triggered the disorder, concurrent mental disorders, habitual lateness, and difficulty attending school or work. PSG did not show any differences in sleep parameters between the two disorders, except for sleep latency. On the MSLT, sleep latency was shorter in those with HS on the second, third, and fourth tests. The present results suggest that focusing on psychosocial factors could be useful for differential diagnosis of the two disorders that appear commonly in adolescents.

Characteristics of detected and undetected dementia among community-dwelling older people in Metropolitan Tokyo.

AIM: Although a series of policies have been adapted to deliver an early diagnosis of dementia, many people living with dementia remain undetected and undiagnosed. The aim of this study is to investigate the characteristics of undetected dementia in community-dwelling older people in Metropolitan Tokyo. METHODS: We conducted a three-step survey. First, the questionnaires were mailed, in total, to 7614 residents aged ≥70 years in one area in Tokyo, and 5430 were retrieved. Secondly, 2020 individuals attended the face-to-face survey, including Mini-Mental State Exam (MMSE). Thirdly, 198 of 335 individuals who scored <24 on MMSE were visited. Diagnosis of dementia, Clinical Dementia Rating and need for social support were assessed by the interdisciplinary team at their home, and psychological variables, sociological variables and sociodemographic variables were evaluated. RESULTS: Among the 198 participants, 78 (39.4%) were assessed to have dementia. Among those who had dementia, 34 had received a previous diagnosis of dementia in a clinical setting, i.e., the rate of undetected dementia among our 198 participants was 56.4%. People living with dementia without a dementia diagnosis tended to have more complex social support needs, particularly in the domains of dementia diagnosis, medical check-ups for physical conditions, continuous medical care and housing support. In addition, they exhibited signs of frailty. CONCLUSIONS: Given that people living with dementia without a dementia diagnosis are at risk of losing housing or physical health, it is a threat to human rights. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.

Psychological and psychiatric symptoms of terminally ill patients with cancer and their family caregivers in the home-care setting: A nation-wide survey from the perspective of bereaved family members in Japan.

OBJECTIVE: The psychological and psychiatric symptoms of terminally ill cancer patients are highly problematic and have been associated with greater burden among caregivers. Until now, the extent of these problems in the home care setting was unclear. METHODS: This retrospective study was conducted as part of a nationwide survey from the perspective of bereaved family members in Japan (J-HOPE3). The bereaved family members rated the symptoms of delirium and suicidal ideation of patients with cancer, and the sleeplessness and depressed mood of family caregivers utilizing home care services in the one month before the patients' deaths. Regression analyses were performed to identify factors associated with caregivers' sleeplessness or depressed mood. RESULTS: Of the 532 subjects analyzed, between 17% and 65% of patients experienced various symptoms of delirium, and 27% suicidal ideation. Among family caregivers, 60% experienced sleeplessness and 35% experienced depressed mood at least once during the week. Caregivers' psychological symptoms were associated with their own poor health status, being the spouse of the patient, and the patients' psychological or psychiatric symptoms. To manage patients' symptoms, 11% of caregivers had consulted psychiatrists or psychologists while another 11% wanted to do so. CONCLUSION: Psychological problems assessed were common among patients with cancer and their family caregivers in the one month of home care prior to the patient's death. An effective complementary care system, run by home-visit physicians, nurses, and experts in mental disorders, is needed.

[Dementia in Patients with Central Nervous System Mycosis].

Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.

[Circadian rhythm and mood disorder].

Mood disorders show a common feature of distorted cycling of biological systems, manifesting, for example, as diurnal mood variation in depression, phasic time course in bipolar disorder, and seasonal mood swing in seasonal affective disorder. Accordingly, circadian dysfunction has been supposed to play an etiological role in mood disorders. Increasing evidence indicates that circadian misalignment between neuroendocrinological rhythm and the timing of sleep correlates with the severity of symptoms. In addition, several genetic studies have suggested that certain clock gene variants play a role in vulnerability to these disorders, and especially bipolar disorders. However, the role of circadian phenotypes and circadian genes in mood spectrum disorders remains unclear, although currently seem to have a pathoplastic rather than a pathogenetic effect.

[Subjective daytime sleepiness in community-dwelling elderly in Japan].

OBJECTIVES: The objective of this study was to assess the prevalence of subjective daytime sleepiness among the community-dwelling elderly population in Japan using the Japanese version of the Epworth Sleepiness Scale (JESS) and to investigate the correlates of excessive daytime sleepiness (EDS). METHODS: Subjects aged 65 years or older, born between April and September, living independently, who resided in 1 district of Tokyo, Japan, were recruited. A total of 3195 subjects meeting the inclusion criteria were mailed a questionnaire that inquired about the JESS, socio-demographic factors, and health-related factors. Of the 2034 elderly individuals who responded to the survey (response rate, 63.7%), 1494 subjects (652 men, 842 women) who completely answered the questionnaire were included in the study (valid response rate, 46.8%). RESULTS: The mean (+/- standard deviation) JESS score was 5.0 +/- 3.8 (men 5.6 +/- 4.1, women 4.4 +/- 3.4, P <0.01). The prevalence of EDS (a cut-off score>10) was 8.8% (men 12.7%, women 5.7%, P< 0.01). The male gender, being employed, having poor mental health and well-being, having lowered activity of daily living (ADL), or having subjective memory impairment were significantly associated with EDS. In the gender-specific models, low social network and subjective memory impairment in men, whereas obesity and lowered ADL in women, were significantly associated with EDS. CONCLUSION: EDS was more frequently observed in men than in women among the community-dwelling elderly population in Japan. A substantial gender difference was found in correlates of EDS. This finding is useful in the clinical management of patients who complain of daytime sleepiness; moreover, it is useful for the management of public health.

[Present status and future of hypnotic drug treatment for insomnia].

Pharmacological treatments of insomnia have become safer since the first benzodiazepine receptor agonist (BzRA) hypnotic was introduced in the 1960's. Though BzRAs could hardly cause a fatal condition even in cases of overdosing, they had inherited the arguments on addiction and withdrawal from the prior studies of barbiturate hypnotics that indicated they are strongly addictive. In the 2000s, it was repeatedly demonstrated that insomnia as well as sleep deprivation underlie the development and deterioration of comorbid diseases such as hypertension, cardiovascular diseases, diabetes and depression, and that the proper use of hypnotic drugs is unlikely to cause tolerance, addiction nor rebound phenomena, but likely to be associated with improvement of QOL. Thus, the 2005's consensus report on chronic insomnia by NIH has recommended general physicians to facilitate insomnia treatment to prevent the development of physical and/or mental disorders. The author reviewed in this article the efficacy and side effects of BzRA hypnotics, a hypnotic drug therapy combined with cognitive and behavioral interventions, uses of melatonin receptor agonist in general and sleep medicine practices, and future utilization of newly-developed orexin antagonists for insomnia treatment.

The association between sleep problems and perceived health status: a Japanese nationwide general population survey.

OBJECTIVE: Sleep problems in humans have been reported to impact seriously on daily function and to have a close association with well-being. To examine the effects of individual sleep problems on physical and mental health, we conducted a nationwide epidemiological survey and examined the associations between sleep problems and perceived health status. METHODS: Cross-sectional surveys with a face-to-face interview were conducted in August and September, 2009, as part of the Nihon University Sleep and Mental Health Epidemiology Project (NUSMEP). Data from 2559 people aged 20 years or older were analyzed (response rate 54.0%). Participants completed a questionnaire on perceived physical and mental health statuses, and sleep problems including the presence or absence of insomnia symptoms (i.e., difficulty initiating sleep [DIS], difficulty maintaining sleep [DMS], and early morning awakening [EMA]), excessive daytime sleepiness (EDS), poor sleep quality (PSQ), short sleep duration (SSD), and long sleep duration (LSD). RESULTS: The prevalence of DIS, DMS, and EMA was 14.9%, 26.6%, and 11.7%, respectively, and 32.7% of the sample reported at least one of them. At the complaint level, the prevalence of EDS, PSQ, SSD, and LSD was 1.4%, 21.7%, 4.0%, and 3.2%, respectively. Multiple logistic regression analyses revealed that DMS, PSQ, SSD, and LSD were independently associated with poor perceived physical health status; DIS, EDS, and PSQ were independently associated with poor perceived mental health status. CONCLUSIONS: This study has demonstrated that sleep problems have individual significance with regard to perceived physical or mental health status.

Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex.

Insomnia is a common problem for people with chronic pain. Cortical GABAergic neurons are part of the neurobiological substrate that underlies homeostatic sleep regulation. In the present study, we confirmed that sciatic nerve ligation caused thermal hyperalgesia and tactile allodynia in mice. In this experimental model for neuropathic pain, we found an increase in wakefulness and a decrease in non-rapid eye movement sleep under a neuropathic pain-like state. Under these conditions, membrane-bound GABA (γ-aminobutyric acid) transporters (GATs) on activated glial fibrillary acidic protein-positive astrocytes were significantly increased in the cingulate cortex, and extracellular GABA levels in this area after depolarization were rapidly decreased by nerve injury. Furthermore, sleep disturbance induced by sciatic nerve ligation was improved by the intracingulate cortex injection of a GAT-3 inhibitor. These findings provide novel evidence that sciatic nerve ligation decreases extracellular-released GABA in the cingulate cortex of mice. These phenomena may, at least in part, explain the insomnia in patients with neuropathic pain. Neuropathic pain-like stimuli suppress the GABAergic transmission with increased GABA (γ-aminobutyric acid) transporters located on activated astrocytes in the cingulate cortex related to sleep disturbance.

[Management of insomnia and hypersomnia associated with psychiatric disorders].

Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic disorders are associated with sleep disorders of various kinds, among which insomnia is most prevalent and important in psychiatric practice. Almost all patients suffering from major depression complain of insomnia. Pharmacological treatment of insomnia associated with major depression shortens the duration to achieve remission of depression. Insomnia has been recently reported to be a risk factor for depression. Hypersomnia is also a major sleep problem in patient suffering from depression. There have been no clinical guide to treat the symptoms of hypersomnia in depression, but some clinical trials treating them with NDRI or adjunctive administration of psychostimulants. In patients with schizophrenia, insomnia is often an early indicator of the aggravation of psychotic symptoms. Electroencephalographic sleep studies have also revealed sleep abnormalities characteristic to mood disorders, schizophrenia and anxiety disorders. A shortened REM sleep latency has been regarded as a biological marker of depression. Reduced amount of deep Non-REM sleep has been reported to be correlated with negative symptoms of schizophrenia. Recently, REM sleep abnormalities were found in teenagers having post-traumatic stress disorder after a boat accident. Although these facts indicate that insomnia plays an important role in the development of psychiatric disorders, there are few hypotheses explaining the cause and effect of insomnia in these disorders. Here, we reviewed recent articles on insomnia and hypersomnia associated with psychiatric disorders together with their clinical managements.

Modeling of tRNA-assisted mechanism of Arg activation based on a structure of Arg-tRNA synthetase, tRNA, and an ATP analog (ANP).

The ATP-pyrophosphate exchange reaction catalyzed by Arg-tRNA, Gln-tRNA and Glu-tRNA synthetases requires the assistance of the cognate tRNA. tRNA also assists Arg-tRNA synthetase in catalyzing the pyrophosphorolysis of synthetic Arg-AMP at low pH. The mechanism by which the 3'-end A76, and in particular its hydroxyl group, of the cognate tRNA is involved with the exchange reaction catalyzed by those enzymes has yet to be established. We determined a crystal structure of a complex of Arg-tRNA synthetase from Pyrococcus horikoshii, tRNA(Arg)(CCU) and an ATP analog with Rfactor = 0.213 (Rfree = 0.253) at 2.0 A resolution. On the basis of newly obtained structural information about the position of ATP bound on the enzyme, we constructed a structural model for a mechanism in which the formation of a hydrogen bond between the 2'-OH group of A76 of tRNA and the carboxyl group of Arg induces both formation of Arg-AMP (Arg + ATP --> Arg-AMP + pyrophosphate) and pyrophosphorolysis of Arg-AMP (Arg-AMP + pyrophosphate --> Arg + ATP) at low pH. Furthermore, we obtained a structural model of the molecular mechanism for the Arg-tRNA synthetase-catalyzed deacylation of Arg-tRNA (Arg-tRNA + AMP --> Arg-AMP + tRNA at high pH), in which the deacylation of aminoacyl-tRNA bound on Arg-tRNA synthetase and Glu-tRNA synthetase is catalyzed by a quite similar mechanism, whereby the proton-donating group (-NH-C+(NH2)2 or -COOH) of Arg and Glu assists the aminoacyl transfer from the 2'-OH group of tRNA to the phosphate group of AMP at high pH.

A prediction system of oxidation reaction as a solid-state stress condition: applied to a pyrrole-containing pharmaceutical compound.

Stress conditions for predicting oxidative degradation products in solid-state pharmaceutical compounds were investigated. 4-Methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl)pyrrole, Compound A, was used as the model compound for this study and its four main degradation products were due to oxidation, as identified by LC-MS and LC-(1)H NMR. In order to develop a prediction system for the oxidation reaction, solid-state Compound A was stored under moisture-saturated conditions. Hydrogen peroxide was added to the solution used to saturate the headspace with moisture and oxygen was substituted for the headspace air, in order to stimulate the oxidation reaction. After optimizing the conditions, a similar degradation product profile to that actually observed in the stability studies was obtained in only 3 days under conditions using 3% hydrogen peroxide at 40 degrees C. The prediction of the oxidative degradation products in a solid-state pharmaceutical compound was successfully achieved in a short term utilizing this newly developed prediction system.

[Update on the treatment of restless legs syndrome].

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the legs, accompanied by uncomfortable and unpleasant sensations that diminish with motor activity and worsen at rest. The symptoms of this syndrome worsen in the evening and at night, leading to difficulty in sleeping. Treatment of RLS includes non-pharmacological intervention and drug therapy. In this article, we examine recent developments in the understanding of the pathophysiology of RLS and review previous articles on the treatment of RLS. Although there have been no reports on formal studies on the nonpharmacologic strategies for RLS symptoms, recommened good sleep hygiene is considered essential to improve the comorbid insomnia. Massaging the affected legs, taking hot baths, and performing mentally demanding tasks have been reported to reduce RLS symptoms. Four categories of medications, namely, dopaminergic agents, opioids, anticonvulsants, and benzodiazepines were identified as frequently prescribed drugs for RLS. Dopaminergic agonists are now considered the first-line treatment of RLS because they are more effective and produce augmentation less frequently as compared to L-dopa. Opioids are prescribed to patients with severe conditions, especially those unresponsive to other treatments. Currently, carbamazepine is not recommended for the treatment of RLS. More recently, studies on the use of anticonvulsants for the treatment of RLS have focused on gabapentin. Benzodiazepines, including clonazepam and nitrazepam, are widely prescribed, but their therapeutic effects on RLS symptoms were rather modest. Therefore, benzodiazepines are mostly used to improve the sleep quality in patients with RLS.

Coping strategies and their correlates with depression in the Japanese general population.

This study's aim was to examine the relation between depression and stress-coping strategy among the general population. The survey was conducted in June 2000, using a large sample representative of the Japanese general population. A total of 24,551 responses from individuals aged 20 years or older were analyzed. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence of depression with two different cut-off points; 16 and 26. Stress-coping strategies were asked based on given examples of actual behaviors covering problem-focused, emotion-focused, and avoidant ones. There was no marked gender difference in the prevalence of a problem-solving strategy, while various types of gender differences were found with respect to the prevalence of emotion-focused and avoidant strategies. In relation to depression, multivariate logistic regression analyses revealed the significantly highest odds ratios (OR) for avoidant coping strategies and the lowest OR for problem-focused ones in both genders. The fact that depression was associated positively with avoidant strategies but negatively with problem-solving strategies indicates that individual stress-coping strategies have their own significance with respect to depression, and may be utilized in establishing an evidence-based cognitive behavioral approach to depressive patients.

Escherichia coli cyclophilin B binds a highly distorted form of trans-prolyl peptide isomer.

Cyclophilins facilitate the peptidyl-prolyl isomerization of a trans-isomer to a cis-isomer in the refolding process of unfolded proteins to recover the natural folding state with cis-proline conformation. To date, only short peptides with a cis-form proline have been observed in complexes of human and Escherichia coli proteins of cyclophilin A, which is present in cytoplasm. The crystal structures analyzed in this study show two complexes in which peptides having a trans-form proline, i.e. succinyl-Ala-trans-Pro-Ala-p-nitroanilide and acetyl-Ala-Ala-trans-Pro-Ala-amidomethylcoumarin, are bound on a K163T mutant of Escherichia coli cyclophilin B, the preprotein of which has a signal sequence. Comparison with cis-form peptides bound to cyclophilin A reveals that in any case the proline ring is inserted into the hydrophobic pocket and a hydrogen bond between CO of Pro and Neta2 of Arg is formed to fix the peptide. On the other hand, in the cis-isomer, the formation of two hydrogen bonds of NH and CO of Ala preceding Pro with the protein fixes the peptide, whereas in the trans-isomer formation of a hydrogen bond between CO preceding Ala-Pro and His47 Nepsilon2 via a mediating water molecule allows the large distortion in the orientation of Ala of Ala-Pro. Although loss of double bond character of the amide bond of Ala-Pro is essential to the isomerization pathway occurring by rotating around its bond, these peptides have forms impossible to undergo proton transfer from the guanidyl group of Arg to the prolyl N atom, which induces loss of double bond character.

[Reading mind from pictures of eyes: theory of mind, language ability, general intellectual ability, and autism].

Some researchers have claimed that theory of mind or 'mind reading' ability, necessary for inferring the mental states of others, depends on language ability. However, previous tests of theory of mind were verbally demanding, and high correlations found might have been an artifact. This paper reports the performance of 22 children with autism, with varying degrees of dysfunction, on a test devised by Baron-Cohen, Jolliffe, Mortimore, and Robertson (1997), based on a relatively nonverbal theory of mind. The test involved inference of mental states from photographs of human eyes. Results indicated that mind reading ability was independent of language ability, general intelligence, or mental age. Test scores were, however, strongly related to the severity of autistic disorder. These results suggest both the independence of mind-reading ability from language ability and general intelligence, and a strong relationship between theory of mind deficit and the autistic disorder.

Changes in regional cerebral blood flow abnormalities in late-life depression following response to electroconvulsive therapy.

The impact of electroconvulsive therapy (ECT) on the regional cerebral blood flow (rCBF) abnormalities in late-life depression is still unknown and the clinical significance of these findings in late-life depression has not been fully discussed. Using single photon emission computed tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO), we examined the changes of rCBF patterns in nine late-life patients with major depressive episodes before and following response to ECT compared with nine age- and sex-matched healthy volunteers. Statistical comparisons were made on both region-of-interest (ROI) and voxel-by-voxel bases. In ROI-based analyses, a mean rCBF was significantly decreased in the patients before ECT compared with the control, significantly increased (normalized) in the patients 2 weeks after ECT compared with that before ECT, and still increased in the patients 12 weeks after ECT compared with that before ECT. In voxel-by-voxel analyses, a significant rCBF reduction was found in the bilateral pre- and subcallosal anterior cingulate cortex, the bilateral caudal orbitofrontal cortex, the right insular cortex and the right posterior middle frontal gyrus in patients before ECT compared with the control, and similar rCBF patterns were shown at 2 weeks and 12 weeks after ECT. We propose the hypothesis that a mean rCBF reduction may have a state-related property while persistent anterior paralimbic hypoperfusion may have a trait-like property, which relates to the relapse vulnerability as well as a tendency toward medication failure and illness chronicity in late-life depression.

Crystal structure of non-allosteric L-lactate dehydrogenase from Lactobacillus pentosus at 2.3 A resolution: specific interactions at subunit interfaces.

L-Lactate dehydrogenase (LDH) from Lactobacillus pentosus is a non-allosteric enzyme, which shows, however, high sequence similarity to allosteric LDHs from certain bacteria. To elucidate the structural basis of the absence of allostery of L. pentosus LDH (LPLDH), we determined the crystal structure of LPLDH at 2.3 A resolution. Bacterial LDHs are tetrameric enzymes composed of identical subunits and exhibit 222 symmetry. The quaternary structure of LPLDH was similar to the active conformation of allosteric LDHs. Structural analysis revealed that the subunit interfaces of LPLDH are optimized mainly through hydrophilic interactions rather than hydrophobic interactions, compared with other LDHs. The subunit interfaces of LPLDH are more specifically stabilized by increased numbers of intersubunit salt bridges and hydrogen bonds, and higher geometrical complementarity. Such high specificity at the subunit interfaces should hinder the rearrangement of the quaternary structure needed for allosteric regulation and thus explain the "non-allostery" of LPLDH.