A workflow for deriving chemical entities from crystallographic data and its application to the Crystallography Open Database.

Knowledge about the 3-dimensional structure, orientation and interaction of chemical compounds is important in many areas of science and technology. X-ray crystallography is one of the experimental techniques capable of providing a large amount of structural information for a given compound, and it is widely used for characterisation of organic and metal-organic molecules. The method provides precise 3D coordinates of atoms inside crystals, however, it does not directly deliver information about certain chemical characteristics such as bond orders, delocalization, charges, lone electron pairs or lone electrons. These aspects of a molecular model have to be derived from crystallographic data using refined information about interatomic distances and atom types as well as employing general chemical knowledge. This publication describes a curated automatic pipeline for the derivation of chemical attributes of molecules from crystallographic models. The method is applied to build a catalogue of chemical entities in an open-access crystallographic database, the Crystallography Open Database (COD). The catalogue of such chemical entities is provided openly as a derived database. The content of this catalogue and the problems arising in the fully automated pipeline are discussed, along with the possibilities to introduce manual data curation into the process.

Sonographic Phrenic Nerve Changes in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity of the affected patients, limits daily activities, and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. Forty-six participants were included in our study, with 23 patients in the ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as an additional diagnostic tool for ALS.

PLBD: protein-ligand binding database of thermodynamic and kinetic intrinsic parameters.

We introduce a protein-ligand binding database (PLBD) that presents thermodynamic and kinetic data of reversible protein interactions with small molecule compounds. The manually curated binding data are linked to protein-ligand crystal structures, enabling structure-thermodynamics correlations to be determined. The database contains over 5500 binding datasets of 556 sulfonamide compound interactions with the 12 catalytically active human carbonic anhydrase isozymes defined by fluorescent thermal shift assay, isothermal titration calorimetry, inhibition of enzymatic activity and surface plasmon resonance. In the PLBD, the intrinsic thermodynamic parameters of interactions are provided, which account for the binding-linked protonation reactions. In addition to the protein-ligand binding affinities, the database provides calorimetrically measured binding enthalpies, providing additional mechanistic understanding. The PLBD can be applied to investigations of protein-ligand recognition and could be integrated into small molecule drug design. Database URL https://plbd.org/.

Graph isomorphism-based algorithm for cross-checking chemical and crystallographic descriptions.

Published reports of chemical compounds often contain multiple machine-readable descriptions which may supplement each other in order to yield coherent and complete chemical representations. This publication presents a method to cross-check such descriptions using a canonical representation and isomorphism of molecular graphs. If immediate agreement between compound descriptions is not found, the algorithm derives the minimal set of simplifications required for both descriptions to arrive to a matching form (if any). The proposed algorithm is used to cross-check chemical descriptions from the Crystallography Open Database to identify coherently described entries as well as those requiring further curation.

The Relationship between Intracranial Pressure and Visual Field Zones in Normal-Tension Glaucoma Patients.

Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP's relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management.

Randomized Double-Blind Placebo-Controlled Trial of the Corticosteroid-Sparing Effects of Immunoglobulin in Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG. METHODS: In this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II-Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available at clinicaltrials.gov/ct2/show/NCT02473965. RESULTS: The primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated. DISCUSSION: In this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different. TRIAL REGISTRATION INFORMATION: The trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) and clinicaltrials.gov (identifier NCT02473965). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

Reperfusion Therapies for Acute Ischemic Stroke in COVID-19 Patients: A Nationwide Multi-Center Study.

(1) Background: Acute ischemic stroke (AIS) is a possible complication of the coronavirus disease 2019 (COVID-19). Safety and efficacy data on reperfusion therapies (RT)-intravenous thrombolysis and endovascular treatment (EVT)-in stroke patients with COVID-19 is lacking. (2) Methods: We performed a retrospective nationwide multi-center pair-matched analysis of COVID-19 patients with AIS who underwent RT. We included adult COVID-19 patients with AIS who were treated with RT between 16 March 2020 and 30 June 2021. All subjects were paired with non-infected controls, matched for age, sex, stroke arterial vascular territory, and RT modality. The primary outcome measure was a favorable functional outcome defined by the modified Rankin scale (mRS 0-2). (3) Results: Thirty-one subjects and thirty-one matched controls were included. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was higher in the COVID-19 group (16 vs. 12, p = 0.028). Rates of ischemic changes and symptomatic intracerebral hemorrhages did not differ significantly between the two groups at 24 h after RT. The median NIHSS 24 h after reperfusion remained significantly higher in the COVID-19 group (16 vs. 5, p = 0.003). MRS 0-2 at discharge was significantly less common in COVID-19 patients (22.6% vs. 51.8%, p = 0.018). Three-month mortality was 54.8% in the COVID-19 group versus 12.9% in controls (p = 0.001). (4) Conclusion: Reperfusion therapies on AIS in COVID-19 patients appear to be safe; however, functional outcomes are significantly worse, and 3-month mortality is higher.

Creutzfeldt-Jakob disease with neuroleptic malignant syndrome.

Creutzfeldt­Jakob disease (CJD) is a rare rapidly progressive fatal neurodegenerative disease. Neuroleptic malignant syndrome (NMS) is a complication of antipsychotic medications which may be used to treat neuropsychiatric symptoms of CJD. We present a case of a 51­year­ old woman with CJD who developed NMS after being prescribed quetiapine.

Effect of aging on vagus somatosensory evoked potentials and ultrasonographic parameters of the vagus nerve.

Vagus somatosensory evoked potentials (VSEP) and ultrasonography can be used to detect functional and structural changes of the vagus nerve (VN) that are hypothesized to be associated with neurodegenerative diseases. However, it has not yet been established whether age-related changes in the VN occur in the healthy population. In this pilot study we included healthy volunteers in the 26-30 and 51-55 age range who comprised the younger (n = 20) and older (n = 20) groups, respectively. VSEP were recorded separately for stimulation of the auricular branch of the left and right VN. The VN CSA was measured in the transverse plane proximal to the carotid bifurcation, at the level of the distal end of the common carotid artery. No differences were found between the younger and older groups when comparing the average VN CSA (2.01 ± 0.20 vs 2.05 ± 0.20, mm2; p = 0.570) or the CSA of the right (2.08 ± 0.19 vs 2.17 ± 0.24, mm2; p = 0.233) or left VN (1.94 ± 0.26 vs 1.93 ± 0.24, mm2; p = 0.911). The right VN was larger than the left in 95% (n = 19) of older participants and in 65% (n = 13) of younger participants (p = 0.055). In comparison with the younger group, older participants showed significantly longer VSEP latencies of all wave components for electrodes C4-F4 and Fz-F3, of P1 for electrodes C3-F3 and of N1 and P2 for electrodes Fz-F4. The results of this study indicate that older age is associated with longer VSEP latencies but not with changes in VN CSA.

Subspecialty training of neurology residents and junior neurologists in the Baltic States.

BACKGROUND: Neurology is a field of increasing subspecialization. There is no published data regarding the proportion of neurology subspecialists in the Baltic States. The aim of this cross-sectional study was to identify factors associated with neurology subspecialty choice, to examine possible differences between neurology residents' and junior neurologists' view of subspecialty, and to assess perceived subspecialty acquisition opportunities and subspecialty attractiveness. METHODS: The research was conducted as an anonymous online survey between December 28, 2020, and January 24, 2021 of neurology residents and neurologists who completed their residency during the last 5 years in the Baltic States. RESULTS: In total, 72 residents and 65 neurologists participated. "Cerebrovascular diseases" and "multiple sclerosis and autoimmune diseases of the nervous system" were rated as the two most attractive subspecialties by residents, whereas "headache" and "clinical neurophysiology" were the most attractive among junior neurologists. "Vertigo and dizziness" and "dementia" were ranked the least attractive among both groups. "Cerebrovascular diseases" were perceived as having the most acquisition opportunities. The two most common determinants of subspecialty choice were "medical content of the subspecialty" and "influence of mentor during undergraduate studies or residency". CONCLUSIONS: Two-thirds of junior neurologists subspecialize in at least one subspecialty, and one-third of residents are already determined to pursue subspecialty training. Junior neurologists rated most outpatient-related subspecialties as more attractive than neurology residents. Between the Baltic States' universities, there was a significant difference in the number of residents who were determined to pursue subspecialty training.

Validation of the Crystallography Open Database using the Crystallographic Information Framework.

Data curation practices of the Crystallography Open Database (COD) are described with additional focus being placed on the formal validation using the Crystallographic Information Framework (CIF). The cif_validate program, capable of validating CIF files against both the DDL1 and the DDLm dictionaries, is presented and used to process the entirety of the COD. Validation results collected from over 450 000 CIF files are demonstrated to be a useful resource in the data maintenance process as well as the development of the underlying ontologies. A set of programs intended to aid in the dictionary migration from DDL1 to DDLm is also presented.

Pain Characteristics and Associations with Quality of Life in Patients with Multiple Sclerosis in Lithuania.

BACKGROUND AND OBJECTIVES: Even though pain in multiple sclerosis (MS) patients is common and possibly associated with reduced quality of life, its exact prevalence and characteristics remain vaguely understood. We aimed to estimate the true extent of pain and its associations with quality of life in Lithuanian MS patients and to compare this data with that of a control group. MATERIALS AND METHODS: Data were collected prospectively at the Department of Neurology, Lithuanian University of Health Sciences Kaunas Clinics. A face-to-face structured interview and a questionnaire were used to collect demographic and clinical data of the MS (n = 120) and control (n = 120) groups. The Expanded Disability Status Scale (EDSS) was used to quantify disability in the MS group. Scores ≥4/10 in the Douleur Neuropathique 4 questionnaire were classified as neuropathic pain. Patients were evaluated using the anxiety and depression subsets of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D), the physical and mental component subsets of the Short Form-12 questionnaire (PSC-12 and MSC-12). RESULTS: The MS and control groups did not differ in pain prevalence (76.7% vs. 65.9%, p = 0.064) or intensity. Lhermitte sign, lower limb, and face pain were more common in the MS group, whereas subjects in the control group were more often affected by lower back, neck, and joint pain. Neuropathic pain and pain lasting longer than 2 years were more common among pain-affected MS patients than among controls. MS patients with pain had higher EDSS, HADS-D, and HADS-A and lower PSC-12 scores than those without pain; however, no difference was found regarding the duration of MS or age. Males with MS and pain had higher MSC-12 and HADS-D scores in comparison to the same subset of females. CONCLUSIONS: Pain affects approximately three out of four patients with MS in Lithuania and is negatively associated with the mental and physical aspects of quality of life.

Local Vibrational Therapy for Essential Tremor Reduction: A Clinical Study.

Background and objectives: tremor is an unintentional and rhythmic movement of any part of the body that is a typical symptom of Essential Tremor (ET). ET impairs the quality of life of patients and is treated with pharmacotherapy. We investigated the tremor reduction efficacy of an innovative vibrational medical device (IMD) in ET patients. Materials and Methods: we conducted a prospective, single-center, single-arm, pragmatic study in ET patients with an extended safety study to evaluate the efficacy and safety of the Vilim Ball-a local hand-arm vibration device that produces vibrations in the frequency range of 8-18 Hz and amplitude from 0 to 2 mm. The primary endpoint was the decrease in the power spectrum after device use. The secondary endpoints were safety outcomes. Results: In total, 17 patients with ET were included in the main study, and no patients withdrew from the main study. The tremor power spectrum (m2/s3 Hz) was lower after the device use, represented as the mean (standard deviation): 0.106 (0.221); median (Md) 0.009 with the interquartile range; IQR, 0.087 vs. 0.042 (0.078); Md = 0.009 with the IQR 0.012; Wilcoxon signed-rank test V = 123; and p = 0.027. Seven patients reported that vibrational therapy was not effective. Two patients reported an increase in tremor after using the device. In the extended safety study, we included 51 patients: 31 patients with ET and 20 with Parkinsonian tremor, where 48 patients reported an improvement in tremor symptoms and 49 in function. No serious adverse events were reported, while two patients in the Parkinsonian tremor group reported a lack of efficacy of the proposed medical device. Conclusions: the device reduces essential tremor in some patients and is safe to use in ET.

Evaluating the functional and structural changes in the vagus nerve: Should the vagus nerve be tested in patients with atrial fibrillation?

One of the multiple factors believed to contribute to the initiation and maintenance of atrial fibrillation (AF) is altered activity of the autonomic nervous system. Debate continues about the role of the vagus nerve (CNX) in AF since its effect depends on the level of its activation as well as on simultaneous sympathetic activation. Surplus either vagal or sympathetic activity may rarely induce the development of AF; however, typically loss of balance between the both systems mediates the induction and maintenance of AF. Vagal stimulation has been proposed as a novel treatment approach for AF because the anti-arrhythmic effects of low-level vagus nerve stimulation have been shown both in patients and animal models. We hypothesize that in typical cases of AF without any clear trigger by either autonomic nervous system, significant changes in vagus somatosensory evoked potentials and a smaller cross-sectional area of CNX could be detected, representing functional and structural changes in CNX, respectively.

Primary Headaches and Sleep Disturbances: A Cause or a Consequence?

AIMS: To evaluate the possible relationship between sleep disturbances and primary headaches. METHODS: This prospective study was carried out in a random group of patients with active primary headaches (case group) and a control group. Patients with active primary headaches were further stratified into two groups: patients with migraine and patients with tension-type headache (TTH). Participants were questioned using the following standardized tests: Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Berlin Sleep Apnea Questionnaire (BSAQ), and a custom-made headache questionnaire. The results of the questionnaires were compared among patients with TTH, patients with migraine, and age- and sex-matched controls. RESULTS: Of the 143 participants, 22.4% had TTH, 30.8% were diagnosed with migraine, and 46.9% did not have a diagnosed headache disorder. Patients with TTH were more likely to have insomnia (ISI score > 7) than patients with migraine (75% vs 50%, respectively) or controls (75% vs 37.3%, respectively) (P = .002). Frequency of poor sleep quality (global PSQI score ≥ 6) was significantly highest in the TTH group (87.5%), while the migraine and control groups had better sleep quality (47.7% and 43.3%, respectively) (P = .0001). TTH patients were more likely to have insufficient sleep (sleep efficiency < 85%) (53.1%) than those with migraine (25%) or the control group (29.9%) (P = .025). CONCLUSION: Patients who suffered from TTH were more likely to have insomnia than patients with migraine or controls. Nearly all patients with TTH had poor sleep quality, which was also observed in approximately half of the individuals in the migraine and control groups. Three-quarters of patients in the TTH group and more than half in the migraine group indicated inadequate sleep as a trigger factor for headache.

Clinical and diagnostic features of patients with familial multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a demyelinating CNS disease. Most MS cases are sporadic, however about 20 percent of them are hereditary (Ramagopalan and Sadovnick, 2011). The incidence of familial MS is greater in regions with the highest prevalence of this disease (in North America, Europe) (Ramagopalan and Sadovnick, 2011). It is still unclear whether heredity affects the progression and severity of the disease. The aim of this study is to assess the effect of heredity on the development of multiple sclerosis and on the course of disease by analyzing the results of disability and severity scales, as well as clinical studies, and comparing them with sporadic cases. METHODS: Our study included 104 patients with MS. The study group was comprised of 38 patients with history of first degree relative also affected by MS; the control group consisted of 66 patients with no family history (sporadic case). The anonymous survey included questions about demographic and clinical characteristics. Diagnostic results of magnetic resonance imaging (MRI), oligoclonal bands (OCBs) and visual evoked potentials (VEP) were evaluated retrospectively from medical records. Disability assessment was made according to expanded disability status scale (EDSS). Multiple Sclerosis Severity Score (MSSS) score was calculated using conversion table based on EDSS score and duration of disease in years. RESULTS: MS patients with first degree relative affected by MS tend to have slower onset of the disease, while control group is more likely to have an acute onset (p < 0.001). The majority of MS with family history considered that their disease is caused by certain factors, while patients in the control group considered that the disease started without any identifiable cause (p < 0.05). Study group more often complained of pyramidal disorders (74% vs. 50%), symptoms related to brainstem (68% vs. 20%) and cortical lesions (47% vs. 20%), headache (37% vs. 9%), back pain (32% vs. 9%) than those in control group, p < 0.05. The degree of disability according to EDSS and MSSS scores were higher in the group of patients with first degree relative with MS (p < 0.05). The number of exacerbations per year was also higher in study group than in the control group (1.4 vs. 0.8; p < 0.05). Patients with a family history have a higher incidence of MRI changes in brainstem (74% vs. 30%) and cerebellum (58% vs. 30%) than the control group (p < 0.01). CONCLUSIONS: MS patients with a family history of MS tend to have slower onset of the disease, while control group is more likely to have an acute onset. Patients with a family history of MS more often complained of brainstem and cortical dysfunction, and pain in head or back. Both the degree of disability according to EDSS and MSSS scores were higher in familial cases. They also have a higher number of exacerbations per year. Patients with a history of first degree relative with MS have a higher incidence of MRI changes in brainstem and cerebellum.

KAMST - Simple method for patients with migraine screening.

Migraine is highly prevalent and disabling disorder, but despite that one of the main problems that remains in the clinical practice is delayed diagnosis and delayed specific treatment that has impact on patients' quality of life and productivity. There should be easy acceptable method to select those patients who might have migraine and who need to be referred to neurologist's consultation. We hypothesize that our created KAMST questionnaire is reliable method to select patients who might have migraine in primary care. To evaluate our hypothesis we made a research that consisted of two parts. Part A consisted of closed type questions made by The International Classification of Headache Disorders 3rd edition diagnostic criteria of migraine without aura. Part B was KAMST questionnaire. 298 patients were questioned. 209 (72%) of them were women and 89 (28%) - men. According to The International Classification of Headache Disorders 3rd edition migraine without aura diagnostic criteria, migraine was diagnosed for 42 (14,1%) patients, and according our KAMST questionnaire - 83 (27,9%). From 42 patients whom migraine was diagnosed with The International Classification of Headache Disorders 3rd edition criteria, 34 (81%) of these patients migraine was diagnosed with KAMST. From 256 patients whom migraine wasn't diagnosed with The International Classification of Headache Disorders 3rd edition criteria, 49 of them (19,1%) migraine was diagnosed with KAMST. We found statistically significant difference between questionnaires. KAMST sensitivity was - 81%, specificity - 81%, predictive positive value - 41%, predictive negative value - 96%, the Cronbach alpha for the total scale was 0,604. Our KAMST questionnaire of migraine is reliable and valid method for patients' screening but has some limitations.

Raman Open Database: first interconnected Raman-X-ray diffraction open-access resource for material identification.

Detailed crystallographic information provided by X-ray diffraction (XRD) is complementary to molecular information provided by Raman spectroscopy. Accordingly, the combined use of these techniques allows the identification of an unknown compound without ambiguity. However, a full combination of Raman and XRD results requires an appropriate and reliable reference database with complete information. This is already available for XRD. The main objective of this paper is to introduce and describe the recently developed Raman Open Database (ROD, http://solsa.crystallography.net/rod). It comprises a collection of high-quality uncorrected Raman spectra. The novelty of this database is its interconnectedness with other open databases like the Crystallography Open Database (http://www.crystallography.net/cod and Theoretical Crystallography Open Database (http://www.crystallography.net/tcod/). The syntax adopted to format entries in the ROD is based on the worldwide recognized and used CIF format, which offers a simple way for data exchange, writing and description. ROD also uses JCAMP-DX files as an alternative format for submitted spectra. JCAMP-DX files are compatible to varying degrees with most commercial Raman software and can be read and edited using standard text editors.

Preclinical signs of Parkinson's disease: A possible association of Parkinson's disease with skin and hair features.

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by loss of dopaminergic neuromelanin containing neurons in the substantia nigra. Peripheral melanin, found in skin and hair, and neuromelanin appear to have some characteristics in common and share the same precursor for their synthesis; therefore, skin and hair features could be associated with PD. We hypothesize that earlier age at onset of hair greying, greater tendency to sunburn, difficulty tanning and dysregulation of sebum production are more common among PD patients due to genetically determined lower constitutive amounts of melanin and accumulation of α-synuclein in the skin, which leads to disrupted synthesis of peripheral melanin and dysregulated sebum secretion. In order to test this hypothesis 32 PD patients and 35 age and gender matched PD-unaffected individuals were included in a pilot study. The median of age at onset of hair greying was 30% lower in the PD group compared to the control group (35 and 50 years, respectively, p = 0.002). Age at onset of hair greying ≤ 41 years predicted the development of PD with 71.0% sensitivity and 70.6% specificity (area under curve = 0.725, 95% confidence interval = 0.601-0.850, p = 0.002). Significant differences were found when comparing skin types between PD patients and the control group (p < 0.001): dry (n = 14, 43.8%) and oily (n = 9, 28.1%) skin types were the most prevalent among individuals with PD, whereas the majority of control subjects reported having normal skin (n = 24, 68.6%). Differences in tanning ability were also found between the groups (p = 0.035): the majority of individuals in the control group (n = 24, 68.6%) and only 12 (37.5%) PD patients reported being able to tan easily. PD patients were also more likely to burn often in comparison to control subjects (n = 21, 65.6% vs n = 10, 28.6%, p = 0.001). Our results support the hypothesis that PD is associated with earlier age at onset of hair greying, greater tendency to sunburn, difficulty tanning and non-normal skin type; however these ideas should be evaluated in a large prospective study in order to draw final conclusions. If such work supports our hypothesis, skin and hair features could be included in a risk-score model to identify individuals at high risk of PD in order to diagnose patients prior to the manifestation of motor symptoms and initiate potential neuroprotective treatment when neuronal loss is minimal.

Using SMILES strings for the description of chemical connectivity in the Crystallography Open Database.

Computer descriptions of chemical molecular connectivity are necessary for searching chemical databases and for predicting chemical properties from molecular structure. In this article, the ongoing work to describe the chemical connectivity of entries contained in the Crystallography Open Database (COD) in SMILES format is reported. This collection of SMILES is publicly available for chemical (substructure) search or for any other purpose on an open-access basis, as is the COD itself. The conventions that have been followed for the representation of compounds that do not fit into the valence bond theory are outlined for the most frequently found cases. The procedure for getting the SMILES out of the CIF files starts with checking whether the atoms in the asymmetric unit are a chemically acceptable image of the compound. When they are not (molecule in a symmetry element, disorder, polymeric species,etc.), the previously published cif_molecule program is used to get such image in many cases. The program package Open Babel is then applied to get SMILES strings from the CIF files (either those directly taken from the COD or those produced by cif_molecule when applicable). The results are then checked and/or fixed by a human editor, in a computer-aided task that at present still consumes a great deal of human time. Even if the procedure still needs to be improved to make it more automatic (and hence faster), it has already yielded more than 160,000 curated chemical structures and the purpose of this article is to announce the existence of this work to the chemical community as well as to spread the use of its results.