, 2001). In addition, the upstream regions of atzA and atzB consist of an identical >7-kbp repeat starting only 5 bp upstream from the start codon of each gene. Each of these repeats contains three divergently transcribed truncated ORFs encoding incomplete subunits of pyruvate dehydrogenase, a complete IS1071 element and an additional transposase. This arrangement suggests that these genes do not contain a proper GSI-IX molecular weight promoter region and are likely transcribed from sequences serendipitously assembled upstream from the corresponding coding sequences. In contrast to the lack of regulation

in the early genes of the pathway, detailed gene expression studies performed using Pseudomonas putida KT2442 (Franklin et al., 1981) as a surrogate

host have revealed that the atzDEF operon is subjected to a complex two-tiered cascade regulatory circuit (reviewed by Govantes et al., 2009) (Fig. 2) reminiscent of that described for the nitrogen fixation (nif) genes in Klebsiella pneumoniae. The first tier of regulation involves the transcriptional activation of the atzR gene, encoding the LTTR AtzR, by the general nitrogen control activator NtrC, as well as atzR repression by its own gene product. In turn, AtzR activates atzDEF transcription in response to two signals that act in an additive fashion: the substrate of the pathway, cyanuric acid, which is sensed directly by AtzR, and nitrogen limitation, which is transmitted to AtzR by the PII signal transduction protein GlnK. Both levels of control are connected by the reciprocal regulation between NtrC and GlnK, as GlnK regulates the activity Ivacaftor concentration of NtrC (García-González et al., 2009) and NtrC activates the expression of GlnK (Hervás et al., 2008, 2009). Nevertheless, it is interesting that the regulation Epigenetics inhibitor of atzR transcription appears to be dispensable for correct atzDEF regulation, as constitutively

synthesized AtzR supports a nearly wild-type regulatory response under a wide range of conditions (García-González et al., 2005). Regulated AtzR synthesis may nevertheless contribute to the energy economy of the cell, as shown by the fact that AtzR is produced in vivo at very low concentrations (Porrúa et al., 2009). Alternatively, strict PatzR regulation may be critical under conditions different from those tested in the laboratory. The divergent atzR-atzDEF promoter region contains all the cis-acting elements required for the regulatory cascade of the cyanuric acid utilization operon, including the PatzR and PatzDEF promoters, and the AtzR-binding site (Fig. 3). The PatzR promoter is a typical σ54-dependent promoter driving the transcription of atzR. PatzR is predicted to be a strong promoter from its similarity to the consensus σ54-RNA polymerase recognition motif (CGGCACN5-TTGCT vs. TGGCAC-N5-TTGCA) (Barrios et al., 1999).

1 The WHO European Region has been free of autochthonous polio cases from 1998, and certification by the WHO in 2002 of this condition led to a modification in vaccine administration. The oral polio vaccine (OPV) has gradually been replaced with the enhanced potency inactivated polio vaccine (IPV), safer than Cabozantinib OPV because it is not associated with the rare

risk of vaccine-associated paralytic poliomyelitis (VAPP).3 In Italy, there is an increased and continuous inflow of refugees from countries where poliomyelitis is still present and this may represent a risk of the wild poliovirus strains being introduced. The Italian region of Puglia (Southern Italy) can be deemed a “border region” because, due to its geographic position, it has to face daily arrivals of refugees. The aim of this study was to evaluate the poliomyelitis immunization level, by titration Selleckchem Doxorubicin of the neutralizing antibody, in a sample of refugees of various nationalities

residing in the Asylum Seeker Center in Bari Palese in Puglia. The study was carried out during 2008 and involved 573 refugees, 520 (90.8%; 95% CI = 88–92.9) males and 53 (9.2%; 95% CI = 7.1 − 12) females. Of these, 546 (95.3%; 95% CI = 93.1 − 96.8) were from Africa and 27 (4.7%; 95% CI = 3.2 − 6.9) from Asia. In particular, 20 residents (3.5%; 95% CI = 2.2 − 5.4) were from Afghanistan and 67 (11.7%; 95% CI = 9.2 − 14.7) from Nigeria. The average age of the population sample was 24.3 (SD = 5.4; range 1–50). Signed informed consent to the study was not obtained from each participant. A 10 mL blood sample was obtained by venipuncture and the serum was separated by centrifugation. Each serum sample was coded and stored at −20°C. The immunity against poliomyelitis was evaluated as described previously.4 Demographic data from the Asylum Center database and the laboratory exam results were analyzed with the statistical software Epi-Info 6.00. Fisher’s exact test was used in the analysis of the difference between proportions. A value of p < 0.05 was considered as significant. An

antibody titer ≥1:8 was found in 571 subjects (99.6%) for poliovirus type 1, in 572 subjects (99.8%) for poliovirus type 2, and in 570 subjects (99.5%) for poliovirus type 3 (Table 1). All the subjects with an antibody titer less than 1:8 were males from Africa: specifically, a 20-year-old Nigerian with antibody titer less than 1:4 for the three types of poliovirus; two Somalis, aged 26 and 20, had antibody titers of 1:4 and 1:8, respectively. The levels of antibody titer did not significantly differ between Africans and Asians (Table 1). Our survey results revealed excellent immunization levels in the immigrants, in line with other studies in Europe in the last 15 years.5,6 However, we cannot exclude the existence of low-immunity pockets in the immigrant population just because they were not detected in our study.

[7] The causes may not only be related to cultural differences and language barriers, but also the economic difficulties, since once non-Japanese people become unemployed like the patient in case 3, re-employment can be somewhat difficult because of the Japanese government restricting the hiring of non-Japanese workers to professional or technical fields. Among the 591 total patients who visited our department for the first time in 2010, 55.2% of them were unemployed. Unemployment seems to be a major cause of psychosomatic disorders.

Regarding family life, there are cultural differences in child-rearing practices that might bring conflict between mixed nationality couples.[8] Moreover, lack of Idasanutlin mouse support from relatives and friends who live outside of Japan or the community is a serious problem, and non-Japanese people tend to feel isolated. If couples maintain a good relationship, BIBW2992 chemical structure this factor has limited influence. However, a lack of support during the break-up of relationships or suffering of conflicts has a serious

effect on a patient’s psychological damage as seen in cases 4 and 5. It is essential to take measures against language barriers. Language barriers, cultural differences, and low health literacy hamper effective communication between patients and health care professionals, and communication errors are related Thalidomide to the safety and quality of health care.[9] For example, adverse events occur when patients with limited English proficiency visit English-speaking doctors in the United States. While the patients in our study were able to consult an English-speaking doctor, Japanese medical

doctors are not generally competent at speaking English. Although medical interpreters in English and other languages have already been introduced to several hospitals in Japan, their number is insufficient. Interpreters in the field of transcultural PSM should particularly be promoted, because explaining psychological symptoms requires details that can be more difficult to explain than physical symptoms. Such detailed information is necessary in order for doctors to make an appropriate diagnosis.[10] In addition, a more comprehensive social support system for non-Japanese people should be introduced by the Japanese government because measures that are being taken to combat the declining birthrate and aging of Japanese society, such as inviting foreign workers to work in Japan, will result in an inevitable increase in expatriates. There were 1,354 PSM doctors in Japan as of 2011. A limitation of our study was that these cases were extracted in our hospitals only, therefore further studies are needed to investigate the present activities for non-Japanese patients by PSM doctors all over Japan. The authors state they have no conflicts of interest to declare.

Consistent with the hypothesis that higher levels of cholinergic neuromodulatory activity reduce opportunity costs in rats performing an attention task, such levels were found to correlate with the degree of task compliance under taxing conditions (Passetti et al., 2000). Furthermore, this hypothesis also predicts the relatively poor

and fluctuating levels of attentional performance in rats exhibiting relatively low GSK3235025 supplier levels of cholinergic neuromodulation during such performance (see Paolone et al., 2013). Likewise, this hypothesis predicts that humans who carry a minor allele of the choline transporter gene, which may limit the dynamic range of neuromodulatory cholinergic activation, self-report greater levels of distractibility in situations that readily allow for discontinuation Mitomycin C price of performance and engagement on alternative behavioral

of cognitive activities (e.g. are easily distracted by a TV or radio playing in the next room). In contrast, such vulnerability to distraction may be more difficult to demonstrate in situations that demand high levels of attention but are relatively devoid of competitive alternatives (Berry et al., 2013). In other words, compared with humans expressing the wild-type gene for this transporter, the variant-expressing subjects, assuming that expression of this allele limits the capacity for cholinergic neurotransmission, may experience higher opportunity costs and assign relative greater utility to engaging in alternative mental or behavioral action. As discussed above, the results of our research cumulatively support the hypothesis that increases in cholinergic neuromodulation enhance prefrontal glutamatergic–cholinergic transient interactions (Fig. 1) and that stimulation of nAChRs

‘import’ the neuromodulatory impact on transients. Our studies on the beneficial effects of alpha4beta2* nAChR agonists on cholinergic transients and SAT performance demonstrated that such benefits are restricted to SAT performance Sclareol that is burdened by the presence of a distractor. Furthermore, nAChR agonist-induced increase in hits was due primarily to an increase in hits on trials where a signal followed extended periods of nonsignal processing, that is, hits for which cholinergic transients are required (Howe et al., 2010). Thus, higher levels of cholinergic neuromodulation increase the probability for cholinergic transients and thus for incongruent hits. These considerations are consistent with the hypothesis that higher levels of cholinergic neuromodulatory activity lower opportunity costs in part by reducing detection uncertainty, thereby stabilising and restoring hit rates and thus performance outcome.

Germany HIV Research and Clinical Care Centre, München: Hans Jäger, Andrea Eberhad, Eva Jägel-Guedes, Tim Theobald, Eva Wolf; Charité, Universitätsmedizin, Berlin: Dirk Schürmann, Thomas Wünsche, Hans Wesselmann; Klinik fur Gastroenterologie Hepatologie und Infektiologie, Düsseldorf: Mark Oette, Klaus Göbels, Stefanie Koch, Ruth Leidel, Arne Kroidl; EPIMED, Berlin: Keikawus Arastéh. Italy Osp. S. Raffaele, Milano: Adriano Lazzarin, Antonella Castagna, Nicola Gianotti; Az. Osp. Polo Universitario ‘L. Sacco’, Milano:

Mauro Moroni, Antonella D’Arminio

Monforte, http://www.selleckchem.com/products/VX-809.html Teresa Bini, Patrizia Biasi; Ospedale Proteasome inhibitor ‘Amedeo di Savoia’, Torino: Giovanni Di Perri, Stefano Bonora, Lorenzo Veronese, Laura Ladetto; A.O. Spedali Civili di Brescia, Brescia: Giampiero Carosi, Giusseppe Paraninfo, Paola Nasta; Univ. Degli Studi ‘La Sapienza’, Roma: Vincenzo Vullo, Anna Paola Massetti, Claudio Maria Mastroianni, Miriam Lichtner, Azzura Ginevra Miccoli. Poland Wojewodzki Szpital, Warszawa: Andrzej Horban, Piotr Pulik, Anna Ignatowska; Katedra I Oddzia, Wroc. Aw: Andrzej Gladyzs, Brygida Knysz, Jacek Gasiorowski. Spain Hospital Santa Creu, Barcelona: Pere Domingo, Montserrat Fuster, Mar Gutierrez, Gracia Mateo, Mercedes Gurgui, Ma Antonia Sambeat, Jose Cadafalch; Hospital Germans Trias, Badalona: Bonaventura Clotet, Angel Ballesteros, Jose Miranda, Jordi Puig Pla; Hospital San Jaume de Calella, Calella:

Josep Ma Llibre, Silvia Valero. “
“We recently showed that a urine albumin/total protein ratio (uAPR) < 0.4 identifies tubular pathology in proteinuric patients. In tubular disorders, proteinuria is usually of low molecular weight and contains relatively little albumin. We tested the hypothesis that uAPR is useful in identifying tubular pathology related to antiretroviral HSP90 use in HIV-infected patients. We retrospectively identified urine protein/creatinine ratios (uPCRs) in HIV-infected patients. A subset of samples had uPCR and urine albumin/creatinie ratio (uACR) measured simultaneously. We classified proteinuric patients (uPCR > 30 mg/mmol) into two groups: those with predominantly ‘tubular’ proteinuria (TP) (uAPR < 0.4) and those with predominantly ‘glomerular’ proteinuria (GP) (uAPR ≥ 0.4).

, 1971; Cowman et al., 1983; Conway et al., 2003). In E. coli, an eightfold increase in the intracellular cysteine concentration promotes oxidative DNA damages by GSK126 order driving the Fenton reaction due to the efficient reduction of Fe3+ by cysteine (Park

& Imlay, 2003). In the B. subtilisΔcymR mutant grown in the presence of cystine, we observe both a fourfold increase in the intracellular cysteine pools and an enhanced sensitivity to paraquat and H2O2 stresses. However, the addition of an iron chelator (dipyridyl) had no positive effect on the viability of the ΔcymR mutant after a paraquat or an H2O2 challenge (data not shown). This suggests more complex mechanisms of stress in addition to the Fenton reaction-mediated

CHIR-99021 ic50 process, as proposed recently for other microorganisms (Almeida et al., 1999; Macomber et al., 2007). H2S also increases the formation of H2O2 and other ROS (Lloyd, 2006). This could also contribute to the oxidative stress sensitivity of the ΔcymR mutant. In accordance with the altered stress response in the ΔcymR mutant, the transcriptome data revealed the differential expression of some oxidative stress-related genes such as katA, ahpF, yoeB, yumC and ykzA (Choi et al., 2006; Even et al., 2006). Tellurite (TeO32−), even at low concentrations, is toxic for most forms of life. Despite the fact that the genetic and biochemical basis underlying bacterial tellurite toxicity is still poorly understood (Chasteen et al., 2009), the identification of tellurite resistance determinants suggests mechanisms involving cysteine metabolism and cellular oxidative Avelestat (AZD9668) stress due to its strong oxidizing ability. Cysteine synthases from various

bacteria and molecules containing cysteine are involved in tellurite resistance via the reductive detoxification of this compound (Chasteen et al., 2009). Interestingly, the ΔcymR mutant of B. subtilis presents a complex phenotype in the presence of tellurite. In this mutant, grown with cystine, we observed a drastic decrease in tellurite toxicity due to the accumulation of a thiol that promotes tellurite detoxification via the formation of nontoxic tellurium as indicated by the black precipitate in the plates (Fig. 4a). The protection against tellurite toxicity disappeared when we opened the lids, indicating that this thiol compound is volatile and probably corresponds to H2S. In a medium containing methionine or in the presence of cystine when the lid is kept open, the inactivation of CymR leads to extreme tellurite sensitivity. Under these conditions, tellurite toxicity might be due to its strong oxidizing ability, leading to oxidative stress (Turner et al., 2007; Chasteen et al., 2009). In conclusion, CymR inactivation results in profound metabolic changes in B. subtilis grown in the presence of cystine including the accumulation of thiol compounds and the depletion of branched chain amino acids.

The nodules lacked lenticels and fixed two times less nitrogen (Rojas-Jiménez et al., 2005). The three R. tropici mutants (ΔolsC, ΔolsE, and ΔolsCΔolsE) lacking OL hydroxylases established their symbiosis only poorly (Vences-Guzmán et al., 2011). As R. tropici is challenged by low pH conditions inside its host plant (Udvardi et al., 1991; Udvardi & Day, 1997), it can be speculated that the observed symbiotic phenotype

is a consequence of the mutants’ increased acid sensitivity. The OL hydroxylase OlsD was first isolated from B. cenocepacia J2315, a β-proteobacterium known as an opportunistic pathogen of humans. González-Silva et al. (2011) originally suggested that 2-hydroxylation of OLs in B. cenocepacia might be performed by an LpxO homolog called OlsD (BCAM2401). OlsD indeed hydroxylated

OL, but the hydroxylation did not occur on the ester-linked fatty acid. Surprisingly, selleck inhibitor data obtained by mass spectrometry suggested that OlsD modifies the amide-linked fatty acid of OLs with a hydroxyl group (Fig. 2), a modification that was previously unknown. Unfortunately, their analysis did not allow for the determination of the exact position of the hydroxyl group. OlsD from B. cenocepacia is a 249-amino-acid protein, apparently lacking transmembrane helices (González-Silva et al., 2011). It is widely distributed within the genus Burkholderia, but homologs are also present in three Serratia strains. The gene coding for the 2-hydroxylase Galunisertib order activity hydroxylating the ester-linked fatty acyl residue in the C-2 position in B. cenocepacia has not been identified yet. Rojas-Jiménez et al. (2005) had described the presence of four different OLs in R. tropici CIAT899. The presence of OlsC alone could not explain this number of distinct structures. Using a functional expression screen conjugating a cosmid bank from R. tropici into S. meliloti, Vences-Guzmán et al. (2011) identified the gene olsE coding for the hydroxylase OlsE. Mass spectrometry analysis showed that OlsE introduced a hydroxyl group in the ornithine moiety. So far,

the exact position of the hydroxylation could not be determined, but ninhydrin staining of the selleck chemicals llc different OLs shows that the hydroxyl group affects the reactivity of the lipid to ninhydrin. Bioinformatic predictions indicate that the OlsE protein (331 amino acids) from R. tropici CIAT899 is highly hydrophobic and might form between 4 and 6 transmembrane helices. OlsE belongs to the fatty acyl hydroxylase superfamily (cl01132), which is characterized by the presence of two copies of the HXHH motif. This superfamily includes fatty acid and carotene hydroxylases, sterol desaturases, and C-4 sterol methyl oxidase (Arthington et al., 1991; Bard et al., 1996; Mitchell & Martin, 1997; Kennedy et al., 2000). A similar motif can be found in membrane-bound fatty acid desaturases such as OLE1 from Saccharomyces cerevisiae and in bacterial alkane hydroxylase and xylene monooxygenase (Kok et al.

Baseline assessment of existing diabetes care can inform such design and implementation. The aim of this study was to inventory diabetes health care resources in Qatar. A prospective survey of private and public health care facilities serving outpatients in the country was conducted. A nine-item questionnaire was administered to determine patient access, multidisciplinary services and availability of drug therapy. Thirty-five (67%) of 52 identified health care settings participated. Services devoted to diabetes care were BAY 73-4506 mouse declared at five hospitals (one private and four public) and 24 clinics (15 private and nine public). The majority were located

in the country’s capital. Few offered services to children and adolescents (20% of hospitals, 55% of clinics). Most were led by general practitioner physicians with limited multidisciplinary contribution (nurses in 73%, dietitians

in 17%). Administration of certain drug therapy may be restricted to specialist prescribers and may be unavailable to non-nationals. Patients with diabetes in Qatar may seek care from an array of private and public health settings. Elements of any comprehensive national plan to address diabetes and its complications must incorporate enhanced training support for primary care physicians, expanded multidisciplinary care and services for children and adolescents. Copyright © 2011 John Wiley & Sons. Diabetes is recognised as a global epidemic affecting some 200 million people worldwide. According to the International Diabetes Federation, this figure is projected to increase to 333 million by 2025.1 Regions AZD4547 datasheet with the highest prevalence are currently found in Gulf Corporation Council countries, including the state of Qatar, an Arab emirate occupying a small peninsula in the Persian Gulf.2 This gas- and oil-rich nation has ioxilan a population of around 1.9 million predominantly comprised of diverse

expatriate populations, of which as many as 700 000 are from South East Asia and possess inherent predispositions towards diabetes.3,4 Estimates of diagnosed diabetes in Qatar have ranged from 12% (all residents) to 17% (among Qatari only) with another 10% characterised as ‘pre-diabetes’.5,6 The high proportion of people in Qatar with impaired glucose tolerance and other associated modifiable risk factors (central obesity, sedentary behaviour) will only contribute to an increased prevalence of diabetes in the country over the coming years.7 Therapeutic targets are identified for glucose, blood pressure and lipid measurements and other modifiable risk factors. These goals are encompassed in a number of international clinical practice guideline documents outlining standards for diabetes care.8–11 Despite availability of such tools, gaps exist in translating evidence-based care into clinical practice.

melitensis OM properties, the survival of BM, BMΔvirB and BM-IVGT

under oxidative, high-salinity and high-osmolarity stresses simulating intracellular environments was compared. As shown in Fig. 4b, the survival of BMΔvirB decreased under these stress conditions when compared with that of BM. The decreased survival of BMΔvirB was recovered in the complementary strain BM-IVGT, indicating that the reduced survival is dependent on the inactivation of T4SS. Members of the genus Brucella are intracellular bacterial pathogens of a number of mammals. The ability of Brucella to invade and replicate in cells has been proven to be linked to its OM properties as well as the structures of the cell envelope. The notion that the Brucella OM plays important roles in virulence this website has AZD3965 been reinforced by the result that the virulence-related two-component regulatory system BvrR/BvrS regulates the expression of OMPs as well as the structure of the lipopolysaccharide (Guzman-Verri et al., 2002; Manterola et al., 2005), suggesting that virulence regulation systems may influence virulence by affecting

the expression of OMPs. A quorum-sensing regulator vjbR was found to be essential for Brucella intracellular survival, and the vjbR mutant also showed considerable modifications in surface structure (Delrue et al., 2005; Uzureau et al., 2007). Delpino et al. (2009) found that three products were detected in the supernatant of wild-type B. abortus, but not its isogenic virB mutant. In a previous study, using comparative

proteomic technology, we analyzed whole bacterial proteins and found that in addition to a number of intracellular survival-related proteins that were differentially expressed in the virB mutant, expression profiles of products of the Omp25/Omp31 family were also changed, implying that T4SS might affect the membrane structure. In the present study, we compared the membrane proteomes of BM and its virB mutant. Many more OMPs were identified to be differentially expressed, confirming that the intracellular survival-related T4SS also affects the expression of OMPs and the OM properties of Brucella. As expected, far more Carbohydrate membrane proteins were identified in OM fractions (Table 1). The Brucella spp. Omp25/Omp31 family comprises seven homologous OMPs: Omp25, Omp25b, Omp25c, Omp25d, Omp31 and Omp31b (Cloeckaert et al., 2002). The expression profiles of Omp25, Omp25b, Omp25c and Omp31 were altered when virB was inactivated. Consistent with results from whole bacterial proteins, more than one protein spot for these proteins was observed on the 2-DE gels. These different protein spots might arise from post-translational modification or breakdown of the OMPs, which has been observed in other bacteria genera (Ying et al., 2005). The different protein products of Omp25 resulting from post-translational modification were validated by the results that transcription of omp25 was altered in 40–200% (Fig. 2).

In contrast, the OSA patient response showed MEP amplitudes of 124%, 152% and 159% of baseline at 10, 20 and 30 min post-intervention, respectively. Group data from 13 patients with OSA and 11 control subjects are shown in Fig. 2B. When normalised to before cTBS, the MEP amplitude showed a significant main effect of time

(F2,315 = 5.49, P = 0.005) and a significant group × time interaction (F2,315 = 3.93, P = 0.02), although there was no main effect of group (F1,22 = 1.78, P = 0.20). Subsequent post hoc tests showed that the MEP amplitude in control subjects at the 10-min time point was significantly lower than at the 30-min time point (P = 0.002). Furthermore, there was a significant difference in MEP amplitude between the patients with OSA EPZ-6438 and control subjects 20 min after cTBS (P = 0.05). Inclusion of the one control subject identified as an outlier in the preliminary analysis (13 patients with OSA and 12 control subjects) did not alter the main findings, with a significant main effect of time (F2,323 = 4.96, P = 0.008) and a significant group × time interaction (F2,323 = 4.71,

P = 0.01), indicating that the main outcomes were not sensitive to exclusion of this subject. Regression plots for comparisons between AHI, ESS, RMT and MEP1 mV are shown in Fig. 3. For all subjects, AHI demonstrated MI-503 concentration significant positive relationships with both RMT (r2 = 0.19, P = 0.03) and MEP1 mV (r2 = 0.22, P = 0.02). ESS also demonstrated similar significant relationships with these measurements (RMT: r2 = 0.19, P = 0.03; MEP1 mV: r2 = 0.19, P = 0.03). Furthermore, minimum O2-saturation during NREM sleep showed significant negative relationships to RMT (r2 = 0.20, P = 0.03) and MEP1 mV (r2 = 0.23, P = 0.02; data not shown). Leisure time activity showed a significant relationship with the change in MEP amplitude

at 10 min (r2 = 0.19, P = 0.03) and 20 min (r2 = 0.29, P = 0.006) post-intervention, with a trend towards a relationship at 30 min post-intervention (P = 0.06). The magnitude of inhibition measured during LICI with a 150-ms ISI also showed a trend towards a relationship at 30 min post-intervention (P = 0.06). No further relationships approached statistical significance. This study is the first to use TMS to investigate neuroplasticity in patients with OSA. The Silibinin main findings were that patients with moderate-to-severe OSA show an abnormal response to cTBS, indicating altered motor cortex plasticity. Furthermore, differences in ICI are unlikely to contribute to this effect. The abnormal response to cTBS suggests that changes in cortical plasticity may be a consequence of OSA pathophysiology. In the present study, excitability of cortical areas innervating a hand muscle was used as an index of global alterations in brain function in patients with OSA, as hand muscles have strong corticospinal projections to motor neurons and are easily activated by TMS (Petersen et al.